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Mechanistic considerations for the use of monoclonal antibodies for cancer therapy

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癌症生物学与医学：英文版 2014年第1期11卷 20-33页

作者： patrick M.Glassman joseph p.balthasar Department of pharmaceutical Sciences School of Pharmacy and Pharmaceutical Sciences University at Buffalo The State University of New York

Since the approval of rituximab in 1997, monoclonal antibodies(mAbs) have become an increasingly important component of therapeutic regimens in oncology. The success of mAbs as a therapeutic class is a result of great strides that have been made in molecular biology and in biotechnology over the past several decades. Currently, there are 14 approved mAb products for oncology indications, and there are ten additional mAbs in late stages of clinical trials. Compared to traditional chemotherapeutic agents, mAbs have several advantages, including a long circulating half-life and high target specificity. Antibodies can serve as cytotoxic agents when administered alone, exerting a pharmacologic effect through several mechanisms involving the antigen binding(Fab) and/or Fc domains of the molecule, and mAbs may also be utilized as drug carriers, targeting a toxic payload to cancer cells. The extremely high affinity of mAbs for their targets, which is desirable with respect to pharmacodynamics(i.e., contributing to the high therapeutic selectivity of mAb), often leads to complex, non-linear, target-mediated pharmacokinetics. In this report, we summarize the pharmacokinetic and pharmacodynamics of mAbs that have been approved and of mAbs that are nearing approval for oncology indications, with particular focus on the molecular and cellular mechanisms responsible for their disposition and efficacy.

关键词：单克隆抗体治疗方案分子生物学药物代谢动力学癌症机械细胞毒性细胞机制

Rising tide: The global surge of type 2 diabetes in children and adolescents demands action now

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World Journal of Diabetes 2024年第5期15卷 797-809页

作者： joseph M pappachan Cornelius James Fernandez Ambika p Ashraf Department of Endocrinology and Metabolism Lancashire Teaching Hospitals NHS TrustPreston PR29HTUnited Kingdom Faculty of Science Manchester Metropolitan UniversityManchester M156BHUnited Kingdom Faculty of Biology Medicine&HealthThe University of ManchesterManchester M139PLUnited Kingdom Department of Endocrinology&Metabolism Pilgrim HospitalUnited Lincolnshire Hospitals NHS TrustBoston PE219QSUnited Kingdom Division of pediatric Endocrinology and Diabetes Department of PediatricsUniversity of Alabama at BirminghamBirminghamAL 35233United States

Childhood-onset obesity has emerged as a major public healthcare challenge across the globe,fueled by an obesogenic environment and influenced by both genetic and epigenetic *** has led to an exponential rise in the incidence of type 2 diabetes mellitus in children and *** looming wave of diabetes-related complications in early adulthood is anticipated to strain the healthcare budgets in most *** there is a collective global effort to curb the devastation caused by the situation,the impact is poised to be pro-found.A multifaceted research effort,governmental legislation,and effective social action are crucial in attaining this *** article delves into the current epidemiological landscape,explores evidence concerning potential risks and consequences,delves into the pathobiology of childhood obesity,and discusses the latest evidence-based management strategies for diabesity.

关键词： Childhood obesity Diabesity Type 2 diabetes mellitus Adolescence Cardiovascular disease pharmacotherapy

Sustainable Biocomposites Materials for Automotive Brake pad Application:An Overview

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Journal of Renewable Materials 2024年第3期12卷 485-511页

作者： joseph O.Dirisu Imhade p.Okokpujie Olufunmilayo O.joseph Sunday O.Oyedepo Oluwasegun Falodun Lagouge K.Tartibu Firdaussi D.Shehu Department of Mechanical Engineering Covenant UniversityOtaOgunNigeria Department of Mechanical and Mechatronics Engineering AFE Babalola UniversityAdoEkitiNigeria Department of Mechanical and Industrial Engineering Technology University of JohannesburgJohannesburg2028South Africa School of Chemical and Metallurgical Engineering University of the WitwatersrandJohannesburgSouth Africa

Research into converting waste into viable eco-friendly products has gained global *** natural fibres and pulverized metallic waste becomes necessary to reduce noxious environmental emissions due to indiscriminately occupying the *** study reviews the literature in the broad area of green composites in search of materials that can be used in automotive brake *** made by biocomposite,rather than fossil fuels,will be favoured.A database containing the tribo-mechanical performance of numerous potential components for the future green composite was established using the technical details of bio-polymers and natural *** development of materials with diverse compositions and varying proportions is now conceivable,and these materials can be permanently connected in fully regulated *** explanation demonstrates that all of these variables affect friction coefficient,resistance to wear from friction and high temperatures,and the operating life of brake pads to varying *** this study,renewable materials for the matrix and reinforcement are screened to determine which have sufficient strength,coefficient of friction,wear resistance properties,and reasonable costs,making them a feasible option for a green *** most significant,intriguing,and unusual materials used in manufacturing brake pads are gathered in this review,which also analyzes how they affect the tribological characteristics of the pads.

关键词： Asbestos brake pad biocomposites green composite mechanical properties natural reinforcement waste

High-yield and rapid isolation of extracellular vesicles by flocculation via orbital acoustic trapping:FLOAT

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Microsystems & Nanoengineering 2024年第1期10卷 313-323页

作者： joseph Rufo peiran Zhang Zeyu Wang Yuyang Gu Kaichun Yang joseph Rich Chuyi Chen Ruoyu Zhong Ke Jin Ye He Jianping Xia Ke Li Jiarong Wu Yingshi Ouyang Yoel Sadovsky Luke p.Lee Tony Jun Huang Department of Mechanical Engineering and Materials Science Duke UniversityDurhamNCUSA Department of Biomedical Engineering Duke UniversityDurhamNCUSA Department of Obstetrics Gynecologyand Reproductive SciencesMagee-Womens Research InstituteUniversity of PittsburghPittsburghPAUSA Department of Microbiology and Molecular Genetics School of MedicineUniversity of PittsburghPittsburghPAUSA Renal Division and Division of Engineering in Medicine Department of MedicineBrigham and Women’s HospitalHarvard Medical SchoolBostonMAUSA Department of Bioengineering Department of Electrical Engineering and Computer ScienceUniversity of CaliforniaBerkeleyBerkeleyCAUSA Department of Biophysics Institute of Quantum BiophysicsSungkyunkwan UniversitySuwonKorea

Extracellular vesicles(EVs)have been identified as promising biomarkers for the noninvasive diagnosis of various ***,challenges in separating EVs from soluble proteins have resulted in variable EV recovery rates and low ***,we report a high-yield(>90%)and rapid(pping(FLOAT).The FLOAT approach utilizes an acoustofluidic droplet centrifuge to rotate and controllably heat liquid *** adding a thermoresponsive polymer flocculant,nanoparticles as small as 20 nm can be rapidly and selectively concentrated at the center of the *** demonstrate the ability of FLOAT to separate urinary EVs from the highly abundant Tamm-Horsfall protein,addressing a significant obstacle in the development of EV-based liquid *** to its high-yield nature,FLOAT reduces biofluid starting volume requirements by a factor of 100(from 20 mL to 200µL),demonstrating its promising potential in point-of-care diagnostics.

关键词： trapping utilize separating

Treatment of Helicobacter pylori with potassium competitive acid blockers:A systematic review and meta-analysis

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World Journal of Gastroenterology 2024年第9期30卷 1213-1223页

作者： joseph Edwin Kanu Jonathan Soldera post Graduate program at Acute Medicine and Gastroenterology University of South WalesCardiff CF371DLUnited Kingdom

BACKGROUND Helicobacter pylori(***)infects over half the global population,causing gastrointestinal diseases like dyspepsia,gastritis,duodenitis,peptic ulcers,GMALT lymphoma,and gastric *** *** is crucial for treating and preventing these *** conventional proton pump inhibitor(ppI)-based triple therapy is effective,there’s growing interest in longer acid suppression *** competitive acid blocker(p-CAB)triple and dual therapy are new regimens for *** *** used in Asian populations,vonoprazan(VpZ)has been recently Food and Drug Administration-approved for *** *** To assess the efficacy of regimens containing p-CABs in eradicating *** *** This study,following pRISMA 2020 guidelines,conducted a systematic review and meta-analysis by searching MEDLINE and Scopus libraries for randomized clinical trials(RCTs)or observational studies with the following command:[("Helicobacter pylori"OR"H pylori")AND("Treatment"OR"Therapy"OR"Eradication")AND("Vonaprazan"OR"potassium-Competitive Acid Blocker"OR"p-CAB"OR"pCAB"OR"Revaprazan"OR"Linaprazan"OR"Soraprazan"OR"Tegoprazan")].Studies comparing the efficacy of p-CABs-based treatment to classical ppIs in eradicating *** were *** criteria included case reports,case series,unpublished trials,or conference *** variables encompassed age,diagnosis method,sample sizes,study duration,intervention and control,and *** eradication method were gathered by two independent ***-analysis was performed in R software,and forest plots were *** A total of 256 references were initially retrieved through the search ***,fifteen studies(7 RCTs,7 retrospective observational studies,and 1 comparative unique study)were included,comparing p-CAB triple therapy to ppI triple *** intention-to-treat analysis involved 8049 patients,with 4471 in the p-CAB intervention g

关键词： Helicobacter pylori infection potassium competitive acid blockers proton pump inhibitors Vonoprazan Amoxicillin

Stability and Time-Step Constraints of Implicit-Explicit Runge-Kutta Methods for the Linearized Korteweg-de Vries Equation

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Communications on Applied Mathematics and Computation 2024年第1期6卷 658-687页

作者： joseph Hunter Zheng Sun Yulong Xing Department of Mathematics The Ohio State UniversityColumbusOH43210USA Department of Mathematics The University of AlabamaTuscaloosaAL35487USA

This paper provides a study on the stability and time-step constraints of solving the linearized Korteweg-de Vries(KdV)equation,using implicit-explicit(IMEX)Runge-Kutta(RK)time integration methods combined with either finite difference(FD)or local discontinuous Galerkin(DG)spatial *** analyze the stability of the fully discrete scheme,on a uniform mesh with periodic boundary conditions,using the Fourier *** the linearized KdV equation,the IMEX schemes are stable under the standard Courant-Friedrichs-Lewy(CFL)conditionτ≤λ***,λis the CFL number,τis the time-step size,and h is the spatial mesh *** study several IMEX schemes and characterize their CFL number as a function ofθ=d/h^(2)with d being the dispersion coefficient,which leads to several interesting *** also investigate the asymptotic behaviors of the CFL number for sufficiently refined meshes and derive the necessary conditions for the asymptotic stability of the IMEX-RK *** numerical experiments are provided in the paper to illustrate the performance of IMEX methods under different time-step constraints.

关键词： Linearized Korteweg-de Vries(KdV)equation Implicit-explicit(IMEX)Runge-Kutta(RK)method Stability Courant-Friedrichs-Lewy(CFL)condition Finite difference(FD)method Local discontinuous Galerkin(DG)method

Wan-Yee joseph Lau:the promoter of modernization and internationalization of Chinese surgery

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Oncology and Translational Medicine 2024年第1期10卷 1-3页

作者： Wan-Yee joseph Lau Faculty of Medicine The Chinese University of Hong KongHong KongChina

To my knowledge,there have been 3 books[1–3]and 2 book chapters written about me.[4–5]For those who are interested in the details of my life,please refer to these books/book *** title of this article is an English translation of the title of the book I refer to as reference 1,which I find appropriate to describe the role that I play in China.

关键词： please details translation

Monogenic diabetes in children:An underdiagnosed and poorly managed clinical dilemma

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World Journal of Diabetes 2024年第6期15卷 1051-1059页

作者： Saptarshi Bhattacharya joseph M pappachan Department of Endocrinology Indraprastha Apollo HospitalsDelhi 110076India Department of Endocrinology and Metabolism Lancashire Teaching Hospitals NHS TrustPreston PR29HTUnited Kingdom Faculty of Science Manchester Metropolitan UniversityManchester M156BHUnited Kingdom Faculty of Biology Medicine and HealthThe University of ManchesterManchester M139PLUnited Kingdom

Monogenic diabetes,constituting 1%-2%of global diabetes cases,arises from single gene defects with distinctive inheritance *** over 50 associated genetic disorders,accurate diagnoses and management of monogenic diabetes remain inadequate,underscoring insufficient clinician *** disease spectrum encompasses maturity-onset diabetes of the young(MODY),characterized by distinct genetic mutations affecting insulin secretion,and neonatal diabetes mellitus(NDM)-a heterogeneous group of severe hyperglycemic disorders in *** diabetes,autoimmune monogenic diabetes,genetic insulin resistance and lipodystrophy syndromes further diversify the monogenic diabetes landscape.A tailored approach based on phenotypic and biochemical factors to identify candidates for genetic screening is recommended for suspected cases of *** diagnosis warrants immediate molecular genetic testing for infants under six *** these genetic defects presents a unique opportunity for precision *** research aimed to develop cost-effective genetic testing methods and gene-based therapy can facilitate appropriate identification and optimize clinical *** and study of new genes offer a valuable opportunity to gain deeper insights into pancreatic cell biology and the pathogenic mechanisms underlying common forms of *** clinical review published in the recent issue of World Journal of Diabetes is such an attempt to fill-in our knowledge gap about this enigmatic disease.

关键词： Monogenic diabetes Maturity-onset diabetes of the young Neonatal diabetes Mitochondrial diabetes Insulin resistance syndromes Genetic testing Next generation sequencing

periodontitis:An often-neglected complication of diabetes

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World Journal of Diabetes 2024年第3期15卷 318-325页

作者： Marina G Kudiyirickal joseph M pappachan primary Care Dental practice The Smile ClinicPreston PR16PZUnited Kingdom Department of Endocrinology and Metabolism Lancashire Teaching Hospitals NHS TrustPreston PR29HTUnited Kingdom Faculty of Science Manchester Metropolitan UniversityManchester M156BHUnited Kingdom Faculty of Biology Medicine and HealthThe University of ManchesterManchester M139PLUnited Kingdom

The bidirectional association between type 2 diabetes mellitus(T2DM)and periodontitis is now well established,resulting in periodontal disease being considered as the 6th major complication of diabetes mellitus(DM)after cardiovascular disease,eye disease,neuropathy,nephropathy,and peripheral vascular *** can worsen the virulence and invasiveness of pathogenic oral microbial flora aggravating the local inflammation and infection in those with periodontal *** the other hand,the chemical and immunological mediators released into the circulation as part of periodontal inflammation worsen the systemic insulin resistance with worsening of *** if undiagnosed or left untreated can also result in eventual tooth loss.A study by Xu et al in the World Journal of Diabetes examined the predictive factors associated with periodontitis in Chinese patients with *** prevalence of periodontitis was found to be 75.7%in this *** on logistic regression analysis,the predictive factors for higher risk were low tooth brushing frequency[odds ratio(OR)=4.3],high triglycerides(TG;OR=3.31),high total cholesterol(TC;OR=2.87),higher glycated hemoglobin(HbA1c;OR=2.55),and higher age(OR=1.05)while higher education level was protective(OR=0.53).However,the most influential variables were HbA1c followed by age,TC,TG,low education level,brushing frequency,and sex on the random forest model(this model showed higher sensitivity for predicting the risk).A good understanding of the predictors for periodontitis in T2DM patients is important in prevention,early detection of susceptible patients,and intervention to improve periodontal health and enable long-term glycaemic control as observed by Xu et al.

关键词： Diabetes mellitus periodontitis predictive factors Cardiovascular disease Glycaemic control