bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Dawn of a Revolution in Personalized Lung Cancer Prevention
Authors: Khuri Fadlo R. 
Published: July 2011

Abstract
Lung cancer prevention and early detection, which have fallen on hard times for more than the past 20 years, seem to have turned a corner toward better times ahead. Exciting new results of randomized controlled trials that targeted the arachidonic acid pathway, including a celecoxib trial reported by Mao and colleagues in this issue of the journal (beginning on page 984) and a trial of the prostacyclin analog iloprost, complement recently reported 20%–30% lung cancer mortality reductions, either with aspirin in targeting the arachidonic acid pathway or with computed tomography screening. The new results show encouraging activity personalized to former smokers and/or people expressing predictive biomarkers. These trials and technological advances in molecular profiling and imaging herald substantial clinical advances on the horizon of this field. Cancer Prev Res; 4(7); 949–53. ©2011 AACR.
Diagnostic Value of Vena Contracta Area in the Quantification of Mitral Regurgitation Severity by Color Doppler 3D Echocardiography
Authors: Zeng Xin , Levine Robert A. , Hua Lanqi , Morris Eleanor L. , Kang Yuejian , Flaherty Mary , Morgan Nina V. , Hung Judy 
Published: July 2011

Background—
Accurate quantification of mitral regurgitation (MR) is important for patient treatment and prognosis. Three-dimensional echocardiography allows for the direct measure of the regurgitant orifice area (ROA) by 3D-guided planimetry of the vena contracta area (VCA). We aimed to (1) establish 3D VCA ranges and cutoff values for MR grading, using the American Society of Echocardiography–recommended 2D integrative method as a reference, and (2) compare 2D and 3D methods of ROA to establish a common calibration for MR grading.

Methods and Results—

Eighty-three patients with at least mild MR underwent 2D and 3D echocardiography. Direct planimetry of VCA was performed by 3D echocardiography. Two-dimensional quantification of MR included 2D ROA by proximal isovelocity surface area (PISA) method, vena contracta width, and ratio of jet area to left atrial area. There were significant differences in 3D VCA among patients with different MR grades. As assessed by receiver operating characteristic analysis, 3D VCA at a best cutoff value of 0.41 cm
2
yielded 97% of sensitivity and 82% of specificity to differentiate moderate from severe MR. There was significant difference between 2D ROA and 3D VCA in patients with functional MR, resulting in an underestimation of ROA by 2D PISA method by 27% as compared with 3D VCA. Multivariable regression analysis showed functional MR as etiology was the only predictor of underestimation of ROA by the 2D PISA method.

Conclusions—
Three-dimensional VCA provides a single, directly visualized, and reliable measurement of ROA, which classifies MR severity comparable to current clinical practice using the American Society of Echocardiography–recommended 2D integrative method. The 3D VCA method improves accuracy of MR grading compared with the 2D PISA method by eliminating geometric and flow assumptions, allowing for uniform clinical grading cutoffs and ranges that apply regardless of etiology and orifice shape.
Echocardiographic Evaluation Before Bidirectional Glenn Operation in Functional Single-Ventricle Heart Disease
Authors: Stern Kenan W.D. , McElhinney Doff B. , Gauvreau Kimberlee , Geva Tal , Brown David W. 
Published: July 2011

Background—
Cardiac catheterization is routinely performed in patients with single ventricle before bidirectional Glenn operation (BDG). There is interest in noninvasive evaluation alone before BDG, but concern for echocardiography successfully imaging the relevant anatomy persists. We evaluated the accuracy of echocardiographic imaging of vascular anatomy.

Methods and Results—
Diagnostic images of 130 patients who had echocardiography and catheterization before BDG were reviewed; diameters of the pulmonary arteries (PAs) and aortic arch were measured, and stenoses were recorded. Patient and procedural factors associated with echocardiographic imaging were analyzed. Median age at echocardiography was 4 months; the most common diagnosis was hypoplastic left heart syndrome (55%). The left PA was imaged by echocardiography in 83 patients (64%), with 4 of 21 stenoses (19%) diagnosed by catheterization identified; similarly, the right PA was imaged in 81 (62%), and 3 of 17 stenoses (18%) were identified. The distal aortic arch was visualized in 104 (80%), with successful identification of 21 of 27 (78%) of coarctations diagnosed by catheterization. Complete vascular echocardiography (visualization of PAs and aortic arch) occurred in 43% and was not obtained more frequently with sedation.

Conclusions—
In a large cohort of patients presenting for BDG, evaluation by echocardiography frequently failed to image the PAs and missed the majority of PA stenoses. Sedation did not appear to improve the performance of echocardiography for evaluation of the PAs. Echocardiography cannot be relied on as the sole investigation before BDG.
Protein Kinase D2 Controls Cardiac Valve Formation in Zebrafish by Regulating Histone Deacetylase 5 Activity
Authors: Just Steffen , Berger Ina M. , Meder Benjamin , Backs Johannes , Keller Andreas , Marquart Sabine , Frese Karen , Patzel Eva , Rauch Gerd-Jörg ,   Tübingen 2000 Screen Consortium, Katus Hugo A. , Rottbauer Wolfgang 
Published: July 2011

Background—
The molecular mechanisms that guide heart valve formation are not well understood. However, elucidation of the genetic basis of congenital heart disease is one of the prerequisites for the development of tissue-engineered heart valves.

Methods and Results—

We isolated here a mutation in zebrafish,
bungee
(

bng
jh177

), which selectively perturbs valve formation in the embryonic heart by abrogating endocardial Notch signaling in cardiac cushions. We found by positional cloning that the
bng
phenotype is caused by a missense mutation (Y849N) in zebrafish
protein kinase D2
(
pkd2
). The
bng
mutation selectively impairs PKD2 kinase activity and hence Histone deacetylase 5 phosphorylation, nuclear export, and inactivation. As a result, the expression of Histone deacetylase 5 target genes Krüppel-like factor 2a and 4a, transcription factors known to be pivotal for heart valve formation and to act upstream of Notch signaling, is severely downregulated in
bungee
(
bng
) mutant embryos. Accordingly, the expression of Notch target genes, such as Hey1, Hey2, and HeyL, is severely decreased in
bng
mutant embryos. Remarkably, downregulation of Histone deacetylase 5 activity in homozygous
bng
mutant embryos can rescue the mutant phenotype and reconstitutes
notch1b
expression in atrioventricular endocardial cells.

Conclusions—
We demonstrate for the first time that proper heart valve formation critically depends on Protein kinase D2-Histone deacetylase 5-Krüppel-like factor signaling.
Development and Validation of a Risk Calculator for Prediction of Cardiac Risk After Surgery
Authors: Gupta Prateek K. , Gupta Himani , Sundaram Abhishek , Kaushik Manu , Fang Xiang , Miller Weldon J. , Esterbrooks Dennis J. , Hunter Claire B. , Pipinos Iraklis I. , Johanning Jason M. , Lynch Thomas G. , Forse R. Armour , Mohiuddin Syed M. , Mooss Aryan N. 
Published: July 2011

Background—
Perioperative myocardial infarction or cardiac arrest is associated with significant morbidity and mortality. The Revised Cardiac Risk Index is currently the most commonly used cardiac risk stratification tool; however, it has several limitations, one of which is its relatively low discriminative ability. The objective of the present study was to develop and validate a predictive cardiac risk calculator.

Methods and Results—
Patients who underwent surgery were identified from the American College of Surgeons' 2007 National Surgical Quality Improvement Program database, a multicenter (>250 hospitals) prospective database. Of the 211 410 patients, 1371 (0.65%) developed perioperative myocardial infarction or cardiac arrest. On multivariate logistic regression analysis, 5 predictors of perioperative myocardial infarction or cardiac arrest were identified: type of surgery, dependent functional status, abnormal creatinine, American Society of Anesthesiologists' class, and increasing age. The risk model based on the 2007 data set was subsequently validated on the 2008 data set (n=257 385). The model performance was very similar between the 2007 and 2008 data sets, with C statistics (also known as area under the receiver operating characteristic curve) of 0.884 and 0.874, respectively. Application of the Revised Cardiac Risk Index to the 2008 National Surgical Quality Improvement Program data set yielded a relatively lower C statistic (0.747). The risk model was used to develop an interactive risk calculator.

Conclusions—
The cardiac risk calculator provides a risk estimate of perioperative myocardial infarction or cardiac arrest and is anticipated to simplify the informed consent process. Its predictive performance surpasses that of the Revised Cardiac Risk Index.
Rapid, Direct Effects of Statin Treatment on Arterial Redox State and Nitric Oxide Bioavailability in Human Atherosclerosis via Tetrahydrobiopterin-Mediated Endothelial Nitric Oxide Synthase Coupling
Authors: Antoniades Charalambos , Bakogiannis Constantinos , Leeson Paul , Guzik Tomasz J. , Zhang Mei-Hua , Tousoulis Dimitris , Antonopoulos Alexios S. , Demosthenous Michael , Marinou Kyriakoula , Hale Ashley , Paschalis Andreas , Psarros Costas , Triantafyllou Costas , Bendall Jennifer , Casadei Barbara , Stefanadis Christodoulos , Channon Keith M. 
Published: July 2011

Background—
Treatment with statins improves clinical outcome, but the exact mechanisms of pleiotropic statin effects on vascular function in human atherosclerosis remain unclear. We examined the direct effects of atorvastatin on tetrahydrobiopterin-mediated endothelial nitric oxide (NO) synthase coupling in patients with coronary artery disease.

Methods and Results—

We first examined the association of statin treatment with vascular NO bioavailability and arterial superoxide (O
2
·−
) in 492 patients undergoing coronary artery bypass graft surgery. Then, 42 statin-naïve patients undergoing elective coronary artery bypass graft surgery were randomized to atorvastatin 40 mg/d or placebo for 3 days before surgery to examine the impact of atorvastatin on endothelial function and O
2
·−
generation in internal mammary arteries. Finally, segments of internal mammary arteries from 26 patients were used in ex vivo experiments to evaluate the statin-dependent mechanisms regulating the vascular redox state. Statin treatment was associated with improved vascular NO bioavailability and reduced O
2
·−
generation in internal mammary arteries. Oral atorvastatin increased vascular tetrahydrobiopterin bioavailability and reduced basal and
N
-nitro-
l
-arginine methyl ester–inhibitable O
2
·−
in internal mammary arteries independently of low-density lipoprotein lowering. In ex vivo experiments, atorvastatin rapidly improved vascular tetrahydrobiopterin bioavailability by upregulating GTP-cyclohydrolase I gene expression and activity, resulting in improved endothelial NO synthase coupling and reduced vascular O
2
·−
. These effects were reversed by mevalonate, indicating a direct effect of vascular hydroxymethylglutaryl-coenzyme A reductase inhibition.

Conclusions—

This study demonstrates for the first time in humans the direct effects of statin treatment on the vascular wall, supporting the notion that this effect is independent of low-density lipoprotein lowering. Atorvastatin directly improves vascular NO bioavailability and reduces vascular O
2
·−
through tetrahydrobiopterin-mediated endothelial NO synthase coupling. These findings provide new insights into the mechanisms mediating the beneficial vascular effects of statins in humans.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01013103.
Low-Density Lipoprotein Receptor–Related Protein 1 Prevents Early Atherosclerosis by Limiting Lesional Apoptosis and Inflammatory Ly-6C
high
Monocytosis
Authors: Yancey Patricia G. , Ding Yu , Fan Daping , Blakemore John L. , Zhang Youmin , Ding Lei , Zhang Jiabao , Linton MacRae F. , Fazio Sergio 
Published: July 2011

Background—
We previously demonstrated that macrophage low-density lipoprotein receptor (LDLR)–related protein 1 (LRP1) deficiency increases atherosclerosis despite antiatherogenic changes including decreased uptake of remnants and increased secretion of apolipoprotein E (apoE). Thus, our objective was to determine whether the atheroprotective effects of LRP1 require interaction with apoE, one of its ligands with multiple beneficial effects.

Methods and Results—

We examined atherosclerosis development in mice with specific deletion of macrophage LRP1 (apoE
−/−
MΦLRP1
−/−
) and in LDLR
−/−
mice reconstituted with apoE
−/−
MΦLRP1
−/−
bone marrow. The combined absence of apoE and LRP1 promoted atherogenesis more than did macrophage apoE deletion alone in both apoE-producing LDLR
−/−
mice (+88%) and apoE
−/−
mice (+163%). The lesions of both mouse models with apoE
−/−
LRP1
−/−
macrophages had increased macrophage content. In vitro, apoE and LRP1 additively inhibit macrophage apoptosis. Furthermore, there was excessive accumulation of apoptotic cells in lesions of both LDLR
−/−
mice (+110%) and apoE
−/−
MΦLRP1
−/−
mice (+252%). The apoptotic cell accumulation was partially due to decreased efferocytosis as the ratio of free to cell-associated apoptotic nuclei was 3.5-fold higher in lesions of apoE
−/−
MΦLRP1
−/−
versus apoE
−/−
mice. Lesion necrosis was also increased (6 fold) in apoE
−/−
MΦLRP1
−/−
versus apoE
−/−
mice. Compared with apoE
−/−
mice, the spleens of apoE
−/−
MΦLRP1
−/−
mice contained 1.6- and 2.4-fold more total and Ly6-C
high
monocytes. Finally, there were 3.6- and 2.4-fold increases in Ly6-C
high
and CC-chemokine receptor 2–positive cells in lesions of apoE
−/−
MΦLRP1
−/−
versus apoE
−/−
mice, suggesting that accumulation of apoptotic cells enhances lesion development and macrophage content by promoting the recruitment of inflammatory monocytes.

Conclusion—
Low-density lipoprotein receptor protein 1 exerts antiatherogenic effects via pathways independent of apoE involving macrophage apoptosis and monocyte recruitment.
Influence of Gravity Waves in the Tropical Upwelling: WACCM Simulations
Authors: Chun Hye-Yeong , Kim Young-Ha , Choi Hyun-Joo , Kim Jung-Yoon 
Published: July 2011

Abstract
The annual cycle of tropical upwelling and contributions by planetary and gravity waves are investigated from climatological simulations using the Whole Atmosphere Community Climate Model (WACCM) including three gravity wave drag (GWD) parameterizations (orographic, nonstationary background, and convective GWD parameterizations). The tropical upwelling is estimated by the residual mean vertical velocity at 100 hPa averaged over 15°S–15°N. This is well matched with an upwelling estimate from the balance of the zonal momentum and the mass continuity. A clear annual cycle of the tropical upwelling is found, with a Northern Hemispheric (NH) wintertime maximum and NH summertime minimum determined primarily by the Eliassen–Palm flux divergence (EPD), along with a secondary contribution from the zonal wind tendency. Gravity waves increase tropical upwelling throughout the year, and of the three sources the contribution by convective gravity wave drag (CGWD) is largest in most months. The relative contribution by all three GWDs to tropical upwelling is not larger than 5%. However, when tropical upwelling is estimated by net upward mass flux between turnaround latitudes where upwelling changes downwelling, annual mean contribution by all three GWDs is up to 19% at 70 hPa by orographic and convective gravity waves with comparable magnitudes. Effects of CGWD on upwelling are investigated by conducting an additional WACCM simulation without CGWD parameterization. It was found that including CGWD parameterization increases tropical upwelling not only directly by adding CGWD forcing, but also indirectly by modulating EPD and zonal wind tendency terms in the tropics.
Changes in the Annual Range of Precipitation under Global Warming
Authors: Chou Chia , Lan Chia-Wei 
Published: July 2011

Abstract
The annual range of precipitation, which is the difference between maximum and minimum precipitation within a year, is examined in climate model simulations under global warming. For global averages, the annual range of precipitation tends to increase as the globe warms. On a regional basis, this enhancement is found over most areas of the world, except for the bands along 30°S and 30°N. The enhancement in the annual range of precipitation is mainly associated with larger upward trends of maximum precipitation and smaller upward trends or downward trends of minimum precipitation. Based on the moisture budget analysis, the dominant mechanism is vertical moisture advection, both on a global average and on a regional scale. The vertical moisture advection, moisture convergence induced by vertical motion, includes the thermodynamic component, which is associated with increased water vapor, and the dynamic component, which is associated with changes in circulation. Generally, the thermodynamic component enhances the annual range of precipitation, while the dynamic component tends to reduce it. Evaporation has a positive contribution to both maximum and minimum precipitation, but very little to the annual range of precipitation. Even though evaporation and horizontal moisture advection are small for a global average, they could be important on a regional basis.
Dysarthria following stroke – the patient’s perspective on management and rehabilitation
Authors: Brady Marian C , Clark Alexander M , Dickson Sylvia , Paton Gillian , Barbour Rosaline S 
Published: July 2011

Objective: To explore the perceptions of people with stroke-related dysarthria in relation to the management and rehabilitation of dysarthria. Design: Qualitative semi-structured interviews. Setting: Community setting Subjects: Twenty-four people with an acquired dysarthria as a result of a stroke in the previous three years. All were living at home at the time of the interview. None exhibited a co-existing impairment (for example, aphasia, apraxia or cognitive impairment) that might have contributed to their communicative experiences. Results: Participants described the considerable efforts they made to maximize their communicative effectiveness prior to, and during, communicative interactions. Activities described included careful articulation and vocal projection as well as more inconspicuous strategies including pre-planning interactions, focused, effortful speech and word substitution. Communication was facilitated by a range of strategies including drafting, rehearsal, manoeuvring and ongoing monitoring and repair. Self-led speech rehabilitation activities were functionally based and often undertaken regularly. Some novel reading-aloud and speaking-aloud activities were described. Conclusion: The quantity and nature of inconspicuous, internalized, cognitive activities people with dysarthria engage in to maximize their communicative effectiveness should be considered in evaluating the impact of dysarthria following stroke. Focusing upon externally observable characteristics alone is insufficient. Challenging, functionally relevant, patient-focused activities, materials and targets are more likely to be perceived by the patient as relevant and worthwhile and are thus more likely to ensure adherence to recommended rehabilitation activities.
Antiphospholipid antibodies in patients with purported ‘chronic Lyme disease’
Authors: Greco TP , Conti-Kelly AM , Greco TP 
Published: July 2011

Background: Antiphospholipid antibody (aPL) positive patients and patients with purported chronic Lyme disease (‘CLD’) share many clinical features. After identifying significant aPL in sera of several index patients with ‘CLD’, we performed aPL tests on all patients referred inwhom ‘CLD’ was suspected, diagnosed or treated. Methods: All patients with suspected, diagnosed or treated ‘CLD’ and reportedly ‘positive’ Lyme assays were studied. aPL testing included anticardiolipin antibodies (aCL), anti-beta-2-glycoprotein-1 antibodies (anti-β2GP1) and lupus anticoagulant (LAC). Patients were classified into four newly described categories of CLD and data was analyzed. Results: One hundred and six patients were evaluated, of whom 82% had neurologic symptoms and 51% rheumatologic symptoms. Eighty-eight of 106 (83%) patients had positive Lyme serologies (enzyme-linked immunosorbent assay [ELISA] 62/106, 58.4%; western blot [WB] 64/106, 60%), while 18/106 (16.9%) were negative or equivocal. aPL was found in all ‘CLD’ categories. aCL and/or anti-β2GP1 were positive in 85/106 (80%), with aCL present in 69/106 (65%) and anti-β2GP1 present in 69/106 (65%). For all assays, IgM isotypes predominated: WB 55/64 (85%), aCL 63/69 (91%), anti-β2GP1 52/69 (75%), aCL and/or anti-β2GP1 74/85 (87%). Anti-β2GP1 assays occurred in higher titer than aCL: 36/69 (52%) versus 63/69 (91%), p<0.001. Seventeen patients had aPL-related events. Only 12/106 (11.3%) had true post-Lyme syndromes (PLS), category IV, or late Lyme disease (LLD). Most patients had been treated for Lyme: 82/106 (79%). Conclusion: aPL occurs frequently in patients with ‘CLD’. IgM anti-β2GP1, IgM aCL and IgM WB were frequently found. Documented PLS or LLD was uncommon. The role of aPL in patients with ‘CLD’ needs further investigation. Lupus (2011) 20, 1372–1377.
Pronounced focal and diffuse brain damage predicts short-term disease evolution in patients with clinically isolated syndrome suggestive of multiple sclerosis
Authors: Sbardella E , Tomassini V , Stromillo ML , Filippini N , Battaglini M , Ruggieri S , Ausili Cefaro L , Raz E , Gasperini C , Sormani MP , Pantano P , Pozzilli C , De Stefano N 
Published: July 2011

Background: In clinically isolated syndrome (CIS), the role of quantitative magnetic resonance imaging (MRI) in detecting prognostic markers is still debated. Objective: To evaluate measures of diffuse brain damage (such as brain atrophy and the ratio of N-acetylaspartate to creatine (NAA/Cr)) in patients with CIS, in addition to focal lesions, as predictors of 1-year disease evolution. Methods: 49 patients with CIS underwent MRI scans to quantify T2-lesions (T2-L) and gadolinium-enhanced lesion (GEL) number at baseline and after 1 year. Along with 25 healthy volunteers, they also underwent combined MRI/magnetic resonance spectroscopy examination to measure normalized brain volumes (NBVs) and NAA/Cr. Occurrence of relapses and new T2-L was recorded over 1 year to assess disease evolution. Results: Occurrence of relapses and/or new T2-L over 1 year divided patients with CIS into ‘active’ and ‘stable’ groups. Active patients had lower baseline NAA/Cr and NBV. Baseline T2-L number, GEL, NAA/Cr and NBV predicted subsequent disease activity. Multivariable logistic regression models showed that both ‘focal damage’ (based on T2-L number and GEL) and ‘diffuse damage’ (based on NBV and NAA/Cr) models predicted disease activity at 1 year with great sensitivity, specificity and accuracy. This was best when the four MRI measures were combined (80% sensitivity, 89% specificity, 83% accuracy). Conclusions: Quantitative MRI measures of diffuse tissue damage such as brain atrophy and NAA/Cr, in addition to measures of focal demyelinating lesions, may predict short-term disease evolution in patients with CIS, particularly when used in combination. If confirmed in larger studies, these findings may have important clinical and therapeutic implications.