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出生前暴露于倍他米松是否对成年后的心理功能和健康相关生活质量产生不良影响

世界核心医学期刊文摘（妇产科学分册） 2006年第2期2卷 1-2页

作者： Dalziel S.R. lim v.k. Lambert A. J.E. Harding 丁福 Liggins Institute University of Auckland Auckland New Zealand

Objectives: To determine if antenatal exposure to betamethasone for the prevention of neonatal respiratory distress syndrome alters psychological functioning and health related quality of life in adulthood. Design: Follow-up of the first and largest double blind, placebo controlled, randomised trial of a single course of antenatal betamethasone for the prevention of neonatal respiratory distress syndrome. Setting: Tertiary obstetric hospital in Auckland, New Zealand. Participants: 192 adult offspring, mean age 31 years, of mothers who took part in a randomised controlled trial of antenatal betamethasone for the prevention of neonatal respiratory distress syndrome (87 exposed to betamethasone and 105 exposed to placebo). Interventions: Mothers received two doses of betamethasone or placebo 24 hours apart. Main outcome measures: Cognitive functioning assessed with Wechsler abbreviated scale of intelligence; working memory and attention assessed with Benton visual retention test, paced auditory serial addition test, and Brown attention deficit disorder scale; psychiatric morbidity assessed with Beck depression inventory II, state-trait anxiety inventory, and schizotypy traits questionnaire; handedness assessed with Edinburgh handedness inventory; health related quality of life assessed with short form 36 health survey. Results: No differences were found between groups exposed to betamethasone and placebo in cognitive functioning, working memory and attention, psychiatric morbidity, handedness, or health related quality of life. Conclusions: Prenatal exposure to a single course of betamethasone does not alter cognitive functioning, working memory and attention, psychiatric morbidity, handedness, or health related quality of life in adulthood. Obstetricians should continue to use a single course of antenatal betamethasone for the prevention of neonatal respiratory distress syndrome.

关键词：倍他米松生活质量心理功能出生前安慰剂对照认知功能注意力缺陷精神病态韦氏智力量表抑郁

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出生前使用倍他米松:纳入随机对照试验31年后的心理功能和健康相关生活质量

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世界核心医学期刊文摘（神经病学分册） 2006年第2期2卷 1-1页

作者： Dalziel S.R. lim v.k. Lambert A. J.E. Harding 郭俊 Liggins Institute University of Auckland Auckland New Zealand

Objectives: To determine if antenatal exposure to betamethasone for the prevention of neonatal respiratory distress syndrome alters psychological functioning and health related quality of life in adulthood. Design: Followup of the first and largest double blind, placebo controlled, randomised trial of a single course of antenatal betamethasone for the prevention of neonatal respiratory distress syndrome. Setting: Tertiary obstetric hospital in Auckland, New Zealand. Participants: 192 adult offspring, mean age 31 years, of mothers who took part in a randomised controlled trial of antenatal betamethasone for the prevention of neonatal respiratory distress syndrome (87 exposed to betamethasone and 105 exposed to placebo). Interventions: Mothers received two doses of betamethasone or placebo 24 hours apart. Main outcome measures: Cognitive functioning assessed with Wechsler abbreviated scale of intelligence; working memory and attention assessed with Benton visual retention test, paced auditory serial addition test, and Brown attention deficit disorder scale; psychiatric morbidity assessed with Beck depression inventory II, statetrait anxiety inventory, and schizotypy traits questionnaire; handedness assessed with Edinburgh handedness inventory; health related quality of life assessed with short form 36 health survey. Results: No differ ences were found between groups exposed to betamethasone and placebo in cognitiv e functioning, working memory and attention, psychiatric morbidity, handedness, or health related quality of life. Conclusions: Prenatal exposure to a single course of betamethasone does not alter cognitive functioning, working memory and attention, psychiatric morbidity, handedness, or health related quality of life in adulthood. Obstetricians should continue to use a single course of antenatal betamethasone for the prevention of neonatal respiratory distress syndrome.

关键词：健康相关生活质量随机对照试验倍他米松心理功能出生前新生儿呼吸窘迫综合征 1年后安慰剂对照预防药物受试者

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Bioorthogonal chemistry:a covalent strategy for the study of biological systems

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Science China Chemistry 2010年第1期53卷 61-70页

作者： lim Reyna k.v. Department of Chemistry State University of New York at Buffalo

The development of genetically encoded,wavelength-tunable fluorescent proteins has provided a powerful imaging tool to the study of protein dynamics and functions in cellular and organismal ***,many biological functions are not directly encoded in the protein primary sequence,e.g.,dynamic regulation afforded by protein posttranslational modifications such as *** meet this challenge,an emerging field of bioorthogonal chemistry has promised to offer a versatile strategy to selectively label a biomolecule of interest and track their dynamic regulations in its native *** strategy has been successfully applied to the studies of all classes of biomolecules in living systems,including proteins,nucleic acids,carbohydrates,and *** the incorporation of a bioorthogonal reporter site-selectively into a biomolecule through either genetic or metabolic approaches has been well established,the development of bioorthogonal reactions that allow fast ligation of exogenous chemical probes with the bioorthogonal reporter in living systems remains in its early ***,we review the recent development of bioorthogonal reactions and their applications in various biological systems,with a detailed discussion about our own work―the development of the tetrazole-based,photoinducible 1,3-dipolar cycloaddition reaction.

关键词： bioorthogonal reaction proteins biotechnology 1 3-dipolar cycloaddition click chemistry tetrazole

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An Immersed Interface Method for the Simulation of Inextensible Interfaces in viscous Fluids

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Communications in Computational Physics 2012年第3期11卷 925-950页

作者： Zhijun Tan D.v.Le k.M.lim B.C.khoo Guangdong Province key Laboratory of Computational Science&School of Mathematics and Computational Science Sun Yat-senUniversityGuangzhou 510275China Institute of High Performance Computing 1 Fusionopolis Way#16-16 ConnexisSingapore 138632Singapore Singapore-MIT Alliance 4 Engineering Drive 3National University of SingaporeSingapore 117576Singapore Department of Mechanical Engineering National University of Singapore10 Kent Ridge CrescentSingapore 119260Singapore

In this paper,an immersed interface method is presented to simulate the dynamics of inextensible interfaces in an incompressible *** tension is introduced as an augmented variable to satisfy the constraint of interface inextensibility,and the resulting augmented system is solved by the GMRES *** this work,the arclength of the interface is locally and globally conserved as the enclosed region undergoes *** forces at the interface are calculated from the configuration of the interface and the computed augmented variable,and then applied to the fluid through the related jump *** governing equations are discretized on a MAC grid via a second-order finite difference scheme which incorporates jump contributions and solved by the conjugate gradient Uzawa-type *** proposed method is applied to several examples including the deformation of a liquid capsule with inextensible interfaces in a shear *** results reveal that both the area enclosed by interface and arclength of interface are conserved well *** provide further evidence on the capability of the present method to simulate incompressible flows involving inextensible interfaces.

关键词： Inextensible interface Stokes flows singular force immersed interface method CGUzawa method front tracking

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Combination strategies for pharmacologic treatment of nonalcoholic steatohepatitis

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World Journal of Gastroenterology 2022年第35期28卷 5129-5140页

作者： Jaspreet Suri Sebastian Borja Joseph k lim Department of Gastroenterology Norwalk HospitalNorwalkCT 06856United States Department of Internal Medicine Norwalk HospitalNorwalkCT 06850United States Section of Digestive Diseases Yale University School of MedicineNew HavenCT 06520United States

Non-alcoholic steatohepatitis (NASH) is defined as hepatic steatosis, inflammation,and hepatocyte injury with or without fibrosis. It has emerged as thesecond leading indication for liver transplantation with a rising death rate in thenon-transplantable population. While there are many drugs in evaluation,currently no approved therapies are on the market for this condition. Given thisimportance, the Food and Drug Administration has provided formal guidanceregarding drug development for stopping or reversing NASH or NASH associatedfibrosis. The complex pathogenesis of NASH and its bidirectional relationshipwith metabolic syndrome has highlighted multiple drugs of interest thataddress metabolic, inflammatory, and fibrotic factors. A few promising liverspecific targets include farnesoid X receptor agonists and peroxisome proliferatoractivatedreceptor agonists. Previously studied drug classes such as glucagon-likepeptide-1 analogs or sodium/glucose transport protein 2 inhibitors have alsodemonstrated ability to improve hepatic steatosis. Here we discuss currentrationale, scientific work, and preliminary data in combining multiple drugs forthe purposes of a multimodal attack on the pathogenesis of NASH. We highlightmultiple Phase 2 and Phase 3 studies that demonstrate the potential to achieve aresponse rate higher than previously assessed monotherapies for this ***, one of these combination strategies may rise above in its safety andefficacy to become a part of a standardized approach to NASH.

关键词： Non-alcoholic steatohepatitis Fatty liver Combination treatment Drug therapy Pharmacologic treatment Clinical trials

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Unravelling the competitive effect of microstructural features on the fracture toughness and tensile properties of near beta titanium alloys

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Journal of Materials Science & Technology 2022年第2期97卷 101-112页

作者： Yang Liu Samuel C.v.lim Chen Ding Aijun Huang Matthew Weyland Department of Materials Science and Engineering Monash UniversityClaytonVIC3800Australia Monash Centre for Additive Manufacturing Monash UniversityNotting HillVIC3168Australia BAOWU Special Metallurgy Co.Ltd. Shanghai200940China Monash Centre for Electron Microscopy Monash UniversityClaytonVIC3800Australia

The competitive effect of microstructural features including primaryα(α_(p)),secondaryα(α_(s)),grain boundaryα(α_(GB)) and β grain size on mechanical properties of a near β Ti alloy were studied with two heat treatment *** relative effect of β grain size and STA(solution treatment and ageing)processing parameters on mechanical properties were quantitatively explored by the application of Taguchi *** results were further explained via correlating microstructure with the fracture toughness and tensile *** was found that large numbers of fine as precipitates and continuous α_(s) played greater roles than other features,resulting in a high strength and very low ductility(ve correlation with fracture *** the samples prepared by BASCA( β anneal slow cooling and ageing)process,improved ductility and fracture toughness were obtained due to a lower density ofα;precipitates,a basket-weave structure and zigzag morphology of α_(GB).For this heat treatment,an increase in prior β grain size had an observable positive effect on fracture *** contradictory effect of β grain size on fracture toughness found in literature was for the first time *** was shown that the microstructure obtained from different processes after β solution has complex effect on mechanical *** complexity derived from the competition between microstructure features and the overall sum of their effect on fracture toughness and tensile properties.A novel table was proposed to quasi-quantitatively unravel these competitive effects.

关键词： Nearβtitanium alloys Microstructural features Competitive effect Fracture toughness βgrain size effect

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Advances in discovery of novel investigational agents for functional cure of chronic hepatitis B:A comprehensive review of phases II and III therapeutic agents

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World Journal of Hepatology 2024年第3期16卷 331-343页

作者： Robert Lam Joseph k lim Section of Digestive Diseases Yale University School of MedicineNew HavenCT 06520United States

Chronic hepatitis B virus(HBv)infection affects over 295 million people globally and an estimated 1.6 million people in the United *** is associated with significant morbidity and mortality due to cirrhosis,liver failure,and liver *** therapy with oral nucleos(t)ide analogues is associated with high rates of virologic suppression,which in turn has been associated with a decreased risk of liver ***,current antiviral regimens are limited by concerns with adverse effects,adherence,resistance,long-term treatment,and ongoing risk for liver *** investigational agents are currently in development and are targeted at achieving functional cure with sustained hepatitis B surface antigen(HBsAg)loss and suppression of HBv *** we review key evidence from phases II and III trials defining the efficacy and safety profiles for key investigational agents for functional cure of chronic hepatitis B,including core/capsid inhibitors,entry inhibitors,RNA interference(siRNA/ASO),HBsAg inhibitors,Toll-like receptor agonists,checkpoint inhibitors,and therapeutic vaccines.

关键词： Hepatitis B virus Treatment Clinical trials RNA interference Entry inhibitors Core inhibitors Immunomodulators

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Nanocellulose,a versatile platform:From the delivery of active molecules to tissue engineering applications

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Bioactive Materials 2022年第3期7卷 566-589页

作者： Tejal v.Patil Dinesh k.Patel Sayan Deb Dutta keya Ganguly Tuhin Subhra Santra ki-Taek lim Department of Biosystems Engineering Institute of Forest ScienceKangwon National UniversityChuncheon24341Republic of Korea Interdisciplinary Program in Smart Agriculture Kangwon National UniversityChuncheon24341Republic of Korea Deptarment of Engineering Design Indian Institute of TechnologyMadras600036India

Nanocellulose,a biopolymer,has received wide attention from researchers owing to its superior physicochemical properties,such as high mechanical strength,low density,biodegradability,and *** can be extracted from wide range of sources,including plants,bacteria,and *** on the extraction process and dimensions(diameter and length),they are categorized into three main types:cellulose nanocrystals(CNCs),cellulose nanofibrils(CNFs),and bacterial nanocellulose(BNC).CNCs are a highly crystalline and needle-like structure,whereas CNFs have both amorphous and crystalline regions in their *** is the purest form of *** nanocellulose properties can be tuned by chemical functionalization,which increases its applicability in biomedical *** review highlights the fabrication of different surface-modified nanocellulose to deliver active molecules,such as drugs,proteins,and ***-mediated delivery of active molecules is profoundly affected by its topographical structure and the interaction between the loaded molecules and *** applications of nanocellulose and its composites in tissue engineering have been ***,the review is concluded with further opportunities and challenges in nanocellulose-mediated delivery of active molecules.

关键词： Nanocellulose Chemical functionalization Drug delivery Protein delivery Plasmid delivery Tissue engineering

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Hepatocellular carcinoma in patients with non-alcoholic fatty liver disease

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World Journal of Gastroenterology 2016年第37期22卷 8294-8303页

作者： Carrie R Wong Mindie H Nguyen Joseph k lim Department of Internal Medicine Yale University School of Medicine Division of Gastroenterology and Hepatology Stanford University School of Medicine Yale Liver Center Section of Digestive Diseases Yale University School of Medicine

Nonalcoholic fatty liver disease(NAFLD) is the most common chronic liver disease in the United States and represents an increasingly important etiology of hepatocellular carcinoma(HCC) with annual cumulative incidence rates ranging from 2% to 12% in cohorts of NAFLD cirrhosis. While the risk of progression of NAFLD to HCC remains higher among patients with fibrosis or cirrhosis, an increasing amount of literature describes NAFLD-HCC as a disease that can occur in the absence of cirrhosis. Efforts to characterize the pathogenesis of NAFLD-HCC have suggested mechanisms that strongly associate with states of hyperinsulinemia and chronic inflammation, cellular mechanisms including adaptive immune responses and hepatic progenitor cell populations, and genetic polymorphisms including mutations of PNPLA3. Current literature describes NAFLD-HCC mostly as a disease of late presentation with lower rates of receipt of curative therapy and worse prognosis. However, a growing body of evidence has reported comparable and potentially more favorable disease-free and overall survival rates among patients with NAFLD-HCC after receipt of curative treatment. This review summarizes current evidence of epidemiology, pathophysiology, disease presentation, demand and receipt of curative therapy, post-treatment outcomes, and overall survival of NAFLD-associated HCC.

关键词： Fatty liver Nonalcoholic steatohepatitis Hepatocellular carcinoma Liver cirrhosis Liver cancer

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Broadband strong optical dichroism in topological Dirac semimetals with Fermi velocity anisotropy

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Chinese Physics B 2020年第7期29卷 128-134页

作者： J lim k J A Ooi C Zhang L k Ang Yee Sin Ang Science Math and TechnologySingapore University of Technology and DesignSingapore School of Energy and Chemical Engineering Xiamen University MalaysiaSelangor Darul Ehsan 43900Malaysia College of Chemistry and Chemical Engineering Xiamen UniversityXiamen 361005China School of Physics University of WollongongNorthfields AvenueNew South Wales 2522Australia

Prototypical three-dimensional(3D)topological Dirac semimetals(DSMs),such as Cd3As2 and Na3Bi,contain electrons that obey a linear momentum-energy dispersion with different Fermi velocities along the three orthogonal momentum *** being extensively studied in recent years,the inherent Fermi velocity anisotropy has often been neglected in the theoretical and numerical studies of 3D *** this omission does not qualitatively alter the physics of light-driven massless quasiparticles in 3D DSMs,it does quantitatively change the optical coefficients which can lead to nontrivial implications in terms of nanophotonics and plasmonics *** we study the linear optical response of 3D DSMs for general Fermi velocity values along each *** the signature conductivity-frequency scaling,σ(ω)∝ω,of 3D Dirac fermion is well-protected from the Fermi velocity anisotropy,the linear optical response exhibits strong linear dichroism as captured by the universal extinction ratio scaling law,Λi j=(vi/v j)^2(where i=j denotes the three spatial coordinates x,y,z,and vi is the i-direction Fermi velocity),which is independent of frequency,temperature,doping,and carrier scattering *** Cd3As2 and Na3Bi3,an exceptionally strong extinction ratio larger than 15 and covering a broad terahertz window is *** findings shed new light on the role of Fermi velocity anisotropy in the optical response of Dirac semimetals and open up novel polarization-sensitive functionalities,such as photodetection and light modulation.

关键词： topological Dirac semimetal optical anisotropy linear dichroismn linear response theory

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