bluuebunny/crossref_metadata_2025 huggingface dataset:
MICROSTRUCTURE AND PROPERTIES OF MAO COMPOSITE COATINGS CONTAINING NANORUTILE TiO2 PARTICLES
Authors: LI ZHENWEI , DI SHICHUN
Published: March 2017

Microarc oxidation (MAO) composite coatings containing rutile TiO2 were produced on 2024 aluminum alloy in an electrolyte with nanorutile TiO2 particles. The microstructure and properties of the composite coatings were analyzed by SEM, EDS, laser confocal microscope, XRD, Vickers hardness tester, scratch test and friction test, respectively. The results showed that the composite coatings consisted of [Formula: see text]-Al2O3, [Formula: see text]-Al2O3, mullite and rutile TiO2. With increasing concentration of rutile TiO2 particles in the electrolyte, the compactness of the composite coatings was improved significantly. The abrasion performance of the microarc oxidation composite coatings containing rutile TiO2 was better than that of MAO coatings without rutile TiO2.
ELECTROCATALYTIC OXIDATION OF ASCORBIC ACID AT POLYPYRROLE THIN FILM INCORPORATING PALLADIUM PARTICLES
Authors: DEHCHAR CHARIF , CHIKOUCHE IMENE , KHERRAT ROCHDI , ZOUGAR SAIDA , ZOUAOUI AHMED
Published: March 2017

In this paper, we report a simple sensing strategy for electrochemical determination of ascorbic acid (AA) using a combination of polypyrrole (PPy) thin film and palladium particles composites deposited onto [Formula: see text]-doped silicon (Si) substrate. A two-step electrochemical process was employed to synthesize the composite films: At first, PPy film (average thickness 200[Formula: see text]nm) was electrogenerated on Si substrate from an organic solution of the pyrrole under galvanostatic conditions. Secondly, palladium particles were electrodeposited on PPy/Si surface from a separate solution by chronoamperometry technique. The surface morphology analysis of the obtained composites shows a uniform dispersion of palladium particles onto the polymer matrix and reveals that the electrodeposition time has a significant effect on the amount and size of the incorporated palladium particles. The electrochemical reactivity of the Pd–PPy/Si-modified electrodes towards the oxidation of AA was studied by cyclic voltammetry method in 0.1[Formula: see text]M, pH 7.0 phosphate buffer solution. The oxidation current was proportional to the concentration of AA in the range of 0.5–10[Formula: see text]mM with a detection limit of 0.2[Formula: see text]mM.
EFFECTS OF THE MIXED Cu/O LAYER ON THE TRANSPORT PROPERTIES OF Cu/EuO-BASED TUNNEL JUNCTIONS
Authors: DAI C. J. , YAN X. H. , XIAO Y. , YUAN J. R. , BI M. X. , LIU J. S.
Published: March 2017

The spin-dependent transport properties of Cu/EuO-based tunnel junctions are investigated by means of the first-principle calculations combined with the non-equilibrium Green’s function (NEGF) method. It is found that the Cu/EuO-based junctions exhibit excellent spin-filtering effect. Furthermore, the mixed Cu/O layer enhances the tunneling of the majority spin through the EuO barrier for the junctions with Cu/O layers due to the fact that the valance-band maximum of the Eu-4[Formula: see text] states shifts to high energies with respect to the Fermi level for these junctions. These results permit the existence of the mixed Cu/O layer in Cu/EuO-based tunnel junctions and promote future applications of these tunnel junctions in spintronic devices.
The Timeliness of Financial Reporting and Fair Values: Evidence from U.S. Banks
Authors: Huang Hua-Wei , Dao Mai , Sun Wen-Chi
Published: March 2017

The public controversies over the implementation of Statement of Financial Accounting Standard No. 157 (SFAS 157) and its impact on the recent financial crisis motivate us to examine the association between fair values and reporting lags. With a sample of U.S. banking institutions, we find that less verifiable fair value information is associated with longer earnings announcement lag and audit report lag. Longer earnings announcement lags resulting from less verifiable fair value information are due to the additional time of managerial estimations. Less verifiable fair values may also result in longer audit report lags due to the added training for auditors. Our study extends the current literature on fair values and reporting lags. Our findings contribute to the contemporary research on the timeliness of financial information disclosures which promotes the efficient functioning of the economy. Moreover, the findings of our study may be of interest to the global regulators, investors and other financial statement users.
Representations of E7, equivalent combinatorics and algebraic varieties
Authors: Xu Xiaoping
Published: March 2017

In our earlier work on a new functor from [Formula: see text]-Mod to [Formula: see text]-Mod, we found a one-parameter ([Formula: see text]) family of inhomogeneous first-order differential operator representations of the simple Lie algebra of type [Formula: see text] in [Formula: see text] variables. Letting these operators act on the space of exponential-polynomial functions that depend on a parametric vector [Formula: see text], we prove that the space forms an irreducible [Formula: see text]-module for any [Formula: see text] if [Formula: see text] is not on an explicitly given projective algebraic variety. Certain equivalent combinatorial properties of the basic oscillator representation of [Formula: see text] over its 27-dimensional module play key roles in our proof. Our result can also be used to study free bosonic field irreducible representations of the corresponding affine Kac–Moody algebra.
Calculation of global and local reactivity descriptors of carbodiimides, a DFT study
Authors: Ramirez-Balderrama Kathy , Orrantia-Borunda Erasmo , Flores-Holguin Norma
Published: March 2017

Carbodiimides have been widely used for different purposes, such as an intermediary to form peptides bonds and esters, which have generated industrial, organic and biological applications. Diisoproylcarbodiimide (DIC), (3-(dimethylamino) propyl)ethylcarbodiimide (EDC) and N,N′-dicyclohexylcarbodiimide (DCC) are the most common carbodiimides, however, there exist other carbodiimides that are not normally used. Twelve carbodiimides including the above mentioned were chosen to study their chemical reactivity as well as their nucleophilic and electrophilic attack sites. Geometry optimization in gas and solution phases was obtained using Density Functional Theory (DFT) through B3LYP with 6-31G(d) and 6-311[Formula: see text]G(d,p) level. Global and local reactivity descriptors were calculated and analyzed such as chemical hardness, ionization potential, electron affinity, Fukui functions, dual descriptor and hypersoftness. The results obtained for geometrical parameters do not have significant differences for gas and solution phase. The introduction of diffuse functions has great impact in electron affinity, modifying notably the values of reactivity descriptors, but didn’t show qualitative differences, since the results found for both basis set calculations show that Cyanamide or CD1 is the most stable and CD11 present greater reactivity of all studied molecules. Also, the hypersoftness results obtained with 6-31G(d) are in agreement with the general affirmation that carbodiimides are easily attacked by nucleophiles and electrophiles in the central carbon–nitrogen double bond.
On Benchmark Problems and Metrics for Decision Space Performance Analysis in Multi-Objective Optimization
Authors: Zhang Bin , Shafi Kamran , Abbass Hussein
Published: March 2017

A number of benchmark problems exist for evaluating multi-objective evolutionary algorithms (MOEAs) in the objective space. However, the decision space performance analysis is a recent and relatively less explored topic in evolutionary multi-objective optimization research. Among other implications, such analysis can lead to designing more realistic test problems, gaining better understanding about optimal and robust design areas, and design and evaluation of knowledge-based optimization algorithms. This paper complements the existing research in this area and proposes a new method to generate multi-objective optimization test problems with clustered Pareto sets in hyper-rectangular defined areas of decision space. The test problem is parametrized to control number of decision variables, number and position of optimal areas in the decision space and modality of fitness landscape. Three leading MOEAs, including NSGA-II, NSGA-III, and MOEA/D, are evaluated on a number of problem instances with varying characteristics. A new metric is proposed that measures the performance of algorithms in terms of their coverage of the optimal areas in the decision space. The empirical analysis presented in this research shows that the decision space performance may not necessarily be reflective of the objective space performance and that all algorithms are sensitive to population size parameter for the new test problems.
Proof of some congruences conjectured by Z.-W. Sun
Authors: Mao Guo-Shuai
Published: March 2017

In this paper, we show that for any prime [Formula: see text], [Formula: see text] and [Formula: see text] where [Formula: see text] denotes the Bernoulli polynomial of degree [Formula: see text]. And we prove that [Formula: see text] and [Formula: see text] where [Formula: see text] stands for the [Formula: see text]th Bernoulli number.

This confirms several conjectures of Z.-W. Sun.
On the number of representations of positive integers by the diagonal quadratic forms in nine variables with coefficients that are ones and twos
Authors: Vepkhvadze Teimuraz
Published: March 2017

The modular properties of generalized theta-functions with characteristics are used to obtain the formulas for the number of representations of positive integers by the diagonal quadratic forms in nine variables with coefficients that are ones and twos.
Local convergence of deformed Euler–Halley-type methods in Banach space under weak conditions
Authors: Argyros Ioannis K. , George Santhosh
Published: March 2017

We present a unified local convergence analysis for deformed Euler–Halley-type methods in order to approximate a solution of a nonlinear equation in a Banach space setting. Our methods include the Euler, Halley and other high order methods. The convergence ball and error estimates are given for these methods under hypotheses up to the first Fréchet derivative in contrast to earlier studies using hypotheses up to the second Fréchet derivative. Numerical examples are also provided in this study.
Morita invariants of semirings-II
Authors: Gupta Sugato , Sardar Sujit Kumar
Published: March 2017

The purpose of this paper is to investigate the counterparts of most of our results on Morita invariants of semirings for semimodules. Among others, we obtain the lattice isomorphisms between the set of all ideals and set of all subsemimodules corresponding to a Morita context of semirings. Also, the preservation of congruences between a semiring and a semimodule corresponding to a Morita context of semirings is established.
(φ,ψ)-derivations of BL-algebras
Authors: Alsatayhi S. , Moussavi A.
Published: March 2017

In this paper, the notions of derivations of types [Formula: see text] and [Formula: see text] on a BL-algebra [Formula: see text] are introduced. We extend the notions of these derivations by introducing the notions of [Formula: see text]-derivations of types [Formula: see text] and [Formula: see text], and discuss some related properties. The conditions for [Formula: see text]-derivations of types [Formula: see text] and [Formula: see text] to be isotone are provided. The set [Formula: see text] is defined and conditions for [Formula: see text] to be a down closed set and an ideal on [Formula: see text] are given where [Formula: see text] is a Boolean algebra and [Formula: see text] is a [Formula: see text]-derivation of type [Formula: see text] on [Formula: see text]. Finally, the relationship between [Formula: see text]-derivations of types [Formula: see text] and [Formula: see text] for a Boolean algebra [Formula: see text] is determined.
The brittle and ductile components of displacement along fault zones
Authors: Homberg C. , Schnyder J. , Roche V. , Leonardi V. , Benzaggagh M.
Published: March 2017

The total offset across a fault zone may include offsets by discontinuous faulting as well as continuous deformation, including fault-related folding. This study investigates the relationships between these two components during fault growth. We established conceptual models for the distributions of displacement due to faulting (i.e. brittle component or near-field displacement), to folding (i.e. ductile component) and to the sum of both (i.e. far-field displacement) for different mechanisms of fault-related folding. We then compared these theoretical displacement profiles with those measured along mesoscale normal faults cutting carbonate-rich sequences in the Southeast Mesozoic sedimentary basin of France. The near-field and far-field displacement profiles follow either a flat-topped or a triangular shape. Several fold mechanisms were recognized, sometimes occurring together along the same fault and represent either fault-propagation folds, shear folds or coherent drag folds. In the last case, local deficit in the fault slip is balanced by folding so that the brittle and ductile components compose together a coherent fault zone. Common characteristics of these faults are a high folding component that can reach up to 75% of the total fault throw, a high displacement gradient (up to 0.5) and a strong fault sinuosity.
Kanamycin Sulphate Loaded PLGA-Vitamin-E-TPGS Long Circulating Nanoparticles Using Combined Coating of PEG and Water-Soluble Chitosan
Authors: Mustafa Sanaul , Devi V. Kusum , Pai Roopa S.
Published: March 2017

Kanamycin sulphate (KS) is a Mycobacterium tuberculosis protein synthesis inhibitor. Due to its intense hydrophilicity, KS is cleared from the body within 8 h. KS has a very short plasma half-life (2.5 h). KS is used in high concentrations to reach the therapeutic levels in plasma, which results in serious nephrotoxicity/ototoxicity. To overcome aforementioned limitations, the current study aimed to develop KS loaded PLGA-Vitamin-E-TPGS nanoparticles (KS-PLGA-TPGS NPs), to act as an efficient carrier for controlled delivery of KS. To achieve a substantial extension in blood circulation, a combined design, affixation of polyethylene glycol (PEG) to KS-PLGA-TPGS NPs and adsorption of water-soluble chitosan (WSC) (cationic deacetylated chitin) to particle surface, was raised for surface modification of NPs. Surface modified NPs (KS-PEG-WSC NPs) were prepared to provide controlled delivery and circulate in the bloodstream for an extended period of time, thus minimizing dosing frequency. In vivo pharmacokinetics and in vivo biodistribution following intramuscular administration were investigated. NPs surface charge was close to neutral +3.61 mV and significantly affected by the WSC coating. KS-PEG-WSC NPs presented striking prolongation in blood circulation, reduced protein binding, and long drew-out the blood circulation half-life with resultant reduced kidney sequestration vis-à-vis KS-PLGA-TPGS NPs. The studies, therefore, indicate the successful formulation development of KS-PEG-WSC NPs with reduced frequency of dosing of KS indicating low incidence of nephrotoxicity/ototoxicity.
Long-Term Body Weight Maintenance among StrongWomen–Healthy Hearts Program Participants
Authors: Seguin Rebecca A. , Folta Sara C. , Nelson Miriam E. , Hanson Karla L. , LaCroix Andrea Z.
Published: March 2017

Background. The repeated loss and regain of body weight, referred to as weight cycling, may be associated with negative health complications. Given today’s obesity epidemic and related interventions to address obesity, it is increasingly important to understand contexts and factors associated with weight loss maintenance. This study examined BMI among individuals who had previously participated in a 12-week, evidence-based, nationally disseminated nutrition and physical activity program designed for overweight and obese middle-aged and older women.Methods. Data were collected using follow-up surveys. Complete height and weight data were available for baseline, 12-week program completion (post-program) and follow-up (approximately 3 years later) for 154 women (response rate = 27.5%; BMI characteristics did not differ between responders and nonresponders).Results. Mean BMI decreased significantly from baseline to post-program (−0.5,P<0.001) and post-program to follow-up (−0.7,P<0.001). Seventy-five percent of survey respondents maintained or decreased BMI post-program to follow-up. Self-efficacy and social support for healthy eating behaviors (but not physical activity) were associated with BMI maintenance or additional weight loss.Conclusions. These findings support the durability of weight loss following participation in a relatively short-term intervention.
Bäcklund Transformations between the KdV Equation and a New Nonlinear Evolution Equation
Authors: Cao Xifang
Published: March 2017

We first give a Bäcklund transformation from the KdV equation to a new nonlinear evolution equation. We then derive two Bäcklund transformations with two pseudopotentials, one of which is from the KdV equation to the new equation and the other from the new equation to itself. As applications, by applying our Bäcklund transformations to known solutions, we construct some novel solutions to the new equation.
Serum ZAG Levels Were Associated with eGFR Mild Decrease in T2DM Patients with Diabetic Nephropathy
Authors: Xu Lingling , Yu Weihong , Niu Meng , Zheng Caixia , Qu Bin , Li Yan , Wang Jing , Huang Ping , Wang O. , Gong Fengying
Published: March 2017

Objective.To investigate the changes of serum zinc-α2-glycoprotein (ZAG) in type 2 diabetes mellitus (T2DM) with eGFR mild decrease.Subjects and Methods.A total of 438 T2DM patients (61.3 ± 4.0 y) were recruited and the demographic, anthropometric, and biochemical parameters were all collected. Serum ZAG levels were determined by commercially available ELISA kits.Results. The proportion of T2DM patients with the high tertile ZAG levels was 11.9% higher in patients with mildly decreased estimated glomerular filtration rate (eGFR) (<90 mL/min/1.73 m2) than those with the low tertile ZAG levelsP=0.038. The probability of theeGFR<90 mL/min/1.73 m2in patients with the high ZAG levels was 94% higher than those with the low serum ZAG levels after adjusting for age, gender, and education [OR = 1.94, 95% CI (1.17–3.23),P=0.0094]. This phenomenon was more likely to be observed in the condition of uACR ≥ 2.7 mg/mmol, WC ≥ 90 cm for men, or WC ≥ 85 cm for women.Conclusion. Serum ZAG levels were firstly found to be related with eGFR in T2DM patients. The patients with the high tertile ZAG levels were more likely to have mildly eGFR decrease, especially for female patients with higher uACR and bigger WC.
Critical Gates Identification for Fault-Tolerant Design in Math Circuits
Authors: Ban Tian , Junior Gutemberg G. S.
Published: March 2017

Hardware redundancy at different levels of design is a common fault mitigation technique, which is well known for its efficiency to the detriment of area overhead. In order to reduce this drawback, several fault-tolerant techniques have been proposed in literature to find a good trade-off. In this paper, critical constituent gates in math circuits are detected and graded based on the impact of an error in the output of a circuit. These critical gates should be hardened first under the area constraint of design criteria. Indeed, output bits considered crucial to a system receive higher priorities to be protected, reducing the occurrence of critical errors. The 74283 fast adder is used as an example to illustrate the feasibility and efficiency of the proposed approach.
Effects of Traumatic Stress Induced in the Juvenile Period on the Expression of Gamma-Aminobutyric Acid Receptor Type A Subunits in Adult Rat Brain
Authors: Lu Cui Yan , Liu De Xiang , Jiang Hong , Pan Fang , Ho Cyrus S. H. , Ho Roger C. M.
Published: March 2017

Studies have found that early traumatic experience significantly increases the risk of posttraumatic stress disorder (PTSD). Gamma-aminobutyric acid (GABA) deficits were proposed to be implicated in development of PTSD, but the alterations of GABA receptor A (GABAAR) subunits induced by early traumatic stress have not been fully elucidated. Furthermore, previous studies suggested that exercise could be more effective than medications in reducing severity of anxiety and depression but the mechanism is unclear. This study used inescapable foot-shock to induce PTSD in juvenile rats and examined their emotional changes using open-field test and elevated plus maze, memory changes using Morris water maze, and the expression of GABAAR subunits (γ2,α2, andα5) in subregions of the brain in the adulthood using western blotting and immunohistochemistry. We aimed to observe the role of GABAAR subunits changes induced by juvenile trauma in the pathogenesis of subsequent PTSD in adulthood. In addition, we investigated the protective effects of exercise for 6 weeks and benzodiazepine (clonazepam) for 2 weeks. This study found that juvenile traumatic stress induced chronic anxiety and spatial memory loss and reduced expression of GABAAR subunits in the adult rat brains. Furthermore, exercise led to significant improvement as compared to short-term BZ treatment.
Cardiac Function Remains Impaired Despite Reversible Cardiac Remodeling after Acute Experimental Viral Myocarditis
Authors: Becher Peter Moritz , Gotzhein Frauke , Klingel Karin , Escher Felicitas , Blankenberg Stefan , Westermann Dirk , Lindner Diana
Published: March 2017

Background. Infection with Coxsackievirus B3 induces myocarditis. We aimed to compare the acute and chronic phases of viral myocarditis to identify the immediate effects of cardiac inflammation as well as the long-term effects after resolved inflammation on cardiac fibrosis and consequently on cardiac function.Material and Methods. We infected C57BL/6J mice with Coxsackievirus B3 and determined the hemodynamic function 7 as well as 28 days after infection. Subsequently, we analyzed viral burden and viral replication in the cardiac tissue as well as the expression of cytokines and matrix proteins. Furthermore, cardiac fibroblasts were infected with virus to investigate if viral infection alone induces profibrotic signaling.Results. Severe cardiac inflammation was determined and cardiac fibrosis was consistently colocalized with inflammation during the acute phase of myocarditis. Declined cardiac inflammation but no significantly improved hemodynamic function was observed 28 days after infection. Interestingly, cardiac fibrosis declined to basal levels as well. Both cardiac inflammation and fibrosis were reversible, whereas the hemodynamic function remains impaired after healed viral myocarditis in C57BL/6J mice.
Stability Analysis of Water‐Resistant Strata in Karst Tunnel Based on Releasable Elastic Strain Energy
Authors: Liu Qin , Wei Lai , Chen Jianxun , Luo Yanbin , Huang Pei , Wang Hongyu , Guo Jiaqi
Published: March 2017

In this paper, the energy instability criterion of water‐resistant strata and rock mass failure index (RMFI) are proposed, respectively, based on releasable elastic strain energy Ue. RMFI is employed to represent the damage extent of water‐resistant strata. When RMFI < 1.0, rock mass is stable. When RMFI = 1.0, rock mass is in the critical instability state. When RMFI > 1.0, rock mass is unstable. The releasable elastic strain energy Ue and RMFI program is performed by FISH programming language of Flac3D software. Then, the authors apply Flac3D software to analyze the distribution law of releasable elastic strain energy Ue and failure zone under different width of concealed karst cave. Finally, combined with the numerical analysis, a case study is carried out to illustrate the rationality, effectiveness, and feasibility through using RMFI to predict safe thickness of water‐resistant strata.
Unilateral Maxillary Sinus Actinomycosis with a Closed Oroantral Fistula
Authors: Cohn Jason E. , Lentner Mark , Li Hui , Nagorsky Matthew
Published: March 2017

Actinomycosis is a bacterial infection due to Actinomyces israelii, a gram-positive, anaerobic organism that normally affects the cervicofacial region. However, facial injury or trauma (i.e., dental procedures) can allow this bacteria to inhabit other regions. There have been rare reports of actinomycosis of the paranasal sinuses. We present a case of a 50-year-old female who originally presented with a suspected oroantral fistula who subsequently was found to have actinomycosis involving her right maxillary sinus. Additionally, the dental extraction site revealed no connection with the maxillary sinus. We discuss the diagnostic approach and management of this patient as it relates to the limited existing literature.
Primary Pulmonary Malignant Melanoma: Report of an Important Entity and Literature Review
Authors: Kyriakopoulos Christos , Zarkavelis George , Andrianopoulou Artemis , Papoudou-Bai Alexandra , Stefanou Dimitrios , Boussios Stergios , Pentheroudakis George
Published: March 2017

Malignant melanoma involving the respiratory tract is nearly always metastatic in origin, and primary tumors are extremely rare. Published data on primary pulmonary malignant melanomas are limited. Up to now 40 relevant cases have been reported in the English literature. Herein, we report a case of a 56-year-old female patient who presented with intracranial metastases due to primary pulmonary melanoma. She underwent bronchoscopy and died 5 months after the initial diagnosis despite the administered biochemotherapy and subsequent immunotherapy. To establish the diagnosis of primary pulmonary malignant melanoma, any extrapulmonary origin was excluded by detailed examination and radiographic imaging. Moreover, an extensive review of the literature regarding this rare entity has been performed.
Consensus Problem of High‐Order Multiagent Systems with Time Delays
Authors: Liu Jianhui , Zhang Bin
Published: March 2017

In this paper, we consider the consensus problem of high‐order multiagent systems on both fixed and switching interaction topologies with time delays. A neighbor‐based protocol is presented, under which we prove that the state errors converge to zero asymptotically if there is a solution to a given Riccati inequality. The proof of our theorem is shown in time domain based on a Lyapunov approach. A numerical example is introduced to indicate the correctness of our analysis.
A Wandering Abdominal Mass in a Neonate: An Enteric Duplication Cyst Mimicking an Ovarian Cyst
Authors: Iijima Shigeo
Published: March 2017

Enteric duplication cysts are rare congenital anomalies that are prenatally diagnosed through antenatal ultrasonography (US). In female patients, however, attention must be paid since these formations might be confused with ovarian cysts. Herein, we present a case of a low birth weight female infant with an enteric duplication cyst. A cystic lesion was detected in the right abdomen of the fetus on antenatal US and magnetic resonance imaging (MRI). Serial US and MRI examinations performed after birth showed a single cyst that wandered from side to side in the abdomen; the initial diagnosis was thought to be an ovarian cyst. During laparotomy, however, it was found to be an enteric duplication cyst with volvulus. To our knowledge, there has been no report of an enteric duplication cyst presenting as a wandering abdominal mass. Our experience indicates that early intervention is necessary for patients who have a wandering abdominal mass to avoid complications and urgent surgery, whether it is an ovarian cyst or an enteric duplication cyst.
Lipocalin-2 Promotes Pancreatic Ductal Adenocarcinoma by Regulating Inflammation in the Tumor Microenvironment
Authors: Gomez-Chou Sobeyda B. , Swidnicka-Siergiejko Agnieszka Katarzyna , Badi Niharika , Chavez-Tomar Myrriah , Lesinski Gregory B. , Bekaii-Saab Tanios , Farren Matthew R. , Mace Thomas A. , Schmidt Carl , Liu Yan , Deng Defeng , Hwang Rosa F. , Zhou Liran , Moore Todd , Chatterjee Deyali , Wang Huamin , Leng Xiaohong , Arlinghaus Ralph B. , Logsdon Craig D. , Cruz-Monserrate Zobeida
Published: March 2017

Lipocalin-2 (LCN2) promotes malignant development in many cancer types. LCN2 is upregulated in patients with pancreatic ductal adenocarcinoma (PDAC) and in obese individuals, but whether it contributes to PDAC development is unclear. In this study, we investigated the effects of Lcn2 depletion on diet-induced obesity, inflammation, and PDAC development. Mice with acinar cell–specific expression of KrasG12D were crossed with Lcn2-depleted animals and fed isocaloric diets with varying amounts of fat content. Pancreas were collected and analyzed for inflammation, pancreatic intraepithelial neoplasia (PanIN), and PDAC. We also used a syngeneic orthotopic PDAC mouse model to study tumor growth in the presence or absence of Lcn2 expression. In addition, to understand the mechanistic role of how LCN2 could be mediating PDAC, we studied LCN2 and its specific receptor solute carrier family 22 member 17 (SLC22A17) in human pancreatic cancer stellate cells (PSC), key mediators of the PDAC stroma. Depletion of Lcn2 diminished extracellular matrix deposition, immune cell infiltration, PanIN formation, and tumor growth. Notably, it also increased survival in both obesity-driven and syngeneic orthotopic PDAC mouse models. LCN2 modulated the secretion of proinflammatory cytokines in PSC of the PDAC tumor microenvironment, whereas downregulation of LCN2-specific receptor SLC22A17 blocked these effects. Our results reveal how LCN2 acts in the tumor microenvironment links obesity, inflammation, and PDAC development. Cancer Res; 77(10); 2647–60. ©2017 AACR
Decision Support and Navigation to Increase Colorectal Cancer Screening among Hispanic Primary Care Patients
Authors: Myers RE , Stello B , Daskalakis C , Sifri R , DiCarlo M , Johnson M , Gonzalez E , Hegarty S , Rivera A , Gordis-Molina L , Shaak K , Quinn A , Careyva B , Anderson-Ortiz R
Published: March 2017

The study compared the impact of a novel decision support and navigation intervention (DSNI) to a mailed standard intervention (SI) on colorectal cancer (CRC) screening among Hispanic patients from 5 primary care practices in the Lehigh Valley Health Network (LVHN). Methods. We randomized surveyed and consented patients who were 50 to 75 years of age and were eligible for CRC screening either to an SI Group (n = 200) or a DSNI Group (n = 200). Following randomization, SI Group participants were mailed a set of standard materials (i.e., a letter from the participant's primary care practice encouraging selection and performance of either colonoscopy screening or a stool blood test (SBT) screening, a SBT kit, and instructions for arranging a colonoscopy appointment. Print materials were provided in English and Spanish. DSNI Group participants were also mailed the standard materials. In addition, DSNI participants received a telephone call from a bilingual patient navigator who reviewed the screening materials and verified the participant's preferred CRC screening test. During the call, the patient navigator used an online Decision Counseling Program© (DCP) to determine the participant's likelihood of test performance and to develop a personalized test preference- and likelihood-based screening plan. The plan was mailed to the participant and his/her primary care practice; and a participant screening status report was sent to the practice at 6 months. Finally, a 6-month survey was targeted to participants in both study groups. Results. Based on 6-month survey and medical records data, we found that CRC screening adherence was significantly higher (OR = 3.48, CI: 2.29, 5.29, P < 0.001) in the DSNI Group (73%) versus the SI Group (44%). Conclusions. A decision support and navigation intervention significantly increased CRC screening adherence among Hispanic primary care patients.
Health System-Based HPV Vaccine Reminders: Randomized Trial Results
Authors: Henrikson N , Zhu W , Nguyen M , Baba L , Berthoud H , Hofstetter A
Published: March 2017

Purpose: Evaluate the impact of health system-based outreach and reminders on human papillomavirus (HPV) vaccine series initiation and completion. Methods: We conducted a 12-month randomized trial at an integrated care system in the Pacific Northwest in 2015–2016. Parents of 10–12 year olds who had not received any doses of HPV vaccine were randomized to an intervention group (mailed letter and brochure followed by an interactive voice recognition (IVR) reminder call encouraging HPV vaccine initiation) or usual care control group. Parents could opt in to receive future messages via SMS text message on all calls. Parents of intervention group children who initiated vaccination were re-randomized to receive either no further reminders or reminders for doses 2/3. We interviewed a subset of 50 parents to assess acceptability of the program. Outcomes were HPV vaccine initiation (within 12 months or 120 days of the initial letter), on-time series completion (within 210 days of initiation), and time to vaccination, assessed with Kaplan-Meier survival analyses. Results: 1624 children were eligible for randomization (46% age 10, 32.9% age 11, 20.4% age 12). The sample was 48.3% female and 64.6% white. Rates of overall HPV vaccine initiation were similar between the intervention and control groups (49.0% and 45.8%, P = 0.26), but initiation within 120 days of outreach was higher in the intervention group (23.6% and 18.8%, P = 0.04). This effect continued through to completion within 12 months (10.3% vs. 6.8%, P = 0.04). Opt-in rates to SMS were low: 24 people completed the opt-in process. Rates of on-time series completion were similar in those who received dose 1 reminders only compared to those who received reminders for all vaccine doses (12.1% and 19.7%, P = 0.10); time-to-completion results were similar. Parent interviews suggested reminders were acceptable and useful. Conclusion: Reminder calls after an outreach letter led to more timely vaccine initiation and overall completion. Reminders beyond the initial letter and reminder call did not appear to impact vaccine series completion. The program was acceptable to parents, though there was low uptake of SMS reminders.
Event-Related Potentials Reflect Deficits in Lexical Access: The N200 in Prematurely Born School-Aged Children
Authors: Korpilahti Pirjo , Valkama Marita , Jansson-Verkasalo Eira
Published: March 2017

Objectives: Children born preterm have a high prevalence of neurocognitive deficits early in life. We examined whether the neural correlates of lexical access are atypical in 9-year-old children born preterm, and whether the findings of acoustic mapping correlate with language- and attention-related skills. Patients and Methods: The subjects were fourteen 9-year-old children born preterm and 14 full-term, typically developing controls. Two auditory event-related potential (ERP) components, the N200 and the N400, were used to assess discrimination response and word recognition. A set of behavioral tests (naming ability, auditory attention, phonological processing, pseudoword repetition, and comprehension of instructions) was performed, and the results were compared with the amplitudes, latencies, and scalp distribution of the ERP results. Results: In prematurely born children, neurophysiological deficits were associated with difficulties in auditory discrimination. The N200 amplitude correlated significantly with auditory attention and pseudoword repetition. The scalp distribution of both the N200 and the N400 was broader in children born preterm than in the controls. Low scores in the neuropsychological tasks referred to difficulties in auditory processing and memory. Conclusions: Children born preterm have difficulties in lexical access together with memory- and attention-related processes, which may have a longstanding impact on their school outcomes and academic skills.
Hormonal and Metabolic Responses to a Single Bout of Resistance Exercise in Prader-Willi Syndrome
Authors: Rubin Daniela A. , Clark Susan J. , Haqq Andrea M. , Castner Diobel M. , Ng Jason , Judelson Daniel A.
Published: March 2017

Background: Prader-Willi syndrome (PWS) is characterized by excessive adiposity. Excess adiposity negatively affects hormonal and metabolic responses to aerobic exercise. This study determined whether PWS and/or adiposity affected hormonal and metabolic responses to resistance exercise. Methods: Eleven children with PWS (11.4 ± 3.1 years, 43.9 ± 7.5% body fat), 12 lean children (9.3 ± 1.4 years, 18.3 ± 4.9% body fat), and 13 obese children (9.6 ± 1.3 years, 40.3 ± 5.2% body fat) participated. The children stepped onto an elevated platform while wearing a weighted vest for 6 sets of 10 repetitions per leg (sets separated by 1 min of rest). For the children with PWS, the platform height was 23.0 cm and vest load was computed as (20% of stature × 50% of lean body mass)/23.0 cm. For the controls, the platform height was 20% of the stature and vest load 50% of the lean body mass. Blood samples were obtained before, immediately after, and during recovery from exercise (+15, +30, and +60 min). Results: All groups had similar catecholamine, insulin, and glucagon responses. The groups showed no major differences in glucose and lactate levels. The PWS children demonstrated earlier increases in fatty acids during recovery and higher glycerol and ketone levels than the controls. Conclusion: The PWS children demonstrated largely intact hormonal, glycolytic, and lipolytic responses to lower-body resistance exercise. In PWS, elevated ketone levels suggest an incomplete fat oxidation.
Tacrolimus Triggers Transient Receptor Potential Vanilloid-1-Dependent Relapse of Pancreatitis-Related Pain in Mice
Authors: Terada Yuka , Tsubota Maho , Sugo Hiiragi , Wakitani Kohei , Sekiguchi Fumiko , Wada Kyoichi , Takada Mitsutaka , Oita Akira , Kawabata Atsufumi
Published: March 2017

Transient receptor potential vanilloid-1 (TRPV1) expressed in nociceptors is directly phosphorylated and activated by protein kinase C, and involved in the signaling of pancreatic pain. On the other hand, Cav3.2 T-type Ca2+ channels expressed in nociceptors are functionally upregulated by phosphorylation with protein kinase A and also play a role in pancreatitis-related pain. Calcineurin, a phosphatase, negatively regulates various channel functions including TRPV1, and calcineurin inhibitor-induced pain syndrome by tacrolimus, a calcineurin inhibitor, used as an immunosuppressant, has been a clinical problem. We thus examined the effect of tacrolimus on pancreatitis-related pain in mice. Repeated treatment with cerulein caused referred hyperalgesia accompanying acute pancreatitis, which was unaffected by tacrolimus. Pancreatitis-related symptoms disappeared in 24 h, whereas the referred hyperalgesia recurred following the administration of tacrolimus, which was abolished by the blockers of TRPV1 but not T-type Ca2+ channels. Thus, tacrolimus appears to cause the TRPV1-dependent relapse of pancreatitis-related pain, suggesting the involvement of calcineurin in the termination of pancreatic pain.
The Effect of the Testis on the Ovary: Structure-Function Relationships in a Neonate with a Unilateral Ovotestis (Ovotesticular Disorder of Sex Development)
Authors: Greeley Siri Atma W. , Littlejohn Elizabeth , Husain Aliya N. , Waggoner Darrel , Gundeti Mohan , Rosenfield Robert L.
Published: March 2017

Aims: To evaluate gonadal function in a newborn with suspected ovotesticular disorder of sex development (DSD). Methods: Gonadal function was evaluated at baseline and after gonadotropin-releasing hormone agonist (GnRHag) stimulation testing. Results: A full-term 46,XX neonate with genital ambiguity produced serum testosterone and anti-Müllerian hormone (AMH) levels appropriate for males within days, while serum estradiol remained prepubertal, both spontaneously and in response to GnRHag stimulation testing. Ovotesticular DSD was diagnosed at laparoscopy: the left gonad was an ovotestis and the right gonad an ovary arrested at the primordial follicle stage of development. Mosaicism for an isochromosome of the Y short arm in 6–18% of gonadal cells was demonstrated. After ovotestis removal at 3 weeks of age, serum AMH became low within a month, but the elevated testosterone was slow to resolve, apparently from ovarian androgenic hyperfunction coincident with ovarian estrogenic hyperfunction and an adult degree of ovarian development. Ovarian morphology and function gradually normalized as neonatal minipuberty waned. Conclusions: In a neonate with genital ambiguity due to ovotesticular DSD, testicular AMH and testosterone production respectively appear to account for the initial arrest of ovarian development and subsequent rapid hyperfunction of the contralateral ovary after ovotestis removal.
Germline Mutations in Triple-Negative Breast Cancer
Authors: Hahnen Eric , Hauke Jan , Engel Christoph , Neidhardt Guido , Rhiem Kerstin , Schmutzler Rita K.
Published: March 2017

Triple-negative breast cancer (TNBC) is associated with a poor prognosis and defines a subgroup of patients who do not benefit from endocrine or anti-HER2 therapy. Rather than being a biological entity, TNBC represents a heterogeneous disease, and further subtyping is necessary to establish targeted therapies. Germline mutational status may serve as a robust biomarker predicting therapy response, especially with respect to compounds challenging the DNA repair machinery. Patients with TNBC usually show an early onset of the disease, as well as a positive family history of breast and/or ovarian cancer in more than one third of all cases, which suggests that TNBC is closely associated with a hereditary disease cause. In unselected TNBC cases, the prevalence of pathogenic germline BRCA1/2 mutations is approximately twice as high as in breast cancer overall. Early age at diagnosis and positive family history are strong predictors for an increased BRCA1/2 mutation probability, which is up to 40% when both risk factors are considered. Apart from BRCA1/2, the rarely mutated breast cancer predisposition genes PALB2 and FANCM have been associated with TNBC. This review summarizes the role of germline mutational status in TNBC pathogenesis. Clinical trials addressing BRCA1/2 mutation carriers are discussed.
Difference in Neutropenia due to Administration Schedule of TAS-102
Authors: Yoshida Yoichiro , Aisu Naoya , Mogi Ai , Komono Akira , Sakamoto Ryohei , Kojima Daibo , Mera Toshiyuki , Hasegawa Suguru
Published: March 2017

TAS-102 significantly improves overall survival in patients with metastatic colorectal cancer. The most common adverse event of TAS-102 is bone marrow suppression, which leads to neutropenia. The incidence of neutropenia is high, and there is no known effective prevention method. Furthermore, the administration method of TAS-102 is complicated. We reported that neutropenia could be avoided by changing to a simple administration method of TAS-102.
The Learning Healthcare System and Cardiovascular Care: A Scientific Statement From the American Heart Association
Authors: Maddox Thomas M. , Albert Nancy M. , Borden William B. , Curtis Lesley H. , Ferguson T. Bruce , Kao David P. , Marcus Gregory M. , Peterson Eric D. , Redberg Rita , Rumsfeld John S. , Shah Nilay D. , Tcheng James E.
Published: March 2017

The learning healthcare system uses health information technology and the health data infrastructure to apply scientific evidence at the point of clinical care while simultaneously collecting insights from that care to promote innovation in optimal healthcare delivery and to fuel new scientific discovery. To achieve these goals, the learning healthcare system requires systematic redesign of the current healthcare system, focusing on 4 major domains: science and informatics, patient-clinician partnerships, incentives, and development of a continuous learning culture. This scientific statement provides an overview of how these learning healthcare system domains can be realized in cardiovascular disease care. Current cardiovascular disease care innovations in informatics, data uses, patient engagement, continuous learning culture, and incentives are profiled. In addition, recommendations for next steps for the development of a learning healthcare system in cardiovascular care are presented.
Development and Validation of a Bilingual Stroke Preparedness Assessment Instrument
Authors: Skolarus Lesli E. , Mazor Kathleen M. , Sánchez Brisa N. , Dome Mackenzie , Biller José , Morgenstern Lewis B.
Published: March 2017

Background and Purpose—

Stroke preparedness interventions are limited by the lack of psychometrically sound intermediate end points. We sought to develop and assess the reliability and validity of the video-Stroke Action Test (video-STAT) an English and a Spanish video-based test to assess people’s ability to recognize and react to stroke signs.

Methods—

Video-STAT development and testing was divided into 4 phases: (1) video development and community-generated response options, (2) pilot testing in community health centers, (3) administration in a national sample, bilingual sample, and neurologist sample, and (4) administration before and after a stroke preparedness intervention.

Results—

The final version of the video-STAT included 8 videos: 4 acute stroke/emergency, 2 prior stroke/nonemergency, 1 nonstroke/emergency, and 1 nonstroke/nonemergency. Acute stroke recognition and action response were queried after each vignette. Video-STAT scoring was based on the acute stroke vignettes only (score range 0–12 best). The national sample consisted of 598 participants, 438 who took the video-STAT in English and 160 who took the video-STAT in Spanish. There was adequate internal consistency (Cronbach α=0.72). The average video-STAT score was 5.6 (SD=3.6), whereas the average neurologist score was 11.4 (SD=1.3). There was no difference in video-STAT scores between the 116 bilingual video-STAT participants who took the video-STAT in English or Spanish. Compared with baseline scores, the video-STAT scores increased after a stroke preparedness intervention (6.2 versus 8.9,
P
<0.01) among a sample of 101 black adults and youth.

Conclusions—

The video-STAT yields reliable scores that seem to be valid measures of stroke preparedness.
Neuronal Death After Hemorrhagic Stroke In Vitro and In Vivo Shares Features of Ferroptosis and Necroptosis
Authors: Zille Marietta , Karuppagounder Saravanan S. , Chen Yingxin , Gough Peter J. , Bertin John , Finger Joshua , Milner Teresa A. , Jonas Elizabeth A. , Ratan Rajiv R.
Published: March 2017

Background and Purpose—

Intracerebral hemorrhage leads to disability or death with few established treatments. Adverse outcomes after intracerebral hemorrhage result from irreversible damage to neurons resulting from primary and secondary injury. Secondary injury has been attributed to hemoglobin and its oxidized product hemin from lysed red blood cells. The aim of this study was to identify the underlying cell death mechanisms attributable to secondary injury by hemoglobin and hemin to broaden treatment options.

Methods—

We investigated cell death mechanisms in cultured neurons exposed to hemoglobin or hemin. Chemical inhibitors implicated in all known cell death pathways were used. Identified cell death mechanisms were confirmed using molecular markers and electron microscopy.

Results—

Chemical inhibitors of ferroptosis and necroptosis protected against hemoglobin- and hemin-induced toxicity. By contrast, inhibitors of caspase-dependent apoptosis, protein or mRNA synthesis, autophagy, mitophagy, or parthanatos had no effect. Accordingly, molecular markers of ferroptosis and necroptosis were increased after intracerebral hemorrhage in vitro and in vivo. Electron microscopy showed that hemin induced a necrotic phenotype. Necroptosis and ferroptosis inhibitors each abrogated death by >80% and had similar therapeutic windows in vitro.

Conclusions—

Experimental intracerebral hemorrhage shares features of ferroptotic and necroptotic cell death, but not caspase-dependent apoptosis or autophagy. We propose that ferroptosis or necroptotic signaling induced by lysed blood is sufficient to reach a threshold of death that leads to neuronal necrosis and that inhibition of either of these pathways can bring cells below that threshold to survival.