bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reducing Artifactual EGFR T790M Mutations in DNA from Formalin-Fixed Paraffin-Embedded Tissue by Use of Thymine-DNA Glycosylase
Authors: Do Hongdo , Molania Ramyar , Mitchell Paul L , Vaiskunaite Rita , Murdoch John D , Dobrovic Alexander 
Published: July 2017

AbstractBACKGROUNDFalse-positive EGFR T790M mutations have been reported in formalin-fixed lung tumors, but the cause of the false positives has not been identified. The T790M mutation results from a C&gt;T change at the cytosine of a CpG dinucleotide. The presence or absence of methylation at this cytosine has different consequences following deamination, resulting in a thymine or uracil, respectively, both of which however result in an artifactual change. Uracil-DNA glycosylase (UDG) can be used to eliminate DNA templates with uracil residues but is not active against artifactual thymines. We therefore investigated the use of thymine-DNA glycosylase (TDG) to reduce artifactual T790M mutations.METHODSFormalin-fixed normal lung tissues and lung squamous cell carcinomas were tested to measure the frequency of false-positive EGFR mutations by use of droplet digital PCR before and after treatment with either UDG or TDG. Methylation at the cytosine at EGFR T790 was assessed by pyrosequencing and by analysis of public databases.RESULTSArtifactual EGFR T790M mutations were detected in all of the archival formalin-fixed normal lung and lung squamous cell carcinomas at mutant allele frequencies of 1% or lower. The cytosine at EGFR T790 showed high levels of methylation in all lung cancer samples and normal tissues. Pretreatment of the formalin-fixed DNA with either UDG or TDG reduced the false EGFR T790M mutations, but a greater reduction was seen with the TDG treatment.CONCLUSIONSBoth U:G and T:G lesions in formalin-fixed tissue are sources of false-positive EGFR T790M mutations. This is the first report of the use of TDG to reduce sequence artifacts in formalin-fixed DNA and is applicable to the accurate detection of mutations arising at methylated cytosines.
Standardization of Free Thyroxine Measurements Allows the Adoption of a More Uniform Reference Interval
Authors: De Grande Linde A C , Van Uytfanghe Katleen , Reynders Dries , Das Barnali , Faix James D , MacKenzie Finlay , Decallonne Brigitte , Hishinuma Akira , Lapauw Bruno , Taelman Paul , Van Crombrugge Paul , Van den Bruel Annick , Velkeniers Brigitte , Williams Paul , Thienpont Linda M 
Published: July 2017

AbstractBACKGROUNDThe IFCC Committee for Standardization of Thyroid Function Tests intended to standardize free thyroxine (FT4) immunoassays. We developed a Système International d'Unités traceable conventional reference measurement procedure (RMP) based on equilibrium dialysis and mass spectrometry. We describe here the latest studies intended to recalibrate against the RMP and supply a proof of concept, which should allow continued standardization efforts.METHODSWe used the RMP to target the standardization and reference interval (RI) panels, which were also measured by 13 manufacturers. We validated the suitability of the recalibrated results to meet specifications for bias (3.3%) and total error (8.0%) determined from biological variation. However, because these specifications were stringent, we expanded them to 10% and 13%, respectively. The results for the RI panel were reported as if the assays were recalibrated. We estimated all but 1 RI using parametric statistical procedures and hypothesized that the RI determined by the RMP was suitable for use by the recalibrated assays.RESULTSTwelve of 13 recalibrated assays had a bias, meeting the 10% specification with 95% confidence; for 7 assays, this applied even for the 3.3% specification. Only 1 assay met the 13% total error specification. Recalibration reduced the CV of the assay means for the standardization panel from 13% to 5%. The proof-of-concept study confirmed our hypothesis regarding the RI but within constraints.CONCLUSIONSRecalibration to the RMP significantly reduced the FT4 immunoassays' bias, so that the RI determined by the RMP was suitable for common use within a margin of 12.5%.
Pediatric reference intervals for 29 Ortho VITROS 5600 immunoassays using the CALIPER cohort of healthy children and adolescents
Authors: Higgins Victoria , Fung Angela W.S. , Chan Man Khun , Macri Joseph , Adeli Khosrow 
Published: July 2017

Abstract

Background:
Accurate reference intervals (RIs) based on a healthy pediatric population are essential for pediatric test result interpretation. The CALIPER project has recruited a large healthy cohort and completed a series of a priori studies to address gaps in pediatric RIs. As immunoassays from different manufacturers for endocrine and special chemistry markers are not standardized and show marked intermethod differences, direct RI studies are needed for each major analytical platform. Here, we report age- and sex-specific pediatric RIs for 29 immunoassays on the Ortho Clinical Diagnostics (Ortho) VITROS® 5600 analyzer.

Methods:
Health information and blood samples were collected from healthy pediatric subjects. Using the Ortho VITROS 5600 Integrated System MicroWell Technology, 29 biomarkers were measured. Analyte concentrations were partitioned by age and sex according to the Harris and Boyd method. After removing outliers, age- and sex-specific RIs and corresponding 90% confidence intervals were calculated according to CLSI guidelines.

Results:
All analytes required age partitioning except β-human chorionic gonadotropin (β-hCG), cancer antigen 15-3 (CA15-3), rubella immunoglobulin G (rubella IgG), and vitamin D. Several analytes including estradiol, progesterone, testosterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), free triiodothyronine (FT3), total triiodothyronine (TT3), total thyroxine (TT4), thyroid uptake, ferritin, intact parathyroid hormone (iPTH), total prostate-specific antigen (tPSA), free prostate-specific antigen (fPSA), cancer antigen 125 (CA125), creatine kinase MB (CK-MB), and myoglobin showed sex differences, observed mostly with the onset of puberty.

Conclusions:
Complex reference value trends were observed across the pediatric age range for several biomarkers examined on Ortho VITROS immunoassays. The availability of VITROS immunoassay RIs will enable accurate laboratory test interpretation and diagnosis for the pediatric population. As recommended by the CLSI EP28-A3c guidelines, implementation of these RIs should be validated for each laboratory’s local pediatric population.
The number of maximal torsion cosets in subvarieties of tori
Authors: Martínez César 
Published: July 2017

Abstract
We present sharp bounds on the number of maximal torsion cosets in a subvariety of the complex algebraic torus

𝔾
m
n

{\mathbb{G}_{\mathrm{m}}^{n}}

.
Our first main result gives a bound in terms of the degree of the defining polynomials.
We also give a bound for the number of isolated torsion point, that is maximal torsion cosets of dimension 0, in terms of the volume of the Newton polytope of the defining polynomials.
This result proves the conjectures of Ruppert and of Aliev and Smyth on the number of isolated torsion points of a hypersurface. These conjectures bound this number in terms of the multidegree and the volume of the Newton polytope of a polynomial defining the hypersurface, respectively.
Fabrication and simulation of 1540-nm transmission by 532-nm excitation in photonic crystal of Er:ZnO film
Authors: Fan Ranran , Lu Fei , Li Kaikai 
Published: July 2017

AbstractErbium (Er)-doped ZnO thin film is fabricated on sapphire substrate by radio frequency magnetron sputtering technology. The as-deposited Er:ZnO film has a good film quality and exhibits excellent single-mode waveguide characteristic. A photonic crystal structure in the Er:ZnO film is fabricated by focused-ion-beam etching. When the film is stimulated by a 532 nm laser, photoluminescence (PL) at 1540 nm can be excited. Simulation results show that the propagation of Er-related emission of 1540 nm will be well restricted along a certain direction in the photonic crystal structure. It provides a novel way to control and confine the transmission of light in ZnO waveguide and will be applicable for the application of Er:ZnO photonic devices.
Baseline tumor Lipiodol uptake after transarterial chemoembolization for hepatocellular carcinoma: identification of a threshold value predicting tumor recurrence
Authors: Matsui Yusuke , Horikawa Masahiro , Jahangiri Noudeh Younes , Kaufman John A. , Kolbeck Kenneth J. , Farsad Khashayar 
Published: July 2017

Abstract

Background
The aim of the study was to evaluate the association between baseline Lipiodol uptake in hepatocellular carcinoma (HCC) after transarterial chemoembolization (TACE) with early tumor recurrence, and to identify a threshold baseline uptake value predicting tumor response.

Patients and methods
A single-institution retrospective database of HCC treated with Lipiodol-TACE was reviewed. Forty-six tumors in 30 patients treated with a Lipiodol-chemotherapy emulsion and no additional particle embolization were included. Baseline Lipiodol uptake was measured as the mean Hounsfield units (HU) on a CT within one week after TACE. Washout rate was calculated dividing the difference in HU between the baseline CT and follow-up CT by time (HU/month). Cox proportional hazard models were used to correlate baseline Lipiodol uptake and other variables with tumor response. A receiver operating characteristic (ROC) curve was used to identify the optimal threshold for baseline Lipiodol uptake predicting tumor response.

Results
During the follow-up period (mean 5.6 months), 19 (41.3%) tumors recurred (mean time to recurrence = 3.6 months). In a multivariate model, low baseline Lipiodol uptake and higher washout rate were significant predictors of early tumor recurrence (P = 0.001 and < 0.0001, respectively). On ROC analysis, a threshold Lipiodol uptake of 270.2 HU was significantly associated with tumor response (95% sensitivity, 93% specificity).

Conclusions
Baseline Lipiodol uptake and washout rate on follow-up were independent predictors of early tumor recurrence. A threshold value of baseline Lipiodol uptake > 270.2 HU was highly sensitive and specific for tumor response. These findings may prove useful for determining subsequent treatment strategies after Lipiodol TACE.
Mixture model-based association analysis with case-control data in genome wide association studies
Authors: Ali Fadhaa , Zhang Jian 
Published: July 2017

AbstractMultilocus haplotype analysis of candidate variants with genome wide association studies (GWAS) data may provide evidence of association with disease, even when the individual loci themselves do not. Unfortunately, when a large number of candidate variants are investigated, identifying risk haplotypes can be very difficult. To meet the challenge, a number of approaches have been put forward in recent years. However, most of them are not directly linked to the disease-penetrances of haplotypes and thus may not be efficient. To fill this gap, we propose a mixture model-based approach for detecting risk haplotypes. Under the mixture model, haplotypes are clustered directly according to their estimated disease penetrances. A theoretical justification of the above model is provided. Furthermore, we introduce a hypothesis test for haplotype inheritance patterns which underpin this model. The performance of the proposed approach is evaluated by simulations and real data analysis. The results show that the proposed approach outperforms an existing multiple testing method.
Análisis de PCR-RFLP del gen de leptina y su asociación con características de la leche en ganado nativo (Bos indicus) de Irán
Authors: Rezaei Mojtaba , Mirhosseini Seyed Ziaeddin , Hossein-Zadeh Navid Ghavi 
Published: July 2017

Se utilizó una muestra ganadera experimental para la caracterización de los genes y las frecuencias genotípicas y evaluar la asociación entre los polimorfismos de longitud del fragmento de restricción BsaAI en el gen de leptina y las características lácteas. Se recolectaron muestras de sangre de 390 vacas proporcionadas por el censo ganadero de la provincia de Guilán en Irán. La extracción de ADN genómico se basó en el método modificado de precipitación salina. El fragmento de 522 bp que comprende la región parcial del exón 3 e intrón 2 del locus del gen de leptina se amplificó mediante PCR-RFLP e iniciadores específicos. La digestión del fragmento amplificado con la enzima de restricción BsaAI reveló dos alelos de A y B con frecuencias de 0.447 y 0.553, y tres genotipos de AA, AB, BB con frecuencias de 0.185, 0.526 y 0.289 en la población estudiada, espectivamente. El resultado del contenido de polimorfismo fue 0.372 y para heterocigosis 0.526. Los resultados demostraron que la población estudiada estaba en equilibrio Hardy-Weinberg. El análisis estadístico indicó que el polimorfismo LEP-BsaAI tiene un efecto significativo en la producción de leche, porcentaje de grasa y proteína de la leche (P<0.01). Animales portadores del genotipo heterocigoto (AB) produjeron 1.17 y 0.7 kg/d más leche que los animales homocigotos AA y BB, respectivamente. Los animales con el genotipo AA tuvieron mayor grasa (0.28 %) y porcentaje de proteína (0.17 %) que el genotipo AB. Tales resultados pueden utilizarse como criterios para facilitar la selección genética en losprogramas de cría animal.
Prevalencia de la translocación robertsoniana 1;29 bovina en hatos ganaderos del estado de Zacatecas, México
Authors: Meza-López Carlos , Lozano-Carbajal Braulio , De la Colina-Flores Federico , Bañuelos-Valenzuela Rómulo , López-Carlos Marco Antonio , Echavarría-Cháirez Francisco G. , Reveles-Torres Luis Roberto 
Published: July 2017

El objetivo del trabajo fue determinar la prevalencia de la Translocación robertsoniana 1;29 (t rob 1;29) en hatos ganaderos del estado de Zacatecas, México. Se obtuvieron muestras sanguíneas de 661 bovinos de las razas Holstein (n= 284), Suizo Americano (n= 213), Suizo Europeo (n= 69), Simmental (n= 13), Angus (n= 5), Criollo (n= 65), Chianina (n= 3) y Charolais (n= 9). Los muestreos se realizaron en nueve municipios de Zacatecas y uno de Agusacalientes. Se registró además la edad, el sexo y el propósito productivo. La identificación de la t rob 1;29 se realizó mediante técnica convencional de citogenética. Se observó una prevalencia general del 4.1 %, sin diferencias (P>0.05) entre machos y hembras (6.0 vs 3.4 % respectivamente), aunque superior (P<0.10) en animales jóvenes vs adultos (5.4 vs 2.6 % respectivamente). Se observaron diferencias raciales (P<0.001), con una mayor prevalencia en la raza Criollo (12.3 %), seguida de la raza Suizo Americano (7.5 %) y menor entre las razas Suizo Europeo (1.4 %), Holstein (0.4 %) y otras (0.0 %). De acuerdo al propósito productivo se encontró una mayor prevalencia (P<0.001) en las explotaciones de doble propósito (12.3 %) que en los dedicadas exclusivamente a la producción de leche (3.3 %) o carne (2.4 %). Con base en estos resultados y debido a los potenciales efectos negativos sobre la productividad del hato, es recomendable el análisis cromosómico de los animales reproductores como práctica rutinaria de identificación de animales portadores de la t rob 1;29, principalmente en los sementales.
Calidad de vida en pacientes con hepatitis C crónica en Colombia
Authors: Yepes Barreto Ismael De Jesús , Carmona Meza Zenen Antonio , Múnera Contreras María Nicol 
Published: July 2017

Introducción: Los datos sobre calidad de vida en pacientes con hepatitis C son escasos en nuestro medio. A la fecha ningún estudio que haya determinado la carga de la enfermedad en esta población en el territorio colombianoObjetivos: Determinar la calidad de vida en pacientes con hepatitis C crónica e identificar sus factores determinantes utilizando la encuesta SF36V2.Metodología: Estudio transversal analítico realizado desde el 01/06/2015 hasta el 31/08/2015. Un encuestador entrenado aplicó la encuesta SF-36 V2 en su versión en castellano (Qualitimetric Inc). La regresión lineal multivariante identificó los factores relacionados con la CVRS. El índice de Charlson estimó el peso de las comorbilidades de la muestra.Resultados: 41 pacientes estuvieron disponibles para el análisis. La media de edad fue de 57 años (DE 12,6). El 50% de los sujetos presentaban cirrosis/fibrosis avanzada. El RCF y el RCM fueron de 48.2 y 45.6, respectivamente. El análisis de regresión lineal univariante identifico al sexo, la edad, el índice de charlson y la presencia de cirrosis hepática como los principales determinantes de la calidad de vida. El índice de charlson expresado como la probabilidad de supervivencia a 10 años fue el único predictor independiente del SFD6. Conclusión: La edad, el sexo, la cirrosis hepática se identificaron como determinantes de la CVRS. El índice de Charlson fue el único predictor independiente de SFD6. La implementación de programas multidisciplinarios son necesarios para el tratamiento integral de los pacientes infectados.
Do Firms Manage Earnings to Influence Credit Ratings? Evidence from Negative Credit Watch Resolutions
Authors: Liu Alfred Zhu , Subramanyam K. R. , Zhang Jieying , Shi Charles 
Published: July 2017

ABSTRACT
We investigate whether issuers on negative credit watch manage earnings upward and whether such earnings management favorably influences the watch resolution. We find that rating, industry, and performance matched discretionary accruals reported during negative watch are significantly higher than their respective pre- and post-watch levels, after controlling for accrual reversal. Consistent with its opportunistic nature, we find that accrual management increases with issuers' incentives to avoid downgrade, and decreases with their earnings management constraints and the strength of the external monitoring. Surprisingly, such accrual management significantly increases the likelihood of a favorable resolution—issuers in the top half of the discretionary accruals distribution are 24 percent less likely to be downgraded than those in the propensity score matched bottom half. We find that issuers that avoid downgrades through income-increasing accrual management significantly underperform those that do not over the ensuing year, mitigating the signaling or measurement error explanations for our results. Finally, we find that accrual management does not reflect attempts to improve short-term credit quality.
JEL Classifications: M41; G29; G38.
El otro Juan Rana
Authors: Sáez Raposo Francisco 
Published: July 2017

El actor español Cosme Pérez constituye un caso único en la historia del teatro. Tras crear el personaje de Juan Rana, a comienzos de la década de los años treinta del siglo XVII (única auténtica máscara, equiparable a las de la ,commedia dell’arte italiana del teatro español), actor y personaje llegaron a fundirse de tal manera que el público ya no pudo concebir la posibilidad de que otro actor “se atreviera” a interpretarlo. Tras la muerte de Cosme, la extraordinaria fama alcanzada por Rana durante casi cuarenta años sobre las tablas motivó a algunos dramaturgos a intentar resucitarlo escénicamente, para perpetuar su éxito. En este artículo se estudian esos intentos, la suerte que corrieron y las consecuencias que el paso del tiempo tuvo en él, convirtiéndolo en un personaje diverso al primigenio.
Health Status of Old Age Population in Bulgaria
Authors: Mourgova Mariana 
Published: July 2017

Abstract
This article examines the health status of the population in Bulgaria at age 65 by gender during the period 2006-2014. The health status is examined by some of the most frequently used demographic indicators, namely life expectancy, based on mortality data and healthy life years and healthy life expectancy, based on mortality, life expectancy and self-perceived health. The main results show that despite of the observed increase in life expectancy at age 65 in Bulgaria during the period it is the lowest compared to other European countries. The share for both men and women reported their health status as without limitations in respect to daily activities decline, while those reported their health status as good increase. These contradictory facts reflect on the measures of health status. Thus, the trend in healthy life years for both sexes decline over the period, whereas the trend in healthy life expectancy increases. Compared with the other European countries, the expected number of years without limitations in Bulgaria is among the largest, while the healthy life expectancy is the lowest. These differences could be explained by the different levels in mortality and the nature of the measures of health status themselves.
Development of SSR markers from transcriptomes for Orinus (Poaceae), an endemic of the Qinghai–Tibetan Plateau
Authors: Liu Yu‐Ping , Su Xu , Luo Wen‐Chun , Lv Ting , Chen Ke‐Long , Harris AJ , Shah Sayed Afzal 
Published: July 2017

Premise of the study:Transcriptomes were used to develop microsatellite markers for the plant genus Orinus (Poaceae), which comprises three species of grasses (O. thoroldii, O. kokonoricus, and O. intermedius) that are widely distributed in the Qinghai–Tibetan Plateau.Methods and Results:Primer pairs were developed for 16 high‐quality simple sequence repeats (SSRs) using transcriptomes. SSRs were amplified in 248 individuals representing the three species of Orinus; the number of alleles per locus ranged from one to seven, with an average of 2.6. The expected and observed heterozygosity per locus varied from 0.00 to 0.83 and from 0.00 to 1.00, respectively, with respective mean values of 0.32 and 0.34.Conclusions:These newly developed SSR markers will be valuable for evaluating the population genetic structure of Orinus throughout its range.
The Curiously Warped Mean Plane of the Kuiper Belt
Authors: Volk Kathryn , Malhotra Renu 
Published: July 2017

Abstract
We measured the mean plane of the Kuiper Belt as a function of semimajor axis. For the classical Kuiper Belt as a whole (the nonresonant objects in the semimajor axis range 42–48 au), we find a mean plane of inclination

and longitude of ascending node

(in the J2000 ecliptic-equinox coordinate system), in accord with theoretical expectations of the secular effects of the known planets. With finer semimajor axis bins, we detect a statistically significant warp in the mean plane near semimajor axes 40–42 au. Linear secular theory predicts a warp near this location due to the

nodal secular resonance; however, the measured mean plane for the 40.3–42 au semimajor axis bin (just outside the

) is inclined

to the predicted plane, a nearly 3σ discrepancy. For the more distant Kuiper Belt objects of semimajor axes in the range 50–80 au, the expected mean plane is close to the invariable plane of the solar system, but the measured mean plane deviates greatly from this: it has inclination

and longitude of ascending node

. We estimate this deviation from the expected mean plane to be statistically significant at the ∼97%–99% confidence level. We discuss several possible explanations for this deviation, including the possibility that a relatively close-in (

au), unseen, small planetary-mass object in the outer solar system is responsible for the warping.