bluuebunny/crossref_metadata_2025_split huggingface dataset:
Population pharmacokinetic modeling of motesanib and its active metabolite, M4, in cancer patients
Authors: Gosselin Nathalie H. , Mouksassi Mohamad‐Samer , Lu Jian‐Feng , Hsu Cheng‐Pang 
Published: April 2015

AbstractMotesanib is a small molecule and potent multikinase inhibitor with antiangiogenic and antitumor activity. Population pharmacokinetic (POPPK) modeling of motesanib and M4, an active metabolite, was performed to assess sources of variability in cancer patients. The analysis included data collected from 451 patients from 8 clinical trials with oral doses of motesanib ranging from 25 to 175 mg, either once daily or twice daily. The POPPK analyses were performed using nonlinear mixed‐effect models with a sequential approach. Covariate effects of demographics and other baseline characteristics were assessed with stepwise covariate modeling. A 2‐compartment model with food effect on absorption parameters fitted the PK data of motesanib well. The effects albumin and sex on apparent clearance (CL/F) of motesanib were statistically significant. The albumin effect was more important but remained below a 25% difference. A 1‐compartment model fitted PK data of M4 well. Effects of race (Asian vs non‐Asian) and dosing frequency were identified as statistically significant covariates on the CL/F of M4. The maximum effect of albumin would result in less than 25% change in motesanib CL/F and as such would not warrant any dosing adjustment. However, faster elimination of M4 in Asian patients requires further investigation.
Parallel sphere detector algorithm providing optimal MIMO detection on massively parallel architectures
Authors: Józsa Csaba M. , Kolumbán Géza , Vidal Antonio M. , Martínez‐Zaldívar Francisco J. , González Alberto 
Published: April 2015

SummaryMultiple‐input multiple‐output (MIMO) systems have attracted considerable attention in wireless communications because they offer a significant increase in data throughput and link coverage without additional bandwidth requirement or increased transmit power. The price that has to be paid is the increased complexity of hardware components and algorithms. The sphere detector (SD) algorithm solves the problem of maximum likelihood (ML) detection for MIMO channels by significantly reducing the search space of possible solutions. The main drawback of the SD algorithm is in its sequential nature, consequently, running it on massively parallel architectures (MPAs) is very inefficient. In order to overcome the drawbacks of the SD algorithm, a new parallel sphere detector (PSD) algorithm is proposed. It implements a novel hybrid tree search method, where the algorithm parallelism is assured by the efficient combination of depth‐first search and breadth‐first search algorithms. A path metric‐based parallel sorting is employed at each intermediate stage. The PSD algorithm is able to adjust its memory requirements and extent of parallelism to fit a wide range of parallel architectures. Mapping details for MPAs are proposed by giving the details of thread dependent, highly parallel building blocks of the algorithm. Based on the building blocks proposed, a mapping to general‐purpose graphics processing unit is provided, and its performance is evaluated. In order to achieve high‐throughput, several levels of parallelism are introduced, and different scheduling strategies are considered. Copyright © 2015 John Wiley & Sons, Ltd.
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Authors: Rinkevich Yuval , Maan Zeshaan N. , Walmsley Graham G. , Sen Subhro K. 
Published: April 2015

ABSTRACTBackground The regrowth of amputated appendage extremities and the distal tips of digits represent models of tissue regeneration in multiple vertebrate taxa. In humans, digit tip injuries, including traumatic amputation and crush injuries, are among the most common type of injury to the human hand. Despite clinical reports demonstrating natural regeneration of appendages in lower vertebrates and human digits, current treatment options are suboptimal, and are complicated by the anatomical complexities and functions of the different tissues within the digits. Results: In light of these challenges, we focus on recent advancements in understanding appendage regeneration from model organisms. We pay special attention to the cellular programs underlying appendage regeneration, where cumulative data from salamanders, fish, frogs, and mice indicate that regeneration occurs by the actions of lineage‐restricted precursors. We focus on pathologic states and the interdependency that exists, in both humans and animal models, between the nail organ and the peripheral nerves for successful regeneration. Conclusions: The increased understanding of regeneration in animal models may open new opportunities for basic and translational research aimed at understanding the mechanisms that support limb regeneration, as well as amelioration of limb abnormalities and pathologies. Developmental Dynamics 244:641–650, 2015. © 2015 Wiley Periodicals, Inc.
Skeletal muscle weakness is related to insulin resistance in patients with chronic heart failure
Authors: Doehner Wolfram , Turhan Guelistan , Leyva Francisco , Rauchhaus Mathias , Sandek Anja , Jankowska Ewa A , von Haehling Stephan , Anker Stefan D 
Published: April 2015

AbstractBackgroundChronic heart failure (CHF) is associated with insulin resistance, indicating impairment in the control of energy metabolism. Insulin resistance in CHF relates to symptomatic status and independently predicts poor prognosis. We sought to determine whether insulin sensitivity is related to skeletal muscle strength in patients with CHF, taking into account muscle size and perfusion.MethodsQuadriceps muscle size (square centimetre cross‐sectional area at mid‐femur level, computed tomography), isometric quadriceps muscle strength [absolute (in N) and strength per unit muscle area (N/cm2)], resting‐leg blood flow (plethysmography) and maximal oxygen consumption (treadmill exercise test) were measured in 33 patients with CHF (left ventricular ejection fraction 28 ± 3.2%, mean ± Standard Error of the mean (SEM)) and 20 healthy controls. Insulin sensitivity was assessed by intravenous glucose tolerance tests and minimal modelling analysis.ResultsRight quadriceps strength (−27.0%, P < 0.0001), strength per muscle area (−18.0%, P < 0.003) and insulin sensitivity (−64.2%, P < 0.001) were lower in patients with CHF. The correlation between insulin sensitivity and absolute muscle strength was significant in the CHF group (r = 0.54, P = 0.001) and borderline in controls (r = 0.47, P = 0.06). This association remained significant between insulin sensitivity and strength per muscle area (CHF: r = 0.52, P < 0.01; controls: r = 0.62, P < 0.05). In stepwise regression analyses in CHF, only insulin sensitivity emerged as a predictor of strength per unit area of muscle [standardized coefficient (SC) = 0.45, P = 0.006; diuretic dose, SC = −0.31, P = 0.051; R2 = 0.37, P = 0.001], while age, left ventricular ejection fraction, maximal oxygen consumption, fasting glucose and insulin and blood flow were excluded. In controls, only insulin sensitivity remained in the final regression model (SC = 0.62, P = 0.004; R2 = 0.39, P = 0.004).ConclusionsThe myofibril contractile function of the quadriceps, i.e. functional quality of skeletal muscle, is strongly related to insulin sensitivity in patients with CHF and in healthy controls, independently of muscle size. Therapies aimed at improving insulin sensitivity in patients with CHF may clarify whether this relationship is causal.
Global variation in clinical profile, management, and post‐discharge outcomes among patients hospitalized for worsening chronic heart failure: findings from the ASTRONAUT trial
Authors: Greene Stephen J. , Fonarow Gregg C. , Solomon Scott D. , Subacius Haris , Maggioni Aldo P. , Böhm Michael , Lewis Eldrin F. , Zannad Faiez , Gheorghiade Mihai ,   for the ASTRONAUT Investigators and Coordinators
Published: April 2015

AimsThis study sought to investigate regional variation in clinical characteristics, therapy utilization, and post‐discharge outcomes among patients hospitalized for heart failure (HHF) enrolled in the multinational ASTRONAUT (Aliskiren Trial on Acute Heart Failure Outcomes) trial.Methods and resultsThe ASTRONAUT trial randomized 1615 HHF patients with ejection fraction ≤40% to aliskiren or placebo. Enrolled patients were from Eastern Europe (n = 495, 30.7%), Asia/Pacific (n = 439, 27.2%), Western Europe (n = 395, 24.5%), Latin America (n = 163, 10.1%), and North America (n = 123, 7.6%). Marked differences were seen across geographic regions in terms of baseline demographics, vital signs, laboratory tests, co‐morbidity burden, and use of guideline‐recommended therapies. All‐cause death at 12 months ranged from 7.3% in North America to 26.7% in Asia/Pacific, with differences largely driven by sudden cardiac death. Rates of repeat HHF at 12 months ranged from 22.7% in Latin America to 43.9% in North America. After adjustment for patient characteristics, region was an independent predictor of death at 12 months, with highest risk in Asia/Pacific (hazard ratio 3.04, 95% confidence interval 1.47–6.29, compared with North America) and lowest risk in North America and Western Europe. There was no association between region and the composite of cardiovascular mortality or HHF.ConclusionFor patients enrolled in this HHF trial, baseline characteristics and risk of death differed markedly by geographic region. Rates of death and repeat HHF demonstrated a general inverse relationship. Global differences in patient characteristics and outcomes should be accounted for when designing future HHF clinical trials.
Identification With All Humanity: The role of self‐definition and self‐investment
Authors: Reese Gerhard , Proch Jutta , Finn Christine 
Published: April 2015

AbstractIdentification With All Humanity (IWAH) relates to higher levels of concern and supportive behavior toward the disadvantaged, stronger endorsement of human rights, and stronger responses in favor of global harmony. So far, IWAH has been conceptualized as a one‐dimensional construct describing the degree with which one identifies with all humans as a superordinate ingroup. However, recent group identification models suggest a multi‐dimensional model to provide a more differentiated approach toward the understanding of the highest level of social identification. Using principal axis (Study 1) and confirmatory (Study 2) factor analyses, we suggest that IWAH sub‐divides into two dimensions—global self‐definition and global self‐investment. Study 2 revealed that global self‐investment was a stronger predictor for both convergent measures (e.g., social dominance orientation and authoritarianism) and behavioral intentions than global self‐definition. Finally, in Study 3, we manipulated IWAH to test its causal effect on donation behavior. Participants in the experimental condition, compared with the control condition, showed higher global self‐investment, which in turn predicted greater giving to global charity. These findings suggest that two dimensions with different behavioral outcomes underlie IWAH.
Selective detection and quantification of carbon nanotubes in soil
Authors: Jeong Junhoe , Lee Yong-ju , Hwang Yu sik , Hong In Seok 
Published: April 2015

Abstract

Carbon nanotubes (CNTs) have been widely applied in many industrial fields. As world production of CNTs increases, the risk of environmental exposure to CNTs also increases. Therefore, to evaluate the impact on the environment, many cell and animal studies have reported on the toxicity of CNTs. It is important to determine the degree of contamination of CNTs in soil and to find the pollution pathways for assessment of the environmental toxicity of CNTs. However, selective detection methods for CNTs in soil or water have rarely been reported. In the present study, a novel technique was developed to quantify the amount of CNTs in soil mixtures using fluorescent SYBR Green I dye after isolation of the CNTs with specific DNA oligomers. As a result, a limit of detection of CNTs in soil was obtained in the range of 250 ppb. This limit can easily be extended to the level of 10 ppb using magnetic well plates with a greater capacity. This method also worked well in the presence of graphene oxide and could be applied to the detection of CNTs in a variety of surroundings (e.g., fish and other tissues). Environ Toxicol Chem 2015;34:1969–1974. © 2015 SETAC
Development of cereal‐based functional food using cereal‐mix substrate fermented with probiotic strain – Pichia kudriavzevii OG32
Authors: Ogunremi Omotade R. , Agrawal Renu , Sanni Abiodun I. 
Published: April 2015

AbstractProbiotic strains contribute to the functionality of foods during fermentation. In this present work, cereal‐mix was fermented with probiotic Pichia kudriavzevii OG32. Selected fermentation parameters and functional properties of the product were determined. The growth of Pichia kudriavzevii OG32 was supported by the cereal‐mix containing 1% salt and 0.2% red chili powder to counts of between 7.46 and 8.22 Log10 cfu/mL within 24 h. Pichia kudriavzevii OG32 increased the viscosity of cereal‐mix with the highest inoculum size (1.84x105cfu/ml) giving the highest viscosity of 1793.6 mPa.S. An inoculum size of 1.98 × 104 cfu/mL gave the most acceptable product based on the sensory evaluation by the panelist. Forty volatile compounds were identified in the fermented product, while acids (32.21%) and esters (32.37%) accounted for the largest proportions. The cereal‐based fermented product scavenged DPPH from 200 μmol/L methanolic solution by 55.71%. Probiotic yeast improved the sensory and some functional properties of cereal‐based substrate during fermentation. This is one of the first reports on the volatile composition of cereal‐based functional food produced with probiotic yeast.
mRNAs and miRNAs in whole blood associated with lung hyperplasia, fibrosis, and bronchiolo‐alveolar adenoma and adenocarcinoma after multi‐walled carbon nanotube inhalation exposure in mice
Authors: Snyder‐Talkington Brandi N. , Dong Chunlin , Sargent Linda M. , Porter Dale W. , Staska Lauren M. , Hubbs Ann F. , Raese Rebecca , McKinney Walter , Chen Bean T. , Battelli Lori , Lowry David T. , Reynolds Steven H. , Castranova Vincent , Qian Yong , Guo Nancy L. 
Published: April 2015

AbstractInhalation exposure to multi‐walled carbon nanotubes (MWCNT) in mice results in inflammation, fibrosis and the promotion of lung adenocarcinoma; however, the molecular basis behind these pathologies is unknown. This study determined global mRNA and miRNA profiles in whole blood from mice exposed by inhalation to MWCNT that correlated with the presence of lung hyperplasia, fibrosis, and bronchiolo‐alveolar adenoma and adenocarcinoma. Six‐week‐old, male, B6C3F1 mice received a single intraperitoneal injection of either the DNA‐damaging agent methylcholanthrene (MCA, 10 µg g−1 body weight) or vehicle (corn oil). One week after injections, mice were exposed by inhalation to MWCNT (5 mg m−3, 5 hours per day, 5 days per week) or filtered air (control) for a total of 15 days. At 17 months post‐exposure, mice were euthanized and examined for the development of pathological changes in the lung, and whole blood was collected and analyzed using microarray analysis for global mRNA and miRNA expression. Numerous mRNAs and miRNAs in the blood were significantly up‐ or down‐regulated in animals developing pathological changes in the lung after MCA/corn oil administration followed by MWCNT/air inhalation, including fcrl5 and miR‐122‐5p in the presence of hyperplasia, mthfd2 and miR‐206‐3p in the presence of fibrosis, fam178a and miR‐130a‐3p in the presence of bronchiolo‐alveolar adenoma, and il7r and miR‐210‐3p in the presence of bronchiolo‐alveolar adenocarcinoma, among others. The changes in miRNA and mRNA expression, and their respective regulatory networks, identified in this study may potentially serve as blood biomarkers for MWCNT‐induced lung pathological changes. Copyright © 2015 John Wiley & Sons, Ltd.
Small‐molecule compounds exhibiting target‐mediated drug disposition — A case example of ABT‐384
Authors: An Guohua , Liu Wei , Dutta Sandeep 
Published: April 2015

AbstractNonlinearities are frequently encountered in pharmacokinetics, and they can occur when 1 or more processes of absorption, distribution, metabolism, and excretion are saturable. One special source of nonlinearity that has been noticed recently is the saturable binding of the drug to a high‐affinity–low‐capacity target, a phenomenon known as target‐mediated drug disposition (TMDD). Although TMDD can occur in both small‐molecule compounds and large‐molecule compounds, the latter has received much more attention because of its high prevalence. With the development of more potent small‐molecule drugs acting on highly specific targets and the availability of increasingly sensitive analytical techniques, small‐molecule compounds exhibiting TMDD have been increasingly reported in the past several years. ABT‐384 is a small‐molecule drug candidate that exhibited significant nonlinear pharmacokinetics, potentially imparted by TMDD, in a first‐in‐human clinical trial conducted in healthy volunteers. Compared with published small‐molecule compounds exhibiting TMDD, ABT‐384 pharmacokinetic characteristics are more consistent with TMDD. To expand current knowledge of TMDD of small‐molecule compounds and increase awareness of this interesting and clinically important phenomenon, in this review the general features of small‐molecule compounds exhibiting TMDD are highlighted, with ABT‐384 provided as an example.
SEFE without Mapping via Large Induced Outerplane Graphs in Plane Graphs
Authors: Angelini Patrizio , Evans William , Frati Fabrizio , Gudmundsson Joachim 
Published: April 2015

AbstractWe show that every n‐vertex planar graph admits a simultaneous embedding without mapping and with fixed edges with any ‐vertex planar graph. In order to achieve this result, we prove that every n‐vertex plane graph has an induced outerplane subgraph containing at least vertices. Also, we show that every n‐vertex planar graph and every n‐vertex planar partial 3‐tree admit a simultaneous embedding without mapping and with fixed edges.
Mutations in the RAS and PI3K pathways are associated with metastatic location in colorectal cancers
Authors: Lan Yuan‐Tzu , Jen‐Kou Lin , Lin Chien‐Hsing , Yang Shung‐Haur , Lin Chun‐Chi , Wang Huann‐Sheng , Chen Wei‐Shone , Lin Tzu‐Chen , Jiang Jeng‐Kai , Chang Shih‐Ching 
Published: April 2015

Background and objectivesIdentification of mutations in the downstream epidermal growth factor receptor (EGFR) signaling pathway could provide important insights of EGFR‐targeted therapies in colorectal cancers. We analyzed the mutation spectra of the PI3K/PTEN/AKT and RAS/RAF/MAPK pathways in colorectal cancers and the associations of these mutations with sites of metastases or recurrence.MethodsThe study population comprised 1,492 retrospectively collected stages I–IV colorectal cancer specimens. Tissue was obtained between 2000 and 2010 at a single hospital. We analyzed 61 hot spots using MALDI–TOF mass spectrometry for nucleic acid analysis.ResultsMutations were found in the RAS pathway in 47.3% of patients and in the PI3K pathway in 14.3% of patients, with 9.2% of patients carrying mutations in both pathways. Both the RAS and PI3K pathway mutations were significantly associated with proximal tumors, mucinous tumors, and microsatellite instability. Tumors carrying a RAS pathway mutation exhibited a higher frequency of lung and peritoneal metastasis than did tumors with a wild‐type gene (P = 0.025 and 0.009, respectively). NRAS gene mutation was significantly associated with lung metastasis (P = 0.001).ConclusionsSomatic mutations in the RAS pathway of the primary tumor in colorectal cancer can influence patterns of metastasis and recurrence. J. Surg. Oncol. 2015 111:905–910. © 2014 Wiley Periodicals, Inc.
Leiomyosarcoma: One disease or distinct biologic entities based on site of origin?
Authors: Worhunsky David J. , Gupta Mihir , Gholami Sepideh , Tran Thuy B. , Ganjoo Kristen N. , van de Rijn Matt , Visser Brendan C. , Norton Jeffrey A. , Poultsides George A. 
Published: April 2015

AbstractBackgroundLeiomyosarcoma (LMS) can originate from the retroperitoneum, uterus, extremity, and trunk. It is unclear whether tumors of different origin represent discrete entities. We compared clinicopathologic features and outcomes following surgical resection of LMS stratified by site of origin.Methods: Patients with LMS undergoing resection at a single institution were retrospectively reviewed. Clinicopathologic variables were compared across sites. Survival was calculated using the Kaplan–Meier method and compared using log‐rank and Cox regression analyses.ResultsFrom 1983 to 2011, 138 patients underwent surgical resection for LMS. Retroperitoneal and uterine LMS were larger, higher grade, and more commonly associated with synchronous metastases. However, disease‐specific survival, recurrence‐free survival, and recurrence patterns were not significantly different across the four sites. Synchronous metastases (HR 3.20, P < 0.001), but not site of origin, size, grade, or margin status, were independently associated with worse DSS. A significant number of recurrences and disease‐related deaths were noted beyond 5 years.ConclusionsAlthough larger and higher grade, retroperitoneal and uterine LMS share similar survival and recurrence patterns with their trunk and extremity counterparts. LMS of various anatomic sites may not represent distinct disease processes based on clinical outcomes. The presence of metastatic disease remains the most important prognostic factor for LMS. J. Surg. Oncol. 2015 111:808–812. © 2014 Wiley Periodicals, Inc.
Fukushima Daiichi: Eintrag radioaktiver Stoffe ins Meer
Authors: Nies Hartmut 
Published: April 2015

AbstractVor vier Jahren kam es im japanischen Kernkraftwerk Fukushima Daiichi infolge eines katastrophalen Tsunamis zu einem schweren Unfall. Große Mengen radioaktiver Stoffe gelangten in den pazifischen Ozean. Welche Folgen hatte die Kontamination des Meeres und was sind die längerfristigen Auswirkungen?
The role of the Bézier extraction operator for T‐splines of arbitrary degree: linear dependencies, partition of unity property, nesting behaviour and local refinement
Authors: May Stefan , Vignollet Julien , de Borst René 
Published: April 2015

SummaryWe determine linear dependencies and the partition of unity property of T‐spline meshes of arbitrary degree using the Bézier extraction operator. Local refinement strategies for standard, semi‐standard and non‐standard T‐splines – also by making use of the Bézier extraction operator – are presented for meshes of even and odd polynomial degrees. A technique is presented to determine the nesting between two T‐spline meshes, again exploiting the Bézier extraction operator. Finally, the hierarchical refinement of standard, semi‐standard and non‐standard T‐spline meshes is discussed. This technique utilises the reconstruction operator, which is the inverse of the Bézier extraction operator. Copyright © 2015 John Wiley & Sons, Ltd.
Novel Carbazole (Cbz)‐Based Carboxylated Functional Monomers: Design, Synthesis, and Characterization
Authors: Mondal Ejabul , Lellouche Jean‐Paul , Naddaka Maria 
Published: April 2015

AbstractA series of novel functional carbazole (Cbz)‐based carboxylated monomers were synthesized and characterized. A Clauson‐Kaas procedure, a deprotection step, amide coupling, and hydrolysis were utilized as key chemical reactions towards the multistep synthesis of monomers in good to excellent isolated yields. The design strategy was further extended to complex carbazole‐COOH monomers incorporated arylazo groups as photoreactive moieties. In addition, photoreactive hybrid carbazole (Cbz)‐pyrrole (Pyr)‐based carboxylated monomers, comprising a pyrrole core linking a carbazole and a photoreactive phenylazide or benzophenone moiety through an amide spacer in the molecular structure, were also synthesized. The latter can be utilized for surface modification of polymeric films in their monomeric form or as polymeric microparticles (MPs).