bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glucose Metabolism Reprogrammed by Overexpression of IKKϵ Promotes Pancreatic Tumor Growth
Authors: Zubair Haseeb , Azim Shafquat , Srivastava Sanjeev Kumar , Ahmad Aamir , Bhardwaj Arun , Khan Mohammad Aslam , Patel Girijesh Kumar , Arora Sumit , Carter James Elliot , Singh Seema , Singh Ajay Pratap 
Published: October 2016

AbstractAberrant expression of the kinase IKKϵ in pancreatic ductal adenocarcinoma (PDAC) has been associated with poor prognosis. In this study, we define a pathobiologic function for IKKϵ in reprogramming glucose metabolism and driving progression in PDAC. Silencing IKKϵ in PDAC cells, which overexpressed it endogenously, was sufficient to reduce malignant cell growth, clonogenic potential, glucose consumption, lactate secretion, and expression of genes involved in glucose metabolism, without impacting the basal oxygen consumption rate. IKKϵ silencing also attenuated c-Myc in a manner associated with diminished signaling through an AKT/GSK3β/c-MYC phosphorylation cascade that promoted MYC nuclear accumulation. In an orthotopic mouse model, IKKϵ-silenced PDAC exhibited a relative reduction in glucose uptake, tumorigenicity, and metastasis. Overall, our findings offer a preclinical mechanistic rationale to target IKKϵ to improve the therapeutic management of PDAC in patients. Cancer Res; 76(24); 7254–64. ©2016 AACR.
Sex-Specific Associations between One-Carbon Metabolism Indices and Posttranslational Histone Modifications in Arsenic-Exposed Bangladeshi Adults
Authors: Howe Caitlin G. , Liu Xinhua , Hall Megan N. , Ilievski Vesna , Caudill Marie A. , Malysheva Olga , Lomax-Luu Angela M. , Parvez Faruque , Siddique Abu B. , Shahriar Hasan , Uddin Mohammad N. , Islam Tariqul , Graziano Joseph H. , Costa Max , Gamble Mary V. 
Published: October 2016

Abstract
Background: Posttranslational histone modifications (PTHMs) are altered by arsenic, an environmental carcinogen. PTHMs are also influenced by nutritional methyl donors involved in one-carbon metabolism (OCM), which may protect against epigenetic dysregulation.
Methods: We measured global levels of three PTHMs, which are dysregulated in cancers (H3K36me2, H3K36me3, H3K79me2), in peripheral blood mononuclear cells (PBMC) from 324 participants enrolled in the Folic Acid and Creatine Trial, a randomized trial in arsenic-exposed Bangladeshi adults. Sex-specific associations between several blood OCM indices (folate, vitamin B12, choline, betaine, homocysteine) and PTHMs were examined at baseline using regression models, adjusted for multiple tests by controlling for the false discovery rate (PFDR). We also evaluated the effects of folic acid supplementation (400 μg/d for 12 weeks), compared with placebo, on PTHMs.
Results: Associations between choline and H3K36me2 and between vitamin B12 and H3K79me2 differed significantly by sex (Pdiff &lt; 0.01 and &lt;0.05, respectively). Among men, plasma choline was positively associated with H3K36me2 (PFDR &lt; 0.05), and among women, plasma vitamin B12 was positively associated with H3K79me2 (PFDR &lt; 0.01). Folic acid supplementation did not alter any of the PTHMs examined (PFDR = 0.80).
Conclusions: OCM indices may influence PTHMs in a sex-dependent manner, and folic acid supplementation, at this dose and duration, does not alter PTHMs in PBMCs.
Impact: This is the first study to examine the influences of OCM indices on PTHMs in a population that may have increased susceptibility to cancer development due to widespread exposure to arsenic-contaminated drinking water and a high prevalence of hyperhomocysteinemia. Cancer Epidemiol Biomarkers Prev; 26(2); 261–9. ©2016 AACR.
Estimating the Population Impact of Lp(a) Lowering on the Incidence of Myocardial Infarction and Aortic Stenosis—Brief Report
Authors: Afshar Mehdi , Kamstrup Pia R. , Williams Ken , Sniderman Allan D. , Nordestgaard Børge G. , Thanassoulis George 
Published: October 2016

Objective—
High lipoprotein(a) (Lp[a]) is the most common genetic dyslipidemia and is a causal factor for myocardial infarction (MI) and aortic stenosis (AS). We sought to estimate the population impact of Lp(a) lowering that could be achieved in primary prevention using the therapies in development.

Approach and Results—
We used published data from 2 prospective cohorts. High Lp(a) was defined as ≥50 mg/dL (≈20th percentile). Relative risk, attributable risk, the attributable risk percentage, population attributable risk, and the population attributable risk percentage were calculated as measures of the population impact. For MI, the event rate was 4.0% versus 2.8% for high versus low Lp(a) (relative risk, 1.46; 95% confidence interval [CI], 1.45–1.46). The attributable risk was 1.26% (95% CI, 1.24–1.27), corresponding to 31.3% (95% CI, 31.0–31.7) of the excess MI risk in those with high Lp(a). The population attributable risk was 0.21%, representing a population attributable risk percentage of 7.13%. For AS, the event rate was 1.51% versus 0.78% for high versus low Lp(a) (relative risk, 1.95; 95% CI, 1.94–1.97). The attributable risk was 0.74% (95% CI, 0.73–0.75), corresponding to 48.8% (95% CI, 48.3–49.3) of the excess AS risk in those with high Lp(a). The population attributable risk was 0.13%, representing a population attributable risk percentage of 13.9%. In sensitivity analyses targeting the top 10% of Lp(a), the population attributable risk percentage was 5.2% for MI and 7.8% for AS.

Conclusions—
Lp(a) lowering among the top 20% of the population distribution for Lp(a) could prevent 1 in 14 cases of MI and 1 in 7 cases of AS, suggesting a major impact on reducing the burden of cardiovascular disease. Targeting the top 10% could prevent 1 in 20 MI cases and 1 in 12 AS cases.
Spatiotemporal Lake Skin Summer Temperature Trends in the Northeast United States
Authors: Torbick Nathan , Ziniti Beth , Wu Shuang , Linder Ernst 
Published: October 2016

Abstract
Lakes have been suggested as an indicator of climate change; however, long-term, systematic records of lake temperature are limited. Satellite remote sensing is capable of supporting lake temperature mapping with the advantage of large-area and systematic observations. The goal of this research application was to assess spatiotemporal trends in lake skin temperature for all lakes over 8 ha across northern New England for the past three decades. Nearly 10 000 Landsat scenes for July, August, and September from 1984 to 2014 were processed using MODTRAN and MERRA parameterizations to generate atmospherically corrected lake skin temperature records. Results show, on average, lakes warmed at a rate of 0.8°C decade−1, with smaller lakes warming at a faster rate. Complementing regression and space–time analyses showed similar results (R2 = 0.63) for lake temperature trends and found lakes, on average, are warming faster than daily maximum or minimum air temperature. No major hot spots were found as lake temperature changes were heterogeneous on a local scale and evenly distributed across the region. Maximum and minimum daily temperature, lake size, and elevation were found as significant drivers of lake temperature. This effort provides the first regionally focused and comprehensive spatiotemporal assessment of thousands (n = 3955) of lakes concentrated in one geographic region. The approach is scalable and adaptable to any region for assessing lake temperature trends and potential drivers.
Satellite Sounder Observations of Contrasting Tropospheric Moisture Transport Regimes: Saharan Air Layers, Hadley Cells, and Atmospheric Rivers
Authors: Nalli Nicholas R. , Barnet Christopher D. , Reale Tony , Liu Quanhua , Morris Vernon R. , Spackman J. Ryan , Joseph Everette , Tan Changyi , Sun Bomin , Tilley Frank , Leung L. Ruby , Wolfe Daniel 
Published: October 2016

Abstract
This paper examines the performance of satellite sounder atmospheric vertical moisture profiles under tropospheric conditions encompassing moisture contrasts driven by convection and advection transport mechanisms, specifically Atlantic Ocean Saharan air layers (SALs), tropical Hadley cells, and Pacific Ocean atmospheric rivers (ARs). Operational satellite sounder moisture profile retrievals from the Suomi National Polar-Orbiting Partnership (SNPP) NOAA Unique Combined Atmospheric Processing System (NUCAPS) are empirically assessed using collocated dedicated radiosonde observations (raobs) obtained from ocean-based intensive field campaigns. The raobs from these campaigns provide uniquely independent correlative truth data not assimilated into numerical weather prediction (NWP) models for satellite sounder validation over oceans. Although ocean cases are often considered “easy” by the satellite remote sensing community, these hydrometeorological phenomena present challenges to passive sounders, including vertical gradient discontinuities (e.g., strong inversions), as well as persistent uniform clouds, aerosols, and precipitation. It is found that the operational satellite sounder 100-layer moisture profile NUCAPS product performs close to global uncertainty requirements in the SAL/Hadley cell environment, with biases relative to raob within 10% up to 350 hPa. In the more difficult AR environment, bias relative to raob is found to be within 20% up to 400 hPa. In both environments, the sounder moisture retrievals are comparable to NWP model outputs, and cross-sectional analyses show the capability of the satellite sounder for detecting and resolving these tropospheric moisture features, thereby demonstrating a near-real-time forecast utility over these otherwise raob-sparse regions.
Weather Radar Spatiotemporal Saliency: A First Look at an Information Theory–Based Human Attention Model Adapted to Reflectivity Images
Authors: Schvartzman David , Torres Sebastián , Yu Tian-You 
Published: October 2016

AbstractForecasters often monitor and analyze large amounts of data, especially during severe weather events, which can be overwhelming. Thus, it is important to effectively allocate their finite perceptual and cognitive resources for the most relevant information. This paper introduces a novel analysis tool that quantifies the amount of spatial and temporal information in time series of constant-elevation weather radar reflectivity images. The proposed Weather Radar Spatiotemporal Saliency (WR–STS) is based on the mathematical model of the human attention system (referred to as saliency) adapted to radar reflectivity images and makes use of information theory concepts. It is shown that WR-STS highlights spatially and temporally salient (attention attracting) regions in weather radar reflectivity images, which can be associated with meteorologically important regions. Its skill in highlighting current regions of interest is assessed by analyzing the WR-STS values within regions in which severe weather is likely to strike in the near future as defined by National Weather Service forecasters. The performance of WR-STS is demonstrated for a severe weather case and analyzed for a set of 10 diverse cases. Results support the hypothesis that WR-STS can identify regions with meteorologically important echoes and could assist in discerning fast-changing, highly structured weather echoes during complex severe weather scenarios, ultimately allowing forecasters to focus their attention and spend more time analyzing those regions.
The protective effects of bone morphogenetic protein-7 against epithelial injury and matrix metalloproteases upregulation induced by silica in vitro
Authors: Liang D , An G , Zhu Z , Wang Y , Yang G , Li X , Niu P , Chen L , Tian L 
Published: October 2016

Objective: We investigate the effects of bone morphogenetic protein-7 (BMP-7) on models with silica-induced and macrophage-mediated fibrosis and its possible mechanisms in vitro. Methods: Rat alveolar II epithelial (RLE-6TN) cells were incubated with the supernatant of mouse macrophage-like cells (RAW264.7) and treated with 0, 25, 50, and 100 μg/mL silica. Using Western blotting, the epithelial markers (surfactant proteins-C and E-cadherin) and the mesenchymal markers (fibronectin (FN) and viminten (Vim)) were detected. After neutralizing the BMP-7, the progress of fibrosis was assessed by the content of hydroxyproline (Hyp) and collagen I, III protein levels as well as the Smad signaling pathway proteins, including phosphorylated Smad1/5(P-Smad1/5) and phosphorylated Smad2/3(P-Smad2/3). Collagen I was also identified by immunofluorescence and pretreated with SB-431542, LDN-193189, or anti-BMP-7-neutralizing antibody. In addition, the levels of matrix metalloproteinase-2 (MMP-2) and MMP-9 were detected using Western blotting. Results: The model of RLE-6TN cells was established successfully, the expressions of Vim, FN, MMP-2, and MMP-9 were upregulated, while the concentration of silica is increased. Neutralizing BMP-7 stimulated the decrease of P-Smad1/5 and the increase of P-Smad2/3, as well as the collagen I, collagen III, FN, and Hyp via Smad signaling pathway. Furthermore, pretreated with LDN-193189 or anti-BMP-7-neutralizing antibody, the expression of collagen I was increased, yet it was decreased with SB-431542 intervention. Conclusion: The activated BMP/Smad and suppressed transforming growth factor-β/Smad pathways could suppress silica-induced fibrosis via a MMP-dependent mechanism. BMP-7 is expected to be the optimized strategy of delaying the interstitial changes.
Why Capitalism?
Authors: Iley-Williamson Dan 
Published: October 2016

An endorsement of capitalism is often thought to be a concession to human selfishness. The thought often runs that while some other socioeconomic system – socialism, perhaps – would be morally preferable, we cannot live up to those high ideals. Jason Brennan has recently attempted to show that this widespread view is mistaken. Even in terms of ideal theory, Brennan argues, capitalism is morally superior to its rival. To make this case, Brennan critiques the work of the late socialist political philosopher, GA Cohen. Brennan argues that Cohen’s justification of socialism is ill-conceived, and in fact, Cohen’s failure helps to reveal that capitalism is morally superior to socialism. In this review article, I argue that Brennan’s critique and attempted counter-claim are unsuccessful. Among other failings, Brennan leaves us with no adequate answer to the question, why capitalism? Cohen GA (2009) Why Not Socialism? Princeton, NJ: Princeton University Press. Brennan J (2014) Why Not Capitalism? New York: Routledge.
Acute effects of the glucagon-like peptide-1 receptor agonist, exenatide, on blood pressure and heart rate responses to intraduodenal glucose infusion in type 2 diabetes
Authors: Thazhath Sony S , Marathe Chinmay S , Wu Tongzhi , Chang Jessica , Khoo Joan , Kuo Paul , Checklin Helen L , Bound Michelle J , Rigda Rachael S , Horowitz Michael , Jones Karen L , Rayner Christopher K 
Published: October 2016

Aim: To evaluate the effects of the glucagon-like peptide-1 receptor agonist, exenatide, on blood pressure and heart rate during an intraduodenal glucose infusion in type 2 diabetes. Methods: Nine subjects with type 2 diabetes were randomised to receive intravenous exenatide or saline control in a crossover design. Glucose (3 kcal min−1) was infused via an intraduodenal manometry catheter for 60 min. Blood pressure, heart rate, and the frequency and amplitude of duodenal pressure waves were measured at regular intervals. Gastrointestinal symptoms were monitored using 100 mm visual analogue scales. Results: During intraduodenal glucose infusion (0–60 min), diastolic ( p(0–60) = 0.03) and mean arterial ( p(0–60) = 0.03) blood pressures and heart rate ( p(0–60) = 0.06; p(0–120) = 0.03)) were higher with exenatide compared to placebo. The increase in the area under the curve for diastolic blood pressure and mean arterial blood pressure was related directly to the suppression of the duodenal motility index with exenatide compared to control ( p = 0.007 and 0.04, respectively). Conclusion: In type 2 diabetes, intravenous exenatide increases mean arterial blood pressure and heart rate during an intraduodenal glucose infusion, supporting the need for further research with exenatide for its potential use in postprandial hypotension.
Balancing Opposing Forces—A Nested Process Evaluation Study Protocol for a Stepped Wedge Designed Cluster Randomized Controlled Trial of an Experience Based Codesign Intervention
Authors: Palmer Victoria Jane , Piper Donella , Richard Lauralie , Furler John , Herrman Helen , Cameron Jacqui , Godbee Kali , Pierce David , Callander Rosemary , Weavell Wayne , Gunn Jane , Iedema Rick 
Published: October 2016

Background: Process evaluations are essential to understand the contextual, relational, and organizational and system factors of complex interventions. The guidance for developing process evaluations for randomized controlled trials (RCTs) has until recently however, been fairly limited. Method/Design: A nested process evaluation (NPE) was designed and embedded across all stages of a stepped wedge cluster RCT called the CORE study. The aim of the CORE study is to test the effectiveness of an experience-based codesign methodology for improving psychosocial recovery outcomes for people living with severe mental illness (service users). Process evaluation data collection combines qualitative and quantitative methods with four aims: (1) to describe organizational characteristics, service models, policy contexts, and government reforms and examine the interaction of these with the intervention; (2) to understand how the codesign intervention works, the cluster variability in implementation, and if the intervention is or is not sustained in different settings; (3) to assist in the interpretation of the primary and secondary outcomes and determine if the causal assumptions underpinning the codesign interventions are accurate; and (4) to determine the impact of a purposefully designed engagement model on the broader study retention and knowledge transfer in the trial. Discussion: Process evaluations require prespecified study protocols but finding a balance between their iterative nature and the structure offered by protocol development is an important step forward. Taking this step will advance the role of qualitative research within trials research and enable more focused data collection to occur at strategic points within studies.
Barriers and facilitators to epilepsy self-management for patients with physical and psychological co-morbidity
Authors: Perzynski Adam T , Ramsey Riane K , Colón-Zimmermann Kari , Cage Jamie , Welter Elisabeth , Sajatovic Martha 
Published: October 2016

ObjectivesThis exploratory study identifies barriers and facilitators to self-management to inform future epilepsy self-management interventions for persons who have epilepsy complicated by co-morbid mental health conditions and serious medical events.MethodsFocus group methods were used in a series of community advisory board meetings. Analysis was conducted using a thematic, constant comparative approach aiming to describe the range of barriers and facilitators salient to participants. There were a total of 22 participants, including 8 health professionals, 9 patients with epilepsy, and 5 care partners. Mean age was 49.1 (SD = 11.0, range 32–69), 11 (50%) were female, and 11 (50%) were male. For those with epilepsy, mean years having epilepsy was 24.7 (SD = 19.9, range 1–58 years).ResultsIndividual psychological barriers (mental illness, fatigue, and psychological distress) prominently interfered with health behaviors. Community and family barriers included stigma, lack of epilepsy knowledge, and poor social support. Facilitators included planning for seizures, learning about medications, stress management, socializing with others, and talking with other epilepsy patients.DiscussionQualitative evidence in this study suggests a linkage between social integration and positive health behaviors. Future efforts to embed patients with epilepsy and their caregivers into clinical care processes could offset barriers and enhance facilitators.
A novel primary-specialist care collaborative demonstration project to improve the access and health care of medically complex patients
Authors: Siu Henry Yu-Hin , Steward Nicole , Peter Jessica , Cooke Laurel , Arnold Donald M , Price David 
Published: October 2016

Objective Medically complex patients experience fragmented health care compounded by long wait times. The MedREACH program was developed to improve access and overall system experience for medically complex patients. Program description MedREACH is a novel primary–tertiary care collaborative demonstration program that features community nursing outreach, community specialist outreach, and a multi-specialty consultation clinic. Methods All 179 patients, referring primary care clinicians, and specialists involved were eligible to participate. Patient and clinician feedback were elicited by feedback surveys. Process measures were evaluated by participant retrospective chart reviews. Community nursing outreach patients completed the Goal Attainment Scale. Results Forty-eight patients and 22 clinicians consented to the feedback survey. About 75% of patients were seen within 2 weeks of referral. Patients spent an average of 3, 1.63, and 1.2 visits with the nursing outreach, multi-specialty clinic, and specialist outreach, respectively. Patients indicated a better medical experience, health enablement, and goals attainment. Family physicians felt more supported in the community management of medically complex patients and, overall, physicians felt MedREACH could improve collaborative care for medically complex patients. Qualitative analysis of clinician responses identified the need for increased mental health services. Discussion MedREACH demonstrates a patient-centered link between primary and tertiary care that could improve health care access and overall experience.
Covered versus bare stents for transjugular intrahepatic portosystemic shunt: an updated meta-analysis of randomized controlled trials
Authors: Qi Xingshun , Tian Yulong , Zhang Wei , Yang Zhiping , Guo Xiaozhong 
Published: October 2016

Background: Transjugular intrahepatic portosystemic shunt (TIPS) is a standard treatment option for the management of portal hypertension in liver cirrhosis. Since the introduction of covered stents, shunt patency has been greatly improved. However, it remains uncertain about whether covered stents could improve survival. A meta-analysis of randomized controlled trials has been performed to compare the outcomes of covered versus bare stents for TIPS. Methods: PubMed, EMBASE, and Cochrane Library databases were searched to identify the relevant randomized controlled trials. Overall survival, shunt patency, and hepatic encephalopathy were the major endpoints. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated. Heterogeneity was calculated. Cochrane risk of bias tool was employed. Results: Overall, 119 papers were identified. Among them, four randomized controlled trials were eligible. Viatorr covered stents alone, Fluency covered stents alone, and Viatorr plus Fluency covered stents were employed in one, two, and one randomized controlled trials, respectively. Risk of bias was relatively low. Meta-analyses demonstrated that the covered-stents group had significantly higher probabilities of overall survival (HR = 0.67, 95% CI = 0.50–0.90, p = 0.008) and shunt patency (HR = 0.42, 95% CI = 0.29–0.62, p < 0.0001) than the bare-stents group. Additionally, the covered-stents group might have a lower risk of hepatic encephalopathy than the bare-stents group (HR = 0.70, 95% CI = 0.49–1.00, p = 0.05). The heterogeneity among studies was not statistically significant in the meta-analyses. Conclusions: Compared with bare stents, covered stents for TIPS may improve the overall survival. In the era of covered stents, the indications for TIPS may be further expanded.