bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of T and B cell repertoire diversity in patients with RAG deficiency
Authors: Lee Yu Nee , Frugoni Francesco , Dobbs Kerry , Tirosh Irit , Du Likun , Ververs Francesca A. , Ru Heng , de Bruin Lisa Ott , Adeli Mehdi , Bleesing Jacob H. , Buchbinder David , Butte Manish J. , Cancrini Caterina , Chen Karin , Choo Sharon , Elfeky Reem A. , Finocchi Andrea , Fuleihan Ramsay L. , Gennery Andrew R. , El-Ghoneimy Dalia H. , Henderson Lauren A. , Al-Herz Waleed , Hossny Elham , Nelson Robert P. , Pai Sung-Yun , Patel Niraj C. , Reda Shereen M. , Soler-Palacin Pere , Somech Raz , Palma Paolo , Wu Hao , Giliani Silvia , Walter Jolan E. , Notarangelo Luigi D.
Published: December 2016

Differences in B and T cell repertoires in patients with RAG deficiency associate with clinical severity.
ECG non-specific ST-T and QTc abnormalities in patients with systemic lupus erythematosus compared with rheumatoid arthritis
Authors: Geraldino-Pardilla Laura , Gartshteyn Yevgeniya , Piña Paloma , Cerrone Marina , Giles Jon T , Zartoshti Afshin , Bathon Joan M , Askanase Anca D
Published: December 2016

Objectives

Cardiovascular disease (CVD) is a leading cause of death in systemic lupus erythematosus (SLE) and in rheumatoid arthritis (RA). Although only explored in one study, ECG non-specific ST-T abnormalities, in addition to corrected QT-interval (QTc) prolongation, were recently reported in an SLE inception cohort. Importantly, these ECG abnormalities are known predictors of CVD mortality in the general population, yet their prevalence in patients with established SLE has not been evaluated.

Methods

We cross-sectionally investigated the presence of non-specific ST-T and QTc abnormalities in 50 patients with SLE, predominantly Hispanic and black, without CVD or SLE-related cardiac involvement and compared them with 139 patients with RA without CVD. Demographics, disease-specific characteristics and CVD risk factors were ascertained and adjusted for.

Results

Patients with SLE (mean age 36±13 years, 92% women, 6 years median disease duration, 96% Hispanics and blacks) had a 3.3-fold higher adjusted prevalence of non-specific ST-T abnormalities (56% vs 17%; p <0.0001) compared with RA, despite the older age and higher percentage of men in the RA group. The QTc was 26 ms longer in SLE compared with RA (p=0.002) in the setting of a higher percentage of women, blacks, Hispanics and higher C reactive protein levels in the SLE group.

Conclusions

This study demonstrates a high prevalence of ECG abnormalities in predominantly Hispanic and black patients with SLE. Longitudinal evaluation of the progression to potentially life-threatening arrhythmias and/or cardiovascular events is warranted.
Novel method of delivery of continuous positive airway pressure for apnea testing during brain death evaluation
Authors: Hubbard Jennifer L , Dirks Rachel C , Veneman Wade L , Davis James W
Published: December 2016

Background

There are several methods for apnea testing for the evaluation of neurological death, including oxygen via T-piece, oxygen cannula inserted into the endotracheal tube, and continuous positive airway pressure (CPAP). Lung suitability for transplantation is determined in part by the partial pressure of arterial oxygen (PaO2) to fraction of inspired oxygen (FiO2; P:F) ratio. We hypothesized that delivery of CPAP during apnea testing using a novel method would improve post-test P:F ratios.

Methods

A retrospective review was performed at a level I trauma center for all patients undergoing apnea testing from 2010 to 2016. The CPAP system used a flow-inflating bag and was made available in 2012. It was used at the discretion of the clinician. Patients were classified as having an apnea test by CPAP or by non-CPAP method (T-piece, oxygen cannula in endotracheal tube, etc). The two groups were compared for baseline characteristics and the primary outcome of postapnea test P:F ratio.

Results

During the study period, 145 patients underwent apnea testing; 67 patients by the CPAP method and 78 by non-CPAP method. There were no significant differences in demographics, mechanism of brain injury, pneumonia rate, smoking status, or antibiotic usage between the two groups. The pretest P:F ratio was similar between groups, but the CPAP group had significantly higher post-test P:F ratio (304 vs 250, p=0.02). There were no reported complications arising from CPAP use.

Conclusions

We describe a novel method of delivering CPAP by a flow-inflating bag during examination for brain death. This method led to improved oxygenation, P:F ratios, and may decrease barotrauma. The flow-inflating bag was inexpensive, easily implemented, and without adverse effects. Multicentered, prospective trials are needed to elicit significant benefit in lung donation and transplantation.

Level of evidence

Level IV, diagnostic tests.
Long-term low dose dietary resveratrol supplement reduces cardiovascular structural and functional deterioration in chronic heart failure in rats
Authors: Ahmet Ismayil , Tae Hyun-Jin , Lakatta Edward G. , Talan Mark
Published: December 2016

A short-term exposure to resveratrol at high dosages exerts a remarkable cardioprotective effect. Whether a long-term exposure to resveratrol at low dosages that can be obtained through consumption of a resveratrol-rich diet is beneficial to heart diseases is unknown. We tested the effects of a resveratrol-enriched diet on cardiovascular remodeling of chronic heart failure (CHF) in rats resulting from permanent ligation of left coronary artery. Two weeks after surgery, rats were started on either a resveratrol-enriched (R; 5 mg/kg per day; n = 23) or normal (Control; n = 23) diet for next 10 months. Serial echocardiography in Control showed a significant decline in LV ejection fraction, increases in LV end-systolic and end-diastolic volumes, and expansion in myocardial infarct from pre-treatment values. In R, compared with Control, there were substantial improvements in those parameters. End-point LV pressure-volume loop analysis showed a significantly improved LV systolic function and AV-coupling, an index of energy transfer efficacy between the heart and aortic tree, in R compared with Control (p < 0.05). Aortic pulse wave velocity, a measure of arterial stiffness, was significantly lower in R (389 ± 15 cm/s; p < 0.05) compared with Control (489 ± 38 cm/s). These results demonstrated that long-term dietary resveratrol supplement reduces cardiovascular structural and functional deterioration in CHF.
Scalar mass stability bound in a simple Yukawa-theory from renormalization group equations
Authors: Jakovác A. , Kaposvári I. , Patkós A.
Published: December 2016

Functional renormalization group (FRG) equations are constructed for a simple Yukawa-model with discrete chiral symmetry, including also the effect of a nonzero composite fermion background beyond the conventional scalar condensate. The evolution of the effective potential of the model, generically depending on two invariants, is explored with the help of power series expansions. Systematic investigation of the effect of a class of irrelevant operators on the lower (stability) bound allows a non-perturbative extension of the maximal cutoff value consistent with any given mass of the scalar field.
Dendritic cells and isolevuglandins in immunity, inflammation, and hypertension
Authors: Dixon Kala B. , Davies Sean S. , Kirabo Annet
Published: December 2016

Hypertension is the major risk factor for morbidity and mortality from myocardial infarction, stroke, heart failure, and chronic kidney disease. Despite its importance, the pathogenesis of essential hypertension is poorly understood. During the past several years, it has become evident that T cells contribute to hypertension. Activated T cells accumulate in the perivascular space and the kidney and release cytokines that promote vascular dysfunction and end-organ damage. Although dendritic cells play a pivotal role in initiating adaptive immune responses, T cells have taken center stage in studies implicating the immune system in the genesis of hypertension. The mechanisms by which T cells are activated and the antigens involved are poorly understood. We recently showed that hypertension is associated with increased dendritic cell production of the TH17 polarizing cytokines, IL-6, IL-1β, and IL-23. This occurs in part by increased superoxide production via NADPH oxidase and protein modification by highly reactive isolevuglandins (IsoLGs). IsoLGs are produced via the isoprostane pathway of free radical-mediated lipid peroxidation and, when adducted to proteins, have the potential to act as neoantigens. In this review, we discuss recent advances in our understanding of the role of antigen-presenting dendritic cells in the pathophysiology of hypertension and highlight potential neoantigens that may contribute to this disease.
A Hybrid Forecasting Model Based on Empirical Mode Decomposition and the Cuckoo Search Algorithm: A Case Study for Power Load
Authors: Heng Jiani , Wang Chen , Zhao Xuejing , Wang Jianzhou
Published: December 2016

Power load forecasting always plays a considerable role in the management of a power system, as accurate forecasting provides a guarantee for the daily operation of the power grid. It has been widely demonstrated in forecasting that hybrid forecasts can improve forecast performance compared with individual forecasts. In this paper, a hybrid forecasting approach, comprising Empirical Mode Decomposition, CSA (Cuckoo Search Algorithm), and WNN (Wavelet Neural Network), is proposed. This approach constructs a more valid forecasting structure and more stable results than traditional ANN (Artificial Neural Network) models such as BPNN (Back Propagation Neural Network), GABPNN (Back Propagation Neural Network Optimized by Genetic Algorithm), and WNN. To evaluate the forecasting performance of the proposed model, a half-hourly power load in New South Wales of Australia is used as a case study in this paper. The experimental results demonstrate that the proposed hybrid model is not only simple but also able to satisfactorily approximate the actual power load and can be an effective tool in planning and dispatch for smart grids.
Computer and Hardware Modeling of Periodically Forcedϕ6-Van der Pol Oscillator
Authors: Adelakun A. O. , Njah A. N. , Olusola O. I. , Wara S. T.
Published: December 2016

Numerical simulation results for the dynamics ofϕ6-systems abound in the literature but their experimental results are yet to be known. This paper presents the chaotic dynamics ofϕ6-Van der Pol oscillator via electronic design, simulation, and hardware implementation. The results obtained are found to be in good agreement with numerical simulation results. The condition for stability of the fixed points is also computed and the method of multiple time scale is used to investigate the dynamical behaviour of the system. Therefore, theϕ6-circuits which have rich dynamics and may have important applications in secure communications, random number generations, cryptography, and so forth have been practically implemented.
Fuzzy Logic versus Classical Logic: An Example in Multiplicative Ideal Theory
Authors: Heubo-Kwegna Olivier A.
Published: December 2016

We discuss a fuzzy result by displaying an example that shows how a classical argument fails to work when one passes from classical logic to fuzzy logic. Precisely, we present an example to show that, in the fuzzy context, the fact that the supremum is naturally used in lieu of the union can alter an argument that may work in the classical context.
Global Stability of Delayed Viral Infection Models with Nonlinear Antibody and CTL Immune Responses and General Incidence Rate
Authors: Miao Hui , Teng Zhidong , Li Zhiming
Published: December 2016

The dynamical behaviors for a five-dimensional viral infection model with three delays which describes the interactions of antibody, cytotoxic T-lymphocyte (CTL) immune responses, and nonlinear incidence rate are investigated. The threshold values for viral infection, antibody response, CTL immune response, CTL immune competition, and antibody competition, respectively, are established. Under certain assumptions, the threshold value conditions on the global stability of the infection-free, immune-free, antibody response, CTL immune response, and interior equilibria are proved by using the Lyapunov functionals method, respectively. Immune delay as a bifurcation parameter is further investigated. The numerical simulations are performed in order to illustrate the dynamical behavior of the model.
Gamma‐Glutamylcysteine Ethyl Ester Protects against Cyclophosphamide‐Induced Liver Injury and Hematologic Alterations via Upregulation of PPARγ and Attenuation of Oxidative Stress, Inflammation, and Apoptosis
Authors: Alqahtani Sultan , Mahmoud Ayman M.
Published: December 2016

Gamma‐glutamylcysteine ethyl ester (GCEE) is a precursor of glutathione (GSH) with promising hepatoprotective effects. This investigation aimed to evaluate the hepatoprotective effects of GCEE against cyclophosphamide‐ (CP‐) induced toxicity, pointing to the possible role of peroxisome proliferator activated receptor gamma (PPARγ). Wistar rats were given GCEE two weeks prior to CP. Five days after CP administration, animals were sacrificed and samples were collected. Pretreatment with GCEE significantly alleviated CP‐induced liver injury by reducing serum aminotransferases, increasing albumin, and preventing histopathological and hematological alterations. GCEE suppressed lipid peroxidation and nitric oxide production and restored GSH and enzymatic antioxidants in the liver, which were associated with downregulation of COX‐2, iNOS, and NF‐κB. In addition, CP administration significantly increased serum proinflammatory cytokines and the expression of liver caspase‐3 and BAX, an effect that was reversed by GCEE. CP‐induced rats showed significant downregulation of PPARγ which was markedly upregulated by GCEE treatment. These data demonstrated that pretreatment with GCEE protected against CP‐induced hepatotoxicity, possibly by activating PPARγ, preventing GSH depletion, and attenuating oxidative stress, inflammation, and apoptosis. Our findings point to the role of PPARγ and suggest that GCEE might be a promising agent for the prevention of CP‐induced liver injury.
Preparation and Characterisation of ZnO/NiO Nanocomposite Particles for Solar Cell Applications
Authors: Kerli S. , Alver Ü.
Published: December 2016

The mixture of ZnO and NiO effect on solar cell has been investigated. ZnO and NiO particles were produced by hydrothermal method and the produced particles were annealed at 500°C for 1 hour. Crystal structure and morphological properties of particles were examined by X-ray diffraction (XRD) and scanning electron microscope (SEM). XRD measurements showed that ZnO particles have a hexagonal wurtzite structure and NiO particles have a cubic structure. SEM results show that both ZnO and NiO particles are the form of nanoparticles. Dye-sensitized solar cells were fabricated by N-719 (Ruthenium) dyes and mixing ZnO/NiO particles in different ratios, 100/0, 50/50, and 0/100. It was observed that the solar cells made with ZnO have the highest performance with the efficiency of 0.542%. In addition, it was observed that when amount of NiO ratio increases in the mixture of ZnO/NiO, the efficiencies of DSSCs were observed to decrease.
Management of Malignant Pleural Effusion with ASEPT® Pleural Catheter: Quality of Life, Feasibility, and Patient Satisfaction
Authors: Dhaliwal Inderdeep , Mahdavian Masoud , Asghari Shabnam , Chun To Wong Benson , Labelle Rosalie , Amjadi Kayvan
Published: December 2016

Objective. The PleurX® IPC system has been used extensively in the past. Over time, management of MPE with the PleurX system can be costly. The new ASEPT pleural catheter, through advantages in design, may ultimately show cost savings. The primary outcome of this study was to evaluate safety and efficacy of the ASEPT system.Method. This single centre, prospective study enrolled 50 patients with MPE, who were followed for as long as they were alive with a catheter. Quality of Life (QoL) was assessed before, at 2 weeks, and 6 weeks after ASEPT catheter insertion using the EORTC QLQ-C30 and LC13 questionnaires. Ease of catheter use and complications were reported by physician and community nurses.Results. 50 patients with MPE with a mean age of64.5±1.9, BDI of2.8±0.9, and ECOG score of3.0±0.7were recruited. No immediate or long-term complications were reported during the study period. Compared to precatheter insertion, global health status (−18,p<0.001), QLQ-C30 dyspnea (−39,p<0.00001), and LC13 dyspnea (−11,p<0.0005) significantly improved at 2 and 6 weeks after intervention. Provider surveys indicated favourable ease of use.Conclusion. The new ASEPT catheter offers a safe and effective option for the management of MPE.
Prevalence and Antimicrobial Resistance ofSalmonellaIsolated from Animal-Origin Food Items in Gondar, Ethiopia
Authors: Ejo Mebrat , Garedew Legesse , Alebachew Zabishwork , Worku Walelgn
Published: December 2016

Salmonellahas been found to be the major cause of foodborne diseases and a serious public health problem in the world, with an increasing concern for the emergence and spread of antimicrobial-resistant strains. A cross-sectional study was conducted between February 2014 and December 2015 on food items of animal origin to assess the prevalence and antimicrobial resistance profiles ofSalmonellaisolates using standard bacteriological methods. The overall prevalence rate of 5.5% was recorded from the total analyzed food items of animal origin.Salmonellaisolates were detected from 12% of raw meat, 8% of minced meat, 2.9% of burger samples, 18% of raw eggs, and 6% of raw milk. Furthermore, antimicrobial susceptibility test identified 47.6% resistantSalmonellaisolates, 28.6% intermediately sensitive isolates, and 23.8% susceptible isolates. AmongSalmonellaisolates tested, 42.6%, 28.6%, and 14.3% were found to be relatively resistant to tetracycline, sulfamethoxazole-trimethoprim, and ampicillin, respectively, while 9.5%–19% were intermediately resistant to tetracycline, amoxicillin, ampicillin, cephalothin, and nitrofurantoin. Therefore, our findings provide the prevalence and drug resistance ofSalmonellafrom foods of animal origin and contribute information to scientists as well as public health researchers to minimize the prevalent and resistant foodborneSalmonellaspecies in Ethiopia.
TAMH: A Useful In Vitro Model for Assessing Hepatotoxic Mechanisms
Authors: Davis Madison , Stamper Brendan D.
Published: December 2016

In vitro models for hepatotoxicity can be useful tools to predict in vivo responses. In this review, we discuss the use of the transforming growth factor-αtransgenic mouse hepatocyte (TAMH) cell line, which is an attractive model to study drug-induced liver injury due to its ability to retain a stable phenotype and express drug-metabolizing enzymes. Hepatotoxicity involves damage to the liver and is often associated with chemical exposure. Since the liver is a major site for drug metabolism, drug-induced liver injury is a serious health concern for certain agents. At the molecular level, various mechanisms may protect or harm the liver during drug-induced hepatocellular injury including signaling pathways and endogenous factors (e.g., Bcl-2, GSH, Nrf2, or MAPK). The interplay between these and other pathways in the hepatocyte can change upon drug or drug metabolite exposure leading to intracellular stress and eventually cell death and liver injury. This review focuses on mechanistic studies investigating drug-induced toxicity in the TAMH line and how alterations to hepatotoxic mechanisms in this model relate to the in vivo situation. The agents discussed herein include acetaminophen (APAP), tetrafluoroethylcysteine (TFEC), flutamide, PD0325901, lapatinib, and flupirtine.
Matrix Quasinorms Induced by Maximal and Minimal Vector Norms
Authors: Park Jong-Do
Published: December 2016

In the set of all vector norms inCn, there exist maximal and minimal complex norms which coincide with the real Euclidean norm inRn. The purpose of this paper is to introduce new quasinorms defined on complex matrices. These two matrix quasinorms are induced by maximal and minimal complex vector norms. We also prove the dual relation between these two quasinorms.
Study on Helicopter Antitorque Device Based on Cross-Flow Fan Technology
Authors: Siliang Du , Zhengfei Tang , Pei Xu , Mengjiang Ji
Published: December 2016

In order to improve low-altitude flight security of single-rotor helicopter, an experimental model of a helicopter antitorque device is developed for wind tunnel test. The model is based on the flow control technology of the cross-flow fan (CFF). Wind tunnel tests show that the model can produce side force. It is concluded that the influence of the CFF rotating speed, the rotor collective pitch, and the forward flight speed on the side force of the model is great. At the same time, the numerical simulation calculation method of the model has been established. Good agreement between experimental and numerical side force and power shows that results of numerical solution are reliable. Therefore, the results in actual helicopter obtained from Computational Fluid Dynamics (CFD) solution are acceptable. This proves that this antitorque device can be used for a helicopter.
Physical and Acoustical Properties of Corn Husk Fiber Panels
Authors: Sari Nasmi Herlina , Wardana I. N. G. , Irawan Yudy Surya , Siswanto Eko
Published: December 2016

This research focuses on the development of a sustainable acoustic material comprising natural fibers of corn husk that were alkali modified by 1%, 2%, 5%, and 8% NaOH. The morphology and the acoustical, physical, and mechanical properties of the resulting fibers were experimentally investigated. Five different types of sample were produced in panel form, the acoustical properties of which were studied using a two-microphone impedance tube test. The porosity, tortuosity, and airflow resistivity of each panel were investigated, tensile tests were conducted, and the morphological aspects were evaluated via scanning electron microscopy. The sound absorption and tensile properties of the treated panels were better than those of raw fiber panels; the treated panels were of high airflow resistivity and had low porosity. Scanning electron micrographs of the surfaces of the corn husk fibers revealed that the different sound absorption properties of these panels were due to roughness and the lumen structures.
Returning for HIV Test Results: A Systematic Review of Barriers and Facilitators
Authors: Ngangue Patrice , Bedard Emmanuelle , Zomahoun Hervé Tchala Vignon , Payne-Gagnon Julie , Fournier Claudia , Afounde Jeannette , Gagnon Marie-Pierre
Published: December 2016

This systematic review aims to identify factors that facilitate or hinder the return for HIV test results. Four electronic databases were searched. Two independent reviewers selected eligible publications based on inclusion/exclusion criteria. Quantitative studies published since 1985 were included. Thirty-six studies were included in the final review. Individual level barriers included sociodemographic characteristics, such as being a male, of young age and low education level, risk behaviours such as injecting drugs, having multiple sexual partners, and psychosocial factors. Older age, higher education level, being a woman, having high self-esteem, having coping skills, and holding insurance coverage were identified as facilitators. Interpersonal barriers and facilitators were linked to risk behaviours of sexual partners. Contextual barriers included essentially the HIV testing center and its characteristics. This review identified the most important factors that need to be addressed to ensure that people return for their HIV test results.
Study of the Influences of Transient Crack Propagation in a Pinion on Time-Varying Mesh Stiffness
Authors: Hu Youmin , Fan Jikai , Yu Jin
Published: December 2016

Cracks in a cracked gear may further propagate by a tiny length in a very short time for several reasons, such as material fatigue and load fluctuations. In this paper, this dynamic process is defined as transient propagation of cracks. This research aims to calculate the time-varying mesh stiffness of gears when transient propagation of cracks arises, which has not been extensively studied in existing literatures. The transient propagation of cracks is modelled. An improved potential energy method is proposed by incorporating the propagation model into the potential energy method. The improved method can also be utilised to calculate the mesh stiffness of gears when transient propagation of cracks arises. Different transient propagation models are considered to simulate the propagation of cracks in a short amount of time. Different deterioration levels of cracks before transient propagation and different lengths and models of transient propagation are also examined. The variation rules of mesh stiffness caused by the transient propagation of cracks are summarised. The influence of the deterioration level of cracks on mesh stiffness variation when transient propagation arises is obtained. Simulation results show that the proposed method accurately calculates time-varying mesh stiffness when transient propagation of cracks arises. Furthermore, the method improves the monitoring of further propagation of cracks in gears from the perspective of time-varying mesh stiffness.
The Rational Solutions and Quasi-Periodic Wave Solutions as well as Interactions ofN-Soliton Solutions for 3 + 1 Dimensional Jimbo-Miwa Equation
Authors: Yang Hongwei , Zhang Yong , Zhang Xiaoen , Chen Xin , Xu Zhenhua
Published: December 2016

The exact rational solutions, quasi-periodic wave solutions, andN-soliton solutions of 3 + 1 dimensional Jimbo-Miwa equation are acquired, respectively, by using the Hirota method, whereafter the rational solutions are also called algebraic solitary waves solutions and used to describe the squall lines phenomenon and explained possible formation mechanism of the rainstorm formation which occur in the atmosphere, so the study on the rational solutions of soliton equations has potential application value in the atmosphere field; the soliton fission and fusion are described based on the resonant solution which is a special form of theN-soliton solutions. At last, the interactions of the solitons are shown with the aid ofN-soliton solutions.
Investigation of Indoor Stability Testing of Polymer Solar Cell
Authors: Kavak Pelin , Alturk Parlak Elif
Published: December 2016

We have fabricated organic solar cell of a new low bandgap polymer poly[4,4-bis(2-ethylhexyl)-4H-cyclopenta[2,1-b:3,4-b′]dithiophene-2,6-diyl-alt-4,7-bis(2-thienyl)-2,1,3-benzothiadiazole-5′,5′′-diyl] (PCPDTTBTT). We have investigated for the first time the stability tests, ISOS-L-1 and ISOS-D-3, of PCPDTTBTT solar cells. Thermal annealing of PCPDTTBTT solar cells at 80°C brought about an improvement of photocurrent generation, stability, and efficiency of the solar cells. T80 value of PCPDTTBTT solar cell is about 150 hours which is close to P3HT (235 h). PCPDTTBTT is very promising polymer for both polymer solar cell efficiency and stability.
Bufalin Inhibits Proliferation and Induces Apoptosis in Osteosarcoma Cells by Downregulating MicroRNA‐221
Authors: Zhang Jianjun , Sha Jingjing , Zhou Yan , Han Kun , Wang Yaling , Su Yang , Yin Xiuyi , Hu Haiyan , Yao Yang
Published: December 2016

Bufalin, a major component of the Chinese medicine ChanSu, which is prepared from the skin and parotid venom glands of toads, has shown cytotoxicity in several malignant tumors. Here, we reported that bufalin inhibited proliferation and induced mitochondria‐dependent apoptosis in U‐2OS and Saos‐2 osteosarcoma cells with intracellular reactive oxygen species (ROS) production. By microRNA (miR) array analysis and quantitative reverse transcription polymerase chain reaction, we found that miR‐221 was downregulated after treatment with bufalin. In accordance with TargetScan prediction and luciferase reporter assay, Bcl2 binding component 3 (BBC3) was the direct target of miR‐221. Furthermore, upregulating miR‐221 by its MIMIC and suppressing BBC3 by small interfering RNA (siRNA) reversed the effects of bufalin on osteosarcoma cells. Collectively, our data indicate that bufalin inhibits cell proliferation and induces mitochondria‐dependent apoptosis in osteosarcoma cells through downregulating miR‐221 and triggering BBC3 expression.
Chebyshev Collocation Method for Parabolic Partial Integrodifferential Equations
Authors: Sameeh M. , Elsaid A.
Published: December 2016

An efficient technique for solving parabolic partial integrodifferential equation is presented. This technique is based on Chebyshev polynomials and finite difference method.A priorierror estimate for the proposed technique is deduced. Some examples are presented to illustrate the validity and efficiency of the presented method.
An Improved Algorithm for Noise Source Localization Based on Equivalent Source Method
Authors: Xu Zhongming , Wang Qinghua , He Yansong , Zhang Zhifei , Li Shu , Li Mengran
Published: December 2016

Near-field acoustical holography (NAH) based on the equivalent source method (ESM) is an efficient method applied for noise source identification. Asl2-norm-based regularization cannot produce a satisfactory solution of the ill-conditioned problem in high frequency, the conventional ESM is restricted to relatively low frequency, and the resolution of conventional ESM in middle to high frequency remains a limitation open to investigation. This article presents an algorithm known as improved functional equivalent source method (IFESM), designed to enhance the resolution of conventional ESM. This method is developed in the framework of wideband acoustical holography (WBH) combining with functional beamforming (FB). Through numerical simulations, it is proved that the proposed method can localize noise with higher resolution compared with WBH and conventional ESM, and the ghosts on noise source map can be suppressed effectively. The validity and the feasibility of the proposed method are manifested by experiments including single-source and coherent-source localization.
Colectomy Rates for Ulcerative Colitis Differ between Ethnic Groups: Results from a 15-Year Nationwide Cohort Study
Authors: Misra Ravi , Askari Alan , Faiz Omar , Arebi Naila
Published: December 2016

Introduction. Previous epidemiological studies suggest a higher rate of pancolonic disease in South Asians (SA) compared with White Europeans (WE). The aim of the study was to compare colectomy rates for ulcerative colitis (UC) in SA to those of WE.Methods. Patients with UC were identified from a national administrative dataset (Hospital Episode Statistics, HES) between 1997 and 2012 according to ICD-10 diagnosis code K51 for UC. The colectomy rate for each ethnic group was calculated as the proportion of patients who underwent colectomy from the total UC cases for that group.Results. Of 212,430 UC cases, 73,318 (35.3%) were coded for ethnicity. There was no significant difference in the colectomy rate between SA and WE (6.93% versus 6.90%). Indians had a significantly higher colectomy rate than WE (9.8% versus 6.9%,p<0.001). Indian patients were 21% more likely to require colectomy for UC compared with WE group (OR: 1.21, 95% CI: 1.04–1.42, andp=0.001).Conclusions. Given the limitations in coding, the colectomy rate in this cohort was higher in Indians compared to WE. A prospectively recruited ethnic cohort study will decipher whether this reflects a more aggressive phenotype or is due to other confounding factors.
Pediatric Traumatic Brain Injury and Autism: Elucidating Shared Mechanisms
Authors: Singh Rahul , Turner Ryan C. , Nguyen Linda , Motwani Kartik , Swatek Michelle , Lucke-Wold Brandon P.
Published: December 2016

Pediatric traumatic brain injury (TBI) and autism spectrum disorder (ASD) are two serious conditions that affect youth. Recent data, both preclinical and clinical, show that pediatric TBI and ASD share not only similar symptoms but also some of the same biologic mechanisms that cause these symptoms. Prominent symptoms for both disorders include gastrointestinal problems, learning difficulties, seizures, and sensory processing disruption. In this review, we highlight some of these shared mechanisms in order to discuss potential treatment options that might be applied for each condition. We discuss potential therapeutic and pharmacologic options as well as potential novel drug targets. Furthermore, we highlight advances in understanding of brain circuitry that is being propelled by improved imaging modalities. Going forward, advanced imaging will help in diagnosis and treatment planning strategies for pediatric patients. Lessons from each field can be applied to design better and more rigorous trials that can be used to improve guidelines for pediatric patients suffering from TBI or ASD.
Ethnobotanical Research at the Kutukú Scientific Station, Morona-Santiago, Ecuador
Authors: Ballesteros Jose Luis , Bracco Francesco , Cerna Marco , Vita Finzi Paola , Vidari Giovanni
Published: December 2016

This work features the results of an ethnobotanical study on the uses of medicinal plants by the inhabitants of the region near to the Kutukú Scientific Station of Universidad Politécnica Salesiana, located in the Morona-Santiago province, southeast of Ecuador. In the surroundings of the station, one ethnic group, the Shuar, has been identified. The survey hereafter reports a total of 131 plant species, with 73 different therapeutic uses.
Enhanced Next Generation Millimeter-Wave Multicarrier System with Generalized Frequency Division Multiplexing
Authors: Shimodaira Hidekazu , Kim Joongheon , Sadri Ali S.
Published: December 2016

Orthogonal Frequency Division Multiplexing (OFDM) is a popular multicarrier technique used to attain high spectral efficiencies. It also has other advantages such as multipath tolerance and ease of implementation. However, OFDM based systems suffer from high Peak-to-Average Power Ratio (PAPR) problem. Because of the nonlinearity of the power amplifiers, the high PAPR causes significant distortion in the transmitted signal for millimeter-wave (mmWave) systems. To alleviate the high PAPR problem, this paper utilizes Generalized Frequency Division Multiplexing (GFDM) which can achieve high spectral efficiency as well as low PAPR. In this paper, we show the performance of GFDM using the IEEE 802.11ad multicarrier frame structures. IEEE 802.11ad is considered one of the most successful industry standards utilizing unlicensed mmWave frequency band. In addition, this paper indicates the feasibility of using GFDM for the future standards such as IEEE 802.11ay. This paper studies the performance improvements in terms of PAPR reduction for GFDM. Based on the performance results, the optimal numbers of subcarriers and subsymbols are calculated for PAPR reduction while minimizing the Bit Error Rate (BER) performance degradation. Moreover, transmitter side ICI (Intercarrier Interference) reduction is introduced to reduce the receiver load.
Lead Selenide Nanostructures Self-Assembled across Multiple Length Scales and Dimensions
Authors: Wujcik Evan K. , Aceto Stephanie R. , Narayanan Radha , Bose Arijit
Published: December 2016

A self-assembly approach to lead selenide (PbSe) structures that have organized across multiple length scales and multiple dimensions has been achieved. These structures consist of angstrom-scale 0D PbSe crystals, synthesized via a hot solution process, which have stacked into 1D nanorods via aligned dipoles. These 1D nanorods have arranged into nanoscale 2D sheets via directional short-ranged attraction. The nanoscale 2D sheets then further aligned into larger 2D microscale planes. In this study, the authors have characterized the PbSe structures via normal and cryo-TEM and EDX showing that this multiscale multidimensional self-assembled alignment is not due to drying effects. These PbSe structures hold promise for applications in advanced materials—particularly electronic technologies, where alignment can aid in device performance.
Association between Body Mass Index and Cancer Survival in a Pooled Analysis of 22 Clinical Trials
Authors: Greenlee Heather , Unger Joseph M. , LeBlanc Michael , Ramsey Scott , Hershman Dawn L.
Published: December 2016

Background: Data are inconsistent on the association between body mass index (BMI) at time of cancer diagnosis and prognosis. We used data from 22 clinical treatment trials to examine the association between BMI and survival across multiple cancer types and stages.

Methods: Trials with ≥5 years of follow-up were selected. Patients with BMI < 18.5 kg/m2 were excluded. Within a disease, analyses were limited to patients on similar treatment regimens. Variable cutpoint analysis identified a BMI cutpoint that maximized differences in survival. Multivariable Cox regression analyses compared survival between patients with BMI above versus below the cutpoint, adjusting for age, race, sex, and important disease-specific clinical prognostic factors.

Results: A total of 11,724 patients from 22 trials were identified. Fourteen analyses were performed by disease site and treatment regimen. A cutpoint of BMI = 25 kg/m2 maximized survival differences. No statistically significant trend across all 14 analyses was observed (mean HR = 0.96; P = 0.06). In no cancer/treatment combination was elevated BMI associated with an increased risk of death; for some cancers there was a survival advantage for higher BMI. In sex-stratified analyses, BMI ≥ 25 kg/m2 was associated with better overall survival among men (HR = 0.82; P = 0.003), but not women (HR = 1.04; P = 0.86). The association persisted when sex-specific cancers were excluded, when treatment regimens were restricted to dose based on body surface area, and when early-stage cancers were excluded.

Conclusion: The association between BMI and survival is not consistent across cancer types and stages.

Impact: Our findings suggest that disease, stage, and gender-specific body size recommendations for cancer survivors may be warranted. Cancer Epidemiol Biomarkers Prev; 26(1); 21–29. ©2016 AACR.

See all the articles in this CEBP Focus section, “The Obesity Paradox in Cancer: Evidence and New Directions.”
Association of Weight Change after Colorectal Cancer Diagnosis and Outcomes in the Kaiser Permanente Northern California Population
Authors: Meyerhardt Jeffrey A. , Kroenke Candyce H. , Prado Carla M. , Kwan Marilyn L. , Castillo Adrienne , Weltzien Erin , Cespedes Feliciano Elizabeth M. , Xiao Jingjie , Caan Bette J.
Published: December 2016

Background: Higher body mass index (BMI) is associated with incident colorectal cancer but not consistently with colorectal cancer survival. Whether weight gain or loss is associated with colorectal cancer survival is largely unknown.

Methods: We identified 2,781 patients from Kaiser Permanente Northern California diagnosed with stages I–III colorectal cancer between 2006 and 2011 with weight and height measurements within 3 months of diagnosis and approximately 18 months after diagnosis. We evaluated associations between weight change and colorectal cancer–specific and overall mortality, adjusted for sociodemographics, disease severity, and treatment.

Results: After completion of treatment and recovery from stage I–III colorectal cancer, loss of at least 10% of baseline weight was associated with significantly worse colorectal cancer–specific mortality (HR 3.20; 95% confidence interval [CI], 2.33–4.39; Ptrend < 0.0001) and overall mortality (HR 3.27; 95% CI, 2.56–4.18; Ptrend < 0.0001). For every 5% loss of baseline weight, there was a 41% increased risk of colorectal cancer–specific mortality (95% CI, 29%–56%). Weight gain was not significantly associated with colorectal cancer–specific mortality (Ptrend = 0.54) or overall mortality (Ptrend = 0.27). The associations were largely unchanged after restricting analyses to exclude patients who died within 6 months and 12 months of the second weight measurement. No significant interactions were demonstrated for weight loss or gain by gender, stage, primary tumor location, or baseline BMI.

Conclusions: Weight loss after diagnosis was associated with worse colorectal cancer–specific mortality and overall mortality. Reverse causation does not appear to explain our findings.

Impact: Understanding mechanistic underpinnings for the association of weight to worse mortality is important to improving patient outcomes. Cancer Epidemiol Biomarkers Prev; 26(1); 30–37. ©2016 AACR.

See all the articles in this CEBP Focus section, “The Obesity Paradox in Cancer: Evidence and New Directions.”
A Glycomics-Based Test Predicts the Development of Hepatocellular Carcinoma in Cirrhosis
Authors: Verhelst Xavier , Vanderschaeghe Dieter , Castéra Laurent , Raes Tom , Geerts Anja , Francoz Claire , Colman Roos , Durand François , Callewaert Nico , Van Vlierberghe Hans
Published: December 2016

Purpose: Cirrhosis is a major risk factor for the development of hepatocellular carcinoma but remains underdiagnosed in the compensated stage. Fibrosis progression and cirrhosis are associated with changes in blood serum glycomic profiles. Previously, the serum glycomics-based GlycoCirrhoTest was shown to identify 50% to 70% of compensated cirrhosis cases in chronic liver disease cohorts, at >90% specificity. This study assessed GlycoCirrhoTest for the risk of hepatocellular carcinoma development in compensated cirrhosis.

Experimental Design: Serum glycomics were analyzed in sera of 133 patients, with compensated cirrhosis collected between 1995 and 2005 in a surveillance protocol for hepatocellular carcinoma using an optimized glycomic technology on a DNA sequencer.

Results: Baseline GlycoCirrhoTest values were significantly increased in patients who developed hepatocellular carcinoma after a median follow-up of 6.4 years as compared with patients who did not. For patients with a baseline GlycoCirrhoTest exceeding 0.2, the HR for hepatocellular carcinoma development over the entire study (Cox regression) was 5.1 [95% confidence interval (CI), 2.2–11.7; P < 0.001], and the HR for hepatocellular carcinoma development within 7 years was 12.1 (95% CI, 2.8–51.6; P = 0.01) based on the cut-off value optimized in the same cohort. An absolute increase in GlycoCirrhoTest of 0.2 was associated with an HR of 10.29 (95% CI, 3.37–31.43; P < 0.001) for developing hepatocellular carcinoma. In comparison, the HR for the development of hepatocellular carcinoma within 7 years for AFP levels above the optimal cutoff in this study (5.75 ng/mL) was 4.65 (95% CI, 1.59–13.61).

Conclusions: This prognostic study suggests that GlycoCirrhoTest is a serum biomarker that identifies compensated cirrhotic patients at risk for developing hepatocellular carcinoma. Screening strategies could be guided by a positive test on GlycoCirrhoTest. Clin Cancer Res; 23(11); 2750–8. ©2016 AACR.
Heterodimeric IL15 Treatment Enhances Tumor Infiltration, Persistence, and Effector Functions of Adoptively Transferred Tumor-specific T Cells in the Absence of Lymphodepletion
Authors: Ng Sinnie Sin Man , Nagy Bethany A. , Jensen Shawn M. , Hu Xintao , Alicea Candido , Fox Bernard A. , Felber Barbara K. , Bergamaschi Cristina , Pavlakis George N.
Published: December 2016

Purpose: Adoptive cell transfer (ACT) is a promising immunotherapeutic approach for cancer. Host lymphodepletion is associated with favorable ACT therapy outcomes, but it may cause detrimental effects in humans. We tested the hypothesis that IL15 administration enhances ACT in the absence of lymphodepletion. We previously showed that bioactive IL15 in vivo comprises a stable complex of the IL15 chain with the IL15 receptor alpha chain (IL15Rα), termed heterodimeric IL15 (hetIL15).

Experimental Design: We evaluated the effects of the combination regimen ACT + hetIL15 in the absence of lymphodepletion by transferring melanoma-specific Pmel-1 T cells into B16 melanoma-bearing mice.

Results: hetIL15 treatment delayed tumor growth by promoting infiltration and persistence of both adoptively transferred Pmel-1 cells and endogenous CD8+ T cells into the tumor. In contrast, persistence of Pmel-1 cells was severely reduced following irradiation in comparison with mice treated with hetIL15. Importantly, we found that hetIL15 treatment led to the preferential enrichment of Pmel-1 cells in B16 tumor sites in an antigen-dependent manner. Upon hetIL15 administration, tumor-infiltrating Pmel-1 cells showed a “nonexhausted” effector phenotype, characterized by increased IFNγ secretion, proliferation, and cytotoxic potential and low level of PD-1. hetIL15 treatment also resulted in an improved ratio of Pmel-1 to Treg in the tumor.

Conclusions: hetIL15 administration improves the outcome of ACT in lymphoreplete hosts, a finding with significant implications for improving cell-based cancer immunotherapy strategies. Clin Cancer Res; 23(11); 2817–30. ©2016 AACR.
Histone Deacetylase 3 Inhibition Overcomes BIM Deletion Polymorphism–Mediated Osimertinib Resistance in EGFR-Mutant Lung Cancer
Authors: Tanimoto Azusa , Takeuchi Shinji , Arai Sachiko , Fukuda Koji , Yamada Tadaaki , Roca Xavier , Ong S. Tiong , Yano Seiji
Published: December 2016

Purpose: The BIM deletion polymorphism is associated with apoptosis resistance to EGFR tyrosine kinase inhibitors (EGFR-TKI), such as gefitinib and erlotinib, in non–small cell lung cancer (NSCLC) harboring EGFR mutations. Here, we investigated whether the BIM deletion polymorphism contributes to resistance against osimertinib, a third-generation EGFR-TKI. In addition, we determined the efficacy of a histone deacetylase (HDAC) inhibitor, vorinostat, against this form of resistance and elucidated the underlying mechanism.

Experimental Design: We used EGFR-mutated NSCLC cell lines, which were either heterozygous or homozygous for the BIM deletion polymorphism, to evaluate the effect of osimertinib in vitro and in vivo. Protein expression was examined by Western blotting. Alternative splicing of BIM mRNA was analyzed by RT-PCR.

Results: EGFR-mutated NSCLC cell lines with the BIM deletion polymorphism exhibited apoptosis resistance to osimertinib in a polymorphism dosage–dependent manner, and this resistance was overcome by combined use with vorinostat. Experiments with homozygous BIM deletion–positive cells revealed that vorinostat affected the alternative splicing of BIM mRNA in the deletion allele, increased the expression of active BIM protein, and thereby induced apoptosis in osimertinib-treated cells. These effects were mediated predominantly by HDAC3 inhibition. In xenograft models, combined use of vorinostat with osimertinib could regress tumors in EGFR-mutated NSCLC cells homozygous for the BIM deletion polymorphism. Moreover, this combination could induce apoptosis even when tumor cells acquired EGFR-T790M mutations.

Conclusions: These findings indicate the importance of developing HDAC3-selective inhibitors, and their combined use with osimertinib, for treating EGFR-mutated lung cancers carrying the BIM deletion polymorphism. Clin Cancer Res; 23(12); 3139–49. ©2016 AACR.