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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and is a leading cause of liver-related *** no effective treatments exist,novel approaches to drug development are ***,outdated terminology and definitions of the disease are hampering efforts to develop new drugs and *** international consensus panel has put forth an influential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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Recent Developments in Metallic Degradable Micromotors for Biomedical and Environmental Remediation Applications

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Nano-Micro Letters 2024年第3期16卷 1-35页

作者： Sourav Dutta Seungmin Noh Roger Sanchis Gual Xiangzhong Chen Salvador Pané bradley J.Nelson Hongsoo Choi Department of Robotics and Mechatronics Engineering Daegu Gyeongbuk Institute of Science and Technology(DGIST)Daegu 42988Republic of Korea DGIST‑ETH Microrobotics Research Center DGISTDaegu 42988Republic of Korea Multi‑Scale Robotics Lab Institute of Robotics and Intelligent SystemsETH Zurich8092 ZurichSwitzerland Institute of Optoelectronics State Key Laboratory of Photovoltaic Science and TechnologyShanghai Frontiers Science Research Base of Intelligent Optoelectronics and PerceptionFudan UniversityShanghai 200433People’s Republic of China

Synthetic micromotor has gained substantial attention in biomedicine and environmental ***-based degradable micromotor composed of magnesium(Mg),zinc(Zn),and iron(Fe)have promise due to their nontoxic fuel-free propulsion,favorable biocompatibility,and safe excretion of degradation products Recent advances in degradable metallic micromotor have shown their fast movement in complex biological media,efficient cargo delivery and favorable biocompatibility.A noteworthy number of degradable metal-based micromotors employ bubble propulsion,utilizing water as fuel to generate hydrogen *** novel feature has projected degradable metallic micromotors for active in vivo drug delivery *** addition,understanding the degradation mechanism of these micromotors is also a key parameter for their design and *** propulsion efficiency and life span govern the overall performance of a degradable metallic *** we review the design and recent advancements of metallic degradable ***,we describe the controlled degradation,efficient in vivo drug delivery,and built-in acid neutralization capabilities of degradable micromotors with versatile biomedical ***,we discuss micromotors’efficacy in detecting and destroying environmental ***,we address the limitations and future research directions of degradable metallic micromotors.

关键词： Magnesium Zinc Iron Biodegradable microrobot Biomedical Environmental

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Influence of previous plane of nutrition on molecular mechanisms regulating the expression of urea and water metabolism related genes in the rumen and kidney of finishing crossbred Angus steers

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Animal Nutrition 2024年第2期17卷 232-243页

作者： Aghata E.Moreira da Silva Arturo Macias Franco bradley S.Ferguson Mozart A.Fonseca College of Agriculture Biotechnology&Natural Resources University of Nevada Department of Animal and Range Sciences Clayton Livestock Research Center New Mexico State University

This study aimed to understand how molecular mechanisms controlling water and urea metabolism at the finishing phase can be affected by previous plane of nutrition of crossbred Angus beef steers. Twentyfour(n = 24) animals were randomly distributed into either a moderate(MP) or high plane of nutrition during the background phase for 85 d. Animals were then blocked by their previous plane and were moved onto a 105-d finishing phase in a 2 × 2 factorial arrangement. The forage-finished group received only high-quality alfalfa hay, whereas the grain-fed group received a high grain diet(80% whole corn and20% alfalfa hay). By the end of the finishing phase, animals were harvested and tissue samples from the rumen and kidney were collected. Changes in gene expression of aquaporins(AQP)-2,-3,-4,-7, ATP1A1,ATP1B1, SGK1, CLIC1(kidney and rumen), UT-A1(kidney only) and UT-B(rumen only), were assayed via real-time q PCR; 18S r RNA was used as an endogenous control. One-way ANOVA followed by Tukey's post hoc analysis was conducted. When animals were from MP, forage-finishing increased the relative abundance of AQP3(P ≤ 0.05), AQP7(P ≤ 0.05), ATP1B1(P ≤ 0.05), and SGK1(P ≤ 0.05) in the kidney when compared to grain-fed animals. In the rumen, for the MP group, AQP7 was differentially expressed in both treatments at the finishing phase(P ≤ 0.01), with forage-finished steers having the highest expression of AQP7. For the MP group, UT-B had a tendency of presenting a higher expression on grainfed animals(P = 0.075). Overall, these results suggest that previous plane can impact expression of genes associated with water and urea metabolism during the finishing phase, namely AQP3, AQP7, ATP1B1, and SGK1 in the kidney, and AQP7 and UT-B in the rumen. The greatest impact observed on gene expression changes of investigated genes at the finishing phase was reflective of animals backgrounded on the moderate previous plane.

关键词： Gene expression Aquaporin Sodium channel Urea transporter

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Spreadability of powders for additive manufacturing:A critical review of metrics and characterisation methods

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Particuology 2024年第10期93卷 211-234页

作者： Fatemeh A.Talebi Zobaideh Haydari Hamid Salehi Mozhdeh Mehrabi Jabbar Gardy Mike bradley Andrew E.Bayly Ali Hassanpour School of Chemical and Process Engineering University of LeedsLeedsLS29JTUK School of Engineering University of GreenwichGreenwichME44TBUK Cormica Limited Listerhills Science ParkCampus RoadBradfordBD71HRUK

Powder bed fusion methods of additive manufacturing (AM) require consistent, reproducible, and uniform layers of powder for the reliable production of high-quality parts, where properties of powder are central to achieving this. Among these properties, powder flowability and spreadability play critical roles in determining the quality of these powder *** extensive research has been conducted on powder flow and spreading behaviour, and on their characterisation, there is little critical comparison and review of these terms in the context of AM. Such a review is necessary to further develop and enhance our comprehension of spreading dynamics and its relation to powder properties in AM *** review paper aims to build a coherent understanding of the correlation between powder characteristics and spreading in powder based additive manufacturing and its impact on manufactured parts. It highlights the current progress in comprehending spreading dynamics, the influence of powder characteristics, environmental conditions, spreading system, and the development of testing tools to assess powder spreadability. Furthermore, the paper critically discusses the challenge of finding appropriate quantitative metrics and recent advances in the use of standardised methods for evaluating powder spreadability.

关键词： Powder spreading Powder flowability Powder properties Quality of layer and final products

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代偿性或失代偿性肝硬化的慢性丙肝患者接受以索磷布韦为基础的治疗方案后的长期临床结局随访

代偿性或失代偿性肝硬化的慢性丙肝患者接受以索磷布韦为基础的治...

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第九届全国疑难及重症肝病大会

作者： Alexander Thompson Maria Buti bradley freilich Michael P.Curry Andrew J.Muir Kathryn Kersey Joe Llewellyn Diana M.Brainard

背景和目的:直接抗病毒药物(DAA)在治疗慢性丙型肝炎方面有重大突破。虽然现在大多数患者都可能实现持续病毒学应答(SVR),但是仍然需要关于长期病毒学和临床结局的数据。最近一项报告建议,DAA治疗成功后,HCC的发病率可能不会降低。这项...

背景和目的:直接抗病毒药物(DAA)在治疗慢性丙型肝炎方面有重大突破。虽然现在大多数患者都可能实现持续病毒学应答(SVR),但是仍然需要关于长期病毒学和临床结局的数据。最近一项报告建议,DAA治疗成功后,HCC的发病率可能不会降低。这项正在进行的注册研究的目的是评估接受以索磷布韦(SOF)为基础的治疗方案后实现SVR的肝硬化患者的长期临床结局。

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Surgeon preferences in the treatment of thumb carpometacarpal osteoarthritis

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World Journal of Orthopedics 2024年第5期15卷 435-443页

作者： Edward J Wu bradley W Fossum Wyatt Vander Voort Christopher O Bayne Robert M Szabo Department of Orthopedic Surgery University of Minnesota Medical SchoolMinneapolisMN 55455United States Department of Orthopaedic Surgery UC Davis School of MedicineSacramentoCA 95817United States

BACKGROUND Primary thumb carpometacarpal(CMC)osteoarthritis is one of the most common conditions encountered by hand *** the vast number of operations that have been proposed,none have demonstrated results significantly superior to trapeziectomy *** The purpose of our study was to determine why surgeons opt for their technique in treating CMC *** A cross-sectional survey of active members of the American Society for Surgery of the Hand was conducted to evaluate the reasons behind their preferred technique in the treatment of isolated thumb CMC *** were contacted by email once and provided with a link to a de-identified survey consisting of 5 treatment questions and 5 demographic *** Of 950 responses were received.40.5%of surgeons preferred trapeziectomy+ligament reconstruction tendon interposition(LRTI),followed by trapeziectomy+suspensionplasty(28.2%),suture button suspension(5.9%),trapeziectomy alone(4.6%),prosthetic arthroplasty(3.2%),arthrodesis(1.1%),and other(6.6%).Proponents of trapeziectomy+LRTI cited familiarity(73.2%),exposure during fellowship(48.8%)and less proximal migration(60%)to be the main reasons affecting their *** who preferred trapeziectomy+suspensionplasty most reported simplicity(74.9%),fewer complications(45.3%),less proximal migration(43.8%),and avoidance of autogenous tissue harvest(42.7%).Advocates of suture button suspension cited avoidance of autogenous tissue harvest(80.4%),shorter immobilization(76.8%),and quicker recovery(73.2%)with their *** of trapeziectomy alone cited simplicity(97.7%),fewer complications(86.4%),and avoidance of autogenous tissue harvest(59.1%).In their comments,45%of surgeons choosing trapeziectomy alone cited evidence as an additional *** of prosthetic arthroplasty cited improved pinch strength(83.3%)and improved range of motion(63.3%),while those preferring arthrodesis cited better pinch strength(90%)and freque

关键词： Thumb carpometacarpal Osteoarthritis Trapeziectomy Ligament reconstruction tendon interposition Suspensionplasty Preferences Trends

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基于丙烯酸-N-琥珀酰亚胺酯共聚物交联剂的壳聚糖水凝胶的生物相容性研究

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材料导报 2024年第12期38卷 234-243页

作者：杨水艳盛扬孙一新蔡仁钦 Mark bradley 张嵘常州大学材料科学与工程学院江苏常州213164 大博医疗科技有限公司基础研究院福建厦门361026 英国爱丁堡大学化学学院英国爱丁堡EH93JJ

壳聚糖作为一种天然的氨基多糖,拥有良好的生物相容性和资源可再生性,但是较差的力学性能限制了其更广泛的应用。本研究以丙烯酸、N-乙烯基吡咯烷酮和丙烯酸-N-琥珀酰亚胺酯为单体聚合得到三元共聚物大分子交联剂,然后将其与壳聚糖溶液... 详细信息

壳聚糖作为一种天然的氨基多糖,拥有良好的生物相容性和资源可再生性,但是较差的力学性能限制了其更广泛的应用。本研究以丙烯酸、N-乙烯基吡咯烷酮和丙烯酸-N-琥珀酰亚胺酯为单体聚合得到三元共聚物大分子交联剂,然后将其与壳聚糖溶液混合后制备壳聚糖水凝胶。采用红外、热重、SEM等对合成的聚合物及壳聚糖凝胶的组成、形貌和热稳定性进行了表征。结果表明,丙烯酸-N-琥珀酰亚胺酯共聚物的数均分子量为111900,具有一定的水溶性,与壳聚糖形成的水凝胶有良好的力学性能、溶胀性能和水蒸气渗透速率。在PBS(pH=7.4)中交联的凝胶膜与酸性条件下制备的凝胶膜相比,热分解温度提高,水接触角变大,力学性能得到较大提升。细胞毒性实验表明壳聚糖凝胶有良好的生物相容性,人脂肪干细胞在壳聚糖凝胶膜上会形成细胞簇并分泌外泌体。将壳聚糖凝胶膜覆盖在脂肪干细胞上,细胞能正常生长并分泌外泌体。因此,壳聚糖凝胶具有负载外泌体后应用于皮肤敷料的潜力。

关键词：壳聚糖丙烯酸-N-琥珀酰亚胺酯水凝胶外泌体

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Post-operative protein supplementation following orthopaedic surgery: A systematic review

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Sports Medicine and Health Science 2024年第1期6卷 16-24页

作者： Andrew George Brendan M.Holderread bradley S.Lambert Joshua D.Harris Patrick C.McCulloch Houston Methodist Orthopedics and Sports Medicine 6445 Main Street Suite 2300HoustonTX77030USA Houston Methodist Orthopedic Biomechanics Research Laboratory 6670 Bertner AveHoustonTX77030USA

Decreased mechanical loading after orthopaedic surgery predisposes patients to develop muscle *** purpose of this review was to assess whether the evidence supports oral protein supplementation can help decrease postoperative muscle atrophy and/or improve patient outcomes following orthopaedic surgery.A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and MetaAnalysis(PRISMA).PubMed(MEDLINE),Embase,Scopus,and Web of Science were searched for randomized controlled trials that assessed protein or amino acid supplementation in patients undergoing orthopaedic *** investigators independently conducted the search using relevant Boolean *** outcomes included functional or physiologic measures of muscle atrophy or *** studies including 611 patients(224 males,387 females)were *** studies evaluated protein supplementation after ACL reconstruction(ACLR),3 after total hip arthroplasty(THA),5 after total knee arthroplasty(TKA),and 3 after surgical treatment of hip *** supplementation showed beneficial effects across all types of *** primary benefit was a decrease in muscle atrophy compared to placebo as measured by muscle cross sectional *** authors also demonstrated improved functional measures and quicker achievement of rehabilitation *** supplementation has beneficial effects on mitigating muscle atrophy in the postoperative period following ACLR,THA,TKA,and surgical treatment of hip *** effects often correlate with improved functional measures and quicker achievement of rehabilitation *** research is needed to evaluate long-term effects of protein supplementation and to establish standardized population-specific regimens that maximize treatment efficacy in the postoperative period.

关键词： Orthopaedic surgery Protein supplementation Systematic review Muscle atrophy

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Long-term olfactory loss post-COVID-19:Pathobiology and potential therapeutic strategies

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World Journal of Otorhinolaryngology-Head and Neck Surgery 2024年第2期10卷 148-155页

作者： Sarah Kim John B.Finlay Tiffany Ko bradley J.Goldstein Department of Head and Neck Surgery&Communication Sciences Duke UniversityDurhamNorth CarolinaUSA Medical Scientist Training Program Duke UniversityDurhamNorth CarolinaUSA Department of Neurobiology Duke UniversityDurhamNorth CarolinaUSA

An acute loss of smell emerged as a striking symptom present in roughly half of the people infected with the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)virus in the early phases of the COVID-19 *** most COVID-19 patients,olfaction recovers over the course of a few ***,a lasting partial or complete loss of smell,often associated with distorted olfactory perceptions termed parosmia,has emerged as a widespread problem impacting at least 5%-10%of those who experience anosmia due to *** inability to offer effective therapies to this hyposmic or anosmic population,comprising millions of patients,highlights an enormous unmet need for the medical ***,we summarize the current understanding of the pathobiology causing acute olfactory loss due to SARS-CoV-2 infection,focusing on how the virus interacts with the peripheral olfactory system,a major site of viral *** also explore the problem of long-COVID olfactory dysfunction,which may accompany other persistent systemic disorders collectively termed postacute sequelae of ***,we discuss an emerging model focused on unresolved immune cell activity driving ongoing ***,we review current and future therapeutic approaches aimed at restoring olfactory function.

关键词： hyposmia inflammation long-COVID parosmia

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新奥尔良当代艺术中心共享办公室美国新奥尔良

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世界建筑导报 2024年第1期39卷 74-78页

作者：无 Neil Alexander(摄影) Sara Essex bradley(摄影) EDR建筑事务所不详

The Shop是一个综合的联合办公项目,位于新奥尔良市中心,坐落在新奥尔良市当代艺术中心(CAC)的三层和四层。面向科技、艺术和文化事业,The Shop成为发展中的创新工业的创业者中心。这座历史悠久的建筑之前被用做K&B的总部和一个杂货冷饮... 详细信息

The Shop是一个综合的联合办公项目,位于新奥尔良市中心,坐落在新奥尔良市当代艺术中心(CAC)的三层和四层。面向科技、艺术和文化事业,The Shop成为发展中的创新工业的创业者中心。这座历史悠久的建筑之前被用做K&B的总部和一个杂货冷饮店,70年代中期被用作当代艺术中心。顶部两层在过去40年中一直没有被充分利用,The Shop的开发标志着对这一空间的第一次大规模整修。

关键词：联合办公当代艺术中心新奥尔良市美国新奥尔良 Shop 冷饮店办公室杂货

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