bluuebunny/crossref_metadata_2025_split huggingface dataset:
A highly efficient and sensitive LC‐MS/MS method for the determination of afatinib in human plasma: application to a metabolic stability study
Authors: Kadi Adnan A. , Abdelhameed Ali S. , Darwish Hany W. , Attwa Mohamed W. , Al‐Shakliah Nasser S. 
Published: December 2015

AbstractAfatinib (AFT) is a new tyrosine kinase inhibitor approved for the treatment of nonsmall cell lung cancer. In the present study, a simple, specific, rapid and sensitive liquid chromatography tandem mass‐spectrometric method for the quantification of AFT in human plasma, was developed and validated. Chromatographic separation of the analytes was accomplished on a reversed‐phase Luna®‐PFP 100 Å column (50 × 2.0 mm; 3.0 μm) maintained at ambient temperature. Isocratic elution was carried out using acetonitrile–water (40:60, v/v) containing 10 mm ammonium formate buffer (pH 4.5) adjusted with formic acid at a flow rate of 0.4 mL min−1. The analytes were monitored by electrospray ionization in positive ion multiple reaction monitoring mode. The method yields a linear calibration plot (r2 = 0.9997) from a quantification range of 0.5–500 ng mL−1 with the lower limit of quantification and lower limit of detection of 1.29 and 0.42 ng mL−1, respectively. The intra‐ and inter‐day precision and accuracy were estimated and found to be in the ranges of 1.53–4.11% for precision and −2.80–0.38% for accuracy. Finally, quantification of afatinib in a metabolic stability study in rat liver microsomes was achieved through the proposed method. Copyright © 2016 John Wiley & Sons, Ltd.
Pre‐concentration of trace amount of bisphenol A in water samples by palm leaf ash and determination with high‐performance liquid chromatography
Authors: Sohrabi Razieh , Bahramifar Nader , Javadian Hamedreza , Agarwal Shilpi , Gupta Vinod Kumar 
Published: December 2015

AbstractPalm leaf ash was characterized and used as low‐cost adsorbent for solid‐phase extraction and preconcentration of bisphenol A (BPA) in real water samples. Analysis of BPA was carried out using HPLC involving Eurospher 100–5‐C18 (25 cm × 4.5 mm, particle size 5 μm) column and water–acetonitrile (40:60, v/v) as mobile phase. The adsorption was achieved quantitatively at a pH of 6 with elution by 3 mL acetonitrile. The limits of detection and enrichment factor were 0.02 μg L−1 and 333, respectively. Under optimum conditions the relative standard deviation (RSD) was 2% (n = 10). Comparison of qualification criteria of presented preconcentration procedure with other research indicated that palm leaf ash adsorbent was better than many of the adsorbents in terms of cost and reusability. Also, the limit of detection, precision and enrichment factor were comparable and even better than the previously reported methods. Finally, the efficiency of method was computed by determination of trace amounts of BPA in sea, river, mineral and tap waters with recoveries of 93.3–105.5% and RSDs of 0.61–3.12%.. Briefly, the developed solid‐phase extraction and Preparative layer chromatography (PLC) methods may be used for bisphenol A monitoring in any environmental water sample. Copyright © 2016 John Wiley & Sons, Ltd.
Development and validation of SPMMTE HPLC method for analysis of profens from human plasma
Authors: Hussain Afzal , Al‐Ajmi Mohamed F. , Amir Samira , Ali Imran 
Published: December 2015

AbstractA fast, selective and reproducible solid‐phase membrane microtip extraction (SPMMTE) HPLC method has been developed and validated for the analyses of ibuprofen, ketoprofen, and flurbiprofen from human plasma. The analysis was carried out on a C18 (150 × 4.6 mm; 5 μm) column. The mobile phase used was water–acetonitrile (55:45, v/v) adjusted to pH 3.0 using trifluoroacetic acid, at a flow rate 0.5 mL/min with a detection wavelength of 225 nm. The values for the capacity factors for the profen samples ranged from 0.47 to 1.50. The values for the selectivity factor (α) for ketoprofen–flurbiprofen, flurbiprofen–ibuprofen and ibuprofen–ketoprofen combinations from human plasma samples were 1.99, 1.00 and 2.10, respectively. The resolution factors (Rs) for ketoprofen–flurbiprofen, flurbiprofen–ibuprofen and ibuprofen–ketoprofen from plasma samples were 3.00, 1.50 and 4.10, respectively. The percentage recoveries of ibuprofen, ketoprofen, and flurbiprofen from human plasma were 75–85%. All of the profens were separated within 7.0 min, indicating a relatively fast method. During the development of the SPMMTE procedure the parameters of pH, contact time, desorption and types of solvents were optimized. The final method was also found to be efficient, effective and inexpensive. Copyright © 2016 John Wiley & Sons, Ltd.
The Casein Kinase 2‐Dependent Phosphorylation of NS5A Domain 3 from Hepatitis C Virus Followed by Time‐Resolved NMR Spectroscopy
Authors: Secci Erica , Luchinat Enrico , Banci Lucia 
Published: December 2015

AbstractHepatitis C virus (HCV) chronically affects millions of individuals worldwide. The HCV nonstructural protein 5A (NS5A) plays a critical role in the viral assembly pathway. Domain 3 (D3) of NS5A is an unstructured polypeptide responsible for the interaction with the core particle assembly structure. Casein kinase 2 (CK2) phosphorylates NS5A‐D3 at multiple sites that have mostly been predicted and only observed indirectly. In order to identify the CK2‐dependent phosphorylation sites, we monitored the reaction between NS5A‐D3 and CK2 in vitro by time‐resolved NMR. We unambiguously identified four serine residues as substrates of CK2. The apparent rate constant for each site was determined from the reaction curves. Ser408 was quickly phosphorylated, whereas the three other serine residues reacted more slowly. These results provide a starting point from which to elucidate the role of phosphorylation in the mechanisms of viral assembly—and in the modulation of the viral activity—at the molecular level.
A New Way Forward in Cancer Drug Discovery: Inhibiting the SWI/SNF Chromatin Remodelling Complex
Authors: Zinzalla Giovanna 
Published: December 2015

AbstractMutations in subunits of the SWI/SNF chromatin remodelling complex are found in 20 % of human cancers. At face value, this would appear to indicate that this multiprotein complex is a potent tumour suppressor. However, it has recently emerged that some mutations in the SWI/SNF complex can have a gain‐of‐function effect and that in other tumours, such as pancreatic cancer, leukaemia, and breast cancer, the wild‐type complex is used to drive cancer. Thus, paradoxically, this “tumour suppressor” has become an attractive target for developing anticancer agents. The SWI/SNF complex makes several protein–protein interactions both within the complex and with a wide range of transcription factors, and targeting these protein–protein interactions is emerging as the best approach to modulating the activity of the complex selectively.
Light‐Activated Reversible Imine Isomerization: Towards a Photochromic Protein Switch
Authors: Berbasova Tetyana , Santos Elizabeth M. , Nosrati Meisam , Vasileiou Chrysoula , Geiger James H. , Borhan Babak 
Published: December 2015

AbstractMutants of cellular retinoic acid‐binding protein II (CRABPII), engineered to bind all‐trans‐retinal as an iminium species, demonstrate photochromism upon irradiation with light at different wavelengths. UV light irradiation populates the cis‐imine geometry, which has a high pKa, leading to protonation of the imine and subsequent “turn‐on” of color. Yellow light irradiation yields the trans‐imine isomer, which has a depressed pKa, leading to loss of color because the imine is not protonated. The protein‐bound retinylidene chromophore undergoes photoinduced reversible interconversion between the colored and uncolored species, with excellent fatigue resistance.
Rationale and indications for coronary chronic total occlusion interventions
Authors: Vo M. N. , Rinfret S. 
Published: December 2015

AbstractChronic total occlusions (CTOs) are commonly found in patients with coronary artery disease and are considered the “final frontier” of coronary intervention. Despite growing interest in percutaneous coronary intervention (PCI) of CTOs along with advances in techniques and equipment, attempt rates remain low. This is most likely due to the fact that CTO PCI remains technically challenging and requires higher resource utilization. Furthermore, there remains controversy regarding the actual clinical benefit of successful CTO PCI. However, there have been a growing number of studies reporting short‐ and long‐term outcomes of CTO revascularization. We therefore sought to review the evidence and potential clinical benefits of successful CTO PCI.Answer questions and earn CME: https://www.wileyhealthlearning.com/Activity2/3691380/Activity.aspx
Hybrid approach to treatment of atrial fibrillation
Authors: Ong C. S. , Kofidis T. 
Published: December 2015

AbstractAtrial fibrillation (AF) is the most common sustained arrhythmia encountered in clinical practice. For years, there has been much interest and much is written with regard to the integrated or hybrid multidisciplinary approach toward cardiovascular care. The hybrid approach has been established in many centers, mostly with respect to ischemic heart disease. However, it is only a new and upcoming trend toward the use of a hybrid approach to treating cardiac arrhythmias. This hybrid approach to treating AF, while not the prevalent practice, is supported by medical literature. This review article examines the hybrid approach to treatment of AF, its benefits, disadvantages, and safety, as well as the long‐term results, based on current available literature. The hybrid approach to treatment of AF, combining surgical epicardial, and catheter endocardial ablation, showed a higher success rate compared to either technique alone. The increasing cooperation and professional intimacy between cardiologists and cardiothoracic surgeons are likely to continue and the hybrid approach, with its benefits while bearing in mind its limitations, may become the gold standard for treatment of drug‐resistant AF for the coming decade and beyond.Answer questions and earn CME: https://www.wileyhealthlearning.com/Activity2/3700532/Activity.aspx
Convenient Access to Fluorescent Probes by Chemoselective Acylation of Hydrazinopeptides: Application to the Synthesis of the First Far‐Red Ligand for Apelin Receptor Imaging
Authors: Margathe Jean‐François , Iturrioz Xavier , Regenass Pierre , Karpenko Iuliia A. , Humbert Nicolas , de Rocquigny Hugues , Hibert Marcel , Llorens‐Cortes Catherine , Bonnet Dominique 
Published: December 2015

AbstractHerein, we develop a convenient method to facilitate the solution‐phase fluorescent labelling of peptides based on the chemoselective acylation of α‐hydrazinopeptides. This approach combines the advantages of using commercially available amine‐reactive dyes and very mild conditions, which are fully compatible with the chemical sensitivity of the dyes. The usefulness of this approach was demonstrated by the labelling of apelin‐13 peptide. Various fluorescent probes were readily synthesized, enabling the rapid optimization of their affinities for the apelin receptor. Thus, the first far‐red fluorescent ligand with sub‐nanomolar affinity for the apelin receptor was characterized and shown to track the receptor efficiently in living cells by fluorescence confocal microscopy.
Homoleptic Two‐Coordinate Silylamido Complexes of Chromium(I), Manganese(I), and Cobalt(I)
Authors: Werncke C. Gunnar , Suturina Elizaveta , Bunting Philip C. , Vendier Laure , Long Jeffrey R. , Atanasov Mihail , Neese Frank , Sabo‐Etienne Sylviane , Bontemps Sébastien 
Published: December 2015

AbstractAnionic two‐coordinate complexes of first‐row transition‐metal(I) centres are rare molecules that are expected to reveal new magnetic properties and reactivity. Recently, we demonstrated that a N(SiMe3)2− ligand set, which is unable to prevent dimerisation or extraneous ligand coordination at the +2 oxidation state of iron, was nonetheless able to stabilise anionic two‐coordinate FeI complexes even in the presence of a Lewis base. We now report analogous CrI and CoI complexes with exclusively this amido ligand and the isolation of a [MnI{N(SiMe3)2}2]22− dimer that features a Mn−Mn bond. Additionally, by increasing the steric hindrance of the ligand set, the two‐coordinate complex [MnI{N(Dipp)(SiMe3)}2]− was isolated (Dipp=2,6‐iPr2‐C6H3). Characterisation of these compounds by using X‐ray crystallography, NMR spectroscopy, and magnetic susceptibility measurements is provided along with ligand‐field analysis based on CASSCF/NEVPT2 ab initio calculations.
Controlled Multi‐functionalization Facilitates Targeted Delivery of Nanoparticles to Cancer Cells
Authors: Hudlikar Manish S. , Li Xiuru , Gagarinov Ivan A. , Kolishetti Nagesh , Wolfert Margreet A. , Boons Geert‐Jan 
Published: December 2015

AbstractA major objective of nanomedicine is to combine in a controlled manner multiple functional entities into a single nanoscale device to target particles with great spatial precision, thereby increasing the selectivity and potency of therapeutic drugs. A multifunctional nanoparticle is described for controlled conjugation of a cytotoxic drug, a cancer cell targeting ligand, and an imaging moiety. The approach is based on the chemical synthesis of polyethylene glycol that at one end is modified by a thioctic acid for controlled attachment to a gold core. The other end of the PEG polymers is modified by a hydrazine, amine, or dibenzocyclooctynol moiety for conjugation with functional entities having a ketone, activated ester, or azide moiety, respectively. The conjugation approach allowed the controlled attachment of doxorubicin through an acid‐labile hydrazone linkage, an Alexa Fluor dye through an amide bond, and a glycan‐based ligand for the cell surface receptor CD22 of B‐cells using strain promoted azide‐alkyne cycloaddition. The incorporation of the ligand for CD22 led to rapid entry of the nanoparticle by receptor‐mediated endocytosis. Covalent attachment of doxorubicin via hydrazone linkage caused pH‐responsive intracellular release of doxorubicin and significantly enhanced the cytotoxicity of nanoparticles. A remarkable 60‐fold enhancement in cytotoxicity of CD22 (+) lymphoma cells was observed compared to non‐ targeted nanoparticles.
Bis‐Sulfonyl O,C,O‐Chelated Metallylenes (Ge, Sn) as Adjustable Ligands for Iron and Tungsten Complexes
Authors: Deak Noémi , Petrar Petronela M. , Mallet‐Ladeira Sonia , Silaghi‐Dumitrescu Luminiţa , Nemeş Gabriela , Madec David 
Published: December 2015

AbstractThe synthesis and characterization of an E2CE2 bis‐sulfonyl aryl pincer ligand and its efficiency for the stabilization of compounds containing low‐valent Group 14 elements (Ge and Sn) are reported. Complexation reaction of these metallylenes with iron or tungsten complexes resulted in the modulation of the oxygen atoms of the sulfonyl groups implicated in the stabilization of the Group 14 elements, demonstrating the original adjustable character of the bis‐sulfonyl O2S‐C‐SO2 aryl pincer.
Cascade Mn‐Mediated γ‐Alkylation/oxa‐Michael Addition of Enones with 1,3‐Dicarbonyls
Authors: Liu Xiaoguang , Chen Xiaohong , Mohr Justin T. 
Published: December 2015

AbstractA radical‐based strategy for regioselective γ‐C−C bond formation/oxa‐conjugate addition, forming the tetrahydrobenzofuran core common to many bioactive natural products is described. The technique utilizes readily available enone derivatives and 1,3‐dicarbonyl compounds as coupling partners in an oxidative formal [3+2] cycloaddition mediated by MnIII. The transformation delivers polycyclic products in good yields and proceeds with complete regiocontrol and excellent stereoselectivity. Sterically encumbered substrates are notably well‐tolerated and bond formation occurs readily to form neopentyl and all‐carbon quaternary centers in good yields. Several stereo‐ and chemoselective transformations of the products are described.
Solubility Switching of Metallophthalocyanines and Their Larger Derivatives upon Encapsulation
Authors: Kondo Kei , Akita Munetaka , Yoshizawa Michito 
Published: December 2015

AbstractMetallophthalocyanines (MPcs) are very useful pigments but scarcely soluble without appropriate functional groups in common solvents. Herein, we report that bent polyaromatic amphiphiles act as excellent solubilizing reagents for nonfunctionalized MPcs and larger MPc derivatives (e.g., CuPc, perhalogenated CuPcs, Cu‐naphthalocyanine, CuPc polymers, and double‐decker MPcs) in neutral water upon encapsulation. The resultant MPc nanocomposites display high stability towards heat and pH change. More importantly, the encapsulated MPcs can be released by simple protocols under mild conditions both into a bulk solvent and onto glass or polymer plates.
Energy and paper recycling: Modelling the time and energy requirements for low consistency batch repulping
Authors: Saville Frank , Martinez Mark , Olson James 
Published: December 2015

AbstractAn analytical model for low‐consistency repulping linking pulp material properties, consistency, temperature, and rotor and vat geometry is provided, which allows for accurate prediction of the time and energy required for repulping in both a 0.25 m3 laboratory‐scale repulper and a 15 m3 industrial‐scale repulper. The model assumes that all deflaking work is done by the repulper rotor in the rotor‐swept volume by turbulence generated by the rotor and that no deflaking occurs in the rest of the vat. Rotor shaft power is split linearly between the breakup of waste paper and dissipation by turbulence. Comparing the model predictions and experimental data for different pulp types, vat fill levels, and pulp suspension consistencies yields a correlation of R2 = 0.99 between all experimental results and the model predictions given the condition of fully turbulent (Reynolds‐independent) repulper rotor operation. The efficiency of the laboratory repulper is reduced from that predicted by the model for very low vat fill levels. This is due to a loss of effectiveness of the baffles at these low levels as indicated by solid body motion of the suspension and reduced rotor power number. This indicates that thorough mixing is a requirement to maximize repulping efficiency. Repulping time and energy savings can be accomplished by increasing the suspension consistency and the rotor‐swept volume/vat volume ratio by either increasing rotor size or reducing vat volume, all while ensuring complete mixing and circulation in the vat.
Development of Highly Potent GAT1 Inhibitors: Synthesis of Nipecotic Acid Derivatives by Suzuki–Miyaura Cross‐Coupling Reactions
Authors: Petrera Marilena , Wein Thomas , Allmendinger Lars , Sindelar Miriam , Pabel Jörg , Höfner Georg , Wanner Klaus T. 
Published: December 2015

AbstractA new series of potent and selective mGAT1 inhibitors has been identified, featuring a nipecotic acid residue and an N‐butenyl linker with a 2‐biphenyl residue at the ω‐position. Docking, combined with MD calculations, revealed a binding mode for the new compounds similar to that of tiagabine, the only mGAT1 inhibitor currently approved as antiepileptic drug. For the synthesis, a Suzuki–Miyaura cross‐coupling reaction was used as a key step by which variously substituted biaryl subunits were assembled. Biological evaluation revealed several compounds that possess binding affinities and inhibitory potencies toward mGAT1, together with subtype selectivities against mGAT2–mGAT4 that were similar to or even higher than those for tiagabine. A derivative carrying the 2′,4′‐dichloro‐2‐biphenyl moiety attached to N‐but‐3‐enylnipecotic acid at the terminal position of the linker chain was found to be the most potent binder, with the racemic form of the compound displaying a binding affinity of 8.05±0.13 (pKi), while the R enantiomer exhibited an affinity value of 8.33±0.06 (pKi).
Using “residual” FNA rinse and body fluid specimens for next‐generation sequencing: An institutional experience
Authors: Wei Shuanzeng , Lieberman David , Morrissette Jennifer J. D. , Baloch Zubair W. , Roth David B. , McGrath Cindy 
Published: December 2015

BACKGROUNDTissue specimens are typically considered optimal for molecular testing; however, in the current era of personalized medicine, cytopathology specimens are increasingly recognized as potential sources for molecular testing. This is often accomplished by using cell block specimens and/or fine‐needle aspiration (FNA) smear preparations. In this study, the authors investigated the feasibility, performance, and quality of “residual” FNA rinse and body effusion fluids used for next‐generation sequencing (NGS).METHODSSequence data were generated from 17 malignancies in 16 patients from 13 FNA (10 lymph nodes, 1 lung, and 2 bone lesions) and 4 effusion (3 pleural and 1 pericardial) specimens. Malignancies included carcinomas (lung, breast, ovarian, and unknown primary), melanoma, and myeloma. Paired NGS testing was performed in 7 patients who had surgical biopsy or cell block specimens available. Routinely processed residual FNA rinse material and body fluids were used for DNA extraction and NGS (targeted gene panel).RESULTSNGS was successfully performed on all 17 specimens. A significant amount of DNA was obtained from the residual FNA rinse (176.3 ng/μL) compared with the paired cell block slides (10.6 ng/μL). Two of the 10 lung adenocarcinomas (20%) demonstrated epidermal growth factor receptor (EGFR) mutations, including 1 leucine‐to‐arginine substitution at codon 858 (L858R) in exon 21 and 1 codon 2235_2249 deletion (resulting in an in‐frame deletion of 5 amino acids from position 746 to 750 [glutamic acid, leucine, arginine, glutamic acid, and alanine]; E746_A750del) in exon 19. Three KRAS [Kirsten rat sarcoma viral oncogene homolog] mutations, 1 BRAF (v‐Raf murine sarcoma viral oncogene homolog B1) mutation, and 1 NRAS (neuroblastoma RAS viral oncogene homolog) mutation were identified in the remaining lung adenocarcinomas. Patients who underwent paired testing demonstrated 100% concordant mutations.CONCLUSIONSTargeted NGS can be performed on residual FNA rinse and body fluid specimens. This approach is particularly important when a paucicellular cell block or biopsy specimen is encountered. Cancer Cytopathol 2016;124:324–29. © 2015 American Cancer Society.
The coefficient of variation as a measure of spectrophotometric repeatability
Authors: Centore Paul 
Published: December 2015

AbstractThe mean color difference from the mean (MCDM) is a standard measure of spectrophotometric repeatability. This article proposes a supplementary measure: the coefficient of variation (CoV), which is the ratio of the standard deviation of the measured reflectances to their mean. The CoV is calculated from the same repeated sample measurements as the MCDM. Unlike the MCDM, the CoV depends only on physical quantities, and not on perceptual quantities; furthermore, a CoV is defined for each wavelength. This article analyzes data from six different spectrophotometer–sample combinations. An important empirical result is that the CoV is nearly constant across wavelengths, except when the reflectance at a particular wavelength is less than about 5%, in which case, measurement variability is markedly greater. Because the MCDM tends to lose this fact through averaging, the CoV is recommended as an adjunct to the MCDM for spectrophotometer analysis and development. The CoV analysis also provides evidence that samples’ surface geometry is a major factor in measurement variability. © 2015 Wiley Periodicals, Inc. Col Res Appl, 41, 571–579, 2016