bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immune responses to transgene and retroviral vector in patients treated with ex vivo–engineered T cells
Authors: Lamers Cor H. J. , Willemsen Ralph , van Elzakker Pascal , van Steenbergen-Langeveld Sabine , Broertjes Marieke , Oosterwijk-Wakka Jeannette , Oosterwijk Egbert , Sleijfer Stefan , Debets Reno , Gratama Jan W. 
Published: October 2010

AbstractAdoptive transfer of immune effector cells that are gene modified by retroviral transduction to express tumor-specific receptors constitutes an attractive approach to treat cancer. In patients with metastatic renal cell carcinoma, we performed a study with autologous T cells genetically retargeted with a chimeric antibody receptor (CAR) directed toward carbonic anhydrase IX (CAIX), an antigen highly expressed in renal cell carcinoma. In the majority of patients, we observed distinct humoral and/or cellular anti–CAIX-CAR T-cell immune responses in combination with a limited peripheral persistence of transferred CAIX-CAR T cells in the majority of patients. Humoral immune responses were anti-idiotypic in nature and neutralized CAIX-CAR–mediated T-cell function. Cellular anti–CAIX-CAR immune responses were directed to the complementarity-determining and framework regions of the CAR variable domains. In addition, 2 patients developed immunity directed against presumed retroviral vector epitopes. Here, we document the novel feature that therapeutic cells, which were ex vivo engineered by means of transduction with a minimal γ-retroviral vector, do express immunogenic vector-encoded epitopes, which might compromise persistence of these cells. These observations may constitute a critical concern for clinical ex vivo γ-retroviral gene transduction in general and CAR-retargeted T-cell therapy in particular, and underscore the need to attenuate the immunogenicity of both transgene and vector.
From pharmaco-therapy to pharmaco-prevention: trends in prescribing to older adults in Ontario, Canada, 1997-2006
Authors: Bajcar Jana M , Wang Li , Moineddin Rahim , Nie Jason X , Tracy C Shawn , Upshur Ross EG 
Published: October 2010

Abstract

Background
The developed world is undergoing a demographic transition with greater numbers of older adults and higher rates of chronic disease. Most elder care is now provided by primary care physicians, who prescribe the majority of medications taken by these patients. Despite these significant trends, little is known about population-level prescribing patterns to primary care patients aged 65+.

Methods
We conducted a population-based retrospective cohort study to examine 10-year prescribing trends among family physicians providing care to patients aged 65+ in Ontario, Canada.

Results
Both crude number of prescription claims and prescription rates (i.e., claims per person) increased dramatically over the 10-year study period. The greatest change was in prescribing patterns for females aged 85+. Dramatic increases were observed in the prescribing of preventive medications, such as those to prevent osteoporosis (+2,347%) and lipid-lowering agents (+697%). And lastly, the number of unique classes of medications prescribed to older persons has increased, with the proportion of older patients prescribed more than 10 classes of medications almost tripling during the study period.

Conclusions
Prescribing to older adults by family physicians increased substantially during the study period. This raises important concerns regarding quality of care, patient safety, and cost sustainability. It is evident that further research is urgently needed on the health outcomes (both beneficial and harmful) associated with these dramatic increases in prescribing rates.
Are component positioning and prosthesis size associated with hip resurfacing failure?
Authors: Marker David R , Zywiel Michael G , Johnson Aaron J , Seyler Thorsten M , Mont Michael A 
Published: October 2010

Abstract

Background
Recent studies suggest that there is a learning curve for metal-on-metal hip resurfacing. The purpose of this study was to assess whether implant positioning changed with surgeon experience and whether positioning and component sizing were associated with implant longevity.

Methods
We evaluated the first 361 consecutive hip resurfacings performed by a single surgeon, which had a mean follow-up of 59 months (range, 28 to 87 months). Pre and post-operative radiographs were assessed to determine the inclination of the acetabular component, as well as the sagittal and coronal femoral stem-neck angles. Changes in the precision of component placement were determined by assessing changes in the standard deviation of each measurement using variance ratio and linear regression analysis. Additionally, the cup and stem-shaft angles as well as component sizes were compared between the 31 hips that failed over the follow-up period and the surviving components to assess for any differences that might have been associated with an increased risk for failure.

Results
Surgeon experience was correlated with improved precision of the antero-posterior and lateral positioning of the femoral component. However, femoral and acetabular radiographic implant positioning angles were not different between the surviving hips and failures. The failures had smaller mean femoral component diameters as compared to the non-failure group (44 versus 47 millimeters).

Conclusions
These results suggest that there may be differences in implant positioning in early versus late learning curve procedures, but that in the absence of recognized risk factors such as intra-operative notching of the femoral neck and cup inclination in excess of 50 degrees, component positioning does not appear to be associated with failure. Nevertheless, surgeons should exercise caution in operating patients with small femoral necks, especially when they are early in the learning curve.
Decreased health-related quality of life in disease-free survivors of differentiated thyroid cancer in Korea
Authors: Lee Ji In , Kim Soo Hyun , Tan Alice H , Kim Hee Kyung , Jang Hye Won , Hur Kyu Yeon , Kim Jae Hyeon , Kim Kwang-Won , Chung Jae Hoon , Kim Sun Wook 
Published: October 2010

Abstract

Background
Concern regarding the health-related quality of life (HRQOL) of long-term survivors of thyroid cancer has risen due to the rapid increase in the incidence of thyroid cancer, which generally has an excellent prognosis. The aim of this study was to evaluate the status of HRQOL in disease-free survivors of differentiated thyroid carcinoma (DTC) and to evaluate the important determinants of HRQOL.

Methods
This was a cross-sectional study in which we interviewed consecutive disease-free survivors of DTC. Three different validated questionnaires ("EORTC QLQ-C30" for various functional domains, the "brief fatigue inventory (BFI)" and the "hospital anxiety and depression scale" (HADS)) were used. Data from a large, population based survey of 1,000 people were used as a control.

Results
The response rate for the questionnaires was 78.9% (316/401). Disease-free survivors of DTC showed a decreased HRQOL in all five functional domains (physical, role, cognitive, emotional, and social) on the EORTC QLQ-C30 compared with controls (P < 0.01). BFI and HADS-anxiety scores also showed greater distress in disease-free survivors of DTC than in controls (P < 0.05). A multiple regression analysis for the determinants of HRQOL showed that the HADS-anxiety, HADS-depression, and BFI scores were the most significant components of decreased HRQOL.

Conclusions
Although disease-free survivors of DTC are expected to have disease-specific survival comparable to the general population, they experience a significantly decreased HRQOL. Anxiety, depression, and fatigue were the major determinants of the decreased HRQOL. Supportive psychological care should be integrated into the management of long-term survivors of DTC.
The Rg1 allele as a valuable tool for genetic transformation of the tomato 'Micro-Tom' model system
Authors: Pino Lilian E , Lombardi-Crestana Simone , Azevedo Mariana S , Scotton Danielle C , Borgo Lucélia , Quecini Vera , Figueira Antonio , Peres Lázaro EP 
Published: October 2010

Abstract

Background
The cultivar Micro-Tom (MT) is regarded as a model system for tomato genetics due to its short life cycle and miniature size. However, efforts to improve tomato genetic transformation have led to protocols dependent on the costly hormone zeatin, combined with an excessive number of steps.

Results
Here we report the development of a MT near-isogenic genotype harboring the allele Rg1 (MT-Rg1), which greatly improves tomato in vitro regeneration. Regeneration was further improved in MT by including a two-day incubation of cotyledonary explants onto medium containing 0.4 μM 1-naphthaleneacetic acid (NAA) before cytokinin treatment. Both strategies allowed the use of 5 μM 6-benzylaminopurine (BAP), a cytokinin 100 times less expensive than zeatin. The use of MT-Rg1 and NAA pre-incubation, followed by BAP regeneration, resulted in high transformation frequencies (near 40%), in a shorter protocol with fewer steps, spanning approximately 40 days from Agrobacterium infection to transgenic plant acclimatization.

Conclusions
The genetic resource and the protocol presented here represent invaluable tools for routine gene expression manipulation and high throughput functional genomics by insertional mutagenesis in tomato.
Is distortion of the bioprosthesis ring a risk factor for early calcification?
Authors: Cereijo Jose Manuel Martinez , Alvarez Jose Rubio , Quiroga Juan Sierra , de Alegria Anxo Martinez , Suarez Peñaranda Jose Manuel 
Published: October 2010

Abstract

Background
As the population ages, bioprosthesis are increasingly being used in cardiac valve replacement. Pericardial bioprosthesis combine an excellent hemodynamic performance with low thrombogenicity, but valve failure associated with calcification remains a concern with these valves. We describe distortion of the bioprosthesis ring as a risk factor for early calcification.

Methods
A total of 510 patients over the age of 70 years underwent isolated aortic valve replacement with the Mitroflow (A12) pericardial bioprosthesis. Thirty two patients (6,2%) have undergone a second aortic valve replacement due to structural valve dysfunction resulting from valve calcification. In all patients a chest radiography and coronary angiography was performed before reoperation. A 64 Multidetector Computed Tomography (MDCT) with retrospective ECG gating study was performed in four patients to evaluate the aortic bioprosthesis.

Results
Chest radiography showed in all patients an irregular bioprosthesis ring. At preoperative coronary angiography a distorted bioprosthesis ring was detected in all patients. Macroscopic findings of the explanted bioprostheses included extensive calcification in all specimens.

Conclusion
There was a possible relationship between early bioprosthetic calcification and radiologic distortion of the bioprosthesis ring.
Radioiodine remnant ablation of differentiated thyroid cancer does not further increase oxidative damage to membrane lipids - early effect
Authors: Makarewicz Jacek , Lewiński Andrzej , Karbownik-Lewińska Małgorzata 
Published: October 2010

Abstract

Introduction
Radioiodine (131I) therapy is widely accepted as an essential part of therapeutic regimens in many cases of differentiated thyroid cancer. Radiation-induced oxidative damage to macromolecules is a well known phenomenon. Frequently examined process to evaluate oxidative damage to macromolecules is lipid peroxidation (LPO), resulting from oxidative damage to membrane lipids. The aim of the study was to examine serum LPO level in hypothyroid (after total thyroidectomy) cancer patients subjected to ablative activities of 131I.

Materials and methods
The study was carried out in 21 patients (18 females and 3 males, average age 52.4 ± 16.5 years) after total thyroidectomy for papillary (17 patients) or follicular (4 patients) thyroid carcinoma. Hypothyroidism was confirmed by increased TSH blood concentration (BRAHMS, Germany), measured before 131I therapy. Activity of 2.8 - 6.9 GBq of 131I was administered to the patients orally as sodium iodide (OBRI, Poland). Concentrations of malondialdehyde + 4-hydroxyalkenals (MDA + 4-HDA), as an index of LPO (LPO-586 kit, Calbiochem, USA), were measured in blood serum just before 131I administration (day "0") and on the days 1-4 after 131I therapy. Sera from 23 euthyroid patients served as controls. Correlations between LPO and TSH or 131I activity were calculated.

Results
Expectedly, serum LPO level, when measured before 131I therapy, was several times higher (p < 0.00001) in cancer patients than in healthy subjects, which is probably due to hypothyroidism caused by total thyroidectomy. However, we did not observe any differences between LPO levels after and before 131I therapy. LPO did not correlate with TSH concentration. In turn, negative correlation was found between 131I activity and LPO level on the day "2" after radioiodine treatment.

Conclusions
Radioiodine remnant ablation of differentiated thyroid cancer does not further increase oxidative damage to membrane lipids, at least early, after therapy.
Mitochondrial Localization and Regulation of BRAFV600E in Thyroid Cancer: A Clinically Used RAF Inhibitor Is Unable to Block the Mitochondrial Activities of BRAFV600E
Authors: Lee Min Hee , Lee Seong Eun , Kim Dong Wook , Ryu Min Jeong , Kim Sung Jin , Kim Sung Joong , Kim Yong Kyoung , Park Ji Hoon , Kweon Gi Ryang , Kim Jin Man , Lee Jung Uee , De Falco Valentina , Jo Young Suk , Shong Minho 
Published: October 2010

Context: The oncogenic BRAFV600E mutation results in an active structural conformation characterized by greatly elevated ERK activity. However, additional cellular effects caused by subcellular action of BRAFV600E remain to be identified.
Objective: To explore these effects, differences in the subcellular localization of wild-type and mutant BRAF in thyroid cancer were investigated.
Results: A significant proportion of endogenous and exogenous BRAFV600E, but not wild-type BRAF, was detected in the mitochondrial fraction, similar to other BRAF mutants including BRAFV600D, BRAFV600K, BRAFV600R, and BRAFG469A, which showed elevated kinase activity and mitochondrial localization. Induced expression of BRAFV600E suppressed the apoptotic responses against staurosporine and TNFα/cycloheximide. Interestingly, the mitochondrial localization and antiapoptotic activities of BRAFV600E were unaffected by sorafenib and U0126 suppression of MAPK kinase (MEK) and ERK activities. Similarly, although the RAF inhibitor sorafenib effectively inhibited MEK/ERK activation, it did not block the mitochondrial localization of BRAFV600E. In addition, inducible expression of BRAFV600E increased the glucose uptake rate and decreased O2 consumption, suggesting that BRAFV600E reduces mitochondrial oxidative phosphorylation, a signature feature of cancer cells. Again, these metabolic alterations resulted by BRAFV600E expression were not affected by the treatment of thyroid cells by sorafenib. Therefore, RAF and MEK inhibitors are unable to block the antiapoptotic activity of BRAFV600E or correct the high glucose uptake rate and glycolytic activity and suppressed mitochondrial oxidative phosphorylation induced by BRAFV600E.
Conclusions: The mitochondrial localization observed in oncogenic BRAF mutants might be related to their altered responses to apoptotic stimuli and characteristic metabolic phenotypes found in thyroid cancer. The inability of MEK and RAF inhibitors, U0126 and sorafenib, respectively, to block the mitochondrial localization of BRAFV600E has additional therapeutic implications for BRAFV600E-positive thyroid cancers.
Spironolactone interference in the immunoassay of androstenedione
Authors: Honour J W , Tsilchorozidou T , Conway G S , Dawnay A 
Published: October 2010

Background In an evaluation of androstenedione results from patient serum samples using the Siemens Immulite 2500 analyser and manual Coat-A-Count (CAC) methods, three outliers were evident with grossly elevated results in the CAC assay. Methods The clinic notes of three patients with apparently high serum androstenedione concentrations by the CAC assay were checked for medications. The samples were all from patients with polycystic ovary syndrome taking 100–200 mg/d of a steroidal antiandrogen (spironolactone). Two other patients on 50 mg spironolactone per day had less markedly higher androstendione results with the CAC assay. In a further five patients who were selected since they were on spironolactone and had high androstenedione results by the CAC method, spironolactone was temporarily withdrawn and fresh blood samples obtained for analysis. Results Spironolactone treatment was associated with higher androstenedione concentrations measured by the CAC assay that reverted to normal on treatment withdrawal. Based on a single test with spironolactone at 1000 ng/mL, the manufacturer reported only 0.109% interference in the CAC assay. Conclusions Spironolactone (and/or its metabolites) may interfere in the Siemens CAC assay for androstenedione but not in the Immulite 2500 assay. This experience highlights the need for information from clinicians on drug treatment when laboratory investigations are requested. Drug interferences in immunoassay are common and need evaluation beyond tests performed to certify laboratory reagents.
The effect on mortality of antipyretics in the treatment of influenza infection: systematic review and meta-analyis
Authors: Eyers Sally , Weatherall Mark , Shirtcliffe Philippa , Perrin Kyle , Beasley Richard 
Published: October 2010

Summary Objective To determine whether antipyretic treatment for influenza infection influences the risk of mortality in animal models and humans. Design A systematic search of Medline, Embase and the Cochrane Register of Controlled Trials was undertaken to identify randomized placebo-controlled trials of antipyretic use in influenza infection in animal models or humans that reported mortality. A quantitative meta-analysis of the risk of death using Peto's one step odds ratio with calculation of the pooled risk of death and standard evaluation of heterogeneity was undertaken. Setting Not applicable. Participants Not applicable. Main outcome measures Risk of mortality associated with antipyretic use in influenza infection. Results Eight studies from three publications met the inclusion criteria. No human studies were identified. The risk of mortality was increased by antipyretic use in influenza-infected animals with a fixed effects pooled odds ratio of 1.34 (95% CI 1.04–1.73). An increased risk was observed with aspirin, paracetamol and diclofenac. Conclusion In animal models, treatment with antipyretics for influenza infection increases the risk of mortality. There are no randomized placebo-controlled trials of antipyretic use in influenza infection in humans that reported data on mortality and a paucity of clinical data by which to assess their efficacy. We suggest that randomized placebo-controlled trials of antipyretic use in human influenza infection are urgently required, and that these are sufficiently powered to investigate a potential effect on mortality.
Moisture Damage in Vented Air Space of Exterior Walls of Wooden Houses
Authors: Umeno Tetsuya , Hokoi Shuichi 
Published: October 2010

Abstract
Most of the exterior walls of wooden houses in Japan have a vented air layer between the exterior cladding and the insulation. This vented air layer is designed to dehumidify the exterior walls by discharging humidity to the outside and allowing outdoor air to enter, thereby decreasing the risk of condensation on the exterior wall during winter. It is assumed that the source of this moisture is the indoor air, and that the outdoor air is drier. However, the outdoor air is often highly humid during the rainy season and may become a source of moisture. The vented air layer also allows rain water to drain away. Any rain water penetrating through the exterior cladding is drained away through the vented air layer. However, rain can also enter the vented air space through the air inlets. Since it takes a certain amount of time for all the rain water to drain away, water may accumulate in the vented air layer and produce high humidity in the exterior wall. In order to evaluate the effectiveness of an exterior wall with a vented air layer, its hygrothermal characteristics should be investigated, taking the effect of rain water into consideration. This paper describes a case of moisture damage where stain appeared on the outer surface of the plywood wall in a wooden residential building. Experiments were carried out in climate chambers to clarify the conditions that are causing stain. Hygrothermal conditions in the vented air layer were simulated using heat, air, and moisture model, and the causes of staining were investigated.
Elements to Improve Galling Resistance Test Results Using the ASTM G98 Method
Authors: Hummel Scott R. 
Published: October 2010

Abstract
The ASTM G98 Standard Test Method for Galling Resistance of Materials describes a relatively easy and quick method to screen materials for galling resistance. It has been used for several decades by material producers to report the galling resistance of their various grades of material. Design engineers subsequently use the data to make informed decisions regarding material selection. One of the most attractive features of the method is the small number of replicates that need to be run to estimate galling resistance. In the minimal case, only two replicates need to be tested. In recent years, however, research has been conducted that exposed several issues with the ASTM G98 method that can lead to reduced accuracy in results. These issues have included stress concentrations in the contact region, inconsistent oxidation layer formation on specimens, and small sampling sets leading to statistically insignificant results, among other issues. In this paper, several problematic issues are described and discussed. Suggestions are given to improve the repeatability of test results while still conforming to the standardized test method.
India's Increasing Skill Premium: Role of Demand and Supply
Authors: Azam Mehtabul 
Published: October 2010

Abstract
Using micro data for India from 1983 to 2005, this paper finds that the tertiary (college)-secondary (high school) wage premium has been increasing in India over the past decade and that this increase differs across age groups. The increase in wage premiums has been driven mostly by younger age groups while older age groups have not experienced any significant increase. Using a demand and supply model with imperfect substitution across age groups (developed in Card and Lemieux, 2001), this paper demonstrates that workers are not perfect substitutes across age groups. The paper finds that the increase in the wage premium has come mostly from demand shifts in favor of workers with a tertiary education. More importantly, the growth rate of demand for tertiary educated workers relative to secondary educated workers was fairly stable in the 1980s and the 1990s. However, the relative supply played an important role not only in determining the extent of increase in wage premium, but also its timing. The increase in relative supply of tertiary workers during 1983-1993 negated the demand shift; as a result, the wage premium did not increase much. But during 1993-1999, the growth rate of the relative supply of tertiary workers decelerated, while relative supply became virtually stagnant during 1999-2004. Both these periods saw an increase in the wage premium as the countervailing supply shift was weak.