bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epigenetic modulation of intestinal Na+/H+ exchanger-3 expression
Authors: Kumar Anoop , Malhotra Pooja , Coffing Hayley , Priyamvada Shubha , Anbazhagan Arivarasu N. , Krishnan Harish R. , Gill Ravinder K. , Alrefai Waddah A. , Gavin David P. , Pandey Subhash C. , Dudeja Pradeep K. , Saksena Seema 
Published: November 2017

Na+/H+ exchanger-3 (NHE3) is crucial for intestinal Na+ absorption, and its reduction has been implicated in infectious and inflammatory bowel diseases (IBD)-associated diarrhea. Epigenetic mechanisms such as DNA methylation are involved in the pathophysiology of IBD. Whether changes in DNA methylation are involved in modulating intestinal NHE3 gene expression is not known. Caco-2 and HuTu 80 cells were used as models of human intestinal epithelial cells. Normal C57/BL6, wild-type, or growth arrest and DNA damage-inducible 45b (GADD45b) knockout (KO) mice were used as in vivo models. NHE3 gene DNA methylation levels were assessed by MBDCap (MethyMiner) assays. Results demonstrated that in vitro methylation of NHE3 promoter construct (p-1509/+127) cloned into a cytosine guanine dinucleotide-free lucia vector decreased the promoter activity in Caco-2 cells. DNA methyltransferase inhibitor 5-azacytidine (10 μM, 24 h) caused a significant decrease in DNA methylation of the NHE3 gene and concomitantly increased NHE3 expression in Caco-2 cells. Similarly, 5-azacytidine treatment increased NHE3 mRNA levels in HuTu 80 cells. 5-Azacytidine treatment for 3 wk (10 mg/kg body wt ip, 3 times/wk) also resulted in an increase in NHE3 expression in the mouse ileum and colon. Small-interfering RNA knockdown of GADD45b (protein involved in DNA demethylation) in Caco-2 cells decreased NHE3 mRNA expression. Furthermore, there was a significant decrease in NHE3 mRNA and protein expression in the ileum and colon of GADD45b KO mice. Our findings demonstrate that NHE3 gene expression is regulated by changes in its DNA methylation. NEW & NOTEWORTHY Our studies for the first time demonstrate that Na+/H+ exchanger-3 gene expression is regulated by an epigenetic mechanism involving DNA methylation.
Tactile perception of the roughness of 3D-printed textures
Authors: Tymms Chelsea , Zorin Denis , Gardner Esther P. 
Published: November 2017

Surface roughness is one of the most important qualities in haptic perception. Roughness is a major identifier for judgments of material composition, comfort, and friction and is tied closely to manual dexterity. Some attention has been given to the study of roughness perception in the past, but it has typically focused on noncontrollable natural materials or on a narrow range of artificial materials. The advent of high-resolution three-dimensional (3D) printing technology provides the ability to fabricate arbitrary 3D textures with precise surface geometry to be used in tactile studies. We used parametric modeling and 3D printing to manufacture a set of textured plates with defined element spacing, shape, and arrangement. Using active touch and two-alternative forced-choice protocols, we investigated the contributions of these surface parameters to roughness perception in human subjects. Results indicate that large spatial periods produce higher estimations of roughness (with Weber fraction = 0.19), small texture elements are perceived as rougher than large texture elements of the same wavelength, perceptual differences exist between textures with the same spacing but different arrangements, and roughness equivalencies exist between textures differing along different parameters. We posit that papillary ridges serve as tactile processing units, and neural ensembles encode the spatial profiles of the texture contact area to produce roughness estimates. The stimuli and the manufacturing process may be used in further studies of tactile roughness perception and in related neurophysiological applications. NEW & NOTEWORTHY Surface roughness is an integral quality of texture perception. We manufactured textures using high-resolution 3D printing, which allows precise specification of the surface spatial topography. In human psychophysical experiments we investigated the contributions of specific surface parameters to roughness perception. We found that textures with large spatial periods, small texture elements, and irregular, isotropic arrangements elicit the highest estimations of roughness. We propose that roughness correlates inversely with the total contacted surface area.
Height, Obesity, and the Risk of TMPRSS2:ERG-Defined Prostate Cancer
Authors: Graff Rebecca E. , Ahearn Thomas U. , Pettersson Andreas , Ebot Ericka M. , Gerke Travis , Penney Kathryn L. , Wilson Kathryn M. , Markt Sarah C. , Pernar Claire H. , Gonzalez-Feliciano Amparo G. , Song Mingyang , Lis Rosina T. , Schmidt Daniel R. , Vander Heiden Matthew G. , Fiorentino Michelangelo , Giovannucci Edward L. , Loda Massimo , Mucci Lorelei A. 
Published: November 2017

Abstract
Background: The largest molecular subtype of primary prostate cancer is defined by the TMPRSS2:ERG gene fusion. Few studies, however, have investigated etiologic differences by TMPRSS2:ERG status. Because the fusion is hormone-regulated and a man's hormonal milieu varies by height and obesity status, we hypothesized that both may be differentially associated with risk of TMPRSS2:ERG-defined disease.
Methods: Our study included 49,372 men from the prospective Health Professionals Follow-up Study. Participants reported height and weight at baseline in 1986 and updated weight biennially thereafter through 2009. Tumor ERG protein expression (a TMPRSS2:ERG marker) was immunohistochemically assessed. We used multivariable competing risks models to calculate HRs and 95% confidence intervals (CIs) for the risk of ERG-positive and ERG-negative prostate cancer.
Results: During 23 years of follow-up, we identified 5,847 incident prostate cancers, among which 913 were ERG-assayed. Taller height was associated with an increased risk of ERG-positive disease only [per 5 inches HR 1.24; 95% confidence interval (CI), 1.03–1.50; Pheterogeneity = 0.07]. Higher body mass index (BMI) at baseline (per 5 kg/m2 HR 0.75; 95% CI, 0.61–0.91; Pheterogeneity = 0.02) and updated BMI over time (per 5 kg/m2 HR 0.86; 95% CI, 0.74–1.00; Pheterogeneity = 0.07) were associated with a reduced risk of ERG-positive disease only.
Conclusions: Our results indicate that anthropometrics may be uniquely associated with TMPRSS2:ERG-positive prostate cancer; taller height may be associated with greater risk, whereas obesity may be associated with lower risk.
Impact: Our study provides strong rationale for further investigations of other prostate cancer risk factors that may be distinctly associated with subtypes. Cancer Epidemiol Biomarkers Prev; 27(2); 193–200. ©2017 AACR.
Aging-Related Disease Risks among Young Thyroid Cancer Survivors
Authors: Blackburn Brenna E. , Ganz Patricia A. , Rowe Kerry , Snyder John , Wan Yuan , Deshmukh Vikrant , Newman Michael , Fraser Alison , Smith Ken , Herget Kimberly , Kim Jaewhan , Kirchhoff Anne C. , Porucznik Christina , Hanson Heidi , Monroe Marcus , Hashibe Mia 
Published: November 2017

Abstract
Background: Thyroid cancer is the most rapidly increasing cancer in the United States, affects a young population, has high survival, and is one of the most common cancers in people under age 40. The aim of this study was to examine the risks of aging-related diseases in a statewide sample of thyroid cancer survivors who were diagnosed &lt;40 years compared with those diagnosed ≥40 and a cancer-free sample.
Methods: Thyroid cancer survivors diagnosed 1997 to 2012 were matched to up to 5 cancer-free individuals on birth year, sex, birth state, using the statewide Utah Population Database. Medical records were used to identify disease diagnoses stratified over three time periods: 1 to 5, &gt;5 to 10, and 10+ years after cancer diagnosis. Cox proportional hazards models were used to estimate hazard ratios with adjustment on matching factors, race, body mass index, and Charlson Comorbidity Index.
Results: There were 3,706 thyroid cancer survivors and 15,587 matched cancer-free individuals (1,365 cases diagnosed &lt;40 years old). Both age groups had increased risks for multiple circulatory health conditions 1 to 5 years after cancer diagnosis compared with cancer-free individuals. Survivors &lt;40 had a higher risk of hypertension, cardiomyopathy, and nutritional deficiencies.
Conclusions: Increased risks for diseases associated with aging were observed for both age groups, with younger thyroid cancer survivors having higher risks for select diseases.
Impact: As thyroid cancer survivors in this study were found to have increased risks for aging-related diseases, future studies are needed to assess what can be done to reduce the increased risks of these long-term health effects. Cancer Epidemiol Biomarkers Prev; 26(12); 1695–704. ©2017 AACR.
Surgical Enlargement of the Aortic Root Does Not Increase the Operative Risk of Aortic Valve Replacement
Authors: Rocha Rodolfo V. , Manlhiot Cedric , Feindel Christopher M. , Yau Terrence M. , Mueller Brigitte , David Tirone E. , Ouzounian Maral 
Published: November 2017

Background:
Surgical aortic root enlargement (ARE) during aortic valve replacement (AVR) allows for larger prosthesis implantation and may be an important adjunct to surgical AVR in the transcatheter valve-in-valve era. The incremental operative risk of adding ARE to AVR has not been established. We aimed to evaluate the early outcomes of patients undergoing AVR with or without ARE.

Methods:
From January 1990 to August 2014, 7039 patients underwent AVR (AVR+ARE, n=1854; AVR, n=5185) at a single institution. Patients with aortic dissection and active endocarditis were excluded. Mean age was 65±14 years and 63% were male. Logistic regression and propensity score matching were used to adjust for unbalanced variables in group comparisons.

Results:

Patients undergoing AVR+ARE were more likely to be female (46% versus 34%,
P
<0.001) and had higher rates of previous cardiac surgery (18% versus 12%,
P
<0.001), chronic obstructive pulmonary disease (5% versus 3%,
P
=0.004), urgent/emergent status (6% versus 4%,
P
=0.01), and worse New York Heart Association status (
P
<0.001). Most patients received bioprosthetic valves (AVR+ARE: 73.4% versus AVR: 73.3%,
P
=0.98) and also underwent concomitant cardiac procedures (AVR+ARE: 68% versus AVR: 67%,
P
=0.31). Mean prosthesis size implanted was slightly smaller in patients requiring AVR+ARE versus AVR (23.4±2.1 versus 24.1±2.3,
P
<0.001). In-hospital mortality was higher after AVR+ARE (4.3% versus 3.0%,
P
=0.008), although when the cohort was restricted to patients undergoing isolated aortic valve replacement with or without root enlargement, mortality was not statistically different (AVR+ARE: 1.7% versus AVR: 1.1%,
P
=0.29). After adjustment for baseline characteristics, AVR+ARE was not associated with an increased risk of in-hospital mortality when compared with AVR (odds ratio, 1.03; 95% confidence interval, 0.75–1.41;
P
=0.85). Furthermore, AVR+ARE was not associated with an increased risk of postoperative adverse events. Results were similar if propensity matching was used instead of multivariable adjustments for baseline characteristics.

Conclusions:
In the largest analysis to date, ARE was not associated with increased risk of mortality or adverse events. Surgical ARE is a safe adjunct to AVR in the modern era.
Statistics of Visual Responses to Image Object Stimuli from Primate AIT Neurons to DNN Neurons
Authors: Dong Qiulei , Wang Hong , Hu Zhanyi 
Published: November 2017

Under the goal-driven paradigm, Yamins et al. ( 2014 ; Yamins & DiCarlo, 2016 ) have shown that by optimizing only the final eight-way categorization performance of a four-layer hierarchical network, not only can its top output layer quantitatively predict IT neuron responses but its penultimate layer can also automatically predict V4 neuron responses. Currently, deep neural networks (DNNs) in the field of computer vision have reached image object categorization performance comparable to that of human beings on ImageNet, a data set that contains 1.3 million training images of 1000 categories. We explore whether the DNN neurons (units in DNNs) possess image object representational statistics similar to monkey IT neurons, particularly when the network becomes deeper and the number of image categories becomes larger, using VGG19, a typical and widely used deep network of 19 layers in the computer vision field. Following Lehky, Kiani, Esteky, and Tanaka ( 2011 , 2014 ), where the response statistics of 674 IT neurons to 806 image stimuli are analyzed using three measures (kurtosis, Pareto tail index, and intrinsic dimensionality), we investigate the three issues in this letter using the same three measures: (1) the similarities and differences of the neural response statistics between VGG19 and primate IT cortex, (2) the variation trends of the response statistics of VGG19 neurons at different layers from low to high, and (3) the variation trends of the response statistics of VGG19 neurons when the numbers of stimuli and neurons increase. We find that the response statistics on both single-neuron selectivity and population sparseness of VGG19 neurons are fundamentally different from those of IT neurons in most cases; by increasing the number of neurons in different layers and the number of stimuli, the response statistics of neurons at different layers from low to high do not substantially change; and the estimated intrinsic dimensionality values at the low convolutional layers of VGG19 are considerably larger than the value of approximately 100 reported for IT neurons in Lehky et al. ( 2014 ), whereas those at the high fully connected layers are close to or lower than 100. To the best of our knowledge, this work is the first attempt to analyze the response statistics of DNN neurons with respect to primate IT neurons in image object representation.
The Third Atmospheric Scientific Experiment for Understanding the Earth–Atmosphere Coupled System over the Tibetan Plateau and Its Effects
Authors: Zhao Ping , Xu Xiangde , Chen Fei , Guo Xueliang , Zheng Xiangdong , Liu Liping , Hong Yang , Li Yueqing , La Zuo , Peng Hao , Zhong Linzhi , Ma Yaoming , Tang Shihao , Liu Yimin , Liu Huizhi , Li Yaohui , Zhang Qiang , Hu Zeyong , Sun Jihua , Zhang Shengjun , Dong Lixin , Zhang Hezhen , Zhao Yang , Yan Xiaolu , Xiao An , Wan Wei , Liu Yu , Chen Junming , Liu Ge , Zhaxi Yangzong , Zhou Xiuji 
Published: November 2017

AbstractThis paper presents the background, scientific objectives, experimental design, and preliminary achievements of the Third Tibetan Plateau (TP) Atmospheric Scientific Experiment (TIPEX-III) for 8–10 years. It began in 2013 and has expanded plateau-scale observation networks by adding observation stations in data-scarce areas; executed integrated observation missions for the land surface, planetary boundary layer, cloud–precipitation, and troposphere–stratosphere exchange processes by coordinating ground-based, air-based, and satellite facilities; and achieved noticeable progress in data applications. A new estimation gives a smaller bulk transfer coefficient of surface sensible heat over the TP, which results in a reduction of the possibly overestimated heat intensity found in previous studies. Summer cloud–precipitation microphysical characteristics and cloud radiative effects over the TP are distinguished from those over the downstream plains. Warm rain processes play important roles in the development of cloud and precipitation over the TP. The lower-tropospheric ozone maximum over the northeastern TP is attributed to the regional photochemistry and long-range ozone transports, and the heterogeneous chemical processes of depleting ozone near the tropopause might not be a dominant mechanism for the summer upper-tropospheric–lower-stratospheric ozone valley over the southeastern TP. The TP thermodynamic function not only affects the local atmospheric water maintenance and the downstream precipitation and haze events but also modifies extratropical atmospheric teleconnections like the Asia–Pacific Oscillation, subtropical anticyclones over the North Pacific and Atlantic, and temperature and precipitation over Africa, Asia, and North America. These findings provide new insights into understanding land–atmosphere coupled processes over the TP and their effects, improving model parameterization schemes, and enhancing weather and climate forecast skills.
The KLIWAS North Sea Climatology. Part II: Assessment against Global Reanalyses
Authors: Schade Nils H. , Sadikni Remon , Jahnke-Bornemann Annika , Hinrichs Iris , Gates Lydia , Tinz Birger , Stammer Detlef 
Published: November 2017

AbstractObservational reference datasets are needed in atmosphere and ocean for quality assessments of climate models and for the evaluation of atmospheric reanalyses. To meet this demand on the regional scale, the Climate Water Navigation (KLIWAS) North Sea climatology (KNSC) was developed. This paper uses KNSC to assess the quality of five atmospheric reanalysis products [ERA-40; ERA-Interim; NCEP-1; 20CR, version 2 (20CRv2); and MERRA] over the North Sea from 1979 to 2001. Differences in sea level pressure (2-m air temperature) can be found in coastal regions for ERA-40/ERA-Interim and MERRA, and are more pronounced during positive (negative) phases of the NAO. 20CRv2 shows biases over the entire North Sea and all seasons of several hectopascals. ERA-40 and ERA-Interim show a negative 2-m air temperature bias relative to KNSC along the coastal mainland of Europe, especially during winter months, possibly a result of a remaining land influence. Mean differences result from winter and fall, mostly remaining within measurement uncertainties. Despite the upgrades in the model setup, ERA-Interim shows negligible differences from ERA-40. 20CRv2 and MERRA show positive (negative) biases during the summer (winter) half year. NCEP-1 follows ERA-40/ERA-Interim but mostly with slightly higher differences. All five reanalyses reproduce the decadal variability and climate shift signals present in KNSC fields. Overall, only 20CRv2 has to be considered as clearly unsatisfactorily regarding biases, MAE, and RMSE compared to all other datasets investigated. This study suggests that similar intercomparison studies, performed over other parts of the world’s oceans, especially coastal regions, can be very helpful in identifying shortcomings in atmospheric reanalysis products.
Using Synthetic Controls to Evaluate the Effect of Unique Interventions: The Case of Say Yes to Education
Authors: Bifulco Robert , Rubenstein Ross , Sohn Hosung 
Published: November 2017

Background: “Place-based” scholarships seek to improve student outcomes in urban school districts and promote urban revitalization in economically challenged cities. Say Yes to Education is a unique district-wide school reform effort adopted in Syracuse, NY, in 2008. It includes full-tuition scholarships for public and private universities, coupled with extensive wraparound support services in schools. Objectives: This study uses synthetic control methods to evaluate the effect of Say Yes on district enrollment and graduation rates. It also introduces the synthetic control method and provides guidance for its use in evaluating single-site interventions. Method: Combining school district-level data from the National Center for Education Statistics’ Common Core of Data and New York State School Report Cards, this article uses synthetic control methods to construct a synthetic comparison district to estimate counterfactual enrollment and graduation trends for Syracuse. Results: We find that Say Yes to Education was associated with enrollment increases in the Syracuse City School District, a district that had previously experienced decades of sustained enrollment declines. We do not find consistent evidence of changes in graduation rates following adoption of the program. Conclusions: Graduation rate analyses demonstrate that estimates of treatment effects can be sensitive to choices that the researcher has to make in applying synthetic control methods, particularly when pretreatment outcome measures appear to have considerable amounts of noise.
Pentobarbital Removal During Continuous Venovenous Hemofiltration: Case Report and Review of the Literature
Authors: Hensler David M. , McConnell Deepika P. , Levasseur-Franklin Kimberly E. , Greathouse Kasey M. 
Published: November 2017

Background: Renal replacement therapy may enhance the elimination of barbiturates. Pentobarbital clearance during continuous venovenous hemofiltration (CVVH) has not been described previously. We report a patient case involving the measurement of serial pentobarbital levels during CVVH and review relevant literature characterizing extracorporeal pentobarbital elimination. Methods: The following is a retrospective report of a previously healthy 26-year-old woman who sustained a severe traumatic brain injury (TBI) and required administration of pentobarbital on hospital day 0 for intracranial pressure (ICP) control. Given concern for interference with the patient’s ongoing neurologic assessments, pentobarbital was discontinued on hospital day 4. The patient’s hospital course was complicated by acute kidney injury (AKI), requiring initiation of CVVH on hospital day 5. Daily serum pentobarbital levels were obtained during CVVH. Results: While on CVVH, the patient’s estimated pentobarbital clearance ranged from 6 to 44 mL/min and the elimination half-life ranged from 17.7 to 65.9 hours. Based on reductions in pentobarbital clearance during CVVH interruption, the elimination of drug was dependent upon extracorporeal removal in this patient. CVVH facilitated pentobarbital elimination in a manner approaching endogenous clearance in healthy individuals. Conclusion: We report clinically significant pentobarbital removal by CVVH in a patient with severe TBI. Application of CVVH may expedite reliable neurologic assessments and facilitate the application of clinical brain death examination following pentobarbital exposure.
Impact of physical activity on the risk of cardiovascular disease in middle-aged and older adults: EPIC Norfolk prospective population study
Authors: Lachman Sangeeta , Boekholdt S Matthijs , Luben Robert N , Sharp Stephen J , Brage Soren , Khaw Kay-Tee , Peters Ron JG , Wareham Nicholas J 
Published: November 2017

Background There is broad consensus that regular physical activity yields major health benefits. However, current guidelines on physical activity are mainly aimed at middle-aged adults. It is unclear whether physical activity also translates into cardiovascular health benefits in older adults. Therefore, we aimed to compare the association between different levels of physical activity and the risk of cardiovascular disease (CVD) in elderly to middle-aged individuals. Methods We analysed data from the EPIC Norfolk prospective population study. Cox proportional hazards models were used to analyse the association between physical activity levels and time to CVD events in three age categories (<55, 55–65 and >65 years). Interaction between age categories and physical activity levels was assessed. Results Analyses were based on 24,502 study participants aged 39–79 years. A total of 5240 CVD events occurred during 412,954 person-years follow-up (median follow-up was 18.0 years). Among individuals aged over 65 years, hazard ratios for CVD were 0.86 (95% confidence interval (CI) 0.78–0.96), 0.87 (95% CI 0.77–0.99) and 0.88 (95% CI 0.77–1.02) in moderately inactive, moderately active and active people, respectively, compared to inactive people. Among people aged 55–65 and less than 55 years, the associations were directionally similar, but not statistically significant. The interaction term between physical activity levels and age categories was not significant ( P = 0.38). Conclusion The inverse association between physical activity and the risk of CVD was significant in elderly and comparable with middle-aged individuals. In addition, we observed that modest levels of physical activity confer benefits in terms of CVD risk, compared to being completely inactive.