bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti-inflammatory, gastroprotective and anti-ulcerogenic effects of red algae Gracilaria changii (Gracilariales, Rhodophyta) extract
Authors: Shu Meng-Hooi , Appleton David , Zandi Keivan , AbuBakar Sazaly 
Published: March 2013

Abstract

Background

Gracilaria changii (Xia et Abbott) Abbott, Zhang et Xia, a red algae commonly found in the coastal areas of Malaysia is traditionally used for foods and for the treatment of various ailments including inflammation and gastric ailments. The aim of the study was to investigate anti-inflammatory, gastroprotective and anti-ulcerogenic activities of a mass spectrometry standardized methanolic extract of Gracilaria changii.

Methods
Methanolic extract of Gracilaria changii (MeOHGCM6 extract) was prepared and standardized using mass spectrometry (MS). Anti-inflammatory activities of MeOHGCM6 extract were examined by treating U937 cells during its differentiation with 10 μg/ml MeOHGCM6 extract. Tumour necrosis factors-α (TNF-α) response level and TNF-α and interleukin-6 (IL-6) gene expression were monitored and compared to that treated by 10 nM betamethasone, an anti-inflammatory drug. Gastroprotective and anti-ulcerogenic activities of MeOHGCM6 extract were examined by feeding rats with MeOHGCM6 extract ranging from 2.5 to 500 mg/kg body weight (b.w.) following induction of gastric lesions. Production of mucus and gastric juice, pH of the gastric juice and non-protein sulfhydryls (NP-SH) levels were determined and compared to that fed by 20 mg/kg b.w. omeprazole (OMP), a known anti-ulcer drug.

Results
MS/MS analysis of the MeOHGCM6 extracts revealed the presence of methyl 10-hydroxyphaeophorbide a and 10-hydroxypheophytin a, known chlorophyll proteins and several unidentified molecules. Treatment with 10 μg/ml MeOHGCM6 extract during differentiation of U937 cells significantly inhibited TNF-α response level and TNF-α and IL-6 gene expression. The inhibitory effect was comparable to that of betamethasone. No cytotoxic effects were recorded for cells treated with the 10 μg/ml MeOHGCM6 extract. Rats fed with MeOHGCM6 extract at 500 mg/kg b.w. showed reduced absolute ethanol-induced gastric lesion sizes by > 99% (p < 0.05). This protective effect was comparable to that conferred by OMP. The pH of the gastric mucus decreased in dose-dependent manner from 5.51 to 3.82 and there was a significant increase in NP-SH concentrations.

Conclusions
Results from the study, suggest that the mass spectrometry standardized methanolic extract of Gracillaria changii possesses anti-inflammatory, gastroprotective and anti-ulcerogenic properties. Further examination of the active constituent of the extract and its mechanism of action is warranted in the future.
The cloud paradigm applied to e-Health
Authors: Vilaplana Jordi , Solsona Francesc , Abella Francesc , Filgueira Rosa , Rius Josep 
Published: March 2013

Abstract

Background
Cloud computing is a new paradigm that is changing how enterprises, institutions and people understand, perceive and use current software systems. With this paradigm, the organizations have no need to maintain their own servers, nor host their own software. Instead, everything is moved to the cloud and provided on demand, saving energy, physical space and technical staff. Cloud-based system architectures provide many advantages in terms of scalability, maintainability and massive data processing.

Methods
We present the design of an e-health cloud system, modelled by an M/M/m queue with QoS capabilities, i.e. maximum waiting time of requests.

Results
Detailed results for the model formed by a Jackson network of two M/M/m queues from the queueing theory perspective are presented. These results show a significant performance improvement when the number of servers increases.

Conclusions
Platform scalability becomes a critical issue since we aim to provide the system with high Quality of Service (QoS). In this paper we define an architecture capable of adapting itself to different diseases and growing numbers of patients. This platform could be applied to the medical field to greatly enhance the results of those therapies that have an important psychological component, such as addictions and chronic diseases.
Prospective cohort study protocol to evaluate the validity and reliability of the Quality of Trauma Care Patient-Reported Experience Measure (QTAC-PREM)
Authors: Bobrovitz Niklas , Santana Maria , Kline Theresa , Kortbeek John , Stelfox Henry T 
Published: March 2013

Abstract

Background
Patient-centeredness is a key component of health care quality. However, patient-centered measures of quality have not been developed in injury care. In response to this challenge, we developed the Quality of Trauma Adult Care Patient-Reported Experience Measure (QTAC-PREM) to measure injured patient experiences with trauma care and pilot-tested the instrument at a single Level 1 trauma centre. The objective of this study is to test the reliability, validity, and feasibility of the QTAC-PREM in multiple Canadian trauma centers and to refine the measure based on the results.

Methods/design
This will be a prospective cohort study of consecutive adult (age ≥ 18 years) patients discharged from three trauma centres in Alberta, Canada with a primary diagnosis of injury. The target sample size is 400 participants to ensure precision for evaluating test-retest reliability. We will assess the psychometric properties of the measure (test-retest reliability, construct validity, internal consistency) and whether these properties vary by patient characteristics. We will also evaluate the predictive validity, convergent validity, and discriminant validity of the measure against other established tools (HCAHPS).

Discussion
A reliable and valid measure of patient reported experiences with injury care may be a valuable tool to evaluate quality of care and guide improvement efforts.
Insights into the role of the junctional region of Plasmodium falciparum dihydrofolate reductase-thymidylate synthase
Authors: Chaianantakul Natpasit , Sirawaraporn Rachada , Sirawaraporn Worachart 
Published: March 2013

Abstract

Background

Plasmodium falciparum dihydrofolate reductase-thymidylate synthase (pf DHFR-TS) is a well-defined target of anti-malarial drug, such as pyrimethamine and cycloguanil. Emergence of malaria parasites resistant to these drugs has been shown to be associated with point mutations of the gene coding for the target enzymes. Although the 3D-structure of P. falciparum bifunctional pf DHFR-TS has been reported previously, relatively little is known about the interactions between the pf DHFR and pf TS domains and the roles of the junctional region that links the two domains together. Therefore, a thorough understanding of the interaction of the two domains and the role of the junctional region of this target is important as the knowledge could assist the development of new effective anti-malarial drugs aimed at overcoming drug-resistant malaria.

Methods
A system was developed to investigate the interaction between pf DHFR and pf TS domains and the role of the junctional region on the activity of the recombinant pf TS. Based on the ability of co-transformed plasmids coding for pf DHFR and pf TS with truncated junctional region to complement the growth of TS-deficient Escherichia coli strain χ2913recA(DE3) on minimum media without thymidine supplementation, active pf TS mutants with minimal length of junctional region were identified. Interactions between active pf DHFR and the pf TS domains were demonstrated by using a bacterial two-hybrid system.

Results
Using TS-deficient E. coli strain χ2913recA(DE3), the authors have shown for the first time that in P. falciparum a junctional region of at least 44 amino acids or longer was necessary for the pf TS domain to be active for the synthesis of thymidylate for the cells. Truncation of the junctional region of the bifunctional pf DHFR-TS further confirmed the above results, and suggested that a critical length of the junctional peptide of pf DHFR-TS would be essential for the activity of TS to catalyze the synthesis of thymidylate.

Conclusion
The present study demonstrated the interactions between the pf DHFR and pf TS domains of the bifunctional pf DHFR-TS, and revealed that the junctional region linking the two protein domains is essential for the expression of catalytically active pf TS domain. The findings could be useful since inhibition of the pf DHFR-TS domain-domain interaction could form a basis for the development of new anti-malarial drugs based on targeting the non-active site region of this important enzyme.
Analyzing the performance of Aloha in string multi-hop underwater acoustic sensor networks
Authors: Yu Hongyang , Yao Nianmin , Cai Shaobin , Han Qilong 
Published: March 2013

Abstract
In this article, we intend to investigate the performance of channel access protocols in multi-hop underwater acoustic sensor networks, which are characterized by long propagation delays and limited channel bandwidth. An analytical model specifically designed for contention-based protocols in multi-hop underwater acoustic networks is identified and validated. The model is based on an underwater network model, called string topology network model, which provides a method for computing the expected network throughput and the probability of packets’ delivery to the gateway from an arbitrary sensor. This study demonstrates an improvement of an existing model, in which a node is implicitly assumed to be able to transmit two packets at the same time, which is not realistic due to the half-duplex character of underwater acoustic channels. Based on our findings, we propose a modified analytical model and evaluate it using NS-3 simulator. Results show that our analytical model is more precise than the existing one.
A boundary integral equation with the generalized Neumann kernel for a mixed boundary value problem in unbounded multiply connected regions
Authors: Al-Hatemi Samer AA , Murid Ali HM , Nasser Mohamed MS 
Published: March 2013

Abstract
In this paper we propose a new method for solving the mixed boundary value problem for the Laplace equation in unbounded multiply connected regions. All simple closed curves making up the boundary are divided into two sets. The Dirichlet condition is given for one set and the Neumann condition is given for the other set. The mixed problem is reformulated in the form of a Riemann-Hilbert (RH) problem which leads to a uniquely solvable Fredholm integral equation of the second kind. Three numerical examples are presented to show the effectiveness of the proposed method.
Application of real-time reverse transcription polymerase chain reaction to the detection the matrix, H5 and H7 genes of avian influenza viruses in field samples from South Korea
Authors: Kim Hye-Ryoung , Oem Jae-Ku , Bae You-Chan , Kang Min-Su , Lee Hee-Soo , Kwon Yong-Kuk 
Published: March 2013

Abstract

Background
The rapid and accurate identification of the H5 and H7 subtypes of avian influenza (AI) virus is an important step for the control and eradication of highly pathogenic AI outbreaks and for the surveillance of AI viruses that have the potential to undergo changes in pathogenicity in poultry and wild birds. Currently, real-time reverse transcription polymerase chain reaction (RRT-PCR) is routinely used for the rapid detection of the H5 and H7 genes, but misidentification is frequent for emergent isolates and viruses isolated from diverse regions due to the high sequence variation among AI viruses.

Findings
In this study, an RRT-PCR method was tested for the detection of matrix, H5 and H7 genes from diverse subtypes of AI viruses and from field samples obtained through AI surveillance in South Korea over the last four years. Both RRT-PCR and conventional experiment (virus isolation using egg inoculation followed by reverse transcription polymerase chain reaction) agreed on the virus-positive samples. And the comparison of the results with 174 clinical samples showed a high level of agreement without decreasing the specificity and sensitivity.

Conclusions
This assay could be useful tool for the rapid detection of AI using the field samples from domestic poultry and wild birds in South Korea, and continuous regional updates is needed to validate primer sets as the AI virus evolves.
MOMENT – Management of Otitis Media with Effusion in Cleft Palate: protocol for a systematic review of the literature and identification of a core outcome set using a Delphi survey
Authors: Harman Nicola L , Bruce Iain A , Callery Peter , Tierney Stephanie , Sharif Mohammad Owaise , O’Brien Kevin , Williamson Paula R 
Published: March 2013

Abstract

Background
Cleft palate (CP) has an incidence of approximately 1 in 700. Children with CP are also susceptible to otitis media with effusion (OME), with approximately 90% experiencing nontrivial OME. There are several approaches to the management of OME in children with CP. The Management of Otitis Media with Effusion in Children with Cleft Palate (MOMENT) study is a feasibility study that includes the development of a core outcome set for use in future trials of the management of OME in children with CP.

Methods/Design
The MOMENT study will include a systematic review of the literature to identify a list of outcomes that have previously been reported. This list of outcomes will be used in a Delphi study with cleft clinicians. The Delphi study is anticipated to include three rounds. The first round will ask clinicians to score the outcome list and to add any outcomes they think are relevant. The second round involves presentation of scores according to stakeholder group and the opportunity for participants to rescore outcomes. To ensure that the opinion of parents and children are sought, qualitative interviews will be completed with a purposive sample in parallel. In the final round of the Delphi process, participants will be shown the distribution of scores, for each outcome, for all stakeholder groups separately as well as a summary of the results concerning outcomes from the qualitative interviews with parents. A final consensus meeting will be held with all stakeholders, including parents and children, to review outcomes.

Discussion
A core outcome set represents the minimum that should be measured in a clinical trial for a particular condition. The MOMENT study will aim to identify a core outcome set that can be used in future trials of the management of OME, improving the consistency of research in this clinical area.
Prognostic variables in patients with primary soft tissue sarcoma of the extremity and trunk treated with neoadjuvant radiotherapy or neoadjuvant sequential chemoradiotherapy
Authors: Bedi Meena , King David M , Shivakoti Mikesh , Wang Tao , Zambrano Eduardo V , Charlson John , Hackbarth Donald , Neilson John , Whitfield Robert , Wang Dian 
Published: March 2013

Abstract

Background
Neoadjuvant radiotherapy (NRT) is an effective strategy to treat soft tissue sarcomas (STS). However, the role of neoadjuvant chemoradiotherapy (NCRT) remains to be determined.

Methods
From May 1999 to July 2010, 112 patients with localized STS of the extremity and trunk who were treated with NRT or NCRT followed by surgery were retrospectively reviewed. Clinical outcomes including overall survival (OS), disease-free survival (DFS), and distant metastasis free survival (DMFS) were calculated using Kaplan-Meier survival analyses. Prognostic variables were determined by univariate (UVA) and multivariate analyses (MVA).

Results
Median follow-up was 37 months. Median RT dose was 50 Gy. Forty-nine patients received NCRT. Overall limb-preservation rate was 99% and local control was 97%. The estimated 3-year OS, DFS, and DMFS were 86%, 68%, and 72%, respectively. Age was the only variable to predict for OS, DFS and DMFS on UVA. Age ≥ 70 predicted for poor OS, stage III disease predicted for poor DFS and DMFS, and the addition of chemotherapy predicted for improved DMFS on MVA.

Conclusions
Excellent rates of local control and limb-preservation were observed in patients with primary STS treated with neoadjuvant therapy followed by surgery. Neoadjuvant sequential chemotherapy followed by radiotherapy may be considered for young patients with stage III STS.
Preoperative hospital length of stay as a modifiable risk factor for mediastinitis after cardiac surgery
Authors: Leung Wai Sang Stephane , Chaturvedi Rakesh , Alam Ahsan , Samoukovic Gordan , de Varennes Benoit , Lachapelle Kevin 
Published: March 2013

Abstract

Background
As high-risk cardiac patients frequently remain within hospital while waiting for surgery, the aim of the present study was to determine the role of preoperative length of hospital stay on mediastinitis, and also, to assess contemporary risk factors for this complication.

Methods
The source population consisted of 6653 consecutive patients undergoing coronary bypass surgery, valve surgery, or both between September 2000 and September 2009 at a single tertiary care hospital. A retrospective cohort analysis was used to assess the effect of 18 preoperative variables, including length of stay, on mediastinitis.

Results
Mediastinitis developed in 108 patients (1.6%) resulting in an in-hospital mortality rate of 13.9%. Independent predictors of mediastinitis included obesity (2.59, CI 1.58-4.23), COPD (2.44, CI 1.55-3.84), diabetes (2.16, CI 1.44-3.24), and impaired estimated glomerular filtration rate. Preoperative hospital stay was also found to be an independent risk factor leading to a 15% increased risk of mediastinitis per week of stay. The primary wound pathogen was coagulase negative staphylococcus (82%) followed by multi-flora isolates (49%), but was unrelated to hospital stay.

Conclusions
In addition to the traditional risk factors, prolonged preoperative hospital stay is also a significant and potentially modifiable predictor for the development of mediastinitis following cardiac surgery. All efforts should be made to minimize the delay in operating on hospitalized patients awaiting heart surgery.
Label-free integrative pharmacology on-target of opioid ligands at the opioid receptor family
Authors: Morse Megan , Sun Haiyan , Tran Elizabeth , Levenson Robert , Fang Ye 
Published: March 2013

Abstract

Background

In vitro pharmacology of ligands is typically assessed using a variety of molecular assays based on predetermined molecular events in living cells. Many ligands including opioid ligands pose the ability to bind more than one receptor, and can also provide distinct operational bias to activate a specific receptor. Generating an integrative overview of the binding and functional selectivity of ligands for a receptor family is a critical but difficult step in drug discovery and development. Here we applied a newly developed label-free integrative pharmacology on-target (iPOT) approach to systematically survey the selectivity of a library of fifty-five opioid ligands against the opioid receptor family. All ligands were interrogated using dynamic mass redistribution (DMR) assays in both recombinant and native cell lines that express specific opioid receptor(s). The cells were modified with a set of probe molecules to manifest the binding and functional selectivity of ligands. DMR profiles were collected and translated to numerical coordinates that was subject to similarity analysis. A specific set of opioid ligands were then selected for quantitative pharmacology determination.

Results
Results showed that among fifty-five opioid ligands examined most ligands displayed agonist activity in at least one opioid receptor expressing cell line under different conditions. Further, many ligands exhibited pathway biased agonism.

Conclusion
We demonstrate that the iPOT effectively sorts the ligands into distinct clusters based on their binding and functional selectivity at the opioid receptor family.
DACT1, an antagonist to Wnt/β-catenin signaling, suppresses tumor cell growth and is frequently silenced in breast cancer
Authors: Yin Xuedong , Xiang Tingxiu , Li LiLi , Su Xianwei , Shu Xingsheng , Luo Xinrong , Huang Jianbo , Yuan Ying , Peng Weiyan , Oberst Michael , Kelly Kathleen , Ren Guosheng , Tao Qian 
Published: March 2013

Abstract
Introduction
Aberrant activation of Wnt/β-catenin signaling plays an important role in the pathogenesis of breast cancer. DACT1 (Dapper/Frodo) has been identified as involved in antagonizing Wnt/β-catenin signaling through interacting with Dishevelled (Dvl), a central mediator of Wnt signaling, whereas its role in breast tumorigenesis remains unclear.

Methods
We examined DACT1 expression in breast cancer cell lines and primary tumors with semiquantitative or quantitative RT-PCR and immunochemistry, and further evaluated the promoter methylation of DACT1 with methylation-specific PCR (MSP). We also explored the tumor-suppressive functions of DACT1 in vivo and in vitro, and its related mechanism in breast cancer.

Results
We identified DACT1 as a methylated target in our breast cancer epigenome study. Here, we further investigated DACT1 expression in multiple breast cell lines and primary tumors, and further studied its function and molecular mechanisms. We found that DACT1 expression was silenced in eight (88.9%) of nine breast cancer cell lines, and its protein levels were obviously reduced in breast tumors compared with paired surgical-margin tissues. Promoter CpG methylation of DACT1 was detected in five (55.6%) of nine breast cancer cell lines and 40 (29.9%) of 134 primary tumors, but not in surgical-margin tissues and normal breast tissues. Demethylation treatment of breast cancer cell lines restored DACT1 expression along with promoter demethylation, suggesting that an epigenetic mechanism mediates DACT1 silencing in breast cancer. Functional assays showed that ectopic expression of DACT1 could inhibit breast tumor cell proliferation in vivo and in vitro through inducing apoptosis, and further suppress tumor cell migration through antagonizing the Wnt/β-catenin signaling pathway.

Conclusions
Our study demonstrates that DACT1 could function as a tumor suppressor but was frequently downregulated in breast cancer.
DNA methylation of distal regulatory sites characterizes dysregulation of cancer genes
Authors: Aran Dvir , Sabato Sivan , Hellman Asaf 
Published: March 2013

Abstract
Background
Abnormal epigenetic marking is well documented in gene promoters of cancer cells, but the study of distal regulatory siteshas lagged behind.We performed a systematic analysis of DNA methylation sites connected with gene expression profilesacross normal and cancerous human genomes.

Results
Utilizing methylation and expression data in 58 cell types, we developed a model for methylation-expression relationships in gene promoters and extrapolated it to the genome. We mapped numerous sites at which DNA methylation was associated with expression of distal genes. These sites bind transcription factors in a methylation-dependent manner, and carry the chromatin marks of a particular class of transcriptional enhancers. In contrast to the traditional model of one enhancer site per cell type, we found that single enhancer sites may define gradients of expression levels across many different cell types. Strikingly, the identified sites were drastically altered in cancers: hypomethylated enhancer sites associated with upregulation of cancer-related genes and hypermethylated sites with downregulation. Moreover, the association between enhancer methylation and gene deregulation in cancerwas significantly stronger than the association of promoter methylationwith gene deregulation.

Conclusions
Methylation of distal regulatory sites is closely related to gene expression levels across the genome. Single enhancers may modulate ranges of cell-specific transcription levels, from constantlyopen promoters. In contrast to the remote relationships between promoter methylation and gene dysregulation in cancer, altered methylation of enhancer sites is closely related to gene expression profiles of transformed cells.