bluuebunny/crossref_metadata_2025_split huggingface dataset:
LC–MS/MS method development for quantification of doxorubicin and its metabolite 13‐hydroxy doxorubicin in mice biological matrices: Application to a pharmaco‐delivery study
Authors: Mazzucchelli Serena , Ravelli Alessandro , Gigli Fausto , Minoli Mauro , Corsi Fabio , Ciuffreda Pierangela , Ottria Roberta 
Published: October 2016

AbstractThis study describes the development of simple, rapid and sensitive liquid chromatography tandem mass spectrometry method for the simultaneous analysis of doxorubicin and its major metabolite, doxorubicinol, in mouse plasma, urine and tissues. The calibration curves were linear over the range 5–250 ng/mL for doxorubicin and 1.25–25 ng/mL for doxorubicinol in plasma and tumor, over the range 25–500 ng/mL for doxorubicin and 1.25–25 ng/mL for doxorubicinol in liver and kidney, and over the range 25–1000 ng/mL for doxorubicin and doxorubicinol in urine. The study was validated, using quality control samples prepared in all different matrices, for accuracy, precision, linearity, selectivity, lower limit of quantification and recovery in accordance with the US Food & Drug Administration guidelines. The method was successfully applied in determining the pharmaco‐distribution of doxorubicin and doxorubicinol after intravenously administration in tumor‐bearing mice of drug, free or nano‐formulated in ferritin nanoparticles or in liposomes. Obtained results demonstrate an effective different distribution and doxorubicin protection against metabolism linked to nano‐formulation. This method, thanks to its validation in plasma and urine, could be a powerful tool for pharmaceutical research and therapeutic drug monitoring, which is a clinical approach currently used in the optimization of oncologic treatments.
Support vector machine classification of arterial volume‐weighted arterial spin tagging images
Authors: Shah Yash S. , Hernandez‐Garcia Luis , Jahanian Hesamoddin , Peltier Scott J. 
Published: October 2016

AbstractIntroductionIn recent years, machine‐learning techniques have gained growing popularity in medical image analysis. Temporal brain‐state classification is one of the major applications of machine‐learning techniques in functional magnetic resonance imaging (fMRI) brain data. This article explores the use of support vector machine (SVM) classification technique with motor‐visual activation paradigm to perform brain‐state classification into activation and rest with an emphasis on different acquisition techniques.MethodsImages were acquired using a recently developed variant of traditional pseudocontinuous arterial spin labeling technique called arterial volume‐weighted arterial spin tagging (AVAST). The classification scheme is also performed on images acquired using blood oxygenation–level dependent (BOLD) and traditional perfusion‐weighted arterial spin labeling (ASL) techniques for comparison.ResultsThe AVAST technique outperforms traditional pseudocontinuous ASL, achieving classification accuracy comparable to that of BOLD contrast images.ConclusionThis study demonstrates that AVAST has superior signal‐to‐noise ratio and improved temporal resolution as compared with traditional perfusion‐weighted ASL and reduced sensitivity to scanner drift as compared with BOLD. Owing to these characteristics, AVAST lends itself as an ideal choice for dynamic fMRI and real‐time neurofeedback experiments with sustained activation periods.
Erlotinib induces the human non–small‐cell lung cancer cells apoptosis via activating ROS‐dependent JNK pathways
Authors: Shan Fenglian , Shao Zewei , Jiang Shenghua , Cheng Zhaozhong 
Published: October 2016

AbstractAlthough erlotinib (ERL) has drawn more and more attention toward its anticancer properties effect, the underlying mechanisms of ERL's anticancer properties effect remain unclear yet. So, the aim of this research was to explore the underlying anticancer mechanisms of ERL and to explore whether the reactive oxygen species (ROS)‐dependent c‐Jun N‐terminal kinase (JNK) pathway contributed to the anticancer properties provided by ERL. In our study, we used MTT assay to detect the anticell growth ability of ERL on human non–small‐cell lung cancer cell lines (A549). The extent of cell apoptosis was determined by Hoechst 33342 staining and fluorescence‐activated cell sorter (FACS) assay. Then, DCFH‐DA and JC‐1 staining were used to monitor intracellular reactive oxygen species (ROS) and mitochondrial membrane potential (MMP), respectively. Finally, the effect of ERL on phosphorylation state of JNK protein and downstream apoptosis concerned proteins were detected by western blotting assay. Results showed that ERL significantly suppressed the growth and reproduction of A549 cells with the concentration rising up in vitro. Hoechst 33342 staining and FACS assay also confirmed the proapoptosis effect of ERL on A549 cells with the concentration rising up. Furthermore, exposure of A549 cells to ERL increased the intracellular ROS production. As expected, intracellular ROS activated the proapoptotic JNK signaling pathway and inhibited the activation of EFGR signaling pathway. Our results also revealed that ERL could induce cell‐cycle arrest at G0/G1 period. Activation of JNK protein decreased MMP and downregulated content of antiapoptotic protein Bcl‐2 concomitant with the upregulated content of proapoptotic protein Bax in A549 cells. In addition, c‐Jun and cleaved caspase‐3 were also activated by the phosphorylated JNK induced by ERL. All of these proapoptosis effect of ERL was reversed by administration of N‐acetylcysteine (NAC), which performed as a ROS scavenger. Our results suggest that ERL induces A549 cells apoptosis via activating ROS‐dependent JNK pathways in human non–small lung cancer cells that provide a new experimental foundation for cancer therapy.
Role of comorbidity on outcome of head and neck cancer: a population‐based study in Thuringia, Germany
Authors: Göllnitz Irene , Inhestern Johanna , Wendt Thomas G. , Buentzel Jens , Esser Dirk , Böger Daniel , Mueller Andreas H. , Piesold Jörn‐Uwe , Schultze‐Mosgau Stefan , Eigendorff Ekkehard , Schlattmann Peter , Guntinas‐Lichius Orlando 
Published: October 2016

AbstractTo examine the impact of comorbidity on overall survival (OS) in a population‐based study of patients with head and neck cancer who were treated between 2009 and 2011. Data of 1094 patients with primary head and neck carcinomas without distant metastasis from the Thuringian cancer registries were evaluated concerning the influence of patient's characteristics and comorbidity on OS. Data on comorbidity prior to head and neck cancer diagnosis was adapted to the Charlson Comorbidity (CCI), age‐adjusted CCI (ACCI), head and neck CCI (HNCCI), simplified comorbidity score (SCS), and to the Adult Comorbidity Evaluation–27 (ACE‐27). Most patients were male (80%; median age: 60 years; 50% stage IV tumors). Smoking, alcohol abuse, and anemia were registered for 38%, 33%, and 23% of the patients, respectively. Predominant therapy was surgery + radiochemotherapy (30%), surgery (29%), and surgery + radiotherapy (21%). Mean CCI, ACCI, HNCCI, SCS and ACE‐27 were 1.0 ± 1.5, 2.6 ± 2.1, 0.6 ± 0.8, 4.4 ± 4.2, and 0.9 ± 0.9, respectively. Median follow‐up was 25.7 months. Multivariable analyses showed that higher age, higher UICC stage, no therapy, including surgery or radiotherapy, alcohol abuse, and anemia, higher comorbidity were independent risk factors for worse OS (all P < 0.05). According to the discriminatory power analysis none of the five comorbidity scores was superior to the other scores to prognosticate OS. This population‐based study showed that comorbidity is frequent in German patients with head and neck cancer and is an important risk factor for poor OS. Comorbidity should be routinely assessed and taken into account in prospective clinical trials.
Salmonella entericaserovar Typhi and gallbladder cancer: a case–control study and meta‐analysis
Authors: Koshiol Jill , Wozniak Aniela , Cook Paz , Adaniel Christina , Acevedo Johanna , Azócar Lorena , Hsing Ann W. , Roa Juan C. , Pasetti Marcela F. , Miquel Juan F. , Levine Myron M. , Ferreccio Catterina ,   the Gallbladder Cancer Chile Working Group
Published: October 2016

AbstractIn Chile, where gallbladder cancer (GBC) rates are high and typhoid fever was endemic until the 1990s, we evaluated the association betweenSalmonella entericaserovar Typhi (S. Typhi) antibodies andGBC. We tested 39GBCcases, 40 gallstone controls, and 39 population‐based controls forS. Typhi Vi antibodies and performed culture and quantitative polymerase chain reaction for the subset with bile, gallstone, tissue, and stool samples available. We calculated gender and education‐adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the association withGBC. We also conducted a meta‐analysis of >1000GBCcases by combining our results with previous studies.GBCcases were more likely to have high Vi antibody titer levels than combined controls (OR: 4.0, 95%CI: 0.9–18.3), althoughS. Typhi was not recovered from bile, gallstone, tissue, or stool samples. In our meta‐analysis, the summary relative risk was 4.6 (95%CI: 3.1–6.8,Pheterogeneity=0.6) for anti‐Vi and 5.0 (95%CI: 2.7–9.3,Pheterogeneity = 0.2) for bile or stool culture. Our results are consistent with the meta‐analysis. Despite differences in study methods (e.g.,S. Typhi detection assay), most studies found a positive association betweenS. Typhi andGBC. However, the mechanism underlying this association requires further investigation
Additive interactions between PRKAA1 polymorphisms and Helicobacter pylori CagA infection associated with gastric cancer risk in Koreans
Authors: Eom Sang‐Yong , Hong Seon‐Mi , Yim Dong–Hyuk , Kwon Hyo‐Jin , Kim Dae‐Hoon , Yun Hyo‐Yung , Song Young‐Jin , Youn Sei‐Jin , Hyun Taisun , Park Joo‐Seung , Kim Byung Sik , Kim Yong‐Dae , Kim Heon 
Published: October 2016

AbstractAlthough several studies reported genetic polymorphisms in protein kinase AMP‐activated alpha 1 catalytic subunit (PRKAA1) and their associations with gastric cancer risk, few have evaluated associations between Helicobacter pylori infection and PRKAA1 gene‐environment interactions. Here, we evaluated the effects of interactions between H. pylori infection and PRKAA1 polymorphisms on gastric cancer risk in Koreans. In this hospital‐based case–control study, PRKAA1 genotypes were analyzed and H. pylori infection and CagA status were examined using a serologic method in 846 pairs of gastric cancer patients and controls matched for age and sex. H. pylori seropositivity was associated with a 1.43‐fold [95% confidence interval: 1.12–1.81] increase in the risk of gastric cancer, and CagA low‐positive titers during H. pylori infection increased the risk by 1.85‐fold (95% confidence interval, 1.38–2.48). Significant positive interaction between the PRKAA1 rs13361707 genotype and H. pylori infection was verified on an additive scale [relative excess risk due to interaction, 0.55; 95% confidence interval, 0.05–1.04; P = 0.030], and the gene‐environment interaction between PRKAA1 rs13361707 and CagA status was also statistically significant (relative excess risk due to interaction, 0.50; 95% confidence interval, 0.30–0.70; P < 0.001). Our results indicated that H. pylori infection, CagA status, and PRKAA1 polymorphisms were risk factors for gastric cancer in Koreans, and that the combination of two of these factors rather than their independent effects synergistically increased the risk.
Guide Strand 3′‐End Modifications Regulate siRNA Specificity
Authors: Valenzuela Rachel A. P. , Onizuka Kazumitsu , Ball‐Jones Alexi A. , Hu Tiannan , Suter Scott R. , Beal Peter A. 
Published: October 2016

AbstractShort interfering RNA (siRNA)‐triggered gene knockdown through the RNA interference (RNAi) pathway is widely used to study gene function, and siRNA‐based therapeutics are in development. However, as the guide strand of an siRNA can function like a natural microRNA (miRNA), siRNAs often repress hundreds of off‐target transcripts with complementarity only to the seed region (nucleotides 2–8) of the guide strand. Here, we describe novel guide strand 3′‐end modifications derived from 1‐ethynylribose (1‐ER) and copper‐catalyzed azide–alkyne cycloaddition reactions and evaluate their impact on target versus miRNA‐like off‐target knockdown. Surprisingly, when positioned at the guide strand 3′‐end, the parent 1‐ER modification substantially reduced off‐target knockdown while having no measurable effect on on‐target knockdown potency. In addition, these modifications were shown to modulate siRNA affinity for the hAgo2 PAZ domain. However, the change in PAZ domain binding affinity was not sufficient to predict the modification's effect on miRNA‐like off targeting.
One‐Pot, Two‐Step Hydroxylation of the Macrocyclic Diterpenoid β‐Cembrenediol Catalyzed by P450 BM3 Mutants
Authors: Le‐Huu Priska , Petrović Dušan , Strodel Birgit , Urlacher Vlada B. 
Published: October 2016

AbstractCytochrome P450 monooxygenases (P450s) are involved in the biosynthesis of a wide range of bioactive secondary metabolites. They often introduce several oxy functionalities at different positions of a substrate through multiple steps and produce a range of oxidized derivatives. Herein, we describe a one‐pot two‐step hydroxylation of the diterpenoid β‐cembrenediol isolated from the plant Nicotiana tabacum. This 14‐membered macrocycle shows neuroprotective effects and is, along with its oxidized derivatives, of pharmaceutical interest. Sequential hydroxylations catalyzed by the regioselective P450 BM3 mutants F87A/I263L and V78A/F87G yielded the epimeric (9S,10R/S)‐β‐cembrenetetraols with a diastereomeric ratio of 48:52. The replacement of the mutant V78A/F87G with L75A/V78A/F87G in the second step improves the diastereomeric ratio up to 10:90. Absolute configurations of the newly introduced hydroxy groups were determined by quantum‐mechanical calculations of NMR spectra.
Superior Electrochemical Oxygen Evolution Enabled by Three‐Dimensional Layered Double Hydroxide Nanosheet Superstructures
Authors: Zhao Dandan , Jiang Kezhu , Pi Yecan , Huang Xiaoqing 
Published: October 2016

AbstractAlthough extensive efforts have been devoted to the pursuit of promising electrocatalysts to lower the overpotential of the oxygen evolution reaction (OER), the design of low‐costing earth‐abundant OER electrocatalysts with desirable performance remains a formidable challenge. Herein, we demonstrate a facile strategy to create ultrathin NiFe layered double hydroxide (LDH) nanosheets grown on carbon nanotubes (CNTs) as superior OER electrocatalysts. Different from previously reported NiFe‐LDH nanomaterials, the newly generated NiFe‐LDH@CNTs exhibit distinct features, including ultrathin building blocks, a 1 D structure, 3 D hierarchical architecture, and the electron effect. Significantly, it was revealed that doping Fe into Ni‐LDH@CNTs optimized the performance for the OER; Ni8Fe‐LDH@CNTs was found to be the most active and is one of the best non‐noble metal catalysts for the OER to date. The catalysts are also highly stable for the OER with little potential shift after an 18 h test. Both X‐band electron spin resonance and X‐ray photoelectron spectroscopy indicated that optimized iron doping resulted in intense interaction between Nix+ and Fe3+ and electron transfer from Nix+ to Fe3+, which thus boosted the OER performance.
Unveiling the Reaction Machinery of the [AuI]‐Catalyzed Synthesis of Substituted Acenes by a [1,5]‐H Shift Cascade Reaction
Authors: Bandini Marco , Cera Gianpiero , Miscione Gian Pietro 
Published: October 2016

AbstractThe reaction mechanism of the gold‐catalyzed synthesis of functionalized acenes via cascade [3,3]‐oxo migration/[1,5]‐H shift is documented by DFT calculations. Interestingly, the overall reaction machinery displays a notable exothermic profile and the pivotal role played by the metal center in the initial [1,3]‐acyloxy migration of 1 was also discovered. Contrarily, contribution of the gold complex in the H shift was negligible as the energy profiles of the gold‐based and metal‐free protocols are very similar in the latest stage.
N‐Oxyl‐Radical‐Catalyzed Intermolecular Aminooxygenation of Styrenes and Inter/intramolecular Aminoalkoxylation of Homoallylic Alcohols
Authors: Weng Shiue‐Shien , Zhang Jia‐Wei 
Published: October 2016

AbstractBy taking advantage of the redox cycle between the reductive N‐oxyl radical and its oxidative oxoammonium counterpart, the N‐oxyl‐radical‐catalyzed intermolecular aminohydroxylation of styrenes with N‐fluorobenzenesulfonimide was developed. Various vinyl arenes were aminohydroxylated in moderate to excellent yields with high regio‐ and diastereoselectivities by using environmentally benign H2O as the oxygen source. In addition, the sequential inter/intramolecular aminoalkoxylation of homoallylic alcohols was also achieved under anhydrous conditions, which allowed the exclusive synthesis of pharmaceutically useful 2‐aryl‐3‐amino‐disubstituted tetrahydrofurans.
Artificial Neural Network Modeling of Hydrodynamics of Liquid‐Solid Circulating Fluidized Beds
Authors: Palkar Ritesh Ramesh , Shilapuram Vidyasagar 
Published: October 2016

AbstractSolids holdup and solids circulation rate are the two important hydrodynamic variables affected by process conditions. These two variables have a significant influence on the performance of a liquid‐solid circulating fluidized bed (LSCFB). An artificial neural network (ANN) methodology was developed and simulated to predict the performance of the LSCFB for the experimental dataset collected under various process conditions. Different statistical parameters were applied to evaluate the prominent and unique characteristic features of the ANN‐predicted parameters. The ANN model successfully predicted the experimental observations and captured the actual nonlinear behavior noticed during the experiments. Model validation confirmed that this data‐driven technique can be used to model such nonlinear systems.
Electrochemical Properties and Reactions of Oxygen‐Containing Organotrifluoroborates and Their Boronic Acid Esters
Authors: Ohtsuka Kazuhiro , Inagi Shinsuke , Fuchigami Toshio 
Published: October 2016

AbstractElectrochemical analyses of anisole, phenoxymethylboronic acid pinacol ester, tetra‐n‐butylammonium phenoxymethyltrifluoroborate, and their benzyloxy analogues were comparatively studied by using cyclic voltammetry measurements, and a marked β‐effect for organotrifluoroborates was found, which was indicated by experimental and theoretical aspects. Organotrifluoroborates were found to have much lower oxidation potentials than the corresponding boronic acid pinacol esters. The oxidation potentials of boronic acid pinacol esters were also significantly decreased in the presence of fluoride ions. This β‐effect is more pronounced than that of the corresponding organosulfur compounds reported previously. Anodic substitution reactions of organotrifluoroborates were successfully carried out in the presence of oxygen nucleophiles to provide regioselectively substituted products in moderate yields. Supporting‐electrolyte‐free electrolysis was also demonstrated.
A Nexus between Theory and Experiment: Non‐Empirical Quantum Mechanical Computational Methodology Applied to Cucurbit[n]uril⋅Guest Binding Interactions
Authors: Hostaš Jiří , Sigwalt David , Šekutor Marina , Ajani Haresh , Dubecký Matúš , Řezáč Jan , Zavalij Peter Y. , Cao Liping , Wohlschlager Christian , Mlinarić‐Majerski Kata , Isaacs Lyle , Glaser Robert , Hobza Pavel 
Published: October 2016

AbstractA training set of eleven X‐ray structures determined for biomimetic complexes between cucurbit[n]uril (CB[7 or 8]) hosts and adamantane‐/diamantane ammonium/aminium guests were studied with DFT‐D3 quantum mechanical computational methods to afford ΔGcalcd binding energies. A novel feature of this work is that the fidelity of the BLYP‐D3/def2‐TZVPP choice of DFT functional was proven by comparison with more accurate methods. For the first time, the CB[n]⋅guest complex binding energy subcomponents [for example, ΔEdispersion, ΔEelectrostatic, ΔGsolvation, binding entropy (−TΔS), and induced fit Edeformation(host), Edeformation(guest)] were calculated. Only a few weeks of computation time per complex were required by using this protocol. The deformation (stiffness) and solvation properties (with emphasis on cavity desolvation) of cucurbit[n]uril (n=5, 6, 7, 8) isolated host molecules were also explored by means of the DFT‐D3 method. A high ρ2=0.84 correlation coefficient between ΔGexptl and ΔGcalcd was achieved without any scaling of the calculated terms (at 298 K). This linear dependence was utilized for ΔGcalcd predictions of new complexes. The nature of binding, including the role of high energy water molecules, was also studied. The utility of introduction of tethered [‐(CH2)nNH3]+ amino loops attached to N,N‐dimethyl‐adamantane‐1‐amine and N,N,N′,N′‐tetramethyl diamantane‐4,9‐diamine skeletons (both from an experimental and a theoretical perspective) is presented here as a promising tool for the achievement of new ultra‐high binding guests to CB[7] hosts. Predictions of not yet measured equilibrium constants are presented herein.
Can a Six‐Letter Alphabet Increase the Likelihood of Photochemical Assault to the Genetic Code?
Authors: Ashwood Brennan , Pollum Marvin , Crespo‐Hernández Carlos E. 
Published: October 2016

AbstractIn 2014, two unnatural nucleosides, d5SICS and dNaM, were shown to selectively base pair and replicate with high fidelity in a modified strain of E. coli, thus effectively expanding its genetic alphabet from four to six letters. More recently, a significant reduction in cell proliferation was reported in cells cultured with d5SICS, and putatively with dNaM, upon exposure to brief periods of near‐visible radiation. The photosensitizing properties of the lowest‐energy excited triplet state of both d5SICS and dNaM were implicated in their cytotoxicity. Importantly, however, the excited‐state mechanisms by which near‐visible excitation populates the triplet states of d5SICS and dNaM are currently unknown. In this study, steady‐state and time‐resolved spectroscopies are combined with quantum‐chemical calculations in order to reveal the excited‐state relaxation mechanisms leading to efficient population of the triplet states in these unnatural nucleosides in solution. It is shown that excitation of d5SICS or dNaM with near‐visible light leads overwhelmingly to ultrafast population of their triplet states on the femtosecond time scale. The results presented in this work lend strong support to the proposal that photoexcitation of these unnatural nucleosides can accelerate oxidatively generated damage to DNA and other biomolecules within the cellular environment.