bluuebunny/crossref_metadata_2025 huggingface dataset:
Skin Cancer Knowledge, Attitudes, and Practices among Chinese Population: A Narrative Review
Authors: Stephens Philip M. , Martin Brian , Ghafari Ghazal , Luong James , Nahar Vinayak K. , Pham Linda , Luo Jiangxia , Savoy Marcelle , Sharma Manoj
Published: June 2018

Skin cancers are becoming a substantial public health problem in China. Fair skin and increased exposure to ultraviolet B (UVB) rays from the sun are among the most substantial risk factors for skin cancer development, thus making the Chinese people vulnerable to this group of diseases. The purpose of this article is to present a narrative review of the knowledge, attitudes, and practices (KAP) related to skin cancers within the Chinese population. A systematic electronic search of MEDLINE (PubMed), CINAHL, ScienceDirect, and Google Scholar databases yielded nine articles that met the inclusion criteria. The review found that although sunscreen application was a commonly used method of skin protection among the general Chinese population, educational interventions enhancing current knowledge and attitudes about the effects of UVB rays on skin from undue sun exposure were limited in many smaller communities of the country. Hence, there is an essential need to design effective, evidence-based educational programs promoting sun protection behaviors in both congregated and sparsely populated areas of China.
EPS Current Tracking Method Research Based on Hybrid Sensitivity H∞ Control Algorithm
Authors: Wu Hairong , Xu Guangfei , Wu Jian , Han Xue , Feng Jiwei , Liu Shifu , Bu Linglong
Published: June 2018

For electric power steering system (EPS), road interference, noise of the sensor, and the uncertainty of the steering system may make EPS control effect and the driver's road sense worse. EPS system which takes advantage of good current tracking ability, good anti-interference ability, and good operation stability is becoming more and more important in automotive research. The traditional H∞ control algorithm can solve the system uncertainty theoretically, but it cannot solve the contradiction between robustness and performance without considering the performance of the system. Therefore, this paper proposes a EPS current tracking method based on the hybrid sensitivity H∞ control algorithm, which takes the current tracking performance as one of the control objectives, so that the system can maximize the robustness and performance. Firstly, the dynamic model of EPS is established. Then, the two-degree-of-freedom vehicle model and tire model are introduced. The state space equation of the system is constructed on the basis of the system state space with random disturbance signals, the hybrid sensitivity H∞ controller is designed in the sensitivity index design, and the proposed algorithm can use weighting function to minimize the performance of the current tracking error as well as the robustness of the yaw rate error in response to robustness. Simulation analysis and experimental verification of EPS system are also carried out. The results show that the control method of the hybrid sensitivity H∞ can better achieve EPS target current tracking, effectively suppress the effect of external interference and noise, improve the system performance and robustness, ensure the driver get good road sense, and improve the system of steering stability.
Compact Ultra‐Wide Band MIMO Antenna System for Lower 5G Bands
Authors: AL-Saif Haitham , Usman Muhammad , Chughtai Muhammad Tajammal , Nasir Jamal
Published: June 2018

This paper presents a novel compact 2 × 2 planar MIMO antenna system with ultra‐wide band capability. Antenna system is specifically designed to target lower 5th generation operating bands ranging from 2 GHz to 12 GHz. This band also covers the IEEE 802.11 a/b/g/n/ac. The antenna array geometry has been simulated using CST MWS. The design is extremely miniaturized with total structure size of 13 × 25 × 0.254 mm3. The simulated and measured results have been presented. Measured and simulated return loss values for designed antenna are less than −10 dB over the operating band and lowest values of −35 dB and −32.5 dB can been seen at 5.2 GHz and 9.2 GHz, respectively, whereas at the center frequency the return loss is −25.2 dB. The mutual coupling between both elements is less than −20 dB over the transmission bandwidth. Simulated and measured radiation patterns in E and H planes at center frequency show nearly isotropic far fields. The maximum gain is measured as 4.8 dB. Promising results of Envelope Correlation Coefficient and gain diversity of the design have been achieved. Simulated and measured results are found in good agreement. The fractional bandwidth of antenna is measured as 143.2% which satisfies its ultra‐wide band response.
Study on Formal Modeling and Safety Verification of Train‐to‐Train Communication
Authors: Feng Haonan
Published: June 2018

VBTC (vehicle‐to‐vehicle communication based train control) has gradually become an important research trend in the field of rail transit. This has resulted in advantages of decreasing the number of pieces of wayside equipment and improving the efficiency of real‐time system communication. Characteristics and mechanism of train‐to‐train communication, as key implementation technology of safety critical system, are given and discussed. A new method, based on the LTS (labelled transition system) model checking, is proposed for verifying the safety properties in the communication procedure. The LTS method is adapted to model system behaviours; analysis and safety verification are checked by means of LTSA (labelled transition system analyzer) software. The results show that it is an efficient method to verify safety properties, as well as to assist the complex system’s design and development.
A Finite State Space Model for Representing the Broadband Infinite Series for Acoustic Reverberation between Parallel Reflecting Planes
Authors: Panza Michael J.
Published: June 2018

The acoustic reverberation between two parallel reflecting planes can be represented by an infinite series of the images caused by the planes. To provide a more useful model for analysis and control, the infinite series version of the Green’s function is converted into a finite state space model that retains the high frequency character that enables broadband noise inputs to be examined. The infinite series is first summed into a very accurate, approximate closed form expression in the time domain in terms of a radical function. The radical is then transformed into an expression containing exponentials which have exact Laplace transforms that lead to an overall closed form transfer function for the system. The system transfer function is transformed into a third-order state space model that theoretically contains all of the frequency characteristics of the infinite series representation. The accuracy of the state space model is examined by comparing it to the infinite series solution for three typical types of acoustical inputs: exponential for impulse noise, single frequency sine for harmonic noise, and a multifrequency Schroeder phased harmonic sequence for random noise.
Isolated Polycystic Liver Disease: An Unusual Cause of Recurrent Variceal Bleed
Authors: Khan Mohammad Saud , Khan Zubair , Javaid Toseef , Akhtar Jamal , Moustafa Abdelmoniem , Lal Amos , Tiwari Abhinav , Taleb Mohammad
Published: June 2018

Isolated polycystic liver disease is a rare disorder. Majority of the patients with isolated polycystic liver disease are asymptomatic with incidental detection of liver cysts on imaging studies done for other purposes. Minority of patients develop symptoms which are mostly secondary to enlarging cysts size and hepatomegaly. Rarely, these patients develop portal hypertension and can present with its clinical manifestations and consequences in the form acute variceal bleeding or recurrent ascites. We present a rare case of 67-year-old female patient with significant history of polycystic liver disease who presented to the hospital with recurrent hematemesis and melena. She underwent esophagogastroduodenoscopy which showed multiple large esophageal varices requiring banding.
Comparison of Pulmonary and Systemic NO‐ and PGI2‐Dependent Endothelial Function in Diabetic Mice
Authors: Fedorowicz Andrzej , Buczek Elżbieta , Mateuszuk Łukasz , Czarnowska Elzbieta , Sitek Barbara , Jasztal Agnieszka , Chmura-Skirlińska Antonina , Dib Mobin , Steven Sebastian , Daiber Andreas , Chlopicki Stefan
Published: June 2018

Diabetes increases the risk of pulmonary hypertension and is associated with alterations in pulmonary vascular function. Still, it is not clear whether alterations in the phenotype of pulmonary endothelium induced by diabetes are distinct, as compared to peripheral endothelium. In the present work, we characterized differences between diabetic complications in the lung and aorta in db/db mice with advanced diabetes. Male, 20‐week‐old db/db mice displayed increased HbA1c and glucose concentration compatible with advanced diabetes. Diabetic lungs had signs of mild fibrosis, and pulmonary endothelium displayed significantly ultrastructural changes. In the isolated, perfused lung from db/db mice, filtration coefficient (Kf,c) and contractile response to TXA2 analogue were enhanced, while endothelial NO‐dependent modulation of pulmonary response to hypoxic ventilation and cumulative production of were impaired, with no changes in immunostaining for eNOS expression. In turn, 6‐keto‐PGF1α release from the isolated lung from db/db mice was increased, as well as immunostaining of thrombomodulin (CD141). In contrast to the lung, NO‐dependent, acetylcholine‐induced vasodilation, ionophore‐stimulated generation, and production of 6‐keto‐PGF1α were all impaired in aortic rings from db/db mice. Although eNOS immunostaining was not changed, that of CD141 was clearly lowered. Interestingly, diabetes‐induced nitration of proteins in aorta was higher than that in the lungs. In summary, diabetes induced marked ultrastructural changes in pulmonary endothelium that were associated with the increased permeability of pulmonary microcirculation, impaired NO‐dependent vascular function, with compensatory increase in PGI2 production, and increased CD141 expression. In contrast, endothelial dysfunction in the aorta was featured by impaired NO‐, PGI2‐dependent function and diminished CD141 expression.
An Exact Dynamic Stiffness Formulation for Predicting Natural Frequencies of Moderately Thick Shells of Revolution
Authors: Chen Xudong , Ye Kangsheng
Published: June 2018

An exact dynamic stiffness formulation is proposed for calculating the natural frequencies of shells of revolution based on the first-order Reissner-Mindlin theory. Equations of motion are reduced to be one-dimensional, should the circumferential wave number is specified, and then are rewritten in Hamilton form. Therefore, a shell of revolution with a moderate thickness is analysed as a special skeletal structure with five degrees of freedom at element ends. Dynamic stiffnesses are constructed directly from the one-dimensional governing vibration equations using classic skeletal theory. Number of natural frequencies below a specific value is counted by applying the Wittrick-Williams (W-W) algorithm, and exact eigenvalues can be simply obtained using bisection method. A solution to the number of clamped-end frequencies J0 in the W-W algorithm is also proposed and proven to be reliable. Numerical examples on a variety of shells with different boundary conditions are investigated, and results are well compared and validated. Influences of a variety of shell parameters on natural frequencies of both cylindrical and spherical shells are discussed in detail, demonstrating that the proposed dynamic stiffness formulation is applicable to analyse natural frequencies of moderately thick shells of revolution with high accuracy.
Embedded Connector in Severe Optimization of Steel Plate for Shear Strengthening of RC Beam: Experimental and Numerical Investigations
Authors: Alam Md. Ashraful , Bakkar Suliman A. , Onik Shahnawaz A. , Mustapha Kamal N.
Published: June 2018

Environmental impact has become one of the major factors taken into consideration for recent civil engineering studies and projects. Thus, researchers have been concentrating on shear strengthening of existing reinforced concrete structure as an upgrade method instead of demolishing and reconstructing. In general, shear strengthening of RC beams using externally bonded steel plate has gained huge popularity. However, premature debonding of plates is the main drawback of the system, which could be mitigated using embedded connector; thus, the dimension of steel plate could be reduced significantly. Furthermore, numerical analysis on shear strengthening of beams using embedded connector would provide a great insight on the structural behavior. The aim of this research is to severely reduce the dimension of the steel plate using embedded connector for shear strengthening of RC beams and to investigate the performances of optimized shear‐strengthened beams through experimental and numerical investigations. The results showed that the dimension of plate was reduced without debonding of the plate if the beam was designed for shear strengthening with the consideration of yield strength of steel plate and shear link. Experimental results showed a maximum increase in failure of 24%. The numerical results predicted accurately the structural performance of beams. The embedded connector had a great effect in deferring and minimizing the debonding failure and accordingly increasing the maximum load of shear failure between 14.5% and 24% compared to control beam.
Computational Modeling of the Interaction of Silver Nanoparticles with the Lipid Layer of the Skin
Authors: Fabara Andrea , Cuesta Sebastián , Pilaquinga Fernanda , Meneses Lorena
Published: June 2018

Silver nanoparticles are recognized for numerous physical, biological, and pharmaceutical applications. Their main uses in the medical field comprise diagnostic and therapeutic applications. In this project, the interaction between silver nanoparticles and the lipid layer of the skin was studied in order to know how nanoparticles behave when they are in contact with the skin. Energies of the silver nanoparticles were calculated through the optimization of silver clusters using density functional theory implemented in the Gaussian program 09W. Biological molecules such as glucose, stearic acid, palmitic acid, and quercetin present in coated nanoparticles and in the skin were also optimized. The silver clusters containing 6 atoms were proven to be the most stable complexes. Moreover, a study of molecular orbital describing HOMO interactions of the clusters was performed showing that the electronic density was around the silver cluster. Molecular dynamics simulation was performed using Abalone program. Silver nanoparticles seemed to have very good clearance properties in our molecular dynamics simulation because over a certain period of time, the silver cluster got far away from the biological molecules.
Fabrication of Hollow Silica Particles Using a Self-Assembled Polyethylene Granule as a Template
Authors: Park Sang-Yul , Kim Hyo-Sun , Yoo Jeseung , Seo Young-Soo
Published: June 2018

We developed a novel method preparing nonspherical hollow silica particles (HSP) using a micron-sized granule self-assembled from partially oxidized PE wax. The morphology of the granule was closely investigated in terms of concentration and acid value of PE wax and cooling rate. Due to the oxidized unit in PE wax, magnetic nanoparticle was incorporated into the granule during the self-assembly, and silica was coated on the granule surface via the self-assembly. Silica-coating condition was studied by varying water content and reaction time. After the PE wax was removed by calcination, nonspherical HSP or magnetic HSP was obtained. This cost-effective HSP is expected to be useful for practical applications.
Intra-Abdominal Hemorrhage following Cardiopulmonary Resuscitation: A Report of Two Cases
Authors: Koutserimpas Christos , Ioannidis Argyrios , Siaperas Petros , Skarpas Andreas , Tellos Andreas , Velimezis Georgios , Karanikas Ioannis
Published: June 2018

Cardiopulmonary resuscitation (CPR) represents an emergency procedure, consisting of chest compressions and artificial ventilation. Two rare cases of intra-abdominal bleeding following cardiac compressions are reported. The first case was a 29-year-old female with massive pulmonary embolism (PE). Following CPR due to cardiac arrest, she showed signs of intra-abdominal bleeding. A liver laceration was found and sutured. The patient passed away, due to massive PE. The second patient was a 62-year-old female, suffering from cardiac arrest due to drowning at sea. CPR was performed in situ. At presentation to the emergency department she showed signs of intra-abdominal bleeding. The origin of the hemorrhage was found to be vessels of the lesser curvature of the stomach, which were ligated. Regarding the first patient PE has already been described as a cause for liver lacerations in CPR due to stasis and liver enlargement. The second case is the first report of gastric vessel injury without gastric rupture/laceration and pneumoperitoneum. Complications of CPR should not represent a drawback to performing cardiac compressions. Parenchymatic injuries have been related to inappropriate technique of chest compressions during basic life support. Therefore, it is of utmost importance for the providers to refresh their knowledge of performing CPR.
The Anticancer Activities of Some Nitrogen Donor Ligands Containing bis-Pyrazole, Bipyridine, and Phenanthroline Moiety Using Docking Methods
Authors: Adeniyi Adebayo A. , Ajibade Peter A.
Published: June 2018

The anticancer study of nitrogen-chelating ligands can be of tremendous help in choosing ligands for the anticancer metal complexes design especially with ruthenium(II). The inhibitory anticancer activities of some nitrogen-chelating ligands containing bis-pyrazole, bipyridine, and phenanthroline were studied using experimental screening against cancer cell and theoretical docking methods.In vitroanticancer activities showed compound11as the most promising inhibitor, and the computational docking further indicates its strong inhibitory activities towards some cancer-related receptors. Among the twenty-one modelled ligands, pyrazole-based compounds7,11, and15are the most promising inhibitors against the selected receptors followed by18and21which are derivatives of pyridine and phenanthroline, respectively. The presence of the carboxylic unit in the top five ligands that displayed stronger inhibitory activities against the selected receptors is an indication that the formation of noncovalent interactions such as hydrogen bonding and a strong electron-withdrawing group in these compounds are very important for their receptor interactions. The thermodynamic properties, the polarizabilities, and the LUMO energy of the compounds are in the same patterns as the observed inhibitory activities.
Dislodged Bonded Molar Tube into Wound during Orthognathic Surgery
Authors: Shaeran Tengku Aszraf Tengku , Samsudin A. R.
Published: June 2018

Introduction. Dislodgement of orthodontic appliance into operation wounds may occur while performing orthognathic surgery. Its occurrence is commonly associated with bonded upper molar tube. Case Report. A 25-year-old gentleman presented with recurrent upper right vestibular abscess three months following a bimaxillary orthognathic surgery. A bonded molar orthodontic tube had dislodged into the wound during the operation. The clinical presentation initially mimics an odontogenic infection until our investigations revealed that it originated from the dislodged appliance. The abscess was drained, the wound site was explored, and the molar tube and neighbouring rigid fixation plates and screws were removed. The patient recovered well following the procedure. Conclusion. Dislodged metal orthodontic appliance in oral wound acts as a foreign body that may exert allergic reactions, infection, or inflammation. Pre- and postoperative intraoral examination of fixed orthodontic appliances including its count should be recorded in orthognathic surgery protocol.
Long-Term In Vivo Evaluation of Chitosan Nerve Guide Properties with respect to Two Different Sterilization Methods
Authors: Stößel Maria , Metzen Jennifer , Wildhagen Vivien M. , Helmecke Olaf , Rehra Lena , Freier Thomas , Haastert-Talini Kirsten
Published: June 2018

Severe peripheral nerve injuries are reconstructed either with autologous nerve grafts (gold standard) or alternatively with clinically approved artificial nerve guides. The most common method used to sterilize these medical products is ethylene oxide gassing (EO). However, this method has several disadvantages. An alternative, which has been barely studied so far, represents beta irradiation (β). In previous studies, we developed an artificial nerve guide made of chitosan (chitosan nerve guide, CNG), a biomaterial that is known to potentially retain toxic residues upon EO sterilization. Therefore, we analyzed the long-term regeneration-supporting and mechanical properties of CNGs upon their sterilization with EO or β and their following application in unilateral repair of 12 mm gaps of the rat sciatic nerve. Over a period of 76 weeks, we serially evaluated the recovery of motor functions, the possible emergence of an inflammation in the surrounding connective tissue, the regrowth of axons into the distal nerve, and possible changes in the material properties. Our first long-term evaluation did not reveal significant differences between both sterilization methods. Thus, β is as appropriate as commonly used EO for sterilization of CNGs; however, it may slightly increase the stiffness of the biomaterial over time.
Establishing Analytical Performance Criteria for the Global Reconnaissance of Antibiotics and Other Pharmaceutical Residues in the Aquatic Environment Using Liquid Chromatography-Tandem Mass Spectrometry
Authors: Angeles Luisa F. , Aga Diana S.
Published: June 2018

The occurrence of antibiotics in the environment from discharges of wastewater treatment plants (WWTPs) and from the land application of antibiotic-laden manure from animal agriculture is a critical global issue because these residues have been associated with the increased emergence of antibiotic resistance in the environment. In addition, other classes of pharmaceuticals and personal care products (PPCPs) have been found in effluents of municipal WWTPs, many of which persist in the receiving environments. Analysis of antibiotics by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in samples from different countries presents unique challenges that should be considered, from ion suppression due to matrix effects, to lack of available stable isotopically labeled standards for accurate quantification. Understanding the caveats of LC-MS/MS is important for assessing samples with varying matrix complexity. Ion ratios between quantifying and qualifying ions have been used for quality assurance purposes; however, there is limited information regarding the significance of setting criteria for acceptable variabilities in their values in the literature. Upon investigation of 30 pharmaceuticals in WWTP influent and effluent samples, and in receiving surface water samples downstream and upstream of the WWTP, it was found that ion ratios have higher variabilities at lower concentrations in highly complex matrices, and the extent of variability may be exacerbated by the physicochemical properties of the analytes. In setting the acceptable ion ratio criterion, the overall mean, which was obtained by taking the average of the ion ratios at all concentrations (1.56 to 100 ppb), was used. Then, for many of the target analytes included in this study, the tolerance range was set at 40% for WWTP influent samples and 30% for WWTP effluent, upstream, and downstream samples. A separate tolerance range of 80% was set for tetracyclines and quinolones, which showed higher variations in the ion ratios compared to the other analytes.
Assessing Effectiveness and Costs in Robot-Mediated Lower Limbs Rehabilitation: A Meta-Analysis and State of the Art
Authors: Carpino Giorgio , Pezzola Alessandra , Urbano Michele , Guglielmelli Eugenio
Published: June 2018

Robots were introduced in rehabilitation in the 90s to meet different needs, that is, reducing the physical effort of therapists. This work consists of a meta-analysis of robot-mediated lower limbs rehabilitation for stroke-affected patients; it aims at evaluating the effectiveness of the robotic approach through the use of wearable robots or operational machines with respect to the conventional approach (i.e., manual rehabilitation therapy). The primary assessed outcome is the patient’s ability to recover walking independence, whereas the secondary outcome is the average walking speed. The therapy acceptability and the treatment costs are also assessed. The assessment shows that the robot-mediated therapy is more effective than the conventional one in reaching the primary outcome. As for the secondary outcome, there is no significant difference between the robotic (wearable robots or operational machines) and the conventional approach. Rehabilitation using wearable robots has a greater acceptability than the conventional one. This does not apply to operational machines. The cost of robotic treatment with wearable robots ranges from double to triple the cost of the conventional approach. On the contrary, rehabilitation using operational machines costs the same as the conventional treatment. Robotic rehabilitation based on operational machines is the most cost-effective approach.
Analysis and Comparison of Bayesian Methods for Measurement Uncertainty Evaluation
Authors: Cheng Yin-bao , Chen Xiao-huai , Li Hong-li , Cheng Zhen-ying , Jiang Rui , Lü Jing , Fu Hua-dong
Published: June 2018

Based on the Bayesian principle, the modern uncertainty evaluation methods can fully integrate prior and current sample information, determine the prior distribution according to historical information, and deduce the posterior distribution by integrating prior distribution and the current sample data with the Bayesian model. As such, it is possible to evaluate uncertainty, updating in real time the uncertainty of the measuring instrument according to regular measurement, and timely reflect the latest information on the accuracy of the measurement system. Based on the Bayesian information fusion and statistical inference principle, the model of uncertainty evaluation is established. The maximum entropy principle and the hill-climbing search optimization algorithm are introduced to determine the prior distribution probability density function and the sample information likelihood function. The probability density function of posterior distribution is obtained by the Bayesian formula to achieve the optimization estimation of uncertainty. Three methods of measurement uncertainty evaluation based on Bayesian analysis are introduced: the noninformative prior, the conjugate prior, and the maximum entropy prior distribution. The advantages and limitations of each method are discussed.
Multicriteria‐Based Location Privacy Preservation in Vehicular Ad Hoc Networks
Authors: Farman Haleem , Jan Bilal , Talha Muhammad , Zar Abi , Javed Huma , Khan Murad , Din Aziz Ud , Han Kijun
Published: June 2018

Vehicular ad hoc networks (VANETs) are the preferable choice for Intelligent Transportation Systems (ITS) because of its prevailing significance in both safety and nonsafety applications. Information dissemination in a multihop fashion along with privacy preservation of source node is a serious but challenging issue. We have used the idea of the phantom node as the next forwarder for data dissemination. The phantom node (vehicle) hides the identity of actual source node thus preserving the location privacy. The selection of the phantom node among the set of alternatives’ candidate vehicles is considered as a multicriteria‐based problem. The phantom node selection problem is solved by using an analytical network process (ANP) by considering different traffic scenarios. The selection is based on different parameters which are distance, speed, trust, acceleration, and direction. The best alternative (target phantom vehicle) is selected through an ANP where all the alternatives are ranked from best to worst. The vehicle having maximum weight is considered to be the best choice as a phantom node. In order to check the stability of the alternatives’ ranking, sensitivity analysis is performed by taking into account different traffic scenarios and interest level of candidate vehicles.
The Effects of Sinapic Acid on the Development of Metabolic Disorders Induced by Estrogen Deficiency in Rats
Authors: Zych Maria , Kaczmarczyk-Sedlak Ilona , Wojnar Weronika , Folwarczna Joanna
Published: June 2018

Sinapic acid is a natural phenolic acid found in fruits, vegetables, and cereals, exerting numerous pharmacological effects. The aim of the study was to investigate the influence of sinapic acid on biochemical parameters related to glucose and lipid metabolism, as well as markers of antioxidant abilities and parameters of oxidative damage in the blood serum in estrogen‐deficient rats. The study was performed on 3‐month‐old female Wistar rats, divided into 5 groups, including sham‐operated control rats, ovariectomized control rats, and ovariectomized rats administered orally with estradiol (0.2 mg/kg) or sinapic acid (5 and 25 mg/kg) for 28 days. The levels of estradiol, progesterone, interleukin 18, insulin, glucose, fructosamine, lipids, and enzymatic and nonenzymatic antioxidants (superoxide dismutase, catalase, and glutathione); total antioxidant capacity; and oxidative damage parameters (thiobarbituric acid‐reactive substances, protein carbonyl groups, and advanced oxidation protein products) were determined in the serum. Estradiol counteracted the carbohydrate and cholesterol metabolism disorders induced by estrogen deficiency. Sinapic acid increased the serum estradiol concentration; decreased insulin resistance and the triglyceride and total cholesterol concentrations; and favorably affected the parameters of antioxidant abilities (reduced glutathione, superoxide dismutase) and oxidative damage (advanced oxidation protein products).
Glucuronide-Linked Antibody–Tubulysin Conjugates Display Activity in MDR+ and Heterogeneous Tumor Models
Authors: Burke Patrick J. , Hamilton Joseph Z. , Pires Thomas A. , Lai Holden W.H. , Leiske Christopher I. , Emmerton Kim K. , Waight Andrew B. , Senter Peter D. , Lyon Robert P. , Jeffrey Scott C.
Published: June 2018

Although antibody–drug conjugates (ADCs) find increasing applications in cancer treatment, de novo or treatment-emergent resistance mechanisms may impair clinical benefit. Two resistance mechanisms that emerge under prolonged exposure include upregulation of transporter proteins that confer multidrug resistance (MDR+) and loss of cognate antigen expression. New technologies that circumvent these resistance mechanisms may serve to extend the utility of next-generation ADCs. Recently, we developed the quaternary ammonium linker system to expand the scope of conjugatable payloads to include tertiary amines and applied the linker to tubulysins, a highly potent class of tubulin binders that maintain activity in MDR+ cell lines. In this work, tubulysin M, which contains an unstable acetate susceptible to enzymatic hydrolysis, and two stabilized tubulysin analogues were prepared as quaternary ammonium-linked glucuronide-linkers and assessed as ADC payloads in preclinical models. The conjugates were potent across a panel of cancer cell lines and active in tumor xenografts, including those displaying the MDR+ phenotype. The ADCs also demonstrated potent bystander activity in a coculture model comprised of a mixture of antigen-positive and -negative cell lines, and in an antigen-heterogeneous tumor model. Thus, the glucuronide–tubulysin drug-linkers represent a promising ADC payload class, combining conjugate potency in the presence of the MDR+ phenotype and robust activity in models of tumor heterogeneity in a structure-dependent manner. Mol Cancer Ther; 17(8); 1752–60. ©2018 AACR.
The Hypoxic Tumor Microenvironment Promotes Invadopodia Formation and Metastasis through LPA1 Receptor and EGFR Cooperation
Authors: Harper Kelly , R. Lavoie Roxane , Charbonneau Martine , Brochu-Gaudreau Karine , Dubois Claire M.
Published: June 2018

Hypoxia, a common feature of solid tumors, has been critically involved in cell invasion and metastasis, but the underlying mechanisms remain poorly understood. Previously, it has been observed that the lysophosphatidic acid receptor 4 (LPA4) signaling axis mediates production of the degradative subcellular structures invadopodia, which are known to be required for metastasis. Here, it is demonstrated that LPA1 (LPAR1) is a common and major receptor used for hypoxia-induced invadopodia production in various cancer cell lines. The widespread use of LPA1 was not due to increased LPA1 expression but rather relied on Src-mediated cross-talk with EGFR. LPA1-mediated phosphorylation of Y845-EGFR under hypoxia led to PI3K/Akt activation, an event that increases the ability of cells to produce invadopodia. Moreover, phospho-Y845-EGFR was upregulated in hypoxic zones of tumors and a combination of EGFR and LPA1 inhibition synergistically suppressed metastasis in vivo.

Implications: This study uncovers an LPA1–EGFR signaling axis that is used for cell invasion in hypoxia and suggests a potential target to impede cancer metastasis. Mol Cancer Res; 16(10); 1601–13. ©2018 AACR.
Lung Cancer: One Disease or Many
Authors: O'Brien Timothy D. , Jia Peilin , Aldrich Melinda C. , Zhao Zhongming
Published: June 2018

Objective: Lung cancer is classified as a single entity comprised of multiple histological subtypes. But how similar are these subtypes on a genetic level? This paper aims to address this question through a concise overview of germline and somatic differences between small cell lung cancer, lung adenocarcinoma, and lung squamous cell carcinoma. Methods: We reveal the weak overlap found between these 3 lung cancer subtypes using published data from one of the largest germline genetic studies on lung cancer to date and somatic mutation data from Catalogue of Somatic Mutations in Cancer (COSMIC). Results: These data indicate that these 3 subtypes share very little with each other at the genetic level. At the germline SNP level, only 24 independent SNPs from 2 chromosomes were shared across all 3 subtypes. We also demonstrate that only 30 unique cancer-specific mutations overlap the 3 subtypes from COSMIC, and that this is fewer than overlapping mutations chosen at random. Finally, we show that only 3 somatic mutational signatures are shared between these 3 subtypes. Conclusion: This paper highlights that these 3 lung cancer subtypes may be distinct diseases at the genetic level. In the era of precision medicine, we feel that these genomic differences will be of utmost importance in the choice of lung cancer therapy in the future.
Rheumatic Disease Autoantibodies in Patients with Autoimmune Thyroid Diseases
Authors: Nisihara Renato , Pigosso Yasmine Gorczevski , Prado Nathalia , Utiyama Shirley R.R. , De Carvalho Gisah A. , Skare Thelma L.
Published: June 2018

Background: Patients with autoimmune thyroid diseases (ATD) such as Graves’ disease (GD) and Hashimoto thyroiditis (HT) may have non-organ specific autoantibodies such as antinuclear antibodies (ANA) and rheumatoid factor (RF). Aim: To study the prevalence of rheumatic autoantibodies in a group of ATD patients without known rheumatic diseases and to evaluate its association with the patients’ epidemiological and treatment profiles. To follow positive non-organ specific autoantibody-positive ATD individuals to investigate whether they will develop a rheumatic disorder. Methods: A sample of 154 ATD patients (70 HT and 84 GD; mean age 45.3 ± 14.2) had determination of ANA by immunofluorescence, using hep-2 cells as substrate, extractable nuclear antigen profile by ELISA kits and RF by latex agglutination. Epidemiological and treatment profiles were obtained through chart review. These patients were followed for the mean period of 5 years, between 2010 and 2015. Results: Positive ANA was found in 17.5% (27/154) of the patients: anti-Ro/SS-A in 4/154 (2.5%); anti-RNP in 4/154 (2.5%), and anti-La/SS-B in 3/154 (1.9%). None had anti-Sm antibodies. RF was detected in 12/154 (7.7%) of ATD patients and was more common in older individuals (p = 0.007). There was a positive association between the presence of RF and ANA (p = 0.03; OR 3.89; 95% CI 1.1–13.3). None of the patients with positive autoantibodies developed clinical rheumatic diseases during the period of observation. Conclusion: We found rheumatic autoantibodies in 17.5% of ATD patients without rheumatic diseases. None of them were associated with the appearance of clinical rheumatic disorder during the period of 5 years.
Risk Stratification of Genetic, Dilated Cardiomyopathies Associated With Neuromuscular Disorders
Authors: van der Bijl Pieter , Delgado Victoria , Bootsma Marianne , Bax Jeroen J.
Published: June 2018

The etiology of dilated cardiomyopathy (DCM) can be grouped as either genetic or nongenetic. More than 50 pathogenic genes have been described, with sarcomeric and lamin A/C mutations being the most common. Mutation carriers for genetic DCM are often asymptomatic until cardiac disease manifests with heart failure, arrhythmias, or sudden cardiac death. Preventive strategies are promising but can only be applied and tested adequately if genetic DCM can be diagnosed at an early stage. Early diagnosis of mutation carriers that may develop overt DCM requires advanced imaging techniques that can detect subtle structural and functional abnormalities. Advanced echocardiographic techniques such as tissue Doppler imaging and speckle tracking strain analysis permit early detection of functional abnormalities, whereas cardiovascular magnetic resonance techniques provide information on tissue characterization and myocardial energetics that may be altered at an early stage. Furthermore, nuclear imaging techniques provide information on cellular function (metabolism, perfusion). Once the diagnosis of overt DCM has been established, various imaging parameters such as echocardiography-based myocardial mechanics and cardiovascular magnetic resonance-based tissue characterization have shown incremental benefit to left ventricular ejection fraction in risk stratification. Further research is required to understand how imaging techniques may help to choose management strategies that could delay progression when instituted early in the course of the disease. The present article reviews the role of imaging in the risk stratification of genetic DCM in general, with specific emphasis on DCM associated with neuromuscular disorders.
Protective Effects of Brain Infarction by
N
-Acetylcysteine Derivatives
Authors: Uemura Takeshi , Watanabe Kenta , Ko Kenta , Higashi Kyohei , Kogure Noriyuki , Kitajima Mariko , Takayama Hiromitsu , Takao Koichi , Sugita Yoshiaki , Sakamoto Akihiko , Terui Yusuke , Toida Toshihiko , Kashiwagi Keiko , Igarashi Kazuei
Published: June 2018

Background and Purpose—

We recently found that acrolein (CH
2
=CH-CHO) is more strongly involved in brain infarction compared with reactive oxygen species. In this study, we looked for acrolein scavengers with less side effects.

Methods—

Photochemically induced thrombosis model mice were prepared by injection of Rose Bengal. Effects of
N
-acetylcysteine (NAC) derivatives on brain infarction were evaluated using the public domain National Institutes of Health image program.

Results—

NAC, NAC ethyl ester, and NAC benzyl ester (150 mg/kg) were administered intraperitoneally at the time of induction of ischemia, or these NAC derivatives (50 mg/kg) were administered 3× at 24-h intervals before induction of ischemia and 1 more administration at the time of induction of ischemia. The size of brain infarction decreased in the order NAC benzyl ester>NAC ethyl ester>NAC in both experimental conditions. Detoxification of acrolein occurred through conjugation of acrolein with glutathione, which was catalyzed by glutathione
S
-transferases, rather than direct conjugation between acrolein and NAC derivatives. The level of glutathione
S
-transferases at the locus of brain infarction was in the order of administration of NAC benzyl ester>NAC ethyl ester>NAC>no NAC derivatives, suggesting that NAC derivatives stabilize glutathione
S
-transferases.

Conclusions—

The results indicate that detoxification of acrolein by NAC derivatives is caused through glutathione conjugation with acrolein catalyzed by glutathione
S
-transferases, which can be stabilized by NAC derivatives. This is a new concept of acrolein detoxification by NAC derivatives.
Growth and Regional Disparities in South America, 1890–1960
Authors: Badia-Miró Marc , Nicolini Esteban A. , Willebald Henry
Published: June 2018

Most of the regional inequality in Argentina, Chile, and Uruguay stems from differences within the countries rather than from disparities across them. Between the end of the nineteenth century and the second third of the twentieth century, Chile evinced considerable inequality and a U-shaped evolution (reduction of inequality and a slight increase in the 1960s), Uruguay a monotonically declining inequality, and Argentina a U-shaped evolution with decreasing disparities until the beginning of the twentieth century and increasing inequality thereafter. Together, the subnational units exhibited substantial inequality at the end of the nineteenth century, a low in the 1940s, and another local maximum that ended with the collapse of the Import Substitution Industrialization (isi) polices of the 1960s and 1970s. Convergence at the national level depended on periods and countries: convergence in Uruguay in all sub-periods; provincial convergence in Argentina only during the first globalization; and a general convergence in Chile that was hampered by outliers during the first globalization. Convergence at the regional level occurred during the first globalization but not during the mid-twentieth century.
Estimating feedforward and feedback effective connections from fMRI time series: Assessments of statistical methods
Authors: Sanchez-Romero Ruben , Ramsey Joseph D. , Zhang Kun , Glymour Madelyn R. K. , Huang Biwei , Glymour Clark
Published: June 2018

We test the adequacies of several proposed and two new statistical methods for recovering the causal structure of systems with feedback from synthetic BOLD time series. We compare an adaptation of the first correct method for recovering cyclic linear systems; Granger causal regression; a multivariate autoregressive model with a permutation test; the Group Iterative Multiple Model Estimation (GIMME) algorithm; the Ramsey et al. non-Gaussian methods; two non-Gaussian methods by Hyvärinen and Smith; a method due to Patel et al.; and the GlobalMIT algorithm. We introduce and also compare two new methods, Fast Adjacency Skewness (FASK) and Two-Step, both of which exploit non-Gaussian features of the BOLD signal. We give theoretical justifications for the latter two algorithms. Our test models include feedback structures with and without direct feedback (2-cycles), excitatory and inhibitory feedback, models using experimentally determined structural connectivities of macaques, and empirical human resting-state and task data. We find that averaged over all of our simulations, including those with 2-cycles, several of these methods have a better than 80% orientation precision (i.e., the probability of a directed edge is in the true structure given that a procedure estimates it to be so) and the two new methods also have better than 80% recall (probability of recovering an orientation in the true structure).
Personality assortative female mating preferences in a songbird
Authors: Pogány Ákos , Vincze Ernő , Szurovecz Zita , Kosztolányi András , Barta Zoltán , Székely Tamás , Riebel Katharina
Published: June 2018

Consistent individual behavioural differences (‘animal personalities’) are documented across a variety of animal taxa. Sexual selection, especially assortative mating has been suggested as a possible mechanism contributing to the maintenance of different personality types within populations but little is known about non-random pair-formation with respect to personality traits in unconstrained choice tests. We here tested whether female mating preferences were non-random with respect to male and female neophobia in zebra finches (Taeniopygia guttata), an important avian model of mate choice and animal personality research. Male and female neophobia was assessed by attaching novel objects to birds’ feeders. Females’ mating preferences were tested with randomly assigned, unfamiliar males in a four-way choice apparatus. Females associated most with males with neophobia scores similar to their own. These results provide evidence that mating preferences and personality traits can covary, supporting evolutionary scenarios of assortative mating contributing to the maintenance of personality traits.
Racism and the Logic of Capital: A Fanonian Reconsideration
Authors: Hudis Peter
Published: June 2018

The last several decades have produced a slew of important studies by Marxists of the logic of capital, as well as numerous explorations by postcolonial theorists of the narratives that structure racial and ethnic discrimination. Far too often, however, these two currents have assumed different or even opposed trajectories, making it all the harder to transcend one-sided class-reductionist analyses and equally one-sided affirmations of identity that bypass or ignore class. In light of the new reality produced by the deepening crisis of neoliberalism and the looming disintegration of the political order that has defined global capitalism since the end of the Cold War, the time has come to revisit theoretical approaches that can help delineate the integrality of race, class and capitalism.
Four Missing Years
Authors: Thomas Martin
Published: June 2018

Thomas Twiss has written a careful, well-documented study of the evolution of Trotsky’s ideas on theUSSRbureaucracy until 1936. He also traces Trotsky’s assessments of the causes and meaning of the Moscow Trials and the Terror in 1936–8; but essentially the detailed study stops in 1936. In fact, Trotsky’s thinking continued to develop in response to new developments after 1936. The puzzle which Trotsky grappled with – the ‘workers’ state’ which is simultaneously the instrument of fascistic terror against the workers by ‘the sole privileged and commanding stratum’ – was connected to puzzles in the more general Marxist theory of the state, which Twiss explores usefully in his opening chapter.
Insurgency in the Indian Northeast: Student Voices from Kolkata
Authors: Mukherjee Kunal
Published: June 2018

The article looks at the different facets of the on-going conflict in the Indian Northeast. After some background information, the article looks at the current political situation. There is a special focus on the voices of students. In the Indian Northeast, students have been actively involved in the insurgency and protest movements. Thus, the primary data for the purposes of this article was collected from students of Northeastern origin in the city of Kolkata. Although Kolkata is not in north-eastern India, it is seen as the gateway to the Indian Northeast and the nearest large city in the region, where people of Northeastern descent often come for their education and employment. The article also argues that out of all the Northeastern states, Manipur is currently the most troubled one. Finally, at the end of the article methods of peace building have been suggested as the way forward.