bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serum C-Telopeptide Collagen Crosslinks and Plasma Soluble VEGFR2 as Pharmacodynamic Biomarkers in a Trial of Sequentially Administered Sunitinib and Cilengitide
Authors: O'Donnell Peter H. , Karovic Sanja , Karrison Theodore G. , Janisch Linda , Levine Matthew R. , Harris Pamela J. , Polite Blase N. , Cohen Ezra E.W. , Fleming Gini F. , Ratain Mark J. , Maitland Michael L. 
Published: July 2015

Abstract
Purpose: Fit-for-purpose pharmacodynamic biomarkers could expedite development of combination antiangiogenic regimens. Plasma sVEGFR2 concentrations ([sVEGFR2]) mark sunitinib effects on the systemic vasculature. We hypothesized that cilengitide would impair microvasculature recovery during sunitinib withdrawal and could be detected through changes in [sVEGFR2].
Experimental Design: Advanced solid tumor patients received 50 mg sunitinib daily for 14 days. For the next 14 days, patients were randomized to arm A (cilengitide 2,000 mg administered intravenously twice weekly) or arm B (no treatment). The primary endpoint was change in [sVEGFR2] between days 14 and 28. A candidate pharmacodynamic biomarker of cilengitide inhibition of integrin αvβ3, serum c-telopeptide collagen crosslinks (CTx), was also measured.
Results: Of 21 patients, 14 (7 per arm) received all treatments without interruption and had all blood samples available for analysis. The mean change and SD of [sVEGFR2] for all sunitinib-treated patients was consistent with previous data. There was no significant difference in the mean change in [sVEGFR2] from days 14 to 28 between the arms [arm A: 2.8 ng/mL; 95% confidence interval (CI), 2.1–3.6 vs. arm B: 2.0 ng/mL; 95% CI, 0.72–3.4; P = 0.22, 2-sample t test]. Additional analyses suggested (i) prior bevacizumab therapy to be associated with unusually low baseline [sVEGFR2] and (ii) sunitinib causes measurable changes in CTx.
Conclusions: Cilengitide had no measurable effects on any circulating biomarkers. Sunitinib caused measurable declines in serum CTx. The properties of [sVEGFR2] and CTx observed in this study inform the design of future combination antiangiogenic therapy trials. Clin Cancer Res; 21(22); 5092–9. ©2015 AACR.
Elevated Total Homocysteine Levels in Acute Ischemic Stroke Are Associated With Long-Term Mortality
Authors: Shi Zhihong , Guan Yalin , Huo Ya Ruth , Liu Shuling , Zhang Meilin , Lu Hui , Yue Wei , Wang Jinhuan , Ji Yong 
Published: July 2015

Background and Purpose—
Total homocysteine (tHcy) levels are associated with secondary vascular events and mortality after stroke. The aim of this study was to investigate whether tHcy levels in the acute phase of a stroke contribute to the recurrence of cerebro-cardiovascular events and mortality.

Methods—
A total of 3799 patients were recruited after hospital admission for acute ischemic stroke. Levels of tHcy were measured within 24 hours after primary admission. Patients were followed for a median of 48 months.

Results—
During the follow-up period, 233 (6.1%) patients died. After adjustment for age, smoking status, diabetes mellitus, and other cardiovascular risk factors, patients in the highest tHcy quartile (>18.6 μmol/L) had a 1.61-fold increased risk of death (adjusted hazard ratio [HR], 1.61; 95% confidence interval [CI], 1.03–2.53) compared with patients in the lowest quartile (≤10 μmol/L). Further subgroup analysis showed that this correlation was only significant in the large-artery atherosclerosis stroke subtype (adjusted HR, 1.80; 95% CI, 1.05–3.07); this correlation was not significant in the small-vessel occlusion subtype (adjusted HR, 0.80; 95% CI, 0.30–2.12). The risk of stroke-related mortality was 2.27-fold higher for patients in the third tHcy quartile (adjusted HR, 2.27; 95% CI, 1.06–4.86) and 2.15-fold more likely for patients in the fourth quartile (adjusted HR, 2.15; 95% CI, 1.01–4.63) than for patients in the lowest tHcy quartile. The risk of cardiovascular-related mortality and the risk of recurrent ischemic stroke were not associated with tHcy levels.

Conclusions—
Our findings suggest that elevated tHcy levels in the acute phase of an ischemic stroke can predict mortality, especially in stroke patients with the large-vessel atherosclerosis subtype.
The plant parasite Pratylenchus coffeae carries a minimal nematode genome
Authors: Burke Mark , Scholl Elizabeth H. , Bird David McK. , Schaff Jennifer E. , Colman Steven D. , Crowell Randy , Diener Stephen , Gordon Oksana , Graham Steven , Wang Xinguo , Windham Eric , Wright Garron M. , Opperman Charles H. 
Published: July 2015

Here we report the genome sequence of the lesion nematode, Pratylenchus coffeae, a significant pest of banana and other staple crops in tropical and sub-tropical regions worldwide. Initial analysis of the 19.67 Mb genome reveals 6712 protein encoding genes, the smallest number found in a metazoan, although sufficient to make a nematode. Significantly, no developmental or physiological pathways are obviously missing when compared to the model free-living nematode Caenorhabditis elegans, which possesses approximately 21 000 genes. The highly streamlined P. coffeae genome may reveal a remarkable functional plasticity in nematode genomes and may also indicate evolutionary routes to increased specialisation in other nematode genera. In addition, the P. coffeae genome may begin to reveal the core set of genes necessary to make a multicellular animal. Nematodes exhibit striking diversity in the niches they occupy, and the sequence of P. coffeae is a tool to begin to unravel the mechanisms that enable the extraordinary success of this phylum as both free-living and parasitic forms. Unlike the sedentary endoparasitic root-knot nematodes (Meloidogyne spp.), P. coffeae is a root-lesion nematode that does not establish a feeding site within the root. Because the P. coffeae nematode genome encodes fewer than half the number of genes found in the genomes of root-knot nematodes, comparative analysis to determine genes P. coffeae does not carry may help to define development of more sophisticated forms of nematode-plant interactions. The P. coffeae genome sequence may help to define timelines related to evolution of parasitism amongst nematodes. The genome of P. coffeae is a significant new tool to understand not only nematode evolution but animal biology in general.
A Hoard of Silver Rhyta of the Achaemenid Circle from Erebuni
Authors: Treister Mikhail Yu. 
Published: July 2015

This paper is devoted to a treasure found in 1968. The hoard in “a large jug”, consisting of three silver rhyta, a silver goblet and a fifth, now missing object, was found during construction works at the foothill of the Erebuni citadel. The silver vessels were preserved in a jug in a flattened condition. Every piece of the Treasure is discussed in detail. Descriptions of the vessels are provided in a catalogue section.The results of our analysis do not contradict the suggestion that the Treasure was possibly hidden inca. 330bc, thus assigning it a date more or less the same as that of the hoard from Pasargadae, which was also hidden in a clay vessel and most probably, like the Erebuni Treasure, coincided with the fall of the Achaemenid Empire.
Laplacian Eigenfunctions for Climate Analysis
Authors: DelSole Timothy , Tippett Michael K. 
Published: July 2015

Abstract
This paper proposes a new method for representing data in a general domain on a sphere. The method is based on the eigenfunctions of the Laplace operator, which form an orthogonal basis set that can be ordered by a measure of length scale. Representing data with Laplacian eigenfunctions is attractive if one wants to reduce the dimension of a dataset by filtering out small-scale variability. Although Laplacian eigenfunctions are ubiquitous in climate modeling, their use in arbitrary domains, such as over continents, is not common because of the numerical difficulties associated with irregular boundaries. Recent advances in machine learning and computational sciences are exploited to derive eigenfunctions of the Laplace operator over an arbitrary domain on a sphere. The eigenfunctions depend only on the geometry of the domain and hence require no training data from models or observations, a feature that is especially useful in small sample sizes. Another novel feature is that the method produces reasonable eigenfunctions even if the domain is disconnected, such as a land domain comprising isolated continents and islands. The eigenfunctions are illustrated by quantifying variability of monthly mean temperature and precipitation in climate models and observations. This analysis extends previous studies by showing that climate models have significant biases not only in global-scale spatial averages but also in global-scale dipoles and other physically important structures. MATLAB and R codes for deriving Laplacian eigenfunctions are available upon request.
How pulmonary function changes after pectus excavatum correction surgery
Authors: Kuru Pinar , Dudakli Asli , Mursaloglu Hakan , Arikan Hazal , Oktay Aysu , Yuksel Mustafa 
Published: July 2015

Aim We aimed to determine the effects of minimally invasive repair of pectus excavatum on pulmonary function and quality of life. Methods Minimally invasive pectus excavatum repair was undertaken in 80 patients with a mean age of 16.91 ± 4.37 years (range 7–30 years) and a mean Haller index of 4.07 ± 1.39; 85% of the patients were male. They and their parents completed the Nuss Questionnaire Modified for Adults, and pulmonary function tests were performed on the patients before and 6 months after the operation. Results The mean Nuss score was 31.06 ± 6.78 before the operation and it increased to 37.1 ± 8.31 ( p = 0.000) 6 months after the operation. Forced vital capacity decreased from 3.70 ± 1.23 to 3.48 ± 1.03 L ( p = 0.05) postoperatively. The percentage of expected forced vital capacity decreased from 83.21% ± 16.97% to 76.52% ± 20.98% ( p = 0.01). There was no significant change in forced expiratory volume in 1 s. The mean ratio of forced expiratory volume in 1 s to forced vital capacity was 86% preoperatively and it increased to 91% postoperatively ( p = 0.000). Conclusions Minimally invasive pectus excavatum repair has a positive impact on the quality of life of pectus excavatum patients, but a negative impact on forced vital capacity. Follow-up studies are needed to assess the long-term changes in pulmonary function after this operation.
Assessment of renal dysfunction with diffusion-weighted imaging: comparing intra-voxel incoherent motion (IVIM) with a mono-exponential model
Authors: Ding Jiule , Chen Jie , Jiang Zhenxing , Zhou Hua , Di Jia , Xing Wei 
Published: July 2015

Background Because renal dysfunction is a worldwide problem, accurate assessment is required for planning treatment and follow-up. Intra-voxel incoherent motion (IVIM) can isolate fast from slow water motion in well-perfused organs and may be helpful in assessing renal dysfunction. Purpose To determine the clinical value of IVIM in the assessment of renal dysfunction compared with a mono-exponential model. Material and Methods Fifty-four consecutive participants (mean age, 53.13 ± 13.96 years) were recruited into this study. The estimated glomerular filtration rate (eGFR) was calculated to classify the participants as having severe renal injury (sRI, eGFR ≤ 30 mL/min/1.73 m2) or not (non-sRI). DWI with seven b-factors was performed. Image analysis was performed by a radiologist to generate an apparent diffusion coefficient map (ADCmon) by mono-exponential model, diffusion coefficient (Dslow and Dfast), and fraction of fast diffusion (Ffast) maps by IVIM. The circular regions of interest were placed at the interface between the cortex and medulla for parameter measurements. Results The ADCmon, Dslow, Dfast, and Ffast were less in sRI than non-sRI ( P < 0.05). ADCmon and Dslow were positively related with eGFR ( P < 0.05). For differentiating sRI from non-sRI, receiver operating characteristic curve indicated no significant difference between the two methods ( P > 0.05). Furthermore, the correlation was 0.93 between ADCmon and Dslow, followed by 0.57 between Dfast and Ffast, 0.48 between ADCmon and Dfast, and 0.34 between ADCmon and Ffast ( P < 0.05). Conclusion The IVIM model contributed little to improving the assessment of renal dysfunction compared with a mono-exponential model.
Who receives contraception counseling when starting new lupus medications? The potential roles of race, ethnicity, disease activity, and quality of communication
Authors: Ferguson S , Trupin L , Yazdany J , Yelin E , Barton J , Katz P 
Published: July 2015

Objective Family planning discussions are an important aspect of medical care for women with systemic lupus erythematosus (SLE) as active disease is a risk factor for poor pregnancy outcomes, and the medications used for treatment can be harmful to the fetus when used during conception and pregnancy. Our objective was to examine the impact of patient perception of quality and type of communication on receiving contraception counseling. Methods Data were derived from patients enrolled in the University of California, San Francisco Lupus Outcomes Study. Individuals participate in a yearly structured telephone interview that includes assessment of contraception counseling when starting new medications, and measures of communication and decision making. Logistic regression was performed to identify predictors of not receiving contraception counseling. Results Of the 68 women included in this analysis, one-third did not receive contraception counseling when starting new medications. Older age, white race, depressive symptoms, and higher SLE disease activity were independently associated with not receiving contraception counseling. Participants who did not receive contraception counseling rated their physicians lower in shared decision-making (SDM) communication. Conclusions This study demonstrates a gap in family planning counseling among women with SLE starting new medications. Future studies to address these potential areas of intervention, including education about the need for contraception through menopause, and mechanisms to engage in SDM surrounding contraception are needed to improve quality of care for women with lupus.
Management of lunotriquetral instability: a review of the literature
Authors: van de Grift T. C. , Ritt M. J. P. F. 
Published: July 2015

Lunotriquetral ligament injury is a relatively common cause of ulnar-sided wrist pain. Injury ranges from partial stable ligament tears to extensive perilunate instability. Clinical decision-making largely depends on the chronicity, instability and cause of the ligament injury. Conservative treatment is generally regarded as first choice of treatment of mild lunotriquetral instability; however, outcome studies on conservative treatment are lacking. Temporary arthroscopic pinning and/or debridement are minimally invasive procedures of preference. In the case of more dissociative injury, surgical interventions may be performed. The literature suggests that soft tissue reconstruction is an effective procedure in this group. Arthrodesis of the lunotriquetral joint is associated with high rates of non-union (up to 57%) and the indications for surgery should therefore be very clear. Methodological issues make it hard to draw firm conclusions from the data. Studies on the effectiveness of conservative management and prospective comparative studies will further improve clinical decision-making in lunotriquetral instability. Level of evidence: N/A
Perioperative Hyperglycemia and Glucose Variability in Gynecologic Laparotomies
Authors: Polderman Jorinde A. W. , Hollmann Markus W. , DeVries J. Hans , Preckel Benedikt , Hermanides Jeroen 
Published: July 2015

Background: The glycemic response and its relation to postoperative complications following gynecologic laparotomies is unknown, although these surgeries carry a substantial risk for postoperative morbidity. Therefore, our objective was to assess the prevalence of perioperative hyperglycemia and glucose variability in women undergoing a gynecologic laparotomy. Methods: In this prospective cohort study, capillary glucose was measured every hour during the perioperative period. The primary outcome measures were the proportion of patients with postoperative hyperglycemia (glucose >180 mg d l-1) and the glucose variability in the intra- and postoperative period. Postoperative complications were assessed as secondary outcome measure. Results: We included 150 women undergoing a gynecologic laparotomy. Perioperative hyperglycemia occurred in 33 patients without diabetes (23.4%) and in 8 patients with diabetes (89%). Glucose variability was significantly higher (mean absolute glucose change [MAG] 11 mg dl-1 hr-1 [IQR 8-18]) in the intraoperative compared to the postoperative period (MAG 10 mg dl-1 hr-1 [IQR 3-16], P = .03). Neither hyperglycemia nor glucose variability was associated with postoperative complications. Conclusions: Hyperglycemia and glucose variability seem to be a minor problem during gynecologic laparotomy. Based on the current data, we would not advocate standardized glucose measurements in every patient without diabetes undergoing gynecologic laparotomy.
Comparative assessment of methods for the computational inference of transcript isoform abundance from RNA-seq data
Authors: Kanitz Alexander , Gypas Foivos , Gruber Andreas J. , Gruber Andreas R. , Martin Georges , Zavolan Mihaela 
Published: July 2015

Abstract
Background
Understanding the regulation of gene expression, including transcription start site usage, alternative splicing, and polyadenylation, requires accurate quantification of expression levels down to the level of individual transcript isoforms. To comparatively evaluate the accuracy of the many methods that have been proposed for estimating transcript isoform abundance from RNA sequencing data, we have used both synthetic data as well as an independent experimental method for quantifying the abundance of transcript ends at the genome-wide level.

Results
We found that many tools have good accuracy and yield better estimates of gene-level expression compared to commonly used count-based approaches, but they vary widely in memory and runtime requirements. Nucleotide composition and intron/exon structure have comparatively little influence on the accuracy of expression estimates, which correlates most strongly with transcript/gene expression levels. To facilitate the reproduction and further extension of our study, we provide datasets, source code, and an online analysis tool on a companion website, where developers can upload expression estimates obtained with their own tool to compare them to those inferred by the methods assessed here.

Conclusions
As many methods for quantifying isoform abundance with comparable accuracy are available, a user’s choice will likely be determined by factors such as the memory and runtime requirements, as well as the availability of methods for downstream analyses. Sequencing-based methods to quantify the abundance of specific transcript regions could complement validation schemes based on synthetic data and quantitative PCR in future or ongoing assessments of RNA-seq analysis methods.
Ethnic Differences in Effects of Maternal Pre-Pregnancy and Pregnancy Adiposity on Offspring Size and Adiposity
Authors: Lin Xinyi , Aris Izzuddin M. , Tint Mya Thway , Soh Shu E. , Godfrey Keith M. , Yeo George Seow-Heong , Kwek Kenneth , Chan Jerry Kok-Yen , Gluckman Peter D. , Chong Yap Seng , Yap Fabian , Holbrook Joanna D. , Lee Yung Seng 
Published: July 2015

Context:Maternal adiposity and overnutrition, both before and during pregnancy, plays a key role in the subsequent development of obesity and metabolic outcomes in offspring.Objective:We explored the hypothesis that maternal adiposity (pre-pregnancy and at 26–28 weeks' gestation) and mid-pregnancy gestational weight gain (GWG) are independently associated with offspring size and adiposity in early childhood, and determined whether these effects are ethnicity dependent.Design:In a prospective mother-offspring cohort study (N = 976, 56% Chinese, 26% Malay, and 18% Indian), we assessed the associations of offspring size (weight, length) and adiposity (subscapular and triceps skinfolds), measured at birth and age 6, 12, 18, and 24 mo, with maternal pre-pregnancy body mass index (ppBMI), mid-pregnancy GWG, and mid-pregnancy four-site skinfold thicknesses (triceps, biceps, subscapular, suprailiac).Results:ppBMI and mid-pregnancy GWG were independently associated with postnatal weight up to 2 y and skinfold thickness at birth. Weight and subscapular and triceps skinfolds at birth increased by 2.56% (95% confidence interval, 1.68–3.45%), 3.85% (2.16–5.57%), and 2.14% (0.54–3.75%), respectively for every SD increase in ppBMI. Similarly, a one-SD increase in GWG increased weight and subscapular and triceps skinfolds at birth by 2.44% (1.66–3.23%), 3.28% (1.75–4.84%), and 3.23% (1.65–4.84%), respectively. ppBMI and mid-pregnancy suprailiac skinfold independently predicted postnatal skinfold adiposity up to 2 years of age, whereas only GWG predicted postnatal length. The associations of GWG with postnatal weight and length were present only among Chinese and Indians, but not Malays (P &lt; .05 for interaction).Conclusions:ppBMI and GWG are independent modifiable factors for child size and adiposity up to 2 years of age. The associations are ethnic-dependent, and underscore the importance of ethnic specific studies before generalizing the applicability of risk factors reported in other populations.
RASopathies: unraveling mechanisms with animal models
Authors: Jindal Granton A. , Goyal Yogesh , Burdine Rebecca D. , Rauen Katherine A. , Shvartsman Stanislav Y. 
Published: July 2015

ABSTRACT
RASopathies are developmental disorders caused by germline mutations in the Ras-MAPK pathway, and are characterized by a broad spectrum of functional and morphological abnormalities. The high incidence of these disorders (∼1/1000 births) motivates the development of systematic approaches for their efficient diagnosis and potential treatment. Recent advances in genome sequencing have greatly facilitated the genotyping and discovery of mutations in affected individuals, but establishing the causal relationships between molecules and disease phenotypes is non-trivial and presents both technical and conceptual challenges. Here, we discuss how these challenges could be addressed using genetically modified model organisms that have been instrumental in delineating the Ras-MAPK pathway and its roles during development. Focusing on studies in mice, zebrafish and Drosophila, we provide an up-to-date review of animal models of RASopathies at the molecular and functional level. We also discuss how increasingly sophisticated techniques of genetic engineering can be used to rigorously connect changes in specific components of the Ras-MAPK pathway with observed functional and morphological phenotypes. Establishing these connections is essential for advancing our understanding of RASopathies and for devising rational strategies for their management and treatment.