bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investing in prospective cohorts for etiologic study of occupational exposures
Authors: Blair A. , Hines C.J. , Thomas K.W. , Alavanja M.C.R. , Freeman L.E. Beane , Hoppin J.A. , Kamel F. , Lynch C.F. , Lubin J.H. , Silverman D.T. , Whelan E. , Zahm S. H. , Sandler D. P. 
Published: January 2015

Prospective cohorts have played a major role in understanding the contribution of diet, physical activity, medical conditions, and genes to the development of many diseases, but have not been widely used for occupational exposures. Studies in agriculture are an exception. We draw upon our experience using this design to study agricultural workers to identify conditions that might foster use of prospective cohorts to study other occupational settings.Prospective cohort studies are perceived by many as the strongest epidemiologic design. It allows updating of information on exposure and other factors, collection of biologic samples before disease diagnosis for biomarker studies, assessment of effect modification by genes, lifestyle, and other occupational exposures, and evaluation of a wide range of health outcomes. Increased use of prospective cohorts would be beneficial in identifying hazardous exposures in the workplace. Occupational epidemiologists should seek opportunities to initiate prospective cohorts to investigate high priority, occupational exposures. Am. J. Ind. Med. 58:113–122, 2015. © 2015 Wiley Periodicals, Inc.
Overview of the National Occupational Mortality Surveillance (NOMS) system: Leukemia and acute myocardial infarction risk by industry and occupation in 30 US states 1985–1999, 2003–2004, and 2007
Authors: Robinson Cynthia F. , Walker James T. , Sweeney Marie H. , Shen Rui , Calvert Geoffrey M. , Schumacher Pam K. , Ju Jun , Nowlin Susan 
Published: January 2015

BackgroundCancer and chronic disease are leading causes of death in the US with an estimated cost of $46 billion.MethodsWe analyzed 11 million cause‐specific deaths of US workers age 18–64 years in 30 states during 1985–1999, 2003–2004, and 2007 by occupation, industry, race, gender, and Hispanic origin.ResultsThe highest significantly elevated proportionate leukemia mortality was observed in engineers, protective service, and advertising sales manager occupations and in banks/savings &loans/credit agencies, public safety, and public administration industries. The highest significantly elevated smoking‐adjusted acute myocardial infarction mortality was noted in industrial and refractory machinery mechanics, farmers, mining machine operators, and agricultural worker occupations; and wholesale farm supplies, agricultural chemical, synthetic rubber, and agricultural crop industries.ConclusionsSignificantly elevated risks for acute myocardial infarction and leukemia were observed across several occupations and industries that confirm existing reports and add new information. Interested investigators can access the NOMS website at http://www.cdc.gov/niosh/topics/NOMS/. Am. J. Ind. Med. 58:123–137, 2015. © 2015 Wiley Periodicals, Inc.
Predictors of Long‐Term Renal Outcome in Lupus Nephritis Trials: Lessons Learned from the Euro‐Lupus Nephritis Cohort
Authors: Dall'Era Maria , Cisternas Miriam G. , Smilek Dawn E. , Straub Laura , Houssiau Frédéric A. , Cervera Ricard , Rovin Brad H. , Mackay Meggan 
Published: January 2015

ObjectiveThere is a need to determine which response measures in lupus nephritis trials are most predictive of good long‐term renal function. We used data from the Euro‐Lupus Nephritis Trial to evaluate the performance of proteinuria, serum creatinine (Cr), and urinary red blood cells (RBCs) as predictors of good long‐term renal outcome.MethodsPatients from the Euro‐Lupus Nephritis Trial with proteinuria, serum Cr, and urinary RBC measurements at 3, 6, or 12 months and with a minimum of 7 years of followup were included (n = 76). We assessed the ability of these clinical biomarkers at 3, 6, and 12 months after randomization to predict good long‐term renal outcome (defined as a serum Cr value ≤1.0 mg/dl) at 7 years. Receiver operating characteristic curves were generated to assess parameter performance at these time points and to select the best cutoff for individual parameters. Sensitivity and specificity were calculated for the parameters alone and in combination.ResultsA proteinuria value of <0.8 gm/day at 12 months after randomization was the single best predictor of good long‐term renal function (sensitivity 81% and specificity 78%). The addition of serum Cr to proteinuria as a composite predictor did not improve the performance of the outcome measure; addition of urinary RBCs as a predictor significantly decreased the sensitivity to 47%.ConclusionThis study demonstrates that the level of proteinuria at 12 months is the individual best predictor of long‐term renal outcome in patients with lupus nephritis. Inclusion of urinary RBCs as part of a composite outcome measure actually undermined the predictive value of the trial data. We therefore suggest that urinary RBCs should not be included as a component of clinical trial response criteria in lupus nephritis.
Interferon‐α and Angiogenic Dysregulation in Pregnant Lupus Patients Who Develop Preeclampsia
Authors: Andrade Danieli , Kim Mimi , Blanco Luz P. , Karumanchi S. Ananth , Koo Gloria C. , Redecha Patricia , Kirou Kyriakos , Alvarez Angela M. , Mulla Melissa J. , Crow Mary K. , Abrahams Vikki M. , Kaplan Mariana J. , Salmon Jane E. 
Published: January 2015

ObjectiveTo investigate whether an elevated interferon‐α (IFNα) level early in pregnancy is associated with poor pregnancy outcomes and to examine the relationship of an elevated IFNα level to angiogenic imbalance.MethodsWomen were enrolled in a longitudinal case–control study of pregnant patients with lupus. Serum samples obtained monthly throughout pregnancy were assayed for IFNα and for the antiangiogenic factor soluble Flt‐1 and the proangiogenic factor placenta growth factor (PlGF). Each of 28 patients with systemic lupus erythematosus (SLE) with a poor pregnancy outcome was matched to an SLE patient with an uncomplicated pregnancy and to a pregnant healthy control. The effects of IFNα and/or soluble Flt‐1 on human endothelial cells and endothelial cell–trophoblast interactions were assessed.ResultsCompared to SLE patients with uncomplicated pregnancies, patients with preeclampsia had increased IFNα levels before clinical symptoms. Patients without autoimmune disease who developed preeclampsia did not have increased IFNα levels. In SLE patients with low IFNα levels, marked angiogenic imbalance (higher soluble Flt‐1, lower PlGF, and higher soluble Flt‐1:PlGF ratios) preceded maternal manifestations of preeclampsia, whereas in SLE patients with high IFNα levels, preeclampsia occurred without evidence of systemic angiogenic imbalance. Treatment of human endothelial cells with soluble Flt‐1 induced expression of sFLT1 messenger RNA, and IFNα dramatically amplified responses to soluble Flt‐1. In a model of spiral artery transformation, only the combination of IFNα and soluble Flt‐1 disrupted the ability of trophoblast cells to remodel endothelial tube structures.ConclusionOur findings identify a new mechanism by which IFNα induces an antiangiogenic milieu and increases the sensitivity of endothelial cells to soluble Flt‐1, and suggest that elevated IFNα levels may contribute to the pathogenesis of preeclampsia in some pregnant patients with SLE.
Identification of Susceptibility Loci in IL6, RPS9/LILRB3, and an Intergenic Locus on Chromosome 21q22 in Takayasu Arteritis in a Genome‐Wide Association Study
Authors: Renauer Paul A. , Saruhan‐Direskeneli Guher , Coit Patrick , Adler Adam , Aksu Kenan , Keser Gokhan , Alibaz‐Oner Fatma , Aydin Sibel Z. , Kamali Sevil , Inanc Murat , Carette Simon , Cuthbertson David , Hoffman Gary S. , Akar Servet , Onen Fatos , Akkoc Nurullah , Khalidi Nader A. , Koening Curry , Karadag Omer , Kiraz Sedat , Langford Carol A. , Maksimowicz‐McKinnon Kathleen , McAlear Carol A. , Ozbalkan Zeynep , Ates Askin , Karaaslan Yasar , Duzgun Nursen , Monach Paul A. , Ozer Huseyin T. E. , Erken Eren , Ozturk Mehmet A. , Yazici Ayten , Cefle Ayse , Onat Ahmet Mesut , Kisacik Bunyamin , Pagnoux Christian , Kasifoglu Timucin , Seyahi Emire , Fresko Izzet , Seo Philip , Sreih Antoine G. , Warrington Kenneth J. , Ytterberg Steven R. , Cobankara Veli , Cunninghame‐Graham Deborah S. , Vyse Timothy J. , Pamuk Omer N. , Tunc S. Ercan , Dalkilic Ediz , Bicakcigil Muge , Yentur Sibel P. , Wren Jonathan D. , Merkel Peter A. , Direskeneli Haner , Sawalha Amr H. 
Published: January 2015

ObjectiveTakayasu arteritis is a rare large vessel vasculitis with incompletely understood etiology. This study was undertaken to perform the first unbiased genome‐wide association analysis of Takayasu arteritis.MethodsTwo independent cohorts of patients with Takayasu arteritis from Turkey and North America were included in our study. The Turkish cohort consisted of 559 patients and 489 controls, and the North American cohort consisted of 134 patients and 1,047 controls of European ancestry. Genotyping was performed using the Omni1‐Quad and Omni2.5 genotyping arrays. Genotyping data were subjected to rigorous quality control measures and subsequently analyzed to discover genetic susceptibility loci for Takayasu arteritis.ResultsWe identified genetic susceptibility loci for Takayasu arteritis with a genome‐wide level of significance in IL6 (rs2069837) (odds ratio [OR] 2.07, P = 6.70 × 10−9), RPS9/LILRB3 (rs11666543) (OR 1.65, P = 2.34 × 10−8), and an intergenic locus on chromosome 21q22 (rs2836878) (OR 1.79, P = 3.62 × 10−10). The genetic susceptibility locus in RPS9/LILRB3 lies within the leukocyte receptor complex gene cluster on chromosome 19q13.4, and the disease risk variant in this locus correlates with reduced expression of multiple genes including the inhibitory leukocyte immunoglobulin‐like receptor gene LILRB3 (P = 2.29 × 10−8). In addition, we identified candidate susceptibility genes with suggestive levels of association (P < 1 × 10−5) with Takayasu arteritis, including PCSK5, LILRA3, PPM1G/NRBP1, and PTK2B.ConclusionOur findings indicate novel genetic susceptibility loci for Takayasu arteritis and uncover potentially important aspects of the pathophysiology of this form of vasculitis.
Contribution of the Interleukin‐6/STAT‐3 Signaling Pathway to Chondrogenic Differentiation of Human Mesenchymal Stem Cells
Authors: Kondo Masahiro , Yamaoka Kunihiro , Sakata Kei , Sonomoto Koshiro , Lin Lin , Nakano Kazuhisa , Tanaka Yoshiya 
Published: January 2015

ObjectiveMesenchymal stem cells (MSCs) are multipotent cells that can differentiate into chondrocytes. Articular cartilage contains MSC‐like chondroprogenitor cells, which suggests their involvement in the maintenance of cartilage homeostasis by a self‐repair mechanism. Interleukin‐6 (IL‐6) is a cytokine with a wide range of physiologic functions, which are produced by MSCs in a steady manner and in large quantities. The purpose of this study was to investigate the involvement of IL‐6 signaling in MSC differentiation into chondrocytes.MethodsHuman bone marrow–derived MSCs were cultured using a pellet culture system in medium containing transforming growth factor β3. Chondrogenic differentiation was detected by cartilage matrix accumulation and chondrogenic marker gene expression.ResultsIL‐6 was detected at a high concentration in culture supernatants during chondrogenic differentiation. The expression of the IL‐6 receptor (IL‐6R) was significantly increased, accompanied by markedly increased phosphorylation and expression of STAT‐3. Addition of IL‐6 and soluble IL‐6R (sIL‐6R) to the chondrogenic culture resulted in concentration‐dependent increases in cartilage matrix accumulation and cartilage marker gene expression (type II collagen/aggrecan/type X collagen). Phosphorylation of the master transcription factor SOX9 was enhanced upon addition of IL‐6 and sIL‐6R. STAT‐3 knockdown suppressed chondrogenic differentiation. IL‐6 and the MSC markers CD166 and nestin were colocalized in macroscopically normal human cartilage taken from the lateral femoral compartment of knees with medial tibiofemoral osteoarthritis.ConclusionDuring differentiation of human MSCs into chondrocytes, the activation of IL‐6/STAT‐3 signaling positively regulated chondrogenic differentiation. The presence of IL‐6 around MSC‐like cells in the cartilage tissue was identified, suggesting that IL‐6 contributes to homeostasis and cartilage self‐repair by promoting chondrogenic differentiation.
Development, validation and initial outcomes of a questionnaire to examine human factors in postgraduate surgical objective structured clinical examinations
Authors: Brennan P A , Konieczny K , Groves J , Parker M , Sherman K P , Foulkes J , Hills S , Featherstone C 
Published: January 2015

Abstract

Background
Human factors including stress, repetition, burnout and fatigue are associated with possible sources of error. Objective structured clinical examinations (OSCEs), where examiners concentrate for long periods, would benefit from a human factors approach to see whether these factors affect consistency of examiner behaviour, attitude and marking. Little has been published for OSCEs, in part due to the lack of a validated tool for collecting data in this setting.

Methods
A 46-item questionnaire was developed based on the Human Factors Analysis and Classification System (HFACS) domains and completed by examiners in the Intercollegiate Membership of the Royal College of Surgeons (MRCS) examination. To refine the questionnaire, an initial analysis focused on response patterns of each item. Cronbach's α was used to assess internal consistency, and a factor analysis was performed to uncover different domains emerging from the data.

Results
A total of 108 examiners completed the questionnaire (90·0 per cent response rate). The questionnaire, refined to 38 items based on an initial analysis of response patterns, showed good reliability for internal consistency (Cronbach's α = 0·76) and test–retest reliability (r = 0·85, n = 48, P &lt; 0·001). Four factors had a close themed resemblance to the original HFACS domains, but were associated with different items, suggesting that the four human-factor domains might be linked to different behaviours and attitudes in an examination setting. Analyses according to sex, professional background and experience highlighted additional stress levels in examiners from one of the surgical Royal Colleges (P &lt;0·001), matching evidence from the situation in that College at the time of this study.

Conclusion
The recognition and further investigation of human factors in OSCEs is needed to improve examiner experience and behaviour in order to influence delivery, candidate experience and quality assurance of these examinations.
An improved computational algorithm for teaching hydraulics of branching pipes in engineering curricula
Authors: Wahba E. M. 
Published: January 2015

ABSTRACTFlow in branching pipes is a well‐known hydraulics problem that is traditionally assigned to mechanical, civil and chemical engineering students in their fluid mechanics introductory course. The conventional solution procedure advocated by fluid mechanics and hydraulics textbooks is based on a tedious trial‐and‐error approach. Although manageable for a simple system of three pipes, the procedure becomes impractical for larger number of pipes. A recent numerical algorithm attempted to eliminate the trial‐and‐error approach; however, the procedure still requires an explicit step for identifying the discharging tanks from the filling ones. In the present study, an efficient numerical algorithm based on a Newton linearization procedure is developed which would eliminate the above mentioned drawbacks. The efficiency of the new procedure is demonstrated by solving a simple three‐pipe problem and a more complicated nine‐pipe problem. The results of the present algorithm are validated against available results in the literature and against the piping software package, EPANET. The proposed procedure could be implemented in a straightforward manner through the MATLAB environment. © 2015 Wiley Periodicals, Inc. Comput Appl Eng Educ 23:537–541, 2015; View this article online at wileyonlinelibrary.com/journal/cae; DOI 10.1002/cae.21624
Differential vital staining of normal fibroblasts and melanoma cells by an anionic conjugated polyelectrolyte
Authors: Magnusson Karin , Appelqvist Hanna , Cieślar‐Pobuda Artur , Wigenius Jens , Karlsson Thommie , Łos Marek J. , Kågedal Bertil , Jonasson Jon , Nilsson K. Peter R. 
Published: January 2015

AbstractMolecular probes for imaging of live cells are of great interest for studying biological and pathological processes. The anionic luminescent conjugated polythiophene (LCP) polythiophene acetic acid (PTAA), has previously been used for vital staining of cultured fibroblasts as well as transformed cells with results indicating differential staining due to cell phenotype. Herein, we investigated the behavior of PTAA in two normal and five transformed cells lines. PTAA fluorescence in normal cells appeared in a peripheral punctated pattern whereas the probe was more concentrated in a one‐sided perinuclear localization in the five transformed cell lines. In fibroblasts, PTAA fluorescence was initially associated with fibronectin and after 24 h partially localized to lysosomes. The uptake and intracellular target in malignant melanoma cells was more ambiguous and the intracellular target of PTAA in melanoma cells is still elusive. PTAA was well tolerated by both fibroblasts and melanoma cells, and microscopic analysis as well as viability assays showed no signs of negative influence on growth. Stained cells maintained their proliferation rate for at least 12 generations. Although the probe itself was nontoxic, photoinduced cellular toxicity was observed in both cell lines upon irradiation directly after staining. However, no cytotoxicity was detected when the cells were irradiated 24 h after staining, indicating that the photoinduced toxicity is dependent on the cellular location of the probe. Overall, these studies certified PTAA as a useful agent for vital staining of cells, and that PTAA can potentially be used to study cancer‐related biological and pathological processes. © 2015 International Society for Advancement of Cytometry
Statistical analysis of molecule colocalization in bioimaging
Authors: Lagache Thibault , Sauvonnet Nathalie , Danglot Lydia , Olivo‐Marin Jean‐Christophe 
Published: January 2015

AbstractThe quantitative analysis of molecule interactions in bioimaging is key for understanding the molecular orchestration of cellular processes and is generally achieved through the study of the spatial colocalization between the different populations of molecules. Colocalization methods are traditionally divided into pixel‐based methods that measure global correlation coefficients from the overlap between pixel intensities in different color channels, and object‐based methods that first segment molecule spots and then analyze their spatial distributions with second‐order statistics. Here, we present a review of such colocalization methods and give a quantitative comparison of their relative merits in different types of biological applications and contexts. We show on synthetic and biological images that object‐based methods are more robust statistically than pixel‐based methods, and allow moreover to quantify accurately the number of colocalized molecules. © 2015 International Society for Advancement of Cytometry
Rare event counting of CD59− red cells in human blood: A 47‐month experience using PNH consensus guidelines for WBC and RBC testing in a reference lab
Authors: Liew Michael , Farley Marjorie , Andreasen John , Parker Charles J. , Wittwer Carl T. 
Published: January 2015

IntroductionParoxysmal nocturnal hemoglobinuria (PNH) is a rare acquired disorder characterized by increased complement‐mediated lysis of erythrocytes (RBCs) because of low/absent glycophosphatidylinositol (GPI) anchors of numerous cell surface proteins.MethodsRare event analysis was applied to 120 million RBCs (12 normal individuals) and 102 million RBCs (102 normal individuals) to establish a reference range and verify a methodology for rare event analysis. Patient PNH testing (n = 10,984) was performed over 47 months using the 2010 consensus guidelines with CD59‐PE and glycophorin A‐FITC for RBCs and FLAER‐Alexa 488, CD33‐PerCP‐Cy5.5, CD15‐APC, CD14‐APC‐Cy7, and CD24‐PE for WBCs.ResultsThe distribution of CD59−RBCs in the normal population was asymmetric with a mean of 5.9, median between 3 and 4, and mode of 2 per million RBCs. The normal range of CD59−RBCs was 0‐17/million RBCs. A natural cutoff of 2.5% of the peak expression of CD59 delineates CD59+ from CD59−populations. The incidence of GPI‐ samples received by the laboratory was 6–7% without correlation to age (P = 0.35) or sex (P = 0.45). The percentage of GPI‐ neutrophils and monocytes were strongly correlated (R2 = 0.96) and usually greater than the percentage of GPI‐ RBCs.ConclusionPNH RBC testing is a good example of rare event analysis applied to clinical cytometry—only 2.5 min are required to collect 1 million RBCs. With an established normal range of CD59−RBCs, the correlation between total cell count and sensitivity for detecting an abnormal population can be calculated using Poisson statistics. © 2015 International Clinical Cytometry Society
Toward mobile Internet‐based layered vehicular networks with efficient access management
Authors: Li Xi , Zhang Heli , Wang Ke 
Published: January 2015

SummaryVehicular networks have been considered as an important part of realizing the ubiquitous mobile Internet services in the near future. This puts forward the challenge of providing more access opportunities and wireless resources to meet the increasing QoS requirements from various applications. Traditional vehicular ad hoc networks afford the access to Internet by dedicated roadside units. In order to resolve the problems resulting from limited RSUs, insufficient resources and unsatisfied user experience, we propose a layered structure for vehicular networks. The vehicles are virtualized as special vehicular small cells (VSCs) within the first layer and then integrated with the layered heterogeneous networks as the second layer. Furthermore, the access management problem is discussed, and then an optimal access strategy has been designed for VSC to choose the proper roadside infrastructure from several candidates. Evaluation model has been derived with consideration on QoS, handover frequency, moving speed, security, and cost. Simulation results have proved the effectiveness of our proposed scheme from the performance evaluation. Copyright © 2015 John Wiley & Sons, Ltd.
Anti‐inflammatory compounds to reduce infarct size in large‐animal models of myocardial infarction: A meta‐analysis
Authors: van Hout G.P.J. , Jansen of Lorkeers S.J. , Wever K.E. , Sena E.S. , van Solinge W.W. , Doevendans P.A. , Pasterkamp G. , Chamuleau S.A.J. , Hoefer I.E. 
Published: January 2015

ABSTRACTTargeting the inflammatory response after myocardial infarction (MI) could potentially prevent infarct expansion, resulting in a preservation of cardiac function. Despite extensive testing in large‐animal models of MI, anti‐inflammatory therapeutics are not incorporated in daily clinical practice. Methodological review of the literature describing the effects of anti‐inflammatory compounds in large‐animal models of MI may provide useful insights into the reasons for the translational failure from preclinical to clinical studies. Moreover, systematic review of these preclinical studies may allow us to determine which anti‐inflammatory agents have the greatest potential to successfully treat MI in the clinic and guide which preclinical setting appears most appropriate to test these future treatment strategies in. The current systematic review protocol provides a detailed description of the design of this systematic review of studies investigating the effects of anti‐inflammatory compounds in large‐animal models of MI.