bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytomegalovirus Vaccine Strain Towne-Derived Dense Bodies Induce Broad Cellular Immune Responses and Neutralizing Antibodies That Prevent Infection of Fibroblasts and Epithelial Cells
Authors: Cayatte Corinne , Schneider-Ohrum Kirsten , Wang Zhaoti , Irrinki Alivelu , Nguyen Nga , Lu Janine , Nelson Christine , Servat Esteban , Gemmell Lorraine , Citkowicz Andrzej , Liu Yi , Hayes Gregory , Woo Jennifer , Van Nest Gary , Jin Hong , Duke Gregory , McCormick A. Louise 
Published: August 2013

ABSTRACT

Human cytomegalovirus (HCMV), a betaherpesvirus, can cause severe disease in immunosuppressed patients and following congenital infection. A vaccine that induces both humoral and cellular immunity may be required to prevent congenital infection. Dense bodies (DBs) are complex, noninfectious particles produced by HCMV-infected cells and may represent a vaccine option. As knowledge of the antigenicity and immunogenicity of DB is incomplete, we explored characterization methods and defined DB production methods, followed by systematic evaluation of neutralization and cell-mediated immune responses to the DB material in BALB/c mice. DBs purified from Towne-infected cultures treated with the viral terminase inhibitor 2-bromo-5,6-dichloro-1-beta-
d
-ribofuranosyl benzimidazole riboside (BDCRB) were characterized by nanoparticle tracking analysis (NTA), two-dimensional fluorescence difference gel electrophoresis (2D-DIGE), immunoblotting, quantitative enzyme-linked immunosorbent assay, and other methods. The humoral and cellular immune responses to DBs were compared to the immunogenicity of glycoprotein B (gB) administered with the adjuvant AddaVax (gB/AddaVax). DBs induced neutralizing antibodies that prevented viral infection of cultured fibroblasts and epithelial cells and robust cell-mediated immune responses to multiple viral proteins, including pp65, gB, and UL48. In contrast, gB/AddaVax failed to induce neutralizing antibodies that prevented infection of epithelial cells, highlighting a critical difference in the humoral responses induced by these vaccine candidates. Our data advance the potential for the DB vaccine approach, demonstrate important immunogenicity properties, and strongly support the further evaluation of DBs as a CMV vaccine candidate.
A Viral Histone H4 Joins to Eukaryotic Nucleosomes and Alters Host Gene Expression
Authors: Hepat Rahul , Song Ji-Joon , Lee Daeweon , Kim Yonggyun 
Published: August 2013

ABSTRACTA viral histone H4 (CpBV-H4) is encoded in a polydnavirus,Cotesia plutellaebracovirus. Its predicted amino acid sequence is highly homologous to that of host insect histone H4 except for an extended N-terminal tail containing 38 amino acids with nine lysine residues. Its expression induces an immunosuppression of target insects by suppressing immune-associated genes, presumably through an epigenetic control. This study analyzed its molecular interaction with eukaryotic host nucleosomes and subsequent regulation of host gene expression. Purified recombinant CpBV-H4 could associate with nucleosomal components (H2A, H2B, H3, and H4) and form an octamer. Transient expression of CpBV-H4 in an insect,Tribolium castaneum, was performed by microinjection of a recombinant expression vector and confirmed by both reverse transcriptase PCR (RT-PCR) and immunoblotting assays. Under this transient expression condition, total RNAs were extracted and read by a deep-sequencing technique. Annotated transcripts were classified into different gene ontology (GO) categories and compared with those of control insects injected with a truncated CpBV-H4. Target genes manipulated by CpBV-H4 expression showing significant differences (fold changes > 109) included all GO categories, including development and immune-associated genes. When the target genes were physically mapped, they were found to be scattered on entire chromosomes ofT. castaneum. In addition, chromatin immunoprecipitation against CpBV-H4 determined 16 nucleosome sites (P< 10−5) of the viral histone incorporation, which were noncoding regions near DNA-binding and inducible genes. These findings suggest that the viral histone H4 alters host gene expression by a direct molecular interaction with insect nucleosomes.
6-O- andN-Sulfated Syndecan-1 Promotes Baculovirus Binding and Entry into Mammalian Cells
Authors: Makkonen Kaisa-Emilia , Turkki Paula , Laakkonen Johanna P. , Ylä-Herttuala Seppo , Marjomäki Varpu , Airenne Kari J. 
Published: August 2013

ABSTRACTBaculoviruses are insect-specific viruses commonly found in nature. They are not able to replicate in mammalian cells but can transduce them when equipped with an appropriate mammalian cell active expression cassette. Although the viruses have been studied in several types of mammalian cells from different origins, the receptor that baculovirus uses to enter or interact with mammalian cells has not yet been identified. Due to the wide tropism of the virus, the receptor has been suggested to be a generally found cell surface molecule. In this article, we investigated the interaction of baculovirus and mammalian cell surface heparan sulfate proteoglycans (HSPG) in more detail. Our data show that baculovirus requires HSPG sulfation, particularlyN- and 6-O-sulfation, to bind to and transduce mammalian cells. According to our results, baculovirus binds specifically to syndecan-1 (SDC-1) but does not interact with SDC-2 to SDC-4 or with glypicans. Competition experiments performed with SDC-1 antibody or recombinant SDC-1 protein inhibited baculovirus binding, and SDC-1 overexpression enhanced baculovirus-mediated transduction. In conclusion, we show that SDC-1, a commonly found cell surface HSPG molecule, has a role in the binding and entry of baculovirus in vertebrate cells. The results presented here reveal important aspects of baculovirus entry and can serve as a basis for next-generation baculovirus vector development for gene delivery.
Mov10 and APOBEC3G Localization to Processing Bodies Is Not Required for Virion Incorporation and Antiviral Activity
Authors: Izumi Taisuke , Burdick Ryan , Shigemi Mayu , Plisov Sergey , Hu Wei-Shau , Pathak Vinay K. 
Published: August 2013

ABSTRACT
Mov10 and APOBEC3G (A3G) localize to cytoplasmic granules called processing bodies (P bodies), incorporate into human immunodeficiency virus type 1 (HIV-1) virions, and inhibit viral replication. The functional relevance of Mov10/A3G P-body localization to virion incorporation and antiviral activity has not been fully explored. We found that a helicase V mutant of Mov10 exhibits significantly reduced localization to P bodies but still efficiently inhibits viral infectivity via virion incorporation. Disruption of the P bodies by DDX6 knockdown also confirmed Mov10 antiviral activity without P-body localization. In addition, overexpression of SRP19, which binds to 7SL RNA, depleted A3G from P bodies but did not affect its virion incorporation. Sucrose gradient sedimentation assays revealed that the majority of Mov10, A3G, HIV-1 RNA, and Gag formed high-molecular-mass (HMM) complexes that are converted to low-molecular-mass (LMM) complexes after RNase A treatment. In contrast, the P-body markers DCP2, LSM1, eIF4e, DDX6, and AGO1 were in LMM complexes, whereas AGO2, an effector protein of the RNA-induced silencing complex that localizes to P bodies, was present in both LMM and HMM complexes. Depletion of AGO2 indicated that RNA-induced silencing function is required for Mov10's ability to reduce Gag expression upon overexpression, but not its virion incorporation or effect on virus infectivity. We conclude that the majority of Mov10 and A3G are in HMM complexes, whereas most of the P-body markers are in LMM complexes, and that virion incorporation and the antiviral activities of Mov10 and A3G do not require their localization to P bodies.
Basic life support skill improvement with newly designed renewal programme: cluster randomised study of small-group-discussion method versus practice-while-watching method
Authors: Na Ji Ung , Lee Tae Rim , Kang Mun Ju , Shin Tae Gun , Sim Min Seob , Jo Ik Joon , Song Keun Jeong , Jeong Yeon Kwon 
Published: August 2013

BackgroundFor the basic life support (BLS) renewal course, we have devised a new educational programme entitled a small-group-discussion (SGD) programme using personalised video-based debriefing.ObjectiveWe compared the efficacy in BLS skill improvement of the SGD programme with the currently used practice-while-watching (PWW) programme, which uses a standardised education video.MethodThis was a prospective, cluster randomised study, conducted in a single centre, over 6 months from May 2009 to October 2009. Training was performed in two groups of participants, each group with a different renewal education programme. The efficacy of the programmes was compared using the modified Cardiff test and skill-reporting manikins.ResultsResults from 2169 participants were analysed: 1061 in the SGD programme group and 1108 in the PWW programme group. There were no differences between groups on the pretest, either in compression or non-compression skills. However, on the post-test, the SGD programme gave better results for both compression skills and non-compression skills.ConclusionsThe new SGD renewal programme is more effective than the PWW programme for improving skills in BLS renewal training.
Operator training requirements and diagnostic accuracy of Fibroscan in routine clinical practice
Authors: Armstrong M J , Corbett C , Hodson J , Marwah N , Parker R , Houlihan D D , Rowe I A , Hazlehurst J M , Brown R , Hübscher S G , Mutimer D 
Published: August 2013

Abstract

Background
Fibroscan is a quick, non-invasive technique used to measure liver stiffness (kPa), which correlates with fibrosis. To achieve a valid liver stiffness evaluation (LSE) the operator must obtain all the following three criteria: (1) ≥10 successful liver stiffness measurements; (2) IQR/median ratio &lt;0.30 and (3) ≥60% measurement success rate.

Objectives
To assess the operator training requirements and the importance of adhering to the LSE validity criteria in routine clinical practice.

Methods
We retrospectively analysed the LSE validity rates of 2311 Fibroscans performed (1 August 2008 to 31 July 2011) in our tertiary liver outpatients department at the University Hospital Birmingham, UK. The diagnostic accuracy of Fibroscan was assessed in 153 patients, by comparing LSE (valid and invalid) with the modified Ishak fibrosis stage on liver biopsy.

Results
Learning curve analysis highlighted that the greatest improvement in validity of LSE rates occurs in the operator's first 10 Fibroscans, reaching 64.7% validity by the 50th Fibroscan. The correlation between LSE and the fibrosis stage on liver biopsy was superior in patients with a valid LSE (n=97) compared with those with an invalid LSE (n=56) (rs 0.577 vs 0.259; p=0.022). Area under receiving operating characteristics for significant fibrosis was greater when LSE was valid (0.83 vs 0.66; p=0.048). Using an LSE cut-off of 8 kPa, the negative predictive value of valid LSE was superior to invalid LSE for the detection of significant (84% vs 71%) and advanced fibrosis (100% vs 93%).

Conclusions
Fibroscan requires minimal operator training (≥10 observed on patients), and when a valid LSE is obtained, it is an accurate tool for excluding advanced liver fibrosis. To ensure the diagnostic accuracy of Fibroscan it is essential that the recommended LSE validity criteria are adhered to in routine clinical practice.
Energizing the Search to Target LKB1-Mutant Tumors
Authors: Marcus Adam I. , Khuri Fadlo R. 
Published: August 2013

Abstract
Summary: LKB1 is the third most frequently mutated gene in non–small cell lung cancer and serves as a master regulator of cell metabolism and polarity across a variety of model organisms. Recent studies are beginning to identify therapeutics that exploit defects associated with LKB1 loss. The work presented here by Liu and colleagues shows that deoxythymidylate kinase is a new potential target in LKB1-deficient tumors and highlights the possibility of a new therapeutic option for this subset of patients with cancer. Cancer Discov; 3(8); 843–5. ©2013 AACR.
See related article by Liu et al., p. 870
Treatment with the CC chemokine-binding protein Evasin-4 improves post-infarction myocardial injury and survival in mice
Authors: Braunersreuther Vincent , Pelli Graziano , Galan Katia , Proudfoot Amanda E. , Belin Alexandre , Vuilleumier Nicolas , Burger Fabienne , Lenglet Sébastien , Caffa Irene , Soncini Debora , Nencioni Alessio , Vallée Jean-Paul , Mach François , Montecucco Fabrizio 
Published: August 2013

summaryChemokines trigger leukocyte trafficking and are implicated in cardiovascular disease pathophysiology. Chemokine-binding proteins, called “Evasins” have been shown to inhibit both CC and CXC chemokinemediated bioactivities. Here, we investigated whether treatment with Evasin-3 (CXC chemokine inhibitor) and Evasin-4 (CC chemokine inhibitor) could influence post-infarction myocardial injury and remodelling. C57Bl/6 mice were submitted in vivo to left coronary artery permanent ligature and followed up for different times (up to 21 days). After coronary occlusion, three intraperitoneal injections of 10 μg Evasin-3, 1 μg Evasin-4 or equal volume of vehicle (PBS) were performed at 5 minutes, 24 hours (h) and 48 h after ischaemia onset. Both anti-chemokine treatments were associated with the beneficial reduction in infarct size as compared to controls. This effect was accompanied by a decrease in post-infarction myocardial leukocyte infiltration, reactive oxygen species release, and circulating levels of CXCL1 and CCL2. Treatment with Evasin-4 induced a more potent effect, abrogating the inflammation already at one day after ischaemia onset. At days 1 and 21 after ischaemia onset, both anti-chemokine treatments failed to significantly improve cardiac function, remodelling and scar formation. At 21-day follow-up, mouse survival was exclusively improved by Evasin-4 treatment when compared to control vehicle. In conclusion, we showed that the selective inhibition of CC chemokines (i.e. CCL5) with Evasin-4 reduced cardiac injury/inflammation and improved survival. Despite the inhibition of CXC chemokine bioactivities, Evasin-3 did not affect mouse survival. Therefore, early inhibition of CC chemokines might represent a promising therapeutic approach to reduce the development of post-infarction heart failure in mice.
Platelet count and outcome in patients with acute venous thromboembolism
Authors: Di Micco Pierpaolo , Ruiz-Giménez Nuria , Nieto José Antonio , Aujesky Drahomir , Molino Fátima del , Valle Reina , Barrón Manuel , Maestre Ana , Monreal Manuel ,   the RIETE Investigators
Published: August 2013

SummaryThe relationship between platelet count and outcome in patients with acute venous thromboembolism (VTE) has not been consistently explored. RIETE is an ongoing registry of consecutive patients with acute VTE. We categorised patients as having very low- (<80,000/μl), low- (80,000/μl to 150,000/μl), normal- (150,000/μl to 300,000/μl), high- (300,000/μl to 450,000/μl), or very high (>450,000/μl) platelet count at baseline, and compared their three-month outcome. As of October 2012, 43,078 patients had been enrolled in RIETE: 21,319 presenting with pulmonary embolism and 21,759 with deep-vein thrombosis. In all, 502 patients (1.2%) had very low-; 5,472 (13%) low-; 28,386 (66%) normal-; 7,157 (17%) high-; and 1,561 (3.6%) very high platelet count. During the three-month study period, the recurrence rate was: 2.8%, 2.2%, 1.8%, 2.1% and 2.2%, respectively; the rate of major bleeding: 5.8%, 2.6%, 1.7%, 2.3% and 4.6%, respectively; the rate of fatal bleeding: 2.0%, 0.9%, 0.3%, 0.5% and 1.2%, respectively; and the mortality rate: 29%, 11%, 6.5%, 8.8% and 14%, respectively. On multivariate analysis, patients with very low-, low-, high- or very high platelet count had an increased risk for major bleeding (odds ratio [OR]: 2.70, 95% confidence interval [CI]: 1.85–3.95; 1.43 [1.18–1.72]; 1.23 [1.03–1.47]; and 2.13 [1.65–2.75]) and fatal bleeding (OR: 3.70 [1.92–7.16], 2.10 [1.48–2.97], 1.29 [0.88–1.90] and 2.49 [1.49–4.15]) compared with those with normal count. In conclusion, we found a U-shaped relationship between platelet count and the three-month rate of major bleeding and fatal bleeding in patients with VTE.
Two novel inhibitory anti-human factor XI antibodies prevent cessation of blood flow in a murine venous thrombosis model
Authors: van Montfoort Maurits L. , Veronique Knaup L. , Arnoud Marquart J. , Bakhtiari Kamran , Castellino Francis J. , Erik Hack C. , Meijers Joost C. M. 
Published: August 2013

SummaryCoagulation factor XI (FXI) is a promising target for anticoagulation, because of its major role in thrombosis and relatively minor role in haemostasis. This implies that inhibition of FXI can prevent thrombosis without causing bleeding. It was our aim to investigate the antithrombotic properties of two novel inhibitory anti-human FXI antibodies (αFXI-175 and αFXI-203). The in vitro properties of both antibodies were analysed using standard clotting assays and calibrated automated thrombography. For the in vivo model we used FXI knockout mice, in which FXI plasma levels were restored with purified human FXI. Thrombosis was induced by applying ferric chloride to the vena cava inferior, after which time to occlusion was analysed. A tail bleeding assay was used to investigate the safety of both antibodies. Using calibrated automated thrombography, both antibodies inhibited thrombin generation initiated via the intrinsic pathway. In contrast, upon tissue factor (TF)-initiated thrombin generation, αFXI-203 did not inhibit thrombin generation, while αFXI-175 inhibited thrombin generation only at low concentrations of TF. In the murine thrombosis model, the vena cava inferior remained patent for 25 minutes (min) in mice treated with αFXI-175 and for 12.5 min in αFXI-203 treated animals, which was significantly longer than in placebo-treated animals (5 min, p<0.05). Neither antibody caused severe blood loss in a tail bleeding assay. In conclusion, the two inhibitory antibodies against FXI prevented cessation of blood flow in a murine thrombosis model without inducing a bleeding tendency.
Progressive Radiation Dose Reduction From Coronary Computed Tomography Angiography in a Statewide Collaborative Quality Improvement Program
Authors: Chinnaiyan Kavitha M. , Boura Judith A. , DePetris Ann , Gentry Ralph , Abidov Aiden , Share David A. , Raff Gilbert L. 
Published: August 2013

Background—
A best-practice intervention previously demonstrated significant dose reduction over a period of one year. We sought to evaluate whether this reduction would be incremental and sustained by promoting new scanner technology in the context of an ongoing quality improvement program during a 3-year period in a statewide registry of coronary computed tomography angiography.

Methods and Results—

In this prospective, controlled, nonrandomized study involving 11 901 patients at 15 Michigan centers participating in the Advanced Cardiovascular Imaging Consortium, radiation doses and image quality were compared between the following periods: control (May to June 2008) versus follow-up I (July 2008 to June 2009) and follow-up I versus follow-up II (July 2009 to April 2011). Intervention during these study periods included continuous education, feedback, and mandatory participation in this initiative. The median radiation dose remained unchanged from control to follow-up I: dose-length product of 697 (interquartile range, 407–1163) to 675 (interquartile range, 418–1146) mGy·cm (
P
=0.93). With the introduction of newer technology in follow-up I period, there was incremental 31% decrease during follow-up II to median dose-length product of 468 (interquartile range, 292–811) mGy·cm (
P
<0.0001). No significant change was noted in the percentage of diagnostic quality scans from follow-up I (92%) to follow-up II (92.7%).

Conclusions—
Although ongoing application of a best-practice algorithm was associated with sustaining previously achieved targets, the use of newer scanner technology resulted in incremental radiation dose reduction in a statewide coronary computed tomography angiography registry without image quality degradation.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00640068.
Effects of Visit-to-Visit Variability in Systolic Blood Pressure on Macrovascular and Microvascular Complications in Patients With Type 2 Diabetes Mellitus
Authors: Hata Jun , Arima Hisatomi , Rothwell Peter M. , Woodward Mark , Zoungas Sophia , Anderson Craig , Patel Anushka , Neal Bruce , Glasziou Paul , Hamet Pavel , Mancia Giuseppe , Poulter Neil , Williams Bryan , MacMahon Stephen , Chalmers John 
Published: August 2013

Background—
Recent evidence suggests that visit-to-visit variability in systolic blood pressure (SBP) and maximum SBP are predictors of cardiovascular disease. However, it remains uncertain whether these parameters predict the risks of macrovascular and microvascular complications in patients with type 2 diabetes mellitus.

Methods and Results—

The Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) was a factorial randomized controlled trial of blood pressure lowering and blood glucose control in patients with type 2 diabetes mellitus. The present analysis included 8811 patients without major macrovascular and microvascular events or death during the first 24 months after randomization. SBP variability (defined as standard deviation) and maximum SBP were determined during the first 24 months after randomization. During a median 2.4 years of follow-up from the 24-month visit, 407 major macrovascular (myocardial infarction, stroke, or cardiovascular death) and 476 microvascular (new or worsening nephropathy or retinopathy) events were observed. The association of major macrovascular and microvascular events with SBP variability was continuous even after adjustment for mean SBP and other confounding factors (both
P
<0.05 for trend). Hazard ratios (95% confidence intervals) for the highest tenth of SBP variability were 1.54 (0.99–2.39) for macrovascular events and 1.84 (1.19–2.84) for microvascular events in comparison with the lowest tenth. For maximum SBP, hazard ratios (95% confidence intervals) for the highest tenth were 3.64 (1.73–7.66) and 2.18 (1.04–4.58), respectively.

Conclusion—
Visit-to-visit variability in SBP and maximum SBP were independent risk factors for macrovascular and microvascular complications in type 2 diabetes mellitus.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique Identifier: NCT00145925.