bluuebunny/crossref_metadata_2025_split huggingface dataset:
Self‐Protective Altruism
Authors: Hirschberger Gilad 
Published: February 2013

AbstractProsocial behavior accentuates the tension between two conflicting human motivations, self‐interest and belongingness. Responding to the needs of others may compromise self‐interest. Acting callously, however, may lead to social disproval. These antagonistic responses are existentially meaningful as belongingness and self‐esteem have been found to regulate death anxiety. In this paper I critically examine three possible hypotheses concerning the tension between egotism and prosociality from a terror management perspective. The first hypothesis, the carpe diem hypothesis, suggests that when death is salient egotistic self‐interest overrides other‐oriented responses. The second hypothesis, the norm salience hypothesis, suggests that when death is salient people will respond according to the momentarily accessible social norm. The third hypothesis, the self‐protective altruism hypothesis, argues that when the prosocial cause reminds people of their fragile, mortal nature people will turn away from helping when death is salient, but when the prosocial cause is benign death salience will increase prosocial responding.
Efficacy of combined antiviral therapy with lamivudine and tenofovir in a liver transplanted girl with de novo hepatitis B virus infection
Authors: Tufano M. , Liccardo D. , Riva S. , Candusso M. , Torre G. , Iorio R. 
Published: February 2013

AbstractThe management of de novo hepatitis B (HBV) infection in children after liver transplantation is not well defined. Because this infection may induce severe liver disease in the graft liver, an efficient antiviral therapy is desirable. Here, we describe the favorable viral outcome observed in a liver transplanted girl with de novo HBV infection following combination therapy with lamivudine and tenofovir.
Improving best‐phase image quality in cardiac CT by motion correction with MAM optimization
Authors: Rohkohl Christopher , Bruder Herbert , Stierstorfer Karl , Flohr Thomas 
Published: February 2013

Purpose:Research in image reconstruction for cardiac CT aims at using motion correction algorithms to improve the image quality of the coronary arteries. The key to those algorithms is motion estimation, which is currently based on 3‐D/3‐D registration to align the structures of interest in images acquired in multiple heart phases. The need for an extended scan data range covering several heart phases is critical in terms of radiation dose to the patient and limits the clinical potential of the method. Furthermore, literature reports only slight quality improvements of the motion corrected images when compared to the most quiet phase (best‐phase) that was actually used for motion estimation. In this paper a motion estimation algorithm is proposed which does not require an extended scan range but works with a short scan data interval, and which markedly improves the best‐phase image quality.Methods:Motion estimation is based on the definition of motion artifact metrics (MAM) to quantify motion artifacts in a 3‐D reconstructed image volume. The authors use two different MAMs, entropy, and positivity. By adjusting the motion field parameters, the MAM of the resulting motion‐compensated reconstruction is optimized using a gradient descent procedure. In this way motion artifacts are minimized. For a fast and practical implementation, only analytical methods are used for motion estimation and compensation. Both the MAM‐optimization and a 3‐D/3‐D registration‐based motion estimation algorithm were investigated by means of a computer‐simulated vessel with a cardiac motion profile. Image quality was evaluated using normalized cross‐correlation (NCC) with the ground truth template and root‐mean‐square deviation (RMSD). Four coronary CT angiography patient cases were reconstructed to evaluate the clinical performance of the proposed method.Results:For the MAM‐approach, the best‐phase image quality could be improved for all investigated heart phases, with a maximum improvement of the NCC value by 100% and of the RMSD value by 81%. The corresponding maximum improvements for the registration‐based approach were 20% and 40%. In phases with very rapid motion the registration‐based algorithm obtained better image quality, while the image quality of the MAM algorithm was superior in phases with less motion. The image quality improvement of the MAM optimization was visually confirmed for the different clinical cases.Conclusions:The proposed method allows a software‐based best‐phase image quality improvement in coronary CT angiography. A short scan data interval at the target heart phase is sufficient, no additional scan data in other cardiac phases are required. The algorithm is therefore directly applicable to any standard cardiac CT acquisition protocol.
Analytical derivation of the b matrix of a time‐efficient isotropic diffusion weighting gradient waveform
Authors: Trampel Robert , Johnson Glyn 
Published: February 2013

Purpose:Diffusion‐weighted magnetic resonance imaging of3He provides information about lung structure. If rotationally invariant measures of diffusion are desired, an equal diffusion weighting in all three spatial directions is necessary to obtain. In order to achieve such isotropic diffusion weighting, gradients have to be applied in these three spatial directions, which can be time consuming. Therefore, the purpose of this study was the analytic derivation of a time‐efficient isotropic diffusion weighting scheme.Methods:The completeb matrix of a preselected gradient waveform was derived analytically. The effect of ramp times and the contribution of the imaging gradients were included in the calculation. The time‐efficient waveform was compared to a standard isotropic diffusion weighting scheme by determining the mean diffusivity of hyperpolarized 3He in human lungs.Results:An analytically derived expression of theb matrix for a time‐efficient gradient scheme allowing isotropic diffusion weighting was derived. Additionally, the b matrix of a common set of imaging gradients was calculated. Diffusion measurements of hyperpolarized 3He in human lungs using the derived optimized gradient scheme and a standard gradient waveform used for isotropic diffusion weighting, respectively, gave results for the mean diffusivity which did not show any statistical difference. However, the echo time using the optimized scheme was reduced by 2.5 ms in comparison with the standard scheme which leads to a theoretical signal increase of 30%.Conclusions:The analytically derivedb matrix allows for the straightforward determination of time‐efficient isotropic diffusion weighting schemes. By using those schemes, a substantial gain in signal can be achieved whereas the resulting values for the mean diffusivity did not show any statistical difference to the values obtained when using standard waveforms for isotropic diffusion weighting.
Development and Optimization of a Novel Assay To Measure Neutralizing Antibodies against Clostridium difficile Toxins
Authors: Xie Jinfu , Zorman Julie , Indrawati Lani , Horton Melanie , Soring Keri , Antonello Joseph M. , Zhang Yuhua , Secore Susan , Miezeiewski Matthew , Wang Su , Kanavage Anthony D. , Skinner Julie M. , Rogers Irene , Bodmer Jean-Luc , Heinrichs Jon H. 
Published: February 2013

ABSTRACT

Clostridium difficile
produces two major virulence toxins, toxin A (TcdA) and toxin B (TcdB). Antitoxin antibodies, especially neutralizing antibodies, have been shown to be associated with a lower incidence of
C. difficile
infection (CDI) recurrence, and antibody levels are predictive of asymptomatic colonization. The development of an assay to detect the presence of neutralizing antibodies in animal and human sera for the evaluation of vaccine efficacy is highly desired. We have developed such an assay, which allows for the quantification of the effect of toxins on eukaryotic cells in an automated manner. We describe here the optimization of this assay to measure toxin potency as well as neutralizing antibody (NAb) activity against
C. difficile
toxins using a design-of-experiment (DOE) methodology. Toxin concentration and source, cell seeding density, and serum-toxin preincubation time were optimized in the assay using Vero cells. The assay was shown to be robust and to produce linear results across a range of antibody concentrations. It can be used to quantify neutralizing antibodies in sera of monkeys and hamsters immunized with
C. difficile
toxoid vaccines. This assay was shown to correlate strongly with traditional assays which rely on labor-intensive methods of determining neutralizing antibody titers by visual microscopic inspection of intoxicated-cell monolayers. This assay has utility for the selection and optimization of
C. difficile
vaccine candidates.
Modified Hodge Test versus Indirect Carbapenemase Test: Prospective Evaluation of a Phenotypic Assay for Detection of Klebsiella pneumoniae Carbapenemase (KPC) in Enterobacteriaceae
Authors: Mathers Amy J. , Carroll Joanne , Sifri Costi D. , Hazen Kevin C. 
Published: February 2013

ABSTRACT

The currently recommended phenotypic test for the detection of carbapenemase-producing members of the family
Enterobacteriaceae
is the modified Hodge test (MHT). However, the MHT lacks specificity. Here we demonstrate an alternative phenotypic test, the indirect carbapenemase test, for the detection of
bla
KPC
-producing isolates that has specificity superior to that of the MHT for non-
Klebsiella Enterobacteriaceae
.
The Repression Domain of the E1B 55-Kilodalton Protein Participates in Countering Interferon-Induced Inhibition of Adenovirus Replication
Authors: Chahal Jasdave S. , Gallagher Courtney , DeHart Caroline J. , Flint S. J. 
Published: February 2013

ABSTRACTTo begin to investigate the mechanism by which the human adenovirus type 5 E1B 55-kDa protein protects against the antiviral effects of type 1 interferon (IFN) (J. S. Chahal, J. Qi, and S. J. Flint, PLoS Pathog.8:e1002853, 2012 [doi:10.1371/journal.ppat.1002853]), we examined the effects of precise amino acid substitution in this protein on resistance of viral replication to the cytokine. Only substitution of residues 443 to 448 of E1B for alanine (E1B Sub19) specifically impaired production of progeny virus and resulted in a large defect in viral DNA synthesis in IFN-treated normal human fibroblasts. Untreated or IFN-treated cells infected by this mutant virus (AdEasyE1Sub19) contained much higher steady-state concentrations of IFN-inducible GBP1 and IFIT2 mRNAs than did wild-type-infected cells and of the corresponding newly transcribed pre-mRNAs, isolated exploiting 5′-ethynyluridine labeling and click chemistry. These results indicated that the mutations created by substitution of residues 443 to 448 for alanine (Sub19) impair repression of transcription of IFN-inducible genes, by the E1B, 55-kDa protein, consistent with their location in a segment required for repression of p53-dependent transcription. However, when synthesized alone, the E1B 55-kDa protein inhibited expression of the p53-regulated genes BAX and MDM2 but had no impact whatsoever on induction of IFIT2 and GBP1 expression by IFN. These observations correlate repression of transcription of IFN-inducible genes by the E1B 55-kDa protein with protection against inhibition of viral genome replication and indicate that the E1B 55-kDa protein is not sufficient to establish such transcriptional repression.
Understanding public drug procurement in India: a comparative qualitative study of five Indian states
Authors: Singh Prabal Vikram , Tatambhotla Anand , Kalvakuntla Rohini , Chokshi Maulik 
Published: February 2013

ObjectiveTo perform an initial qualitative comparison of the different procurement models in India to frame questions for future research in this area; to capture the finer differences between the state models through 53 process and price parameters to determine their functional efficiencies.DesignQualitative analysis is performed for the study. Five states: Tamil Nadu, Kerala, Odisha, Punjab and Maharashtra were chosen to ensure heterogeneity in a number of factors such as procurement type (centralised, decentralised or mixed); autonomy of the procurement organisation; state of public health infrastructure; geography and availability of data through Right to Information Act (RTI). Data on procurement processes were collected through key informant analysis by way of semistructured interviews with leadership teams of procuring organisations. These process data were validated through interviews with field staff (stakeholders of district hospitals, taluk hospitals, community health centres and primary health centres) in each state. A total of 30 actors were interviewed in all five states. The data collected are analysed against 52 process and price parameters to determine the functional efficiency of the model.ResultsThe analysis indicated that autonomous procurement organisations were more efficient in relation to payments to suppliers, had relatively lower drug procurement prices and managed their inventory more scientifically.ConclusionsThe authors highlight critical success factors that significantly influence the outcome of any procurement model. In a way, this study raises more questions and seeks the need for further research in this arena to aid policy makers.
Oncolytic Vaccinia Virus Disrupts Tumor-Associated Vasculature in Humans
Authors: Breitbach Caroline J. , Arulanandam Rozanne , De Silva Naomi , Thorne Steve H. , Patt Richard , Daneshmand Manijeh , Moon Anne , Ilkow Carolina , Burke James , Hwang Tae-Ho , Heo Jeong , Cho Mong , Chen Hannah , Angarita Fernando A. , Addison Christina , McCart J. Andrea , Bell John C. , Kirn David H. 
Published: February 2013

Abstract
Efforts to selectively target and disrupt established tumor vasculature have largely failed to date. We hypothesized that a vaccinia virus engineered to target cells with activation of the ras/MAPK signaling pathway (JX-594) could specifically infect and express transgenes (hGM-CSF, β-galactosidase) in tumor-associated vascular endothelial cells in humans. Efficient replication and transgene expression in normal human endothelial cells in vitro required either VEGF or FGF-2 stimulation. Intravenous infusion in mice resulted in virus replication in tumor-associated endothelial cells, disruption of tumor blood flow, and hypoxia within 48 hours; massive tumor necrosis ensued within 5 days. Normal vessels were not affected. In patients treated with intravenous JX-594 in a phase I clinical trial, we showed dose-dependent endothelial cell infection and transgene expression in tumor biopsies of diverse histologies. Finally, patients with advanced hepatocellular carcinoma, a hypervascular and VEGF-rich tumor type, were treated with JX-594 on phase II clinical trials. JX-594 treatment caused disruption of tumor perfusion as early as 5 days in both VEGF receptor inhibitor-naïve and -refractory patients. Toxicities to normal blood vessels or to wound healing were not evident clinically or on MRI scans. This platform technology opens up the possibility of multifunctional engineered vaccinia products that selectively target and infect tumor-associated endothelial cells, as well as cancer cells, resulting in transgene expression, vasculature disruption, and tumor destruction in humans systemically. Cancer Res; 73(4); 1265–75. ©2012 AACR.
Melanoma Genetic Testing, Counseling, and Adherence to Skin Cancer Prevention and Detection Behaviors
Authors: Glanz Karen , Volpicelli Kathryn , Kanetsky Peter A. , Ming Michael E. , Schuchter Lynn M. , Jepson Christopher , Domchek Susan M. , Armstrong Katrina 
Published: February 2013

AbstractBackground: Little is known about the impact of knowledge of CDKN2A and MC1R genotype on melanoma prevention behaviors like sun avoidance and skin examination in the context of familial melanoma.Methods: Seventy-three adults with a family history of melanoma were randomly assigned to be offered individualized CDKN2A and MC1R genotyping results in the context of a genetic counseling session, or the standard practice of not being offered counseling or disclosure of genotyping results. Mixed effects or longitudinal logistic models were used to determine whether the intervention affected change in sun protection habits, skin examinations, and perception and beliefs related to melanoma risk, prevention, and genetic counseling.Results: All participants in the intervention group who attended genetic counseling sessions chose to receive their test results. From baseline to follow-up, participants in the intervention group reported an increase in the frequency of skin self-examinations compared with a slight decrease in the control group (P = 0.002). Participants in the intervention group reported a smaller decrease in frequency of wearing a shirt with long sleeves than did participants in the control group (P = 0.047). No effect of the intervention was noted for other outcomes.Conclusions: Feedback of CDKN2A and MC1R genotype among families without known pathogenic CDKN2A mutations does not seem to decrease sun protection behaviors.Impact: While disclosure of CDKN2A and MC1R genotype did not have negative effects on prevention, the benefits of communicating this information remain unclear. The small number of families who tested positive for CDKN2A mutations in this study is a limitation. Cancer Epidemiol Biomarkers Prev; 22(4); 607–14. ©2013 AACR.
Activator Protein-2α Mediates Carbon Monoxide–Induced Stromal Cell–Derived Factor-1α Expression and Vascularization in Ischemic Heart
Authors: Lin Heng-Huei , Chen Yen-Hui , Chiang Ming-Tsai , Huang Pei-Ling , Chau Lee-Young 
Published: February 2013

Objective—
Increased cardiac stromal cell-derived factor-1α (SDF-1α) expression promotes neovascularization and myocardial repair after ischemic injury through recruiting stem cells and reducing cardiomyocyte death. Previous studies have shown that heme oxygenase-1 and its reaction byproduct, carbon monoxide (CO), induce SDF-1α expression in ischemic heart. However, the mechanism underlying heme oxygenase-1/CO-induced cardiac SDF-1α expression remains elusive. This study aims to investigate the signaling pathway and the transcriptional factor that mediate CO-induced SDF-1α gene expression and cardioprotection.

Approach and Results—
CO gas and a CO-releasing compound, tricarbonyldichlororuthenium (II) dimer, dose-dependently induced SDF-1α expression in primary neonatal cardiomyocytes and H9C2 cardiomyoblasts. Promoter luciferase-reporter assay, electrophoretic mobility shift assay, and chromatin immunoprecipitation demonstrated that the activator protein 2α (AP-2α) mediated tricarbonyldichlororuthenium (II) dimer-induced SDF-1α gene transcription. Tricarbonyldichlororuthenium (II) dimer induced AP-2α expression via protein kinase B (AKT)-dependent signaling. AKT inhibition or AP-2α knockdown reduced tricarbonyldichlororuthenium (II) dimer-induced SDF-1α expression. Coronary ligation induced transient increases of cardiac AP-2α and SDF-1α expression, which were declined at 1 week postinfarction in mice. Periodic exposure of coronary-ligated mice to CO (250 ppm for 1 hour/day, 6 days) resumed the induction of AP-2α and SDF-1α gene expression in infarcted hearts. Immunohistochemistry and echocardiography performed at 4 weeks after coronary ligation revealed that CO treatment enhanced neovascularization in the myocardium of peri-infarct region and improved cardiac function. CO-mediated SDF-1α expression and cardioprotection was ablated by intramyocardial injection of lentivirus bearing specific short hairpin RNA targeting AP-2α.

Conclusions—
Our data demonstrate that AKT-dependent upregulation of AP-2α is essential for CO-induced SDF-1α expression and myocardial repair after ischemic injury.
Genetic Variation in
PEAR1
Is Associated With Platelet Aggregation and Cardiovascular Outcomes
Authors: Lewis Joshua P. , Ryan Kathleen , O’Connell Jeffrey R. , Horenstein Richard B. , Damcott Coleen M. , Gibson Quince , Pollin Toni I. , Mitchell Braxton D. , Beitelshees Amber L. , Pakzy Ruth , Tanner Keith , Parsa Afshin , Tantry Udaya S. , Bliden Kevin P. , Post Wendy S. , Faraday Nauder , Herzog William , Gong Yan , Pepine Carl J. , Johnson Julie A. , Gurbel Paul A. , Shuldiner Alan R. 
Published: February 2013

Background—
Aspirin or dual antiplatelet therapy with aspirin and clopidogrel is a standard therapy for patients who are at increased risk for cardiovascular events. However, the genetic determinants of variable response to aspirin (alone and in combination with clopidogrel) are not known.

Methods and Results—

We measured ex vivo platelet aggregation before and after dual antiplatelet therapy in individuals (n=565) from the Pharmacogenomics of Anti-Platelet Intervention (PAPI) Study and conducted a genome-wide association study of drug response. Significant findings were extended by examining genotype and cardiovascular outcomes in 2 independent aspirin-treated cohorts: 227 percutaneous coronary intervention patients and 1000 patients of the International Verapamil SR/Trandolapril Study (INVEST) Genetic Substudy (INVEST-GENES). Results from the genome-wide association study revealed a strong association between single-nucleotide polymorphisms on chromosome 1q23 and post–dual antiplatelet therapyplatelet aggregation. Further genotyping revealed rs12041331 in the platelet endothelial aggregation receptor-1 (
PEAR1
) gene to be most strongly associated with dual antiplatelet therapy response (
P
=7.66×10
−9
). In white and black patients undergoing percutaneous coronary intervention, A-allele carriers of rs12041331 were more likely to experience a cardiovascular event or death compared with GG homozygotes (hazard ratio, 2.62; 95% confidence interval, 0.96–7.10;
P
=0.059; and hazard ratio, 3.97; 95% confidence interval, 1.10–14.31;
P
=0.035, respectively). In aspirin-treated INVEST-GENES patients, rs12041331 A-allele carriers had significantly increased risk of myocardial infarction compared with GG homozygotes (odds ratio, 2.03; 95% confidence interval, 1.01–4.09;
P
=0.048).

Conclusion—

Common genetic variation in
PEAR1
may be a determinant of platelet response and cardiovascular events in patients on aspirin alone or in combination with clopidogrel.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifiers: NCT00799396 and NCT00370045