bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chronic Pretreatment of Metformin is Associated with the Reduction of the No‐Reflow Phenomenon in Patients with Diabetes Mellitus After Primary Angioplasty for Acute Myocardial Infarction
Authors: Zhao Jing‐Lin , Fan Chao‐Mei , Yang Yue‐Jin , You Shi‐Jie , Gao Xin , Zhou Qiong , Pei Wei‐Dong 
Published: July 2011

SUMMARYIntroduction: Metformin is one of the most commonly prescribed antihyperglycemic agents for the treatment of type 2 diabetes. However, little is known about the effect of metformin on no‐reflow in diabetic patients. Aim: In this study, we investigated retrospectively whether chronic pretreatment with metformin was associated with no‐reflow in diabetic patients who underwent primary coronary intervention for acute myocardial infarction (AMI). Results: A total of 154 consecutive diabetic patients who underwent primary angioplasty for a first ST‐segment elevation myocardial infarction were studied. No‐reflow was defined as a final TIMI flow of ≤2 or final TIMI flow of 3 with a myocardial blush grade of <2. The no‐reflow phenomenon was found in 53 of 154 patients. There were no significant differences in clinical characteristics between the patients with and without metformin pretreatment. However, the 65 patients receiving chronic metformin treatment before admission had lower incidence of the no‐reflow than those without it (4.2 and 14.6%, P < 0.05). Multivariable logistic regression analysis revealed that absence of metformin pretreatment was a significant predictor of the no‐reflow along with high‐burden thrombus, ejection fraction on admission and anterior AMI. Conclusion: These results suggested that chronic pretreatment with metformin may be associated with the reduction of the no‐reflow phenomenon in patients with diabetes mellitus after primary angioplasty for AMI.
Novel DNA sequence isolated from blood donors with high transaminase levels
Authors: Satoh Koei , Iwata‐Takakura Akiko , Osada Naoki , Yoshikawa Akira , Hoshi Yuji , Miyakawa Keiko , Gotanda Yuko , Satake Masahiro , Tadokoro Kenji , Mizoguchi Hideaki 
Published: July 2011

Aim:  In Japan, the etiology of 10–20% of cases of acute hepatitis remains unclarified. This study was conducted to verify the agent causing non‐A–E hepatitis.Methods:  Serum samples from 500 blood donors with elevated alanine aminotransferase (ALT) levels were screened by polymerase chain reaction using primers constructed from conserved areas of RNA virus helicase. The sequence obtained was investigated for viral properties.Results:  Four blood samples were found to contain a novel DNA sequence of 9496 bp, which was designated KIs‐V. KIs‐V was sensitive to the restriction enzyme SalI and BstXI. Rolling‐circle amplification produced an excessive amount of KIs‐V DNA. In sucrose density gradient ultracentrifugation, KIs‐V banded at a 1.158‐g/cm3 density. Detergent treatment increased the density of KIs‐V. There was no KIs‐V DNA amplification from human leukocyte DNA. Serial filtration suggested that KIs‐V was included in a 30–50‐nm size particle. In silico analysis revealed that KIs‐V contained 13 potential genes, none of which showed homology to any viral proteins reported. One gene showed similarity to a DNA polymerase domain. Strong signals for transcription initiation and a CpG island were identified. The nucleotide composition of KIs‐V showed a characteristic feature of circular DNA genomes that contain a replication origin and a terminus. In a preliminary study, KIs‐V was frequently identified among hepatitis E virus antibody positive individuals with elevated ALT levels.Conclusion:  A new sequence KIs‐V was isolated from blood donors with elevated ALT levels. It was suggested that KIs‐V is a double‐stranded circular DNA genome derived from a novel category of enveloped viruses.
Variation in postsampling treatment of avian blood affects ecophysiological interpretations
Authors: Hoye Bethany J. 
Published: July 2011

Summary1. The fluid component of blood is widely used in ecophysiological investigations, including measures of immune function and stable isotope ecology. After blood collection, delayed separation of blood extracellular fluids from red blood cells is known to affect the concentration of a wide range of biochemical compounds in the resulting fluid, as does prevention of clotting (producing plasma) when compared with blood allowed to clot (producing serum).2. One challenge when investigating immune function and stable isotope ecology, therefore, is discriminating variation because of the effect of the biological factors of interest from potential methodological artefacts. This study assesses how seven widely used measures of immune function and stable isotope composition respond both to delayed separation of the cellular and fluid components and to the clotting of blood samples from two species of waterfowl.3. Samples that remained uncentrifuged for up to 12 h did not differ from those centrifuged within 15 min of sampling from the same individuals, indicating that samples from a wide range of field conditions may remain highly comparable. However, the outcome of three of the four immunological assays and two of the three isotopic analyses was highly dependent on the type of fluid, with higher immunological activity and higher relative concentrations of heavy carbon and total nitrogen in plasma compared to serum.4. Researchers interested in immune function and stable isotope ecology may obtain the most useful results by ensuring that they use a single fluid type in their investigations.
In Vitro and In Vivo Selective Antitumor Activity of a Novel Orally Bioavailable Proteasome Inhibitor MLN9708 against Multiple Myeloma Cells
Authors: Chauhan Dharminder , Tian Ze , Zhou Bin , Kuhn Deborah , Orlowski Robert , Raje Noopur , Richardson Paul , Anderson Kenneth C. 
Published: July 2011

Abstract
Purpose: The success of bortezomib therapy for treatment of multiple myeloma (MM) led to the development of structurally and pharmacologically distinct novel proteasome inhibitors. In the present study, we evaluated the efficacy of one such novel orally bioactive proteasome inhibitor MLN9708/MLN2238 in MM using well-established in vitro and in vivo models.
Experimental Design: MM cell lines, primary patient cells, and the human MM xenograft animal model were used to study the antitumor activity of MN2238.
Results: Treatment of MM cells with MLN2238 predominantly inhibits chymotrypsin-like activity of the proteasome and induces accumulation of ubiquitinated proteins. MLN2238 inhibits growth and induces apoptosis in MM cells resistant to conventional and bortezomib therapies without affecting the viability of normal cells. In animal tumor model studies, MLN2238 is well tolerated and inhibits tumor growth with significantly reduced tumor recurrence. A head-to-head analysis of MLN2238 versus bortezomib showed a significantly longer survival time in mice treated with MLN2238 than mice receiving bortezomib. Immununostaining of MM tumors from MLN2238-treated mice showed growth inhibition, apoptosis, and a decrease in associated angiogenesis. Mechanistic studies showed that MLN2238-triggered apoptosis is associated with activation of caspase-3, caspase-8, and caspase-9; increase in p53, p21, NOXA, PUMA, and E2F; induction of endoplasmic reticulum (ER) stress response proteins Bip, phospho-eIF2-α, and CHOP; and inhibition of nuclear factor kappa B. Finally, combining MLN2238 with lenalidomide, histone deacetylase inhibitor suberoylanilide hydroxamic acid, or dexamethasone triggers synergistic anti-MM activity.
Conclusion: Our preclinical study supports clinical evaluation of MLN9708, alone or in combination, as a potential MM therapy. Clin Cancer Res; 17(16); 5311–21. ©2011 AACR.
Breast Cancer Cells Proliferation Is Regulated by Tyrosine Phosphatase SHP1 through c-jun N-Terminal Kinase and Cooperative Induction of RFX-1 and AP-4 Transcription Factors
Authors: Amin Shahreen , Kumar Ashok , Nilchi Ladan , Wright Kathryn , Kozlowski Maya 
Published: July 2011

Abstract
In this study, we show that proliferation of breast cancer cells is suppressed by IGF-1–activated JNK MAPK pathway. The molecular mechanism by which c-jun-NH,-kinase (JNK) activation induces antiproliferative signals in IGF-1–stimulated breast cancer cells remains unknown. Tyrosine phosphatase SHP1 is known to negatively regulate signal transduction pathways activated by cell surface receptors including IGF-1. Moreover, SHP1 transcript and protein levels are increased in epithelial tumors. Therefore, we hypothesized that IGF-activated JNK induces expression of SHP1 in breast cancer cells. To further clarify the role of SHP1 in tumor growth, we correlated the proliferation rates of breast adenocarcinoma cells with SHP1 expression and JNK activation. We show that proliferation of serum- or IGF-1–stimulated breast adenocarcinoma cells is negatively regulated by SHP1 and show for the first time that IGF-1–activated JNK induces SHP1 expression in MCF-7 cells used as experimental model. In an attempt to understand the mechanism by which serum- or IGF-1–activated JNK induces SHP1 expression resulting in suppression of cell proliferation, we reveal for the first time that in serum- or IGF-1–stimulated breast cancer MCF-7 cells, JNK induces SHP1 expression through the binding of AP-4 and RFX-1 transcription factors to the epithelial tissue–specific SHP1 promoter. Overall, we show for the first time that IGF-1–stimulated proliferation of breast adenocarcinoma cells is negatively regulated by SHP1 through activation of JNK. Mol Cancer Res; 9(8); 1112–25. ©2011 AACR.
Effects of Supplemental Vitamin D and Calcium on Biomarkers of Inflammation in Colorectal Adenoma Patients: A Randomized, Controlled Clinical Trial
Authors: Hopkins Myfanwy H. , Owen Joy , Ahearn Thomas , Fedirko Veronika , Flanders W. Dana , Jones Dean P. , Bostick Roberd M. 
Published: July 2011

AbstractVitamin D and calcium affect several pathways involved in inflammation, tumor growth, and immune surveillance relevant to carcinogenesis. Also, epidemiologic evidence indicates that calcium and vitamin D may reduce risk for developing colorectal adenomas and cancer. To investigate the effects of calcium and vitamin D on biomarkers of inflammation in colorectal adenoma patients, we conducted a pilot, randomized, double-blind, placebo-controlled, 2 × 2 factorial clinical trial (n = 92) of 2 g/d calcium and/or 800 IU/d vitamin D3 supplementation versus placebo over 6 months. Plasma concentrations of proinflammatory markers [C-reactive protein (CRP), TNF-α, interleukin (IL)-6, IL-1β, and IL-8] and an anti-inflammatory marker (IL-10) were measured using ELISAs. After 6 months of treatment, in the vitamin D3 supplementation group, CRP decreased 32% overall (P = 0.11), 37% in men (P = 0.05), and 41% among non–nonsteroidal anti-inflammatory drug (NSAID) users (P = 0.05) relative to placebo. In the vitamin D3 supplementation group, TNF-α decreased 13%, IL-6 32%, IL-1β 50%, and IL-8 15%; in the calcium supplementation group, IL-6 decreased 37%, IL-8 11%, and IL-1β 27%. Although these changes were not statistically significant, a combined inflammatory markers z-score decreased 77% (P = 0.003) in the vitamin D3 treatment group overall, 83% (P = 0.01) among men, and 48% among non-NSAID users (P = 0.01). There was no evidence of synergy between vitamin D3 and calcium or effects on IL-10. These preliminary results are consistent with a pattern of reduction in tumor-promoting inflammation biomarkers with vitamin D3 or calcium supplementation alone and support further investigation of vitamin D3 as a chemopreventive agent against inflammation and colorectal neoplasms. Cancer Prev Res; 4(10); 1645–54. ©2011 AACR.
Plasminogen Regulates Stromal Cell–Derived Factor-1/CXCR4–Mediated Hematopoietic Stem Cell Mobilization by Activation of Matrix Metalloproteinase-9
Authors: Gong Yanqing , Fan Yi , Hoover-Plow Jane 
Published: July 2011

Objective—
Granulocyte colony-stimulating factor (G-CSF) is a widespread therapeutic agent for stimulation of hematopoietic progenitor and stem cell (HPSC) mobilization from bone marrow (BM). Plasminogen (Plg) has been shown to be critical for HPSC mobilization. Here, we investigated the role of Plg in G-CSF-induced HPSC mobilization and the underlying mechanism.

Methods and Results—
By using gene-targeted mice, our data show that Plg is required for G-CSF-induced HPSC egress to sinusoidal capillaries in BM and subsequent mobilization to peripheral circulation. G-CSF induced Plg-dependent activation of matrix metalloproteinase-9 (MMP-9) in BM, and MMP-9 neutralization or deficiency suppressed HPSC migration and mobilization. Reconstitution of MMP-9 activity by BM transplantation after lentiviral overexpression rescued HPSC mobilization in Plg-deficient mice, indicating that MMP-9 activation is required for Plg-mediated HPSC mobilization. Interestingly, after G-CSF simulation, Plg downregulated stromal cell–derived factor-1 in BM and spatiotemporally regulated the expression of C-X-C chemokine receptor type 4 (CXCR4) on mobilized HPSCs, and reconstitution of MMP-9 activity in Plg-deficient mice reversed CXCR4 expression on HPSCs in plasma and BM, suggesting that CXCR4 serves as a new downstream signal of Plg/MMP-9 in HPSC mobilization.

Conclusion—
Our data elucidated a novel mechanism that Plg regulates MMP-9-dependent CXCR4 expression to facilitate HPSC mobilization in response to G-CSF.
Dual Manganese-Enhanced and Delayed Gadolinium-Enhanced MRI Detects Myocardial Border Zone Injury in a Pig Ischemia-Reperfusion Model
Authors: Dash Rajesh , Chung Jaehoon , Ikeno Fumiaki , Hahn-Windgassen Annett , Matsuura Yuka , Bennett Mihoko V. , Lyons Jennifer K. , Teramoto Tomohiko , Robbins Robert C. , McConnell Michael V. , Yeung Alan C. , Brinton Todd J. , Harnish Phillip P. , Yang Phillip C. 
Published: July 2011

Background—

Gadolinium (Gd)-based delayed-enhancement MRI (DEMRI) identifies nonviable myocardium but is nonspecific and may overestimate nonviable territory. Manganese (Mn
2+
)-enhanced MRI (MEMRI) denotes specific Mn
2+
uptake into viable cardiomyocytes. We performed a dual-contrast myocardial assessment in a porcine ischemia-reperfusion (IR) model to test the hypothesis that combined DEMRI and MEMRI identifies viable infarct border zone (BZ) myocardium in vivo.

Methods and Results—

Sixty-minute left anterior descending coronary artery IR injury was induced in 13 adult swine. Twenty-one days post-IR, 3-T cardiac MRI was performed. MEMRI was obtained after injection of 0.7 mL/kg Mn
2+
contrast agent. DEMRI was then acquired after injection of 0.2 mmol/kg Gd. Left ventricular (LV) mass, infarct, and function were analyzed. Subtraction of MEMRI defect from DEMRI signal identified injured BZ myocardium. Explanted hearts were analyzed by 2,3,5-triphenyltetrazolium chloride stain and tissue electron microscopy to compare infarct, BZ, and remote myocardium. Average LV ejection fraction was reduced (30±7%). MEMRI and DEMRI infarct volumes correlated with 2,3,5-triphenyltetrazolium chloride stain analysis (MEMRI,
r
=0.78; DEMRI,
r
=0.75;
P
<0.004). MEMRI infarct volume percentage was significantly lower than that of DEMRI (14±4% versus 23±4%;
P
<0.05). BZ MEMRI signal-to-noise ratio (SNR) was intermediate to remote and core infarct SNR (7.5±2.8 versus 13.2±3.4 and 2.9±1.6;
P
<0.0001), and DEMRI BZ SNR tended to be intermediate to remote and core infarct SNR (8.4±5.4 versus 3.3±0.6 and 14.3±6.6;
P
>0.05). Tissue electron microscopy analysis exhibited preserved cell structure in BZ cardiomyocytes despite transmural DEMRI enhancement.

Conclusions—
The dual-contrast MEMRI-DEMRI detects BZ viability within DEMRI infarct zones. This approach may identify injured, at-risk myocardium in ischemic cardiomyopathy.
Withdrawal of Antithrombotic Agents and Its Impact on Ischemic Stroke Occurrence
Authors: Broderick Joseph P. , Bonomo Jordan B. , Kissela Brett M. , Khoury Jane C. , Moomaw Charles J. , Alwell Kathleen , Woo Daniel , Flaherty Matthew L. , Khatri Pooja , Adeoye Opeolu , Ferioli Simona , Kleindorfer Dawn O. 
Published: July 2011

Background and Purpose—
Antithrombotic medications (anticoagulants and antiplatelets) are often withheld in the periprocedural period and after bleeding complications to limit the risk of new or recurrent bleeding. These medications are also stopped by patients for various reasons such as cost, side effects, or unwillingness to take medication.

Methods—
Patient records from the population-based Greater Cincinnati/Northern Kentucky Stroke Study were reviewed to identify cases of ischemic stroke in 2005 and determine the temporal association of strokes with withdrawal of antithrombotic medication. Ischemic strokes and reasons for medication withdrawal were identified by study nurses for subsequent physician review.

Results—
In 2005, 2197 cases of ischemic stroke among residents of the region were identified through hospital discharge records. Of the 2197 ischemic strokes, 114 (5.2%) occurred within 60 days of an antithrombotic medication withdrawal, 61 (53.5%) of these after stoppage of warfarin and the remainder after stoppage of an antiplatelet medication. Of the strokes after withdrawal, 71 (62.3%) were first-ever and 43 (37.7%) were recurrent; 54 (47.4%) occurred after withdrawal of medication by a physician in the periprocedural period.

Conclusions—
The withdrawal of antiplatelet and antithrombotic medications in the 60 days preceding an acute ischemic stroke was associated with 5.2% of ischemic strokes in our study population. This finding emphasizes the need for thoughtful decision-making concerning antithrombotic medication use in the periprocedural period and efforts to improve patient compliance.
Hierarchical Cluster Analysis of a Convection-Allowing Ensemble during the Hazardous Weather Testbed 2009 Spring Experiment. Part I: Development of the Object-Oriented Cluster Analysis Method for Precipitation Fields
Authors: Johnson Aaron , Wang Xuguang , Kong Fanyou , Xue Ming 
Published: July 2011

Abstract
Convection-allowing ensemble forecasts with perturbations to model physics, dynamics, and initial (IC) and lateral boundary conditions (LBC) generated by the Center for the Analysis and Prediction of Storms for the NOAA Hazardous Weather Testbed (HWT) Spring Experiments provide a unique opportunity to understand the relative impact of different sources of perturbation on convection-allowing ensemble diversity. Such impacts are explored in this two-part study through an object-oriented hierarchical cluster analysis (HCA) technique.
In this paper, an object-oriented HCA algorithm, where the dissimilarity of precipitation forecasts is quantified with a nontraditional object-based threat score (OTS), is developed. The advantages of OTS-based HCA relative to HCA using traditional Euclidean distance and neighborhood probability-based Euclidean distance (NED) as dissimilarity measures are illustrated by hourly accumulated precipitation ensemble forecasts during a representative severe weather event.
Clusters based on OTS and NED are more consistent with subjective evaluation than clusters based on traditional Euclidean distance because of the sensitivity of Euclidean distance to small spatial displacements. OTS improves the clustering further compared to NED. Only OTS accounts for important features of precipitation areas, such as shape, size, and orientation, and OTS is less sensitive than NED to precise spatial location and precipitation amount. OTS is further improved by using a fuzzy matching method. Application of OTS-based HCA for regional subdomains is also introduced. Part II uses the HCA method developed in this paper to explore systematic clustering of the convection-allowing ensemble during the full 2009 HWT Spring Experiment period.
Hierarchical Cluster Analysis of a Convection-Allowing Ensemble during the Hazardous Weather Testbed 2009 Spring Experiment. Part II: Ensemble Clustering over the Whole Experiment Period
Authors: Johnson Aaron , Wang Xuguang , Xue Ming , Kong Fanyou 
Published: July 2011

Abstract
Twenty-member real-time convection-allowing storm-scale ensemble forecasts with perturbations to model physics, dynamics, initial conditions (IC), and lateral boundary conditions (LBC) during the NOAA Hazardous Weather Testbed Spring Experiment provide a unique opportunity to study the relative impact of different sources of perturbation on convection-allowing ensemble diversity. In Part II of this two-part study, systematic similarity/dissimilarity of hourly precipitation forecasts among ensemble members from the spring season of 2009 are identified using hierarchical cluster analysis (HCA) with a fuzzy object-based threat score (OTS), developed in Part I. In addition to precipitation, HCA is also performed on ensemble forecasts using the traditional Euclidean distance for wind speed at 10 m and 850 hPa, and temperature at 500 hPa.
At early lead times (3 h, valid at 0300 UTC) precipitation forecasts cluster primarily by data assimilation and model dynamic core, indicating a dominating impact of models, with secondary clustering by microphysics. There is an increasing impact of the planetary boundary layer (PBL) scheme on clustering relative to the microphysics scheme at later lead times. Forecasts of 10-m wind speed cluster primarily by the PBL scheme at early lead times, with an increasing impact of LBC at later lead times. Forecasts of midtropospheric variables cluster primarily by IC at early lead times and LBC at later lead times. The radar and Mesonet data assimilation (DA) show its impact, with members without DA in a distinct cluster, through the 12-h lead time (valid at 1200 UTC) for both precipitation and nonprecipitation variables. The implication for optimal ensemble design for storm-scale forecasts is also discussed.
A Direct Method for Constructing Refined Regions in Unstructured Conforming Triangular–Hexagonal Computational Grids: Application to OLAM
Authors: Walko Robert L. , Avissar Roni 
Published: July 2011

Abstract
A scheme is presented for constructing refined regions of 2D unstructured computational meshes composed of triangular cells. The method preserves the conforming property of the original unrefined mesh and does not produce hanging nodes. The procedure consists of 1) doubling the resolution of triangles inside a specified closed region by adding three edges inside each triangle that connect the midpoints of its three edges; and 2) constructing one or more transition rows immediately outside the refined area by removing and adding edges in order to maintain the conforming property, to regulate the abruptness of the change in resolution, and to keep triangle shapes as close as possible to equilateral. The latter requirement is met partly by restricting the number of edges that meet at any vertex to values of 5, 6, or 7. The method for constructing the transition rows is the main new contribution of this work. Two variants of the construction are described, and for one variant, the number of transition rows is varied from 1 to 5. All construction is noniterative and is therefore extremely rapid, making the method suitable for dynamic mesh refinement. Final adjustment of gridcell shapes is performed iteratively, but this can be limited to only the transition rows and then converges very rapidly. A suitable constraint on triangle shapes that is applied in the adjustment process and satisfies the criterion for a Delaunay mesh naturally extends the mesh refinement algorithm to its dual-Voronoi diagram, which is composed primarily of hexagons plus a few pentagons and heptagons. The refinement method is tested on both Delaunay and Voronoi meshes in the Ocean–Land–Atmosphere Model (OLAM) using shallow-water test case 5. A choice of two or three transition rows is found to be optimal, although using five can increase accuracy slightly.