bluuebunny/crossref_metadata_2025_split huggingface dataset:
Costing the scaling-up of human resources for health: lessons from Mozambique and Guinea Bissau
Authors: Tyrrell Amanda K , Russo Giuliano , Dussault Gilles , Ferrinho Paulo 
Published: July 2010

Abstract

Introduction
In the context of the current human resources for health (HRH) crisis, the need for comprehensive Human Resources Development Plans (HRDP) is acute, especially in resource-scarce sub-Saharan African countries. However, the financial implications of such plans rarely receive due consideration, despite the availability of much advice and examples in the literature on how to conduct HRDP costing. Global initiatives have also been launched recently to standardise costing methodologies and respective tools.

Methods
This paper reports on two separate experiences of HRDP costing in Mozambique and Guinea Bissau, with the objective to provide an insight into the practice of costing exercises in information-poor settings, as well as to contribute to the existing debate on HRH costing methodologies. The study adopts a case-study approach to analyse the methodologies developed in the two countries, their contexts, policy processes and actors involved.

Results
From the analysis of the two cases, it emerged that the costing exercises represented an important driver of the HRDP elaboration, which lent credibility to the process, and provided a financial framework within which HRH policies could be discussed. In both cases, bottom-up and country-specific methods were designed to overcome the countries' lack of cost and financing data, as well as to interpret their financial systems. Such an approach also allowed the costing exercises to feed directly into the national planning and budgeting process.

Conclusions
The authors conclude that bottom-up and country-specific costing methodologies have the potential to serve adequately the multi-faceted purpose of the exercise. It is recognised that standardised tools and methodologies may help reduce local governments' dependency on foreign expertise to conduct the HRDP costing and facilitate regional and international comparisons. However, adopting pre-defined and insufficiently flexible tools may undermine the credibility of the costing exercise, and reduce the space for policy negotiation opportunities within the HRDP elaboration process.
Mass spectrometry-based analysis of therapy-related changes in serum proteome patterns of patients with early-stage breast cancer
Authors: Pietrowska Monika , Polanska Joanna , Marczak Lukasz , Behrendt Katarzyna , Nowicka Elzbieta , Stobiecki Maciej , Polanski Andrzej , Tarnawski Rafal , Widlak Piotr 
Published: July 2010

Abstract

Background
The proteomics approach termed proteome pattern analysis has been shown previously to have potential in the detection and classification of breast cancer. Here we aimed to identify changes in serum proteome patterns related to therapy of breast cancer patients.

Methods
Blood samples were collected before the start of therapy, after the surgical resection of tumors and one year after the end of therapy in a group of 70 patients diagnosed at early stages of the disease. Patients were treated with surgery either independently (26) or in combination with neoadjuvant chemotherapy (5) or adjuvant radio/chemotherapy (39). The low-molecular-weight fraction of serum proteome was examined using MALDI-ToF mass spectrometry, and then changes in intensities of peptide ions registered in a mass range between 2,000 and 14,000 Da were identified and correlated with clinical data.

Results
We found that surgical resection of tumors did not have an immediate effect on the mass profiles of the serum proteome. On the other hand, significant long-term effects were observed in serum proteome patterns one year after the end of basic treatment (we found that about 20 peptides exhibited significant changes in their abundances). Moreover, the significant differences were found primarily in the subgroup of patients treated with adjuvant therapy, but not in the subgroup subjected only to surgery. This suggests that the observed changes reflect overall responses of the patients to the toxic effects of adjuvant radio/chemotherapy. In line with this hypothesis we detected two serum peptides (registered m/z values 2,184 and 5,403 Da) whose changes correlated significantly with the type of treatment employed (their abundances decreased after adjuvant therapy, but increased in patients treated only with surgery). On the other hand, no significant correlation was found between changes in the abundance of any spectral component or clinical features of patients, including staging and grading of tumors.

Conclusions
The study establishes a high potential of MALDI-ToF-based analyses for the detection of dynamic changes in the serum proteome related to therapy of breast cancer patients, which revealed the potential applicability of serum proteome patterns analyses in monitoring the toxicity of therapy.
Investigating the synchronization of hippocampal neural network in response to acute nicotine exposure
Authors: Akkurt David , Akay Yasemin M , Akay Metin 
Published: July 2010

Abstract
Previous studies suggested that γ oscillations in the brain are associated with higher order cognitive function including selective visual attention, motor task planning, sensory perception, working memory and dreaming REM sleep. These oscillations are mainly observed in cortical regions and also occur in neocortical and subcortical areas and the hippocampus. In this paper, we investigate the influence of acute exposure to nicotine on the complexity of hippocampal γ oscillations.
Using the approximate entropy method, the influence of acute nicotine exposure on the hippocampal γ oscillations was investigated. The hippocampal γ oscillations have been generated in response to the 100 Hz stimulus and isolated using the visual inspection and spectral analysis method. Our central hypothesis is that acute exposure to nicotine significantly reduces the complexity of hippocampal γ oscillations. We used brain-slice recordings and the approximate entropy method to test this hypothesis. The approximate entropy (complexity) values of the hippocampal γ oscillations are estimated from the 14 hippocampal slices. Our results show that it takes at least 100 msec to see any hippocampal activities in response to the 100 Hz stimulus. These patterns noticeably changed after 100 msec until 300 msec after the stimulus Finally, they were less prominent after 300 msec. We have analyzed the isolated hippocampal γ oscillations (between 150 and 250 msec after the stimulus) using the approximate entropy (ApEn) method. Our results showed that the ApEn (complexity) values of hippocampal γ oscillations during nicotine exposure were reduced compared to those of hippocampal γ oscillations during control, and washout. This reduction was much more significant in response to acute nicotine exposure (p < 0.05) compared to those during control and washout conditions. These results suggest that the neural firing becomes regular and the hippocampal networks become synchronized in response to nicotine exposure.
Factors associated with mosquito pool positivity and the characterization of the West Nile viruses found within Louisiana during 2007
Authors: Christofferson Rebecca C , Roy Alma F , Mores Christopher N 
Published: July 2010

Abstract

Background
West Nile virus (WNV) is an arbovirus of public health importance in the genus Flavivirus, a group of positive sense RNA viruses. The NS3 gene has a high level of substitutions and is phylogenetically informative. Likewise, substitutions in the envelope region have been postulated to enable viruses to subvert immune responses. Analysis of these genes among isolates from positive mosquitoes collected in Louisiana illustrates the variation present in the regions and provides improved insight to a phylogenetic model. Employing a GIS eco-regionalization method, we hypothesized that WNV pool positivity was correlated with regional environmental characteristics. Further, we postulated that the phylogenetic delineations would be associated with variations in regional environmental conditions.

Results
Type of regional land cover was a significant effect (p < 0.0001) in the positive pool prediction, indicating that there is an ecological component driving WNV activity. Additionally, month of collection was significant (p < 0.0001); and thus there is a temporal component that contributes to the probability of getting a positive mosquito pool. All virus isolates are of the WNV 2002 lineage. There appears to be some diversity within both forested and wetland areas; and the possibility of a distinct clade in the wetland samples.

Conclusions
The phylogenetic analysis shows that there has been no reversion in Louisiana from the 2002 lineage which replaced the originally introduced strain. Our pool positivity model serves as a basis for future testing, and could direct mosquito control and surveillance efforts. Understanding how land cover and regional ecology effects mosquito pool positivity will greatly help focus mosquito abatement efforts. This would especially help in areas where abatement programs are limited due to either funding or man power. Moreover, understanding how regional environments drive phylogenetic variation will lead to a greater understanding of the interactions between ecology and disease prevalence.
GTC: A web server for integrating systems biology data with web tools and desktop applications
Authors: Tenenbaum Dan , Bare J Christopher , Baliga Nitin S 
Published: July 2010

Abstract
Gaggle Tool Creator (GTC) is a web application which provides access to public annotation, interaction, orthology, and genomic data for hundreds of organisms, and enables instant analysis of the data using many popular web-based and desktop applications.
Nm23-H1 suppresses hepatocarcinoma cell adhesion and migration on fibronectin by modulating glycosylation of integrin beta1
Authors: She Shangyang , Xu Boying , He Min , Lan Xiuwan , Wang Qiuyan 
Published: July 2010

Abstract

Background
Nm23 gene was isolated as a metastatic suppressor gene. The antimetastatic effect of Nm23 has been an enigma for more than 10 years. Little is known about its molecular mechanisms. In this study we overexpressed Nm23-H1 in H7721 cells and observed reduction of cell adhesion, migration and extension of actin stress fibers in cells stimulated by fibronectin (Fn).

Methods
pcDNA3/Nm23-H1 was introduced into H7721 cells, and expression of Nm23-H1 was monitored by RT-PCR and western blot. Cell adhesion, actin extension and wound-induced migration assays were done on dishes coated with fibronectin. Phosphorylation of focal adhesion kinase (FAK) and total amount of integrin alpha5 and beta1 in Nm23-H1 transfected cells and control cells were measured by western blot. Flow cytometry was used to detect expression of surface alpha5 and beta1 integrin. N-glycosylation inhibitor tunicamycin was used to deglycosylate the integrin beta1 subunit.

Results
Overexpression of nm23-H1 in H7721 cells reduced cell adhesion, migration and extension of actin stress fibers on dishes coated with Fn. Phosphorylation of FAK in Nm23-H1 transfected cells was also attenuated. Integrin alpha5 and beta1 gene messages were unaltered in nm23-H1 overexpressed cells as detected by RT-PCR. However, while cell surface integrin alpha5 was unchanged, surface expression of beta1 integrin was downregulated. Western blot also showed that the total amounts of integrin alpha5 and beta1 were unaltered, but the level of mature integrin beta1 isoform was decreased significantly. Furthermore, partially glycosylated precursor beta1 was increased, which indicated that the impaired glycosylation of integrin beta1 precursor might contribute to the loss of cell surface integrin beta1 in nm23-H1 overexpressed cells.

Conclusion
These results suggest that by modulating glycosylation of integrin beta1, nm23-H1 down-regulates integrin beta1 subunit on cell surface and mediates intracellular signaling and subsequent suppression of the invasive process, including cell adhesion and migration.
Targeted gene therapy of nasopharyngeal cancer in vitro and in vivo by enhanced thymidine kinase expression driven by human TERT promoter and CMV enhancer
Authors: Shen Cong-Xiang , Wen Zhong , Qian Yu-Hong , Mu Shao-Feng , Guan Xiao-Fang 
Published: July 2010

Abstract

Background/Aim
To explore the therapeutic effects of thymidine kinase (TK) expressed by enhanced vector pGL3-basic- hTERTp-TK-EGFP-CMV driven by human telomerase reverse transcriptase promoter (hTERTp) as well as cytomegalovirus immediate early promoter enhancer (CMV).

Materials/Methods
Enhanced TK-EGFP expression was confirmed by fluorescent microscopy, real time PCR and telomerase activity. Its effects were examined by survival of tumor cells NPC 5-8F and MCF-7, index of xenograft implanted in nude mice and histology.

Results
Compared with non-enhanced vector pGL3-basic-TK-hTERTp-EGFP, TK expressed by the enhanced vector significantly decreased NPC 5-8F and MCF-7 cell survival rates after ganciclovir (GCV) treatment (p < 0.001) and tumor progress in nude mice with NPC xenograft and treated with GCV, without obvious toxicity to mouse liver and kidney.

Conclusion
The enhanced TK expression vector driven by hTERTp with CMV enhancer has brighter clinical potentials in nasopharyngeal carcinoma therapy than the non-enhanced vector.
Respiratory symptoms and disease characteristics as predictors of pulmonary function abnormalities in patients with rheumatoid arthritis: an observational cohort study
Authors: Pappas Dimitrios A , Giles Jon T , Connors Geoffrey , Lechtzin Noah , Bathon Joan M , Danoff Sonye K 
Published: July 2010

Abstract
Introduction
Lung involvement is a common extra-articular manifestation of rheumatoid arthritis (RA) that confers significant morbidity and mortality. The objective of the present study is to assess which respiratory symptoms and patient and disease characteristics are most highly associated with pulmonary function test (PFT) abnormalities in an RA patient cohort without clinical cardiovascular disease.

Methods
A total of 159 individuals with RA and without clinically evident cardiovascular disease were evaluated. Respiratory symptoms were assessed with the Lung Tissue Research Consortium questionnaire and all patients underwent evaluation with PFTs. Demographic, lifestyle, RA disease and treatment characteristics were collected. Subclinical coronary artery disease was assessed by cardiac computed tomography. Multivariable regression analysis was used to identify pulmonary symptoms and nonpulmonary parameters associated with PFT abnormalities. Areas under the receiver operating characteristic curves (AUC) were calculated to evaluate the discrimination of these variables for identifying patients with PFT abnormalities.

Results
Respiratory symptoms were reported by 42% of the patient population. Although only 6% carried a prior diagnosis of lung disease, PFT abnormalities were identified in 28% of the subjects. Symptoms combined with other patient and RA characteristics (body mass index, current smoking, anti-cyclic citrullinated peptide antibodies, and current prednisone use) performed satisfactorily in predicting the PFT abnormalities of obstruction (AUC = 0.91, 95% confidence interval = 0.78 to 0.98), restriction (AUC = 0.79, 95% confidence interval = 0.75 to 0.93) and impaired diffusion (AUC = 0.85, 95% confidence interval = 0.59 to 0.92). Co-morbid subclinical coronary artery disease did not modify these relationships.

Conclusions
Assessment of respiratory symptoms along with a limited number of clinical parameters may serve as a useful and inexpensive clinical tool for identifying RA patients in need of further pulmonary investigation.
Does an increase in body mass index over 10 years affect knee structure in a population-based cohort study of adult women?
Authors: Brennan Sharon L , Cicuttini Flavia M , Pasco Julie A , Henry Margaret J , Wang Yuanyuan , Kotowicz Mark A , Nicholson Geoff C , Wluka Anita E 
Published: July 2010

Abstract
Introduction
Although obesity is a modifiable risk factor for knee osteoarthritis (OA), the effect of weight gain on knee structure in young and healthy adults has not been examined. The aim of this study was to examine the relationship between body mass index (BMI), and change in BMI over the preceding 10-year period, and knee structure (cartilage defects, cartilage volume and bone marrow lesions (BMLs)) in a population-based sample of young to middle-aged females.

Methods
One hundred and forty-two healthy, asymptomatic females (range 30 to 49 years) in the Barwon region of Australia, underwent magnetic resonance imaging (MRI) during 2006 to 2008. BMI measured 10 years prior (1994 to 1997), current BMI and change in BMI (accounting for baseline BMI) over this period, was assessed for an association with cartilage defects and volume, and BMLs.

Results
After adjusting for age and tibial plateau area, the risk of BMLs was associated with every increase in one-unit of baseline BMI (OR 1.14 (95% CI 1.03 to 1.26) P = 0.009), current BMI (OR 1.13 (95% CI 1.04 to 1.23) P = 0.005), and per one unit increase in BMI (OR 1.14 (95% CI 1.03 to 1.26) P = 0.01). There was a trend for a one-unit increase in current BMI to be associated with increased risk of cartilage defects (OR 1.06 (95% CI 1.00 to 1.13) P = 0.05), and a suggestion that a one-unit increase in BMI over 10 years may be associated with reduced cartilage volume (-17.8 ml (95% CI -39.4 to 3.9] P = 0.10). Results remained similar after excluding those with osteophytes.

Conclusions
This study provides longitudinal evidence for the importance of avoiding weight gain in women during early to middle adulthood as this is associated with increased risk of BMLs, and trend toward increased tibiofemoral cartilage defects. These changes have been shown to precede increased cartilage loss. Longitudinal studies will show whether avoiding weight gain in early adulthood may play an important role in diminishing the risk of knee OA.
Doxorubicin downregulates cell surface B7-H1 expression and upregulates its nuclear expression in breast cancer cells: role of B7-H1 as an anti-apoptotic molecule
Authors: Ghebeh Hazem , Lehe Cynthia , Barhoush Eman , Al-Romaih Khaldoon , Tulbah Asma , Al-Alwan Monther , Hendrayani Siti-Faujiah , Manogaran Pulicat , Alaiya Ayodele , Al-Tweigeri Taher , Aboussekhra Abdelilah , Dermime Said 
Published: July 2010

Abstract
Introduction
B7-H1 (PD-L1, CD274) is a T cell inhibitory molecule expressed in many types of cancer, leading to immune escape of tumor cells. Indeed, in previous reports we have shown an association of B7-H1 expression with high-risk breast cancer patients.

Methods
In the current study, we used immunohistochemistry, immunofluorescence and Western blot techniques to investigate the effect of neoadjuvant chemotherapy on the expression of B7-H1 in breast cancer cells.

Results
Among tested chemotherapeutic agents, doxorubicin was the most effective in downregulating cell surface expression of B7-H1 in vitro. These results were validated in vivo in a xenograft mouse model, as well as in murine heart tissue known to constitutively express B7-H1. The doxorubicin-dependent cell surface downregulation of B7-H1 was accompanied by an upregulation of B7-H1 in the nucleus. This re-distribution of B7-H1 was concurrent with a similar translocation of phosphorylated AKT to the nucleus. Inhibition of the PI3K/AKT pathway abrogated the doxorubicin-mediated nuclear up-regulation of B7-H1, suggesting an involvement of PI3K/AKT pathway in the nuclear up-regulation of B7-H1. Interestingly, siRNA knock down of B7-H1 lead to an increase in spontaneous apoptosis, as well as doxorubicin-induced apoptosis, which indicates an anti-apoptotic role for B7-H1 in breast cancer cells. The novel discovery of B7-H1 expression in the nuclei of breast cancer cells suggests that B7-H1 has functions other than inhibition of T cells.

Conclusions
Our findings explain the previously reported immunomodulatory effect of anthracyclines on cancer cells, and provide a link between immunoresistance and chemoresistance. Finally these results suggest the use of dual combinatorial agents to inhibit B7-H1 beside chemotherapy, in breast cancer patients.
Physicians' and nurses' opinions on selective decontamination of the digestive tract and selective oropharyngeal decontamination: a survey
Authors: Jongerden Irene P , de Smet AnneMarie G , Kluytmans Jan A , te Velde Leo F , Dennesen Paul J , Wesselink Ronald M , Bouw Martijn P , Spanjersberg Rob , Bogaers-Hofman Diana , van der Meer Nardo J , de Vries Jaap W , Kaasjager Karin , van Iterson Mat , Kluge Georg H , van der Werf Tjip S , Harinck Hubertus I , Bindels Alexander J , Pickkers Peter , Bonten Marc J 
Published: July 2010

Abstract
Introduction
Use of selective decontamination of the digestive tract (SDD) and selective oropharyngeal decontamination (SOD) in intensive care patients has been controversial for years. Through regular questionnaires we determined expectations concerning SDD (effectiveness) and experience with SDD and SOD (workload and patient friendliness), as perceived by nurses and physicians.

Methods
A survey was embedded in a group-randomized, controlled, cross-over multicenter study in the Netherlands in which, during three 6-month periods, SDD, SOD or standard care was used in random order. At the end of each study period, all nurses and physicians from participating intensive care units received study questionnaires.

Results
In all, 1024 (71%) of 1450 questionnaires were returned by nurses and 253 (82%) of 307 by physicians. Expectations that SDD improved patient outcome increased from 71% and 77% of respondents after the first two study periods to 82% at the end of the study (P = 0.004), with comparable trends among nurses and physicians. Nurses considered SDD to impose a higher workload (median 5.0, on a scale from 1 (low) to 10 (high)) than SOD (median 4.0) and standard care (median 2.0). Both SDD and SOD were considered less patient friendly than standard care (medians 4.0, 4.0 and 6.0, respectively). According to physicians, SDD had a higher workload (median 5.5) than SOD (median 5.0), which in turn was higher than standard care (median 2.5). Furthermore, physicians graded patient friendliness of standard care (median 8.0) higher than that of SDD and SOD (both median 6.0).

Conclusions
Although perceived effectiveness of SDD increased as the trial proceeded, both among physicians and nurses, SOD and SDD were, as compared to standard care, considered to increase workload and to reduce patient friendliness. Therefore, education about the importance of oral care and on the effects of SDD and SOD on patient outcomes will be important when implementing these strategies.

Trial registration
ISRCTN35176830.