bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanisms responsible for reduced erythropoiesis during androgen deprivation therapy in men with prostate cancer
Authors: Gagliano-Jucá Thiago , Pencina Karol M. , Ganz Tomas , Travison Thomas G. , Kantoff Philip W. , Nguyen Paul L. , Taplin Mary-Ellen , Kibel Adam S. , Li Zhuoying , Huang Grace , Edwards Robert R. , Nemeth Elizabeta , Basaria Shehzad
Published: October 2018

Androgen deprivation therapy (ADT) is a mainstay of treatment for prostate cancer (PCa). As androgens stimulate erythropoiesis, ADT is associated with a reduction in hematocrit, which in turn contributes to fatigue and related morbidity. However, the mechanisms involved in ADT-induced reduction in erythropoiesis remain unclear. We conducted a 6-mo prospective cohort study and enrolled men with PCa about to undergo ADT (ADT-Group) and a control group of men who had previously undergone prostatectomy for localized PCa and were in remission (Non-ADT Group). All participants had normal testosterone levels at baseline. Fasting blood samples were collected at baseline, 12 wk, and 24 wk after initiation of ADT; samples were obtained at the same intervals from enrollment in the Non-ADT group. Blood count, iron studies, erythropoietin, erythroferrone, and hepcidin levels were measured. Seventy participants formed the analytical sample (31 ADT, 39 Non-ADT). ADT was associated with a significant reduction in erythrocyte count (estimated mean difference = −0.2×106cells/µl, 95%CI = −0.3 to −0.1×106cells/µl, P < 0.001), hematocrit (−1.9%, 95%CI = −2.7 to −1.1%, P < 0.001), and hemoglobin (−0.6 g/dl, 95%CI = −0.8 to −0.3 g/dl, P < 0.001). Serum hepcidin concentration increased in the ADT-group (18 ng/ml, P < 0.001); however, iron concentrations did not change (−1.1 µg/dl, P = 0.837). Ferritin levels increased in men on ADT (60 ng/ml, P < 0.001). Iron binding capacity, transferrin saturation, erythroferrone, and erythropoietin did not change. Nine men undergoing ADT developed new-onset anemia. In conclusion, reduced proliferation of marrow erythroid progenitors leads to ADT-induced reduction in erythropoiesis. Future studies should evaluate the role of selective androgen receptor modulators in the treatment of ADT-induced anemia.
Improving pregnancy outcomes in humans through studies in sheep
Authors: Morrison Janna L. , Berry Mary J. , Botting Kimberley J. , Darby Jack R. T. , Frasch Martin G. , Gatford Kathryn L. , Giussani Dino A. , Gray Clint L. , Harding Richard , Herrera Emilio A. , Kemp Matthew W. , Lock Mitchell C. , McMillen I. Caroline , Moss Timothy J. , Musk Gabrielle C. , Oliver Mark H. , Regnault Timothy R. H. , Roberts Claire T. , Soo Jia Yin , Tellam Ross L.
Published: October 2018

Experimental studies that are relevant to human pregnancy rely on the selection of appropriate animal models as an important element in experimental design. Consideration of the strengths and weaknesses of any animal model of human disease is fundamental to effective and meaningful translation of preclinical research. Studies in sheep have made significant contributions to our understanding of the normal and abnormal development of the fetus. As a model of human pregnancy, studies in sheep have enabled scientists and clinicians to answer questions about the etiology and treatment of poor maternal, placental, and fetal health and to provide an evidence base for translation of interventions to the clinic. The aim of this review is to highlight the advances in perinatal human medicine that have been achieved following translation of research using the pregnant sheep and fetus.
Endocrine Modulation in Long‐Term Karate Practitioners
Authors: Vera Francisca M. , Manzaneque Juan M. , Carranque Gabriel A. , Rodríguez-Peña Francisco M. , Sánchez-Montes Soledad , Blanca María J.
Published: October 2018

Purpose. Karate is a martial arts discipline which is widely practiced in the Western world as a form of self‐defense, as well as a discipline to achieve physical and mental balance. However, little is known with respect to its specific psychobiological effects, particularly in relation to the influence that it may exert on the endocrine system. Thus, in the present study, we examined the effects of karate on several hormonal parameters of the Hypothalamic‐Pituitary‐Adrenal and Hypothalamic‐Pituitary‐Thyroid axes in long‐time practitioners. Methods. Twenty‐two healthy volunteer subjects (12 experimental and 10 controls) participated in the study. Experimental subjects were karate players with a minimum of 3 years of practice in this discipline. Blood samples for the quantification of hormonal parameters were taken in both groups. The Mann‐Whitney U test was performed for each variable in order to analyze the differences between groups. Results. Statistically significant differences were found in cortisol and thyroid hormones, with the karate group showing lower levels of these hormones as compared to control. Conclusions. These findings, therefore, reveal that long‐term karate practice is associated with a significant endocrine modulation, which suggests interesting psychobiological and clinical implications. Further research is needed to verify these preliminary results, as well as properly assessing its possible use as a psychosomatic intervention tool.
Adaptive Black Hole Algorithm for Solving the Set Covering Problem
Authors: Soto Ricardo , Crawford Broderick , Olivares Rodrigo , Taramasco Carla , Figueroa Ignacio , Gómez Álvaro , Castro Carlos , Paredes Fernando
Published: October 2018

Evolutionary algorithms have been used to solve several optimization problems, showing an efficient performance. Nevertheless, when these algorithms are applied they present the difficulty to decide on the appropriate values of their parameters. Typically, parameters are specified before the algorithm is run and include population size, selection rate, and operator probabilities. This process is known as offline control and is even considered as an optimization problem in itself. On the other hand, parameter settings or control online is a variation of the algorithm original version. The main idea is to vary the parameters so that the algorithm of interest can provide the best convergence rate and thus may achieve the best performance. In this paper, we propose an adaptive black hole algorithm able to dynamically adapt its population according to solving performance. For that, we use autonomous search which appeared as a new technique that enables the problem solver to control and adapt its own parameters and heuristics during solving in order to be more efficient without the knowledge of an expert user. In order to test this approach, we resolve the set covering problem which is a classical optimization benchmark with many industrial applications such as line balancing production, crew scheduling, service installation, and databases, among several others. We illustrate encouraging experimental results, where the proposed approach is able to reach various global optimums for a well-known instance set from Beasley’s OR-Library, while improving various modern metaheuristics.
Seismic Response for Wave Propagation across Joints with Equally and Unequally Close‐Open Behaviours
Authors: Zhang Qi , Li Zhengliang , Yu Tao
Published: October 2018

The interaction between rock joints and seismic waves is critical in rock engineering when rock mass is suffered from human‐induced or natural earthquakes. Stress wave propagation across rock joints is usually dependent on the seismic response of the joints. Wave propagation may cause joints close or open under the in situ stress. In this paper, the seismic response for wave propagation with an arbitrary incident angle impinging on joints is studied. Both reflection and transmission usually occurring at the two interfaces of the joint are considered, respectively. Wave propagation equations with equally and unequally close‐open behaviours are deduced firstly, which can be applied for the general cases of arbitrary incident P‐ or S‐wave. Then, wave propagation across joints with normal and oblique incident P‐ and S‐waves is analyzed by considering the equally and unequally close‐open behaviours and verified by comparing with the existing methods. Finally, several parametric studies are conducted to evaluate the effect of in situ stress on transmitted waves, the effect of the incident frequency on the maximum deformation of joints, and the effect of the incident angle on the maximum deformation of joints. The wave propagation equations derived in the study are more feasible and can well analyze the seismic response of wave propagation for the most general cases of different incident waveforms.
Urinary Metabolomics Study of Patients with Gout Using Gas Chromatography-Mass Spectrometry
Authors: Li Qianqian , Wei Shuangshuang , Wu Dehong , Wen Chengping , Zhou Jia
Published: October 2018

Objectives. Gout is a common type of inflammatory arthritis. The aim of this study was to detect urinary metabolic changes in gout patients which may contribute to understanding the pathological mechanism of gout and discovering potential metabolite markers. Methods. Urine samples from 35 gout patients and 29 healthy volunteers were analyzed by gas chromatography–mass spectrometry (GC–MS). Orthogonal partial least-squares discriminant analysis (OPLS-DA) was performed to screen differential metabolites between two groups, and the variable importance for projection (VIP) values and Student’s t-test results were combined to define the significant metabolic changes caused by gout. Further, binary logistic regression analysis was performed to establish a model to distinguish gout patients from healthy people, and receiver operating characteristic (ROC) curve was made to evaluate the potential for diagnosis of gout. Result. A total of 30 characteristic metabolites were significantly different between gout patients and controls, mainly including amino acids, carbohydrates, organic acids, and their derivatives, associated with perturbations in purine nucleotide synthesis, amino acid metabolism, purine metabolism, lipid metabolism, carbohydrate metabolism, and tricarboxylic acid cycle. Binary logistic regression and ROC curve analysis showed the combination of urate and isoxanthopterin can effectively discriminate the gout patients from controls with the area under the curve (AUC) of 0.879. Conclusion. Thus, the urinary metabolomics study is an efficient tool for a better understanding of the metabolic changes of gout, which may support the clinical diagnosis and pathological mechanism study of gout.
TLE1 Positive Clear Cell Sarcoma of the Kidney: A Case Report and Review of the Literature
Authors: Naous Rana
Published: October 2018

Clear cell sarcoma of the kidney (CCSK) is an uncommon malignant tumor of uncertain histogenesis that occurs most commonly in childhood. Histologically, CCSK can mimic myxoid variant of synovial sarcoma (SS); however, the double positivity for CD99 and TLE1 in SS helps in excluding CCSK. Herein, we report a rare case of CCSK arising in the left kidney of a 3-year-old girl. The mass grossly measured 9.5 cm in maximum dimension and histologically showed the classic arborizing fibrovascular septae and background myxoid matrix that is usually seen in CCSK. The tumor however was double positive for CD99 and TLE1 which made it difficult to discriminate it from the myxoid variant of SS based on histopathological examination and immunophenotype alone, and genetic analysis for SYT gene rearrangement was required to reach a definitive diagnosis. Although there have been previous case reports of CCSK with positive expression of CD99 and negative TLE1, to our knowledge, this is the first case of CCSK expressing both CD99 and TLE1.
4-Hydroxycoumarin Derivative:N-(diphenylmethyl)-2-[(2-oxo-2H-chromen-4-yl)oxy]acetamide Interaction with Human Serum Albumin
Authors: Chinnathambi Shanmugavel , Karthikeyan Subramani , Rajendiran Mangaiyarkarsi , Udayakumar Kanniyappan , Manoharan Arunkumar , Kandasamy Saravanan , Hanagata Nobutaka
Published: October 2018

In this study, the interaction between the coumarin derivative:N-(diphenylmethyl)-2-[(2-oxo-2H-chromen-4-yl)oxy]acetamide, biologically active drug, and human serum albumin (HSA) was investigated by using various optical spectroscopy techniques along with the computational technique. The results of steady-state fluorescence spectroscopy show that the static quenching occurred while increasing the coumarin drug concentration into HSA. Also, the binding constant (K) and thermodynamical parameters of enthalpy change (ΔH°), entropy change (ΔS°), and Gibbs free energy change (ΔG°) were calculated at different temperatures (293 K, 298 K, and 303 K). The results are in good agreement with those of molecular docking studies, and also, the docking study was carried out to understand the hydrogen bonding and hydrophobic interaction between human serum albumin and coumarin derivative. In addition to the docking, charge distribution analysis was done to understand the internal stability of coumarin derivative active sites of human serum albumin. Further time-resolved emission spectroscopy (TRES) studies were carried out between free HSA and HSA-coumarin complex, and the result confirms the presence of the drug in the protein molecule without cytotoxicity.
Ls-II: An Improved Locust Search Algorithm for Solving Optimization Problems
Authors: Camarena Octavio , Cuevas Erik , Pérez-Cisneros Marco , Fausto Fernando , González Adrián , Valdivia Arturo
Published: October 2018

The Locust Search (LS) algorithm is a swarm-based optimization method inspired in the natural behavior of the desert locust. LS considers the inclusion of two distinctive nature-inspired search mechanism, namely, their solitary phase and social phase operators. These interesting search schemes allow LS to overcome some of the difficulties that commonly affect other similar methods, such as premature convergence and the lack of diversity on solutions. Recently, computer vision experiments in insect tracking methods have conducted to the development of more accurate locust motion models than those produced by simple behavior observations. The most distinctive characteristic of such new models is the use of probabilities to emulate the locust decision process. In this paper, a modification to the original LS algorithm, referred to as LS-II, is proposed to better handle global optimization problems. In LS-II, the locust motion model of the original algorithm is modified incorporating the main characteristics of the new biological formulations. As a result, LS-II improves its original capacities of exploration and exploitation of the search space. In order to test its performance, the proposed LS-II method is compared against several the state-of-the-art evolutionary methods considering a set of benchmark functions and engineering problems. Experimental results demonstrate the superior performance of the proposed approach in terms of solution quality and robustness.
Cholinergic Mechanisms of Target Oddball Stimuli Detection: The Late “P300-Like” Event-Related Potential in Rats
Authors: Ahnaou A. , Biermans R. , Drinkenburg W. H. I. M.
Published: October 2018

Event-related potentials (ERPs) and oscillations (EROs) provide powerful tools for studying the brain’s synaptic function underlying information processing. The P300 component of ERPs indexing attention and working memory shows abnormal amplitude and latency in neurological and psychiatric diseases that are sensitive to pharmacological agents. In the active auditory oddball discriminant paradigm, behavior and auditory-evoked potentials (AEPs) were simultaneously recorded in awake rats to investigate whether P300-like potentials generated in rats responding to rare target oddball tones are sensitive to subcutaneous modulation of the cholinergic tone by donepezil (1 mg/kg) and scopolamine (0.64 mg/kg). After operant training, rats consistently discriminate rare target auditory stimuli from frequent irrelevant nontarget auditory stimuli by a higher level of correct lever presses (i.e., accuracy) in target trials associated with a food reward. Donepezil attenuated the disruptive effect of scopolamine on the level of accuracy and premature responses in target trials. Larger P300-like peaks with early and late components were revealed in correct rare target stimuli trials as compared to frequent tones. Donepezil enhanced the peak amplitude of the P300-like component to target stimuli and evoked slow theta and gamma oscillations, whereas scopolamine altered the amplitude of the P300-like component and EROs to target stimuli. Pretreatment with donepezil attenuated effects of scopolamine on the peak amplitude of the P300-like component and on EROs. This study provides evidence that AEP P300-like responses can be elicited by rats engaged in attentive and memory processing of target stimuli and outline the relevance of the cholinergic system in stimulus discrimination processing. The findings highlight the sensitivity of this translational index for investigating brain circuits and/or novel pharmacological agents, which modulate cholinergic transmission associated with increased allocation of attentional resources.
Safety of Natural Insecticides: Toxic Effects on Experimental Animals
Authors: Mossa Abdel-Tawab H. , Mohafrash Samia M. M. , Chandrasekaran Natarajan
Published: October 2018

Long-term application and extensive use of synthetic insecticides have resulted in accumulating their residues in food, milk, water, and soil and cause adverse health effects to human and ecosystems. Therefore, application of natural insecticides in agriculture and public health sectors has been increased as alternative to synthetic insecticides. The question here is, are all natural insecticides safe. Therefore, the review presented here focuses on the safety of natural insecticides. Natural insecticides contain chemical, mineral, and biological materials and some products are available commercially, e.g., pyrethrum, neem, spinosad, rotenone, abamectin,Bacillus thuringiensis(Bt), garlic, cinnamon, pepper, and essential oil products. It can induce hepatotoxicity, renal toxicity, hematotoxicity, reproductive toxicity, neurotoxicity, and oxidative stress. It can induce mutagenicity, genotoxicity, and carcinogenicity in mammals. Some natural insecticides and active compounds from essential oils are classified in categories Ib (Highly hazardous) to U (unlikely toxic). Therefore, the selectivity and safety of natural insecticides not absolute and some natural compounds are toxic and induce adverse effects to experimental animals. In concussion, all natural insecticides are not safe and the term “natural” does not mean that compounds are safe. In this respect, the term “natural” is not synonymous with “organic” and not all-natural insecticide products are acceptable in organic farmers.
Research on Properties of High‐Performance Cement Mortar for Semiflexible Pavement
Authors: Sun Yazhen , Cheng Yuanyuan , Ding Min , Yuan Xuezhong , Wang Jinchang
Published: October 2018

Cement mortar is one of the most important components of semiflexible pavement materials; however, the effects of cement mortar formulation on the performance and the grouting rate are rarely studied. Therefore, the optimum formulation of high‐performance cement mortar (HPCM) for different types and contents was studied, and the grouting effect of the cement mortar was studied by rutting tests. The results show that polycarboxylate superplasticizer, expansion admixture, and accelerating admixture have different influences on the workability, the strength, and the drying shrinkage of HPCM, and the working ability of HPCM is good by adding these three admixtures. The strength at 7 days is 1.3 to 4 times that of the existing specifications, and the shrinkage rate is less than 0.2. The HPCM has higher early strength, and the strength development is stable in the later period compared with the other research studies. The semiflexible material has better pavement performance when the grouting rate is greater than 90%.
Class of Analytic Function Related with Uniformly Convex and Janowski’s Functions
Authors: Rasheed Akhter , Hussain Saqib , Zaighum Muhammad Asad , Darus Maslina
Published: October 2018

In this paper, we introduce a new subclass of analytic functions in open unit disc. We obtain coefficient estimates, extreme points, and distortion theorem. We also derived the radii of close-to-convexity and starlikeness for this class.
Adaptive DDoS Attack Detection Method Based on Multiple-Kernel Learning
Authors: Cheng Jieren , Zhang Chen , Tang Xiangyan , Sheng Victor S. , Dong Zhe , Li Junqi
Published: October 2018

Distributed denial of service (DDoS) attacks has caused huge economic losses to society. They have become one of the main threats to Internet security. Most of the current detection methods based on a single feature and fixed model parameters cannot effectively detect early DDoS attacks in cloud and big data environment. In this paper, an adaptive DDoS attack detection method (ADADM) based on multiple-kernel learning (MKL) is proposed. Based on the burstiness of DDoS attack flow, the distribution of addresses, and the interactivity of communication, we define five features to describe the network flow characteristic. Based on the ensemble learning framework, the weight of each dimension is adaptively adjusted by increasing the interclass mean with a gradient ascent and reducing the intraclass variance with a gradient descent, and the classifier is established to identify an early DDoS attack by training simple multiple-kernel learning (SMKL) models with two characteristics including interclass mean squared difference growth (M-SMKL) and intraclass variance descent (S-SMKL). The sliding window mechanism is used to coordinate the S-SMKL and M-SMKL to detect the early DDoS attack. The experimental results indicate that this method can detect DDoS attacks early and accurately.
Xingnao Jieyu Decoction Ameliorates Poststroke Depression through the BDNF/ERK/CREB Pathway in Rats
Authors: Li Tao , Wang Dou , Zhao Bingbing , Yan Yongmei
Published: October 2018

Background. The neurotrophic pathway regulated by the brain‐derived neurotrophic factor (BDNF) plays a crucial role in the pathogenesis of poststroke depression (PSD). How the traditional Chinese medicine compound preparation Xingnao Jieyu (XNJY) decoction regulates the neurotrophic pathway to treat PSD is unclear. Objective. This study aimed to investigate the antidepressant effect of XNJY decoction on a rat model of PSD and the molecular mechanism intervening in the neurotrophic pathway. Methods. After a middle cerebral artery occlusion model was established, chronic unpredictable mild stress was applied for 21 days to prepare a PSD model. XNJY groups and a fluoxetine (Flu) group of rats were intragastrically administered with XNJY and Flu, respectively, for 21 consecutive days. Depressive‐like behaviors, including sucrose preference, open field test, and forced swimming test, were assessed. The survival and apoptosis of cortical and hippocampal neurons were evaluated by immunofluorescence assay and TUNEL staining. The contents of serotonin (5‐HT), norepinephrine (NE), and BDNF in the cortex and hippocampus were determined by ELISA. The protein levels of BDNF, p‐ERK/ERK, and p‐CREB/CREB in the cortical and hippocampal regions were tested by Western blot. Results. The depressive‐like behaviors markedly improved after XNJY and Flu treatment. XNJY and Flu promoted neuronal survival and protected cortical and hippocampal neurons from apoptosis. XNJY also increased the contents of 5‐HT, NE, and BDNF and recovered the protein levels of p‐ERK/ERK, p‐CREB/CREB, and BDNF in the cortical and hippocampal regions. Conclusion. These results indicated that the XNJY decoction exerts an obvious antidepressant effect, which may be due to the regulation of the BDNF/ERK/CREB signaling pathway.
Delay-Dependent Robust H∞ Performance for Uncertain Neutral Systems with Mixed Time-Varying Delays and Nonlinear Perturbations
Authors: Singkibud Peerapongpat , Hiep Luu Thi , Niamsup Piyapong , Botmart Thongchai , Mukdasai Kanit
Published: October 2018

This paper deals with the problems of delay-dependent stability and H∞ performance for uncertain neutral systems with time-varying delays, and nonlinear perturbations. The time-varying delays are neutral, discrete, and distributed time-varying delays that the upper bounds for the delays are available. The restrictions on the derivatives of the discrete and distributed time-varying delays are removed, which mean that a fast discrete time-varying delay is allowed. The uncertainties under consideration are nonlinear time-varying parameter perturbations and norm-bounded uncertainties, respectively. Firstly, by applying a novel Lyapunov-Krasovskii functional approach, Wirtinger-based integral inequality, Peng-Park’s integral inequality, decomposition technique of constant matrix, descriptor model transformation, Leibniz Newton formula and utilization of zero equation, and improved delay-dependent bounded real lemmas (BRL) for systems are established in terms of linear matrix inequalities (LMIs). Then, based on the obtained BRL, some less conservative delay-dependent stability criteria of uncertain neutral systems with mixed time-varying delays and nonlinear perturbations are obtained and improved H∞ performance criterion with the framework of LMIs is introduced. Finally, some numerical examples are given to illustrate that the presented method is effective.
Gastric Cancer Cell Lines Have DifferentMYC-Regulated Expression Patterns but Share a Common Core of Altered Genes
Authors: Maués Jersey Heitor da S. , Ribeiro Helem Ferreira , Pinto Giovanny R. , Lopes Luana de Oliveira , Lamarão Letícia M. , Pessoa Carla Mariana F. , Moreira-Nunes Caroline de Fátima Aquino , Carvalho Raimundo Miranda de , Assumpção Paulo P. , Rey Juan A. , Burbano Rommel M. Rodríguez
Published: October 2018

MYCis an oncogene responsible for excessive cell growth in cancer, enabling transcriptional activation of genes involved in cell cycle regulation, metabolism, and apoptosis, and is usually overexpressed in gastric cancer (GC). By using siRNA and Next-Generation Sequencing (NGS), we identifiedMYC-regulated differentially expressed Genes (DEGs) in three Brazilian gastric cancer cell lines representing the histological subtypes of GC (diffuse, intestinal, and metastasis). The DEGs were picked usingSailfishsoftware, followed by Gene Set Enrichment Analysis (GSEA) and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway analysis using KEGG. We found 11 significantly enriched gene sets by using enrichment score (ES), False Discovery Rate (FDR), and nominal P-values. We identified a total of 5.471 DEGs with correlation over (80%). In diffuse-type and in metastatic GC cell lines,MYC-silencing caused DEGs downregulation, while the intestinal-type GC cells presented overall DEGs upregulation afterMYCsiRNA depletion. We were able to detect 11 significant gene sets when comparing our samples to the hallmark collection of gene expression, enriched mostly for the following hallmarks: proliferation, pathway, signaling, metabolic, and DNA damage response. When we analyzed our DEGs considering KEGG metabolic pathways, we found 12 common branches covering a wide range of biological functions, and three of them were common to all three cell lines: ubiquitin-mediated proteolysis, ribosomes, and system and epithelial cell signaling inHelicobacter pyloriinfection. The GC cell lines used in this study share 14MYC-regulated genes, but their gene expression profile is different for each histological subtype of GC. Our results present a computational analysis ofMYC-related signatures in GC, and we present evidence that GC cell lines representing distinct histological subtypes of this disease have differentMYC-regulated expression profiles but share a common core of altered genes. This is an important step towards the understanding ofMYC’s role in gastric carcinogenesis and an indication of probable new drug targets in stomach cancer.
Cordycepin Accelerates Osteoblast Mineralization and Attenuates Osteoclast Differentiation In Vitro
Authors: Yu Su-Bin , Kim Hye-Jin , Kang Hae-Mi , Park Bong-Soo , Lee Ji-Hye , Kim In-Ryoung
Published: October 2018

Bone homeostasis destruction is triggered by the uncontrolled activity of osteoblasts and osteoclasts. Targeting both the regulation of bone formation and resorption is a promising strategy for treating bone disorders. Cordycepin is a major component of Chinese caterpillar fungus Cordyceps militaris. It exerts a variety of biological actions in various cells and animal models. However, its function on bone metabolism remains unclear. In the present study, we discovered a dual‐action function of cordycepin in murine MC3T3‐E1 and RAW264.7 cells. MC3T3‐E1 cells were cultured in an osteogenic medium in the presence of 1 μM cordycepin for up two weeks. Cordycepin was used for effects of osteoblast and osteoclast differentiation. Cell viability was measured using the MTT assay. Osteoblast differentiation was confirmed by alizarin red staining, ALP activity, western blot, and real‐time PCR. Osteoclast differentiation and autophagic activity were confirmed via TRAP staining, pit formation assay, confocal microscopy, western blot, and real‐time PCR. Cordycepin promoted osteoblast differentiation, matrix mineralization, and induction of osteoblast markers via BMP2/Runx2/Osterix pathway. On the other hand, RAW264.7 cells were differentiated into osteoclast by RANKL treatment for 72 h. 1 μM cordycepin significantly inhibited RANKL‐induced osteoclast formation and resorption activity through disturbing the actin ring‐formatted sealing zone and activating cathepsin K and MMP9. These findings indicate that cordycepin might be an innovative dual‐action therapeutic agent for bone disease caused by an imbalance of osteoblasts and osteoclasts.
A Cheating Detectable Privacy-Preserving Data Sharing Scheme for Cloud Computing
Authors: Wang Xin , Yang Bo , Xia Zhe , Zhao Yanqi , Yu Huifang
Published: October 2018

Cloud computing provides a new, attractive paradigm for the effective sharing of storage and computing resources among global consumers. More and more enterprises have begun to enter the field of cloud computing and storing data in the cloud to facilitate the sharing data among users. However, in many cases, users may be concerned about data privacy, trust, and integrity. It is challenging to provide data sharing services without sacrificing these security requirements. In this paper, a data sharing scheme of reliable, secure, and privacy protection based on general access structure is introduced. The proposed scheme is not only effective and flexible, but also is capable of protecting privacy for the cloud owner, supporting data sharing under supervision, enabling accountability of users’ decryption keys, and identifying cheaters if some users behave dishonestly. Security analysis and efficiency analysis demonstrate that our proposed scheme has better performance in computational costs compared with most related works. The scheme is versatile to be used in various environments. For example, it is particularly suitable to be employed to protect personal health data and medical diagnostic data in information medical environment.
Relevance of Incorporating Cavity Shape Change in Modelling the Ductile Failure of Metals
Authors: Ould Ouali Mohand
Published: October 2018

The purpose of this paper is to assess the relevance of considering the cavities shape change in the context of physically based modelling of the ductile rupture in metals. Two thermomechanical models have been used in this study: the GTN model, developed by Gurson, Tvergaard, and Needleman for spherical cavities keeping their shape unchanged during loading, and the GLD model, proposed by Gologanu, Leblond, and Devaux for ellipsoidal cavities that can change their shape. The GTN and GLD models have been extended to take into account material thermal heating due to plastic dissipation. These two constitutive laws have been implemented into the commercial finite element code Abaqus/Explicit in order to simulate the necking of a round bar and the failure of a sheet deep drawing. The results showed the importance of incorporating the shape effects of the cavities for a correct description of the material failure.
Immunotoxicological Evaluation of Schinus molle L. (Anacardiaceae) Essential Oil in Lymphocytes and Macrophages
Authors: Duarte Jonathaline Apollo , Zambrano Léa Augusta de Bairros , Quintana Luciane Dias , Rocha Mariana Balhego , Schmitt Elizandra Gomes , Boligon Aline Augusti , Anraku de Campos Marli Matiko , Oliveira Luís Flávio Souza de , Machado Michel Mansur
Published: October 2018

Schinus molle L. is used to treat various diseases; however, the literature lacks information regarding its possible immunotoxic effects. The aim of the study was to investigate the immunotoxic effects of essential oil from leaves of Schinus molle L. in cultures of human lymphocytes and macrophages. The cultures were treated with essential oil (EO) of Schinus molle L. and subsequently subjected to genotoxic analysis (comet assay), mutagenic analysis (micronucleus frequency and chromosomal aberration), and cytotoxic (cell viability) and functional parameters (interleukins secretions). Our analyses have determined that the essential oil from leaves of Schinus molle L. presents several compounds with α‐pinene being the major compound; in addition, the compound verbenene was firstly identified; genotoxic effects were detected only in macrophages and only at the two highest concentrations tested. An important finding is that Schinus molle L. oil causes an activation of the immune system. This action has its mechanism centered by the cascade nitric oxide‐interleukin‐10‐tumor necrosis factor alpha.
Trends in Survival of Patients with Primary Gastric Diffuse Large B-Cell Lymphoma: An Analysis of 7051 Cases in the SEER Database
Authors: Liu Pan-pan , Xia Yi , Bi Xi-wen , Wang Yu , Sun Peng , Yang Hang , Li Zhi-ming , Jiang Wen-qi
Published: October 2018

Treatment modalities for primary gastric diffuse large B-cell lymphoma (PG-DLBCL) have changed significantly during the past decades. However, limited information on the trends of clinical outcome of PG-DLBCL patients has been reported. Here, we conducted a retrospective analysis using the Surveillance, Epidemiology, and End Results (SEER) database to compare the survival trends of PG-DLBCL patients from 1973 to 2014. Patients were divided into 2 eras based on the year of diagnosis in relation to immunotherapy with the anti-CD20 antibody rituximab that was approved in 1997 and became a widely used drug in 2000. There was a significant improvement in survival among PG-DLBCL patients diagnosed in the 2001–2014 era (n=4186) compared to patients diagnosed in the 1973–2000 era (n=2865), with the 5-year overall survival rates of 53% and 47%, respectively (p=0.001). Multivariable analysis revealed that the 2001–2014 era (HR = 0.892, p=0.001) was associated with lower mortality and that patients of older age, Black race, advanced stage, and male gender were associated with poor prognosis. Although outcome of PG-DLBCL has significantly improved over time, more effective therapies are needed for older patients to further improve their survival.
A MOOC Video Viewing Behavior Analysis Algorithm
Authors: Luo Yong , Zhou Guochang , Li Jianping , Xiao Xiao
Published: October 2018

MOOCs (massive open online courses) are developing rapidly, but they also face many problems. As the MOOC’s most important resource, the course videos have a very important influence on the learning. This article defines the ratio R (R=Average  viewing  duration/Video  length), which reflects the popularity of the video. By analyzing the relationship between the video length, release time, and R, we found a significant negative linear correlation between video length and R and video release time and R. However, when the number of videos is less than the threshold, the release time has less influence on R. This paper presents a video viewing behavior analysis algorithm based on multiple linear regression. The residual independence test proved that the algorithm has a good approximation to the data. It can predict the popularity of similar course videos to help producers optimize video design.
Unilateral and Bilateral PNIF in Quality Control of Nasal Septal Surgery
Authors: Døsen Liv Kari , Kvinnesland Knut , TarAngen Magnus , Shiryaeva Olga , Gay Caryl , Haye Rolf
Published: October 2018

The aim of this study was to explore the usefulness of unilateral, combined unilateral (left + right), and bilateral peak nasal inspiratory flow (PNIF) measurements in assessing the results of nasal septal surgery. Nasal obstruction was recorded subjectively and objectively before and 4 months after nasal septoplasty using a visual analogue scale (VAS) and a PNIF meter. Nasal septoplasty (58 patients) and septoplasty with turbinoplasty (68 patients) were performed on 126 patients (85 males; 41 females) with a mean age of 32.8 years. The results showed a significant improvement in VAS scores, as well as unilateral, combined unilateral, and bilateral PNIF values after both septoplasty and septoplasty with turbinoplasty. Septoplasty with turbinoplasty showed better improvement in VAS and PNIF scores than septoplasty alone and this was significant for bilateral PNIF scores. The best unilateral pre- and postoperative correlations between VAS and PNIF measurements were found using the lower of the two unilateral PNIF scores, irrespective of side. In the total material, VAS/PNIF correlations were mostly significant, but weak (all r<0.30). We found VAS and PNIF to be useful instruments in reporting results of surgery. The weak correlations between VAS and PNIF measurements suggest that these subjective and objective instruments may target different aspects of nasal obstruction.
Notch Signaling Activation Enhances Human Adipose-Derived Stem Cell Retinal Differentiation
Authors: Huang Yuqiang , Ng Tsz Kin , Chen Chong-Bo , Huang Bing , Liang Jiajian , Pang Chi Pui , Zhang Mingzhi
Published: October 2018

Retinal disease treatment by stem cell-based replacement relies on stem cell differentiation into retinal cells. We previously demonstrated that human periodontal ligament-derived stem cells can be directed into retinal lineage upon induction. Here, we report the transdifferentiation potential of human adipose-derived stem cells (ASCs) into retinal lineage and its enhancement by Notch signaling modulation. Human ASCs, isolated from abdominal fat, expressed mesenchymal but not hematopoietic stem cell markers, and they can differentiate into adipocytes, chondrocytes, and osteoblasts in vitro. Upon noggin/Dkk-1/IGF-1 induction, the treated ASCs showed elevated expression of retinal progenitor, retinal ganglion, and photoreceptor cell markers as well as the glutamate-evoked calcium response, which was not observed in the noninduced cells. Compared to the regular induction treatment, Notch signaling activation by JAG1 enhanced the expression of retinal progenitor and precursor markers without affecting the glutamate-evoked calcium response. In contrast, Notch signaling inhibition by DAPT showed more retinal ganglion cells, but delayed the response to glutamate stimulation. In summary, our results revealed that human ASCs possess a retinal transdifferentiation potential upon noggin/Dkk-1/IGF-1 induction, which can further be enhanced by Notch signaling activation.
HybridHAM: A Novel Hybrid Heuristic for Finding Hamiltonian Cycle
Authors: Seeja K. R.
Published: October 2018

Hamiltonian Cycle Problem is one of the most explored combinatorial problems. Being an NP-complete problem, heuristic approaches are found to be more powerful than exponential time exact algorithms. This paper presents an efficient hybrid heuristic that sits in between the complex reliable approaches and simple faster approaches. The proposed algorithm is a combination of greedy, rotational transformation and unreachable vertex heuristics that works in three phases. In the first phase, an initial path is created by using greedy depth first search. This initial path is then extended to a Hamiltonian path in second phase by using rotational transformation and greedy depth first search. Third phase converts the Hamiltonian path into a Hamiltonian cycle by using rotational transformation. The proposed approach could find Hamiltonian cycles from a set of hard graphs collected from the literature, all the Hamiltonian instances (1000 to 5000 vertices) given in TSPLIB, and some instances of FHCP Challenge Set. Moreover, the algorithm has O(n3) worst case time complexity. The performance of the algorithm has been compared with the state-of-the-art algorithms and it was found that HybridHAM outperforms others in terms of running time.
The Effects of Power Levels/Time Periods for Sputtering Cobalt onto Carbon Nanotubes/Graphene Composites and Cobalt Annealed on the Characteristics of Anode Materials for Lithium-Ion Batteries
Authors: Lin Chuen-Chang , Shen You-Lun , Wu An-Na
Published: October 2018

Carbon nanotubes/graphene composites are directly grown on nickel foil without additional catalysts by chemical vapor deposition (CVD). Next, the cobalt is deposited on carbon nanotubes/graphene composites by radio frequency (RF) sputtering with different power levels and time periods. Then, the cobalt is transformed into cobalt oxide by annealing. A longer time period of sputtering leads to higher specific capacity. Furthermore, the electrochemical stability of cobalt oxide/carbon nanotubes/graphene composites is higher than that of cobalt oxide.
Exact Approach to Uniform Time-Varying Magnetic Field
Authors: Bologna Mauro
Published: October 2018

In this paper, we will find in terms of Fourier integrals an exact expression for the magnetic and electric fields generated by an infinite solenoid where an arbitrary current density J(t) flows. Considering the central region of an infinite solenoid, we will obtain an exact expression relating the flowing current and the magnetic and electric fields as functions of the time. Being an exact expression, it will allow us to go beyond the quasistatic approximation. The result can apply in theoretical problems and experimental setups where the flowing current may change abruptly in time, such as pulsed or stochastic currents.
Transcriptomic and Protein Analysis of Small-cell Bladder Cancer (SCBC) Identifies Prognostic Biomarkers and DLL3 as a Relevant Therapeutic Target
Authors: Koshkin Vadim S. , Garcia Jorge A. , Reynolds Jordan , Elson Paul , Magi-Galluzzi Cristina , McKenney Jesse K. , Isse Kumiko , Bishop Evan , Saunders Laura R. , Balyimez Aysegul , Rashid Summya , Hu Ming , Stephenson Andrew J. , Fergany Amr F. , Lee Byron H. , Haber Georges-Pascal , Dowlati Afshin , Gilligan Timothy , Ornstein Moshe C. , Rini Brian I. , Abazeed Mohamed E. , Mian Omar Y. , Grivas Petros
Published: October 2018

Purpose:

Transcriptomic profiling can shed light on the biology of small-cell bladder cancer (SCBC), nominating biomarkers, and novel therapeutic targets.

Experimental Design:

Sixty-three patients with SCBC had small-cell histology confirmed and quantified by a genitourinary pathologist. Gene expression profiling was performed for 39 primary tumor samples, 1 metastatic sample, and 6 adjacent normal urothelium samples (46 total) from the same cohort. Protein levels of differentially expressed therapeutic targets, DLL3 and PDL1, and also CD56 and ASCL1, were confirmed by IHC. A SCBC PDX model was utilized to assess in vivo efficacy of DLL3-targeting antibody–drug conjugate (ADC).

Results:

Unsupervised hierarchical clustering of 46 samples produced 4 clusters that correlated with clinical phenotypes. Patients whose tumors had the most “normal-like” pattern of gene expression had longer overall survival (OS) compared with the other 3 clusters while patients with the most “metastasis-like” pattern had the shortest OS (P = 0.047). Expression of DLL3, PDL1, ASCL1, and CD56 was confirmed by IHC in 68%, 30%, 52%, and 81% of tissue samples, respectively. In a multivariate analysis, DLL3 protein expression on >10% and CD56 expression on >30% of tumor cells were both prognostic of shorter OS (P = 0.03 each). A DLL3-targeting ADC showed durable antitumor efficacy in a SCBC PDX model.

Conclusions:

Gene expression patterns in SCBC are associated with distinct clinical phenotypes ranging from more indolent to aggressive disease. Overexpression of DLL3 mRNA and protein is common in SCBC and correlates with shorter OS. A DLL3-targeted ADC demonstrated in vivo efficacy superior to chemotherapy in a PDX model of SCBC.
Patritumab with Cetuximab plus Platinum-Containing Therapy in Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck: An Open-Label, Phase Ib Study
Authors: Dillon Magnus T. , Grove Lorna , Newbold Kate L. , Shaw Heather , Brown Nicholas F. , Mendell Jeanne , Chen Shuquan , Beckman Robert A. , Jennings Anne , Ricamara Marivic , Greenberg Jonathan , Forster Martin , Harrington Kevin J.
Published: October 2018

Purpose:

Patritumab plus cetuximab with platinum as first-line therapy for patients with recurrent and/or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN) was evaluated for safety and to determine the recommended phase II combination dose.

Patients and Methods:

Patients aged ≥18 years with confirmed R/M SCCHN received intravenous patritumab (18 mg/kg loading dose; 9 mg/kg maintenance dose every 3 weeks) + cetuximab (400 mg/m2 loading dose; 250 mg/m2 maintenance dose weekly) + cisplatin (100 mg/m2 every 3 weeks) or carboplatin (AUC of 5) for six cycles or until toxicity, disease progression, or withdrawal. Primary endpoints were dose-limiting toxicities [DLT; grade ≥3 (21-day observation period)] and treatment-emergent adverse events (TEAE). Pharmacokinetics, human antihuman antibodies (HAHA), tumor response, progression-free survival (PFS), and overall survival (OS) were assessed.

Results:

Fifteen patients completed a median (range) of 8.7 (2.0–20.7) patritumab cycles. No DLTs were reported. Serious adverse events were reported in 9 patients (patritumab-related n = 4). TEAEs (N = 15 patients) led to patritumab interruption in 7 patients. Patritumab-related dose reductions were reported in 1 patient. Patritumab (18 mg/kg) pharmacokinetics (N = 15) showed mean (SD) AUC0–21d of 2,619 (560) μg/day/mL and maximum concentration of 499.9 (90.4) μg/mL. All patients were HAHA-negative at study end (single, transient low titer in 1 patient). Tumor response rate (complete plus partial response; N = 15) was 47%. Median (95% confidence interval) PFS and OS (N = 15) were 7.9 (3.7–9.7) and 13.5 (6.6–17.5) months, respectively.

Conclusions:

Patritumab (18 mg/kg loading dose, 9 mg/kg maintenance dose) plus cetuximab/platinum was tolerable, active in SCCHN, and selected as the phase II dose regimen.