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Redefinition of Fatty Liver disease from NAFLd to MAFLd through the Lens of drug development and Regulatory Science

Journal of Clinical and Translational Hepatology 2022年第2期10卷 374-382页

作者： Yasser Fouad Melissa Palmer Minjun Chen Arie Regev Rajarshi Banerjee Rob Myers Robert Riccio Richard Torstenson Ramy Younes Puneet SArora Henrik Landgren Morten A.Karsdal Martin Blake david A.Shapiro Hans-Juergen Gruss Muhammad Y.Sheikh dina Attia Steven Bollipo alastair d.smith Bradley Freilich Robert G.Gish detlef Schuppan department of Gastroenterology Hepatologyand Endemic MedicineFaculty of MedicineMinia UniversityMiniaEgypt Gan-nex/Ascletis Pharma Co Ltd BeijingChina Liver Consulting LLC New YorkNYUSA division of Bioinformatics and Biostatis-tics National Center for Toxicological ResearchUS Food and Drug AdministrationJeffersonARUSA Eli Lilly and Company IndianapolisINUSA Perspectum diagnostics Ltd OxfordUK Gilead Sciences Inc Foster CityCAUSA Syneos Health LLC MorrisvilleNCUSA Allergan Marlow International BuckinghamshireUKAstraZenecaCambridgeUK Boehringer Ingel-heim International GmbHIngelheimGermany Genentech IncSouth San FranciscoCAUSA AbbVie MarlowBuck-inghamshireUK Nordic Bioscience A/S HerlevDenmark Resonance Health BurswoodWAAustralia Intercept Phar-maceuticals Inc San DiegoCAUSA Fresno Clinical Research Center FresnoCAUSA Gastroenterology and Hepatology department Beni-Suef UniversityBeni SuefEgypt department of Gastroenterology and Endoscopy John Hunter HospitalNewcastleNSWAustralia School of Medicine and Public Health University of NewcastleNewcastleNSWAustralia Kan-sas City Research Institute Kansas CityMOUSA division of Gastroenterology and Hepatology Loma Linda UniversityLoma LindaCAUSA Institute of Translational Immunology and Research Center for Immune Therapy University Medical CenterMainzGermany division of Gastroenterology Beth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMAUSA

Metabolic(dysfunction)-associated fatty liver disease(MAFLd)affects a third of the population and is a leading cause of liver-related *** no effective treatments exist,novel approaches to drug development are ***,outdated terminology and definitions of the disease are hampering efforts to develop new drugs and *** international consensus panel has put forth an influential proposal for the disease to be renamed from nonalcoholic fatty liver disease(NAFLd)to MAFLd,includ-ing a proposal for how the disease should be *** allies with the many stakeholders in MAFLd care―including patients,patients’advocates,clinicians,researchers,nurse and allied health groups,regional societies,and others―we are aware of the negative consequences of the NAFLd term and *** share the sense of urgency for change and will act in new ways to achieve our *** there is much work to be done to overcome clinical inertia and reverse worrisome recent trends,the MAFLd initiative provides a firm foundation to build *** provides a roadmap for moving for-ward toward more efficient care and affordable,sustainable drug and device innovation in MAFLd *** hope it will bring promising new opportunities for a brighter future for MAFLd care and improve care and outcomes for patients of one of the globe’s largest and costliest public health *** this viewpoint,we have revisited this initiative through the perspectives of drug development and regulatory science.

关键词： NAFLd MAFLd NASH Fatty liver disease Liver Fibrosis

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Genotypic diversity of a dominant C_(4) grass across a long-term fire frequency gradient

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Journal of Plant Ecology 2013年第6期6卷 448-458页

作者： Cynthia C.Chang Melinda d.smith department of Ecology and Evolutionary Biology Yale UniversityNew HavenCT 06511USA department of Biology University of WashingtonSeattleWA 98195USA department of Biology Colorado State UniversityFort CollinsCO 80523USA

Aims and Methods diversity-disturbance research has focused on community diversity,but disturbance frequency could impact diversity within species as well,with important consequences for community diversity and ecosystem *** examined patterns of genetic diversity of a dominant grass species,Andropogon gerardii,in native North American tallgrass prairie sites located in eastern Kansas that have been subjected to a gradient of fire frequency treatments(burned every 1,2,4 or 20 years)since the *** addition,we were able to assess the relationships between genetic diversity of ***,species diversity and productivity across this range of fire *** Findings We found no significant relationships between genetic diversity of *** at the local scale(1 m^(2) plot level)and disturbance frequency(burned 2 to 32 times over a 38-year period).However,at the site level(*** all plots sampled within a site,~100 m^(2))there were differences in genotype richness and composition,as well as genomic dissimilarity among individuals of *** richness was greatest for the site burned at an intermediate(4-year)frequency and lowest for the infrequently(20-year)burned *** addition,genotypes found in the frequently burned sites were more similar from each other than expected by random chance than those found in the infrequently burned *** composition of *** was not significantly different between the frequently burned sites(annual vs.2 year)but did differ between frequently burned and infrequently burned sites(1 and 2 year vs.4 and 20 year,etc.).Together,these results suggest site-level ecological sorting of genotypes in intact prairie across a broad gradient of disturbance frequencies,likely driven by alterations in environmental *** fire promotes the abundance of dominant grass species,reduces plant community diversity and impacts ecosystem processes such as *** study suggests that

关键词： Andropogon gerardii disturbance frequency genetic relatedness genetic-species diversity relationship genotype richness intermediate disturbance hypothesis productivity tallgrass prairie

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Multiple sclerosis is at a checkpoint: advancing the program

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Neural Regeneration Research 2025年第3期20卷 811-812页

作者： Brandon C.smith Jessica L.Williams department of Neurosciences Lerner Research InstituteCleveland ClinicClevelandOHUSA department of Biological Geologicaland Environmental SciencesCleveland State UniversityClevelandOHUSA

Multiple sclerosis(MS) is a chronic inflammatory and demyelinating disease of the central nervous system(CNS). Patients with MS experience sensory and motor function loss due to myelin and/or axon damage perpetuated b... 详细信息

关键词： Hauser sclerosis damage

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Role of granulocyte macrophage colony stimulating factor in regeneration of the central nervous system

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Neural Regeneration Research 2016年第6期11卷 902-903页

作者： Ushananthini Shanmugalingam Nafisa M.Jadavji Patrice d.smith department of Neuroscience Carleton University

Traditionally,it has been thought that the mammalian central nervous system（CNS）does not *** due to the inhibitory extracellular environment post-injury as well as the limited intrinsic characteristics of adult post... 详细信息

关键词： granulocyte macrophage colony regeneration stimulating intrinsic Figure neuronal subunit glial

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Extracellular matrix synthesis in vascular disease:hypertension,and atherosclerosis

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The Journal of Biomedical Research 2014年第1期28卷 25-39页

作者： Markella Ponticos Barbara d.smith Centre for Rheumatology & Connective Tissue diseases Division of Medicine-InflammationRoyal Free & University College Medical SchoolUniversity College London department of Biochemistry Boston University School of Medicine

Extracellular matrix （ECM） within the vascular network provides both a structural and regulatory role. The ECM is a dynamic composite of multiple proteins that form structures connecting cells within the network. Blood vessels are distended by blood pressure and, therefore, require ECM components with elasticity yet with enough tensile strength to resist rupture. The ECM is involved in conducting mechanical signals to cells. Most importantly, ECM regulates cellular function through chemical signaling by controlling activation and bioavail- ability of the growth factors. Cells respond to ECM by remodeling their microenvironment which becomes dys- regulated in vascular diseases such hypertension, restenosis and atherosclerosis. This review examines the cellu- lar and ECM components of vessels, with specific emphasis on the regulation of collagen type I and implications in vascular disease.

关键词： extracellular matrix vascular disease

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Polyethylene glycol has immunoprotective effects on sciatic allografts, but behavioral recovery and graft tolerance require neurorrhaphy and axonal fusion

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Neural Regeneration Research 2025年第4期20卷 1192-1206页

作者： Tyler A.smith Liwen Zhou Cameron L.Ghergherehchi Michelle Mikesh Cathy Z.Yang Haley O.Tucker JuliAnne Allgood Jared S.Bushman George d.Bittner department of Molecular Biosciences University of Texas at AustinAustinTXUSA department of Neuroscience University of Texas at AustinAustinTXUSA division of Pharmaceutical Sciences University of WyomingLaramieWYUSA

Behavioral recovery using(viable)peripheral nerve allografts to repair ablation-type(segmental-loss)peripheral nerve injuries is delayed or poor due to slow and inaccurate axonal ***,such peripheral nerve allografts undergo immunological rejection by the host immune *** contrast,peripheral nerve injuries repaired by polyethylene glycol fusion of peripheral nerve allografts exhibit excellent behavioral recovery within weeks,reduced immune responses,and many axons do not undergo Wallerian *** relative contribution of neurorrhaphy and polyethylene glycol-fusion of axons versus the effects of polyethylene glycol per se was unknown prior to this *** hypothesized that polyethylene glycol might have some immune-protective effects,but polyethylene glycol-fusion was necessary to prevent Wallerian degeneration and functional/behavioral *** examined how polyethylene glycol solutions per se affect functional and behavioral recovery and peripheral nerve allograft morphological and immunological responses in the absence of polyethylene glycol-induced axonal ***-type sciatic nerve injuries in outbred Sprague–dawley rats were repaired according to a modified protocol using the same solutions as polyethylene glycol-fused peripheral nerve allografts,but peripheral nerve allografts were loose-sutured(loose-sutured polyethylene glycol)with an intentional gap of 1–2 mm to prevent fusion by polyethylene glycol of peripheral nerve allograft axons with host *** to negative control peripheral nerve allografts not treated by polyethylene glycol and in contrast to polyethylene glycol-fused peripheral nerve allografts,animals with loose-sutured polyethylene glycol peripheral nerve allografts exhibited Wallerian degeneration for all axons and myelin degeneration by 7 days postoperatively and did not recover sciatic-mediated behavioral functions by 42 days *** morphological signs of rejection,such as col

关键词： allograft rejection axotomy macrophage myelin nerve repair polyethylene glycol(PEG) sciatic nerve T cell transplantation Wallerian degeneration

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The pleiotropic effects of tissue plasminogen activator in the brain:implications for stroke recovery

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Neural Regeneration Research 2016年第9期11卷 1401-1402页

作者： Julia A.Grummisch Nafisa M.Jadavji Patrice d.smith department of Neuroscience Carleton University

Tissue plasminogen activator （tPA） use in the treatment of isch- emic stroke： tPA is a serine protease that catalyzes the breakdown of blood dots. Because of its thrombolytic properties, tPA is used to treat specific types of stroke, including ischemia, but is contra- indicated for treatment of hemorrhagic stroke or head trauma. Although a life saving and powerful ＇dot buster＇, tPA has a short therapeutic window. When administered outside of this prescribed timeframe, research suggests that tPA can produce neurotoxic ef- fects in the brain, due in part to activation of several signalling pro- cesses associated with cell apoptosis, degradation of the extracel- lular matrix, and increase in the permeability of the neurovascular unit （Yepes et al., 2009）. Concerted research has been dedicated to- ward understanding the mechanisms mediating the impact of tPA on the brain, using both in vivo and in vitro animal models.

关键词： The pleiotropic effects of tissue plasminogen activator in the brain PA

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The genetic framework for development of nephrolithiasis

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Asian Journal of Urology 2017年第1期4卷 18-26页

作者： Vinaya Vasudevan Patrick Samson Arthur d.smith Zeph Okeke smith Institute for Urology Hofstra Northwell School of MedicineLake SuccessNYUSA

Over 1%-15% of the population worldwide is affected by nephrolithiasis,which remains the most common and costly disease that urologists manage *** of atrisk individuals remains a theoretical and technological *** search for monogenic causes of stone disease has been largely unfruitful and a technological challenge;however,several candidate genes have been implicated in the development of *** this review,we will review current data on the genetic inheritance of stone disease,as well as investigate the evolving role of genetic analysis and counseling in the management of nephrolithiasis.

关键词： Genetics Hypercalciuria Nephrolithiasis Urolithiasis Calcium sensing receptor Cystinuria Medullary sponge kidney Autosomal dominant polcystic kidney disease Uric acid nephrolithiasis Hypercalciuria

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新型镍基高温合金在模拟燃煤锅炉环境中的腐蚀

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金属学报 2004年第6期40卷 659-663页

作者：赵双群谢锡善 Gaylord d.smith 北京科技大学高温合金研究室 Special Metals Corporation HuntingtonWV 25705USA

在人工合成的煤灰/烟气环境中研究了一种新型镍基高温合金550℃和700℃的腐蚀行为和腐蚀机理.结果表明,合金在550℃发生了不均匀的点蚀,表面形成了一层很薄的Cr_2O_3膜,腐蚀按照硫化机制发展.合金在700℃腐蚀时,初期发生了氧化和硫化腐... 详细信息

在人工合成的煤灰/烟气环境中研究了一种新型镍基高温合金550℃和700℃的腐蚀行为和腐蚀机理.结果表明,合金在550℃发生了不均匀的点蚀,表面形成了一层很薄的Cr_2O_3膜,腐蚀按照硫化机制发展.合金在700℃腐蚀时,初期发生了氧化和硫化腐蚀,表面生成了保护性的氧化膜,并有内硫化物析出.由于合金表面生成CoO并在表面形成熔融态硫酸盐而逐渐进入加速腐蚀阶段,使合金遭受严重的低温热腐蚀.腐蚀产物外层为疏松的混合尖晶石化合物,内层为致密的氧化物层,在腐蚀层、腐蚀层与基体界面和Cr元素贫化区内分布着硫化物.合金耐腐蚀性能的迅速退化是合金表面Co及其氧化物在混合熔盐中的溶解所致.

关键词：镍基高温合金煤灰/烟气低温热腐蚀腐蚀机制

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The effects of hazardous working conditions on burnout in Macao nurses

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International Journal of Nursing Sciences 2015年第1期2卷 86-92页

作者： Sydney X.Hu Andrew L.Luk Graeme d.smith The Kiang Wu Nursing College of Macao Macao SARPR China Nethersole Institute of Continuing Holistic Health Education Hong KongChina School of Nursing Midwifery&Social CareEdinburgh Napier UniversityUK

Objective:To examine the effects of various hazardous factors in working environments on burnout in a cohort of clinical nurses in ***:A cross-sectional survey was used to examine specific workplace hazards for burnout in qualified nurses(n=424)in *** equation modeling(SEM)was used to analyze relationships between specific hazards and manifestations of ***:In the final model,workplace hazards accounted for 73%of the variance of burnout with a standardized regression weight of *** measures of the model fit were *** hazards,threats of violence,and physical environmental hazards were found to significantly contribute to two major determinants of burnout,emotional exhaustion and ***:Workplace environmental hazards increased the risk of burnout amongst clinical nurses in *** management of these factors may help to protect nursing staff and reduce the risk of burnout and attrition from the nursing profession.

关键词： Nurses Hazardous work environments Burnout Stress

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