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Immunotherapy of gastric cancer:Present status and future perspectives

World Journal of Gastroenterology 2024年第8期30卷 779-793页

作者： john K Triantafillidis manousos m Konstadoulakis Apostolos E Papalois Inflammatory Bowel Disease Unit “Metropolitan General”HospitalHolargos 15562AtticaGreece.Hellenic Society for Gastrointestinal Oncology354 Iera OdosChaidari 12461AtticaGreece Second Department of Surgery University of Athens School of MedicineAretaieion HospitalAthens 11528AtticaGreece Unit of Surgical Research and Training Second Department of SurgeryUniversity of AthensSchool of MedicineAretaieion HospitalAthens 11528AtticaGreece

In this editorial,we comment on the article entitled“Advances and key focus areas in gastric cancer immunotherapy:A comprehensive scientometric and clinical trial review(1999-2023),”which was published in the recent issue of the World Journal of *** focused on the results of the authors’bibliometric analysis concerning gastric cancer immunotherapy,which they analyzed in depth by compiling the relevant publications of the last 20 *** that,we briefly describe the most recent data concerning the epidemiological parameters of gastric cancer(GC)in different countries,attempting to give an interpretation based on the etiological factors involved in the etiopathogenesis of the *** then briefly discuss the conservative treatment(chemotherapy)of the various forms of this malignant *** describe the treatment of resectable tumors,locally advanced neoplasms,and unresectable(advanced)*** attention is given to modern therapeutic approaches with emphasis on immunotherapy,which seems to be the future of GC treatment,especially in combination with *** is also a thorough analysis of the results of the study under review in terms of the number of scientific publications,the countries in which the studies were conducted,the authors,and the scientific centers of origin,as well as the clinical studies in ***,an attempt is made to draw some conclusions and to point out possible future directions.

关键词： Gastric cancer Chemotherapy Immunotherapy Immune checkpoint inhibitors Bibliometrics Scientometrics

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Inflammation-associated microsatellite alterations:mechanisms and significance in the prognosis of patients with colorectal cancer

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World Journal of Gastrointestinal Oncology 2018年第1期10卷 1-14页

作者： minoru Koi Stephanie S Tseng-Rogenski john m Carethers Department of Internal medicine and Comprehensive Cancer Center University of MichiganAnn ArborMI 48109-5368United States

microsatellite alterations within genomic DNA frameshift as a result of defective DNA mismatch repair(mmR). About 15% of sporadic colorectal cancers(CRCs) manifest hypermethylation of the DNA mmR gene mLH1, resulting in mono-and di-nucleotide frameshifts to classify it as microsatellite instability-high(mSI-H) and hypermutated, and due to frameshifts at coding microsatellites generating neo-antigens, produce a robust protective immune response that can be enhanced with immune checkpoint blockade. more commonly, approximately 50% of sporadic nonmSI-H CRCs demonstrate frameshifts at di-and tetra-nucleotide microsatellites to classify it as mSIlow/elevated microsatellite alterations at selected tetranucleotide repeats(EmAST) as a result of functional somatic inactivation of the DNA mmR protein mSH3 via a nuclear-to-cytosolic displacement. The trigger for mSH3 displacement appears to be inflammation and/or oxidative stress, and unlike mSI-H CRC patients, patients with mSI-L/EmAST CRCs show poor prognosis. These inflammatory-associated microsatellite alterations are a consequence of the local tumor microenvironment, and in theory, if the microenvironment is manipulated to lower inflammation, the microsatellite alterations and mSH3 dysfunction should be corrected. Here we describe the mechanisms and significance of inflammatory-associated microsatellite alterations, and propose three areas to deeply explore the consequences and prevention of inflammation's effect upon the DNA mmR system.

关键词： microsatellite instability microsatellite stable Elevated microsatellite alterations at selected tetranucleotide repeats Colorectal cancer mismatch repair Inflammation mSH3

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Convergence Properties of Local Defect Correction Algorithm for the Boundary Element method

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Computer modeling in Engineering & Sciences 2019年第4期119卷 207-225页

作者： Godwin Kakuba john m.mango martijn J.H.Anthonissen makerere University P.O.Box 7062KampalaUganda Eindhoven University of Technology P.O.Box 5135600 MB EindhovenThe Netherlands

Sometimes boundary value problems have isolated regions where the solution changes ***,when solving numerically,one needs a fine grid to capture the high *** fine grid can be implemented as a composite coarse-fine grid or as a global fine *** cheaper way of obtaining the composite grid solution is the use of the local defect correction *** technique is an algorithm that combines a global coarse grid solution and a local fine grid solution in an iterative way to estimate the solution on the corresponding composite *** algorithm is relatively new and its convergence properties have not been studied for the boundary element *** this paper the objective is to determine convergence properties of the algorithm for the boundary element ***,we formulate the algorithm as a fixed point iterative scheme,which has also not been done before for the boundary element method,and then study the properties of the iteration *** show that we can always expect ***,the algorithm opens up a real alternative for application in the boundary element method for problems with localised regions of high activity.

关键词： Local defect defect correction composite grids integral equation methods boundary elements

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Paleoproterozoic volcanic rocks in the southern margin of the North China Craton, central China:Implications for the Columbia supercontinent

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Geoscience Frontiers 2019年第4期10卷 1543-1560页

作者： Changming Wang Xinyu He Emmanuel john m. Carranza Chengmin Cui State Key Laboratory of Geological Processes and mineral Resources China University of GeosciencesBeijing 100083China Centre for Exploration Targeting University of Western AustraliaPerthWestern Australia 6009Australia China Non-ferrous metals Resource Geological Survey Beijing 100012China Discipline of Geological Sciences University of KwaZulu-NatalWestville CampusDurban 3629South Africa

The volcanic rocks of the Xiong’er Group are situated in the southern margin of the North China Craton(NCC).Research on the Xiong er Group is important to understand the tectonic evolution of the NCC and the Columbia supercontinent during the *** this study,to constrain the age of the Xiong’er volcanic rocks and identify its tectonic environment,we report zircon LA-ICP-mS data with Hf isotope,whole-rock major and trace element compositions and Sr-Nd-Pb-Hf isotopes of the volcanic rocks of the Xiong’er *** Xiong’er volcanic rocks mainly consist of basaltic andesite,*** and rhyolite,with minor *** new sets of data combined with those from previous studies indicate that Xiong’er volcanism should have lasted from 1827 ma to 1746 ma as the major phase of the *** volcanics have extremely low *** and Ni contents,are enriched in LREEs and LILEs but depleted in HFSEs(Nb,Ta,and Ti),similar to arc-related volcanic *** are characterized by negative zirconεHft values of-17.4 to 8.8,whole-rock initial 87Sr/86Sr values of 0.7023 to 0.7177 andεNd(t)values of-10.9 to *** Pb isotopes(206Pb/204Pb=14.366-16.431,207Pb/204Pb=15.106-15.371,208Pb/204Pb=32.455-37.422).The available elemental and Sr-Nd-Pb-Hf isotope data suggest that the Xiong’er volcanic rocks were sourced from a mantle contaminated by continental *** volcanic rocks of the Xiong’er Group might have been generated by high-degree partial melting of a lithospheric mantle that was originally modified by oceanic subduction in the ***,we suggest that the subduction-modified lithospheric mantle occurred in an extensional setting during the breakup of the Columbia supercontinent in the Late Paleoproterozoic,rather than in an arc setting.

关键词： Volcanic rocks Geochronology Sr-Nd-Pb-Hf isotopes Paleoproterozoic North China Craton Supercontinent Columbia

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Aerodynamics of a Tandem-Bladed Axial Compressor Rotor under Circumferential Distortion at Different Rotational Speeds

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Journal of Thermal Science 2024年第4期33卷 1340-1356页

作者： Amit KUmAR Jerry T.john A.m.PRADEEP R.A.DAKKERmANS Dragan KOZULOVIC Department of Aerospace Engineering Indian Institute of Technology BombayMumbai400076India Department of Automotive and Aeronautical Engineering Hamburg University of Applied Sciences20099HamburgGermany Institute of Jet Propulsion Bundeswehr University Munich85577NeubibergGermany

For most aircraft engines,inflow distortion is *** distortion is known to degrade the aerodynamic performance and stable operating limits of a *** rotor configuration is an arrangement that effectively controls the growth of the boundary layer over the suction surface of the ***,a higher total pressure rise can be achieved through this unconventional design approach involving the splitting of the blade into forward and aft *** is expected that the effect of inlet flow distortion would be more severe for a tandem-rotor design due to the greater flow turning inherent in such ***,this aspect needs to be thoroughly *** present study discusses the effect of circumferential distortion on the tandem-rotor at different rotational ***-annulus RANS simulations using ANSYS CFX are used in the present *** performance of the rotor at a particular flow coefficient and different rotational speeds is *** total pressure and efficiency are observed to drop at lower mass flow rates under the influence of circumferential *** loss region in each blade passage is mainly associated with the blade wake,tip leakage vortex,secondary flow,and boundary ***,their contribution varies from passage to passage,particularly in the distorted *** the lower span,the wake width is found to be higher than that at a higher *** to the redistribution of the mass flow,the circumferential extent reduces at a higher *** the undistorted sector,the strength of the tip leakage vortex is significantly higher at the design rotational speed than at lower *** distortion near the tip region promotes an early vortex breakdown even at the design operating *** adversely affects the total pressure,efficiency,and stall *** clean flow conditions,this phenomenon is only observed near the stall *** the design operating condition,the breakdown of the forward rotor tip l

关键词： tandem rotor circumferential distortion loss tip leakage vortex vortex breakdown diffusion factor aerodynamics of compressor blade

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Towards smart self-clearing glaucoma drainage device

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microsystems & Nanoengineering 2018年第1期4卷 73-84页

作者： Hyunsu Park Amir Hossein Raffiee Simon W.m.john Arezoo m.Ardekani Hyowon Lee Weldon School of Biomedical Engineering Birck Nanotechnology CenterCenter for Implantable DevicesPurdue UniversityWest LafayetteIN 47907USA School of mechanical Engineering Purdue UniversityWest LafayetteIN 47907USA Howard Hughes medical Institute The Jackson LaboratoryBar HarborME 04609USA

For patients who are unresponsive to pharmacological treatments of glaucoma,an implantable glaucoma drainage devices(GDD)are often used to manage the intraocular ***,the microscale channel that removes excess aqueous humor from the anterior chamber often gets obstructed due to biofouling,which necessitates additional surgical *** we demonstrate the proof-of-concept for smart self-clearing GDD by integrating magnetic microactuators inside the drainage tube of *** magnetic microactuators can be controlled using externally applied magnetic fields to mechanically clear biofouling-based obstruction,thereby eliminating the need for surgical *** this work,our prototype magnetic microactuators were fabricated using low-cost maskless photolithography to expedite design *** fabricated devices were evaluated for their static and dynamic mechanical *** transient numerical analysis,the fluid–structure interaction of our microactuator inside a microtube was characterized to better understand the amount of shear force generated by the device ***,the anti-biofouling performance of our device was evaluated using fluorescein isothiocyanate labeled bovine serum *** microactuators were effective in removing proteinaceous film deposited on device surface as well as on the inner surface of the microchannel,which supports our hypothesis that a smart self-clearing GDD may be possible by integrating microfabricated magnetic actuators in chronically implanted microtubes.

关键词： fouling integrating removing

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Finite Element modeling in Drilling of Nimonic C-263 Alloy Using Deform-3D

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Computer modeling in Engineering & Sciences 2019年第3期118卷 679-692页

作者： m.Nagaraj A.john Presin Kumar C.Ezilarasan Rishab Betala Research Scholar Department of Mechanical EngineeringHindustan Institute of Technology and ScienceChennai-603103India Associate Professor Department of Mechanical EngineeringHindustan Institute of Technology and ScienceChennai-603103India Professor Department of Mechanical EngineeringSMK Fomra Institute of TechnologyKelambakkamChennai-603103India Design Engineer ARE PEE PolymerGummidipoondiTiruvallur-601201India

The paper proposes a simulated 3D Finite Element model(FEm)for drilling of Nickel based super alloy known as Nimonic *** Lagrangian finite element model-based simulations were performed to determine the thrust force,temperature generation,effective stress,and effective *** simulations were performed according to the L27 orthogonal array.A perfect plastic work piece was assumed,and the shape is considered to be *** spindle speed,feed rate,and point angle were considered as the input *** work piece was modeled by johnson-Cook(JC)material model and tungsten carbide(WC)was chosen as the drill bit and the body was assumed to be *** demonstrative results of the thrust force and the temperature at drill bit cutting edge were substantiated with the simulated results and a percentage error was observed within 10%.Further,simulated results of effective stress and strain were also observed.

关键词： Nimonic C-263 Thrust force temperature effective stress effective strain deform-3D simulation

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Tuning the intentional corona of cerium oxide nanoparticles to promote angiogenesis via fibroblast growth factor 2 signalling

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Regenerative Biomaterials 2022年第1期9卷 963-978页

作者： Lu Fu Rupeng Li john m.Whitelock megan S.Lord Graduate School of Biomedical Engineering UNSW SydneySydneyNSW 2052Australia School of minerals and Energy Resources Engineering UNSW SydneySydneyNSW 2052Australia

Inadequate angiogenesis is a hallmark of conditions including cardiovascular diseases,stroke and chronic diabetic wounds,which exhibit tissue ischaemia ensuring that therapeutic strategies to promote angiogenesis are of great ***,many angiogenic treatments involve the delivery of growth factors which have limited clinical success due to poor stability,high manufacturing cost and poor *** oxide nanoparticles(nanoceria)can either promote or inhibit angiogenesis depending on their surface corona ***,nanoceria were functionalized with an intentional heparin corona,a polysaccharide which binds and signals growth factors,of different chain lengths and surface grafting density to establish their effect on *** nanoparticles promoted angiogenesis in vivo with the surface grafting density positively correlated with angiogenesis over the widest concentration range;however,chain length did not play a *** heparin–nanoceria supported fibroblast growth factor 2(FGF2)signalling in vitro and promoted FGF2-mediated angiogenesis in *** nanoparticles were internalized by endothelial cells in vitro where they trafficked to the lysosomes and reduced cell viability suggesting that the angiogenic activity of heparin–nanoceria is mediated in the extracellular ***,this study adds to our knowledge of the angiogenic effects of heparin–nanoceria towards finding new angiogenic treatments.

关键词： cerium oxide nanoparticle endothelial angiogenesis

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Prototype chemical synapse chip for spatially patterned neurotransmitter stimulation of the retina ex vivo

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microsystems & Nanoengineering 2017年第1期3卷 59-70页

作者： Corey m.Rountree Ashwin Raghunathan john B.Troy Laxman Saggere Department of mechanical and Industrial Engineering University of Illinois at ChicagoChicagoIL 60607USA Department of Biomedical Engineering Northwestern UniversityEvanstonIL 60208USA

Biomimetic stimulation of the retina with neurotransmitters,the natural agents of communication at chemical synapses,could be more effective than electrical stimulation for treating blindness from photoreceptor degenerative *** studies have demonstrated the feasibility of neurotransmitter stimulation by injecting glutamate,a primary retinal neurotransmitter,into the retina at isolated single ***,we demonstrate spatially patterned multisite stimulation of the retina with glutamate,offering the first experimental evidence for applicability of this strategy for translating visual patterns into afferent neural *** accomplish pattern stimulation,we fabricated a special microfluidic device comprising an array of independently addressable microports connected to tiny on-chip glutamate reservoirs via *** device prefilled with glutamate was interfaced with explanted rat retinas placed over a multielectrode array(mEA)with the retinal ganglion cells(RGC)contacting the electrodes and photoreceptor surface contacting the *** independently and simultaneously activating a subset of the microports with modulated pressure pulses,small boluses of glutamate were convectively injected at multiple sites in alphabet patterns over the photoreceptor *** found that the glutamate-driven RGC responses recorded through the mEA system were robust and spatially laid out in patterns strongly resembling the injection *** stimulations were also highly localized with spatial resolutions comparable to or better than electrical retinal *** findings suggest that surface stimulation of the retina with neurotransmitters in pixelated patterns of visual images is feasible and an artificial chemical synapse chip based on this approach could potentially circumvent the limitations of electrical retinal prostheses.

关键词： artificial vision neurotransmitter stimulation photoreceptor degeneration retina synapse chip visual prosthesis

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Interface-induced warping in hybrid two-dimensional materials

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Nano Research 2015年第6期8卷 2015-2023页

作者： john m. Aired Zhuhua Zhang Zhili Hu Boris I. Yakobson Department of material Science and Nanoengineering Rice University Houston Texas 77005 USA

Two-dimensional hybrid materials consisting of heterogeneous domains have been of great interest. Using empirical molecular dynamical simulation, we show that the morphology of such hybrid 2D materials can extend into the third dimension via strong warping intrinsic to the interfaces between the domains. The interface warping stems from the compressive stress in the domain with a larger lattice constant and even penetrates into the stretched domain. Based on classic plate theory, we analytically quantify the amplitude, wave length and penetration depth of the interface warping as functions of the lattice mismatch, achieving good agreement with the simulations. moreover, we propose that periodically placing pentagon-heptagon dislocations along the interface can eliminate the warping in the 2D material and such defective interface can be more favorable than the warped one over a critical domain size, which is consistent with recent experimental observations. Our results suggest that the interface warping in 2D hybrid materials should be considered in further exploring their promising properties.

关键词： graphene interface rippling mechanical property hybrid 2D materials

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