bluuebunny/crossref_metadata_2025_split huggingface dataset:
DNA Damage-Inducible Gene, Reprimo Functions as a Tumor Suppressor and Is Suppressed by Promoter Methylation in Gastric Cancer
Authors: Ooki Akira , Yamashita Keishi , Yamaguchi Kensei , Mondal Anupom , Nishimiya Hiroshi , Watanabe Masahiko 
Published: August 2013

Abstract
In several types of human cancer, the gene expression of Reprimo, a highly glycosylated protein, is frequently silenced via methylation of its promoter. The aim of this study was to characterize the epigenetic inactivation of Reprimo and its biologic function and clinical relevance in gastric cancer. The correlation between Reprimo methylation and clinical relevance was assessed in 83 primary human gastric cancer tissues. The effects of Reprimo expression were also examined using in vitro and in vivo assays. Reprimo methylation was cancer specific and frequently observed. In two gastric cancer cell lines without Reprimo methylation, we observed faint or weak Reprimo expression under normal conditions and high expression under DNA-damaging conditions. In four gastric cancer cell lines with Reprimo methylation, however, Reprimo expression remained faint even under DNA-damaging conditions, with expression being restored in combination with agents that induce demethylation. Enforced Reprimo expression robustly inhibited cell proliferation and anchorage-independent colony formation and enhanced DNA damage-induced apoptosis. Inverse effects were observed via siRNA-mediated knockdown of endogenous Reprimo. Reprimo expression inhibited tumorigenesis in vivo. Reprimo methylation was also associated with a poor response in patients with gastric cancer treated with chemotherapy (P¼ 0.028), and a poor prognosis in patients with advanced gastric cancer (P¼ 0.03). In conclusion, Reprimo expression is normally induced in response to DNA damage, acting as a novel tumor suppressor in gastric cancer. However, Reprimo methylation abrogates its expression and effects. The clinical assessment of Reprimo promoter methylation may serve not only as a predictive marker for chemotherapy, but also as a marker for tumor aggressiveness. Mol Cancer Res; 11(11); 1362–74. ©2013 AACR.
Tpl2 Kinase Impacts Tumor Growth and Metastasis of Clear Cell Renal Cell Carcinoma
Authors: Lee Hye Won , Joo Kyeung Min , Lim Joung Eun , Cho Hyun Jung , Cho Hee Jin , Park Min Chul , Seol Ho Jun , Seo Seong Il , Lee Jung-Il , Kim Sunghoon , Jeong Byong Chang , Nam Do-Hyun 
Published: August 2013

Abstract
Due to the innate high metastatic ability of renal cell carcinoma (RCC), many patients with RCC experience local or systemic relapses after surgical resection. A deeper understanding of the molecular pathogenesis underlying advanced RCC is essential for novel innovative therapeutics. Tumor progression locus 2 (Tpl2), upregulated in various tumor types, has been reported to be associated with oncogenesis and metastatic progression via activation of the MAPK signaling pathway. Herein, the relevance of Tpl2 in tumor growth and metastasis of RCC is explored. Inspection of The Cancer Genome Atlas (TCGA) indicated that Tpl2 overexpression was significantly related to the presence of metastases and poor outcome in clear cell RCC (ccRCC), which is the most aggressive subtype of RCC. Moreover, expression of Tpl2 and CXCR4 showed a positive correlation in ccRCC patients. Depletion of Tpl2 by RNAi or activity by a Tpl2 kinase inhibitor in human ccRCC cells remarkably suppressed MAPK pathways and impaired in vitro cell proliferation, clonogenicity, anoikis resistance, migration, and invasion capabilities. Similarly, orthotopic xenograft growth and lung metastasis were significantly inhibited by Tpl2 silencing. Furthermore, Tpl2 knockdown reduced CXCL12-directed chemotaxis and chemoinvasion accompanied with impaired downstream signaling, indicating potential involvement of Tpl2 in CXCR4-mediated metastasis. Taken together, these data indicate that Tpl2 kinase is associated with and contributes to disease progression of ccRCC.
Implications: Tpl2 kinase activity has prognostic and therapeutic targeting potential in aggressive clear cell renal cell carcinoma. Mol Cancer Res; 11(11); 1375–86. ©2013 AACR.
Discrete Prepotential as an Indicator of Successful Ablation in Patients With Coronary Cusp Ventricular Arrhythmia
Authors: Hachiya Hitoshi , Yamauchi Yasuteru , Iesaka Yoshito , Yagishita Atsuhiko , Sasaki Takeshi , Higuchi Koji , Kawabata Mihoko , Sugiyama Koji , Tanaka Yasuaki , Kusa Shigeki , Nakamura Hiroaki , Miyazaki Shinsuke , Taniguchi Hiroshi , Isobe Mitsuaki , Hirao Kenzo 
Published: August 2013

Background—
Although coronary cusp (CC) ventricular arrhythmia (VA) can be treated by catheter ablation, reliable indicators of successful ablation sites have not been fully identified.

Methods and Results—
This study comprised 392 patients undergoing radiofrequency catheter ablation for outflow tract-VA at 3 institutions from January 2007 to August 2012. The successful ablation site was on the left CC or right CC in 35 (8.9%) of the 392 patients. In 9 (26%) of these 35 patients, a discrete prepotential was recognized, 5 of whom had left CC-VAs and 4 of whom had right CC-VAs. Radiofrequency catheter ablation was successful at the site of the prepotential in all 9 of these patients. The duration of the isoelectric line between the end of the discrete prepotential and the onset of the ventricular electrogram was 27±13 ms. The time from onset of the discrete prepotential at the successful ablation site on the CC to the QRS onset (activation time) was 69±20 ms (range, 50–98 ms). Pace mapping was graded as excellent at the successful ablation site in only 1 patient. No discrete prepotential was recorded in any successful right outflow tract-VA ablation case in this study.

Conclusions—
A discrete prepotential was seen in 9 (26%) of 35 patients with CC-VA. In left and right CC-VA, the site of a discrete prepotential with ≥50 ms activation time may indicate a successful ablation site.
Prevalence, Characteristics, Mapping, and Catheter Ablation of Potential Rotors in Nonparoxysmal Atrial Fibrillation
Authors: Lin Yenn-Jiang , Lo Men-Tzung , Lin Chen , Chang Shih-Lin , Lo Li-Wei , Hu Yu-Feng , Hsieh Wan-Hsin , Chang Hung-Yu , Lin Wen-Yu , Chung Fa-Po , Liao Jo-Nan , Chen Yun-Yu , Hanafy Dicky , Huang Norden E. , Chen Shih-Ann 
Published: August 2013

Background—
Identification of critical atrial substrates in patients with nonparoxysmal atrial fibrillation (AF) failing to respond to pulmonary vein isolation is important. This study investigated the signal characteristics, substrate nature, and ablation results of rotors during AF.

Methods and Results—

In total, 53 patients (age=55±8), 31 with persistent AF and 22 with long-lasting AF, underwent pulmonary vein isolation and substrate modification of complex fractionated atrial electrograms. Small-radius-reentrant rotors were identified from signal analyses of the dominant frequency and fractionation interval and nonlinear analyses (newly developed, beat-to-beat nonlinear measurement of the repetitiveness of the electrogram morphology >6 seconds). In 15% of the patients, activation maps demonstrated occurrences of rotor-like small-radius reentrant circuits (n=9; 1.1 per patient; cycle length=110±21 ms; diameter=11±6 mm) with fibrillation occurring outside these areas. Rotors were identified by conventional point-by-point mapping and signal analyses and were subsequently eradicated by catheter ablation in these patients. Persistent AF for <1 year, a smaller left atrial size, substrates with higher mean voltages and shorter total activation durations predicted a higher incidence of rotors (all
P
<0.05). In the multivariable model, areas of reentrant circuits exhibited a higher dominant frequency, kurtosis, and higher degree of a beat-to-beat electrogram similarity than areas without or outside the rotors (all
P
<0.05).

Conclusions—
Rotor-like re-entry with fibrillatory conduction was found in a limited number of patients with nonparoxysmal AF after pulmonary vein isolation. Those areas were characterized by rapid repetitive activity with a high degree of electrogram similarity.
Evaluation and Reduction of Asymptomatic Cerebral Embolism in Ablation of Atrial Fibrillation, But High Prevalence of Chronic Silent Infarction
Authors: Verma Atul , Debruyne Philippe , Nardi Stefano , Deneke Thomas , DeGreef Yves , Spitzer Stefan , Balzer Jörn O. , Boersma Lucas 
Published: August 2013

Background—
This prospective, multicenter study sought to evaluate the incidence of asymptomatic cerebral emboli (ACE) during ablation of atrial fibrillation (AF) using a multielectrode radiofrequency (MER) system when specific procedural changes were applied.

Methods and Results—

Sixty subjects (age 60±10 years; 87% paroxysmal; CHADS
2
score, 0.6±0.7) undergoing AF ablation with a circular MER catheter were studied. Three procedural changes were specified: (1) ablation was performed under therapeutic vitamin K antagonist and heparin to maintain activated clotting time >350 seconds; (2) submerged loading of the catheter into the introducer before sheath insertion to minimize air ingress; and (3) either the distal or proximal electrode of the circular MER catheter was deactivated to prevent inadvertent bipolar radiofrequency interaction. MRI was performed <7 days preablation and 2 days postablation. Subjects with new cerebral findings after ablation underwent repeat MRI after 1 month. An acute ACE lesion was defined by a new hyperintensity on diffusion-weighted and fluid-attenuated inversion recovery cerebral MRI sequences. Neurological function was evaluated at baseline, postablation, and 1 month. All target pulmonary veins were isolated. In 60% (36/60) of patients, pre-existing cerebral lesions were seen on the preprocedure MRI (8 lesions per subject; interquartile range, 3–22). New postprocedural ACE occurred in only 1/60 patients (incidence, 1.7%; 95% confidence interval, 0.04–8.9), which was no longer visible on MRI after 1 month.

Conclusions—
Applying procedural changes to MER ablation significantly reduces the ACE incidence to 1.7%, which is on the low end of reported ACE rates of any technology.

Clinical Trial Registration Information—
ClinicalTrials.gov; Identifier: NCT01520532.
Extracellular Matrix Turnover Biomarkers Predict Long-Term Left Ventricular Remodeling After Myocardial Infarction
Authors: Eschalier Romain , Fertin Marie , Fay Renaud , Bauters Christophe , Zannad Faïez , Pinet Florence , Rossignol Patrick 
Published: August 2013

Background—
Extracellular matrix turnover plays a key role in wound repair after myocardial infarction (MI). The aim of the study was to evaluate whether biomarkers of myocardial fibrosis measurements 1 month after MI may predict left ventricular (LV) remodeling.

Methods and Results—

This prospective multicenter study included 246 patients with a first anterior Q-wave MI. Echocardiographic studies were performed at hospital discharge and 12 months after MI. Brain natriuretic peptide as well as biomarkers of myocardial fibrosis (type 1 collagen telopeptide, aminoterminal propeptide of type I procollagen, aminoterminal propeptide of type III procollagen) were measured 1 month after MI in 218 patients. In multivariate analysis, aminoterminal propeptide of type III procollagen/type 1 collagen telopeptide ratio ≤1 (odds ratio [95% confidence interval], 1.86 [1.02–3.39];
P
=0.043) 1 month after MI and brain natriuretic peptide >100 pg/mL (2.35 [1.28–4.31];
P
=0.006) were associated with a pejorative LV remodeling, whereas LV ejection fraction at discharge (per 5% increment; 0.78 [0.65–0.94];
P
=0.01) was independently associated with lower rates of detrimental LV remodeling at 12 months. Patients with high brain natriuretic peptide and aminoterminal propeptide of type III procollagen/type 1 collagen telopeptide ratio ≤1, measured 1 month after MI, had the highest risk of developing a primary composite event (cardiovascular death or hospitalization for worsening heart failure; 14 events per 216 patients;
P
=0.0001) during a 3-year follow-up.

Conclusions—
Myocardial fibrosis turnover after MI is associated with LV remodeling. Low aminoterminal propeptide of type III procollagen/type 1 collagen telopeptide ratio (≤1) at 1 month is predictive, in addition to brain natriuretic peptide and LV ejection fraction, of detrimental LV remodeling as well as cardiovascular deaths and hospitalizations for heart failure.
Atrial Fibrillation, Stroke Risk, and Warfarin Therapy Revisited
Authors: Björck Staffan , Palaszewski Bo , Friberg Leif , Bergfeldt Lennart 
Published: August 2013

Background and Purpose—
Atrial fibrillation (AF) is a major risk factor for ischemic stroke. This study aims to update the knowledge about AF and associated stroke risk and benefits of anticoagulation.

Methods—
We extracted data from the hospital, specialized outpatient, and primary healthcare and drug registries in a Swedish region with 1.56 million residents. We identified all individuals who had received an AF diagnosis during the previous 5 years; all stroke events during 2010; and patients with AF aged ≥50 years who had received warfarin during 2009.

Results—
AF had been diagnosed in 38 446 subjects who were alive at the beginning of 2010 (prevalence of 3.2% in the adult [≥20 years] population); ≈46% received warfarin therapy. In 2010, there were 4565 ischemic stroke events and 861 intracranial hemorrhages. AF had been diagnosed in 38% of ischemic events (≥50% among those aged ≥80 years) and in 23% of intracranial hemorrhages. An AF diagnosis was often lacking in hospital discharge records after stroke events. Warfarin therapy was associated with an odds ratio of 0.50 (confidence interval, 0.43–0.57) for ischemic stroke and, despite an increased risk of intracranial hemorrhage, an odds ratio of 0.57 (confidence interval, 0.50–0.64) for the overall risk for stroke.

Conclusions—
AF is more common than present guidelines suggest. The attributable risk of AF for ischemic stroke increases with age and is close to that of hypertension in individuals aged ≥80 years. Because a majority of patients with AF with increased risk for stroke had not received anticoagulation therapy, there is a large potential for improvement.
Ambulatory Blood Pressure in Patients With Lacunar Stroke
Authors: Klarenbeek Pim , van Oostenbrugge Robert J. , Rouhl Rob P.W. , Knottnerus Iris L.H. , Staals Julie 
Published: August 2013

Background and Purpose—
Asymptomatic lacunar infarcts, white matter lesions, cerebral microbleeds, and enlarged perivascular spaces are MRI markers of cerebral small vessel disease (cSVD). Higher blood pressure (BP) levels are associated with the presence of these markers separately, but the association with the total burden of cSVD on brain MRI, expressed by the simultaneous presence of multiple markers of cSVD (a compound score), has not been investigated.

Methods—
We performed 24-hour ambulatory BP monitoring in 122 patients with first-ever lacunar stroke. On brain MRI, we scored the presence of each marker of cSVD. One point was awarded for the presence of each marker, producing a score between 0 and 4. Associations with BP levels were tested with ordinal regression analyses.

Results—
Eighteen (15%) patients had no markers of cSVD, and 6 (5%) patients had 4 markers. Most patients (45; 37%) had 2 different markers. After correction for age and sex, higher 24-hour, day, and night systolic (24-hour odds ratio, 1.25; 95% confidence interval, 1.02–1.52 per 10 mm Hg) and diastolic (24-hour odds ratio, 1.32; 95% confidence interval, 1.12–1.56 per 5 mm Hg) BP were all significantly associated with an increasing total burden of cSVD.

Conclusions—
We found a positive association of ambulatory BP levels with total burden of cSVD on brain MRI. With increasing BP levels, there is a piling up of damage in the brain. We suggest that further cSVD studies also consider viewing the total burden in addition to each of the MRI markers separately.
Antiplatelet Loading Improves Behavioral Outcome in a Rabbit Model of Stroke
Authors: Meyer Dawn M. , Compton Peggy , Eastwood Jo-Ann , Gylys Karen , Zivin Justin A. 
Published: August 2013

Background and Purpose—
No approved acute therapy exists for thousands of patients with ischemic stroke who present ineligible for thrombolytics. The purpose of this proof-of-concept study was to evaluate the efficacy of acute antiplatelet loading on stroke outcome in the rabbit small clot embolic model.

Methods—

Sixty male New Zealand white rabbits were embolized via small clots into the middle cerebral artery. Two hours later, animals were treated with (1) aspirin (5 mg/kg; n=20); (2) usual dual antiplatelet loading (aspirin 10 mg/kg+clopidogrel 10 mg/kg; n=20); or (3) high-dose dual antiplatelet loading (aspirin 10 mg/kg+clopidogrel 30 mg/kg; n=20). The coprimary outcomes were as follows: (1) platelet inhibition and (2) behavioral outcome as measured by the P
50
(milligrams of clot that leads to neurological dysfunction in 50% of animals in a group).

Results—

There was a significant difference in 3-hour arachidonic acid and ADP (
P
<0.011); 6-hour collagen and ADP (
P
<0.01,
P
<0.01); and 24-hour collagen, arachidonic acid, and ADP (
P
=0.02,
P
<0.01,
P
<0.01) platelet inhibition. The behavioral outcome was significantly better in the usual dual antiplatelet loading versus aspirin group (
P
=0.02).

Conclusions—
This study suggests that usual dual antiplatelet loading is clinically beneficial in a validated model of acute stroke. Study of usual dual antiplatelet loading in acute stroke is warranted to provide treatment to stroke victims ineligible for current therapies.
Sex Differences in the Use of Early Do-Not-Resuscitate Orders After Intracerebral Hemorrhage
Authors: Nakagawa Kazuma , Vento Megan A. , Seto Todd B. , Koenig Matthew A. , Asai Susan M. , Chang Cherylee W.J. , Hemphill J. Claude 
Published: August 2013

Background and Purpose—
Studies show that women are more likely to receive do-not-resuscitate (DNR) orders after acute medical illnesses than men. However, the sex differences in the use of DNR orders after acute intracerebral hemorrhage (ICH) have not been described.

Methods—
We conducted a retrospective study of consecutive patients hospitalized for acute ICH at a tertiary stroke center between 2006 and 2010. Unadjusted and multivariable logistic regression analyses were performed to test for associations between female sex and early (<24 hours of presentation) DNR orders.

Results—

A total of 372 consecutive ICH patients without preexisting DNR orders were studied. Overall, 82 (22%) patients had early DNR orders after being hospitalized with ICH. In the fully adjusted model, early DNR orders were more likely in women (odds ratio, 3.18; 95% confidence interval, 1.51–6.70), higher age (odds ratio, 1.09 per year; 95% confidence interval, 1.05–1.12), larger ICH volume (odds ratio, 1.01 per cm
3
; 95% confidence interval, 1.01–1.02), and lower initial GCS score (odds ratio, 0.76 per point; 95% confidence interval, 0.69–0.84). Early DNR orders were less likely when the patients were transferred from another hospital (odds ratio, 0.28, 95% confidence interval, 0.11–0.76).

Conclusions—
Women are more likely to receive early DNR orders after ICH than men. Further prospective studies are needed to determine factors contributing to the sex variation in the use of early DNR order after ICH.
Thomas Taylor’s Dissent from Some 18th-Century Views on Platonic Philosophy: The Ethical and Theological Context
Authors: Catana Leo 
Published: August 2013

Abstract
Thomas Taylor’s interpretation of Plato’s works in 1804 was condemned as guilty by association immediately after its publication. Taylor’s 1804 and 1809 reviewer thus made a hasty generalisation in which the qualities of Neoplatonism, assumed to be negative, were transferred to Taylor’s own interpretation, which made use of Neoplatonist thinkers. For this reason, Taylor has typically been marginalised as an interpreter of Plato.
This article does not deny the association between Taylor and Neoplatonism. Instead, it examines the historical and historiographical reasons for the reviewer’s assumption that Neoplatonic readings of Plato are erroneous by definition. In particular, it argues that the reviewer relied on, and tacitly accepted, ethical and theological premises going back to the historiography of philosophy developed by Jacob Brucker in his Historia critica philosophiae (1742-44). These premises were an integral part of Brucker’s Lutheran religiosity and thus theologically and ethically biased. If these premises are identified, articulated and discussed critically—which they have not been so far in connection with Taylor’s reception—it becomes less obvious that the reviewer was justified in his assumption that the Neoplatonic reading was erroneous by definition. This, in turn, leaves Taylor’s Plato interpretation in a more respectable position.
Chremistica ribhoi sp. n. (Hemiptera: Cicadidae) from North-East India and its mass emergence
Authors: HAJONG SUDHANYA RAY , YAAKOP SALMAH 
Published: August 2013

The genus Chremistica Stål, 1870 is reported from the northeastern region of India for the first time. A new species, Chremistica ribhoi, is described from this region and male genitalia illustrations and scanning electron microscope photographs of the pygofer for C. ribhoi are presented. Observations on mass emergence of C. ribhoi are described.
Angular Momentum Transports and Synoptic Flow Patterns Associated with Tropical Cyclone Size Change
Authors: Chan Kelvin T. F. , Chan Johnny C. L. 
Published: August 2013

AbstractThis paper is the second part of a comprehensive study on tropical cyclone (TC) size. In Part I, the climatology of TC size and strength over the western North Pacific (WNP) and the North Atlantic was established based on the Quick Scatterometer (QuikSCAT) data. In this second part, the mechanisms that are likely responsible for TC size changes are explored through analyses of angular momentum (AM) transports and synoptic flow patterns associated with the TC. Changes in AM transport in the upper and lower troposphere appear to be important factors that affect TC intensity and size, respectively. The change in TC intensity is positively related to the change in the upper-tropospheric AM export, while the change in TC size is positively proportional to the change in the lower-tropospheric AM import. An examination of the synoptic flow patterns associated with WNP TCs suggests that changes in the synoptic flow near the TC are important in determining the change in TC size, with developments of the lower-tropospheric anticyclonic flows (one to the east and one to the west) bordering the TC being favorable for TC growth and a weakening of the subtropical high to the southeast for TC size reduction. A recurving TC tends to grow if the lower-tropospheric westerlies to its west increase. Moreover, a northward TC movement is related to the change in TC size. For example, a higher northward-moving speed is found for a larger TC, which also agrees well with the AM transport concept.