bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of Difluoromethylornithine for the Chemoprevention of Barrett's Esophagus and Mucosal Dysplasia
Authors: Sinicrope Frank A. , Broaddus Russell , Joshi Nina , Gerner Eugene , Half Elizabeth , Kirsch Ilan , Lewin Jan , Morlan Bruce , Hong Waun Ki 
Published: June 2011

Abstract
Patients with Barrett's esophagus (BE) and dysplasia are candidates for chemopreventive strategies to reduce cancer risk. We determined the effects of difluoromethylornithine (DMFO) on mucosal polyamines, gene expression, and histopathology in BE. Ten patients with BE and low-grade dysplasia participated in a single-arm study of DFMO (0.5 g/m2/d) given continuously for 6 months. Esophagoscopy with biopsies was conducted at baseline, 3, 6, and 12 months. Dysplasia was graded by a gastrointestinal pathologist. Audiology was assessed (at baseline and at 6 months). Mucosal polyamines were measured by high-performance liquid chromatography. Microarray-based gene expression was analyzed using a cDNA two-color chip. DFMO suppressed levels of the polyamines putrescine (P = 0.02) and spermidine (P = 0.02) and the spermidine/spermine ratio (P &lt; 0.01) in dysplastic BE (6 months vs. baseline) that persisted at 6 months following drug cessation. Among the top 25 modulated genes, we found those regulating p53-mediated cell signaling (RPL11), cell-cycle regulation (cyclin E2), and cell adhesion and invasion (Plexin1). DFMO downregulated Krüppel-like factor 5 (KLF5), a transcription factor promoting cell proliferation, and suppressed RFC5 whose protein interacts with proliferating cell nuclear antigen. Histopathology showed regression of dysplasia (n = 1), stable disease (n = 8), and progression to high-grade dysplasia (n = 1). Polyamines were suppressed in the responder to a greater extent than in stable cases. DFMO was well tolerated, and one patient had subclinical, unilateral ototoxicity. DFMO suppressed mucosal polyamines and modulated genes that may be mechanistically related to its chemopreventive effect. Further study of DFMO for the chemoprevention of esophageal cancer in BE patients is warranted. Cancer Prev Res; 4(6); 829–39. ©2011 AACR.
Bexarotene Plus Erlotinib Suppress Lung Carcinogenesis Independent of KRAS Mutations in Two Clinical Trials and Transgenic Models
Authors: Dragnev Konstantin H. , Ma Tian , Cyrus Jobin , Galimberti Fabrizio , Memoli Vincent , Busch Alexander M. , Tsongalis Gregory J. , Seltzer Marc , Johnstone David , Erkmen Cherie P. , Nugent William , Rigas James R. , Liu Xi , Freemantle Sarah J. , Kurie Jonathan M. , Waxman Samuel , Dmitrovsky Ethan 
Published: June 2011

Abstract
The rexinoid bexarotene represses cyclin D1 by causing its proteasomal degradation. The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) erlotinib represses cyclin D1 via different mechanisms. We conducted a preclinical study and 2 clinical/translational trials (a window-of-opportunity and phase II) of bexarotene plus erlotinib. The combination repressed growth and cyclin D1 expression in cyclin-E- and KRAS/p53-driven transgenic lung cancer cells. The window-of-opportunity trial in early-stage non–small-cell lung cancer (NSCLC) patients (10 evaluable), including cases with KRAS mutations, repressed cyclin D1 (in tumor biopsies and buccal swabs) and induced necrosis and inflammatory responses. The phase II trial in heavily pretreated, advanced NSCLC patients (40 evaluable; a median of two prior relapses per patient (range, 0–5); 21% with prior EGFR-inhibitor therapy) produced three major clinical responses in patients with prolonged progression-free survival (583-, 665-, and 1,460-plus days). Median overall survival was 22 weeks. Hypertriglyceridemia was associated with an increased median overall survival (P = 0.001). Early PET (positron emission tomographic) response did not reliably predict clinical response. The combination was generally well tolerated, with toxicities similar to those of the single agents. In conclusion, bexarotene plus erlotinib was active in KRAS-driven lung cancer cells, was biologically active in early-stage mutant KRAS NSCLC, and was clinically active in advanced, chemotherapy-refractory mutant KRAS tumors in this study and previous trials. Additional lung cancer therapy or prevention trials with this oral regimen are warranted. Cancer Prev Res; 4(6); 818–28. ©2011 AACR.
Oral Iloprost Improves Endobronchial Dysplasia in Former Smokers
Authors: Keith Robert L. , Blatchford Patrick J. , Kittelson John , Minna John D. , Kelly Karen , Massion Pierre P. , Franklin Wilbur A. , Mao Jenny , Wilson David O. , Merrick Daniel T. , Hirsch Fred R. , Kennedy Timothy C. , Bunn Paul A. , Geraci Mark W. , Miller York E. 
Published: June 2011

AbstractThere are no established chemopreventive agents for lung cancer, the leading cause of cancer death in the United States. Prostacyclin levels are low in lung cancer and supplementation prevents lung cancer in preclinical models. We carried out a multicenter double-blind, randomized, phase II placebo-controlled trial of oral iloprost in current or former smokers with sputum cytologic atypia or endobronchial dysplasia. Bronchoscopy was performed at study entry and after completion of six months of therapy. Within each subject, the results were calculated by using the average score of all biopsies (Avg), the worst biopsy score (Max), and the dysplasia index (DI). Change in Avg was the primary end point, evaluated in all subjects, as well as in current and former smokers. The accrual goal of 152 subjects was reached and 125 completed both bronchoscopies (60/75 iloprost, 65/77 placebo). Treatment groups were well matched for age, tobacco exposure, and baseline histology. Baseline histology was significantly worse for current smokers (Avg 3.0) than former smokers (Avg 2.1). When compared with placebo, former smokers receiving oral iloprost exhibited a significantly greater improvement in Avg (0.41 units better, P = 0.010), in Max (1.10 units better, P = 0.002), and in DI (12.45%, P = 0.006). No histologic improvement occurred in current smokers. Oral iloprost significantly improves endobronchial histology in former smokers and deserves further study to determine if it can prevent the development of lung cancer. Cancer Prev Res; 4(6); 793–802. ©2011 AACR.
Biomarkers in Exploring the Frontiers of Diagnosis, Prognosis, and Therapy of Barrett's Esophagus
Authors: Yachimski Patrick , Peek Richard M. 
Published: June 2011

Abstract
Barrett's esophagus (BE) is the principal risk factor for esophageal adenocarcinoma. BE patients currently undergo periodic endoscopic surveillance with tissue sampling and histopathologic assessment for dysplasia. They frequently are prescribed proton pump inhibitors to pharmacologically suppress gastric acid that is the cause of BE. These standard endoscopic and pharmacologic approaches for managing BE are crude at best. Identification of novel tissue biomarkers within BE may allow for more accurate endoscopic risk stratification and provide potential targets for chemoprevention. Cancer Prev Res; 4(6); 783–6. ©2011 AACR.
Human Aldose Reductase Expression Accelerates Atherosclerosis in Diabetic Apolipoprotein E−/− Mice
Authors: Vedantham Srinivasan , Noh HyeLim , Ananthakrishnan Radha , Son Ni , Hallam Kellie , Hu Yunying , Yu Shuiquing , Shen Xiaoping , Rosario Rosa , Lu Yan , Ravindranath Thyyar , Drosatos Konstantinos , Huggins Lesley Ann , Schmidt Ann Marie , Goldberg Ira J. , Ramasamy Ravichandran 
Published: June 2011

Objective—
There are several pathways that mediate the aberrant metabolism of glucose and that might induce greater vascular damage in the setting of diabetes. The polyol pathway mediated by aldose reductase (AR) has been postulated to be one such pathway. However, it has been reported that AR reduces toxic lipid aldehydes and, under some circumstances, might be antiatherogenic.

Methods and Results—
Atherosclerosis development was quantified in 2 lines of transgenic mice expressing human AR (hAR) crossed on the apolipoprotein E knockout background. The transgenes were used to increase the normally low levels of this enzyme in wild-type mice. Both generalized hAR overexpression and hAR expression via the Tie 2 promoter increased lesion size in streptozotocin diabetic mice. In addition, pharmacological inhibition of AR reduced lesion size.

Conclusion—
Although in some settings AR expression might reduce levels of toxic aldehydes, transgenic expression of this enzyme within the artery wall leads to greater atherosclerosis.
White Matter Hyperintensity Penumbra
Authors: Maillard Pauline , Fletcher Evan , Harvey Danielle , Carmichael Owen , Reed Bruce , Mungas Dan , DeCarli Charles 
Published: June 2011

Background and Purpose—
White matter hyperintensities (WMHs) are associated with progressive age-related cognitive decline and cardiovascular risk factors, but their biological relevance as indicators of generalized white matter injury is unclear. Diffusion tensor imaging provides more sensitive indications of subtle white matter disruption and can therefore clarify whether WMHs represent foci of generalized white matter damage that extends over a broader neighborhood.

Methods—
Two hundred eight participants from the University of California, Davis Alzheimer's Disease Center received a comprehensive clinical evaluation and brain MRI including fluid-attenuated inversion recovery and diffusion tensor imaging sequences. Voxelwise maps of WMHs were produced from fluid-attenuated inversion recovery using a standardized WMH detection protocol. Fractional anisotropy maps were calculated from diffusion tensor imaging. All WMH and fractional anisotropy maps were coregistered to a standardized space. For each normal-appearing white matter voxel in each subject fluid-attenuated inversion recovery scan, a neighborhood white matter injury score was calculated that increased with increasing number and proximity of WMH in the vicinity of the normal-appearing white matter voxel. Fractional anisotropy was related to neighborhood white matter injury using a nonlinear mixed effect model controlling for relevant confounding factors.

Results—

Fractional anisotropy was found to decrease as neighborhood white matter injury increased (β=−0.0017/%,
P
<0.0001) with an accelerated rate (
P
<0.0001) for neighborhood white matter injury >0.4. An increase of 1% in neighborhood white matter injury score was associated with a decrease in mean fractional anisotropy of 0.012 (
P
<0.001).

Conclusions—
WMH may represent foci of more widespread and subtle white matter changes rather than distinct, sharply delineated anatomic abnormalities. We use the term white matter hyperintensities penumbra to explain this phenomenon.
Biases and Model Agreement in Projections of Climate Extremes over the Tropical Pacific
Authors: Perkins Sarah E. 
Published: June 2011

AbstractUsing the Coupled Model Intercomparison Project phase 3 (CMIP3) general circulation models (GCMs), projections of a range of climate extremes are explored for the western Pacific. These projections include the 1-in-20-yr return levels and a selection of climate indices for minimum temperature, maximum temperature, and precipitation, and they are compared to corresponding mean projections for the Special Report on Emission Scenarios (SRES) A2 scenario during 2081–2100. Models are evaluated per variable based on their ability to simulate current extremes, as well as the overall daily distribution. Using the standardized evaluation scores for each variable, models are divided into four subsets where ensemble variability is calculated to measure model uncertainty and biases are calculated in respect to the multimodel ensemble (MME). Results show that higher uncertainty in projections of climate extremes exists when compared to the mean, even in those subsets consisting of higher-skilled models. Higher uncertainty exists for precipitation projections than for temperature, and biases and uncertainties in the 1-in-20-yr precipitation events are an order of magnitude higher than the corresponding mean. Poorer performing models exhibit a cooler bias in the mean and 1-in-20-yr return levels for maximum and minimum temperature, and ensemble variability is low among all subsets of mean minimum temperature, especially the lower-skilled subsets. Higher-skilled models project 1-in-20-yr precipitation return levels that are more intense than in the MME. The frequency of temperature extremes increase dramatically; however, this is explained by the underpinning small temperature range of the region. Although some systematic biases occur in the higher- and lower-skilled models and omitting the poorer performers is recommended, great care should be exercised when interpreting the reduction of uncertainty because the ensemble variability among the remaining models is comparable and in some cases greater than the MME. Such results should be treated on a case-by-case basis.
Impact of Upstream Urbanization on the Urban Heat Island Effects along the Washington–Baltimore Corridor
Authors: Zhang Da-Lin , Shou Yi-Xuan , Dickerson Russell R. , Chen Fei 
Published: June 2011

AbstractAlthough there has been considerable research on urban heat island (UHI) effects, most of the previous studies have attributed UHI effects to localized, surface processes. In this study, the impact of upstream urbanization on enhanced UHI effects is examined using surface observations and numerical simulations of an extreme UHI event that occurred on 9 July 2007 over Baltimore, Maryland. Under southwesterly wind, Baltimore experienced higher peak surface temperatures and higher pollution concentrations than did the larger urban area of Washington, D.C. Results from a coupled ultrahigh-resolution mesoscale–urban canopy model with 2001 National Land Cover Data show an advective contribution from upstream urbanization to the UHI event. This dynamical process is demonstrated by replacing Baltimore or its upstream urban areas by natural vegetation (in the model), indicating that the UHI effects could be reduced by as much as 25%. An analysis of the urban–bay interaction reveals the importance of horizontal wind direction in determining the intensity of bay breezes and the urban boundary layer structures. In addition, the vertical growth and structures of UHI effects are shown as layered “hot plumes” in the mixed layer with pronounced rising motions, and these plumes can be advected many kilometers downstream. These findings suggest that judicious land use and urban planning, especially in rapidly developing countries, could help to alleviate UHI consequences, including heat stress and smog. They also have important implications for improving the prediction of urban weather, including the initiation of moist convection, air quality, and other environment-related problems.
Boundary Layer Turbulence and Orographic Precipitation Growth in Cold Clouds: Evidence from Profiling Airborne Radar Data
Authors: Geerts Bart , Miao Qun , Yang Yang 
Published: June 2011

Abstract
Airborne vertically pointing Doppler radar data collected in 10 winter storms over the Medicine Bow Range in Wyoming are used to examine the importance of boundary layer (BL) turbulence for orographic precipitation growth. In all 10 cases, the cloud-base temperature was below 0°C and the bulk Froude number was more than 1.0, implying little or no blocking of the flow by the mountain barrier. Seven of the 10 storms sampled were postfrontal, with weak static stability and relatively shallow cloud tops.
Doppler vertical velocity transects depict an approximately 1-km-deep turbulent layer draped over the terrain, sometimes clearly distinct from the stratified flow in the free troposphere aloft, where vertical motion is largely controlled by gravity wave dynamics. Spectral analysis of near-surface Doppler vertical velocity data in terrain-following coordinates reveals an inertial subrange with decreasing power with height toward the BL top. The composite of radar data profiles from the 10 flights is analyzed in frequency-by-altitude diagrams, with altitude expressed above ground level. These diagrams indicate a wide range of vertical velocities in the BL, and rapid snow growth within the BL as air rises through the cloud base, especially when BL turbulence is more intense. This snow growth is concentrated on the windward side of mountains, above the terrain–cloud base intersection. The dominant snow growth mechanism in the BL (i.e., by accretion or vapor deposition) cannot be established because of restrictions in aircraft flight level over complex terrain. Snow aggregation may have contributed to the observed rapid increase in reflectivity in the BL along the windward slope.
Nocturnal Aerosol Optical Depth Measurements with a Small-Aperture Automated Photometer Using the Moon as a Light Source
Authors: Berkoff Timothy A. , Sorokin Mikail , Stone Tom , Eck Thomas F. , Hoff Raymond , Welton Ellsworth , Holben Brent 
Published: June 2011

Abstract
A method is described that enables the use of lunar irradiance to obtain nighttime aerosol optical depth (AOD) measurements using a small-aperture photometer. In this approach, the U.S. Geological Survey lunar calibration system was utilized to provide high-precision lunar exoatmospheric spectral irradiance predictions for a ground-based sensor location, and when combined with ground measurement viewing geometry, provided the column optical transmittance for retrievals of AOD. Automated multiwavelength lunar measurements were obtained using an unmodified Cimel-318 sunphotometer sensor to assess existing capabilities and enhancements needed for day/night operation in NASA’s Aerosol Robotic Network (AERONET). Results show that even existing photometers can provide the ability for retrievals of aerosol optical depths at night near full moon. With an additional photodetector signal-to-noise improvement of 10–100, routine use over the bright half of the lunar phase and a much wider range of wavelengths and conditions can be achieved. Although the lunar cycle is expected to limit the frequency of observations to 30%–40% compared to solar measurements, nevertheless this is an attractive extension of AERONET capabilities.
Modeling the Measurements of Cochlear Microcirculation and Hearing Function after Loud Noise
Authors: Arpornchayanon Warangkana , Canis Martin , Suckfuell Markus , Ihler Fritz , Olzowy Bernhard , Strieth Sebastian 
Published: June 2011

ObjectiveRecent findings support the crucial role of microcirculatory disturbance and ischemia for hearing impairment especially after noise‐induced hearing loss (NIHL). The aim of this study was to establish an animal model for in vivo analysis of cochlear microcirculation and hearing function after a loud noise to allow precise measurements of both parameters in vivo.Study DesignRandomized controlled trial.SettingAnimal study.Subjects and MethodsAfter assessment of normacusis (0 minutes) using evoked auditory brainstem responses (ABRs), noise (106‐dB sound pressure level [SPL]) was applied to both ears in 6 guinea pigs for 30 minutes while unexposed animals served as controls. In vivo fluorescence microscopy of the stria vascularis capillaries was performed after surgical exposure of 1 cochlea. ABR measurements were derived from the contralateral ear.ResultsAfter noise exposure, red blood cell velocity was reduced significantly by 24.3% (120 minutes) and further decreased to 44.5% at the end of the observation (210 minutes) in contrast to stable control measurements. Vessel diameters were not affected in both groups. A gradual decrease of segmental blood flow became significant (38.1%) after 150 minutes compared with controls. Hearing thresholds shifted significantly from 20.0 ± 5.5 dB SPL (0 minutes) to 32.5 ± 4.2 dB SPL (60 minutes) only in animals exposed to loud noise.ConclusionWith regard to novel treatments targeting the stria vascularis in NIHL, this standardized model allows us to analyze in detail cochlear microcirculation and hearing function in vivo.
Effects of virtual reality training on functional reaching movements in people with Parkinson’s disease: a randomized controlled pilot trial
Authors: Ma Hui-Ing , Hwang Wen-Juh , Fang Jing-Jing , Kuo Jui-Kun , Wang Ching-Yi , Leong Iat-Fai , Wang Tsui-Ying 
Published: June 2011

Objective: To investigate whether practising reaching for virtual moving targets would improve motor performance in people with Parkinson’s disease. Design: Randomized pretest–posttest control group design. Setting: A virtual reality laboratory in a university setting. Participants: Thirty-three adults with Parkinson’s disease. Interventions: The virtual reality training required 60 trials of reaching for fast-moving virtual balls with the dominant hand. The control group had 60 practice trials turning pegs with their non-dominant hand. Main outcome measures: Pretest and posttest required reaching with the dominant hand to grasp real stationary balls and balls moving at different speeds down a ramp. Success rates and kinematic data (movement time, peak velocity and percentage of movement time for acceleration phase) from pretest and posttest were recorded to determine the immediate transfer effects. Results: Compared with the control group, the virtual reality training group became faster ( F = 9.08, P = 0.005) and more forceful ( F = 9.36, P = 0.005) when reaching for real stationary balls. However, there was no significant difference in success rate or movement kinematics between the two groups when reaching for real moving balls. Conclusion: A short virtual reality training programme improved the movement speed of discrete aiming tasks when participants reached for real stationary objects. However, the transfer effect was minimal when reaching for real moving objects.
Is social work a green profession? An examination of environmental beliefs
Authors: Shaw Terry V 
Published: June 2011

• Summary: Social work has developed to meet the needs of an industrializing society. As environmental concerns have increased, national, and international social work organizations have called on social workers to incorporate issues of the environment into their professional practice. Although there is a small body of literature related to social work and the environment, the profession has not fully embraced the need to incorporate these issues into social work education or practice. This cross-sectional survey in the United States of a random sample of National Association of Social Workers (NASW) members ( n = 373) was designed to gauge the environmental knowledge and attitudes of social work professionals. • Findings: Though social work shares many of the same underlying tenets of groups interested in environmental justice, results suggest that social workers as a profession are no more, nor less, environmentally friendly than the general population. • Applications: By failing to incorporate ecological issues facing the United States and abroad, our current social policies are at best not sustainable, and at worst dangerous for our continued social well-being. Social workers can play a leading role through an understanding of the interrelationship that exists between people and the environment, the integration of environmental issues into their social work practice, and advocating for vulnerable populations.