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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

Biliary brush cytology:Factors associated with positive yields on biliary brush cytology

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World Journal of Gastroenterology 2008年第4期14卷 569-573页

作者： Nasim Mahmoudi robert Enns Jack Amar Jaber AlAli Eric lam Jennifer Telford St Paul's Hospital University of British ColumbiaVancouver British ColumbiaCanada

AIM: To evaluate the yield of brushing biliary strictures and the factors associated with a positive result in biliary strictures. METHODS: Data on all consecutive patients (01/02 -10/05) who were identified to have a biliary stricture and who underwent biliary brush cytology were collected. The yield of positive biliary brush cytology was evaluated and compared to results with the gold standard for diagnosis (defi ned as either defi nitive surgical histology or clinical course). Additionally,associated factors of positive results including stricture location,gender,age,mass size,length of stricture,and dilatation prior to brushing cytology were assessed. RESULTS: From 199 patients who had brushing cytology samples (10 patients were excluded due to lack of gold standard diagnosis),77 patients had positive brushing cytology (yield 41%). Variables associated with positive cytology brushing on initial endoscopic retrograde cholangiography were age 1.02 (1.00-1.05),mass size > 1 cm 2.22 (1.01-4.89) and length of stricture > 1 cm 3.49 (1.18-10.2). The sensitivity of biliary brushing was 61%,its specifi city 98%,the positive predictive value reached 99%,and the negative predictive value was 57%. CONCLUSION: Our results revealed a 41% positive yield from brushing cytology. The sensitivity of biliary brushing cytology in our center was 61% and the specif icity was 98%. Predictors of positive yield include older age,mass size > 1 cm,and stricture length of > 1 cm.

关键词： Biliary Endoscopic retrograde cholangiopanc reatography Pancreas Gallbladder Ampulla

Disharmonious Ventricular Relationship and Topology for the Given Atrioventricular *** Diagnostic Approach Using 3D Modeling and Printing

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Congenital Heart Disease 2022年第5期17卷 495-504页

作者： Shi-Joon Yoo Ankavipar Saprungruang Christopher Z.lam robert H.Anderson Department of Diagnostic Imaging Hospital for Sick ChildrenUniversity of TorontoTorontoCanada Division of Cardiology Department of PediatricsLabatt Family Heart CentreHospital for Sick ChildrenUniversity of TorontoTorontoCanada Biosciences Division Newcastle UniversityNewcastle-upon-TyneUK

In the last issue,two case reports separately present examples of the extremely rare and complex congenital heart diseases that show concordant atrioventricular connections to the L-looped ventricles in the presence of situs *** cases highlight that the relationship between the two ventricles within the ventricular mass is not always harmonious with the given atrioventricular *** disharmony between the connections and relationships requires careful assessment of the three basic facets of cardiac building blocks,namely their morphology,the relationship of their component parts,and their connections with the adjacent segments.3D imaging and printing can now facilitate an otherwise difficult diagnosis in such complex *** of either the 3D images or the models permit accurate assessment of the ventricular topologic pattern by creating the right ventricular en-face septal view,thus facilitating placement of the observer’s *** we now emphasize,an alternative approach,which might prove more attractive to imagers,is to rotate the ventricular mass to provide the ventricular apical view,thus permitting determination of the ventricular relationship without using the hands.

关键词： Segmental approach disharmony between connection and relationship ventricular loop pattern ventricular topology juxtaposition of atrial appendages 3D modeling 3D printing

Factors associated with incomplete small bowel capsule endoscopy studies

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World Journal of Gastroenterology 2010年第42期16卷 5329-5333页

作者： Mitchell M Lee Andrew Jacques Eric lam Ricky Kwok Pardis Lakzadeh Ajit Sandhar Brandon Segal Sigrid Svarta Joanna Law robert Enns St Paul's Hospital University of British Columbia770-1190 Hornby StreetVancouverBritish Columbia V6Z 2K5Canada

AIM:To identify patient risk factors associated with incomplete small bowel capsule endoscopy(CE) ***:Data from all CE procedures performed at ***'s Hospital in Vancouver,British Columbia,Canada,between December 2001 and June 2008 were collected and analyzed on a retrospective *** collection for complete and incomplete CE study groups included patient demographics as well as a number of potential risk factors for incomplete CE including indication for the procedure,hospitalization,diabetes mellitus with or without end organ damage,limitations in mobility,renal insufficiency,past history of bowel obstruction,abdominal surgery,abdominal radiation therapy and opiate *** factors were analyzed using a univariable and multivariable logistic regression ***:From a total of 535 CE procedures performed,158 were incomplete(29.5%).The univariable analysis showed that CE procedures performed for overt gastrointestinal bleeding(P = 0.002),and for patients with a prior history of abdominal surgery(P = 0.023) or bowel obstruction(P = 0.023) were significantly associated with incomplete CE *** on opiate medications(P = 0.094) as well as hospitalized patients(P = 0.054) were not statistically significant,but did show a trend towards incomplete *** multivariable analysis showed that independent risk factors for an incomplete CE procedure include prior history of bowel obstruction [odds ratios(OR) 2.77,P = 0.02,95% confidence intervals(CI):1.17-6.56] and procedures performed for gastrointestinal bleeding(Occult OR 2.04,P = 0.037,95% CI:1.04-4.02 and Overt OR 2.69,P = 0.002,95% CI:1.44-5.05).Patients with a prior history of abdominal surgery(OR 1.46,P = 0.068,95% CI:0.97-2.19),those taking opiate medications(OR 1.54,P = 0.15,95% CI:0.86-2.76) and hospitalized patients(OR 1.82,P = 0.124,95% CI:0.85-3.93) showed a trend towards statistical ***:We have identified a number of risk factors for incomplete CE procedures

关键词： Capsule Capsule endoscopy Incomplete endoscopy

Real- world evaluation of Brainomix e- Stroke software

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Stroke & Vascular Neurology 2024年第5期9卷 497-504页

作者： Dermot Mallon Matthew Fallon Eirini Blana Cillian McNamara Arathi Menon Chak lam Ip Jack Garnham Tarek Yousry Peter Cowley robert Simister David Doig Lysholm Department of Neuroradiology National Hospital for Neurology and NeurosurgeryUniversity College London Hospitals NHS Foundation TrustLondonUK UCL Queen Square Institute of Neurology LondonUK Comprehensive Stroke Centre University College London Hospitals NHS Foundation TrustLondonUK

Background and purpose Brainomix e-Stroke is an artificial intelligence-based decision support tool that aids the interpretation of CT imaging in the context of acute *** e-Stroke has the potential to improve the speed and accuracy of diagnosis,real-world validation is *** aim of this study was to prospectively evaluate the performance of Brainomix e-Stroke in an unselected cohort of patients with suspected acute ischaemic *** The study cohort included all patients admitted to the University College London Hospital Hyperacute Stroke Unit between October 2021 and April *** e-ASPECTS and e-CTA,the ground truth was determined by a neuroradiologist with access to all clinical and imaging *** e-CTP,the values of the core infarct and ischaemic penumbra were compared with those derived from ***,an alternate software used at our *** 1163 studies were performed in 551 patients admitted during the study *** these,1130(97.2%)were successfully processed by e-Stroke in an average of *** identifying acute middle cerebral artery territory ischaemia,e-ASPECTS had an accuracy of 77.0%and was more specific(83.5%)than sensitive(58.6%).The accuracy for identifying hyperdense thrombus was lower(69.1%),which was mainly due to many false positives(positive predictive value of 22.9%).Identification of acute haemorrhage was highly accurate(97.8%)with a sensitivity of 100%and a specificity of 97.6%;false positives were typically caused by areas of *** accuracy of e-CTA for large vessel occlusions was 91.5%.The core infarct and ischaemic penumbra volumes provided by e-CTP strongly correlated with those provided by ***(ρ=0.804—0.979).Conclusion Brainomix e-Stroke software provides rapid and reliable analysis of CT imaging in the acute stroke setting although,in line with the manufacturer’s guidance,it should be used as an adjunct to expert interpretation rather than a standalone decision-making tool.

关键词： admitted false Stroke

Supertransport of excitons in atomically thin organic semiconductors at the 2D quantum limit

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Light(Science & Applications) 2020年第1期9卷 907-919页

作者： Ankur Sharma Linglong Zhang Jonathan O.Tollerud Miheng Dong Yi Zhu robert Halbich Tobias Vogl Kun Liang Hieu T.Nguyen Fan Wang Shilpa Sanwlani Stuart K.Earl Daniel Macdonald Ping Koy lam Jeffrey A.Davis Yuerui Lu Research School of Electrical Energy and Materials EngineeringCollege of Engineering and Computer ScienceThe Australian National UniversityCanberraACT 2601Australia Optical Sciences Centre Swinburne University of TechnologyHawthornVIC 3122Australia ARC Centre of Excellence for Future Low-Energy Electronics Technology Australia Centre for Quantum Computation and Communication Technology Department of Quantum ScienceResearch School of Physics and EngineeringThe Australian National UniversityActonACT 2601Australia School of Mechatronical Engineering Beijing Institute of TechnologyBeijing 100081China Institute for Biomedical Materials and Devices(IBMD) Faculty of ScienceUniversity of Technology SydneySydneyNSW 2007Australia

Long-range and fast transport of coherent excitons is important for the development of high-speed excitonic circuits and quantum computing ***,most of these coherent excitons have only been observed in some low-dimensional semiconductors when coupled with cavities,as there are large inhomogeneous broadening and dephasing effects on the transport of excitons in their native states in ***,by confining coherent excitons at the 2D quantum limit,we first observed molecular aggregation-enabled‘supertransport’of excitons in atomically thin two-dimensional(2D)organic semiconductors between coherent states,with a measured high effective exciton diffusion coefficient of ~346.9 cm^(2)/s at room *** value is one to several orders of magnitude higher than the values reported for other organic molecular aggregates and low-dimensional inorganic *** coupling to any optical cavities,the monolayer pentacene sample,a very clean 2D quantum system(~1.2 nm thick)with high crystallinity(J-type aggregation)and minimal interfacial states,showed superradiant emission from Frenkel excitons,which was experimentally confirmed by the temperature-dependent photoluminescence(PL)emission,highly enhanced radiative decay rate,significantly narrowed PL peak width and strongly directional in-plane *** coherence in monolayer pentacene samples was observed to be delocalised over~135 molecules,which is significantly larger than the values(a few molecules)observed for other organic thin *** addition,the supertransport of excitons in monolayer pentacene samples showed highly anisotropic *** results pave the way for the development of future high-speed excitonic circuits,fast OLEDs,and other optoelectronic devices.

关键词： transport quantum coherent

Constitutive androstane receptor:A tumor suppressor and a biomarker for favorable prognosis of liver diseases

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Genes & Diseases 2024年第6期11卷 88-90页

作者： Sarah Da Won Bae Romario Nguyen Lawrence Yuen Vincent lam Jacob George Liang Qiao Storr Liver Centre Westmead institute for Medical ResearchUniversity of Sydneyand Westmead HospitalWestmeadNSW2145Australia Department of Surgery Westmead HospitalWestmeadNSW2145Australia

Constitutive androstane receptor(CAR)is a nuclear receptor that is encoded by the gene NR113(nuclear receptor subfamily 1 group I member 3)and is almost exclusively expressed in the liver.1 As reported in our recent publication,CAR is well established as a xenosensor for drugs and energy metabolism with newer implications in the regulation of normal liver physiology and liver regeneration.

关键词： metabolism drugs liver

Recent advances in operational tropical cyclone genesis forecast

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Tropical Cyclone Research and Review 2023年第4期12卷 323-340页

作者： K.K.Hon robert Ballard Eric Blake Steph Bond Robb Gile Daniel Halperin Charles Helms Hoang lam Xinyan Lyu Mrutyunjay Mohapatra Monica Sharma Akira Shimokobe Ralf Toumi Seonghee Won Hong Kong Observatory Hong KongChina Regional Specialized Meteorological Center Honolulu HonoluluUSA National Hurricane Center Miami FLUSA Bureau of Meteorology MelbourneAustralia Philippine Atmospheric Geophysicaland Astronomical Services AdministrationDepartment of Science and TechnologyQuezon CityPhilippines Embry-Riddle Aeronautical University USA National Aeronautics and Space Administration MarylandUSA Vietnam Meteorological and Hydrological Administration HanoiViet Nam China Meteorological Administration BeijingChina Regional Specialized Meteorological Center New Delhi New DelhiIndia Regional Specialized Meteorological Center Tokyo-Typhoon Centre TokyoJapan Department of Physics Imperial College LondonUK Korea Meteorological Administration SeoulRepublic of Korea

Tropical cyclone(TC)genesis prediction is a major scientific challenge to the TC operation and research *** report surveys the current status of TC genesis forecasts by a number of major operational centers covering the key ocean basins across both *** IWTC-9,we see an emergence of probabilistic TC genesis forecast products by operational centers,typically supported by the statistical processing of a combination of ensemble prediction and satellite analysis,covering time periods of couple of days to weeks *** prevalence of multi-center grand ensemble approach highlights the uncertainties involved and the forecast challenges in quantitative genesis *** operational practice might differ across agencies,verification efforts generally report a steady or slightly improving skill level in terms of reliability,which likely results from the continual improvement in global numerical weather prediction capability.

关键词： Cyclogenesis Tropical cyclone genesis Ensemble Prediction Operational Forecasting Probabilistic Verification Survey Global

Identification of factors associated with sedation tolerance in 5000 patients undergoing outpatient colonoscopy:Canadian tertiary center experience

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World Journal of Gastrointestinal Endoscopy 2016年第20期8卷 770-776页

作者： Alexandra Shingina George Ou Oliver Takach Sigrid Svarta Ricky Kwok Jessica Tong Kieran Donaldson Eric lam robert Enns Department of Gastroenterology Faculty of MedicineUniversity of TorontoToronto General Hospital Department of Gastroenterology Faculty of MedicineUniversity of British Columbia Division of Gastroenterology Saint Paul Hospital

AIM To develop a prediction model aimed at identifying patients that may require higher than usual sedation doses during *** A retrospective chart review on 5000 patients who underwent an outpatient colonoscopy at ***'s Hospital from 2009 to 2010 was conducted in order to develop a model for identifying patients who will require increased doses of *** predictor variables including age,gender,endoscopy indication,high sedation requirements during previous endoscopies,difficulty of the procedure,bowel preparation quality,interventions,findings as well as current use of benzodiazepines,opioids and alcohol were *** outcome of study was the use ofhigh dose of sedation agents for the *** particular,the high dose of sedation was defined as fentanyl greater than 50 mcg and midazolam greater than 3 *** Analysis of 5282 patients(mean age 57 ± 12,49% female) was *** common indication for the procedure was screening colonoscopy(57%).Almost half of our patients received doses exceeding Fentanyl 50 mcg and Midazolam 3 *** regression models identified the following variables associated with high sedation:Younger age(OR=0.95 95%CI:0.94-0.95;P lammatory Bowel Disease(OR=1.45,95%CI:1.04-2.03;P=0.02) as indications for the procedure;difficult procedure as defined by gastroenterologist(OR=1.73,95%CI:1.48-2.03;P lammatory bowel disease as an indication(OR=3.17,95%CI:1.58-6.37;P=0.002);difficult procedure as defined by an endoscopist(OR=5.13 95%CI:2.97-8.85;P=0.0001) and current use of opioids,benzodiazepines or antidepressants(OR=2.88,95%CI:1.74-4.77;P=0.001) having the highest predictive value of high sedation require

关键词： Colonoscopy Sedation Sedation tolerance Fentanyl Midazolam Predictive model