bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of On-Treatment Platelet Reactivity Between Triple Antiplatelet Therapy With Cilostazol and Standard Dual Antiplatelet Therapy in Patients Undergoing Coronary Interventions
Authors: Panchal Hemang B. , Shah Tejaskumar , Patel Parthavkumar , Albalbissi Kais , Molnar Janos , Coffey Brandon , Khosla Sandeep , Ramu Vijay 
Published: July 2013

Background: The recent literature has shown that triple antiplatelet therapy with cilostazol in addition to the standard dual antiplatelet therapy with aspirin and clopidogrel may reduce platelet reactivity and improve clinical outcomes following percutaneous coronary intervention. The purpose of this meta-analysis is to compare the efficacy of triple antiplatelet therapy and dual antiplatelet therapy in regard to on-treatment platelet reactivity. Methods: Nine studies (n = 2179) comparing on-treatment platelet reactivity between dual antiplatelet therapy (n = 1193) and triple antiplatelet therapy (n = 986) in patients undergoing percutaneous coronary intervention were included. Primary end points were P2Y12 reaction unit (PRU) and platelet reactivity index (PRI). Secondary end points were platelet aggregation with adenosine diphosphate (ADP) 5 and 20 µmol/L and P2Y12% inhibition. Mean difference (MD) and 95% confidence intervals (CI) were computed and 2-sided α error <.05 was considered as a level of significance. Results: Compared to dual antiplatelet therapy, triple antiplatelet therapy had significantly lower maximum platelet aggregation with ADP 5 µmol/L (MD: −14.4, CI: −21.6 to −7.2, P < .001) and 20 µmol/L (MD: −14.9, CI: −22.9 to −6.8, P < .001), significantly lower PRUs (MD: −45, CI: −59.4 to −30.6, P < .001) and PRI (MD: −26, CI: −36.8 to −15.2, P < .001), and significantly higher P2Y12% inhibition (MD: 18.5, CI: 2.3 to 34.6, P = .025). Conclusion: Addition of cilostazol to conventional dual antiplatelet therapy significantly lowers platelet reactivity and may explain a decrease in thromboembolic events following coronary intervention; however, additional studies evaluating clinical outcomes will be helpful to determine the benefit of triple antiplatelet therapy.
Genetic and epigenetic analysis of putative breast cancer stem cell models
Authors: Balic Marija , Schwarzenbacher Daniela , Stanzer Stefanie , Heitzer Ellen , Auer Martina , Geigl Jochen B , Cote Richard J , Datar Ram H , Dandachi Nadia 
Published: July 2013

Abstract

Background
Cancer stem cell model hypothesizes existence of a small proportion of tumor cells capable of sustaining tumor formation, self-renewal and differentiation. In breast cancer, these cells were found to be associated with CD44+CD24-low and ALDH+ phenotype. Our study was performed to evaluate the suitability of current approaches for breast cancer stem cell analyses to evaluate heterogeneity of breast cancer cells through their extensive genetic and epigenetic characterization.

Methods
Breast cancer cell lines MCF7 and SUM159 were cultured in adherent conditions and as mammospheres. Flow cytometry sorting for CD44, CD24 and ALDH was performed. Sorted and unsorted populations, mammospheres and adherent cell cultures were subjected to DNA profiling by array CGH and methylation profiling by Epitect Methyl qPCR array. Methylation status of selected genes was further evaluated by pyrosequencing. Functional impact of methylation was evaluated by mRNA analysis for selected genes.

Results
Array CGH did not reveal any genomic differences. In contrast, putative breast cancer stem cells showed altered methylation levels of several genes compared to parental tumor cells.

Conclusions
Our results underpin the hypothesis that epigenetic mechanisms seem to play a major role in the regulation of CSCs. However, it is also clear that more efficient methods for CSC enrichment are needed. This work underscores requirement of additional approaches to reveal heterogeneity within breast cancer.
Strong convergence of a self-adaptive method for the split feasibility problem
Authors: Yao Yonghong , Postolache Mihai , Liou Yeong-Cheng 
Published: July 2013

Abstract
Self-adaptive methods which permit step-sizes being selected self-adaptively are effective methods for solving some important problems, e.g., variational inequality problems. We devote this paper to developing and improving the self-adaptive methods for solving the split feasibility problem. A new improved self-adaptive method is introduced for solving the split feasibility problem. As a special case, the minimum norm solution of the split feasibility problem can be approached iteratively.

MSC:47J25, 47J20, 49N45, 65J15.
Vulvar “proximal-type” epithelioid sarcoma: report of a case and review of the literature
Authors: Patrizi Lodovico , Corrado Giacomo , Saltari Maria , Perracchio Letizia , Scelzo Chiara , Piccione Emilio , Vizza Enrico 
Published: July 2013

Abstract

Background
The “proximal-type” epithelioid sarcoma is a very rare kind of mesenchimal tumor characterized by the difficulty in histological diagnosis and the very aggressive biological behavior.

Case
We report of a case of a 63 years old woman with a vulvar “proximal-type” epithelioid sarcoma that underwent a radical surgical staging followed by an adjuvant radiotherapy. She is on follow-up care for 14 months and there is no clinical evidence of disease.

Conclusion
Even if quite rare the proximal type epithelioid sarcoma should be regarded as a separate entity of particularly aggressive biologic behaviour. Its diagnosis attracts controversies and criticism related to the surgical approach and the choice of an adjuvant therapy.

Virtual slides
The virtual slide(s) for this article can be found here:http://www.diagnosticpathology.diagnomx.eu/vs/1508554852942125
Evaluation of a combinatorial approach to prion inactivation using an oxidizing agent, SDS, and proteinase K
Authors: Smith Jodi D , Nicholson Eric M , Greenlee Justin J 
Published: July 2013

Abstract

Background
Prions demonstrate an unusual resistance to methods effective at inactivating conventional microorganisms. This has resulted in a very tangible and difficult infection control challenge to the medical and veterinary communities, as well as animal agriculture and related industries. Currently accepted practices of harsh chemical treatments such as prolonged exposure to sodium hydroxide or sodium hypochlorite, or autoclaving are not suitable in many situations. Less caustic and more readily applicable treatments to contaminated environments are therefore desirable. We recently demonstrated that exposure of the RML scrapie agent to a commercial product containing sodium percarbonate (SPC-P) with or without sodium dodecyl sulfate (SDS) rendered PrPSc sensitive to proteinase K (PK), but did not eliminate infectivity. The current study was designed to evaluate the efficacy of a combinatorial approach to inactivating prions by exposing RML-positive brain homogenate to SPC-P and SDS followed by PK. Treated samples were evaluated for PrPSc-immunoreactivity by western blot, and residual infectivity by mouse bioassay.

Results
Treatment of infected brain homogenate with SPC-P and SDS followed by PK exposure resulted in a 4–5 log10 reduction in infectivity when bioassayed in tga20 mice.

Conclusions
This study demonstrates that exposure of the RML scrapie agent to SPC-P and SDS followed by PK markedly reduces, but does not eliminate infectivity. The results of this study encourage further investigation into whether consecutive or concomitant exposure to sodium percarbonate, SDS, and a protease may serve as a viable and non-caustic option for prion inactivation.
Bulk milk ELISA and the diagnosis of parasite infections in dairy herds: a review
Authors: Sekiya Mary , Zintl Annetta , Doherty Michael L 
Published: July 2013

AbstractThe bulk milk enzyme-linked immune sorbent assay (ELISA) is a rapid and inexpensive method of assessing herd exposure to pathogens that is increasingly being used for the diagnosis of parasite infections in dairy herds. In this paper, with the dairy herd health veterinarian in mind, we review the principles of the assay and the recent literature on the potential role of bulk milk ELISA for the diagnosis of ostertagiosis, fasciolosis, parasitic bronchitis due to cattle lung worm and neosporosis. It is generally accepted that assay results reflect exposure to the parasite rather than the presence of active infection. Bulk milk ELISA can be a useful tool for the veterinary practitioner as a component of a herd health monitoring programme or in the context of a herd health investigation. It can also play a role in regional or national surveillance programmes. However, the results need to be interpreted within the context of the herd-specific health management, the milk production pattern and the parasite life cycle.
Ets-1 global gene expression profile reveals associations with metabolism and oxidative stress in ovarian and breast cancers
Authors: Verschoor Meghan L , Verschoor Chris P , Singh Gurmit 
Published: July 2013

AbstractBackgroundThe Ets-1 proto-oncogene is frequently upregulated in cancer cells, with known involvement in cancer angiogenesis, metastasis, and more recently energy metabolism. In this study we have performed various bioinformatic analyses on existing microarray data to further clarify the role of Ets-1 in ovarian cancer, and validated these results with functional assays.MethodsFunctional pathway analyses were conducted on existing microarray data comparing 2008 and 2008-Ets1 ovarian cancer cells. Methods included over-representation analysis, functional class scoring and pathway topology, and network representations were visualized in Cytoscape. Oxidative stress regulation was examined in ovarian cancer cells by measuring protein expression and enzyme activity of glutathione peroxidases, as well as intracellular reactive oxygen species using dichlorofluorescin fluorescence. A stable Ets-1 knockdown MDA-MB-231 cell line was created using short hairpin RNA, and glycolytic dependence of these cells was measured following treatment with 2-deoxy-D-glucose and Hoechst nuclear staining to determine cell number. High-resolution respirometry was performed to measure changes in basal oxygen flux between MDA-MB-231 cells and MDA-Ets1KD variants.ResultsEnrichments in oxidoreductase activity and various metabolic pathways were observed upon integration of the different analyses, suggesting that Ets-1 is important in their regulation. As oxidative stress is closely associated with these pathways, we functionally validated our observations by showing that Ets-1 overexpression resulted in decreased reactive oxygen species with increased glutathione peroxidase expression and activity, thereby regulating cellular oxidative stress. To extend our findings to another cancer type, we developed an Ets-1 knockdown breast cancer cell model, which displayed decreased glycolytic dependence and increased oxygen consumption following Ets-1 knockdown confirming our earlier findings.ConclusionsCollectively, this study confirms the important role of Ets-1 in the regulation of cancer energy metabolism in ovarian and breast cancers. Furthermore, Ets-1 is a key regulator of oxidative stress in ovarian cancer cells by mediating alterations in glutathione antioxidant capacity.
Depletion of myocardial glucose is observed during endotoxemic but not hemorrhagic shock in a porcine model
Authors: Chew Michelle S , Shekar Kiran , Brand Björn A , Norin Carl , Barnett Adrian G 
Published: July 2013

Abstract
Introduction
Metabolic dysfunction is one of the hallmarks of sepsis yet little is known about local changes in key organs such as the heart. The aim of this study was to compare myocardial metabolic changes by direct measurements of substrates, such as glucose, lactate and pyruvate, using microdialysis (MD) in in-vivo porcine endotoxemic and hemorrhagic shock. To assess whether these changes were specific to the heart, we simultaneously investigated substrate levels in skeletal muscle.

Methods
Twenty-six female pigs were randomized to three groups: control (C) n = 8, endotoxemic shock (E) n = 9 and hemorrhagic shock (H) n = 9. Interstitial myocardial pyruvate, lactate and glucose were measured using MD. Skeletal muscle MD was also performed in all three groups.

Results
Marked decreases in myocardial glucose were observed in the E group but not in the H group compared to controls (mean difference (CI) in mmol/L: C versus E -1.5(-2.2 to -0.8), P <0.001; H versus E -1.1(-1.8 to -0.4), P = 0.004; C versus H -0.4(-1.1 to 0.3), P = 0.282). Up to four-fold increases in myocardial pyruvate and three-fold increases in lactate were seen in both shock groups with no differences between the two types of shock. There was no evidence of myocardial anaerobic metabolism, with normal lactate:pyruvate (L:P) ratios seen in all animals regardless of the type of shock.
In skeletal muscle, decreases in glucose concentrations were observed in the E group only (mean difference: C versus E -0.8(-1.4 to -0.3), P = 0.007). Although skeletal muscle lactate increased in both shock groups, this was accompanied by increases in pyruvate in the E group only (mean difference: C versus E 121(46 to 195), P = 0.003; H versus E 77(7 to 147), P = 0.032; C versus H 43(-30 to 43), P = 0.229). The L:P ratio was increased in skeletal muscle in response to hemorrhagic, but not endotoxemic, shock.

Conclusions
Endotoxemia, but not hemorrhage, induces a rapid decrease of myocardial glucose levels. Despite the decrease in glucose, myocardial lactate and pyruvate concentrations were elevated and not different than in hemorrhagic shock. In skeletal muscle, substrate patterns during endotoxemic shock mimicked those seen in myocardium. During hemorrhagic shock the skeletal muscle response was characterized by a lack of increase in pyruvate and higher L:P ratios.
Hence, metabolic patterns in the myocardium during endotoxemic shock are different than those seen during hemorrhagic shock. Skeletal muscle and myocardium displayed similar substrate patterns during endotoxemic shock but differed during hemorrhagic shock.
Therapeutic drug monitoring of amikacin in septic patients
Authors: Duszynska Wieslawa , Taccone Fabio Silvio , Hurkacz Magdalena , Kowalska-Krochmal Beata , Wiela-Hojeńska Anna , Kübler Andrzej 
Published: July 2013

Abstract
Introduction
Use of higher than standard doses of amikacin (AMK) has been proposed during sepsis, especially to treat less susceptible bacterial strains. However, few data are available on drug concentrations during prolonged therapy and on potential adverse events related to this strategy.

Methods
Sixty-three critically ill patients who required AMK administration for the treatment of severe infection were included in this study. After a loading dose (LD, 18 to 30 mg/kg), the daily regimen was adapted using therapeutic drug monitoring (TDM) of both peak (Cpeak) and trough (Cmin) concentrations. Target concentrations had to give a ratio of at least 8 between Cpeak and the minimal inhibitory concentration (MIC) of the isolated pathogen. A Cmin >5 mg/L was considered as potentially nephrotoxic. We recorded clinical and microbiological responses, the development of acute kidney injury (AKI) during therapy and ICU mortality.

Results
The median AMK LD was 1500 (750 to 2400) mg, which resulted in a Cpeak/MIC ≥8 in 40 (63%) patients. Increasing the dose in the 23 patients with a Cpeak/MIC <8 resulted in optimal Cpeak/MIC in 15 of these patients (79%). In 23 patients (37%), Cmin was >5mg/L after the LD, notably in the presence of altered renal function at the onset of therapy, needing prolongation of drug administration. Overall, only 11 patients (17%) required no dose or interval adjustment during AMK therapy. Clinical cure (32/37 (86%) vs. 16/23 (70%), P = 0.18)) and microbiological eradication (29/35 (83%) vs. 14/23 (61%), P = 0.07) were higher in patients with an initial optimal Cpeak/MIC than in the other patients. The proportion of patients with clinical cure significantly improved as the Cpeak/MIC increased (P = 0.006). Also, increased time to optimal Cpeak was associated with worse microbiological and clinical results. AKI was identified in 15 patients (24%) during AMK therapy; 12 of these patients already had altered renal function before drug administration. Survivors (n = 47) had similar initial Cpeak/MIC ratios but lower Cmin values compared to nonsurvivors.

Conclusions
TDM resulted in adjustment of AMK therapy in most of our septic patients. Early achievement of an optimal Cpeak/MIC ratio may have an impact on clinical and microbiological responses, but not on outcome. In patients with impaired renal function prior to treatment, AMK therapy may be associated with a further decline in renal function.
AMPKα1 deficiency amplifies proinflammatory myeloid APC activity and CD40 signaling
Authors: Carroll Kelly Casey , Viollet Benoit , Suttles Jill 
Published: July 2013

ABSTRACTAMPK is a serine/threonine kinase that regulates energy homeostasis and metabolic stress in eukaryotes. Previous work from our laboratory, as well as by others, has provided evidence that AMPKα1 acts as a negative regulator of TLR-induced inflammatory function. Herein, we demonstrate that AMPKα1-deficient macrophages and DCs exhibit heightened inflammatory function and an enhanced capacity for antigen presentation favoring the promotion of Th1 and Th17 responses. Macrophages and DCs generated from AMPKα1-deficient mice produced higher levels of proinflammatory cytokines and decreased production of the anti-inflammatory cytokine IL-10 in response to TLR and CD40 stimulation as compared with WT cells. In assays of antigen presentation, AMPKα1 deficiency in the myeloid APC and T cell populations contributed to enhanced IL-17 and IFN-γ production. Focusing on the CD154–CD40 interaction, we found that CD40 stimulation resulted in increased phosphorylation of ERK1/2, p38, and NF-κB p65 and decreased activation of the anti-inflammatory Akt -GSK3β-CREB pathway in DCs deficient for AMPKα1. Our data demonstrate that AMPKα1 serves to attenuate LPS and CD40-mediated proinflammatory activity of myeloid APCs and that AMPKα1 activity in both APC and T cells contributes to T cell functional polarization during antigen presentation.
Longitudinal Decline of β-Cell Function: Comparison of a Direct Method vs a Fasting Surrogate Measure: The Insulin Resistance Atherosclerosis Study
Authors: Festa A. , Haffner S. M. , Wagenknecht L. E. , Lorenzo C. , Hanley A. J. G. 
Published: July 2013

Abstract

Context:
β-Cell function (BCF) declines over the course of type 2 diabetes, but little is known about BCF changes across glucose tolerance status (GTS) categories, and comparisons of direct vs surrogate measures.

Objective:
To assess longitudinal changes in BCF across GTS.

Design:
The Insulin Resistance Atherosclerosis Study is a multicenter, observational, epidemiologic study.

Setting:
Four clinical centers in the US that could identify subjects likely to have impaired fasting glucose (IFG) or impaired glucose tolerance (IGT).

Patients:
We compared longitudinal changes in BCF in 1052 subjects over 5 years. Subjects were categorized according to baseline GTS: normal glucose tolerance (NGT: n = 547), impaired fasting glucose or impaired glucose tolerance (IFG/IGT: n = 341), and newly diagnosed type 2 diabetes (n = 164).

Interventions:
None.

Main Outcome Measures:
BCF was assessed from a frequently sampled iv glucose tolerance test (AIR, acute insulin response), and the homeostasis model assessment of BCF (HOMA B).

Results:
NGT and IFG/IGT subjects increased their insulin secretion over time, whereas those with type 2 diabetes experienced either decline or little change in BCF. After adjustment for demographic variables and change in insulin resistance, change in HOMA B underestimated the magnitude of changes in BCF, as assessed by change in AIR. Relative to NGT, the 5-year change in insulin secretion in IFG/IGT and type 2 diabetes was 31% and 70% lower (by HOMA B) and 50% and 80% lower (by AIR).

Conclusions:
The decline in BCF over time in IFG/IGT and type 2 diabetes may be more pronounced than previously estimated; HOMA B may underestimate this decline significantly.
Wind Energy Data Analysis and Resource Mapping of Geba Catchment, North Ethiopia
Authors: Bayray Mulu , Mustefa Anwar , Yohannes Ftwi , Kiros Hailay , Haileslasie Asfafaw , Gebray Petros , Hayelom Mesele , Dagne Addisu 
Published: July 2013

Wind energy potential in Ethiopia is estimated to be enormous due to local peculiar landscape situations. However, the country started to utilize the potential only very recently. One of the reasons for low utilization of wind energy in Ethiopia is the absence of reliable and accurate wind energy resource data. Development of reliable and accurate wind atlas helps to identify candidate sites for wind energy applications and facilitates the planning and implementation of wind energy projects. This paper presents wind energy data analysis and wind atlas of Geba catchment in North Ethiopia. The work reported in this paper is based on wind data collected over a period of one year from measuring masts in six different sites in Tigray Ethiopia. The data was analyzed using various statistical software to evaluate the wind energy potential of the area. Average wind speed and power density, distribution of the wind prevailing direction, turbulence intensity and wind shear profile of each site were determined. Wind Atlas Analysis and Application Programme (WAsP) was used to generate the wind atlas of the area and to develop the wind speed and power density maps. The data analysis indicates that the average wind speed at 10 m above ground level (a.g.l.) varies from 3.7 m/s to 6.64 m/s. The mean power density at 10 m a.g.l varies from 64 W/m2 to 301 W/m2. The prevailing wind directions are East and South East directions. The wind resource map developed by WAsP at 50 m indicated that the catchment has good wind power potential having mean wind speed and power density of 6.5 m/s and 288 W/m2, respectively.
Book Reviews
Authors: Saltzman Matthew J. 
Published: July 2013

The INFORMS Journal on Computing Book Reviews section covers books on subjects at the interface between operations research and computer science. We welcome books on theory, applications, computer systems, and generally any subject covered by a JOC area, or any combination of these. This includes both printed and electronic books. In addition, we consider comparative reviews, i.e., several books on one relevant topic. Team reviews are also possible, particularly for a large, broad-scope book such as an encyclopedia. Please send your suggestions for books to be reviewed to the JOC Book Reviews Editor. This issue contains two reviews of books that approach the general topic of algorithms from different perspectives. David Bader, professor at Georgia Tech's College of Computing, reviews A Guide to Experimental Algorithmics, by Catherine McGeoch. This book, aimed at software developers, describes the practice of performance analysis and tuning of software. Topics include strategies for test-driven development, experimental designs, and statistical analysis techniques. Lance Fortnow's The Golden Ticket: P, NP, and the Search for the Impossible is a book for general readers about complexity theory. The reviewer is Mike Trick, senior associate dean of Carnegie Mellon's Tepper School of Business, and a widely-read blogger about operations research. The book attempts to introduce the nonspecialist reader to the field of algorithmic complexity and the problem of whether P = NP. To the extent that it is successful, it should help improve the general public's understanding of the work that computational operations researchers do.