bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomic and Molecular Characterization of Malignant Peripheral Nerve Sheath Tumor Identifies the IGF1R Pathway as a Primary Target for Treatment
Authors: Yang Jilong , Ylipää Antti , Sun Yan , Zheng Hong , Chen Kexin , Nykter Matti , Trent Jonathan , Ratner Nancy , Lev Dina C. , Zhang Wei 
Published: November 2011

Abstract
Purpose: Malignant peripheral nerve sheath tumor (MPNST) is a rare sarcoma that lacks effective therapeutic strategies. We gain insight into the most recurrent genetically altered pathways with the purpose of scanning possible therapeutic targets.
Experimental Design: We conducted a microarray-based comparative genomic hybridization profiling of two cohorts of primary MPNST tissue samples including 25 patients treated at The University of Texas MD Anderson Cancer Center and 26 patients from Tianjin Cancer Hospital. Immunohistochemistry (IHC) and cell biology detection and validation were carried out on human MPNST tissues and cell lines.
Results: Genomic characterization of 51 MPNST tissue samples identified several frequently amplified regions harboring 2,599 genes and regions of deletion including 4,901 genes. At the pathway level, we identified a significant enrichment of copy number–altering events in the insulin-like growth factor 1 receptor (IGF1R) pathway, including frequent amplifications of the IGF1R gene itself. To validate the IGF1R pathway as a potential target in MPNSTs, we first confirmed that high IGF1R protein correlated with worse tumor-free survival in an independent set of samples using IHC. Two MPNST cell lines (ST88-14 and STS26T) were used to determine the effect of attenuating IGF1R. Inhibition of IGF1R in ST88-14 cells using siRNAs or an IGF1R inhibitor, MK-0646, led to significant decreases in cell proliferation, invasion, and migration accompanied by attenuation of the PI3K/AKT and mitogen-activated protein kinase pathways.
Conclusion: These integrated genomic and molecular studies provide evidence that the IGF1R pathway is a potential therapeutic target for patients with MPNST. Clin Cancer Res; 17(24); 7563–73. ©2011 AACR.
Climate Simulations with an Isentropic Finite-Volume Dynamical Core
Authors: Chen Chih-Chieh , Rasch Philip J. 
Published: November 2011

Abstract
This paper discusses the impact of changing the vertical coordinate from a hybrid pressure to a hybrid-isentropic coordinate within the finite-volume (FV) dynamical core of the Community Atmosphere Model (CAM). Results from a 20-yr climate simulation using the new model coordinate configuration are compared to control simulations produced by the Eulerian spectral and FV dynamical cores of CAM, which both use a pressure-based (σ − P) coordinate. The same physical parameterization package is employed in all three dynamical cores.
The isentropic modeling framework significantly alters the simulated climatology and has several desirable features. The revised model produces a better representation of heat transport processes in the atmosphere leading to much improved atmospheric temperatures. The authors show that the isentropic model is very effective in reducing the long-standing cold temperature bias in the upper troposphere and lower stratosphere, a deficiency shared among most climate models. The warmer upper troposphere and stratosphere seen in the isentropic model reduces the global coverage of high clouds, which is in better agreement with observations. The isentropic model also shows improvements in the simulated wintertime mean sea level pressure field in the Northern Hemisphere.
Traffic light food labelling in schools and beyond
Authors: Pettigrew Simone , Pescud Melanie , Donovan Robert J 
Published: November 2011

Objective: The present study investigated stakeholders’ reactions to the introduction of a traffic light food classification system in primary and secondary school canteens. Design: Interviews and focus groups were conducted with stakeholders approximately 18 months after the introduction of the traffic light system, followed by telephone and web-based surveys. Setting: The context of the study was Western Australia, where a comprehensive healthy food policy was recently introduced in government schools. Method: Stakeholder groups included parents, principals, teachers, canteen managers, and representatives of parents and citizens committees. Results: Participants reported high levels of acceptance of the traffic light system and supported its extension to nutrition education programmes targeting children and parents. Conclusion: The results suggest that there is likely to be considerable support for an extension of the traffic light policy to the health curriculum in schools and into other food provision contexts.
Prisoners’ self-reported health and attitudes to health promotion initiatives in a Scottish Prison
Authors: Pulford AJ , Aspinall E , Hardie S , Murphy L , McDevitt RM , Watts M 
Published: November 2011

Objective: To explore prisoners’ views on their own health, health promotion and harm reduction measures, prior to a period of significant change in the way these services are delivered in the prison setting. Design: Structured interviews with prisoners as part of a wider Health Needs Assessment of a local prison. Setting: A high security prison in the West of Scotland with capacity for 700 male prisoners. Methods: A structured questionnaire with prisoners recruited from education, regular wings, and protection wings. Responses were analysed using thematic analysis and statistical techniques. Results: Seventy-nine prisoners were interviewed. Most prisoners reported their health as good or excellent, despite reporting high levels of risk-taking behaviour. Nearly half thought their health had improved since incarceration, citing reduced drug and alcohol use and healthier lifestyles. Prisoners expressed mixed views on harm reduction initiatives, with concerns around confidentiality, bullying, and being exposed to drug use or sexual activity in their ‘home’ environment. Conclusion: This study indicates the importance of listening to prisoners’ views about health promotion and harm reduction initiatives, and also of challenging their perceptions of what constitutes ‘good health’ and risk-taking behaviour. It also highlights the importance of environmental factors on prisoners’ health both within the prison and upon release.
Engaging ‘gay’ businesses in HIV prevention ‘Everywhere’: Findings from a qualitative study in eight European cities
Authors: Sherriff Nigel , McDonnell Elizabeth , Bogen-Johnston Leanne , Tunstall Ben , O’Brien Oonagh ,   on behalf of the Everywhere Consortium
Published: November 2011

Objective: ‘Gay’ businesses providing physical and virtual sex spaces for men who have sex with men (MSM) have been shown empirically to be useful sites for public health and health promotion interventions. While HIV incidence in Europe has been more or less stable in recent years, the number of infections attributed to MSM has continued to increase with new cases almost doubling in Western and Central Europe between 2000 and 2006. Set within the context of the Everywhere Project, the objective of this study was to explore the feasibility and acceptability to ‘gay’ businesses of developing and implementing a European model of HIV prevention focusing on MSM that provides common prevention standards across eight European countries. Design: A qualitative study Setting: ‘Gay’ businesses that bring men together and facilitate sex between them in ‘gay’ tourist destinations and other European capital cities. Method: Semi-structured qualitative interviews were conducted with 54 ‘gay’ business representatives from different European cities. Interviews were recorded, transcribed, translated, and analyzed using a ‘framework’ approach. Results: Many representatives of ‘gay’ businesses reported being willing to provide HIV prevention activities that target MSM in their venues and perceive this as part of improving their corporate image of being a socially responsible enterprise. However, concerns were voiced around issues such as fear of alienating customers, and inciting stigma and discrimination, safe-sex fatigue and lack of knowledge of prevention messages, as well as the need for appropriate condom and lubricant distribution networks. Businesses also reflected on the potential benefits and disadvantages of being involved in a scheme that provides a common and recognizable framework for HIV prevention across multiple European countries. Conclusions: Early conclusions from this exploratory research suggest that a European-wide model of HIV prevention is acceptable and feasible to those working in ‘gay’ businesses. Further investigations, however, are required to develop solutions in order to overcome identified social, cultural and practical barriers.
Perioperative Management of Obstructive Sleep Apnea
Authors: Dhanda Patil Reena , Patil Yash J. 
Published: November 2011

Objectives/Hypothesis(1) To determine the presence of Veterans Affairs (VA) institutional guidelines for the perioperative management of obstructive sleep apnea (OSA); (2) to examine current use of preoperative screening tools for OSA in the VA; and (3) to understand current VA practice patterns regarding postoperative disposition of patients with OSA.Study DesignSurvey study.SettingVeterans Affairs hospitals with surgical services; sample size 102 facilities.SubjectsVeterans Affairs health care providers.MethodsThe authors surveyed health care providers at VA hospitals using a survey tool developed by the authors.ResultsThe response rate was 80%. A variety of preoperative screening tools for OSA were used by respondents, most commonly American Society of Anesthesiologists guidelines (53%). A policy for postoperative disposition of known and presumed OSA was present in 26% and 19% of responses, respectively. Of those respondents reporting a formal postoperative care policy, 48% and 30% admitted patients to a monitored ward bed and surgical intensive care unit, respectively. Of the 74% of respondents unaware of an institutional policy, Anesthesia and Surgery worked together to dictate postoperative disposition of patients with known OSA 73% of the time. The degree of OSA was ranked as the most important factor (58%) influencing postoperative disposition. Ten percent of respondents reported a major perioperative complication attributable to OSA in the past year.ConclusionThis survey study elucidates the heterogeneity of preoperative screening for and postoperative care of veterans with OSA. Future investigators may use these data to formalize institutional policies with regard to patients with OSA, with potentially significant impacts on patient care and usage of financial resources.
Managing Cancer and Living Meaningfully (CALM): A qualitative study of a brief individual psychotherapy for individuals with advanced cancer
Authors: Nissim Rinat , Freeman Emily , Lo Chris , Zimmermann Camilla , Gagliese Lucia , Rydall Anne , Hales Sarah , Rodin Gary 
Published: November 2011

Background: Although psychosocial care has been regarded as central to palliative and supportive care, there have been few empirically tested approaches to individual intervention. Aim: The subjective experience of advanced cancer patients receiving a new manualized brief individual psychotherapy, referred to as Managing Cancer and Living Meaningfully (CALM), was examined prior to the initiation of a randomized controlled trial testing the effectiveness of this intervention. Design: Semi-structured interviews were conducted with patients who had a diagnosis of advanced cancer, and who underwent the intervention. Setting/Participants: Patients were recruited from a large urban regional cancer center in Toronto, Canada. The 10 interviewees included seven women and three men. All had completed between three to six CALM sessions prior to the interview. Results: The CALM intervention was associated with profound and unique patient-identified benefits and no patient-identified risks or concerns. Five interrelated benefits of the intervention were identified: (1) a safe place to process the experience of advanced cancer; (2) permission to talk about death and dying; (3) assistance in managing the illness and navigating the healthcare system; (4) resolution of relational strain; and (5) an opportunity to ‘be seen as a whole person’ within the healthcare system. These benefits were regarded by participants as unique in their cancer journey. Conclusions: Findings from a qualitative study suggest that the CALM intervention provides substantial benefits for patients with advanced cancer prior to the end of life. Findings informed the development of a randomized controlled trial to evaluate the effectiveness of this intervention.
Predicting the spontaneous termination of atrial fibrillation based on Poincare section in the electrocardiogram phase space
Authors: Parvaneh Saman , Hashemi Golpayegani Mohammad Reza , Firoozabadi Mohammad , Haghjoo Majid 
Published: November 2011

Atrial fibrillation (AF) is a commonly encountered cardiac arrhythmia. Predicting the conditions under which AF terminates spontaneously is an important task that would bring great benefit to both patients and clinicians. In this study, a new method was proposed to predict spontaneous AF termination by employing the points of section (POS) coordinates along a Poincare section in the electrocardiogram (ECG) phase space. The AF Termination Database provided by PhysioNet for the Computers in Cardiology Challenge 2004 was applied in the present study. It includes one training dataset and two testing datasets, A and B. The present investigation was initiated by producing a two-dimensional reconstructed phase space (RPS) of the ECG. Then, a Poincare line was drawn in a direction that included the maximum point distribution in the RPS and also passed through the origin of the RPS coordinate system. Afterward, the coordinates of the RPS trajectory intersections with this Poincare line were extracted to capture the local behavior related to the arrhythmia under investigation. The POS corresponding to atrial activity were selected with regard to the fact that similar ECG morphologies such as P waves, which are corresponding to atrial activity, distribute in a specific region of the RPS. Thirteen features were extracted from the selected intersection points to quantify their distributions. To select the best feature subset, a genetic algorithm (GA), in combination with a support vector machine (SVM), was applied to the training dataset. Based on the selected features and trained SVM, the performance of the proposed method was evaluated using the testing datasets. The results showed that 86.67% of dataset A and 80% of dataset B were correctly classified. This classification accuracy is in the same range as or higher than that of recent studies in this area. These results show that the proposed method, in which no complicated QRST cancelation algorithm was used, has the potential to predict AF termination.
In situ vaccination against mycosis fungoides by intratumoral injection of a TLR9 agonist combined with radiation: a phase 1/2 study
Authors: Kim Youn H. , Gratzinger Dita , Harrison Cameron , Brody Joshua D. , Czerwinski Debra K. , Ai Weiyun Z. , Morales Anjali , Abdulla Farah , Xing Leon , Navi Daniel , Tibshirani Robert J. , Advani Ranjana H. , Lingala Bharathi , Shah Sumit , Hoppe Richard T. , Levy Ronald 
Published: November 2011

Abstract
We have developed and previously reported on a therapeutic vaccination strategy for indolent B-cell lymphoma that combines local radiation to enhance tumor immunogenicity with the injection into the tumor of a TLR9 agonist. As a result, antitumor CD8+ T cells are induced, and systemic tumor regression was documented. Because the vaccination occurs in situ, there is no need to manufacture a vaccine product. We have now explored this strategy in a second disease: mycosis fungoides (MF). We treated 15 patients. Clinical responses were assessed at the distant, untreated sites as a measure of systemic antitumor activity. Five clinically meaningful responses were observed. The procedure was well tolerated and adverse effects consisted mostly of mild and transient injection site or flu-like symptoms. The immunized sites showed a significant reduction of CD25+, Foxp3+ T cells that could be either MF cells or tissue regulatory T cells and a similar reduction in S100+, CD1a+ dendritic cells. There was a trend toward greater reduction of CD25+ T cells and skin dendritic cells in clinical responders versus nonresponders. Our in situ vaccination strategy is feasible also in MF and the clinical responses that occurred in a subset of patients warrant further study with modifications to augment these therapeutic effects. This study is registered at www.clinicaltrials.gov as NCT00226993.
FTY720 increases CD74 expression and sensitizes mantle cell lymphoma cells to milatuzumab-mediated cell death
Authors: Alinari Lapo , Mahoney Emilia , Patton John , Zhang Xiaoli , Huynh Lenguyen , Earl Christian T. , Mani Rajeswaran , Mao Yicheng , Yu Bo , Quinion Carl , Towns William H. , Chen Ching-Shih , Goldenberg David M. , Blum Kristie A. , Byrd John C. , Muthusamy Natarajan , Prætorius-Ibba Mette , Baiocchi Robert A. 
Published: November 2011

AbstractMantle cell lymphoma (MCL) is an aggressive B-cell malignancy with a short median survival despite multimodal therapy. FTY720, an immunosuppressive drug approved for the treatment of multiple sclerosis, promotes MCL cell death concurrent with down-modulation of phospho-Akt and cyclin D1 and subsequent cell-cycle arrest. However, the mechanism of FTY720-mediated MCL cell death remains to be fully clarified. In the present study, we show features of autophagy blockage by FTY720 treatment, including accumulation of autolysosomes and increased LC3-II and p62 levels. We also show that FTY720-induced cell death is mediated by lysosomal membrane permeabilization with subsequent translocation of lysosomal hydrolases to the cytosol. FTY720-mediated disruption of the autophagic-lysosomal pathway led to increased levels of CD74, a potential therapeutic target in MCL that is degraded in the lysosomal compartment. This finding provided rationale for examining combination therapy with FTY720 and milatuzumab, an anti-CD74 mAb. Treatment of MCL cell lines and primary tumor cells with FTY720 and milatuzumab resulted in statistically significant enhanced cell death, which was synergistic in blastic variant MCL cell lines. Significant in vivo therapeutic activity of combination treatment was also demonstrated in a preclinical, in vivo model of MCL. These findings support clinical evaluation of this combination in patients with MCL.
Identification of common and cell type specific LXXLL motif EcR cofactors using a bioinformatics refined candidate RNAi screen in Drosophila melanogastercell lines
Authors: Davis Melissa B , SanGil Inigo , Berry Grace , Olayokun Rashidat , Neves Lori H 
Published: November 2011

Abstract
Background
During Drosophila development, titers of the steroid ecdysone trigger and maintain temporal and tissue specific biological transitions. Decades of evidence reveal that the ecdysone response is both unique to specific tissues and distinct among developmental timepoints. To achieve this diversity in response, the several isoforms of the Ecdysone Receptor, which transduce the hormone signal to the genome level, are believed to interact with tissue specific cofactors. To date, little is known about the identity of these cofactor interactions; therefore, we conducted a bioinformatics informed, RNAi luciferase reporter screen against a subset of putative candidate cofactors identified through an in silico proteome screen. Candidates were chosen based on criteria obtained from bioinformatic consensus of known nuclear receptor cofactors and homologs, including amino acid sequence motif content and context.

Results
The bioinformatics pre-screen of the Drosophila melanogaster proteome was successful in identifying an enriched putative candidate gene cohort. Over 80% of the genes tested yielded a positive hit in our reporter screen. We have identified both cell type specific and common cofactors which appear to be necessary for proper ecdysone induced gene regulation. We have determined that certain cofactors act as co-repressors to reduce target gene expression, while others act as co-activators to increase target gene expression. Interestingly, we find that a few of the cofactors shared among cell types have a reversible roles to function as co-repressors in certain cell types while in other cell types they serve as co-activators. Lastly, these proteins are highly conserved, with higher order organism homologs also harboring the LXXLL steroid receptor interaction domains, suggesting a highly conserved mode of steroid cell target specificity.

Conclusions
In conclusion, we submit these cofactors as novel components of the ecdysone signaling pathway in order to further elucidate the dynamics of steroid specificity.
Functional microRNA screening using a comprehensive lentiviral human microRNA expression library
Authors: Poell Jos B , van Haastert Rick J , Cerisoli Francesco , Bolijn Anne S , Timmer Lisette M , Diosdado-Calvo Begoña , Meijer Gerrit A , van Puijenbroek Andre AFL , Berezikov Eugene , Schaapveld Roel QJ , Cuppen Edwin 
Published: November 2011

Abstract

Background
MicroRNAs (miRNAs) are a class of small regulatory RNAs that target sequences in messenger RNAs (mRNAs) to inhibit their protein output. Dissecting the complexities of miRNA function continues to prove challenging as miRNAs are predicted to have thousands of targets, and mRNAs can be targeted by dozens of miRNAs.

Results
To systematically address biological function of miRNAs, we constructed and validated a lentiviral miRNA expression library containing 660 currently annotated and 422 candidate human miRNA precursors. The miRNAs are expressed from their native genomic backbone, ensuring physiological processing. The arrayed layout of the library renders it ideal for high-throughput screens, but also allows pooled screening and hit picking. We demonstrate its functionality in both short- and long-term assays, and are able to corroborate previously described results of well-studied miRNAs.

Conclusions
With the miRNA expression library we provide a versatile tool for the systematic elucidation of miRNA function.