bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of societal and practice contexts on health professionals’ clinical reasoning: a scoping study protocol
Authors: Carrier Annie , Levasseur Mélanie , Freeman Andrew , Mullins Gary , Quénec'hdu Suzanne , Lalonde Louise , Gagnon Michaël , Lacasse Francis 
Published: May 2013

IntroductionIn a context of constrained resources, the efficacy of interventions is a pivotal aim of healthcare systems worldwide. Efficacy of healthcare interventions is highly compromised if clinical reasoning (CR), the process that practitioners use to plan, direct, perform and reflect on client care, is not optimal. The CR process of health professionals is influenced by the institutional dimension (ie, legal, regulatory, administrative and organisational aspects) of their societal and practice contexts. Although several studies have been conducted with respect to the institutional dimension influencing health professionals’ CR, no clear integration of their results is yet available. The aim of this study is to synthesise and disseminate current knowledge on the influence of the institutional dimension of contexts on health professionals’ CR.Methods and analysisA scoping study of the scientific literature from January 1980 to March 2013 will be undertaken to summarise and disseminate research findings about the influence of the institutional dimension on CR. Numerous databases (n=18) from three relevant fields (healthcare, health law and politics and management) will be searched. Extended search strategies will include the manual search of bibliographies, health-related websites, public registries and journals of interest. Data will be collected and analysed using a thematic chart and content analysis. A systematic multidisciplinary team approach will allow optimal identification of relevant studies, as well as effective and valid content analysis and dissemination of the results.DiscussionThis scoping study will provide a rigorous, accurate and up-to-date synthesis of existing knowledge regarding: (1) those aspects of the institutional dimension of health professionals’ societal and practice contexts that impact their CR and (2) how these aspects influence health professionals’ CR. Through the synergy of a multidisciplinary research team from a wide range of expertise, clinical pertinence and an exhaustive dissemination of results to knowledge-users will be ensured.
Portrait of rural emergency departments in Quebec and utilisation of the Quebec Emergency Department Management Guide: a study protocol
Authors: Fleet Richard , Archambault Patrick , Légaré France , Chauny Jean-Marc , Lévesque Jean-Frédéric , Ouimet Mathieu , Dupuis Gilles , Haggerty Jeannie , Poitras Julien , Tanguay Alain , Simard-Racine Geneviève , Gauthier Josée 
Published: May 2013

IntroductionEmergency departments are important safety nets for people who live in rural areas. Moreover, a serious problem in access to healthcare services has emerged in these regions. The challenges of providing access to quality rural emergency care include recruitment and retention issues, lack of advanced imagery technology, lack of specialist support and the heavy reliance on ambulance transport over great distances. The Quebec Ministry of Health and Social Services published a new version of theEmergency Department Management Guide, a document designed to improve the emergency department management and to humanise emergency department care and services. In particular, theGuiderecommends solutions to problems that plague rural emergency departments. Unfortunately, no studies have evaluated the implementation of the proposed recommendations.Methods and analysisTo develop a comprehensive portrait of all rural emergency departments in Quebec, data will be gathered from databases at the Quebec Ministry of Health and Social Services, the Quebec Trauma Registry and from emergency departments and ambulance services managers. Statistics Canada data will be used to describe populations and rural regions. To evaluate the use of the 2006Emergency Department Management Guideand the implementation of its various recommendations, an online survey and a phone interview will be administered to emergency department managers. Two online surveys will evaluate quality of work life among physicians and nurses working at rural emergency departments. Quality-of-care indicators will be collected from databases and patient medical files. Data will be analysed using statistical (descriptive and inferential) procedures.Ethics and disseminationThis protocol has been approved by the CSSS Alphonse–Desjardins research ethics committee (Project MP-HDL-1213-011). The results will be published in peer-reviewed scientific journals and presented at one or more scientific conferences.
Patterns and trends in Pakistan's heterogeneous HIV epidemic
Authors: Reza Tahira , Melesse Dessalegn Y , Shafer Leigh Anne , Salim Momina , Altaf Arshad , Sonia Altaf , Jayaraman Gayatri C , Emmanuel Faran , Thompson Laura H , Blanchard James F 
Published: May 2013

BackgroundConsiderable HIV transmission occurs among injection drug users (IDUs) in Pakistan and recently the HIV prevalence has been increasing among male (MSW),hijra(transgender; HSW) and female (FSW) sex workers. We describe past and estimate future patterns of HIV emergence among these populations in several cities in Pakistan.MethodsThe density of these key populations per 1000 adult men was calculated using 2011 mapping data from Karachi, Lahore, Faisalabad, Larkana, Peshawar and Quetta, and surveillance data were used to assess bridging between these key populations. We used the UNAIDS Estimation and Projection Package model to estimate and project HIV epidemics among these key populations in Karachi, Lahore, Faisalabad and Larkana.ResultsThe density and bridging of key populations varied across cities. Lahore had the largest FSW population (11.5/1000 adult men) and the smallest IDU population (1.7/1000 adult men). Quetta had the most sexual and drug injection bridging between sex workers and IDUs (6.7%, 7.0% and 3.8% of FSW, MSW and HSW, respectively, reported injecting drugs). Model evidence suggests that by 2015 HIV prevalence is likely to reach 17–22% among MSWs/HSWs in Karachi, 44–49% among IDUs in Lahore and 46–66% among IDUs in Karachi. Projection suggests the prevalence may reach as high as 65–75% among IDUs in Faisalabad by 2025. HIV prevalence is also estimated to increase among FSWs, particularly in Karachi and Larkana.ConclusionsThere is a need to closely monitor regional and subpopulation epidemic patterns and implement prevention programmes customised to local epidemics.
Understanding the latency benefits of multi-cloud webservice deployments
Authors: Wu Zhe , Madhyastha Harsha V. 
Published: May 2013

To minimize user-perceived latencies, webservices are often deployed across multiple geographically distributed data centers. The premise of our work is that webservices deployed across multiple cloud infrastructure services can serve users from more data centers than that possible when using a single cloud service, and hence, offer lower latencies to users.
In this paper, we conduct a comprehensive measurement study to understand the potential latency benefits of deploying webservices across three popular cloud infrastructure services - Amazon EC2, Google Compute Engine (GCE), and Microsoft Azure. We estimate that, as compared to deployments on one of these cloud services, users in up to half the IP address prefixes can have their RTTs reduced by over 20% when a webservice is deployed across the three cloud services. When we dig deeper to understand these latency benefits, we make three significant observations. First, when webservices shift from single-cloud to multi-cloud deployments, a significant fraction of prefixes will see latency benefits simply by being served from a different data center in the same location. This is because routing inefficiencies that exist between a prefix and a nearby data center in one cloud service are absent on the path from the prefix to a nearby data center in a different cloud service. Second, despite the latency improvements that a large fraction of prefixes will perceive, users in several locations (e.g., Argentina and Israel) will continue to incur RTTs greater than 100ms even when webservices span three large-scale cloud services (EC2, GCE, and Azure). Finally, we see that harnessing the latency benefits offered by multi-cloud deployments is likely to be challenging in practice; our measurements show that the data center which offers the lowest latency to a prefix often fluctuates between different cloud services, thus necessitating replication of data.
Critical Role of STAT3 in IL-6–Mediated Drug Resistance in Human Neuroblastoma
Authors: Ara Tasnim , Nakata Rie , Sheard Michael A. , Shimada Hiroyuki , Buettner Ralf , Groshen Susan G. , Ji Lingyun , Yu Hua , Jove Richard , Seeger Robert C. , DeClerck Yves A. 
Published: May 2013

Abstract
Drug resistance is a major cause of treatment failure in cancer. Here, we have evaluated the role of STAT3 in environment-mediated drug resistance (EMDR) in human neuroblastoma. We determined that STAT3 was not constitutively active in most neuroblastoma cell lines but was rapidly activated upon treatment with interleukin (IL)-6 alone and in combination with the soluble IL-6 receptor (sIL-6R). Treatment of neuroblastoma cells with IL-6 protected them from drug-induced apoptosis in a STAT3-dependent manner because the protective effect of IL-6 was abrogated in the presence of a STAT3 inhibitor and upon STAT3 knockdown. STAT3 was necessary for the upregulation of several survival factors such as survivin (BIRC5) and Bcl-xL (BCL2L1) when cells were exposed to IL-6. Importantly, IL-6–mediated STAT3 activation was enhanced by sIL-6R produced by human monocytes, pointing to an important function of monocytes in promoting IL-6–mediated EMDR. Our data also point to the presence of reciprocal activation of STAT3 between tumor cells and bone marrow stromal cells including not only monocytes but also regulatory T cells (Treg) and nonmyeloid stromal cells. Thus, the data identify an IL-6/sIL-6R/STAT3 interactive pathway between neuroblastoma cells and their microenvironment that contributes to drug resistance. Cancer Res; 73(13); 3852–64. ©2013 AACR.
Cancer Stem–like Cell Marker CD44 Promotes Bone Metastases by Enhancing Tumorigenicity, Cell Motility, and Hyaluronan Production
Authors: Hiraga Toru , Ito Susumu , Nakamura Hiroaki 
Published: May 2013

Abstract
CD44, an adhesion molecule that binds to the extracellular matrix, primarily to hyaluronan (HA), has been implicated in cancer cell migration, invasion, and metastasis. CD44 has also recently been recognized as a marker for stem cells of several types of cancer. However, the roles of CD44 in the development of bone metastasis are unclear. Here, we addressed this issue by using bone metastatic cancer cell lines, in which CD44 was stably knocked down. Tumor sphere formation and cell migration and invasion were significantly inhibited by CD44 knockdown. Furthermore, the downregulation of CD44 markedly suppressed tumorigenicity and bone metastases in nude mice. Of note, the number of osteoclasts decreased in the bone metastases. Microarray analysis revealed that the expression of HA synthase 2 was downregulated in CD44-knockdown cells. The localization of HA in the bone metastatic tumors was also markedly reduced. We then examined the roles of CD44–HA interaction in bone metastasis using 4-methylumbelliferone (4-MU), an inhibitor of HA synthesis. 4-MU decreased tumor sphere and osteoclast-like cell formation in vitro. Moreover, 4-MU inhibited bone metastases in vivo with reduced number of osteoclasts. These results collectively suggest that CD44 expression in cancer cells promotes bone metastases by enhancing tumorigenicity, cell migration and invasion, and HA production. Our results also suggest the possible involvement of CD44-expressing cancer stem cells in the development of bone metastases through interaction with HA. CD44–HA interaction could be a potential target for therapeutic intervention for bone metastases. Cancer Res; 73(13); 4112–22. ©2013 AACR.
Meat-Related Mutagens and Pancreatic Cancer: Null Results from a Clinic-Based Case–Control Study
Authors: Jansen Rick J. , Robinson Dennis P. , Frank Ryan D. , Stolzenberg-Solomon Rachael Z. , Bamlet William R. , Oberg Ann L. , Rabe Kari G. , Olson Janet E. , Petersen Gloria M. , Sinha Rashmi , Anderson Kristin E. 
Published: May 2013

Abstract
Background: Pancreatic cancer is a devastating disease for which the role of dietary factors remains inconclusive. The study objective was to evaluate risk of pancreatic cancer associated with meat preparation methods and meat-related mutagen consumption using a clinic-based case–control design.
Methods: There were 384 cases and 983 controls; subjects provided demographic information and completed a 144-item food frequency questionnaire, which was used to estimate meat mutagen intake using the National Cancer Institute's CHARRED database (Bethesda, MD). Logistic regression was used to calculate ORs and 95% confidence intervals (CI), adjusted for factors including age, sex, cigarette smoking, body mass index, and diabetes mellitus.
Results: Overall, the findings were null with respect to meat mutagen intake and pancreatic cancer.
Conclusions: The results do not support an association between well-done meat or meat-related mutagen intake and pancreatic cancer and contrast with generally increased risks reported in previous studies.
Impact: These data contribute to evidence about pancreatic cancer and potentially carcinogenic compounds in meat. Cancer Epidemiol Biomarkers Prev; 22(7); 1336–9. ©2013 AACR.
Stearoyl-CoA Desaturase 1 Is a Novel Molecular Therapeutic Target for Clear Cell Renal Cell Carcinoma
Authors: von Roemeling Christina A. , Marlow Laura A. , Wei Johnny J. , Cooper Simon J. , Caulfield Thomas R. , Wu Kevin , Tan Winston W. , Tun Han W. , Copland John A. 
Published: May 2013

Abstract
Purpose: We set out to identify Stearoyl-CoA desaturase 1 (SCD1) as a novel molecular target in clear cell renal cell carcinoma (ccRCC) and examine its role in tumor cell growth and viability in vitro and in vivo independently as well as in combination with current U.S. Food and Drug Administration (FDA)-approved regimens.
Experimental Design: Patient normal and ccRCC tissue samples and cell lines were examined for SCD1 expression. Genetic knockdown models and targeted inhibition of SCD1 through use of a small molecule inhibitor, A939572, were analyzed for growth, apoptosis, and alterations in gene expression using gene array analysis. Therapeutic models of synergy were evaluated utilizing pharmacologic inhibition of SCD1 with the tyrosine kinase inhibitors (TKI) sunitinib and pazopanib, and the mTOR inhibitor temsirolimus.
Results: Our studies identify increased SCD1 expression in all stages of ccRCC. Both genetic knockdown and pharmacologic inhibition of SCD1 decreased tumor cell proliferation and induced apoptosis in vitro and in vivo. Upon gene array, quantitative real-time PCR, and protein analysis of A939572-treated or SCD1 lentiviral knockdown samples, induction of endoplasmic reticulum stress response signaling was observed, providing mechanistic insight for SCD1 activity in ccRCC. Furthermore, combinatorial application of A939572 with temsirolimus synergistically inhibited tumor growth in vitro and in vivo.
Conclusions: Increased SCD1 expression supports ccRCC viability and therefore we propose it as a novel molecular target for therapy either independently or in combination with an mTOR inhibitor for patients whose disease cannot be remedied with surgical intervention, such as in cases of advanced or metastatic disease. Clin Cancer Res; 19(9); 2368–80. ©2013 AACR.
Conjunctival Melanomas Harbor BRAF and NRAS Mutations and Copy Number Changes Similar to Cutaneous and Mucosal Melanomas
Authors: Griewank Klaus G. , Westekemper Henrike , Murali Rajmohan , Mach Monika , Schilling Bastian , Wiesner Thomas , Schimming Tobias , Livingstone Elisabeth , Sucker Antje , Grabellus Florian , Metz Claudia , Süsskind Daniela , Hillen Uwe , Speicher Michael R. , Woodman Scott E. , Steuhl Klaus-Peter , Schadendorf Dirk 
Published: May 2013

Abstract
Purpose: Conjunctival melanoma is a rare but potentially deadly tumor of the eye. Despite effective local therapies, recurrence and metastasis remain frequent. Once the tumor has metastasized, treatment options are limited and the prognosis is poor. To date, little is known of the genetic alterations in conjunctival melanomas.
Experimental Design: We conducted genetic analysis of 78 conjunctival melanomas, to our knowledge the largest cohort reported to date. An oncogene hotspot array was run on 38 samples, screening for a panel of known cancer-relevant mutations. Thirty tumors were analyzed for genome-wide copy number alterations (CNA) using array-based comparative genomic hybridization. Sanger sequencing of selected target mutations was conducted in all samples.
Results: BRAF mutations were identified in 23 of 78 (29%) tumors. NRAS mutations, previously not recognized as relevant in conjunctival melanoma, were detected in 14 of 78 (18%) tumors. We found CNAs affecting various chromosomes distributed across the genome in a pattern reminiscent of cutaneous and mucosal melanoma but differing markedly from uveal melanoma.
Conclusions: The presence of NRAS or BRAF mutations in a mutually exclusive pattern in roughly half (47%) of conjunctival melanomas and the pattern of CNAs argue for conjunctival melanoma being closely related to cutaneous and mucosal melanoma but entirely distinct from uveal melanoma. Patients with metastatic conjunctival melanoma should be considered for therapeutic modalities available for metastatic cutaneous and mucosal melanoma including clinical trials of novel agents. Clin Cancer Res; 19(12); 3143–52. ©2013 AACR.
Walking Impairment Questionnaire Improves Mortality Risk Prediction Models in a High-Risk Cohort Independent of Peripheral Arterial Disease Status
Authors: Nead Kevin T. , Zhou Margaret , Caceres Roxanne Diaz , Olin Jeffrey W. , Cooke John P. , Leeper Nicholas J. 
Published: May 2013

Background—
The Walking Impairment Questionnaire (WIQ) is a subjective measure of patient-reported walking performance developed for peripheral arterial disease. The purpose of this study is to examine whether this simple tool can improve the predictive capacity of established risk models and whether the WIQ can be used in patients without peripheral arterial disease.

Methods and Results—

At baseline we assessed the walking distance, stair-climbing, and walking speed WIQ category scores among individuals who were undergoing coronary angiography. During a median follow-up of 5.0 years, there were 172 mortalities among 1417 study participants. Adjusted Cox proportional hazards models showed that all 3 WIQ categories independently predicted future all-cause and cardiovascular mortality, including among individuals without peripheral arterial disease (
P
<0.001). Compared with the cardiovascular risk factors model, we observed significantly increased risk discrimination with a C-index of 0.741 (change in C-index, 0.040; 95% confidence interval, 0.011–0.068) and 0.832 (change in C-index, 0.080; 95% confidence interval, 0.034–0.126) for all-cause and cardiovascular mortality, respectively. Examination of risk reclassification using the net reclassification improvement index showed a 48.4% (
P
<0.001) improvement for all-cause mortality and a 77.4% (
P
<0.001) improvement for cardiovascular mortality compared with the cardiovascular risk factors model.

Conclusions—
All 3 WIQ categories independently predicted future all-cause and cardiovascular mortality. Importantly, we found that this subjective measure of walking ability could be extended to patients without peripheral arterial disease. The addition of the WIQ scores to established cardiovascular risk models significantly improved risk discrimination and reclassification, suggesting broad clinical use for this simple, inexpensive test.
A metadata-aware application for remote scoring and exchange of tissue microarray images
Authors: Morris Lorna , Tsui Andrew , Crichton Charles , Harris Steve , Maccallum Peter H , Howat William J , Davies Jim , Brenton James D , Caldas Carlos 
Published: May 2013

AbstractBackgroundThe use of tissue microarrays (TMA) and advances in digital scanning microscopy has enabled the collection of thousands of tissue images. There is a need for software tools to annotate, query and share this data amongst researchers in different physical locations.ResultsWe have developed an open source web-based application for remote scoring of TMA images, which exploits the value of Microsoft Silverlight Deep Zoom to provide a intuitive interface for zooming and panning around digital images. We use and extend existing XML-based standards to ensure that the data collected can be archived and that our system is interoperable with other standards-compliant systems.ConclusionThe application has been used for multi-centre scoring of TMA slides composed of tissues from several Phase III breast cancer trials and ten different studies participating in the International Breast Cancer Association Consortium (BCAC). The system has enabled researchers to simultaneously score large collections of TMA and export the standardised data to integrate with pathological and clinical outcome data, thereby facilitating biomarker discovery.