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A novel saliva-based miRNA profile to diagnose and predict oral cancer

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International Journal of Oral Science 2024年第1期16卷 97-109页

作者： Jaikrishna Balakittnen Chameera Ekanayake weeramange Daniel F.wallace Pascal h.G.Duijf Alexandre S.Cristino Gunter hartel Roberto A.Barrero Touraj Taheri Liz Kenny Sarju Vasani Martin Batstone Omar Breik Chamindie Punyadeera Saliva&Liquid Biopsy Translational Laboratory Griffith Institute for Drug DiscoveryGriffith UniversityNathanQLDAustralia Department of Medical Laboratory Sciences Faculty of Allied Health SciencesUniversity of JaffnaJaffnaSri Lanka Menzies health Institute Griffith UniversityGold CoastQLDAustralia School of Biomedical Sciences Faculty of HealthQueensland University of TechnologyBrisbaneQLDAustralia Centre for Cancer Biology Clinical and Health SciencesUniversity of South Australia&SA PathologyAdelaideSAAustralia Institute of Clinical Medicine Faculty of MedicineUniversity of OsloOsloNorway Department of Medical Genetics Oslo University HospitalOsloNorway griffith.Institute for Drug Discovery Griffith UniversityNathanQLDAustralia QIMR Berghofer Medical Research Institute Statistics UnitBrisbaneQLDAustralia School of Public health The University of QueenslandBrisbaneQLDAustralia School of Nursing Queensland University of TechnologyBrisbaneQLDAustralia eResearch Research InfrastructureAcademic DivisionQueensland University of TechnologyBrisbaneQLDAustralia Department of Anatomical Pathology Royal Brisbane and Women’s HospitalHerstonQLDAustralia Faculty of Medicine The University of QueenslandBrisbaneQLDAustralia Royal Brisbane and women’s hospital Cancer Care ServicesHerstonQLDAustralia Department of Otolaryngology Royal Brisbane and Women’s HospitalHerstonQLDAustralia Department of Oral and Maxillofacial Surgery Royal Brisbane and Women’s HospitalHerstonQLDAustralia

Oral cancer (OC) is the most common form of head and neck cancer. Despite the high incidence and unfavourable patient outcomes, currently, there are no biomarkers for the early detection of OC. This study aims to discover, develop, and validate a novel saliva-based microRNA signature for early diagnosis and prediction of OC risk in oral potentially malignant disorders (OPMD).The Cancer Genome Atlas (TCGA) miRNA sequencing data and small RNA sequencing data of saliva samples were used to discover differentially expressed miRNAs. Identified miRNAs were validated in saliva samples of OC (n=50), OPMD (n=52), and controls(n=60) using quantitative real-time PCR. Eight differentially expressed miRNAs (miR-7-5p, miR-10b-5p, miR-182-5p, miR-215-5p,miR-431-5p, miR-486-3p, miR-3614-5p, and miR-4707-3p) were identified in the discovery phase and were validated. The efficiency of our eight-miRNA signature to discriminate OC and controls was:area under curve (AUC):0.954, sensitivity:86%, specificity:90%,positive predictive value (PPV):87.8%and negative predictive value (NPV):88.5%whereas between OC and OPMD was:AUC:0.911,sensitivity:90%, specificity:82.7%, PPV:74.2%and NPV:89.6%. we have developed a risk probability score to predict the presence or risk of OC in OPMD patients. we established a salivary miRNA signature that can aid in diagnosing and predicting OC,revolutionising the management of patients with OPMD. Together, our results shed new light on the management of OC by salivary miRNAs to the clinical utility of using miRNAs derived from saliva samples.

关键词： specificity salivary diagnosis

On the Volume Conservation of the Immersed Boundary Method

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Communications in Computational Physics 2012年第7期12卷 401-432页

作者： Boyce E.griffith Leon h.Charney Division of Cardiology New York University School of Medicine550 First AvenueNew YorkNew York 10016USA

The immersed boundary(IB)method is an approach to problems of fluid-structure interaction in which an elastic structure is immersed in a viscous incompressible *** IB formulation of such problems uses a Lagrangian description of the structure and an Eulerian description of the *** is well known that some versions of the IB method can suffer from poor volume *** have been introduced to improve the volume-conservation properties of the IB method,but they either have been fairly specialized,or have used complex,nonstandard Eulerian finite-difference *** this paper,we use quasi-static and dynamic benchmark problems to investigate the effect of the choice of Eulerian discretization on the volume-conservation properties of a formally second-order accurate IB *** consider both collocated and staggered-grid discretization *** the tests considered herein,the staggered-grid IB scheme generally yields at least a modest improvement in volume conservation when compared to cell-centered methods,and in many cases considered in this work,the spurious volume changes exhibited by the staggered-grid IB method are more than an order of magnitude smaller than those of the collocated *** also compare the performance of cell-centered schemes that use either exact or approximate projection *** find that the volumeconservation properties of approximate projection IB methods depend strongly on the formulation of the projection *** used with the IB method,we find that pressure-free approximate projection methods can yield extremely poor volume conservation,whereas pressure-increment approximate projection methods yield volume conservation that is nearly identical to that of a cell-centered exact projection method.

关键词： Immersed boundary method fluid-structure interaction collocated discretization staggered-grid discretization exact projection method approximate projection method volume conservation

Comparative untargeted proteomic analysis of ADME proteins and tumor antigens for tumor cell lines

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Acta Pharmaceutica Sinica B 2018年第2期8卷 252-260页

作者： Xiaomei Gu Qing Xiao Qian Ruan Yuezhong Shu Ashok Dongre Ramaswamy Iyer w.griffith.humphreys Yurong Lai Pharmaceutical Candidate Optimization Bristol-Myers Squibb Company Genomics Bristol-Myers Squibb Company

In the present study, total membrane proteins from tumor cell lines including hepG2, hep3 B2,h226, Ovcar3 and N87 were extracted and digested with γLys C and trypsin. The resulting peptide lysate were pre-fractionated and subjected to untargeted quantitative proteomics analysis using a high resolution mass spectrometer. The mass spectra were processed by the Max Quant and the protein abundances were estimated using total peak area(TPA) method. A total of 6037 proteins were identified, and the analysis resulted in the identification of 2647 membrane proteins. Of those, tumor antigens and absorption,metabolism, disposition and elimination(ADME) proteins including UDP-glucuronosyltransferase,cytochrome P450, solute carriers and ATP-binding cassette transporters were detected and disclosed significant variations among the cell lines. The principal component analysis was performed for the cluster of cell lines. The results demonstrated that h226 is closely related with N87, while hep3 B2 aligned with hepG2. The protein cluster of Ovcar3 was apart from that of other cell lines investigated. By providing for the first time quantitative untargeted proteomics analysis, the results delineated the expression profiles of membrane proteins. These findings provided a useful resource for selecting targets of choice for anticancer therapy through advancing data obtained from preclinical tumor cell line models to clinical outcomes.

关键词： Cancer cell lines Untargeted quantitative proteomics Tumor-associated membrane proteins Cytochrome P450 ABC transporters SLC transporters

Simulating an Elastic Ring with Bend and Twist by an Adaptive Generalized Immersed Boundary Method

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Communications in Computational Physics 2012年第7期12卷 433-461页

作者： Boyce E.griffith.Sookkyung Lim Leon h.Charney Division of Cardiology Department of MedicineNew York University School ofMedicine550 First AvenueNew YorkNew York 10016USA Department of Mathematical Sciences University of Cincinnati839 Old Chemistry BuildingCincinnatiOhio 45221USA

Many problems involving the interaction of an elastic structure and a viscous fluid can be solved by the immersed boundary(IB)*** the IB approach to such problems,the elastic forces generated by the immersed structure are applied to the surrounding fluid,and the motion of the immersed structure is determined by the local motion of the ***,the IB method has been extended to treatmore general elasticity models that include both positional and rotational degrees of *** such models,force and torque must both be applied to the *** positional degrees of freedomof the immersed structuremove according to the local linear velocity of the fluid,whereas the rotational degrees of freedom move according to the local angular *** paper introduces a spatially adaptive,formally second-order accurate version of this generalized immersed boundary *** use this adaptive scheme to simulate the dynamics of an elastic ring immersed in *** describe the elasticity of the ring,we use an unconstrained version of Kirchhoff rod *** demonstrate empirically that our numerical scheme yields essentially second-order convergence rates when applied to such *** also study dynamical instabilities of such fluid-structure systems,and we compare numerical results produced by our method to classical analytic results from elastic rod theory.

关键词： Immersed boundary method Kirchhoff rod theory adaptive mesh refinement

Tissue distribution and tumor uptake of folate receptor–targeted epothilone folate conjugate,BMS-753493,in CD2F1 mice after systemic administration

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Acta Pharmaceutica Sinica B 2016年第5期6卷 460-467页

作者： hong Shen Lifei wang weiqi Chen Krista Menard Yang hong Yuan Tian Samuel J.Bonacorsi w.griffith.humphreys Francis Y.Lee Jinping Gan Pharmaceutical Candidate Optimization Bristol-Myers Squibb Research & Development Discovery Oncology Bristol-Myers Squibb Research & Development Chemistry Bristol-Myers Squibb Research & Development

To assess targeting of an epothilone folate conjugate(BMS-753493) to the folate receptor(FR)-overexpressed tumor in mice bearing both FRt and FR– tumors,a series of experiments were conducted by quantitative whole-body autoradiography(QwBA) and LC–MS/MS following *** of BMS-753493 or its active moiety,BMS-748285 in mice bearing FRt(98M109) and FR–(M109) *** sh.wed [3h]BMS-753493–derived radioactivity was extensively distributed to various *** FR over-expressing 98M109 tumors sh.wed consistently higher level of radioactivity than FR-negative tumors(i.e.,M109 tumors) up to 48 h post dose of [3h]BMS-753493,despite the magnitude of difference between the tumors is relatively small(generally 3 5-fold).The radioactivity level in 98M109 tumors was 2 12-fold of normal tissues except intestine/content at 48 h post *** selective radioactivity uptake into 98M109 tumors over M109 or normal tissues was observed after *** of the active epothilone,[3h]***–MS/MS measurements demonstrated that the concentrations of BMS-748285,presumably from hydrolysis of the folate conjugate,in 98M109 tumors were greater than those in M109 tumors after *** of BMS-753493(2–3-fold) whereas no differential uptake in the tumors following BMS-748285 *** data were consistent with radioactivity *** results demonstrated that the folate conjugation in BMS-753493 enabled moderately preferential distribution of the active epothilone to FR overexpressing 98M109 tumors,thereby supporting targeted delivery of cytotoxics through the folate receptor.

关键词： Folate receptor Tumor selective targeting Folate receptor–expressing tumor Epothilone folate conjugate Tissue distribution Tumor uptake

Avoiding the will O’ the wisp: Challenges in Measuring high Levels of Immunization Coverage with Precision

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world Journal of Vaccines 2014年第3期4卷 97-99页

作者： David w. Brown Anthony h. Burton griffith.Feeney Marta Gacic-Dobo Scarsdale Solutions New York USA United Nations Children’s Fund New York USA world health Organization Geneva Switzerland

There have been tremendous improvements in immunization coverage since the Expanded Programme on Immunization was launched. we highlight inherent challenges in measuring immunization coverage with precision as coverage levels increase due to the sensitivity of coverage to the accuracy of target population estimates. In fact, when comparing across groups at high levels of coverage, error in target population estimates can obscure differences in immunization coverage.

关键词： Immunization Vaccination Coverage Population Precision

Efficient Variable-Coefficient Finite-Volume Stokes Solvers

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Communications in Computational Physics 2014年第10期16卷 1263-1297页

作者： Mingchao Cai Andy Nonaka John B.Bell Boyce E.griffith.Aleksandar Donev Courant Institute of Mathematical Sciences New York UniversityNew YorkNY 10012USA. Center for Computational Sciences and Engineering Lawrence Berkeley National LaboratoryBerkeleyCA 94720USA. Leon h.Charney Division of Cardiology Department of MedicineNew York University School of MedicineNYUSA. Department of Mathematics University of North CarolinaChapel HillNC 27599USA

we investigate several robust preconditioners for solving the saddle-point linear systems that arise from spatial discretization of unsteady and steady variablecoefficient Stokes equations on a uniform staggered *** on the success of using the classical projection method as a preconditioner for the coupled velocitypressure system[***,***.,228(2009),pp.7565–7595],as well as established techniques for steady and unsteady Stokes flow in the finite-element literature,we construct preconditioners that employ independent generalized helmholtz and Poisson solvers for the velocity and pressure *** demonstrate that only a single cycle of a standard geometric multigrid algorithm serves as an effective inexact solver for each of these *** to traditional wisdom,we find that the Stokes problem can be solved nearly as efficiently as the independent pressure and velocity subproblems,making the overall cost of solving the Stokes system comparable to the cost of classical projection or fractional step methods for incompressible flow,even for steady flow and in the presence of large density and viscosity *** of the five preconditioners considered here are found to be robust to GMRES restarts and to increasing problem size,making them suitable for large-scale *** work opens many possibilities for constructing novel unsplit temporal integrators for finite-volume spatial discretizations of the equations of low Mach and incompressible flow dynamics.

关键词： Stokes flow variable density variable viscosity saddle point problems projection method preconditioning GMRES.

持久性脑炎损伤和百日咳预防接种:这种长篇叙述快要结束了吗?

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微生物学免疫学进展 1990年第2期18卷 39-49页

作者： griffith.A h 张绪和

于1933～1944年间,一种安全、有效的铝吸附白喉—破伤风—百日咳疫苗(DTP)在美国获得了发展和普遍理解,导致了百日咳发病率的逐渐下降和为已经有效地保持了40年以上的预防接种规划灌了信心。这和英国扰嚷的百日咳预防接种历史形成了对比... 详细信息

于1933～1944年间,一种安全、有效的铝吸附白喉—破伤风—百日咳疫苗(DTP)在美国获得了发展和普遍理解,导致了百日咳发病率的逐渐下降和为已经有效地保持了40年以上的预防接种规划灌了信心。这和英国扰嚷的百日咳预防接种历史形成了对比,在英国对可用疫苗效果的怀疑,延误了在全国积极推广使用直至1957年,此后的一些报告进一步散播了关于效果和安全性的疑虑。于1974年,当国立残疾儿童医院,关于发生在接种DTP后的神经系统病例系列被作为电视记录片的基础材料播映后,群众性宣传工具卷入了安全性的争端。卫生及社会安全部(DhSS)对此作出了反应,设立了两项接种后副反应病例记录的回顾性研究和两项前瞻性研究。前瞻性研究之一:全国幼儿脑病研究(NCES)被认为是权威性的有对照的病例研究。

关键词：百日咳预防接种持久性脑炎疫苗

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基于重组人胶原构建角膜替代物

高分子通报 2010年第8期 1-6页

作者：刘文广 May griffith.Frank Li 天津大学材料科学与工程学院天津300072 Department of Cellular and Molecular Medicine University of Ottawa

作为细胞外基的重要成分,胶原在组织工程支架中应用广泛。但目前报道的动物胶原存在传播病毒和免疫原反应等隐患。而基因工程方法生产的重组人胶原(RhC)具有生物安全性和性能优异等特点。本文主要介绍近几年以碳二亚胺和N-羟基琥珀酰亚... 详细信息

作为细胞外基的重要成分,胶原在组织工程支架中应用广泛。但目前报道的动物胶原存在传播病毒和免疫原反应等隐患。而基因工程方法生产的重组人胶原(RhC)具有生物安全性和性能优异等特点。本文主要介绍近几年以碳二亚胺和N-羟基琥珀酰亚胺对重组人Ⅰ型(RhC-Ⅰ)和重组人Ⅲ型(RhC-Ⅲ)胶原浓溶液进行交联构建的RhC角膜替代物、重组胶原/磷酸胆碱互穿聚合物网络水凝胶角膜替代物、重组胶原/含糖聚合物互穿聚合物网络水凝胶角膜替代物的研究进展,并概述了RhC-Ⅲ角膜替代物的I期临床实验结果。

关键词：重组人胶原角膜替代物水凝胶