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Effects of SARS-CoV-2 infection on incidence and treatment strategies of hepatocellular carcinoma in people with chronic liver disease

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World Journal of Hepatology 2024年第2期16卷 211-228页

作者： Lung-Yi Mak Matthew Shing Hin Chung Xue Li francisco tsz tsun lai Eric Yuk Fai Wan Celine Sze Ling Chui Franco Wing Tak Cheng Esther Wai Yin Chan Ching Lung Cheung Ivan Chi Ho Au Xi Xiong Wai-Kay Seto Man-Fung Yuen Carlos King Ho Wong Ian Chi Kei Wong Department of Medicine The University of Hong KongHong KongChina State Key Laboratory of Liver Research The University of Hong KongHong KongChina Department of Pharmacology and Pharmacy The University of Hong KongHong KongChina Laboratory of Data Discovery for Health(D24H) Hong Kong Science and Technology ParkHong KongChina Department of Family Medicine and Primary Care The University of Hong KongHong KongChina School of Nursing The University of Hong KongHong KongChina School of Public Health The University of Hong KongHong KongChina Research Department of Practice and Policy University College LondonLondon WC1E 6BTUnited Kingdom Aston School of Pharmacy Aston UniversityBirmingham B47ETUnited Kingdom

BACKGROUND Chronic liver disease(CLD)was associated with adverse clinical outcomes among people with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)*** To determine the effects of SARS-CoV-2 infection on the incidence and treatment strategy of hepatocellular carcinoma(HCC)among patients with *** A retrospective,territory-wide cohort of CLD patients was identified from an electronic health database in Hong *** with confirmed SARS-CoV-2 infection[coronavirus disease 2019(COVID-19)+CLD]between January 1,2020 and October 25,2022 were identified and matched 1:1 by propensity-score with those without(COVID-19-CLD).Each patient was followed up until death,outcome event,or November 15,*** outcome was incidence of *** outcomes included all-cause mortality,adverse hepatic outcomes,and different treatment strategies to HCC(curative,non-curative treatment,and palliative care).Analyses were further stratified by acute(within 20 d)and post-acute(21 d or beyond)phases of SARS-CoV-2 *** rate ratios(IRRs)were estimated by Poisson regression *** Of 193589 CLD patients(>95%non-cirrhotic)in the cohort,55163 patients with COVID-19+CLD and 55163 patients with COVID-19-CLD were included after 1:1 propensity-score *** 249-d median follow-up,COVID-19+CLD was not associated with increased risk of incident HCC(IRR:1.19,95%CI:0.99-1.42,P=0.06),but higher risks of receiving palliative care for HCC(IRR:1.60,95%CI:1.46-1.75,P<0.001),compared to *** both acute and post-acute phases of infection,COVID-19+CLD were associated with increased risks of allcause mortality(acute:IRR:7.06,95%CI:5.78-8.63,P<0.001;post-acute:IRR:1.24,95%CI:1.14-1.36,P<0.001)and adverse hepatic outcomes(acute:IRR:1.98,95%CI:1.79-2.18,P<0.001;post-acute:IRR:1.24,95%CI:1.13-1.35,P<0.001),compared to *** Although CLD patients with SARS-CoV-2 infection were not associated with increased risk of HCC,they

关键词： SARS-CoV-2 infection Chronic liver disease Long COVID Post-COVID-19 syndrome Cirrhosis Hepatocellular carcinoma

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Beta-blockers and physical frailty in patients with endstage liver disease

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World Journal of Gastroenterology 2018年第33期24卷 3770-3775页

作者： Selena Z Kuo Blanca Lizaola Hilary Hayssen Jennifer C lai Division of Gastroenterology/Hepatology Department of Medicine University of CaliforniaSan Francisco

AIM To investigate beta-blocker(BB) use in patients with cirrhosis and determine their effects on physical frailty and overall *** Adult outpatients with cirrhosis listed for liver transplantation underwent testing of physical frailty using the performance-based Liver Frailty Index, comprised of chair stands, grip strength, and balance testing, as well as self-reported assessments of exhaustion and physical activity. BB use was assessed from medical chart review. Univariable and multivariable logistic regression were performed to determine BB use and their association with measures of physical frailty. Competing risk analyses were performed to determine the effect of BB use on wait-list mortality, as defined by death or delisting for being too sick for *** Of 344 patients, 35% were female, median age was 60, median model for end stage liver disease was 15, and 53% were prescribed a BB. Compared to those not on BB, patients on BB were similar except for percentage female(25% vs 46%; P < 0.001) and BMI(29 vs 28; P = 0.008). With respect to tests of physical frailty, BB use was not associated with increased odds of frailty(by the Liver Frailty Index), exhaustion, or low physical activity. BB use was, however, significantly associated with a decreased adjusted risk of mortality(SHR 0.55; P = 0.005).CONCLUSION In patients with cirrhosis awaiting liver transplantation, BB use is not associated with physical frailty. We confirmed the known survival benefits with BB use, and concerns about adverse effects should not deter their utilization when indicated.

关键词： Beta-blockers Cirrhosis End-stage liver disease Frailty

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Frailty is independently associated with increased hospitalisation days in patients on the liver transplant waitlist

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World Journal of Gastroenterology 2017年第5期23卷 899-905页

作者： Marie Sinclair Eduard Poltavskiy Jennifer L Dodge Jennifer C lai Gastroenterology and Hepatology University of CaliforniaSan FranciscoCa 94143United States

AIMTo investigate the impact of physical frailty on risk of hospitalisation in cirrhotic patients on the liver transplant *** listed for liver transplantation at a single centre underwent frailty assessments using the Fried Frailty Index, consisting of grip strength, gait speed, exhaustion, weight loss, and physical activity. Clinical and biochemical data including MELD score as collected at the time of assessment. The primary outcome was number of hospitalised days per year; secondary outcomes included incidence of infection. Univariable and multivariable analysis was performed using negative binomial regression to associate baseline parameters including frailty with clinical outcomes and estimated incidence rate ratios (IRR).RESULTSOf 587 cirrhotics, 64% were male, median age (interquartile range) was 60 (53-64) years and MELD score was 15 (12-18). Median Fried Frailty Index was 2 (1-3); 31.6% were classified as frail (fried frailty ≥ 3). During 12 mo of follow-up, 43% required at least 1 hospitalisation; 38% of which involved major infection. 107/184 (58%) frail and 142/399 (36%) non-frail patients were hospitalised at least once (P < 0.001). In univariable analysis, Fried Frailty Index was associated with total hospitalisation days per year (IRR = 1.51, 95%CI: 1.28-1.77; P ≤ 0.001), which remained significant on multivariable analysis after adjustment for MELD, albumin, and gender (IRR for frailty of 1.21, 95%CI: 1.02-1.44; P = 0.03). Incidence of infection was not influenced by *** cirrhotics on the liver transplant waitlist, physical frailty is a significant predictor of hospitalisation and total hospitalised days per year, independent of liver disease severity.

关键词： Hospitalisation Infection Cirrhosis Frailty Transplantation

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Women on the liver transplantation waitlist are at increased risk of hospitalization compared to men

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World Journal of Gastroenterology 2019年第8期25卷 980-988页

作者： Jessica B Rubin Marie Sinclair Robert S Rahimi Elliot B Tapper Jennifer C lai Division of Gastroenterology and Hepatology Department of MedicineUniversity of California-San FranciscoSan FranciscoCA 94143 United States Department of Gastroenterology and Hepatology Austin HealthHeidelberg 3084VictoriaAustralia Department of Medicine the University of MelbourneMelbourne 3010VictoriaAustralia Division of Hepatology Annette C.and Harold C.Simmons Transplant InstituteBaylor University Medical CenterDallasTX 75346United States Division of Gastroenterology and Hepatology University of MichiganAnn ArborMI 48109United States

BACKGROUND Hospital admissions are common among patients with cirrhosis,but patient factors associated with hospitalization have not been well *** recent data suggesting increased liver transplant waitlist dropout among women,we hypothesized that women on the liver transplant waitlist would have increased rates of hospitalization compared with *** To evaluate the role of gender on risk of hospitalization for patients on the liver transplant waitlist,in order to help explain gender disparities in waitlist *** Patients listed for liver transplant at a single center in the United States were prospectively enrolled in the Functional Assessment in Liver Transplantation *** included in this retrospective analysis included those enrolled between March 2012 and December 2014 with at least 12 mo of follow up and without hepatocellular *** primary and secondary outcomes were hospitalization and total inpatient days within 12 mo,*** and negative binomial regression associated baseline factors with *** Of the 392 patients,41%were female,with median(interquartile range)age 58 years(52-63)and model for end-stage liver disease 18(15-22).Within 12 mo,186(47%)patients were hospitalized≥1 time;48%were readmitted,with a median of 8(4-15)inpatient *** women than men were hospitalized(54%vs 43%;P=0.03).In univariable analysis,female sex was associated with an increased risk of hospitalization[odds ratios(OR)1.6,95%confidence interval(CI)1.0-2.4;P=0.03],which remained significant on adjusted multivariable analysis(OR 1.6,95%CI:1.1-2.6;P=0.03).Female gender was also associated with an increased number of inpatient days within 12 mo in both univariable and multivariable *** Women with cirrhosis on the liver transplant waitlist have more hospitalizations and inpatient days in one year compared with men,suggesting that the experience of cirrhosis differs between men and women,despite

关键词： Gender Cirrhosis Liver transplantation waitlist Hospitalization Readmission Women

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Functional groups of Sahelian trees in a semiarid agroforestry system of Senegal

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Journal of Plant Ecology 2018年第3期11卷 375-384页

作者： Joseph S.Diémé Mayécor Diouf Cristina Armas Graciela MRusch francisco I.Pugnaire Estación Experimental de ZonasÁridas Consejo Superior de Investigaciones CientíficasCtra.de Sacramento s/n04120 La CañadaAlmeríaSpain Centre National de Recherches Forestières Institut Sénégalais de Recherches Agricoles(CNRF/ISRA)DakarSenegal Norwegian Institute for Nature Research TrondheimNorway

Aims Addressing plant responses to water stress is critical to understand the structure of plant communities in water-limited environments and to forecast their resilience to future changes in *** a semiarid agroforestry system in the Sahelian savannah of Leona(Senegal),we selected nine common tree species and explored their stress-resistance *** species represent a variety of life forms and are of high regional socio-economic *** hypothesized that different species would show different suites of traits to cope with water stress and expected to identify functional groups differing in strategies to withstand water *** Along a dry and a wet season,we monitored four traits reflecting above-and below-ground strategies of resource acquisition such as predawn leaf water potential(ψpd),specific leaf area(SLA),leaf thickness and leaf area index(lai).We also measured two mor-phological traits:trunk diameter and tree *** andψpd were measured six times during the dry and rainy seasons,and the other traits were measured *** Findings We identified two functional classes subdivided into two func-tional groups of each *** first class included deciduous and semi-deciduous species that generally had large SLA,low leaf thickness and small-to-intermediate inter-seasonal varia-tions inψ*** second class included evergreen species of two functional groups that differ in SLA,leaf thickness and the mag-nitude of inter-seasonal variations ofψpd throughout the *** four functional groups identified in this study represent plant strategies differing in their response to changing environmental conditions.

关键词： Acacia tortilis Adansonia digitata Balanites aegyptiaca Celtis integrifolia Combretum glutinosum Faidherbia albida functional traits Neocarya macrophyla Sclerocarya birrea Tamarindus indica water stress

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Perturbation of GABAsynapses in vestibular nucleus during a postnatal critical period impacts onthe establishment of spatial recognition

Perturbation of GABAsynapses in vestibular nucleus during a ...

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中国神经科学学会第十届全国学术会议

作者： Wen-Qiang CHEN Chun-Wai MA francisco Paulo BOTELHO Wei SHI Chun-Hong lai Daisy Kwok-Yan SHUM Ymg-Shmg CHAN Departments of Physiology Li Ka Shing Faculty of Medicine The University of Hong Kong Departments of Biochemistry Li Ka Shing Faculty of Medicine The University of Hong Kong

The transformation of vestibular cues into spatial orientation signals is essential for navigation in the *** understand how spatial coding is shaped during the development of neural circuitry,the role of neurotransmission within the neonatal vestibular nucleus(VN) in the establishment of a spatial map needs to be *** whole-cell patch-clamp recording in brainstem slices,we found that most VN neurons of postnatal day(P) 3-5 rats exhibited long-term depression of GABA receptor-mediated evoked-postsynaptic *** this stage,these currents were excitatory in *** P14,only a small proportion of VN neurons exhibited long-term depression but these currents became inhibitory in *** results indicatea postnatal period duringwhich there is a change in the efficacyof GABAergic VN *** further study the role of GABAergic transmission in VN on developing acquisition of spatial recognition,we implanted above the VN of P1 or P14 rats with Elvax slice loaded with GABA receptor antagonist *** pups were allowed to recover and testedat different *** of a vestibular-related spatial map in thalamus,an upstream relay of the neural circuitry for balance,was observed in adult rats pre-treated with bicuculline at P1 but not in those pre-treated at *** tested with a path integration task at the adult stage,rats pretreated with bicuculline at P1 had significantly prolonged training time and deficiency in behavioral parameters(including searching time,returning time,heading angle,and number of errors in dark/new location probe tests).Comparable deficits were also observed with selective lesion of vestibular-related subnuclei in the adult *** pretreated at P14 however showed no significant difference in tight,dark,and new location probe ***,we have demonstrated that a postnatal critical period exists for developmental establishment of a neural circuitry for spatial reference and acquisition of s

关键词： vestibular nucleus spatial navigation thalamus postnatal critical period

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NPRportrait 1.0:A three-level benchmark for non-photorealistic rendering of portraits

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Computational Visual Media 2022年第3期8卷 445-465页

作者： Paul L.Rosin Yu-Kun lai David Mould Ran Yi Itamar Berger Lars Doyle Seungyong Lee Chuan Li Yong-Jin Liu Amir Semmo Ariel Shamir Minjung Son Holger Winnemöller School of Computer Science and Informatics Cardiff UniversityCardiffUK School of Computer Science Carleton UniversityOttawaCanada Department of Computer Science and Technology Tsinghua UniversityBeijingChina Reichman University(the Interdisciplinary Center) HerzliyaIsrael Department of Computer Science and Engineering Pohang University of Science and TechnologyPohangRepublic of Korea Lambda Labs Inc.San FranciscoUSA Hasso Plattner Institute University of PotsdamPotsdamGermany Multimedia Processing Laboratory Samsung Advanced Institute of TechnologySuwonRepublic of Korea Adobe Systems Inc.San JoseUSA

Recently,there has been an upsurge of activity in image-based non-photorealistic rendering(NPR),and in particular portrait image stylisation,due to the advent of neural style transfer(NST).However,the state of performance evaluation in this field is poor,especially compared to the norms in the computer vision and machine learning ***,the task of evaluating image stylisation is thus far not well defined,since it involves subjective,perceptual,and aesthetic *** make progress towards a solution,this paper proposes a new structured,threelevel,benchmark dataset for the evaluation of stylised portrait *** criteria were used for its construction,and its consistency was validated by user ***,a new methodology has been developed for evaluating portrait stylisation algorithms,which makes use of the different benchmark levels as well as annotations provided by user studies regarding the characteristics of the *** perform evaluation for a wide variety of image stylisation methods(both portrait-specific and general purpose,and also both traditional NPR approaches and NST)using the new benchmark dataset.

关键词： non-photorealistic rendering(NPR) image stylization style transfer portrait evaluation benchmark

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Recent advances in the translation of drug metabolism and pharmacokinetics science for drug discovery and development

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Acta Pharmaceutica Sinica B 2022年第6期12卷 2751-2777页

作者： Yurong lai Xiaoyan Chu Li Di Wei Gao Yingying Guo Xingrong Liu Chuang Lu Jialin Mao Hong Shen Huaping Tang Cindy Q.Xia Lei Zhang Xinxin Ding Drug Metabolism Gilead Sciences Inc.Foster CityCA 94404USA Department of Pharmacokinetics Pharmacodynamics and Drug MetabolismMerck&Co.Inc.KenilworthNJ 07033USA Pharmacokinetics Dynamics and MetabolismPﬁzer Worldwide Research and DevelopmentGrotonCT 06340USA Eli Lilly and Company IndianapolisIN 46221USA Drug Metabolism and Pharmacokinetics BiogenCambridgeMA 02142USA Drug Metabolism and Pharmacokinetics Accent TherapeuticsInc.LexingtonMA 02421USA Department of Drug Metabolism and Pharmacokinetics GenentechA Member of the Roche GroupSouth San FranciscoCA 94080USA Drug Metabolism and Pharmacokinetics Department Bristol-Myers Squibb CompanyPrincetonNJ 08540USA Bioanalysis and Biomarkers Glaxo Smith KlineKing of the PrussiaPA 19406USA Department of Drug Metabolism and Pharmacokinetics Takeda Pharmaceuticals International Co.CambridgeMA 02139USA Ofﬁce of Research and Standards Ofﬁce of Generic DrugsCDERFDASilver SpringMD 20993USA Department of Pharmacology and Toxicology College of PharmacyUniversity of ArizonaTucsonAZ 85721USA Current afﬁliation:Translational Medicine EMD Serono Research&Development InstituteInc.BillericaMA 01821USA Current afﬁliation:Drug Metabolism Gilead Sciences Inc.Foster CityCA 94404USA

Drug metabolism and pharmacokinetics(DMPK) is an important branch of pharmaceutical *** nature of ADME(absorption,distribution,metabolism,excretion) and PK(pharmacokinetics) inquiries during drug discovery and development has evolved in recent years from being largely descriptive to seeking a more quantitative and mechanistic understanding of the fate of drug candidates in biological *** progress has been made in the past decade,not only in the characterization of physiochemical properties of drugs that influence their ADME,target organ exposure,and toxicity,but also in the identification of design principles that can minimize drug-drug interaction(DDI) potentials and reduce the *** importance of membrane transporters in drug disposition,efficacy,and safety,as well as the interplay with metabolic processes,has been increasingly *** increases in investments on new modalities beyond traditional small and large molecule drugs,such as peptides,oligonucleotides,and antibody-drug conjugates,necessitated further innovations in bioanalytical and experimental tools for the characterization of their ADME *** this review,we highlight some of the most notable advances in the last decade,and provide future perspectives on potential major breakthroughs and innovations in the translation of DMPK science in various stages of drug discovery and development.

关键词： Drug discovery and development New drug application Biologics license application Pharmacokinetics ADME New modalities Model-informed drug development Micro-physiological systems

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Cancer in the parasitic protozoans Trypanosoma brucei and Toxoplasma gondii

Cancer in the parasitic protozoans Trypanosoma brucei and To...

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中国畜牧兽医学会兽医寄生虫学分会第十三次学术研讨会

作者： Zhao-Rong Lun De-Hua lai Yan-Zi Wen Ling-Ling Zheng Ji-Long Shen Ting-Bo Yang Wen-Liang Zhou Liang-Hu Qu Geoff Hide francisco J.Ayala Center for Parasitic Organisms State Key Laboratory of BiocontrolSchool of Life SciencesSun Yat-Sen University Ecosystems and Environment and Biomedical Research Centres School of Environment and Life SciencesUniversity of Salford The Key Laboratories of Pathogen Biology and Zoonoses Anhui Province and Department of ParasitologyAnhui Medical University Department of Ecology and Evolutionary Biology University of California

Cancer is a general name for more than 100 malignant *** is postulated that all cancers start from a single abnormal cell that grows out of *** cancers can cause serious consequences and deaths.A great progress has been made in cancer research which significantly improved our knowledge to understand the nature and mechanisms of the disease,but the origins of cancer are far from being well understood due to limitations of suitable model systems and to the complexities of the *** view of the fact that the cancers are found in various species of vertebrates and other metazoa,here,we suggest that cancer also occurs in parasitic protozoans such as Trypanosoma brucei,a blood parasite,and Toxoplasma gondii,an obligate intracellular *** treatment,these protozoan cancers may cause severe disease and death in mammals including *** simpler genomes of these single cell organisms,in combination with their complex life cycles and fascinating life cycle differentiation processes,may help us to better understand the origins of cancers,in particular,leukemias.

关键词： Malignancy single cell organisms mammals evolution transmissible

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Discovery of 15-Lipoxygenase activators

Discovery of 15-Lipoxygenase activators

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生命的分子机器及其调控网络——2012年全国生物化学与分子生物学学术大会

作者： Hu Meng Christopher L.McClendon Ying Liu Luhua lai BNLMS State Key Laboratory for Structural Chemistry of Unstable and Stable SpeciesCollege of Chemistry and Molecular EngineeringPeking University Department of Pharmaceutical Chemistry University of CaliforniaSan Francisco BNLMS State Key Laboratory for Structural Chemistry of Unstable and Stable SpeciesCollege of Chemistry and Molecular Engineering& Center for Quantitative Biology Peking University

Human reticulocyte 15-lipoxygenase(15-LOX) is a 75 kDa fatty acid dioxygenases that con-tain 1 gram atom non-heme,nonsulfur -bound iron per mole *** humans,15-LOX acts upon arachidonic acid(AA) to create a number of important lipid mediators in-cluding lipoxins which possess numerous anti-inflammatory bioactivities towards *** studies on 15-LOX suggest that up-regulating the activity of 15-LOX may help relieve the symptoms of some inflammation related ***,activat-ors to 15-LOX may lead to the discovery of new anti-inflammatory *** find or design an

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