bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantitative measurement of HER2 expression in breast cancers: comparison with ‘real-world’ routine HER2 testing in a multicenter Collaborative Biomarker Study and correlation with overall survival
Authors: Yardley Denise A , Kaufman Peter A , Huang Weidong , Krekow Lea , Savin Michael , Lawler William E , Zrada Stephen , Starr Alexander , Einhorn Harvey , Schwartzberg Lee S , Adams John W , Lie Yolanda , Paquet Agnes C , Sperinde Jeff , Haddad Mojgan , Anderson Steve , Brigino Marlon , Pesano Rick , Bates Michael P , Weidler Jodi , Bosserman Linda 
Published: March 2015

Abstract
Introduction
Accurate assessment of HER2 status is critical in determining appropriate therapy for breast cancer patients but the best HER2 testing methodology has yet to be defined. In this study, we compared quantitative HER2 expression by the HERmark™ Breast Cancer Assay (HERmark) with routine HER2 testing by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), and correlated HER2 results with overall survival (OS) of breast cancer patients in a multicenter Collaborative Biomarker Study (CBS).

Methods
Two hundred and thirty-two formalin-fixed, paraffin-embedded breast cancer tissues and local laboratory HER2 testing results were provided by 11 CBS sites. HERmark assay and central laboratory HER2 IHC retesting were retrospectively performed in a blinded fashion. HER2 results by all testing methods were obtained in 192 cases.

Results
HERmark yielded a continuum of total HER2 expression (H2T) ranging from 0.3 to 403 RF/mm2 (approximately 3 logs). The distribution of H2T levels correlated significantly (P <0.0001) with all routine HER2 testing results. The concordance of positive and negative values (equivocal cases excluded) between HERmark and routine HER2 testing was 84% for local IHC, 96% for central IHC, 85% for local FISH, and 84% for local HER2 status. OS analysis revealed a significant correlation of shorter OS with HER2 positivity by local IHC (HR = 2.6, P = 0.016), central IHC (HR = 3.2, P = 0.015), and HERmark (HR = 5.1, P <0.0001) in this cohort of patients most of whom received no HER2-targeted therapy. The OS curve of discordant low (HER2 positive but H2T low, 10% of all cases) was aligned with concordant negative (HER2 negative and H2T low, HR = 1.9, P = 0.444), but showed a significantly longer OS than concordant positive (HER2 positive and H2T high, HR = 0.31, P = 0.024). Conversely, the OS curve of discordant high (HER2 negative but H2T high, 9% of all cases) was aligned with concordant positive (HR = 0.41, P = 0.105), but showed a significantly shorter OS than concordant negative (HR = 41, P <0.0001).

Conclusions
Quantitative HER2 measurement by HERmark is highly sensitive, accurately quantifies HER2 protein expression and correlates well with routine HER2 testing. When HERmark and local HER2 results were discordant, HERmark more accurately predicted overall survival.
Application of the 2013 ACR/EULAR classification criteria for systemic sclerosis to patients with Raynaud’s phenomenon
Authors: Park Jin-Su , Park Min-Chan , Song Jason Jungsik , Park Yong-Beom , Lee Soo-Kon , Lee Sang-Won 
Published: March 2015

Abstract
Introduction
We investigated how many patients, who presented with Raynaud’s phenomenon (RP) and who had not been classified as systemic sclerosis (SSc), would be reclassified as SSc, if the 2013 American College of Rheumatology (ACR)/the European League Against Rheumatism (EULAR) classification criteria were used. We also analyzed the predictive values of the reclassification as SSc in those patients.

Methods
We consecutively enrolled 64 patients with RP and 60 patients with SSc. We applied the new classification criteria to them, reclassified them, and compared variables between those who were newly classified as SSc and those who were not or previously classified as SSc.

Results
Seventeen of 64 patients (26.5%), who presented with RP, but did not fulfill the 1980 ACR classification criteria, were newly classified as SSc by the 2013 ACR/EULAR classification criteria. The newly classified patients as SSc showed increased frequencies of sclerodactyly, digital tip ulcer, telangiectasia, abnormal nailfold capillaries and the presence of anti-centromere antibody, compared to those not and telangiectasia and anti-centromere antibody, compared to the previously classified patients. For the reclassification as SSc, the variables with independent predictive value were sclerodactyly (odds ratio (OR) 60.025), telangiectasia (OR 13.353) and the presence of anti-centromere antibody (OR 11.168).

Conclusions
Overall, 26.5% of the patients, who presented with RP, but who did not fulfill the 1980 ACR classification criteria, were newly classified as SSc according to the 2013 ACR/EULAR classification criteria. Sclerodactyly, telangiectasia, and the presence of anti-centromere antibody had independent predictive value for reclassifying patients with RP as SSc.
Lung disease as a determinant of cognitive decline and dementia
Authors: Dodd James W 
Published: March 2015

AbstractAlmost 40 million people currently live with dementia but this is estimated to double over the next 20 years; despite this, research identifying modifiable risk factors is scarce. There is increasing evidence that cognitive impairment is more frequent in those with chronic lung disease than those without. Chronic obstructive pulmonary disease affects 210 million people, with cognitive impairment present in 60% of certain populations. Co-morbid cognitive dysfunction also appears to impact on important outcomes such as quality of life, hospitalisation and survival. This review summarises the evidence of an association between cognition, impaired lung function and obstructive lung disease. It goes on to examine the contribution of neuro-imaging to our understanding of the underlying pathophysiology. While the mechanisms of brain pathology and cognitive impairment are likely to be complex and multi-factorial, there is evidence to suggest a key role for occult cerebrovascular damage independent of traditional vascular risk factors, including smoking.
Paediatric leukaemia DNA methylation profiling using MBD enrichment and SOLiD sequencing on archival bone marrow smears
Authors: Wong Nicholas CL , Meredith Gavin D , Marnellos George , Dudas Miroslav , Parkinson-Bates Mandy , Halemba Suh , Chatterton Zac , Maksimovic Jovana , Ashley David M , Mechinaud Francoise , Craig Jeffrey M , Saffery Richard 
Published: March 2015

Abstract

Background:
Acute Lymphoblastic Leukaemia (ALL) is the most common cancer in children. Over the past four decades, research has advanced the treatment of this cancer from a less than 60% chance of survival to over 85% today. The causal molecular mechanisms remain unclear. Here, we performed sequencing-based genomic DNA methylation profiling of eight paediatric ALL patients using archived bone marrow smear microscope slides.

Findings:
SOLiD™ sequencing data was collected from Methyl-Binding Domain (MBD) enriched fractions of genomic DNA. The primary tumour and remission bone marrow sample was analysed from eight patients. Four patients relapsed and the relapsed tumour was analysed. Input and MBD-enriched DNA from each sample was sequenced, aligned to the hg19 reference genome and analysed for enrichment peaks using MACS (Model-based Analysis for ChIP-Seq) and HOMER (Hypergeometric Optimization of Motif EnRichment). In total, 3.67 gigabases (Gb) were sequenced, 2.74 Gb were aligned to the reference genome (average 74.66% alignment efficiency). This dataset enables the interrogation of differential DNA methylation associated with paediatric ALL. Preliminary results reveal concordant regions of enrichment indicative of a DNA methylation signature.

Conclusion:
Our dataset represents one of the first SOLiD™MBD-Seq studies performed on paediatric ALL and is the first to utilise archival bone marrow smears. Differential DNA methylation between cancer and equivalent disease-free tissue can be identified and correlated with existing and published genomic studies. Given the rarity of paediatric haematopoietic malignancies, relative to adult counterparts, our demonstration of the utility of archived bone marrow smear samples to high-throughput methylation sequencing approaches offers tremendous potential to explore the role of DNA methylation in the aetiology of cancer.
Bacterial and viral identification and differentiation by amplicon sequencing on the MinION nanopore sequencer
Authors: Kilianski Andy , Haas Jamie L , Corriveau Elizabeth J , Liem Alvin T , Willis Kristen L , Kadavy Dana R , Rosenzweig C Nicole , Minot Samuel S 
Published: March 2015

Abstract

Background
The MinION™ nanopore sequencer was recently released to a community of alpha-testers for evaluation using a variety of sequencing applications. Recent reports have tested the ability of the MinION™ to act as a whole genome sequencer and have demonstrated that nanopore sequencing has tremendous potential utility. However, the current nanopore technology still has limitations with respect to error-rate, and this is problematic when attempting to assemble whole genomes without secondary rounds of sequencing to correct errors. In this study, we tested the ability of the MinION™ nanopore sequencer to accurately identify and differentiate bacterial and viral samples via directed sequencing of characteristic genes shared broadly across a target clade.

Results
Using a 6 hour sequencing run time, sufficient data were generated to identify an E. coli sample down to the species level from 16S rDNA amplicons. Three poxviruses (cowpox, vaccinia-MVA, and vaccinia-Lister) were identified and differentiated down to the strain level, despite over 98% identity between the vaccinia strains. The ability to differentiate strains by amplicon sequencing on the MinION™ was accomplished despite an observed per-base error rate of approximately 30%.

Conclusions
While nanopore sequencing, using the MinION™ platform from Oxford Nanopore in particular, continues to mature into a commercially available technology, practical uses are sought for the current versions of the technology. This study offers evidence of the utility of amplicon sequencing by demonstrating that the current versions of MinION™ technology can accurately identify and differentiate both viral and bacterial species present within biological samples via amplicon sequencing.
Efficacy of intravenous sedation and oral nifedipine in dental implant patients with preoperative hypertension - a retrospective study of 516 cases
Authors: Kimura Motoshi , Takasugi Yoshihiro , Hanano Shigeyoshi , Terabe Katsuyuki , Kimura Yuko 
Published: March 2015

Abstract

Background
To examine the effects of intravenous sedation and oral nifedipine on blood pressure and pulse rate in patients with perioperative high blood pressure undergoing implant surgery, the clinical records of dental implant patients managed by intravenous sedation at our outpatient dental offices were retrospectively evaluated.

Methods
A total of 516 clinical charts were evaluated. The subjects were divided into two groups: a normotensive group with no history of hypertension and a hypertensive group with a history of hypertension. The patients in the hypertensive group were further divided into two subgroups: with or without nifedipine administration before operation. Systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse rate (PR), and rate pressure product (RPP) were assessed.

Results
In 30 patients (33%) of the hypertensive group, the high blood pressure on arrival obviously declined to around or less than 160 mmHg; in the remaining patients in the group who showed a mean SBP of 182.1 ± 13.8 mmHg on arrival, the blood pressure did not decrease after a 30-min rest. Oral nifedipine administered to the patients with sustained high blood pressure decreased SBP to 144.7 ± 23.1 mmHg in 28.1 ± 9.3 min after administration, comparable to that in hypertensive patients without nifedipine.

Conclusions
For patients with stage 2 hypertension before operation, it may be difficult to maintain the recommended blood pressure during surgery by only intravenous sedation; reduction of blood pressure by antihypertensive drugs may be necessary.
C-Reactive Protein As a Marker of Melanoma Progression
Authors: Fang Shenying , Wang Yuling , Sui Dawen , Liu Huey , Ross Merrick I. , Gershenwald Jeffrey E. , Cormier Janice N. , Royal Richard E. , Lucci Anthony , Schacherer Christopher W. , Gardner Julie M. , Reveille John D. , Bassett Roland L. , Wang Li-E , Wei Qingyi , Amos Christopher I. , Lee Jeffrey E. 
Published: March 2015

Purpose To investigate the association between blood levels of C-reactive protein (CRP) in patients with melanoma and overall survival (OS), melanoma-specific survival (MSS), and disease-free survival. Patients and Methods Two independent sets of plasma samples from a total of 1,144 patients with melanoma (587 initial and 557 confirmatory) were available for CRP determination. Kaplan-Meier method and Cox regression were used to evaluate the relationship between CRP and clinical outcome. Among 115 patients who underwent sequential blood draws, we evaluated the relationship between change in disease status and change in CRP using nonparametric tests. Results Elevated CRP level was associated with poorer OS and MSS in the initial, confirmatory, and combined data sets (combined data set: OS hazard ratio, 1.44 per unit increase of logarithmic CRP; 95% CI, 1.30 to 1.59; P < .001; MSS hazard ratio, 1.51 per unit increase of logarithmic CRP; 95% CI, 1.36 to 1.68; P < .001). These findings persisted after multivariable adjustment. As compared with CRP < 10 mg/L, CRP ≥ 10 mg/L conferred poorer OS in patients with any-stage, stage I/II, or stage III/IV disease and poorer disease-free survival in those with stage I/II disease. In patients who underwent sequential evaluation of CRP, an association was identified between an increase in CRP and melanoma disease progression. Conclusion CRP is an independent prognostic marker in patients with melanoma. CRP measurement should be considered for incorporation into prospective studies of outcome in patients with melanoma and clinical trials of systemic therapies for those with melanoma.
Progesterone Receptor Transcriptome and Cistrome in Decidualized Human Endometrial Stromal Cells
Authors: Mazur Erik C. , Vasquez Yasmin M. , Li Xilong , Kommagani Ramakrishna , Jiang Lichun , Chen Rui , Lanz Rainer B. , Kovanci Ertug , Gibbons William E. , DeMayo Francesco J. 
Published: March 2015

Abstract
Decidualization is a complex process involving cellular proliferation and differentiation of the endometrial stroma that is required to establish and support pregnancy. Progesterone acting via its nuclear receptor, the progesterone receptor (PGR), is a critical regulator of decidualization and is known to interact with certain members of the activator protein-1 (AP-1) family in the regulation of transcription. In this study, we identified the cistrome and transcriptome of PGR and identified the AP-1 factors FOSL2 and JUN to be regulated by PGR and important in the decidualization process. Direct targets of PGR were identified by integrating gene expression data from RNA sequencing with the whole-genome binding profile of PGR determined by chromatin immunoprecipitation followed by deep sequencing (ChIP-seq) in primary human endometrial stromal cells exposed to 17β-estradiol, medroxyprogesterone acetate, and cAMP to promote in vitro decidualization. Ablation of FOSL2 and JUN attenuates the induction of 2 decidual marker genes, IGFBP1 and PRL. ChIP-seq analysis of genomic binding revealed that FOSL2 is bound in proximity to 8586 distinct genes, including nearly 80% of genes bound by PGR. A comprehensive assessment of the PGR-dependent decidual transcriptome integrated with the genomic binding of PGR identified FOSL2 as a potentially important transcriptional coregulator of PGR via direct interaction with regulatory regions of genes actively regulated during decidualization.
GlycA: A Composite Nuclear Magnetic Resonance Biomarker of Systemic Inflammation
Authors: Otvos James D , Shalaurova Irina , Wolak-Dinsmore Justyna , Connelly Margery A , Mackey Rachel H , Stein James H , Tracy Russell P 
Published: March 2015

AbstractBACKGROUNDNuclear magnetic resonance (NMR) spectra of serum obtained under quantitative conditions for lipoprotein particle analyses contain additional signals that could potentially serve as useful clinical biomarkers. One of these signals that we named GlycA originates from a subset of glycan N-acetylglucosamine residues on enzymatically glycosylated acute-phase proteins. We hypothesized that the amplitude of the GlycA signal might provide a unique and convenient measure of systemic inflammation.METHODSWe developed a spectral deconvolution algorithm to quantify GlycA signal amplitudes from automated NMR LipoProfile® test spectra and assessed analytic precision and biological variability. Spectra of acute-phase glycoproteins and serum fractions were analyzed to probe the origins of the GlycA signal. GlycA concentrations obtained from archived NMR LipoProfile spectra of baseline plasma from 5537 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) were used to assess associations with demographic and laboratory parameters including measures of inflammation.RESULTSMajor acute-phase protein contributors to the serum GlycA signal are α1-acid glycoprotein, haptoglobin, α1-antitrypsin, α1-antichymotrypsin, and transferrin. GlycA concentrations were correlated with high-sensitivity C-reactive protein (hsCRP) (r = 0.56), fibrinogen (r = 0.46), and interleukin-6 (IL-6) (r = 0.35) (all P &lt; 0.0001). Analytic imprecision was low (intra- and interassay CVs 1.9% and 2.6%, respectively) and intraindividual variability, assessed weekly for 5 weeks in 23 healthy volunteers, was 4.3%, lower than for hsCRP (29.2%), cholesterol (5.7%), and triglycerides (18.0%).CONCLUSIONSGlycA is a unique inflammatory biomarker with analytic and clinical attributes that may complement or provide advantages over existing clinical markers of systemic inflammation.
Modulation of Electron-Acoustic Waves in a Plasma with Vortex Electron Distribution
Authors: Demiray Hilmi 
Published: March 2015

Abstract
In the present work, employing a one-dimensional model of a plasma composed of a cold electron fluid, hot electrons obeying a trapped/vortex-like distribution and stationary ions, we study the amplitude modulation of electron-acoustic waves by use of the conventional reductive perturbation method. Employing the field equations with fractional power type of nonlinearity, we obtained the nonlinear Schrödinger equation as the evolution equation of the same order of nonlinearity. Seeking a harmonic wave solution with progressive wave amplitude to the evolution equation it is found that the NLS equation with fractional power assumes envelope type of solitary waves.
Modelling and Optimization of CO2Absorption in Pneumatic Contactors Using Artificial Neural Networks Developed with Clonal Selection-Based Algorithm
Authors: Cozma Petronela , Drăgoi Elena Niculina , Mămăligă Ioan , Curteanu Silvia , Wukovits Walter , Friedl Anton , Gavrilescu Maria 
Published: March 2015

AbstractOur research focuses on the application of airlift contactors (ALRs) for the decontamination of CO2-containing gas streams, such as biogas. To assess the performance of ALRs during CO2absorption, a complex experimental programme was applied in a laboratory-scale rectangular pneumatic contactor, able to operate either as a bubble column or as an airlift reactor. Using the experimental data, a model based onartificial neural network (ANN)was developed. The algorithm for determining the optimal neural network model and for reactor optimization isclonal selection (CS), belonging toartificial immune systemclass, which is a new computational intelligence paradigm based on the principles of the vertebrate immune system. To improve its capabilities and the probability for highly suitable models and input combinations, addressing maximum efficiency, aBack-Propagation (BK)algorithm – a supervised learning method based on the delta rule – is used as a local search procedure. It is applied in a greedy manner for the best antibody found in each generation. Since the highest affinity antibodies are cloned in the next generation, the effect ofBKon the suitability of the individuals propagates into a large proportion of the population. In parallel with theBKhybridization of the basicCS–ANNcombination, a series of normalization procedures are included for improving the overall results provided by the new algorithm callednCS-MBK(normalizedClonal Selection-Multilayer Perceptron Neural NetworkandBack-Propagationalgorithm). The optimization allowed for achieving the optimal reactor configuration, which leads to a maximum amount of CO2dissolved in water.
Price Dependence between Different Beef Cuts and Quality Grades: A Copula Approach at the Retail Level for the U.S. Beef Industry
Authors: Panagiotou Dimitrios , Stavrakoudis Athanassios 
Published: March 2015

Abstract
The objective of this study is to assess the degree and the structure of price dependence between different cuts of the beef industry in the USA. This is pursued using the statistical tool of copulas. To this end, it utilizes retail monthly data of beef cuts, within and between the quality grades of Choice and Select, over the period 2000–2014. For the Choice quality grade, there was evidence of asymmetric price co-movements between all six pairs of beef cuts under consideration. No evidence of asymmetric price co-movements was found between the three pairs of beef cuts for the Select quality grade. For the pairs of beef cuts formed between the Choice and Select quality grades, the empirical results point to the existence of price asymmetry only for the case of the chuck roast cut.
Connecting linguistic variation and non-linguistic behaviour
Authors: MacFarlane Andrew Euan , Hay Jennifer 
Published: March 2015

AbstractThis paper reviews well-established results from sociolinguistics and social psychology, presents recent results at the interface of the two, and argues that – together – the literature predicts unexplored interactions between non-linguistic behavioural patterns and linguistic variation. It is well documented in sociolinguistics that individuals shift their speech patterns in response to their interlocutors and environment, and that this can sometimes be quite subtle and automatic. That is – speech can be affected by environmental primes. We explore the degree to which speech may alsoactas a prime. Results from the social psychology literature suggest that linguistic choices should have consequences for our non-linguistic behaviours (such as claimed attitudes, or physical movements). Behavioural experiences throughout our lives might also shape and influence our linguistic repertoires. We present a range of literature related to this question, and present some preliminary evidence that speech can indeed act as a behavioural prime.