bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long term expression of bicistronic vector driven by the FGF-1 IRES in mouse muscle
Authors: Allera-Moreau Camille , Delluc-Clavières Aurélie , Castano Caroline , Van den Berghe Loïc , Golzio Muriel , Moreau Marc , Teissié Justin , Arnal Jean-François , Prats Anne-Catherine 
Published: October 2007

Abstract

Background
Electrotransfer of plasmid DNA into skeletal muscle is a promising strategy for the delivery of therapeutic molecules targeting various muscular diseases, cancer and lower-limb ischemia. Internal Ribosome Entry Sites (IRESs) allow co-expression of proteins of interest from a single transcriptional unit. IRESs are RNA elements that have been found in viral RNAs as well as a variety of cellular mRNAs with long 5' untranslated regions. While the encephalomyocarditis virus (EMCV) IRES is often used in expression vectors, we have shown that the FGF-1 IRES is equally active to drive short term transgene expression in mouse muscle. To compare the ability of the FGF-1 IRES to drive long term expression against the EMCV and FGF-2 IRESs, we performed analyses of expression kinetics using bicistronic vectors that express the bioluminescent renilla and firefly luciferase reporter genes. Long term expression of bicistronic vectors was also compared to that of monocistronic vectors. Bioluminescence was quantified ex vivo using a luminometer and in vivo using a CCD camera that monitors luminescence within live animals.

Results
Our data demonstrate that the efficiency of the FGF-1 IRES is comparable to that of the EMCV IRES for long term expression of bicistronic transgenes in mouse muscle, whereas the FGF-2 IRES has a very poor activity. Interestingly, we show that despite the global decrease of vector expression over time, the ratio of firefly to renilla luciferase remains stable with bicistronic vectors containing the FGF-1 or FGF-2 IRES and is slightly affected with the EMCV IRES, whereas it is clearly unstable for mixed monocistronic vectors. In addition, long term expression more drastically decreases with monocistronic vectors, and is different for single or mixed vector injection.

Conclusion
These data validate the use of bicistronic vectors rather than mixed monocistronic vectors for long term expression, and support the use of the FGF-1 IRES. The use of a cellular IRES over one of viral origin is of particular interest in the goal of eliminating viral sequences from transgenic vectors. In addition, the FGF-1 IRES, compared to the EMCV IRES, has a more stable activity, is shorter in length and more flexible in terms of downstream cloning of second cistrons. Finally, the FGF-1 IRES is very attractive to develop multicistronic expression cassettes for gene transfer in mouse muscle.
A web-based laboratory information system to improve quality of care of tuberculosis patients in Peru: functional requirements, implementation and usage statistics
Authors: Blaya Joaquin A , Shin Sonya S , Yagui Martin JA , Yale Gloria , Suarez Carmen Z , Asencios Luis L , Cegielski J Peter , Fraser Hamish SF 
Published: October 2007

Abstract

Background
Multi-drug resistant tuberculosis patients in resource-poor settings experience large delays in starting appropriate treatment and may not be monitored appropriately due to an overburdened laboratory system, delays in communication of results, and missing or error-prone laboratory data. The objective of this paper is to describe an electronic laboratory information system implemented to alleviate these problems and its expanding use by the Peruvian public sector, as well as examine the broader issues of implementing such systems in resource-poor settings.

Methods
A web-based laboratory information system "e-Chasqui" has been designed and implemented in Peru to improve the timeliness and quality of laboratory data. It was deployed in the national TB laboratory, two regional laboratories and twelve pilot health centres. Using needs assessment and workflow analysis tools, e-Chasqui was designed to provide for improved patient care, increased quality control, and more efficient laboratory monitoring and reporting.

Results
Since its full implementation in March 2006, 29,944 smear microscopy, 31,797 culture and 7,675 drug susceptibility test results have been entered. Over 99% of these results have been viewed online by the health centres. High user satisfaction and heavy use have led to the expansion of e-Chasqui to additional institutions. In total, e-Chasqui will serve a network of institutions providing medical care for over 3.1 million people. The cost to maintain this system is approximately US$0.53 per sample or 1% of the National Peruvian TB program's 2006 budget.

Conclusion
Electronic laboratory information systems have a large potential to improve patient care and public health monitoring in resource-poor settings. Some of the challenges faced in these settings, such as lack of trained personnel, limited transportation, and large coverage areas, are obstacles that a well-designed system can overcome. e-Chasqui has the potential to provide a national TB laboratory network in Peru. Furthermore, the core functionality of e-Chasqui as been implemented in the open source medical record system OpenMRS http://www.openmrs.org for other countries to use.
Measuring global health inequity
Authors: Reidpath Daniel D , Allotey Pascale 
Published: October 2007

Abstract

Background
Notions of equity are fundamental to, and drive much of the current thinking about global health. Health inequity, however, is usually measured using health inequality as a proxy – implicitly conflating equity and equality. Unfortunately measures of global health inequality do not take account of the health inequity associated with the additional, and unfair, encumbrances that poor health status confers on economically deprived populations.

Method
Using global health data from the World Health Organization's 14 mortality sub-regions, a measure of global health inequality (based on a decomposition of the Pietra Ratio) is contrasted with a new measure of global health inequity. The inequity measure weights the inequality data by regional economic capacity (GNP per capita).

Results
The least healthy global sub-region is shown to be around four times worse off under a health inequity analysis than would be revealed under a straight health inequality analysis. In contrast the healthiest sub-region is shown to be about four times better off. The inequity of poor health experienced by poorer regions around the world is significantly worse than a simple analysis of health inequality reveals.

Conclusion
By measuring the inequity and not simply the inequality, the magnitude of the disparity can be factored into future economic and health policy decision making.
Impact of reduced vancomycin susceptibility on the therapeutic outcome of MRSA bloodstream infections
Authors: Neoh Hui-min , Hori Satoshi , Komatsu Mitsutaka , Oguri Toyoko , Takeuchi Fumihiko , Cui Longzhu , Hiramatsu Keiichi 
Published: October 2007

Abstract

Background
The aim of this study was to determine whether clinical outcome of patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia was correlated with vancomycin susceptibility of the corresponding strains.

Methods
A retrospective study on MRSA bacteraemia was performed at a teaching hospital between January 1998 and October 2005 by linking vancomycin susceptibility profiles of patients' isolates with hospitalization data.

Results
A total of 20 out of 209 MRSA bacteraemia patients were treated with vancomycin for at least 5 days with adequate trough levels, and fulfilled the study's inclusion and exclusion criteria. Twenty-two S. aureus isolates from these patients' blood cultures were identified as MRSA, including two hetero-VISA from separate patients and two VISA with vancomycin MIC of 4 mg/L from one patient. Between patients who showed 'good' vancomycin response and patients who did not, there was a significant difference (p < 0.01) in their corresponding MRSAs' vancomycin susceptibility expressed by 'area under curve' (AUC) of population analysis. Significant correlations were found between AUC and initial vancomycin therapeutic response parameters of 'days till afebrile' (r = 0.828, p < 0.01) and 'days till CRP ≦ 30% of maximum' (r = 0.627, p < 0.01)

Conclusion
Our study results caution healthcare personnel that early consideration should be given to cases with a poor vancomycin treatment response that could signify the involvement of MRSA with reduced susceptibility to vancomycin.
Identification of a panel of sensitive and specific DNA methylation markers for lung adenocarcinoma
Authors: Tsou Jeffrey A , Galler Janice S , Siegmund Kimberly D , Laird Peter W , Turla Sally , Cozen Wendy , Hagen Jeffrey A , Koss Michael N , Laird-Offringa Ite A 
Published: October 2007

AbstractBackgroundLung cancer is the number one cancer killer of both men and women in the United States. Three quarters of lung cancer patients are diagnosed with regionally or distantly disseminated disease; their 5-year survival is only 15%. DNA hypermethylation at promoter CpG islands shows great promise as a cancer-specific marker that would complement visual lung cancer screening tools such as spiral CT, improving early detection. In lung cancer patients, such hypermethylation is detectable in a variety of samples ranging from tumor material to blood and sputum. To date the penetrance of DNA methylation at any single locus has been too low to provide great clinical sensitivity. We used the real-time PCR-based method MethyLight to examine DNA methylation quantitatively at twenty-eight loci in 51 primary human lung adenocarcinomas, 38 adjacent non-tumor lung samples, and 11 lung samples from non-lung cancer patients.ResultsWe identified thirteen loci showing significant differential DNA methylation levels between tumor and non-tumor lung; eight of these show highly significant hypermethylation in adenocarcinoma: CDH13, CDKN2A EX2, CDX2, HOXA1, OPCML, RASSF1, SFPR1, and TWIST1 (p-value << 0.0001). Using the current tissue collection and 5-fold cross validation, the four most significant loci (CDKN2A EX2, CDX2, HOXA1 and OPCML) individually distinguish lung adenocarcinoma from non-cancer lung with a sensitivity of 67–86% and specificity of 74–82%. DNA methylation of these loci did not differ significantly based on gender, race, age or tumor stage, indicating their wide applicability as potential lung adenocarcinoma markers. We applied random forests to determine a good classifier based on a subset of our loci and determined that combined use of the same four top markers allows identification of lung cancer tissue from non-lung cancer tissue with 94% sensitivity and 90% specificity.ConclusionThe identification of eight CpG island loci showing highly significant hypermethylation in lung adenocarcinoma provides strong candidates for evaluation in patient remote media such as plasma and sputum. The four most highly ranked loci, CDKN2A EX2, CDX2, HOXA1 and OPCML, which show significant DNA methylation even in stage IA tumor samples, merit further investigation as some of the most promising lung adenocarcinoma markers identified to date.
Study of molecular mechanisms of pro-apoptotic activity of NCX 4040, a novel nitric oxide-releasing aspirin, in colon cancer cell lines
Authors: Tesei Anna , Rosetti Marco , Ulivi Paola , Fabbri Francesco , Medri Laura , Vannini Ivan , Bolla Manlio , Amadori Dino , Zoli Wainer 
Published: October 2007

AbstractBackgroundDespite numerous studies aimed at verifying the antitumor activity of nitric oxide-releasing nonsteroidal antiflammatory drugs (NO-NSAIDs), little is known about the molecular targets responsible for their antineoplastic properties. In the present study, we investigated the mechanisms underlying the cytotoxicity of NCX 4040, a novel NO-aspirin with promising antineoplastic action, inin vitrohuman colon cancer models.MethodsThe effect on tumor growth was evaluated in four human colon cancer cell lines (LoVo, LRWZ, WiDr and LoVo Dx) by sulforhodamine B assay, oxidative stress by immunohistochemistry, apoptosis by laddering assay, mitochondrial membrane potential (ΔΨm) by flow cytometry, and apoptosis- and chemoresistance-related markers by western-blot and real-time method, respectively. Prostaglandin E2levels were determined by ELISA.ResultsNCX 4040 produced a higher cytotoxic effect in all the cell lines than that produced by other NO donors tested. In particular, in LoVo and LRWZ cells, NCX 4040 induced a cytocidal effect and apoptosis through p53 and NAG-1 expression, an early ΔΨmcollapse, and a sequential release of cytoplasmatic cytochrome c and caspase -9 and -3 active forms. 8-hydroxyguanine lesions, indicative of oxidative stress, were also observed. Conversely, in WiDr line, the drug caused a cytocidal effect, albeit not through apoptosis, and a concomitant increase in COX-2 activity. In LoVo Dx line, characterized by high levels drug resistance and DNA repair-related markers, only a cytostatic effect was observed, again in concomitance with the increase in COX-2 enzyme activity.ConclusionThis study highlights the multiplicity of mechanisms involved in sensitivity or resistance to NCX 4040 and could provide useful indications for tailored therapy by identifying potentially drug-responsive tumors.
Optimal ex vivo expansion of neutrophils from PBSC CD34+ cells by a combination of SCF, Flt3-L and G-CSF and its inhibition by further addition of TPO
Authors: Tura Olga , Barclay G Robin , Roddie Huw , Davies John , Turner Marc L 
Published: October 2007

Abstract

Background
Autologous mobilised peripheral blood stem cell (PBSC) transplantation is now a standard approach in the treatment of haematological diseases to reconstitute haematopoiesis following myeloablative chemotherapy. However, there remains a period of severe neutropenia and thrombocytopenia before haematopoietic reconstitution is achieved. Ex vivo expanded PBSC have been employed as an adjunct to unmanipulated HSC transplantation, but have tended to be produced using complex cytokine mixtures aimed at multilineage (neutrophil and megakaryocyte) progenitor expansion. These have been reported to reduce or abrogate neutropenia but have little major effect on thrombocytopenia. Selective megakaryocyte expansion has been to date ineffective in reducing thrombocytopenia. This study was implemented to evaluate neutrophil specific rather than multilineage ex vivo expansion of PBSC for specifically focusing on reduction or abrogation of neutropenia.

Methods
CD34+ cells (PBSC) were enriched from peripheral blood mononuclear cells following G-CSF-mobilisation and cultured with different permutations of cytokines to determine optimal cytokine combinations and doses for expansion and functional differentiation and maturation of neutrophils and their progenitors. Results were assessed by cell number, morphology, phenotype and function.

Results
A simple cytokine combination, SCF + Flt3-L + G-CSF, synergised to optimally expand and mature neutrophil progenitors assessed by cell number, phenotype, morphology and function (superoxide respiratory burst measured by chemiluminescence). G-CSF appears mandatory for functional maturation. Addition of other commonly employed cytokines, IL-3 and IL-6, had no demonstrable additive effect on numbers or function compared to this optimal combination. Addition of TPO, commonly included in multilineage progenitor expansion for development of megakaryocytes, reduced the maturation of neutrophil progenitors as assessed by number, morphology and function (respiratory burst activity).

Conclusion
Given that platelet transfusion support is available for autologous PBSC transplantation but granulocyte transfusion is generally lacking, and that multilineage expanded PBSC do not reduce thrombocytopenia, we suggest that instead of multilineage expansion selective neutrophil expansion based on this relatively simple cytokine combination might be prioritized for development for clinical use as an adjunct to unmanipulated PBSC transplantation to reduce or abrogate post-transplant neutropenia.
The E5 protein of the human papillomavirus type 16 down-regulates HLA-I surface expression in calnexin-expressing but not in calnexin-deficient cells
Authors: Gruener Myriam , Bravo Ignacio G , Momburg Frank , Alonso Angel , Tomakidi Pascal 
Published: October 2007

AbstractThe human papillomavirus type 16 E5 protein (HPV16 E5) down-regulates surface expression of HLA-I molecules. The molecular mechanisms underlying this effect are so far unknown. Here we show that HPV16 E5 down-regulates HLA-I surface expression in calnexin-containing but not in calnexin-deficient cells. Immunoprecipitation experiments reveal that calnexin and HPV16E5 can be co-precipitated and that this association depends on the presence of a wild-type first hydrophobic region of E5. When an E5 mutant (M1) in which the first putative transmembrane helix had been disrupted was used for the transfections calnexin-E5 co-precipitation was strongly impaired. In addition, we show that the M1 mutant is only able to marginally down-regulate HLA-I surface expression compared to the wild-type protein. Besides, we demonstrate that E5 forms a ternary complex with calnexin and the heavy chain of HLA-I, which is mediated by the first hydrophobic region of the E5 protein. On the basis of our results we conclude that formation of this complex is responsible for retention of HLA-I molecules in the ER of the cells.
Depression and anxiety in epilepsy: the association with demographic and seizure-related variables
Authors: Kimiskidis Vasilios K , Triantafyllou Nikolaos I , Kararizou Eleni , Gatzonis Stergios-Stylianos , Fountoulakis Konstantinos N , Siatouni Anna , Loucaidis Panagiotis , Pseftogianni Dimitra , Vlaikidis Nikolaos , Kaprinis George S 
Published: October 2007

Abstract

Background
Depression and anxiety are common psychiatric symptoms in patients with epilepsy, exerting a profound negative effect on health-related quality of life. Several issues, however, pertaining to their association with psychosocial, seizure-related and medication factors, remain controversial. Accordingly, the present study was designed to investigate the association of interictal mood disorders with various demographic and seizure-related variables in patients with newly-diagnosed and chronic epilepsy.

Methods
We investigated 201 patients with epilepsy (51.2% males, mean age 33.2 ± 10.0 years, range 16–60) with a mean disease duration of 13.9 ± 9.5 years. Depression and anxiety were assessed in the interictal state with the Beck Depression Inventory, 21-item version (BDI-21) and the state and trait subscales of the State-Trait Anxiety Inventory (STAI-S and STAI-T), respectively. The association of mood disorders with various variables was investigated with simple and multiple linear regression analyses.

Results
High seizure frequency and symptomatic focal epilepsy (SFE) were independent determinants of depression, together accounting for 12.4% of the variation of the BDI-21. The STAI-S index was significantly associated with the type of epilepsy syndrome (SFE). Finally, high seizure frequency, SFE and female gender were independent determinants of trait anxiety accounting for 14.7% of the variation of the STAI-T.

Conclusion
Our results confirm the prevailing view that depression and anxiety are common psychological disorders in epileptics. It is additionally concluded that female gender, high seizure frequency and a symptomatic epilepsy syndrome are independent risk factors for the development of anxiety and/or depression.
Factors that help injecting drug users to access and benefit from services: A qualitative study
Authors: Neale Joanne , sheard Laura , Tompkins Charlotte NE 
Published: October 2007

Abstract

Background
International research shows that injecting drug users (IDUs) can encounter many barriers when they try to access drug treatment and other services. However, the existing literature is mostly quantitative and does not consider the kinds of factors that injectors themselves identify as enabling them to access and benefit from services. Responding to this gap in knowledge, our paper explores IDUs' own suggestions for improving service engagement and their reports of other factors enabling them to seek help.

Methods
Semi-structured qualitative interviews were conducted with 75 current illicit drug injectors in three geographically diverse areas of West Yorkshire, England. Recruitment was through needle exchange programmes, with additional snowball sampling to ensure inclusivity of gender, ethnicity and primary drug injected. Transcribed data were analysed thematically using Framework.

Results
Although participants were often satisfied with current access to services, they made three broad suggestions for improving engagement. These were: providing more services (more providers and more forms of support); better operation of existing services (including better communication systems and more flexibility around individual needs); and staffing-related improvements (particularly, less judgemental and more understanding staff attitudes). Other factors identified as important enablers of help seeking were: having supporting relationships (particularly with family members); personal circumstances/life events (especially becoming a parent); and an injector's state of mind (such as feeling motivated and positive).

Conclusion
A range of practical suggestions for improving IDUs' access to drug treatment and other services are identified.
Unilateral pedicle screws asymmetric tethering: an innovative method to create idiopathic deformity
Authors: Zhang Yonggang , Wang Yan , Zheng Guoquan , Zhang Xuesong , Zhang Ruyi , Zhang Wei 
Published: October 2007

Abstract

Objective
To evaluate the feasibility of the method that unilateral pedicle screws asymmetric tethering in concave side in combination with convex rib resection for creating idiopathic deformity.

Summary of background data
Various methods are performed to create idiopathic deformity. Among these methods, posterior asmmetric tethering of the spine shows satisfying result, but some drawbacks related to the current posterior asymmetric tether were still evident.

Materials and methods
Unilateral pedicle screws asymmetric tethering was performed to 14 female goats (age: 5–8 week-old, weight: 6–8 kg) in concave side in combination with convex rib resection. Dorsoventral and lateral plain radiographs were taken of each thoracic spine in the frontal and sagittal planes right after the surgery and later every 4 weeks.

Results
All animals ambulated freely after surgery. For technical reasons, 2 goats were excluded (one animal died for anesthetic during the surgery, and one animal was lost for instrumental fail due to postoperative infection). Radiography showed that 11 goats exhibited scoliosis with convex toward to the right side, and as the curve increased with time, only 1 goat showed nonprogressive. The initial scoliosis generated in the progressors after the procedures measured 29.0° on average (range 23.0°–38.5°) and increased to 43.0° on average (range 36.0°–58.0°) over 8 to 10 weeks. The average progression of 14.0° was measured. The curvature immediately after tethering surgery (the initial Cobb angle) did have a highly significant correlation with the final curvature (p < 0.001). The progressive goats showed an idiopathic-like deformity not only by radiography, but in general appearance.

Conclusion
Unilateral pedicle screws asymmetric tethering is a practical method to create experimental scoliosis, especially for those who would like to study the correction of this deformity.