bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chronic Use of NSAIDs and/or Statins Does Not Affect PSA or PSA Velocity in Men at High Risk for Prostate Cancer
Authors: Algotar Amit M. , Behnejad Roxanna , Stratton M. Suzanne , Stratton Steven P. 
Published: July 2014

Abstract
Background: PSA and PSA velocity (PSAV, rate of PSA change over time) are biomarkers for diagnosis and prognosis of prostate cancer. Men who are at high risk for prostate cancer also have associated comorbidities for which they are taking NSAIDs and statins for long periods; therefore, it is important to understand the effect of these medications on markers used to assess prostate cancer risk.
Methods: Using a population of 699 men, multiple linear regressions were used to investigate the associations between PSA and concomitant medications, and mixed-effects models were used to investigate these associations with PSAV.
Results: After adjusting for selenium use, age, race, body mass index, and pack-years of smoking, aspirin, other NSAIDs, or statins did not demonstrate statistically significant associations with PSA (P = 0.79, 0.68, and 0.79, respectively) or PSAV (P = 0.23, 0.43, and 0.84, respectively). Results were not altered upon stratifying the sample between men who developed prostate cancer during the course of the study and those who did not.
Conclusions: Results from this study indicate that chronic use of aspirin, other NSAIDs, or statins did not affect PSA levels or PSAV in men at high risk for prostate cancer. Larger prospective studies designed to investigate these relationships are needed to confirm this result.
Impact: Long-term use of NSAIDs or statins in men at high risk for prostate cancer may not interfere with the diagnosis or prognosis of this disease, and supports appropriate use of these medications with regard to prostate cancer risk. Cancer Epidemiol Biomarkers Prev; 23(10); 2196–8. ©2014 AACR.
SMAD4 Suppresses AURKA-Induced Metastatic Phenotypes via Degradation of AURKA in a TGFβ-Independent Manner
Authors: Jia Lina , Lee Hun Seok , Wu Chun Fu , Kundu Juthika , Park Sang Gyu , Kim Ryong Nam , Wang Li-Hui , Erkin Özgür Cem , Choi Jong-Sun , Chae Seoung Wan , Yang Ho Bin , Choi Yoon-La , Shin Young Kee 
Published: July 2014

Abstract
SMAD4 has been suggested to inhibit the activity of the WNT/β-catenin signaling pathway in cancer. However, the mechanism by which SMAD4 antagonizes WNT/β-catenin signaling in cancer remains largely unknown. Aurora A kinase (AURKA), which is frequently overexpressed in cancer, increases the transcriptional activity of β-catenin/T-cell factor (TCF) complex by stabilizing β-catenin through the inhibition of GSK-3β. Here, SMAD4 modulated AURKA in a TGFβ-independent manner. Overexpression of SMAD4 significantly suppressed AURKA function, including colony formation, migration, and invasion of cell lines. In addition, SMAD4 bound to AURKA induced degradation of AURKA by the proteasome. A luciferase activity assay revealed that the transcriptional activity of the β-catenin/TCF complex was elevated by AURKA, but decreased by SMAD4 overexpression. Moreover, target gene analysis showed that SMAD4 abrogated the AURKA-mediated increase of β-catenin target genes. However, this inhibitory effect of SMAD4 was abolished by overexpression of AURKA or silencing of AURKA in SMAD4-overexpressed cells. Meanwhile, the SMAD4-mediated repression of AURKA and β-catenin was independent of TGFβ signaling because blockage of TGFβR1 or restoration of TGFβ signaling did not prevent suppression of AURKA and β-catenin signaling by SMAD4. These results indicate that the tumor-suppressive function of SMAD4 is mediated by downregulation of β-catenin transcriptional activity via AURKA degradation in a TGFβ-independent manner.
Implications: SMAD4 interacts with AURKA and antagonizes its tumor-promoting potential, thus demonstrating a novel mechanism of tumor suppression. Mol Cancer Res; 12(12); 1779–95. ©2014 AACR.
Convergence of Nanotechnology and Cancer Prevention: Are We There Yet?
Authors: Menter David G. , Patterson Sherri L. , Logsdon Craig D. , Kopetz Scott , Sood Anil K. , Hawk Ernest T. 
Published: July 2014

Abstract
Nanotechnology is emerging as a promising modality for cancer treatment; however, in the realm of cancer prevention, its full utility has yet to be determined. Here, we discuss the potential of integrating nanotechnology in cancer prevention to augment early diagnosis, precision targeting, and controlled release of chemopreventive agents, reduced toxicity, risk/response assessment, and personalized point-of-care monitoring. Cancer is a multistep, progressive disease; the functional and acquired characteristics of the early precancer phenotype are intrinsically different from those of a more advanced anaplastic or invasive malignancy. Therefore, applying nanotechnology to precancers is likely to be far more challenging than applying it to established disease. Frank cancers are more readily identifiable through imaging and biomarker and histopathologic assessment than their precancerous precursors. In addition, prevention subjects routinely have more rigorous intervention criteria than therapy subjects. Any nanopreventive agent developed to prevent sporadic cancers found in the general population must exhibit a very low risk of serious side effects. In contrast, a greater risk of side effects might be more acceptable in subjects at high risk for cancer. Using nanotechnology to prevent cancer is an aspirational goal, but clearly identifying the intermediate objectives and potential barriers is an essential first step in this exciting journey. Cancer Prev Res; 7(10); 973–92. ©2014 AACR.
Olive Oil Polyphenols Enhance High-Density Lipoprotein Function in Humans
Authors: Hernáez Álvaro , Fernández-Castillejo Sara , Farràs Marta , Catalán Úrsula , Subirana Isaac , Montes Rosa , Solà Rosa , Muñoz-Aguayo Daniel , Gelabert-Gorgues Anna , Díaz-Gil Óscar , Nyyssönen Kristiina , Zunft Hans-Joachim F. , de la Torre Rafael , Martín-Peláez Sandra , Pedret Anna , Remaley Alan T. , Covas María-Isabel , Fitó Montserrat 
Published: July 2014

Objective—
Olive oil polyphenols have shown beneficial properties against cardiovascular risk factors. Their consumption has been associated with higher cholesterol content in high-density lipoproteins (HDL). However, data on polyphenol effects on HDL quality are scarce. We, therefore, assessed whether polyphenol-rich olive oil consumption could enhance the HDL main function, its cholesterol efflux capacity, and some of its quality-related properties, such HDL polyphenol content, size, and composition.

Approach and Results—

A randomized, crossover, controlled trial with 47 healthy European male volunteers was performed. Participants ingested 25 mL/d of polyphenol-poor (2.7 mg/kg) or polyphenol-rich (366 mg/kg) raw olive oil in 3-week intervention periods, preceded by 2-week washout periods. HDL cholesterol efflux capacity significantly improved after polyphenol-rich intervention versus the polyphenol-poor one (+3.05% and −2.34%, respectively;
P
=0.042). Incorporation of olive oil polyphenol biological metabolites to HDL, as well as large HDL (HDL
2
) levels, was higher after the polyphenol-rich olive oil intervention, compared with the polyphenol-poor one. Small HDL (HDL
3
) levels decreased, the HDL core became triglyceride-poor, and HDL fluidity increased after the polyphenol-rich intervention.

Conclusions—
Olive oil polyphenols promote the main HDL antiatherogenic function, its cholesterol efflux capacity. These polyphenols increased HDL size, promoted a greater HDL stability reflected as a triglyceride-poor core, and enhanced the HDL oxidative status, through an increase in the olive oil polyphenol metabolites content in the lipoprotein. Our results provide for the first time a first-level evidence of an enhancement in HDL function by polyphenol-rich olive oil.
Impact of Phospholipid Transfer Protein on Nascent High-Density Lipoprotein Formation and Remodeling
Authors: Ji Ailing , Wroblewski Joanne M. , Webb Nancy R. , van der Westhuyzen Deneys R. 
Published: July 2014

Objective—
Phospholipid transfer protein (PLTP), which binds phospholipids and facilitates their transfer between lipoproteins in plasma, plays a key role in lipoprotein remodeling, but its influence on nascent high-density lipoprotein (HDL) formation is not known. The effect of PLTP overexpression on apolipoprotein A-I (apoA-I) lipidation by primary mouse hepatocytes was investigated.

Approach and Results—
Overexpression of PLTP through an adenoviral vector markedly affected the amount and size of lipidated apoA-I species that were produced in hepatocytes in a dose-dependent manner, ultimately generating particles that were <7.1 nm but larger than lipid-free apoA-I. These <7.1-nm small particles generated in the presence of overexpressed PLTP were incorporated into mature HDL particles more rapidly than apoA-I both in vivo and in vitro and were less rapidly cleared from mouse plasma than lipid-free apoA-I. The <7.1-nm particles promoted both cellular cholesterol and phospholipid efflux in an ATP-binding cassette transporter A1–dependent manner, similar to apoA-I in the presence of PLTP. Lipid-free apoA-I had a greater efflux capacity in the presence of PLTP than in the absence of PLTP, suggesting that PLTP may promote ATP-binding cassette transporter A1–mediated cholesterol and phospholipid efflux. These results indicate that PLTP alters nascent HDL formation by modulating the lipidated species and by promoting the initial process of apoA-I lipidation.

Conclusions—
Our findings suggest that PLTP exerts significant effects on apoA-I lipidation and nascent HDL biogenesis in hepatocytes by promoting ATP-binding cassette transporter A1–mediated lipid efflux and the remodeling of nascent HDL particles.
Reciprocal Effects of Systemic Inflammation and Brain Natriuretic Peptide on Adiponectin Biosynthesis in Adipose Tissue of Patients With Ischemic Heart Disease
Authors: Antonopoulos Alexios S. , Margaritis Marios , Coutinho Patricia , Digby Janet , Patel Rikhil , Psarros Constantinos , Ntusi Ntobeko , Karamitsos Theodoros D. , Lee Regent , De Silva Ravi , Petrou Mario , Sayeed Rana , Demosthenous Michael , Bakogiannis Constantinos , Wordsworth Paul B. , Tousoulis Dimitris , Neubauer Stefan , Channon Keith M. , Antoniades Charalambos 
Published: July 2014

Objective—
To explore the role of systemic inflammation in the regulation of adiponectin levels in patients with ischemic heart disease.

Approach and Results—

In a cross-sectional study of 575 subjects, serum adiponectin was compared between healthy subjects, patients with coronary artery disease with no/mild/severe heart failure (HF), and patients with nonischemic HF. Adiponectin expression and release from femoral, subcutaneous and thoracic adipose tissue was determined in 258 additional patients with coronary artery bypass grafting. Responsiveness of the various human adipose tissue depots to interleukin-6, tumor necrosis factor-α, and brain natriuretic peptide (BNP) was examined by using ex vivo models of human fat. The effects of inducible low-grade inflammation were tested by using the model of
Salmonella typhi
vaccine-induced inflammation in healthy individuals. In the cross-sectional study, HF strikingly increased adiponectin levels. Plasma BNP was the strongest predictor of circulating adiponectin and its release from all adipose tissue depots in patients with coronary artery bypass grafting, even in the absence of HF. Femoral AT was the depot with the least macrophages infiltration and the largest adipocyte cell size and the only responsive to systemic and ex vivo proinflammatory stimulation (effect reversible by BNP). Low-grade inflammation reduced circulating adiponectin levels, while circulating BNP remained unchanged.

Conclusions—
This study demonstrates the regional variability in the responsiveness of human adipose tissue to systemic inflammation and suggests that BNP (not systemic inflammation) is the main driver of circulating adiponectin in patients with advanced atherosclerosis even in the absence of HF. Any interpretation of circulating adiponectin as a biomarker should take into account the underlying disease state, background inflammation, and BNP levels.
Thyroid Hormones and Coronary Artery Calcification in Euthyroid Men and Women
Authors: Zhang Yiyi , Kim Bo-Kyoung , Chang Yoosoo , Ryu Seungho , Cho Juhee , Lee Won-Young , Rhee Eun-Jung , Kwon Min-Jung , Rampal Sanjay , Zhao Di , Pastor-Barriuso Roberto , Lima Joao A. , Shin Hocheol , Guallar Eliseo 
Published: July 2014

Objective—
Overt and subclinical hypothyroidism are risk factors for atherosclerosis. It is unclear whether thyroid hormone levels within the normal range are also associated with atherosclerosis measured by coronary artery calcium (CAC).

Approach and Results—

We conducted a cross-sectional study of 41 403 apparently healthy young and middle-aged men and women with normal thyroid hormone levels. Free thyroxin, free triiodothyronine, and thyroid-stimulating hormone levels were measured by electrochemiluminescent immunoassay. CAC score was measured by multidetector computed tomography. The multivariable adjusted CAC ratios comparing the highest versus the lowest quartile of thyroid hormones were 0.74 (95% confidence interval, 0.60–0.91;
P
for trend <0.001) for free thyroxin, 0.81 (0.66–1.00;
P
for trend=0.05) for free triiodothyronine, and 0.78 (0.64–0.95;
P
for trend=0.01) for thyroid-stimulating hormone. Similarly, the odds ratios for detectable CAC (CAC >0) comparing the highest versus the lowest quartiles of thyroid hormones were 0.87 (0.79–0.96;
P
for linear trend <0.001) for free thyroxin, 0.90 (0.82–0.99;
P
for linear trend=0.02) for free triiodothyronine, and 0.91 (0.83–1.00;
P
for linear trend=0.03) for thyroid-stimulating hormone.

Conclusions—
In a large cohort of apparently healthy young and middle-aged euthyroid men and women, low-normal free thyroxin and thyroid-stimulating hormone were associated with a higher prevalence of subclinical coronary artery disease and with a greater degree of coronary calcification.
Intraventricular Thrombolysis in Intracerebral Hemorrhage Requiring Ventriculostomy
Authors: Moradiya Yogesh , Murthy Santosh B. , Newman-Toker David E. , Hanley Daniel F. , Ziai Wendy C. 
Published: July 2014

Background and Purpose—
Intraventricular thrombolysis (IVT) is a promising treatment in facilitating intraventricular clot resolution after intraventricular hemorrhage. We examined in-hospital outcomes and resource utilization after thrombolysis in patients with intraventricular hemorrhage requiring ventriculostomy in a real-world setting.

Methods—
We identified adult patients with primary diagnosis of nontraumatic intracerebral hemorrhage requiring ventriculostomy from the Nationwide Inpatient Sample from 2002 to 2011. We compared demographic and hospital characteristics, comorbidities, inpatient outcomes, and resource utilization measures between patients treated with IVT and those managed with ventriculostomy, but without IVT. Population estimates were extrapolated using standard Nationwide Inpatient Sample weighting algorithms.

Results—

We included 34 044 patients in the analysis, of whom 1133 (3.3%) received IVT. The thrombolysis group had significantly lower inpatient mortality (32.4% versus 41.6%;
P
=0.001) and it remained lower after controlling for baseline demographics, hospital characteristics, comorbidity, case severity, and withdrawal of care status (adjusted odds ratio, 0.670; 95% confidence interval, 0.520–0.865;
P
=0.002). There was a trend toward favorable discharge (home or rehabilitation) among the thrombolysis cohort (adjusted odds ratio, 1.335; 95% confidence interval, 0.983–1.812;
P
=0.064). The adjusted rates of bacterial meningitis and ventricular shunt placement were similar between groups. The thrombolysis group had longer length of stay and higher inflation-adjusted cost of care, but cost of care per day length of stay was similar to the non-IVT group.

Conclusions—
IVT for intracerebral hemorrhage requiring ventriculostomy resulted in lower inpatient mortality and a trend toward favorable discharge outcome with similar rates of inpatient complications compared with the non-IVT group.
Rehearsing Biological Motion in Working Memory: An EEG Study
Authors: Gao Zaifeng , Bentin Shlomo , Shen Mowei 
Published: July 2014

Abstract
Holding biological motion (BM), the movements of animate entities, in working memory (WM) is important to our daily social life. However, how BM is maintained in WM remains unknown. The current study investigated this issue and hypothesized that, analogous to BM perception, the human mirror neuron system (MNS) is involved in rehearsing BM in WM. To examine the MNS hypothesis of BM rehearsal, we used an EEG index of mu suppression (8–12 Hz), which has been linked to the MNS. Using a change detection task, we manipulated the BM memory load in three experiments. We predicted that mu suppression in the maintenance phase of WM would be modulated by the BM memory load; moreover, a negative correlation between the number of BM stimuli in WM and the degree of mu suppression may emerge. The results of Experiment 1 were in line with our predictions and revealed that mu suppression increased as the memory load increased from two to four BM stimuli; however, mu suppression then plateaued, as WM could only hold, at most, four BM stimuli. Moreover, the predicted negative correlation was observed. Corroborating the findings of Experiment 1, Experiment 2 further demonstrated that once participants used verbal codes to process the motion information, the mu suppression or modulation by memory load vanished. Finally, Experiment 3 demonstrated that the findings in Experiment 1 were not limited to one specific type of stimuli. Together, these results provide evidence that the MNS underlies the process of rehearsing BM in WM.
Autobiographically Significant Concepts: More Episodic than Semantic in Nature? An Electrophysiological Investigation of Overlapping Types of Memory
Authors: Renoult Louis , Davidson Patrick S. R. , Schmitz Erika , Park Lillian , Campbell Kenneth , Moscovitch Morris , Levine Brian 
Published: July 2014

Abstract
A common assertion is that semantic memory emerges from episodic memory, shedding the distinctive contexts associated with episodes over time and/or repeated instances. Some semantic concepts, however, may retain their episodic origins or acquire episodic information during life experiences. The current study examined this hypothesis by investigating the ERP correlates of autobiographically significant (AS) concepts, that is, semantic concepts that are associated with vivid episodic memories. We inferred the contribution of semantic and episodic memory to AS concepts using the amplitudes of the N400 and late positive component, respectively. We compared famous names that easily brought to mind episodic memories (high AS names) against equally famous names that did not bring such recollections to mind (low AS names) on a semantic task (fame judgment) and an episodic task (recognition memory). Compared with low AS names, high AS names were associated with increased amplitude of the late positive component in both tasks. Moreover, in the recognition task, this effect of AS was highly correlated with recognition confidence. In contrast, the N400 component did not differentiate the high versus low AS names but, instead, was related to the amount of general knowledge participants had regarding each name. These results suggest that semantic concepts high in AS, such as famous names, have an episodic component and are associated with similar brain processes to those that are engaged by episodic memory. Studying AS concepts may provide unique insights into how episodic and semantic memory interact.
A Time Travel Dialogue
Authors: Carroll John W. 
Published: July 2014

Is time travel just a confusing plot device deployed by science fiction authors and Hollywood filmmakers to amaze and amuse? Or might empirical data prompt a scientific hypothesis of time travel? Structured on a fascinating dialogue involving a distinguished physicist, Dr. Rufus, a physics graduate student and a computer scientist this book probes an experimentally supported hypothesis of backwards time travel – and in so doing addresses key metaphysical issues, such as causation, identity over time and free will. The setting is the Jefferson National Laboratory during a period of five days in 2010. Dr. Rufus’s experimental search for the psi-lepton and the resulting intractable data spurs the discussion on time travel. She and her two colleagues are pushed by their observations to address the grandfather paradox and other puzzles about backwards causation, with attention also given to causal loops, multi-dimensional time, and the prospect that only the present exists. Sensible solutions to the main puzzles emerge, ultimately advancing the case for time travel really being possible.
'A Time Travel Dialogue' addresses the possibility of time travel, approaching familiar paradoxes in a rigorous, engaging, and fun manner. It follows in the long philosophical tradition of using dialogue to present philosophical ideas and arguments, but is ground breaking in its use of the dialogue format to introduce readers to the metaphysics of time travel, and is also distinctive in its use of lab results to drive philosophical analysis. The discussion of data that might decide whether time is one-dimensional (one timeline) or multi-dimensional (branching time) is especially novel.
A Method for Wind Speed Forecasting in Airports Based on Nonparametric Regression
Authors: Rozas-Larraondo Pablo , Inza Iñaki , Lozano Jose A. 
Published: July 2014

Abstract
Wind is one of the parameters best predicted by numerical weather models, as it can be directly calculated from the physical equations of pressure that govern its movement. However, local winds are considerably affected by topography, which global numerical weather models, due to their limited resolution, are not able to reproduce. To improve the skill of numerical weather models, statistical and data analysis methods can be used. Machine learning techniques can be applied to train a model with data coming from both the model and observations in the area of interest. In this paper, a new method based on nonparametric multivariate locally weighted regression is studied for improving the forecasted wind speed of a numerical weather model. Wind direction data are used to build different regression models, as a way of accounting for the effect of surrounding topography. The use of this technique offers similar levels of accuracy for wind speed forecasts compared with other machine learning algorithms with the advantage of being more intuitive and easy to interpret.