bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rho-Associated Coiled-Coil-Containing Kinase 2 Deficiency in Bone Marrow–Derived Cells Leads to Increased Cholesterol Efflux and Decreased Atherosclerosis
Authors: Zhou Qian , Mei Yu , Shoji Takuhito , Han Xinbing , Kaminski Karol , Oh Goo Taeg , Ongusaha Pat P. , Zhang Kunzhong , Schmitt Hannah , Moser Martin , Bode Christoph , Liao James K. 
Published: September 2012

Background—
Macrophages play a central role in the development of atherosclerosis. However, the signaling pathways that regulate their function are not well understood. The Rho-associated coiled-coil-containing kinases (ROCK1 and ROCK2) are serine-threonine protein kinases that are involved in the regulation of the actin cytoskeleton. Recent studies suggest that ROCK1 in macrophages and bone marrow–derived cells mediates atherogenesis. However, a similar role for ROCK2 in the pathogenesis of atherosclerosis has not been determined.

Methods and Results—

The bone marrows from wild-type, ROCK2
+/−
, and ROCK2
−/−
mice were transplanted into irradiated recipient low-density lipoprotein receptor
−/−
mice, and atherosclerosis was induced with a 16-week high-cholesterol diet. Compared with wild-type bone marrow–transplanted mice, ROCK2
+/−
bone marrow–transplanted and ROCK2
−/−
bone marrow–transplanted mice showed substantially less lipid accumulation in the aorta (8.46±1.42% and 9.80±2.34% versus 15.64±1.89%;
P
<0.01 for both) and decreased atherosclerotic lesions in the subaortic sinus (158.1±44.4 and 330.1±109.5×10
3
μm
2
versus 520.2±125.7×10
3
μm
2
;
P
<0.01 for both). These findings correlated with decreased foam cell formation (2.27±0.57 versus 4.10±0.3;
P
<0.01) and increased cholesterol efflux (17.65±0.6 versus 9.75±0.8;
P
<0.05) in ROCK2-deficient mice that are mediated, in part, through the peroxisome proliferator-activated receptor-γ/liver X receptor/ATP-binding cassette transporter A1 pathway in macrophages.

Conclusions—
ROCK2 contributes to atherosclerosis, in part, by inhibiting peroxisome proliferator-activated receptor-γ–mediated reverse cholesterol transport in macrophages, which contributes to foam cell formation. These findings suggest that inhibition of ROCK2 in macrophages may have therapeutic benefits in preventing the development of atherosclerosis.
Will Delays in Treatment Jeopardize the Population Benefit From Extending the Time Window for Stroke Thrombolysis?
Authors: Pitt Martin , Monks Thomas , Agarwal Paritosh , Worthington David , Ford Gary A. , Lees Kennedy R. , Stein Ken , James Martin A. 
Published: September 2012

Background and Purpose—
Pooled analyses show benefits of intravenous alteplase (recombinant tissue-type plasminogen activator) treatment for acute ischemic stroke up to 4.5 hours after onset despite marketing approval for up to 3 hours. However, the benefit from thrombolysis is critically time-dependent and if extending the time window reduces treatment urgency, this could reduce the population benefit from any extension.

Methods—
Based on 3830 UK patients registered between 2005 to 2010 in the Safe Implementation of Treatments in Stroke–International Stroke Thrombolysis Registry (SITS-ISTR), a Monte Carlo simulation was used to model recombinant tissue-type plasminogen activator treatment up to 4·5 hours from onset and assess the impact (numbers surviving with little or no disability) from changes in hospital treatment times associated with this extended time window.

Results—
We observed a significant relation between time remaining to treat and time taken to treat in the UK SITS-ISTR data set after adjustment for censoring. Simulation showed that as this “deadline effect” increases, an extended treatment time window entails that an increasing number of patients are treated at a progressively lower absolute benefit to a point where the population benefit from extending the time window is entirely negated.

Conclusions—
Despite the benefit for individual patients treated up to 4.5 hours after onset, the population benefit may be reduced or lost altogether if extending the time window results in more patients being treated but at a lower absolute benefit. A universally applied reduction in hospital arrival to treatment times of 8 minutes would confer a population benefit as large as the time window extension.
Identification of a Genetic Variant Common to Moyamoya Disease and Intracranial Major Artery Stenosis/Occlusion
Authors: Miyawaki Satoru , Imai Hideaki , Takayanagi Shunsaku , Mukasa Akitake , Nakatomi Hirofumi , Saito Nobuhito 
Published: September 2012

Background and Purpose—
The c.14576G>A variant in ring finger protein 213 (RNF213) was recently identified as a susceptibility gene variant for moyamoya disease (MMD). The occurrence of c.14576G>A variant was evaluated in patients with intracranial major artery stenosis/occlusion (ICASO) without signs of MMD (non-MMD ICASO), as well as in patients with MMD and other cerebrovascular diseases as controls.

Methods—
This single-hospital–based case-control study was completed in 7 months (from October 2011–April 2012) at Department of Neurosurgery, The University of Tokyo Hospital. The occurrence of c.14576G>A variant was analyzed in 41 patients with non-MMD ICASO, in 48 with MMD, in 21 with cervical disease, in 61 with cerebral aneurysm, and in 25 normal subjects.

Results—
Nine of 41 patients (21.9%) with non-MMD ICASO and 41 of 48 (85.4%) with MMD had the c.14576G>A variant. One of 61 patients (1.6%) with cerebral aneurysm and no patients with cervical disease or normal subjects had the variant. Comparison of each phenotype group with the normal subjects showed that presence of c.14576G>A variant had significant associations with MMD (odds ratio [OR], 292.8; 95% confidence interval [CI], 15.4–5153.0; P<0.0001) and with non-MMD ICASO (OR, 14.9; 95% CI, 0.82–268.4; P=0.01), but no association with either cerebral aneurysm (OR, 1.2; 95% CI, 0.04–32.0; P=1.00) or cervical disease (OR, 1.1; 95% CI, 0.02–62.3; P=1.00).

Conclusions—
The present study indicates that a particular subset of Japanese patients with non-MMD ICASO has a genetic variant associated with MMD. Therefore, we propose the existence of a new entity of ICASO caused by the c.14576G>A variant in RNF213.
Poststroke Hypertension in Africa
Authors: Kaddumukasa Martin , Ddumba Edward , Duncan Pamela , Goldstein Larry B. 
Published: September 2012

Background and Purpose—
Little is known about the frequency of hypertension and related knowledge in Africans who have had a stroke. The objective of this study was to determine the frequency of hypertension, its control, and associated knowledge among patients with and without a history of stroke at Uganda’s main referral hospital.

Methods—
Subjects with a history of stroke (n=157) were compared with stroke-free control subjects (n=149). Demographics and clinical characteristics were recorded and hypertension-related knowledge assessed by questionnaire. Multiple logistic regression including cases and control subjects was used to determine factors independently associated with blood pressure control and hypertension-related knowledge.

Results—

A total of 69.4% of cases versus 54.7% of control subjects were hypertensive at the time of the research visit (
P
=0.001). Univariable analyses showed the odds of having good blood pressure control (OR, 0.53; 95% CI, 0.33–0.84;
P
=0.006) and good hypertension knowledge (OR, 0.35; 95% CI, 0.22–0.56;
P
<0.0001) were lower in cases. Age <40 years (
P
=0.002), good hypertension-related knowledge (
P
=0.002), and poorer medication adherence (
P
<0.0001) were independently associated with poorer blood pressure control. Those with a history of hypertension had better hypertension-related knowledge (
P
=0.001), but knowledge was poorer among cases (
P
<0.0001).

Conclusion—
Hypertension is common in Ugandans with and without a history of stroke. Barriers to effective blood pressure control in Uganda other than patient knowledge need to be identified.
Uruguay 2008
Authors: Ruffinelli Jorge 
Published: September 2012

The year 2008 was prolific in terms of documentary film production in Uruguay. This type of Uruguayan cinema, which dates to the 1960s, was interrupted by the military dictatorship (1973–1984), and on the return of democracy it was very slow to recover. In 2008, however, it showed great vitality as political expression and great diversity in the artistic forms it employed in observing and interpreting the reality of the recent past. El año 2008 fue prolífico en lo que concierne la producción del cine documental en Uruguay. Este tipo de cine uruguayo, que data a los 1960, se interrumpió con la dictadura militar (1973–1984), y en la vuelta a la democracia se recuperó muy lentamente. Sin embargo en 2008 mostró gran vitalidad como expresión política y gran diversidad en las formas artísticas que se empleaban en observar e interpretar la realidad del pasado reciente.
Clinical Outcomes among HIV/Tuberculosis-Coinfected Patients Developing Immune Reconstitution Inflammatory Syndrome after HAART Initiation in South India
Authors: Kumarasamy N. , Venkatesh Kartik K. , Vignesh R. , Devaleenal B. , Poongulali S. , Yepthomi Tokuga , Flanigan Timothy P. , Benson Constance , Mayer Kenneth H. 
Published: September 2012

Introduction: We determine the frequency and immunological outcome of developing immune reconstitution inflammatory syndrome (IRIS) among HIV/tuberculosis (TB)–coinfected Indians receiving highly active antiretroviral therapy (HAART). Methods: Patients coinfected with TB and HIV who initiated HAART were classified based on treatment outcomes (IRIS and non-IRIS) utilizing an observational HIV/AIDS cohort. Results: A total of 1731 HIV/TB-coinfected patients initiated HAART, and 95 of these patients (5.5%) developed TB-IRIS, with an incidence rate of 0.26 per 100 person-years. Patients who developed IRIS had significantly higher CD4 counts than non-IRIS patients at the time of initiating HAART, as well as after 6 months, 18 months, and 24 months following HAART initiation ( P < .05). Conclusions: HIV/TB-coinfected patients who developed IRIS following HAART initiation had equivalent clinical outcomes compared with their HIV/TB-coinfected counterparts who did not develop IRIS, suggesting minimal long-term risks associated with IRIS.
Early uptake of seasonal influenza vaccines incorporated with pH1N1 strain among regularly vaccinated healthcare workers
Authors: Poon Chin Man , Lee Shui Shan , Lee Sing 
Published: September 2012

Objectives: This study aims to assess the vaccination uptake and attitudes of healthcare workers (HCWs) towards seasonal influenza vaccination after incorporating pandemic H1N1 (pH1N1) strain in the vaccines. Methods: A self-administered anonymous questionnaire was issued to nurses registered with any of three collaborating nursing associations in Hong Kong. Results: A total of 709 questionnaires were completed, representing a response rate of 28.4%. The coverage of 2010/11 seasonal influenza vaccines was 24.1%. It was lower than that of 2009/10 seasonal influenza vaccines, in which pH1N1 strain was not yet included (37.1%), but higher than that of monovalent pH1N1 vaccines introduced during the pandemic in 2009 (14.2%). The reduction in the number of vaccinated HCWs varied among sub-groups classified by age, duration of employment, type of contacts with patients or past seasonal influenza vaccination record. Early recipients of the vaccine were more likely to have already been vaccinated in the preceding year (odds ratio (OR)=2.95, 95% confidence interval (95% CI) =1.15–7.59) and showed an intention to be vaccinated in the following year (OR=2.78, 95% CI=1.13–6.83). However, incorporation of pH1N1 strain in trivalent seasonal vaccines did not significantly increase the desire for vaccination. Conclusion: In addition to upholding the efficacy and safety standard of influenza vaccines, compliance and acceptance strategies shall be developed as early as possible, and tailored to the needs of different sub-groups.
Chemokine-mediated tissue recruitment of CXCR3+ CD4+ T cells plays a major role in the pathogenesis of chronic GVHD
Authors: Croudace Joanne E. , Inman Charlotte F. , Abbotts Ben. E. , Nagra Sandeep , Nunnick Jane , Mahendra Prem , Craddock Charles , Malladi Ram , Moss Paul A. H. 
Published: September 2012

Abstract
Chemokines regulate the migration of hemopoietic cells and play an important role in the pathogenesis of many immune-mediated diseases. Intradermal recruitment of CD8+ T cells by CXCL10 is a central feature of the pathogenesis of cutaneous acute GVHD (aGVHD), but very little is known about the pathogenesis of chronic GVHD (cGVHD). Serum concentrations of the 3 CXCR3-binding chemokines, CXCL9, CXCL10, and CXCL11, were found to be markedly increased in patients with active cGVHD of the skin (n = 8). An 80% decrease in CD4+ cells expressing CXCR3 was seen in the blood of these patients (n = 5), whereas CD4+ cells were increased in tissue biopsies and were clustered around the central arterioles of the dermis. The well-documented increase in expression of CXCL10 in aGVHD therefore diversifies in cGVHD to include additional members of the CXCR3-binding family and leads to preferential recruitment of CD4+ T cells. These observations reveal a central role for chemokine-mediated recruitment of CXCR3+ T cells in cGVHD.
ESTclean: a cleaning tool for next-gen transcriptome shotgun sequencing
Authors: Tae Hongseok , Ryu Dongsung , Sureshchandra Suhas , Choi Jeong-Hyeon 
Published: September 2012

Abstract

Background
With the advent of next-generation sequencing (NGS) technologies, full cDNA shotgun sequencing has become a major approach in the study of transcriptomes, and several different protocols in 454 sequencing have been invented. As each protocol uses its own short DNA tags or adapters attached to the ends of cDNA fragments for labeling or sequencing, different contaminants may lead to mis-assembly and inaccurate sequence products.

Results
We have designed and implemented a new program for raw sequence cleaning in a graphical user interface and a batch script. The cleaning process consists of several modules including barcode trimming, sequencing adapter trimming, amplification primer trimming, poly-A tail trimming, vector screening and low quality region trimming. These modules can be combined based on various sequencing applications.

Conclusions
ESTclean is a software package not only for cleaning cDNA sequences, but also for helping to develop sequencing protocols by providing summary tables and figures for sequencing quality control in a graphical user interface. It outperforms in cleaning read sequences from complicated sequencing protocols which use barcodes and multiple amplification primers.
Gene duplications contribute to the overrepresentation of interactions between proteins of a similar age
Authors: Fokkens Like , Hogeweg Paulien , Snel Berend 
Published: September 2012

Abstract

Background
The study of biological networks and how they have evolved is fundamental to our understanding of the cell. By investigating how proteins of different ages are connected in the protein interaction network, one can infer how that network has expanded in evolution, without the need for explicit reconstruction of ancestral networks. Studies that implement this approach show that proteins are often connected to proteins of a similar age, suggesting a simultaneous emergence of interacting proteins. There are several theories explaining this phenomenon, but despite the importance of gene duplication in genome evolution, none consider protein family dynamics as a contributing factor.

Results
In an S. cerevisiae protein interaction network we investigate to what extent edges that arise from duplication events contribute to the observed tendency to interact with proteins of a similar age. We find that part of this tendency is explained by interactions between paralogs. Age is usually defined on the level of protein families, rather than individual proteins, hence paralogs have the same age. The major contribution however, is from interaction partners that are shared between paralogs. These interactions have most likely been conserved after a duplication event. To investigate to what extent a nearly neutral process of network growth can explain these results, we adjust a well-studied network growth model to incorporate protein families. Our model shows that the number of edges between paralogs can be amplified by subsequent duplication events, thus explaining the overrepresentation of interparalog edges in the data. The fact that interaction partners shared by paralogs are often of the same age as the paralogs does not arise naturally from our model and needs further investigation.

Conclusion
We amend previous theories that explain why proteins of a similar age prefer to interact by demonstrating that this observation can be partially explained by gene duplication events. There is an ongoing debate on whether the protein interaction network is predominantly shaped by duplication and subfunctionalization or whether network rewiring is most important. Our analyses of S. cerevisiae protein interaction networks demonstrate that duplications have influenced at least one property of the protein interaction network: how proteins of different ages are connected.
Intraclass correlation coefficients in the Brazilian network for surveillance of severe maternal morbidity study
Authors: Haddad Samira M , Sousa Maria H , Cecatti Jose G , Parpinelli Mary A , Costa Maria L , Souza Joao P ,   for the Brazilian Network for Surveillance of Severe Maternal Morbidity Group
Published: September 2012

Abstract

Background
The purpose of the study was to evaluate intraclass correlation coefficients (ICC) of variables concerning personal characteristics, structure, outcome and process in the Brazilian Network for Surveillance of Severe Maternal Morbidity study conducted to identify severe maternal morbidity/near miss cases using the World Health Organization criteria.

Method
It was a cross-sectional, multicenter study involving 27 hospitals providing care for pregnant women in Brazil. Cluster size and the mean size of the primary sampling unit were described. Estimated prevalence rates, ICC, their respective 95% confidence intervals, the design effect and the mean cluster size were presented for each variable.

Results
Overall, 9,555 cases of severe maternal morbidity (woman admitted with potentially life-threatening conditions, near miss events or death) were included in the study. ICC ranged from < 0.001 to 0.508, with a median of 0.035. ICC was < 0.1 for approximately 75% of the variables. For process-related variables, median ICC was 0.09, with 0.021 for those related to outcome. These findings confirm data from previous studies. Homogeneity may be considered minor, thus increasing reliability of these findings.

Conclusions
These results may be used to design new cluster trials in maternal and perinatal health and to help calculate sample sizes.
Urinary bisphenol A concentrations in girls from rural and urban Egypt: a pilot study
Authors: Nahar Muna S , Soliman Amr S , Colacino Justin A , Calafat Antonia M , Battige Kristen , Hablas Ahmed , Seifeldin Ibrahim A , Dolinoy Dana C , Rozek Laura S 
Published: September 2012

AbstractBackgroundExposure to endocrine active compounds, including bisphenol A (BPA), remains poorly characterized in developing countries despite the fact that behavioral practices related to westernization have the potential to influence exposure. BPA is a high production volume chemical that has been associated with metabolic dysfunction as well as behavioral and developmental effects in people, including children. In this pilot study, we evaluate BPA exposure and assess likely pathways of exposure among girls from urban and rural Egypt.MethodsWe measured urinary concentrations of total (free plus conjugated) species of BPA in spot samples in urban (N = 30) and rural (N = 30) Egyptian girls, and compared these concentrations to preexisting data from age-matched American girls (N = 47) from the U.S. National Health and Nutrition Examination Survey (NHANES). We also collected anthropometric and questionnaire data regarding food storage behaviors to assess potential routes of exposure.ResultsUrban and rural Egyptian girls exhibited similar concentrations of urinary total BPA, with median unadjusted values of 1.00 and 0.60 ng/mL, respectively. Concentrations of urinary BPA in this group of Egyptian girls (median unadjusted: 0.70 ng/mL) were significantly lower compared to age-matched American girls (median unadjusted: 2.60 ng/mL) according to NHANES 2009-2010 data. Reported storage of food in plastic containers was a significant predictor of increasing concentrations of urinary BPA.ConclusionsDespite the relatively low urinary BPA concentrations within this Egyptian cohort, the significant association between food storage behaviors and increasing urinary BPA concentration highlights the need to understand food and consumer product patterns that may be closing the gap between urban and rural lifestyles.
EGFR/Src/Akt signaling modulates Sox2 expression and self-renewal of stem-like side-population cells in non-small cell lung cancer
Authors: Singh Sandeep , Trevino Jose , Bora-Singhal Namrata , Coppola Domenico , Haura Eric , Altiok Soner , Chellappan Srikumar P 
Published: September 2012

AbstractBackgroundCancer stem cells are thought to be responsible for the initiation and progression of cancers. In non-small cell lung cancers (NSCLCs), Hoechst 33342 dye effluxing side population (SP) cells are shown to have stem cell like properties. The oncogenic capacity of cancer stem-like cells is in part due to their ability to self-renew; however the mechanistic correlation between oncogenic pathways and self-renewal of cancer stem-like cells has remained elusive. Here we characterized the SP cells at the molecular level and evaluated its ability to generate tumors at the orthotopic site in the lung microenvironment. Further, we investigated if the self-renewal of SP cells is dependent on EGFR mediated signaling.ResultsSP cells were detected and isolated from multiple NSCLC cell lines (H1650, H1975, A549), as well as primary human tumor explants grown in nude mice. SP cells demonstrated stem-like properties including ability to self-renew and grow as spheres; they were able to generate primary and metastatic tumors upon orthotopic implantation into the lung of SCID mice. In vitro study revealed elevated expression of stem cell associated markers like Oct4, Sox2 and Nanog as well as demonstrated intrinsic epithelial to mesenchymal transition features in SP cells. Further, we show that abrogation of EGFR, Src and Akt signaling through pharmacological or genetic inhibitors suppresses the self-renewal growth and expansion of SP-cells and resulted in specific downregulation of Sox2 protein expression. siRNA mediated depletion of Sox2 significantly blocked the SP phenotype as well as its self-renewal capacity; whereas other transcription factors like Oct4 and Nanog played a relatively lesser role in regulating self-renewal. Interestingly, Sox2 was elevated in metastatic foci of human NSCLC samples.ConclusionsOur findings suggest that Sox2 is a novel target of EGFR-Src-Akt signaling in NSCLCs that modulates self-renewal and expansion of stem-like cells from NSCLC. Therefore, the outcome of the EGFR-Src-Akt targeted therapy may rely upon the expression and function of Sox2 within the NSCLC-CSCs.