bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ex vivo infection of human embryonic spinal cord neurons prior to transplantation into adult mouse cord
Authors: Márton Gábor , Tombácz Dóra , Tóth Judit S , Szabó András , Boldogköi Zsolt , Dénes Ádám , Hornyák Ákos , Nógrádi Antal 
Published: May 2010

Abstract

Background
Genetically modified pseudorabies virus (Prv) proved suitable for the delivery of foreign genes to rodent embryonic neurons ex vivo and maintaining foreign gene expression after transplantation into spinal cord in our earlier study. The question arose of whether human embryonic neurons, which are known to be more resistant to Prv, could also be infected with a mutant Prv. Specifically, we investigated whether a mutant Prv with deleted ribonucleotide reductase and early protein 0 genes has the potential to deliver marker genes (gfp and β-gal) into human embryonic spinal cord neurons and whether the infected neurons maintain expression after transplantation into adult mouse cord.

Results
The results revealed that the mutant Prv effectively infected human embryonic spinal cord neurons ex vivo and the grafted cells exhibited reporter gene expression for several weeks. Grafting of infected human embryonic cells into the spinal cord of immunodeficient (rnu-/rnu-) mice resulted in the infection of some of the host neurons.

Discussion
These results suggest that Prv is suitable for the delivery of foreign genes into transplantable human cells. This delivery method may offer a new approach to use genetically modified cells for grafting in animal models where spinal cord neuronal loss or axon degeneration occurs.
Development and application of a biomarker assay for determining the pharmacodynamic activity of an antagonist candidate biotherapeutic antibody to IL21R in whole blood
Authors: Arai Maya , Jain Sadhana , Weaver Amy A , Hill Andrew A , Guo Yongjing , Bree Andrea G , Smith Michael F , Allen Scott W , LaVallie Edward R , Young Deborah , Bloom Laird , Adkins Karissa , O'Toole Margot 
Published: May 2010

Abstract

Background
In preparation for potential clinical development of Ab-01, an antagonistic antibody directed against the IL21R, studies were undertaken to address translational medicine needs that fall into four categories: 1) development of a pharmacodynamic biomarker assay suitable for use in the clinic, 2) demonstration that Ab-01 has the desired biological activity in vitro and in vivo in cynomolgus monkeys, the preferred safety study species, 3) pre-clinical in vivo proof-of-concept that the assay can be used to detect Ab-01 pharmacodynamic (PD) activity in treated subjects, and 4) comprehensive assessment of the agonistic potential of Ab-01 when cross-linked. This report and a recently published companion report address the first three of these needs. The fourth has been addressed in a separate study.

Methods
Genes that change RNA expression upon ex vivo rhIL21 stimulation of whole blood were identified in human and cynomolgus monkey. The inhibitory effects of exogenously added Ab-01 were measured ex vivo in human and monkey, and the in vivo inhibitory effects of Ab-01 treatment were measured in monkey.

Results
Stimulation of whole human blood for 2 hours with rhIL21 induced robust increases in RNA expression of 6 genes. This response was blocked by Ab-01, indicating that the assay is suitable for measuring Ab-01 activity in blood. rhIL21 induced expression of a similar set of genes in cynomolgus monkey blood. This response was blocked with Ab-01, thus demonstrating that Ab-01 has the desired activity in the species, and that safety studies done in cynomolgus monkeys are relevant. Proof -of-concept for using this assay system to detect PD activity in vivo was generated by measuring the response in monkey blood to ex vivo rhIL21 stimulation before and 5 minutes following in vivo Ab-01 administration.

Conclusions
A robust PD biomarker assay suitable for clinical use has been developed in human whole blood. The successful adaptation of the assay to cynomolgus monkeys has enabled the demonstration of Ab-01 activity both in vitro and in vivo in monkey, thus validating the use of this species in safety studies and establishing proof-of-concept for using this PD assay system to aid in dose selection in clinical studies.
Health and historical levels of freedom
Authors: Biggs Samantha L , Dell Evelyn M , Dixon Vanessa L , Joffres Michel R , Beyrer Chris , Wilson Kumanan , Orbinski James J , Edward Mills J 
Published: May 2010

Abstract

Background
The link between political freedom and health is unclear. We aimed to determine the association by exploring the relationship of historical and cumulative freedom levels with important health outcomes.

Methods
We obtained countrywide health indicators for life expectancy, infant mortality, maternal mortality ratio, % low birth weight babies, Gini coefficient (a measure of wealth inequality) and various markers of freedom based on political rights and civil liberties. We applied multivariable logistic regression to examine the association between health indicators and within-country years of freedom as determined by Freedom House rankings.

Results
The total proportion of free years from 1972-2005, the duration of current freedom level, and the Gini coefficient show independent positive associations with health indicators, which remain after the adjustment for national wealth, total government expenditure, and spending on health. Countries identified as having high total proportion of free years demonstrated significantly better health outcomes than countries with low levels of freedom (life expectancy, Odds Ratio [OR] 7.2, 95% Confidence Interval [CI], 2.3-22.6, infant mortality OR 19.6, 95% CI, 5.6-67.7, maternal mortality ratio, OR 24.3, 95% CI, 6.2-94.9, and % low birth weight babies OR 3.8, 95% CI, 1.4-10.8). This was also the case for infant mortality (OR 3.4, 95% CI, 1.0-8.4), maternal mortality ratio (OR 4.0, 95% CI, 1.2-12.8), and % low birth weight babies (OR 2.6, 95% CI, 1.0-6.6) among countries considered as having medium levels of freedom.

Interpretation
We found strong associations between country-level freedom and important health outcomes. The cumulative level of freedom over time shows stronger associations with all health indicators than the duration of current freedom level.
Four-dimensional dosimetry validation and study in lung radiotherapy using deformable image registration and Monte Carlo techniques
Authors: Huang Tzung-Chi , Liang Ji-An , Dilling Thomas , Wu Tung-Hsin , Zhang Geoffrey 
Published: May 2010

Abstract
Thoracic cancer treatment presents dosimetric difficulties due to respiratory motion and lung inhomogeneity. Monte Carlo and deformable image registration techniques have been proposed to be used in four-dimensional (4D) dose calculations to overcome the difficulties. This study validates the 4D Monte Carlo dosimetry with measurement, compares 4D dosimetry of different tumor sizes and tumor motion ranges, and demonstrates differences of dose-volume histograms (DVH) with the number of respiratory phases that are included in 4D dosimetry. BEAMnrc was used in dose calculations while an optical flow algorithm was used in deformable image registration and dose mapping. Calculated and measured doses of a moving phantom agreed within 3% at the center of the moving gross tumor volumes (GTV). 4D CT image sets of lung cancer cases were used in the analysis of 4D dosimetry. For a small tumor (12.5 cm3) with motion range of 1.5 cm, reduced tumor volume coverage was observed in the 4D dose with a beam margin of 1 cm. For large tumors and tumors with small motion range (around 1 cm), the 4D dosimetry did not differ appreciably from the static plans. The dose-volume histogram (DVH) analysis shows that the inclusion of only extreme respiratory phases in 4D dosimetry is a reasonable approximation of all-phase inclusion for lung cancer cases similar to the ones studied, which reduces the calculation in 4D dosimetry.
Diagnosis and mortality in 47,XYY persons: a registry study
Authors: Stochholm Kirstine , Juul Svend , Gravholt Claus H 
Published: May 2010

AbstractBackgroundSex chromosomal abnormalities are relatively common, yet many aspects of these syndromes remain unexplored. For instance epidemiological data in47,XYYpersons are still limited.MethodsUsing a national Danish registry, we identified 208 persons with47,XYYor a compatible karyotype, whereof 36 were deceased; all were diagnosed from 1968 to 2008. For further analyses, we identified age matched controls from the male background population (n = 20,078) in Statistics Denmark. We report nationwide prevalence data, data regarding age at diagnosis, as well as total and cause specific mortality data in these persons.ResultsThe average prevalence was 14.2 47,XYY persons per 100,000, which is reduced compared to the expected 98 per 100,000. Their median age at diagnosis was 17.1 years. We found a significantly decreased lifespan from 77.9 years (controls) to 67.5 years (47,XYYpersons). Total mortality was significantly increased compared to controls, with a hazard ratio of 3.6 (2.6-5.1). Dividing the causes of deaths according to the International Classification of Diseases, we identified an increased hazard ratio in all informative chapters, with a significantly increased ratio in cancer, pulmonary, neurological and unspecified diseases, and trauma.ConclusionWe here present national epidemiological data regarding47,XYYsyndrome, including prevalence and mortality data, showing a significantly delay to diagnosis, reduced life expectancy and an increased total and cause specific mortality.
Comparison of original (2003) and revised (2008) national guidelines for reporting of cerebrospinal fluid spectrophotometric scanning for suspected subarachnoid haemorrhage against patient outcome
Authors: Griffiths Melanie J , Chow Elaine , Panting Mark D , Ford Clare , Gama Rousseau 
Published: May 2010

Background National guidelines for cerebrospinal fluid (CSF) analysis and its reporting in suspected subarachnoid haemorrhage (SAH) were published in 2003, but revised in 2008 to give greater clarity in interpretation. It is not known whether the less ambiguous reporting of 2008 guidelines may lead to a false assurance and adversely affect patient outcome. We, therefore, re-interpreted scans reported under the 2003 guidelines, using the 2008 guidelines and compared these reports against final diagnosis and patient outcome obtained from a retrospective case-note review audit. Methods We identified requests for CSF xanthochromia studies from the laboratory system between September 2006 and August 2007. Spectroscopy scans were then retrieved and re-interpreted using the 2008 guidelines. The original reports and re-interpreted scans were compared against diagnosis and patient outcome using case-note review. Results We received 93 requests for CSF spectroscopy on 90 patients. Fourteen requests were not processed due to insufficient sample, but of these three patients had a repeat lumbar puncture (LP). Two further requests were not processed at the request of the clinician as they were no longer clinically indicated. Therefore, 77 spectroscopic scans were re-interpreted. The revised guidelines re-classified 11 previously equivocal scans into the not supportive of SAH category. On case-note review, one patient had a subsequent fatal SAH. The remaining 10 were given non-SAH final diagnoses and none had similar further inpatient episodes for at least 12 months and up to 18 months following LP. Conclusions The revised (2008) national guidelines for the analysis of CSF in suspected SAH offer greater clarity in reporting without adversely affecting patient outcome.
Elevated tumour marker: an indication for imaging?
Authors: McMahon Colm J , Crowley Vivion , McCarroll Nuala , Dunne Ruth , Keogan Mary T 
Published: May 2010

Introduction The purpose of this study was to evaluate the utility of imaging examinations in patients with elevated tumour markers when (a) the tumour marker is not validated for as a primary diagnostic test; (b) the patient had no personal history of cancer and (c) the patient had no other imaging indication. Materials and methods Patients without known cancer who had abnormal carcinoembryonic antigen, CA19-9, CA125 and/or CA15-3 serology over a one-year period were included. A retrospective medical record review was performed to assess the number of these cases who underwent imaging because of ‘elevated tumour marker’ in the absence of a clinical indication for imaging. The number and result of these imaging studies were evaluated. Results Eight hundred and nineteen patients were included. Of those, 25 patients (mean age: 67.8 [range 41–91] y), were imaged to evaluate: ‘elevated tumour marker’. They underwent 29 imaging studies (mean [±standard deviation (SD)] per patient = 1.2 [±0.4]), and had 42 elevated tumour marker serology tests (mean [±SD] per patient = 1.7 [±0.7]). Four patients had >1 imaging test. No patient had an imaging study which diagnosed a malignancy or explained the elevated tumour marker. Conclusion The non-judicious use of tumour markers can prompt further unnecessary investigations including imaging. In this study, there was no positive diagnostic yield for imaging performed for investigation of ‘elevated tumour marker’. ‘Elevated tumour marker’, in the absence of a known underlying malignancy, should not be considered an independent indication for imaging.
Cigarette smoking and serum liver enzymes: the role of alcohol and inflammation
Authors: Wannamethee S Goya , Shaper A Gerald 
Published: May 2010

Background and aims Smoking may affect the liver through inflammatory pathways and may aggravate the pathogenic effects of alcohol on the liver. We have examined the relationship between cigarette smoking and liver enzymes and the role of alcohol and C-reactive protein (CRP), a marker of inflammation. Methods The subjects consisted of 4595 men aged 40–59 y with no history of coronary heart disease drawn from general practices in 24 British towns. Results Cigarette smoking was significantly associated with increased levels of gamma-glutamyl transferase (GGT) and alkaline phosphatase (ALP) ( P < 0.0001) and was inversely associated with increased aspartate aminotransferase (AST) after adjustment for alcohol intake, body mass index and physical activity. Compared with never smokers, heavy cigarette smokers (≥40/day) were associated with increased odds of elevated GGT (≥23 IU/L) (adjusted odds ratio [OR] 1.56 [1.08, 2.27]), which was abolished after adjustment for CRP (adjusted OR 1.27 [0.87, 1.86]). There was a significant interaction between smoking and alcohol on GGT. In the absence of heavy drinking, there was no association between smoking and GGT after adjustment for CRP. Among heavy drinkers, smoking was associated with increased levels of GGT independent of CRP. Smoking was associated with increased odds of elevated ALP (≥11 IU/L) (adjusted OR 3.95 [2.77, 5.62]), which persisted after adjustment for CRP and white cell count (adjusted OR 2.90 [1.99–4.23]), possibly reflecting increased bone cell activity. Conclusion The findings suggest that cigarette smoking does not cause liver injury, but may enhance the effects of alcohol on liver cell injury in heavy drinkers.
Increases in urinary creatinine and blood pressure during early pregnancy in pre-eclampsia
Authors: Kuromoto Koichi , Watanabe Mikio , Adachi Kazushige , Ohashi Kazutomo , Iwatani Yoshinori 
Published: May 2010

Background It is important to predict the development of pre-eclampsia (PE) during early pregnancy to prevent its occurrence later on. In this study, we studied urinary biochemical parameters and blood pressure (BP) during and after pregnancy to find useful parameters for predicting PE. Methods A case-control study was performed in 25 PE patients and 172 normotensive pregnant women. Twelve biochemical parameters were measured in spot urine, and the systolic and diastolic BPs were measured using an automated device during pregnancy and six to eight weeks after birth. Results A multiple logistic regression analysis showed that the combinations of urinary creatinine (Cr) and systolic BP (SBP) in the first trimester of pregnancy (8.9 ± 2.6 weeks), and of urinary inorganic phosphorus (IP)/Cr and SBP in the second trimester of pregnancy (19.0 ± 1.6 weeks) were useful for predicting PE. The area under the curve in the receiver operator characteristic curve of the combination of urinary Cr and SBP in the first trimester was 0.85 (95% confidence interval [CI] 0.74–0.96), and that of the combination of urinary IP/Cr and SBP in the second trimester was 0.91 (95% CI: 0.86–0.97). When used 249 mg/dL in urinary Cr and 128 mmHg in SBP as their cut-off points, the combination in the first trimester increased the accuracy (sensitivity 75% and specificity 95%) in predicting PE, as compared with that of urinary Cr (29%, 99%) or SBP (50%, 98%). Conclusions Combination of urinary Cr and SBP in early pregnancy and that of urinary IP/Cr and SBP in mid-pregnancy are useful for the prediction of PE.
High-dose hook effect in six automated human chorionic gonadotrophin assays
Authors: Al-Mahdili Huda A , Jones Graham R D 
Published: May 2010

Background The high-dose hook effect is a well-known phenomenon of two-site immunoassays including those for human chorionic gonadotrophin (hCG). We investigated the occurrence of a high-dose hook effect in six routinely available hCG assays using a sample with a total hCG concentration of approximately 3,600,000 IU/L. Method Dilutions of a sample with high hCG concentration were analysed using six common methods: Advia Centaur, Immulite 2000, Dimension RxL, Unicel DxI 800, Roche E170 and Abbott Architect. The measured concentrations and corresponding assay signals were obtained for each method. Performance was compared with manufacturer claims. Results Four of the tested platforms demonstrated a clear high-dose hook effect, while the other methods showed no hook effect at the highest level tested. Conclusion Our results indicate that the hook effect may occur in some hCG assays, although the risk of reporting falsely low results was in most cases at higher concentrations than those indicated in manufacturers' product information. Assay design plays a major role in its occurrence. Laboratories should be aware of the assay limitations in this regard.
Prediabetes is not all about obesity: association between plasma leptin and prediabetes in lean rural Chinese adults
Authors: Wang Guoying , Liu Xin , Christoffel Katherine Kaufer , Zhang Shanchun , Wang Binyan , Liu Rong , Li Zhiping , Liu Xue , Brickman Wendy J , Zimmerman Donald , Xu Xiping , Wang Xiaobin 
Published: May 2010

ObjectiveThis study investigated the associations of plasma leptin levels with insulin resistance (IR) and prediabetes in relatively lean, rural Chinese men and women.Design and methodsThis study included 574 subjects aged 21–45 years from a community-based twin cohort. Plasma leptin concentrations were measured by sandwich immunoassays using flowmetric xMAP technology. Prediabetes was defined based on fasting plasma glucose and 75-g oral glucose tolerance test. Multivariate linear and logistic regression analyses were used to investigate gender-specific associations of leptin with IR measures and prediabetes, adjusting for intra-twin correlation, measures of adiposity, and other pertinent covariates.ResultsThe body mass index is 22.3±2.7 kg/m2 in men and 22.5±2.7 kg/m2 in women. Leptin levels were positively associated with IR. Individuals with higher tertiles of leptin also had increased risk of prediabetes with odds ratios (OR) of 2.6 (95% confidence interval (CI): 1.4–5.1) and 4.3 (95% CI: 2.1–8.7) in men; OR of 1.1 (95% CI: 0.6–2.1) and 3.1 (95% CI 1.5–6.2) in women for second and third tertile respectively. These associations were attenuated after further adjusting for adiposity measurements only in men. The leptin–prediabetes associations disappeared after adjusting for the homeostatic model assessment of IR in both genders.ConclusionIn this sample of relatively lean rural Chinese adults, plasma leptin levels were associated with IR and prediabetes in a dose–response fashion, which were not totally explained by adiposity. Our data emphasize that prediabetes is not all about obesity, and leptin may be an additional biomarker for screening individuals at high risk for prediabetes in this population.
(Pre-)Clinical Pharmacology and Activity of Pazopanib, a Novel Multikinase Angiogenesis Inhibitor
Authors: Hamberg Paul , Verweij Jaap , Sleijfer Stefan 
Published: May 2010

Abstract
Pazopanib is a recently approved, novel tyrosine kinase inhibitor specifically designed to impair angiogenesis by abrogating vascular endothelial growth factor receptor 2 (VEGFR-2) to exert its function. Pazopanib inhibits VEGF-induced endothelial cell proliferation in vitro and angiogenesis in vivo and demonstrates antitumor activity in mouse models. Furthermore, the pazopanib concentration resulting in maximal inhibition of VEGFR-2 phosphorylation in vivo was in line with the steady-state concentration required to inhibit growth of tumor xenografts, suggesting that pazopanib's mechanism of action is indeed through VEGFR-2 inhibition.
In a phase I trial, a generally well-tolerated dose was identified at which the majority of patients achieved pazopanib plasma concentrations above the concentration required for maximal in vivo inhibition of VEGFR-2 phosphorylation in preclinical models. Administered as monotherapy, evidence of antitumor activity was observed in phase II studies in several tumor types, including soft tissue sarcoma, renal cell cancer (RCC), ovarian cancer, and non-small cell lung cancer. Recently, the U.S. Food and Drug Administration granted approval for treatment with pazopanib in patients with RCC based on the longer progression-free survival time observed with this agent in a placebo-controlled, randomized trial. This review summarizes the preclinical and clinical pharmacokinetics and pharmacodynamics of pazopanib, as well as data on clinical activity, that ultimately resulted in its recent approval.
Scaling Up Local Perceptions of Poverty to Country Level: A Proof of Concept for Rural Honduras
Authors: Leclerc Gregoire 
Published: May 2010

AbstractThis work is about bringing together different perceptions of poverty to improve the design of poverty alleviation policies. A case study in Honduras shows how locally derived poverty indicators, developed from village‐level participatory appraisals of perceptions of poverty, can be extrapolated to country level using raw census data. The “well‐being index,” an average of several indicators, is robust and reflects actual local perceptions with 90% accuracy at village level. Because the index includes information that corresponds to the real‐life situation of the poor, I suggest that policymakers consider building and using such bottom‐up indicators. This implies a shift from economic to critical thinking that would lead to policies that are more easily adopted and monitored locally.
Poverty and Well‐Being in Indian Cities During the Reforms Era
Authors: Chandrasekhar S. , Mukhopadhyay Abhiroop 
Published: May 2010

AbstractThis paper seeks to understand temporal changes in poverty and well‐being in Indian cities during the era of economic reforms. The evidence on improvements in well being is mixed. During this period, there was an increase in the number of urban poor. Using two nationally representative samples, we compare the joint distribution of monthly per capita expenditure (a private good) and access to drainage (a public good) in slums and non‐slum areas of Indian cities to understand changes in well being. A comparison at two points in time, 1993 and 2002, suggests that the share of slum dwellers in urban poor has declined. However, we do not find evidence for improvement in the well‐being of slum dwellers over time. We do find that non‐slum urban dwellers are better off in 2002 compared to 1993.