bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthesis and Evaluation of the Novel Prostamide, 15-Deoxy, Δ12,14-Prostamide J2, as a Selective Antitumor Therapeutic
Authors: Ladin Daniel A. , Soliman Eman , Escobedo Rene , Fitzgerald Timothy L. , Yang Li V. , Burns Colin , Van Dross Rukiyah 
Published: March 2017

Abstract
15-deoxy, Δ12,14-prostaglandin J2-ethanolamide, also known as 15-deoxy, Δ12,14-prostamide J2 (15d-PMJ2) is a novel product of the metabolism of arachidonoyl ethanolamide (AEA) by COX-2. 15d-PMJ2 preferentially induced cell death and apoptosis in tumorigenic A431 keratinocytes and B16F10 melanoma cells compared with nontumorigenic HaCaT keratinocytes and Melan-A melanocytes. Activation of the ER stress execution proteins, PERK and CHOP10, was evaluated to determine whether this process was involved in 15d-PMJ2 cell death. 15d-PMJ2 increased the phosphorylation of PERK and expression of CHOP10 in tumorigenic but not nontumorigenic cells. The known ER stress inhibitors, salubrinal and 4-phenylbutaric acid, significantly inhibited 15d-PMJ2–mediated apoptosis, suggesting ER stress as a primary apoptotic mediator. Furthermore, the reactive double bond present within the cyclopentenone structure of 15d-PMJ2 was identified as a required moiety for the induction of ER stress apoptosis. The effect of 15d-PMJ2 on B16F10 melanoma growth was also evaluated by dosing C57BL/6 mice with 0.5 mg/kg 15d-PMJ2. Tumors of animals treated with 15d-PMJ2 exhibited significantly reduced growth and mean weights compared with vehicle and untreated animals. TUNEL and IHC analysis of tumor tissues showed significant cell death and ER stress in tumors of 15d-PMJ2–treated compared with control group animals. Taken together, these findings suggest that the novel prostamide, 15d-PMJ2, possesses potent antitumor activity in vitro and in vivo. Mol Cancer Ther; 16(5); 838–49. ©2017 AACR.
Fatty Acid Synthesis Intermediates Represent Novel Noninvasive Biomarkers of Prostate Cancer Chemoprevention by Phenethyl Isothiocyanate
Authors: Singh Krishna B. , Singh Shivendra V. 
Published: March 2017

Abstract
Increased de novo synthesis of fatty acids is a distinctive feature of prostate cancer, which continues to be a leading cause of cancer-related deaths among American men. Therefore, inhibition of de novo fatty acid synthesis represents an attractive strategy for chemoprevention of prostate cancer. We have shown previously that dietary feeding of phenethyl isothiocyanate (PEITC), a phytochemical derived from edible cruciferous vegetables such as watercress, inhibits incidence and burden of poorly differentiated prostate cancer in transgenic adenocarcinoma of mouse prostate (TRAMP) model. The current study was designed to test the hypothesis of whether fatty acid intermediate(s) can serve as noninvasive biomarker(s) of prostate cancer chemoprevention by PEITC using archived plasma and tumor specimens from the TRAMP study as well as cellular models of prostate cancer. Exposure of prostate cancer cells (LNCaP and 22Rv1) to pharmacologic concentrations of PEITC resulted in downregulation of key fatty acid metabolism proteins, including acetyl-CoA carboxylase 1 (ACC1), fatty acid synthase (FASN), and carnitine palmitoyltransferase 1A (CPT1A). The mRNA expression of FASN and CPT1A as well as acetyl-CoA levels were decreased by PEITC treatment in both cell lines. PEITC administration to TRAMP mice also resulted in a significant decrease in tumor expression of FASN protein. Consistent with these findings, the levels of total free fatty acids, total phospholipids, triglyceride, and ATP were significantly lower in the plasma and/or prostate tumors of PEITC-treated TRAMP mice compared with controls. The current study is the first to implicate inhibition of fatty acid synthesis in prostate cancer chemoprevention by PEITC. Cancer Prev Res; 10(5); 279–89. ©2017 AACR.
Cardiac Resynchronization Therapy Reduces Ventricular Arrhythmias in Primary but Not Secondary Prophylactic Implantable Cardioverter Defibrillator Patients
Authors: Sapp John L. , Parkash Ratika , Wells George A. , Yetisir Elizabeth , Gardner Martin J. , Healey Jeffrey S. , Thibault Bernard , Sterns Laurence D. , Birnie David , Nery Pablo B. , Sivakumaran Soori , Essebag Vidal , Dorian Paul , Tang Anthony S.L. 
Published: March 2017

Background—
The RAFT (Resynchronization in Ambulatory Heart Failure Trial) demonstrated that cardiac resynchronization therapy (CRT) reduced both mortality and heart failure hospitalizations in patients with functional class II or III heart failure and widened QRS. We examined the influence of CRT on ventricular arrhythmias in patients with primary versus secondary prophylaxis defibrillator indications.

Methods and Results—

All ventricular arrhythmias among RAFT study participants were downloaded and adjudicated by 2 blinded reviewers with an overreader for disagreements and committee review for remaining discrepancies. Incidence of ventricular arrhythmias among patients randomized to CRT-D versus implantable cardioverter defibrillator (ICD) were compared within the groups of patients treated for primary prophylaxis and for secondary prophylaxis. Of 1798 enrolled patients, 1764 had data available for adjudication and were included. Of these, 1531 patients were implanted for primary prophylaxis, while 233 patients were implanted for secondary prophylaxis; 884 patients were randomized to ICD and 880 to CRT-D. During 5953.6 patient-years of follow-up, there were 11 278 appropriate ICD detections of ventricular arrhythmias. In the primary prophylaxis group, CRT-D significantly reduced incidence ventricular arrhythmias in comparison to ICD (hazard ratio, 0.86; 95% confidence interval, 0.74–0.99;
P
=0.044). This effect was not seen in the secondary prophylaxis group (hazard ratio, 1.14; 95% confidence interval, 0.82–1.58;
P
=0.45). CRT-D was not associated with significant differences in overall ventricular arrhythmia burden in either group.

Conclusions—
CRT reduced the rate of onset of new ventricular arrhythmias detected by ICDs in patients without a history of prior ventricular arrhythmias. This effect was not observed among patients who had prior ventricular arrhythmias.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00251251.
Monocyte Chemotactic Protein-1–Interleukin-6–Osteopontin Pathway of Intra-Aneurysmal Tissue Healing
Authors: Hosaka Koji , Rojas Kelley , Fazal Hanain Z. , Schneider Matheus B. , Shores Jorma , Federico Vincent , McCord Matthew , Lin Li , Hoh Brian 
Published: March 2017

Background and Purpose—
We have previously demonstrated that the local delivery of monocyte chemotactic protein-1 (MCP-1) via an MCP-1–releasing poly(lactic-co-glycolic acid)–coated coil promotes intra-aneurysmal tissue healing. In this study, we demonstrate that interleukin-6 (IL-6) and osteopontin are downstream mediators in the MCP-1–mediated aneurysm-healing pathway.

Methods—
Murine carotid aneurysms were created in C57BL/6 mice. Drug-releasing coils (MCP-1, IL-6, and osteopontin) and control poly(lactic-co-glycolic acid) coils were created and then implanted into the aneurysms to evaluate their intra-aneurismal–healing capacity. To investigate the downstream mediators for aneurysm healing, blocking antibodies for IL-6 receptor and osteopontin were given to the mice implanted with the MCP-1–releasing coils. A histological analysis of both murine and human aneurysms was utilized to cross-validate the data.

Results—
We observed increased expression of IL-6 in MCP-1-coil–treated aneurysms and not in control-poly(lactic-co-glycolic acid)-only–treated aneurysms. MCP-1–mediated intra-aneurysmal healing is inhibited in mice given blocking antibody to IL-6 receptor. MCP-1–mediated intra-aneurysmal healing is also inhibited by blocking antibody to osteopontin. The role of IL-6 in intra-aneurysmal healing is in recruiting of endothelial cells and fibroblasts. Local delivery of osteopontin to murine carotid aneurysms via osteopontin-releasing coil significantly promotes intra-aneurysmal healing, but IL-6–releasing coil does not, suggesting that IL-6 cannot promote aneurysm healing independent of MCP-1. In the MCP-1–mediated aneurysm healing, osteopontin expression is dependent on IL-6; inhibition of IL-6 receptor significantly inhibits osteopontin expression in MCP-1–mediated aneurysm healing.

Conclusions—
Our findings suggest that IL-6 and osteopontin are key downstream mediators of MCP-1–mediated intra-aneurysmal healing.
Regional Comparison of Multiphase Computed Tomographic Angiography and Computed Tomographic Perfusion for Prediction of Tissue Fate in Ischemic Stroke
Authors: d’Esterre Christopher D. , Trivedi Anurag , Pordeli Pooneh , Boesen Mari , Patil Shivanand , Hwan Ahn Seong , Najm Mohamed , Fainardi Enrico , Shankar Jai Jai Shiva , Rubiera Marta , Almekhlafi Mohammed A. , Mandzia Jennifer , Khaw Alexander V. , Barber Philip , Coutts Shelagh , Hill Michael D. , Demchuk Andrew M. , Sajobi Tolulope , Forkert Nils D. , Goyal Mayank , Lee Ting-Yim , Menon Bijoy K. 
Published: March 2017

Background and Purpose—
Within different brain regions, we determine the comparative value of multiphase computed tomographic angiography (mCTA) and computed tomographic perfusion (CTP) in predicting follow-up infarction.

Methods—
Patients with M1-middle cerebral artery occlusions were prospectively included in this multicenter study. Regional analysis was performed for each patient within Alberta Stroke Program Early CT Score regions M2 to M6. Regional pial vessel filling was assessed on mCTA in 3 ways: (1) Washout of contrast within pial vessels; (2) Extent of maximal pial vessel enhancement compared with contralateral hemisphere; (3) Delay in maximal pial vessel enhancement compared with contralateral hemisphere. Cerebral blood flow, cerebral blood volume, and Tmax data were extracted within these Alberta Stroke Program Early CT Score regions. Twenty-four- to 36-hour magnetic resonance imaging/CT was assessed for infarct in each Alberta Stroke Program Early CT Score region (defined as >20% infarction within that region). Mixed effects logistic regression models were used to compare mCTA and CTP parameters when predicting brain infarction. Area under the receiver operating characteristics was used to assess discriminative value of statistical models.

Results—

Seventy-seven patients were included. mCTA parameter washout and CTP parameter Tmax were significantly associated with follow-up infarction in all models (
P
<0.05). The area under the receiver operating characteristic for mCTA models ranged from 92% to 94% and was not different compared with all CTP models (
P
>0.05). Mean Tmax and cerebral blood volume values were significantly different between each washout score (
P
<0.01) and each delay score category (
P
<0.01). Mean Tmax, cerebral blood flow, and cerebral blood volume values were significantly different between each extent score category (
P
<0.05).

Conclusions—
Similar to CTP, multiphase CTA can be used to predict tissue fate regionally in acute ischemic stroke patients.
Practical Necessity and the Fulfilment of the Plan of Nature in Kant’s Idea for a Universal History
Authors: James David 
Published: March 2017

Abstract
I explore the role of practical necessity in Kant’s essay Idea for a Universal History with a Cosmopolitan Aim. This form of necessity arises on the basis of social and interstate antagonism and Kant appeals to it with the aim of avoiding the introduction of a standpoint that is external to the agents whose attitudes and actions are being described. In connection with the role that Kant accords to practical necessity in the establishment of the legal and political conditions required to fulfil the ‘plan of nature’ in the course of history, I argue that in this essay he fails to identify a mechanism that would explain a fundamental moral change in that which motivates human beings once these conditions have been established. This in turn invites questions concerning the kind of universal history that Kant proposes. In particular, I argue that the choice of historical material that it demands could, in certain circumstances, be regarded as counterpurposive in relation to the aim of nature of which Kant speaks in the same essay.
Lagrangian Kinematic Criterion for the Breaking of Shoaling Waves
Authors: Itay Uri , Liberzon Dan 
Published: March 2017

AbstractAn experimental study was conducted with the aim of validating the Lagrangian kinematic criterion (LKC) for the case of breaking of shoaling waves. Monochromatic wave trains were generated in a large wave flume and allowed to shoal and break naturally on an artificial inclination changeable shore, thus allowing inspection of a range of slopes. Instantaneous horizontal Lagrangian water surface velocity was measured by particle tracking velocimetry and compared to the instantaneous propagation speed of the crest on a verge of breaking, the latter calculated using time series produced by resistance-type wave gauges staged along the flume. The inception of a breaker was found to occur when the monotonically increasing horizontal water velocity on the crest, during the process of steepening, approached that of the slowing steep crest, thus confirming the LKC for shoaling conditions. In addition, an objective method of breaking detection was developed utilizing the phase–time method and wavelet analysis by recognizing a specific pattern in the instantaneous local frequency fluctuations. The two main expected contributions of this study are the formation of an applicable criterion for breaking occurrences in shoaling waves and development of a wave breaking detection method independent of human decision. Incorporation of the suggested criterion into existing waves prediction models can be a significant contribution to maritime projects efficiency, whereas the breakers detection method will be useful for conducting further experimental research on waves breaking both in laboratory installations and in the highly unstable environment of an open sea.
Benchmarking Aided Decision Making in a Signal Detection Task
Authors: Bartlett Megan L. , McCarley Jason S. 
Published: March 2017

Objective: A series of experiments examined human operators’ strategies for interacting with highly (93%) reliable automated decision aids in a binary signal detection task. Background: Operators often interact with automated decision aids in a suboptimal way, achieving performance levels lower than predicted by a statistically ideal model of information integration. To better understand operators’ inefficient use of decision aids, we compared participants’ automation-aided performance levels with the predictions of seven statistical models of collaborative decision making. Method: Participants performed a binary signal detection task that asked them to classify random dot images as either blue or orange dominant. They made their judgments either unaided or with assistance from a 93% reliable automated decision aid that provided either graded (Experiments 1 and 3) or binary (Experiment 2) cues. We compared automation-aided performance with the predictions of seven statistical models of collaborative decision making, including a statistically optimal model and Robinson and Sorkin’s contingent criterion model. Results and Conclusion: Automation-aided sensitivity hewed closest to the predictions of the two least efficient collaborative models, well short of statistically ideal levels. Performance was similar whether the aid provided graded or binary judgments. Model comparisons identified potential strategies by which participants integrated their judgments with the aid’s. Application: Results lend insight into participants’ automation-aided decision strategies and provide benchmarks for predicting automation-aided performance levels.
Shooter–System Performance Variability as a Function of Recoil Dynamics
Authors: Morelli Frank , Neugebauer Jennifer M. , Haynes Courtney A. , Fry Thomas C. , Ortega Samson V. , Struve Douglas J. , LaFiandra Michael E. , Larkin Gabriella B. 
Published: March 2017

Objective: The goal of this study was to quantify shooter performance relative to subtle variations in recoil energy. Background: Marksmanship performance remains undefined for subtle distinctions in weapon recoil energy across common small-arms platforms. Method: Weapons were customized using multiple components and ammunition types. Firing scenarios were designed to examine the effect of recoil energy on shooter timing and accuracy. Results: The results suggest that recoil condition does not affect timing during firing sequences designed to elicit differences in timed-fire performance. Recoil condition did, however, influence shot placement, with accuracy decreasing as the energy associated with firing increased. Subjective recoil estimations were quantified according to relative magnitude and spatial distribution of perceived energy transferred at shooter–weapon surface contact locations. Conclusion: The absence of differences in time to engage may be reflective of resistance to recoil-induced point-of-aim deviation based on experience. Distinctions in performance were revealed despite subtle differences in recoil energy between conditions. An instrument that may be sensitive to shooter perception of subtle differences in recoil energy during firing was also developed. Application: The findings inform performance expectations for small-arms systems relative to recoil energy levels transferred to the shooter during dynamic firing events.
Hidden Gaussian Markov model for distributed fault detection in wireless sensor networks
Authors: Saihi Marwa , Zouinkhi Ahmed , Boussaid Boumedyen , Abdelkarim Mohamed Naceur , Andrieux Guillaume 
Published: March 2017

Wireless sensor networks are based on a large number of sensor nodes used to measure information like temperature, acceleration, displacement, or pressure. The measurements are used to estimate the state of the monitored system or area. However, the quality of the measurements must be guaranteed to ensure the reliability of the estimated state of the system. Actually, sensors can be used in a hostile environment such as, on a battle field in the presence of fires, floods, earthquakes. In these environments as well as in normal operation, sensors can fail. The failure of sensor nodes can also be caused by other factors like: the failure of a module (such as the sensing module) due to the fabrication process models, loss of battery power and so on. A wireless sensor network must be able to identify faulty nodes. Therefore, we propose a probabilistic approach based on the Hidden Markov Model to identify faulty sensor nodes. Our proposed approach predicts the future state of each node from its actual state, so the fault could be detected before it occurs. We use an aided judgment of neighbour sensor nodes in the network. The algorithm analyses the correlation of the sensors’ data with respect to its neighbourhood. A systematic approach to divide a network on cliques is proposed to fully draw the neighbourhood of each node in the network. After drawing the neighbourhood of each node (cliques), damaged cliques are identified using the Gaussian distribution theorem. Finally, we use the Hidden Markov Model to identify faulty nodes in the identified damaged cliques by calculating the probability of each node to stay in its normal state. Simulation results demonstrate our algorithm is efficient even for a huge wireless sensor network unlike previous approaches.
Migraine and vascular disease biomarkers: A population-based case-control study
Authors: Tietjen Gretchen E , Khubchandani Jagdish , Herial Nabeel , Palm-Meinders Inge H , Koppen Hille , Terwindt Gisela M , van Buchem Mark A , Launer Lenore J , Ferrari Michel D , Kruit Mark C 
Published: March 2017

Background The underpinnings of the migraine-stroke association remain uncertain, but endothelial activation is a potential mechanism. We evaluated the association of migraine and vascular disease biomarkers in a community-based population. Methods Participants (300 women, 117 men) were recruited as a part of the Dutch CAMERA 1 (Cerebral Abnormalities in Migraine, an Epidemiologic Risk Analysis) study. Participants were aged 30–60 (mean 48) years, 155 migraine had with aura (MA), 128 migraine without aura (MO), and 134 were controls with no severe headaches. Plasma concentrations of fibrinogen, Factor II, D-dimer, high sensitivity C-reactive protein (hs-CRP), and von Willebrand factor antigen were compared between groups, also stratifying by sex. Results Fibrinogen and hs-CRP were elevated in migraineurs compared to controls. In logistic regression analyses, MO and MA had increased likelihood of elevated fibrinogen, and MA had increased likelihood of elevated Factor II and hs-CRP. Fibrinogen and Factor II were associated with MA in women but not men. In the migraine subgroup, the total number of years of aura, but not headache, predicted elevated hs-CRP, and the average number of aura, but not headache, attacks predicted all biomarkers but Factor II. Conclusions Elevated vascular biomarkers were associated with migraine, particularly MA, as well as with years of aura and number of aura attacks.
High-mobility group box protein 1 expression in inflammatory diseases of the middle ear
Authors: Bellussi Luisa Maria , Vindigni Carla , Cocca Serena , Butorano Marie Aimee Gloria Munezero , Livi Walter , Corallo Giulia , Passali Desiderio 
Published: March 2017

High-mobility group box 1 (HMGB1) is a nuclear non-histone protein, playing a critical role as a mediator between innate and acquired immunity; when released extracellularly, it coordinates the cellular stress response (under necrosis, bacterial lipopolysaccharide stimulation) and acts as an inflammatory marker and cytokine. The aim of the study was to demonstrate whether HMGB1 is over-expressed in chronic middle-ear pathologies and whether the entity of expression and the localization are correlated with the degree of the inflammatory reaction, thus suggesting that HMGB1 may play a crucial role in chronic inflammatory disorders of the middle ear, as already demonstrated in other airway diseases. We analyzed 30 samples of middle-ear mucosa in patients affected by chronic suppurative otitis media with ear drum perforation with/without cholesteatoma and otosclerosis as control. The distribution of HMGB1 was evaluated as nuclear, cytoplasmic, and/or extracellular staining. The inflammatory cells observed in the biopsies were mostly lymphocytes and plasmacells. A statistically significant difference in inflammation score between otosclerosis and chronic otitis samples ( P < 0.01; Anova test) and between otosclerosis and cholesteatoma samples ( P < 0.05; Anova test) was observed; the HMGB1 positivity was in accordance with the density of the inflammatory infiltrate. HMGB1 is over-expressed in chronic middle-ear pathologies and may play a role in the progression of the inflammatory process from recurrent acute otitis media to chronic suppurative otitis media.