bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distinct p53 Gene Signatures Are Needed to Predict Prognosis and Response to Chemotherapy in ER-Positive and ER-Negative Breast Cancers
Authors: Coutant Charles , Rouzier Roman , Qi Yuan , Lehmann-Che Jacqueline , Bianchini Giampaolo , Iwamoto Takayuki , Hortobagyi Gabriel N. , Symmans W. Fraser , Uzan Serge , Andre Fabrice , de Thé Hugues , Pusztai Lajos 
Published: January 2011

Abstract
Purpose: Estrogen receptor-positive (ER+) and -negative (ER) breast cancers are molecularly distinct diseases. We hypothesized that p53 mutations may lead to different transcriptional changes and carry different prognostic value in these two different types of cancers.
Experimental Design: We developed a 39-gene p53 signature derived from 213 ER+ and a separate 30-gene signature from 38 ER− cancers with known mutation status and tested their prognostic and chemotherapy response predictive values in ER+ and ER− cancers, respectively.
Results: External validation to predict p53 status (n = 103) showed sensitivity and specificity of 89% and 54% for the 39-gene signature, and 82% and 61% for the 30-gene signature. The 39-gene signature was predictive of worse distant metastasis free survival in ER+ cancers in two separate prognostic data sets (n = 255, HR: 2.3, P = 0.005 and n = 198, HR: 2.17, P = 0.09). It also predicted for poor prognosis even with adjuvant tamoxifen therapy (n = 277, HR = 2.43, P &lt; 0.0001) but it was not prognostic in ER− cancers. It was also associated with higher chemotherapy sensitivity in ER+ but not in ER− cancers. The prognostic and predictive values remained significant in multivariate analysis. The 30-gene, ER−, p53 signature showed no prognostic or predictive values in ER+ cancers but it was associated with better prognosis in ER− cancers. It also had no chemotherapy response predictive value in ER− or ER+ cancers.
Conclusions: P53 dysfunction is prognostically most relevant in ER+ cancers and supports the hypothesis that different predictive or prognostic markers will be needed for different molecular subsets of breast cancer. Clin Cancer Res; 17(8); 2591–601. ©2011 AACR.
Steerable Versus Nonsteerable Sheath Technology in Atrial Fibrillation Ablation
Authors: Piorkowski Christopher , Eitel Charlotte , Rolf Sascha , Bode Kerstin , Sommer Philipp , Gaspar Thomas , Kircher Simon , Wetzel Ulrike , Parwani Abdul Shokor , Boldt Leif-Hendrik , Mende Meinhard , Bollmann Andreas , Husser Daniela , Dagres Nikolaos , Esato Masahiro , Arya Arash , Haverkamp Wilhelm , Hindricks Gerhard 
Published: January 2011

Background—
Steerable sheath technology is designed to facilitate catheter access, stability, and tissue contact in target sites of atrial fibrillation (AF) catheter ablation. We hypothesized that rhythm control after interventional AF treatment is more successful using a steerable as compared with a nonsteerable sheath access.

Methods and Results—

One hundred thirty patients with paroxysmal or persistent drug-refractory AF undergoing their first ablation procedure were prospectively included in a randomized fashion in 2 centers. Ablation was performed by 10 operators with different levels of clinical experience. Treatment outcome was measured with serial 7-day Holter ECGs and additional symptom-based arrhythmia documentation. Single procedure success (freedom from AF and/or atrial macroreentrant tachycardia) was significantly higher in patients ablated with a steerable sheath (78% versus 55% after 3 months,
P
=0.005; 76% versus 53% after 6 months,
P
=0.008). Rate of pulmonary vein isolation, procedure duration, and radiofrequency application time did not differ significantly, whereas fluoroscopy time was lower in the steerable sheath group (33±14 minutes versus 45±17 minutes,
P
<0.001). Complication rates showed no significant difference (3.2% versus 5%,
P
=0.608). On multivariable analysis, steerable sheath usage remained the only powerful predictor for rhythm outcome after 6 months of follow-up (hazard ratio, 2.837 [1.197 to 6.723]).

Conclusions—
AF catheter ablation using a manually controlled, steerable sheath for catheter navigation resulted in a significantly higher clinical success rate, with comparable complication rates and with a reduction in periprocedural fluoroscopy time.

Clinical Trial Registration—

URL:
http://clinicaltrials.gov
. Unique identifier: NCT00469638.
The Incidence and Long-Term Clinical Outcome of Iatrogenic Atrial Septal Defects Secondary to Transseptal Catheterization With a 12F Transseptal Sheath
Authors: Singh Sheldon M. , Douglas Pamela S. , Reddy Vivek Y. 
Published: January 2011

Background—
Studies assessing the presence of a residual iatrogenic atrial septal defect (iASD) after transseptal catheterization with 8F transseptal sheaths have suggested that the majority of these iASDs close within 6 months. However, these studies have been limited by small patient numbers and short follow-up. Additionally, there are a number of novel catheter procedures in interventional cardiology and electrophysiology that use larger transseptal sheaths. The objective of this study was to assess the incidence of and complications associated with iASDs in a large cohort of patients undergoing transseptal catheterization with a 12F transseptal sheath.

Methods and Results—
Patients (n=253) without a preexisting interatrial shunt undergoing WATCHMAN implantation as part of the PROTECT AF study were included in this current study. Patients underwent transesophageal echocardiography with echo-contrast immediately after the procedure and at 45 days and 6 months and 12 months. Eighty-seven percent of patients had an iASD immediately after the procedure, the majority of which sealed by 6 months (incidence of iASD, 34% at 45 days, 11% at 6 months, 7% at 12 months). Whereas the majority of iASDs were >3 mm in diameter immediately after the procedure, the minority of iASD were >3 mm during the follow-up period. Additionally, interatrial shunting was predominantly left-to-right when an iASD was present. There was no significant difference in the rate of stroke and/or systemic embolism during the follow-up period in patients with or without iASD.

Conclusions—
Transseptal catheterization procedures with a large-diameter transseptal sheath have a high spontaneous closure rate of iASDs that is not associated with an increased rate of stroke/systemic embolization during long-term follow-up.
Micro wind turbine performance under real weather conditions in urban environment
Authors: Glass A. , Levermore G. 
Published: January 2011

The aim of this article is to evaluate the performance of micro wind turbines in a built-up environment. For this purpose, five independent micro wind turbine systems, consisting of two distinctly different models, were tested and evaluated under real life conditions over a period of 12 months. This article provides an overview of the experimental set-up used to test the two different micro wind turbines and then goes on to present the basic background theory for horizontal axis micro wind turbines and the variation of coefficient of performance with wind speed. The wind potentials at the test site were assessed to determine the theoretical outputs of the turbines which were compared with the measured outputs over a year. The measured outputs were disappointingly low. One reason for this is turbulence, for which directional turbulence (lateral turbulence) has been shown to be a key indicator, better than the standard wind speed (longitudinal) turbulence. Another factor is the inverter efficiency and power consumption, which is not negligible. Finally the theoretical paybacks under the 2010 Feed-in Tariffs were calculated along with estimated carbon savings. Practical application: Renewables such as wind turbines are increasingly being designed and installed to help achieve lower carbon buildings. The output of micro turbines, however, can be disappointing due to lateral turbulence and inverter consumptions. These factors are explained so that designers can be aware and assess the likely outputs more accurately.
Bcr-Abl ubiquitination and Usp9x inhibition block kinase signaling and promote CML cell apoptosis
Authors: Sun Hanshi , Kapuria Vaibhav , Peterson Luke F. , Fang Dexing , Bornmann William G. , Bartholomeusz Geoffrey , Talpaz Moshe , Donato Nicholas J. 
Published: January 2011

Abstract
Although chronic myelogenous leukemia (CML) is effectively controlled by Bcr-Abl kinase inhibitors, resistance to inhibitors, progressive disease, and incomplete eradication of Bcr-Abl–expressing cells are concerns for the long-term control and suppression of this disease. We describe a novel approach to targeting key proteins in CML cells with a ubiquitin-cycle inhibitor, WP1130. Bcr-Abl is rapidly modified with K63-linked ubiquitin polymers in WP1130-treated CML cells, resulting in its accumulation in aggresomes, where is it unable to conduct signal transduction. Induction of apoptosis because of aggresomal compartmentalization of Bcr-Abl was observed in both imatinib-sensitive and -resistant cells. WP1130, but not Bcr-Abl kinase inhibitors, directly inhibits Usp9x deubiquitinase activity, resulting in the down-regulation of the prosurvival protein Mcl-1 and facilitating apoptosis. These results demonstrate that ubiquitin-cycle inhibition represents a novel and effective approach to blocking Bcr-Abl kinase signaling and reducing Mcl-1 levels to engage CML cell apoptosis. This approach may be a therapeutic option for kinase inhibitor–resistant CML patients.
Lack of cathepsin activities alter or prevent the development of lung granulomas in a mouse model of sarcoidosis
Authors: Samokhin Andriy O , Gauthier Jacques Yves , Percival M David , Brömme Dieter 
Published: January 2011

Abstract

Background
Remodeling of lung tissues during the process of granuloma formation requires significant restructuring of the extra-cellular matrix and cathepsins K, L and S are among the strongest extra-cellular matrix degrading enzymes. Cathepsin K is highly expressed in various pathological granulomatous infiltrates and all three enzymes in their active form are detected in bronchoalveolar lavage fluids from patients with sarcoidosis. Granulomatous inflammation is driven by T-cell response and cathepsins S and L are actively involved in the regulation of antigen presentation and T-cell selection. Here, we show that the disruption of the activities of cathepsins K, L, or S affects the development of lung granulomas in a mouse model of sarcoidosis.

Methods
Apolipoprotein E-deficient mice lacking cathepsin K or L were fed Paigen diet for 16 weeks and lungs were analyzed and compared with their cathepsin-expressing littermates. The role of cathepsin S in the development of granulomas was evaluated using mice treated for 8 weeks with a potent and selective cathepsin S inhibitor.

Results
When compared to wild-type litters, more cathepsin K-deficient mice had lung granulomas, but individually affected mice developed smaller granulomas that were present in lower numbers. The absence of cathepsin K increased the number of multinucleated giant cells and the collagen content in granulomas. Cathepsin L deficiency resulted in decreased size and number of lung granulomas. Apoe-/- mice treated with a selective cathepsin S inhibitor did not develop lung granulomas and only individual epithelioid cells were observed.

Conclusions
Cathepsin K deficiency affected mostly the occurrence and composition of lung granulomas, whereas cathepsin L deficiency significantly reduced their number and cathepsin S inhibition prevented the formation of granulomas.
Differential effect of corn oil-based low trans structured fat on the plasma and hepatic lipid profile in an atherogenic mouse model: comparison to hydrogenated trans fat
Authors: Cho Yun-Young , Kwon Eun-Young , Kim Hye-Jin , Jeon Seon-Min , Lee Ki-Teak , Choi Myung-Sook 
Published: January 2011

Abstract

Background

Trans fat are not desirable in many aspects on health maintenance. Low trans structured fats have been reported to be relatively more safe than trans fats.

Methods
We examined the effects of low trans structured fat from corn oil (LC), compared with high trans fat shortening, on cholesterol and fatty acid metabolism in apo E deficient mice which is an atherogenic animal model. The animals were fed a high trans fat (10% fat: commercial shortening (CS)) or a low trans fat (LC) diet for 12 weeks.

Results
LC decreased apo B and hepatic cholesterol and triglyceride concentration compared to the CS group but significantly increased plasma total cholesterol and triglyceride concentration and fecal lipids with a simultaneous increase in HDL-cholesterol level, apo A-I, and the ratio of HDL-cholesterol to total cholesterol (HTR). Reduction of hepatic lipid levels by inclusion of LC intake was observed alongside modulation of hepatic enzyme activities related to cholesterol esterification, fatty acid metabolism and fecal lipids level compared to the CS group. The differential effects of LC intake on the plasma and hepatic lipid profile seemed to be partly due to the fatty acid composition of LC which contains higher MUFA, PUFA and SFA content as well as lower content of trans fatty acids compared to CS.

Conclusions
We suggest that LC may exert a dual effect on plasma and hepatic lipid metabolism in an atherogenic animal model. Accordingly, LC, supplemented at 10% in diet, had an anti-atherogenic effect on these apo E

-/-
mice, and increased fecal lipids, decreased hepatic steatosis, but elevated plasma lipids. Further studies are needed to verify the exact mode of action regarding the complex physiological changes and alteration in lipid metabolism caused by LC.
Changes in the vascular cell adhesion molecule-1, intercellular adhesion molecule-1 and c-reactive protein following administration of aqueous extract of piper sarmentosum on experimental rabbits fed with cholesterol diet
Authors: Amran Adel A , Zakaria Zaiton , Othman Faizah , Das Srijit , Al-Mekhlafi Hesham M , Nordin Nor-Anita MM 
Published: January 2011

AbstractBackgroundInflammation process plays an important role in the development of atherosclerosis. Hypercholesterolemia is one of the major risk factors for atherosclerosis. The present study aimed to evaluate the effect of aqueous extract ofPiper sarmentosum (P.s)on inflammatory markers like vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and C-reactive protein (CRP).MethodsForty two male New Zealand white rabbits were divided equally into seven groups; (i) C- control group fed normal rabbit chow (ii) CH- cholesterol diet (1%cholesterol) (iii) X1- 1% cholesterol with water extract ofP.s(62.5 mg/kg) (iv) X2- 1% cholesterol with water extract ofP.s(125 mg/kg (v) X3- 1% cholesterol with water extract ofP.s(250 mg/kg) (vi) X4- 1% cholesterol with water extract ofP.s(500 mg/kg) and (vii) SMV group fed with 1% cholesterol supplemented with simvistatin drug (1.2 mg/kg). All animals were treated for 10 weeks. Blood serum was taken for observing the inflammatory markers at the beginning and end of the experiment.ResultsRabbits fed with 1% cholesterol diet (CH) showed significant increase in the level of VCAM-1, ICAM-1 and CRP compared to the C group. The levels of VCAM-1, ICAM-1 and CRP in the 1% cholesterol group and supplemented withP.s(500 mg/kg) were significantly reduced compared to the cholesterol group. Similar results were also reported with simvistatin group.ConclusionThese results suggest that the supplementation ofPiper sarmentosumextract could inhibit inflammatory markers which in turn could prevent atherosclerosis.
Case Report: Successful non-operative management of spontaneous splenic rupture in a patient with babesiosis
Authors: Tobler William D , Cotton Deborah , Lepore Timothy , Agarwal Suresh , Mahoney Eric J 
Published: January 2011

Abstract

Background
Babesiosis is a zoonotic disease transmitted by the Ixodes tick species. Infection often results in sub-clinical manifestations; however, patients with this disease can become critically ill. Splenic rupture has been a previously reported complication of babesiosis, but treatment has always led to splenectomy. Asplenia places a patient at greater risk for overwhelming post-splenectomy infection from encapsulated bacteria, Lyme disease, Ehrlichia as well as Babesia microti. Therefore, avoiding splenectomy in these patients must be considered by the physician; particularly, if the patient is at risk for re-infection by living in an endemic area.

Case Presentation
A 54 year-old male from the northeast United States presented with left upper quadrant abdominal pain associated with fever, chills, night sweats and nausea. A full evaluation revealed active infection with Babesia microti and multiple splenic lacerations. This patient was successfully treated with appropriate pharmacological therapy and non-operative observation for the splenic injury.

Conclusion
Patients diagnosed with Babesia microti infection are becoming more common, especially in endemic areas. Although clinical manifestations are usually minimal, this infection can present with significant injuries leading to critical illness. We present the successful non-operative treatment of a patient with splenic rupture due to babesiosis infection.
Perception of Deqi by Chinese and American acupuncturists: a pilot survey
Authors: Hui Kathleen KKS , Sporko Tara N , Vangel Mark G , Li Ming , Fang Jiliang , Lao Lixing 
Published: January 2011

Abstract

Background
In acupuncture, deqi is the sensory experience related to clinical efficacy. As the first study taking into account cultural differences on deqi sensation, this pilot survey aims to corroborate the acupuncturists' general experience in clinical practice with functional magnetic resonance imaging (fMRI) findings.

Methods
Questionnaires were distributed to acupuncturists of TCM (traditional Chinese medicine)hospitals and acupuncturists attending workshops and seminars in the United States and China. Questions covered clinical significance of deqi, patient attitude and the nature of some pain-related sensations elicited by manual needling.

Results
47 out of a total of 86 acupuncturists agreed that dull pain was deqi and over half regarded it beneficial, while sharp pain was non-deqi and harmful instead. The patients' attitude toward deqi sensation showed a difference between US and China. There was no other dimension showing a difference.

Conclusion
Results of this pilot survey indicate that the acupuncturists' perception is consistent with our previous fMRI findings. Results showed almost complete agreement that dull pain is considered deqi and beneficial to treatment, while sharp pain is not deqi and harmful. Particularly, dull pain was deqi and was beneficial to treatment whereas sharp pain was not. Patients in China liked the deqi experience whereas those in the US did not.
Evidence-based genomic diagnosis characterized chromosomal and cryptic imbalances in 30 elderly patients with myelodysplastic syndrome and acute myeloid leukemia
Authors: Bajaj Renu , Xu Fang , Xiang Bixia , Wilcox Katherine , DiAdamo Autumn J , Kumar Rachana , Pietraszkiewicz Alexandra , Halene Stephanie , Li Peining 
Published: January 2011

Abstract

Background
To evaluate the clinical validity of genome-wide oligonucleotide array comparative genomic hybridization (aCGH) for detecting somatic abnormalities, we have applied this genomic analysis to 30 cases (13 MDS and 17 AML) with clonal chromosomal abnormalities detected in more than 50% of analyzed metaphase cells.

Results
The aCGH detected all numerical chromosomal gains and losses from the mainline clones and 113 copy number alterations (CNAs) ranging from 0.257 to 102.519 megabases (Mb). Clinically significant recurrent deletions of 5q (involving the RPS14 gene), 12p12.3 (ETV6 gene), 17p13 (TP53 gene), 17q11.2 (NF1 gene) and 20q, double minutes containing the MYC gene and segmental amplification involving the MLL gene were further characterized with defined breakpoints and gene contents. Genomic features of microdeletions at 17q11.2 were confirmed by FISH using targeted BAC clones. The aCGH also defined break points in a derivative chromosome 6, der(6)t(3;6)(q21.3;p22.2), and an isodicentric X chromosome. However, chromosomally observed sideline clonal abnormalities in five cases were not detected by aCGH.

Conclusions
Our data indicated that an integrated cytogenomic analysis will be a better diagnostic scheme to delineate genomic contents of chromosomal and cryptic abnormalities in patients with MDS and AML. An evidence-based approach to interpret somatic genomic findings was proposed.
Pathogenic effect of interleukin-17A in induction of Sjögren's syndrome-like disease using adenovirus-mediated gene transfer
Authors: Nguyen Cuong Q , Yin Hongen , Lee Byung Ha , Carcamo Wendy C , Chiorini John A , Peck Ammon B 
Published: January 2011

Abstract
Introduction
Sjögren's syndrome (SS) involves a chronic, progressive inflammation primarily of the salivary and lacrimal glands leading to decreased levels of saliva and tears resulting in dry mouth and dry eye diseases. Seminal findings regarding TH17 cell populations that secrete predominantly interleukin (IL)-17A have been shown to play an important role in an increasing number of autoimmune diseases, including SS. In the present study, we investigated the function of IL-17A on the development and onset of SS.

Methods
Adenovirus serotype 5 (Ad5) vectors expressing either IL-17A or LacZ were infused via retrograde cannulation into the salivary glands of C57BL/6J mice between 6 and 8 weeks of age or between 15 and 17 weeks of age. The mice were characterized for SS phenotypes.

Results
Disease profiling indicated that SS-non-susceptible C57BL/6J mice whose salivary glands received the Ad5-IL17A vector developed a SS-like disease profile, including the appearance of lymphocytic foci, increased cytokine levels, changes in antinuclear antibody profiles, and temporal loss of saliva flow.

Conclusions
Induction of SS pathology by IL-17A in SS-non-susceptible mice strongly suggests that IL-17A is an important inflammatory cytokine in salivary gland dysfunction. Thus, localized anti-IL17 therapy may be effective in preventing glandular dysfunction.