bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of a risk assessment tool for contact tracing people after contact with infectious patients while travelling by bus or other public ground transport: a Delphi consensus approach
Authors: Mohr Oliver , Hermes Julia , Schink Susanne B , Askar Mona , Menucci Daniel , Swaan Corien , Goetsch Udo , Monk Philip , Eckmanns Tim , Poggensee Gabriele , Krause Gérard 
Published: October 2013

BackgroundTracing persons who have been in contact with an infectious patient may be very effective in preventing the spread of communicable diseases. However, criteria to decide when to conduct contact tracing are not well established. We have investigated the available evidence for contact tracing with a focus on public ground transport aiming to give guidance in what situations contact tracing should be considered.MethodsRelevant infectious diseases suitable for contact tracing in ground transport and a set of disease-specific epidemiological criteria were defined through literature search and structured multistep expert consultations. We developed continuous scales for each criterion to be rated for its relevance to contact tracing in ground transport. We used the Delphi method with an international expert panel to position the values of criteria on the respective scales.ResultsThe study led to the development of the ‘Contact Tracing-Risk Assessment Profile’ (CT-RAP), a decision-making instrument, taking into account pathogen-specific as well as situation-specific criteria. This report describes the methodology of this instrument and presents two examples of ready-to-use CT-RAP for tuberculosis and for meningococcal disease in public ground transport.DiscussionThe systematic and transparent use of the CT-RAP for tuberculosis and meningococcal disease is likely to facilitate reasonable, efficient and user-friendly decisions with respect to contact tracing. New CT-RAPs for additional pathogens and different settings such as schools and kindergartens are being planned.
Cardiovascular health knowledge, attitude and practice/behaviour in an urbanising community of Nepal: a population-based cross-sectional study from Jhaukhel-Duwakot Health Demographic Surveillance Site
Authors: Vaidya Abhinav , Aryal Umesh Raj , Krettek Alexandra 
Published: October 2013

ObjectivesThis study determined the knowledge, attitude and practice/behaviour of cardiovascular health in residents of a semiurban community of Nepal.DesignTo increase the understanding of knowledge, attitude and practice/behaviour towards cardiovascular health, we conducted in-home interviews using a questionnaire based on the WHO STEPwise approach to surveillance and other resources, scoring all responses. We also recorded blood pressure and took anthropometric measurements.SettingOur study was conducted as part of the Heart-Health-Associated Research and Dissemination in the Community project in the Jhaukhel-Duwakot Health Demographic Surveillance Site in two urbanising villages near Kathmandu.ParticipantsThe study population included 777 respondents from six randomly selected clusters in both villages.ResultsSeventy per cent of all participants were women and 26.9% lacked formal education. The burden of cardiovascular risk factors was high; 20.1% were current smokers, 43.3% exhibited low physical activity and 21.6% were hypertensive. Participants showed only poor knowledge of heart disease causes; 29.7% identified hypertension and 11% identified overweight and physical activity as causes, whereas only 2.2% identified high blood sugar as causative. Around 60% of respondents did not know any heart attack symptoms compared with 20% who knew 2–4 symptoms. Median percentage scores for knowledge, attitude and practice/behaviour were 79.3, 74.3 and 48, respectively. Nearly 44% of respondents had insufficient knowledge and less than 20% had highly satisfactory knowledge. Among those with highly satisfactory knowledge, only 14.7% had a highly satisfactory attitude and 19.5% and 13.9% had satisfactory and highly satisfactory practices, respectively.ConclusionsOur study demonstrates a gap between cardiovascular health knowledge, attitude and practice/behaviour in a semiurban community in a low-income nation, even among those already affected by cardiovascular disease.
EGFR expression in pancreatic adenocarcinoma. Relationship to tumour morphology and cell adhesion proteins
Authors: Handra-Luca Adriana , Hammel Pascal , Sauvanet Alain , Lesty Claude , Ruszniewski Philippe , Couvelard Anne 
Published: October 2013

AimsWe aimed to study epidermal growth factor receptor (EGFR) expression in surgically resected pancreatic ductal adenocarcinomas (PDACs) by immunohistochemistry and their relationship to clinicopathological features, cell proliferation and cell adhesion protein expression.MethodsA total of 99 PDACs were analysed on tissue microarrays for EGFR, E-cadherin and β-catenin expression patterns in tumour cells. The percentage of cells expressing the three proteins (membrane, cytoplasm or nuclear pattern) and of Ki67-positive tumour cells was assessed. Tumour protein expression was studied with regard to clinicomorphological features, Ki67 index and for postsurgical survival.ResultsMembrane tumour EGFR correlated with histological poor differentiation (dedifferentiation), increased number of mitoses and severe tumour cell atypia (pleiomorphism) as well as with aberrant adhesion protein expression such as nuclear β-catenin and cytoplasmic E-cadherin. Cytoplasmic tumour E-cadherin correlated with an increased Ki67-positive tumour cell component, whereas nuclear E-cadherin correlated with a shorter postsurgical overall survival, as well as with tumour necrosis and an abundant clear cell component.ConclusionsIn conclusion, the results of our study suggest a complex role for EGFR in PDAC carcinogenesis, tumour expression of this protein being associated with tumour dedifferentiation, mitotic activity or pleiomorphism, as well as with aberrant tumour cell adhesion protein expression.
Serum pepsinogen reference intervals in apparently healthy Chinese population with latex enhanced turbidimetric immunoassay
Authors: Huang Meng , Tang Ai-Guo , Mu Sa , Yang Jing-Jing , Xiang Zhong-Yuan , Liu Bo , Yang Jia-Jin 
Published: October 2013

AimSerum pepsinogen (sPG) has been used to help in diagnosing atrophic corpus gastritis and in screening for gastric cancer non-invasively. There are as yet no reports on sPG reference intervals (RIs) with latex enhanced turbidimetric immunoassay (LIA). In this study, we established the RIs for sPG in a healthy Chinese population using LIA.MethodsSerum PGI and PGII levels in a healthy population (aged 17–80 years) were measured simultaneously using LIA. RIs were determined following Clinical Laboratory and Standards Institute C28-A3 guidelines using a non-parametric method.Results95% RIs in men (ng/mL) were: ≤40 years old, 25.53–100.76 for PGI and ≤24.42 for PGII; 41–50 years old, 26.62–124.74 for PGI and ≤26.81 for PGII; and 51–80 years old, 30.40–153.25 for PGI and ≤32.62 for PGII. Corresponding RIs for women (ng/mL) were: ≤40 years old, 21.20–87.44 for PGI and ≤25.53 for PGII; and 41–80 years, 26.40–127.46 for PGI and ≤30.18 for PGII. 95% RI for PGI/PGII in both men and women at any age was ≥2.51.ConclusionsWe established the RIs for sPG using LIA in a healthy Chinese population, which can provide a reference for clinical and laboratory studies.
AXL Is a Key Regulator of Inherent and Chemotherapy-Induced Invasion and Predicts a Poor Clinical Outcome in Early-Stage Colon Cancer
Authors: Dunne Philip D. , McArt Darragh G. , Blayney Jaine K. , Kalimutho Murugan , Greer Samanda , Wang Tingting , Srivastava Supriya , Ong Chee Wee , Arthur Ken , Loughrey Maurice , Redmond Keara , Longley Daniel B. , Salto-Tellez Manuel , Johnston Patrick G. , Van Schaeybroeck Sandra 
Published: October 2013

Abstract
Purpose: Despite the use of 5-fluorouracil (5-FU)–based adjuvant treatments, a large proportion of patients with high-risk stage II/III colorectal cancer will relapse. Thus, novel therapeutic strategies are needed for early-stage colorectal cancer. Residual micrometastatic disease from the primary tumor is a major cause of patient relapse.
Experimental Design: To model colorectal cancer tumor cell invasion/metastasis, we have generated invasive (KRASMT/KRASWT/+chr3/p53-null) colorectal cancer cell subpopulations. Receptor tyrosine kinase (RTK) screens were used to identify novel proteins that underpin the migratory/invasive phenotype. Migration/invasion was assessed using the XCELLigence system. Tumors from patients with early-stage colorectal cancer (N = 336) were examined for AXL expression.
Results: Invasive colorectal cancer cell subpopulations showed a transition from an epithelial-to-mesenchymal like phenotype with significant increases in migration, invasion, colony-forming ability, and an attenuation of EGF receptor (EGFR)/HER2 autocrine signaling. RTK arrays showed significant increases in AXL levels in all invasive sublines. Importantly, 5-FU treatment resulted in significantly increased migration and invasion, and targeting AXL using pharmacologic inhibition or RNA interference (RNAi) approaches suppressed basal and 5-FU–induced migration and invasion. Significantly, high AXL mRNA and protein expression were found to be associated with poor overall survival in early-stage colorectal cancer tissues.
Conclusions: We have identified AXL as a poor prognostic marker and important mediator of cell migration/invasiveness in colorectal cancer. These findings provide support for the further investigation of AXL as a novel prognostic biomarker and therapeutic target in colorectal cancer, in particular in the adjuvant disease in which EGFR/VEGF–targeted therapies have failed. Clin Cancer Res; 20(1); 164–75. ©2013 AACR.
Modeling RAS Phenotype in Colorectal Cancer Uncovers Novel Molecular Traits of RAS Dependency and Improves Prediction of Response to Targeted Agents in Patients
Authors: Guinney Justin , Ferté Charles , Dry Jonathan , McEwen Robert , Manceau Gilles , Kao KJ , Chang Kai-Ming , Bendtsen Claus , Hudson Kevin , Huang Erich , Dougherty Brian , Ducreux Michel , Soria Jean-Charles , Friend Stephen , Derry Jonathan , Laurent-Puig Pierre 
Published: October 2013

Abstract
Purpose: KRAS wild-type status is an imperfect predictor of sensitivity to anti-EGF receptor (EGFR) monoclonal antibodies in colorectal cancer, motivating efforts to identify novel molecular aberrations driving RAS. This study aimed to build a quantitative readout of RAS pathway activity to (i) uncover molecular surrogates of RAS activity specific to colorectal cancer, (ii) improve the prediction of cetuximab response in patients, and (iii) suggest new treatment strategies.
Experimental Design: A model of RAS pathway activity was trained in a large colorectal cancer dataset and validated in three independent colorectal cancer patient datasets. Novel molecular traits were inferred from The Cancer Genome Atlas colorectal cancer data. The ability of the RAS model to predict resistance to cetuximab was tested in mouse xenografts and three independent patient cohorts. Drug sensitivity correlations between our model and large cell line compendiums were performed.
Results: The performance of the RAS model was remarkably robust across three validation datasets. (i) Our model confirmed the heterogeneity of the RAS phenotype in KRAS wild-type patients, and suggests novel molecular traits driving its phenotype (e.g., MED12 loss, FBXW7 mutation, MAP2K4 mutation). (ii) It improved the prediction of response and progression-free survival (HR, 2.0; P &lt; 0.01) to cetuximab compared with KRAS mutation (xenograft and patient cohorts). (iii) Our model consistently predicted sensitivity to MAP–ERK kinase (MEK) inhibitors (P &lt; 0.01) in two cell panel screens.
Conclusions: Modeling the RAS phenotype in colorectal cancer allows for the robust interrogation of RAS pathway activity across cell lines, xenografts, and patient cohorts. It demonstrates clinical utility in predicting response to anti-EGFR agents and MEK inhibitors. Clin Cancer Res; 20(1); 265–72. ©2013 AACR.
Off-Target Effects of c-MET Inhibitors on Thyroid Cancer Cells
Authors: Zhou Yan , Zhao Conghui , Gery Sigal , Braunstein Glenn D. , Okamoto Ryoko , Alvarez Rocio , Miles Steven A. , Doan Ngan B. , Said Jonathan W. , Gu Jiang , Phillip Koeffler H. 
Published: October 2013

Abstract
Aberrantly activated c-MET signaling occurs in several cancers, promoting the development of c-MET inhibitors. In this study, we found that eight of eight thyroid cancer cell lines (including six anaplastic thyroid cell lines) have prominent expression of c-MET protein. Fifty percent of the thyroid cancer cell lines (four of eight) were growth inhibited by two small molecule c-MET inhibitors (tivantinib and crizotinib) associated with apoptosis and G2–M cell-cycle arrest. However, crizotinib did not inhibit 50% proliferation of thyroid cancer cells (SW1736 and TL3) at a concentration at which the drug completely inhibited ligand-stimulated c-MET phosphorylation. However, tivantinib was less potent than crizotinib at inhibiting c-MET phosphorylation, but was more potent than crizotinib at decreasing cell growth. Suppressing c-MET protein expression and phosphorylation using siRNA targeting c-MET did not induce cell-cycle arrest and apoptosis. Taken together, tivantinib and crizotinib have off-target(s) activity, contributing to their antitumor activity. In vivo study showed that crizotinib markedly inhibited the growth of thyroid cancer cells (SW1736) in immunodeficient mice. In summary, c-MET inhibitors (tivantinib and crizotinib) suppress the growth of aggressive thyroid cancer cells, and this potential therapeutic benefit results from their non–MET-targeting effects. Mol Cancer Ther; 13(1); 134–43. ©2013 AACR.
Sorafenib Suppresses JNK-Dependent Apoptosis through Inhibition of ZAK
Authors: Vin Harina , Ching Grace , Ojeda Sandra S. , Adelmann Charles H. , Chitsazzadeh Vida , Dwyer David W. , Ma Haiching , Ehrenreiter Karin , Baccarini Manuela , Ruggieri Rosamaria , Curry Jonathan L. , Ciurea Ana M. , Duvic Madeleine , Busaidy Naifa L. , Tannir Nizar M. , Tsai Kenneth Y. 
Published: October 2013

Abstract
Sorafenib is U.S. Food and Drug Adminstration–approved for the treatment of renal cell carcinoma and hepatocellular carcinoma and has been combined with numerous other targeted therapies and chemotherapies in the treatment of many cancers. Unfortunately, as with other RAF inhibitors, patients treated with sorafenib have a 5% to 10% rate of developing cutaneous squamous cell carcinoma (cSCC)/keratoacanthomas. Paradoxical activation of extracellular signal–regulated kinase (ERK) in BRAF wild-type cells has been implicated in RAF inhibitor–induced cSCC. Here, we report that sorafenib suppresses UV-induced apoptosis specifically by inhibiting c-jun–NH2–kinase (JNK) activation through the off-target inhibition of leucine zipper and sterile alpha motif–containing kinase (ZAK). Our results implicate suppression of JNK signaling, independent of the ERK pathway, as an additional mechanism of adverse effects of sorafenib. This has broad implications for combination therapies using sorafenib with other modalities that induce apoptosis. Mol Cancer Ther; 13(1); 221–9. ©2013 AACR.
Plastin Polymorphisms Predict Gender- and Stage-Specific Colon Cancer Recurrence after Adjuvant Chemotherapy
Authors: Ning Yan , Gerger Armin , Zhang Wu , Hanna Diana L. , Yang Dongyun , Winder Thomas , Wakatsuki Takeru , Labonte Melissa J. , Stintzing Sebastian , Volz Nico , Sunakawa Yu , Stremitzer Stefan , El-Khoueiry Rita , Lenz Heinz-Josef 
Published: October 2013

Abstract
Tumor recurrence after curative resection remains a major problem in patients with locally advanced colorectal cancer treated with adjuvant chemotherapy. Genetic single-nucleotide polymorphisms (SNP) may serve as useful molecular markers to predict clinical outcomes in these patients and identify targets for future drug development. Recent in vitro and in vivo studies have demonstrated that the plastin genes PLS3 and LCP1 are overexpressed in colon cancer cells and play an important role in tumor cell invasion, adhesion, and migration. Hence, we hypothesized that functional genetic variations of plastin may have direct effects on the progression and prognosis of locally advanced colorectal cancer. We tested whether functional tagging polymorphisms of PLS3 and LCP1 predict time to tumor recurrence (TTR) in 732 patients (training set, 234; validation set, 498) with stage II/III colorectal cancer. The PLS3 rs11342 and LCP1 rs4941543 polymorphisms were associated with a significantly increased risk for recurrence in the training set. PLS3 rs6643869 showed a consistent association with TTR in the training and validation set, when stratified by gender and tumor location. Female patients with the PLS3 rs6643869 AA genotype had the shortest median TTR compared with those with any G allele in the training set [1.7 vs. 9.4 years; HR, 2.84; 95% confidence interval (CI), 1.32–6.1; P = 0.005] and validation set (3.3 vs. 13.7 years; HR, 2.07; 95% CI, 1.09–3.91; P = 0.021). Our findings suggest that several SNPs of the PLS3 and LCP1 genes could serve as gender- and/or stage-specific molecular predictors of tumor recurrence in stage II/III patients with colorectal cancer as well as potential therapeutic targets. Mol Cancer Ther; 13(2); 528–39. ©2013 AACR.
Correcting Marine Surface Winds Simulated in Atmospheric Models Using Spatially and Temporally Varying Linear Regression
Authors: Durrant Tom H. , Greenslade Diana J. M. , Simmonds Ian , Woodcock Frank 
Published: October 2013

Abstract
This study examines the application of three different variations of linear-regression corrections to the surface marine winds from the Australian Bureau of Meteorology’s recently implemented operational atmospheric model. A simple correction over the entire domain is found to inadequately account for geographical variation in the wind bias. This is addressed by considering corrections that vary in space. Further, these spatially varying corrections are extended to vary in time. In an operational environment, the error characteristics of the wind forcing can be expected to change over time with the evolution of the atmospheric model. This in turn requires any applied correction to be monitored and maintained. Motivated by a desire to avoid this manual maintenance, a self-learning correction method is proposed whereby spatially and temporally varying corrections are calculated in real time from a moving window of historical comparisons between observations and preceding forecasts. This technique is shown to effectively remove both global and regionally varying wind speed biases.
Adenotonsillectomy vs Observation for Management of Mild Obstructive Sleep Apnea in Children
Authors: Volsky Peter G. , Woughter Meghan A. , Beydoun Hind A. , Derkay Craig S. , Baldassari Cristina M. 
Published: October 2013

ObjectiveTo determine the impact of adenotonsillectomy vs observation on quality of life (QOL) in children with mild obstructive sleep apnea (OSA).Study DesignProspective, nonrandomized trial.SettingTertiary children's hospital.Subjects and MethodsSixty‐four children (ages 3‐16 years) with mild OSA (apnea hypopnea index between 1 and 5 on polysomnogram) completed the study. Caregivers chose between management options of adenotonsillectomy and observation and completed validated QOL instruments (OSA‐18 and Children's Health Questionnaire) at baseline, early, and late follow‐ups. The primary outcome measure was QOL.ResultsThirty patients chose adenotonsillectomy, while 34 were observed. Total OSA‐18 scores at baseline were significantly poorer (P =. 01) in the surgery group (72.3) compared with the observation group (58.5). Four months following surgery, OSA‐18 scores improved by 39.1 points over baseline (P =. 0001), while there was no change for the observation group (P =. 69). After 8 months, OSA‐18 scores remained improved in the surgery group, and observation group scores improved by 13.4 points over baseline (P =. 005). While OSA‐18 scores at the late follow‐up visit were poorer in the observation group, the difference was not statistically significant (P =. 05). Six observation patients opted for adenotonsillectomy during the study.ConclusionQuality of life significantly improves in children with mild OSA after adenotonsillectomy. In children with mild OSA who are observed, QOL improvements at early follow‐up are less pronounced, but significant improvements in QOL are evident after 8 months. QOL instruments may be useful tools to help providers determine which children with mild OSA may benefit from early intervention.
An Introduction of Genetics in Otosclerosis: A Systematic Review
Authors: Bittermann Arnold J. N. , Wegner Inge , Noordman Bo Jan , Vincent Robert , van der Heijden Geert J. M. G. , Grolman Wilko 
Published: October 2013

ObjectiveTo present an easy to read systematic review concerning the genetic etiology of otosclerosis to help health care providers in counseling otosclerosis patients more accurately.Data SourcesPubMed, Embase, CINAHL, and the Cochrane Library.Review MethodsStudies on the genetic etiology of otosclerosis were selected. Association studies and family‐based studies were included for further review. After quality assessment (risk of bias), data were extracted from the included studies. When available, odds ratios were presented. In case of corresponding genetic anomalies between the studies, it was the aim to combine results.ResultsThe number of available studies with low risk of bias is limited to 2 association studies and 1 family‐based study. These high‐quality studies show that otosclerosis in Japanese patients is not linked to the NOG gene and that a polymorphism in the Sp1 binding site located on the COL1A1 gene is associated with otosclerosis as well as OTSC1. Association and family‐based studies with moderate risk of bias show a statistically significant association with the ACE gene, AGT gene, OTSC2, RELN gene, TGFB1 gene, 11q13.1, OTSC2, OTSC5, OTSC8, and OTSC10. These results may be spurious associations due to their bias and low statistical power.ConclusionThe present systematic review shows that there is scattered evidence of limited quality and a lack of replication studies. It is not possible to point out 1 or more responsible genes, which play a key role within the genetic pathophysiologic mechanism of otosclerosis.