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Dynamic phenotypic heterogeneity and the evolution of multiple RNA subtypes in hepatocellular carcinoma:the PLANET study

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National Science Review 2022年第3期9卷 96-109页

作者： Weiwei Zhai Hannah Lai Neslihan Arife Kaya Jianbin Chen Hechuan Yang Bingxin Lu Jia Qi Lim Siming Ma sin chi chew Khi Pin Chua Jacob Josiah Santiago Alvarez Pauline Jieqi Chen Mei Mei Chang Lingyan Wu Brian K.P.Goh Alexander Yaw-Fui Chung Chung Yip Chan Peng Chung Cheow Ser Yee Lee Juinn Huar Kam Alfred Wei-chieh Kow Iyer Shridhar Ganpathi Rawisak Chanwat Jidapa Thammasiri Boon Koon Yoong Diana Bee-Lan Ong Vanessa H.de Villa Rouchelle D.Dela Cruz Tracy Jiezhen Loh Wei Keat Wan Zeng Zeng Anders Jacobsen Skanderup Yin Huei Pang Krishnakumar Madhavan Tony Kiat-Hon Lim Glenn Bonney Wei Qiang Leow Valerie chew Yock Young Dan Wai Leong Tam Han Chong Toh Roger Sik-Yin Foo Pierce Kah-Hoe Chow Genome Institute of singapore Agency for Science Technology and Research Key Laboratory of Zoological Systematics and Evolution Institute of Zoology Chinese Academy of Sciences Center for Excellence in Animal Evolution and Genetics Chinese Academy of Sciences School of Biological Sciences Nanyang Technological University Division of Biosciences Faculty of Life Sciences Division of Surgery and Surgical Oncology National Cancer Centre Department of Hepato-Pancreato-Biliary and Transplant Surgery Singapore General Hospital Division of Hepatobiliary and Pancreatic Surgery Department of Surgery University Surgical Cluster National University Health System Hepato-Pancreato-Biliary Surgery Unit Department of Surgery National Cancer Institute Division of Pathology National Cancer Institute Department of Surgery Faculty of Medicine University of Malaya Department of Surgery and Center for Liver Disease Management and Transplantation The Medical City 13. Department of Laboratories The Medical City Department of Pathology Singapore General Hospital Institute for Infocomm Research ASTAR Department of Pathology National University Health System Translational Immunology Institute (TII) Sing Health Duke-NUS Academic Medical Centre Division of Gastroenterology and Hepatology University Medicine Cluster National University Hospital Department of Biochemistry Yong Loo Lin School of Medicine National University of Singapore Cancer Science Institute of singapore National University of Singapore Division of Medical Oncology National Cancer Center Singapore Cardiovascular Research Institute National University of Singapore National University Healthcare System singhealth-Duke-NUS Academic Surgery Program Duke-NUS Graduate Medical School Institute of Molecular and Cell Biology Agency for Science Technology and Research

Intra-tumor heterogeneity(ITH) is a key challenge in cancer treatment, but previous studies have focused mainly on the genomic alterations without exploring phenotypic(transcriptomic and immune)heterogeneity. Using one of the largest prospective surgical cohorts for hepatocellular carcinoma(HCC)with multi-region sampling, we sequenced whole genomes and paired transcriptomes from 67 HCC patients(331 samples). We found that while genomic ITH was rather constant across stages, phenotypic ITH had a very different trajectory and quickly diversified in stage Ⅱ patients. Most strikingly, 30% of patients were found to contain more than one transcriptomic subtype within a single tumor. Such phenotypic ITH was found to be much more informative in predicting patient survival than genomic ITH and explains the poor efficacy of single-target systemic therapies in HCC. Taken together, we not only revealed an unprecedentedly dynamic landscape of phenotypic heterogeneity in HCC, but also highlighted the importance of studying phenotypic evolution across cancer types.

关键词： NADH oxidase H2O2 production oxidative phosphorylation

Modeling of environmental influence in structural health assessment for reinforced concrete buildings

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Earthquake Engineering and Engineering Vibration 2010年第2期9卷 295-306页

作者： Ka-Veng Yuen sin-chi Kuok Department of Civil and Environmental Engineering Univeristy of Macao

One branch of structural health monitoring (SHM) utilizes dynamic response measurements to assess the structural integrity of civil infrastructures. In particular,modal frequency is a widely adopted indicator for structural damage since its square is proportional to structural stiffness. However,it has been demonstrated in various SHM projects that this indicator is substantially affected by fluctuating environmental conditions. In order to provide reliable and consistent information on the health status of the monitored structures,it is necessary to develop a method to filter this interference. This study attempts to model and quantify the environmental influence on the modal frequencies of reinforced concrete buildings. Daily structural response measurements of a twenty-two story reinforced concrete building were collected and analyzed over a one-year period. The Bayesian spectral density approach was utilized to identify the modal frequencies of this building and it was clearly seen that the temperature and humidity fluctuation induced notable variations. A mathematical model was developed to quantify the environmental effects and model complexity was taken into consideration. Based on a Timoshenko beam model,the full model class was constructed and other reduced-order model class candidates were obtained. Then,the Bayesian modal class selection approach was employed to select the one with the most suitable complexity. The proposed model successfully characterizes the environmental influence on the modal frequencies. Furthermore,the estimated uncertainty of the model parameters allows for assessment of the reliability of the prediction. This study not only improves the understanding about the monitored structure,but also establishes a systematic approach for reliable health assessment of reinforced concrete buildings.

关键词： Bayesian inference model selection reinforced concrete building structural health monitoring temperature and humidity effects Timoshenko beam

Detecting changes in long-period site responses after the M_w 7.6 chi-chi earthquake, Taiwan, using strong motion records

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Earthquake Engineering and Engineering Vibration 2015年第2期14卷 217-228页

作者： Teng-To Yu chi-Shin Wu Youg-sin Cheng Department of Resources Engineering Cheng Kung University (NCKU)

Temporal changes in site effects are obtained using the HVSR(horizontal-to-vertical spectral ratio) method and strong motion records after the M w 7.6 chi-chi earthquake, Taiwan. Seismic data recorded between 1995 and 2010 are used, comprising 3,708 data from 15 stations adjacent to the Chelungpu fault. Temporal fl uctuations are determined by analyzing the site effect variation using a time–frequency variation(TFV) diagram based on these seismic data. Stations adjacent to the fault show signifi cant disturbances in the resonance frequency at 16–26 Hz. Station TCU129 shows a 40% drop in fundamental frequency after the main shock, and a gradual return to the original state over nine years. For stations located farther from the fault zone, sudden changes in tectonic stress play a dominant role in temporal changes to the HVSR. An impact analysis of the directional factor confi rms our fi nding that the proximity of the fault to seismic stations has the most infl uence on data.

关键词： chi-chi earthquake horizontal-to-vertical spectral

Study of the attenuation relationship for the Wenchuan M_s 8.0 earthquake

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Earthquake Engineering and Engineering Vibration 2015年第1期14卷 1-11页

作者： sin-chi Kuok Iok-Tong Ng Ka-Veng Yuen Faculty of Science and Technology University of Macao

Prediction of peak ground acceleration is an essential element in engineering seismology and it has received great attention in last few decades. In this paper, a comprehensive database of the strong-motion records of the 2008 great Wenchuan Ms 8.0 earthquake is analyzed to investigate the seismic attenuation relationship and the directivity effects. In contrast to most existing seismic attenuation models, the proposed model considers explicitly the directivity effect which has primary influence on the magnitude of ground motion. Bayesian model updating is used to obtain the model parameters and the associated uncertainty. Comparative study is performed with the well-known Boore-Joyner-Fumal empirical formula. Results show that consideration of the directivity effect is vital in modeling the seismic attenuation relationship.

关键词： Bayesian inference Boore-Joyner-Fumal attenuation relationship directivity peak ground acceleration seismic attenuation model

Endoscope-guided pneumatic dilation for treatment of esophageal achalasia

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World Journal of Gastroenterology 2010年第4期16卷 411-417页

作者： Seng-Kee Chuah Tsung-Hui Hu chi-sin Changchien Gastrointestinal Motility Unit Division of HepatogastroenterologyChang Gang Memorial HospitalKaohsiung Medical CenterNo.123Ta-Pei RoadNiaosung HsiangKaohsiung 833TaiwanChina Chang Gung University College of Medicine No.123Ta-Pei RoadNiaosung HsiangKaohsiung 833TaiwanChina

Pneumatic dilation(PD) is considered to be the first line nonsurgical therapy for *** principle of the procedure is to weaken the lower esophageal sphincter by tearing its muscle fibers by generating radial *** endoscope-guided procedure is done without fluoroscopic *** usually use a lowcompliance balloon such as Rigiflex dilator to perform endoscope-guided PD for the treatment of esophageal *** has the advantage of determining mucosal injury during the dilation process,so that a repeat endoscopy is not needed to assess the mucosal *** studies have shown that endoscope-guided PD is an efficient and safe nonsurgical therapy with results that compare well with other treatment *** the results may be promising,long-term follow-up is required in the near future.

关键词： Esophagoscopy Dilatation Esophageal achalasia

Poling Effects of Dielectric and Optical Properties on Pb(Zn1/3Nb2/3)1-xTixO3 Crystal

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Journal of Rare Earths 2006年第Z1期24卷 166-168页

作者： Tu chi Shun Wang Fu Tang chien R R Hugo Schmidt V chew L L Graduate Inst.of Applied Science and Engineering Fu Jen University Taipei 242 China Graduate Inst.of Applied Science and Engineering Fu Jen University Taipei 242 China Department of Physics Montana State University Bozeman MT 59717 USA Department of Physics Montana State University Bozeman MT 59717 USA Department of Mechanical Engineering National University of Singapore Singapore

Dipolar relaxation and dielectric/piezoelectric resonance in a (001)-cut Pb(Zn1/3Nb2/3)0.9Ti0.1O3 (PZNT10%) single crystal before and after electric (E)-field poling were presented. Dielectric permittivities were measured as functions of temperature, frequency and poling E-field strength. Frequency-dependent dielectric spectroscopy in the poled sample exhibits multiple piezoelectric resonances between 0.1 and 1 MHz, which can be described by the forced-damped-oscillator model. The resonant spectra show significant changes while phase transitions are taking place. The unpoled crystal shows almost no optical birefringence, indicating that the average structure symmetry is isotropic. Birefringence of the crystal is significantly enhanced by a prior E-field poling.

关键词： Pb(Zn1/3Nb2/3)1-xTixO3 dielectric permittivity phase transitions refractive indices

Liu-stain quick cytodiagnosis of ultrasound-guided fine needle aspiration in diagnosis of liver tumors

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World Journal of Gastroenterology 2007年第3期13卷 448-451页

作者： chi-sin Changchien Jing-Houng Wang Chao-Hung Hung chien-Hung Chen Chuan-Mo Lee Division of Hepato-Gastroenterology Department of Internal Medicine Chang-Gung Memorial Hospital Kaohsiung Medical Center Chang Gung University College of Medicine Taiwan China

AIM： To combine ultrasound-guided fine-needle aspiration （US-FNA） and Liu （Riu） stain to make a quick study on liver tumor lesions. METHODS： Two hundred and twenty-eight aspirations from 232 patients were completely studied. The operator himself made the quick cytodiagnosis of US-FNA smear stained by Liu method within thirty minutes. The US-FNA specimen was also sent to the pathological department for cytological study and cellblock histology. The result of our Uu-stain quick cytodiagnosis in each patient was confirmed by the final cytopathological diagnosis from pathological report. RESULTS： Among 228 samples, the quick cytodiagnosis revealed 146 malignancies, 81 benign lesions and one inadequate specimen. Cytopathological diagnosis from the pathological department revealed 150 malignancies, and 78 benign lesions. Four well-differentiated hepatocellular carcinomas （HCCs） were under-diagnosed by quick cytodiagnosis as benign and 3 benign lesions were over-diagnosed as well-differentiated HCCs. Compared with cytopathological diagnosis, quick cytodiagnosis correctly diagnosed 143 malignancies and 77 benign lesions. Except for the one inadequate specimen in quick cytodiagnosis, the accuracy of quick cytodiagnosis was 96.9% （220/227）, and its sensitivity, specificity and positive and negative predictive values were 97.9%, 95.1%, 97.3% and 96.3%, respectively. CONCLUSION： Liu-stain quick cytodiagnosis is a fast, convenient, safe and effective method for hepatologists in clinic practice to diagnose liver tumor. In few cases of well-differentiated HCC, Liu-stain quick cytodiagnosis has its limitation.

关键词： Liver tumor Cytology Ultrasound guided FNA Liu stain

Endosonographic surveillance of 1-3 cm gastric submucosal tumors originating from muscularis propria

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World Journal of Gastroenterology 2017年第12期23卷 2194-2200页

作者： ming-luen hu keng-liang wu chi-sin changchien seng-kee chuah yi-chun chiu division of hepato-gastroenterology department of internal medicine kaohsiung chang gung memorial hospital and chang gung university college of medicine

AIM To observe the natural course of 1-3 cm gastric submucosal tumors originating from the muscularis propria(SMTMPs).METHODS By reviewing the computerized medical records over a period of 14 years(2000-2013), patients with 1-3 cm gastric SMTMPs who underwent at least two endoscopic ultrasound(EUS) examinations were enrolled. Tumor progression was defined as a ≥ 1.2 times enlargement in tumor diameter observed during EUS surveillance. All patients were divided into stationary and progressive subgroups and further analyzed. We also reviewed the patients in the progressive subgroup again in *** A total of 88 patients were studied, including 25 in the progressive subgroup. The mean time of EUS surveillance was 24.6 mo in the stationary subgroup and 30.7 mo in the progressive subgroup. Risk factors for tumor progression included larger tumor size and irregular border. Initial tumor size > 14.0 mm may be considered a cut-off size for predicting tumor progression. Seventeen patients underwent surgery, of whom 13 had gastrointestinal stromal tumors(GISTs) and 4 had leiomyomas. Tumor progression was found only in patients with GISTs. All of the tumors exhibited benign behaviors without metastasis until *** Most 1-3 cm gastric SMTMPs(71.6%) are indolent. Tumor progression was found only in GISTs, and it is a good predictor for differentiating GISTs from leiomyomas. Predictors of tumor progression include larger tumor size(> 14.0 mm) and irregular border.

关键词： Gastrointestinal stromal tumor Submucosal tumors originating from the muscularis propria Stomach Endosonographic surveillance

2011 update on esophageal achalasia

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World Journal of Gastroenterology 2012年第14期18卷 1573-1578页

作者： Seng-Kee Chuah Pin-I Hsu Keng-Liang Wu Deng-Chyang Wu Wei-Chen Tai chi-sin Changchien Division of Gastroenterology Kaohsiung ChangGung Memorial Hospital College of Medicine Chang GungUniversity Kaohsiung 833 Taiwan Division of Gastroenterology Department of Inter-nal Medicine Kaohsiung Veterans General Hospital NationalYang-Ming University Kaohsiung 813 Taiwan Cancer Center Division of Gastroenterol-ogy Department of Internal Medicine Kaohsiung MedicalUniversity Hospital Kaohsiung Medical University Kaohsiung807 Taiwan

There have been some breakthroughs in the diagnosis and treatment of esophageal achalasia in the past few ***,the introduction of high-resolution manometry with pressure topography plotting as a new diagnostic tool has made it possible to classify achalasia into three *** most favorable outcome is predicted for patients receiving treatment for type Ⅱ achalasia (achalasia with compression).Patients with typeⅠ(classic achalasia) and type Ⅲ achalasia (spastic achalasia) experience a less favorable ***,the first multicenter randomized controlled trial published by the European Achalasia Trial group reported 2-year follow-up results indicating that laparoscopic Heller myotomy was not superior to endoscopic pneumatic dilation (PD).Although the follow-up period was not long enough to reach a convincing conclusion,it merits the continued use of PD as a generally available technique in ***,the novelendoscopic technique peroral endoscopic myotomy is a promising option for treating achalasia,but it requires increased experience and cautious *** all this good news,the bottom line is a real break-through from the basic studies to identify the actual cause of achalasia that may impede treatment success is still anticipated.

关键词： Esophageal achalasia High resolution manometry Endoscopic pneumatic dilations Minimally invasive surgical procedures Peroral endoscopic myotomy