bluuebunny/crossref_metadata_2025_split huggingface dataset:
Magnetic Resonance Imaging of Carotid Atherosclerotic Plaque in Clinically Suspected Acute Transient Ischemic Attack and Acute Ischemic Stroke
Authors: Parmar Jaywant P. , Rogers Walter J. , Mugler John P. , Baskurt Erol , Altes Talissa A. , Nandalur Kiran R. , Stukenborg George J. , Phillips C. Douglas , Hagspiel Klaus D. , Matsumoto Alan H. , Dake Michael D. , Kramer Christopher M. 
Published: November 2010

Background—
Carotid atherosclerotic plaque rupture is thought to cause transient ischemic attack (TIA) and ischemic stroke (IS). Pathological hallmarks of these plaques have been identified through observational studies. Although generally accepted, the relationship between cerebral thromboembolism and in situ atherosclerotic plaque morphology has never been directly observed noninvasively in the acute setting.

Methods and Results—

Consecutive acutely symptomatic patients referred for stroke protocol magnetic resonance imaging/angiography underwent additional T1- and T2-weighted carotid bifurcation imaging with the use of a 3-dimensional technique with blood signal suppression. Two blinded reviewers performed plaque gradings according to the American Heart Association classification system. Discharge outcomes and brain magnetic resonance imaging results were obtained. Image quality for plaque characterization was adequate in 86 of 106 patients (81%). Eight TIA/IS patients with noncarotid pathogenesis were excluded, yielding 78 study patients (38 men and 40 women with a mean age of 64.3 years, SD 14.7) with 156 paired watershed vessel/cerebral hemisphere observations. Thirty-seven patients had 40 TIA/IS events. There was a significant association between type VI plaque (demonstrating cap rupture, hemorrhage, and/or thrombosis) and ipsilateral TIA/IS (
P
<0.001). A multiple logistic regression model including standard Framingham risk factors and type VI plaque was constructed. Type VI plaque was the dominant outcome-associated observation achieving significance (
P
<0.0001; odds ratio, 11.66; 95% confidence interval, 5.31 to 25.60).

Conclusions—
In situ type VI carotid bifurcation region plaque identified by magnetic resonance imaging is associated with ipsilateral acute TIA/IS as an independent identifier of events, thereby supporting the dominant disease pathophysiology.
Identification of Genomic Predictors of Atrioventricular Conduction
Authors: Denny Joshua C. , Ritchie Marylyn D. , Crawford Dana C. , Schildcrout Jonathan S. , Ramirez Andrea H. , Pulley Jill M. , Basford Melissa A. , Masys Daniel R. , Haines Jonathan L. , Roden Dan M. 
Published: November 2010

Background—

Recent genome-wide association studies in which selected community populations are used have identified genomic signals in
SCN10A
influencing PR duration. The extent to which this can be demonstrated in cohorts derived from electronic medical records is unknown.

Methods and Results—

We performed a genome-wide association study on 2334 European American patients with normal ECGs without evidence of prior heart disease from the Vanderbilt DNA databank, BioVU, which accrues subjects from routine patient care. Subjects were identified by combinations of natural language processing, laboratory queries, and billing code queries of deidentified medical record data. Subjects were 58% female, of mean (±SD) age 54±15 years, and had mean PR intervals of 158±18 ms. Genotyping was performed with the use of the Illumina Human660W-Quad platform. Our results identify 4 single nucleotide polymorphisms (rs6800541, rs6795970, rs6798015, rs7430477) linked to
SCN10A
associated with PR interval (
P
=5.73×10
−7
to 1.78×10
−6
).

Conclusions—
This genome-wide association study confirms a gene heretofore not implicated in cardiac pathophysiology as a modulator of PR interval in humans. This study is one of the first replication genome-wide association studies performed with the use of an electronic medical records–derived cohort, supporting their further use for genotype-phenotype analyses.
Proteomic Analysis of Lung Tissues From Patients With Pulmonary Arterial Hypertension
Authors: Abdul-Salam Vahitha B. , Wharton John , Cupitt John , Berryman Mark , Edwards Robert J. , Wilkins Martin R. 
Published: November 2010

Background—
Pulmonary arterial hypertension is a disorder of vascular remodeling causing increased resistance to pulmonary blood flow. The expression of proteins in lungs from pulmonary arterial hypertension patients was investigated in an unbiased approach to further understand the pathobiology of this disease.

Methods and Results—
Label-free liquid chromatography tandem mass spectrometry was used to compare protein profiles in surgical samples of lungs from 8 patients with pulmonary arterial hypertension and 8 control subjects. More than 300 proteins were detected. On the basis of robust criteria, the levels of 25 proteins varied between the 2 groups. The majority of upregulated proteins were associated with cell growth, proliferation, and cell metabolism. Novel findings included an increased expression of chloride intracellular channel 4, receptor for advanced glycation end products, and periostin. Increased expression of chloride intracellular channel 4, a multifunctional protein involved in angiogenesis, and several signaling pathways implicated in pulmonary arterial hypertension—transforming growth factor-β, vascular endothelial growth factor, and bone morphogenetic protein—was confirmed by Western blotting and localized predominantly to endothelial cells in occlusive and plexiform vascular lesions.

Conclusions—
Label-free proteomics identified differences in the expression of several proteins in the pulmonary arterial hypertension lung, many of which are relevant to the disease process. Increased expression of chloride intracellular channel 4 may be pertinent to the disorganized angiogenesis of plexiform lesions.
Diagnostic Study of the Effects of a Large City on Heavy Rainfall as Revealed by an Ensemble Simulation: A Case Study of Central Tokyo, Japan
Authors: Inamura Tomohiko , Izumi Takeki , Matsuyama Hiroshi 
Published: November 2010

Abstract
This study was undertaken to investigate the effects of a large city on heavy rainfall in Tokyo, Japan, based on an ensemble simulation with a large number of members. An ensemble simulation (24 members) of eight brief heavy rainfall events that occurred from 1999 to 2007 was performed. The ensemble simulation was performed using five objective analysis datasets [Japanese 25-yr Reanalysis (JRA-25), Regional Analysis (RANAL), NCEP Final Operational Global Analysis (NCEP-FNL), NCEP–Department of Energy Global Reanalysis 2 (NCEP/DOE-R2), and Global Analysis (GANAL)]. Land-use distributions of two types were prepared for numerical simulations: actual land use and virtual land use, in which all urban land use was converted to vegetation. Each member was simulated using actual land use and virtual land use. The effects of the urban area were then assessed by comparing the results of these simulations. Results indicate no large differences in the wind systems of the Kanto plain (roughly 100 km × 100 km), where Tokyo is located, even if cities were converted entirely to vegetation. The influence of cities on wind systems of this scale was negligible. However, changes of wind convergence were found leeward of the urban area, which increased the horizontal vapor flux there. The precipitation also increased there due to the urban effects, despite the decrease in vertical vapor flux from the land surface. It is concluded that urban effects for Tokyo alter the wind characteristics leeward of the urban area and develop wind convergence and rainfall there.
The Effect of Signal-to-Noise Ratio on the Study of Sea Level Trends
Authors: Hamlington B. D. , Leben R. R. , Nerem R. S. , Kim K.-Y. 
Published: November 2010

Abstract
Extracting secular sea level trends from the background ocean variability is limited by how well one can correct for the time-varying and oscillating signals in the record. Many geophysical processes contribute time-dependent signals to the data, making the sea level trend difficult to detect. In this paper, cyclostationary empirical orthogonal functions (CSEOFs) are used to quantify and improve the signal-to-noise ratio (SNR) between the secular trend and the background variability, obscuring this trend in the altimetric sea level record by identifying and removing signals that are physically interpretable. Over the 16-yr altimetric record the SNR arising from the traditional least squares method for estimating trends can be improved from 4.0% of the ocean having an SNR greater than one to 9.9% when using a more sophisticated statistical method based on CSEOFs. From a standpoint of signal detection, this implies that the secular trend in a greater portion of the ocean can be estimated with a higher degree of confidence. Furthermore, the CSEOF method improves the standard error on the least squares estimates of the secular trend in 97% of the ocean. The convergence of the SNR as the record length is increased is used to estimate the SNR of sea level trends in the near future as more measurements become available from near-global altimetric sampling.
Expression of ARC (apoptosis repressor with caspase recruitment domain), an antiapoptotic protein, is strongly prognostic in AML
Authors: Carter Bing Z. , Qiu Yi Hua , Zhang Nianxiang , Coombes Kevin R. , Mak Duncan H. , Thomas Deborah A. , Ravandi Farhad , Kantarjian Hagop M. , Koller Erich , Andreeff Michael , Kornblau Steven M. 
Published: November 2010

Abstract
Regulators of apoptosis in acute myeloid leukemia (AML) have been extensively studied and are considered excellent therapeutic targets. Apoptosis repressor with caspase recruitment domain (ARC), an antiapoptotic protein originally found to be involved in apoptosis of cardiac cells, was recently demonstrated to be overexpressed in several solid tumors. To assess its importance in AML, we profiled ARC expression in 511 newly diagnosed AML patients using a validated robust reverse-phase protein array and correlated ARC levels with clinical outcomes. ARC was variably expressed in samples from patients with AML. ARC level was not associated with cytogenetic groups or with FLT-3 mutation status. However, patients with low or medium ARC protein levels had significantly better outcomes than those with high ARC levels: longer overall survival (median, 53.9 or 61.6 vs 38.9 weeks, P = .0015) and longer remission duration (median, 97.6 or 44.7 vs 31.1 weeks, P = .0007). Multivariate analysis indicated that ARC was a statistically significant independent predictor of survival in AML (P = .00013). Inhibition of ARC promoted apoptosis and sensitized cytosine arabinoside-induced apoptosis in OCI-AML3 cells. These results suggest that ARC expression levels are highly prognostic in AML and that ARC is a potential therapeutic target in AML.
Detection and isolation of cell-derived microparticles are compromised by protein complexes resulting from shared biophysical parameters
Authors: György Bence , Módos Károly , Pállinger Éva , Pálóczi Krisztina , Pásztói Mária , Misják Petra , Deli Mária A. , Sipos Áron , Szalai Anikó , Voszka István , Polgár Anna , Tóth Kálmán , Csete Mária , Nagy György , Gay Steffen , Falus András , Kittel Ágnes , Buzás Edit I. 
Published: November 2010

AbstractNumerous diseases, recently reported to associate with elevated microvesicle/microparticle (MP) counts, have also long been known to be characterized by accelerated immune complex (IC) formation. The goal of this study was to investigate the potential overlap between parameters of protein complexes (eg, ICs or avidin-biotin complexes) and MPs, which might perturb detection and/or isolation of MPs. In this work, after comprehensive characterization of MPs by electron microscopy, atomic force microscopy, dynamic light-scattering analysis, and flow cytometry, for the first time, we drive attention to the fact that protein complexes, especially insoluble ICs, overlap in biophysical properties (size, light scattering, and sedimentation) with MPs. This, in turn, affects MP quantification by flow cytometry and purification by differential centrifugation, especially in diseases in which IC formation is common, including not only autoimmune diseases, but also hematologic disorders, infections, and cancer. These data may necessitate reevaluation of certain published data on patient-derived MPs and contribute to correct the clinical laboratory assessment of the presence and biologic functions of MPs in health and disease.
Identification of a variant form of tyrosine phosphatase LYP
Authors: Wang Shaofeng , Dong Hongbo , Han Jiayu , Ho Wanting T , Fu Xueqi , Zhao Zhizhuang J 
Published: November 2010

Abstract

Background
Protein tyrosine phosphatases (PTPs) are important cell signaling regulators with major pathological implications. LYP (also known as PTPN22) is an intracellular enzyme initially found to be predominately expressed in lymphocytes. Importantly, an allelic R620W variant of LYP is strongly associated with multiple autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, type 1 diabetes, and autoimmune thyroid disease.

Results
In this study, we isolated a novel isoform of LYP designated LYP3. LYP3 differs from LYP1, the known isoform of LYP, in that it lacks a 28 amino acid segment right after the R620W site embedded in a proline-rich protein-protein interaction motif. Genomic sequence analysis revealed that LYP3 resulted from alternative splicing of the LYP gene located on chromosome 1p 13.3-13.1. Reverse transcription PCR analyses of 48 human tissues demonstrated that both LYP1 and LYP3 are predominantly expressed in primary and secondary lymphoid tissues but the relative expression levels of the two isoforms varies in different human tissues and individuals.

Conclusions
We thus identified a new variant form of LYP and conducted a comprehensive analysis of LYP tissue expressions. Considering the pathogenesis of LYP R620W, we believe that the expression of LYP3 may have an important role in regulating activity and function of LYP and may be implicated in autoimmune diseases.
Role of 14-3-3σ in poor prognosis and in radiation and drug resistance of human pancreatic cancers
Authors: Li Zhaomin , Dong Zizheng , Myer David , Yip-Schneider Michele , Liu Jianguo , Cui Ping , Schmidt C Max , Zhang Jian-Ting 
Published: November 2010

Abstract

Background
Pancreatic cancer is the fourth leading cause of death in the US. Unlike other solid tumors such as testicular cancer which are now curable, more than 90% of pancreatic cancer patients die due to lack of response to therapy. Recently, the level of 14-3-3σ mRNA was found to be increased in pancreatic cancers and this increased expression may contribute to the failure in treatment of pancreatic cancers. In the present study, we tested this hypothesis.

Methods
Western blot analysis was used to determine 14-3-3σ protein level in fresh frozen tissues and was correlated to clinical outcome. A stable cell line expressing 14-3-3σ was established and the effect of 14-3-3σ over-expression on cellular response to radiation and anticancer drugs were tested using SRB assay and clonogenic assays. Cell cycle distribution and apoptosis analyses were performed using propidium iodide staining and PARP cleavage assays.

Results
We found that 14-3-3σ protein level was increased significantly in about 71% (17 of 24) of human pancreatic cancer tissues and that the 14-3-3σ protein level in cancers correlated with lymph node metastasis and poor prognosis. Furthermore, we demonstrated that over-expression of 14-3-3σ in a pancreatic cancer cell line caused resistance to γ-irradiation as well as anticancer drugs by causing resistance to treatment-induced apoptosis and G2/M arrest.

Conclusion
The increased level of 14-3-3σ protein likely contributes to the poor clinical outcome of human pancreatic cancers by causing resistance to radiation and anticancer drugs. Thus, 14-3-3σ may serve as a prognosis marker predicting survival of pancreatic cancer patients and guide the clinical treatment of these patients.
Utilisation, contents and costs of prenatal care under a rural health insurance (New Co-operative Medical System) in rural China: lessons from implementation
Authors: Long Qian , Zhang Tuohong , Hemminki Elina , Tang Xiaojun , Huang Kun , Xiao Shengbin , Tolhurst Rachel 
Published: November 2010

Abstract

Background
In China, the New Co-operative Medical System (NCMS), a rural health insurance system, has expanded nationwide since 2003. This study aims to describe prenatal care use, content and costs of care in one county where prenatal care is included in the NCMS and two counties where it is not. It also explores the perceptions of stakeholders of the prenatal care benefit package in order to understand the strengths and weaknesses of the approach in the context of rural China and to draw lessons from early implementation.

Methods
This study is based on the data from a cross-sectional survey and a qualitative investigation conducted in 2009. A survey recruited women giving birth in 2008, including 544 women in RC County (which covered prenatal care) and 619, and 1071 in other two counties (which did not). The qualitative investigation in RC included focus group discussions with women giving birth before or after 2007, individual interviews with local policy makers and health managers, NCMS managers and obstetric doctors in township hospitals.

Results
There were no significant differences in prenatal care use between RC County (which covered prenatal care) and other two counties (which did not): over 70% of women started prenatal visits early and over 60% had five or more visits. In the three counties: a small proportion of women received the number of haemoglobin and urine tests recommended by the national guideline; 90% of women received more ultrasound tests than recommended; and the out-of-pocket expenditure for prenatal care consumed a high proportion of women's annual income in the low income group. In RC: only 20% of NCMS members claimed the reimbursement; the qualitative study found that the reimbursement for prenatal care was not well understood by women and had little influence on women's decisions to make prenatal visits; and several women indicated that doctors suggested them taking more expensive tests.

Conclusions
Whether or not prenatal care was included in the NCMS, prenatal care use was high, but the contents of care were not provided following the national guideline and more expensive tests were recommended by doctors. Costs were substantial for the poor.
Side-by-side analysis of five clinically tested anti-EpCAM monoclonal antibodies
Authors: Münz Markus , Murr Alexander , Kvesic Majk , Rau Doris , Mangold Susanne , Pflanz Stefan , Lumsden John , Volkland Jörg , Fagerberg Jan , Riethmüller Gert , Rüttinger Dominik , Kufer Peter , Baeuerle Patrick A , Raum Tobias 
Published: November 2010

AbstractBackgroundEpithelial cell adhesion molecule (EpCAM) is frequently and highly expressed on human carcinomas. The emerging role of EpCAM as a signalling receptor and activator of the wnt pathway, and its expression on tumor-initiating cells, further add to its attractiveness as target for immunotherapy of cancer. Thus far, five conventional monoclonal IgG antibodies have been tested in cancer patients. These are murine IgG2a edrecolomab and its murine/human chimeric IgG1 antibody version, and humanized, human-engineered and fully human IgG1 antibodies 3622W94, ING-1, and adecatumumab (MT201), respectively. Here we compared all anti-EpCAM antibodies in an attempt to explain differences in clinical activity and safety.MethodsWe recombinantly produced all antibodies but murine edrecolomab and investigated them for binding affinity, EpCAM epitope recognition, ADCC and CDC, and inhibition of breast cancer cell proliferation.ResultsING-1 and 3622W94 bound to EpCAM with much higher affinity than adecatumumab and edrecolomab. Edrecolomab, ING-1, and 3622W94 all recognized epitopes in the exon 2-encoded N-terminal domain of EpCAM, while adecatumumab recognized a more membrane proximal epitope encoded by exon 5. All antibodies induced lysis of EpCAM-expressing cancer cell lines by both ADCC and CDC with potencies that correlated with their binding affinities. The chimeric version of edrecolomab with a human Fcγ1 domain was much more potent in ADCC than the murine IgG2a version. Only adecatumumab showed a significant inhibition of MCF-7 breast cancer cell proliferation in the absence of complement and immune cells.ConclusionA moderate binding affinity and recognition of a distinct domain of EpCAM may best explain why adecatumumab showed a larger therapeutic window in cancer patients than the two high-affinity IgG1 antibodies ING-1 and 3622W94, both of which caused acute pancreatitis.
Increasing CD44+/CD24- tumor stem cells, and upregulation of COX-2 and HDAC6, as major functions of HER2 in breast tumorigenesis
Authors: Wang Kai-Hung , Kao An-Pei , Chang Chia-Cheng , Lee Jau-Nan , Hou Ming-Feng , Long Cheng-Yu , Chen Hung-Sheng , Tsai Eing-Mei 
Published: November 2010

AbstractBackgroundCancer cells are believed to arise primarily from stem cells. CD44+/CD24-have been identified as markers for human breast cancer stem cells. Although, HER2 is a well known breast cancer oncogene, the mechanisms of action of this gene are not completely understood. Previously, we have derived immortal (M13SV1), weakly tumorigenic (M13SV1R2) and highly tumorigenic (M13SV1R2N1) cell lines from a breast epithelial cell type with stem cell phenotypes after successive SV40 large T-antigen transfection, X-ray irradiation and ectopic expression of HER2/C-erbB2/neu. Recently, we found that M13SV1R2 cells became non-tumorigenic after growing in a growth factor/hormone-deprived medium (R2d cells).ResultsIn this study, we developed M13SV1R2N1 under the same growth factor/hormone-deprived condition (R2N1d cells). This provides an opportunity to analyze HER2 effect on gene expression associated with tumorigenesis by comparative study of R2d and R2N1d cells with homogeneous genetic background except HER2 expression. The results reveal distinct characters of R2N1d cells that can be ascribed to HER2: 1) development of fast-growing tumors; 2) high frequency of CD44+/CD24-cells (~50% for R2N1d vs. ~10% for R2d); 3) enhanced expression of COX-2, HDAC6 mediated, respectively, by MAPK and PI3K/Akt pathways, and many genes associated with inflammation, metastasis, and angiogenesis. Furthermore, HER2 expression can be down regulated in non-adhering R2N1d cells. These cells showed longer latent period and lower rate of tumor development compared with adhering cells.ConclusionsHER2 may induce breast cancer by increasing the frequency of tumor stem cells and upregulating the expression of COX-2 and HDAC6 that play pivotal roles in tumor progression.