bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigation of autophagy and differentiation of myenteric interstitial cells of Cajal in the pathogenesis of gastric motility disorders in rats with functional dyspepsia
Authors: Zhang Li‐min , Zeng Li‐jun , Deng Jing , Zhang Yu‐qin , Wang Yu‐jiao , Xie Tian‐yi , Ling Jiang‐hong 
Published: December 2017

AbstractInterstitial cells of Cajal (ICC), especially myenteric interstitial cells of Cajal (ICC‐MY), are key to gastrointestinal motility. However, their role in the pathogenesis of functional dyspepsia (FD) is unclear. Therefore, autophagy and differentiation of ICC‐MY were investigated to elucidate the pathogenesis of gastric motility disorder in FD. FD model was induced by chronic stress via tail clamping in rats, which was assessed by the vital signs of rats, gastric emptying rate result, and histology. The ultrastructure of ICC‐MY was examined using transmission electron microscope. In ICC‐MY, changes in autophagic biomarkers (Beclin1 and LC3B) and differentiation biomarkers (c‐kit and SCF) were evaluated with in situ hybridization, quantitative real time PCR, immunofluorescence, and Western blot, respectively. The FD model was successfully induced in rats, as evidenced by the abnormal vital signs (such as loss of appetite, liquid excreta, less activity, and slower weight gain), the decrease in gastric emptying rates, and little pathological change in gastric antrum tissue. Compared with the control group, FD caused increased organelle denaturation or reduction and increase in vacuolization. FD also promoted generation of autophagosomes in ICC‐MY. Moreover, increased the expression of Beclin1 and LC3B, but decreased expression of c‐kit and SCF. Excessive autophagy and abnormal differentiation of ICC‐MY may contribute to the pathogenesis of gastric motility disorder in FD.
Cost comparison by treatment arm and center‐level variations in cost and inpatient days on the phase III high‐risk B acute lymphoblastic leukemia trial AALL0232
Authors: DiNofia Amanda M. , Seif Alix E. , Devidas Meenakshi , Li Yimei , Hall Matthew , Huang Yuan‐Shung V. , Cahen Viviane , Hunger Stephen P. , Winick Naomi J. , Carroll William L. , Fisher Brian T. , Larsen Eric C. , Aplenc Richard 
Published: December 2017

AbstractThe Children's Oncology Group (COG) develops and implements multi‐institutional clinical trials with the primary goal of assessing the efficacy and safety profile of treatment regimens for various pediatric cancers. However, the monetary costs of treatment regimens are not measured. AALL0232 was a COG randomized phase III trial for children with acute lymphoblastic leukemia that found that dexamethasone (DEX) was a more effective glucocorticoid than prednisone (PRED) in patients younger than 10 years, but PRED was equally effective and less toxic in older patients. In addition, high‐dose methotrexate (HD‐MTX) led to better survival than escalating doses of methotrexate (C‐MTX). Cost data from the Pediatric Health Information System database were merged with clinical data from the COG AALL0232 trial. Total and component costs were compared between treatment arms and across hospitals. Inpatient costs were higher in the HD‐MTX and DEX arms when compared to the C‐MTX and PRED arms at the end of therapy. There was no difference in cost between these arms at last follow‐up. Considerable variation in total costs existed across centers to deliver the same therapy that was driven by differences in inpatient days and pharmacy costs. The more effective regimens were found to be more expensive during therapy but were ultimately cost‐neutral in longer term follow‐up. The variations in cost across centers suggest an opportunity to standardize resource utilization for patients receiving similar therapies, which could translate into reduced healthcare expenditures.
Evaluation of β‐Amino Acid Replacements in Protein Loops: Effects on Conformational Stability and Structure
Authors: Mortenson David E. , Kreitler Dale F. , Thomas Nicole C. , Guzei Ilia A. , Gellman Samuel H. , Forest Katrina T. 
Published: December 2017

Abstractβ‐Amino acids have a backbone that is expanded by one carbon atom relative to α‐amino acids, and β residues have been investigated as subunits in protein‐like molecules that adopt discrete and predictable conformations. Two classes of β residue have been widely explored in the context of generating α‐helix‐like conformations: β3‐amino acids, which are homologous to α‐amino acids and bear a side chain on the backbone carbon adjacent to nitrogen, and residues constrained by a five‐membered ring, such the one derived from trans‐2‐aminocyclopentanecarboxylic acid (ACPC). Substitution of α residues with their β3 homologues within an α‐helix‐forming sequence generally causes a decrease in conformational stability. Use of a ring‐constrained β residue, however, can offset the destabilizing effect of α→β substitution. Here we extend the study of α→β substitutions, involving both β3 and ACPC residues, to short loops within a small tertiary motif. We start from previously reported variants of the Pin1 WW domain that contain a two‐, three‐, or four‐residue β‐hairpin loop, and we evaluate α→β replacements at each loop position for each variant. By referral to the ϕ,ψ angles of the native structure, one can choose a stereochemically appropriate ACPC residue. Use of such logically chosen ACPC residues enhances conformational stability in several cases. Crystal structures of three β‐containing Pin1 WW domain variants show that a native‐like tertiary structure is maintained in each case.
Chk1 activation attenuates sensitivity of lapatinib in HER2‐positive gastric cancer
Authors: Bai Ming , Song Na , Che Xiaofang , Wang Xiaoxun , Qu Xiujuan , Liu Yunpeng 
Published: December 2017

AbstractThe ATM and Rad3‐related (ATR)/checkpoint kinase 1 (Chk1) pathway plays a pivotal role in DNA damage sensor and modulating homologous recombination. Recently, emerging evidence demonstrated that Chk1 phosphorylation was associated with chemotherapy and radiotherapy resistance. In this study, we explored the effect of ATR/Chk1 pathway on regulating lapatinib sensitivity in human epidermal growth factor receptor‐2 (HER2)‐positive gastric cancer cell lines. We selected two HER2‐positive gastric cancer cell lines, and NCI‐N87 cells exhibited higher sensitivity than MKN7 cells. Application of lapatinib inhibited phosphorylated HER2 and EGFR and the formation of epidermal growth factor receptor (EGFR)/HER2 complex in both cells. In NCI‐N87 cells, lapatinib induced G1 arrest and reduced Chk1 phosphorylation through inhibiting the expression of DNA topoisomerase 2‐binding protein 1 (TopBP1). While in MKN7 cells, no significant cell cycle transition was found and phosphorylated Chk1 was mildly upregulated. Inhibition of Chk1 phosphorylation enhanced the lapatinib sensitivity of MKN7 cells, which was shown by potentiated anti‐proliferative effect, G1 arrest, downregulation of phosphorylated AKT and ERK along with aggravated DNA damage. In addition, increased Chk1 phosphorylation in NCI‐N87 cells attenuated lapatinib‐induced anti‐proliferative effect and G1 arrest, and abrogated reduced phosphorylated AKT and ERK. Taken together, our study provides a novel mechanism for regulating lapatinib sensitivity in HER2 positive gastric cancer cells, suggesting a new strategy in clinical treatment.
Effect of ECM2 expression on bovine skeletal muscle‐derived satellite cell differentiation
Authors: Liu Chang , Tong Huili , Li Shufeng , Yan Yunqin 
Published: December 2017

AbstractExtracellular matrix components have important regulatory functions during cell proliferation and differentiation. In recent study, extracellular matrix were shown to have a strong effect on skeletal muscle differentiation. Here, we aimed to elucidate the effects of extracellular matrix protein 2 (ECM2), an extracellular matrix component, on the differentiation of bovine skeletal muscle‐derived satellite cells (MDSCs). Western blot and immunofluorescence analyses were used to elucidate the ECM2 expression pattern in bovine MDSCs during differentiation in vitro. CRISPR/Cas9 technology was used to activate or inhibit ECM2 expression to study its effects on the in vitro differentiation of bovine MDSCs. ECM2 expression was shown to increase gradually during bovine MDSC differentiation, and the levels of this protein were higher in more highly differentiated myotubes. ECM2 activation promoted MDSC differentiation, whereas its suppression inhibited the differentiation of these cells. Here, for the first time, we demonstrated the importance of ECM2 expression during bovine MDSC differentiation; these results could lead to treatments that help to increase beef cattle muscularity.
Routine exercise testing could not predict T‐wave oversensing in a patient after a subcutaneous implantable cardioverter‐defibrillator implant
Authors: Konishi Shozo , Minamiguchi Hitoshi , Ozu Kentaro , Mizuno Hiroya , Hikoso Shungo , Yamaguchi Osamu , Sakata Yasushi 
Published: December 2017

Key Clinical MessageSubcutaneous implantable cardioverter‐defibrillators (S‐ICDs) are susceptible to T‐wave oversensing (TWOS) caused by high rate‐dependent QRS–T morphology changes. We experienced an inappropriate S‐ICD shock due to TWOS, which could not be predicted by routine exercise testing. A newly available high‐pass filter might be effective for avoiding this.
Highly Dispersed Ultrafine Palladium Nanoparticles Enabled by Functionalized Porous Organic Polymer for Additive‐Free Dehydrogenation of Formic Acid
Authors: Cui Caiyan , Tang Yujiao , Ziaee Muhammad Asad , Tian Dongxu , Wang Ruihu 
Published: December 2017

AbstractFormic acid (FA) is one of the most favorable chemical hydrogen storage materials for renewable energy transformation, the development of efficient heterogeneous catalysts for ultraclean H2 generation from FA in the absence of any alkalis or additives under mild conditions remains a major challenge. Here, we present a porous organic polymer containing triphenylamine (TPA) and 2,6‐bis(1,2,3‐triazol‐4‐yl)pyridyl (BTP) units (TB‐POP). The ultrafine palladium nanoparticles (NPs) with an average size of 1.5±0.6 nm can be facilely generated using convenient methods and are uniformly dispersed over the TB‐POP support. TPA and BTP units are homogeneously arranged in the host framework of TB‐POP; they serve as effective alternatives of basic sites to deprotonate FA into formate intermediates. Pd@TB‐POP has demonstrated remarkable catalytic activity and high selectivity in additive‐free dehydrogenation of aqueous FA solution. The value of initial turnover frequency (TOF) at 50 °C is as high as 1344 h−1. In sharp contrast, the use of sodium formate as an additive in the catalytic system results in the decrement of catalytic activity. The ultrafine palladium NPs are effectively immobilized during dehydrogenation of FA, and no aggregation of palladium NPs is observed after consecutive catalytic runs.
Stoichiometry‐Controlled Inversion of Supramolecular Chirality in Nanostructures Co‐assembled with Bipyridines
Authors: Wang Fang , Feng Chuan‐Liang 
Published: December 2017

AbstractTo control supramolecular chirality of the co‐assembled nanostructures, one of the remaining issues is how stoichiometry of the different molecules involved in co‐assembly influence chiral transformation. Through co‐assembly of achiral 1,4‐bis(pyrid‐4‐yl)benzene and chiral phenylalanine‐glycine derivative hydrogelators, stoichiometry is found to be an effective tool for controlling supramolecular chirality inversion processes. This inversion is mainly mediated by a delicate balance between intermolecular hydrogen bonding interactions and π–π stacking of the two components, which may subtly change the stacking of the molecules, in turn, the self‐assembled nanostructures. This study exemplifies a simplistic way to invert the handedness of chiral nanostructures and provide fundamental understanding of the inherent principles of supramolecular chirality.
Shape‐Persistent [4+4] Imine Cages with a Truncated Tetrahedral Geometry
Authors: Lauer Jochen C. , Zhang Wen‐Shan , Rominger Frank , Schröder Rasmus R. , Mastalerz Michael 
Published: December 2017

AbstractThe synthesis of shape‐persistent organic cage compounds is often based on the usage of multiple dynamic covalent bond formation (such as imines) of readily available precursors. By careful choice of the precursors geometry, the geometry and size of the resulting cage can be accurately designed and indeed a number of different geometries and sizes have been realized to date. Despite of this fact, little is known about the precursors conformational rigidity and steric preorganization of reacting functional groups on the outcome of the reaction. Herein, the influence of conformational rigidity in the precursors on the formation of a [4+4] imine cage with truncated tetrahedral geometry is discussed.
High‐Mobility Self‐Assembling Truxenone‐Based n‐Type Organic Semiconductors
Authors: Gómez‐Esteban Sandra , Benito‐Hernandez Angela , Termine Roberto , Hennrich Gunther , Navarrete Juan T. López , Ruiz Delgado M. Carmen , Golemme Attilio , Gómez‐Lor Berta 
Published: December 2017

AbstractThe synthesis, self‐assembly, and semiconducting properties of a series of disk‐like truxenone derivatives, functionalized with three peripheral long alkyl chains, either directly attached or distanced by linking phenyl or ethynyl groups, are reported. The strategy of distancing the alkyl chains from the central aromatic cores induces in these discotics well‐ordered columnar assemblies and has a favorable effect on their charge‐carrier mobility. Electron mobility values above 1 cm2 V−1 S−1 were determined for a truxenone functionalized with three peripheral decynyl chains by means of the space charge–limited current technique. DFT calculations help to rationalize the high mobility values found for these new truxenone‐based systems, indicating efficient intermolecular electronic couplings (fostered by a favorable stacking configuration) and moderate intramolecular reorganization energies for electrons in the origin of such high mobilities.
Wurster‐Type Nanographenes as Stable Diradical Dications
Authors: Desroches Maude , Morin Jean‐Francois 
Published: December 2017

AbstractThree new and stable diradical dications based on the 4,10‐dibromoanthanthrone have been synthesized and characterized. In their dicationic state, the amines show a biradical character in the ground state. Their magnetic properties have been investigated by NMR and EPR spectroscopies. The dicationic salts shows strong and broad optical absorption in the near‐infrared region. The main driving force to obtain a ground state biradical is the high steric hindrance that prevents planarization of the diphenylamines with the anthanthrone aromatic core. The radical cations are isolated in two perpendicular π‐systems as demonstrated by X‐ray diffraction structures. This work provides a new bridging unit in the search for biradical bis(triarylamines) salts.
Chirality of 20‐membered unclosed cryptand: Macroring distortion via lariat arm modification
Authors: Jurczak Janusz , Sobczuk Adam , Dąbrowa Kajetan , Lindner Marcin , Niedbała Patryk , Stepniak Pawel 
Published: December 2017

AbstractSome of 19‐membered unclosed cryptands were recognized as chiral species in a solid state. While, in terms of 20‐membered macrocycle, we tune the lariat arm, developing the synthesis of α‐ and β‐naphthyl terminated moieties to gain the structural control over chirality phenomena of these systems. Indirect synthetic approach delineates the way to reach both target structures. Solely, macrocycle functionalized with the β‐naphthyl group is capable of desirable interactions with the frame of entity inducing its stronger bending that leads to the chiral crystals formation. Their structural features were examined by single crystal X‐ray diffraction and chiroptical method, represented by ECD/UV spectroscopy.
Magnetic drug targeting simulations in blood flows with fluid‐structure interaction
Authors: Calandrini Sara , Capodaglio Giacomo , Aulisa Eugenio 
Published: December 2017

AbstractWe present fluid‐structure interaction simulations of magnetic drug targeting (MDT) in blood flows. In this procedure, a drug is attached to ferromagnetic particles to externally direct it to a specific target after it is injected inside the body. The goal is to minimize the healthy tissue affected by the treatment and to maximize the number of particles that reach the target location. Magnetic drug targeting has been studied both experimentally and theoretically by several authors. In recent years, computational fluid dynamics simulations of MDT in blood flows have been conducted to obtain further insight on the combination of parameters that provide the best capture efficiency. However, to this day, no computational study addressed MDT in a fluid‐structure interaction setting. With this paper, we aim to fill this gap and investigate the impact of the solid deformation on the capture efficiency.
A compartment–quasi‐3D multiscale approach for drug absorption, transport, and retention in the human lungs
Authors: Kannan Ravishekar (Ravi) , Singh Narender , Przekwas Andrzej 
Published: December 2017

AbstractMost current models used for modeling the pulmonary drug absorption, transport, and retention are 0D compartmental models where the airways are generally split into the airways and alveolar sections. Such block models deliver low fidelity solutions and the spatial lung drug concentrations cannot be obtained. Other approaches use high fidelity CFD models with limited capabilities due to their exorbitant computational cost. Recently, we presented a novel, fast‐running and robust quasi‐3D (Q3D) model for modeling the pulmonary airflow. This Q3D method preserved the 3D lung geometry, delivered extremely accurate solutions, and was 25 000 times faster in comparison to the CFD methods. In this paper, we present a Q3D‐compartment multiscale combination to model the pulmonary drug absorption, transport, and retention. The initial deposition is obtained from CFD simulations. The lung absorption compartment model of Yu and Rosania is adapted to this multiscale format. The lung is modeled in the Q3D format till the eighth airway generation. The remainder of the lung along with the systemic circulation and elimination processes was modeled using compartments. The Q3D model is further adapted, by allowing for various heterogeneous annular lung layers. This allows us to model the drug transport across the layers and along the lung. Using this multiscale model, the spatiotemporal drug concentrations in the different lung layers and the temporal concentration in the plasma are obtained. The concentration profile in the plasma was found to be better aligned with the experimental findings in comparison with compartmental model for the standard test cases. Thus, this multiscale model can be used to optimize the target‐specific drug delivery and increase the localized bioavailability, thereby facilitating applications from the bench to bedside for various patient/lung‐disease variations.
3′‐O‐Caged 2′‐Deoxynucleoside Triphosphates for Light‐Mediated, Enzyme‐Catalyzed, Template‐Independent DNA Synthesis
Authors: Mathews Anu Stella , Yang Haikang , Montemagno Carlo 
Published: December 2017

AbstractSynthesis, purification, and characterization of 3′‐O‐caged 2′‐deoxyribonucleoside triphosphates (dNTPs), namely 3′‐O‐(2‐nitrobenzyl)‐2′‐deoxy ribonucleoside triphosphates (NB‐dNTPs) and 3′‐O‐(4,5‐dimethoxy‐2‐nitrobenzyl)‐2′‐deoxy ribonucleoside triphosphates (DMNB‐dNTPs), are discussed in detail. A total of eight 3′‐O‐caged dNTPs are synthesized with specific protocols depending on the nitrogenous base on the first carbon, i.e., adenine, guanine, thymine, and cytosine, as well as the photo‐cleavable group, i.e, 2‐nitrobenzyl and 4,5‐ dimethoxy‐2‐nitrobenzyl, to be attached in the 3′‐O position. The purification of the synthesized compounds is done using ion‐exchange and flash chromatography; this is followed by structural confirmation by nuclear magnetic resonance (NMR) and mass spectroscopy (MS). The efficiency of the designed compounds is tested by conducting and evaluating UV‐cleaving experiments at 365 nm with proton NMR and LC‐MS curves. Finally, the application of the 3′‐O‐cagged dNTPs in template‐independent, enzyme‐catalyzed, photo‐mediated oligonucleotide synthesis is demonstrated. © 2017 by John Wiley & Sons, Inc.
Salivary intercellular adenosine triphosphate testing in primary caretakers: An examination of statistical significance versus diagnostic predictability
Authors: Bill Crystal , Danielson Judy A. , Jones Robert S. 
Published: December 2017

AbstractA primary caretaker is a potential reservoir of bacteria for an infant child and can be evaluated during a child's caries risk assessment. The aim of this study was to investigate an indirect method for assessing Streptococcus mutans and Streptococcus sobrinus (MS) and lactobacillus (LB) levels in a caretaker's saliva. Thirty‐eight primary caretakers participated in the study to determine whether a 2‐step method to assess the intracellular adenosine triphosphate (ATP) levels in saliva (saliva i‐ATP method) predicted higher MS and LB levels. This method was tested against a 1‐step swab‐based total ATP testing of dental plaque (plaque t‐ATP method). Receiver operating characteristic (ROC) curves were used to examine the relationship between specificity and sensitivity of the two diagnostic tests. Although the area under the ROC curves of both the saliva i‐APT (0.823) and the plaque t‐ATP (0.774) methods were shown to be statistically different (p < .05) than the null hypothesis test of a random coin flip, the diagnostic predictability of the ATP tests to assess high levels of MS and LB remained low. The optimal cutoff, which was defined by the Youden index, for the saliva i‐ATP method produced a sensitivity/specificity of 60.7/100.0 for MS and 78.6/88.9 for LB. Applying these results to populations of low or high bacterial level prevalence produced undesirable positive and negative predictive values for future potential patients. A pair‐wise comparison of both area under the ROC curve values of the saliva i‐ATP and plaque t‐ATP did not find a statistically significant difference in using one test over the other (MS, p = .629; LB, p = .737). The findings of this study can educate dental clinicians that diagnostic tests, such as the 2‐step saliva i‐ATP method, can be found to be statistically significant but not ideal for patient use in terms of diagnostic predictability.