bluuebunny/crossref_metadata_2025_split huggingface dataset:
Flood frequency under the influence of trends in the Pearl River basin, China: changing patterns, causes and implications
Authors: Zhang Qiang , Gu Xihui , Singh Vijay P. , Xiao Mingzhong , Xu Chong‐Yu 
Published: June 2014

AbstractUsing a nonstationary flood frequency model, this study investigates the impact of trends on the estimation of flood frequencies and flood magnification factors. Analysis of annual peak streamflow data from 28 hydrological stations across the Pearl River basin, China, shows that: (1) northeast parts of the West and the North River basins are dominated by increasing annual peak streamflow, whereas decreasing trends of annual peak streamflow are prevailing in other regions of the Pearl River basin; (2) trends significantly impact the estimation of flood frequencies. The changing frequency of the same flood magnitude is related to the changing magnitude or significance/insignificance of trends, larger increasing frequency can be detected for stations with significant increasing trends of annual peak streamflow and vice versa, and smaller increasing magnitude for stations with not significant increasing annual peak streamflow, pointing to the critical impact of trends on estimation of flood frequencies; (3) larger‐than‐1 flood magnification factors are observed mainly in the northeast parts of the West River basin and in the North River basin, implying magnifying flood processes in these regions and a higher flood risk in comparison with design flood‐control standards; and (4) changes in hydrological extremes result from the integrated influence of human activities and climate change. Generally, magnifying flood regimes in the northeast Pearl River basin and in the North River basin are mainly the result of intensifying precipitation regime; smaller‐than‐1 flood magnification factors along the mainstream of the West River basin and also in the East River basin are the result of hydrological regulations of water reservoirs. Copyright © 2014 John Wiley & Sons, Ltd.
Simulating Biomolecular Folding and Function by Native‐Structure‐Based/Go‐Type Models
Authors: Sinner Claude , Lutz Benjamin , John Shalini , Reinartz Ines , Verma Abhinav , Schug Alexander 
Published: June 2014

AbstractThe 2013 Nobel Prize in Chemistry highlights how crucial computer simulations have become for many scientific and engineering fields. Nowadays, scientific progress is not only driven by the interplay of new experimental measurements and increasingly sophisticated theoretical frameworks, but also by an incredible toolbox of complex computational models meeting ubiquitously available computing power and data storage facilities. Quantum mechanical (QM) calculations can be condensed into molecular mechanics (MM) force fields and coupled QM/MM calculations can derive atomic and molecular properties of biomolecular or materials science systems with high accuracy. Pure MM simulations driven by Monte Carlo or molecular dynamics algorithms are widely applied in biological chemistry/physics and can investigate large biomolecular systems, such as proteins, DNA, or RNA. One coarse‐grained class of these models, native‐structure‐based or Go models, are based on energy landscape theory and the principle of minimal frustration. Herein, an ensemble of converging pathways guide protein folding on a funnel‐like shape of the entire energy landscape towards the native state. Simulations based on these ideas have been tremendously successful in explaining protein folding and function. Their history and recent application highlights are reviewed.
An innovative three‐dimensional gelatin foam culture system for improved study of glioblastoma stem cell behavior
Authors: Yang Meng‐Yin , Chiao Ming‐Tsang , Lee Hsu‐Tung , Chen Chien‐Min , Yang Yi‐Chin , Shen Chiung‐Chyi , Ma Hsin‐I. 
Published: June 2014

AbstractThree‐dimensional (3‐D) tissue engineered constructs provide a platform for examining how the local extracellular matrix contributes to the malignancy of various cancers, including human glioblastoma multiforme. Here, we describe a simple and innovative 3‐D culture environment and assess its potential for use with glioblastoma stem cells (GSCs) to examine the diversification inside the cell mass in the 3‐D culture system. The dissociated human GSCs were cultured using gelatin foam. These cells were subsequently identified by immunohistochemical staining, reverse transcriptase‐polymerase chain reaction, and Western blot assay. We demonstrate that the gelatin foam provides a suitable microenvironment, as a 3‐D culture system, for GSCs to maintain their stemness. The gelatin foam culture system contributes a simplified assessment of cell blocks for immunohistochemistry assay. We show that the significant transcription activity of hypoxia and the protein expression of inflammatory responses are detected at the inside of the cell mass in vitro, while robust expression of PROM1/CD133 and hypoxia‐induced factor‐1 alpha are detected at the xenografted tumor in vivo. We also examine the common clinical trials under this culture platform and characterized a significant difference of drug resistance. The 3‐D gelatin foam culture system can provide a more realistic microenvironment through which to study the in vivo behavior of GSCs to evaluate the role that biophysical factors play in the hypoxia, inflammatory responses and subsequent drug resistance. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 103B: 618–628, 2015.
Effect of oxide layer modification of CoCr stent alloys on blood activation and endothelial behavior
Authors: Milleret Vincent , Ziogas Algirdas , Buzzi Stefano , Heuberger Roman , Zucker Arik , Ehrbar Martin 
Published: June 2014

AbstractCoCr alloys, in particular MP35N and L605, are extensively used in biomedical implants, for example for coronary stents. In practice, these alloys present a moderately hydrophobic surface which leads to significant platelet adhesion and consequently to risk of early thrombosis or in‐stent restenosis. Surface modification of biomedical implants is known to alter their biological performances. In this study we focused on the alteration of in vitro biological responses of human cells contacting CoCr surfaces with engineered oxide layers. XPS analysis was performed to determine the composition of the oxide layer of differently treated CoCr while the bulk properties were not modified. An extensive characterization of the surfaces was performed looking at surface roughness, wettability and charge. After static exposure to blood, strongly reduced platelet and increased polymorphonuclear neutrophil adhesion were observed on treated versus untreated surfaces. Comparisons of treated and untreated samples provide evidence for wettability being an important player for platelet adhesion, although multiple factors including surface oxide chemistry and charge might control polymorphonuclear neutrophil adhesion. The differently treated surfaces were shown to be equally suitable for endothelial cell proliferation. We herein present a novel approach to steer biological properties of CoCr alloys. By adjusting their oxide layer composition, substrates were generated which are suitable for endothelial cell growth and at the same time show an altered (reduced) blood contact activation. Such treatments are expected to lead to stents of highly reproducible quality with minimal thrombogenicity and in‐stent restenosis, while maintaining rapid re‐endothelialization after coronary angioplasty. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 103B: 629–640, 2015.
Biosimilar monoclonal antibodies: A Canadian regulatory perspective on the assessment of clinically relevant differences and indication extrapolation
Authors: Scott Bradley J. , Klein Agnes V. , Wang Jian 
Published: June 2014

AbstractMonoclonal antibodies have become mainstays of treatment for many diseases. After more than a decade on the Canadian market, a number of authorized monoclonal antibody products are facing patent expiry. Given their success, most notably in the areas of oncology and autoimmune disease, pharmaceutical and biotechnology companies are eager to produce their own biosimilar versions and have begun manufacturing and testing for a variety of monoclonal antibody products. In October of 2013, the first biosimilar monoclonal antibody products were approved by the European Medicines Agency (Remsima™ and Inflectra™). These products were authorized by Health Canada shortly after; however, while the EMA allowed for extrapolation to all of the indications held by the reference product, Health Canada limited extrapolation to a subset of the indications held by the reference product, Remicade®. The purpose of this review is to discuss the Canadian regulatory framework for the authorization of biosimilar mAbs with specific discussion around the clinical requirements for establishing (bio)‐similarity and to present the principles that are used in the clinical assessment of New Drug Submissions for intended biosimilar monoclonal antibodies. Health Canada's current views regarding indication extrapolation, product interchangeability, and post‐market surveillance are discussed as well.
Pharmacokinetics of renally excreted drug dexpramipexole in subjects with impaired renal function
Authors: He Ping , Kerr Doug , Marbury Thomas , Ries Daniel , Farwell Wildon , Stecher Scott , Dong Yingwen , Wei Dong , Rogge Mark 
Published: June 2014

AbstractThis phase I, open‐label, single‐dose study evaluated the pharmacokinetics, safety, and tolerability of renally excreted drug dexpramipexole in subjects with normal and impaired renal function, i.e. mild, moderate, severe renal impairment, or end‐stage renal disease (ESRD) requiring hemodialysis when matched by age and sex. Dexpramipexole area under the curves (AUCs), but not Cmax, were significantly increased with the severity of renal impairment after a single dose administration. The geometric mean ratio of dose‐normalized AUC(0–72) was 1.4, 1.7, 2.7, and 4.5, respectively, in mild, moderate, severe renal impairment, and ESRD subjects when compared to healthy subjects. There was a strong association between renal function (eGFR) and dexpramipexole CLr. The slope (90% confidence interval(CI)) of eGFR and renal clearance (CLr) in the regression model was 3.1 (2.4, 3.7). Dexpramipexole elimination in ESRD subjects during both dialysis and non‐dialysis (i.e., interval between dialysis) was insignificant. Single 75 mg and 150 mg doses of dexpramipexole were well tolerated, and the safety profile was comparable across renal function groups. Extensive drug accumulation may occur with repeated dosing in patients with significant renal impairment. It is recommended that dexpramipexole not to be given to patients with severe renal impairment or in those with ESRD.
The pharmacokinetics, pharmacodynamics, and safety of baricitinib, an oral JAK 1/2 inhibitor, in healthy volunteers
Authors: Shi Jack G. , Chen Xuejun , Lee Fiona , Emm Thomas , Scherle Peggy A. , Lo Yvonne , Punwani Naresh , Williams William V. , Yeleswaram Swamy 
Published: June 2014

AbstractBaricitinib (also known as LY3009104 or INCB028050), a novel and potent small molecule inhibitor of Janus kinase family of enzymes (JAKs) with selectivity for JAK1 and JAK2, is currently in clinical development for the treatment of rheumatoid arthritis (RA) and other inflammatory disorders. Two double‐blind, randomized, and placebo‐controlled studies were conducted to evaluate single ascending doses of 1–20 mg and multiple ascending doses of 2–20 mg QD and 5 mg BID for 10 or 28 days in healthy volunteers. Following oral administration, baricitinib plasma concentration typically attains its peak value within 1.5 hours postdose and subsequently declines in a bi‐exponential fashion. Baricitinib demonstrates dose‐linear and time‐invariant pharmacokinetics, with low oral‐dose clearance (17 L/h) and minimal systemic accumulation observed following repeat dosing. The mean renal clearance of baricitinib was determined to be ∼12 L/h. [Correction added after publication 12 November 2014: in the preceding sentence, “2 L/h” was changed to “12 L/h.”] The effect of a high‐fat meal on baricitinib pharmacokinetics was insignificant. The pharmacodynamics of baricitinib, evaluated by the inhibition of STAT3 phosphorylation following cytokine stimulation in the whole blood ex vivo, was well correlated with baricitinib plasma concentrations. Baricitinib was generally safe and well tolerated, with no serious treatment‐related adverse events (AEs) reported from either of the studies. An expected rapidly reversible, dose‐related decline in absolute neutrophil count was seen with baricitinib.
Multi‐scalar influence of weather and climate on very large‐fires in the Eastern United States
Authors: Barbero Renaud , Abatzoglou John T. , Kolden Crystal A. , Hegewisch Katherine C. , Larkin Narasimhan K. , Podschwit Harry 
Published: June 2014

ABSTRACTA majority of area burned in the Eastern United States (EUS) results from a limited number of exceptionally large wildfires. Relationships between climatic conditions and the occurrence of very large‐fires (VLF) in the EUS were examined using composite and climate‐niche analyses that consider atmospheric factors across inter‐annual, sub‐seasonal and synoptic temporal scales. While most large‐fires in the EUS coincided with below normal fuel moisture and elevated fire weather, VLF preferentially occurred during a long‐term drought accompanied by more acute sub‐seasonal drought realized through fuel moisture stress and elevated fire‐weather conditions. These results were corroborated across the EUS, with varying influences of drought, fire danger and fire weather discriminating VLF from other large fires across different geographical regions. We also show that the probability of VLF conditioned by fire occurrence increases when long‐term drought, depleted fuel moisture and elevated fire weather align. This framework illustrates the compounding role of different timescales in VLF occurrence and serves as a basis for improving VLF predictions with seasonal climate forecasts and climate change scenarios.
Retracted: Acid‐Catalyzed Aquation of Ni(II)‐Hydrazone Complexes: Kinetics and Solvent Effect
Authors: Mohamad Ahmad Desoky M. , Rabia Mostafa K. , Ismail Nabawia M. , Mahmoud Ali Abdo 
Published: June 2014

ABSTRACTComplexes of the type [Ni(L)(H2O)]Cl2·nH2O, where L = 2‐pyridyl‐3‐isatinbishydrazone ligands, have been synthesized and characterized on the bases of elemental analysis, molar conductance, IR, electronic spectra, and thermal analysis (TGA and DTA). Acid‐catalyzed aquation of the Ni(II) isatin‐bishydrazone complexes was followed spectrophotometrically in various water–methanol and water–acetone mixtures at temperature 298 K. Kinetic behavior of the acid aquation is a linear rate law, indicating that the acid‐catalyzed aquation of these complexes in water–methanol and water–acetone mixtures follows a rate law with kobs = k2[H+]. The effect of the mole fraction of the ganic solvent, i.e., methanol and acetone, on the acid aquation has been analyzed; the decrease in the rate constant values with increasing of the methanol or acetone ratios is attributable to the effect of the co‐organic solvent on the initial states of the acid aquation by the destabilization of the H+ ion.
Nucleophilic Substitution Reactions of 2‐Methoxy‐3‐X‐5‐nitrothiophenes: Effect of Substituents and Structure–Reactivity Correlations
Authors: ECHAIEB A. , GABSI W. , BOUBAKER T. 
Published: June 2014

ABSTRACTA kinetic study is reported for reactions of 2‐methoxy‐3‐X‐5‐nitrothiophenes 1a–d (X = SO2CH3, CO2CH3, CONH2, H) with piperidine in different solvents at 20°C. It is shown that the reactions take place through a SNAr mechanism with the initial nucleophilic addition step being rate limiting. The satisfactory Hammett correlations (log k1 vs. σ) obtained in the present system confirms that a 3‐X substituent exerts an effect on the 2‐position of the same type as that exerted from the 5‐position. The second‐order rate constants associated with these reactions are employed to determine the electrophilicity parameters E of the thiophenes 1a–d according to the relationship log k (20°C) = s(E + N) (Angew. Chem., Int. Ed. Engl. 1994, 33, 938–957). The E values of 1a–d are found to cover a range from −21.33 to −17.18, going from 1d, the least reactive, to 1a, the most reactive thiophene. Interestingly, a linear correlation (r2 = 0.9910) between the electrophilicity parameters E determined in this work and the Hammett's σ constants values has been observed and discussed. On the other hand, we have found that the reported rate constants of some thiophenes 1 complexation by the methoxide ion in methanol are 3.5–73.5 times higher than predicted by Mayr's approach.
Impact of thyroid nodule size on prevalence and post‐test probability of malignancy: A systematic review
Authors: Shin Jennifer J. , Caragacianu Diana , Randolph Gregory W. 
Published: June 2014

Objectives/HypothesisLarge thyroid nodules may be associated with higher risk of malignancy and less‐accurate fine‐needle aspiration (FNA) results, but there is currently no overarching consensus. We therefore tested two null hypotheses: 1) thyroid nodule size >3 to 4 cm is not associated with a higher baseline prevalence of malignancy (i.e., the associated pretest probability is the same, regardless of size), and 2) thyroid nodule size >3 to 4 cm is not associated with worse diagnostic accuracy (i.e., the associated sensitivity, false‐negative rate, and post‐test probability of malignancy is not affected by nodule diameter).Study DesignComputerized searches of PubMed, Embase, and The Cochrane Library through July 2013 were performed, supplemented with manual searches.MethodsA priori criteria were defined to determine inclusion and exclusion of studies. Searches and data extraction were performed by independent reviewers and focused on FNA histopathologic findings and their relationship to nodule size, study design, and potential confounders.ResultsCriterion‐meeting studies (n = 15) included a total of 13,180 participants. The preponderance of prospective comparative studies showed a statistically significantly higher prevalence of malignancy in large nodules. Although data are mixed, evidence from the best‐reported studies suggests sensitivity, false‐negative rates, and frequency of true negatives among benign FNA results are worse in large nodules.ConclusionsLarge nodules have a higher pretest probability of malignancy. Data from larger studies suggest reduced FNA diagnostic accuracy in nodules >3 to 4 cm in diameter. Surgery represents a reasonable clinical option for nodules >3 cm.Level of EvidenceNA Laryngoscope, 125:263–272, 2015
Classification for animal vocal fold surgery: Resection margins impact histological outcomes of vocal fold injury
Authors: Imaizumi Mitsuyoshi , Thibeault Susan L. , Leydon Ciara 
Published: June 2014

Objectives/HypothesisExtent of vocal fold injury impacts the nature and timing of wound healing and voice outcomes. However, depth and extent of the lesion created to study wound healing in animal models vary across studies, likely contributing to different outcomes. Our goal was to create a surgery classification system to enable comparison of postoperative outcomes across animal vocal fold wound‐healing studies.Study DesignProspective, controlled animal study.MethodsRats underwent one of three types of unilateral vocal fold surgeries classified by depth and length of resection. The surgeries were: for subepithelial injury, resection of epithelium and superficial layer of the lamina propria at the midmembranous portion of the vocal fold; for transmucosal injury, resection of epithelium and lamina propria; and for transmuscular injury, resection of epithelium, lamina propria, and superficial portion of the vocalis muscle. Wound healing was evaluated histologically at various time points up to 35 days postinjury.ResultsComplete healing occurred by 14 days postsurgery for subepithelial injury, and by day 35 for transmucosal injury. Injury remained present at day 35 for transmuscular injury.ConclusionsTiming and completeness of healing varied by extent and depth of resection. Scarless healing occurred rapidly following subepithelial injury, whereas scarring was observed at 5 weeks after transmuscular injury. The proposed classification system may facilitate comparison of surgical outcomes across vocal fold wound‐healing studies.Levels of EvidenceN/A. Laryngoscope, 124:E437–E444, 2014
Seeing is believing: Objectively evaluating the impact of facial reanimation surgery on social perception
Authors: Dey Jacob K. , Ishii Lisa E. , Byrne Patrick J. , Boahene Kofi D. O. , Ishii Masaru 
Published: June 2014

Objectives/HypothesisObjectively measure the ability of facial reanimation surgery to normalize the appearance of facial paralysis using eye‐tracking technology.Study DesignProspective randomized controlled experiment.MethodsAn eye‐tracker system was used to record the eye‐movement patterns, called scanpaths, of 86 naïve observers gazing at pictures of paralyzed faces (House‐Brackmann IV–VI), smiling and in repose; before and after facial reanimation surgery; as well as normal, nonparalyzed faces. Observers gazed at each face for 10 seconds. Fixation durations for all predefined facial areas of interest were analyzed using mixed‐effects linear regression.ResultsObservers spent the majority of time (6.6 of 10 seconds) gazing in the central triangle region (eyes, nose, and mouth) of normal faces and paralyzed faces. There were significant deviations in fixation within the central triangle of paralyzed faces as compared to normal faces. Total fixation on the eyes remained conserved. However, total nose fixation decreased and mouth fixation increased on paralyzed faces. Facial reanimation surgery normalized many of the hemifacial gaze asymmetries caused by unilateral facial paralysis, and restored a normal distribution of gaze between the functional and paralyzed sides of the face and mouth.ConclusionThere were objective differences in the way observers directed their attention to facial features when viewing normal and paralyzed faces. After facial reanimation surgery, the attentional distraction caused by facial feature irregularities was reduced. These findings are important additions to the emerging body of objective evidence indicating the effectiveness of reanimation surgery; they also suggest opportunities to optimize reconstruction.Level of EvidenceN/A. Laryngoscope, 124:2489–2497, 2014
Depression and anxiety in amyotrophic lateral sclerosis: Correlations between the distress of patients and caregivers
Authors: Chen Dezhi , Guo Xiaoyan , Zheng Zhenzhen , Wei Qianqian , Song Wei , Cao Bei , Huang Rui , Yang Rong , Shang Huifang 
Published: June 2014

ABSTRACTIntroduction: Depression and anxiety are common in amyotrophic lateral sclerosis (ALS) patients and caregivers. Methods: In this study we investigated 93 ALS patients and their 93 caregivers. Depression and anxiety were quantified by the Hamilton Depression Rating Scale and Hamilton Anxiety Rating Scale, respectively. Results: Very strong correlations between depression and anxiety were found among patients and their caregivers. The severity of depression and anxiety of patients correlated moderately with that of their caregivers. No correlations were found between the severity of depression and anxiety and ALS Functional Rating Scale–Revised (ALSFRS‐R) score or for disease duration among patients and caregivers. However, severity of depression and anxiety in caregivers correlated with their age. Conclusions: Depression and anxiety in ALS patients and their caregivers were associated closely with each other but not with physical disability or disease duration in our Chinese population. Muscle Nerve 51: 353–357, 2015