bluuebunny/crossref_metadata_2025 huggingface dataset:
Phase-Coupled Oscillations in the Brain: Nonlinear Phenomena in Cellular Signalling
Authors: Rai Vikas , Nadar Sreenivasan Rajamoni , Khan Riaz A.
Published: March 2013

We report the existence of phase-coupled oscillations in a model neural system. The model consists of a group of excitatory principal cells in interaction with local inhibitory interneurons. The voltages across the membranes of excitatory cells are governed primarily by calcium and potassium ion conductivities. The number of potassium channels open at any given instant changes in accordance with a deterministic law. The time scale of this change is set by a constant which depends on midpoint potentials at which potassium and calcium currents are half-activated. The growth of mean membrane potential of excitatory principal cells is controlled by that of the inhibitory interneurons. Nonlinear oscillatory system associated with these limit cycles starting from two different initial conditions maintain a definite phase relationship. The phase-coupled oscillations in electrical activity of the neuronal cells carry together amplitude, phase, and time information for cellular signaling. This mechanism supports an energy efficient way of information processing in the central nervous system. The information content is encoded as persistent periodic oscillations represented by stable limit cycles in the phase space.
Conductivity and Complex Electrical Formalism of the Iron-Doped PbLaTiO3 Ferroelectric Relaxor
Authors: Omari Lhaj Hachemi , Sayouri Salaheddine
Published: March 2013

Polycrystalline perovskite nanomaterials (Pb0.88La0.12)(FexTi1-x)0.97O3 were prepared by sol-gel reaction method. The crystal structure examined by X-ray powder diffraction indicates that the material was single phase with pseudocubic structure. EDX and SEM studies were carried out in order to evaluate the quality and purity of the compounds. The crystal symmetry, space group, and unit cell dimensions were determined from Cell-Ref software, whereas crystallite size was estimated from Scherrer’s formula. A correlation between grain size and diffuse character for the samples has been observed. Dielectric studies exhibit a diffuse phase transition characterized by a strong temperature and frequency dispersion of the permittivity and a relaxor behaviour. We have observed that dielectric constant decreases and ac conductivity increases with the frequency. The dielectric relaxation has been modeled using the Curie-Weiss and modified Curie-Weiss laws. The calculated activation energy Ea for x=1% and 3% was between 0.91–2.1 eV and 0.425–1.08 eV, respectively. The relaxation times were estimated from the Arrhenius law.
Rhabdomyolysis Secondary to Bee Sting
Authors: Akdur Okhan , Can Serdar , Afacan Göksu
Published: March 2013

Insect stings belonging to Hymenoptera defined as wasps, yellow jackets, bees, or hornets by human usually result in unserious clinical pictures that go with pain. Rhabdomyolysis following a bee sting is a rare condition. This paper emphasizes “rhabdomyolysis” as a rare complication of this frequently observed envenomation. Rare but severe clinical results may occur due to multiple bee stings, such as intravascular hemolysis, rhabdomyolysis, acute renal insufficiency, and hepatic dysfunction. In bee stings as in our case, clinicians should be alert for rhabdomyolysis in cases with generalized body and muscle pain. Early onset alkaline diuresis and management in patients with rhabdomyolysis are vital in protecting the renal functions and preventing morbidity and mortality.
Effect of GutGard in the Management ofHelicobacter pylori: A Randomized Double Blind Placebo Controlled Study
Authors: Puram Sreenivasulu , Suh Hyung Chae , Kim Seung Un , Bethapudi Bharathi , Joseph Joshua Allan , Agarwal Amit , Kudiganti Venkateswarlu
Published: March 2013

A randomized, double blind placebo controlled study was conducted to evaluate the efficacy of GutGard (root extract ofGlycyrrhiza glabra) in the management ofHelicobacter pylori(H. pylori) gastric load. Participants diagnosed withH. pyloriinfection were randomly assigned to two groups to orally receive 150 mg of GutGard (n=55) or placebo (n=52) once daily for 60 days.H. pyloriinfection was assessed using13C-urea breath test (13C-UBT) at days 0, 30, and 60. Stool Antigen test (HpSA) was also performed on days 0, 30, and 60. Repeated measures of analysis of variance (RMANOVA), chi-square, and Fisher's exact probability tests were used to compare the treatment outcomes. A significant interaction effect between group and time (P=0.00) and significant difference in mean Delta Over Baseline (DOB) values between GutGard (n=50) and placebo (n=50) treated groups after intervention period were observed. On day 60, the results of HpSA test were negative in 28 subjects (56%) in GutGard treated group whereas in placebo treated group only 2 subjects (4%) showed negative response; the difference between the groups was statistically significant. On day 60, the results of13C-UBT were negative in 24 (48%) in GutGard treated group and the difference between the groups was statistically significant. The findings suggest GutGard is effective in the management ofH. pylori.
Randomized Controlled Trials of Proximal Femoral Nail Antirotation in Lateral Decubitus and Supine Position on Treatment of Intertrochanteric Fractures
Authors: Xue Li , Zha Li , Chen Qin , Liang Yi-jian , Li Kang-ren , Zhou Zheng , Guan Jin-long , Qin Hui , Li You-ping
Published: March 2013

The objective of this study was to compare the clinical results and complications of proximal femoral nail antirotation (PFNA) on treatment of intertrochanteric fractures in 120 elderly Chinese patients using Randomized Controlled Trials (RCTs). Totaly 120 cases enrolled were randomly assigned to a lateral decubitus position group and supine position group. The hospital stay, operating time, intraoperative blood loss, length of incision, X‐ray fluoroscopy time, and out‐of‐bed activity time in the lateral decubitus position group were significantly lower than those in the supine position group. There was not statistical significance on union time and Harris values in the two position groups. Moreover, only complications of superficial wound infection were observed in the lateral decubitus position group, but two complications of deep venous thrombosis and wound deep infection were found in the supine position group. The present findings suggested that PFNA applied in elderly patients with intertrochanteric fracture can get satisfactory effects, and the treatment of intertrochanteric fractures using lateral decubitus position showed a satisfactory clinical outcome and a lower radiological complication rate.
Two Novel Norwithasteroids with Unusual Six- and Seven-Membered Ether Rings in Side Chain from Flos Daturae
Authors: Yang Bing-You , Xia Yong-Gang , Wang Yan-Yan , Wang Qiu-Hong , Kuang Hai-Xue
Published: March 2013

Chemical investigation of 50% ethanol eluate fraction of macroporous resin for the flower of Datura metel L. collected in Jiangsu province of China resulted in the isolation of two novel naturally occurring norwithasteroids, baimantuoluoline I (1) and baimantuoluoside J (2). Their structures were elucidated as 5α, 6β, 12β-trihydroxy-1-oxo-2-en-ergosta-21,24;22,29-diepoxy-26-carboxylic acid (1) and 5α, 6β, 12β, 25-tetrahydroxy-1-oxo-2-en-ergosta-21,24;22,29-diepoxy-26-carboxylic acid (2) on the basis of extensive spectroscopic analysis, including 1D, 2D-NMR, and HR-ESI-MS. According to the literatures, this study represents the first report of the norwithasteroids in the side chain with unusual six- and seven-membered ether rings instead of those with an unmodified skeleton (δ-lactone or δ-lactol side chain) and a modified skeleton (γ-lactone or γ-lactol side chain) in the family of withanolides. Meanwhile, compounds 1 and 2 were evaluated for their immunosuppressive activity against mice splenocyte proliferation in vitro.
On Polynomial Stability of Variational Nonautonomous Difference Equations in Banach Spaces
Authors: Megan Mihail , Ceauşu Traian , Tomescu Mihaela Aurelia
Published: March 2013

Our goal in this paper is to give characterizations for some concepts of polynomial stability for variational nonautonomous difference equations. The obtained results can be considered generalizations for the case of variational nonautonomous difference equations of some theorems proved by Barbashin (1967), Datko (1973), and Lyapunov (1992), for evolution operators.
Anthrax Lethal Toxin Inhibits the Production of Proinflammatory Cytokines
Authors: Wu Aiguo , Shiloach Joseph , Alibek Darya , Li Lydia Yue , Bradburne Christopher , Alibek Ken
Published: March 2013

In previous studies, we have found that anthrax lethal toxin (LeTx) induces apoptosis in both murine macrophages and human peripheral blood mononuclear cells (PBMCs). In this study, we further report that bacterial cell wall (CW) components of Bacillus (B.) anthracis are powerful inducers of proinflammatory cytokines from the PBMCs. These effects are deprived when the LeTx is present. The major causative element for this suppression is lethal factor (LF) rather than protective antigen (PA). These results indicate that the roles of LeTx in anthrax pathogenesis, particularly its effects on cytokine production, should be reevaluated as our findings and other reports are controversial to the conventional concept.
Transcatheter Arterial Chemoembolization Based on Hepatic Hemodynamics for Hepatocellular Carcinoma
Authors: Murata Satoru , Mine Takahiko , Ueda Tatsuo , Nakazawa Ken , Onozawa Shiro , Yasui Daisuke , Kumita Shin-ichiro
Published: March 2013

Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third leading cause of cancer‐related deaths in the world. The Barcelona Clinic Liver Cancer (BCLC) classification has recently emerged as the standard classification system for clinical management of patients with HCC. According to the BCLC staging system, curative therapies (resection, transplantation, and percutaneous ablation) can improve survival in HCC patients diagnosed at an early stage and offer potential long‐term curative effects. Patients with intermediate‐stage HCC benefit from transcatheter arterial chemoembolization (TACE), and those diagnosed at an advanced stage receive sorafenib, a multikinase inhibitor, or conservative therapy. Most patients receive palliative or conservative therapy only, and approximately 50% of patients with HCC are candidates for systemic therapy. TACE is often recommended for advanced‐stage HCC patients all over the world because these patients desire therapy that is more effective than systemic chemotherapy or conservative treatment. This paper aims to summarize both the published data and important ongoing studies for TACE and to discuss technical improvements in TACE for advanced‐stage HCC.
Idiopathic Gingival Fibromatosis Rehabilitation: A Case Report with Two-Year Followup
Authors: Jayachandran Mahesh , Kapoor Shalini , Mahesh Rethi
Published: March 2013

Gingival enlargements are quite common and may be either inflammatory, noninflammatory, or a combination of both. Gingival hyperplasia is a bizarre condition causing esthetic, functional, psychological, and masticatory disturbances of the oral cavity. Causes of gingival enlargement can be due to plaque accumulation, due to poor oral hygiene, inadequate nutrition, or systemic hormonal stimulation (Bakaeen and Scully, 1998). It can occur as an isolated disease or as part of a syndrome or chromosomal abnormality. A progressive fibrous enlargement of the gingiva is a facet of idiopathic fibrous hyperplasia of the gingiva (Carranza and Hogan, 2002; Gorlin et al., 1976). It is described variously asfibromatosis gingivae, gingivostomatitis, hereditary gingival fibromatosis, idiopathic fibromatosis, familial elephantiasis,anddiffuse fibroma. We present a case of idiopathic gingival fibromatosis with its multidisciplinary approach of management.
Adjunctive Therapies to Cerclage for the Prevention of Preterm Birth: A Systematic Review
Authors: DeFranco Emily A. , Valent Amy Miyoshi , Newman Tondra , Regan Jodi , Smith Jessica , Muglia Louis J.
Published: March 2013

The aim of this paper is to provide a thorough summary of published studies that have assessed the efficacy of adjunctive therapies used in addition to cervical cerclage as a preventive measure for preterm birth. We limited our paper to patients treated with cerclage plus an additional prophylactic therapy compared to a reference group of women with cerclage alone. The specific adjunctive therapies included in this systematic review are progesterone, reinforcing or second cerclage placement, tocolytics, antibiotics, bedrest, and pessary. We searched PubMed and Cochrane databases without date criteria with restriction to English language and human studies and performed additional bibliographic review of selected articles and identified 305 total studies for review. Of those, only 12 studies compared the use of an adjunctive therapy with cerclage to a reference group of cerclage alone. None of the 12 were prospective randomized clinical trials. No comparative studies were identified addressing the issues of antibiotics, bedrest, or pessary as adjunctive treatments to cerclage. None of the 12 studies included in this paper demonstrated a clear benefit of any adjunctive therapy used in addition to cerclage over and above cerclage used alone; however, few studies with small numbers limited the strength of the conclusions.
Scaled Diagonal Gradient-Type Method with Extra Update for Large-Scale Unconstrained Optimization
Authors: Farid Mahboubeh , Leong Wah June , Malekmohammadi Najmeh , Mamat Mustafa
Published: March 2013

We present a new gradient method that uses scaling and extra updating within the diagonal updating for solving unconstrained optimization problem. The new method is in the frame of Barzilai and Borwein (BB) method, except that the Hessian matrix is approximated by a diagonal matrix rather than the multiple of identity matrix in the BB method. The main idea is to design a new diagonal updating scheme that incorporates scaling to instantly reduce the large eigenvalues of diagonal approximation and otherwise employs extra updates to increase small eigenvalues. These approaches give us a rapid control in the eigenvalues of the updating matrix and thus improve stepwise convergence. We show that our method is globally convergent. The effectiveness of the method is evaluated by means of numerical comparison with the BB method and its variant.
Spatial Dispersal of Douglas-Fir Beetle Populations in Colorado and Wyoming
Authors: Withrow John R. , Lundquist John E. , Negrón José F.
Published: March 2013

Bark beetles (Coleoptera: Curculionidae: Scolytinae) are mortality agents to multiple tree species throughout North America. Understanding spatiotemporal dynamics of these insects can assist management, prediction of outbreaks, and development of “real time” assessments of forest susceptibility incorporating insect population data. Here, dispersal of Douglas-fir beetle (Dendroctonus pseudotsugae Hopk.) is estimated over four regions within Colorado and Wyoming from 1994 to 2010. Infestations mapped from aerial insect surveys are utilized as a proxy variable for Douglas-fir beetle (DFB) activity and analyzed via a novel GIS technique that co-locates infestations from adjacent years quantifying distances between them. Dispersal distances of DFB infestations were modeled with a cumulative Gaussian function and expressed as a standard dispersal distance (SDD), the distance at which 68% of infestations dispersed in a given flight season. Average values of SDD ranged from under 1 kilometer for the region of northwestern Colorado to over 2.5 kilometers for infestations in Wyoming. A statistically significant relationship was detected between SDD and infestation area in the parent year, suggesting that host depletion and density-dependent factors may influence dispersal. Findings can potentially provide insight for managers—namely, likelihood of DFB infestation increase for locations within two to five kilometers of an existing infestation.
Intraoperatively Diagnosed Tracheal Tear after Using an NIM EMG ETT with Previously Undiagnosed Tracheomalacia
Authors: Joshi Minal , Mardakh Simon , Yarmush Joel , Kamath H. , Schianodicola Joseph , Mendoza Ernesto
Published: March 2013

Tracheal rupture is a rare complication of endotracheal intubation. We present a case of tracheal rupture that was diagnosed intraoperatively after the use of an NIM EMG endotracheal tube. A 66-year-old female with a recurrent multinodular goiter was scheduled for total thyroidectomy. Induction of anesthesia was uncomplicated. Intubation was atraumatic using a 6 mm NIM EMG endotracheal tube (ETT). Approximately 90 minutes into the surgery, a tracheal tear was suspected. After confirming the diagnosis, conservative treatment with antibiotic coverage was favored. The patient made a full recovery with no complications. Diagnosis of the tracheal tear was made intraoperatively, prompting early management.
Numerical Simulation of Geostress and Pore Pressure Evolution around Oil or Water Well under Different Injection-Production Ratio
Authors: Jian-jun Liu , Xian-bin Yu , Jin-zhou Zhao
Published: March 2013

Geostress evolution in the process of oil field development can directly influence wellbore stability. Therefore, it is significant to strengthen the research of the evolution rule for well drilling and casing protection. Considering the interaction between reservoir seepage and stress fields, a mathematical model to characterize the stress evolution around wellbore was built. Using the FEM Software ABAQUS, through numerical simulation, the authors studied the evolution features of pore pressure and stress changes with time under different injection-production ratio, which disclosed the dynamic change regulation of pore pressure and stress of surrounding rock nearby the injection and production wells. These results may have implications in the treatment of wellbore stability and optimizing the injection and production processes during oil and gas production.
NGAL and Metabolomics: The Single Biomarker to Reveal the Metabolome Alterations in Kidney Injury
Authors: Noto A. , Cibecchini F. , Fanos V. , Mussap M.
Published: March 2013

Conditions affecting kidney structure and function can be considered acute or chronic, depending on their duration. Acute kidney injury (AKI) is one of a number of acute kidney diseases and consists of an abrupt decline in kidney function after an injury leading to functional and structural changes. The widespread availability of enabling technologies has accelerated the rate of novel biomarker discovery for kidney injury. The introduction of novel biomarkers in clinical practice will lead to better preventative and therapeutic interventions and to improve outcomes of critically ill patients. A number of biomarkers of functional change and cellular damage are under evaluation for early diagnosis, risk assessment, and prognosis of AKI. Neutrophil gelatinase-associated lipocalin (NGAL) has emerged as the most promising biomarker of kidney injury; this protein can be measured by commercially available methods in whole blood, plasma, serum, and urine. Concomitantly, metabolomics appears to be a snapshot of the chemical fingerprints identifying specific cellular processes. In this paper, we describe the role of NGAL for managing AKI and the potential benefits deriving from the combined clinical use of urine NGAL and metabolomics in kidney disease.
Cerebrospinal Fluid Biomarkers for Kii Amyotrophic Lateral Sclerosis/Parkinsonism-Dementia Complex
Authors: Nakayama Yui , Morimoto Satoru , Yoneda Misao , Kuzuhara Shigeki , Kokubo Yasumasa
Published: March 2013

Objective. Amyotrophic lateral sclerosis/parkinsonism-dementia complex is classified as one of the tauopathies. Methods. The total tau, phosphorylated tau, and amyloid β42 levels were assayed in cerebrospinal fluid from patients with Kii amyotrophic lateral sclerosis/parkinsonism-dementia complex (), Alzheimer’s disease (), Parkinson’s disease (), amyotrophic lateral sclerosis (), and controls () using specific enzyme-linked immunosorbent assay methods. Results. Total tau and phosphorylated tau did not increase and amyloid β42 was relatively reduced in Kii amyotrophic lateral sclerosis/parkinsonism-dementia complex. Relatively reduced amyloid β42 might discriminate Kii amyotrophic lateral sclerosis/parkinsonism-dementia complex from amyotrophic lateral sclerosis and Parkinson’s disease, and the ratios of phosphorylated-tau to amyloid β42 could discriminate Kii amyotrophic lateral sclerosis/parkinsonism-dementia complex from Alzheimer’s disease. Conclusions. Cerebrospinal fluid analysis may be useful to differentiate amyotrophic lateral sclerosis/parkinsonism-dementia complex from Alzheimer’s disease, amyotrophic lateral sclerosis, and Parkinson’s disease.
A Spectral Solenoidal-Galerkin Method for Rotating Thermal Convection between Rigid Plates
Authors: Yıldırım Cihan , Yarımpabuç Durmuş , Tarman Hakan I.
Published: March 2013

The problem of thermal convection between rotating rigid plates under the influence of gravity is treated numerically. The approach uses solenoidal basis functions and their duals which are divergence free. The representation in terms of the solenoidal bases provides ease in the implementation by a reduction in the number of dependent variables and equations. A Galerkin procedure onto the dual solenoidal bases is utilized in order to reduce the governing system of partial differential equations to a system of ordinary differential equations for subsequent parametric study. The Galerkin procedure results in the elimination of the pressure and is facilitated by the use of Fourier-Legendre spectral representation. Numerical experiments on the linear stability of rotating thermal convection and nonlinear simulations are performed and satisfactorily compared with the literature.
Aggressive Giant Cell Reparative Granuloma of the Nasal Cavity
Authors: Ishinaga Hajime , Otsu Kazuya , Mouri Genshin , Takeuchi Kazuhiko
Published: March 2013

Giant cell reparative granuloma (GCRG) is an uncommon and nonneoplastic reactive tumor that involves the maxilla and mandible in the region of the head and neck. It is rare in the nasal cavity, and it might be misdiagnosed. We reported a very aggressive GCRG with intracranial invasion, which was treated surgically via a combined approach of a lateral rhinotomy with a craniotomy by bilateral coronal incision. The pathology was consistent with GCRG. A short literature review about diagnosis, clinical behavior, and treatment of this tumor entity is given.
An Uncommon Cause of Shortness of Breath in a Young Puerpera
Authors: Prueksaritanond Suartcha , Ali Alaa M. , Aronu Godson Nnamdi , Hussain Nasir , Ganjoo Anubha , Mirrakhimov Aibek E. , Barbaryan Aram
Published: March 2013

Acute postpartum dyspnea in a young, previously healthy adult encompasses numerous conditions. One should be aware of various differential diagnoses including delayed postpartum preeclampsia-induced pulmonary edema where the occurrence is rare but a significant one due its deleterious consequences. We report a case of 26-year-old gravida 1/para 1 female who presented to the hospital with progressive dyspnea after 1 week of normal spontaneous vaginal delivery. On physical examination, her blood pressure was severely elevated. Her clinical signs and symptoms were consistent with pulmonary edema, but diagnostic tests excluded the cardiogenic causes. Further test revealed proteinuria. The patient was diagnosed with delayed postpartum preeclampsia.
RPE Adenocarcinoma as the Presenting Sign of Bronchogenic Carcinoma: Diagnostic Dilemma in the Management of a Case
Authors: Adulkar Namrata , Radhakrishnan Santhi , Vidhya N. , Kim Usha
Published: March 2013

Neoplasms of retinal pigment epithelium are rare and must be differentiated from choroidal melanoma. The possibility of a metastatic disease with possible primary sites as lung, breast, or kidney should be ruled out. Herein we report a case of adenocarcinoma arising from the RPE with a lung lesion suspicious of bronchogenic carcinoma. In this paper, ocular symptoms were the first sign of a systemic malignancy.
Inflammatory Myofibroblastic Tumor: A Rare Tumor in the Tongue
Authors: Yucel Ekici Nur , Bayindir Tuba , Kizilay Ahmet , Aydin Nasuhi Engin
Published: March 2013

Inflammatory myofibroblastic tumor is composed of myofibroblast and inflammatory cell infiltration of the tissue. Malign transformation and recurrence rate of this tumor is rare and accepted as benign fibroinflammatory disease. The main etiology is unclear, but infection, trauma, and immunologic event are accused. In this study, we presented a 75-year-old man with a mass on his tongue, which was diagnosed as “inflammatory myofibroblastic tumor.” This type of tumor is rarely seen in the tongue and might be difficult to diagnose. Complete mass excision was provided for an adaquete treatment.
Lesion of Aggregated Monocytes and Mesothelial Cells: Mesothelial/Monocytic Incidental Cardiac Lesion
Authors: Erinanç Hilal , Günday Murat , Saba Tonguç , Özülkü Mehmet , Sezgin Atilla
Published: March 2013

A 58-year-old woman with a history of childhood acute rheumatic fever and resultant mitral valve stenosis was admitted to our cardiovascular surgery clinic complaining of tachycardia, dyspnea, and chest pain. After clinical and radiological findings were evaluated, mitral valve replacement, tricuspid De Vega annuloplasty and plication, and resection of giant left atrium were performed. Atrial thrombus was removed from the top of the left atrial wall. Operation material considered as thrombus was sent to a pathology laboratory for histopathological examination. It was diagnosed with mesothelial/monocytic incidental cardiac lesion (cardiac MICE). Microscopic sections revealed that morphological features of the lesion were different from thrombus. The lesion was composed of a cluster of histiocytoid cells with abundant cytoplasm and oval shaped nuclei and epithelial-like cells resembling mesothelial cells within a fibrin network. Epithelial-like cells formed a papillary configuration in the focal areas. Mitotic figures were absent. Here we present a case which was incidentally found in a patient who underwent mitral valve replacement surgery, as a thrombotic lesion on the left atrium wall.
Morphology of Middle Cerebral Artery Aneurysms: Impact on Surgical Strategy and on Postoperative Outcome
Authors: Schebesch Karl-Michael , Proescholdt Martin , Steib Kathrin , Ullrich Odo-Winfried , Herbst Andreas , Rennert Janine , Brawanski Alexander
Published: March 2013

The outcome of middle cerebral artery (MCA) aneurysm clipping depends on the presence of subarachnoid hemorrhage (SAH). Moreover, it is influenced by anatomical features of the aneurysm and its parent artery. We hypothesized that morphological characteristics of the aneurysm may be predictive for postoperative outcome. Therefore, we identified radiographic assessable details that predicted the surgical difficulty and the risk for new ischemia. The angiograms of 151 consecutive patients (82 presenting with SAH) were analyzed in a standardized fashion focusing on 12 defined morphological aspects. The results were correlated to intraoperative rupture and to postoperative ischemia. Aneurysms presenting with SAH were associated with irregular shape, larger maximum diameter, and larger dome-to-base distance (DBD) and were located more frequently on the M2 segment. Multivariate analysis revealed 6 independent predictors for intraoperative rupture: SAH, location on M2 segment, DBD, maximum diameter, diameter of the parent MCA, and the presence of branching vessel. Independent predictors of surgery-related ischemia were identified: SAH, irregular shape, location on M2 segment, DBD, and the neck-to-vessel ratio (NVR). In MCA aneurysms, independent predictors for the risk of rupture intraoperatively and for the postsurgical outcome were the presence of SAH, location on the M2-segment, size (DBD), and the broadness of the neck.
Comment on “An Approximation to Solution of Space and Time Fractional Telegraph Equations by He's Variational Iteration Method”
Authors: Wang Yi-Hong , Huang Lan-Lan
Published: March 2013

The variational iteration method was applied to the time fractional telegraph equation and some variational iteration formulae were suggested in (Sevimlican, 2010). Those formulae are improved by Laplace transform from which the approximate solutions of higher accuracies can be obtained.
Anti-Inflammatory Dimethylfumarate: A Potential New Therapy for Asthma?
Authors: Seidel Petra , Roth Michael
Published: March 2013

Asthma is a chronic inflammatory disease of the airways, which results from the deregulated interaction of inflammatory cells and tissue forming cells. Beside the derangement of the epithelial cell layer, the most prominent tissue pathology of the asthmatic lung is the hypertrophy and hyperplasia of the airway smooth muscle cell (ASMC) bundles, which actively contributes to airway inflammation and remodeling. ASMCs of asthma patients secrete proinflammatory chemokines CXCL10, CCL11, and RANTES which attract immune cells into the airways and may thereby initiate inflammation. None of the available asthma drugs cures the disease—only symptoms are controlled. Dimethylfumarate (DMF) is used as an anti-inflammatory drug in psoriasis and showed promising results in phase III clinical studies in multiple sclerosis patients. In regard to asthma therapy, DMF has been anecdotally reported to reduce asthma symptoms in patients with psoriasis and asthma. Here we discuss the potential use of DMF as a novel therapy in asthma on the basis ofin vitrostudies of its inhibitory effect on ASMC proliferation and cytokine secretion in ASMCs.
A Novel Method for Training an Echo State Network with Feedback-Error Learning
Authors: Løvlid Rikke Amilde
Published: March 2013

Echo state networks are a relatively new type of recurrent neural networks
that have shown great potentials for solving non-linear, temporal
problems. The basic idea is to transform the low dimensional temporal input
into a higher dimensional state, and then train the output connection
weights to make the system output the target information. Because only
the output weights are altered, training is typically quick and computationally
efficient compared to training of other recurrent neural networks.
This paper investigates using an echo state network to learn the inverse
kinematics model of a robot simulator with feedback-error-learning. In
this scheme teacher forcing is not perfect, and joint constraints on the
simulator makes the feedback error inaccurate. A novel training method
which is less influenced by the noise in the training data is proposed and
compared to the traditional ESN training method.
Comparison of QCT and DXA: Osteoporosis Detection Rates in Postmenopausal Women
Authors: Li Na , Li Xin-min , Xu Li , Sun Wei-jie , Cheng Xiao-guang , Tian Wei
Published: March 2013

Objective. To compare the osteoporosis detection rates in postmenopausal women when measuring bone mineral density (BMD) with quantitative computed tomography (QCT) in the spine versus dual X-ray absorptiometry (DXA) in the spine and hip and to investigate the reasons for the discrepancy between the two techniques.Methods. Spinal volumetric BMD was measured with QCT, and areal spinal and hip BMDs were measured with DXA in 140 postmenopausal women. We calculated the osteoporosis detection rate for the two methods. Lumbar CT images of patients who had a discrepancy between QCT and DXA findings were reviewed to evaluate vertebral fractures, spinal degeneration, and abdominal aortic calcification.Results. For the entire 140 patients, the detection rate was 17.1% for DXA and 46.4% for QCT, a significant difference (P< 0.01). Of the 41 patients with conflicting diagnoses, 7 whose diagnosis by QCT was osteoporosis had vertebral fractures even though their DXA findings did not indicate osteoporosis. Varying degrees of spinal degeneration were seen in all of the 41 patients.Conclusion. QCT may avoid the overestimation of BMD by DXA associated with spinal degeneration, abdominal aortic calcification, and other sclerotic lesions. It may be more sensitive than DXA for detecting osteoporosis in postmenopausal women.
In VivoDetermination of Vitamin D Function Using Transgenic Mice Carrying a Human Osteocalcin Luciferase Reporter Gene
Authors: Nakanishi Tomoko , Saito Rumiko , Taniguchi Makoto , Oda Haruka , Soma Atsumi , Yasunaga Mayu , Yamane Mariko , Sato Kenzo
Published: March 2013

Vitamin D is an essential factor for ossification, and its deficiency causes rickets. Osteocalcin, which is a noncollagenous protein found in bone matrix and involved in mineralization and calcium ion homeostasis, is one of the major bone morphogenetic markers and is used in the evaluation of osteoblast maturation and osteogenic activation. We established transgenic mouse line expressing luciferase under the control of a 10-kb osteocalcin enhancer/promoter sequence. Using these transgenic mice, we evaluated the active forms of vitamins D2 and D3 for their bone morphogenetic function byin vivobioluminescence. As the result, strong activity for ossification was observed with 1α,25-hydroxyvitamin D3. Our mouse system can offer a feasible detection method for assessment of osteogenic activity in the development of functional foods and medicines by noninvasive screening.
PPARδAgonist GW501516 Inhibits PDGF-Stimulated Pulmonary Arterial Smooth Muscle Cell Function Related to Pathological Vascular Remodeling
Authors: Liu Guangjie , Li Xuan , Li Yan , Tang Xin , Xu Jie , Li Ran , Hao Peng , Sun Yongchang
Published: March 2013

Pulmonary arterial hypertension (PAH) is a severe and progressive disease, a key feature of which is pulmonary vascular remodeling. Growth factors, cytokines, and lipid mediators are involved in this remodeling process. Recent reports suggest that the peroxisome proliferator-activated receptors (PPARs) play important roles in the regulation of cell growth and differentiation as well as tissue wounding and repair. In this study, we examined the role of PPARδin the regulation of proliferation, migration, collagen synthesis, and chemokine production in human pulmonary arterial smooth muscle cells (HPASMCs). The data showed that PPARδwas the most abundant isoform in HPASMCs. PPARδwas upregulated in HPASMCs treated with PDGF, which is the major mediator in pulmonary vascular remodeling. Activation of PPARδby GW501516, a specific PPARδligand, significantly inhibited PDGF-induced proliferation in HPASMCs. The inhibitory effect of GW501516 on HPASMCs was associated with decreased expression of cyclin D1, cyclin D3, CDK2, and CDK4 as well as increased expression of the cell cycle inhibitory genes G0S2 andP27kip1. Pretreatment of HPASMCs with GW501516 significantly inhibited PDGF-induced cell migration and collagen synthesis. GW501516 also significantly attenuated TNF-mediated expression of MCP-1. These results suggest that PPARδmay be a potential therapeutic target against the progression of vascular remodeling in PAH.
Dissemination and Implementation Research Funded by the US National Institutes of Health, 2005–2012
Authors: Tinkle Mindy , Kimball Richard , Haozous Emily A. , Shuster George , Meize-Grochowski Robin
Published: March 2013

Dissemination and implementation (D&I) research is a growing area of science focused on overcoming the science-practice gap by targeting the distribution of information and adoption of interventions to public health and clinical practice settings. This study examined D&I research projects funded under specific program announcements by the US National Institutes of Health (NIH) from 2005 to 2012. The authors described the projects’ D&I strategies, funding by NIH Institute, focus, characteristics of the principal investigators (PIs) and their organizations, and other aspects of study design and setting. Results showed 46 R01s, 6 R03s, and 24 R21s funded totaling $79.2 million. The top funders were the National Cancer Institute and the National Institute of Mental Health, together providing 61% of funding. The majority of PIs were affiliated with Schools of Medicine or large, nonprofit research organizations and think tanks. Only 4% of projects were to PIs with appointments at Schools of Nursing, with 7% of the funding. The most commonly funded projects across all of the studies focused on cancer control and screening, substance abuse prevention and treatment, and mental health services. Typically implemented in community and organizational settings, D&I research provides an excellent opportunity for team science, including nurse scientists and interdisciplinary collaborators.
Nonfunctioning Juxtaglomerular Cell Tumor
Authors: Sakata Ryoko , Shimoyamada Hiroaki , Yanagisawa Masahiro , Murakami Takayuki , Makiyama Kazuhide , Nakaigawa Noboru , Inayama Yoshiaki , Ohashi Kenichi , Nagashima Yoji , Yao Masahiro , Kubota Yoshinobu
Published: March 2013

The juxtaglomerular cell tumor (JGCT) is a rare renal tumor characterized by excessive renin secretion causing intractable hypertension and hypokalemia. However, asymptomatic nonfunctioning JGCT is extremely rare. Here, we report a case of nonfunctioning JGCT in a 31-year-old woman. The patient presented with a left renal tumor without hypertension or hypokalemia. Under a clinical diagnosis of renal cell carcinoma, radical nephrectomy was performed. The tumor was located in the middle portion adjacent to the renal pelvis, measuring 2 cm in size. Pathologically, the tumor was composed of cuboidal cells forming a solid arrangement, immunohistochemically positive for renin. Based on these findings, the tumor was diagnosed as JGCT. In cases with hyperreninism, preoperative diagnosis of JGCT is straightforward but difficult in nonfunctioning case. Generally, JGCT presents a benign biological behavior. Therefore, we should take nonfunctioning JGCT into the differential diagnoses for renal tumors, especially in younger patients to avoid excessive surgery.
Function of the p38MAPK-HSP27 Pathway in Rat Lung Injury Induced by Acute Ischemic Kidney Injury
Authors: Ma Tao , Liu Xiao Wei , Liu Zhi
Published: March 2013

This study aims to observe the changes and the function of p38MAPK-HSP27 signaling pathways in acute lung injury (ALI) induced by acute ischemic kidney injury in rats. Wistar rats were randomly divided into Group A (control group), Group B (acute kidney injury group), and Group C (acute kidney injury +SB203580). The concentration of protein in BALF, neutrophil counts, PI, W/D; the concentration of TNF-α, IL-6, and IL-1βin plasma and BALF; and the concentrations of MDA and NO in the lung tissue started to increase 2 h after the experiment in Group B, which showed a significant difference compared with those in Groups A and C. The expressions of p-p38MAPK and p-HSP27 in the lung tissue began to increase 2 h after the experiment in Group B, which was different from those in Groups A and C. A significant increase was observed in the F-actin expression in Group B than that in Group A. In Group B, the correlation of cytokine TNF-α, IL-6, and p-p38MAPK in BALF was positive. Acute kidney injury (AKI) induced by bilateral renal arteriovenous clamp closure could activate p38MAPK-HSP27 signaling pathways and induce lung injury, which blocks the p38MAPK-HSP27 signal pathway to reduce the risk of lung injury.
Inhibition of NF-κB–Mediated Signaling by the Cyclin-Dependent Kinase Inhibitor CR8 Overcomes Prosurvival Stimuli to Induce Apoptosis in Chronic Lymphocytic Leukemia Cells
Authors: Cosimo Emilio , McCaig Alison M. , Carter-Brzezinski Luke J.M. , Wheadon Helen , Leach Michael T. , Le Ster Karine , Berthou Christian , Durieu Emilie , Oumata Nassima , Galons Hervé , Meijer Laurent , Michie Alison M.
Published: March 2013

Purpose: Chronic lymphocytic leukemia (CLL) is currently incurable with standard chemotherapeutic agents, highlighting the need for novel therapies. Overcoming proliferative and cytoprotective signals generated within the microenvironment of lymphoid organs is essential for limiting CLL progression and ultimately developing a cure.

Experimental Design: We assessed the potency of cyclin-dependent kinase (CDK) inhibitor CR8, a roscovitine analog, to induce apoptosis in primary CLL from distinct prognostic subsets using flow cytometry–based assays. CLL cells were cultured in in vitro prosurvival and proproliferative conditions to mimic microenvironmental signals in the lymphoid organs, to elucidate the mechanism of action of CR8 in quiescent and proliferating CLL cells using flow cytometry, Western blotting, and quantitative real-time PCR.

Results: CR8 was 100-fold more potent at inducing apoptosis in primary CLL cells than roscovitine, both in isolated culture and stromal-coculture conditions. Importantly, CR8 induced apoptosis in CD40-ligated CLL cells and preferentially targeted actively proliferating cells within these cultures. CR8 treatment induced downregulation of the antiapoptotic proteins Mcl-1 and XIAP, through inhibition of RNA polymerase II, and inhibition of NF-κB signaling at the transcriptional level and through inhibition of the inhibitor of IκB kinase (IKK) complex, resulting in stabilization of IκBα expression.

Conclusions: CR8 is a potent CDK inhibitor that subverts pivotal prosurvival and proproliferative signals present in the tumor microenvironment of CLL patient lymphoid organs. Our data support the clinical development of selective CDK inhibitors as novel therapies for CLL. Clin Cancer Res; 19(9); 2393–405. ©2013 AACR.
Assessment of Audit Methodologies for Bias Evaluation of Tumor Progression in Oncology Clinical Trials
Authors: Zhang Jenny J. , Zhang Lijun , Chen Huanyu , Murgo Anthony J. , Dodd Lori E. , Pazdur Richard , Sridhara Rajeshwari
Published: March 2013

As progression-free survival (PFS) has become increasingly used as the primary endpoint in oncology phase III trials, the U.S. Food and Drug Administration (FDA) has generally required a complete-case blinded independent central review (BICR) of PFS to assess and reduce potential bias in the investigator or local site evaluation. However, recent publications and FDA analyses have shown a high correlation between local site evaluation and BICR assessments of the PFS treatment effect, which questions whether complete-case BICR is necessary. One potential alternative is to use BICR as an audit tool to detect evaluation bias in the local site evaluation. In this article, the performance characteristics of two audit methods proposed in the literature are evaluated on 26 prospective, randomized phase III registration trials in nonhematologic malignancies. The results support that a BICR audit to assess potential bias in the local site evaluation is a feasible approach. However, implementation and logistical challenges need further consideration and discussion. Clin Cancer Res; 19(10); 2637–45. ©2013 AACR.
Effect of Intermittent Dosing Regimens of Erlotinib on Methylnitrosourea-Induced Mammary Carcinogenesis
Authors: Lubet Ronald A. , Szabo Eva , Iwata Kenneth K. , Gill Stanley C. , Tucker Chris , Bode Ann , Steele Vernon E. , Juliana M. Margaret , Nicastro Holly L. , Grubbs Clinton J.
Published: March 2013

EGF receptor (EGFR) inhibitors are used in the therapy of lung and pancreatic cancers and effectively prevent cancers in multiple animal models. Although daily dosing with erlotinib is effective, weekly dosing may reduce toxicity and have advantages, particularly for prevention. We tested alternative dosing regimens for preventive/therapeutic efficacy in a rat mammary cancer model. For prevention, erlotinib was administered by gavage beginning 5 days after methylnitrosourea (MNU). For therapy and biomarker studies, rats with palpable mammary cancers were treated for six weeks or for six days, respectively. Experiment A, erlotinib (6 mg/kg body weight/day, intragastric): daily (7 times/week); one day on/one day off; and two days on/two days off. All regimens decreased tumor incidence, increased tumor latency, and decreased cancer multiplicity versus controls (P < 0.01). However, intermittent dosing was less effective than daily dosing (P < 0.05). Experiment B, erlotinib (6 mg/kg body weight/day) daily or two days on/two days off or one time per week at 42 mg/kg body weight. All regimens reduced cancer incidence and multiplicity versus controls (P < 0.01). Interestingly, daily and weekly dosing were equally effective (P > 0.5). Experiment C, erlotinib administered at 42 or 21 mg/kg body weight 1 time per week, decreased tumor incidence and multiplicity (P < 0.01). Erlotinib had a serum half-life of ≤8 hours and weekly treatment yielded effective serum levels for ≤48 hours. Daily or weekly treatment of cancer bearing rats reduced mammary tumor size 25% to 35%, whereas control cancers increased >250%. Levels of phosphorylated extracellular signal-regulated kinase (ERK) were strongly decreased in rats treated daily/weekly with erlotinib. Thus, altering the dose of erlotinib retained most of its preventive and therapeutic efficacy, and based on prior clinical studies, is likely to reduce its toxicity. Cancer Prev Res; 6(5); 448–54. ©2013 AACR.
De-Repression of PDGFRβ Transcription Promotes Acquired Resistance to EGFR Tyrosine Kinase Inhibitors in Glioblastoma Patients
Authors: Akhavan David , Pourzia Alexandra L. , Nourian Alex A. , Williams Kevin J. , Nathanson David , Babic Ivan , Villa Genaro R. , Tanaka Kazuhiro , Nael Ali , Yang Huijun , Dang Julie , Vinters Harry V. , Yong William H. , Flagg Mitchell , Tamanoi Fuyuhiko , Sasayama Takashi , James C. David , Kornblum Harley I. , Cloughesy Tim F. , Cavenee Webster K. , Bensinger Steven J. , Mischel Paul S.
Published: March 2013

Acquired resistance to tyrosine kinase inhibitors (TKI) represents a major challenge for personalized cancer therapy. Multiple genetic mechanisms of acquired TKI resistance have been identified in several types of human cancer. However, the possibility that cancer cells may also evade treatment by co-opting physiologically regulated receptors has not been addressed. Here, we show the first example of this alternate mechanism in brain tumors by showing that EGF receptor (EGFR)-mutant glioblastomas (GBMs) evade EGFR TKIs by transcriptionally de-repressing platelet-derived growth factor receptor β (PDGFRβ). Mechanistic studies show that EGFRvIII signaling actively suppresses PDGFRβ transcription in an mTORC1- and extracellular signal–regulated kinase-dependent manner. Genetic or pharmacologic inhibition of oncogenic EGFR renders GBMs dependent on the consequently de-repressed PDGFRβ signaling for growth and survival. Importantly, combined inhibition of EGFR and PDGFRβ signaling potently suppresses tumor growth in vivo. These data identify a novel, nongenetic TKI resistance mechanism in brain tumors and provide compelling rationale for combination therapy.

Significance: These results provide the first clinical and biologic evidence for receptor tyrosine kinase (RTK) “switching” as a mechanism of resistance to EGFR inhibitors in GBM and provide a molecular explanation of how tumors can become “addicted” to a nonamplified, nonmutated, physiologically regulated RTK to evade targeted treatment. Cancer Discov; 3(5); 534–47. ©2013 AACR.

This article is highlighted in the In This Issue feature, p. 471