bluuebunny/crossref_metadata_2025_split huggingface dataset:
CD4+ T-Helper Type 1 Cytokines and Trastuzumab Facilitate CD8+ T-cell Targeting of HER2/neu–Expressing Cancers
Authors: Datta Jashodeep , Xu Shuwen , Rosemblit Cinthia , Smith Jenessa B. , Cintolo Jessica A. , Powell Daniel J. , Czerniecki Brian J. 
Published: March 2015

Abstract
Vaccination strategies incorporating the immunodominant HLA-A2–restricted HER2/neu-derived peptide 369–377 (HER2369–377) are increasingly utilized in HER2/neu-expressing cancer patients. The failure of postvaccination HER2369–377-specific CD8+ T cells to recognize HLA-A2posHER2/neu-expressing cells in vitro, however, has been attributed to impaired MHC class I/HLA-A2 presentation observed in HER2/neu-overexpressing tumors. We reconcile this controversy by demonstrating that HER2369–377 is directly recognized by high functional-avidity HER2369–377-specific CD8+ T cells—either genetically modified to express a novel HER2369–377 TCR or sensitized using HER2369–377-pulsed type 1–polarized dendritic cells (DC1)—on class I–abundant HER2low, but not class I–deficient HER2high, cancer cells. Importantly, a critical cooperation between CD4+ T-helper type-1 (Th1) cytokines IFNγ/TNFα and HER2/neu-targeted antibody trastuzumab is necessary to restore class I expression in HER2high cancers, thereby facilitating recognition and lysis of these cells by HER2369–377-specific CD8+ T cells. Concomitant induction of PD-L1 on HER2/neu-expressing cells by IFNγ/TNF and trastuzumab, however, has minimal impact on DC1-sensitized HER2369–377-CD8+ T-cell–mediated cytotoxicity. Although activation of EGFR and HER3 signaling significantly abrogates IFNγ/TNFα and trastuzumab-induced class I restoration, EGFR/HER3 receptor blockade rescues class I expression and ensuing HER2369–377-CD8+ cytotoxicity of HER2/neu-expressing cells. Thus, combinations of CD4+ Th1 immune interventions and multivalent targeting of HER family members may be required for optimal anti-HER2/neu CD8+ T-cell–directed immunotherapy. Cancer Immunol Res; 3(5); 455–63. ©2015 AACR.
Roles of Acyl-CoA:Diacylglycerol Acyltransferases 1 and 2 in Triacylglycerol Synthesis and Secretion in Primary Hepatocytes
Authors: Li Chen , Li Lena , Lian Jihong , Watts Russell , Nelson Randal , Goodwin Bryan , Lehner Richard 
Published: March 2015

Objective—
Very low–density lipoprotein assembly and secretion are regulated by the availability of triacylglycerol. Although compelling evidence indicates that the majority of triacylglycerol in very low–density lipoprotein is derived from re-esterification of lipolytic products released by endoplasmic reticulum–associated lipases, little is known about roles of acyl-CoA:diacylglycerol acyltransferases (DGATs) in this process. We aimed to investigate the contribution of DGAT1 and DGAT2 in lipid metabolism and lipoprotein secretion in primary mouse and human hepatocytes.

Approach and Results—

We used highly selective small-molecule inhibitors of DGAT1 and DGAT2, and we tracked storage and secretion of lipids synthesized de novo from [
3
H]acetic acid and from exogenously supplied [
3
H]oleic acid. Inactivation of individual DGAT activity did not affect incorporation of either radiolabeled precursor into intracellular triacylglycerol, whereas combined inactivation of both DGATs severely attenuated triacylglycerol synthesis. However, inhibition of DGAT2 augmented fatty acid oxidation, whereas inhibition of DGAT1 increased triacylglycerol secretion, suggesting preferential channeling of separate DGAT-derived triacylglycerol pools to distinct metabolic pathways. Inactivation of DGAT2 impaired cytosolic lipid droplet expansion, whereas DGAT1 inactivation promoted large lipid droplet formation. Moreover, inactivation of DGAT2 attenuated expression of lipogenic genes. Finally, triacylglycerol secretion was significantly reduced on DGAT2 inhibition without altering extracellular apolipoprotein B levels.

Conclusions—
Our data suggest that DGAT1 and DGAT2 can compensate for each other to synthesize triacylglycerol, but triacylglycerol synthesized by DGAT1 is preferentially channeled to oxidation, whereas DGAT2 synthesizes triacylglycerol destined for very low–density lipoprotein assembly.
Sex Differences in Reperfusion in Young Patients With ST-Segment–Elevation Myocardial Infarction
Authors: D’Onofrio Gail , Safdar Basmah , Lichtman Judith H. , Strait Kelly M. , Dreyer Rachel P. , Geda Mary , Spertus John A. , Krumholz Harlan M. 
Published: March 2015

Background—
Sex disparities in reperfusion therapy for patients with acute ST-segment–elevation myocardial infarction have been documented. However, little is known about whether these patterns exist in the comparison of young women with men.

Methods and Results—

We examined sex differences in rates, types of reperfusion therapy, and proportion of patients exceeding American Heart Association reperfusion time guidelines for ST-segment–elevation myocardial infarction in a prospective observational cohort study (2008–2012) of 1465 patients 18 to 55 years of age, as part of the US Variations in Recovery: Role of Gender on Outcomes of Young AMI Patients (VIRGO) study at 103 hospitals enrolling in a 2:1 ratio of women to men. Of the 1238 patients eligible for reperfusion, women were more likely to be untreated than men (9% versus 4%,
P
=0.002). There was no difference in reperfusion strategy for the 695 women and 458 men treated. Women were more likely to exceed in-hospital and transfer time guidelines for percutaneous coronary intervention than men (41% versus 29%; odds ratio, 1.65; 95% confidence interval, 1.27–2.16), more so when transferred (67% versus 44%; odds ratio, 2.63; 95% confidence interval, 1.17–4.07); and more likely to exceed door-to-needle times (67% versus 37%; odds ratio, 2.62; 95% confidence interval, 1.23–2.18). After adjustment for sociodemographic, clinical, and organizational factors, sex remained an important factor in exceeding reperfusion guidelines (odds ratio, 1.72; 95% confidence interval, 1.28–2.33).

Conclusions—
Young women with ST-segment–elevation myocardial infarction are less likely to receive reperfusion therapy and more likely to have reperfusion delays than similarly aged men. Sex disparities are more pronounced among patients transferred to percutaneous coronary intervention institutions or who received fibrinolytic therapy.
Regional Variation in the Incidence and Outcomes of In-Hospital Cardiac Arrest in the United States
Authors: Kolte Dhaval , Khera Sahil , Aronow Wilbert S. , Palaniswamy Chandrasekar , Mujib Marjan , Ahn Chul , Iwai Sei , Jain Diwakar , Sule Sachin , Ahmed Ali , Cooper Howard A. , Frishman William H. , Bhatt Deepak L. , Panza Julio A. , Fonarow Gregg C. 
Published: March 2015

Background—
Regional variation in the incidence and outcomes of in-hospital cardiac arrest (IHCA) is not well studied and may have important health and policy implications.

Methods and Results—

We used the 2003 to 2011 Nationwide Inpatient Sample databases to identify patients ≥18 years of age who underwent cardiopulmonary resuscitation (
International Classification of Diseases, Ninth Edition, Clinical Modification
procedure codes 99.60 and 99.63) for IHCA. Regional differences in IHCA incidence, survival to hospital discharge, and resource use (total hospital cost and discharge disposition among survivors) were analyzed. Of 838 465 patients with IHCA, 162 270 (19.4%) were in the Northeast, 159 581 (19.0%) were in the Midwest, 316 201 (37.7%) were in the South, and 200 413 (23.9%) were in the West. Overall IHCA incidence in the United States was 2.85 per 1000 hospital admissions. IHCA incidence was lowest in the Midwest and highest in the West (2.33 and 3.73 per 1000 hospital admissions, respectively). Compared with the Northeast, risk-adjusted survival to discharge was significantly higher in the Midwest (odds ratio, 1.33; 95% confidence interval, 1.31–1.36), South (odds ratio, 1.21; 95% confidence interval, 1.19–1.23), and West (odds ratio, 1.25; 95% confidence interval, 1.23–1.27). IHCA survival increased significantly from 2003 to 2011 in the United States and in all regions (all
P
trend
<0.001). Total hospital cost was highest in the West, whereas discharge to skilled nursing facility and use of home health care among survivors was highest in the Northeast.

Conclusions—
We observed significant regional variation in IHCA incidence, survival, and resource use in the United States. This variation was explained only partially by differences in patient and hospital characteristics. Further studies are needed to identify other potential factors responsible for these regional differences to improve outcomes after IHCA.
Surgeon Case Volume and 30-Day Mortality After Carotid Endarterectomy Among Contemporary Medicare Beneficiaries
Authors: Kumamaru Hiraku , Jalbert Jessica J. , Nguyen Louis L. , Gerhard-Herman Marie D. , Williams Lauren A. , Chen Chih-Ying , Seeger John D. , Liu Jun , Franklin Jessica M. , Setoguchi Soko 
Published: March 2015

Background and Purpose—
After the 2005 National Coverage Determination to reimburse carotid artery stenting (CAS) for Medicare beneficiaries, the number of CAS procedures increased and carotid endarterectomy (CEA) decreased. We evaluated trends in surgeons’ past-year CEA case-volume and 30-day mortality after CEA, and their association before and after the National Coverage Determination.

Methods—
In a retrospective cohort study of patients undergoing CEA (2001–2008) and CAS (2005–2008) using Medicare data, we described yearly trends of CEA and CAS rates, patient characteristics, and 30-day mortality after CEA. We used logistic regression adjusting for patient- and surgeon-level factors to assess the effect of surgeon case volume on 30-day mortality after CEA.

Results—
We identified 454 717 CEA and 27 943 CAS patients. Patients undergoing CEA in recent years were older and had more comorbidities than earlier years. CEA rates per 10 000 beneficiaries declined from 18.1 in 2002 to 12.7 in 2008, whereas median surgeon past-year case-volume declined from 27 to 21. The CAS rates peaked at 2.3 per 10 000 beneficiaries in 2006 but declined to 1.8 in 2008, resulting in declining overall revascularization procedure rates during 2005 to 2008. Thirty day post-CEA mortality was 1.40% (95% confidence interval, 1.34–1.47) in 2001 to 2002 and 1.17% (1.10–1.24) in 2007 to 2008. Surgeon’s past-year case-volume of <10 was associated with higher 30-day mortality consistently during 2001 to 2008.

Conclusions—
The rate of CEA procedures decreased substantially during 2001 to 2008, as did surgeon past-year case-volume. The postprocedural mortality in Medicare beneficiaries was high compared with trial patients but somewhat improved over time. Those operated by lower past-year case-volume surgeons had increased mortality.
Safety of Intravenous Thrombolysis in Stroke Mimics
Authors: Tsivgoulis Georgios , Zand Ramin , Katsanos Aristeidis H. , Goyal Nitin , Uchino Ken , Chang Jason , Dardiotis Efthimios , Putaala Jukka , Alexandrov Anne W. , Malkoff Marc D. , Alexandrov Andrei V. 
Published: March 2015

Background and Purpose—
Shortening door-to-needle time may lead to inadvertent intravenous thrombolysis (IVT) administration in stroke mimics (SMs). We sought to determine the safety of IVT in SMs using prospective, single-center data and by conducting a comprehensive meta-analysis of reported case-series.

Methods—
We prospectively analyzed consecutive IVT-treated patients during a 5-year period at a tertiary care stroke center. A systematic review and meta-analysis of case-series reporting safety of IVT in SMs and confirmed acute ischemic stroke were conducted. Symptomatic intracerebral hemorrhage was defined as imaging evidence of ICH with an National Institutes of Health Stroke scale increase of ≥4 points. Favorable functional outcome at hospital discharge was defined as a modified Rankin Scale score of 0 to 1.

Results—

Of 516 consecutive IVT patients at our tertiary care center (50% men; mean age, 60±14 years; median National Institutes of Health Stroke scale, 11; range, 3–22), SMs comprised 75 cases. Symptomatic intracerebral hemorrhage occurred in 1 patient, whereas we documented no cases of orolingual edema or major extracranial hemorrhagic complications. In meta-analysis of 9 studies (8942 IVT-treated patients), the pooled rates of symptomatic intracerebral hemorrhage and orolingual edema among 392 patients with SM treated with IVT were 0.5% (95% confidence interval, 0%–2%) and 0.3% (95% confidence interval, 0%–2%), respectively. Patients with SM were found to have a significantly lower risk for symptomatic intracerebral hemorrhage compared with patients with acute ischemic stroke (risk ratio=0.33; 95% confidence interval, 0.14–0.77;
P
=0.010), with no evidence of heterogeneity or publication bias. Favorable functional outcome was almost 3-fold higher in patients with SM in comparison with patients with acute ischemic stroke (risk ratio=2.78; 95% confidence interval, 2.07–3.73;
P
<0.00001).

Conclusions—
Our prospective, single-center experience coupled with the findings of the comprehensive meta-analysis underscores the safety of IVT in SM.
Mutational Spectrum and Clinical Features of Patients With ACTG1 Mutations Identified by Massively Parallel DNA Sequencing
Authors: Miyagawa Maiko , Nishio Shin-ya , Ichinose Aya , Iwasaki Satoshi , Murata Takaaki , Kitajiri Shin-ichiro , Usami Shin-ichi 
Published: March 2015

Objectives: ACTG1 has been reported to be a causative gene for autosomal dominant sensorineural hearing loss, DFNA20/26. In this study we sought to clarify the detailed mutational spectrum, clinical features, and genotype-phenotype correlations. Methods: Massively parallel DNA sequencing (MPS) of 63 target candidate genes was used to screen 1120 Japanese hearing loss patients. Results: MPS screening successfully identified 4 ACTG1 mutations in 5 families. The majority of patients showed high frequency–involved progressive hearing loss, with the age of onset mostly in the first or second decade. One patient received electric acoustic stimulation (EAS), which showed a good outcome. Conclusions: Target exon-sequencing using MPS was proven to be a powerful new clinical diagnostic tool for the identification of rare causative genes such as ACTG1. The present clinical findings not only confirmed those previous reports but also provided important new clinical information.
Guarding the guardian: ‘Article 258 TFEU complaints’ before the European Ombudsman
Authors: Tsadiras Alexandros 
Published: March 2015

The infringement procedure of Article 258 TFEU has been consistently viewed by the EU administration and judges as a bipolar bargaining game between the European Commission and the defaulting member state, in which individuals have no role to play. The European Ombudsman's efforts to triangularize the infraction process have resulted in the introduction of a number of soft-law, non-justiciable commitments for the Commission, which are currently set out in the 2012 Communication on its relations with complainants. This article considers the Ombudsman's contribution in the field of infringement complaints by empirically examining the application of the principal provisions of the Commission's Communication in his decision-making. The resulting finding is that Article 258 TFEU complainants have substantially benefited from the Ombudsman's creativity beyond the tight constraints of legality. Points for practitioners The analysis brings to the fore a number of key soft-law, non-justiciable commitments that the European Union administration is expected to honour in its everyday dealings with the European citizenry. The discussion also explores the transformative impact that extra-judicial means for the delivery of administrative justice can have on the ethos and praxis of supranational management. The European Commission's reaction to the European Ombudsman's investigative pressure and the resultant restraints on the former's discretionary powers are useful lessons, which transcend the European Union context and could set the tone for relevant developments in the domestic spheres of the EU member states.
Non-fatal acute haemorrhagic leukoencephalitis following snake bite: A case report
Authors: Prabhakar Appaswamy Thirumal , kamanahalli Ragavendra , Sivadasan Ajith , Joseph Elizabeth , Viggeswarpu Surekha 
Published: March 2015

Acute haemorrhagic leukoencephalitis (AHL) is a fulminant inflammatory disease of cerebral white matter, characterised by demyelination and haemorrhagic necrosis. The outcome is usually fatal with only few survivors. An unusual presentation of a 44–year-old South Indian farmer who developed AHL following a snake bite is reported. Though the initial brain imaging showed extensive involvement of the white matter with multiple haemorrhagic foci, the patient improved spontaneously with no specific therapy. A repeat magnetic resonance imaging of the brain 28 days after the snake bite confirmed radiological improvement.
Lessons learned from the casualties of war: battlefield medicine and its implication for global trauma care
Authors: Chatfield-Ball Catherine , Boyle Peter , Autier Philippe , van Wees Sibylle Herzig , Sullivan Richard 
Published: March 2015

Summary According to the Global Burden of Disease, trauma is now responsible for five million deaths each year. High-income countries have made great strides in reducing trauma-related mortality figures but low–middle-income countries have been left behind with high trauma-related fatality rates, primarily in the younger population. Much of the progress high-income countries have made in managing trauma rests on advances developed in their armed forces. This analysis looks at the recent advances in high-income military trauma systems and the potential transferability of those developments to the civilian health systems particularly in low–middle-income countries. It also evaluates some potential lifesaving trauma management techniques, proven effective in the military, and the barriers preventing these from being implemented in civilian settings.
Endogenous Cycles in Rural to Urban Migration
Authors: Gangopadhyay Partha 
Published: March 2015

We argue that the cost of rural–urban migration may act as an effective entry deterrence for successful migration to the urban sector. This cost results in some form of price rationing as the cash holding of a typical rural household falls short of the required cost. We demonstrate that certain endogenous forces will mesh in with the government policies to generate cumulative improvements in terms of trade in favour of the rural sector. Such improvements in terms of trade are shown to close the gap between the cost and the cash holding of a rural household. As a result, the rate of migration is positively related to the improvements in terms of trade in favour of agriculture. On the other hand, the terms of trade are shown to be inversely related to the rate of migration from agriculture. We establish, for the first time to the best of our understanding, that an endogenously driven and self-sustaining migration cycle would emerge from the rich dynamics involving migration flows and intersectoral terms of trade. We also demonstrates the possibility of a complex dynamics that can characterize the rural–urban migration and the attending development process. One can argue, on the basis of this type of complex dynamics, development process can be unpredictable and highly fragile. In other words, the principles of econophysics can offer an important new framework to understand labour flows in a complex society. JEL: J31, C78
The reliability and validity of cervical auscultation in the diagnosis of dysphagia: a systematic review
Authors: Lagarde Marloes LJ , Kamalski Digna MA , van den Engel-Hoek Lenie 
Published: March 2015

Objective: To systematically review the available evidence for the reliability and validity of cervical auscultation in diagnosing the several aspects of dysphagia in adults and children suffering from dysphagia. Data sources: Medline (PubMed), Embase and the Cochrane Library databases. Review methods: The systematic review was carried out applying the steps of the PRISMA-statement. The methodological quality of the included studies were evaluated using the Dutch ‘Cochrane checklist for diagnostic accuracy studies’. Results: A total of 90 articles were identified through the search strategy, and after applying the inclusion and exclusion criteria, six articles were included in this review. In the six studies, 197 patients were assessed with cervical auscultation. Two of the six articles were considered to be of ‘good’ quality and three studies were of ‘moderate’ quality. One article was excluded because of a ‘poor’ methodological quality. Sensitivity ranges from 23%–94% and specificity ranges from 50%–74%. Inter-rater reliability was ‘poor’ or ‘fair’ in all studies. The intra-rater reliability shows a wide variance among speech language therapists. Conclusion: In this systematic review, conflicting evidence is found for the validity of cervical auscultation. The reliability of cervical auscultation is insufficient when used as a stand-alone tool in the diagnosis of dysphagia in adults. There is no available evidence for the validity and reliability of cervical auscultation in children. Cervical auscultation should not be used as a stand-alone instrument to diagnose dysphagia.
Do Postoperative Platelet-Rich Plasma Injections Accelerate Early Tendon Healing and Functional Recovery After Arthroscopic Supraspinatus Repair?
Authors: Wang Allan , McCann Philip , Colliver Jess , Koh Eamon , Ackland Timothy , Joss Brendan , Zheng Minghao , Breidahl Bill 
Published: March 2015

Background: Tendon-bone healing after rotator cuff repair directly correlates with a successful outcome. Biological therapies that elevate local growth-factor concentrations may potentiate healing after surgery. Purpose: To ascertain whether postoperative and repeated application of platelet-rich plasma (PRP) to the tendon repair site improves early tendon healing and enhances early functional recovery after double-row arthroscopic supraspinatus repair. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: A total of 60 patients underwent arthroscopic double-row supraspinatus tendon repair. After randomization, half the patients received 2 ultrasound-guided injections of PRP to the repair site at postoperative days 7 and 14. Early structural healing was assessed with MRI at 16 weeks, and cuff appearances were graded according to the Sugaya classification. Functional scores were recorded with the Oxford Shoulder Score; Quick Disability of the Arm, Shoulder and Hand; visual analog scale for pain; and Short Form–12 quality-of-life score both preoperatively and at postoperative weeks 6, 12, and 16; isokinetic strength and active range of motion were measured at 16 weeks. Results: PRP treatment did not improve early functional recovery, range of motion, or strength or influence pain scores at any time point after arthroscopic supraspinatus repair. There was no difference in structural integrity of the supraspinatus repair on MRI between the PRP group (0% full-thickness retear; 23% partial tear; 77% intact) and the control group (7% full-thickness retear; 23% partial tear; 70% intact) at 16 weeks postoperatively ( P = .35). Conclusion: After arthroscopic supraspinatus tendon repair, image-guided PRP treatment on 2 occasions does not improve early tendon-bone healing or functional recovery.