bluuebunny/crossref_metadata_2025 huggingface dataset:
Analytical Method for Evaluating the Ground Surface Settlement Caused by Tail Void Grouting Pressure in Shield Tunnel Construction
Authors: Wu Changsheng , Zhu Zhiduo
Published: July 2018

The tail void grouting is a key step in shield tunnel construction and has an important influence on the loading on the surrounding soil and on the resulting settlement. In order to estimate the ground surface settlement caused by tail void grouting pressure in tunnel construction, the loading on the surrounding soil is simplified as an expansion problem of the cylindrical cavity in semi‐infinite elastic space. A simple analytical formula is deduced by using the virtual image technique and Fourier transform solutions. The effectiveness of the proposed method is verified by case studies. The effects of elastic modulus, tail void grouting pressure, tunnel radius, and tunnel depth on the ground surface heave are conducted. The results indicate that the computed results are in accordance with Ye’s solution and it is more rational to consider the ground surface heave induced by tail void grouting pressure in the prediction of ground settlement due to shield excavation. Moreover, the ground surface heave owing to tail void grouting pressure resembled a Gaussian distributed curve. Thus, no matter the ground surface subsidence or ground surface heave can be predicted by means of adding the presented empirical formula to the Peck formula which cannot predict the ground surface heave. The ground surface heave decreases with an increase in elastic modulus. On the contrary, as the tail void grouting pressure and tunnel radius increase, the ground surface heave increases, respectively. The ground surface heave first steadily increases and then declines gradually with the tunnel depth increase.
On Some Convergence Properties of the Modified Ishikawa Scheme for Asymptotic Demicontractive Self-Mappings with Matricial Parameterizing Sequences
Authors: De la Sen M.
Published: July 2018

This paper is focused on the modified Ishikawa iterative scheme by admitting that the parameterizing sequences might be vectors of distinct components. It is also assumed that the auxiliary self-mapping which supports the iterative scheme is asymptotically demicontractive.
The Wolf Hidden behind the Clots: Catastrophic Antiphospholipid Antibody Syndrome
Authors: Soe Myat Han , Agarwal Krishna Adit , Akough-Weir Alueshima
Published: July 2018

Catastrophic antiphospholipid syndrome (CAPS) is a rare but highly fatal clinical syndrome that occurs in up to 1% of patients with antiphospholipid syndrome (APS). The diagnosis of CAPS is often delayed because its presentation with multiple organ thromboses can be confused with other thrombotic microangiopathies and severe sepsis. We report a case of CAPS in a patient with APS and systemic lupus erythematosus (SLE) presenting with thrombotic storm precipitated by trauma, cytomegalovirus (CMV) infection, and noncompliance with anticoagulation therapy. Our case reflects the “two-hit hypothesis” of APS in which the presence of antiphospholipid antibodies (first hit) increases the thrombophilic risk, and thromboses take place in the presence of another thrombophilic condition such as CMV infection in our case. In this case review, we discuss the diagnostic challenges and management of CAPS. In clinical practice, we aim to stress the importance of thorough evaluation and management of precipitating events such as infections in addition to timely diagnosis and treatment of this catastrophic clinical entity.
Combination of Genetic Markers and Age Effectively Facilitates the Identification of People with High Risk of Preeclampsia in the Han Chinese Population
Authors: Zhou Lu , Hui Xinjie , Yuan Huijuan , Liu Yinglin , Wang Yejun
Published: July 2018

Objective. This study aimed to analyze the possible association between known genetic risks and preeclampsia in a Han Chinese population. Methods. A total of 156 patients with preeclampsia and 286 healthy Han Chinese women were enrolled and genotyped for 27 genetic alleles associated with preeclampsia in different populations. The association between the genotypes of the individual alleles and preeclampsia and the possible interaction among the alleles were analyzed. Finally logistic models were trained with the genotypes of possible alleles contributing to preeclampsia. Results. Seven alleles were significantly or marginally significantly associated with preeclampsia, which involved six genes (rs4762 in AGT, rs1800896 in IL-10, rs1800629 and rs1799724 in TNFα, rs2070744 in NOS3, rs7412 in APOE, and rs2549782 in ERAP2). A multilocus interaction analysis further disclosed an interaction among seven alleles. A logistic model showing individual or synergetic contribution to preeclampsia could reach ~0.67 preeclampsia prediction accuracy in the Han Chinese population, while integration of age information could improve the performance to ~0.75 accuracy using a fivefold training-testing evaluation strategy. Conclusions. The genetic factors were closely associated with preeclampsia in the Han Chinese population despite large ethnicity heterogeneity. The genotypes of different alleles also had synergetic interactions.
Extensive Multiple Sclerosis Reactivation after Switching from Fingolimod to Rituximab
Authors: Holmøy Trygve , Torkildsen Øivind , Zarnovicky Svetozar
Published: July 2018

During treatment with fingolimod, B cells are redistributed from blood to secondary lymphoid organs, where they are protected from the effect of anti-CD20 and other cell-depleting therapies. We describe a multiple sclerosis patient who had almost complete depletion of B cells in blood during and shortly after treatment with fingolimod. He developed severe disease activity resembling immune reconstitution syndrome after switching from fingolimod to rituximab, with first dose being six weeks after fingolimod cessation. Following recommendations from the Swedish MS Association, rituximab treatment was started as one single dose of 1000 mg. In patients treated with fingolimod, pathogenic B cells may still be sequestered in secondary lymph nodes if this dose is given early. To deplete such B cells as they egress from the lymph nodes, we propose that a second dose of rituximab a few weeks after the first dose should be considered.
Parameter and State Estimation of Shear Buildings Using Spline Interpolation and Linear Integral Filters
Authors: Concha Antonio , Alvarez-Icaza Luis
Published: July 2018

A parameter identification method and a high gain observer are proposed in order to identify the model and to recover the state of a seismically excited shear building using acceleration responses of the ground and instrumented floors levels, as well as the responses at noninstrumented floors, which are reconstructed by means of cubic spline shape functions. The identification method can be implemented online or offline and uses Linear Integral Filters, whose bandwidth must enclose the spectrum of a seismically excited building. On the other hand, the proposed state observer estimates the displacements and velocities of all the structure floors using the model estimated by the identification method. The observer allows obtaining a fast response and reducing the state estimation error, while depending on a single gain. The performance of the parameter and state estimators is verified through experiments carried out on a five‐story small scale building.
Nonalcoholic Fatty Liver Disease Is Associated with Increased Atrial Fibrillation Risk in an Elderly Chinese Population: A Cross-Sectional Study
Authors: Zhang Yu , Li Peifei , Miao Min , Liu Yi , Pan Yue , Xu Lu , Zhu Zhongwei , Xu Chengfu , Xu Lei
Published: July 2018

Background. Atrial fibrillation and nonalcoholic fatty liver disease are two pathological conditions that are highly prevalent worldwide and share multiple CVD risk factors. There are rare researches performed among elderly adults.Aims. We conducted this cross-sectional analysis of elderly adults (≥65 years) to investigate the association between atrial fibrillation and nonalcoholic fatty liver disease.Methods. We analyzed clinical data of the elderly adults (≥ 65 years) who had health examination in Zhenhai Lianhua Hospital, Ningbo, China, in 2014.Results. 522 of the 1688 participants were diagnosed with nonalcoholic fatty liver disease, and 39 participants were diagnosed as having atrial fibrillation. Nonalcoholic fatty liver disease was associated with risk factors for AF in the elderly Chinese population (OR 1.95, 95% CI 1.03-3.69). Adjustments for age, gender, systolic blood pressure, fasting plasma glucose,γ-glutamyl transpeptidase, high-density lipoprotein, triglycerides, total cholesterol and albumin, nonalcoholic fatty liver disease, and prevalent atrial fibrillation remained statistically significant (OR 2.76, 95% CI 1.32-5.77).Conclusions. Our results show that nonalcoholic fatty liver disease is associated with an increased risk of atrial fibrillation in an elderly Chinese population.
The Effectiveness of Orofacial Pain Therapy in Indonesia: A Cross-Sectional Study
Authors: Maulina T. , Yubiliana G. , Rikmasari R.
Published: July 2018

Objective(s). As the most complained oral problems in Indonesia, the therapy of orofacial pain has to be constantly evaluated. The objective of the current study was to evaluate the effectiveness of orofacial pain therapy in Indonesia. Method(s). This study recruited 5412 (3816 female; 1596 male) participants from 27 districts in West Java province. Half of the participants (2714) were recruited from those who were treated at community health centers whilst the rest were those who were treated at private dental clinics. A Likert-scale questionnaire that consists of nine questions that were divided to three subsections was used. The first subsection of the questionnaire evaluated the participants’ post-therapy basic oral functions (three questions), and the second part evaluated the participants’ post-therapy pain intensity and frequency (three questions), whilst the last part evaluated the participants’ post-therapy activities (three questions). All data were then cross-tabulated and correlated by using Spearman correlation. Result. The current study revealed that out of 5412 participants, 4023 (74.33%) participants claimed that the therapy has enabled them to perform their work activity as usual, whilst 2576 (59.2%) claimed that the therapy has decreased the intensity of the pain moderately. A significant (p < 0.01) correlation (r = 0.1) between the type of dental facility visited and the total score of the therapy effectiveness was revealed. Conclusion. The therapy of orofacial pain in Indonesian sample was proven to be effective. Further study evaluating the reasons underlying the current results is of importance.
Pulmonary Vein Thrombosis Associated with Metastatic Follicular Thyroid Carcinoma: A Case Report and Review
Authors: Mavromati Maria , Gerber Annick , John Gregor
Published: July 2018

Pulmonary vein thrombosis (PVT) mainly occurs following lung transplantation but cases associated with thoracic malignancy have also been described. We describe here the first case of PVT in an asymptomatic patient with metastatic follicular thyroid carcinoma.
Knowledge Level, Attitude, and Behaviors of Farmers in Çukurova Region regarding the Use of Pesticides
Authors: Öztaş Dilek , Kurt Burak , Koç Ayşegül , Akbaba Muhsin , İlter Hüseyin
Published: July 2018

Introduction and Purpose. Farmers are particularly at high risk of pesticide exposure due to added risk from occupational exposure. The aim of this study is to evaluate knowledge level of farmers in the Çukurova region of the effects of pesticides, toxic symptoms, and protective equipment as well as assessing their attitudes and practices regarding pesticides. Material and Method. A total of 420 seasonal agricultural workers in Karataş District of Adana Province, Turkey, were included in the study. The questionnaire form consisting of 3 sections was administered using face-to-face interview method. Results. The mean age of the participants was 40.2±10.6 years. They were engaged in farming for a mean duration of 18.5±10.6 years. All of them used pesticides, but none of them had been trained on the use of pesticides. Only 26.2% of them stored pesticides in a private depot. The farmers who took empty pesticide containers to special collection bins or centers constituted only 4.3% of them. While 84.0% of them thought that pesticides could have a negative impact on human health, 5.0% of them had experienced a medical problem and 1.0% of them were poisoned after applying pesticides. Conclusion. The results show that knowledge level of farmers of safe use of pesticides is very inadequate. This lack of knowledge adversely affects workers’ quality of life as well as occupational health and safety. Appropriate training programs should be organized to increase their level of knowledge.
Cerebral Ischemic Postconditioning Plays a Neuroprotective Role through Regulation of Central and Peripheral Glutamate
Authors: You Jiulin , Feng Liangshu , Xin Meiying , Ma Di , Feng Jiachun
Published: July 2018

Following cerebral ischemia/reperfusion (I/R) injury, a series of pathophysiological processes are stimulated in both the central nervous system (CNS) and the periphery, including, but not limited to, the peripheral immune and endocrine systems and underregulation of the neuroendocrine-immune network. Glutamate (Glu) is an important excitatory neurotransmitter in the CNS; its excitotoxicity following cerebral ischemia has been a focus of study for several decades. In addition, as a novel immunoregulator, Glu also regulates immune activity in both the CNS and periphery and may connect the CNS and periphery through regulation of the neuroendocrine-immune network. Ischemic postconditioning (IPostC) is powerful and activates various endogenous neuroprotective mechanisms following cerebral I/R, but only a few studies have focused on the mechanisms associated with Glu to date. Given that Glu plays an important and complex pathophysiological role, the understanding of Glu-related mechanisms of IPostC is an interesting area of research, which we review here.
Hepatoprotective Effect of Polysaccharides Isolated from Dendrobium officinale against Acetaminophen‐Induced Liver Injury in Mice via Regulation of the Nrf2‐Keap1 Signaling Pathway
Authors: Lin Guosheng , Luo Dandan , Liu Jingjing , Wu Xiaoli , Chen Jinfen , Huang Qionghui , Su Lingye , Zeng Lei , Wang Hongfeng , Su Ziren
Published: July 2018

The effect of polysaccharides isolated from Dendrobium officinale (DOP) on acetaminophen‐ (APAP‐) induced hepatotoxicity and the underlying mechanisms involved are investigated. Male Institute of Cancer Research (ICR) mice were randomly assigned to six groups: (1) control, (2) vehicle (APAP, 230 mg/kg), (3) N‐acetylcysteine (100 mg/kg), (4) 50 mg/kg DOP, (5) 100 mg/kg DOP, and (6) 200 mg/kg DOP. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in the serum and glutathione (GSH), malondialdehyde (MDA), catalase (CAT), total antioxidant capacity (T‐AOC), myeloperoxidase (MPO), and reactive oxygen species (ROS) levels in the liver were determined after the death of the mice. The histological examination of the liver was also performed. The effect of DOP on the Kelch‐like ECH‐associated protein 1‐ (Keap1‐) nuclear factor erythroid 2‐related factor 2 (Nrf2) signaling pathway was evaluated using Western blot analysis and real‐time polymerase chain reaction (PCR). The results showed that DOP treatment significantly alleviated the hepatic injury. The decrease in ALT and AST levels in the serum and ROS, MDA, and MPO contents in the liver, as well as the increases in GSH, CAT, and T‐AOC in the liver, were observed after DOP treatment. DOP treatment significantly induced the dissociation of Nrf2 from the Nrf2−Keap1 complex and promoted the Nrf2 nuclear translocation. Subsequently, DOP‐mediated Nrf2 activation triggered the transcription and expressions of the glutamate–cysteine ligase catalytic (GCLC) subunit, glutamate–cysteine ligase regulatory subunit (GCLM), heme oxygenase‐1 (HO‐1), and NAD(P)H dehydrogenase quinone 1 (NQO1) in APAP‐treated mice. The present study revealed that DOP treatment exerted potentially hepatoprotective effects against APAP‐induced liver injury. Further investigation about mechanisms indicated that DOP exerted the hepatoprotective effect by suppressing the oxidative stress and activating the Nrf2−Keap1 signaling pathway.
Genotoxicity of Copper and Nickel Nanoparticles in Somatic Cells of Drosophila melanogaster
Authors: Carmona Erico R. , García-Rodríguez Alba , Marcos Ricard
Published: July 2018

Copper and nickel nanoparticles (Cu-NPs and Ni-NPs, respectively) are used in a variety of industrial applications, such as semiconductors, catalysts, sensors, and antimicrobial agents. Although studies on its potential genotoxicity already exist, few of them report in vivo data. In the present study we have used the wing-spot assay in Drosophila melanogaster to determine the genotoxic activity of Cu-NPs and Ni-NPs, and these data have been compared with those obtained with their microparticle forms (MPs). Additionally, a complete physical characterization of NPs using transmission electronic microscopy (TEM), dynamic light scattering (DLS), and laser Doppler velocimetry (LDV) techniques was also performed. Results obtained with Cu-NPs and Cu-MPs indicate that both failed to induce an increase in the frequency of mutant spots formation in the wings of the adults, suggesting a lack of genotoxicity in somatic cells of D. melanogaster. However, when Ni-NPs and Ni-MPs were evaluated, a significant increase of small single spots and total mutant spots was observed only for Ni-NPs (P<0.05) at the highest dose assessed. Thus, the genotoxicity of Ni-NPs seem to be related to their nanoscale size, because no genotoxic effects have been reported with their microparticles and ions. This study is the first assessing the in vivo genotoxic potential of Cu-NPs and Ni-NPs in the Drosophila model.
Effects of Modified Zhisou Powder on Airway Mucus Production in Chronic Obstructive Pulmonary Disease Model Rats with Cold‐Dryness Syndrome
Authors: Zhen Gao , Jing Wang , Jing Jing , Xu Dan , Zheng Li , Li Fengsen
Published: July 2018

Objective. In China, the Chinese medicine formula modified zhisou powder (MZP) is commonly used to treat COPD with cold‐dryness syndrome (CDSCOPD) to relieve cough and sputum. However, the underlying mechanisms of MZP on treating CDSCOPD remain to be elucidated. Methods. COPD and CDSCOPD rat models were established; MZP was given to CDSCOPD rats in the last 7 days of the 97‐day model establishment. Then the rats were subjected to lung function measurement. Pathological changes in lungs were observed through paraffin section and H&E staining. The mRNA and protein levels of AQP1, 4, and 5 and Muc5AC and Muc5B in lung were determined by quantitative RT‐PCR and western blotting. NE levels was determined by ELISA. Results. The impaired lung functions were observed in rats exposed to cigarette smoke. Among all parameters evaluating lung functions, only tidal volume demonstrates a further decrease in CDSCOPD when compared with COPD, indicating further impaired pulmonary ventilation functions upon cold‐dryness stimulation. The intervention of MZP effectively improved lung functions parameters, prevented the inflammations, and eliminated the increases of AQP4 and 5 and the decrease of Muc5AC in lung. Conclusion. MZP probably improves pulmonary functions in CDSCOPD through inhibiting lung inflammation, increasing expressions of AQPs, and decreasing Muc5AC expression in lung.
A Chipless RFID Method of 2D Localization Based on Phase Acquisition
Authors: Barbot Nicolas , Perret Etienne
Published: July 2018

This paper explores the performance of object localization using chipless tags. We show that it is possible to localize a tag (or an object attached to it) by measuring the phase offset between a known position and the position to estimate. This method provides better accuracy compared to classical ones based on received signal strength indicator (RSSI) or round-trip time of flight. We show that submillimeter precision for distance measurement and an error of less than 4 mm for localization can be achieved. These results point the way toward new kinds of sensors and user interfaces using chipless tags which can be contactless and 3D. This new possibility is in addition to the identification functionality which is inherent to the use of chipless tags.
In Vitro and In Vivo Quality Evaluation of Glibenclamide Tablets Marketed in Addis Ababa, Ethiopia
Authors: Kassahun Haile , Asres Kaleab , Ashenef Ayenew
Published: July 2018

Good quality drugs fulfilling the regulatory parameters and produced per the current good manufacturing (CGMP) standards are very critical for best therapeutic outcome in patient therapy. Hence, this study assesses quality as well as physicochemical bioequivalence of five brands of glibenclamide tablets marketed in Addis Ababa using in vitro and in vivo methods. Friability, disintegration, dissolution, and assay for the content of active ingredients were evaluated using the methods described in the British Pharmacopeia (2009) and United States Pharmacopeia (2007). All the brands of glibenclamide tablets complied with the official specification for hardness, friability, disintegration, and assay. Difference factor (f1) values were less than 15 and similarity factor (f2) values were greater than 50 for all products of glibenclamide. The hypoglycemic effect of different products of glibenclamide tablets was evaluated on normoglycemic mice. The in vivo studies indicated that there is no significant difference in percent reduction of blood glucose level between the brands of glibenclamide and the innovator product (p > 0.05). Hence, based on the in vivo results and in vitro dissolution studies, the brands might be substituted with the innovator product in clinical practice.
A Reduction in ADAM17 Expression Is Involved in the Protective Effect of the PPAR-α Activator Fenofibrate on Pressure Overload-Induced Cardiac Hypertrophy
Authors: Zeng Si-Yu , Lu Hui-Qin , Yan Qiu-Jiang , Zou Jian
Published: July 2018

The peroxisome proliferator-activated receptor-α (PPAR-α) agonist fenofibrate ameliorates cardiac hypertrophy; however, its mechanism of action has not been completely determined. Our previous study indicated that a disintegrin and metalloproteinase-17 (ADAM17) is required for angiotensin II-induced cardiac hypertrophy. This study aimed to determine whether ADAM17 is involved in the protective action of fenofibrate against cardiac hypertrophy. Abdominal artery constriction- (AAC-) induced hypertensive rats were used to observe the effects of fenofibrate on cardiac hypertrophy and ADAM17 expression. Primary cardiomyocytes were pretreated with fenofibrate (10 μM) for 1 hour before being stimulated with angiotensin II (100 nM) for another 24 hours. Fenofibrate reduced the ratios of left ventricular weight to body weight (LVW/BW) and heart weight to body weight (HW/BW), left ventricular anterior wall thickness (LVAW), left ventricular posterior wall thickness (LVPW), and ADAM17 mRNA and protein levels in left ventricle in AAC-induced hypertensive rats. Similarly, in vitro experiments showed that fenofibrate significantly attenuated angiotensin II-induced cardiac hypertrophy and diminished ADAM17 mRNA and protein levels in primary cardiomyocytes stimulated with angiotensin II. In summary, a reduction in ADAM17 expression is associated with the protective action of PPAR-α agonists against pressure overload-induced cardiac hypertrophy.
A Prediction Method of Mobile User Preference Based on the Influence between Users
Authors: Shi Yancui , Cao Jianhua , Xiong Congcong , Zhang Xiankun
Published: July 2018

User preference will be impacted by other users. To accurately predict mobile user preference, the influence between users is introduced into the prediction model of user preference. First, the mobile social network is constructed according to the interaction behavior of the mobile user, and the influence of the user is calculated according to the topology of the constructed mobile social network and mobile user behavior. Second, the influence between users is calculated according to the user’s influence, the interaction behavior between users, and the similarity of user preferences. When calculating the influence based on the interaction behavior, the context information is considered; the context information and the order of user preferences are considered when calculating the influence based on the similarity of user preferences. The improved collaborative filtering method is then employed to predict mobile user preferences based on the obtained influence between users. Finally, the experiment is executed on the real data set and the integrated data set, and the results show that the proposed method can obtain more accurate mobile user preferences than those of existing methods.
Nonlinear Stress Analysis of Flexible Pile Composite Foundation by Energy Method
Authors: Wu Youping , Fu Liangming , Wu Wenping , Cao Yuanyuan , Zhou Xuanyang
Published: July 2018

To calculate the stress of cement‐soil pile (flexible pile) in composite foundation accurately and overcome the defective preposition that the pile and the soil are elastic, the nonlinear analysis and calculation of pile‐soil stress by adopting the energy method are performed. First, on the basis of the universally adopted load transfer method, it is assumed that the friction and the relative displacement of the pile shaft conform with the elastic‐plastic relationship. Then, the modified Cam‐clay model is introduced to calculate the compressive amount of soil around the pile. Further, the stress and strain characteristics curve of the flexible pile is used to calculate the compression of the pile, deducing the energy equation of the pile and soil around the pile, establishing the total potential energy expression of the flexible pile composite foundation, and the load sharing value and the corresponding stress value of the pile‐soil are obtained based on the minimum potential energy principle. Finally, this method is verified by indoor laboratory model test and the reported case. The results show that the calculated solutions are in agreement with the measurements; therefore, the calculation method is reasonable.
An Overview of Nature-Inspired, Conventional, and Hybrid Methods of Autonomous Vehicle Path Planning
Authors: Ayawli Ben Beklisi Kwame , Chellali Ryad , Appiah Albert Yaw , Kyeremeh Frimpong
Published: July 2018

Safe and smooth mobile robot navigation through cluttered environment from the initial position to goal with optimal path is required to achieve intelligent autonomous ground vehicles. There are countless research contributions from researchers aiming at finding solution to autonomous mobile robot path planning problems. This paper presents an overview of nature-inspired, conventional, and hybrid path planning strategies employed by researchers over the years for mobile robot path planning problem. The main strengths and challenges of path planning methods employed by researchers were identified and discussed. Future directions for path planning research is given. The results of this paper can significantly enhance how effective path planning methods could be employed and implemented to achieve real-time intelligent autonomous ground vehicles.
Dipeptidyl-Peptidase 4 Inhibitor Sitagliptin Ameliorates Hepatic Insulin Resistance by Modulating Inflammation and Autophagy in ob/ob Mice
Authors: Zheng Wenbin , Zhou Jing , Song Shasha , Kong Wen , Xia Wenfang , Chen Lulu , Zeng Tianshu
Published: July 2018

Obesity and type 2 diabetes are the most common metabolic diseases globally. They are associated with inflammation, oxidative stress, autophagy, and insulin resistance. Sitagliptin, a dipeptidyl-peptidase 4 inhibitor, has been reported to show multiple biological activities beyond the antidiabetic property. This study was aimed at investigating the effect of sitagliptin on hepatic steatosis, insulin resistance, inflammation, and autophagy and exploring the underlying molecular mechanism. In the current study, ob/ob mice, a mouse model of genetic obesity and diabetes, were administered via gavage with sitagliptin 50 mg/kg daily for 4 weeks. Changes in glycolipid metabolism, inflammatory responses, and autophagy in the liver were evaluated. Body weight gain, lipid metabolic disorder, and hepatic steatosis as well as systemic and hepatic insulin sensitivity in ob/ob mice were significantly attenuated after sitagliptin treatment. Furthermore, sitagliptin decreased inflammatory responses by regulating macrophage M1/M2 polarization and inhibiting the activities of NF-κB and JNK. Moreover, sitagliptin increased the levels of phosphorylation of AMPK and decreased those of mTOR. This study indicates that sitagliptin significantly ameliorates the development of hepatic steatosis and insulin resistance in ob/ob mice by inhibiting inflammatory responses and activating autophagy via AMPK/mTOR signaling pathway.
Prognostic Significance of P16INK4a Expression in Penile Squamous Cell Carcinoma: A Meta-Analysis with Trial Sequential Analysis
Authors: Zhang Jiayi , Zhang Hengcheng , Xiu Yanyan , Cheng Hong , Gu Min , Song Ninghong
Published: July 2018

Background. Recently, P16INK4a expression has been shown to be correlated with cancer-specific survival (CSS) in penile squamous cell carcinoma (SCC). Therefore, we performed this meta-analysis to clarify the prognostic value of P16INK4a for penile SCC. Methods. A systematic search was performed in PubMed, Embase, and Web of Science to identify all relevant articles up to May 25, 2017. Hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) of included studies were pooled to estimate the prognostic value. Trial sequential analysis (TSA) was performed to assess the quantity and strength of survival evidence. Results. Five retrospective studies consisting of 323 cases were finally included. We found that P16INK4a positive expression was significantly associated with a better CSS of penile SCC (HR=0.45, 95%CI: 0.30-0.67, P<0.001). No heterogeneity or publication bias was noted among the included studies. Furthermore, TSA demonstrated that the findings were based on sufficient evidence. Conclusions. P16INK4a positive expression is independently associated with improved CSS for patients with penile SCC.
Heun Functions and Some of Their Applications in Physics
Authors: Hortaçsu M.
Published: July 2018

Most of the theoretical physics known today is described by using a small number of differential equations. For linear systems, different forms of the hypergeometric or the confluent hypergeometric equations often suffice to describe the system studied. These equations have power series solutions with simple relations between consecutive coefficients and/or can be represented in terms of simple integral transforms. If the problem is nonlinear, one often uses one form of the Painlevé equations. There are important examples, however, where one has to use higher order equations. Heun equation is one of these examples, which recently is often encountered in problems in general relativity and astrophysics. Its special and confluent forms take names as Mathieu, Lamé, and Coulomb spheroidal equations. For these equations whenever a power series solution is written, instead of a two-way recursion relation between the coefficients in the series, we find one between three or four different ones. An integral transform solution using simpler functions also is not obtainable. The use of this equation in physics and mathematical literature exploded in the later years, more than doubling the number of papers with these solutions in the last decade, compared to time period since this equation was introduced in 1889 up to 2008. We use SCI data to conclude this statement, which is not precise, but in the correct ballpark. Here this equation will be introduced and examples for its use, especially in general relativity literature, will be given.
Urban Lawn Monitoring in Smart City Environments
Authors: Marín José , Parra Lorena , Rocher Javier , Sendra Sandra , Lloret Jaime , Mauri Pedro V. , Masaguer Alberto
Published: July 2018

Control over water usage for irrigation purposes is a key factor in order to achieve the sustainability in agriculture. The irrigation of urban lawns represents a high percentage of the urban water usage. The use of information and communication technology (ICT) offers the possibility of monitoring the grass state in order to adjust the irrigation regime. In this paper, we propose an Arduino-based system with a camera set on a drone. The drone flies along the garden taking pictures of the grass. Those pictures are processed with a rule-based algorithm that classifies them according to the grass quality. Pictures can be tagged in three categories: high coverage, low coverage, or very low coverage. After designing our algorithm, twelve pictures are used to verify its correct operation. The results show a 100% hit rate. To analyze the suitability of using drones to perform this task, we carried out a comparative study for gardens with different sizes, where the drone and a similar system mounted on a small autonomous vehicle have been used. The results show that, for gardens bigger than 1000 m2, the use of drone is needed due to the time consumed by the vehicle to cover the entire surface. Finally, we show the results of sending the image information after processing it in different manners.
Highly Unequal Three-Port Power Divider: Theory and Implementation
Authors: Wu Duolong , Serban Adriana , Karlsson Magnus , Gong Shaofang
Published: July 2018

A three-port power divider consisting of a directional coupler, a Wilkinson power divider, and two transmission lines connected to them is proposed. Theoretical analysis reveals that highly unequal power division can be achieved by a feedback mechanism of two transmission lines along with the coupling coefficient of the directional coupler and the power division ratio of the Wilkinson power divider. The three-port power divider inherits the performance characteristics of high isolation, low reflection coefficients at all ports, and the minimum number of components. The proposed power divider is designed at 5.8 GHz and fabricated and evaluated through measurements. It demonstrates that electromagnetic simulation results are in good agreement with theoretical prediction and measurement results. The three-port power divider is compact in the planar form, so it can be easily integrated into radio frequency front ends.
Healthcare Professional’s Perception of Patient Safety Measured by the Hospital Survey on Patient Safety Culture: A Systematic Review and Meta-Analysis
Authors: Okuyama Julia Hiromi Hori , Galvao Tais Freire , Silva Marcus Tolentino
Published: July 2018

Objective.To assess the culture of patient safety in studies that employed the hospital survey on patient safety culture (HSOPS) in hospitals around the world.Method.We searched MEDLINE, EMBASE, SCOPUS, CINAHL, and SciELO. Two researchers selected studies and extracted the following data: year of publication, country, percentage of physicians and nurses, sample size, and results for the 12 HSOPS dimensions. For each dimension, a random effects meta-analysis with double-arcsine transformation was performed, as well as meta-regressions to investigate heterogeneity, and tests for publication bias.Results.59 studies with 755,415 practitioners surveyed were included in the review. 29 studies were conducted in the Asian continent and 11 in the United States. On average studies scored 9 out of 10 methodological quality score. Of the 12 HSOPS dimensions, six scored under 50% of positivity, with “nonpunitive response to errors” the lowest one. In the meta-regression, three dimensions were shown to be influenced by the proportion of physicians and five by the continent where survey was held.Conclusions.The HSOPS is widely used in several countries to assess the culture of patient safety in hospital settings. The culture of culpability is the main weakness across studies. Encouraging event reporting and learning from errors should be priorities in hospitals worldwide.
A Human-Robot Interaction Based Coordination Control Method for Assistive Walking Devices and an Assessment of Its Stability
Authors: Zhang Xia , Ge Wenliang , Fu Hao , Chen Renxiang , Luo Tianhong , Hashimoto Minoru
Published: July 2018

A biologically inspired motion control method is introduced to ameliorate the flexibility and multijoint autonomy of assistive walking devices based on human-robot interactions (HRIs). A new HRI-based coordination control system consisting of a hip central pattern generator (CPG) control, a knee hierarchical impedance control, and a hip-knee linkage control is also investigated. Simulations and walking experiments are carried out which demonstrate that (i) the self-oscillation and external communication characteristics of the CPG are capable of realizing ideal master/slave hip joint trajectories. In addition, symmetrical inhibition in the CPG unit is essential for maintaining the antiphase motion of the left and right hip joints. (ii) High and low hierarchical impedance control laws allow appropriate knee joint torque to be calculated to maintain posture during the support and swing phases as walking proceeds. (iii) A hip-knee joint linkage mechanism which incorporates a hip joint CPG control and knee joint impedance control allows natural and relevant hip-knee trajectories to be realized. The stability of the HRI-based coordination control method is also confirmed using Lyapunov stability theory.
The MDM2/MDMX-p53 Antagonist PM2 Radiosensitizes Wild-Type p53 Tumors
Authors: Spiegelberg Diana , Mortensen Anja C. , Lundsten Sara , Brown Christopher J. , Lane David P. , Nestor Marika
Published: July 2018

Radiotherapy amplifies p53 expression in cancer cells with wild-type (wt) p53. Blocking the negative regulators MDM2 and MDMX stabilizes p53 and may therefore potentiate radiotherapy outcomes. In this study, we investigate the efficacy of the novel anti-MDM2/X stapled peptide PM2 alone and in combination with external gamma radiation in vitro and in vivo. PM2 therapy combined with radiotherapy elicited synergistic therapeutic effects compared with monotherapy in cells with wt p53 in both in vitro and in vivo assays, whereas these effects did not manifest in p53 −/− cells. Biodistribution and autoradiography of 125I-PM2 revealed high and retained uptake homogenously distributed throughout the tumor. In mice carrying wt p53 tumors, PM2 combined with radiotherapy significantly prolonged the median survival by 50%, whereas effects of PM2 therapy on mutant and p53 −/− tumors were negligible. PM2-dependent stabilization of p53 was confirmed with ex vivo immunohistochemistry. These data demonstrate the potential of the stapled peptide PM2 as a radiotherapy potentiator in vivo and suggest that clinical application of PM2 with radiotherapy in wt p53 cancers might improve tumor control.

Significance: These findings contribute advances to cancer radiotherapy by using novel p53-reactivating stapled peptides as radiosensitizers in wild-type p53 cancers. Cancer Res; 78(17); 5084–93. ©2018 AACR.
Targeting USP7 Identifies a Metastasis-Competent State within Bone Marrow–Resident Melanoma CTCs
Authors: Vishnoi Monika , Boral Debasish , Liu Haowen , Sprouse Marc L. , Yin Wei , Goswami-Sewell Debalina , Tetzlaff Michael T. , Davies Michael A. , Oliva Isabella C. Glitza , Marchetti Dario
Published: July 2018

Systemic metastasis is the major cause of death from melanoma, the most lethal form of skin cancer. Although most patients with melanoma exhibit a substantial gap between onset of primary and metastatic tumors, signaling mechanisms implicated in the period of metastatic latency remain unclear. We hypothesized that melanoma circulating tumor cells (CTC) home to and reside in the bone marrow during the asymptomatic phase of disease progression. Using a strategy to deplete normal cell lineages (Lin−), we isolated CTC-enriched cell populations from the blood of patients with metastatic melanoma, verified by the presence of putative CTCs characterized by melanoma-specific biomarkers and upregulated gene transcripts involved in cell survival and prodevelopment functions. Implantation of Lin− population in NSG mice (CTC-derived xenografts, i.e., CDX), and subsequent transcriptomic analysis of ex vivo bone marrow–resident tumor cells (BMRTC) versus CTC identified protein ubiquitination as a significant regulatory pathway of BMRTC signaling. Selective inhibition of USP7, a key deubiquinating enzyme, arrested BMRTCs in bone marrow locales and decreased systemic micrometastasis. This study provides first-time evidence that the asymptomatic progression of metastatic melanoma can be recapitulated in vivo using patient-isolated CTCs. Furthermore, these results suggest that USP7 inhibitors warrant further investigation as a strategy to prevent progression to overt clinical metastasis.

Significance: These findings provide insights into mechanism of melanoma recurrence and propose a novel approach to inhibit systematic metastatic disease by targeting bone marrow-resident tumor cells through pharmacological inhibition of USP7.

Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/18/5349/F1.large.jpg. Cancer Res; 78(18); 5349–62. ©2018 AACR.
Loss of XIST in Breast Cancer Activates MSN-c-Met and Reprograms Microglia via Exosomal miRNA to Promote Brain Metastasis
Authors: Xing Fei , Liu Yin , Wu Shih-Ying , Wu Kerui , Sharma Sambad , Mo Yin-Yuan , Feng Jiamei , Sanders Stephanie , Jin Guangxu , Singh Ravi , Vidi Pierre-Alexandre , Tyagi Abhishek , Chan Michael D. , Ruiz Jimmy , Debinski Waldemar , Pasche Boris C. , Lo Hui-Wen , Metheny-Barlow Linda J. , D'Agostino Ralph B , Watabe Kounosuke
Published: July 2018

Up to 30% of patients with metastatic breast cancer eventually develop brain metastasis, yet the pathologic mechanism behind this development remains poorly understood. Here, we profiled long noncoding RNAs in brain metastatic tumors from patients with breast cancer and found that the X-inactive–specific transcript (XIST) was significantly downregulated in these tissues. XIST expression levels inversely correlated with brain metastasis, but not with bone metastasis in patients. Silencing of XIST preferentially promoted brain metastatic growth of XISThigh cells in our xenograft models. Moreover, knockout of XIST in mice mammary glands accelerated primary tumor growth as well as metastases in the brain. Decreased expression of XIST stimulated epithelial–mesenchymal transition and activated c-Met via MSN-mediated protein stabilization, which resulted in the promotion of stemness in the tumor cells. Loss of XIST also augmented secretion of exosomal miRNA-503, which triggered M1–M2 polarization of microglia. This M1–M2 conversion upregulated immune suppressive cytokines in microglia that suppressed T-cell proliferation. Furthermore, we screened an FDA-approved drug library and identified fludarabine as a synthetic lethal drug for XISTlow breast tumor cells and found that fludarabine blocked brain metastasis in our animal model. Our results indicate that XIST plays a critical role in brain metastasis in breast cancer by affecting both tumor cells and the tumor microenvironment and that the XIST-mediated pathway may serve as an effective target for treating brain metastasis.

Significance: These findings describe mechanisms of how loss of the lncRNA XIST promotes brain metastasis in breast cancer and identify fludarabine as a potential therapeutic agent that specifically eliminates XISTlow tumor cells in the brain. Cancer Res; 78(15); 4316–30. ©2018 AACR.
Altered White Matter Diffusivity of the Cingulum Angular Bundle in Posttraumatic Stress Disorder
Authors: Averill Christopher L. , Averill Lynnette A. , Wrocklage Kristen M. , Scott J. Cobb , Akiki Teddy J. , Schweinsburg Brian , Southwick Steven M. , Krystal John H. , Abdallah Chadi G.
Published: July 2018

Purpose of the Study: Prior studies showed posttraumatic stress disorder (PTSD)-related alterations in white matter integrity, but most of these studies have used region-based approaches. We address this limitation by investigating the relationship between PTSD severity and fractional anisotropy (FA) using a tract-based approach. Procedures: Structural and diffusion magnetic resonance imaging were acquired from 67 combat-exposed US Veterans and processed using FSL/FreeSurfer TRActs Constrained by UnderLying Anatomy. Partial correlations were conducted between PTSD severity and FA of the cingulum and uncinate fasciculi covarying for age, sex, and head motion. Results: Only FA of the left cingulum angular bundle (CAB) was positively correlated with PTSD symptom severity (r = 0.433, p = 0.001, df = 57) and remained significant after Bonferroni correction. Conclusions: This finding may imply greater organization of the CAB with increasing PTSD severity. The CAB connects directly to the cingulate cortex and the hippocampal subiculum, critical nodes of the default mode network, as well as being implicated in neurodegeneration pathology, decision-making, and executive functions, which may help explain previously shown alterations in this network in PTSD. Message of the Paper: Further study of white matter tract integrity in PTSD is warranted, particularly to investigate whether the CAB connections with both higher-order cognitive functioning and emotion processing regions contribute to the pathophysiology and comorbidity of PTSD.
The Gut Microbiota and Healthy Aging: A Mini-Review
Authors: Kim Sangkyu , Jazwinski S. Michal
Published: July 2018

The gut microbiota shows a wide inter-individual variation, but its within-individual variation is relatively stable over time. A functional core microbiome, provided by abundant bacterial taxa, seems to be common to various human hosts regardless of their gender, geographic location, and age. With advancing chronological age, the gut microbiota becomes more diverse and variable. However, when measures of biological age are used with adjustment for chronological age, overall richness decreases, while a certain group of bacteria associated with frailty increases. This highlights the importance of considering biological or functional measures of aging. Studies using model organisms indicate that age-related gut dysbiosis may contribute to unhealthy aging and reduced longevity. The gut microbiome depends on the host nutrient signaling pathways for its beneficial effects on host health and lifespan, and gut dysbiosis disrupting the interdependence may diminish the beneficial effects or even have reverse effects. Gut dysbiosis can trigger the innate immune response and chronic low-grade inflammation, leading to many age-related degenerative pathologies and unhealthy aging. The gut microbiota communicates with the host through various biomolecules, nutrient signaling-independent pathways, and epigenetic mechanisms. Disturbance of these communications by age-related gut dysbiosis can affect the host health and lifespan. This may explain the impact of the gut microbiome on health and aging.
Impairments in the Comprehension of Indoor Object/Body Part Words and Family Relationships in a Patient with Aphasia due to Cerebral Infarction of the Left Parietal and Temporal Lobes
Authors: Takahashi Nobuhiro , Kawamura Minpei , Kobayashi Yasutaka
Published: July 2018

The present report discusses the case of a 73-year-old right-handed man who exhibited signs of aphasia caused by cerebral infarction in the left temporoparietal region. Neuropsychological evaluation revealed that he had difficulty in comprehending words related to indoor objects, body parts, and family relationships, compared to his vocabulary comprehension in other semantic categories. Although several reports have described cases in whom category-specific impairments in word comprehension are observed, few have documented cases in whom these impairments are accompanied by impairments in the comprehension of words indicating family relationships. Words in each of these three categories derive their meanings and notation from spatial relationships. Therefore, it is likely that the patient’s impairments were caused by difficulty in comprehending spatial relationships due to left parietal lobe damage.