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Community-centered Disease Severity Assessment of Metabolic Dysfunction-associated Fatty Liver Disease

Journal of Clinical and Translational Hepatology 2023年第5期11卷 1061-1068页

作者： Jee-Fu Huang Pei-Chien Tsai ming-Lun Yeh Chung-Feng Huang Ching-I Huang Mei-Hsuan Lee Po-Yau Hsu Chih-Wen Wang Yu-Ju Wei Po-Cheng Liang Yi-Hung Lin Meng-Hsuan hsieh Jeng-Fu Yang ming-yen hsieh Tyng-Yuan Jang ming-Jong Bair Zu-Yau Lin Chia-yen Dai ming-Lung Yu Wan-Long Chuang Hepatobiliary Division Department of Internal MedicineKaohsiung Medical University HospitalKaohsiung Medical UniversityKaohsiung Graduate Institute of Clinical Medicine Kaohsiung Medical UniversityKaohsiung Faculty of Internal Medicine College of MedicineKaohsiung Medical UniversityKaohsiung Center for Liquid Biopsy and Cohort Research Kaohsiung Medical UniversityKaohsiung Institute of Clinical Medicine National Yang Ming Chiao Tung UniversityTaipei Department of Preventive Medicine Kaohsiung Medical University HospitalKaohsiung Division of Gastroenterology Department of Internal MedicineTaitung Mackay Memorial HospitalTaitung Mackay Medical College New Taipei City School of Medicine and Doctoral Program of Clinical and Experimental Medicine College of MedicineNational Sun Yat-sen UniversityKaohsiung Center of Excellence for Metabolic Associated Fatty Liver Disease National Sun Yat-sen UniversityKaohsiung

Background and Aims:Disease severity across the different diagnostic categories of metabolic dysfunction-associated fatty liver disease(MAFLD)remains *** study assessed the fibrosis stages and features of MAFLD between different *** also aimed to investigate the associations between advanced fibrosis and risk ***:This multicenter cross-sectional study enrolled adults participating in liver disease screening in the *** were stratified following MAFLD diagnostic criteria,to group A(395 patients)for type 2 diabetes,group B(1,818 patients)for body mass index(BMI)>23 kg/m^(2),and group C(44 patients)for BMI≤23kg/m^(2) with at least two metabolic *** fibrosis was defined as a fibrosis-4 index>***:Between 2009 and 2020,1,948 MAFLD patients were recruited,including 478 with concomitant liver *** fibrosis was observed in 125 patients.A significantly larger proportion of patients in group C(25.0%)than in group A(7.6%)and group B(5.8%)had advanced fibrosis (p<0.01).Logistic regression analysis found that hepatitis B virus(HBV)/hepatitis C virus(HCV)coinfection(odds ratio[OR]:12.14,95%confidence interval[CI]:4.04-36.52;p<0.01),HCV infection(OR:7.87,95%CI:4.78-12.97;p<0.01),group C(OR:6.00,95%CI:2.53-14.22;p<0.01),and TC/LDL-C(OR:1.21,95%CI:1.06-1.38;p<0.01)were significant predictors of advanced ***:A higher proportion of lean MAFLD patients with metabolic abnormalities had advanced *** infection was significantly associated with advanced fibrosis.

关键词： Metabolic dysfunction-associated fatty liver disease Fibrosis-4 index Advanced fibrosis Community screening Viral hepatitis

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Outreach onsite treatment with a simplified pangenotypic directacting anti-viral regimen for hepatitis C virus micro-elimination in a prison

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World Journal of Gastroenterology 2022年第2期28卷 263-274页

作者： Chun-Ting Chen ming-Ying Lu Meng-Hsuan hsieh Pei-Chien Tsai Tsai-Yuan hsieh ming-Lun Yeh Ching-I Huang Yi-Shan Tsai Yu-Min Ko Ching-Chih Lin Kuan-Yu Chen Yu-Ju Wei Po-Yao Hsu Cheng-Ting Hsu Tyng-Yuan Jang Ta-Wei Liu Po-Cheng Liang ming-yen hsieh Zu-Yau Lin Chung-Feng Huang Jee-Fu Huang Chia-yen Dai Wan-Long Chuang Yu-Lueng Shih ming-Lung Yu Division of Gastroenterology and Hepatology Department of Internal MedicineTri-Service General Hospital Penghu BranchNational Defense Medical CenterPenghu County 88041Taiwan Division of Gastroenterology and Hepatology Department of Internal MedicineTri-Service General HospitalNational Defense Medical CenterTaipei 11490Taiwan Division of Hepatobiliary Department of Internal Medicine and Hepatitis CenterKaohsiung Medical University HospitalKaohsiung 80708Taiwan School of Medicine and Hepatitis Research Center College of Medicineand Center for Liquid Biopsy and Cohort ResearchKaohsiung Medical UniversityKaohsiung 80708Taiwan National Pingtung University of Science and Technology Pingtung 912Taiwan

BACKGROUND Prisoners are at risk of hepatitis C virus(HCV)infection,especially among the people who inject drugs(PWID).We implemented an outreach strategy in combination with universal mass screening and immediate onsite treatment with a simplified pan-genotypic direct-acting antivirals(DAA)regimen,12 wk of sofosbuvir/velpatasvir,in a PWID-dominant prison in *** To implement an outreach strategy in combination with universal mass screening and immediate onsite treatment with a simplified pan-genotypic DAA regimen in a PWID-dominant prison in *** HCV-viremic patients were recruited for onsite treatment program for HCV micro-elimination with a pangenotypic DAA regimen,12 wk of sofosbuvir/velpatasvir,from two cohorts in Penghu Prison,either identified by mass screen or in outpatient clinics,in September *** group of HCV-viremic patients identified sporadically in outpatient clinics before mass screening were enrolled as a control *** primary endpoint was sustained virological response(SVR12,defined as undetectable HCV ribonucleic acid(RNA)12 wk after end-of-treatment).RESULTS A total of 212 HCV-viremic subjects were recruited for HCV micro-elimination campaign;91 patients treated with sofosbuvir/Ledipasvir or glecaprevir/pibrentasvir before mass screening were enrolled as a *** HCV microelimination group had significantly lower proportion of diabetes,hypertension,hyperlipidemia,advanced fibrosis and chronic kidney diseases,but higher levels of HCV *** SVR12 rate was comparable between the HCV microelimination and control groups,95.8%(203/212)vs 94.5%(86/91),respectively,in intent-to-treat analysis,and 100%(203/203)vs 98.9%(86/87),respectively,in perprotocol *** was no virological failure,treatment discontinuation,and serious adverse event among sofosbuvir/velpatasvir-treated patients in the HCV micro-elimination *** Outreach mass screening followed by immediate onsite treatment with a simplified pange

关键词： Direct-acting antivirals Sofosbuvir Velpatasvir People who inject drugs Universal screen

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Dynamics of cytokines predicts risk of hepatocellular carcinoma among chronic hepatitis C patients after viral eradication

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World Journal of Gastroenterology 2022年第1期28卷 140-153页

作者： ming-Ying Lu ming-Lun Yeh Ching-I Huang Shu-Chi Wang Yi-Shan Tsai Pei-Chien Tsai Yu-Min Ko Ching-Chih Lin Kuan-Yu Chen Yu-Ju Wei Po-Yao Hsu Cheng-Ting Hsu Tyng-Yuan Jang Ta-Wei Liu Po-Cheng Liang ming-yen hsieh Zu-Yau Lin Shinn-Cherng Chen Chung-Feng Huang Jee-Fu Huang Chia-yen Dai Wan-Long Chuang ming-Lung Yu Hepatitis Center and Hepatobiliary Division Department of Internal MedicineKaohsiung Medical University HospitalKaohsiung 80708Taiwan School of Medicine and Hepatitis Research Center College of MedicineCenter for Cancer Research and Center for Liquid BiopsyKaohsiung Medical UniversityKaohsiung 80708Taiwan Department of Medical Laboratory Science and Biotechnology Kaohsiung Medical UniversityKaohsiung 80708Taiwan Health Management Center Department of Community MedicineKaohsiung Medical University HospitalKaohsiung 80708Taiwan Institute of Biomedical Sciences National Sun Yat-Sen UniversityKaohsiung 80708Taiwan

BACKGROUND Chronic hepatitis C virus(HCV)infection induces profound alterations in the cytokine and chemokine signatures in peripheral *** of HCV by antivirals results in host immune modification,which may interfere with immune-mediated cancer *** HCV patients who remain at risk of hepatocellular carcinoma(HCC)following HCV eradication remains an unmet *** hypothesized that antiviral therapy-induced immune reconstruction may be relevant to HCC *** To investigate the impact of differential dynamics of cytokine expression on the development of HCC following successful antiviral *** One hundred treatment-naïve HCV patients with advanced fibrosis(F3/4)treated with direct-acting antivirals(DAAs)or peginterferon/ribavirin who achieved sustained virologic response[SVR,defined as undetectable HCV RNA throughout 12 wk(SVR12)for the DAA group or 24 wk(SVR24)for the interferon group after completion of antiviral therapy]were enrolled since *** primary endpoint was the development of new-onset *** HCC surveillance(abdominal ultrasound andα-fetoprotein)was performed every six months during the ***,64 serum cytokines were detected by the multiplex immunoassay at baseline and 24 wk after *** HCC developed in 12 of the 97 patients over 459 person-years after HCV *** univariate analysis,the Fibrosis-4 index(FIB-4),hemoglobin A1c(HbA1c),the dynamics of tumor necrosis factor-α(TNF-α),and TNF-like weak inducer of apoptosis(TWEAK)after antiviral therapy were significant HCC *** multivariate Cox regression model showed thatΔTNF-α(≤-5.7 pg/mL)was the most important risk factor for HCC(HR=11.54,95%CI:2.27-58.72,P=0.003 in overall cases;HR=9.98,95%CI:1.88-52.87,P=0.007 in the interferon group).An HCC predictive model comprising FIB-4,HbA1c,ΔTNF-α,andΔTWEAK had excellent performance,with 3-,5-,10-,and 13-year areas under the curve of 0.882,0.864,0.903,and 1.000,r

关键词： Hepatitis C virus Hepatocellular carcinoma Sustained virologic response Tumor necrosis factor-α Tumor necrosis factor-like weak inducer of apoptosis Cytokine

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Co-infection of SENV-D among chronic hepatitis C patients treated with combination therapy with high-dose interferon-alfa and ribavirin

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World Journal of Gastroenterology 2005年第27期11卷 4241-4245页

作者： Chia-yen Dai Wan-Long Chuang Wen-Yu Chang Shinn-Chemg Chen Li-Po Lee ming-yen hsieh Nei-Jen Hou Zu-Yau Un ming-Yuh hsieh Liang-yen Wang ming-Lung Yu Hepatobiliary Division Department of Internal MedicineKaohsiung Medical University Hospital Kaohsiung Taiwan China Department of Internal Medicine Kaohsiung Municipal Hsiao-Kang Hospital Kaohsiung TaiwanChina Department of Occupational Medicine Kaohsiung Municipal Hsiao-Kang Hospital Kaohsiung Taiwan China

AIM: The clinical significance of co-infection of SENV-D among patients with chronic hepatitis C (CHC) and response of both viruses to combination therapy with high-dose interferon-alfa (IFN) plus ribavirin remain uncertain and are being ***: Total 164 (97 males and 67 females, the mean age 48.1±11.4 years, range: 20-73 years, 128histologically proved) naive CHC patients were enrolled in this study. SENV-D DNA was tested by PCR *** of serum HCV RNA was performed using a standardized automated qualitative RT-PCR assay (COBAS AMPLICOR HCV Test, version 2.0). HCV genotypes 1a,1b, 2a, 2b, and 3a were determined by using genotypespecific primers. Pretreatment HCV RNA levels were determined by using the branched DNA assay (Quantiplex HCV RNA 3.0). There are 156 patients receiving combination therapy with IFN 6 MU plus ribavirin for 24 wk and the response to therapy is ***: Sixty-one (37.2%) patients were positive for SENV-D DNA and had higher mean age than those who were negative (50.7±10.6 years vs46.6±11.6 years,P = 0.026). The rate of sustained viral response (SVR)for HCV and SENV-D were 67.3% (105/156) and 56.3%(27/48), respectively. By univariate analysis, the higher rate of SVR was significantly related to HCV genotype non-1b (P＜0.001), younger ages (P = 0.014), lower pretreatment levels of HCV RNA (P = 0.019) and higher histological activity index (HAI) score for intralobular regeneration and focal necrosis (P = 0.037). By multivariate analyses, HCV genotype non-1b, younger age and lower pretreatment HCV RNA levels were significantly associated with HCV SVR (odds ratio (OR)/95% confidence interval (CI): 12.098/0.02-0.19, 0.936/0.890-0.998, and 3.131/1.080-9.077, respectively). The SVR of SENV-D was higher among patients clearing SENV-D than those who had viremia at the end of therapy (P = 0.04).CONCLUSION: Coexistent SENV-D infection, apparently associated with higher ages, is found in more than onethird Taiwan Residents

关键词：钴元素慢性丙型肝炎干扰素-α 用药剂量病毒唑

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Origins of perturbations in dayside equatorial ground magnetograms

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Earth and Planetary Physics 2024年第1期8卷 215-221页

作者： Syau-Yun W.hsieh David G.Sibeck The Johns Hopkins University Applied Physics Laboratory LaurelMarylandUSA NASA Goddard Space Flight Center GreenbeltMarylandUSA

To determine the cause(s)of perturbations seen in dayside equatorial ground magnetograms,we conducted a systematic survey of simultaneous ground-based and geosynchronous satellite-based observations during the 90-day period from December 1,2020 to February 28,*** examined Huancayo ground magnetometer observations from 14:00:00 to 20:00:00 UT each day,during which Huancayo passed through local *** those data we chose perturbation events selected on the basis of large(>20 nT)event amplitude and classified the selected events as responding primarily to solar wind pressure,or to variations in the north/south component of the interplanetary magnetic field(IMF Bz),or perhaps in part to *** results show that an equivalent number of events were identified for each model during this 90-day *** in the lagged solar wind dynamic pressure routinely correspond to nearly simultaneous sudden impulses recorded at both geosynchronous orbit and on the *** in IMF Bz produce erosion signatures at geosynchronous orbit and can correspond to ground events if lag times for reconnection to enhance convection in the magnetosphere are taken into account.

关键词： dayside magnetosphere dayside equatorial ionosphere geosynchronous magnetic field

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Management of retroperitoneal high-grade serous carcinoma of unknown origin:A case report

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World Journal of Clinical Cases 2024年第6期12卷 1190-1195页

作者： Wen-Lin hsieh Dah-Ching Ding Department of Obstetrics and Gynecology Hualien Tzu Chi HospitalBuddhist Tzu Chi Medical FoundationTzu Chi UniversityHualien 970Taiwan Institute of Medical Sciences Tzu Chi UniversityHualien 970TaiwanTaiwan

BACKGROUND Retroperitoneal high-grade serous carcinoma(HGSC)of unknown origin is a sporadic tumor that can originate from ovarian ***,we report the case of a woman with retroperitoneal HGSC of unknown origin and describe how she was diagnosed and *** SUMMARY A 71-year-old female presented with the tumor marker CA125 elevated to 1041.9 U/mL upon a regular health *** tomography revealed retroperitoneal lymph node ***,positron emission tomography scanning revealed lesions with increased F-18 fluorodeoxyglucose uptake at the *** a result,she underwent laparoscopic lymph node resection,and pathology revealed metastatic adenocarcinoma with CK7(+),PAX8(+),WT1(+),PR(-),and p53 mutational loss of expression,indicating that the origin may be from the *** patient was admitted to our ward and underwent laparoscopic staging;however,the pathological results were *** the suspicion of retroperitoneal HGSC of unknown origin,chemotherapy and targeted therapy were *** marker levels decreased after *** We present a case of HGSC of unknown origin managed using retroperitoneal lymphadenectomy,staging surgery,chemotherapy,and targeted therapy.

关键词： High-grade serous carcinoma Retroperitoneum Origin Chemotherapy Lymph node Case report

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Automated and miniaturized screening of antibiotic combinations via robotic-printed combinatorial droplet platform

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1801-1813页

作者： Fangchi Shao Hui Li Kuangwen hsieh Pengfei Zhang Sixuan Li Tza-Huei Wang Department of Biomedical Engineering Johns Hopkins UniversityBaltimoreMD 21218USA Department of Mechanical Engineering Johns Hopkins UniversityBaltimoreMD 21218USA

Antimicrobial resistance(AMR)has become a global health crisis in need of novel *** this end,antibiotic combination therapies,which combine multiple antibiotics for treatment,have at-tracted significant attention as a potential approach for combating *** facilitate advances in anti-biotic combination therapies,most notably in investigating antibiotic interactions and identifying synergistic antibiotic combinations however,there remains a need for automated high-throughput plat-forms that can create and examine antibiotic combinations on-demand,at scale,and with minimal reagent *** address these challenges,we have developed a Robotic-Printed Combinatorial Droplet(RoboDrop)platform by integrating a programmable droplet microfuidic device that generates antibiotic combinations in nanoliter droplets in automation,a robotic arm that arranges the droplets in an array,and a camera that images the array of thousands of droplets in *** further implement a resazurin-based bacterial viability assay to accelerate our antibiotic combination *** a demonstration,we use RoboDrop to corroborate two pairs of antibiotics with known interactions and subsequently identify a new synergistic combination of cefsulodin,penicillin,and oxacillin against a model *** *** therefore envision RoboDrop becoming a useful tool to efficiently identify new synergistic antibiotic combinations toward combating AMR.

关键词： Droplet microfluidics Antimicrobial resistance Antibiotic combinatorial screening Contact printing Robotics Pharmaceutical analysis High-throughput Antibiotic interactions

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Programming nonlinear propagation for efficient optical learning machines

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Advanced Photonics 2024年第1期6卷 73-83页

作者： Ilker Oguz Jih-Liang hsieh Niyazi Ulas Dinc Ugur Tegin Mustafa Yildirim Carlo Gigli Christophe Moser Demetri Psaltis École Polytechnique Fédérale de Lausanne Institute of Electrical and Micro EngineeringEcublensSwitzerland Koc University Department of Electrical and Electronics EngineeringIstanbulTurkey

The ever-increasing demand for training and inferring with larger machine-learning models requires more efficient hardware solutions due to limitations such as power dissipation and *** is a promising contender for providing lower power computation,since light propagation through a nonabsorbing medium is a lossless ***,to carry out useful and efficient computations with light,generating and controlling nonlinearity optically is a necessity that is still *** fibers(MMFs)have been shown that they can provide nonlinear effects with microwatts of average power while maintaining parallelism and low *** propose an optical neural network architecture that performs nonlinear optical computation by controlling the propagation of ultrashort pulses in MMF by wavefront *** a surrogate model,optimal sets of parameters are found to program this optical computer for different tasks with minimal utilization of an electronic *** show a remarkable decrease of 97%in the number of model parameters,which leads to an overall 99%digital operation reduction compared to an equivalently performing digital neural *** further demonstrate that a fully optical implementation can also be performed with competitive accuracies.

关键词： neural networks nonlinear optics fiber optics surrogate optimization neuromorphic computing wavefront shaping

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Generic Interpretable Reaction Condition Predictions with Open Reaction Condition Datasets and Unsupervised Learning of Reaction Center

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Research 2024年第2期2023卷 773-794页

作者： Xiaorui Wang Chang-Yu hsieh Xiaodan Yin Jike Wang Yuquan Li Yafeng Deng Dejun Jiang Zhenxing Wu Hongyan Du Hongming Chen Yun Li Huanxiang Liu Yuwei Wang Pei Luo Tingjun Hou Xiaojun Yao Dr.Neher's Biophysics Laboratory for lnnovative Drug Discovery State Key Laboratory of Quality Research in Chinese MedicineMacao Institute for Applied Research in Medicine and HealthMacao University of Science and TechnologyMacao999078China innovation Institute for Artificial Intelligence in Medicine of Zhejiang University College of Pharmaceutical SciencesZhejiang UniversityHangzhou310058China Faculty of Applied Sciences Macao Polytechnic UniversityMacao999078China College of Chemistry and Chemical Engineering Lanzhou UniversityLanzhou730000China Carbon Silicon AI Technology Co. LtdHangzhouZhejiang 310018China Center of Chemistry and Chemical Biology Guangzhou Regenerative Medicine and Health Guangdong LaboratoryGuangzhou 510530China College of Pharmacy Shaanxi University of Chinese MedicineXianyangShaanxi712044China

Effective synthesis planning powered by deep learning(DL)can significantly accelerate the discovery of new drugs and ***,most DL-assisted synthesis planning methods offer either none or very limited capability to recommend suitable reaction conditions(RCs)for their reaction ***,the prediction of RCs with a DL framework is hindered by several factors,including:(a)lack of a standardized dataset for benchmarking,(b)lack of a general prediction model with powerful representation,and(c)lack of *** address these issues,we first created 2 standardized RC datasets covering a broad range of reaction classes and then proposed a powerful and interpretable Transformer-based RC predictor named *** careful design of the model architecture,pretraining method,and training strategy,Parrot improved the overall top-3 prediction accuracy on catalysis,solvents,and other reagents by as much as 13.44%,compared to the best previous model on a newly curated ***,the mean absolute error of the predicted temperatures was reduced by about 4℃.Furthermore,Parrot manifests strong generalization capacity with superior cross-chemical-space prediction *** analysis indicates that Parrot effectively captures crucial chemical information and exhibits a high level of interpretability in the prediction of *** proposed model Parrot exemplifies how modern neural network architecture when appropriately pretrained can be versatile in making reliable,generalizable,and interpretable recommendation for RCs even when the underlying training dataset may still be limited in diversity.

关键词： versatile absolute generalization

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Adaptive Fourier Decomposition of the First Three SARS-CoV-2 Infection Waves with Epidemic Intervention—London,UK,2020-2022

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China CDC weekly 2024年第21期6卷 478-486,I0006-I0008页

作者： Zige Liu Guibin Lu Cheokieng Vong Zhiqi Zeng Wei He Zhijie Lin Cuiyun Lin Kaichin hsieh Zifeng Yang Arlindo L.Oliveira Chitin Hon Department of Engineering Science Faculty of Innovation EngineeringMacao University of Science and TechnologyMacao SARChina Queen Ethelburga’s Collegiate Thorpe Underwood EstateYorkUK State Key Laboratory of Respiratory Disease National Clinical Research Center for Respiratory DiseaseGuangzhou Institute of Respiratory HealthThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou CityGuangdong ProvinceChina Respiratory Disease AI Laboratory on Epidemic and Medical Big Data Instrument Applications Department of Engineering ScienceFaculty of Innovation EngineeringMacao University of Science and TechnologyMacao SARChina Guangzhou Key Laboratory for Clinical Rapid Diagnosis and Early Warning of Infectious Diseases KingMed School of Laboratory MedicineGuangzhou Medical UniversityGuangzhou CityGuangdong ProvinceChina Faculty of Innovation Engineering School of Computer Science and EngineeringMacao University of Science and TechnologyMacao SARChina University College London UCL Faculty of Engineering SciencesLondonUK Guangzhou Laboratory Guangzhou CityGuangdong ProvinceChina Instituto de Engenharia de Sistemas e Computadores:Investigação e Desenvolvimento em Lisboa LisboaPortugal Instituto Superior Técnico Universidade de LisboaLisboaPortugal

Background:This study provides a detailed analysis of the daily fluctuations in coronavirus disease 2019(COVID-19)case numbers in London from January 31,2020 to February 24,*** primary objective was to enhance understanding of the interactions among government pandemic responses,viral mutations,and the subsequent changes in COVID-19 case ***:We employed the adaptive Fourier decomposition(AFD)method to analyze diurnal changes and further segmented the AFD into novel multi-component groups consisting of one to three *** restructured components were rigorously evaluated using Pearson correlation,and their effectiveness was compared with other signal analysis *** study introduced a novel approach to differentiate individual components across various time-frequency scales using basis decomposition ***:Analysis of London’s daily COVID-19 data using AFD revealed a strong correlation between the“stay at home”directive and high-frequency components during the first epidemic *** indicates the need for sustained implementation of vaccination policies to maintain their ***:The AFD component method provides a comprehensive analysis of the immediate and prolonged impact of governmental policies on the spread of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).This robust tool has proven invaluable for analyzing COVID-19 pandemic data,offering critical insights that guide the formulation of future preventive and public health strategies.

关键词： offering sustained London

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