bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cancer Stem Cells: Constantly Evolving and Functionally Heterogeneous Therapeutic Targets
Authors: Yang Tao , Rycaj Kiera , Liu Zhong-Min , Tang Dean G. 
Published: April 2014

Abstract
Elucidating the origin of and dynamic interrelationship between intratumoral cell subpopulations has clear clinical significance in helping to understand the cellular basis of treatment response, therapeutic resistance, and tumor relapse. Cancer stem cells (CSC), together with clonal evolution driven by genetic alterations, generate cancer cell heterogeneity commonly observed in clinical samples. The 2013 Shanghai International Symposium on Cancer Stem Cells brought together leaders in the field to highlight the most recent progress in phenotyping, characterizing, and targeting CSCs and in elucidating the relationship between the cell-of-origin of cancer and CSCs. Discussions from the symposium emphasize the urgent need in developing novel therapeutics to target the constantly evolving CSCs. Cancer Res; 74(11); 2922–7. ©2014 AACR.
Correlation of Somatic Mutations and Clinical Outcome in Melanoma Patients Treated with Carboplatin, Paclitaxel, and Sorafenib
Authors: Wilson Melissa A. , Zhao Fengmin , Letrero Richard , D'Andrea Kurt , Rimm David L. , Kirkwood John M. , Kluger Harriet M. , Lee Sandra J. , Schuchter Lynn M. , Flaherty Keith T. , Nathanson Katherine L. 
Published: April 2014

Abstract
Purpose: Sorafenib is an inhibitor of VEGF receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), and RAF kinases, amongst others. We assessed the association of somatic mutations with clinicopathologic features and clinical outcomes in patients with metastatic melanoma treated on E2603, comparing treatment with carboplatin, paclitaxel ± sorafenib (CP vs. CPS).
Experimental Design: Pretreatment tumor samples from 179 unique individuals enrolled on E2603 were analyzed. Genotyping was performed using a custom iPlex panel interrogating 74 mutations in 13 genes. Statistical analysis was performed using Fisher exact test, logistic regression, and Cox proportional hazards models. Progression-free survival (PFS) and overall survival were estimated using Kaplan–Meier methods.
Results: BRAF and NRAS mutations were found at frequencies consistent with other metastatic melanoma cohorts. BRAF-mutant melanoma was associated with worse performance status, increased number of disease sites, and younger age at diagnosis. NRAS-mutant melanoma was associated with better performance status, fewer sites of disease, and female gender. BRAF and NRAS mutations were not significantly predictive of response or survival when treated with CPS versus CP. However, patients with NRAS-mutant melanoma trended toward a worse response and PFS on CP than those with BRAF-mutant or WT/WT melanoma, an association that was reversed for this group on the CPS arm.
Conclusions: This study of somatic mutations in melanoma is the last prospectively collected phase III clinical trial population before the era of BRAF-targeted therapy. A trend toward improved clinical response in patients with NRAS-mutant melanoma treated with CPS was observed, possibly due to the effect of sorafenib on CRAF. Clin Cancer Res; 20(12); 3328–37. ©2014 AACR.
Prevention of Contrast-Induced Nephropathy With N-Acetylcysteine or Sodium Bicarbonate in Patients With ST-Segment–Myocardial Infarction
Authors: Thayssen Per , Lassen Jens Flensted , Jensen Svend Eggert , Hansen Knud Nørregaard , Hansen Henrik Steen , Christiansen Evald Høj , Junker Anders , Ravkilde Jan , Thuesen Leif , Veien Karsten Tange , Jensen Lisette Okkels 
Published: April 2014

Background—
Contrast-induced nephropathy (CIN) is a serious condition in patients with ST-segment–elevation myocardial infarction treated with primary percutaneous coronary intervention. We compared the risk of acute CIN and the influence of preventive strategies in patients with ST-segment–elevation myocardial infarction undergoing primary percutaneous coronary intervention.

Methods and Results—

A total of 720 patients were randomized in the Prevention of Contrast-induced Nephropathy in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention (CINSTEMI) trial. Patients were randomly assigned in a 1:1:1:1 ratio to receive hydration with sodium chloride together with 1 of 4 prophylactic regimes (1) N-acetylcysteine (NAC), (2) sodium bicarbonate (NaHCO
3
) infusion, (3) NAC in combination with NaHCO
3
, or (4) hydration with sodium chloride infusion alone. Patients in cardiogenic shock were excluded. Acute CIN was defined as an increase in serum creatinine concentration >25% from the baseline value within a 3-day period. Overall, CIN occurred in 141 (21.9%) patients. The prevention treatment with NAC, NaHCO
3
, or the combined NAC and NaHCO
3
did not reduce the rate of CIN significantly compared with hydration with intravenous sodium chloride infusion alone (20.1% versus 20.1% versus 20.8% versus 26.5%;
P
=NS). However, an increase in serum creatinine >25% from the baseline value to 30 day was significantly lower in patients treated with combined NAC and NaHCO
3
(18.7% versus 19.1% versus 9.2% versus 21.3%;
P
=0.033).

Conclusions—

Treatment with NAC or NaHCO
3
did not reduce the rate of acute CIN significantly. Combined treatment with NAC and NaHCO
3
may reduce the risk of renal dysfunction after 30 days.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01160627.
Strategies Used by Hospitals to Improve Speed of Tissue-Type Plasminogen Activator Treatment in Acute Ischemic Stroke
Authors: Xian Ying , Smith Eric E. , Zhao Xin , Peterson Eric D. , Olson DaiWai M. , Hernandez Adrian F. , Bhatt Deepak L. , Saver Jeffrey L. , Schwamm Lee H. , Fonarow Gregg C. 
Published: April 2014

Background and Purpose—
The benefits of intravenous tissue-type plasminogen activator in acute ischemic stroke are time dependent, and several strategies have been reported to be associated with more rapid door-to-needle (DTN) times. However, the extent to which hospitals are using these strategies and their association with DTN times have not been well studied.

Methods—
We surveyed 304 Get With The Guidelines-Stroke hospitals joining Target: Stroke regarding their baseline use of strategies to reduce DTN times in the January 2008 to December 2009 time frame before the initiation of Target: Stroke and determined the association between hospital strategies and DTN times.

Results—
Among 5460 patients receiving tissue-type plasminogen activator within 3 hours of symptom onset in surveyed hospitals, the median DTN time was 72 minutes (interquartile range, 55–94). Reported use of the different strategies varied considerably. Of 11 hospital strategies analyzed individually by multivariable analysis, 3 strategies were independently associated with shorter DTN times. These included rapid triage/stroke team notification (209/304 [69%] hospitals, 8.1-minute reduction in DTN time), single-call activation system (190/304 [63%] hospitals, 4.3 minutes), and tissue-type plasminogen activator stored in the emergency department (189/304 [62%] hospitals, 3.5 minutes). When analyzed incrementally, hospitals that used a greater number of strategies had shorter DTN times with 1.3 minutes (adjusted mean difference) saved for each strategy implemented (14 minutes if all strategies were used).

Conclusions—
Although the majority of participating hospitals reported using some strategy to reduce delays in tissue-type plasminogen activator administration for acute ischemic stroke, the strategies applied vary considerably and those most strongly associated with shorter DTN times were applied relatively less frequently.
Risk Factors, Stroke Prevention Treatments, and Prevalence of Cerebral Microbleeds in the Framingham Heart Study
Authors: Romero José Rafael , Preis Sarah R. , Beiser Alexa , DeCarli Charles , Viswanathan Anand , Martinez-Ramirez Sergi , Kase Carlos S. , Wolf Philip A. , Seshadri Sudha 
Published: April 2014

Background and Purpose—
Cerebral microbleeds (CMBs) are associated with increased risk of stroke and poor cognition. Vascular risk factors and medications used for stroke prevention may increase the risk of CMB. We examined the prevalence of CMB and the association of these risk factors with CMB, postulating that risk factors for cerebral amyloid angiopathy would be associated with lobar CMB and markers of hypertensive vasculopathy with deep CMB.

Methods
—

We include 1965 Framingham Original and Offspring participants (age, 66.5±11.0 years; 54% women) and evaluated the age- and sex-specific prevalence of CMB. We related various vascular and genetic (apolipoprotein E [
APOE
]) risk factors and medication use to the presence of CMB overall and stratified by brain location (deep, lobar, or mixed).

Results
—

CMBs were observed in 8.8% of participants, being mostly lobar (63%). CMB prevalence increased with age (
P
<0.0001) and was higher in men (
P
<0.001). Hypertension increased risk of any CMB, and in deep and mixed locations (
P
<0.05), and low total cholesterol and
APOE
ε4 increased risk of lobar CMB (
P
<0.05). Statin use increased risk of lobar and mixed location CMB (
P
<0.05). The latter association was not affected by adjustment for cholesterol levels or concomitant medication use.

Conclusions
—

We observed the expected association of hypertension with deep CMB and low cholesterol and
APOE
ε4 with lobar CMB. In addition, statin use was independently associated with CMB risk. This potential adverse effect of statin use needs to be examined in other cohorts.
Myeloperoxidase in Human Intracranial Aneurysms
Authors: Gounis Matthew J. , Vedantham Srinivasan , Weaver John P. , Puri Ajit S. , Brooks Christopher S. , Wakhloo Ajay K. , Bogdanov Alexei A. 
Published: April 2014

Background and Purpose—
Noninvasive imaging identifying a predictive biomarker of the bleeding risk of unruptured intracranial aneurysms (UIAs) is needed. We investigated a potential biomarker of UIA instability, myeloperoxidase, in human aneurysm tissue.

Methods
—

Human brain aneurysms were harvested after clipping and were histologically and biochemically evaluated for the presence of myeloperoxidase. Of the tissue collected, 3 were from ruptured aneurysms and 20 were from UIAs. For each UIA, its 5-year aneurysm rupture risk was determined using the Population, Hypertension, Age, Size of Aneurysm, Earlier Subarachnoid Hemorrhage From Another Aneurysm and Site of Aneurysm (PHASES) model.

Results
—

All ruptured aneurysms were myeloperoxidase positive. Of the UIAs, half were myeloperoxidase positive. The median 5-year aneurysm rupture risk was higher for myeloperoxidase-positive UIA (2.28%) than myeloperoxidase-negative UIA (0.69%), and the distributions were statistically different (
P
<0.005, Wilcoxon–Mann–Whitney test). The likelihood for myeloperoxidase-positive UIA was significantly associated (
P
=0.031) with aneurysm rupture risk (odds ratio, 4.79; 95% confidence limits, 1.15–19.96).

Conclusions
—

Myeloperoxidase is associated with PHASES estimated risk of aneurysm rupture and may potentially be used as an imaging biomarker of aneurysm instability.
Seasonal Forecasting of North China Summer Rainfall Using a Statistical Downscaling Model
Authors: Guo Yan , Li Jianping , Li Yun 
Published: April 2014

AbstractA statistical downscaling model was developed with reanalysis data and applied to forecast northern China summer rainfall (NCSR) using the outputs of the real-time seasonal Climate Forecast System, version 2 (CFSv2). Large-scale climate signals in sea level pressure, 850-hPa meridional wind, and 500-hPa geopotential height as well as several well-known climate indices were considered as potential predictors. Through correlation analysis and stepwise screening, two “optimal” predictors (i.e., sea level pressure over the southwestern Indian Ocean and 850-hPa meridional wind over eastern China) were selected to fit the regression equation. Model reliability was validated with independent data during a test period (1991–2012), in which the simulated NCSR well represented the observed variability with a correlation coefficient of 0.59 and a root-mean-square error of 18.6%. The statistical downscaling model was applied to forecast NCSR for a 22-yr period (1991–2012) using forecast predictors from the CFSv2 with lead times from 1 to 6 months. The results showed much better forecast skills than that directly from the CFSv2 for all lead months, except the 3-month-lead example. The biggest improvement occurred in the 1-month-lead forecast, in which the hit rate increased to 77.3% from 45.5% in the CFSv2 forecast. In the forecast of rainfall at 15 stations, the statistical downscaling model also showed superior capability when compared with the CFSv2, with forecast skill being improved at 73% of stations. In particular, 13 of 15 stations obtained a hit rate exceeding 55%.
Occurrence of Winter Stratospheric Sudden Warming Events and the Seasonal Timing of Spring Stratospheric Final Warming
Authors: Hu Jinggao , Ren Rongcai , Xu Haiming 
Published: April 2014

Abstract
Based on the NCEP–NCAR reanalysis dataset covering 1958–2012, this paper demonstrates a statistically significant relationship between the occurrence of major stratospheric sudden warming events (SSWs) in midwinter and the seasonal timing of stratospheric final warming events (SFWs) in spring. Specifically, early spring SFWs that on average occur in early March tend to be preceded by non-SSW winters, while late spring SFWs that on average take place up until early May are mostly preceded by SSW events in midwinter. Though the occurrence (absence) of SSW events in midwinter may not always be followed by late (early) SFWs in spring, there is a much higher (lower) probability of late SFWs than early SFWs in spring after SSW (non-SSW) winters, particularly when the winter SSWs occur no earlier than early January or in the period from late January to early February. Diagnosis shows that, corresponding to an SSW (non-SSW) winter and the following late (early)-SFW spring, intensity of planetary wave activity in the stratosphere tends to evolve out of phase from midwinter to the following spring, being anomalously stronger (weaker) in winter and anomalously weaker (stronger) in spring. Furthermore, the strengthening of the western Eurasian high, which appears during early to mid-January in late-SFW years but does not appear until late February to mid-March in early-SFW years, always precedes the strengthening of planetary wave activity in the stratosphere and thus acts as a tropospheric precursor to the seasonal timing of SFWs.
Hydroclimatic Controls on the Means and Variability of Vegetation Phenology and Carbon Uptake
Authors: Koster R. D. , Walker G. K. , Collatz G. J. , Thornton P. E. 
Published: April 2014

Abstract
Long-term, global offline (land only) simulations with a dynamic vegetation phenology model are used to examine the control of hydroclimate over vegetation-related quantities. First, with a control simulation, the model is shown to capture successfully (though with some bias) key observed relationships between hydroclimate and the spatial and temporal variations of phenological expression. In subsequent simulations, the model shows that (i) the global spatial variation of seasonal phenological maxima is controlled mostly by hydroclimate, irrespective of distributions in vegetation type; (ii) the occurrence of high interannual moisture-related phenological variability in grassland areas is determined by hydroclimate rather than by the specific properties of grassland; and (iii) hydroclimatic means and variability have a corresponding impact on the spatial and temporal distributions of gross primary productivity (GPP).
Compensation between Resolved Wave Driving and Parameterized Orographic Gravity Wave Driving of the Brewer–Dobson Circulation and Its Response to Climate Change
Authors: Sigmond Michael , Shepherd Theodore G. 
Published: April 2014

Abstract
Following recent findings, the interaction between resolved (Rossby) wave drag and parameterized orographic gravity wave drag (OGWD) is investigated, in terms of their driving of the Brewer–Dobson circulation (BDC), in a comprehensive climate model. To this end, the parameter that effectively determines the strength of OGWD in present-day and doubled CO2 simulations is varied. The authors focus on the Northern Hemisphere during winter when the largest response of the BDC to climate change is predicted to occur. It is found that increases in OGWD are to a remarkable degree compensated by a reduction in midlatitude resolved wave drag, thereby reducing the impact of changes in OGWD on the BDC. This compensation is also found for the response to climate change: changes in the OGWD contribution to the BDC response to climate change are compensated by opposite changes in the resolved wave drag contribution to the BDC response to climate change, thereby reducing the impact of changes in OGWD on the BDC response to climate change. By contrast, compensation does not occur at northern high latitudes, where resolved wave driving and the associated downwelling increase with increasing OGWD, both for the present-day climate and the response to climate change. These findings raise confidence in the credibility of climate model projections of the strengthened BDC.
Accuracy Progressive Calculation of Lagrangian Trajectories from a Gridded Velocity Field
Authors: Chu Peter C. , Fan Chenwu 
Published: April 2014

Abstract
Reduction of computational error is a key issue in computing Lagrangian trajectories using gridded velocities. Computational accuracy enhances from using the first term (constant velocity scheme), the first two terms (linear uncoupled scheme), the first three terms (linear coupled scheme), to using all four terms (nonlinear coupled scheme) of the two-dimensional interpolation. A unified “analytical form” is presented in this study for different truncations. Ordinary differential equations for predicting Lagrangian trajectory are linear using the constant velocity/linear uncoupled schemes (both commonly used in atmospheric and ocean modeling), the linear coupled scheme, and the nonlinear using the nonlinear coupled scheme (both proposed in this paper). The location of the Lagrangian drifter inside the grid cell is determined by two algebraic equations that are solved explicitly with the constant velocity/linear uncoupled schemes, and implicitly using the Newton–Raphson iteration method with the linear/nonlinear coupled schemes. The analytical Stommel ocean model on the f plane is used to illustrate great accuracy improvement from keeping the first term to keeping all the terms of the two-dimensional interpolation.
Lean Six Sigma Applied to Ultrasound Guided Needle Biopsy in the Head and Neck
Authors: Matt Bruce H. , Woodward‐Hagg Heather K. , Wade Christopher L. , Butler Penny D. , Kokoska Mimi S. 
Published: April 2014

Objectives(1) Confirm the positive value stream of office‐based ultrasound using Lean Six Sigma; (2) demonstrate how ultrasound reduces time to diagnosis, costs, patient inconvenience and travel, exposure to ionizing radiation, intravenous contrast, and laboratory tests.Study DesignCase series with historical controls using chart review.SettingTertiary Veterans Administration Hospital (university‐affiliated).Subjects and MethodsPatients with a consult request or decision for ultrasound guided fine needle aspiration (USFNA) from 2006 to 2012. Process evaluation using Lean Six Sigma methodologies; years study conducted: 2006‐2012; outcome measurements: type of diagnostic tests and imaging studies including CT scans with associated radiation exposure, time to preliminary and final cytopathologic diagnosis, episodes of patient travel.ResultsValue stream mapping prior to and after implementing office‐based ultrasound confirmed the time from consult request or decision for USFNA to completion of the USFNA was reduced from a range of 0 to 286 days requiring a maximum 17 steps to a range of 0 to 48 days, necessitating only a maximum of 9 steps. Office‐based USFNA for evaluation of head and neck lesions reduced costs, time to diagnosis, risks and inconvenience to patients, radiation exposure, unnecessary laboratory, and patient complaints while increasing staff satisfaction. In addition, office‐based ultrasound also changed the clinical management of specific patients.ConclusionLean Six Sigma reduces waste and optimizes quality and accuracy in manufacturing. This is the first known application of Lean Six Sigma to office‐based USFNA in the evaluation of head and neck lesions. The literature supports the value of office‐based ultrasound to patients and health care systems.
Sophono in Pediatric Patients: The Experience of an Italian Tertiary Care Center
Authors: Marsella Pasquale , Scorpecci Alessandro , Vallarino Maria Vittoria , Di Fiore Simona , Pacifico Concettina 
Published: April 2014

ObjectiveSince 2011, a transcutaneous bone‐anchored auditory implant (Sophono) has been available for patients affected by bilateral, conductive hearing loss that cannot be corrected by surgery. To date, very few cases of device application in the pediatric population have been described. The aim of the present study is to report on complications, functional outcome, and health‐related quality of life of the first pediatric cases in Italy.Study DesignCase series with planned data collection.SettingTertiary care pediatric center.Subjects and MethodsOf 25 candidates with bilateral, conductive hearing loss screened between January 2012 and July 2013, 6 were included in the study (3 male and 3 female; median age, 9 years; age range, 5‐17 years). Data concerning surgery, complications, functional outcome, and health‐related quality of life were gathered prospectively.ResultsNo major intraoperative complications occurred. Postoperative complications included 1 patient developing a skin ulceration below the external magnet and 1 patient reporting pain from using the device for more than 4 hours a day consecutively. Median free‐field pure tone average (0.5‐3 kHz) with the device was 32.5 dB HL, and median functional gain was 33 dB HL. Median Glasgow Children's Benefit Inventory score was +42.ConclusionSophono implants can be a valuable alternative to percutaneous implants in patients with bilateral, conductive hearing loss. To ensure the success of the treatment, several precautions should be taken, including a careful preoperative assessment of skull bone thickness and a close postoperative follow‐up of the skin under the external processor, especially over the first months.