bluuebunny/crossref_metadata_2025_split huggingface dataset:
A pilot study of angiotensin converting enzyme (ACE) genotype and return of spontaneous circulation following out-of-hospital cardiac arrest
Authors: Lindner Thomas W , Deakin Charles D , Aarsetøy Hildegunn , Rubertsson Sten , Heltne Jon-Kenneth , Søreide Eldar 
Published: August 2014

ObjectiveIn the last few years the genetic influence on health and disease outcome has become more apparent. The ACE genotype appears to play a significant role in the pathophysiology of several disease processes. This pilot study aims at showing the feasibility to examine the genetic influence of the ACE genotype on return of spontaneous circulation (ROSC) in out-of-hospital cardiac arrest (OHCA).MethodsWe performed a prospective observational study of all OHCAs of presumed cardiac origin in a well-defined population. We collected prehospital blood samples for the determination of ACE genotype and used this information together with Utstein template parameters in a multivariable analysis to examine the relationship between ROSC and ACE genotype.ResultsWe collect blood samples in 156 of 361 patients with OHCA of presumed cardiac origin, 127 samples were analysed (mean age 67 years, 86% male, 79% witnessed OHCA, 80% bystander CPR, 62% had a shockable rhythm, ROSC 77%). Distribution of the ACE gene polymorphisms: insertion polymorphism (II) n=22, 17%, insertion/deletion polymorphism (ID) n=66, 52% and deletion polymorphism (DD) n=39, 31%. We found no significant association between ACE II vs ACE DD/DI and ROSC (OR 1.72; CI 0.52 to 5.73; p=0.38). Other ACE genotype groupings (II/ID vs DD or II vs DD) did not change the overall finding of lack of impact of ACE genotype on ROSC.ConclusionsThis pilot study did not indicate a significant association between ACE gene polymorphism and ROSC. However, it has demonstrated that prehospital genetic studies including blood sampling are feasible and ethically acceptable.
NQO1 Suppresses NF-κB–p300 Interaction to Regulate Inflammatory Mediators Associated with Prostate Tumorigenesis
Authors: Thapa Dinesh , Meng Peng , Bedolla Roble G. , Reddick Robert L. , Kumar Addanki P. , Ghosh Rita 
Published: August 2014

Abstract
NADPH reductase NAD(P)H:quinone oxidoreductase 1 (NQO1) is needed to maintain a cellular pool of antioxidants, and this enzyme may contribute to tumorigenesis on the basis of studies in NQO1-deficient mice. In this work, we sought deeper insights into how NQO1 contributes to prostate carcinogenesis, a setting in which oxidative stress and inflammation are established contributors to disease development and progression. In the TRAMP mouse model of prostate cancer, NQO1 was highly expressed in tumor cells. NQO1 silencing in prostate cancer cells increased levels of nuclear IKKα and NF-κB while decreasing the levels of p53, leading to interactions between NF-κB and p300 that reinforce survival signaling. Gene expression analysis revealed upregulation of a set of immune-associated transcripts associated with inflammation and tumorigenesis in cells in which NQO1 was attenuated, with IL8 confirmed functionally in cell culture as one key NQO1-supported cytokine. Notably, NQO1-silenced prostate cancer cells were more resistant to androgen deprivation. Furthermore, NQO1 inhibition increased migration, including under conditions of androgen deprivation. These results reveal a molecular link between NQO1 expression and proinflammatory cytokine signaling in prostate cancer. Furthermore, our results suggest that altering redox homeostasis through NQO1 inhibition might promote androgen-independent cell survival via opposing effects on NF-κB and p53 function. Cancer Res; 74(19); 5644–55. ©2014 AACR.
AXL Inhibition Sensitizes Mesenchymal Cancer Cells to Antimitotic Drugs
Authors: Wilson Catherine , Ye Xiaofen , Pham Thinh , Lin Eva , Chan Sara , McNamara Erin , Neve Richard M. , Belmont Lisa , Koeppen Hartmut , Yauch Robert L. , Ashkenazi Avi , Settleman Jeff 
Published: August 2014

Abstract
Molecularly targeted drug therapies have revolutionized cancer treatment; however, resistance remains a major limitation to their overall efficacy. Epithelial-to-mesenchymal transition (EMT) has been linked to acquired resistance to tyrosine kinase inhibitors (TKI), independent of mutational resistance mechanisms. AXL is a receptor tyrosine kinase associated with EMT that has been implicated in drug resistance and has emerged as a candidate therapeutic target. Across 643 human cancer cell lines that were analyzed, elevated AXL was strongly associated with a mesenchymal phenotype, particularly in triple-negative breast cancer and non–small cell lung cancer. In an unbiased screen of small-molecule inhibitors of cancer-relevant processes, we discovered that AXL inhibition was specifically synergistic with antimitotic agents in killing cancer cells that had undergone EMT and demonstrated associated TKI resistance. However, we did not find that AXL inhibition alone could overcome acquired resistance to EGFR TKIs in the EMT setting, as previously reported. These findings reveal a novel cotreatment strategy for tumors displaying mesenchymal features that otherwise render them treatment refractory. Cancer Res; 74(20); 5878–90. ©2014 AACR.
A Recombinant Modified Vaccinia Ankara Vaccine Encoding Epstein–Barr Virus (EBV) Target Antigens: A Phase I Trial in UK Patients with EBV-Positive Cancer
Authors: Taylor Graham S. , Jia Hui , Harrington Kevin , Lee Lip Wai , Turner James , Ladell Kristin , Price David A. , Tanday Manjit , Matthews Jen , Roberts Claudia , Edwards Ceri , McGuigan Lesley , Hartley Andrew , Wilson Steve , Hui Edwin P. , Chan Anthony T. C. , Rickinson Alan B. , Steven Neil M. 
Published: August 2014

AbstractPurpose: Epstein–Barr virus (EBV) is associated with several cancers in which the tumor cells express EBV antigens EBNA1 and LMP2. A therapeutic vaccine comprising a recombinant vaccinia virus, MVA-EL, was designed to boost immunity to these tumor antigens. A phase I trial was conducted to demonstrate the safety and immunogenicity of MVA-EL across a range of doses.Experimental Design: Sixteen patients in the United Kingdom (UK) with EBV-positive nasopharyngeal carcinoma (NPC) received three intradermal vaccinations of MVA-EL at 3-weekly intervals at dose levels between 5 × 107 and 5 × 108 plaque-forming units (pfu). Blood samples were taken at screening, after each vaccine cycle, and during the post-vaccination period. T-cell responses were measured using IFNγ ELISpot assays with overlapping EBNA1/LMP2 peptide mixes or HLA-matched epitope peptides. Polychromatic flow cytometry was used to characterize functionally responsive T-cell populations.Results: Vaccination was generally well tolerated. Immunity increased after vaccination to at least one antigen in 8 of 14 patients (7/14, EBNA1; 6/14, LMP2), including recognition of epitopes that vary between EBV strains associated with different ethnic groups. Immunophenotypic analysis revealed that vaccination induced differentiation and functional diversification of responsive T-cell populations specific for EBNA1 and LMP2 within the CD4 and CD8 compartments, respectively.Conclusions: MVA-EL is safe and immunogenic across diverse ethnicities and thus suitable for use in trials against different EBV-positive cancers globally as well as in South-East Asia where NPC is most common. The highest dose (5 × 108 pfu) is recommended for investigation in current phase IB and II trials. Clin Cancer Res; 20(19); 5009–22. ©2014 AACR.
Low Levels of Low-Density Lipoprotein-C Associated With Proprotein Convertase Subtilisin Kexin 9 Inhibition Do Not Increase the Risk of Hemorrhagic Transformation
Authors: Tran-Dinh Alexy , Levoye Angélique , Lambert Gilles , Louedec Liliane , Journé Clément , Meilhac Olivier , Amarenco Pierre 
Published: August 2014

Background and Purpose—
Low levels of low-density lipoprotein-cholesterol (LDL-C) are suspected to be associated with a risk of hemorrhagic transformation after ischemic stroke. We assessed the risk of hemorrhagic transformation after cerebral ischemia/reperfusion in mice with low levels of LDL-C resulting from proprotein convertase subtilisin kexin 9 (PCSK9) deficiency.

Methods—

PCSK9
−/−
and PCSK9
+/+
mice were fed with a high-fat/high-cholesterol (21%/0.15%) diet for 1 month. Plasma lipids were measured using colorimetric assays. PCSK9
−/−
and PCSK9
+/+
mice (n=15 per group) were subjected to a 4-hour intraluminal occlusion of the middle cerebral artery followed by 20 hours of reperfusion. Spontaneous hemorrhagic transformation was assessed by quantification of hemoglobin in ischemic tissue. In vitro, a cell model of blood–brain barrier was used to test endothelial barrier integrity in response to decreasing concentrations of LDL-C from 1 to 0.25g/L in ischemia/reperfusion conditions.

Results—

PCSK9
−/−
mice had lower LDL-C, high-density lipoprotein-cholesterol, and total cholesterol levels than PCSK9
+/+
mice before and after 1 month on the high-fat/high-cholesterol diet. Hemoglobin concentration in ischemic cerebral tissue was not different between PCSK9
−/−
and PCSK9
+/+
mice (31.5 [18.9–60.1] and 32.8 [14.7–69.9] ng/mg protein, respectively;
P
=0.81). Infarct volume was also similar in both groups (
P
=0.66). Incubation of human cerebral endothelial cells with decreasing concentrations of LDL-C under ischemia/reperfusion conditions did not alter blood–brain barrier permeability.

Conclusions—
Low levels of LDL-C did not increase the risk of hemorrhagic transformation after cerebral ischemia/reperfusion in mice. Our observations suggest that PCSK9 inhibition, leading to LDL-C lowering, should not increase hemorrhagic complications after acute ischemic stroke.
Influence of Liquid Water Content and Temperature on the Form and Growth of Branched Planar Snow Crystals in a Cloud
Authors: Takahashi Tsuneya 
Published: August 2014

Abstract
How liquid water content (LWC) and temperature affect the growth of branched planar snow crystals is poorly understood. To address this issue, a vertical supercooled cloud tunnel was used to grow 167 individual snow crystals for 10 min under nearly constant conditions. The LWC varied within 0.07–0.76 g m−3 and average temperature varied from −12.4° to −16.3°C, with the latter varying by at most 0.2°C per run.
The crystal habits are divided mainly by temperature, warm to cold, into nine regions: sector above −12.5°C; then broad branch to −13.0°C; and then stellar, dendrite, and fern to −14.5°C. Then the pattern reverses, with dendrite to −14.8°C, stellar to −15.7°C, broad branch to −16.1°C, and finally sector. From −13.3° to −13.8°C, stellar changes to dendrite with LWC increase as well as with temperature decrease. From −13.8° to −14.5°C, dendrites coexist with ferns below an LWC of 0.25 g m−3, but only ferns exist at higher LWC. At other temperatures, a higher LWC does not produce greater side-branch development. Nevertheless, an increase of LWC produces heavier crystals (particularly crystals larger than 1 mm across), despite the crystal diameters being independent of LWC. Stellars at −14.9°C have the maximum mass and diameter, whereas ferns at about −14.3°C have the maximum basal-plane area and minimum fall speed. The apparent crystal density varies with temperature, with two local minima for stellars near −13.3° and −15.3°C and a local maximum for ferns near −14.2°C.
Improving the Prediction of the Summer Asian–Pacific Oscillation Using the Interannual Increment Approach
Authors: Huang Yanyan , Wang Huijun , Fan Ke 
Published: August 2014

Abstract
The summer Asian–Pacific oscillation (APO) is a dominant teleconnection pattern over the extratropical Northern Hemisphere that links the large-scale atmospheric circulation anomalies over the Asian–North Pacific Ocean sector. In this study, the direct Development of a European Multimodel Ensemble System for Seasonal-to-Interannual Prediction (DEMETER) model outputs from 1960 to 2001, which are limited in predicting the interannual variability of the summer Asian upper-tropospheric temperature and the decadal variations, are applied using the interannual increment approach to improve the predictions of the summer APO. By treating the year-to-year increment as the predictand, the interannual increment scheme is shown to significantly improve the predictive ability for the interannual variability of the summer Asian upper-tropospheric temperature and the decadal variations. The improvements for the interannual and interdecadal summer APO variability predictions in the interannual increment scheme relative to the original scheme are clear and significant. Compared with the DEMETER direct outputs, the statistical model with two predictors of APO and sea surface temperature anomaly over the Atlantic shows a significantly improved ability to predict the interannual variability of the summer rainfall over the middle and lower reaches of the Yangtze River valley (SRYR). This study therefore describes a more efficient approach for predicting the APO and the SRYR.
On the Estimation of Lagrangian Diffusivity: Influence of Nonstationary Mean Flow
Authors: Qian Yu-Kun , Peng Shiqiu , Liang Chang-Xia , Lumpkin Rick 
Published: August 2014

Abstract
Eddy–mean flow decomposition is crucial to the estimation of Lagrangian diffusivity based on drifter data. Previous studies have shown that inhomogeneous mean flow induces shear dispersion that increases the estimated diffusivity with time. In the present study, the influences of nonstationary mean flows on the estimation of Lagrangian diffusivity, especially the asymptotic behavior, are investigated using a first-order stochastic model, with both idealized and satellite-based oceanic mean flows. Results from both experiments show that, in addition to inhomogeneity, nonstationarity of mean flows that contain slowly varying signals, such as a seasonal cycle, also cause large biases in the estimates of diffusivity within a time lag of 2 months if a traditional binning method is used. Therefore, when assessing Lagrangian diffusivity over regions where a seasonal cycle is significant [e.g., the Indian Ocean (IO) dominated by monsoon winds], inhomogeneity and nonstationarity of the mean flow should be simultaneously taken into account in eddy–mean flow decomposition. A temporally and spatially continuous fit through the Gauss–Markov (GM) estimator turns out to be very efficient in isolating the effects of inhomogeneity and nonstationarity of the mean flow, resulting in estimates that are closest to the true diffusivity, especially in regions where strong seasonal cycles exist such as the eastern coast of Somalia and the equatorial IO.
A Retrospective Evaluation of Response to Vitamin D Supplementation in Obese Versus Nonobese Patients
Authors: Bryant Ginelle A. , Koenigsfeld Carrie Foust , Lehman Nicholas P. , Smith Hayden L. , Logemann Craig D. , Phillips Kirk T. 
Published: August 2014

Objective: To evaluate the impact of body mass index (BMI) on vitamin D status following ergocalciferol therapy. Methods: A retrospective evaluation of patients aged 18 years and older with a baseline serum 25(OH)D < 30 ng/mL who received prescription ergocalciferol 50 000 IU at any dose between July 2009 and November 2011 was conducted. Patients were included if pre- and posttreatment 25(OH)D levels were available within 3 months of therapy. Results: Two hundred and thirteen patients were included in the study with 52% having a BMI ≥30 kg/m2. Thirty-eight different ergocalciferol regimens were prescribed, and the majority of patients (66.2%) received a regimen consisting of 50 000 IU once weekly for variable durations. Mean 25(OH)D levels increased from 18.8 ± 6.6 ng/mL at baseline to 35.0 ± 13.8 ng/mL with 61.0% (n = 130) of patients having attained vitamin D sufficiency, 25(OH)D ≥ 30 ng/mL, with their prescribed ergocalciferol regimen. Obese patients with a BMI ≥30 were less likely to attain vitamin D sufficiency following replacement than patients with a BMI <30 kg/m2 (52% vs 71%; P = .0161). Conclusion: Our study demonstrated an overall moderate response rate to replacement therapy with ergocalciferol and considerable variability in vitamin D replacement strategies initiated by primary care providers. Based on our findings, elevated BMI ≥30 kg/m2 may impact the likelihood of attaining vitamin D sufficiency with ergocalciferol.
Urine β2-microglobulin is associated with clinical disease activity and renal involvement in female patients with systemic lupus erythematosus
Authors: Choe J-Y , Park S-H , Kim S-K 
Published: August 2014

Objective We investigated the association of serum and urine β2-microglobulin (β2MG) with renal involvement and clinical disease activity in systemic lupus erythematosus (SLE). Methods Sixty-four female patients with SLE were enrolled. We assessed SLE disease activity (SLEDAI)-2K and measured serum and urine β2MG levels, as well as complement (C3 and C4) and anti-dsDNA levels. According to the SLEDAI scores, two groups were categorized: low (0–5 of SLEDAI) and high (6–19 of SLEDAI) disease activity groups. The presence of renal involvement was determined by renal SLEDAI score. Statistical analysis was performed using Spearman’s correlation analysis, Mann-Whitney U test, multivariate regression analysis, and logistic regression analysis. Results Urine β2MG levels were significantly different between low and high SLEDAI groups ( p = 0.001), but not for serum β2MG levels ( p = 0.579). Patients with renal involvement showed higher urine β2MG levels compared to those without renal involvement ( p < 0.001), but again there was not a difference in serum β2MG levels ( p = 0.228). Urine β2MG was closely associated with SLEDAI ( r = 0.363, p = 0.003), renal SLEDAI ( r = 0.479, p < 0.001), urine protein/Cr ( r = 0.416, p = 0.001), and ESR ( r = 0.347, p = 0.006), but not serum β2MG ( r = 0.245, p = 0.051). Urine β2MG level was identified as a surrogate for renal involvement ( p = 0.009, OR = 1.017, 95% CI 1.004–1.030) and overall disease activity ( p = 0.009, OR = 1.020, 95% CI 1.005–1.036). Conclusions We demonstrated that urine β2MG levels are associated with renal involvement and overall clinical disease activity in SLE.
Estimating prevalence and burden of major disorders of the brain in Nepal: cultural, geographic, logistic and philosophical issues of methodology
Authors: Risal Ajay , Manandhar Kedar , Steiner Timothy J , Holen Are , Koju Rajendra , Linde Mattias 
Published: August 2014

Abstract

Background
Headache, anxiety and depression are major disorders of the brain in terms of their prevalence and the burdens and costs they impose on society. Nationwide population-based studies of these disorders are necessary to inform health policy but, in research-naïve and resource-poor countries such as Nepal, a host of methodological problems are encountered: cultural, geographic, logistic and philosophical.

Methods
Expert consensus was sought among researchers from different professional and cultural backgrounds in planning and conceptualizing an epidemiological study and adapting established methods to the special situation and circumstances of Nepal.

Results
The methodological problems were sorted into different themes: study design; climate; geography, access and transport; sociocultural issues; safety of interviewers. Each of these was dealt with separately, and their inter-relationships explored, in finding solutions that were sometimes pragmatic. A cross-sectional questionnaire-based study, with teams of interviewers visiting households across the three physiographic divisions (with extremes in altitude) in each of the five development regions of the country, would enable national sampling with sociocultural representativeness. However, the study instruments and interviews would be in Nepali only. Transport and access challenges were considerable, and their solutions combined travel by air, bus, river and foot, with allowances for rain-damaged roads, collapsed bridges and cancelled scheduled flights. The monsoon would render many routes impassable, and therefore set an absolute time limitation. Engaging participants willingly in the enquiry would be the key to success, and several tactics would be employed to enhance the success of this, most importantly enlisting the support of local community volunteers in each study site.

Conclusion
Anticipating problems in advance of investing substantial resources in a large nationwide epidemiological study in Nepal was a sensible precaution. The difficulties could be resolved or circumvented without expected compromise in scientific quality. Expert consensus was an effective means of achieving this outcome.
Effects of multiwalled carbon nanotubes and triclocarban on several eukaryotic cell lines: elucidating cytotoxicity, endocrine disruption, and reactive oxygen species generation
Authors: Simon Anne , Maletz Sibylle X , Hollert Henner , Schäffer Andreas , Maes Hanna M 
Published: August 2014

AbstractTo date, only a few reports about studies on toxic effects of carbon nanotubes (CNT) are available, and their results are often controversial. Three different cell lines (rainbow trout liver cells (RTL-W1), human adrenocortical carcinoma cells (T47Dluc), and human adrenocarcinoma cells (H295R)) were exposed to multiwalled carbon nanotubes, the antimicrobial agent triclocarban (TCC) as well as the mixture of both substances in a concentration range of 3.13 to 50 mg CNT/L, 31.25 to 500 μg TCC/L, and 3.13 to 50 mg CNT/L + 1% TCC (percentage relative to carbon nanotubes concentration), respectively. Triclocarban is a high-production volume chemical that is widely used as an antimicrobial compound and is known for its toxicity, hydrophobicity, endocrine disruption, bioaccumulation potential, and environmental persistence. Carbon nanotubes are known to interact with hydrophobic organic compounds. Therefore, triclocarban was selected as a model substance to examine mixture toxicity in this study. The influence of multiwalled carbon nanotubes and triclocarban on various toxicological endpoints was specified: neither cytotoxicity nor endocrine disruption could be observed after exposure of the three cell lines to carbon nanotubes, but the nanomaterial caused intracellular generation of reactive oxygen species in all cell types. For TCC on the other hand, cell vitality of 80% could be observed at a concentration of 2.1 mg/L for treated RTL-W1 cells. A decrease of luciferase activity in the ER Calux assay at a triclocarban concentration of 125 μg/L and higher was observed. This effect was less pronounced when multiwalled carbon nanotubes were present in the medium. Taken together, these results demonstrate that multiwalled carbon nanotubes induce the production of reactive oxygen species in RTL-W1, T47Dluc, and H295R cells, reveal no cytotoxicity, and reduce the bioavailability and toxicity of the biocide triclocarban.
Spectral characteristics of scintillations producing ionospheric irregularities in the Indian region
Authors: Banola S. , Pathan B. M. , Rao D. R. K. , Chandra H. 
Published: August 2014

Abstract
VHF amplitude scintillations were recorded at Tirunelveli (8.7°N, 77.7°E; 0.6°N dip Latitude), Pondicherry (12°N, 79.1°E; 4.4°N dip Latitude) and Mumbai, (19°N, 73°E; 13.5°N dip Latitude) for the years 1992–1996 using the 250 MHz radio beacon from the geostationary satellite FLEETSAT (73°E). The recorded digital scintillation data for few nights are analyzed to estimate scintillation index (S
4), fade rates, auto-correlation functions and power spectral densities for every 2.5 minute sample during the period of the scintillation activity. The power spectral slopes are shallower for the scintillation at the generation phase and steeper towards the decay phase, which indicates the erosion of smaller scale sizes towards the decay phase.