bluuebunny/crossref_metadata_2025 huggingface dataset:
A coarse Cartan–Hadamard theorem with application to the coarse Baum–Connes conjecture
Authors: Fukaya Tomohiro , Oguni Shin-ichi
Published: October 2018

We establish a coarse version of the Cartan–Hadamard theorem, which states that proper coarsely convex spaces are coarsely homotopy equivalent to the open cones of their ideal boundaries. As an application, we show that such spaces satisfy the coarse Baum–Connes conjecture. Combined with the result of Osajda–Przytycki, it implies that systolic groups and locally finite systolic complexes satisfy the coarse Baum–Connes conjecture.
Automatic analysis of microblogging data to aid in emergency management
Authors: Manna Sukanya
Published: October 2018

Microblogging platforms like Twitter, in the recent years, have become one of the important sources of information for a wide spectrum of users. As a result, these platforms have become great resources to provide support for emergency management. During any crisis, it is necessary to sieve through a huge amount of social media texts within a short span of time to extract meaningful information from them. Extraction of emergency-specific information, such as topic keywords or landmarks or geo-locations of sites, from these texts plays a significant role in building an application for emergency management. This paper thus highlights different aspects of automatic analysis of tweets to help in developing such an application. Hence, it focuses on: (1) identification of crisis-related tweets using machine learning, (2) exploration of topic model implementations and looking at its effectiveness on short messages (as short as 140 characters); and performing an exploratory data analysis on short texts related to crises collected from Twitter, and looking at different visualizations to understand the commonality and differences between topics and different crisis-related data, and (3) providing a proof of concept for identifying and retrieving different geo-locations from tweets and extracting the GPS coordinates from this data to approximately plot them in a map.
Interpretation of regional-scale distribution of high Hg in soils of karst area in southwest China
Authors: Nie Lanshi , Liu Xuemin , Wang Xueqiu , Liu Hanliang , Wang Wei
Published: October 2018

The abundance and spatial distribution of mercury in soil samples covering nearly the whole of China (
c
. 9 million km
2
) were obtained by the China Geochemical Baseline (CGB) project from 2008 to 2015. From the data and maps, it was found that the Hg contents both in the top (0–25 cm) and deep soil (below 100 cm or C-horizon) of the karst area in southwestern China are richer than that of any other geographical landscape areas. Median Hg values for this karst area are 113 and 90 µg/kg respectively (
n
 = 126), in the top and bottom soils, much higher than the corresponding data of 26 and 18 µg/kg for the entire country (
n
 = 3380). This regional-scale high Hg distribution is due mainly to high Hg geochemical backgrounds in bedrock and soil formation on limestone. A large-scale epithermal metallogenic domain developed in southwestern China and the extensive distribution of Lower Cambrian black shale in southwest China led to a high Hg geochemical background for parent rocks of soils. The chemical weathering of carbonate minerals and the geochemical behaviour of Hg in the epigenetic environment result in Hg enrichment by ferric oxides, iron hydroxide and organic carbon in limestone soils. Human activities mostly result in local-scale Hg anomalies, but have little effect on this regional-scale anomaly.
Experimental myofascial trigger point creation in rodents
Authors: Margalef Ramon , Sisquella Marc , Bosque Marc , Romeu Clara , Mayoral Orlando , Monterde Sonia , Priego Mercedes , Guerra-Perez Rafael , Ortiz Nicolau , Tomàs Josep , Santafe Manel M.
Published: October 2018

Myofascial pain syndrome is one of the most common forms of muscle pain. In this syndrome, pain is originated by the so-called trigger points, which consists of a set of palpable contraction knots in the muscle. It has been proposed that a high, spontaneous neurotransmission may be involved in the generation of these contraction knots. To confirm this hypothesis, we exposed mouse muscles to an anticholinesterasic agent to increase the neurotransmision in the synaptic cleft in two different conditions, in vivo and ex vivo experiments. Using intracellular recordings, a sharp increase in the spontaneous neurotransmission in the levator auris longus muscle and a lower increase in the diaphragm muscle could be seen. Likewise, electromyography recordings reveal an elevated endplate noise in gastrocnemius muscle of treated animals. These changes are associated with structural changes such as abundant neuromuscular contracted zones observed by rhodaminated α-bungarotoxin and the presence of abundant glycosaminoglycans around the contraction knots, as shown by Alcian PAS staining. In a second set of experiments, we aimed at demonstrating that the increases in the neurotransmission reproduced most of the clinical signs associated to a trigger point. We exposed rats to the anticholinesterase agent neostigmine, and 30 min afterward we observed the presence of palpable taut bands, the echocardiographic presence of contraction knots, and local twitch responses upon needle stimulation. In summary, we demonstrated that increased neurotransmission induced trigger points in both rats and mice, as evidenced by glycosaminoglycans around the contraction zones as a novel hallmark of this pathology.

NEW & NOTEWORTHY In rodents, when neostigmine was injected subcutaneously, the neuromuscular neurotransmission increased, and several changes can be observed: an elevated endplate noise compared with normal endplate noise, as evidenced by electromyographyc recording; many muscular fibers with contraction knots (narrower sarcomeres and locally thickened muscle fiber) surrounded by infiltration of connective tissue like glycosaminoglycans molecules; and palpable taut bands and local twitch responses upon needle stimulation. Several of these signs are also observed in humans with muscle pain.
Impact of short-term exercise training intensity on β-cell function in older obese adults with prediabetes
Authors: Malin Steven K. , Francois Monique E. , Eichner Natalie Z. M. , Gilbertson Nicole M. , Heiston Emily M. , Fabris Chiara , Breton Marc
Published: October 2018

The effect of work-matched exercise intensity on β-cell function is unknown in people with prediabetes before clinical weight loss. We determined if short-term moderate continuous (CONT) vs. high-intensity interval (INT) exercise increased β-cell function. Thirty-one subjects (age: 61.4 ± 2.5 yr; body mass index: 32.1 ± 1.0 kg/m2) with prediabetes [American Diabetes Association criteria, 75-g oral glucose tolerance test (OGTT)] were randomized to work-matched CONT (70% HRpeak) or INT (3 min 90% HRpeak and 3 min 50% HRpeak) exercise for 60 min/day over 2 wk. A 75-g 2-h OGTT was conducted after an overnight fast, and plasma glucose, insulin, C-peptide, and free fatty acids were determined for calculations of skeletal muscle [oral minimal model (OMM)], hepatic (homeostatic model of insulin resistance), and adipose (Adipose-IR) insulin sensitivity. β-Cell function was defined from glucose-stimulated insulin secretion (GSIS, deconvolution modeling) and the disposition index (DI). Glucagon-like polypeptide-1 [GLP-1(active)] and glucose-dependent insulinotropic polypeptide (GIP) were also measured during the OGTT, along with peak oxygen consumption and body composition. CONT and INT increased skeletal muscle- but not hepatic- or adipose-derived DI ( P < 0.05). Although both treatments tended to reduce fasting GLP-1(active) ( P = 0.08), early phase GLP-1(active) increased post-CONT and INT training ( P < 0.001). Interestingly, CONT exercise increased fasting GIP compared with decreases in INT ( P = 0.02). Early and total-phase skeletal muscle DI correlated with decreased total glucose area under the curve ( r = −0.52, P = 0.002 and r = −0.50, P = 0.003, respectively). Independent of intensity, short-term training increased pancreatic function adjusted to skeletal muscle in relation to improved glucose tolerance in adults with prediabetes. Exercise also uniquely affected GIP and GLP-1(active). Further work is needed to elucidate the dose-dependent mechanism(s) by which exercise impacts glycemia.

NEW & NOTEWORTHY Exercise is cornerstone for reducing blood glucose, but whether high-intensity interval training is better than moderate continuous exercise is unclear in people with prediabetes before weight loss. We show that 2 wk of exercise training, independent of intensity, increased pancreatic function in relation to elevated glucagon-like polypeptide-1 secretion. Furthermore, β-cell function, but not insulin sensitivity, was also correlated with improved glucose tolerance. These data suggest that β-cell function is a strong predictor of glycemia regardless of exercise intensity.
Serum Cortisol as a Predictor of Major Adverse Pulmonary Event in Emergency Department Acutely Dyspneic Patients
Authors: Dikme Ozlem , Dikme Ozgur
Published: October 2018

Cortisol is a steroid hormone released from the adrenal glands in response to stressful conditions. Elevated cortisol levels have been described in stress, but it is unclear whether these are associated with adverse outcomes. In this study, we assess whether cortisol levels drawn in patients presenting with dyspnea to the ED were a predictor of major adverse pulmonary event (MAPE). In 87 patients presenting with dyspnea to the ED, cortisol levels were determined. Patients were then assessed to determine the following MAPE: endotracheal intubation (ETI) in the ED, admission to the intensive care unit (ICU), and in-hospital all-cause mortality. Forty-four patients (50.6%) were female and 33 (37.9%) were diagnosed with heart failure. Cortisol levels in patients with and without MAPE were 34.3μg/dL and 23.8μg/dL, respectively (p<0.001). Also, cortisol levels were found higher in patients intubated in the ED than nonintubated patients (54.2μg/dL vs 25.7μg/dL, p<0.001), higher in patients admitted to the ICU (38.7μg/dL vs 24 μg/dL, p<0.001), and higher in patients who died in hospital (50μg/dL vs 24.3μg/dL, p<0.001). The area under the ROC curve using cortisol to detect any component of MAPE—ETI or ICU admission or in-hospital all-cause mortality—was 0.76 (95% CI, 0.65-0.84). A cortisol value of 31.4μg/dL had sensitivity of 70.8% and specificity of 79.4% for predicting MAPE. Patients in the MAPE group had higher serum cortisol levels than those without any MAPE. Cortisol may be used as a marker to predict MAPE in nontraumatic acutely dyspneic adult patients on ED admission.
Adomian Decomposition Method with Modified Bernstein Polynomials for Solving Ordinary and Partial Differential Equations
Authors: Qasim Ahmed Farooq , AL-Rawi Ekhlass S.
Published: October 2018

In this paper, we used Bernstein polynomials to modify the Adomian decomposition method which can be used to solve linear and nonlinear equations. This scheme is tested for four examples from ordinary and partial differential equations; furthermore, the obtained results demonstrate reliability and activity of the proposed technique. This strategy gives a precise and productive system in comparison with other traditional techniques and the arrangements methodology is extremely straightforward and few emphasis prompts high exact solution. The numerical outcomes showed that the acquired estimated solutions were in appropriate concurrence with the correct solution.
High-Level Interpretation of Urban Road Maps Fusing Deep Learning-Based Pixelwise Scene Segmentation and Digital Navigation Maps
Authors: Fernández Carlos , Muñoz-Bulnes Jesús , Fernández-Llorca David , Parra Ignacio , García-Daza Iván , Izquierdo Rubén , Sotelo Miguel Á.
Published: October 2018

This paper addresses the problem of high-level road modeling for urban environments. Current approaches are based on geometric models that fit well to the road shape for narrow roads. However, urban environments are more complex and those models are not suitable for inner city intersections or other urban situations. The approach presented in this paper generates a model based on the information provided by a digital navigation map and a vision-based sensing module. On the one hand, the digital map includes data about the road type (residential, highway, intersection, etc.), road shape, number of lanes, and other context information such as vegetation areas, parking slots, and railways. On the other hand, the sensing module provides a pixelwise segmentation of the road using a ResNet-101 CNN with random data augmentation, as well as other hand-crafted features such as curbs, road markings, and vegetation. The high-level interpretation module is designed to learn the best set of parameters of a function that maps all the available features to the actual parametric model of the urban road, using a weighted F-score as a cost function to be optimized. We show that the presented approach eases the maintenance of digital maps using crowd-sourcing, due to the small number of data to send, and adds important context information to traditional road detection systems.
Pharmacologic Effect of Miao Medicine Illicium simonsii Maxim. on Collagen‐Induced Arthritis in Rats
Authors: Zhang Qing-zhong , Hu Xian-yun , Yao Wen-qin , Wan Xiao-li , Liang Zi-cong , Dang Rong-min , Yang Zheng-min , Xia Ya-lan
Published: October 2018

Objectives. To study the pharmacologic effect and mechanism of action of Miao medicine Illicium simonsii Maxim. (ISM) in treating rheumatoid arthritis. Methods. Sixty rats were randomly divided to six groups: normal control (normal), collagen‐induced arthritis (CIA) model (model), CIA + tripterygium glycosides (TG), CIA + ISM high dose oral (ISM‐H), CIA + ISM low‐dose oral (ISM‐L), and CIA + ISM topical application (ISM‐T). The treatment doses were selected based on published reports and folk medicine practice. The outcome measurements included paw swelling, joint pathology, organ index, blood count, T helper 17 (Th17) cell count, and interleukin‐6 (IL‐6) level. Results. Compared to the CIA model group, all treatment groups showed a significant reduction in paw swelling, blood vessel pathology, Th17 cell count, and IL‐6 levels (p < 0.05 or p < 0.01). All treatment groups showed alleviated foot swelling and lower total number of white blood cells, and these effects were observed earlier with oral ISM than topical ISM. The effect of ISM was weaker than that of TG. In addition, less organ damage was observed with topical ISM than oral ISM but better than TG. Conclusions. These results suggest that, by downregulating Th17 cells, ISM inhibits the production of Il‐6, thereby alleviating the proliferation of endothelial and rheumatoid‐like cells and leukocytosis in CIA rats, ultimately eliminating foot swelling.
Exercise‐Induced Reductive Stress Is a Protective Mechanism against Oxidative Stress in Peripheral Blood Mononuclear Cells
Authors: Spanidis Ypatios , Veskoukis Aristidis S. , Papanikolaou Christina , Stagos Dimitrios , Priftis Alexandros , Deli Chariklia K. , Jamurtas Athanasios Z. , Kouretas Demetrios
Published: October 2018

Eccentric exercise is a well‐studied modality that induces oxidative stress and muscle damage. Furthermore, it promotes inflammatory response in which peripheral blood mononuclear cells (PBMCs) are the major mediators. Although free radicals are necessary in a specific range of concentrations, yet unknown, it remains unclear whether reductive redox status (i.e., increased antioxidant defenses and impaired free radical generation) is beneficial or not. Thus, the aim of the present investigation was to examine the effects of reductive stress and the impact of reduced glutathione (GSH) baseline values on the ability of PBMCs to counteract oxidative stress induced by a potent oxidative agent. PBMCs were isolated from the blood of subjects who performed eccentric exercise and treated with t-BOOH for 24 h. The subjects were clustered in the reductive and the oxidative group on the basis of increased or decreased GSH concentration postexercise compared to preexercise values, respectively. According to our results in PBMCs, lipid peroxidation levels as depicted by thiobarbituric acid reactive substances (TBARS) remained unchanged in the reductive group contrary to the observed enhancement in the oxidative group. In addition, GSH concentration and catalase activity increased in the reductive group, whereas they were not affected in the oxidative group. In conclusion, the effects of an oxidizing agent on the redox status of PBMCs isolated from the blood of athletes after acute eccentric exercise are dependent on the baseline values of GSH in erythrocytes. Otherwise, reductive stress defined by increased GSH levels is a protective mechanism, at least when followed by an oxidative stimulus.
Strategic Interaction between Operators in the Context of Spectrum Sharing for 5G Networks
Authors: Sacoto-Cabrera Erwin J. , Sanchis-Cano Angel , Guijarro Luis , Vidal José Ramón , Pla Vicent
Published: October 2018

5G networks will make network sharing agreements between mobile operators technically possible. However, depending on the agreed and implemented quality‐of‐service isolation, the provision of services may lead to unsustainable business cases. In this paper, the economic feasibility of such arrangements is analyzed for the case of two operators. Concretely, while one network operator owns the spectrum, one virtual operator does not, and each one provides service to its subscriber base. Two sharing alternatives, namely, pooling and priority sharing, are studied regarding the profits that each operator gets. We conclude that the network operator is worse off under any circumstances under a pooling agreement, while a lump sum payment may leave the network operator better off under a priority sharing agreement.
Survival Model of Drivers’ Speed Reduction Time at Bicycle Crossroads: A Driving Simulator Study
Authors: Bella Francesco , Silvestri Manuel
Published: October 2018

The main objective of this study was to assess the effectiveness of several countermeasures at bicycle crossroads on drivers’ behavior during the driver–cyclist interaction (a cyclist that crosses the road) by the use of a driving simulator. Three treatments of the cyclist crossroads were investigated: baseline condition (no treatment), raised island, and the colored paved markings. Forty-two participants drove a suburban scenario with several bicycle crossroads having difference configurations and presence/absence of cyclist. Overall, 252 speed profiles were plotted from 150 m before each crossroad of which 23 showed non-yield events: 12 for the baseline condition, 6 for the colored paved markings, and 5 for the raised island. The method of the survival analysis was applied to model the driver speed reduction time (the elapsed time to pass from the initial speed to the minimum speed during the yielding maneuver) with the use of the Weibull distribution. The model identified the average deceleration, the drivers’ age, and the countermeasure condition as significant explanatory variables. The survival curves highlighted that for the colored paved markings the driver adopted longer values of the speed reduction times and then a less aggressive driver’s braking behavior. Moreover, the outcomes of the questionnaire confirmed that the colored paved markings were considered to be the most effective in terms of driving aid.
Nanoindentation Hardness Distribution and Strain Field and Fracture Evolution in Dissimilar Friction Stir‐Welded AA 6061‐AA 5A06 Aluminum Alloy Joints
Authors: Peng Guangjian , Ma Yi , Hu Jiangjiang , Jiang Weifeng , Huan Yong , Chen Zhitong , Zhang Taihua
Published: October 2018

Aluminum alloy AA 6061‐T651 and 5A06‐H112 rolled plates were successfully welded by friction stir welding (FSW) at three rotation speeds of 600, 900, and 1200 rpm with two transverse speeds of 100 and 150 mm/min. Mechanical properties and strain field evolution of FSW AA 6061‐AA 5A06 were characterized by the uniaxial tension and digital image correlation (DIC) tests. Furthermore, the hardness distribution map of whole cross section was obtained via the nanoindentation method with 700 indents. Both DIC and nanoindentation results reveal that the heat‐affected zone (HAZ) of AA 6061 alloy is the softest area in the weldment, and the fracture happens in this region. The microstructure evolution characterized by electron‐backscatter diffraction (EBSD) indicates that the continuous dynamic recrystallization is the primary grain structure evolution in the stirring zone, and the grain refinement helps improve the mechanical properties. Analyses of the micro‐ and macrofeatures of the fracture surfaces via scanning electron microscopy (SEM) and optical microscope suggest that the increasing of heat input could enlarge the size of HAZ and reduce the slant angle of HAZ and thus lead the fracture angle to decrease and cause the dimples change from inclined ones to normal ones.
Chemical Potentials of Light Flavor Quarks from Yield Ratios of Negative to Positive Particles in Au+Au Collisions at RHIC
Authors: Gao Ya-Qin , Lao Hai-Ling , Liu Fu-Hu
Published: October 2018

The transverse momentum spectra of π-, π+, K-, K+, p¯, and p produced in Au+Au collisions at center-of-mass energy sNN=7.7, 11.5, 19.6, 27, 39, 62.4, 130, and 200 GeV are analyzed in the framework of a multisource thermal model. The experimental data measured at midrapidity by the STAR Collaboration are fitted by the (two-component) standard distribution. The effective temperature of emission source increases obviously with the increase of the particle mass and the collision energy. At different collision energies, the chemical potentials of up, down, and strange quarks are obtained from the antiparticle to particle yield ratios in given transverse momentum ranges available in experiments. With the increase of logarithmic collision energy, the chemical potentials of light flavor quarks decrease exponentially.
Research on Fault Evolution Feature Extraction and Identification of Sun Gear Cracks in Planetary Gearbox Based on Volterra High-Order Kernel Generalized Frequency Response Graphic Analysis
Authors: Wang Haitao , Kang Zhenya , Shi Lichen , Wang Kun , Li Kun
Published: October 2018

In this paper, relying on the Volterra series nonlinear system model and the high-order kernel Hilbert’s reconstructed kernel fast solved algorithm, a fault feature frequency domain identification method based on Volterra high-order kernel generalized frequency response graph analysis is proposed. Firstly, the method uses the system input and output vibration signals to determine the Volterra model. Then, the Volterra high-order kernel function is solved quickly by reproducing kernel Hilbert space method, and the generalized frequency response function is used to identify the model. Finally, multidimensional high-order spectral pattern analysis is used to separate and extract the fault and degree characteristic information implied by frequency and phase coupling in the third-order kernel function. Following the theoretical approach, in the experimental part, this paper uses the planetary gearbox fault loading test rig to complete the data collection and establishes the Volterra experimental model through the measured data. The generalized frequency responses of each order kernel function are compared and analyzed and the capability of distinguishing and the adaptability of different order kernel functions for the degree of crack failure are discussed. The effects of changing the memory length of the Volterra model and the order of the kernel function on the recognition result are verified. The final experimental results show that the use of reproducing kernel Hilbert space can effectively avoid the dimension disaster problem that occurs in the high-order kernel solution process. Moreover, the third-order kernel can describe more intuitively the nonlinear system model under multifactor coupling than the second-order kernel. Finally, Volterra series model the third-order kernel’s generalized frequency response can effectively distinguish between nondefective and faulty gears, and its resolution is enough to distinguish the degree of failure of gear cracks.
Improved Ant Colony Optimization for Weapon-Target Assignment
Authors: Hu Xinwu , Luo Pengcheng , Zhang Xiaonan , Wang Jun
Published: October 2018

Weapon-target assignment (WTA) which is crucial in cooperative air combat explores assigning weapons to targets with the objective of minimizing the threats from those targets. Based on threat functions, there are four WTA models constrained by the payload and other tactical requirements established. The improvements of ant colony optimization are integrated with respect to the rules of path selection, pheromone update, and pheromone concentration interval, and algorithm AScomp is proposed based on the elite strategy of ant colony optimization (ASrank). We add garbage ants to ASrank; when the pheromone is updated, the elite ants are rewarded and the garbage ants are punished. A WTA algorithm is designed based on the improved ant colony optimization (WIACO). For the purpose of demonstration of WIACO in air combat, a real-time WTA simulation algorithm (RWSA) is proposed to provide the results of average damage, damage rate, and kill ratio. The following conclusions are drawn: (1) the third WTA model, considering the threats of both sides and hit probabilities, is the most effective among the four; (2) compared to the traditional ant colony algorithm, the WIACO requires fewer iterations and avoids local optima more effectively; and (3) WTA is better conducted when any fighter is shot down or any fighter’s missiles run out than along with the flight.
Use of Expectation Disconfirmation Theory to Test Patient Satisfaction with Asynchronous Telemedicine for Diabetic Retinopathy Detection
Authors: Serrano Christina I. , Shah Vishal , Abràmoff Michael D.
Published: October 2018

Objective. The purpose of the study is to extend research on patient satisfaction with telemedicine services by employing the theoretical framework of Expectation Disconfirmation Theory (EDT) for diabetic retinopathy screenings focusing on rural patients. Method. Adult subjects (n=220) with diabetes were recruited from a single family practice office in rural Iowa. Subjects completed a “pre” survey concerning their forward-looking perceptions of telemedicine prior to using telemedicine for detection of diabetic retinopathy and a “post” survey after they received recommendations from the distant ophthalmologists. Results. All hypotheses of the EDT model were supported. Patient satisfaction is influenced by both patients’ expectations (P<.001) and disconfirmation of expectations (P<.001), and patient satisfaction has a positive impact on patient preference for telemedicine services (P<.001). Overall, patients who received telemedicine services were highly satisfied with telemedicine and developed a favorable disposition towards telemedicine services. Conclusions. The EDT model is a viable framework to study patient satisfaction of telemedicine services. While previous feasibility studies have shown that telemedicine for diabetic retinopathy screenings yields diagnostic efficacy, this study applies a theoretical framework to demonstrate the viability of telemedicine for diabetic retinopathy screenings in rural areas.
A Fast Screen and Shape Recognition Algorithm for Multiple Change-Point Detection
Authors: Zhuang Dan , Liu Youbo
Published: October 2018

A Fast Screen and Shape Recognition (FSSR) algorithm is proposed with complexity down to O(n) for the multiple change-point detection problems. The proposed FSSR algorithm includes two steps. First, by dividing the data into several subsegments, FSSR algorithm can quickly lock some small subsegments that are likely to contain change-points. Second, through a point by point search in each selected subsegment, FSSR algorithm determines the precise location of the change-point. The simulation study shows that FSSR has obvious speed and stability advantages. Particularly, the sparser the change-points is, the better result will be achieved from FRRS. Finally, we apply FSSR to two real applications to demonstrate its feasibility and robustness. One is the problem of DNA copy number variations identifying; another is the problem of operation scenarios reduction for renewable integrated electrical distribution network.
B‐Spline Impulse Response Functions of Rigid Bodies for Fluid‐Structure Interaction Analysis
Authors: Zhou-Bowers S. , Rizos D. C.
Published: October 2018

Reduced 3D dynamic fluid‐structure interaction (FSI) models are proposed in this paper based on a direct time‐domain B‐spline boundary element method (BEM). These models are used to simulate the motion of rigid bodies in infinite or semi‐infinite fluid media in real, or near real, time. B‐spline impulse response function (BIRF) techniques are used within the BEM framework to compute the response of the hydrodynamic system to transient forces. Higher‐order spatial and temporal discretization is used in developing the kinematic FSI model of rigid bodies and computing its BIRFs. Hydrodynamic effects on the massless rigid body generated by an arbitrary transient acceleration of the body are computed by a mere superposition of BIRFs. Finally, the dynamic models of rigid bodies including inertia effects are generated by introducing the kinematic interaction model to the governing equation of motion and solve for the response in a time‐marching scheme. Verification examples are presented and demonstrate the stability, accuracy, and efficiency of the proposed technique.
Deep Learning to Distinguish Recalled but Benign Mammography Images in Breast Cancer Screening
Authors: Aboutalib Sarah S. , Mohamed Aly A. , Berg Wendie A. , Zuley Margarita L. , Sumkin Jules H. , Wu Shandong
Published: October 2018

Purpose:

False positives in digital mammography screening lead to high recall rates, resulting in unnecessary medical procedures to patients and health care costs. This study aimed to investigate the revolutionary deep learning methods to distinguish recalled but benign mammography images from negative exams and those with malignancy.

Experimental Design:

Deep learning convolutional neural network (CNN) models were constructed to classify mammography images into malignant (breast cancer), negative (breast cancer free), and recalled-benign categories. A total of 14,860 images of 3,715 patients from two independent mammography datasets: Full-Field Digital Mammography Dataset (FFDM) and a digitized film dataset, Digital Dataset of Screening Mammography (DDSM), were used in various settings for training and testing the CNN models. The ROC curve was generated and the AUC was calculated as a metric of the classification accuracy.

Results:

Training and testing using only the FFDM dataset resulted in AUC ranging from 0.70 to 0.81. When the DDSM dataset was used, AUC ranged from 0.77 to 0.96. When datasets were combined for training and testing, AUC ranged from 0.76 to 0.91. When pretrained on a large nonmedical dataset and DDSM, the models showed consistent improvements in AUC ranging from 0.02 to 0.05 (all P > 0.05), compared with pretraining only on the nonmedical dataset.

Conclusions:

This study demonstrates that automatic deep learning CNN methods can identify nuanced mammographic imaging features to distinguish recalled-benign images from malignant and negative cases, which may lead to a computerized clinical toolkit to help reduce false recalls.
Forecasting Future Trends in Obesity across Europe: The Value of Improving Surveillance
Authors: Pineda Elisa , Sanchez-Romero Luz Maria , Brown Martin , Jaccard Abbygail , Jewell Jo , Galea Gauden , Webber Laura , Breda João
Published: October 2018

Objective: To project the prevalence of obesity across the WHO European region and examine whether the WHO target of halting obesity at 2010 levels by 2025 is achievable. Methods: BMI data were collected from online databases and the literature. Past and present BMI trends were extrapolated to 2025 using a non-linear categorical regression model fitted to nationally representative survey data. Where only 1 year of data was available, a flat trend was assumed. Where no data were available, proxy country data was used adjusted for demographics. Results: By 2025, obesity is projected to increase in 44 countries. If present trends continue, 33 of the 53 countries are projected to have an obesity prevalence of 20% or more. The highest prevalence is projected for Ireland (43%, 95% confidence interval (CI): 28-58%). Lithuania, Finland, and the Netherlands were each estimated to have an absolute increase of 2 percentage points in the prevalence of obesity between 2015 and 2025. Discussion: The quality of BMI data across Europe is highly variable, with fewer than 50% of the 53 countries having measured nationally representative data and often not enough data to interpret projections meaningfully. Nevertheless, the prevalence of obesity in the European Region appears to be increasing in most countries and, with it, the health and economic burden of its associated diseases. This paints a concerning picture of the future burden of obesity-related noncommunicable diseases across the region. Greater and continued effort for the implementation of effective preventive policies and interventions is required from governments.
Nasal Symptom Questionnaire: Our Proposed Scoring System and Prognostic Factors in Chronic Rhinosinusitis
Authors: Saito Takahiro , Tsuzuki Kenzo , Nishikawa Hiroki , Okazaki Ken , Hashimoto Kengo , Sakagami Masafumi
Published: October 2018

Objectives: We aimed to verify the usefulness of our proposed nasal symptom questionnaire (NSQ) scoring system and to determine predictors linked to the improvement in nasal symptoms in chronic rhinosinusitis (CRS) patients undergoing endoscopic sinus surgery (ESS). Patients and Methods: Ninety-one CRS patients undergoing ESS and 144 volunteers with results of NSQ available were enrolled. The NSQ consists of 10 items. Receiver-operating-characteristic (ROC) curve, area under the ROC curve (AUC), internal consistency, and test-retest reproducibility of the NSQ were analyzed. The relationship of the NSQ score with the visual analogue scale (VAS) was examined. After classifying into two groups, i.e., (i) “improvement group” and (ii) “no-improvement group,” factors linked to the improvement in NSQ after ESS were investigated. Results: ROC-AUC (0.9318), the Cronbach α coefficient (0.8696), and the test-retest coefficient (0.8131) showed high reliability. NSQ score significantly correlated with VAS in both pre- (p < 0.0001, rs = 0.6007) and postoperative stages (p < 0.0001, rs = 0.5975). The postoperative NSQ scores significantly decreased compared with baseline levels (p < 0.0001). In multivariate analysis, the computed tomography (CT) score by the Lund-Mackay scoring system revealed to be significant (p = 0.0481). Conclusion: Our proposed NSQ scoring system was well verified. The CT score can be helpful for predicting the improvement in nasal symptoms after ESS in CRS patients.
Novel Eye Plaque Designs for Brachytherapy of Iris and Ciliary Body Melanoma and the First Clinical Application
Authors: Liu Wu , Kim Jenna May , Young Benjamin K. , Nath Ravinder , Chen Zhe , Decker Roy H. , Astrahan Melvin A. , Pointdujour-Lim Renelle
Published: October 2018

Background: While traditional eye plaque brachytherapy can be used for the treatment of iris melanoma, it faces challenges of poor patient tolerability due to cornea-plaque touch caused by radius of curvature mismatch and potential dosimetric inaccuracy from incomplete coverage. We present novel plaque designs and the first clinical application of the plaques for iris melanoma. Methods: Two dome-shaped plaques (EP2132 and EP1930) were designed to vault above the cornea to treat tumors of the iris and ciliary body. Image-based treatment planning of the first 2 clinical cases using the EP2132 plaque covered the tumor base plus a 2 mm margin and the involved ciliary body with at least 75 Gy to the tumor apex. Results: The tumors decreased in size following treatment. The patients tolerated the treatment well. There was no adverse event associated with the traditional iris plaques, such as decreased vision, pain, corneal edema, glaucoma, or cataract. Conclusion: The novel dome-shaped plaques for the treatment of iris melanoma provide effective dose distribution, improved surgical maneuverability, and increased tolerability for the patient. This plaque model can be used to treat iris melanoma of various sizes, configurations, and locations, including the ciliary body. The need for a customized plaque platform for each patient is minimized.
Patient Preference and Physician Perceptions of Patient Preference for Oral Pharmaceutical Formulations: Results from a Real-Life Survey
Authors: MacKenzie-Smith Lara , Marchi Paolo , Thorne Helen , Timeus Susan , Young Ryan , Le Calvé Perrine
Published: October 2018

Background: Pharmaceutical treatment prescribed according to patient preference for a formulation may have a positive impact on adherence to treatment and consequently on treatment outcomes. Aim: This study aimed at understanding patient preference for pharmaceutical formulations and attributes that trigger patient preference and physician perception of patient preference. Methods: Between August and September 2017, gastroenterologists and patients with mild to moderate ulcerative colitis from France, Germany, Spain, and the UK participated in an online survey. The investigation was exploratory in nature, and descriptive results are presented. Results: Patient (n = 380) preference appears to be driven by the appearance (format, shape, size, and color – 44%), number of units per administration (39%), and number of administrations per day (17%). Gastroenterologist (n = 159) preference is instead driven by the number of administrations per day (55%), number of units per day (26%), and tablet size (19%). Overall, 254 (67%) patients preferred a tablet formulation, 111 (29%) preferred granules, and 15 (4%) other formulations. According to gastroenterologist perception of patient preference, only 49% of patients prefer tablets, 38% prefer granules, and 13% have no preference. After switching from granules to tablets, 25% patients expressed negative feelings for granules. However, after switching from tablets to granules, 44% of patients still have positive perceptions of tablets. Among patients receiving tablets (n = 255), 18 (7%) perceived their treatment to be not at all effective versus 16 (13%) patients receiving granules (n = 125). A similar proportion of patients in the two groups perceived their treatment as extremely effective (48 vs. 46%, respectively). Conclusions: Patients generally prefer tablets. Patient and gastroenterologist perception of patient preference for different oral drug formulations is triggered by the same attributes but with inverse importance. To improve adherence, patients should be involved in the choice of the treatment formulation.
Allele-Specific Detection of SLC22A2 rs316019 Variants Associated with Metformin Disposition through the Kidney
Authors: Islam Tasmia , Rahman Md. Siddiqur , Paul Nilanjana , Akhteruzzaman Sharif , Sajib Abu Ashfaqur
Published: October 2018

Background: Metformin is prescribed as a first-line drug to treat type 2 diabetes. It is excreted directly and primarily through the SLC22A2 gene-encoded OCT2 transporter in the kidney. rs316019 (c.808G>T, p.270A>S) is the most common variant of SLC22A2, which affects its capacity to clear metformin from the body. Metformin increases the plasma lactate level in a concentration-dependent manner by inhibiting mitochondrial respiration and may lead to a condition known as metformin-associated lactic acidosis (MALA). MALA is a potentially life-threatening complication that can occur within the clinical doses of metformin. Therefore, dose adjustments based on the SLC22A2 rs316019 variants may be beneficial to maximize the efficacy and minimize the toxicity of metformin. Objective: This study was carried out to develop a simple and fast method to define genotype at the rs316019 locus. This method was applied to estimate the rs316019 allele frequencies in the Bangladeshi population. Methods: We designed allele-specific primers to determine genotype at the rs316019 locus using allele-specific polymerase chain reaction (AS-PCR). AS-PCR data were confirmed by targeted sequencing of randomly selected samples. Results: The DNA sequence chromatograms showed the exact genotypes predicted through the AS-PCR method. A proportion of 79.62, 18.01, and 2.37% of Bangladeshi individuals have GG, GT, and TT genotypes, respectively. Conclusion: We report here a simple and fast method to define ge­notypes at the rs316019 locus in diabetic patients who are under metformin regimen. Allele frequencies at the rs316019 locus in the Bangladeshi population are close to those reported in other populations.
Action of Protein Tyrosine Kinase Inhibitors on the Hypotonicity-Stimulated Trafficking Kinetics of Epithelial Na+ Channels (ENaC) in Renal Epithelial Cells: Analysis Using a Mathematical Model
Authors: Marunaka Rie , Taruno Akiyuki , Yamamoto Toshiro , Kanamura Narisato , Marunaka Yoshinori
Published: October 2018

Background/Aims: Epithelial Na+ channels (ENaCs) play crucial roles in control of blood pressure by determining the total amount of renal Na+ reabsorption, which is regulated by various factors such as aldosterone, vasopressin, insulin and osmolality. The intracellular trafficking process of ENaCs regulates the amount of the ENaC-mediated Na+ reabsorption in the collecting duct of the kidney mainly by determining the number of ENaC expressed at the apical membrane of epithelial cells. Although we previously reported protein tyrosine kinases (PTKs) contributed to the ENaC-mediated epithelial Na+ reabsorption, we have no information on the role of PTKs in the intracellular ENaC trafficking. Methods: Using the mathematical model recently established in our laboratory, we studied the effect of PTKs inhibitors (PTKIs), AG1296 (10 µM: an inhibitor of the PDGF receptor (PDGFR)) and AG1478 (10 µM: an inhibitor of the EGF receptor (EGFR)) on the rates of the intracellular ENaC trafficking in renal epithelial A6 cells endogenously expressing ENaCs. Results: We found that application of PTKIs significantly reduced the insertion rate of ENaC to the apical membrane by 56%, the recycling rate of ENaC by 83%, the cumulative time of an individual ENaC staying in the apical membrane by 27%, the whole life-time after the first insertion of ENaC by 47%, and the cumulative Na+ absorption by 61%, while the degradation rate was increased to 3.8-fold by application of PTKIs. These observations indicate that PTKs contribute to the processes of insertion, recycling and degradation of ENaC in the intracellular trafficking process under a hypotonic condition. Conclusion: The present study indicates that application of EGFR and PDGFR-inhibitable PTKIs reduced the insertion rate (kI), and the recycling rate (kR) of ENaCs, but increased degradation rate (kD) in renal A6 epithelial cells under a hypotonic condition. These observations indicate that hypotonicity increases the surface expression of ENaCs by increasing the insertion rate (kI) and the recycling rate (kR) of ENaCs associated with a decrease in the degradation rate but without any significant effects on the endocytotic rate (kE) in EGFR and PDGFR-related PTKs-mediated pathways.
Tip60 Suppresses Cholangiocarcinoma Proliferation and Metastasis via PI3k-AKT
Authors: Zhang Yaodong , Ji Guwei , Han Sheng , Shao Zicheng , Lu Zefa , Huo Liqun , Zhang Jiawei , Yang Renjie , Feng Qinchao , Shen Hao , Wang Hongwei , Li Xiangcheng
Published: October 2018

Background/Aims: Aberrant expression of Tip60 is associated with progression in many cancers. However, the role of Tip60 in cancer progression remains contradictory. The aim of this study was to investigate the clinical significance, biological functions and underlying mechanisms of Tip60 deregulation in cholangiocarcinoma (CCA) for the first time. Methods: Quantitative real-time PCR (QRT-PCR), western blotting and immunohistochemistry staining (IHC) were carried out to measure Tip60 expression in CCA tissues and cell lines. Kaplan–Meier analysis and the log-rank test were used for survival analysis. In vitro, cell proliferation was evaluated by flow cytometry and CCK-8, colony formation, and EDU assays. Migration/ invasion was evaluated by trans-well assays. Phosphokinase array was used to confirm the dominant signal regulated by Tip60. Tumor growth and metastasis were demonstrated in vivo using a mouse model. Results: Tip60 was notably downregulated in CCA tissues, which was associated with greater tumor size, venous invasion, and TNM stage. Down-regulation of Tip60 was associated with tumor progression and poorer survival in CCA patients. In vitro and in vivo studies demonstrated that Tip60 suppressed growth and metastasis throughout the progression of CCA. We further identified the PI3K/AKT pathway as a dominant signal of Tip60 and suggested that Tip60 regulated CCA cell proliferation and metastasis via PT3K-AKT pathway. Pearson analysis revealed that PTEN was positively correlated with the Tip60 level in CCA tissues. Conclusion: Tip60, as a tumor suppressor in CCA via the PI3K/AKT pathway, might be a promising therapeutic target or prognostic marker for CCA.
Glucagon-Like Peptide-1 Modulates Cholesterol Homeostasis by Suppressing the miR-19b-Induced Downregulation of ABCA1
Authors: Yao Yue , Li Qiang , Wang Wei , Zhang Jinchao , Gao Ping , Xu Yi 
Published: October 2018

Background/Aims: Abnormal regulation of cholesterol homeostasis is associated with type 2 diabetes mellitus (T2DM) and multiple other diseases. Glucagon-like peptide-1 (GLP-1) has unique effects on modulating hepatic lipid metabolism. However, the mechanism behind these is largely unknown. The aim of this study was to investigate the effects of GLP-1 on cholesterol-induced lipotoxicity in hepatocytes and examine the underlying mechanisms. Methods: Cell viability was determined by CCK-8. Caspase-3 detection was used to assess the effects of GLP-1 on cholesterol-induced apoptosis. TNF-α and IL-6 as the inflammatory markers were measured by ELISA. The alterations of miR-19b and ATP-binding cassette transporter A1 (ABCA1) resulting from high-fat diet/cholesterol incubation or GLP-1 were detected by real-time PCR and western blot. Results: GLP-1 markedly up-regulated the expression of ABCA1 protein, but didn’t affect peroxisome proliferator-activated receptor α (PPAR-α) protein. The miR-19b levels were significantly down-regulated in GLP-1-treated groups. The inhibition and overexpression of miR-19b were established to explore the effects of a GLP-1-mediated alteration in miR-19b. Cholesterol transport assays revealed that treatment with GLP-1 alone or together with miR-19b inhibitor significantly enhanced ABCA1-dependent cholesterol efflux, resulting in reduced total cholesterol. Further, histological examination was used to detect lipid accumulation. Cholesterol significantly attenuated cell viability, promoted hepatic cell apoptosis, and facilitated lipid accumulation, and these effects could be reversed by GLP-1. Conclusion: GLP-1 may affect cholesterol homeostasis by regulating the expression of miR-19b and ABCA1.