bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ecto-5′-Nucleotidase, CD73, Is an Endothelium-Derived Hyperpolarizing Factor Synthase
Authors: Ohta Masanori , Toyama Kazuyoshi , Gutterman David D. , Campbell William B. , Lemaître Vincent , Teraoka Ryutaro , Miura Hiroto 
Published: January 2013

Objective—
Adenosine dilates human coronary arteries by activating potassium channels in an endothelial cell-independent manner. Cell surface ecto-5′-nucleotidase (CD73) rapidly dephosphorylates extracellular adenosine 5′-monophosphate to adenosine. We tested the hypothesis that coronary vasodilation to adenine nucleotides is mediated by an endothelial CD73-dependent, extracellular production of adenosine that acts as an endothelium-derived hyperpolarizing factor.

Methods and Results—
Videomicroscopy showed that adenine nucleotides, but not inosine, potently dilated and hyperpolarized human coronary arteries independent of nitric oxide, prostacyclin, and classical endothelium-derived hyperpolarizing factors, whereas endothelial denudation, adenosine receptor antagonism, adenosine deaminase, or CD73 blockers reduced vasodilations. Liquid chromatography–electrospray ionization–mass spectrometry revealed adenosine accumulation in perfusates from arteries in the presence of adenosine 5′-diphosphate. CD73 was localized on the cell surface of endothelial cells, but not of vascular smooth muscle cells, and its deficiency suppressed vasodilation of mouse coronary arteries to adenine nucleotides and augmented vasodilation to adenosine. Adenosine dose-dependently dilated and hyperpolarized human coronary arteries to a similar extent as adenosine 5′-diphosphate.

Conclusion—
Coronary vasodilation to adenine nucleotides is associated with endothelial CD73-dependent production of extracellular adenosine that acts as an endothelium-derived hyperpolarizing factor by relaxing and hyperpolarizing underlying vascular smooth muscle cells via activating adenosine receptors. Thus, CD73 is a novel endothelium-derived hyperpolarizing factor synthase in human and mouse coronary arteries.
Analysis of Stromal Cell Secretomes Reveals a Critical Role for Stromal Cell–Derived Hepatocyte Growth Factor and Fibronectin in Angiogenesis
Authors: Newman Andrew C. , Chou Wayne , Welch-Reardon Katrina M. , Fong Ashley H. , Popson Stephanie A. , Phan Duc Thien , Sandoval Daniel R. , Nguyen Dananh P. , Gershon Paul D. , Hughes Christopher C. W. 
Published: January 2013

Objective—
Angiogenesis requires tightly coordinated crosstalk between endothelial cells (ECs) and stromal cells, such as fibroblasts and smooth muscle cells. The specific molecular mechanisms moderating this process are still poorly understood.

Methods and Results—
Stromal cell–derived factors are essential for EC sprouting and lumen formation. We therefore compared the abilities of 2 primary fibroblast isolates and a primary smooth muscle cell isolate to promote in vitro angiogenesis, and analyzed their secretomes using a combination of nano liquid chromatography-mass spectrometry/mass spectrometry, quantitative PCR, and ELISA. Each isolate exhibited a different level of angiogenic ability. Using quantitative MS, we then compared the secretomes of a fibroblast isolate exhibiting low angiogenic activity, a fibroblast isolate exhibiting high angiogenic activity, and human umbilical vein ECs. High angiogenic fibroblast supernatants exhibited an overabundance of proteins associated with extracellular matrix constituents compared with low angiogenic fibroblasts or ECs. Finally, small interfering RNA technology and purified protein were used to confirm a role for stromal cell–derived hepatocyte growth factor and fibronectin in inducing EC sprouting.

Conclusion—
Differences in stromal cell ability to induce angiogenesis are a result of differences in the secreted proteomes of both extracellular matrix proteins and proangiogenic growth factors.
HMGB1 Expression and Secretion Are Increased Via TWEAK–Fn14 Interaction in Atherosclerotic Plaques and Cultured Monocytes
Authors: Moreno Juan A. , Sastre Cristina , Madrigal-Matute Julio , Muñoz-García Begoña , Ortega Luis , Burkly Linda C. , Egido Jesús , Martín-Ventura Jose L. , Blanco-Colio Luis M. 
Published: January 2013

Objective—
High-mobility group box 1 (HMGB1), a DNA-binding cytokine expressed mainly by macrophages, contributes to lesion progression and chronic inflammation within atherosclerotic plaque. It has been suggested that different cytokines could regulate HMGB1 expression in monocytes. We have analyzed the effect of tumor necrosis factor–like weak inducer of apoptosis (TWEAK) on HMGB1 expression both in vivo and in vitro.

Methods and Results—

Expression of TWEAK and its receptor fibroblast growth factor–inducible 14 (Fn14) was positively correlated with HMGB1 in human carotid atherosclerotic plaques. TWEAK increased HMGB1 mRNA expression and protein secretion in human acute monocytic leukemia cell line cultured monocytes. TWEAK-mediated HMGB1 increase was only observed in M1 macrophages but not in M2 ones. These effects were reversed using blocking anti-Fn14 antibody or nuclear factor-kappa B and phosphotidylinositol-3 kinase inhibitors. TWEAK also increased monocyte chemoattractant protein-1 secretion in human acute monocytic leukemia cell line cells, an effect blocked with an HMGB1 small interfering RNA. Systemic TWEAK injection in ApoE
−/−
mice increased HMGB1 protein expression in the aortic root and mRNA expression in total aorta of ApoE
−/−
mice. Conversely, TWEAK-blocking antibodies diminished HMGB1 protein and mRNA expression compared with IgG-treated mice.

Conclusion—
Our results indicate that TWEAK can regulate expression and secretion of HMGB1 in monocytes/macrophages, participating in the inflammatory response associated with atherosclerotic plaque development.
Subarachnoid Hemorrhage in a Multimodal Approach Heavily Weighted Toward Mechanical Thrombectomy With Solitaire Stent in Acute Stroke
Authors: Yoon Woong , Jung Min Young , Jung Se Hee , Park Man Seok , Kim Joon Tae , Kang Heoung Keun 
Published: January 2013

Background and Purpose—
Subarachnoid hemorrhage (SAH) may appear on computerized tomography scans after mechanical thrombectomy for acute ischemic stroke. The incidence and prognosis of this observation remain unknown. We investigated the frequency and clinical consequences of SAH after treating acute ischemic stroke with a multimodal approach heavily weighted toward mechanical thrombectomy with Solitaire stent.

Methods—
Seventy-four consecutive patients with acute ischemic stroke underwent mechanical thrombectomy with a Solitaire stent as a first-line treatment. Nonenhanced computerized tomography scans were performed before, immediately after, and 24 hours after treatment to detect SAH. Clinical outcome was assessed after treatment, on day 1, at discharge, and at 3 months. Clinical and radiological data were compared between patients with and without SAH.

Results—

Twelve patients (16.2%) exhibited SAH associated with pure SAH (n=4) or mixed SAH and contrast extravasation (n=8). The SAH was located in the ipsilateral Sylvian fissure (n=11) or bilateral parietooccipital sulci (n=1). Patients with SAH had no periprocedural vessel perforations or arterial dissections and no postprocedural neurological deteriorations. Rescue angioplasty was performed more frequently in SAH group than in control group (33.3% vs 9.7%;
P
=0.05). Patients with SAH and those without had similar recanalization rates and clinical outcomes.

Conclusions—
SAH on post-therapeutic computerized tomography scans were not uncommon after primary mechanical thrombectomy with a Solitaire stent, but they seemed to be benign. Rescue angioplasty and unidentified, small vessel ruptures due to mechanical stretch during stent retrieval might give rise to these lesions.
Resonant Diurnal Oscillations and Mean Alongshore Flows Driven by Sea/Land Breeze Forcing in the Coastal Southern California Bight
Authors: Nam SungHyun , Send Uwe 
Published: January 2013

Abstract
This study presents observations of the cross-sectional structure of resonant response to sea/land breezes (SLBs) off Huntington Beach (HB) in the Southern California Bight (SCB). A resonant response to local diurnal wind stress fluctuations associated with SLB forcing occurs intermittently and produces strong diurnal oscillations of flow and temperature resulting from enhanced work of the diurnal local wind on the sea surface. At nighttime (daytime), a coherent cross-sectional circulation with offshore (onshore) currents in the surface layer (upper 15 m) and onshore (offshore) currents in the intermediate layer around 20 m are generated, with a three-layered vertical structure on the outer shelf. The authors find a net cross-shore eddy heat flux (net cooling of nearshore water) during the period of strong response to SLB, that is, a rectified mean heat flux and steeper isotherms resulting from the diurnal SLB fluctuations. The steepened mean isotherms are also found to be in thermal–wind balance with intensified mean equatorward flow, which thus can also be generated by the resonant SLB dynamics. Similar rectified onshore transport of other quantities is expected, relevant for biogeochemical processes. The distribution of maximum diurnal kinetic energy in time and across the shelf supports the concept that subinertial shears create the sufficient condition for resonant response to SLB forcing.
TLR9-mediated siRNA delivery for targeting of normal and malignant human hematopoietic cells in vivo
Authors: Zhang Qifang , Hossain Dewan Md Sakib , Nechaev Sergey , Kozlowska Anna , Zhang Wang , Liu Yong , Kowolik Claudia M. , Swiderski Piotr , Rossi John J. , Forman Stephen , Pal Sumanta , Bhatia Ravi , Raubitschek Andrew , Yu Hua , Kortylewski Marcin 
Published: January 2013

Key PointsCpG(A)-siRNA oligonucleotides allow for targeting genes specifically in human TLR9+ immune cells and blood cancer cells. Tumoricidal and immunostimulatory properties of CpG(A)-STAT3 siRNA provide a novel therapeutic opportunity for hematologic malignancies.
Production of mycobacterial cell wall glycopeptidolipids requires a member of the MbtH-like protein family
Authors: Tatham Elizabeth , sundaram Chavadi Sivagami , Mohandas Poornima , Edupuganti Uthamaphani R , Angala Shiva K , Chatterjee Delphi , Quadri Luis E N 
Published: January 2013

Abstract

Background
Glycopeptidolipids (GPLs) are among the major free glycolipid components of the outer membrane of several saprophytic and clinically-relevant Mycobacterium species. The architecture of GPLs is based on a constant tripeptide-amino alcohol core of nonribosomal peptide synthetase origin that is N-acylated with a 3-hydroxy/methoxy acyl chain synthesized by a polyketide synthase and further decorated with variable glycosylation patterns built from methylated and acetylated sugars. GPLs have been implicated in many aspects of mycobacterial biology, thus highlighting the significance of gaining an understanding of their biosynthesis. Our bioinformatics analysis revealed that every GPL biosynthetic gene cluster known to date contains a gene (referred herein to as gplH) encoding a member of the MbtH-like protein family. Herein, we sought to conclusively establish whether gplH was required for GPL production.

Results
Deletion of gplH, a gene clustered with nonribosomal peptide synthetase-encoding genes in the GPL biosynthetic gene cluster of Mycobacterium smegmatis, produced a GPL deficient mutant. Transformation of this mutant with a plasmid expressing gplH restored GPL production. Complementation was also achieved by plasmid-based constitutive expression of mbtH, a paralog of gplH found in the biosynthetic gene cluster for production of the siderophore mycobactin of M. smegmatis. Further characterization of the gplH mutant indicated that it also displayed atypical colony morphology, lack of sliding motility, altered capacity for biofilm formation, and increased drug susceptibility.

Conclusions
Herein, we provide evidence formally establishing that gplH is essential for GPL production in M. smegmatis. Inactivation of gplH also leads to a pleiotropic phenotype likely to arise from alterations in the cell envelope due to the lack of GPLs. While genes encoding MbtH-like proteins have been shown to be needed for production of siderophores and antibiotics, our study presents the first case of one such gene proven to be required for production of a cell wall component. Furthermore, our results provide the first example of a mbtH-like gene with confirmed functional role in a member of the Mycobacterium genus. Altogether, our findings demonstrate a critical role of gplH in mycobacterial biology and advance our understanding of the genetic requirements for the biosynthesis of an important group of constituents of the mycobacterial outer membrane.
The university münster model surgery system for orthognathic surgery. Part II – KD-MMS
Authors: Ehmer Ulrike , Joos Ulrich , Ziebura Thomas , Flieger Stefanie , Wiechmann Dirk 
Published: January 2013

Abstract

Background
Model surgery is an integral part of the planning procedure in orthognathic surgery. Most concepts comprise cutting the dental cast off its socket. The standardized spacer plates of the KD-MMS provide for a non-destructive, reversible and reproducible means of maxillary and/or mandibular plaster cast separation.

Methods
In the course of development of the system various articulator types were evaluated with regard to their capability to provide a means of realizing the concepts comprised of the KD-MMS. Special attention was dedicated to the ability to perform three-dimensional displacements without cutting of plaster casts. Various utilities were developed to facilitate maxillary displacement in accordance to the planning. Objectives of this development comprised the ability to implement the values established in the course of two-dimensional ceph planning.

Results
The system - KD-MMS comprises a set of hardware components as well as a defined procedure. Essential hardware components are red spacer and blue mounting plates. The blue mounting plates replace the standard yellow SAM mounting elements. The red spacers provide for a defined leeway of 8 mm for three-dimensional movements. The non-destructive approach of the KD-MMS makes it possible to conduct different model surgeries with the same plaster casts as well as to restore the initial, pre-surgical situation at any time. Thereby, surgical protocol generation and gnathologic splint construction are facilitated.

Conclusions
The KD-MMS hardware components in conjunction with the defined procedures are capable of increasing efficiency and accuracy of model surgery and splint construction. In cases where different surgical approaches need to be evaluated in the course of model surgery, a significant reduction of chair time may be achieved.
Preoperative chemoradiotherapy for locally advanced gastric cancer
Authors: Pepek Joseph M , Chino Junzo P , Willett Christopher G , Palta Manisha , Blazer III Dan G , Tyler Douglas S , Uronis Hope E , Czito Brian G 
Published: January 2013

Abstract

Background
To examine toxicity and outcomes for patients treated with preoperative chemoradiotherapy (CRT) for gastric cancer.

Methods
Patients with gastroesophageal (GE) junction (Siewert type II and III) or gastric adenocarcinoma who underwent neoadjuvant CRT followed by planned surgical resection at Duke University between 1987 and 2009 were reviewed. Overall survival (OS), local control (LC) and disease-free survival (DFS) were estimated using the Kaplan-Meier method. Toxicity was graded according to the Common Toxicity Criteria for Adverse Events version 4.0.

Results
Forty-eight patients were included. Most (73%) had proximal (GE junction, cardia and fundus) tumors. Median radiation therapy dose was 45 Gy. All patients received concurrent chemotherapy. Thirty-six patients (75%) underwent surgery. Pathologic complete response and R0 resection rates were 19% and 86%, respectively. Thirty-day surgical mortality was 6%. At 42 months median follow-up, 3-year actuarial OS was 40%. For patients undergoing surgery, 3-year OS, LC and DFS were 50%, 73% and 41%, respectively.

Conclusions
Preoperative CRT for gastric cancer is well tolerated with acceptable rates of perioperative morbidity and mortality. In this patient cohort with primarily advanced disease, OS, LC and DFS rates in resected patients are comparable to similarly staged, adjuvantly treated patients in randomized trials. Further study comparing neoadjuvant CRT to standard treatment approaches for gastric cancer is indicated.
Low-field magnetic resonance imaging study on carpal arthritis in systemic sclerosis - low-grade erosive arthritis of carpal bones is an unexpected and frequent disease manifestation
Authors: Akbayrak Elif , Dinser Robert , Müller-Ladner Ulf , Tarner Ingo H 
Published: January 2013

Abstract
Introduction
The aim of the present study was to assess the prevalence and characteristics of subclinical arthritis of carpal and metacarpophalangeal joints in patients with systemic sclerosis (SSc).

Methods
Low-field (0.2 T) magnetic resonance imaging (MRI) was performed in consecutive patients with SSc attending our center between January 2010 and March 2011. Results were assessed in a standardized manner using the Rheumatoid Arthritis Magnetic Resonance Imaging Score (RAMRIS) and standardized assessments of all hand joints. Patients with arthritis due to overlap syndromes were excluded.

Results
Of 38 inpatients and eight outpatients who were screened for inclusion, 30 patients participated in the study and 26 patients could be evaluated. Erosions, bone marrow edema, synovitis, and joint effusions were found in 87%, 37%, 68%, and 58%, respectively, and 24% of patients had additional tenovaginitis. Arthritis affected only a low number of joints per analyzed hand. All bones and joints could be affected, but synovitis and bone marrow edema occurred predominantly in the proximal row of carpal bones, most frequently affecting the lunate bone. The extent of inflammatory changes measured with the RAMRIS correlated significantly with the functional status assessed with the validated German functional score questionnaire Funktionsfragebogen Hannover.

Conclusion
Low-grade arthritic changes on low-field MRI are frequent in patients with pure SSc. The features of arthritis in SSc differ from rheumatoid arthritis. The distribution, the MRI pattern and the predilection for the lunate bone raise the hypothesis that arthritis in SSc may be caused not only by immunological inflammation but also by ischemic mechanisms.
Management of chronic obstructive pulmonary disease in India: a systematic review
Authors: Mckay Ailsa J , Pa Mahesh , Patel Raju Kk , Majeed Azeem 
Published: January 2013

Objectives Chronic diseases are fast becoming the largest health burden in India. Despite this, their management in India has not been well studied. We aimed to systematically review the nature and efficacy of current management strategies for chronic obstructive pulmonary disease (COPD) in India. Methods We used database searches (MEDLINE, EMBASE, IndMED, CENTRAL and CINAHL), journal hand-searches, scanning of reference lists and contact with experts to identify studies for systematic review. We did not review management strategies aimed at chronic diseases more generally, nor management of acute exacerbations. Due to the heterogeneity of reviewed studies, meta-analysis was not appropriate. Thus, narrative methods were used. Setting India Participants All adult populations resident in India Main outcome measures 1. Trialled interventions and outcomes 2. Extent and efficacy of current management strategies 3. Above outcomes by subgroup Results We found information regarding current management – particularly regarding the implementation of national guidelines and primary prevention – to be minimal. This led to difficulty in interpreting studies of management strategies, which were varied and generally of positive effect. Data regarding current management outcomes were very few. Conclusions The current understanding of management strategies for COPD in India is limited due to a lack of published data. Determination of the extent of current use of management guidelines, availability and use of treatment, and current primary prevention strategies would be useful. This would also provide evidence on which to interpret existing and future studies of management outcomes and novel interventions.
Epitope Specificity and IgG Subclass Distribution of Autoantibodies to Cardiac Troponin
Authors: Savukoski Tanja , Twarda Aleksandra , Hellberg Sanna , Ristiniemi Noora , Wittfooth Saara , Sinisalo Juha , Pettersson Kim 
Published: January 2013

BACKGROUND
Autoantibodies to cardiac troponins (cTnAAbs) can interfere with the measurement of cardiac troponin I (cTnI) by immunoassays for the diagnosis of myocardial infarction. Therefore, we determined the cTnI binding sites and IgG subclasses of circulating cTnAAbs.

METHODS
We studied epitope specificity with sandwich-type immunoassays by measuring the recovery of troponin complex added to 10 cTnAAb-negative and 10 cTnAAb-positive sera from healthy volunteers. To study the IgG subclasses, we analyzed admission and 3-month follow-up sera from chest pain patients with a reference assay measuring total IgG (14 cTnAAb negative and 14 cTnAAb positive at 3 months) and with 4 subclass-specific assays measuring exclusively IgG subclasses 1–4.

RESULTS
Mean recoveries of troponin complex in cTnAAb-positive samples for single cTnI epitopes ranged from 37% to 211%, being lowest for the cTnI midfragment (aa 30–110). However, the lowest sample-specific recoveries, 4%–92%, showed that none of the studied epitopes completely escaped the cTnAAb-related interference. Eight chest pain patients of the cTnAAb-positive group became positive between sampling points, and according to all 5 cTnAAb assays, specific signals were generally higher at follow-up. IgG4, with the highest prevalence, was detected in 68% of samples in the cTnAAb-positive group.

CONCLUSIONS
IgG subclass studies confirm that cTnAAb formation may be triggered/boosted in acute cardiac events. This new information about the epitope specificity of cTnAAbs should be used to reevaluate existing recommendations regarding use of midfragment epitopes in cTnI assays. To circumvent the negative interference of the highly heterogeneous cTnAAbs, use of 3 or more unconventionally selected epitopes should be considered.
Conflict and Diplomacy in the South China Sea
Authors: Simon Sheldon W. 
Published: January 2013

Abstract
Disputes over sovereignty and freedom of navigation in the South China Sea (SCS) involve both the claimants and major maritime powers. Two starkly different approaches to the SCS conflict are discussed: (1) diplomacy among the claimants either bilaterally or multilaterally; (2) if diplomacy fails, the claimants are building their militaries to assert their rights through force.