bluuebunny/crossref_metadata_2025_split huggingface dataset:
Venous thromboembolism risk associated with protracted work- and computer-related seated immobility: A case-control study
Authors: Braithwaite Irene , Healy Bridget , Cameron Laird , Weatherall Mark , Beasley Richard 
Published: August 2016

Objective To examine the association between venous thromboembolism and prolonged work- and computer-related seated immobility. Design A case-control study. Participants and setting Cases were 200 patients attending venous thromboembolism clinics with a history of deep vein thrombosis and/or pulmonary embolism in the past six months, and controls were 200 patients treated in fracture clinic for an upper limb injury in the past six months. Main outcome measures Logistic regression was used to estimate the association between venous thromboembolism and prolonged work- and computer-related seated immobility in the 28 days before the index event. Prolonged work- and computer-related seated immobility was defined firstly as a categorical variable with at least 10 h seated in a 24-h period, including at least 2 h without getting up; and secondly as the actual time spent seated in a 24-h period. Results Prolonged work- and computer-related seated immobility (categorical variable) was present in 36 (18%) cases and 31 (15.5%) controls. In multivariate analysis, there was no significant association between prolonged seated immobility and venous thromboembolism, odds ratio 1.18 (95% CI 0.56 to 2.48), P = 0.67. For the mean and maximum number of hours seated in a 24-h period, the odds ratios for the association per additional hour seated with venous thromboembolism were 1.08 (95% CI 1.01 to 1.6), P = 0.02 and 1.04 (95% CI 0.99 to 1.09), P = 0.08, respectively. Conclusion This study found a weak association between venous thromboembolism and prolonged work- and computer-related seated immobility, with increasing mean hours seated associated with a higher risk of venous thromboembolism.
miR-146b antagomir–treated human Tregs acquire increased GVHD inhibitory potency
Authors: Lu Yunjie , Hippen Keli L. , Lemire Amanda L. , Gu Jian , Wang Weizhi , Ni Xuhao , Ranganathan Parvathi , Levine Bruce L. , Riley James L. , June Carl H. , Turka Laurence A. , Munn David H. , Garzon Ramiro , Lu Ling , Blazar Bruce R. 
Published: August 2016

Key Points
tTregs express high miR-146b levels and downregulate TRAF6 mRNA and NF-κB activation, which is essential for tTreg function. miR-146b antagomir enhances in vitro and in vivo tTreg suppression and persistence as well as xenogenic GVHD lethality.
BRG1 interacts with GLI2 and binds Mef2c gene in a hedgehog signalling dependent manner during in vitro cardiomyogenesis
Authors: Fair Joel Vincent , Voronova Anastassia , Bosiljcic Neven , Rajgara Rashida , Blais Alexandre , Skerjanc Ilona Sylvia 
Published: August 2016

Abstract
Background
The Hedgehog (HH) signalling pathway regulates cardiomyogenesis in vivo and in differentiating P19 embryonal carcinoma (EC) cells, a mouse embryonic stem (mES) cell model. To further assess the transcriptional role of HH signalling during cardiomyogenesis in stem cells, we studied the effects of overexpressing GLI2, a primary transducer of the HH signalling pathway, in mES cells.

Results
Stable GLI2 overexpression resulted in an enhancement of cardiac progenitor-enriched genes, Mef2c, Nkx2-5, and Tbx5 during mES cell differentiation. In contrast, pharmacological blockade of the HH pathway in mES cells resulted in lower expression of these genes. Mass spectrometric analysis identified the chromatin remodelling factor BRG1 as a protein which co-immunoprecipitates with GLI2 in differentiating mES cells. We then determined that BRG1 is recruited to a GLI2-specific Mef2c gene element in a HH signalling-dependent manner during cardiomyogenesis in P19 EC cells, a mES cell model.

Conclusions
Thus, we propose a mechanism where HH/GLI2 regulates the expression of Mef2c by recruiting BRG1 to the Mef2c gene, most probably via chromatin remodelling, to ultimately regulate in vitro cardiomyogenesis.
A pilot investigation of the prevalence of US‐detectable forefoot joint pathology and reported foot‐related disability in participants with systemic lupus erythematosus
Authors: Mukherjee Sandeep , Cherry Lindsey , Zarroug Jalaa , Culliford David , Bowen Catherine , Arden Nigel , Edwards Christopher 
Published: August 2016

AbstractBackgroundThe main aim of this study was to determine the prevalence of US‐detectable forefoot bursae, metatarsophalangeal (MTP) joint and metacarpophalangeal (MCP) joint synovial hypertrophy (SH), Power Doppler (PD) signal or erosion in participants with systemic lupus erythematosus (SLE). A secondary aim was to determine the strength of potential association between patient reported foot‐related disability and US‐detected forefoot bursae, MTP joint SH, PD signal or erosion in participants with SLE.MethodA cross‐sectional observational study of 20 participants with SLE was completed to determine the prevalence of US‐detected forefoot bursal, MTP and MCP joint pathology. Patient‐reported foot‐related impairment and activity limitation (accumulatively referred to as disability) were also recorded. Spearmans' Rank Correlation analyses were completed to determine the potential strength of association between US‐detected pathology and patient report disability.ResultsThe prevalence of MTP joint SH and PD was 80 % (16/20) and 10 % (2/20), respectively. The prevalence of MCP joint SH and PD was 60 % (12/20) and 30 % (6/20) respectively. A significant association was noted between PD scores for the MTP joints and MCP joints (r = 0.556; p = 0.011) although this was not demonstrated for SH scores (r = 0.176; p = 0.459). Significant associations between forefoot bursal prevalence and MTP joint PD were noted (r = 0.467; p = 0.038). The prevalence of bursae and bursal PD (grade 2 or above) was 100 % (20/20) and 10 % (2/20), respectively. Moderate foot‐related impairment and activity limitation was reported by 95 and 85 % of participants respectively.ConclusionThis pilot study suggests that US‐detected MTP, MCP joint and forefoot bursal abnormalities may be prevalent in participants with SLE and they may experience a moderate level of foot‐related disability. Further research is required to substantiate these preliminary findings.
Study on chemotaxis and chemokinesis of bone marrow-derived mesenchymal stem cells in hydrogel-based 3D microfluidic devices
Authors: Yoon Dayoung , Kim Hyerim , Lee Eojin , Park Min Hee , Chung Seok , Jeon Hojeong , Ahn Cheol-Hee , Lee Kangwon 
Published: August 2016

Abstract

Background
Controlling the fate of mesenchymal stems cells (MSCs) including proliferation, migration and differentiation has recently been studied by many researchers in the tissue engineering field. Especially, recruitment of stem cells to injury sites is the first and crucial step in tissue regeneration. Although significant progress has been made in the chemotactic migration of MSCs, MSC migration in three dimensional environments remains largely unknown. We developed a 3D hydrogel-based microfluidic-device to study the migration behavior of human MSCs in the presence of stromal-cell derived factor-1α (SDF-1α), interleukin 8 (IL-8) and Substance P (SP) which have been utilized as chemoattractant candidates of human mesenchymal stem cells (hMSCs).

Results

We systematically investigated the chemotactic migration behaviors of hMSCs and their responses to SDF-1α, IL-8, and SP. SDF-1α was shown to be the most fascinating chemoattractant candidate among those factors at a certain time point. We also found that each chemokine showed different chemoattractant abilities according to their concentration. In the case of SP, this factor showed chemokinesis not chemotaxis. Especially at a 7–8 × 10
−8
M concentration range, the chemokinesis ability driven by SP was further increased. The data suggest that some factors at the optimal concentration exhibit chemokinesis or chemotaxis in a 3D hydrogel-based microfluidic device.

Conclusion
In this study on chemotaxis and chemokinesis of hMSCs, the system parameters such as chemokine concentration, system stability, and 2D or 3D microenvironment are critically important to obtain meaningful results.
Subtype-Dependent Relationship Between Young Age at Diagnosis and Breast Cancer Survival
Authors: Partridge Ann H. , Hughes Melissa E. , Warner Erica T. , Ottesen Rebecca A. , Wong Yu-Ning , Edge Stephen B. , Theriault Richard L. , Blayney Douglas W. , Niland Joyce C. , Winer Eric P. , Weeks Jane C. , Tamimi Rulla M. 
Published: August 2016

Purpose Young women are at increased risk for developing more aggressive subtypes of breast cancer. Although previous studies have shown a higher risk of breast cancer recurrence and death among young women with early-stage breast cancer, they have not adequately addressed the role of tumor subtype in outcomes. Methods We examined data from women with newly diagnosed stage I to III breast cancer presenting to one of eight National Comprehensive Cancer Network centers between January 2000 and December 2007. Multivariable Cox proportional hazards models were used to assess the relationship between age and breast cancer–specific survival. Results A total of 17,575 women with stage I to III breast cancer were eligible for analysis, among whom 1,916 were ≤ 40 years of age at diagnosis. Median follow-up time was 6.4 years. In a multivariable Cox proportional hazards model controlling for sociodemographic, disease, and treatment characteristics, women ≤ 40 years of age at diagnosis had greater breast cancer mortality (hazard ratio [HR], 1.4; 95% CI, 1.2 to 1.7). In stratified analyses, age ≤ 40 years was associated with statistically significant increases in risk of breast cancer death among women with luminal A (HR, 2.1; 95% CI, 1.4 to 3.2) and luminal B (HR 1.4; 95% CI, 1.1 to 1.9) tumors, with borderline significance among women with triple-negative tumors (HR, 1.4; 95% CI, 1.0 to 1.8) but not among those with human epidermal growth factor receptor 2 subtypes (HR, 1.2; 95% CI, 0.8 to 1.9). In an additional model controlling for detection method, young age was associated with significantly increased risk of breast cancer death only among women with luminal A tumors. Conclusion The effect of age on survival of women with early breast cancer seems to vary by breast cancer subtype. Young age seems to be particularly prognostic in women with luminal breast cancers.
The BATTLE-2 Study: A Biomarker-Integrated Targeted Therapy Study in Previously Treated Patients With Advanced Non–Small-Cell Lung Cancer
Authors: Papadimitrakopoulou Vassiliki , Lee J. Jack , Wistuba Ignacio I. , Tsao Anne S. , Fossella Frank V. , Kalhor Neda , Gupta Sanjay , Byers Lauren Averett , Izzo Julie G. , Gettinger Scott N. , Goldberg Sarah B. , Tang Ximing , Miller Vincent A. , Skoulidis Ferdinandos , Gibbons Don L. , Shen Li , Wei Caimiao , Diao Lixia , Peng S. Andrew , Wang Jing , Tam Alda L. , Coombes Kevin R. , Koo Ja Seok , Mauro David J. , Rubin Eric H. , Heymach John V. , Hong Waun Ki , Herbst Roy S. 
Published: August 2016

Purpose By applying the principles of real-time biopsy, biomarker-based, adaptively randomized studies in non–small-cell lung cancer (NSCLC) established by the Biomarker-Integrated Approaches of Targeted Therapy for Lung Cancer Elimination (BATTLE) trial, we conducted BATTLE-2 (BATTLE-2 Program: A Biomarker-Integrated Targeted Therapy Study in Previously Treated Patients With Advanced Non-Small Cell Lung Cancer), an umbrella study to evaluate the effects of targeted therapies focusing on KRAS-mutated cancers. Patients and Methods Patients with advanced NSCLC (excluding sensitizing EGFR mutations and ALK gene fusions) refractory to more than one prior therapy were randomly assigned, stratified by KRAS status, to four arms: (1) erlotinib, (2) erlotinib plus MK-2206, (3) MK-2206 plus AZD6244, or (4) sorafenib. Tumor gene expression profiling–targeted next-generation sequencing was performed to evaluate predictive and prognostic biomarkers. Results Two hundred patients, 27% with KRAS-mutated (KRAS mut+) tumors, were adaptively randomly assigned to erlotinib (n = 22), erlotinib plus MK-2206 (n = 42), MK-2206 plus AZD6244 (n = 75), or sorafenib (n = 61). In all, 186 patients were evaluable, and the primary end point of an 8-week disease control rate (DCR) was 48% (arm 1, 32%; arm 2, 50%; arm 3, 53%; and arm 4, 46%). For KRAS mut+ patients, DCR was 20%, 25%, 62%, and 44% whereas for KRAS wild-type patients, DCR was 36%, 57%, 49%, and 47% for arms 1, 2, 3, and 4, respectively. Median progression-free survival was 2.0 months, not different by KRAS status, 1.8 months for arm 1, and 2.5 months for arms 2 versus arms 3 and 4 in KRAS mut+ patients (P = .04). Median overall survival was 6.5 months, 9.0 and 5.1 months for arms 1 and 2 versus arms 3 and 4 in KRAS wild-type patients (P = .03). Median overall survival was 7.5 months in mesenchymal versus 5 months in epithelial tumors (P = .02). Conclusion Despite improved progression-free survival on therapy that did not contain erlotinib for KRAS mut+ patients and improved prognosis for mesenchymal tumors, better biomarker-driven treatment strategies are still needed.
Innovative Approach to the Transformation of the Organizations Personnel Policy in Connection With Mental Values Changes of Young Employees
Authors: Ширшова  , Shirshova O. , Дементьева  , Dementeva D. 
Published: August 2016

The article examines an innovative approach to change and correct the personnel policy of the company according to the young employees using the knowledge
of generational theory. In the last years the same category of employees is young generation Y, this is why we can see the obvious change of mental values and
attitudes of young people in the context of beliefs and expectations of the employer. The article analyzes the theoretical aspects of strategic human resource
management, and presents a program of development of young professionals. Realization of this program allows overcoming the differences of generations
of managers and subordinates within the company.
The Impact of Competing Ads on Click Performance in Sponsored Search
Authors: Agarwal Ashish , Mukhopadhyay Tridas 
Published: August 2016

Our research examines the impact of competing ads on click performance of an ad in sponsored search. We use a unique data set of 1,267 advertiser keyword pairs with differing ad quality related to 360 keywords from a search engine to evaluate the click performance. We find that competing high-quality ads, appearing above the focal ad, have a lower negative effect on the click performance as compared to competing low-quality ads. We also find that this effect of competing ads varies with the ad position and the type of keyword. In general, the negative effect of competing high-quality ads decreases at low positions as compared to high positions. Furthermore, this decrease in the negative effect of competing high-quality ads is more substantial for specific keywords.Our results reveal consumer behavior in evaluating different quality ads in sponsored search. More specifically, our results suggest that consumers use the presence of high-quality competing ads as a signal of higher quality of the focal ad. Our findings can help advertisers better evaluate their relative performance for different positions for various types of keywords. This can also help evaluate the efficacy of the auction design mechanism.
5‐HT2B receptor antagonists attenuate myofibroblast differentiation and subsequent fibrotic responses in vitro and in vivo
Authors: Löfdahl Anna , Rydell‐Törmänen Kristina , Müller Catharina , Martina Holst C. , Thiman Lena , Ekström Gunilla , Wenglén Christina , Larsson‐Callerfelt Anna‐Karin , Westergren‐Thorsson Gunilla 
Published: August 2016

AbstractPulmonary fibrosis is characterized by excessive accumulation of connective tissue, along with activated extracellular matrix (ECM)‐producing cells, myofibroblasts. The pathological mechanisms are not well known, however serotonin (5‐HT) and 5‐HT class 2 (5‐HT2) receptors have been associated with fibrosis. The aim of the present study was to investigate the role of 5‐HT2B receptors in fibrosis, using small molecular 5‐HT2B receptor antagonists EXT5 and EXT9, with slightly different receptor affinity. Myofibroblast differentiation [production of alpha‐smooth muscle actin (α‐SMA)] and ECM synthesis were quantified in vitro, and the effects of the receptor antagonists were evaluated. Pulmonary fibrosis was also modeled in mice by subcutaneous bleomycin administrations (under light isoflurane anesthesia), and the effects of receptor antagonists on tissue density, collagen‐producing cells, myofibroblasts and decorin expression were investigated. In addition, cytokine expression was analyzed in serum. Lung fibroblasts displayed an increased α‐SMA (P < 0.05) and total proteoglycan production (P < 0.01) when cultured with TGF‐β1 together with 5‐HT, which were significantly reduced with both receptor antagonists. Following treatment with EXT5 or EXT9, tissue density, expression of decorin, number of collagen‐producing cells, and myofibroblasts were significantly decreased in vivo compared to bleomycin‐treated mice. Receptor antagonization also significantly reduced systemic levels of TNF‐α and IL‐1β, indicating a role in systemic inflammation. In conclusion, 5‐HT2B receptor antagonists have potential to prevent myofibroblast differentiation, in vitro and in vivo, with subsequent effect on matrix deposition. The attenuating effects of 5‐HT2B receptor antagonists on fibrotic tissue remodeling suggest these receptors as novel targets for the treatment of pulmonary fibrosis.
Parallel reverse genetic screening in mutant human cells using transcriptomics
Authors: Gapp Bianca V , Konopka Tomasz , Penz Thomas , Dalal Vineet , Bürckstümmer Tilmann , Bock Christoph , Nijman Sebastian MB 
Published: August 2016

AbstractReverse genetic screens have driven gene annotation and target discovery in model organisms. However, many disease‐relevant genotypes and phenotypes cannot be studied in lower organisms. It is therefore essential to overcome technical hurdles associated with large‐scale reverse genetics in human cells. Here, we establish a reverse genetic approach based on highly robust and sensitive multiplexed RNA sequencing of mutant human cells. We conduct 10 parallel screens using a collection of engineered haploid isogenic cell lines with knockouts covering tyrosine kinases and identify known and unexpected effects on signaling pathways. Our study provides proof of concept for a scalable approach to link genotype to phenotype in human cells, which has broad applications. In particular, it clears the way for systematic phenotyping of still poorly characterized human genes and for systematic study of uncharacterized genomic features associated with human disease.
Health Concept and Knowledge Management: Twenty-five Years of Evolution
Authors: Cornet R. , Chute C. G. 
Published: August 2016

Summary
Objectives: The fields of health terminology, classification, ontology, and related information models have evolved dramatically over the past 25 years. Our objective was to review notable trends, described emerging or enabling technologies, and highlight major terminology systems during the interval.
Methods: We review the progression in health terminology systems informed by our own experiences as part of the community involved in this work, reinforced with literature review and citation.
Results: The transformation in size, scope, complexity, and adoption of health terminological systems and information models has been tremendous, on the scale of orders of magnitude.
Conclusion: The present “big science” era of inference and discovery in biomedicine would not have been possible or scalable absent the growth and maturation of health terminology systems and information models over the past 25 years.
Parent Experience With False-Positive Newborn Screening Results for Cystic Fibrosis
Authors: Hayeems Robin Z. , Miller Fiona A. , Barg Carolyn J. , Bombard Yvonne , Kerr Elizabeth , Tam Karen , Carroll June C. , Potter Beth K. , Chakraborty Pranesh , Davies Christine , Milburn Jennifer , Patton Sarah , Bytautas Jessica P. , Taylor Louise , Price April , Gonska Tanja , Keenan Katherine , Ratjen Felix , Guttmann Astrid 
Published: August 2016

BACKGROUND:
The risk of psychosocial harm in families of infants with false-positive (FP) newborn bloodspot screening (NBS) results for cystic fibrosis (CF) is a longstanding concern. Whether well designed retrieval and confirmatory testing systems can mitigate risks remains unknown.

METHODS:
Using a mixed-methods cohort design, we obtained prospective self-report data from mothers of infants with FP CF NBS results 2 to 3 months after confirmatory testing at Ontario’s largest follow-up center, and from a randomly selected control sample of mothers of screen negative infants from the same region. Mothers completed a questionnaire assessing experience and psychosocial response. A sample of mothers of FP infants completed qualitative interviews.

RESULTS:
One hundred thirty-four mothers of FP infants (response rate, 55%) and 411 controls (response rate, 47%) completed questionnaires; 54 mothers of FP infants were interviewed. Selected psychosocial response measures did not detect psychosocial distress in newborns or 1 year later (P &gt; .05). Mothers recalled distress during notification of the positive result and in the follow-up testing period related to fear of chronic illness, but valued the screening system of care in mitigating concerns.

CONCLUSIONS:
Although immediate distress was reported among mothers of FP infants, selected psychometric tools did not detect these concerns. The NBS center from which mothers were recruited minimizes delay between notification and confirmatory testing and ensures trained professionals are communicating results and facilitating follow-up. These factors may explain the presence of minimal psychosocial burden. The screening system reflected herein may be a model for NBS programs working to minimize FP-related psychosocial harm.
The Doctrine of Discovery as a Doctrine of Domination
Authors: Greenberg Joy H. 
Published: August 2016

Sheldon Wolfchild (dir.), The Doctrine of Discovery: Unmasking the Domination Code (38Plus2 Productions, 2014), DVD, $50US. Steven T. Newcomb, Pagans in the Promised Land: Decoding the Doctrine of Christian Discovery (Golden, CO: Fulcrum Books, 2008), 216 pp., $19.95US (pbk). ISBN: 978-1-55591-642-8.