bluuebunny/crossref_metadata_2025_split huggingface dataset:
MicroRNA MIR21 and T Cells in Colorectal Cancer
Authors: Mima Kosuke , Nishihara Reiko , Nowak Jonathan A. , Kim Sun A. , Song Mingyang , Inamura Kentaro , Sukawa Yasutaka , Masuda Atsuhiro , Yang Juhong , Dou Ruoxu , Nosho Katsuhiko , Baba Hideo , Giovannucci Edward L. , Bowden Michaela , Loda Massimo , Giannakis Marios , Bass Adam J. , Dranoff Glenn , Freeman Gordon J. , Chan Andrew T. , Fuchs Charles S. , Qian Zhi Rong , Ogino Shuji 
Published: September 2015

Abstract
The complex interactions between colorectal neoplasia and immune cells in the tumor microenvironment remain to be elucidated. Experimental evidence suggests that microRNA MIR21 (miR-21) suppresses antitumor T-cell–mediated immunity. Thus, we hypothesized that tumor MIR21 expression might be inversely associated with T-cell density in colorectal carcinoma tissue. Using 538 rectal and colon cancer cases from the Nurses' Health Study and the Health Professionals Follow-up Study, we measured tumor MIR21 expression by a quantitative reverse-transcription PCR assay. Densities of CD3+, CD8+, CD45RO (PTPRC)+, and FOXP3+ cells in tumor tissue were determined by tissue microarray immunohistochemistry and computer-assisted image analysis. Ordinal logistic regression analysis was conducted to assess the association of MIR21 expression (ordinal quartiles as a predictor variable) with T-cell density (ordinal quartiles as an outcome variable), adjusting for tumor molecular features, including microsatellite instability; CpG island methylator phenotype; KRAS, BRAF, and PIK3CA mutations; and LINE-1 methylation. We adjusted the two-sided α level to 0.012 for multiple hypothesis testing. Tumor MIR21 expression was inversely associated with densities of CD3+ and CD45RO+ cells (Ptrend &lt; 0.0005). The multivariate odds ratio of the highest versus lowest quartile of MIR21 for a unit increase in quartile categories of CD3+ or CD45RO+ cells was 0.44 [95% confidence interval (CI), 0.28 to 0.68] or 0.41 (95% CI, 0.26–0.64), respectively. Our data support a possible role of tumor epigenetic deregulation by noncoding RNA in suppressing the antitumor T-cell–mediated adaptive immune response and suggest MIR21 as a potential target for immunotherapy and prevention in colorectal cancer. Cancer Immunol Res; 4(1); 33–40. ©2015 AACR.
Efficacy of a Cancer Vaccine against ALK-Rearranged Lung Tumors
Authors: Voena Claudia , Menotti Matteo , Mastini Cristina , Di Giacomo Filomena , Longo Dario Livio , Castella Barbara , Merlo Maria Elena Boggio , Ambrogio Chiara , Wang Qi , Minero Valerio Giacomo , Poggio Teresa , Martinengo Cinzia , D'Amico Lucia , Panizza Elena , Mologni Luca , Cavallo Federica , Altruda Fiorella , Butaney Mohit , Capelletti Marzia , Inghirami Giorgio , Jänne Pasi A. , Chiarle Roberto 
Published: September 2015

Abstract
Non–small cell lung cancer (NSCLC) harboring chromosomal rearrangements of the anaplastic lymphoma kinase (ALK) gene is treated with ALK tyrosine kinase inhibitors (TKI), but the treatment is successful for only a limited amount of time; most patients experience a relapse due to the development of drug resistance. Here, we show that a vaccine against ALK induced a strong and specific immune response that both prophylactically and therapeutically impaired the growth of ALK-positive lung tumors in mouse models. The ALK vaccine was efficacious also in combination with ALK TKI treatment and significantly delayed tumor relapses after TKI suspension. We found that lung tumors containing ALK rearrangements induced an immunosuppressive microenvironment, regulating the expression of PD-L1 on the surface of lung tumor cells. High PD-L1 expression reduced ALK vaccine efficacy, which could be restored by administration of anti–PD-1 immunotherapy. Thus, combinations of ALK vaccine with TKIs and immune checkpoint blockade therapies might represent a powerful strategy for the treatment of ALK-driven NSCLC. Cancer Immunol Res; 3(12); 1333–43. ©2015 AACR.
Improving Anticoagulation Measurement
Authors: Razouki Zayd , Burgess James F. , Ozonoff Al , Zhao Shibei , Berlowitz Dan , Rose Adam J. 
Published: September 2015

Background—
Percent time in therapeutic range (TTR) and international normalized ratio (INR) variability both measure warfarin control and are associated with outcomes independently. Here, we examine the advantages of a warfarin composite measure (WCM), which summarizes the 2 when measuring patient outcomes. We also examine how the measure chosen would affect anticoagulation clinic performance rankings.

Methods and Results—
We constructed WCM using an equally weighted method, adding standardized TTR to standardized log-transformed INR variability using 103 897 warfarin-experienced patients from 100 anticoagulation clinics. We examined the association of WCM with ischemic stroke, major bleeding, and fatal bleeding, using a subset of patients with atrial fibrillation (n=40 404). We divided patients into quintiles based on their level of control for TTR, log INR variability, and WCM. We calculated the hazard ratios for ischemic stroke, major bleeding, and fatal bleeding stratified by these quintiles. WCM hazard ratios for stroke and fatal bleeding showed the largest difference between excellent control and poorest control quintile compared with TTR and log INR variability, but not for major bleeding. In addition, we compared site rankings obtained using each of our 3 performance measures. Kappa scores for identifying outlier and nonoutlier clinics between WCM and its components were moderate (κ=0.56 for TTR and κ=0.62 for log INR variability) but was weak between TTR and log INR variability (κ=0.13).

Conclusions—
WCM produces the largest range of risk for warfarin complications, widening the floor ceiling effects that limit the use of TTR and INR variability as separate measures. Anticoagulation clinics ranking changed considerably according to the anticoagulation measure that was selected.
Differences Between US and UK Adults in Stroke Preparedness
Authors: Dombrowski Stephan U. , Ford Gary A. , Morgenstern Lewis B. , White Martin , Sniehotta Falko F. , Mackintosh Joan E. , Gellert Paul , Skolarus Lesli E. 
Published: September 2015

Background and Purpose—
Although time-dependent treatment is available, most people delay contacting emergency medical services for stroke. Given differences in the healthcare system and public health campaigns, exploring between-country differences in stroke preparedness may identify novel ways to increase acute stroke treatment.

Methods—

A survey was mailed to population-based samples in Ingham County, Michigan, US (n=2500), and Newcastle upon Tyne, UK (n=2500). Surveys included stroke perceptions and stroke/nonstroke scenarios to assess recognition and response to stroke. Between-country differences and associations with stroke preparedness were examined using
t
tests and linear mixed models.

Results—
Overall response rate was 27.4%. The mean age of participants was 55 years, and 58% were female. US participants were better in recognizing stroke (70% versus 63%, d=0.27) and were more likely to call emergency medical services (55% versus 52%, d=0.11). After controlling for demographics and comorbidities, US participants remained more likely to recognize stroke but were not more likely to respond appropriately. A greater belief that medical treatment can help with stroke and understanding of stroke was associated with improved stroke recognition and response.

Conclusions—
Overall, stroke recognition and response were moderate. US participants were modestly better at recognizing stroke, although there was little difference in response to stroke. Future stroke awareness interventions could focus more on stroke outcome expectations and developing a greater understanding of stroke among the public.
Clinically Confirmed Stroke With Negative Diffusion-Weighted Imaging Magnetic Resonance Imaging
Authors: Makin Stephen D.J. , Doubal Fergus N. , Dennis Martin S. , Wardlaw Joanna M. 
Published: September 2015

Background and Purpose—
We sought to establish whether the presence (versus absence) of a lesion on magnetic resonance imaging (MRI) with diffusion weighting (DWI-MRI) at presentation with acute stroke is associated with worse clinical outcomes at 1 year.

Methods—
We recruited consecutive patients with a nondisabling ischemic stroke and performed DWI-MRI. Patients were followed up at 1 year to establish stroke recurrence (clinical or on MRI), cognitive impairment (Addenbrooke Cognitive Assessment Revised,<88) and modified Rankin Scale.

Results—

A median of 4 days post stroke, one third (76/264; 29%) of patients did not have a DWI lesion (95% confidence interval, 23%–35%). There was no statistically significant difference between those with and without a DWI lesion with respect to age or vascular risk factors. Patients without a lesion were more likely to be women or have previous stroke. At 1 year, 11 of 76 (14%) patients with a DWI-negative index stroke had a clinical diagnosis of recurrent stroke or transient ischemic attack, 33% had cognitive impairment (Addenbrooke Cognitive Assessment Revised <88), and 40% still had modified Rankin Scale >1, no different from DWI-positive patients; DWI-positive patients were more likely to have a new lesion on MRI (14%), symptomatic or asymptomatic, than DWI-negative patients (2%;
P
=0.02). Our data were consistent with 6 other studies (total n=976), pooled proportion of DWI-negative patients was 21% (95% confidence interval, 12%–32%).

Conclusions—
Nearly one third of patients with nondisabling stroke do not have a relevant lesion on acute DWI-MRI. Patients with negative DWI-MRI had no better prognosis than patients with a lesion. DWI-negative stroke patients should receive secondary prevention.
An Improved Algorithm for the Detection of Cirrus Clouds in the Tibetan Plateau Using VIIRS and MODIS Data
Authors: Xia L. , Zhao F. , Ma Y. , Sun Z. W. , Shen X. Y. , Mao K. B. 
Published: September 2015

AbstractCirrus clouds play an important role in the global radiation budget balance. However, the existing MODIS and Visible Infrared Imaging Radiometer Suite (VIIRS) cirrus cloud test algorithms struggle to provide accurate cirrus cloud information for the Tibetan Plateau region. In this study, the 1.38-μm cirrus cloud test was improved by adding 11-μm brightness temperature and a multiday average land surface temperature test. An algorithm sensitivity analysis indicated that the proposed algorithm lowered the threshold of the existing 1.38-μm algorithm to 0.005 in the winter and did not produce any observable misclassifications. Compared to the existing 1.38-μm cirrus test algorithm, the accuracy validation indicated that the improved algorithm detected 31.7% more cirrus clouds than the existing VIIRS 1.38-μm cirrus test and yielded 14% fewer misclassifications than the MODIS 1.38-μm cirrus test.
Air Oxygen Calibration of Oxygen Optodes on a Profiling Float Array
Authors: Johnson Kenneth S. , Plant Joshua N. , Riser Stephen C. , Gilbert Denis 
Published: September 2015

AbstractAanderaa optode sensors for dissolved oxygen show remarkable stability when deployed on profiling floats, but these sensors suffer from poor calibration because of an apparent drift during storage (storage drift). It has been suggested that measurement of oxygen in air, during the period when a profiling float is on the surface, can be used to improve sensor calibration and to determine the magnitude of sensor drift while deployed in the ocean. The effect of air calibration on oxygen measurement quality with 47 profiling floats that were equipped with Aanderaa oxygen optode sensors is assessed. Recalibrated oxygen concentration measurements were compared to Winkler oxygen titrations that were made at the float deployment stations and to the World Ocean Atlas 2009 oxygen climatology. Recalibration of the sensor using air oxygen reduces the sensor error, defined as the difference from Winkler oxygen titrations in the mixed layer near the time of deployment, by about tenfold when compared to errors obtained with the factory calibration. The relative error of recalibrated sensors is <1% in surface waters. A total of 29 floats were deployed for time periods in excess of one year in ice-free waters. Linear changes in the percent of atmospheric oxygen reported by the sensor, relative to the oxygen partial pressure expected from the NCEP air pressure, range from −0.9% to +1.3% yr−1 with a mean of 0.2% ± 0.5% yr−1. Given that storage drift for optode sensors is only negative, it is concluded that there is no evidence for sensor drift after they are deployed and that other processes are responsible for the linear changes.
Capabilities and Limitations of Convection-Permitting WRF Simulations of Lake-Effect Systems over the Great Salt Lake
Authors: McMillen John D. , Steenburgh W. James 
Published: September 2015

AbstractAlthough previous studies suggest that the Weather Research and Forecasting (WRF) Model can produce physically realistic banded Great Salt Lake–effect (GSLE) precipitation features, the accuracy and reliability of these simulations for forecasting applications remains unquantified. The ability of the WRF to simulate nonbanded GSLE features is also unknown. This paper uses subjective, traditional, and object-based verification to evaluate convection-permitting (1.33-km grid spacing) WRF simulations of 11 banded and 8 nonbanded GSLE events. In all simulations, the WRF was configured with the Thompson microphysics and the Yonsei University (YSU) planetary boundary layer parameterizations. Subjectively, a majority of the simulations of banded GSLE events produce physically realistic precipitation features. In contrast, simulations of nonbanded GSLE events rarely produce physically realistic precipitation features and sometimes erroneously produce banded precipitation features. Simulations of banded GSLE events produce equitable threat scores (ETSs) comparable to other convective-storm verification studies, whereas simulations of nonbanded events exhibit lower ETSs. Object-based verification shows that the WRF tends to generate precipitation to the right (relative to the flow) and downstream of observed. These results, although based on a specific WRF parameterization suite, suggest that deterministic prediction of GSLE using convection-permitting models will prove challenging in practice with current numerical models. In addition, identifying and addressing the causes of the rightward and downstream precipitation bias is necessary to achieve optimal performance from future probabilistic and/or deterministic high-resolution forecast systems.
Predictors of Nodal Metastasis in Parotid Malignancies
Authors: Xiao Christopher C. , Zhan Kevin Y. , White‐Gilbertson Shai J. , Day Terry A. 
Published: September 2015

Objective(1) To identify predictors of nodal disease in parotid malignancies using various clinical and pathologic variables. (2) To examine the effect of nodal disease on overall survival (OS) in parotid cancersStudy DesignRetrospective database review.SettingNational Cancer Data Base (1998‐2012).Subjects and MethodsWe identified all cases of primary parotid malignancies in the United States between 1998 and 2012 in the National Cancer Data Base. Eight histopathologies, constituting >80% of all cases, were examined for nodal metastasis and survival.ResultsWe identified 22,653 cases of primary parotid cancer. Eight major histologies were studied, with mucoepidermoid carcinoma (31%), acinic cell carcinoma (18%), adenocarcinoma (14%), and adenoid cystic carcinoma (9%) being most common. Regional nodal disease incidence was 24.4% overall and varied by histopathology. Salivary ductal carcinoma had the highest incidence of both nodal metastasis and occult lymph node metastasis. Overall, N0 patients lived significantly longer than N+ (5‐year OS, 79% vs 40%; P <. 001). Low‐grade disease had significantly better survival than high‐grade (5‐year OS, 88% vs 69%; P <. 001). Occult nodal disease was found in 10.2% and varied by histopathology.ConclusionRegional lymph node metastasis significantly decreases survival in many parotid malignancies. High‐grade cancers had higher incidences of regional disease than did low grade. Adenocarcinoma had the highest mortality when regional disease was present. Incidence of occult disease varied by histology, but incidence was <10% for all low‐grade disease. High T stage and grade are significant independent predictors of nodal disease for most histopathologies.
Using Remote Communication Technology in Insulin Pump Training
Authors: Parks Linda , Kim Tae Youn 
Published: September 2015

Purpose: This feasibility study was designed to examine if remote communication technology can be used in the technical training of an insulin pump in adults with diabetes who were familiar with insulin pump therapy. Methods: Surveys were emailed to 69 individuals who purchased an insulin pump and had been trained by the manufacturer’s diabetes educators. In consultation with providers, participants were given the choice of receiving training in a face-to-face meeting or via remote communication technology. The survey consisted of 27 questions asking participants’ characteristics, device proficiency, confidence, and their satisfaction with the insulin pump and the training method. Differences between the 2 groups were examined using bivariate analyses. Results: There were 17 participants in the remote group and 20 participants in the face-to-face group. Participants had a mean age of 40.9 ± 14.3 years, had diabetes for 24.3 ± 13.8 years, and used an insulin pump for 9.8 ± 4.9 years. The participants in both groups were not statistically different in age, diabetes history, years on insulin pump, device proficiency, confidence, or satisfaction with the training method. The remote group reported less graduate-level education ( P < .05) and higher satisfaction scores with the insulin pump training ( P < .05). Conclusion: Although this study has limitations associated with the small sample size and self-selection bias, the results suggest that remote communication technology may be an effective tool to provide technical training to adults who are familiar with insulin pump therapy. Additional research is required to determine the effectiveness of the remote insulin pump training.
Elevated Intact Proinsulin Levels During an Oral Glucose Challenge Indicate Progressive ß-Cell Dysfunction and May Be Predictive for Development of Type 2 Diabetes
Authors: Pfützner Andreas , Hermanns Iris , Ramljak Sanja , Demircik Filiz , Pfützner Anke H. , Kann Peter H. , Weber Matthias M. 
Published: September 2015

Background: Elevated fasting intact proinsulin is a biomarker of late-stage ß-cell-dysfunction associated with clinically relevant insulin resistance. In this pilot investigation, we explored the potential value of measuring intact proinsulin as a functional predictor of ß-cell exhaustion during an oral glucose tolerance test (OGTT). Methods: The study was performed with 31 participants, 11 of whom were healthy subjects (7 female, age: 59 ± 20 years), 10 had impaired glucose tolerance (IGT, 6 female, 62 ± 10 years), and 10 had known type 2 diabetes (T2DM, 5 female, 53 ± 11 years, HbA1c: 7.0 ± 0.6%, disease duration: 8 ± 5 years). During OGTT, blood was drawn after 0 hours, 1 hour, and 2 hours for determination of glucose and intact proinsulin. Five years later, patients were again contacted to assess their diabetes status and the association to the previous OGTT results was analyzed. Results: The OGTT (0 hours/1 hour/2 hours) results were as follows: healthy subjects: glucose: 94 ± 8 mg/dL/140 ± 29 mg/dL/90 ± 24 mg/dL, intact proinsulin: 3 ± 2 pmol/L/10 ± 7 pmol/L/10 ± 5 pmol/L); IGT: glucose: 102 ± 9 mg/dL/158 ± 57 mg/dL/149 ± 34 mg/dL, intact proinsulin: 7 ± 4 pmol/L/23 ± 8 pmol/L/28 ± 6 pmol/L; T2DM: glucose: 121 ± 20 mg/dL/230 ± 51 mg/dL/213 ± 34 mg/dL; intact proinsulin: 7 ± 7 pmol/L/26 ± 9 pmol/L/27 ± 10 pmol/L). Five years later, all of the IGT and 2 of the healthy subjects had developed T2DM and one had devloped IGT. All of them had elevated 2-hour proinsulin values in the initial OGTT, while patients with normal intact proinsulin results did not develop diabetes. Conclusions: Elevated 2-hour intact proinsulin levels during OGTT were predictive for later type 2 diabetes development. Further studies need to confirm our findings in larger populations.
Distinguishing between determinate and indeterminate growth in a long-lived mammal
Authors: Mumby Hannah S. , Chapman Simon N. , Crawley Jennie A. H. , Mar Khyne U. , Htut Win , Thura Soe Aung , Aung Htoo Htoo , Lummaa Virpi 
Published: September 2015

AbstractBackgroundThe growth strategy of a species influences many key aspects of its life-history. Animals can either grow indeterminately (throughout life), or grow determinately, ceasing at maturity. In mammals, continued weight gain after maturity is clearly distinguishable from continued skeletal growth (indeterminate growth). Elephants represent an interesting candidate for studying growth because of their large size, long life and sexual dimorphism. Objective measures of their weight, height and age, however, are rare.ResultsWe investigate evidence for indeterminate growth in the Asian elephantElephas maximususing a longitudinal dataset from a semi-captive population. We fit growth curves to weight and height measurements, assess sex differences in growth, and test for indeterminate growth by comparing the asymptotes for height and weight curves. Our results show no evidence for indeterminate growth in the Asian elephant; neither sex increases in height throughout life, with the majority of height growth completed by the age of 15 years in females and 21 years in males. Females show a similar pattern with weight, whereas males continue to gain weight until over age 50. Neither sex shows any declines in weight with age.ConclusionsThese results have implications for understanding mammalian life-history, which could include sex-specific differences in trade-offs between size and reproductive investment.