bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patient-centered, comparative effectiveness of esophageal cancer screening: protocol for a comparative effectiveness research study to inform guidelines for evidence-based approach to screening and surveillance endoscopy
Authors: Kramer Jennifer R , Arney Jennifer , Chen John , Richardson Peter , Duan Zhigang , Street Richard L , Hinojosa-Lindsey Marilyn , Naik Aanand D , El-Serag Hashem B 
Published: August 2012

Abstract

Background
The comparative effectiveness (CE) of endoscopic screening (versus no screening) for Barrett’s esophagus (BE) in patients with GERD symptoms, or among different endoscopic surveillance strategies in patients with BE, for the early detection of esophageal adenocarcinoma (EA) is unknown. Furthermore, it is unclear if patients or providers have or will adopt any of these strategies (screening only, screening and surveillance, vs. none), irrespective of their effectiveness. Endoscopic screening and surveillance is expensive and can be risky. Therefore, it is imperative to establish the CE and acceptability about the risks and outcomes related to these practices to better inform expert recommendations and provider-patient decisions.

Methods/Results
We propose a mixed methods study which will involve: (1) an analysis of secondary databases (VA and VA-Medicare linked datasets for 2004–09) to examine CE of endoscopic screening and surveillance in an observational study cohort (an estimated 680,000 patients with GERD; 25,000–30,000 with BE; and 3,000 with EA); (2) a structured electronic medical record (EMR) review on a national sample of patients using VA EMRs to verify all EA cases, identify cancer stage, cancer-targeted therapy, and validate the screening and surveillance endoscopy; and (3) qualitative in depth interviews with patients and providers to elicit preferences, norms, and behaviors to explain clinical contexts of these findings and address gaps arising from the CE study.

Conclusion
This study will compare clinical strategies for detecting and monitoring BE, a pre-cancerous lesion. Additionally, by eliciting acceptability of these strategies for patients and providers, we will be able to propose effective and feasible strategies that are likely to be implemented in routine use. Findings will inform recommendations for clinical practice guidelines. Our innovative approach is consistent with the methodological standards of patient-centered outcomes research, and our findings will offer a significant contribution to the literature on cancer surveillance.

Trial Registration
Not applicable
Variation in apoptosis mechanisms employed by malaria parasites: the roles of inducers, dose dependence and parasite stages
Authors: Matthews Holly , Ali Medhat , Carter Victoria , Underhill Ann , Hunt Jennifer , Szor Hannah , Hurd Hilary 
Published: August 2012

Abstract

Background

Plasmodium berghei ookinetes exhibit an apoptotic phenotype when developing within the mosquito midgut lumen or when cultured in vitro. Markers of apoptosis increase when they are exposed to nitric oxide or reactive oxygen species but high concentrations of hydrogen peroxide cause death without observable signs of apoptosis. Chloroquine and other drugs have been used to induce apoptosis in erythrocytic stages of Plasmodium falciparum and to formulate a putative pathway involving cysteine protease activation and mitochondrial membrane permeabilization; initiated, at least in the case of chloroquine, after its accumulation in the digestive vacuole causes leakage of the vacuole contents. The lack of a digestive vacuole in ookinetes prompted the investigation of the effect of chloroquine and staurosporine on this stage of the life cycle. Finally, the suggestion that apoptosis may have evolved as a strategy employed by ookinetes to increase the fitness of surviving parasites was explored by determining whether increasing the ecological triggers parasite density and nutrient depletion induced apoptosis.

Methods
Ookinetes were grown in culture then either exposed to hydrogen peroxide, chloroquine or staurosporine, or incubated at different densities and in different media. The proportion of ookinetes displaying positive markers for apoptosis in treated samples was compared with controls and results were analyzed using analysis of variance followed by a Turkey’s test, or a Kruskal-Wallis test as appropriate.

Results
Hydrogen peroxide below 50 μM triggered apoptosis but cell membranes were rapidly compromised by higher concentrations, and the mode of death could not be defined. Both chloroquine and staurosporine cause a significant increase in ookinetes with condensed chromatin, caspase-like activity and, in the case of chloroquine, phosphatidylserine translocation and DNA fragmentation (not investigated for staurosporine). However, mitochondrial membrane potential remained intact. No relationship between ookinete density and apoptosis was detected but nutrient depletion significantly increased the proportion of ookinetes with chromatin condensation in four hours.

Conclusions
It is proposed that both a mitochondrial and an amitochondrial apoptotic pathway may be involved, dependent upon the trigger that induces apoptosis, and that pathways may differ between erythrocytic stages and ookinetes, or between rodent and human malaria parasites.
High-throughput sorting of mosquito larvae for laboratory studies and for future vector control interventions
Authors: Marois Eric , Scali Christina , Soichot Julien , Kappler Christine , Levashina Elena A , Catteruccia Flaminia 
Published: August 2012

Abstract

Background
Mosquito transgenesis offers new promises for the genetic control of vector-borne infectious diseases such as malaria and dengue fever. Genetic control strategies require the release of large number of male mosquitoes into field populations, whether they are based on the use of sterile males (sterile insect technique, SIT) or on introducing genetic traits conferring refractoriness to disease transmission (population replacement). However, the current absence of high-throughput techniques for sorting different mosquito populations impairs the application of these control measures.

Methods
A method was developed to generate large mosquito populations of the desired sex and genotype. This method combines flow cytometry and the use of Anopheles gambiae transgenic lines that differentially express fluorescent markers in males and females.

Results
Fluorescence-assisted sorting allowed single-step isolation of homozygous transgenic mosquitoes from a mixed population. This method was also used to select wild-type males only with high efficiency and accuracy, a highly desirable tool for genetic control strategies where the release of transgenic individuals may be problematic. Importantly, sorted males showed normal mating ability compared to their unsorted brothers.

Conclusions
The developed method will greatly facilitate both laboratory studies of mosquito vectorial capacity requiring high-throughput approaches and future field interventions in the fight against infectious disease vectors.
Mathematical modelling of the action potential of human embryonic stem cell derived cardiomyocytes
Authors: Paci Michelangelo , Sartiani Laura , Del Lungo Martina , Jaconi Marisa , Mugelli Alessandro , Cerbai Elisabetta , Severi Stefano 
Published: August 2012

Abstract

Background
Human embryonic stem cell derived cardiomyocytes (hESC-CMs) hold high potential for basic and applied cardiovascular research. The development of a reliable simulation platform able to mimic the functional properties of hESC-CMs would be of considerable value to perform preliminary test complementing in vitro experimentations.

Methods
We developed the first computational model of hESC-CM action potential by integrating our original electrophysiological recordings of transient-outward, funny, and sodium-calcium exchanger currents and data derived from literature on sodium, calcium and potassium currents in hESC-CMs.

Results
The model is able to reproduce basal electrophysiological properties of hESC-CMs at 15 40 days of differentiation (Early stage). Moreover, the model reproduces the modifications occurring through the transition from Early to Late developmental stage (50-110, days of differentiation). After simulated blockade of ionic channels and pumps of the sarcoplasmic reticulum, Ca2+ transient amplitude was decreased by 12% and 33% in Early and Late stage, respectively, suggesting a growing contribution of a functional reticulum during maturation. Finally, as a proof of concept, we tested the effects induced by prototypical channel blockers, namely E4031 and nickel, and their qualitative reproduction by the model.

Conclusions
This study provides a novel modelling tool that may serve useful to investigate physiological properties of hESC-CMs.
MicroRNA expression in ovarian carcinoma and its correlation with clinicopathological features
Authors: Lee Heejeong , Park Chul Soo , Deftereos Georgios , Morihara Janice , Stern Joshua E , Hawes Stephen E , Swisher Elizabeth , Kiviat Nancy B , Feng Qinghua 
Published: August 2012

AbstractBackgroundMicroRNA (miRNA) expression is known to be deregulated in ovarian carcinomas. However, limited data is available about the miRNA expression pattern for the benign or borderline ovarian tumors as well as differential miRNA expression pattern associated with histological types, grades or clinical stages in ovarian carcinomas. We defined patterns of microRNA expression in tissues from normal, benign, borderline, and malignant ovarian tumors and explored the relationship between frequently deregulated miRNAs and clinicopathologic findings, response to therapy, survival, and association with Her-2/neu status in ovarian carcinomas.MethodsWe measured the expression of nine miRNAs (miR-181d, miR-30a-3p, miR-30c, miR-30d, miR-30e-3p, miR-368, miR-370, miR-493-5p, miR-532-5p) in 171 formalin-fixed, paraffin-embedded ovarian tissue blocks as well as six normal human ovarian surface epithelial (HOSE) cell lines using Taqman-based real-time PCR assays. Her-2/neu overexpression was assessed in ovarian carcinomas (n = 109 cases) by immunohistochemistry analysis.ResultsExpression of four miRNAs (miR-30c, miR-30d, miR-30e-3p, miR-370) was significantly different between carcinomas and benign ovarian tissues as well as between carcinoma and borderline tissues. An additional three miRNAs (miR-181d, miR-30a-3p, miR-532-5p) were significantly different between borderline and carcinoma tissues. Expression of miR-532-5p was significantly lower in borderline than in benign tissues. Among ovarian carcinomas, expression of four miRNAs (miR-30a-3p, miR-30c, miR-30d, miR-30e-3p) was lowest in mucinous and highest in clear cell samples. Expression of miR-30a-3p was higher in well-differentiated compared to poorly differentiated tumors (P = 0.02), and expression of miR-370 was higher in stage I/II compared to stage III/IV samples (P = 0.03). In multivariate analyses, higher expression of miR-181d, miR-30c, miR-30d, and miR-30e-3p was associated with significantly better disease-free or overall survival. Finally, lower expression of miR-30c, miR-30d, miR-30e-3p and miR-532-5p was significantly associated with overexpression of Her-2/neu.ConclusionsAberrant expression of miRNAs is common in ovarian tumor suggesting involvement of miRNA in ovarian tumorigenesis. They are associated with histology, clinical stage, survival and oncogene expression in ovarian carcinoma.
Cytomegalovirus seropositivity is associated with glucose regulation in the oldest old. Results from the Leiden 85-plus Study
Authors: Chen Sijia , JM de Craen Anton , Raz Yotam , Derhovanessian Evelyna , Vossen CTM Ann , Westendorp GJ Rudi , Pawelec Graham , Maier Andrea B 
Published: August 2012

AbstractBackgroundCytomegalovirus (CMV) infection has been reported to contribute to the pathogenesis of type 1 diabetes and post-transplantation diabetes. However, CMV infection has not been evaluated as a possible risk factor for type 2 diabetes. Our aim was to investigate potential associations between CMV seropositivity, CMV IgG antibody level and glucose regulation in the oldest old.ResultsCMV seropositive subjects were more likely to have type 2 diabetes (17.2% vs 7.9%, p = 0.016), had a higher level of HbA1c (p = 0.014) and higher non-fasting glucose (p = 0.024) in the oldest olds. These associations remained significant after adjustment for possible confounders. CMV IgG antibody level was not significantly associated with glucose regulation (all p > 0.05).ConclusionsIn the oldest old, CMV seropositivity is significantly associated with various indicators of glucose regulation. This finding suggests that CMV infection might be a risk factor for the development of type 2 diabetes in the elderly.
A novel walking speed estimation scheme and its application to treadmill control for gait rehabilitation
Authors: Yoon Jungwon , Park Hyung-Soon , Damiano Diane Louise 
Published: August 2012

Abstract

Background
Virtual reality (VR) technology along with treadmill training (TT) can effectively provide goal-oriented practice and promote improved motor learning in patients with neurological disorders. Moreover, the VR + TT scheme may enhance cognitive engagement for more effective gait rehabilitation and greater transfer to over ground walking. For this purpose, we developed an individualized treadmill controller with a novel speed estimation scheme using swing foot velocity, which can enable user-driven treadmill walking (UDW) to more closely simulate over ground walking (OGW) during treadmill training. OGW involves a cyclic acceleration-deceleration profile of pelvic velocity that contrasts with typical treadmill-driven walking (TDW), which constrains a person to walk at a preset constant speed. In this study, we investigated the effects of the proposed speed adaptation controller by analyzing the gait kinematics of UDW and TDW, which were compared to those of OGW at three pre-determined velocities.

Methods
Ten healthy subjects were asked to walk in each mode (TDW, UDW, and OGW) at three pre-determined speeds (0.5 m/s, 1.0 m/s, and 1.5 m/s) with real time feedback provided through visual displays. Temporal-spatial gait data and 3D pelvic kinematics were analyzed and comparisons were made between UDW on a treadmill, TDW, and OGW.

Results
The observed step length, cadence, and walk ratio defined as the ratio of stride length to cadence were not significantly different between UDW and TDW. Additionally, the average magnitude of pelvic acceleration peak values along the anterior-posterior direction for each step and the associated standard deviations (variability) were not significantly different between the two modalities. The differences between OGW and UDW and TDW were mainly in swing time and cadence, as have been reported previously. Also, step lengths between OGW and TDW were different for 0.5 m/s and 1.5 m/s gait velocities, and walk ratio between OGS and UDW was different for 1.0 m/s gait velocities.

Conclusions
Our treadmill control scheme implements similar gait biomechanics of TDW, which has been used for repetitive gait training in a small and constrained space as well as controlled and safe environments. These results reveal that users can walk as stably during UDW as TDW and employ similar strategies to maintain walking speed in both UDW and TDW. Furthermore, since UDW can allow a user to actively participate in the virtual reality (VR) applications with variable walking velocity, it can induce more cognitive activities during the training with VR, which may enhance motor learning effects.
The role of crude saliva and purified salivary mucins in the inhibition of the Human Immunodeficiency Virus type 1
Authors: Peacocke Julia , Lotz Zoe , de Beer Corena , Roux Paul , Mall Anwar S 
Published: August 2012

Abstract

Background
Sub-Saharan Africa is the world’s worst HIV-AIDS affected region. More interventions to manage this pandemic are urgently required. Transmission of the virus through an exchange of saliva is rarely known to occur. This project sought to verify statistically previous findings in our laboratory, that crude saliva from uninfected individuals together with its purified mucin components inhibited HIV-1, whilst mucins from infected saliva did not show this inhibition, in an in vitro assay.

Methods

Saliva was extracted in 4 M guanidinium hydrochloride and proteolytic inhibitors at pH 6.5, followed by the isolation of MUC5B and MUC7 by Sepharose 4B gel filtration and further purification of these mucins by density-gradient ultra-centrifugation in caesium chloride. Agarose gel electrophoresis, Western blotting and amino acid compositional analysis determined the size, purity and identity of the mucins. The inhibitory activity of crude saliva and purified MUC5B and MUC7, from HIV negative (n=20) and HIV positive (n=20) donors, was tested by their incubation with subtype C HIV-1 and subsequent infection of peripheral blood mononuclear cells (PBMCs). PCR was done on tandem repeat regions of MUC5B and MUC7 DNA to investigate whether any association existed between gene polymorphism and susceptibility to infection.

Results
There was an inter-individual variation in the amounts of MUC5B and MUC7 in saliva. In contrast to previous studies, crude saliva and purified mucins from both HIV negative and HIV positive individuals inhibited the infection of HIV-1 in an in vitro assay. DNA analysis of the tandem repeat regions of MUC5B and MUC7 revealed no difference between groups.

Conclusions
Crude saliva and its mucins, MUC5B and MUC7, from both uninfected controls and HIV positive individuals inhibited HIV-1 in an in vitro assay.
Using psychological theory to inform methods to optimize the implementation of a hand hygiene intervention
Authors: Boscart Veronique M , Fernie Geoff R , Lee Jae H , Jaglal Susan B 
Published: August 2012

Abstract

Background
Careful hand hygiene (HH) is the single most important factor in preventing the transmission of infections to patients, but compliance is difficult to achieve and maintain. A lack of understanding of the processes involved in changing staff behaviour may contribute to the failure to achieve success. The purpose of this study was to identify nurses’ and administrators’ perceived barriers and facilitators to current HH practices and the implementation of a new electronic monitoring technology for HH.

Methods
Ten key informant interviews (three administrators and seven nurses) were conducted to explore barriers and facilitators related to HH and the impact of the new technology on outcomes. The semi structured interviews were based on the Theoretical Domains Framework by Michie et al. and conducted prior to intervention implementation. Data were explored using an inductive qualitative analysis approach. Data between administrators and nurses were compared.

Results
In 9 of the 12 domains, nurses and administrators differed in their responses. Administrators believed that nurses have insufficient knowledge and skills to perform HH, whereas the nurses were confident they had the required knowledge and skills. Nurses focused on immediate consequences, whereas administrators highlighted long-term outcomes of the system. Nurses concentrated foremost on their personal safety and their families’ safety as a source of motivation to perform HH, whereas administrators identified professional commitment, incentives, and goal setting. Administrators stated that the staff do not have the decision processes in place to judge whether HH is necessary or not. They also highlighted the positive aspects of teams as a social influence, whereas nurses were not interested in group conformity or being compared to others. Nurses described the importance of individual feedback and self-monitoring in order to increase their performance, whereas administrators reported different views.

Conclusions
This study highlights the benefits of using a structured approach based on psychological theory to inform an implementation plan for a behavior change intervention. This work is an essential step towards systematically identifying factors affecting nurses’ behaviour associated with HH.
Contemporary incidence and risk factors for carotid artery disease in patients referred for coronary artery bypass surgery
Authors: Wanamaker Kelly M , Moraca Robert J , Nitzberg Diane , Magovern George J 
Published: August 2012

Abstract

Background
In the past decade, there has been an increase in the amount of patients with medical co-morbidities referred for coronary artery bypass surgery (CABG). Significant carotid artery disease in patients undergoing CABG procedures increases the risk of neurological complications. We review the results of routine carotid screening in patients undergoing CABG to determine the contemporary incidence and risk factors for carotid artery disease.

Methods
Between 2008 through 2010, 673 patients were referred for isolated coronary artery bypass surgery at a single institution. Patients were identified through a systematic review of The Department of Cardiothoracic Surgery Society of Thoracic Surgery Outcomes Database. A retrospective analysis of prospectively collected demographic, clinical data and outcomes were performed. All patients with screening preoperative carotid duplex were reviewed. We defined the degree of carotid disease as: none to mild stenosis (<50%), moderate stenosis (50-69%), severe stenosis (70-99%). Multivariate analysis was performed to identify risk factors.

Results
559 (83%) patients underwent screening preoperative carotid ultrasonography prior to CABG. The incidence of carotid artery disease (>50% stenosis) was 36% with 18% unilateral moderate disease, 10% bilateral moderate and 8% severe disease. Risk factors associated with carotid artery disease included: advanced age, renal failure, previous stroke, peripheral vascular disease, left main coronary artery disease, and previous myocardial infarction.

Conclusions
There is a significant incidence of carotid artery stenosis in patients referred for CABG. Routine screening will identify patients with carotid artery disease and may reduce the risk of postoperative stroke.
ROCK-phosphorylated vimentin modifies mutant huntingtin aggregation via sequestration of IRBIT
Authors: Bauer Peter O , Hudec Roman , Goswami Anand , Kurosawa Masaru , Matsumoto Gen , Mikoshiba Katsuhiko , Nukina Nobuyuki 
Published: August 2012

Abstract

Background
Huntington's Disease (HD) is a fatal hereditary neurodegenerative disease caused by the accumulation of mutant huntingtin protein (Htt) containing an expanded polyglutamine (polyQ) tract. Activation of the channel responsible for the inositol-induced Ca2+ release from ensoplasmic reticulum (ER), was found to contribute substantially to neurodegeneration in HD. Importantly, chemical and genetic inhibition of inositol 1,4,5-trisphosphate (IP3) receptor type 1 (IP3R1) has been shown to reduce mutant Htt aggregation.

Results
In this study, we propose a novel regulatory mechanism of IP3R1 activity by type III intermediate filament vimentin which sequesters the negative regulator of IP3R1, IRBIT, into perinuclear inclusions, and reduces its interaction with IP3R1 resulting in promotion of mutant Htt aggregation. Proteasome inhibitor MG132, which causes polyQ proteins accumulation and aggregation, enhanced the sequestration of IRBIT. Furthermore we found that IRBIT sequestration can be prevented by a rho kinase inhibitor, Y-27632.

Conclusions
Our results suggest that vimentin represents a novel and additional target for the therapy of polyQ diseases.