bluuebunny/crossref_metadata_2025 huggingface dataset:
Design a Smart Control Strategy to Implement an Intelligent Energy Safety and Management System
Authors: Wang Jing-Min , Yang Ming-Ta
Published: October 2014

The energy saving and electricity safety are today a cause for increasing concern for homes and buildings. Integrating the radio frequency identification (RFID) and ZigBee wireless sensor network (WSN) mature technologies, the paper designs a smart control strategy to implement an intelligent energy safety and management system (IESMS) which performs energy measuring, controlling, monitoring, and saving of the power outlet system. The presented RFID and billing module is used to identify user, activate smart power outlet (SPO) module, deduct payable for electricity, and cut off power supply to the outlets by taking away the RFID card. Further work on the SPO module, a control strategy based on the minimum effect and first-in first-out rule, is designed to autonomously shut down some of the power outlets instantly to prevent electrical circuit overload. In addition, the WSN transfers the power parameters of each SPO module to central energy monitoring platform, and the monitoring platform with graphical user interface (GUI) displays the real-time information and power charge of the electricity. Numerous tests validate the proposed IESMS and the effectiveness of the smart control strategy. The empirical findings may provide some valuable references for smart homes or smart buildings.
Lifestyle Behaviors and Self-Rated Health: The Living for Health Program
Authors: Zarini Gustavo G. , Vaccaro Joan A. , Canossa Terris Maria A. , Exebio Joel C. , Tokayer Laura , Antwi Janet , Ajabshir Sahar , Cheema Amanpreet , Huffman Fatma G.
Published: October 2014

Background. Lack of adherence to dietary and physical activity guidelines has been linked to an increase in chronic diseases in the United States (US). The aim of this study was to assess the association of lifestyle behaviors with self-rated health (SRH).Methods. This cross-sectional study used self-reported data from Living for Health Program (N=1,701) which was conducted from 2008 to 2012 in 190 health fair events in South Florida, US.Results. Significantly higher percent of females as compared to males were classified as obese (35.4% versus 27.0%), reported poor/fair SRH (23.4% versus 15.0%), and were less physically active (33.9% versus 25.4%). Adjusted logistic regression models indicated that both females and males were more likely to report poor/fair SRH if they consumed≤2 servings of fruits and vegetables per day (OR=2.14, 95% CI 1.30–3.54;OR=2.86, 95% CI 1.12–7.35, resp.) and consumed mostly high fat foods (OR=1.58, 95% CI 1.03–2.43;OR=3.37, 95% CI 1.67–2.43, resp.). The association of SRH with less physical activity was only significant in females (OR=1.66, 95% CI 1.17–2.35).Conclusion. Gender differences in health behaviors should be considered in designing and monitoring lifestyle interventions to prevent cardiovascular diseases.
Unique Presentation of Akinetic Mutism and Coexisting Thyroid Storm Relating to Stroke
Authors: Kurukumbi Mohankumar , Dang Thao , Crossley Najeeb , Esame Alice , Jayam-Trouth Annapurni
Published: October 2014

Akinetic mutism is described in various clinical presentations but typically is defined as a state wherein the patient appears awake but does not move or speak. It can be divided into two different subtypes; the most common subtypes depend on the lesion location, mesencephalic-diencephalic region, also called apathetic akinetic mutism (somnolent mutism), and those involving the anterior cingulate gyrus and adjacent frontal lobes called hyperpathic akinetic mutism. The pathway of akinetic mutism is believed to originate from circuits that link the frontal and subcortical structures. This case reports a 48-year-old African American female with bilateral anterior cerebral artery stroke and akinetic mutism with coexisting thyroid storm. This patient with bilateral anterior cerebral artery infarcts presented with characteristics that are typical for akinetic mutism such as having intact eye movements but an inability to respond to auditory or visual commands. With the incidence of bilateral anterior cerebral artery (ACA) ischemic stroke being rare and the incidence of akinetic mutism secondary to ischemic stroke even rarer, we suspect that this patient potentially had a unilateral occlusion of anomalous anterior cerebral vasculature.
The Influence of Inner Component and Topographical Properties on Tribological Parameters of Injection-Moulded Microparts
Authors: Fischer Christopher , Drummer Dietmar
Published: October 2014

Tribological parameters are dependent upon inter alia, inner component properties which may vary with the temperature-time behaviour of the polymer melt used. This temperature-time behaviour can be influenced by dynamic mould temperature control. The present paper presents a new dynamic tempering concept, which enables a targeted temperature-time control via shifting a mould cavity within two different tempered mould areas at a defined point in time. By influencing the temperature-time development by means of a mould temperature and isothermal holding time variation, micro tensile bars with different inner component properties are produced. To show the influence of inner component properties on tribological parameters, pin-on-disc wear tests are performed. Furthermore, tribological tests with different surface topographies are performed to show the influence of topographical properties on tribological parameters. Results indicate that the tribological properties of microparts are mainly influenced by the nature of the skin near layers, which can be influenced by the application of different mould temperatures. Variations in the isothermal holding time show no significant impact on the material examined. A more distinct roughness of the disc surface topography not only shows higher values for the measured tribological parameters but also different wear behaviour in general.
Evaluation of Cytotoxicity and Genotoxicity ofAcacia aromaLeaf Extracts
Authors: Mattana C. M. , Cangiano M. A. , Alcaráz L. E. , Sosa A. , Escobar F. , Sabini C. , Sabini L. , Laciar A. L.
Published: October 2014

Acacia aroma, native plant from San Luis, Argentina, is commonly used as antiseptic and for healing of wounds. The present study was conducted to investigate thein vitrocytotoxicity and genotoxicity of hot aqueous extract (HAE) and ethanolic extract (EE) ofA. aroma. The cytotoxic activity was assayed by neutral red uptake assay on Vero cell. Cell treatment with a range from 100 to 5000 μg/mL of HAE and EE showed that 500 μg/mL and 100 μg/mL were the maximum noncytotoxic concentrations, respectively. The CC50was 658 μg/mL for EE and 1020 μg/mL for HAE. The genotoxicity was tested by the single-cell gel electrophoresis comet assay. The results obtained in the evaluation of DNA cellular damage exposed to varied concentrations of the HAE showed no significant genotoxic effect at range of 1–20 mg/mL. The EE at 20 mg/mL showed moderate genotoxic effect related to the increase of the DNA percentage contained in tail of the comet; DNA was classified in category 2. At concentrations below 5 mg/mL, the results of cytotoxicity and genotoxicity of aqueous and ethanolic extracts ofAcacia aromaguarantee the safety at cell and genomic level. However further studies are needed for longer periods including animal models to confirm the findings.
Application of Radial Basis Function Method for Solving Nonlinear Integral Equations
Authors: Zhang Huaiqing , Chen Yu , Guo Chunxian , Fu Zhihong
Published: October 2014

The radial basis function (RBF) method, especially the multiquadric (MQ) function, was proposed for one- and two-dimensional nonlinear integral equations. The unknown function was firstly interpolated by MQ functions and then by forming the nonlinear algebraic equations by the collocation method. Finally, the coefficients of RBFs were determined by Newton’s iteration method and an approximate solution was obtained. In implementation, the Gauss quadrature formula was employed in one-dimensional and two-dimensional regular domain problems, while the quadrature background mesh technique originated in mesh-free methods was introduced for irregular situation. Due to the superior interpolation performance of MQ function, the method can acquire higher accuracy with fewer nodes, so it takes obvious advantage over the Gaussian RBF method which can be revealed from the numerical results.
Hemophagocytic Lymphohistiocytosis in Association with Primary Cutaneous Anaplastic Large Cell Lymphoma
Authors: Basheer Aneesh , Padhi Somanath , Nagarajan Ramesh , Boopathy Vinoth , Mookkappan Sudhagar , Iqbal Nayyar
Published: October 2014

Hemophagocytic lymphohistiocytosis (HLH) has a well known association with lymphomas, especially of T cell origin. Prognosis of lymphoma associated HLH is very poor, especially in T cell lymphomas; and, therefore, early diagnosis might alter the outcome. Though association of HLH with systemic anaplastic large cell lymphoma (ALCL) is known, its occurrence in primary cutaneous ALCL (C-ALCL) is distinctly rare. We aim to describe a case of C-ALCL (anaplastic lymphoma kinase (ALK)−) in an elderly male who succumbed to the complication of associated HLH, which was possibly triggered by coexistent virus infection. We briefly present the literatures on lymphoma associated HLH and discuss the histopathological differentials of cutaneous CD30+ lymphoproliferative disorders. We do suggest that HLH may pose diagnostic challenges in the evaluation of an underlying lymphoma and hence warrants proper evaluation for the underlying etiologies and/or triggering factors.
Optical and Thermal Properties of Zn/Al-Layered Double Hydroxide Nanocomposite Intercalated with Sodium Dodecyl Sulfate
Authors: Babakhani Samaneh , Talib Zainal Abidin , Hussein Mohd Zobir , Ahmed Abdullah Ahmed Ali
Published: October 2014

Zn/Al-LDH-SDS nanocomposites have been prepared using a coprecipitation method in different molar ratio of Zn2+/Al3+= 2, 3, and 4 at pH = 10 and different concentrations of sodium dodecyl sulfate solution (0.2 M, 0.4 M, and 0.8 M). The XRD and FTIR data show the successful intercalation of SDS into the LDH interlayer. The XRD diffractogram showed that the basal spacing forZn/Al–NO3-is 0.89 nm compared to 2.54–2.61 nm for the Zn/Al-SDS nanocomposite. Optical band gap of the samples was calculated using Kubelka-Munk model. Due to the presence of LDH phase, two band gap energies (Eg1andEg2) were observed. The values ofEg1andEg2were found around 4.8 eV and 3.75 eV for Zn/Al-LDH (r= 2, 3, and 4). The values of band gap of LDH-SDS nanocomposites were found to increase to around 4.2 eV and 5.2 eV. For Zn4Al-LDH-SDS with 0.4 M and 0.8 M of SDS, only one energy gap at around 3.23 eV was observed. The optical band gap ofSO42-phase increased as the amount of SDS increases. Thermal diffusivity of the resulted nanocomposite was also investigated.
Type 2C Phosphatase 1 ofArtemisia annuaL. Is a Negative Regulator of ABA Signaling
Authors: Zhang Fangyuan , Fu Xueqing , Lv Zongyou , Shen Qian , Yan Tingxian , Jiang Weiming , Wang Guofeng , Sun Xiaofen , Tang Kexuan
Published: October 2014

The phytohormone abscisic acid (ABA) plays an important role in plant development and environmental stress response. Additionally, ABA also regulates secondary metabolism such as artemisinin in the medicinal plantArtemisia annuaL. Although an earlier study showed that ABA receptor, AaPYL9, plays a positive role in ABA-induced artemisinin content improvement, many components in the ABA signaling pathway remain to be elucidated inArtemisia annuaL. To get insight of the function of AaPYL9, we isolated and characterized an AaPYL9-interacting partner, AaPP2C1. The coding sequence of AaPP2C1 encodes a deduced protein of 464 amino acids, with all the features of plant type clade A PP2C. Transcriptional analysis showed that the expression level of AaPP2C1 is increased after ABA, salt, and drought treatments. Yeast two-hybrid and bimolecular fluorescence complementation assays (BiFC) showed that AaPYL9 interacted with AaPP2C1. The P89S, H116A substitution in AaPYL9 as well as G199D substitution or deletion of the third phosphorylation site-like motif in AaPP2C1 abolished this interaction. Furthermore, constitutive expression of AaPP2C1 conferred ABA insensitivity compared with the wild type. In summary, our data reveals that AaPP2C1 is an AaPYL9-interacting partner and involved in the negative modulation of the ABA signaling pathway inA. annuaL.
Ginsenosides Rg1 from Panax ginseng: A Potential Therapy for Acute Liver Failure Patients?
Authors: Zhao Jinqiu , Shi Zhengyu , Liu Shu , Li Jiajun , Huang Wenxiang
Published: October 2014

Acute liver failure (ALF) is a rapidly progressing critical illness with a high mortality rate. Circulating inflammatory cytokines, such as tumor necrosis factor‐α (TNF‐α), play a significant role in the pathophysiology of ALF through promoting hepatocellular apoptosis. Ginsenoside Rg1, the primary active ingredient in Panax ginseng (also termed Asian or Korean ginseng), has been reported to inhibit TNF‐α production and has been shown to significantly attenuate liver fibrosis development. Here, we assessed ginsenoside Rg1’s potential as a therapy for ALF by investigating the effect of ginsenoside Rg1 treatment on circulating inflammatory markers, hepatocellular apoptosis, and relevant apoptotic signaling pathways in a well‐established murine ALF model. We found that ginsenoside Rg1 significantly reduces liver damage in a murine ALF model through inhibiting TNF‐α‐induced, caspase‐dependent hepatocellular apoptosis. These results support the further investigation of ginsenoside Rg1 as a therapeutic candidate for ALF.
Complex Molecules at Liquid Interfaces: Insights from Molecular Simulation
Authors: Cheung David L.
Published: October 2014

The behaviour of complex molecules, such as nanoparticles, polymers, and proteins, at liquid interfaces is of increasing importance in a number of areas of science and technology. It has long been recognised that solid particles adhere to liquid interfaces, which provides a convenient method for the preparation of nanoparticle structures or to modify interfacial properties. The adhesion of proteins at liquid interfaces is important in many biological processes and in a number of materials applications of biomolecules. While the reduced dimensions of these particles make experimental investigation challenging, molecular simulations provide a natural means for the study of these systems. In this paper I will give an overview of some recent work using molecular simulation to investigate the behaviour of complex molecules at liquid interfaces, focusing on the relationship between interfacial adsorption and molecular structure, and outline some avenues for future research.
Deflection of Resilient Materials for Reduction of Floor Impact Sound
Authors: Lee Jung-Yoon , Kim Jong-Mun
Published: October 2014

Recently, many residents living in apartment buildings in Korea have been bothered by noise coming from the houses above. In order to reduce noise pollution, communities are increasingly imposing bylaws, including the limitation of floor impact sound, minimum thickness of floors, and floor soundproofing solutions. This research effort focused specifically on the deflection of resilient materials in the floor sound insulation systems of apartment houses. The experimental program involved conducting twenty-seven material tests and ten sound insulation floating concrete floor specimens. Two main parameters were considered in the experimental investigation: the seven types of resilient materials and the location of the loading point. The structural behavior of sound insulation floor floating was predicted using the Winkler method. The experimental and analytical results indicated that the cracking strength of the floating concrete floor significantly increased with increasing the tangent modulus of resilient material. The deflection of the floating concrete floor loaded at the side of the specimen was much greater than that of the floating concrete floor loaded at the center of the specimen. The Winkler model considering the effect of modulus of resilient materials was able to accurately predict the cracking strength of the floating concrete floor.
Changing Interdigestive Migrating Motor Complex in Rats under Acute Liver Injury
Authors: Liu Mei , Zheng Su-Jun , Xu Weihong , Zhang Jianying , Chen Yu , Duan Zhongping
Published: October 2014

Gastrointestinal motility disorder is a major clinical manifestation of acute liver injury, and interdigestive migrating motor complex (MMC) is an important indicator. We investigated the changes and characteristics of MMC in rats with acute liver injury. Acute liver injury was created byD-galactosamine, and we recorded the interdigestive MMC using a multichannel physiological recorder and compared the indexes of interdigestive MMC. Compared with normal controls, antral MMC Phase I duration was significantly prolonged and MMC Phase III duration was significantly shortened in the rats with acute liver injury. The duodenal MMC cycle and MMC Phases I and IV duration were significantly prolonged and MMC Phase III duration was significantly shortened in the rats with acute liver injury. The jejunal MMC cycle and MMC Phases I and IV duration were significantly prolonged and MMC Phase III duration was significantly shortened in the rats with acute liver injury compared with normal controls. Compared with the normal controls, rats with acute liver injury had a significantly prolonged interdigestive MMC cycle, related mainly to longer MMC Phases I and IV, shortened MMC Phase III, and MMC Phase II characterized by increased migrating clustered contractions, which were probably major contributors to the gastrointestinal motility disorders.
Assessment of Knowledge and Practices regarding Injection Safety and Related Biomedical Waste Management amongst Interns in a Tertiary Care Teaching Hospital, Delhi
Authors: Acharya Anita Shankar , Priyanka  , Khandekar Jyoti , Bachani Damodar
Published: October 2014

Injuries caused by needle sticks and sharps due to unsafe injection practices are the most common occupational hazard amongst health care personnel. The objectives of our study were to determine the existing knowledge and practices of interns and change in their level following an information education and communication (IEC) package regarding safe injection practices and related biomedical waste management and to determine the status of hepatitis B vaccination. We conducted a follow-up study among all (106) interns in a tertiary care teaching hospital, Delhi. A predesigned semistructured questionnaire was used. IEC package in the form of hands-on workshop and power point presentation was used. A highly significant (P<0.001) improvement in the knowledge of interns was observed after intervention with respect to the “three criteria of a safe injection” and cleaning of injection site. Thus, the baseline knowledge of interns was good in certain aspects of injection safety, namely, diseases transmitted by unsafe injections and their prevention. We conclude that IEC intervention package was effective in significantly improving the interns’ knowledge regarding safe injection practices and biomedical waste management. Almost two-thirds of interns were immunised against hepatitis B before the intervention and this proportion rose significantly after the intervention.
Effects of Atrazine on Reproductive Health of Nondiabetic and Diabetic Male Rats
Authors: Jestadi Dinesh Babu , Phaniendra Alugoju , Babji Undru , Shanmuganathan Bhavatharini , Periyasamy Latha
Published: October 2014

The aim of the present study was to investigate the effects of low dose of atrazine on reproductive system of male Wistar rats. 16 rats were divided into four groups of four animals each. Group I (nondiabetic) and group III (diabetic) animals served as controls that received safflower oil (300 μL/kg bw/day), respectively. Group II (nondiabetic) and group IV (diabetic) animals received atrazine (300 μg/kg bw/day). Nonsignificant decrease in the activities of antioxidant and steroidogenic enzymes and sperm parameters suggests that atrazine did not produce any effect on reproductive system of rats. Histological findings also revealed that atrazine at a dose of 300 μg/kg bw did not produce any testicular toxic effects in nondiabetic and diabetic atrazine treated rats. Low dose of atrazine did not show reproductive toxicity in rats. To know the effects of atrazine in diabetic rats further studies have to be carried out with increased concentration of atrazine.
NMDA Receptor-Dependent Metaplasticity by High-Frequency Magnetic Stimulation
Authors: Tokay Tursonjan , Kirschstein Timo , Rohde Marco , Zschorlich Volker , Köhling Rüdiger
Published: October 2014

High-frequency magnetic stimulation (HFMS) can elicit N-methyl-D-aspartate (NMDA) receptor-dependent long-term potentiation (LTP) at Schaffer collateral-CA1 pyramidal cell synapses. Here, we investigated the priming effect of HFMS on the subsequent magnitude of electrically induced LTP in the CA1 region of rat hippocampal slices using field excitatory postsynaptic potential (fEPSP) recordings. In control slices, electrical high-frequency conditioning stimulation (CS) could reliably induce LTP. In contrast, the same CS protocol resulted in long-term depression when HFMS was delivered to the slice 30 min prior to the electrical stimulation. HFMS-priming was diminished when applied in the presence of the metabotropic glutamate receptor antagonists (RS)-α-methylserine-O-phosphate (MSOP) and (RS)-α-methyl-4-carboxyphenylglycine (MCPG). Moreover, when HFMS was delivered in the presence of the NMDA receptor-antagonist D-2-amino-5-phosphonovalerate (50 µM), CS-induced electrical LTP was again as high as under control conditions in slices without priming. These results demonstrate that HFMS significantly reduced the propensity of subsequent electrical LTP and show that both metabotropic glutamate and NMDA receptor activation were involved in this form of HFMS-induced metaplasticity.
A Computational Framework for Tracing the Origins of Genomic Islands in Prokaryotes
Authors: Wan Peng , Che Dongsheng
Published: October 2014

Genomic islands (GIs) are chunks of genomic fragments that are acquired from nongenealogical organisms through horizontal gene transfer (HGT). Current researches on studying donor-recipient relationships for HGT are limited at a gene level. As more GIs have been identified and verified, the way of studying donor-recipient relationships can be better modeled by using GIs rather than individual genes. In this paper, we report the development of a computational framework for detecting origins of GIs. The main idea of our computational framework is to identify GIs in a query genome, search candidate genomes that contain genomic regions similar to those GIs in the query genome by BLAST search, and then filter out some candidate genomes if those similar genomic regions are also alien (detected by GI detection tools). We have applied our framework in finding the GI origins for Mycobacterium tuberculosis H37Rv, Herminiimonas arsenicoxydans, and three Thermoanaerobacter species. The predicted results were used to establish the donor-recipient network relationships and visualized by Gephi. Our studies have shown that donor genomes detected by our computational approach were mainly consistent with previous studies. Our framework was implemented with Perl and executed on Windows operating system.
Body Mass Index and Its Role in Total Laparoscopic Hysterectomy
Authors: Bhandari Shilpa , Agrawal Pallavi , Singh Aparna
Published: October 2014

Objective. To evaluate operative and perioperative outcomes in patients undergoing total laparoscopic hysterectomy according to their body mass index. Method. A retrospective study was performed for patients undergoing total laparoscopic hysterectomy at a tertiary care center for a period of 4 years. Patients were divided into two groups: obese (BMI > 30 Kg/m2) and nonobese (BMI < 30 Kg/m2). Duration of surgery, intraoperative blood loss, successful laparoscopic completion, and intraoperative complications were compared in two groups. Result. A total of 253 patients underwent total laparoscopic hysterectomy from January 2010 to December 2013. Out of them, 105 women (41.5%) had a BMI of more than 30 kg/m2. Overall, the mean blood loss was 85.79 ± 54.17 mL; the operative time was 54.17 ± 19.83 min. The surgery was completed laparoscopically in 244 (96.4%) women while laparotomy was done in 4 cases and vaginal suturing and closure of vault were done in 5 cases. Risk of vaginal assistance was higher in obese patients whereas out of the 4 conversions to laparotomy 3 had BMI < 30 kg/m2. The operative time was increased as the BMI of patient increased. Conclusions. Total laparoscopic hysterectomy is a safe and effective procedure for obese patients and can be performed with an efficacy similar to that in nonobese patients.
Acute Cardiogenic Shock Induced by Infusional 5-Fluorouracil
Authors: Sulpher Jeffrey , Dattilo Franco , Dent Susan , Turek Michele , Reaume M. Neil , Johnson Christopher
Published: October 2014

A 49-year-old patient with metastatic carcinoma of the bladder and no prior history of heart disease presented with diffuse ST elevation, elevated troponins, and biventricular dysfunction requiring intensive care unit admission and inotropic support after receiving her first course of infusional 5-fluorouracil (5-FU). Over the course of several days, the patient’s cardiac function and clinical status returned to baseline. A follow-up echocardiogram performed 5 days after initial presentation revealed an ejection fraction of 59 percent, with no evidence of wall motion abnormalities. Subsequent 5-FU chemotherapy was discontinued, and the patient went on to receive second-line chemotherapy.
Hybrid Artificial Bee Colony Algorithm and Particle Swarm Search for Global Optimization
Authors: Chun-Feng Wang , Kui Liu , Pei-Ping Shen
Published: October 2014

Artificial bee colony (ABC) algorithm is one of the most recent swarm intelligence based algorithms, which has been shown to be competitive to other population‐based algorithms. However, there is still an insufficiency in ABC regarding its solution search equation, which is good at exploration but poor at exploitation. To overcome this problem, we propose a novel artificial bee colony algorithm based on particle swarm search mechanism. In this algorithm, for improving the convergence speed, the initial population is generated by using good point set theory rather than random selection firstly. Secondly, in order to enhance the exploitation ability, the employed bee, onlookers, and scouts utilize the mechanism of PSO to search new candidate solutions. Finally, for further improving the searching ability, the chaotic search operator is adopted in the best solution of the current iteration. Our algorithm is tested on some well‐known benchmark functions and compared with other algorithms. Results show that our algorithm has good performance.
Treating Methamphetamine-Induced Resistant Psychosis with Clozapine
Authors: Seddigh Ruohollah , keshavarz-Akhlaghi Amir-Abbas , Shariati Behnam
Published: October 2014

Background. Methamphetamine-induced psychosis (MIP) in Iran has turned into a serious issue in terms of health and treatment, lacking any obvious treatment methods for its resistant cases.Aims of Case Report. In the present study, a number of two cases of treatment of MIP with clozapine, which were resistant to the treatment with other antipsychotics, have been reported. Both cases completely responded to the treatment in only 2 weeks and no signs of psychosis relapse were seen in an 8-9 follow-up.Conclusion. Because of its particular pharmacologic features, clozapine may be effective in treating MIP.
Simultaneous Estimation of Four Antitussive Components from Herbal Cough Syrup by HPTLC
Authors: Deore Sharada L. , Jaju Payal S. , Baviskar Bhushan A.
Published: October 2014

A new simple, rapid, selective and precise high performance thin layer chromatographic (HPTLC) method has been developed for simultaneous estimation of vasicine, glycyrrhizin, eugenol, and cineole in herbal cough syrup. The retention factors of vasicine, glycyrrhizin, eugenol, and cineole are 0.53, 0.44, 0.75, and 0.77, respectively. Chromatography was performed on 60F254 percolated TLC plate using n-hexane : ethyl acetate : glacial acetic acid (8.5 : 1.0 : 0.5 v/v/v). Methods are validated according to ICH guidelines and can be adopted for the routine analysis of vasicine, glycyrrhizin, eugenol and cineole in herbal cough syrup.
Emergency Surgery for Metastatic Melanoma
Authors: Mantas Dimitrios , Tsaparas Petros , Charalampoudis Petros , Gogas Helen , Kouraklis Gregory
Published: October 2014

Visceral metastases from malignant melanoma (stage M1c) confer a very poor prognosis, as documented on the most recent revised version of the TNM/AJCC staging system. Emergency surgery for intra-abdominal complications from the disease is rare. We report on our 5-year single institution experience with surgical management of metastatic melanoma to the viscera in the emergent setting. From 2009 to 2013, 14 patients with metastatic melanoma were admitted emergently due to an acute abdomen. Clinical manifestations encompassed intestinal obstruction and bleeding. Surgical procedures involved multiple enterectomies with primary anastomoses in 8 patients, and one patient underwent splenectomy, one adrenalectomy, one right colectomy, one gastric wedge resection, one gastrojejunal anastomosis, and one transanal debulking, respectively. The 30-day mortality was 7 percent. Median follow-up was 14 months. Median overall survival was 14 months. Median disease free survival was 7.5 months. One-year overall survival was 64.2 percent and 2-year overall survival was 14.2 percent. Emergency surgery for metastatic melanoma to the viscera is rare. Elective curative surgery combined with novel cytotoxic systemic therapies is under investigation in an attempt to grant survival benefit in melanoma patients with visceral disease.
Unraveling Exercise Addiction: The Role of Narcissism and Self-Esteem
Authors: Bruno Antonio , Quattrone Diego , Scimeca Giuseppe , Cicciarelli Claudio , Romeo Vincenzo Maria , Pandolfo Gianluca , Zoccali Rocco Antonio , Muscatello Maria Rosaria Anna
Published: October 2014

The aim of this study was to assess the risk of exercise addiction (EA) in fitness clubs and to identify possible factors in the development of the disorder. The Exercise Addiction Inventory (EAI), the Narcissistic Personality Inventory (NPI), and the Coopersmith Self-Esteem Inventory (SEI) were administered to a sample of 150 consecutive gym attenders recruited in fitness centers. Based on EAI total score, high EA risk group (HEAn=51) and a low EA risk group (LEAn=69) were identified. HEA reported significantly higher total score (mean = 20.2 versus 14.6) on the NPI scale and lower total score (mean = 32.2 versus 36.4) on the SEI scale than LEA. A stepwise regression analysis indicated that only narcissism and self-esteem total scores (F=5.66;  df=2;  P=0.006)were good predictors of days per week exercise. The present study confirms the direct and combined role of both labile self-esteem and high narcissism in the development of exercise addiction as predictive factors towards the risk of addiction. Multidisciplinary trained health care providers (physiatrists, psychologists, and psychiatrists) should carefully identify potential overexercise conditions in order to prevent the potential risk of exercise addiction.
Homeoprotein Six2 Promotes Breast Cancer Metastasis via Transcriptional and Epigenetic Control of E-Cadherin Expression
Authors: Wang Chu-An , Drasin David , Pham Catherine , Jedlicka Paul , Zaberezhnyy Vadym , Guney Michelle , Li Howard , Nemenoff Raphael , Costello James C. , Tan Aik-Choon , Ford Heide L.
Published: October 2014

Misexpression of developmental transcription factors occurs often in human cancers, where embryonic programs may be reinstated in a context that promotes or sustains malignant development. In this study, we report the involvement of the kidney development transcription factor Six2 in the metastatic progression of human breast cancer. We found that Six2 promoted breast cancer metastasis by a novel mechanism involving both transcriptional and epigenetic regulation of E-cadherin. Downregulation of E-cadherin by Six2 was necessary for its ability to increase soft agar growth and in vivo metastasis in an immunocompetent mouse model of breast cancer. Mechanistic investigations showed that Six2 represses E-cadherin expression by upregulating Zeb2, in part, through a microRNA-mediated mechanism and by stimulating promoter methylation of the E-cadherin gene (Cdh1). Clinically, SIX2 expression correlated inversely with CDH1 expression in human breast cancer specimens, corroborating the disease relevance of their interaction. Our findings establish Six2 as a regulator of metastasis in human breast cancers and demonstrate an epigenetic function for SIX family transcription factors in metastatic progression through the regulation of E-cadherin. Cancer Res; 74(24); 7357–70. ©2014 AACR.
Impact of Chronic Graft-versus-Host Disease on Late Relapse and Survival on 7,489 Patients after Myeloablative Allogeneic Hematopoietic Cell Transplantation for Leukemia
Authors: Boyiadzis Michael , Arora Mukta , Klein John P. , Hassebroek Anna , Hemmer Michael , Urbano-Ispizua Alvaro , Antin Joseph H. , Bolwell Brian J. , Cahn Jean-Yves Y. , Cairo Mitchell S. , Cutler Corey S. , Flowers Mary E. , Gale Robert P. , Herzig Roger , Isola Luis M. , Jacobsohn David A. , Jagasia Madan H. , Klumpp Thomas R. , Lee Stephanie J. , Petersdorf Effie W. , Santarone Stella , Spellman Stephen R. , Schouten Harry C. , Verdonck Leo F. , Wingard John R. , Weisdorf Daniel J. , Horowitz Mary M. , Pavletic Steven Z.
Published: October 2014

Purpose: Malignancy relapse remains a major obstacle for successful allogeneic hematopoietic cell transplantation (HCT). Chronic graft-versus-host disease (cGVHD) is associated with fewer relapses. However, when studying effects of cGVHD on relapse, it is difficult to separate from acute GVHD effects as most cases of cGVHD occur within the first year after transplant at the time when acute GVHD is still active.

Experimental Design: This study based on CIBMTR registry data investigated cGVHD and its association with the incidence of late relapse and survival in 7,489 patients with acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myelogenous leukemia (CML), and myelodysplastic syndromes (MDS), who were leukemia free at 12 months after myeloablative allogeneic HCT.

Results: Forty-seven percent of the study population was diagnosed with cGVHD at 12 months after transplant. The protective effect of cGVHD on late relapse was present only in patients with CML [RR, 0.47; 95% confidence interval (CI), 0.37–0.59; P < 0.0001). cGVHD was significantly associated with higher risk of treatment-related mortality (TRM; RR, 2.43; 95% CI, 2.09–2.82; P < 0.0001) and inferior overall survival (RR, 1.56; 95% CI, 1.41–1.73; P < 0.0001) for all diseases. In patients with CML, all organ sites and presentation types of cGVHD were equally associated with lower risk of late relapse.

Conclusions: These results indicate that clinically relevant antileukemia effects of cGVHD on late relapses are present only in CML but not in AML, ALL, or MDS. Chronic GVHD in patients who are 1-year survivors after myeloablative allogeneic HCT is primarily associated with higher TRM and inferior survival. Clin Cancer Res; 21(9); 2020–8. ©2014 AACR.

See related commentary by Gill, p. 1981
Low Expression of the E3 Ubiquitin Ligase CBL Confers Chemoresistance in Human Pancreatic Cancer and Is Targeted by Epidermal Growth Factor Receptor Inhibition
Authors: Kadera Brian E. , Toste Paul A. , Wu Nanping , Li Luyi , Nguyen Andrew H. , Dawson David W. , Donahue Timothy R.
Published: October 2014

Purpose: Expression of CBL, an ubiquitin ligase, is decreased in 60% of human pancreatic ductal adenocarcinomas (PDAC) and is associated with shorter overall survival. We sought to determine how low CBL directly contributes to clinically more aggressive PDAC.

Experimental Design: Human PDACs were stained for CBL, pEGFR, and EGFR. CBL-low was modeled in PDAC cells (Panc-1, L3.6pl, and AsPC-1) via transient transfection (siRNA) or stable knockdown (shRNA). Cell viability and apoptosis were measured by MTT assays and FACS. Immunoblot and a phospho-receptor tyrosine kinase (pRTK) array were used to probe signal transduction. NOD-scid-IL2Rγnull mice were subcutaneously implanted with PDAC or PDACCBL-low cells on opposite flanks and treated with gemcitabine ± erlotinib for ≥4 weeks.

Results: There was an inverse correlation between CBL and pEGFR protein expression in 12 of 15 tumors. CBL knockdown increased PDAC resistance to gemcitabine and 5-fluorouracil (5-FU) by upregulating pEGFR (Y1068), pERK, and pAKT. A pRTK array of PDACCBL-low cells revealed additional activated tyrosine kinases but all to a much lower magnitude than EGFR. Increased chemoresistance from low CBL was abrogated by the EGFR inhibitor erlotinib both in vitro and in vivo. Erlotinib+gemcitabine–treated PDACCBL-low cells exhibited greater apoptosis by cleaved PARP, caspase-3, and Annexin V/PI.

Conclusions: Low CBL causes chemoresistance in PDAC via stress-induced EGFR activation that can be effectively abrogated by EGFR inhibition. These results suggest that dysregulation of ubiquitination is a key mechanism of EGFR hyperactivation in PDAC and that low CBL may define PDAC tumors likely to respond to erlotinib treatment. Clin Cancer Res; 21(1); 157–65. ©2014 AACR.
Combined MEK and PI3K Inhibition in a Mouse Model of Pancreatic Cancer
Authors: Alagesan Brinda , Contino Gianmarco , Guimaraes Alexander R. , Corcoran Ryan B. , Deshpande Vikram , Wojtkiewicz Gregory R. , Hezel Aram F. , Wong Kwok-Kin , Loda Massimo , Weissleder Ralph , Benes Cyril , Engelman Jeffrey A. , Bardeesy Nabeel
Published: October 2014

Purpose: Improved therapeutic approaches are needed for the treatment of pancreatic ductal adenocarcinoma (PDAC). As dual MEK and PI3K inhibition is presently being used in clinical trials for patients with PDAC, we sought to test the efficacy of combined targeting of these pathways in PDAC using both in vitro drug screens and genetically engineered mouse models (GEMM).

Experimental Design: We performed high-throughput screening of >500 human cancer cell lines (including 46 PDAC lines), for sensitivity to 50 clinically relevant compounds, including MEK and PI3K inhibitors. We tested the top hit in the screen, the MEK1/2 inhibitor, AZD6244, for efficacy alone or in combination with the PI3K inhibitors, BKM120 or GDC-0941, in a KrasG12D-driven GEMM that recapitulates the histopathogenesis of human PDAC.

Results: In vitro screens revealed that PDAC cell lines are relatively resistant to single-agent therapies. The response profile to the MEK1/2 inhibitor, AZD6244, was an outlier, showing the highest selective efficacy in PDAC. Although MEK inhibition alone was mainly cytostatic, apoptosis was induced when combined with PI3K inhibitors (BKM120 or GDC-0941). When tested in a PDAC GEMM and compared with the single agents or vehicle controls, the combination delayed tumor formation in the setting of prevention and extended survival when used to treat advanced tumors, although no durable responses were observed.

Conclusions: Our studies point to important contributions of MEK and PI3K signaling to PDAC pathogenesis and suggest that dual targeting of these pathways may provide benefit in some patients with PDAC. Clin Cancer Res; 21(2); 396–404. ©2014 AACR.
Effects of BRCA1- and BRCA2-Related Mutations on Ovarian and Breast Cancer Survival: A Meta-analysis
Authors: Zhong Qian , Peng Hong-Ling , Zhao Xia , Zhang Lin , Hwang Wei-Ting
Published: October 2014

Purpose: To estimate the effects of BRCA1 and BRCA2 mutations on ovarian cancer and breast cancer survival.

Experimental Design: We searched PubMed and EMBASE for studies that evaluated the associations between BRCA mutations and ovarian or breast cancer survival. Meta-analysis was conducted to generate combined HRs with 95% confidence intervals (CI) for overall survival (OS) and progression-free survival (PFS).

Results: From 1,201 unique citations, we identified 27 articles that compared prognosis between BRCA mutation carriers and noncarriers in patients with ovarian or breast cancer. Fourteen studies examined ovarian cancer survival and 13 studies examined breast cancer survival. For ovarian cancer, meta-analysis demonstrated that both BRCA1 and BRCA2 mutation carriers had better OS (HR, 0.76; 95% CI, 0.70–0.83 for BRCA1 mutation carriers; HR, 0.58; 95% CI, 0.50–0.66 for BRCA2 mutation carriers) and PFS (HR, 0.65; 95% CI, 0.52–0.81 for BRCA1 mutation carriers; HR, 0.61; 95% CI, 0.47–0.80 for BRCA2 mutation carriers) than noncarriers, regardless of tumor stage, grade, or histologic subtype. Among patients with breast cancer, BRCA1 mutation carriers had worse OS (HR, 1.50; 95% CI, 1.11–2.04) than noncarriers but were not significantly different from noncarriers in PFS. BRCA2 mutation was not associated with breast cancer prognosis.

Conclusions: Our analyses suggest that BRCA mutations are robust predictors of outcomes in both ovarian and breast cancers and these mutations should be taken into account when devising appropriate therapeutic strategies. Clin Cancer Res; 21(1); 211–20. ©2014 AACR.
Utilization of the Eμ-Myc Mouse to Model Heterogeneity of Therapeutic Response
Authors: Rempel Rachel E. , Jiang Xiaolei , Fullerton Paul , Tan Tuan Zea , Ye Jieru , Lau Jieying Amelia , Mori Seiichi , Chi Jen-Tsan , Nevins Joseph R. , Friedman Daphne R.
Published: October 2014

Human aggressive B-cell non-Hodgkin lymphomas (NHL) encompass the continuum between Burkitt lymphoma and diffuse large B-cell lymphoma (DLBCL), and display considerable clinical and biologic heterogeneity, most notably related to therapy response. We previously showed that lymphomas arising in the Eμ-Myc transgenic mouse are heterogeneous, mirroring genomic differences between Burkitt lymphoma and DLBCL. Given clinical heterogeneity in NHL and the need to develop strategies to match therapeutics with discrete forms of disease, we investigated the extent to which genomic variation in the Eμ-Myc model predicts response to therapy. We used genomic analyses to classify Eμ-Myc lymphomas, link Eμ-Myc lymphomas with NHL subtypes, and identify lymphomas with predicted resistance to conventional and NF-κB–targeted therapies. Experimental evaluation of these predictions links genomic profiles with distinct outcomes to conventional and targeted therapies in the Eμ-Myc model, and establishes a framework to test novel targeted therapies or combination therapies in specific genomically defined lymphoma subgroups. In turn, this will rationally inform the design of new treatment options for aggressive human NHL. Mol Cancer Ther; 13(12); 3219–29. ©2014 AACR.
Inhibition of HSP90 by AT13387 Delays the Emergence of Resistance to BRAF Inhibitors and Overcomes Resistance to Dual BRAF and MEK Inhibition in Melanoma Models
Authors: Smyth Tomoko , Paraiso Kim H.T. , Hearn Keisha , Rodriguez-Lopez Ana M. , Munck Joanne M. , Haarberg H. Eirik , Sondak Vernon K. , Thompson Neil T. , Azab Mohammad , Lyons John F. , Smalley Keiran S.M. , Wallis Nicola G.
Published: October 2014

Emergence of clinical resistance to BRAF inhibitors, alone or in combination with MEK inhibitors, limits clinical responses in melanoma. Inhibiting HSP90 offers an approach to simultaneously interfere with multiple resistance mechanisms. Using the HSP90 inhibitor AT13387, which is currently in clinical trials, we investigated the potential of HSP90 inhibition to overcome or delay the emergence of resistance to these kinase inhibitors in melanoma models. In vitro, treating vemurafenib-sensitive cells (A375 or SK-MEL-28) with a combination of AT13387 and vemurafenib prevented colony growth under conditions in which vemurafenib treatment alone generated resistant colonies. In vivo, when AT13387 was combined with vemurafenib in a SK-MEL-28, vemurafenib-sensitive model, no regrowth of tumors was observed over 5 months, although 2 of 7 tumors in the vemurafenib monotherapy group relapsed in this time. Together, these data suggest that the combination of these agents can delay the emergence of resistance. Cell lines with acquired vemurafenib resistance, derived from these models (A375R and SK-MEL-28R) were also sensitive to HSP90 inhibitor treatment; key clients were depleted, apoptosis was induced, and growth in 3D culture was inhibited. Similar effects were observed in cell lines with acquired resistance to both BRAF and MEK inhibitors (SK-MEL-28RR, WM164RR, and 1205LuRR). These data suggest that treatment with an HSP90 inhibitor, such as AT13387, is a potential approach for combating resistance to BRAF and MEK inhibition in melanoma. Moreover, frontline combination of these agents with an HSP90 inhibitor could delay the emergence of resistance, providing a strong rationale for clinical investigation of such combinations in BRAF-mutated melanoma. Mol Cancer Ther; 13(12); 2793–804. ©2014 AACR.
Indeterminate Pulmonary Nodules: Risk for Having or for Developing Lung Cancer?
Authors: Massion Pierre P. , Walker Ronald C.
Published: October 2014

This perspective discusses the report by Pinsky and colleagues, which addresses whether noncalcified pulmonary nodules identified on CT screening carry short- and long-term risk for lung cancer. We are facing challenges related to distinguishing a large majority of benign nodules from malignant ones and among those a majority of aggressive from indolent cancers. Key questions in determining individual probabilities of disease, given their history, findings on CT, and upcoming biomarkers of risk, remain most challenging. Reducing the false positives associated with current low-dose computed tomography practices and identification of individuals who need therapy and at what time during tumor surveillance could reduce costs and morbidities associated with unnecessary interventions. Cancer Prev Res; 7(12); 1173–8. ©2014 AACR.
Gamma Knife Radiosurgery of Paracentral Epilepsy
Authors: McGonigal Aileen , Bartolomei Fabrice , Gavaret Martine , Chauvel Patrick , Régis Jean
Published: October 2014

Background: In pharmacoresistant focal epilepsies involving the central region, risk of motor deficit generally contraindicates cortical resection. Gamma knife radiosurgery (GK) is an established treatment for mesial temporal epilepsy and epilepsy associated with hypothalamic hamartoma. Objectives: To explore the safety profile and efficacy of GK in motor cortex epilepsies. Methods: Four patients (18-31 years) with intractable focal sensorimotor epilepsy seizures arising from the paracentral lobule, demonstrated by stereoelectroencephalography, in whom conventional surgery was contraindicated because of motor deficit risk underwent GK. A marginal dose of 24 Gy was delivered to a focal zone involving the paracentral lobule. Results Volume of treatment ranged from 1.6 to 3.18 cm3 (median: 2.34). No motor deficit or other adverse effect occurred. Follow-up was available for at least 3 years (range: 36-78 months; median: 49). No complication of GK, including motor deficit, occurred. Two patients achieved an Engel class 1B outcome and 2 were unchanged. Both of the patients who improved had gradual disappearance of objective motor ictal semiology (6-12 months after GK), preceding reduced seizure frequency (12-18 months onwards). Cerebral MRI showed no change. Conclusions: GK is a potentially useful treatment for focal paracentral epilepsies where conventional surgery would carry an unacceptable risk of motor deficit.