bluuebunny/crossref_metadata_2025_split huggingface dataset:
Complex shaped detachable platinum coil system for the treatment of cerebral aneurysms: The Codman Trufill DCS and Trufill DCS Orbit Detachable Coil System COMPLEX Registry final results
Authors: Bendok Bernard R , Rahme Rudy J ,   for the Complex Registry Group*
Published: November 2011

ObjectiveTo report on an electronic database with longitudinal information on the use of bare platinum coils for the endovascular occlusion of cerebral aneurysms. We report here the final analysis of the data.MethodsFrom 1 May 2004 to 10 July 2007, a global registry was conducted at 36 centers in the USA, Europe and Latin America. 303 patients were enrolled, of whom 299 patients were treated with bare detachable platinum coils (mostly Trufill Detachable Coil System (DCS) Orbit coils). Short and long term anatomical and clinical data were collected. Logistic regression analysis was used to examine the association of selected patient characteristics to outcomes of recanalization and retreatment.Results313 aneurysms, ruptured and unruptured, were treated in the 299 patients. Follow-up data were available on 185 patients: 150 (81%) had a 3–6 month follow-up, 63 (34%) had a 1 year follow-up and five (3%) had a 2 year follow-up. This paper reviews the status of 185 patients with follow-up data available at this time. Immediately postprocedure, 114 (58%) aneurysms were completely obliterated, 40 (20%) residual neck, 23 (12%) residual aneurysm and 19 (10%) dog ear. Of 174 aneurysms in 167 patients with angiographic follow-up, 137 (79%) remained stable or improved, nine (5%) showed aneurysm regrowth, 26 (15%) showed compaction and two (1%) had migrated. At 3–6 months, 11 of the 174 (6%) aneurysms were re-treated.ConclusionThese results confirm previous outcome data of endovascular occlusion of cerebral aneurysms with Trufill DCS Orbit complex shaped detachable platinum coils. Complications related to the device were rare.
Rapamycin Induces Bad Phosphorylation in Association with Its Resistance to Human Lung Cancer Cells
Authors: Liu Yan , Sun Shi-Yong , Owonikoko Taofeek K. , Sica Gabriel L. , Curran Walter J. , Khuri Fadlo R. , Deng Xingming 
Published: November 2011

AbstractInhibition of mTOR signaling by rapamycin has been shown to activate extracellular signal-regulated kinase 1 or 2 (ERK1/2) and Akt in various types of cancer cells, which contributes to rapamycin resistance. However, the downstream effect of rapamycin-activated ERKs and Akt on survival or death substrate(s) remains unclear. We discovered that treatment of human lung cancer cells with rapamycin results in enhanced phosphorylation of Bad at serine (S) 112 and S136 but not S155 in association with activation of ERK1/2 and Akt. A higher level of Bad phosphorylation was observed in rapamycin-resistant cells compared with parental rapamycin-sensitive cells. Thus, Bad phosphorylation may contribute to rapamycin resistance. Mechanistically, rapamycin promotes Bad accumulation in the cytosol, enhances Bad/14-3-3 interaction, and reduces Bad/Bcl-XL binding. Rapamycin-induced Bad phosphorylation promotes its ubiquitination and degradation, with a significant reduction of its half-life (i.e., from 53.3–37.5 hours). Inhibition of MEK/ERK by PD98059 or depletion of Akt by RNA interference blocks rapamycin-induced Bad phosphorylation at S112 or S136, respectively. Simultaneous blockage of S112 and S136 phosphorylation of Bad by PD98059 and silencing of Akt significantly enhances rapamycin-induced growth inhibition in vitro and synergistically increases the antitumor efficacy of rapamycin in lung cancer xenografts. Intriguingly, either suppression of Bad phosphorylation at S112 and S136 sites or expression of the nonphosphorylatable Bad mutant (S112A/S136A) can reverse rapamycin resistance. These findings uncover a novel mechanism of rapamycin resistance, which may promote the development of new strategies for overcoming rapamycin resistance by manipulating Bad phosphorylation at S112 and S136 in human lung cancer. Mol Cancer Ther; 11(1); 45–56. ©2011 AACR.
PI3K and STAT3: A New Alliance
Authors: Vogt Peter K. , Hart Jonathan Ross 
Published: November 2011

Abstract
Recent proteomic data have uncovered an interdependence of PI3K (phosphatidylinositol 3-kinase) and STAT3. In PI3K-transformed murine cells, STAT3 is phosphorylated on Y705 and activated in a PI3K-dependent manner, and dominant-negative STAT3 interferes with PI3K-induced oncogenic transformation. Phosphorylation of STAT3 in PI3K-transformed murine cells is mediated by the TEC (tyrosine kinase expressed in hepatocellular carcinoma) kinase BMX (bone marrow tyrosine kinase gene in chromosome X) and observations in glioblastoma stem cells reveal similar critical roles for STAT3 and BMX. These new data document an important role of STAT3 in PI3K-driven oncogenic transformation and mark BMX as a promising therapeutic target that could enhance the effectiveness of PI3K inhibitors.
Significance: The PI3K–TOR and STAT3 signaling pathways represent two distinct regulatory networks. The discovery of a functional link between these pathways is significant for our understanding of PI3K- and STAT3-driven oncogenic mechanisms and identifies the TEC kinase BMX as a new cancer target. Cancer Discovery; 1(6); 481–86. ©2011 AACR.
Relation of Lipid Gene Scores to Longitudinal Trends in Lipid Levels and Incidence of Abnormal Lipid Levels Among Individuals of European Ancestry
Authors: Lutsey Pamela L. , Rasmussen-Torvik Laura J. , Pankow James S. , Alonso Alvaro , Smolenski Derek J. , Tang Weihong , Coresh Josef , Volcik Kelly A. , Ballantyne Christie M. , Boerwinkle Eric , Folsom Aaron R. 
Published: November 2011

Background—
Multiple genetic loci have been associated with blood lipid levels. We tested the hypothesis that persons with an unfavorable lipid gene profile would experience a greater increase in lipid levels and a higher incidence of abnormal lipid levels relative to those with more-favorable lipid gene profiles.

Methods and Results—

A total of 9328 individuals of European descent (aged 45–64 years) in the ARIC (Atherosclerosis Risk in Communities) study were followed for 9 years. Separate gene scores were created for each lipid phenotype on the basis of 95 loci identified in a published genome-wide association study of >100 000 people of European-descent. Adjusted linear and survival models were used to estimate associations with lipid levels and incidence of lipid-lowering medication or abnormal lipid levels. Age and sex interactions were also explored. The cross-sectional difference (mg/dL) per 1 SD was −1.89 for high-density lipoprotein cholesterol (HDL-C), 9.5 for low-density lipoprotein cholesterol (LDL-C), and 22.8 for triglycerides (
P
<5×10
−34
for all). Longitudinally, overall triglyceride levels rose over time, and each 1-SD greater triglyceride gene score was associated with an average increase in triglyceride levels of 0.3 mg/dL (
P
=0.003) over 3 years. The HDL-C, LDL-C, and total cholesterol gene scores were not related to change. All lipid gene scores were positively related to incidence of abnormal lipid levels over follow-up (hazard ratios per SD range, 1.15–1.36).

Conclusions—
Associations of genetic variants with lipid levels over time are complex. The triglyceride gene score was positively related to change in triglycerides levels, but similar longitudinal results were not observed for LDL-C or HDL-C levels. Unfavorable gene scores were nevertheless related to higher incidence of abnormal levels.
Generating test reference years from the UKCP09 projections and their application in building energy simulations
Authors: Du H , Underwood CP , Edge JS 
Published: November 2011

In this study, test reference year (TRY) data for three UK cities are generated from the new UKCP09 climate change projections 1 for a variety of future time horizons and carbon emission scenario assumptions. The data are applied to the energy simulation of three commercial buildings and one house for the three city locations (London, Manchester and Edinburgh), three future time horizons in this century and three carbon emission scenarios. Results are compared with those generated using alternative TRYs from two other research groups who used UKCP09 1 as well as with the existing TRY data sets which form the CIBSE Future Weather Years 2 in order to produce robust results. Results of future simulations of peak summer operative temperatures, peak cooling demand, annual cooling energy, peak heating demand and annual heating energy are presented for the four building case studies benchmarked against control weather data for the period 1960–1989. The results show increasing internal operative temperatures (non-air-conditioned) and increasing air-conditioning demands (air-conditioned) throughout this century and though peak heating demands remain similar to control data, annual heating energy consumptions can be expected to fall sharply. Practical applications: Currently, practitioners can use Test Reference Years for use in building energy simulations. In 2009, the CIBSE released Future Weather Years, which go further by allowing practitioners to explore the thermal and comfort behaviour of buildings at future time horizons thus helping to ‘future proof’ a design. In 2009, the United Kingdom Climate Impacts Programme released a new generation of climate change scenario data (the UKCP09 climate change projections) using probabilistic methods. These are the most comprehensive data yet and provides a greater degree of detail than was available to generate the CIBSE Future Weather Years. It is therefore likely that the new data will gradually become the normal basis for investigating future building thermal and comfort response. In this study, a sample of TRY is generated from the UKCP09 data and applied to the simulation of a sample of ‘real’ buildings. The results are compared with both the existing CIBSE Future Weather Years as well as with Test Reference Years generated using UKCP09 by two other research groups. The results provide a robust way forward for simulating building thermal and comfort response using future weather data.
Prevalence of Musculoskeletal Injuries in Swedish Elite Track and Field Athletes
Authors: Jacobsson Jenny , Timpka Toomas , Kowalski Jan , Nilsson Sverker , Ekberg Joakim , Renström Per 
Published: November 2011

Background: Little is known of injury patterns in track and field (athletics). Injury prevalence has been proposed as the most appropriate measure of the injury rate in sports where athletes are at risk for overuse problems. Purpose: To ascertain 1-year retrospective and current prevalence of injury in elite track and field athletes to help plan injury prevention programs for this sport. Study Design: Descriptive epidemiology study. Methods: Two hundred seventy-eight youth (16 years old) and adult athletes from an eligible study population of 321 athletes were included. Results: The 1-year retrospective injury prevalence was 42.8% (95% confidence interval [CI], 36.9%-49.0%); the point prevalence was 35.4% (95% CI, 29.7%-41.4%). The diagnosis group displaying the highest injury prevalence was inflammation and pain in the gradual onset category (1-year prevalence, 20.9%; 95% CI, 16.2%-26.2%; and point prevalence, 23.2%; 95% CI, 18.4%-28.7%). A strong tendency for higher 1-year prevalence of 16.5% (95% CI, 12.2%-21.4%) than point prevalence of 8.5% (95% CI, 5.5%-12.5%) was recorded for sudden onset injuries in the diagnosis group sprain, strain, and rupture. The body region showing the highest injury prevalence was the knee and lower leg with 15.0% (95% CI, 11.0%-19.8%) 1-year prevalence and 13.7% (95% CI, 9.8%-18.3%) point prevalence, followed by the Achilles tendon, ankle, and foot/toe with 11.7% (95% CI, 8.2%-16.1%) 1-year prevalence and 11.4% (95% CI, 7.9%-15.8%) point prevalence. Conclusion: The injury prevalence is high among Swedish elite track and field athletes. Most of the injuries affect the lower extremities and are associated with a gradual onset. Although it is associated with a potential recall bias, the 1-year retrospective prevalence measure captured more sudden onset injuries than the point prevalence measure. Future prospective studies in track and field are needed to identify groups of athletes at increased risk.
Bleeding Risk Secondary to Deep Vein Thrombosis Prophylaxis in Patients With Lower Gastrointestinal Bleeding
Authors: Deutsch Gary B. , Kandel Anuj R. , Knobel Denis , Gupta Rajeev , Ritter Garry , Marini Corrado P. , Barrera Rafael 
Published: November 2011

Introduction: Deep vein thrombosis (DVT) and pulmonary embolism (PE) continue to pose a major burden on the health care system in the United States. The precise timing of anticoagulation initiation in critically ill patients with recent or active lower gastrointestinal bleeding (LGIB) is not well defined. We set out to study the safety and efficacy of early heparin administration for DVT prophylaxis in these patients. Methods: A review of all patients admitted to the ICU with a diagnosis of LGIB over a 13-year period was performed. A total of 60 patients received subcutaneous heparin along with mechanical prophylaxis, whereas 59 patients had intermittent pneumatic compression devices alone. Results: There was no difference in morbidity or mortality between the groups who received heparin and the nonheparin cohort. Neither of the groups developed a DVT or PE during the study period. Patients who received heparin had a median ICU LOS of 3 days, when compared with 2 days for patients who did not receive heparin ( P < .0118). There was a significant association between units of blood received during the first 24 hours in the ICU and heparin usage ( P < .0229). Those administered heparin received more units (median 3) than those who did not receive heparin (median 2). Conclusions: Administration of subcutaneous heparin increases the transfusion requirements and LOS in ICU patients with LGIB. After 24 hours, however, the blood transfusion requirements are equivalent. DVT prophylaxis in patients with a diagnosis of LGIB should be initiated after 24 hours of ICU admission.
Characteristic Markers of the WNT Signaling Pathways Are Differentially Expressed in Osteoarthritic Cartilage
Authors: Thorfve A. , Dehne T. , Lindahl A. , Brittberg M. , Pruss A. , Ringe J. , Sittinger M. , Karlsson C. 
Published: November 2011

Objective: It is well known that expression of markers for WNT signaling is dysregulated in osteoarthritic (OA) bone. However, it is still not fully known if the expression of these markers also is affected in OA cartilage. The aim of this study was therefore to examine this issue. Methods: Human cartilage biopsies from OA and control donors were subjected to genome-wide oligonucleotide microarrays. Genes involved in WNT signaling were selected using the BioRetis database, KEGG pathway analysis was searched using DAVID software tools, and cluster analysis was performed using Genesis software. Results from the microarray analysis were verified using quantitative real-time PCR and immunohistochemistry. In order to study the impact of cytokines for the dysregulated WNT signaling, OA and control chondrocytes were stimulated with interleukin-1 and analyzed with real-time PCR for their expression of WNT-related genes. Results: Several WNT markers displayed a significantly altered expression in OA compared to normal cartilage. Interestingly, inhibitors of the canonical and planar cell polarity WNT signaling pathways displayed significantly increased expression in OA cartilage, while the Ca2+/WNT signaling pathway was activated. Both real-time PCR and immunohistochemistry verified the microarray results. Real-time PCR analysis demonstrated that interleukin-1 upregulated expression of important WNT markers. Conclusions: WNT signaling is significantly affected in OA cartilage. The result suggests that both the canonical and planar cell polarity WNT signaling pathways were partly inhibited while the Ca2+/WNT pathway was activated in OA cartilage.
One-Year Clinical and Radiological Results of a Prospective, Investigator-Initiated Trial Examining a Novel, Purely Autologous 3-Dimensional Autologous Chondrocyte Transplantation Product in the Knee
Authors: Fickert Stefan , Gerwien Philip , Helmert Benjamin , Schattenberg Torsten , Weckbach Sabine , Kaszkin-Bettag Marietta , Lehmann Lars 
Published: November 2011

Background: The 3-dimensional autologous chondrocyte transplantation (ACT3D) comprises isolation of chondrocytes from cartilage biopsies, cultivation to spheroids, and transplantation into the cartilage defect. Objectives: To evaluate the patients’ general health and functionality and to assess the defect repair after ACT3D with spheroids by MRI and MOCART scoring. Methods: Thirty-seven patients with isolated chondral lesions of the knee underwent ACT3D with spheroids through medial arthrotomy. Patient-administered scores were assessed at baseline (day before transplantation), at 6 weeks, and at 3, 6, and 12 months. MRI and MOCART scoring were performed at 3 and 12 months after ACT3D. Results: Patients were diagnosed with full-thickness patellofemoral ( n = 16), femoral condylar ( n = 18), or both defect types ( n = 3), International Cartilage Repair Society (ICRS) grade 3 or 4, with defect sizes between 1.0 and 12.0 cm2. On average, 59.5 spheroids/cm2 in defect size were transplanted. An overall statistically significant improvement from baseline to 12 months was observed for all assessment scores (Lysholm, International Knee Documentation Committee [IKDC], SF-36, Tegner) combined with a significant reduction in the visual analog scale (VAS) for pain and an advanced defect filling. Subgroup analyses revealed a positive clinical outcome independent on defect size, defect locations, spheroid dosage, age, duration of symptoms, and severity of complaints at baseline. Seven patients experienced in total 8 adverse events, of which knee joint effusion and blocking were assessed as possibly or probably related to ACT3D. Conclusions: The patient-administered assessment scores along with the fast defect filling with ACT3D using spheroids demonstrated an increase in activity level and quality of life after a 1-year follow-up.
A novel hybrid CFH/CFHR3 gene generated by a microhomology-mediated deletion in familial atypical hemolytic uremic syndrome
Authors: Francis Nigel J. , McNicholas Bairbre , Awan Atif , Waldron Mary , Reddan Donal , Sadlier Denise , Kavanagh David , Strain Lisa , Marchbank Kevin J. , Harris Claire L. , Goodship Timothy H. J. 
Published: November 2011

AbstractGenomic disorders affecting the genes encoding factor H (fH) and the 5 factor H related proteins have been described in association with atypical hemolytic uremic syndrome. These include deletions of CFHR3, CFHR1, and CFHR4 in association with fH autoantibodies and the formation of a hybrid CFH/CFHR1 gene. These occur through nonallelic homologous recombination secondary to the presence of large segmental duplications (macrohomology) in this region. Using multiplex ligation-dependent probe amplification to screen for such genomic disorders, we have identified a large atypical hemolytic uremic syndrome family where a deletion has occurred through microhomology-mediated end joining rather than nonallelic homologous recombination. In the 3 affected persons of this family, we have shown that the deletion results in formation of a CFH/CFHR3 gene. We have shown that the protein product of this is a 24 SCR protein that is secreted with normal fluid-phase activity but marked loss of complement regulation at cell surfaces despite increased heparin binding. In this study, we have therefore shown that microhomology in this area of chromosome 1 predisposes to disease associated genomic disorders and that the complement regulatory function of fH at the cell surface is critically dependent on the structural integrity of the whole molecule.
Interaction of HTLV-1 Tax with minichromosome maintenance proteins accelerates the replication timing program
Authors: Boxus Mathieu , Twizere Jean-Claude , Legros Sébastien , Kettmann Richard , Willems Luc 
Published: November 2011

AbstractThe Tax oncoprotein encoded by the human T-cell leukemia virus type 1 plays a pivotal role in viral persistence and pathogenesis. Human T-cell leukemia virus type 1–infected cells proliferate faster than normal lymphocytes, expand through mitotic division, and accumulate genomic lesions. Here, we show that Tax associates with the minichromosome maintenance MCM2-7 helicase complex and localizes to origins of replication. Tax modulates the spatiotemporal program of origin activation and fires supplementary origins at the onset of S phase. Thereby, Tax increases the DNA replication rate, accelerates S phase progression, but also generates a replicative stress characterized by the presence of genomic lesions. Mechanistically, Tax favors p300 recruitment and histone hyperacetylation at late replication domains, advancing their replication timing in early S phase.
Allelic methylation levels of the noncoding VTRNA2-1 located on chromosome 5q31.1 predict outcome in AML
Authors: Treppendahl Marianne Bach , Qiu Xiangning , Søgaard Alexandra , Yang Xiaojing , Nandrup-Bus Cecilie , Hother Christoffer , Andersen Mette Klarskov , Kjeldsen Lars , Möllgaard Lars , Hellström-Lindberg Eva , Jendholm Johan , Porse Bo T. , Jones Peter A. , Liang Gangning , Grønbæk Kirsten 
Published: November 2011

AbstractDeletions of chromosome 5q are associated with poor outcomes in acute myeloid leukemia (AML) suggesting the presence of tumor suppressor(s) at the locus. However, definitive identification of putative tumor suppressor genes remains controversial. Here we show that a 106-nucleotide noncoding RNA vault RNA2-1 (vtRNA2-1), previously misannotated as miR886, could potentially play a role in the biology and prognosis of AML. vtRNA2-1 is transcribed by polymerase III and is monoallelically methylated in 75% of healthy individuals whereas the remaining 25% of the population have biallelic hypomethylation. AML patients without methylation of VTRNA2-1 have a considerably better outcome than those with monoallelic or biallelic methylation (n = 101, P = .001). We show that methylation is inversely correlated with vtRNA2-1 expression, and that 5-azanucleosides induce vtRNA2-1 and down-regulate the phosphorylated RNA-dependent protein kinase (pPKR), whose activity has been shown to be modulated by vtRNA2-1. Because pPKR promotes cell survival in AML, the data are consistent with vtRNA2-1 being a tumor suppressor in AML. This is the first study to show that vtRNA2-1 might play a significant role in AML, that it is either mono- or biallelically expressed in the blood cells of healthy individuals, and that its methylation state predicts outcome in AML.