bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of cellularity, genomic DNA yields, and technical platforms for BRAF mutational testing in thyroid fine‐needle aspirate samples
Authors: Dyhdalo Kathryn , MacNamara Stephen , Brainard Jennifer , Underwood Dawn , Tubbs Raymond , Yang Bin 
Published: October 2013

BACKGROUNDBRAF mutation V600E (substitution Val600Glu) is a molecular signature for papillary thyroid carcinoma (PTC). Testing for BRAF mutation is clinically useful in providing prognostic prediction and facilitating accurate diagnosis of PTC in thyroid fine‐needle aspirate (FNA) samples.METHODSThis study assessed the correlation of cellularity with DNA yield and compared 2 technical platforms with different sensitivities in detection of BRAF mutation in cytologic specimens. Cellularity was evaluated based on groups of 10+ cells on a ThinPrep slide: 1+ (1‐5 groups), 2+ (6‐10 groups), 3+ (11‐20 groups), and 4+ (> 20 groups). Genomic DNA was extracted from residual materials of thyroid FNAs after cytologic diagnosis.RESULTSApproximately 49% of thyroid FNA samples had low cellularity (1‐2+). DNA yield is proportionate with increased cellularity and increased nearly 4‐fold from 1+ to 4+ cellularity in cytologic samples. When applied to BRAF mutational assay, using a cutoff of 6 groups of follicular cells with 10+ cells per group, 96.7% of cases yielded enough DNA for at least one testing for BRAF mutation. Five specimens (11.6%) with lower cellularity did not yield sufficient DNA for duplicate testing. Comparison of Sanger sequencing to allele‐specific polymerase chain reaction methods shows the latter confers better sensitivity in detection of BRAF mutation, especially in limited cytologic specimens with a lower percentage of malignant cells.CONCLUSIONSThis study demonstrates that by using 6 groups of 10+ follicular cells as a cutoff, nearly 97% of thyroid FNA samples contain enough DNA for BRAF mutational assay. Careful selection of a molecular testing system with high sensitivity facilitates the successful conduction of molecular testing in limited cytologic specimens. Cancer (Cancer Cytopathol) 2014;122:114–22 © 2013 American Cancer Society.
Personalizing Anticoagulant and Antiplatelet Therapeutics: A Timely Task
Authors: Gurwitz David 
Published: October 2013

AbstractIn spite of new therapeutics and diagnostics, thrombosis‐related diseases including heart failure and stroke remain the leading cause of death globally and a major healthcare burden. Pharmacogenomic studies may reduce the burden of thrombotic diseases by aiding treatment individualization with the most appropriate anti‐coagulant and anti‐platelet therapeutics. Discovering and validating biomarkers for improved personalized treatment of thrombotic diseases will require massive investment. A concerted dedicated effort built upon a public‐private partnership is warranted for addressing this foremost public health concern.
Will One Size of Anticoagulant Dosage Fit All?
Authors: Bloemen Saartje , De Laat Marieke , De Laat Bas , Hemker Hendrik Coenraad , Al Dieri Raed 
Published: October 2013

Abstract

Enabling Technology, Genomics, Proteomics
Preclinical Research

New, direct thrombin and factor Xa inhibitors have been developed to reduce the well‐established drawbacks of currently available anticoagulants such as a protracted duration of action and high inter‐ and intra‐individual variation of dose‐effect. New anticoagulants are noninferior and no less effective for thromboprophylaxis than low‐molecular‐weight heparins or vitamin K antagonists. They are currently administered at fixed doses without control of their effect on the clotting system. Whether they need monitoring cannot be answered because relevant data are lacking and present means of monitoring are inadequate. The individual response to a standard dose of (any) anticoagulant—the modern direct inhibitors included—is highly variable (∼30%), and the clinical effect of all anticoagulants is not dose independent. Therefore a fixed dose that is optimal for the average patient is suboptimal for a fair percentage of patients that are low responders (risk of re‐thrombosis) and dangerous for an equally high percentage of high responders (risk of bleeding). A better understanding of individual differences in the response, either low or high, to anticoagulants, irrespective of their mode of action, should be a primary objective for pharmacotherapy over the next decade.
Novel Approach to Diagnostics of Thrombocytosis: mRNA and miRNA Profiling of Blood Platelets
Authors: Gnatenko Dmitri V. 
Published: October 2013

Abstract

Preclinical Research

Thrombocytosis is a condition characterized by excessive numbers of platelets in blood. Chronic myeloproliferative diseases—including essential thrombocythemia—are among potential causes of high platelet count. Thrombosis of large arteries, stroke, and heart attack are among the major causes of mortality associated with essential thrombocythemia. Currently there is no direct diagnostic test for this disease leading to diagnosis by exclusion. Recent studies demonstrate that messenger RNA (mRNA) and microRNA (miRNA) profiling of human blood platelets can be used to discriminate patients with essential thrombocythemia from healthy control subjects and from patients with reactive thrombocytosis. This paper provides a brief overview of mRNA and miRNA biomarkers for thrombocytosis and discusses the development of a minimally invasive diagnostic assay for essential thrombocythemia. Advances in mRNA and miRNA profiling technology and progress in data analysis have made possible the generation of such an assay, which would significantly benefit patients with essential thrombocythemia and clinical hematologists.
Vanilloid‐Like Agents: Potential Therapeutic Targeting of Platelets?
Authors: Adams Murray J. , Almaghrabi Safa Y. , Ahuja Kiran D. K. , Geraghty Dominic P. 
Published: October 2013

Abstract

Preclinical Research

Capsaicinoids are the “hot” compounds present in placental tissues of Capsicum fruits that are responsible for capsicum's pungency. Capsaicinoids belong to the broader class of vanilloids that activate the nonselective cation channel, transient receptor potential vanilloid‐1 (TRPV1). Endogenous vanilloids include arachidonic acid derivatives that have different affinities for TRPV1 and are increasingly recognized as an important group of signaling molecules affecting tissue injury, pain, and inflammation. Furthermore, some endogenous vanilloids have high affinity for cannabinoid receptors (CB1 and CB2), which are present in platelets. The most well‐known and widely studied plant‐derived vanilloid, capsaicin, is reported to have antiplatelet properties, but the mechanism of action is uncertain. This article will briefly review the mechanisms involved in platelet activation and aggregation, discuss the properties of vanilloids and their receptor, TRPV1, and discuss whether the effects of vanilloids, and particularly capsaicinoids, on platelets may be exploited for therapeutic benefit.
Impact and Diagnosis of Antiplatelet Therapy Resistance in Patients Undergoing Cardiac Surgery
Authors: Gasparovic Hrvoje , Petricevic Mate , Biocina Bojan 
Published: October 2013

Abstract

Clinical Development Phases I‐III Regulatory, Quality, Manufacturing

Coronary artery bypass grafting (CABG) is highly effective in the treatment of severe coronary artery disease. Antiplatelet therapy is a critical component of the medical management of patients following CABG. Patient idiosyncrasies in responsiveness to antiplatelet agents, however, lead to variable suppression of platelet aggregation. This problem is underscored by inconsistent findings from the different laboratory instruments used to document antiplatelet drug responsiveness and its uncertain clinical impact. The laboratory results reveal a spectrum of platelet inhibition effects. The cutoff values discriminating between “resistance” and “response” to antiplatelet therapy often rely solely on definition. It is therefore not surprising that regular testing for antiplatelet therapy response has neither been routinely instituted in a wider clinical arena nor is there unequivocal evidence to support it. The purpose of this review is to offer insight into the incidence and clinical impact of antiplatelet therapy resistance in patients undergoing surgical myocardial revascularization.
Projected marine climate change: effects on copepod oxidative status and reproduction
Authors: Vehmaa Anu , Hogfors Hedvig , Gorokhova Elena , Brutemark Andreas , Holmborn Towe , Engström‐Öst Jonna 
Published: October 2013

AbstractZooplankton are an important link between primary producers and fish. Therefore, it is crucial to address their responses when predicting effects of climate change on pelagic ecosystems. For realistic community‐level predictions, several biotic and abiotic climate‐related variables should be examined in combination. We studied the combined effects of ocean acidification and global warming predicted for year 2100 with toxic cyanobacteria on the calanoid copepod, Acartia bifilosa. Acidification together with higher temperature reduced copepod antioxidant capacity. Higher temperature also decreased egg viability, nauplii development, and oxidative status. Exposure to cyanobacteria and its toxin had a negative effect on egg production but, a positive effect on oxidative status and egg viability, giving no net effects on viable egg production. Additionally, nauplii development was enhanced by the presence of cyanobacteria, which partially alleviated the otherwise negative effects of increased temperature and decreased pH on the copepod recruitment. The interactive effects of temperature, acidification, and cyanobacteria on copepods highlight the importance of testing combined effects of climate‐related factors when predicting biological responses.
Combining food web and species distribution models for improved community projections
Authors: Pellissier Loïc , Rohr Rudolf P. , Ndiribe Charlotte , Pradervand Jean‐Nicolas , Salamin Nicolas , Guisan Antoine , Wisz Mary 
Published: October 2013

AbstractThe ability to model biodiversity patterns is of prime importance in this era of severe environmental crisis. Species assemblage along environmental gradients is subject to the interplay of biotic interactions in complement to abiotic filtering and stochastic forces. Accounting for complex biotic interactions for a wide array of species remains so far challenging. Here, we propose using food web models that can infer the potential interaction links between species as a constraint in species distribution models. Using a plant–herbivore (butterfly) interaction dataset, we demonstrate that this combined approach is able to improve species distribution and community forecasts. The trophic interaction network between butterfly larvae and host plant was phylogenetically structured and driven by host plant nitrogen content allowing forecasting the food web model to unknown interactions links. This combined approach is very useful in rendering models of more generalist species that have multiple potential interaction links, where gap in the literature may occur. Our combined approach points toward a promising direction for modeling the spatial variation in entire species interaction networks.
The Synergetic Interplay of Weak Interactions in the Ion‐Pair Recognition of Quaternary and Diquaternary Ammonium Salts by Halogenated Resorcinarenes
Authors: Kodiah Beyeh N. , Göth Melanie , Kaufmann Lena , Schalley Christoph A. , Rissanen Kari 
Published: October 2013

AbstractThe influence of halogens on the noncovalent interactions of different upper‐rim‐substituted hexylresorcinarenes with quaternary and diquaternary ammonium iodide salts was investigated in the gas phase by electrospray ionization Fourier‐transform ion‐cyclotron‐resonance (ESI‐FTICR) mass spectrometry and in solution by 1H NMR titration studies. The electronic nature of the substituents on the upper rim of the resorcinarene was directly reflected in the order of binding strengths of the hosts towards quaternary and diquaternary ammonium cations in the gas phase. In solution, the opposite trend was observed, with generally higher binding constants for the diquaternary over the quaternary salts. This phenomenon is explained by the synergetic effect originating from the interaction of the halogenated resorcinarenes with the counteranions through enhanced hydrogen bonding, leading to ion‐pair binding in solution. The electronegativity of the halogens renders the hydrogen of the hydroxy group more acidic, and hence enforces hydrogen bonding in solution. The collective effect of several weak interactions is manifested in solution, thereby emphasizing the benefits of comparing solution and gas‐phase studies in recognition processes.
Rh‐Catalyzed Diarylamine Synthesis by Intermolecular C–H Amination of Heteroarylarenes
Authors: Tang Conghui , Yuan Yizhi , Cui Yuxin , Jiao Ning 
Published: October 2013

AbstractA novel and efficient Rh‐catalyzed intermolecular C–H amination of heteroarylarenes with aryl azides has been developed. This procedure does not require an oxidant, releases N2 as the only byproduct, and provides an efficient approach to diarylamines with broad functional‐group tolerance.
Development and validation of a biotic ligand model for predicting chronic toxicity of lead to Ceriodaphnia dubia
Authors: Nys Charlotte , Janssen Colin R. , Mager Edward M. , Esbaugh Andrew J. , Brix Kevin V. , Grosell Martin , Stubblefield William A. , Holtze Keith , De Schamphelaere Karel A.C. 
Published: October 2013

Abstract

While it is increasingly being recognized that biotic ligand models (BLMs) are valuable in the risk assessment of metals in aquatic systems, the development of chronic BLMs has been less advanced for lead than for other metals. The authors investigated the univariate effects of Ca and pH on the chronic reproductive toxicity of Pb to Ceriodaphnia dubia at 4 levels. Calcium influenced chronic Pb toxicity to C. dubia only to a relatively small extent, whereas a high pH (8.2) provided strong protection against Pb toxicity (compared with lower pH levels). Based on this data set, a chronic Pb BLM for C. dubia was developed. The effect of pH was modeled as a single biotic ligand site competition by H+ with a log stability constant for binding of H+ to the biotic ligand (KHBL) of 7.6, while no other competitive constants were needed. The developed BLM was shown, in an independent validation with 3 other data sets, to be capable of predicting chronic Pb toxicity to different clones of C. dubia by an error of less than a factor of 2 in most synthetic and natural waters considered. The results add to the growing evidence that BLM–based risk assessment or water-quality criteria for Pb are likely to be more appropriate relative to hardness-based assessments or criteria. Environ Toxicol Chem 2014;33:394–403. © 2013 SETAC
An approach to assess the regulatory relevance of microevolutionary effects in ecological risk assessment of chemicals: A case study with cadmium
Authors: Coninck Dieter I.M. De , Janssen Colin R. , Schamphelaere Karel A.C. De 
Published: October 2013

Abstract

The authors suggest an approach to assess the regulatory relevance of microevolutionary effects of chemicals based on a comparison of concentrations at which microevolutionary effects have been reported in the literature and conventionally derived ecotoxicological threshold concentrations. The authors found reports of microevolutionary effects of cadmium in freshwater organisms at hardness-normalized concentrations between 0.5 µg Cd L−1 and 6290 µg Cd L−1 (normalized to a hardness of 50 mg CaCO3 L−1). These concentrations were at least 1.5 times higher than the hardness-normalized hazardous concentration for 5% of the organisms of 0.34 µg Cd L−1. This suggests that there is no immediate need to consider microevolutionary effects of Cd in environmental risk assessments of freshwater environments. However, some other aspects should be kept in mind as well. First, microevolutionary effects have so far only been investigated at few, relatively high concentrations of Cd and not encompassing the 5% hazardous concentration. Second, different types of microevolutionary effects or investigated ecotoxicological end points may influence the conclusions of the suggested comparative approach. Finally, factors influencing the bioavailability of Cd were not commonly reported in the literature, which made normalization of concentrations at which evolutionary effects occurred impossible and affected the number of studies that could be evaluated in the suggested approach. Environ Toxicol Chem 2014;33:453–457. © 2013 SETAC
The rhizotoxicity of metal cations is related to their strength of binding to hard ligands
Authors: Kopittke Peter M. , Menzies Neal W. , Wang Peng , McKenna Brigid A. , Wehr J. Bernhard , Lombi Enzo , Kinraide Thomas B. , Blamey F. Pax C. 
Published: October 2013

Abstract

Mechanisms whereby metal cations are toxic to plant roots remain largely unknown. Aluminum, for example, has been recognized as rhizotoxic for approximately 100 yr, but there is no consensus on its mode of action. The authors contend that the primary mechanism of rhizotoxicity of many metal cations is nonspecific and that the magnitude of toxic effects is positively related to the strength with which they bind to hard ligands, especially carboxylate ligands of the cell-wall pectic matrix. Specifically, the authors propose that metal cations have a common toxic mechanism through inhibiting the controlled relaxation of the cell wall as required for elongation. Metal cations such as Al3+ and Hg2+, which bind strongly to hard ligands, are toxic at relatively low concentrations because they bind strongly to the walls of cells in the rhizodermis and outer cortex of the root elongation zone with little movement into the inner tissues. In contrast, metal cations such as Ca2+, Na+, Mn2+, and Zn2+, which bind weakly to hard ligands, bind only weakly to the cell wall and move farther into the root cylinder. Only at high concentrations is their weak binding sufficient to inhibit the relaxation of the cell wall. Finally, different mechanisms would explain why certain metal cations (for example, Tl+, Ag+, Cs+, and Cu2+) are sometimes more toxic than expected through binding to hard ligands. The data presented in the present study demonstrate the importance of strength of binding to hard ligands in influencing a range of important physiological processes within roots through nonspecific mechanisms. Environ Toxicol Chem 2014;33:268–277. © 2013 SETAC
Influence of environmental factors in thein vitrodehydration of hydrogel and silicone hydrogel contact lenses
Authors: Martín‐Montañez Vicente , López‐Miguel Alberto , Arroyo Cristina , Mateo María E. , González‐Méijome José M. , Calonge Margarita , González‐García María J. 
Published: October 2013

AbstractPurpose: To analyzein vitrothe influence of different environmental conditions on the dehydration pattern of seven currently marketed hydrogel (Hy) and silicone hydrogel (Si‐Hy) contact lenses (CL). Methods: Three Hy and four Si‐Hy CLs were evaluated. CLs were exposed to four different relative humidity (RH) conditions (5%, 30%, 50%, and 70%) and two air flow (AF) rates (0 and 2.75 m/seg) within an environmental chamber. Dehydration was assessed using the gravimetric method. Data were taken at baseline, 5, 10, 15, 20, 30, 45, 60, 90, and 120 minutes of exposure. Dehydration rate (DR), valid dehydration (VD) and stabilization time were calculated. Results: The interaction between RH, AF and the type of the CL material had a significant effect (p ≤ 0.03) on DR up to 60 minutes. The maximum differences in VD values among CL occurred around 15 minutes exposure varying from 25.16% to 42.75%. Stabilization time was quicker under the 5%RH with AF condition than under 70% RH without AF one for most CLs. Conclusions: Lower RH seems to increase CL dehydration being further accelerated with the AF presence. The dehydration pattern is material dependent, thus current marketed CLs behave differently under several controlled environmental conditions. Futurein vivostudies should confirm these outcomes. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 102B: 764–771, 2014.
Three‐dimensional collagen scaffold enhances the human adenoid cystic carcinoma cancer stem cell and epithelial–mesenchymal transition properties
Authors: Liu Li‐Jun , Zhang Jing , Xiao Zhi‐Feng , Dai Bin , Sun Mo‐Yi , Chen Lei , Chen Bing 
Published: October 2013

AbstractThree‐dimensional (3D) cell culture may provide the architectures similar to the in vivo natural extracellular matrix condition for in vitro cultured cells. In this work, a 3D collagen scaffold was used to culture the adenoid cystic carcinoma (ACC) cells. The results showed that the 3D scaffold not only induced the diversification of cell morphologies but also increased the cell proliferation. The transcription of matrix metalloproteinase and epithelial–mesenchymal transition were significantly increased in the cells cultured in 3D collagen scaffolds. In addition, the expression of cancer stem cell (CSC) markers of Sox2 and Oct4 were higher than that in 2D cultured cells. The 3D cultured ACC‐83 cells showed more resistance to chemotherapeutic drugs. Thus, the 3D collagen scaffold could provide a useful model for CSCs study and anticancer therapeutics research in vitro. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 102B: 772–780, 2014.
Micro‐CT and PET analysis of bone regeneration induced by biodegradable scaffolds as carriers for dental pulp stem cells in a rat model of calvarial “critical size” defect: Preliminary data
Authors: Annibali Susanna , Bellavia Diana , Ottolenghi Livia , Cicconetti Andrea , Cristalli Maria Paola , Quaranta Roberta , Pilloni Andrea 
Published: October 2013

AbstractBone regeneration strategies in dentistry utilize biodegradable scaffolds seeded with stem cells able to induce bone formation. However, data on regeneration capacity of these tissue engineering constructs are still deficient. In this study micro‐Computed tomography (micro‐CT) and positron emission tomography (PET) analyses were used to investigate bone regeneration induced by two scaffolds [Granular deproteinized bovine bone (GDPB) and Beta‐tricalcium phosphate (β‐TCP)] used alone or in combination with dental pulp stem cells (DPSC) in a tissue engineered construct implanted in a rat critical calvarial defect. Bone mineral density (BMD) and standard uptake value (SUV) of tracer incorporation were measured after 2, 4, 8, and 12 weeks post‐implant. The results showed that: (1) GDPB implants were mostly well positioned, as compared to ß‐TCP; (2) GDPB induced higher BMD and SUV values within the cranial defect as compared to ß‐TCP, either alone or in combination with stem cells; (3) addition of DPSC to the grafts did not significantly induce an increase in BMD and SUV values as compared to the scaffolds grafted alone, although a small tendency to increase was observed. Thus our study demonstrates that GDPB, when used to fill critical calvarial defects, induces a greater percentage of bone formation as compared to ß‐TCP. Moreover, this study shows that addition of DPSC to pre‐wetted scaffolds has the potential to ameliorate bone regeneration process, although the set of optimal conditions requires further investigation. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 102B: 815–825, 2014.