bluuebunny/crossref_metadata_2025 huggingface dataset:
Antimicrobial Effects of Antipyretics
Authors: Zimmermann Petra , Curtis Nigel
Published: January 2017

Antipyretics are some of the most commonly used drugs. Since they are often coadministered with antimicrobial therapy, it is important to understand the interactions between these two classes of drugs. Our review is the first to summarize the antimicrobial effects of antipyretic drugs and the underlying mechanisms involved. Antipyretics can inhibit virus replication, inhibit or promote bacterial or fungal growth, alter the expression of virulence factors, change the surface hydrophobicity of microbes, influence biofilm production, affect the motility, adherence, and metabolism of pathogens, interact with the transport and release of antibiotics by leukocytes, modify the susceptibility of bacteria to antibiotics, and induce or reduce the frequency of mutations leading to antimicrobial resistance. While antipyretics may compromise the efficacy of antimicrobial therapy, they can also be beneficial, for example, in the management of biofilm-associated infections, in reducing virulence factors, in therapy of resistant pathogens, and in inducing synergistic effects. In an era where it is becoming increasingly difficult to find new antimicrobial drugs, targeting virulence factors, enhancing the efficacy of antimicrobial therapy, and reducing resistance may be important strategies.
Characterization of β-
d
-
N
4
-Hydroxycytidine as a Novel Inhibitor of Chikungunya Virus
Authors: Ehteshami Maryam , Tao Sijia , Zandi Keivan , Hsiao Hui-Mien , Jiang Yong , Hammond Emily , Amblard Franck , Russell Olivia O. , Merits Andres , Schinazi Raymond F.
Published: January 2017

Chikungunya virus (CHIKV) represents a reemerging global threat to human health. Recent outbreaks across Asia, Europe, Africa, and the Caribbean have prompted renewed scientific interest in this mosquito-borne alphavirus. There are currently no vaccines against CHIKV, and treatment has been limited to nonspecific antiviral agents, with suboptimal outcomes. Herein, we have identified β-
d
-
N
4
-hydroxycytidine (NHC) as a novel inhibitor of CHIKV. NHC behaves as a pyrimidine ribonucleoside and selectively inhibits CHIKV replication in cell culture.
The Severity of Plasmodium falciparum Infection Is Associated with Transcript Levels of
var
Genes Encoding Endothelial Protein C Receptor-Binding P. falciparum Erythrocyte Membrane Protein 1
Authors: Mkumbaye Sixbert I. , Wang Christian W. , Lyimo Eric , Jespersen Jakob S. , Manjurano Alphaxard , Mosha Jacklin , Kavishe Reginald A. , Mwakalinga Steven B. , Minja Daniel T. R. , Lusingu John P. , Theander Thor G. , Lavstsen Thomas
Published: January 2017

By attaching infected erythrocytes to the vascular lining,
Plasmodium falciparum
parasites leave blood circulation and avoid splenic clearance. This sequestration is central to pathogenesis. Severe malaria is associated with parasites expressing an antigenically distinct
P. falciparum
erythrocyte membrane protein 1 (PfEMP1) subset mediating binding to endothelial receptors. Previous studies indicate that PfEMP1 adhesins with so-called CIDRα1 domains capable of binding endothelial protein C receptor (EPCR) constitute the PfEMP1 subset associated with severe pediatric malaria. To analyze the relative importance of different subtypes of CIDRα1 domains, we compared Pf
emp1
transcript levels in children with severe malaria (including 9 fatal and 114 surviving cases), children hospitalized with uncomplicated malaria (
n
= 42), children with mild malaria not requiring hospitalization (
n
= 10), and children with parasitemia and no ongoing fever (
n
= 12). High levels of transcripts encoding EPCR-binding PfEMP1 were found in patients with symptomatic infections, and the abundance of these transcripts increased with disease severity. The compositions of CIDRα1 subtype transcripts varied markedly between patients, and none of the subtypes were dominant. Transcript-level analyses targeting other domain types indicated that subtypes of DBLβ or DBLζ domains might mediate binding phenomena that, in conjunction with EPCR binding, could contribute to pathogenesis. These observations strengthen the rationale for targeting the PfEMP1-EPCR interaction by vaccines and adjunctive therapies. Interventions should target EPCR binding of all CIDRα1 subtypes.
Is diabetes prevalence higher among HIV-infected individuals compared with the general population? Evidence from MMP and NHANES 2009–2010
Authors: Hernandez-Romieu Alfonso C , Garg Shikha , Rosenberg Eli S , Thompson-Paul Angela M , Skarbinski Jacek
Published: January 2017

Background

Nationally representative estimates of diabetes mellitus (DM) prevalence among HIV-infected adults in the USA are lacking, and whether HIV-infected adults are at increased risk of DM compared with the general adult population remains controversial.

Methods

We used nationally representative survey (2009–2010) data from the Medical Monitoring Project (n=8610 HIV-infected adults) and the National Health and Nutrition Examination Survey (n=5604 general population adults) and fit logistic regression models to determine and compare weighted prevalences of DM between the two populations, and examine factors associated with DM among HIV-infected adults.

Results

DM prevalence among HIV-infected adults was 10.3% (95% CI 9.2% to 11.5%). DM prevalence was 3.8% (CI 1.8% to 5.8%) higher in HIV-infected adults compared with general population adults. HIV-infected subgroups, including women (prevalence difference 5.0%, CI 2.3% to 7.7%), individuals aged 20–44 (4.1%, CI 2.7% to 5.5%), and non-obese individuals (3.5%, CI 1.4% to 5.6%), had increased DM prevalence compared with general population adults. Factors associated with DM among HIV-infected adults included age, duration of HIV infection, geometric mean CD4 cell count, and obesity.

Conclusions

1 in 10 HIV-infected adults receiving medical care had DM. Although obesity contributes to DM risk among HIV-infected adults, comparisons to the general adult population suggest that DM among HIV-infected persons may develop at earlier ages and in the absence of obesity.
Systematic Review of β Blocker, Aspirin, and Statin in Critically Ill Patients: Importance of Severity of Illness and Cardiac Troponin
Authors: Rothenberg Florence G , Clay Michael B , Jamali Hina , Vandivier-Pletsch Robin H
Published: January 2017

Non-cardiac critically ill patients with type II myocardial infarction (MI) have a high risk of mortality. There are no evidence-based interventions to mitigate this risk. We systematically reviewed the literature regarding the use of medications known to reduce mortality in patients with cardiac troponin (cTn) elevation due to type I MI (β blockers, statin, and aspirin) in studies of critically ill patients without Type I MI. All PubMed publications between 1976–2/19/16 were reviewed. Search terms included: β blocker or aspirin or statin and intensive care unit (ICU) or critically ill or sepsis; 497 primary references were obtained. Inclusion criteria were as follows: (1) study population consisted of critically ill patients in the ICU with non-cardiovascular illnesses, (2) mortality end point, (3) severity of illness (or injury) was measured, and (4) the antiplatelet agent was primarily aspirin. Retrospective investigations, prospective observational studies, meta-analysis, systematic review, and randomized controlled trials were included; case reports were excluded. 25 primary references were obtained. The data were extracted and tabulated using data collection headings as follows: article title, first author/year/reference number, study type/design, population studied, outcome and intervention, and study question addressed. Evidence was not graded as the majority of studies were non-randomized (low-to-moderate quality). 11 studies were found through bibliography reviews for a total of 36 references. In conclusion, β blockers, statins, and aspirin may play a role in reducing mortality in non-cardiac critically ill patients. Benefit appears to be related to severity of illness, for which cTn may be a marker.
Ossicle development of the crinoid Florometra serratissima through larval stages
Authors: Comeau Ariane , Bishop Cory D. , Cameron Christopher B.
Published: January 2017

Crinoids are the oldest living class of echinoderm and sister group to the remaining eleutherozoan clade and so are key to discussions on the evolution and development of the echinoderm skeleton. Here we present the intraspecific variation of ossicle development of the feather star Florometra serratissima (A.H. Clark, 1907) during its three larval stages: doliolaria, cystidean, and early pentacrinoid. To induce settlement, larvae were cultured on a sea table in glass bowls containing coralline algae. The soft tissues of 60 larvae were dissolved to isolate and to observe the ossicles with compound microscopy and scanning electron microscopy. From the late doliolaria stage to 56-day-old pentacrinoids, a total of four types of ossicle developed: oral plates, basal plates, columnar stalk ossicles, and an attachment disk. Occasionally, an additional plate was found under the basal plates, which may represent a vestigial infrabasal plate. The shape of the attachment disk was plastic to accommodate the substrate. Crinoid ossicle development is variable in size, shape, and number, and the timing of development is asynchronous; traits that may have contributed to the early rapid radiation and phenotypic disparity of echinoderms.
Beam on beam control: Beyond the particle approximation
Authors: Smyth Noel F. , Tope Bryan
Published: January 2017

The all-optical control of the trajectory of a nonlinear optical beam propagating in a nematic liquid crystal cell is studied using a combination of modulation theory and full numerical solutions of the governing nematic equations. In detail, the output position of a signal beam is controlled via its interaction with a second, co-propagating control beam. The input positions of both the signal and control beams are fixed, with the output position of the signal beam determined by the input angle of the control beam. A simple modulation theory based on treating the optical beams as mechanical particles in a potential well is found to give only adequate agreement with numerical solutions. However, extending this modulation theory to include the detailed profiles of the beams, so that the beams are treated as rigid bodies moving in a potential well, leads to simple, extended equations which determine the input angle of the control beam required for a given output position of the signal beam. The predictions of this extended particle theory, or rigid body theory, are compared with full numerical solutions of the nematic equations and excellent agreement is found.
Characterization of Product Probability Measures on ℝd in Terms of Their Orthogonal Polynomials
Authors: Accardi Luigi , Dhahri Abdallah , Dhahri Ameur
Published: January 2017

In paper [1] the d-dimensional analogue of the Jacobi parameters has been individuated in a pair of sequences ((a.|n0),(Ω∼n)), where (a.|n0) is a sequence of Hermitean matrices and Ω∼n(n ∈ ℕ) a positive definite kernel with values in the linear operators on the n-th space of the orthogonal gradation. In this paper we prove that product measures on ℝd are characterized by the property that the (a.|n0) are diagonal and the (Ω∼n) quasidiagonal (see Definition 2 below) in the orthogonal polynomial basis.
Goldeneye: Tomorrow Never Dies (or a field Only Lives Twice)
Authors: Marshall John D. , Tucker Owain D. , Lovelock Cliff E. , Darker Sebastian J. , Annia Carlos E. , Hognestad Jon B.
Published: January 2017

The Goldeneye gas–condensate field lies in the Moray Firth Basin of the North Sea and illustrates the potential for further field life after the normal end of production. It was discovered in 1996 in a three-way dip-closed structure in the Lower Cretaceous Captain Sandstone. Five development wells were drilled from a single production platform and first gas was produced in 2004.

The field pressure decline indicated partial aquifer support and no compartmentalization. Approaching the end of production, the opportunity arose to propose Goldeneye as a store for CO
2
. The cap-rock seal was capable of containing gas and the removed hydrocarbons left a significant volume that could be refilled without raising pressures above original conditions. The field's good reservoir properties were favourable for injection, the wellstock and infrastructure were modern, and CO
2
sources were available close by.

The different requirements of a storage project called for a detailed understanding of the overburden to guard against possible leak paths and to identify secondary containment. Furthermore, greater understanding of the aquifer was needed as it limits storage volumes through its impact on reservoir pressures. Updated interpretation, analysis and modelling demonstrated that Goldeneye is an excellent potential CO
2
storage site, which gives it a possible second span of life helping to offset UK CO
2
emissions.
Telomerase Mechanism of Telomere Synthesis
Authors: Wu R. Alex , Upton Heather E. , Vogan Jacob M. , Collins Kathleen
Published: January 2017

Telomerase is the essential reverse transcriptase required for linear chromosome maintenance in most eukaryotes. Telomerase supplements the tandem array of simple-sequence repeats at chromosome ends to compensate for the DNA erosion inherent in genome replication. The template for telomerase reverse transcriptase is within the RNA subunit of the ribonucleoprotein complex, which in cells contains additional telomerase holoenzyme proteins that assemble the active ribonucleoprotein and promote its function at telomeres. Telomerase is distinct among polymerases in its reiterative reuse of an internal template. The template is precisely defined, processively copied, and regenerated by release of single-stranded product DNA. New specificities of nucleic acid handling that underlie the catalytic cycle of repeat synthesis derive from both active site specialization and new motif elaborations in protein and RNA subunits. Studies of telomerase provide unique insights into cellular requirements for genome stability, tissue renewal, and tumorigenesis as well as new perspectives on dynamic ribonucleoprotein machines.
Hard Physical Work Intensifies the Occupational Consequence of Physician-Diagnosed Back Disorder: Prospective Cohort Study with Register Follow-Up among 10,000 Workers
Authors: Sundstrup Emil , Andersen Lars Louis
Published: January 2017

While musculoskeletal pain is common in the population, less is known about its labor market consequences in relation to physical activity at work. This study investigates whether hard physical work aggravates the consequences of back disorder. Using Cox regression analyses, we estimated the joint association of physical activity at work and physician-diagnosed back disorder in 2010 with the risk of register-based long-term sickness absence (LTSA) of at least 6 consecutive weeks during 2011-2012 among 9,544 employees from the general working population (Danish Work Environment Cohort Study). Control variables were age, gender, psychosocial work environment, smoking, leisure physical activity, BMI, depression, and mental health. At baseline, 19.4% experienced high low-back pain intensity (≥5, 0–9 scale) and 15.2% had diagnosed back disorder. While high pain intensity was a general predictor for LTSA, physician-diagnosed back disorder was a stronger predictor among those with hard physical work (HR 2.23; 95% CI 1.68–2.96) compared with light work (HR 1.40; 95% CI 1.09–1.80). Similarly, physician-diagnosed back disorder with simultaneous high pain intensity predicted LTSA to a greater extent among those with hard physical work. In conclusion, the occupational consequence of physician-diagnosed back disorder on LTSA is greater among employees with hard physical work.
Selenium and Thyroid Disease: From Pathophysiology to Treatment
Authors: Ventura Mara , Melo Miguel , Carrilho Francisco
Published: January 2017

Introduction.Selenium is a micronutrient embedded in several proteins. In adults, the thyroid is the organ with the highest amount of selenium per gram of tissue. Selenium levels in the body depend on the characteristics of the population and its diet, geographic area, and soil composition. In the thyroid, selenium is required for the antioxidant function and for the metabolism of thyroid hormones.Methods.We performed a review of the literature on selenium’s role in thyroid function using PubMed/MEDLINE.Results.Regarding thyroid pathology, selenium intake has been particularly associated with autoimmune disorders. The literature suggests that selenium supplementation of patients with autoimmune thyroiditis is associated with a reduction in antithyroperoxidase antibody levels, improved thyroid ultrasound features, and improved quality of life. Selenium supplementation in Graves’ orbitopathy is associated with an improvement of quality of life and eye involvement, as well as delayed progression of ocular disorders. The organic form of selenium seems to be the preferable formulation for supplementation or treatment.Conclusion.Maintaining a physiological concentration of selenium is a prerequisite to prevent thyroid disease and preserve overall health. Supplementation with the organic form is more effective, and patients with autoimmune thyroiditis seem to have benefits in immunological mechanisms. Selenium supplementation proved to be clinically beneficial in patients with mild to moderate Graves’ orbitopathy.
A Theoretical Analysis of Why Hybrid Ensembles Work
Authors: Hsu Kuo-Wei
Published: January 2017

Inspired by the group decision making process, ensembles or combinations of classifiers have been found favorable in a wide variety of application domains. Some researchers propose to use the mixture of two different types of classification algorithms to create a hybrid ensemble. Why does such an ensemble work? The question remains. Following the concept of diversity, which is one of the fundamental elements of the success of ensembles, we conduct a theoretical analysis of why hybrid ensembles work, connecting using different algorithms to accuracy gain. We also conduct experiments on classification performance of hybrid ensembles of classifiers created by decision tree and naïve Bayes classification algorithms, each of which is a top data mining algorithm and often used to create non-hybrid ensembles. Therefore, through this paper, we provide a complement to the theoretical foundation of creating and using hybrid ensembles.
Juvenile Breast Hypertrophy: A Successful Breast Reduction of 14.9% Body Weight without Recurrence in a 5-Year Follow-Up
Authors: Hisham Akmal , Abd Latib Marzida , Basiron Normala
Published: January 2017

Juvenile hypertrophy of the breast (JHB) is a rare and relentless disease affecting women in the peripubertal period. We present a 13-year-old girl with massive bilateral JHB, successfully treated with a breast reduction and free nipple graft technique. A total of 7300 grams of breast tissue had been removed, accounting for 14.9% of the patient’s total body weight. Prophylactic hormonal therapy was not commenced. During the 5-year follow-up period, there was no recurrence and the patient remains satisfied with the aesthetic outcome. A recent meta-analysis study indicates that subcutaneous mastectomy is associated with reduced risk of recurrence, but it is more deforming and the aesthetic result is inferior to a reduction mammaplasty. In patients treated with the latter technique, some evidence exists suggesting that the use of a free nipple graft is associated with a less frequent risk of recurrence than a pedicle technique. This present case is unique as it demonstrates the clinical course of this patient at a considerably longer follow-up period than most reported studies. We adhered to the limited available evidence and highlight the long-term reliability of breast reduction with free nipple grafting as the first line surgical option in JHB, eliminating the need for repeated surgeries.
A Parametric Sharpe Ratio Optimization Approach for Fuzzy Portfolio Selection Problem
Authors: Liu Ying , Li Ya-Nan
Published: January 2017

When facing to make a portfolio decision, investors may care more about every portfolio’s performance on a return and risk trade‐off. In this paper, a new low partial moment measurement that only punishes the loss risk is defined for selection variables based on L‐S integral. Furthermore, a new performance measure for portfolio evaluation is proposed to generalize the Sharpe ratio in the fuzzy context. With the optimal performance criterion, a new parametric Sharpe ratio portfolio optimization model is developed wherein uncertain returns are presented as parametric interval‐valued fuzzy variables. To make the proposed model easy to solve, we transform the fractional programming into an equivalent form and solve it with domain decomposition method (DDM). Finally, we apply the proposed performance measure into a portfolio selection problem, compare the computational results in different cases, and analyze the influence of different parameters on the optimal portfolio.
Coalbed Methane Production System Simulation and Deliverability Forecasting: Coupled Surface Network/Wellbore/Reservoir Calculation
Authors: Zhou Jun , Liang Guangchuan , Deng Tao , Zhou Shiwei , Gong Jing
Published: January 2017

As an unconventional energy, coalbed methane (CBM) mainly exists in coal bed with adsorption, whose productivity is different from conventional gas reservoir. This paper explains the wellbore pressure drop, surface pipeline network simulation, and reservoir calculation model of CBM. A coupled surface/wellbore/reservoir calculation architecture was presented, to coordinate the gas production in each calculation period until the balance of surface/wellbore/reservoir. This coupled calculation method was applied to a CBM field for predicting production. The daily gas production increased year by year at the first time and then decreased gradually after several years, while the daily water production was reduced all the time with the successive decline of the formation pressure. The production of gas and water in each well is almost the same when the structure is a star. When system structure is a dendritic surface system, the daily gas production ranked highest at the well which is the nearest to the surface system collection point and lowest at the well which is the farthest to the surface system collection point. This coupled calculation method could be used to predict the water production, gas production, and formation pressure of a CBM field during a period of time.
African Ancestry Gradient Is Associated with Lower Systemic F2‐Isoprostane Levels
Authors: Annor Francis , Goodman Michael , Thyagarajan Bharat , Okosun Ike , Doumatey Ayo , Gower Barbara A. , Il’yasova Dora
Published: January 2017

Context. Low levels of systemic F2‐isoprostanes (F2‐IsoP) increase the risk of diabetes and weight gain and were found in African Americans. Low F2‐IsoPs could reflect an unfavorable metabolic characteristic, namely, slow mitochondrial metabolism in individuals with African ancestry. Objective. To examine differences in plasma F2‐IsoPs in three groups with a priori different proportion of African ancestry: non‐Hispanic Whites (NHWs), US‐born African Americans (AAs), and West African immigrants (WAI). Design. Cross‐sectional study. Setting. Georgia residents recruited from church communities. Participants. 218 males and females 25–74 years of age, who are self‐identified as NHW (n = 83), AA (n = 56), or WAI (n = 79). Main Outcome Measure(s). Plasma F2‐IsoPs quantified by gas chromatography‐mass spectrometry. Results. After adjustment for age, gender, obesity, and other comorbidities, WAI had lower levels of plasma F2‐IsoP than AA (beta‐coefficient = −9.8, p < 0.001) and AA had lower levels than NHW (beta‐coefficient = −30.3, p < 0.001). Similarly, among healthy nonobese participants, F2‐IsoP levels were lowest among WAI, followed by AA, and the highest levels were among NHW. Conclusion. Plasma F2‐IsoPs are inversely associated with African ancestry gradient. Additional studies are required to test whether optimization of systemic F2‐IsoP levels can serve as means to improve race‐specific lifestyle and pharmacological intervention targeted to obesity prevention and treatment.
Social Isolation Alters Social and Mating Behavior in the R451C Neuroligin Mouse Model of Autism
Authors: Burrows E. L. , Eastwood A. F. , May C. , Kolbe S. C. , Hill T. , McLachlan N. M. , Churilov L. , Hannan A. J.
Published: January 2017

Autism spectrum disorder (ASD) is a neurodevelopmental disorder typified by impaired social communication and restrictive and repetitive behaviors. Mice serve as an ideal candidate organism for studying the neural mechanisms that subserve these symptoms. The Neuroligin-3 (NL3) mouse, expressing a R451C mutation discovered in two Swedish brothers with ASD, exhibits impaired social interactions and heightened aggressive behavior towards male mice. Social interactions with female mice have not been characterized and in the present study were assessed in maleNL3R451Cand WT mice. Mice were housed in social and isolation conditions to test for isolation-induced increases in social interaction. Tests were repeated to investigate potential differences in interaction in naïve and experienced mice. We identified heightened interest in mating and atypical aggressive behavior inNL3R451Cmice.NL3R451Cmice exhibited normal social interaction with WT females, indicating that abnormal aggressive behavior towards females is not due to altered motivation to engage. Social isolation rearing heightened interest in social behavior in all mice. Isolation housing selectively modulated the response to female pheromones inNL3R451Cmice. This study is the first to show altered mating behavior in theNL3R451Cmouse and has provided new insights into the aggressive phenotype in this model.
Musical Tone Law Method for the Structural Damage Detection
Authors: Yang Weisong , Xu Weixiao , Guo Xun , Yang Liguo
Published: January 2017

Damage detection tests of inclined cables, steel pipes, spherical shells, and an actual cable-stayed bridge were conducted based on the proposed musical tone law method. The results show that the musical tone law method could be used in the damage detection of isotropic material structures with simple shape, like cables, pipes, plates, and shells. Having distinct spectral lines like a comb with a certain interval distribution rule is the main characteristic of the music tone law. Damage detection baseline could be established by quantizing the fitting relationship between modal orders and the corresponding frequency values. The main advantage of this method is that it could be used in the structural damage detection without vibration information of an intact structure as a reference.
Scattering and Bound States of a Spin-1/2 Neutral Particle in the Cosmic String Spacetime
Authors: Andrade Fabiano M. , Filgueiras Cleverson , Silva Edilberto O.
Published: January 2017

In this paper the relativistic quantum dynamics of a spin-1/2 neutral particle with a magnetic moment μ in the cosmic string spacetime is reexamined by applying the von Neumann theory of self-adjoint extensions. Contrary to previous studies where the interaction between the spin and the line of charge is neglected, here we consider its effects. This interaction gives rise to a point interaction: ∇·E=(2λ/α)δ(r)/r. Due to the presence of the Dirac delta function, by applying an appropriated boundary condition provided by the theory of self-adjoint extensions, irregular solutions for the Hamiltonian are allowed. We address the scattering problem obtaining the phase shift, S-matrix, and the scattering amplitude. The scattering amplitude obtained shows a dependency with energy which stems from the fact that the helicity is not conserved in this system. Examining the poles of the S-matrix we obtain an expression for the bound states. The presence of bound states for this system has not been discussed before in the literature.
Alcoholic Extract of Eclipta alba Shows In Vitro Antioxidant and Anticancer Activity without Exhibiting Toxicological Effects
Authors: Yadav Navneet Kumar , Arya Rakesh Kumar , Dev Kapil , Sharma Chetan , Hossain Zakir , Meena Sanjeev , Arya K. R. , Gayen J. R. , Datta Dipak , Singh R. K.
Published: January 2017

As per WHO estimates, 80% of people around the world use medicinal plants for the cure and prevention of various diseases including cancer owing to their easy availability and cost effectiveness. Eclipta alba has long been used in Ayurveda to treat liver diseases, eye ailments, and hair related disorders. The promising medicinal value of E. alba prompted us to study the antioxidant, nontoxic, and anticancer potential of its alcoholic extract. In the current study, we evaluated the in vitro cytotoxic and antioxidant effect of the alcoholic extract of Eclipta alba (AEEA) in multiple cancer cell lines along with control. We have also evaluated its effect on different in vivo toxicity parameters. Here, we found that AEEA was found to be most active in most of the cancer cell lines but it significantly induced apoptosis in human breast cancer cell lines by disrupting mitochondrial membrane potential and DNA damage. Moreover, AEEA treatment inhibited migration in both MCF 7 and MDA‐MB‐231 cells in a dose dependent manner. Further, AEEA possesses robust in vitro antioxidant activity along with high total phenolic and flavonoid contents. In summary, our results indicate that Eclipta alba has enormous potential in complementary and alternative medicine for the treatment of cancer.
Combined PET Imaging of the Inflammatory Tumor Microenvironment Identifies Margins of Unique Radiotracer Uptake
Authors: Zinnhardt Bastian , Pigeon Hayet , Thézé Benoit , Viel Thomas , Wachsmuth Lydia , Fricke Inga B. , Schelhaas Sonja , Honold Lisa , Schwegmann Katrin , Wagner Stefan , Faust Andreas , Faber Cornelius , Kuhlmann Michael T. , Hermann Sven , Schäfers Michael , Winkeler Alexandra , Jacobs Andreas H.
Published: January 2017

The tumor microenvironment is highly heterogeneous. For gliomas, the tumor-associated inflammatory response is pivotal to support growth and invasion. Factors of glioma growth, inflammation, and invasion, such as the translocator protein (TSPO) and matrix metalloproteinases (MMP), may serve as specific imaging biomarkers of the glioma microenvironment. In this study, noninvasive imaging by PET with [18F]DPA-714 (TSPO) and [18F]BR-351 (MMP) was used for the assessment of localization and quantification of the expression of TSPO and MMP. Imaging was performed in addition to established clinical imaging biomarker of active tumor volume ([18F]FET) in conjunction with MRI. We hypothesized that each imaging biomarker revealed distinct areas of the heterogeneous glioma tissue in a mouse model of human glioma. Tracers were found to be increased 1.4- to 1.7-fold, with [18F]FET showing the biggest volume as depicted by a thresholding-based, volumes of interest analysis. Tumor areas, which could not be detected by a single tracer and/or MRI parameter alone, were measured. Specific compartments of [18F]DPA-714 (14%) and [18F]BR-351 (11%) volumes along the tumor rim could be identified. [18F]DPA-714 (TSPO) and [18F]BR-351 (MMP) matched with histology. Glioma-associated microglia/macrophages (GAM) were identified as TSPO and MMP sources. Multitracer and multimodal molecular imaging approaches may allow us to gain important insights into glioma-associated inflammation (GAM, MMP). Moreover, this noninvasive technique enables characterization of the glioma microenvironment with respect to the disease-driving cellular compartments at the various disease stages. Cancer Res; 77(8); 1831–41. ©2017 AACR.
Estimating TP53 Mutation Carrier Probability in Families with Li–Fraumeni Syndrome Using LFSPRO
Authors: Peng Gang , Bojadzieva Jasmina , Ballinger Mandy L. , Li Jialu , Blackford Amanda L. , Mai Phuong L. , Savage Sharon A. , Thomas David M. , Strong Louise C. , Wang Wenyi
Published: January 2017

Background: Li–Fraumeni syndrome (LFS) is associated with germline TP53 mutations and a very high lifetime cancer risk. Algorithms that assess a patient's risk of inherited cancer predisposition are often used in clinical counseling. The existing LFS criteria have limitations, suggesting the need for an advanced prediction tool to support clinical decision making for TP53 mutation testing and LFS management.

Methods: Based on a Mendelian model, LFSPRO estimates TP53 mutation probability through the Elston–Stewart algorithm and consequently estimates future risk of cancer. With independent datasets of 1,353 tested individuals from 867 families, we evaluated the prediction performance of LFSPRO.

Results: LFSPRO accurately predicted TP53 mutation carriers in a pediatric sarcoma cohort from MD Anderson Cancer Center in the United States, the observed to expected ratio (OE) = 1.35 (95% confidence interval, 0.99–1.80); area under the receiver operating characteristic curve (AUC) = 0.85 (0.75–0.93); a population-based sarcoma cohort from the International Sarcoma Kindred Study in Australia, OE = 1.62 (1.03–2.55); AUC = 0.67 (0.54–0.79); and the NCI LFS study cohort, OE = 1.28 (1.17–1.39); AUC = 0.82 (0.78–0.86). LFSPRO also showed higher sensitivity and specificity than the classic LFS and Chompret criteria. LFSPRO is freely available through the R packages LFSPRO and BayesMendel.

Conclusions: LFSPRO shows good performance in predicting TP53 mutations in individuals and families in varied situations.

Impact: LFSPRO is more broadly applicable than the current clinical criteria and may improve clinical management for individuals and families with LFS. Cancer Epidemiol Biomarkers Prev; 26(6); 837–44. ©2017 AACR.
DNA Damage Response and Repair Gene Alterations Are Associated with Improved Survival in Patients with Platinum-Treated Advanced Urothelial Carcinoma
Authors: Teo Min Yuen , Bambury Richard M. , Zabor Emily C. , Jordan Emmet , Al-Ahmadie Hikmat , Boyd Mariel E. , Bouvier Nancy , Mullane Stephanie A. , Cha Eugene K. , Roper Nitin , Ostrovnaya Irina , Hyman David M. , Bochner Bernard H. , Arcila Maria E. , Solit David B. , Berger Michael F. , Bajorin Dean F. , Bellmunt Joaquim , Iyer Gopakumar , Rosenberg Jonathan E.
Published: January 2017

Purpose: Platinum-based chemotherapy remains the standard treatment for advanced urothelial carcinoma by inducing DNA damage. We hypothesize that somatic alterations in DNA damage response and repair (DDR) genes are associated with improved sensitivity to platinum-based chemotherapy.

Experimental Design: Patients with diagnosis of locally advanced and metastatic urothelial carcinoma treated with platinum-based chemotherapy who had exon sequencing with the Memorial Sloan Kettering–Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) assay were identified. Patients were dichotomized based on the presence/absence of alterations in a panel of 34 DDR genes. DDR alteration status was correlated with clinical outcomes and disease features.

Results: One hundred patients were identified, of which 47 harbored alterations in DDR genes. Patients with DDR alterations had improved progression-free survival (9.3 vs. 6.0 months, log-rank P = 0.007) and overall survival (23.7 vs. 13.0 months, log-rank P = 0.006). DDR alterations were also associated with higher number mutations and copy-number alterations. A trend toward positive correlation between DDR status and nodal metastases and inverse correlation with visceral metastases were observed. Different DDR pathways also suggested variable impact on clinical outcomes.

Conclusions: Somatic DDR alteration is associated with improved clinical outcomes in platinum-treated patients with advanced urothelial carcinoma. Once validated, it can improve patient selection for clinical practice and future study enrollment. Clin Cancer Res; 23(14); 3610–8. ©2017 AACR.
Differentiated State of Initiating Tumor Cells Is Key to Distinctive Immune Responses Seen in H-RasG12V–Induced Squamous Tumors
Authors: Podolsky Michael A. , Bailey Jacob T. , Gunderson Andrew J. , Oakes Carrie J. , Breech Kyle , Glick Adam B.
Published: January 2017

Heterogeneity in tumor immune responses is a poorly understood yet critical parameter for successful immunotherapy. In two doxycycline-inducible models where oncogenic H-RasG12V is targeted either to the epidermal basal/stem cell layer with a Keratin14-rtTA transgene (K14Ras), or committed progenitor/suprabasal cells with an Involucrin-tTA transgene (InvRas), we observed strikingly distinct tumor immune responses. On threshold doxycycline levels yielding similar Ras expression, tumor latency, and numbers, tumors from K14Ras mice had an immunosuppressed microenvironment, whereas InvRas tumors had a proinflammatory microenvironment. On a Rag1−/− background, InvRas mice developed fewer and smaller tumors that regressed over time, whereas K14Ras mice developed more tumors with shorter latency than Rag1+/+ controls. Adoptive transfer and depletion studies revealed that B-cell and CD4 T-cell cooperation was critical for tumor yield, lymphocyte polarization, and tumor immune phenotype in Rag1+/+ mice of both models. Coculture of tumor-conditioned B cells with CD4 T cells implicated direct contact for Th1 and regulatory T cell (Treg) polarization, and CD40-CD40L for Th1, Th2, and Treg generation, a response not observed from splenic B cells. Anti-CD40L caused regression of InvRas tumors but enhanced growth in K14Ras, whereas a CD40 agonist mAb had opposite effects in each tumor model. These data show that position of tumor-initiating cells within a stratified squamous epithelial tissue provokes distinct B- and CD4 T-cell interactions, which establish unique tumor microenvironments that regulate tumor development and response to immunotherapy. Cancer Immunol Res; 5(3); 198–210. ©2017 AACR.
Physical Activity and Incident Hypertension in African Americans
Authors: Diaz Keith M. , Booth John N. , Seals Samantha R. , Abdalla Marwah , Dubbert Patricia M. , Sims Mario , Ladapo Joseph A. , Redmond Nicole , Muntner Paul , Shimbo Daichi
Published: January 2017

There is limited empirical evidence to support the protective effects of physical activity in the prevention of hypertension among African Americans. The purpose of this study was to examine the association of physical activity with incident hypertension among African Americans. We studied 1311 participants without hypertension at baseline enrolled in the Jackson Heart Study, a community-based study of African Americans residing in Jackson, Mississippi. Overall physical activity, moderate–vigorous physical activity, and domain-specific physical activity (work, active living, household, and sport/exercise) were assessed by self-report during the baseline examination (2000–2004). Incident hypertension, assessed at examination 2 (2005–2008) and examination 3 (2009–2013), was defined as the first visit with systolic/diastolic blood pressure ≥140/90 mm Hg or self-reported antihypertensive medication use. Over a median follow-up of 8.0 years, there were 650 (49.6%) incident hypertension cases. The multivariable-adjusted hazard ratios (95% confidence interval) for incident hypertension comparing participants with intermediate and ideal versus poor levels of moderate–vigorous physical activity were 0.84 (0.67–1.05) and 0.76 (0.58–0.99), respectively (
P
trend=0.038). A graded, dose–response association was also present for sport/exercise-related physical activity (Quartiles 2, 3, and 4 versus Quartile 1: 0.92 [0.68–1.25], 0.87 [0.67–1.13], 0.75 [0.58–0.97], respectively;
P
trend=0.032). There were no statistically significant associations observed for overall physical activity, or work, active living, and household-related physical activities. In conclusion, the results of the current study suggest that regular moderate–vigorous physical activity or sport/exercise-related physical activity may reduce the risk of developing hypertension in African Americans.
Invasion of Cooperation in Scale-Free Networks: Accumulated versus Average Payoffs
Authors: Ichinose Genki , Sayama Hiroki
Published: January 2017

It is well known that cooperation cannot be an evolutionarily stable strategy for a non-iterative game in a well-mixed population. In contrast, structured populations favor cooperation, since cooperators can benefit each other by forming local clusters. Previous studies have shown that scale-free networks strongly promote cooperation. However, little is known about the invasion mechanism of cooperation in scale-free networks. To study microscopic and macroscopic behaviors of cooperators' invasion, we conducted computational experiments on the evolution of cooperation in scale-free networks where, starting from all defectors, cooperators can spontaneously emerge by mutation. Since the evolutionary dynamics are influenced by the definition of fitness, we tested two commonly adopted fitness functions: accumulated payoff and average payoff. Simulation results show that cooperation is strongly enhanced with the accumulated payoff fitness compared to the average payoff fitness. However, the difference between the two functions decreases as the average degree increases. As the average degree increases, cooperation decreases for the accumulated payoff fitness, while it increases for the average payoff fitness. Moreover, for the average payoff fitness, low-degree nodes play a more important role in spreading cooperative strategies than for the accumulated payoff fitness.
Online Gait Learning for Modular Robots with Arbitrary Shapes and Sizes
Authors: Weel Berend , D'Angelo M. , Haasdijk Evert , Eiben A. E.
Published: January 2017

Evolutionary robotics using real hardware is currently restricted to evolving robot controllers, but the technology for evolvable morphologies is advancing quickly. Rapid prototyping (3D printing) and automated assembly are the main enablers of robotic systems where robot offspring can be produced based on a blueprint that specifies the morphologies and the controllers of the parents. This article addresses the problem of gait learning in newborn robots whose morphology is unknown in advance. We investigate a reinforcement learning method and conduct simulation experiments using robot morphologies with different size and complexity. We establish that reinforcement learning does the job well and that it outperforms two alternative algorithms. The experiments also give insights into the online dynamics of gait learning and into the influence of the size, shape, and morphological complexity of the modular robots. These insights can potentially be used to predict the viability of modular robotic organisms before they are constructed.
Canada Acute Coronary Syndrome Score: A Preprocedural Risk Score for Contrast-Induced Nephropathy After Primary Percutaneous Coronary Intervention
Authors: Liu Yuan-Hui , Jiang Lei , Duan Chong-Yang , He Peng-Cheng , Liu Yong , Tan Ning , Chen Ji-Yan
Published: January 2017

In patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention, contrast-induced nephropathy (CIN) is a serious complication associated with poor outcomes. We assessed the predictive value of the Canada Acute Coronary Syndrome (C-ACS) score for CIN in these patients. A total of 394 consecutive patients with STEMI were enrolled and divided into 3 groups according to their C-ACS scores—group 1, score 0; group 2, score 1; and group 3, score ≥2. The clinical outcomes were CIN and major adverse clinical events (MACEs) during hospital and follow-up; 8.4% of patients developed CIN. Patients with high C-ACS scores were more likely to develop CIN, in-hospital death, and MACEs ( P < .001). The C-ACS score was an independent predictor of CIN (odds ratio = 2.87; 95% confidence interval = 1.78-4.63; P < .001) and risk factor for long-term MACEs. The C-ACS score had good predictive values for CIN, in-hospital morality, MACEs, and long-term mortality. Patients with high C-ACS risk scores exhibited a worse survival rate than those with low scores (death, P = .02; MACEs, P = .006). In conclusion, in patients with STEMI, the C-ACS could predict CIN and clinical outcomes.
Disparities in Health Supervision for Children With Down Syndrome
Authors: Williams Katie , Wargowski David , Eickhoff Jens , Wald Ellen
Published: January 2017

Increasing evidence suggests children with Down syndrome do not receive recommended health care services. We retrospectively assessed adherence to the 2001 American Academy of Pediatrics health supervision guidelines for 124 children with Down syndrome. Cervical spine radiographs were completed for 94% of children, often preoperatively. Adherence to complete blood count recommendations was 55% (95% CI 44% to 66%); lower for males ( P = .01) and children with private medical insurance ( P = .04). Adherence to thyroid function recommendations was 61% (95% CI 54% to 67%); higher for children seen by a pediatrician ( P = .002) and with known thyroid disease ( P < .0001). Adherence to audiology and ophthalmology recommendations was 33% (95% CI 27% to 40%) and 43% (95% CI 37% to 50%), respectively. Adherence rates were higher for children referred to an otolaryngologist ( P = .0002) and with known eye disease ( P < .0001). Future efforts should identify barriers to care and improve adherence to recommended screening.
Circumcision of the Heart: Extrinsic and Intrinsic Religiosity in Romans 1–5
Authors: Carson Marion L. S.
Published: January 2017

The question of whether Paul objecting to works righteousness, or Jewish religious pride continues to dominate discussion of Romans 1–5. This paper takes a different approach. Drawing on Allport’s and Ross’s theory of Extrinsic and Intrinsic Religion, it suggests that, when Paul speaks of faith, he is thinking of a deeply-held spirituality which seeks God for himself (‘circumcision of the heart’). He sets this over and above self-serving religiosity, a tendency which is found in all religious communities and which he fears is threatening the church at Rome. The paper explores the implications of this interpretation for some recent exegetical debates and for contemporary pastoral practice.
Who Leads the Party? On Membership Size, Selectorates and Party Oligarchy
Authors: Schumacher Gijs , Giger Nathalie
Published: January 2017

We examine the degree to which party leaders dominate their parties over time and across countries and analyse how leadership domination relates to formal aspects of party organisation. Moreover, we analyse whether antidotes against leadership domination – widening the selectorate and increasing the membership – explain change in leadership domination. For this purpose, we use a new dataset that brings together different sources of party data over time and between countries. We find that leadership domination indeed has increased over time, but still a lot of variation exists between parties. We also demonstrate that widening the selectorate – for example, letting members elect the party leader – and increasing membership boosts leadership domination. In other words, the antidotes against leadership domination do not work.