bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypermethylated and downregulated MEIS2 are involved in stemness properties and oxaliplatin‐based chemotherapy resistance of colorectal cancer
Authors: Wang Xiaojie , Ghareeb Waleed M. , Zhang Yiyi , Yu Qian , Lu Xingrong , Huang Ying , Huang Shenghui , Sun Yanwu , Chi Pan 
Published: March 2019

AbstractThe resistance against oxaliplatin (L‐OHP) based regimens remains a major obstacle for its efficient usage in treating metastatic colorectal cancer (mCRC). In this study, we performed weighted gene coexpression network analysis (WGCNA) to systematically screen the relevant hub genes for L‐OHP resistance using the raw microarray data of 30 consecutive mCRC samples from our earlier study (GSE69657). The results were further confirmed through datasets from Gene Expression Omnibus (GEO). From L‐OHP resistance module, nine genes in both the coexpression and protein–protein interaction networks were chosen as hub genes. Among these genes, Meis Homeobox 2 (MEIS2) had the highest correlation with L‐OHP resistance (r = −0.443) and was deregulated in L‐OHP resistant tissues compared with L‐OHP sensitive tissues in both our own dataset and GSE104645 testing dataset. The receiver operating characteristic curve validated that MEIS2 had a good ability in predicting L‐OHP response in both our own dataset (area under the curve [AUC] = 0.802) and GSE104645 dataset (AUC = 0.746). Then, the down expression of MEIS2 was observed in CRC tissue compared with normal tissue in 12 GEO‐sourced datasets and The Cancer Genome Atlas (TCGA) and was correlated with poor event‐free survival. Furthermore, analyzing methylation data from TCGA showed that MEIS2 had increased promoter hypermethylation. In addition, MEIS2 expression was significantly decreased in CRC stem cells compared with nonstem cells in two GEO datasets (GSE14773 and GSE24747). Further methylation analysis from GSE104271 demonstrated that CRC stem cells had higher MEIS2 promoter methylation levels in cg00366722 and cg00610348 sites. Gene set enrichment analysis showed that MEIS2 might be involved in the Wnt/β‐catenin pathway. In the overall view, MEIS2 had increased promoter hypermethylation and was downregulated in poor L‐OHP response mCRC tissues. MEIS2 might be involved in the Wnt/β‐catenin pathway to maintain CRC stemness, which leads to L‐OHP resistance.
RA promotes proliferation of primordial germ cell‐like cells differentiated from porcine skin‐derived stem cells
Authors: Yan Hong‐Chen , Li Lin , Liu Jing‐Cai , Wang Yu‐Feng , Liu Xue‐Lian , Ge Wei , Dyce Paul W. , Li Lan , Sun Xiao‐Feng , Shen Wei , Cheng Shun‐Feng 
Published: March 2019

AbstractPrevious studies have shown that primordial germ cell‐like cells (PGCLCs) can be obtained from human, porcine and mouse skin‐derived stem cells (SDSCs). In this paper, we found retinoic acid (RA), the active derivative of vitamin A, accelerated the growth of porcine primordial germ cells (pPGCs) and porcine PGCLCs (pPGCLCs) which were derived from porcine SDSCs (pSDSCs). Moreover, flow cytometry results revealed that the proliferation promoting effect of RA was attenuated by U0126, a specific inhibitor of extracellular signal‐regulated kinase (ERK). Western blot analysis showed the protein level of ERK, phosphorylated ERK, cyclin D1 (CCND1), and cyclin‐dependent kinase 2 (CDK2) increased after stimulation with RA, and this effect could also be abolished by U0126. Our data revealed that ablation of ERK expression by U0126 should significantly decrease proliferation of pPGCLCS. This reduction was because CCND1 and CDK2 proteins level decrease and subsequently the pPGCLCs were arrested in the G0/G1 phase. In addition, we also confirmed RA indeed promoted the proliferation of pPGCs isolated from porcine fetal genital ridges in vitro. Furthermore, our data indicated that DNA methylation pattern were changed in pPGCLCs and this pattern were more similar to pPGCs.
Incorporation of Gene‐Environment Interaction Terms Improved the Predictive Accuracy of Tacrolimus Stable Dose Algorithms in Chinese Adult Renal Transplant Recipients
Authors: Tang Jie , Xu Jing , Zhang Yue‐Li , Liu Rong , Liu Mou‐Ze , Hu Yong‐Fang , Shao Ming‐Jie , Zhu Li‐Jun , Cao Shan , Xin Hua‐Wen , Feng Gui‐Wen , Shang Wen‐Jun , Meng Xiang‐Guang , Zhang Li‐Rong , Ming Ying‐Zi , Zhang Wei , Zhou Gan 
Published: March 2019

AbstractThe narrow therapeutic window of tacrolimus necessitates daily monitoring and predictive algorithms based on genetic and nongenetic factors. In this study, we constructed predictive algorithms for tacrolimus stable dose in a retrospective cohort of 1045 Chinese renal transplant recipients. All patients were genotyped forCYP3A420230T>C (rs2242480),CYP3A4T>C (rs4646437),CYP3A5*3 6898A>G (rs776746),ABCB1129T>C (rs3213619);ABCB1c.1236C>T (rs01128503),ABCB1c.2677G>T/A (rs2032582) andABCB1c.3435C>T (rs1045642) polymorphisms, and the effects of gene‐gene and gene‐environment interactions on the predictive accuracy of algorithm were evaluated. In wild‐typeCYP3A4rs2242480 (TT) carriers, patients who took calcium channel blockers had lower tacrolimus stable doses than those without the concomitant medications (P< 1 × 10−4). In contrast, there was no significant difference in mutant type patients. Similarly, the tacrolimus stable doses in wild‐typeCYP3A5rs776746 carriers who had hypertension were higher than those without hypertension (P= 4.10 × 10−3). More importantly, dose‐predictive algorithms with interaction terms showed higher accuracy and better performance than those without interaction terms. Our finding suggested that wild‐typeCYP3A4rs2242480 (TT) carriers should be more cautious to take tacrolimus when they are coadministrated with calcium channel blockers, andCYP3A5rs776746 (AA) carriers may need higher tacrolimus dosage when they are in combination with hypertension.
c-Abl kinase regulates neutrophil extracellular trap formation, inflammation, and tissue damage in severe acute pancreatitis
Authors: Madhi Raed , Rahman Milladur , Mörgelin Matthias , Thorlacius Henrik 
Published: March 2019

Abstract
Neutrophil extracellular traps (NETs) are involved in acute pancreatitis (AP) but mechanisms controlling NET expulsion in AP are incompletely understood. Herein, we examined the role of c-Abelson (c-Abl) kinase in NET formation and tissue damage in severe AP. AP was induced by taurocholate infusion into pancreatic duct or intraperitoneal administration of l-arginine in mice. Pancreatic, lung, and blood samples were collected and levels of phosphorylated c-Abl kinase, citrullinated histone 3, DNA-histone complexes, myeloperoxidase, amylase, cytokines, and CXC chemokines were quantified. Citrullinated histone 3, reactive oxygen species (ROS), and NET formation were determined in bone marrow neutrophils. Taurocholate challenge increased phosphorylation of c-Abl kinase and levels of citrullinated histone 3 in the pancreas as well as DNA-histone complexes in the plasma. Administration of the c-Abl kinase inhibitor GZD824 not only abolished activation of c-Abl kinase but also decreased levels of citrullinated histone 3 in the pancreas and DNA-histone complexes in the plasma of animals with AP. Moreover, GZD824 decreased plasma levels of amylase, IL-6, and MMP-9 as well as edema, acinar cell necrosis, hemorrhage, CXC chemokine formation, and neutrophil infiltration in the inflamed pancreas. A beneficial effect of c-Abl kinase inhibition was confirmed in l-arginine-induced pancreatitis. In vitro, inhibition of c-Abl kinase reduced TNF-α-induced formation of ROS, histone 3 citrullination, and NETs in isolated bone marrow neutrophils. Our findings demonstrate that c-Abl kinase regulates NET formation in the inflamed pancreas. In addition, inhibition of c-Abl kinase reduced pancreatic tissue inflammation, and damage in AP. Thus, targeting c-Abl kinase might be a useful way to protect the pancreas in severe AP.
Mechanistic insights into intramolecular phosphate group transfer during collision induced dissociation of phosphopeptides
Authors: Bailey Laura S. , Alves Mélanie , Galy Nicolas , Patrick Amanda L. , Polfer Nicolas C. 
Published: March 2019

AbstractWe report on the rearrangement chemistry of model phosphorylated peptides during collision‐induced dissociation (CID), where intramolecular phosphate group transfers are observed from donor to acceptor residues. Such “scrambling” could result in inaccurate modification localization, potentially leading to misidentifications. Systematic studies presented herein provide mechanistic insights for the unusually high phosphate group rearrangements presented some time ago by Reid and coworkers (Proteomics 2013, 13 [6], 964‐973). It is postulated here that a basic residue like histidine can play a key role in mediating the phosphate group transfer by deprotonating the serine acceptor site. The proposed mechanism is consistent with the observation that fast collisional activation by collision‐cell CID and higher‐energy collisional dissociation (HCD) can shut down rearrangement chemistry. Additionally, the rearrangement chemistry is highly dependent on the charge state of the peptide, mirroring previous studies that less rearrangement is observed under mobile proton conditions.
Comparison of the efficacy of sofosbuvir plus ribavirin in Chinese patients with genotype 3a or 3b HCV infection
Authors: Huang Rui , Rao Huiying , Xie Qing , Gao Zhiliang , Li Wu , Jiang Deyuan , Mo Hongmei , Massetto Benedetta , Stamm Luisa M. , Brainard Diana M. , Wei Lai 
Published: March 2019

AbstractBackground and AimGenotype 3b hepatitis C virus (HCV) infection represents approximately 50% of patients with genotype 3 in China. We compared the efficacy of sofosbuvir (SOF) plus ribavirin (RBV) in Chinese patients with genotype 3a and 3b HCV.MethodsThe analyzed data are from a phase 3, open‐label study of SOF plus RBV for 24 weeks conducted in China. The primary endpoint for the trial was sustained virologic response at 12 weeks after the end of therapy (SVR12).ResultsOf 126 patients included in this analysis, 58 (46%) had genotype 3a and 68 (54%) had genotype 3b. Both the subtypes were similar in age, sex, body mass index, IL28B, and baseline HCV RNA. However, more treatment‐experienced and cirrhotic patients were in the genotype 3b group. All 100% of patients with genotype 3a (95% confidence interval [CI], 94‐100), and 91% (95% CI, 82‐97) of patients with genotype 3b achieved SVR12 (P = 0.030). For treatment‐experienced patients with genotype 3b, the SVR12 rate was 73% (95% CI, 39‐94) and 88% (95% CI, 64‐99) among patients with and without cirrhosis (P = 1.00), respectively.ConclusionSOF plus RBV for 24 weeks in patients with HCV genotype 3 infection resulted in high rates of SVR. However, the SVR12 rate among patients with genotype 3b was lower than that observed in patients with genotype 3a infection, particularly among treatment‐experienced patients with cirrhosis.
Ultra‐wideband antenna for wearable Internet of Things devices and wireless body area network applications
Authors: Mustaqim Muhammad , Khawaja Bilal A. , Chattha Hassan T. , Shafique Kinza , Zafar Muhammad J. , Jamil Mohsin 
Published: March 2019

AbstractThis paper presents a compact and planar ultra‐wideband (UWB) antenna, designed and characterized for the wearable Internet of Things (IoT) devices and wireless body area network (WBAN) applications. Two different substrates, ie, FR4 (h = 1.6 mm) and denim textile substrate (h = 1 mm), are used in the process of design and fabrication of the proposed antenna. The dimensions of the proposed antenna are 31 mm × 42 mm for FR4 substrate and 70 mm × 56 mm for denim textile substrate. The antenna structure consists of a rectangular radiating patch with two symmetrical staircase‐shaped slits. A reduced ground plane technique is used for the purpose of improving impedance bandwidth, which is further enhanced by the insertion of a small notch in the reduced ground plane which has improved the overall impedance matching characteristics of the proposed UWB antenna. The measured impedance bandwidth for S11 < −10 dB and gain of the FR4 and denim textile substrate UWB antennas are 7.71 GHz/5.12 dBi and 7.95 GHz/3.57 dBi, respectively. The ADS momentum simulator is used for antenna simulations, and the simulated and measured results are generally found in good agreements.
Enhanced laser surface ablation with an integrated photoacoustic imaging and high intensity focused ultrasound system
Authors: Hazlewood David , Yang Xinmai 
Published: March 2019

Background and ObjectiveCombined laser and ultrasound treatments have been found to have synergistic effects, which may be of particular note in dermatology. We aim to investigate the potential of this technology for dermatology through in vitro and ex vivo experiments.MethodsIn vitro tissue phantoms made of agar and tattoo ink and tattooed ex vivo chicken breast tissue were used. An integrated photoacoustic imaging and high intensity focused ultrasound (HIFU) system, using a 5‐ns tunable OPO laser system and a 5 MHz HIFU transducer, was used to perform photoacoustic analysis to identify the optical contrast, and perform combined laser and ultrasound ablation. On the tissue phantoms, lines of ablation were created under various operating conditions. The samples were then quantified to determine the level of ablation. Same procedures were performed on the tattooed chicken breast tissue and the tattoo was removed by using combined laser and ultrasound.ResultsAblation in the in vitro tissue phantoms was observed with properly synchronized laser and ultrasound while no ablation was found with either laser or ultrasound alone. Increases to the intensity or pulse duration of ultrasound caused an increase in ablation to the samples. The tattoo was removed from the ex vivo chicken breast using combined laser and ultrasound with a radiant exposure of 1.2 J/cm2 while laser and ultrasound alone were unable to remove the tattoo.ConclusionsWe determined that by supplementing nanosecond laser pulses with ultrasound, ablation, and tattoo removal can be achieved at laser radiant exposures levels would otherwise be ineffective. The area of ablation can be adjusted through changes in the intensity and duration of the ultrasound burst with a constant laser intensity. Additionally, the system can be used to perform photoacoustic analysis of the tissue to estimate the relative optical absorbance at various available wavelengths, allowing for pretreatment analysis. Lasers Surg. Med. 9999:1–9, 2019. © 2019 Wiley Periodicals, Inc.
Polyacrylic Acid‐Based Coordination Supramolecular Elastomer with High Strength, Excellent Fatigue‐Resistance, and Self‐Recovery Properties
Authors: Wu Jia , Niu Wenbin , Zhang Shufen , Wu Suli , Ma Wei , Tang Bingtao 
Published: March 2019

AbstractSupramolecular elastomers have attracted extensive attention due to their excellent mechanical properties. Herein, inspired by the concept of a dual cross‐linked network structure, a dual‐component coordination supramolecular elastomer is prepared via photopolymerization of three monomers combined with zinc ion (Zn2+)‐crosslinked low molecular weight polyacrylic acid (PAA). The covalent network of three monomers serves as a soft component forming the supporting network. The network of Zn2+ crosslinked low molecular weight PAA forms the hard component. The covalent network is crosslinked and locked by the coordinated network. This compact network contributes to improving the comprehensive mechanical properties. The optimal elastomer is that the molar ratio of carboxylic of low molecular weight PAA with Zn2+ is 1:0.5. The tensile and compression stress of the optimal elastomer are 4.08 and 6.90 MPa, respectively. The loading–unloading cycles can reach 1000 times without fracture. The self‐recovery ratios of the tensile and compression modes reaches 80% and 95%, respectively.
A Three‐Armed Polymer with Tunable Self‐Assembly and Self‐Healing Properties Based on Benzene‐1,3,5‐tricarboxamide and Metal–Ligand Interactions
Authors: Li Chunmei , Tan Jiaojun , Guan Zhibin , Zhang Qiuyu 
Published: March 2019

AbstractThe dynamic nature of supramolecules makes them useful in the fields of smart devices. The combination of multiple dynamic interactions in one material may bring some enhanced properties in mechanical property, self‐healing property, or recyclability. Thus, it is significantly meaningful to design new materials with multi‐dynamic bonds and clarify their bonding mechanisms. Here, a novel three‐armed polymer based on benzene‐1,3,5‐tricarboxamide (BTA) is developed and the polymer could be further complexed by metal ions to form dynamic zinc–imidazole interactions. In this system, BTA is located in the center, and the ligand‐functionalized monomer is copolymerized with n‐butyl acrylate to form three chains. This is the first time BTA is introduced to a self‐healing system to endow the polymer with assembly and self‐healing properties. The composition, chemical structure, assembly behavior, mechanical properties, and self‐healing properties of the polymer are investigated. It is revealed that the assembly behavior of the polymer depends on the BTA contents and time. The mechanical property can be easily tuned by ligand/metal ratio and is significantly adjusted by the polymer chain length and environment humidity. Long polymer chains not only contribute to good mechanical property but also promote the self‐healing process due to the effective physical entanglement.
Tumor suppressor KIF1Bβ regulates mitochondrial apoptosis in collaboration with YME1L1
Authors: Ando Koji , Yokochi Tomoki , Mukai Akira , Wei Gao , Li Yuanyuan , Kramer Sonja , Ozaki Toshinori , Maehara Yoshihiko , Nakagawara Akira 
Published: March 2019

AbstractKIF1Bβ, a member of the kinesin superfamily of motor proteins, is a haploinsufficient tumor suppressor mapped to chromosome 1p36.2, which is frequently deleted in neural crest–derived tumors, including neuroblastoma and pheochromocytoma. While KIF1Bβ acts downstream of the nerve growth factor (NGF) pathway to induce apoptosis, further molecular functions of this gene product have largely been unexplored. In this study, we report that KIF1Bβ destabilizes the morphological structure of mitochondria, which is critical for cell survival and apoptosis. We identified YME1L1, a mitochondrial metalloprotease responsible for the cleavage of the mitochondrial GTPase OPA1, as a physical interacting partner of KIF1Bβ. KIF1Bβ interacted with YME1L1 through its death‐inducing region, as initiated the protease activity of YME1L1 to cleave the long forms of OPA1, resulting in mitochondrial fragmentation. Overexpression of YME1L1 promoted apoptosis, while knockdown of YME1L1 promoted cell growth. High YME1L1 expression was significantly associated with a better prognosis in neuroblastoma. Furthermore, in NGF‐deprived PC12 cells, KIF1Bβ and YME1L1 were upregulated, accompanied by mitochondrial fragmentation and apoptotic cell death. Small interfering RNA–mediated knockdown of either protein alone, however, remarkably inhibited the NGF depletion–induced apoptosis. Our findings indicate that tumor suppressor KIF1Bβ plays an important role in intrinsic mitochondria–mediated apoptosis through the regulation of structural and functional dynamics of mitochondria in collaboration with YME1L1. Dysfunction of the KIF1Bβ/YME1L1/OPA1 mechanism may be involved in malignant biological features of neural crest–derived tumors as well as the initiation and progression of neurodegenerative diseases.
Stimulus Sensitive Foot Myoclonus: A Clue to Coeliac Disease
Authors: Jesús Silvia , Latorre Anna , Vinuela Angel , Fahn Stanley , Bhatia Kailash P. , Balint Bettina 
Published: March 2019

ABSTRACTBackgroundCoeliac disease (CD) is an autoimmune enteropathy that may feature extraintestinal manifestations including cerebellar ataxia and myoclonus.Methods and ResultsA descriptive series of five patients with CD who presented with prominent stimulus‐sensitive foot myoclonus.ConclusionsStimulus‐sensitive foot myoclonus is a distinct clinical sign and may be a useful clue to the diagnosis of CD.
An S‐ to Ku‐wideband low‐noise amplifier using asymmetric π filter and shunt‐peaking technique with simultaneous input match and noise flatness
Authors: Jing Kai , Yu Ningmei , Quan Xing 
Published: March 2019

AbstractA single‐stage S to Ku band (2‐18 GHz) low noise amplifier (LNA) employing asymmetric π input match network and inductive shunt‐peaking technique in 0.18 μm SiGe BiCMOS is presented. Shunt‐shunt feedback is utilized to ensure wide operating as well as form a noise suppression topology. With the process of SiGe heterojunction bipolar transistor (HBT) featuring f
T/fmax of 240/280 GHz, the measurement of the proposed LNA results in S11 below −10 dB, S21 of 19.6 ± 0.8 dB and 2.2‐3.2 dB noise figure (NF) from 2 to 18 GHz, drawing 9 mA DC current from a 3.3 V supply.
SpinStudioJ: A cross‐platform NMR data acquisition and processing workbench based on a plug‐in architecture
Authors: Liu Zao , Chen Zhiwei 
Published: March 2019

AbstractFlexibility and extensibility are important issues in the design of nuclear magnetic resonance (NMR) software, as these determine the ability to integrate a variety of continuously evolving data acquisition and processing methods. Here, SpinStudioJ is introduced. It is an NMR data acquisition and processing workbench with a plug‐in‐based architecture. The workbench is based on Eclipse Rich Client Platform, which provides a plug‐and‐play runtime mechanism and rich graphical user interface functionality. New data acquisition methods and processing algorithms can be easily integrated into the SpinStudioJ workbench by defining extension points, without the need to redistribute existing modules. The software is independent of operating systems, as it leverages the cross‐platform feature of the Java virtual machine.
Analysis of magnetization transfer (MT) influence on quantitative mapping of T2 relaxation time
Authors: Radunsky Dvir , Blumenfeld‐Katzir Tamar , Volovyk Osnat , Tal Assaf , Barazany Daniel , Tsarfaty Galia , Ben‐Eliezer Noam 
Published: March 2019

PurposeMulti‐echo spin‐echo (MESE) protocol is the most effective tool for mapping T2 relaxation in vivo. Still, MESE extensive use of radiofrequency pulses causes magnetization transfer (MT)‐related bias of the water signal, instigated by the presence of macromolecules (MMP). Here, we analyze the effects of MT on MESE signal, alongside their impact on quantitative T2 measurements.MethodsStudy used 3 models: in vitro urea phantom, ex vivo horse brain, and in vivo human brain. MT ratio (MTR) was measured between single‐SE and MESE protocols under different scan settings including varying echo train lengths, number of slices, and inter‐slice gap. MTR and T2 values were extracted for each model and protocol.ResultsMT interactions biased MESE signals, and in certain settings, the corresponding T2 values. T2 underestimation of up to 4.3% was found versus single‐SE values in vitro and up to 13.8% ex vivo, correlating with the MMP content. T2 bias originated from intra‐slice saturation of the MMP, rather than from indirect saturation in multi‐slice acquisitions. MT‐related signal attenuation was caused by slice crosstalk and/or partial T1 recovery, whereas smaller contribution was caused by MMP interactions. Inter‐slice gap had a similar effect on in vivo MTR (21.2%), in comparison to increasing the number of slices (18.9%).ConclusionsMT influences MESE protocols either by uniformly attenuating the entire echo train or by cumulatively attenuating the signal along the train. Although both processes depend on scan settings and MMP content, only the latter will cause underestimation of T2.