bluuebunny/crossref_metadata_2025_split huggingface dataset:
NRE: a tool for exploring neutral loci in the human genome
Authors: Arbiza Leonardo , Zhong Elaine , Keinan Alon 
Published: November 2012

Abstract

Background
Analyzing regions of the genome where genetic variation is free from the confounding effects of natural selection is essential for many population genetic studies. Several recent studies in humans have stressed the large effect of natural selection at linked neutral sites and have shown that the choice of putatively neutral regions can have a marked effect on estimates of demographic history.

Results
NRE (Neutral Region Explorer) provides a mechanism for the easy extraction and analysis of nearly neutral regions from the human genome. It can combine many genomic filters, including filters for selection, recombination rate, genetic distance to the nearest gene, percent overlap with annotated regions, and user-provided loci. The program implements a two-step filtering process for greater versatility, allowing users to compile a basic set of neutrality criteria, explore their effect, and use this knowledge to refine filtering. Results can be instantly downloaded in standard formats, along with summary and ranking statistics, or exported to genome browsers such as those from the 1000 Genomes and UCSC. The applicability and value of NRE are demonstrated through an example in the estimation of the ratio of chromosome X-to-autosomal effective population size using different strategies for the selection of neutral regions.

Conclusions
The combined features of NRE make possible the sort of flexible, rigorous mining and analysis of neutral loci increasingly demanded by population genetic studies. NRE is available at http://nre.cb.bscb.cornell.edu.
Self-reported adherence with the use of a device in a clinical trial as validated by electronic monitors: the VIBES study
Authors: Jeffrey Brianne A , Hannan Marian T , Quinn Emily K , Zimmerman Sheryl , Barton Bruce A , Rubin Clinton T , Kiel Douglas P 
Published: November 2012

Abstract

Background
Adherences to treatments that require a behavioral action often rely on self-reported recall, yet it is vital to determine whether real time self reporting of adherence using a simple logbook accurately captures adherence. The purpose of this study was to determine whether real time self-reported adherence is an accurate measurement of device usage during a clinical trial by comparing it to electronic recording.

Methods
Using data collected from older adult men and women (N=135, mean age 82.3 yrs; range 66 to 98 yrs) participating in a clinical trial evaluating a vibrating platform for the treatment of osteoporosis, daily adherence to platform treatment was monitored using both self-reported written logs and electronically recorded radio-frequency identification card usage, enabling a direct comparison of the two methods over one year. Agreement between methods was also evaluated after stratification by age, gender, time in study, and cognition status.

Results
The two methods were in high agreement (overall intraclass correlation coefficient = 0.96). The agreement between the two methods did not differ between age groups, sex, time in study and cognitive function.

Conclusions
Using a log book to report adherence to a daily intervention requiring a behavioral action in older adults is an accurate and simple approach to use in clinical trials, as evidenced by the high degree of concordance with an electronic monitor.

Trial registration
Clinicaltrials.gov NCT00396994
Integrated working between residential care homes and primary care: a survey of care homes in England
Authors: Gage Heather , Dickinson Angela , Victor Christina , Williams Peter , Cheynel Jerome , Davies Sue L , Iliffe Steve , Froggatt Katherine , Martin Wendy , Goodman Claire 
Published: November 2012

Abstract

Background
Older people living in care homes in England have complex health needs due to a range of medical conditions, mental health needs and frailty. Despite an increasing policy expectation that professionals should operate in an integrated way across organisational boundaries, there is a lack of understanding between care homes and the National Health Service (NHS) about how the two sectors should work together, meaning that residents can experience a poor "fit" between their needs, and services they can access. This paper describes a survey to establish the current extent of integrated working that exists between care homes and primary and community health and social services.

Methods
A self-completion, online questionnaire was designed by the research team. Items on the different dimensions of integration (funding, administrative, organisational, service delivery, clinical care) were included. The survey was sent to a random sample of residential care homes with more than 25 beds (n = 621) in England in 2009. Responses were analysed using quantitative and qualitative methods.

Results
The survey achieved an overall response rate of 15.8%. Most care homes (78.7%) worked with more than one general practice. Respondents indicated that a mean of 14.1 professionals/ services (other than GPs) had visited the care homes in the last six months (SD 5.11, median 14); a mean of .39 (SD.163) professionals/services per bed. The most frequent services visiting were district nursing, chiropody and community psychiatric nurses. Many (60%) managers considered that they worked with the NHS in an integrated way, including sharing documents, engaging in integrated care planning and joint learning and training. However, some care home managers cited working practices dictated by NHS methods of service delivery and priorities for care, rather than those of the care home or residents, a lack of willingness by NHS professionals to share information, and low levels of respect for the experience and knowledge of care home staff.

Conclusions
Care homes are a hub for a wide range of NHS activity, but this is ad hoc with no recognised way to support working together. Integration between care homes and local health services is only really evident at the level of individual working relationships and reflects patterns of collaborative working rather than integration. More integrated working between care homes and primary health services has the potential to improve quality of care in a cost- effective manner, but strategic decisions to create more formal arrangements are required to bring this about. Commissioners of services for older people need to capitalise on good working relationships and address idiosyncratic patterns of provision to care homes.The low response rate is indicative of the difficulty of undertaking research in care homes.
Rapid and accurate detection of RMP- and INH- resistant Mycobacterium tuberculosisin spinal tuberculosis specimens by CapitalBio™ DNA microarray: A prospective validation study
Authors: Zhang Zehua , Li Litao , Luo Fei , Cheng Peng , Wu Feng , Wu Zheng , Hou Tianyong , Zhong Min , Xu Jianzhong 
Published: November 2012

Abstract

Background
DNA microarrays can detect tuberculosis and its multi-drug resistant form in M. tuberculosis isolates and sputum specimens with high sensitivity and specificity. However, no performance data currently exists for its use in spinal tuberculosis specimens. This study was aimed to assess the performance of the CapitalBio™ DNA microarray in the detection of isoniazid (INH) and rifampicin (RMP) resistance in spinal tuberculosis compared with the BACT/MGIT 960 system.

Methods
From March 2009 to December 2011, 153 consecutive patients from Southwest Hospital, Chongqing with clinically and pathologically diagnosed spinal tuberculosis were enrolled into this study. Specimens collected during surgery from the tuberculosis patients were subjected to M. tuberculosis species identification and drug-resistance detection by the CapitalBio™ DNA microarray, and results were compared with those obtained from the absolute concentration drug susceptibility testing.

Results
The CapitalBio™ DNA microarray achieved 93.55% sensitivity for the correct M. tuberculosis species identification of the 93 specimens that tested positive for spinal tuberculosis through culture. In addition, twenty-seven additional patients (45.0%) were detected by the DNA microarray to be positive for M. tuberculosis among sixty spinal tuberculosis patients who were culture negative. Moreover, the DNA microarray had a sensitivity of 88.9% and a specificity of 90.7% for RMP resistance, and the microarray had a sensitivity of 80.0% and a specificity of 91.0% for INH resistance. The mean turn-around time of M. tuberculosis species identification and drug resistance detection using the DNA microarray was 5.8 (range, 4–9) hours.

Conclusions
The CapitalBio™ DNA microarray is a feasible and accurate tool for the species identification of M. tuberculosis and for directly detecting RMP and INH resistance from spinal tuberculosis specimens in fewer than 9 hours.
MicroRNA-100 is a potential molecular marker of non-small cell lung cancer and functions as a tumor suppressor by targeting polo-like kinase 1
Authors: Liu Jing , Lu Kai-Hua , Liu Zhi-Li , Sun Ming , De Wei , Wang Zhao-Xia 
Published: November 2012

AbstractBackgroundPolo-like kinase 1 (PLK1) is highly expressed in many human cancers and regulates critical steps in mitotic progression. Previously, we have reported that PLK1 was overexpressed in non-small cell lung cancer (NSCLC), but the underlying molecular mechanisms are not well understood. By using microRNA (miR) target prediction algorithms, we identified miR-100 that might potentially bind the 3’-untranslated region of PLK1 transcripts. The purpose of this study was to investigate the roles of miR-100 and its association with PLK1 in NSCLC development.MethodsTaqman real-time quantitative RT-PCR assay was performed to detect miR-100 expression 10 NSCLC tissues and corresponding nontumor tissues. Additionally, the expression of miR-100 in 110 NSCLC tissues and its correlation with clinicopathological factors or prognosis of patients was analyzed. Finally, the effects of miR-100 expression on growth, apoptosis and cell cycle of NSCLC cells by posttranscriptionally regulating PLK1 expression were determined.ResultsMiR-100 was significantly downregulated in NSCLC tissues, and low miR-100 expression was found to be closely correlated with higher clinical stage, advanced tumor classification and lymph node metastasis of patients. The overall survival of NSCLC patients with low miR-100 was significantly lower than that of those patients with high miR-100, and univariate and multivariate analyses indicated that low miR-100 expression might be a poor prognostic factor. Also, miR-100 mimics could lead to growth inhibition, G2/M cell cycle arrest and apoptosis enhancement in NSCLC cells. Meanwhile, miR-100 mimics could significantly inhibit PLK1 mRNA and protein expression and reduce the luciferase activity of a PLK1 3’ untranslated region-based reporter construct in A549 cells. Furthermore, small interfering RNA (siRNA)-mediated PLK1 downregulation could mimic the effects of miR-100 mimics while PLK1 overexpression could partially rescue the phenotypical changes of NSCLC cells induced by miR-100 mimics.ConclusionsOur findings indicate that low miR-100 may be a poor prognostic factor for NSCLC patients and functions as a tumor suppressor by posttranscriptionally regulating PLK1 expression.
Overexpression of Snail is associated with lymph node metastasis and poor prognosis in patients with gastric cancer
Authors: Shin Na Ri , Jeong Eun Hui , Choi Chang In , Moon Hyun Jung , Kwon Chae Hwa , Chu In Sun , Kim Gwang Ha , Jeon Tae Yong , Kim Dae Hwan , Lee Jae Hyuk , Park Do Youn 
Published: November 2012

AbstractBackgroundEpithelial–mesenchymal transition (EMT) plays a significant role in tumor progression and invasion. Snail is a known regulator of EMT in various malignant tumors. This study investigated the role of Snail in gastric cancer.MethodsWe examined the effects of silenced or overexpressed Snail using lenti-viral constructs in gastric cancer cells. Immunohistochemical analysis of tissue microarrays from 314 patients with gastric adenocarcinoma (GC) was used to determine Snail’s clinicopathological and prognostic significance. Differential gene expression in 45 GC specimens with Snail overexpression was investigated using cDNA microarray analysis.ResultsSilencing of Snail by shRNA decreased invasion and migration in GC cell lines. Conversely, Snail overexpression increased invasion and migration of gastric cancer cells, in line with increased VEGF and MMP11. Snail overexpression (≥75% positive nuclear staining) was also significantly associated with tumor progression (P < 0.001), lymph node metastases (P = 0.002), lymphovascular invasion (P = 0.002), and perineural invasion (P = 0.002) in the 314 GC patients, and with shorter survival (P = 0.023). cDNA microarray analysis revealed 213 differentially expressed genes in GC tissues with Snail overexpression, including genes related to metastasis and invasion.ConclusionSnail significantly affects invasiveness/migratory ability of GCs, and may also be used as a predictive biomarker for prognosis or aggressiveness of GCs.
National Essential Medicines List and policy practice: A case study of China’s health care reform
Authors: Tian Xin , Song Yaran , Zhang Xinping 
Published: November 2012

Abstract

Background
In 2009, China implemented the national essential medicines system by enacting the National Essential Medicines List 2009. According to the policy of this system, primary health care institutions can only stock and use essential medicines on the prescribed List. Meanwhile, each province can choose to make its own list of supplemented medicines. The goal of the study is to provide suggestions for emerging problems and identify future policy-making trends.

Methods
In this study, we statistically analyzed the National Essential Medicines List 2009 and lists of supplemented medicines of all 29 provinces. We also examined the rationality of such medicines based on the DELPHI method and literature review, after which we studied the provincial supplements in relation to the national essential medicines system.

Results
We demonstrated that the National Essential Medicines List 2009 provides a comprehensive coverage of diseases as well as reasonable varieties of drugs for their treatment. The average number of supplemented medicines in 29 provinces is 207, with each medicine included in 2.9 provincial lists on average. Only 2.6% supplemented medicines are included by more than half of the provinces (>15), indicating great regional variance. Among the 32 most frequently supplemented medicines, only 18 meet the selection principles, including two with strict usage restrictions.

Conclusion
The structure and selection of the National Essential Medicines List 2009 are relatively reasonable. The main problems, however, include the excessive and non-scientific selection of medicines on the supplemented medicines list. The function of the provincial lists of supplemented medicines has not been achieved, which has influenced the effectiveness of the national essential medicines system in China.
Enhancing solubility of deoxyxylulose phosphate pathway enzymes for microbial isoprenoid production
Authors: Zhou Kang , Zou Ruiyang , Stephanopoulos Gregory , Too Heng-Phon 
Published: November 2012

Abstract

Background
Recombinant proteins are routinely overexpressed in metabolic engineering. It is well known that some over-expressed heterologous recombinant enzymes are insoluble with little or no enzymatic activity. This study examined the solubility of over-expressed homologous enzymes of the deoxyxylulose phosphate pathway (DXP) and the impact of inclusion body formation on metabolic engineering of microbes.

Results
Four enzymes of this pathway (DXS, ISPG, ISPH and ISPA), but not all, were highly insoluble, regardless of the expression systems used. Insoluble dxs (the committed enzyme of DXP pathway) was found to be inactive. Expressions of fusion tags did not significantly improve the solubility of dxs. However, hypertonic media containing sorbitol, an osmolyte, successfully doubled the solubility of dxs, with the concomitant improvement in microbial production of the metabolite, DXP. Similarly, sorbitol significantly improved the production of soluble and functional ERG12, the committed enzyme in the mevalonate pathway.

Conclusion
This study demonstrated the unanticipated findings that some over-expressed homologous enzymes of the DXP pathway were highly insoluble, forming inclusion bodies, which affected metabolite formation. Sorbitol was found to increase both the solubility and function of some of these over-expressed enzymes, a strategy to increase the production of secondary metabolites.
Cycloartane-3,24,25-triol inhibits MRCKα kinase and demonstrates promising anti prostate cancer activity in vitro
Authors: Lowe Henry I C , Watson Charah T , Badal Simone , Toyang Ngeh J , Bryant Joseph 
Published: November 2012

Abstract

Background
Given the high occurrence of prostate cancer worldwide and one of the major sources of the discovery of new lead molecules being medicinal plants, this research undertook to investigate the possible anti-cancer activity of two natural cycloartanes; cycloartane-3,24,25-diol (extracted in our lab from Tillandsia recurvata) and cycloartane-3,24,25-triol (purchased). The inhibition of MRCKα kinase has emerged as a potential solution to restoring the tight regulation of normal cellular growth, the loss of which leads to cancer cell formation.

Methods
Kinase inhibition was investigated using competition binding (to the ATP sites) assays which have been previously established and authenticated and cell proliferation was measured using the WST-1 assay.

Results
Cycloartane-3,24,25-triol demonstrated strong selectivity towards the MRCKα kinase with a Kd50 of 0.26 μM from a total of 451 kinases investigated. Cycloartane-3,24,25-triol reduced the viability of PC-3 and DU145 cell lines with IC50 values of 2.226 ± 0.28 μM and 1.67 ± 0.18 μM respectively.

Conclusions
These results will prove useful in drug discovery as Cycloartane-3,24,25-triol has shown potential for development as an anti-cancer agent against prostate cancer.
A mechanical model for predicting the probability of osteoporotic hip fractures based in DXA measurements and finite element simulation
Authors: López Enrique , Ibarz Elena , Herrera Antonio , Mateo Jesús , Lobo-Escolar Antonio , Puértolas Sergio , Gracia Luis 
Published: November 2012

Abstract

Background
Osteoporotic hip fractures represent major cause of disability, loss of quality of life and even mortality among the elderly population. Decisions on drug therapy are based on the assessment of risk factors for fracture, from BMD measurements. The combination of biomechanical models with clinical studies could better estimate bone strength and supporting the specialists in their decision.

Methods
A model to assess the probability of fracture, based on the Damage and Fracture Mechanics has been developed, evaluating the mechanical magnitudes involved in the fracture process from clinical BMD measurements. The model is intended for simulating the degenerative process in the skeleton, with the consequent lost of bone mass and hence the decrease of its mechanical resistance which enables the fracture due to different traumatisms. Clinical studies were chosen, both in non-treatment conditions and receiving drug therapy, and fitted to specific patients according their actual BMD measures. The predictive model is applied in a FE simulation of the proximal femur. The fracture zone would be determined according loading scenario (sideway fall, impact, accidental loads, etc.), using the mechanical properties of bone obtained from the evolutionary model corresponding to the considered time.

Results
BMD evolution in untreated patients and in those under different treatments was analyzed. Evolutionary curves of fracture probability were obtained from the evolution of mechanical damage. The evolutionary curve of the untreated group of patients presented a marked increase of the fracture probability, while the curves of patients under drug treatment showed variable decreased risks, depending on the therapy type.

Conclusion
The FE model allowed to obtain detailed maps of damage and fracture probability, identifying high-risk local zones at femoral neck and intertrochanteric and subtrochanteric areas, which are the typical locations of osteoporotic hip fractures.
The developed model is suitable for being used in individualized cases. The model might better identify at-risk individuals in early stages of osteoporosis and might be helpful for treatment decisions.
Neurobehavioral function and low-level exposure to brominated flame retardants in adolescents: a cross-sectional study
Authors: Kiciński Michał , Viaene Mineke K , Den Hond Elly , Schoeters Greet , Covaci Adrian , Dirtu Alin C , Nelen Vera , Bruckers Liesbeth , Croes Kim , Sioen Isabelle , Baeyens Willy , Van Larebeke Nicolas , Nawrot Tim S 
Published: November 2012

Abstract

Background
Animal and in vitro studies demonstrated a neurotoxic potential of brominated flame retardants, a group of chemicals used in many household and commercial products to prevent fire. Although the first reports of detrimental neurobehavioral effects in rodents appeared more than ten years ago, human data are sparse.

Methods
As a part of a biomonitoring program for environmental health surveillance in Flanders, Belgium, we assessed the neurobehavioral function with the Neurobehavioral Evaluation System (NES-3), and collected blood samples in a group of high school students. Cross-sectional data on 515 adolescents (13.6-17 years of age) was available for the analysis. Multiple regression models accounting for potential confounders were used to investigate the associations between biomarkers of internal exposure to brominated flame retardants [serum levels of polybrominated diphenyl ether (PBDE) congeners 47, 99, 100, 153, 209, hexabromocyclododecane (HBCD), and tetrabromobisphenol A (TBBPA)] and cognitive performance. In addition, we investigated the association between brominated flame retardants and serum levels of FT3, FT4, and TSH.

Results
A two-fold increase of the sum of serum PBDE’s was associated with a decrease of the number of taps with the preferred-hand in the Finger Tapping test by 5.31 (95% CI: 0.56 to 10.05, p = 0.029). The effects of the individual PBDE congeners on the motor speed were consistent. Serum levels above the level of quantification were associated with an average decrease of FT3 level by 0.18 pg/mL (95% CI: 0.03 to 0.34, p = 0.020) for PBDE-99 and by 0.15 pg/mL (95% CI: 0.004 to 0.29, p = 0.045) for PBDE-100, compared with concentrations below the level of quantification. PBDE-47 level above the level of quantification was associated with an average increase of TSH levels by 10.1% (95% CI: 0.8% to 20.2%, p = 0.033), compared with concentrations below the level of quantification. We did not observe effects of PBDE’s on neurobehavioral domains other than the motor function. HBCD and TBBPA did not show consistent associations with performance in the neurobehavioral tests.

Conclusions
This study is one of few studies and so far the largest one investigating the neurobehavioral effects of brominated flame retardants in humans. Consistently with experimental animal data, PBDE exposure was associated with changes in the motor function and the serum levels of the thyroid hormones.