bluuebunny/crossref_metadata_2025_split huggingface dataset:
Accelerometer-based measures in physical activity surveillance: current practices and issues
Authors: Pedišić Željko , Bauman Adrian 
Published: November 2014

ObjectiveSelf-reports of physical activity (PA) have been the mainstay of measurement in most non-communicable disease (NCD) surveillance systems. To these, other measures are added to summate to a comprehensive PA surveillance system. Recently, some national NCD surveillance systems have started using accelerometers as a measure of PA. The purpose of this paper was specifically to appraise the suitability and role of accelerometers for population-level PA surveillance.MethodsA thorough literature search was conducted to examine aspects of the generalisability, reliability, validity, comprehensiveness and between-study comparability of accelerometer estimates, and to gauge the simplicity, cost-effectiveness, adaptability and sustainability of their use in NCD surveillance.ConclusionsAccelerometer data collected in PA surveillance systems may not provide estimates that are generalisable to the target population. Accelerometer-based estimates have adequate reliability for PA surveillance, but there are still several issues associated with their validity. Accelerometer-based prevalence estimates are largely dependent on the investigators’ choice of intensity cut-off points. Maintaining standardised accelerometer data collections in long-term PA surveillance systems is difficult, which may cause discontinuity in time-trend data. The use of accelerometers does not necessarily produce useful between-study and international comparisons due to lack of standardisation of data collection and processing methods. To conclude, it appears that accelerometers still have limitations regarding generalisability, validity, comprehensiveness, simplicity, affordability, adaptability, between-study comparability and sustainability. Therefore, given the current evidence, it seems that the widespread adoption of accelerometers specifically for large-scale PA surveillance systems may be premature.
Association of the vitamin D binding protein polymorphisms with the risk of type 2 diabetes mellitus: a meta-analysis
Authors: Wang Gaoshuai , Li Yuqian , Li Linlin , Yu Fei , Cui Lingling , Ba Yue , Li Wenjie , Wang Chongjian 
Published: November 2014

ObjectivePrevious studies on the association between vitamin D binding protein (DBP) polymorphisms and the risk of type 2 diabetes mellitus (T2DM) have produced conflicting results. The purpose of this meta-analysis was to examine whetherDBPpolymorphisms are associated with the risk of T2DM.DesignSystematic review and meta-analysis.MethodsAll eligible studies were searched and acquired from the Cochrane, Pubmed, ISI, CNKI (Chinese) and Wanfang (Chinese) databases. ORs with corresponding 95% CIs were computed to estimate the association betweenDBPpolymorphisms and T2DM. In addition, heterogeneity test, meta-regression and sensitivity analysis were also conducted.ResultsSix studies, which included 1191 cases and 882 controls, met the inclusion criteria and were included in the meta-analysis. The results showed that no significant associations were found between codon 416 and codon 420 polymorphisms in theDBPand the risk of T2DM in the overall analyses. In stratified analysis, significant associations between the codon 420 polymorphism and T2DM were found in Asians (allele Lys vs Thr: OR (95% CI) 1.49 (1.19 to 1.85), genotype Lys/Thr versus Thr/Thr: OR (95% CI) 1.80 (1.36 to 2.38), and Lys/Thr+Lys/Lys versus Thr/Thr: OR (95% CI) 1.81 (1.37 to 2.39), respectively) but not in Caucasians. For the codon 416, the significant association with T2DM was also detected in Asians (genotype Glu/Asp+Glu/Glu vs Asp/Asp: OR (95% CI) 1.36 (1.04 to 1.78)) but not in Caucasians.ConclusionsThis meta-analysis demonstrated that theDBPpolymorphism was moderately associated with increased susceptibility to T2DM in Asians, but a similar association was not found in Caucasians. It suggested that ethnicity might be the potential factor associated with heterogeneity.
A meta-analysis of the effectiveness of crew resource management training in acute care domains
Authors: O'Dea Angela , O'Connor Paul , Keogh Ivan 
Published: November 2014

Abstract
The healthcare industry has seen an increase in the adoption of team training, such as crew resource management (CRM), to improve teamwork and coordination within acute care medical teams. A meta-analysis was carried out in order to quantify the effects of CRM training on reactions, learning, behaviour and clinical care outcomes. Biases in the research evidence are identified and recommendations for training development and evaluation are presented. PUBMED, EMBASE and PsychInfo were systematically searched for all relevant papers. Peer reviewed papers published in English between January 1985 and September 2013, which present empirically based studies focusing on interventions to improve team effectiveness in acute health care domains, were included. A total of 20 CRM-type team training evaluation studies were found to fulfil the a priori criteria for inclusion in the meta-analysis. Overall, CRM trained participants responded positively to CRM (mean score 4.25 out of a maximum of 5), the training had large effects on participants’ knowledge (d=1.05), a small effect on attitudes (d=0.22) and a large effect on behaviours (d=1.25). There was insufficient evidence to support an effect on clinical care outcomes or long term impacts. The findings support the premise that CRM training can positively impact teamwork in healthcare and provide estimates of the expected effects of training. However, there is a need for greater precision in outcome assessment, improved standardisation of methods and measures, and more robust research design. Stronger evidence of effectiveness will require multi-level, multicentre, multispecialty and longitudinal studies.
Effects of increased stocking density and heat stress on growth, performance, carcase characteristics and skeletal properties in turkeys
Authors: Jankowski J. , Mikulski D. , Tatara M. R. , Krupski W. 
Published: November 2014

Effects of increased stocking density and heat stress on growth, feed conversion, carcase characteristics and skeletal system properties in turkeys were determined. One‐day‐old males (n=1674) were divided into two weight‐matched groups exposed to different environmental conditions. Controls were reared at a stocking density of 2.8 birds/m2 and at thermo‐neutral temperature (TnT group), while the experimental group was exposed to heat‐stress (HSID group) and reared at a stocking density of 3.4 birds/m2 and ambient temperature increased by 5°C. At 28 days of age, 27 birds from each group were sacrificed, while at 126 days of age, 54 birds from each group were slaughtered. Increased stocking density and ambient temperature during the first four weeks of life increased the body weight (BW) of turkeys and weight, length, volume, vertical internal and horizontal external diameters of the tibia in the HSID group compared with the TnT group (P<0.05). In turkeys older than four weeks, increased stocking density and ambient temperature significantly decreased daily feed intake, final BW and relative weight of drumstick muscle by 4.7 per cent, 4.0 per cent and 3.3 per cent, respectively (P<0.05). The weight, length, volume, vertical and horizontal diameters, cross‐sectional area, second moment of inertia, volumetric bone mineral density, maximum elastic strength and ultimate strength of bones were significantly lower in turkeys in the HSID group (P<0.05) at 126 days compared with turkeys in the TnT group at the same age. These results indicate that, up to four weeks of age, turkeys tolerate increased stocking density and heat stress better than birds between 5 and 18 weeks of age.
Efficacy of diclazuril and toltrazuril in the prevention of coccidiosis in dairy calves under field conditions
Authors: Zechner G. , Bauer C. , Jacobs J. , Goossens L. , Vertenten G. , Taylor M. A. 
Published: November 2014

A blinded, controlled, randomised field study was undertaken on two commercial dairy farms in Germany to compare the efficacy of the anticoccidials, diclazuril and toltrazuril in the prevention of bovine coccidiosis. A total of 86 calves aged between five and six weeks were randomly allocated to two treatment and one untreated control groups. Calves were monitored for 78 days post‐treatment by clinical observation, bodyweight gain, faecal oocyst counts (FOCs) and coccidia species differentiation. Strategic treatments had no significant effect on bodyweight gains (P>0.05). Whilst the number of diarrhoea days was similar for all three groups from days 1 to 41, there was a significant difference in the number and percentage of diarrhoea days from day 42 with the diclazuril‐treated group showing only one diarrhoea day compared with 9 days (P=0.0195) and 18 days (P=0.0027) for the control and toltrazuril‐treated groups, respectively. FOCs in control calves fluctuated throughout the period of study indicating continued coccidia challenge. FOCs in the diclazuril‐treated calves declined to low levels post‐treatment, increasing to occasional counts >500 oocysts per gram of faeces (OPG) between days 27 and 42, but thereafter remained low. Calves treated with toltrazuril also showed low FOCs until day 40 but then showed several peaks of oocyst output >500 OPG coinciding with days of diarrhoea.
Four-in-One Antibodies Have Superior Cancer Inhibitory Activity against EGFR, HER2, HER3, and VEGF through Disruption of HER/MET Crosstalk
Authors: Hu Shi , Fu Wenyan , Xu Weihao , Yang Yang , Cruz Melissa , Berezov Sandra D. , Jorissen Daniel , Takeda Hiroaki , Zhu Wangdong 
Published: November 2014

Abstract
The anti-HER receptor antibodies cetuximab, trastuzumab, and pertuzumab are used widely in clinic to treat metastatic cancer. However, activation of the extensive crosstalk among the HER receptors as well as other RTKs, particularly HER-MET crosstalk, has emerged as a likely source of drug resistance. In this study, we developed two new types of tetra-specific antibodies that recognize EGFR, HER2, HER3, and VEGF. These tetra-specific antibodies, termed FL518 (four-in-one antibody) and CRTB6 (tetra-specific, tetravalent antibody), not only inhibited signaling mediated by these receptors in vitro and in vivo but unexpectedly also disrupted HER-MET crosstalk. When compared with two-in-one antibodies and a series of bispecific antibodies in multiple tumor models, FL518 and CRTB6 were more broadly efficacious. We further showed that tetra-specific antibodies were far more effective than bispecific antibodies in inhibiting the growth of anti–HER-resistant cancer cells, which exhibited elevated levels of MET activation both in vitro and in vivo. Overall, our results establish a new principle to achieve combined HER inhibition and limit drug resistance using a single antibody. Cancer Res; 75(1); 159–70. ©2014 AACR.
Recurrent BRCA1 and BRCA2 Mutations in Mexican Women with Breast Cancer
Authors: Torres-Mejía Gabriela , Royer Robert , Llacuachaqui Marcia , Akbari Mohammad R. , Giuliano Anna R. , Martínez-Matsushita Louis , Angeles-Llerenas Angélica , Ortega-Olvera Carolina , Ziv Elad , Lazcano-Ponce Eduardo , Phelan Catherine M. , Narod Steven A. 
Published: November 2014

Abstract
Background: Germline mutations in the BRCA1 and BRCA2 genes confer an estimated 58% to 80% lifetime risk of breast cancer. In general, screening is done for cancer patients if a relative has been diagnosed with breast or ovarian cancer. There are few data on the prevalence of mutations in these genes in Mexican women with breast cancer and this hampers efforts to develop screening policies in Mexico.
Methods: We screened 810 unselected women with breast cancer from three cities in Mexico (Mexico City, Veracruz, and Monterrey) for mutations in BRCA1 and BRCA2, including a panel of 26 previously reported mutations.
Results: Thirty-five mutations were identified in 34 women (4.3% of total) including 20 BRCA1 mutations and 15 BRCA2 mutations. Twenty-two of the 35 mutations were recurrent mutations (62.8%). Only five of the 34 mutation carriers had a first-degree relative with breast cancer (three with BRCA1 and two with BRCA2 mutations).
Conclusion: These results support the rationale for a strategy of screening for recurrent mutations in all women with breast cancer in Mexico, as opposed to restricting screening to those with a sister or mother with breast or ovarian cancer.
Impact: These results will impact cancer genetic testing in Mexico and the identification of at-risk individuals who will benefit from increased surveillance. Cancer Epidemiol Biomarkers Prev; 24(3); 498–505. ©2014 AACR.
Endogenous Sex Hormones and Breast Density in Young Women
Authors: Jung Seungyoun , Stanczyk Frank Z. , Egleston Brian L. , Snetselaar Linda G. , Stevens Victor J. , Shepherd John A. , Van Horn Linda , LeBlanc Erin S. , Paris Kenneth , Klifa Catherine , Dorgan Joanne F. 
Published: November 2014

Abstract
Background: Breast density is a strong risk factor for breast cancer and reflects epithelial and stromal content. Breast tissue is particularly sensitive to hormonal stimuli before it fully differentiates following the first full-term pregnancy. Few studies have examined associations between sex hormones and breast density among young women.
Methods: We conducted a cross-sectional study among 180 women ages 25 to 29 years old who participated in the Dietary Intervention Study in Children 2006 Follow-up Study. Eighty-five percent of participants attended a clinic visit during their luteal phase of menstrual cycle. Magnetic resonance imaging measured the percentage of dense breast volume (%DBV), absolute dense breast volume (ADBV), and absolute nondense breast volume (ANDBV). Multiple-linear mixed-effect regression models were used to evaluate the association of sex hormones and sex hormone–binding globulin (SHBG) with %DBV, ADBV, and ANDBV.
Results: Testosterone was significantly positively associated with %DBV and ADBV. The multivariable geometric mean of %DBV and ADBV across testosterone quartiles increased from 16.5% to 20.3% and from 68.6 to 82.3 cm3, respectively (Ptrend ≤ 0.03). There was no association of %DBV or ADBV with estrogens, progesterone, non–SHBG-bound testosterone, or SHBG (Ptrend ≥ 0.27). Neither sex hormones nor SHBG was associated with ANDBV except progesterone; however, the progesterone result was nonsignificant in analysis restricted to women in the luteal phase.
Conclusions: These findings suggest a modest positive association between testosterone and breast density in young women.
Impact: Hormonal influences at critical periods may contribute to morphologic differences in the breast associated with breast cancer risk later in life. Cancer Epidemiol Biomarkers Prev; 24(2); 369–78. ©2014 AACR.
Preexisting MEK1P124 Mutations Diminish Response to BRAF Inhibitors in Metastatic Melanoma Patients
Authors: Carlino Matteo S. , Fung Carina , Shahheydari Hamideh , Todd Jason R. , Boyd Suzanah C. , Irvine Mal , Nagrial Adnan M. , Scolyer Richard A. , Kefford Richard F. , Long Georgina V. , Rizos Helen 
Published: November 2014

Abstract
Background: MEK1 mutations in melanoma can confer resistance to BRAF inhibitors, although preexisting MEK1P124 mutations do not preclude clinical responses. We sought to determine whether recurrent, preexisting MEK1P124 mutations affected clinical outcome in BRAF inhibitor–treated patients with melanoma.
Methods: Data from four published datasets were analyzed to determine whether preexisting MEK1P124 mutations affect radiologic response or progression-free survival (PFS) in patients with BRAFV600-mutant metastatic melanoma treated with vemurafenib or dabrafenib. The effects of MEK1P124 mutations on MAPK pathway activity and response to BRAF inhibition were also investigated in a series of cell models.
Results: In a pooled analysis of 123 patients, the presence of a pretreatment MEK1P124 mutation (N = 12, 10%) was associated with a poorer RECIST response (33% vs. 72% in MEK1P124Q/S vs. MEK1P124 wild-type, P = 0.018), and a shorter PFS (median 3.1 vs. 4.8 months, P = 0.004). Furthermore, MEK1P124Q/S mutations were shown to have independent kinase activity and introduction of these mutations into a BRAF-mutant melanoma cell line diminished inhibition of ERK phosphorylation by dabrafenib and enhanced clonogenic survival in the presence of dabrafenib compared with cells ectopically expressing wild-type MEK1. Consistent with these data, two BRAF-mutant cell lines with endogenous MEK1P124 mutations showed intermediate sensitivity to dabrafenib, but were highly sensitive to downstream inhibition of MEK or ERK.
Conclusion: Taken together, our data indicate that preexisting MEK1P124 mutations are associated with a reduced response to BRAF inhibitor therapy and identify a subset of patients with BRAF-mutant melanoma likely to benefit from combination therapies involving MEK or ERK inhibitors. Clin Cancer Res; 21(1); 98–105. ©2014 AACR.
Metabolic Imaging of Pancreatic Ductal Adenocarcinoma Detects Altered Choline Metabolism
Authors: Penet Marie-France , Shah Tariq , Bharti Santosh , Krishnamachary Balaji , Artemov Dmitri , Mironchik Yelena , Wildes Flonné , Maitra Anirban , Bhujwalla Zaver M. 
Published: November 2014

Abstract
Purpose: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive and lethal disease that develops relatively symptom-free and is therefore advanced at the time of diagnosis. The absence of early symptoms and effective treatments has created a critical need for identifying and developing new noninvasive biomarkers and therapeutic targets.
Experimental Design: We investigated the metabolism of a panel of PDAC cell lines in culture and noninvasively in vivo with 1H magnetic resonance spectroscopic imaging (MRSI) to identify noninvasive biomarkers and uncover potential metabolic targets.
Results: We observed elevated choline-containing compounds in the PDAC cell lines and tumors. These elevated choline-containing compounds were easily detected by increased total choline (tCho) in vivo, in spectroscopic images obtained from tumors. Principal component analysis of the spectral data identified additional differences in metabolites between immortalized human pancreatic cells and neoplastic PDAC cells. Molecular characterization revealed overexpression of choline kinase (Chk)-α, choline transporter 1 (CHT1), and choline transporter–like protein 1 (CTL1) in the PDAC cell lines and tumors.
Conclusions: Collectively, these data identify new metabolic characteristics of PDAC and reveal potential metabolic targets. Total choline detected with 1H MRSI may provide an intrinsic, imaging probe–independent biomarker to complement existing techniques in detecting PDAC. The expression of Chk-α, CHT1, and CTL1 may provide additional molecular markers in aspirated cytological samples. Clin Cancer Res; 21(2); 386–95. ©2014 AACR.
A Phase I Trial of AT9283 (a Selective Inhibitor of Aurora Kinases) in Children and Adolescents with Solid Tumors: A Cancer Research UK Study
Authors: Moreno Lucas , Marshall Lynley V. , Pearson Andrew D.J. , Morland Bruce , Elliott Martin , Campbell-Hewson Quentin , Makin Guy , Halford Sarah E.R. , Acton Gary , Ross Philip , Kazmi-Stokes Shamim , Lock Victoria , Rodriguez Ana , Lyons John F. , Boddy Alan V. , Griffin Melanie J. , Yule Murray , Hargrave Darren 
Published: November 2014

AbstractPurpose: A phase I trial of AT9283 (a multitargeted inhibitor of Aurora kinases A and B) was conducted in children and adolescents with solid tumors, to identify maximum-tolerated dose (MTD), safety, efficacy, pharmacokinetics, and pharmacodynamic (PD) activity.Experimental Design: AT9283 was administered as a 72-hour continuous intravenous infusion every 3 weeks. A rolling-six design, explored six dose levels (7, 9, 11.5, 14.5, 18.5, and 23 mg/m2/d). Pharmacokinetic and PD assessments, included inhibition of phospho-histone 3 (pHH3) in paired skin punch biopsies.Results: Thirty-three patients were evaluable for toxicity. There were six dose-limiting toxicities and the MTD was 18.5 mg/m2/d. Most common drug-related toxicities were hematologic (neutropenia, anemia, and thrombocytopenia in 36.4%, 18.2%, and 21.2% of patients), which were grade ≥3 in 30.3%, 6.1%, and 3% of patients. Nonhematologic toxicities included fatigue, infections, febrile neutropenia and ALT elevation. One patient with central nervous system–primitive neuroectodermal tumor (CNS-PNET) achieved a partial response after 16 cycles and 3 cases were stable for four or more cycles. Plasma concentrations were comparable with those in adults at the same dose level, clearance was similar although half-life was shorter (4.9 ± 1.5 hours, compared with 8.4 ± 3.7 hours in adults). Inhibition of Aurora kinase B was shown by reduction in pHH3 in 17 of 18 patients treated at ≥11.5 mg/m2/d.Conclusion: AT9283 was well tolerated in children and adolescents with solid tumors with manageable hematologic toxicity. Target inhibition was demonstrated. Disease stabilization was documented in intracranial and extracranial pediatric solid tumors and a phase II dose determined. Clin Cancer Res; 21(2); 267–73. ©2014 AACR.
A Novel MAPK–microRNA Signature Is Predictive of Hormone-Therapy Resistance and Poor Outcome in ER-Positive Breast Cancer
Authors: Miller Philip C. , Clarke Jennifer , Koru-Sengul Tulay , Brinkman Joeli , El-Ashry Dorraya 
Published: November 2014

Abstract
Purpose: Hyperactivation of ERK1/2 MAPK (hMAPK) leads to loss of estrogen receptor (ER) expression and poor outcome in breast cancer. microRNAs (miRNA) play important regulatory roles and serve as biomarkers of disease. Here, we describe molecular, pathologic, and clinical outcome associations of an hMAPK–miRNA expression signature in breast cancer.
Experimental Design: An hMAPK–miRNA signature was identified, and associations of this signature with molecular and genetic alterations, gene expression, pathologic features, and clinical outcomes were determined in primary breast cancers from training data and validated using independent datasets. Univariate and multivariate analyses identified subsignatures associated with increased disease recurrence and poorer disease survival among ER-positive (ER+) patients, respectively.
Results: High-hMAPK–miRNA status significantly correlated with ER-negativity, enrichment for basal and HER2-subtypes, and reduced recurrence-free and disease-specific survival in publicly available datasets. A robust determination of a recurrence signature and a survival signature identified hMAPK–miRNAs commonly associated with poor clinical outcome, and specific subsets associated more closely with either disease recurrence or disease survival, especially among ER+ cancers of both luminal A and luminal B subtypes. Multivariate analyses indicated that these recurrence and survival signatures significantly associated with increased risk of disease-specific death and disease recurrence in ER+ cancer and ER+ cancers treated with hormone therapy.
Conclusions: We report an hMAPK–miRNA signature and two subsignatures derived from it that associate significantly with adverse clinical features, poor clinical outcome, and poor response to hormone therapy in breast cancer, thus identifying potential effectors of MAPK signaling, and novel predictive and prognostic biomarkers or therapeutic targets in breast cancer. Clin Cancer Res; 21(2); 373–85. ©2014 AACR.