bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular Pathways: Induction of Polyploidy as a Novel Differentiation Therapy for Leukemia
Authors: Krause Diane S. , Crispino John D. 
Published: August 2013

Abstract
Differentiation therapy has emerged as a powerful way to target specific hematologic malignancies. One of the best examples is the use of all-trans retinoic acid (ATRA) in acute promyelocytic leukemia (APL), which has significantly improved the outcome for patients with this specific form of acute myeloid leukemia (AML). In considering how differentiation therapy could be used in other forms of AML, we predicted that compounds that induce terminal differentiation of megakaryocytes would be effective therapies for the megakaryocytic form of AML, named acute megakaryocytic leukemia (AMKL). We also speculated that such agents would reduce the burden of abnormal hematopoietic cells in primary myelofibrosis and alter the differentiation of megakaryocytes in myelodysplastic syndromes. Using a high-throughput chemical screening approach, we identified small molecules that promoted many features of terminal megakaryocyte differentiation, including the induction of polyploidization, the process by which cells accumulate DNA to 32N or greater. As the induction of polyploidization is an irreversible process, cells that enter this form of the cell cycle do not divide again. Thus, this would be an effective way to reduce the tumor burden. Clinical studies with polyploidy inducers, such as aurora kinase A inhibitors, are under way for a wide variety of malignancies, whereas trials specifically for AMKL and PMF are in development. This novel form of differentiation therapy may be clinically available in the not-too-distant future. Clin Cancer Res; 19(22); 6084–8. ©2013 AACR.
Combining Erlotinib and Cetuximab Is Associated with Activity in Patients with Non–Small Cell Lung Cancer (Including Squamous Cell Carcinomas) and Wild-TypeEGFRor Resistant Mutations
Authors: Wheler Jennifer J. , Tsimberidou Apostolia M. , Falchook Gerald S. , Zinner Ralph G. , Hong David S. , Fok Jansina Y. , Fu Siqing , Piha-Paul Sarina A. , Naing Aung , Kurzrock Razelle 
Published: August 2013

AbstractPreclinical data suggest that combined EGF receptor (EGFR) targeting with an EGFR tyrosine kinase inhibitor and an anti-EGFR monoclonal antibody may be superior over single-agent targeting. Therefore, as part of a phase I study, we analyzed the outcome of 20 patients with non–small cell lung cancer treated with the combination of erlotinib and cetuximab. EGFR mutation status was ascertained in a Clinical Laboratory Improvement Amendment–approved laboratory. There were 10 men; median number of prior therapies was five. Overall, two of 20 patients (10%) achieved partial response (PR), one of whom had a TKI-resistant EGFR insertion in exon 20, time to treatment failure (TTF) = 24+ months, and the other patient had squamous cell histology (EGFR wild-type), TTF = 7.4 months. In addition, three of 20 patients (15%) achieved stable disease (SD) ≥6 six months (one of whom had wild-type EGFR and squamous cell histology, and two patients had an EGFR TKI-sensitive mutation, one of whom had failed prior erlotinib therapy). Combination therapy with ertotinib plus cetuximab was well tolerated. The most common toxicities were rash, diarrhea, and hypomagnesemia. The recommended phase II dose was erlotinib 150 mg oral daily and cetuximab 250 mg/m2 i.v. weekly. In summary, erlotinib and cetuximab treatment was associated with SD ≥ six months/PR in five of 20 patients with non–small cell lung cancer (25%), including individuals with squamous histology, TKI-resistant EGFR mutations, and wild-type EGFR, and those who had progressed on prior erlotinib after an initial response. This combination warrants further study in select populations of non–small cell lung cancer. Mol Cancer Ther; 12(10); 2167–75. ©2013 AACR.
Reduced Aflatoxin Exposure Presages Decline in Liver Cancer Mortality in an Endemic Region of China
Authors: Chen Jian-Guo , Egner Patricia A. , Ng Derek , Jacobson Lisa P. , Muñoz Alvaro , Zhu Yuan-Rong , Qian Geng-Sun , Wu Felicia , Yuan Jian-Min , Groopman John D. , Kensler Thomas W. 
Published: August 2013

Abstract
Primary liver cancer (PLC) is the third leading cause of cancer mortality globally. In endemic areas of sub-Saharan Africa and Asia, PLC largely arises from chronic infection with hepatitis B virus (HBV) and ingestion of aflatoxins. Although synergistic interactions between these two risk factors have been observed in cohort studies in China, here we determined the impact of agricultural reforms in the 1980s leading to diminished maize consumption and implementation of subsidized universal vaccination against HBV in the 2000s on PLC primary prevention. A population-based cancer registry was used to track PLC mortality in Qidong, China and was compared with the timeline of HBV immunization. Randomly selected serum samples from archived cohort collections from the 1980s to present were analyzed for aflatoxin biomarkers. More than 50% reductions in PLC mortality rates occurred across birth cohorts from the 1960s to the 1980s for Qidongese less than 35 years of age although all were born before universal vaccination of newborns. Median levels of the aflatoxin biomarker decreased from 19.3 pg/mg albumin in 1989 to undetectable (&lt;0.5 pg/mg) by 2009. A population attributable benefit of 65% for reduced PLC mortality was estimated from a government-facilitated switch of dietary staple from maize to rice; 83% of this benefit was in those infected with HBV. Food policy reforms in China resulted in a dramatic decrease in aflatoxin exposure, which, independent of HBV vaccination, reduced liver cancer risk. The extensive HBV vaccine coverage now in place augurs even greater risk reductions in the future. Cancer Prev Res; 6(10); 1038–45. ©2013 AACR.
Myocardial Tissue Remodeling in Adolescent Obesity
Authors: Shah Ravi V. , Abbasi Siddique A. , Neilan Tomas G. , Hulten Edward , Coelho‐Filho Otavio , Hoppin Alison , Levitsky Lynne , de Ferranti Sarah , Rhodes Erinn T. , Traum Avram , Goodman Elizabeth , Feng Henry , Heydari Bobak , Harris William S. , Hoefner Daniel M. , McConnell Joseph P. , Seethamraju Ravi , Rickers Carsten , Kwong Raymond Y. , Jerosch‐Herold Michael 
Published: August 2013

Background
Childhood obesity is a significant risk factor for cardiovascular disease in adulthood. Although ventricular remodeling has been reported in obese youth, early tissue‐level markers within the myocardium that precede organ‐level alterations have not been described.

Methods and Results

We studied 21 obese adolescents (mean age, 17.7±2.6 years; mean body mass index [
BMI
], 41.9±9.5 kg/m
2
, including 11 patients with type 2 diabetes [T2D]) and 12 healthy volunteers (age, 15.1±4.5 years;
BMI
, 20.1±3.5 kg/m
2
) using biomarkers of cardiometabolic risk and cardiac magnetic resonance imaging (
CMR
) to phenotype cardiac structure, function, and interstitial matrix remodeling by standard techniques. Although left ventricular ejection fraction and left atrial volumes were similar in healthy volunteers and obese patients (and within normal body size‐adjusted limits), interstitial matrix expansion by
CMR
extracellular volume fraction (
ECV
) was significantly different between healthy volunteers (median, 0.264; interquartile range [IQR], 0.253 to 0.271), obese adolescents without T2D (median, 0.328; IQR, 0.278 to 0.345), and obese adolescents with T2D (median, 0.376; IQR, 0.336 to 0.407;
P
=0.0001).
ECV
was associated with
BMI
for the entire population (
r
=0.58,
P
<0.001) and with high‐sensitivity C‐reactive protein (
r
=0.47,
P
<0.05), serum triglycerides (
r
=0.51,
P
<0.05), and hemoglobin A1c (
r
=0.76,
P
<0.0001) in the obese stratum.

Conclusions
Obese adolescents (particularly those with T2D) have subclinical alterations in myocardial tissue architecture associated with inflammation and insulin resistance. These alterations precede significant left ventricular hypertrophy or decreased cardiac function.
Mortality After Ischemic Stroke in Patients With Acute Myocardial Infarction
Authors: Brammås Anna , Jakobsson Stina , Ulvenstam Anders , Mooe Thomas 
Published: August 2013

Background and Purpose—
Acute myocardial infarction (AMI) increases the risk of ischemic stroke, and mortality among these patients is high. Here, we aimed to estimate the 1-year mortality reliably after AMI complicated by ischemic stroke. We also aimed to identify trends over time for mortality during 1998–2008, as well as factors that predicted increased or decreased mortality.

Methods—
Data for 173 233 unselected patients with AMI were collected from the Swedish Register of Information and Knowledge about Swedish Heart Intensive Care Admissions registry for 1998–2008. Specifically, we analyzed 1-year follow-up and mortality data for patients with AMI with and without ischemic stroke. Kaplan–Meyer analysis was used to analyze mortality trends over time, and Cox regression analysis was used to identify uni- and multivariate predictors of mortality.

Results—
The 1-year mortality was 36.5% for AMI complicated by ischemic stroke and 18.3% for AMI without stroke. Mortality decreased over time in patients with and without ischemic stroke. The absolute decreases in mortality were 9.4% and 7.5%, respectively. Reperfusion and secondary preventive therapies were associated with a decreased mortality rate.

Conclusions—
Mortality after AMI complicated by an ischemic stroke is very high but decreased from 1998 to 2008. The increased use of evidence-based therapies explains the improved prognosis.
Higher Risk of Recurrent Ischemic Events in Patients With Intracranial In-Stent Restenosis
Authors: Jin Min , Fu Xian , Wei Yuzhen , Du Bin , Xu Xiao-Tong , Jiang Wei-Jian 
Published: August 2013

Background and Purpose—
Reliable data concerning prognosis of patients with intracranial in-stent restenosis (ISR) is lacking. We prospectively studied long-term outcomes of patients with and without a catheter angiography-verified ISR.

Methods—
Between September 2001 and May 2009, 540 consecutive patients with symptomatic intracranial atherosclerosis received stenting treatment at our institute. Of them, 226 patients with 233 stented arteries had catheter angiography follow-up after stenting and were enrolled into this study. They were clinically followed up until the end of December 2011. Primary end point was ischemic stroke or transient ischemic attack in the territory of the stented artery after the catheter angiography follow-up. ISR was defined as a catheter angiography-verified stenosis of ≥50% within or immediately adjacent (within range of 3 mm) to the implanted stent.

Results—

During a mean follow-up of 38.9 months, 27 (11.6%, 27/233) primary end point events were recorded. The risk of primary end point in ISR group was higher compared with non-ISR group (21.1% [12/57] versus 8.5% [15/176]; hazard ratio, 2.94; 95% confidence interval, 1.37–6.30;
P
=0.005). Multivariable analysis showed that the ISR was an independent risk factor for the primary end point (hazard ratio, 2.79; 95% confidence interval, 1.20–6.49;
P
=0.017). The median occurrence time of primary end point was 9.9 (interquartile range, 5.0, 21.1) months in ISR group, earlier than that in non-ISR group (26.6 [13.1, 52.9] months;
P
=0.01).

Conclusions—
In-stent restenosis after stenting of intracranial atherosclerosis is significantly associated with an increased risk and an earlier occurrence of recurrent ischemic events in the territory of the stented intracranial artery.
New Model for Predicting Surgical Feeding Tube Placement in Patients With an Acute Stroke Event
Authors: Dubin Perry H. , Boehme Amelia K. , Siegler James E. , Shaban Amir , Juengling Jenifer , Albright Karen C. , Martin-Schild Sheryl 
Published: August 2013

Background and Purpose—
The need for surgical feeding tube placement after acute stroke can be uncertain and associated with further morbidity.

Methods—
Retrospective data were recorded and compared across patients with acute ischemic stroke and intracerebral hemorrhage. We identified all feeding tubes placed as percutaneous endoscopic gastrostomy (PEG) tubes. A prediction score for PEG tube placement was developed separately for patients with acute ischemic stroke and intracerebral hemorrhage using logistic regression models of variables known by 24 hours from admission.

Results—
Of 407 patients included, 51 (12.5%) underwent PEG tube placement (25 acute ischemic stroke and 26 intracerebral hemorrhage). The odds of a patient with acute ischemic stroke with PEG score ≥3 of getting a PEG are greater than those with PEG score <3 (odds ratio, 15.68; 95% confidence interval, 4.55–54.01). The odds of a patient with intracerebral hemorrhage with PEG score ≥3 of getting a PEG are greater than those with PEG score <3 (odds ratio, 12.49; 95% confidence interval, 1.54–101.29).

Conclusions—
The PEG score, comprised by variables known within the first day of admission, may be a powerful predictor of PEG placement in patients with acute stroke.
Intensity of Anticoagulation and Clinical Outcomes in Acute Cardioembolic Stroke
Authors: Nakamura Asako , Ago Tetsuro , Kamouchi Masahiro , Hata Jun , Matsuo Ryu , Kuroda Junya , Kuwashiro Takahiro , Sugimori Hiroshi , Kitazono Takanari 
Published: August 2013

Background and Purpose—
The relationship between the intensity of anticoagulation at the onset of acute cardioembolic stroke and clinical outcome after stroke is unclear. Here, we elucidated the relationship between prothrombin time–international normalized ratio (PT-INR) values on admission and clinical outcomes in patients with acute cardioembolic stroke.

Methods—
A total of 602 patients from the Fukuoka Stroke Registry in Japan who had been treated with warfarin but developed cardioembolic stroke were enrolled. The patients were classified into 3 groups according to their PT-INR values on admission: PT-INR <1.50, 411 patients; PT-INR 1.50 to 1.99, 146 patients; and PT-INR ≥2.00, 45 patients. The associations between PT-INR categories and severe neurological deficits (National Institutes of Health Stroke Scale ≥10) on admission and poor functional outcome (modified Rankin scale 4–6) at discharge were investigated using a logistic regression analysis.

Results—
Neurological deficits on admission were less severe, and functional outcome at discharge was more favorable as the PT-INR level on admission increased. The multivariate analysis revealed that severe neurological deficits were inversely associated with PT-INR on admission (PT-INR 1.50–1.99: odds ratio, 0.66; 95% confidence interval, 0.43–1.00; PT-INR ≥2.00: odds ratio, 0.41; 95% confidence interval, 0.20–0.83; compared with a reference group of PT-INR <1.50). Poor functional outcome was less likely in patients with PT-INR ≥2.00 (odds ratio, 0.20; 95% confidence interval, 0.06–0.55) after adjustment for confounders.

Conclusions—
Prestroke PT-INR ≥2.0 is associated with favorable clinical outcomes after acute cardioembolic stroke.
Urban Emissions of CO2 from Davos, Switzerland: The First Real-Time Monitoring System Using an Atmospheric Inversion Technique
Authors: Lauvaux Thomas , Miles Natasha L. , Richardson Scott J. , Deng Aijun , Stauffer David R. , Davis Kenneth J. , Jacobson Gloria , Rella Chris , Calonder Gian-Paul , DeCola Philip L. 
Published: August 2013

AbstractAnthropogenic emissions from urban areas represent 70% of the fossil fuel carbon emitted globally according to carbon emission inventories. The authors present here the first operational system able to monitor in near–real time daily emission estimates, using a mesoscale atmospheric inversion framework over the city of Davos, Switzerland, before, during, and after the World Economic Forum 2012 Meeting (WEF-2012). Two instruments that continuously measured atmospheric mixing ratios of greenhouse gases (GHGs) were deployed at two locations from 23 December 2011 to 3 March 2012: one site was located in the urban area and the other was out of the valley in the surrounding mountains. Carbon dioxide, methane, and carbon monoxide were measured continuously at both sites. The Weather Research and Forecasting mesoscale atmospheric model (WRF), in four-dimensional data assimilation mode, was used to simulate the transport of GHGs over the valley of Davos at 1.3-km resolution. Wintertime emissions prior to the WEF-2012 were about 40% higher than the initial annual inventory estimate, corresponding to the use of heating fuel in the winter. Daily inverse fluxes were highly correlated with the local climate, especially during the severe cold wave that affected most of Europe in early February 2012. During the WEF-2012, emissions dropped by 35% relative to the first month of the deployment, despite similar temperatures and the presence of several thousand participants at the meeting. On the basis of composite diurnal cycles of hourly CO/CO2 ratios, the absence of traffic peaks during the WEF-2012 meeting indicated that change in road emissions is potentially responsible for the observed decrease in the city emissions during the meeting.
Changes in Seasonal Predictability due to Global Warming
Authors: DelSole Timothy , Yan Xiaoqin , Dirmeyer Paul A. , Fennessy Mike , Altshuler Eric 
Published: August 2013

Abstract
The change in predictability of monthly mean temperature in a future climate is quantified based on the Community Climate System Model, version 4. According to this model, the North Atlantic overtakes the El Niño–Southern Oscillation (ENSO) as the dominant area of seasonal predictability by 2095. This change arises partly because ENSO becomes less variable and partly because the ENSO teleconnection pattern expands into the Atlantic. Over land, the largest change in temperature predictability occurs in the tropics and is predominantly due to a decrease in ENSO variability. The southern peninsula of Africa and northeast South America are predicted to experience significant drying in a future climate, which decreases the effective heat capacity and memory, and hence increases variance independently of ENSO changes. Extratropical land areas experience enhanced precipitation in a future climate, which decreases temperature variance by the same mechanism. Finally, the model predicts that surface temperatures near the poles will become more predictable and less variable in a future climate, primarily because melting sea ice exposes the underlying sea surface temperature, which is more predictable owing to its longer time scale. Some of these results, especially the change in ENSO variance, are known to be model dependent. This paper also advances the use of information theory to quantify predictability, including 1) deriving a quantitative relation between predictability of the first and second kinds; 2) showing how differences in predictability can be decomposed in two dramatically different ways, facilitating physical interpretation; and 3) proposing a sample estimate of mutual information whose significance can be tested using standard techniques.
Subseasonal Analysis of Precipitation Variability in the Blue Nile River Basin
Authors: Berhane Fisseha , Zaitchik Benjamin , Dezfuli Amin 
Published: August 2013

Abstract
The Ethiopian portion of the Blue Nile River basin is subject to significant interannual variability in precipitation. As this variability has implications for local food security and transboundary water resources, numerous studies have been directed at improved understanding and, potentially, predictability of the Blue Nile rainy season (June–September) precipitation. Taken collectively, these studies present a wide range of large-scale drivers associated with precipitation variability in the Blue Nile: El Niño–Southern Oscillation (ENSO), the Indian summer monsoon, sea level pressure (SLP) anomalies over the Arabian Peninsula and Gulf of Guinea, the quasi-biennial oscillation (QBO), and dynamics of the tropical easterly jet (TEJ) and African easterly jet (AEJ) have all been emphasized to varying degrees. This study aims to reconcile these diverse analyses by evaluating teleconnection patterns and potential mechanisms of association on the subseasonal scale. It is found that associations with the TEJ, Pacific modes of variability, and the Indian monsoon are strongest in the late rainy season. Mid–rainy season precipitation (July and August) shows mixed associations with Pacific/Indian Ocean variability and Atlantic Ocean indices, along with connections to regional pressure patterns and the AEJ. June precipitation is negatively correlated with SLP over the equatorial Atlantic and upper-tropospheric geopotential height. June and July precipitation show little significant correlation with the sea surface temperature over the equatorial Pacific Ocean. The observed intraseasonal evolution of teleconnections across the rainy season indicates that subseasonal analysis is required to advance understanding and prediction of Blue Nile precipitation variability.
Interhemispheric Influence of the Northern Summer Monsoons on Southern Subtropical Anticyclones
Authors: Lee Sang-Ki , Mechoso Carlos R. , Wang Chunzai , Neelin J. David 
Published: August 2013

Abstract
The southern subtropical anticyclones are notably stronger in austral winter than summer, particularly over the Atlantic and Indian Ocean basins. This is in contrast with the Northern Hemisphere (NH), in which subtropical anticyclones are more intense in summer according to the “monsoon heating” paradigm. To better understand the winter intensification of southern subtropical anticyclones, the present study explores the interhemispheric response to monsoon heating in the NH during austral winter. A specially designed suite of numerical model experiments is performed in which summer monsoons in the NH are artificially weakened. These experiments are performed with both an atmospheric general circulation model and a simple two-layer model. The highlight of the findings presented here is that during the boreal summer enhanced tropical convection activity in the NH plays important roles in either maintaining or strengthening the southern subtropical anticyclones. Enhanced NH convection largely associated with the major summer monsoons produces subsidence over the equatorial oceans and the tropical Southern Hemisphere via interhemispheric meridional overturning circulations and increases the sea level pressure locally. In addition, suppressed convection over some regions of climatological subsidence produces stationary barotropic Rossby waves that propagate far beyond the tropics. These stationary barotropic Rossby waves and those forced directly by the summer heating in the NH are spatially phased to strengthen the southern subtropical anticyclones over all three oceans. The interhemispheric response to the NH summer monsoons is most dramatic in the South Pacific, where the subtropical anticyclone nearly disappears in the austral winter without the influence of the NH.