bluuebunny/crossref_metadata_2025_split huggingface dataset:
The ADP-Ribosyltransferase Domain of the Effector Protein ExoS Inhibits Phagocytosis of Pseudomonas aeruginosa during Pneumonia
Authors: Rangel Stephanie M. , Logan Latania K. , Hauser Alan R. 
Published: June 2014

ABSTRACT

Pseudomonas aeruginosa
is a Gram-negative pathogen commonly associated with nosocomial infections such as hospital-acquired pneumonia. It uses a type III secretion system to deliver effector proteins directly into the cytosol of host cells. Type III secretion in
P. aeruginosa
has been linked to severe disease and worse clinical outcomes in animal and human studies. The majority of
P. aeruginosa
strains secrete ExoS, a bifunctional toxin with GTPase-activating protein and ADP-ribosyltransferase activities. Numerous
in vitro
studies have investigated the targets and cellular effects of ExoS, linking both its enzymatic activities with inhibition of bacterial internalization. However, little is known about how this toxin facilitates the progression of infection
in vivo
. In this study, we used a mouse model to investigate the role of ExoS in inhibiting phagocytosis during pneumonia. We first confirmed previous findings that the ADP-ribosyltransferase activity of ExoS, but not the GTPase-activating protein activity, was responsible for bacterial persistence and decreased host survival in this model. We then used two distinct assays to demonstrate that ExoS inhibited phagocytosis during pneumonia. In contrast to the findings of several
in vitro
studies, this
in vivo
inhibition was also dependent on the ADP-ribosyltransferase activity, but not the GTPase-activating protein activity, of ExoS. These results demonstrate for the first time the antiphagocytic function of ExoS in the context of an actual infection and indicate that blocking the ADP-ribosyltransferase activity of ExoS may have potential therapeutic benefit.

IMPORTANCE
Pseudomonas aeruginosa
is a major cause of hospital-acquired infections. To cause severe disease, this bacterium uses a type III secretion system that delivers four effector proteins, ExoS, ExoT, ExoU, and ExoY, into host cells. The majority of
P. aeruginosa
strains secrete ExoS, a bifunctional toxin with GTPase-activating protein and ADP-ribosyltransferase activities. In cell culture models, both enzymatic activities have been associated with decreased bacterial internalization. However, our study is the first to examine a role for ExoS in blocking phagocytosis in an animal model. We report that ExoS does inhibit phagocytosis during pneumonia. The ADP-ribosyltransferase activity, but not the GTPase-activating protein activity, of ExoS is necessary for this effect. Our findings highlight the ability of
P. aeruginosa
to manipulate the inflammatory response during pneumonia to facilitate bacterial survival.
Systematic review of incidence and complications of herpes zoster: towards a global perspective
Authors: Kawai Kosuke , Gebremeskel Berhanu G , Acosta Camilo J 
Published: June 2014

ObjectiveThe objective of this study was to characterise the incidence rates of herpes zoster (HZ), also known as shingles, and risk of complications across the world.DesignWe systematically reviewed studies examining the incidence rates of HZ, temporal trends of HZ, the risk of complications including postherpetic neuralgia (PHN) and HZ-associated hospitalisation and mortality rates in the general population. The literature search was conducted using PubMed, EMBASE and the WHO library up to December 2013.ResultsWe included 130 studies conducted in 26 countries. The incidence rate of HZ ranged between 3 and 5/1000 person-years in North America, Europe and Asia-Pacific, based on studies using prospective surveillance, electronic medical record data or administrative data with medical record review. A temporal increase in the incidence of HZ was reported in the past several decades across seven countries, often occurring before the introduction of varicella vaccination programmes. The risk of developing PHN varied from 5% to more than 30%, depending on the type of study design, age distribution of study populations and definition. More than 30% of patients with PHN experienced persistent pain for more than 1 year. The risk of recurrence of HZ ranged from 1% to 6%, with long-term follow-up studies showing higher risk (5–6%). Hospitalisation rates ranged from 2 to 25/100 000 person-years, with higher rates among elderly populations.ConclusionsHZ is a significant global health burden that is expected to increase as the population ages. Future research with rigorous methods is important.
Safer cycling in the urban road environment: study approach and protocols guiding an Australian study
Authors: Stevenson Mark , Johnson Marilyn , Oxley Jennie , Meuleners Lynn , Gabbe Belinda , Rose Geoffrey 
Published: June 2014

BackgroundMuch of the research into cyclist safety in Australia has focused on behaviour with less focus on the impact of the urban transport environment on cyclist safety. A greater understanding of the urban transport system and the improvements needed to create a safer cycling environment are essential if cyclists are to be safe and increased cycling participation targets are to be achieved. The proposed study will use existing cyclist crash data along with unique cyclist exposure data to develop road infrastructure prototypes that improve cyclists’ safety and evaluate the effectiveness of these prototypes in a cycling simulator.Methods and designThis study will be conducted in two Australian cities namely Perth and Melbourne as both cities have policies that strongly advocate cycling. Two methods of data collection will be employed: (1) in-depth crash investigations of injured cyclists; and (2) video footage of cyclist exposure through a naturalistic cycling study of non-injured cyclists. The findings from these two methods will be used to develop new urban road design prototypes which will be tested with a sample of cyclists and motorists in safe environment namely, a cycling simulator and a driving simulator.DiscussionBy designing and evaluating safer environments for cyclists, this study will identify solutions that reduce the risk of road trauma and importantly, support this alternative mode of transport and thereby contribute to a reduction in traffic-related emissions and pollution and enhance sustainable economic and social connectivity.
Reasons provided for requesting a termination of pregnancy in the UK
Authors: Wokoma Tonye Telema , Jampala Malathi , Bexhell Helen , Guthrie Kate A , Lindow Stephen W 
Published: June 2014

ObjectiveTo determine the main reasons for termination of pregnancy (TOP) requests in a UK city.DesignA survey requesting reasons for a pregnancy termination from women attending a TOP clinic.SettingA TOP pre-assessment clinic in Hull and East Yorkshire Hospitals, UK.PopulationA cohort of pregnant women requesting a TOP in the first trimester.MethodsA confidential, anonymous, self-administered questionnaire requesting demographic information about age, education, ethnicity and marital status. The questionnaire also asked for the main reasons underlying the TOP request. The main outcome measures were (1) reasons for TOP requests and (2) correlations between the reasons provided and demographic characteristics.ResultsA total of 274 women participated in the study and 527 reasons were given. The most common reason was money worries (21.0%) followed closely by contraception failure (20.5%). The third most common reason was the anticipated effect on education or the woman's career (14.6%) Over half (59.5%) of the women were single and 8.8% were divorced or separated. Twenty-eight per cent of the respondents were aged 21 years and below, 36.1% were aged 22–29 years and 29.2% were over 30 years of age.ConclusionsThe main reasons for TOP requests included financial constraints, contraceptive failure, completion of family, and potential interruption of education or career. These reasons differed with age groups and marital status. Focused qualitative research on reasons for a TOP will provide further knowledge and understanding that is needed to enable optimal service provision and policy planning.
Podpeč limestone: a heritage stone from Slovenia
Authors: Kramar S. , Bedjanič M. , Mirtič B. , Mladenović A. , Rožič B. , Skaberne D. , Gutman M. , Zupančič N. , Cooper B. 
Published: June 2014

Abstract

Podpeč Limestone is characterized by its dark grey or nearly black colour, contrasting with white fossil shells of the mollusc
Lithiotis
. This formation, which has been dated as Lower Jurassic, occurs in southern and southwestern Slovenia and is particularly conspicuous in areas SW of Ljubljana. The main quarry, which is not active, is located near the village of Podpeč near Ljubljana and has been recognized as a geological site of national importance; as such, it is officially protected as a natural monument. The utilization of Podpeč Limestone was first documented during the Roman period in Slovenia. At the end of the 5th century AD, with the decline of the Roman Empire, stone-cutting ceased at Podpeč for many centuries. Towards the end of the 19th century Podpeč Limestone became better-known. During the first half of the 20th century significant stonecutting workshops were established in Podpeč with most stone being supplied from the main quarry. The internationally renowned Slovenian architect Jože Plečnik (1872–1957) used Podpeč Limestone in various Slovenian buildings, some of national importance. The utilization and national recognition of Podpeč Limestone within Slovenia provide abundant support for its nomination as a Global Heritage Stone Resource.
Prognostic B-cell Signatures Using mRNA-Seq in Patients with Subtype-Specific Breast and Ovarian Cancer
Authors: Iglesia Michael D. , Vincent Benjamin G. , Parker Joel S. , Hoadley Katherine A. , Carey Lisa A. , Perou Charles M. , Serody Jonathan S. 
Published: June 2014

Abstract
Purpose: Lymphocytic infiltration of tumors predicts improved survival in patients with breast cancer. Previous studies have suggested that this survival benefit is confined predominantly to the basal-like subtype. Immune infiltration in ovarian tumors is also associated with improved prognosis. Currently, it is unclear what aspects of the immune response mediate this improved outcome.
Experimental Design: Using The Cancer Genome Atlas mRNA-seq data and a large microarray dataset, we evaluated adaptive immune gene expression by genomic subtype in breast and ovarian cancer. To investigate B-cells observed to be prognostic within specific subtypes, we developed methods to analyze B-cell population diversity and degree of somatic hypermutation (SHM) from B-cell receptor (BCR) sequences in mRNA-seq data.
Results: Improved metastasis-free/progression-free survival was correlated with B-cell gene expression signatures, which were restricted mainly to the basal-like and HER2-enriched breast cancer subtypes and the immunoreactive ovarian cancer subtype. Consistent with a restricted epitope-driven response, a subset of basal-like and HER2-enriched breast tumors and immunoreactive ovarian tumors showed high expression of a low-diversity population of BCR gene segments. More BCR segments showed improved prognosis with increased expression in basal-like breast tumors and immunoreactive ovarian tumors compared with other subtypes. Basal-like and HER2-enriched tumors exhibited more BCR sequence variants in regions consistent with SHM.
Conclusion: Taken together, these data suggest the presence of a productive and potentially restricted antitumor B-cell response in basal-like breast and immunoreactive ovarian cancers. Immunomodulatory therapies that support B-cell responses may be a promising therapeutic approach to targeting these B-cell infiltrated tumors. Clin Cancer Res; 20(14); 3818–29. ©2014 AACR.
Twisting and Ironing: Doxorubicin Cardiotoxicity by Mitochondrial DNA Damage
Authors: Nitiss Karin C. , Nitiss John L. 
Published: June 2014

Abstract
Anthracyclines are active clinical agents that have multiple mechanisms of cytotoxicity. Cardiotoxicity by anthracyclines limits the therapeutic potential of these agents, but mechanisms leading to cardiotoxicity remain controversial. Transgenic mice that lack mitochondrial topoisomerase I are hypersensitive to doxorubicin cardiotoxicity, providing support for cardiotoxicity arising from damage of mitochondrial DNA. Clin Cancer Res; 20(18); 4737–9. ©2014 AACR.
Transcriptional Roles of PARP1 in Cancer
Authors: Schiewer Matthew J. , Knudsen Karen E. 
Published: June 2014

Abstract
Poly (ADP-ribose) polymerase-1 (PARP1) is an abundant, ubiquitously expressed NAD+-dependent nuclear enzyme that has prognostic value for a multitude of human cancers. PARP1 activity serves to poly (ADP-ribose)-ylate the vast majority of known client proteins and affects a number of cellular and biologic outcomes, by mediating the DNA damage response (DDR), base-excision repair (BER), and DNA strand break (DSB) pathways. PARP1 is also critically important for the maintenance of genomic integrity, as well as chromatin dynamics and transcriptional regulation. Evidence also indicates that PARP-directed therapeutics are “synthetic lethal” in BRCA1/2-deficient model systems. Strikingly, recent studies have unearthed exciting new transcriptional-regulatory roles for PARP1, which has profound implications for human malignancies and will be reviewed herein. Mol Cancer Res; 12(8); 1069–80. ©2014 AACR.
Emergence of HPV16-Positive Oropharyngeal Cancer in Black Patients Over Time: University of Maryland 1992–2007
Authors: Zandberg Dan P. , Liu Sandy , Goloubeva Olga G. , Schumaker Lisa M. , Cullen Kevin J. 
Published: June 2014

Abstract
While we previously reported a striking racial difference in the prevalence of human papilloma virus (HPV)–positive squamous cell carcinoma of the oropharynx (OPSCC), less is known about differences in outcomes and trends over time in OPSCC by HPV status and race. We conducted a retrospective analysis of 467 patients with OPSCC treated at the University of Maryland Greenebaum Cancer Center (Baltimore, MD) between 1992 and 2007, of which 200 had tissue available for HPV16 testing. HPV16-positive patients were significantly more likely to be white, with 45.5% of whites and 15.5% of blacks testing positive for HPV16. There was a significant increase in HPV16-positive OPSCC for all patients over time from 15.6% in 1992 to 1995 to 43.3% in 2004 to 2007 (P = 0.01). From 1992 to 1995, 33% of white patients were HPV16-positive, with no black patients positive. From 2004 to 2007, 17.7% of black patients and 54% of white patients were HPV16-positive. White and black patients with HPV16-positive tumors had an identical and favorable overall survival (OS; median, 8.1 and 8.1 years, respectively). However, among HPV16-negative patients, whites had an improved OS compared with blacks (median, 2.3 vs. 0.9 years, respectively; P = 0.02), including when analyzed in a multivariable Cox regression model. From 1992 to 2007, the percentage of HPV16-positive OPSCC increased for white patients and was seen for the first time in black patients. While survival for HPV-positive black and white patients was similar and favorable, outcomes for HPV-negative patients were poor, with blacks having worse survival even after controlling for baseline characteristics.Cancer Prev Res; 8(1); 12–19. ©2014 AACR.
See related article by E. Cohen and C. Fakhry, p. 9
A morte do autor: um retorno à cena do crime
Authors: Bellei Sérgio Luiz Prado 
Published: June 2014

O questionamento radical do sujeito cartesiano promovido pela crítica pós-estruturalista a partir da década de sessenta do século passado abriu caminho para a reformulação do conceito de “autor”. Entendido anteriormente como marcado pela imaginação criadora capaz de dar origem a grandes obras literárias, percebidas como expressões universais e supremas do espírito humano, começa o autor a perder a sua força cultural à medida que as novas teorias declaram a sua morte ou restringem a sua atividade anteriormente sacralizada a uma “função autoral” que tem por objetivo a prática repressora da disseminação incontrolável de sentido. O presente ensaio pretende revisitar o momento iconoclasta da morte do autor, com o objetivo de avaliar possíveis contribuições para o pensamento de uma ética da leitura no momento contemporâneo.
Everolimus-Eluting Stents Improve Vascular Response in a Diabetic Animal Model
Authors: Habib Anwer , Karmali Vinit , John Michael C. , Polavarapu Rohini , Nakazawa Gaku , Pachura Kim , Davis Talina , Kolodgie Frank D. , Virmani Renu , Finn Aloke V. 
Published: June 2014

Background—
Preclinical evaluation of the vascular response of drug-eluting stents is limited especially in the setting of diabetes mellitus preventing the evaluation of changes in drug-eluting stent design and eluted drugs after clinical use.

Methods and Results—
Cultured human aortic endothelial cells were used to assess the differences between sirolimus and its analog, everolimus, in the setting of hyperglycemia on various cellular functions necessary for endothelial recovery. A diabetic rabbit model of iliac artery stenting was used to compare histological and morphometric characteristics of the vascular response to everolimus-eluting, sirolimus-eluting, and bare metal stent placement. Under hyperglycemic conditions, sirolimus impaired human aortic endothelial cell barrier function, migration, and proliferation to a greater degree compared with everolimus. In our in vivo model of diabetes mellitus, endothelialization at 28 days was significantly lower and endothelial integrity was impaired in sirolimus-eluting stent compared with both everolimus-eluting and bare metal stents. Neointimal area, uncovered struts, and fibrin deposition were significantly higher in sirolimus-eluting compared with everolimus-eluting and bare metal stents.

Conclusions—
Use of everolimus-eluting stent results in improved vascular response in our preclinical models of diabetes mellitus.
Emergence of the Primary Pediatric Stroke Center
Authors: Bernard Timothy J. , Rivkin Michael J. , Scholz Kelley , deVeber Gabrielle , Kirton Adam , Gill Joan Cox , Chan Anthony K. , Hovinga Collin A. , Ichord Rebecca N. , Grotta James C. , Jordan Lori C. , Benedict Susan , Friedman Neil R. , Dowling Michael M. , Elbers Jorina , Torres Marcela , Sultan Sally , Cummings Dana D. , Grabowski Eric F. , McMillan Hugh J. , Beslow Lauren A. , Amlie-Lefond Catherine 
Published: June 2014

Background and Purpose—
In adult stroke, the advent of thrombolytic therapy led to the development of primary stroke centers capable to diagnose and treat patients with acute stroke rapidly. We describe the development of primary pediatric stroke centers through preparation of participating centers in the Thrombolysis in Pediatric Stroke (TIPS) trial.

Methods—
We collected data from the 17 enrolling TIPS centers regarding the process of becoming an acute pediatric stroke center with capability to diagnose, evaluate, and treat pediatric stroke rapidly, including use of thrombolytic therapy.

Results—

Before 2004, <25% of TIPS sites had continuous 24-hour availability of acute stroke teams, MRI capability, or stroke order sets, despite significant pediatric stroke expertise. After TIPS preparation, >80% of sites now have these systems in place, and all sites reported increased readiness to treat a child with acute stroke. Use of a 1- to 10-Likert scale on which 10 represented complete readiness, median center readiness increased from 6.2 before site preparation to 8.7 at the time of site activation (
P
≤0.001).

Conclusions—
Before preparing for TIPS, centers interested in pediatric stroke had not developed systematic strategies to diagnose and treat acute pediatric stroke. TIPS trial preparation has resulted in establishment of pediatric acute stroke centers with clinical and system preparedness for evaluation and care of children with acute stroke, including use of a standardized protocol for evaluation and treatment of acute arterial stroke in children that includes use of intravenous tissue-type plasminogen activator.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01591096.
Length of Occlusion Predicts Recanalization and Outcome After Intravenous Thrombolysis in Middle Cerebral Artery Stroke
Authors: Rohan Vladimir , Baxa Jan , Tupy Radek , Cerna Lenka , Sevcik Petr , Friesl Michal , Polivka Jiri , Polivka Jiri , Ferda Jiri 
Published: June 2014

Background and Purpose—
The length of large vessel occlusion is considered a major factor for therapy in patients with ischemic stroke. We used 4D-CT angiography evaluation of middle cerebral artery occlusion in prediction of recanalization and favorable clinical outcome and after intravenous thrombolysis (IV-tPA).

Methods—
In 80 patients treated with IV-tPA for acute complete middle cerebral artery/M1 occlusion determined using CT angiography and temporal maximum intensity projection, calculated from 4D-CT angiography, the length of middle cerebral artery proximal stump, occlusion in M1 or M1 and M2 segment were measured. Univariate and multivariate analyses were performed to define independent predictors of successful recanalization after 24 hours and favorable outcome after 3 months.

Results—

The length of occlusion was measureable in all patients using temporal maximum intensity projection. Recanalization thrombolysis in myocardial infarction 2 to 3 was achieved in 37 individuals (46%). The extension to M2 segment as a category (odds ratio, 4.58; 95% confidence interval, 1.39–15.05;
P
=0.012) and the length of M1 segment occlusion (odds ratio, 0.82; 95% confidence interval, 0.73–0.92;
P
=0.0007) with an optimal cutoff value of 12 mm (sensitivity 0.67; specificity 0.71) were significant independent predictors of recanalization. Favorable outcome (modified Rankin scale 0–2) was achieved in 25 patients (31%), baseline National Institutes of Health Stroke Scale (odds ratio, 0.82; 95% confidence interval, 0.72–0.93;
P
=0.003) and the length of occlusion M1 in segment (odds ratio, 0.79; 95% confidence interval, 0.69–0.91;
P
=0.0008) with an optimal cutoff value of 11 mm (sensitivity 0.74; specificity 0.76) were significant independent predictors of favorable outcome.

Conclusions—
The length of middle cerebral artery occlusion is an independent predictor of successful IV-tPA treatment.
Two new desma-less species of Theonella Gray, 1868 (Demospongiae: Astrophorida: Theonellidae), from the Great Barrier Reef, Australia,and a re-evaluation of one species assigned previously to Dercitus Gray, 1867
Authors: HALL KATHRYN A. , EKINS MERRICK G. , HOOPER JOHN N.A. 
Published: June 2014

Extensive surveys of the biodiversity on the seafloor of the inter-reef regions of the Great Barrier Reef, Australia, have resulted in the collection of large numbers of sponges, many of which are likely new to science. Identification of these sponges, however, was made difficult by the absence in some specimens of key diagnostic characters, such as megascleres. We used an integrated approach to the taxonomy of these sponges, incorporating morphological examination by SEM, analysis of DNA sequence data (using the COI barcoding fragment of mtDNA) and preliminary studies of the chemistry of the sponges, to describe the new species, which were found to contain no native spicules other than acanthose microrhabds. Here, we propose two new species of Theonella Gray, 1868: Theonella deliqua n. sp. (found in association with a single unidentified species of siliquariid mollusc) and Theonella maricae n. sp. from the Great Barrier Reef. Further, we propose the new combination of Theonella xantha (Sutcliffe, Hooper and Pitcher 2010) n. comb. for another microrhabd-only-bearing species. On the basis of our gene trees, we recognise Theonella (and Theonellidae Lendenfeld, 1903) within Astrophorida Sollas, 1887. We discuss the potential for chemotaxonomic and DNA-based insights into the origins and radiation of species of Theonella and explore the evolutionary significance of the reduced morphology of the three additional species recognised here.