bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combined Parthenolide and Balsalazide Have Enhanced Antitumor Efficacy Through Blockade of NF-κB Activation
Authors: Kim Se-Lim , Kim Seong Hun , Park Young Ran , Liu Yu-Chuan , Kim Eun-Mi , Jeong Hwan-Jeong , Kim Yo Na , Seo Seung Young , Kim In Hee , Lee Seung Ok , Lee Soo Teik , Kim Sang-Wook 
Published: November 2016

AbstractBalsalazide is a colon-specific prodrug of 5-aminosalicylate that is associated with a reduced risk of colon cancer in patients with ulcerative colitis. Parthenolide, a strong NF-κB inhibitor, has recently been demonstrated to be a promising therapeutic agent, promoting apoptosis of cancer cells. In the current study, the antitumor effect of balsalazide combined with parthenolide in human colorectal cancer cells and colitis-associated colon cancers (CAC) was investigated. The results demonstrate that the combination of balsalazide and parthenolide markedly suppress proliferation, nuclear translocation of NF-κB, IκB-α phosphorylation, NF-κB DNA binding, and expression of NF-κB targets. Apoptosis via NF-κB signaling was confirmed by detecting expression of caspases, p53 and PARP. Moreover, treatment of a CAC murine model with parthenolide and balsalazide together resulted in significant recovery of body weight and improvement in histologic severity. Administration of parthenolide and balsalazide to CAC mice also suppressed carcinogenesis as demonstrated by uptake of 18F-fluoro-2-deoxy-D-glucose (FDG) using micro-PET/CT scans. These results demonstrate that parthenolide potentiates the efficacy of balsalazide through synergistic inhibition of NF-κB activation and the combination of dual agents prevents colon carcinogenesis from chronic inflammation.Implications: This study represents the first evidence that combination therapy with balsalazide and parthenolide could be a new regimen for colorectal cancer treatment. Mol Cancer Res; 15(2); 141–51. ©2016 AACR.
Eradication of Canine Diffuse Large B-Cell Lymphoma in a Murine Xenograft Model with CD47 Blockade and Anti-CD20
Authors: Weiskopf Kipp , Anderson Katie L. , Ito Daisuke , Schnorr Peter J. , Tomiyasu Hirotaka , Ring Aaron M. , Bloink Kristin , Efe Jem , Rue Sarah , Lowery David , Barkal Amira , Prohaska Susan , McKenna Kelly M. , Cornax Ingrid , O'Brien Timothy D. , O'Sullivan M. Gerard , Weissman Irving L. , Modiano Jaime F. 
Published: November 2016

Abstract
Cancer immunotherapies hold much promise, but their potential in veterinary settings has not yet been fully appreciated. Canine lymphomas are among the most common tumors of dogs and bear remarkable similarity to human disease. In this study, we examined the combination of CD47 blockade with anti-CD20 passive immunotherapy for canine lymphoma. The CD47/SIRPα axis is an immune checkpoint that regulates macrophage activation. In humans, CD47 is expressed on cancer cells and enables evasion from phagocytosis. CD47-blocking therapies are now under investigation in clinical trials for a variety of human cancers. We found the canine CD47/SIRPα axis to be conserved biochemically and functionally. We identified high-affinity SIRPα variants that antagonize canine CD47 and stimulate phagocytosis of canine cancer cells in vitro. When tested as Fc fusion proteins, these therapeutic agents exhibited single-agent efficacy in a mouse xenograft model of canine lymphoma. As robust synergy between CD47 blockade and tumor-specific antibodies has been demonstrated for human cancer, we evaluated the combination of CD47 blockade with 1E4-cIgGB, a canine-specific antibody to CD20. 1E4-cIgGB could elicit a therapeutic response against canine lymphoma in vivo as a single agent. However, augmented responses were observed when combined with CD47-blocking therapies, resulting in synergy in vitro and in vivo and eliciting cures in 100% of mice bearing canine lymphoma. Our findings support further testing of CD47-blocking therapies alone and in combination with CD20 antibodies in the veterinary setting. Cancer Immunol Res; 4(12); 1072–87. ©2016 AACR.
Extended-Duration Betrixaban Reduces the Risk of Stroke Versus Standard-Dose Enoxaparin Among Hospitalized Medically Ill Patients
Authors: Gibson C. Michael , Chi Gerald , Halaby Rim , Korjian Serge , Daaboul Yazan , Jain Purva , Arbetter Douglas , Goldhaber Samuel Z. , Hull Russel , Hernandez Adrian F. , Gold Alex , Bandman Olga , Harrington Robert A. , Cohen Alexander T. 
Published: November 2016

Background:
Stroke is a morbid and potentially mortal complication among patients hospitalized with acute medical illness. The potential of extended-duration thromboprophylaxis with the factor Xa inhibitor betrixaban to reduce the risk of stroke compared with standard-dose enoxaparin in this population was assessed in this retrospective APEX trial substudy (Acute Medically Ill Venous Thromboembolism Prevention With Extended Duration Betrixaban).

Methods:
Hospitalized acutely medically ill subjects (n=7513) were randomized in a double-dummy double-blind fashion to either extended-duration oral betrixaban (80 mg once daily for 35–42 days) or standard-dose subcutaneous enoxaparin (40 mg once daily for 10±4 days) for venous thromboprophylaxis. Stroke events were adjudicated by an independent, blinded event adjudication committee.

Results:

The mean age of study participants was 76 years; 45% were male; 13% had had a stroke; and 45% had congestive heart failure. There were fewer all-cause strokes (0.54% versus 0.97%; relative risk [RR]=0.56; 95% confidence interval, 0.32–0.96;
P
=0.032; adjusted RR=0.43%; number needed to treat=233) and ischemic strokes (0.48% versus 0.91%; RR=0.53; 95% confidence interval, 0.30–0.94;
P
=0.026; adjusted RR=0.43%; number needed to treat=233) among patients treated with betrixaban versus enoxaparin through 77 days of follow-up. Among high-risk subjects, those with congestive heart failure or ischemic stroke as their index event, betrixaban reduced the risk of all-cause stroke (0.72% versus 1.48%; RR=0.49; 95% confidence interval, 0.26–0.90;
P
=0.019; adjusted RR=0.76%; number needed to treat=132) and ischemic stroke (0.63% versus 1.38%; RR=0.45; 95% confidence interval, 0.24–0.87;
P
=0.014; adjusted RR=0.75%; number needed to treat=134) compared with enoxaparin.

Conclusions:
Among hospitalized medically ill patients, extended-duration betrixaban significantly reduced all-cause stroke and ischemic stroke through 77 days of follow-up

Clinical Trial Registration:

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01583218.
Hydrogen Peroxide‐Responsive Nanoparticle Reduces Myocardial Ischemia/Reperfusion Injury
Authors: Bae Soochan , Park Minhyung , Kang Changsun , Dilmen Serkan , Kang Tae Hi , Kang Dong Goo , Ke Qingen , Lee Seung Uk , Lee Dongwon , Kang Peter M. 
Published: November 2016

Background

During myocardial ischemia/reperfusion (I/R), a large amount of reactive oxygen species (
ROS
) is produced. In particular, overproduction of hydrogen peroxide (H
2
O
2
) is considered to be a main cause of I/R‐mediated tissue damage. We generated novel H
2
O
2
‐responsive antioxidant polymer nanoparticles (
PVAX
and
HPOX
) that are able to target the site of
ROS
overproduction and attenuate the oxidative stress‐associated diseases. In this study, nanoparticles were examined for their therapeutic effect on myocardial I/R injury.

Methods and Results

The therapeutic effect of nanoparticles during cardiac I/R was evaluated in mice. A single dose of
PVAX
(3 mg/kg) showed a significant improvement in both cardiac output and fraction shortening compared with poly(lactic‐coglycolic acid) (
PLGA
) particle, a non‐H
2
O
2
‐activatable nanoparticle.
PVAX
also significantly reduced the myocardial infarction/area compared with
PLGA
(48.7±4.2 vs 14.5±2.1). In addition,
PVAX
effectively reduced caspase‐3 activation and
TUNEL
‐positive cells compared with
PLGA
. Furthermore,
PVAX
significantly decreased
TNF
‐α and
MCP
‐1 m
RNA
levels. To explore the antioxidant effect of
PVAX
by scavenging
ROS
, dihydroethidium staining was used as an indicator of
ROS
generation.
PVAX
effectively suppressed the generation of
ROS
caused by I/R, whereas a number of dihydroethidium‐positive cells were observed in a group with
PLGA
I/R. In addition,
PVAX
significantly reduced the level of
NADPH
oxidase (
NOX
) 2 and 4 expression, which favors the reduction in
ROS
generation after I/R.

Conclusions

Taken together, these results suggest that H
2
O
2
‐responsive antioxidant
PVAX
has tremendous potential as a therapeutic agent for myocardial I/R injury.
Impact of Insurance Status on Outcomes and Use of Rehabilitation Services in Acute Ischemic Stroke: Findings From Get With The Guidelines‐Stroke
Authors: Medford‐Davis Laura N. , Fonarow Gregg C. , Bhatt Deepak L. , Xu Haolin , Smith Eric E. , Suter Robert , Peterson Eric D. , Xian Ying , Matsouaka Roland A. , Schwamm Lee H. 
Published: November 2016

Background
Insurance status affects access to care, which may affect health outcomes. The objective was to determine whether patients without insurance or with government‐sponsored insurance had worse quality of care or in‐hospital outcomes in acute ischemic stroke.

Methods and Results

Multivariable logistic regressions with generalized estimating equations stratified by age under or at least 65 years were adjusted for patient demographics and comorbidities, presenting factors, and hospital characteristics to determine differences in in‐hospital mortality and postdischarge destination. We included 589 320 ischemic stroke patients treated at 1604 US hospitals participating in the Get With The Guidelines‐Stroke program between 2012 and 2015. Uninsured patients with hypertension, high cholesterol, or diabetes mellitus were less likely to be taking appropriate control medications prior to stroke, to use an ambulance to arrive to the
ED
, or to arrive early after symptom onset. Even after adjustment, the uninsured were more likely than the privately insured to die in the hospital (<65 years,
OR
1.33 [95%
CI
1.22‐1.45]; ≥65 years
OR
1.54 [95%
CI
1.34‐1.75]), and among survivors, were less likely to go to inpatient rehab (<65
OR
0.63 [95%
CI
0.6‐0.67]; ≥65
OR
0.56 [95%
CI
0.5‐0.63]). In contrast, patients with Medicare and Medicaid were more likely to be discharged to a Skilled Nursing Facility (<65 years
OR
2.08 [
CI
1.96‐2.2];
OR
2.01 [95%
CI
1.91‐2.13]; ≥65 years
OR
1.1 [95%
CI
1.07‐1.13];
OR
1.41 [95%
CI
1.35‐1.46]).

Conclusions
Preventative care prior to ischemic stroke, time to presentation for acute treatment, access to rehabilitation, and in‐hospital mortality differ by patient insurance status.
The Word as Dialogue: The Lyrical Apostrophe vis-à-vis the Dialogic Theory of Mikhail Bakhtin
Authors: Szávai Dorottya 
Published: November 2016

The present paper aims to explore aspects of Bakhtin’s dialogic model and, in a wider sense, of discourse and language theory, which can be related to the dialogic structures of the lyrical genre.
We propose to reread Bakhtin’s dialogic theory, approaching it from other (mainly postmodern) literary discourses, and to situate Bakhtin’s oeuvre, which “stands alone” and is hard to fit into theoretical trends, in literary theory.
We consider it especially significant to approach the dialogic devices of Bakhtin’s theory from the perspective of literary hermeneutics and deconstruction.
Early surgery after angiography in patients scheduled for valve replacement
Authors: Dayan Victor , Stanham Roberto , Soca Gerardo , Genta Fernando , Mariño Jorge , Lorenzo Alvaro 
Published: November 2016

Background There are limited data regarding the risks of cardiac surgery early after coronary angiography in patients scheduled for isolated aortic and/or mitral valve replacement. Our aim was to evaluate the risk of early surgery after coronary angiography in these patients. Methods We retrospectively analyzed data of 1044 patients who underwent isolated aortic and/or mitral valve replacement from 2006 to 2014. Baseline, operative, and postoperative variables were collected. The patients were divided into 3 groups based on the interval between coronary angiography and surgery: ≤3 days ( n = 216), 4–7 days ( n = 109), and ≥8 days ( n = 719). We evaluated hospital mortality and postoperative acute kidney injury. Subgroup analysis was performed according to preoperative creatinine clearance. Results Postoperative creatinine clearance was lower in patients who underwent surgery ≤3 days after coronary angiography (63.57 ± 38.52 mL min−1) compared to ≥8 days after coronary angiography (74.56 ± 54.25 mL min−1, p = 0.015). Patients who underwent surgery ≤3 days after coronary angiography had higher hospital mortality when preoperative creatinine clearance was ≤60 mL min−1 (12% vs. 4% for creatinine clearance ≤and >60 mL min−1, respectively; p = 0.039). Predictors of hospital mortality were New York Heart Association class and postoperative creatinine clearance. Conclusion Hospital mortality was higher in patients with decreased preoperative renal function who underwent surgery within the first 3 days after coronary angiography. Delaying surgery in this subgroup of patients could be a good strategy.
ALCAM (CD166) is involved in extravasation of monocytes rather than T cells across the blood–brain barrier
Authors: Lyck Ruth , Lécuyer Marc-André , Abadier Michael , Wyss Christof B , Matti Christoph , Rosito Maria , Enzmann Gaby , Zeis Thomas , Michel Laure , García Martín Ana B , Sallusto Federica , Gosselet Fabien , Deutsch Urban , Weiner Joshua A , Schaeren-Wiemers Nicole , Prat Alexandre , Engelhardt Britta 
Published: November 2016

Activated leukocyte cell adhesion molecule (ALCAM) has been proposed to mediate leukocyte migration across the blood–brain barrier (BBB) in multiple sclerosis or experimental autoimmune encephalomyelitis (EAE). Here, we confirmed vascular ALCAM expression in human brain tissue samples in situ and on two different human in vitro BBB models. Antibody-mediated inhibition of ALCAM reduced diapedesis of human CD4+ Th1 but not of Th17 cells across the human BBB in vitro. In accordance to human Th1 cells, mouse Th1 cells showed reduced diapedesis across an ALCAM−/− in vitro BBB model under static but no longer under flow conditions. In contrast to the limited role of ALCAM in T cell extravasation across the BBB, we found a contribution of ALCAM to rolling, adhesion, and diapedesis of human CD14+ monocytes across the human BBB under flow and static conditions. Taken together, our study highlights the potential differences in the CNS expression of ALCAM in mouse and human and supports a prominent role for ALCAM in the multi-step extravasation of monocytes across the BBB.
Impact of iterative reconstruction on image quality of low-dose CT of the lumbar spine
Authors: Alshamari Muhammed , Geijer Mats , Norrman Eva , Lidén Mats , Krauss Wolfgang , Jendeberg Johan , Magnuson Anders , Geijer Håkan 
Published: November 2016

Background Iterative reconstruction (IR) is a recent reconstruction algorithm for computed tomography (CT) that can be used instead of the standard algorithm, filtered back projection (FBP), to reduce radiation dose and/or improve image quality. Purpose To evaluate and compare the image quality of low-dose CT of the lumbar spine reconstructed with IR to conventional FBP, without further reduction of radiation dose. Material and Methods Low-dose CT on 55 patients was performed on a Siemens scanner using 120 kV tube voltage, 30 reference mAs, and automatic dose modulation. From raw CT data, lumbar spine CT images were reconstructed with a medium filter (B41f) using FBP and four levels of IR (levels 2–5). Five reviewers scored all images on seven image quality criteria according to the European guidelines on quality criteria for CT, using a five-grade scale. A side-by-side comparison was also performed. Results There was significant improvement in image quality for IR (levels 2–4) compared to FBP. According to visual grading regression, odds ratios of all criteria with 95% confidence intervals for IR2, IR3, IR4, and IR5 were: 1.59 (1.39–1.83), 1.74 (1.51–1.99), 1.68 (1.46–1.93), and 1.08 (0.94–1.23), respectively. In the side-by-side comparison of all reconstructions, images with IR (levels 2–4) received the highest scores. The mean overall CTDIvol was 1.70 mGy (SD 0.46; range, 1.01–3.83 mGy). Image noise decreased in a linear fashion with increased strength of IR. Conclusion Iterative reconstruction at levels 2, 3, and 4 improves image quality of low-dose CT of the lumbar spine compared to FPB.
Effects of kynurenic acid analogue 1 (KYNA-A1) in nitroglycerin-induced hyperalgesia: Targets and anti-migraine mechanisms
Authors: Greco Rosaria , Demartini Chiara , Zanaboni Anna Maria , Redavide Elisa , Pampalone Selena , Toldi Joseph , Fülöp Ferenc , Blandini Fabio , Nappi Giuseppe , Sandrini Giorgio , Vécsei László , Tassorelli Cristina 
Published: November 2016

Background Trigeminal sensitization represents a major mechanism underlying migraine attacks and their recurrence. Nitroglycerin (NTG) administration provokes spontaneous migraine-like headaches and in rat, an increased sensitivity to the formalin test. Kynurenic acid (KYNA), an endogenous regulator of glutamate activity and its analogues attenuate NTG-induced neuronal activation in the nucleus trigeminalis caudalis (NTC). The anti-hyperalgesic effect of KYNA analogue 1 (KYNA-A1) was investigated on animal models specific for migraine pain. Aim Rats made hyperalgesic by NTG administration underwent the plantar or orofacial formalin tests. The effect of KYNA-A1 was evaluated in terms of nocifensive behavior and of neuronal nitric oxide synthase (nNOS), calcitonin gene-related peptide (CGRP) and cytokines expression in areas involved in trigeminal nociception. Results KYNA-A1 abolished NTG-induced hyperalgesia in both pain models; NTG alone or associated to formalin injection induced an increased mRNA expression of CGRP, nNOS and cytokines in the trigeminal ganglia and central areas, which was reduced by KYNA-A1. Additionally, NTG caused a significant increase in nNOS immunoreactivity in the NTC, which was prevented by KYNA-A1. Conclusion Glutamate activity is likely involved in mediating hyperalgesia in an animal model specific for migraine. Its inhibition by means of a KYNA analogue modulates nNOS, CGRP and cytokines expression at peripheral and central levels.
Hippocampus and amygdala volume in relation to migraine frequency and prognosis
Authors: Liu Hung-Yu , Chou Kun-Hsien , Lee Pei-Lin , Fuh Jong-Ling , Niddam David M , Lai Kuan-Lin , Hsiao Fu-Jung , Lin Yung-Yang , Chen Wei-Ta , Wang Shuu-Jiun , Lin Ching-Po 
Published: November 2016

Objectives To investigate the structural changes of hippocampus and amygdala and their relationships with migraine frequency and prognosis. Methods Hippocampus and amygdala volumes were measured by 3-T brain magnetic resonance imaging (MRI) in 31 controls and 122 migraine patients who were categorized into eight groups by headache frequency: group 1 (1–2 headache days/month), 2 (3–4), 3 (5–7), 4 (8–10), 5 (11–14), 6 (15–19), 7 (20–24), and 8 (25–30). Headache frequency was reassessed 2 years later and a frequency reduction ≥50% was regarded a good outcome. Results Hippocampus and amygdala volumes fluctuated in patient groups but did not differ from the controls. In migraine patients, the bilateral hippocampus volumes peaked in group 3. The volumes and headache frequencies correlated positively in groups 2–3 on bilateral sides (L: r = 0.44, p = 0.007; R: r = 0.35, p = 0.037), and negatively in groups 3–7 on the left side (5–24 days/month; L: r = −0.31, p = 0.004) and groups 3–8 on the right side ( r = −0.31, p = 0.002). The left amygdala volume also peaked in group 3, and correlated with headache frequency in groups 1–3 ( r = 0.34, p = 0.020) and groups 3–6 ( r = −0.30, p = 0.012). The volumetric changes of the right amygdala with headache frequency did not reach statistical significance. At 2-year follow-up, the right hippocampus volume was positively associated with a good migraine outcome after adjustment of headache frequency (OR 4.72, p = 0.024). Conclusions Hippocampus and amygdala display a structural plasticity linked to both headache frequency and clinical outcome of migraine.
Gender wage differences in Nigerian self and paid employment: Do marriage and children matter?
Authors: Nwaka Ikechukwu Darlington , Guven-Lisaniler Fatma , Tuna Gulcay 
Published: November 2016

AbstractThis article investigates gender differences in Nigeria, in the impact of marriage and children on location in the self or waged employment sector, and on income from work. Findings show that the pay structure varies across employment sectors – waged and self-employed – and that the determinants of employment sector vary by gender and family roles. Differences in human capital investment and geopolitical zones also need to be considered. The estimates in the study reveal that there is a marriage premium for both males and females in the waged labour market, but partially support Becker’s (1991) gender-based household specialisation model in terms of the relative incidence of self-employment. There is a wage penalty for married women with children in the paid-employment labour market, but motherhood is also negatively associated with income levels for self-employed women. We also find a fatherhood penalty for paid-employed men. Nevertheless, overall, the gender difference is higher in relatively less regulated self-employment compared to the more regulated paid employment labour market. Findings therefore offer some policy inputs but also suggest the need for further research into the causes of the gender pay gap in self- and paid employment, and thus into the overall wage gap in Nigeria that inhibits women’s labour market participation and welfare.
Effect of Direct Ligament Repair and Tenodesis Reconstruction on Simulated Subtalar Joint Instability
Authors: Choisne Julie , Hoch Matthew C. , Alexander Ian , Ringleb Stacie I. 
Published: November 2016

Background: Subtalar instability is associated with up to 80% of patients presenting with chronic ankle instability but is often not considered in the diagnosis or treatment. Operative procedures to repair ankle instability have shown good clinical results, but the effects of these reconstruction procedures on isolated subtalar instability are not well understood. The goal of this study was to investigate the effect of the Gould modification of the Broström procedure and a new tenodesis reconstruction procedure on ankle and subtalar joint kinematics after simulating a subtalar injury. Methods: Kinematic data were collected on 7 cadaveric ankles during inversion through the range of ankle flexion and during internal rotation. Testing was performed on the intact foot; after sectioning the calcaneofibular ligament, cervical ligament, and interosseous talocalcaneal ligament; after the Gould modification of the Broström procedure was performed; and after tenodesis was performed and sutures from the Gould modification removed. Results: The Gould modification of the Broström procedure significantly decreased subtalar and ankle inversion motion and subtalar internal rotation compared to the unstable condition. The tenodesis method restricted internal rotation at the subtalar joint and ankle inversion compared to the intact state. Conclusion: Both operative procedures improved stability of the ankle complex, but tenodesis was unable to restore subtalar inversion and restricted ankle inversion in maximum plantarflexion. Clinical Relevance: The Gould modification of Broström ligament repair may be a favorable operative procedure for the restoration of subtalar and ankle joint kinematics.