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Intranasal administration of a single dose of a candidate live attenuated vaccine derived from an NSP16-deficient SARS-CoV-2 strain confers sterilizing immunity in animals

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Cellular & Molecular Immunology 2022年第5期19卷 588-601页

作者： Zi-Wei Ye Chon Phin Ong Kaiming Tang Yilan Fan Cuiting Luo Runhong Zhou Peng Luo Yun Cheng Victor Sebastien Gray Pui Wang Hin Chu Jasper Fuk-Woo Chan Kelvin Kai-Wang To Honglin Chen Zhiwei Chen kwok-yung yuen Guang Sheng Ling Shuofeng Yuan Dong-Yan Jin Department of Microbiology Li Ka Shing Faculty of MedicineThe University of Hong Kong102 Pokfulam RoadPokfulamHong KongChina State Key Laboratory of Emerging Infectious Diseases The University of Hong Kong102 Pokfulam RoadPokfulamHong KongChina School of Biomedical Sciences Li Ka Shing Faculty of MedicineThe University of Hong Kong21 Sassoon RoadPokfulamHong KongChina

Live attenuated vaccines might elicit mucosal and sterilizing immunity against SARS-CoV-2 that the existing mRNA,adenoviral vector and inactivated vaccines fail to ***,we describe a candidate live attenuated vaccine strain of SARS-CoV-2 in which the NSP16 gene,which encodes 2′-O-methyltransferase,is catalytically disrupted by a point *** virus,designated d16,was severely attenuated in hamsters and transgenic mice,causing only asymptomatic and nonpathogenic infection.A single dose of d16 administered intranasally resulted in sterilizing immunity in both the upper and lower respiratory tracts of hamsters,thus preventing viral spread in a contact-based transmission *** also robustly stimulated humoral and cell-mediated immune responses,thus conferring full protection against lethal challenge with SARS-CoV-2 in a transgenic mouse *** neutralizing antibodies elicited by d16 effectively cross-reacted with several SARS-CoV-2 *** immunoglobulin A was detected in the blood and nasal wash of vaccinated *** work provides proof-of-principle evidence for harnessing NSP16-deficient SARS-CoV-2 for the development of live attenuated vaccines and paves the way for further preclinical studies of d16 as a prototypic vaccine strain,to which new features might be introduced to improve safety,transmissibility,immunogenicity and efficacy.

关键词： Live attenuated vaccine NSP16 2'-O-methyltransferase T-cell response Mucosal immunity Sterilizing immunity

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Characteristics of Emission Non-nulling Pulsars Through Simulation

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Research in Astronomy and Astrophysics 2024年第4期24卷 91-102页

作者： Rai yuen Xinjiang Astronomical Observatory Chinese Academy of SciencesUrumqi 830011China Xinjiang Key Laboratory of Radio Astrophysics Chinese Academy of SciencesUrumqi 830011China Key Laboratory of Radio Astronomy Chinese Academy of SciencesNanjing 210008China SIfA School of PhysicsUniversity of SydneySydneyNSW2006Australia

We investigate the population and several properties of radio pulsars whose emission does not null(non-nulling)through simulation of a large pulsar *** from a pulsar is identified as non-nulling if(i)the emission does not cease across the whole pulse profile,and(ii)the emission is ***(i),we adopt a model for switching in the plasma charge density,and emission persists if the charge density is ***(ii),we assume that detectable emission originates from source points where it is emitted tangentially to the magnetic field-line and parallel to the *** find that pulsars exhibiting non-nulling emission possess obliquity angles with an average of 42°.5,and almost half the samples maintain a duty cycle between 0.05 and ***,the pulsar population is not fixed but dependent on the obliquity angle,with the population peaking at 20°.In addition,three evolutionary phases are identified in the pulsar population as the obliquity angle evolves,with the majority of samples having an obliquity angle between 20°and 65°.Our results also suggest that emission from a pulsar may evolve between nulling and non-nulling during its lifetime.

关键词： radiation mechanisms:non thermal stars:neutron (stars:)pulsars:general

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Targeting papain-like protease for broad-spectrum coronavirus inhibition

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Protein & Cell 2022年第12期13卷 940-953页

作者： Shuofeng Yuan Xiaopan Gao Kaiming Tang Jian-Piao Cai Menglong Hu Peng Luo Lei Wen Zi-Wei Ye Cuiting Luo Jessica Oi-Ling Tsang Chris Chun-Yiu Chan Yaoqiang Huang Jianli Cao Ronghui Liang Zhenzhi Qin Bo Qin Feifei Yin Hin Chu Dong-Yan Jin Ren Sun Jasper Fuk-Woo Chan Sheng Cui kwok-yung yuen State Key Laboratory of Emerging Infectious Diseases Li Ka Shing Faculty of MedicineThe University of Hong KongPokfulamHong Kong SARChina Department of Microbiology Li Ka ShingFaculty of MedicineThe University of Hong KongPokfulamHong Kong SARChina NHC Key Laboratory of Systems Biology of Pathogens Institute of Pathogen BiologyChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China School of Biomedical Sciences Li Ka Shing Faculty of MedicineThe University of Hong KongPokfulamHong Kong SARChina Department of Molecular and Medical Pharmacology David Geffen School of MedicineUniversity of California Los AngelesLos AngelesCAUSA Key Laboratory of Tropical Translational Medicine of Ministry of Education Hainan Medical UniversityHaikou 571199China Academician Workstation of Hainan Province Hainan Medical UniversityHaikou 571199China Hainan Medical University-The University of Hong Kong Joint Laboratory of Tropical Infectious Diseases The University of Hong KongPokfulamHong Kong Special Administrative RegionChina Guangzhou Laboratory Guangzhou 510320China Department of Clinical Microbiology and Infection Control The University of Hong Kong-Shenzhen HospitalShenzhen 518053China

The emergence of SARS-CoV-2 variants of concern and repeated outbreaks of coronavirus epidemics in the past two decades emphasize the need for next-generation pan-coronaviral *** the multi-functional papain-like protease(PLpro)domain of the viral nsp3 holds ***,none of the known coronavirus PLpro inhibitors has been shown to be in vivo ***,we screened a structurally diverse library of 50,080 compounds for potential coronavirus PLpro inhibitors and identified a noncovalent lead inhibitor F0213 that has broad-spectrum anti-coronaviral activity,including against the Sarbecoviruses(SARSCoV-1 and SARS-CoV-2),Merbecovirus(MERS-CoV),as well as the Alphacoronavirus(hCoV-229E and hCoVOC43).Importantly,F0213 confers protection in both SARS-CoV-2-infected hamsters and MERS-CoV-infected human DPP4-knockin mice.F0213 possesses a dual therapeutic functionality that suppresses coronavirus replication via blocking viral polyprotein cleavage,as well as promoting antiviral immunity by antagonizing the PLpro deubiquitinase *** the significant difference of substrate recognition,mode of inhibition studies suggest that F0213 is a competitive inhibitor against SARS2-PLpro via binding with the 157K amino acid residue,whereas an allosteric inhibitor of MERSPLpro interacting with its 271E *** proof-ofconcept findings demonstrated that PLpro is a valid target for the development of broad-spectrum anticoronavirus *** orally administered F0213 may serve as a promising lead compound for combating the ongoing COVID-19 pandemic and future coronavirus outbreaks.

关键词： protease inhibitor coronavirus Nsp3 antiviral

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SARS病人SARS冠状病毒核壳抗原抗体的变化规律

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南方医科大学学报 2003年第7期23卷 637-639页

作者：车小燕,郝卫,丘立文,潘玉先,廖志勇,徐华,陈金军,候金林,Patrick CY Woo,Susanna KP Lau,kwok yung yuen,黄震第一军医大学珠江医院香港大学微生物系第一军医大学珠江医院广东广州510282 广东广州510282 广东广州510282 广东广州510282 广东广州510282 广东广州510282 广东广州510515 广东广州510515 第一军医大学珠江医院中心实验室香港广东广州510282 香港广东广州510282 第一军医大学珠江医院中心实验室第一军医大学珠江医院中心实验室第一军医大学珠江医院中心实验室第一军医大学珠江医院中心实验室第一军医大学珠江医院中心实验室第一军医大学南方医院感染内科第一军医大学南方医院感染内科香港大学微生物系

目的通过监测SARS冠状病毒感染患者的抗体水平,阐明SARS冠状病毒感染机体免疫应答的机制并探讨血清学诊断的意义。方法采用基因重组SARS冠状病毒核壳抗原(N)建立间接ELISA法,检测健康人和SARS患者急性期和恢复期多点血清中特异性IgG和Ig... 详细信息

目的通过监测SARS冠状病毒感染患者的抗体水平,阐明SARS冠状病毒感染机体免疫应答的机制并探讨血清学诊断的意义。方法采用基因重组SARS冠状病毒核壳抗原(N)建立间接ELISA法,检测健康人和SARS患者急性期和恢复期多点血清中特异性IgG和IgM抗体。以D450值=2.1×200例健康人血清中特异性IgG和IgM抗体均值作为抗体阳性判断的临界值。结果IgM和IgG的阳性临界值分别为0.233 和0.239。以此对13例SARS病人急性期和恢复期IgM和IgG抗体检测结果进行判断,结果发现:发病1周内,IgM和IgG抗体检测均为阴性;发病第2周,IgM和IgG检出阳性率分别为83.3%和66.7%;第3周均为100%;发病第2个月,IgM检出阳性率为61.5%,至第3个月,IgM检出阳性率为38.5%;IgG至第1个月时达到高峰,第3个月仍维持在高水平。结论机体产生针对SARS冠状病毒核壳抗原的抗体持续时间长,提示SARS冠状病毒核壳抗原具有强免疫原性,在SARS冠状病毒致病机制中可能起重要的作用、在SARS的血清学诊断方面具有重要的价值。

关键词：严重急性呼吸道综合征 SARS冠状病毒核壳蛋白血清学试验

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The Therapeutic Effect of Pamidronate on Lethal Avian Influenza A H7N9 Virus Infected Humanized Mice

The Therapeutic Effect of Pamidronate on Lethal Avian Influe...

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第十届全国免疫学学术大会

作者： Jian Zheng Wai-Lan Wu Yinping Liu Zheng Xiang Ming Liu kwok-Hung Chan Siu-Ying Lau kwok-Tai Lam Kelvin Kai-Wang To Joseph Fuk-Woo Chan Lanjuan Li Honglin Chen Yu-Lung Lau kwok-yung yuen Wenwei Tu Department of Paediatrics & Adolescent Medicine University of Hong Kong State Key Laboratory of Emerging Infectious Diseases Department of Microbiology University of Hong Kong Guangzhou Institute of Respiratory Diseases Guangzhou Medical University State Key Laboratory for Diagnosis and Treatment of Infectious Diseases first Affiliated HospitalCollege of Medicine Zhejiang University

Objective:A novel avian influenza virus H7N9 infection occurred among human populations since *** thelack of sustained human-to-human transmission limited the epidemics caused by H7N9,the late presentation of most patients and the emergence of neuraminidase-resistant strains made the development of novel antiviral strategy against H7N9 in urgent *** this study,we evaluated the potential of pamidronate,a pharmacological phosphoantigen that can specifically boost human Vdelta2-T-cell,on treating H7N9 virus-infected humanized ***:H7N9-infected humanized mice were treated with a human equivalent dose of pamidronate or saline of equivalent volume via injected intraperitoneal injection,or oseltamivir or saline of equivalent volume by oral *** weight change and survival of infected mice were monitored *** indicated time points,lungs from different groups were harvested for pathology examination,while the viral loads and the levels of human pro-inflammatory cytokines and chemokines in the supernatants of homogenized lung tissue were ***:Our results showed that intraperitoneal injection of pamidronate could potently decrease the morbidity and mortality of H7N9-infected mice through controlling both viral replication and inflammation in affected *** importantly,pamidronate treatment starting from 3 days after infection could still significantly ameliorate the severity of diseases in infected mice and improve their survival chance,whereas orally oseltamivir treatment starting at the same time showed no therapeutic *** for the mechanisms underlying pamidronate-based therapy,our in vitro data demonstrated that its antiviral effects were mainly mediated by human Vdelta2-T-cell through their secretion of IFN-γand cytotoxicity against virus-infected host cells dependent on the expressions of perforin,granzyme B and ***:As pamidronate has been used for osteoporosis treatment for more than 20 years,pamidr

关键词： Vdelta2-T cell Amidronate Oseltamivir Humanized mice

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Asymptotics for the joint tail probability of bidimensional randomly weighted sums with applications to insurance

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Science China Mathematics 2024年第1期67卷 163-186页

作者： Yang Yang Shaoying Chen Kam Chuen yuen School of Statistics and Data Science Nanjing Audit UniversityNanjing 211815China Department of Statistics and Actuarial Science The University of Hong KongHong Kong 999077China

This paper studies the joint tail behavior of two randomly weighted sums∑_(i=1)^(m)Θ_(i)X_(i)and∑_(j=1)^(n)θ_(j)Y_(j)for some m,n∈N∪{∞},in which the primary random variables{X_(i);i∈N}and{Y_(i);i∈N},respectively,are real-valued,dependent and heavy-tailed,while the random weights{Θi,θi;i∈N}are nonnegative and arbitrarily dependent,but the three sequences{X_(i);i∈N},{Y_(i);i∈N}and{Θ_(i),θ_(i);i∈N}are mutually *** two types of weak dependence assumptions on the heavy-tailed primary random variables and some mild moment conditions on the random weights,we establish some(uniformly)asymptotic formulas for the joint tail probability of the two randomly weighted sums,expressing the insensitivity with respect to the underlying weak dependence *** applications,we consider both discrete-time and continuous-time insurance risk models,and obtain some asymptotic results for ruin probabilities.

关键词： asymptotic joint tail behavior randomly weighted sum heavy-tailed distribution dependence insurance risk model

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Targeting calcium signaling in Alzheimer’s disease: challenges and promising therapeutic avenues

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Neural Regeneration Research 2024年第3期19卷 501-502页

作者： LinLin Song YongPei Tang Betty yuen Kwan Law Neher’s Biophysics Laboratory for Innovative Drug Discovery State Key Laboratory of Quality Research in Chinese MedicineMacao University of Science and TechnologyMacao Special Administration RegionChina

The critical role of calcium dyshomeostasis in the pathogenesis of Alzheimer’s disease(AD):AD is a progressive neurodegenerative disease characterized by cognitive decline,memory impairment,and behavioral *** an estimated 50 million people being affected worldwide,the incidence of AD is constantly increasing *** hallmark of AD is the accumulation of amyloid-beta protein(Aβ)in the form of amyloid plaques and hyperphosphorylated tau protein in the form of neurofibrillary ***,increasing evidence suggests that calcium ion(Ca2+)dysregulation also plays a crucial role in the pathogenesis of AD(Calvo-Rodriguez and Bacskai,2021).As a key second messenger,Ca2+regulates a wide range of cellular processes,including the release of neurotransmitters,gene expression,and cell ***^(2+)also regulates the activity of Calcium/calmodulin-dependent protein kinase II,which is critical for synaptic plasticity,learning,and memory(Kaushik et al.,2022).Alternation in the Ca^(2+)signal is an early event in the pathogenesis of AD,which can lead to synaptic dysfunction,neuronal loss,and cognitive impairment.

关键词： Alzheimer homeostasis globally

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A prospective cohort of men with localized prostate cancer on active surveillance protocol in Hong Kong,China:what did we learn?

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Asian Journal of Andrology 2024年第3期26卷 245-249页

作者： Xiaobo Wu Ivan Ching-Ho Ko Cindy Yeuk-Lam Hong Samuel Chi-Hang Yee Jeremy yuen-Chun Teoh Samson Yun-Sang Chan Ho-Man Tam Chi-kwok Chan Chi-Fai Ng Peter Ka-Fung Chiu SH Ho Urology Centre Department of SurgeryFaculty of MedicineThe Chinese University of Hong KongHong KongChina

This study aimed to report the outcomes of active surveillance(AS)in the management of low-risk prostate cancer(PCa).It recruited87 men who were prospectively followed up according to the Prostate Cancer Research International Active Surveillance(PRIAS)protocol with local adaptation at SH Ho Urology Centre,Prince of Wales Hospital,Hong Kong,*** investigated the predictorsof disease progression and found that baseline prostate-specific antigen density(PSAD)and the presence of the highest ProstateImaging-Reporting and Data System(PI-RADS)score 5 lesion on magnetic resonance imaging(MRI)are significantly correlatedwith disease ***,men with PSAD>0.2 ng ml^(−2)or PI-RADS 4 or 5 lesions had significantly worse upgradingfree survival compared to those with PSAD≤0.2 ng ml−2 and PI-RADS 2 or 3 *** study concludes that AS is a safe andeffective management strategy for selected patients to defer radical treatment and that most disease progression can be detectedafter the first repeated *** combination of PSAD>0.2 ng ml^(−2)and PI-RADS 4 or 5 lesions may serve as a useful predictorof early disease progression and provide a guide to optimize follow-up protocols for men in different risk groups.

关键词： active surveillance cohort localized prostate cancer

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Spreadsheet quality assurance:a literature review

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Frontiers of Computer Science 2024年第2期18卷 61-82页

作者： Pak-Lok POON Man Fai LAU yuen Tak YU Sau-Fun TANG School of Engineering and Technology Central Queensland UniversityMelbourne 3000Australia Department of Computing Technologies Swinburne University of TechnologyHawthorn 3122Australia Department of Computer Science City University of Hong KongHong Kong SAR 999077China The Royal Victorian Eye and Ear Hospital East Melbourne 3002Australia

Spreadsheets are very common for information processing to support decision making by both professional developers and non-technical end ***,business intelligence and artificial intelligence are increasingly popular in the industry nowadays,where spreadsheets have been used as,or integrated into,intelligent or expert systems in various application ***,it has been repeatedly reported that faults often exist in operational spreadsheets,which could severely compromise the quality of conclusions and decisions based on the *** a view to systematically examining this problem via survey of existing work,we have conducted a comprehensive literature review on the quality issues and related techniques of spreadsheets over a 35.5-year period(from January 1987 to June 2022)for target journals and a 10.5-year period(from January 2012 to June 2022)for target *** other findings,two major ones are:(a)Spreadsheet quality is best addressed throughout the whole spreadsheet life cycle,rather than just focusing on a few specific stages of the life cycle.(b)Relatively more studies focus on spreadsheet testing and debugging(related to fault detection and removal)when compared with spreadsheet specification,modeling,and design(related to development).As prevention is better than cure,more research should be performed on the early stages of the spreadsheet life *** by our comprehensive review,we have identified the major research gaps as well as highlighted key research directions for future work in the area.

关键词： decision support system end-user computing end-user programming Excel spreadsheet

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Incidence of urinary incontinence following endoscopic laser enucleation of the prostate by en-bloc and non-en-bloc techniques:a multicenter,real-world experience of 5068 patients

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Asian Journal of Andrology 2024年第3期26卷 233-238页

作者： Daniele Castellani Vineet Gauhar Khi yung Fong Mario Sofer Moisés Rodríguez Socarrás Azimdjon N Tursunkulov Lie kwok Ying Sarvajit Biligere Ho Yee Tiong Dean Elterman Abhay Mahajan Mark Taratkin Sorokin Nikolai Ivanovich Tanuj Pal Bhatia Dmitry Enikeev Nariman Gadzhiev Mohammed Taif Bendigeri Jeremy yuen-Chun Teoh Marco Dellabella Fernando Gómez Sancha Bhaskar Kumar Somani Thomas Reinhard William Herrmann Urology Unit IRCCS INRCAAncona 60127Italy Urology Unit Marche University HospitalLe Marche Polytechnic UniversityAncona 60126Italy Department of Urology Ng Teng Fong General HospitalSingapore 609606Singapore Yong Loo Lin School of Medicine National University of SingaporeSingapore 117597Singapore Department of Urology Tel Aviv Sourasky Medical CenterAffiliated to the Sackler School of MedicineTel Aviv UniversityTel Aviv 6423906Israel Department of Urology and Robotic Surgery ICUA-Clínica CEMTROMadrid 28701Spain Urology Division Akfa Medline HospitalTashkent 100211Uzbekistan Advanced Urology Gleneagles HospitalSingapore 258499Singapore Department of Urology National University HospitalSingapore 119228Singapore Divisionof Urology Department of SurgeryUniversity of TorontoOntarioToronto M5G 2C4Canada Department of Urology Mahatma Gandhi Mission’s Medical College and HospitalAurangabad 431003India Institute for Urology and Reproductive Health Sechenov UniversityMoscow119435Russian Federation Department of Urologyand Andrology Lomonosov Moscow State UniversityMoscow 119992Russian Federation Department of Urology Sarvodaya Hospital and Research CentreFaridabadHaryana 121006India Department of Urology Medical University of ViennaVienna 1090Austria Department of Urology Saint-Petersburg State University HospitalSaint-Petersburg 199034Russian Federation Department of Urology Asian Institute of Nephrology and UrologyHyderabad 500082India S.H.Ho UrologyCentre Department of SurgeryFaculty of MedicineThe Chinese University of Hong KongHong Kong 96H2+Q9China Department of Urology University Hospitals Southampton NHS TrustSouthampton SO166YDUnited Kingdom Department of Urology Cantonal Hospital Thurgau AGFraunfeld 8500Switzerland

We aim to evaluate the incidence of incontinence following laser endoscopic enucleation of the prostate(EEP)comparing en-bloc(Group 1)versus 2-lobe/3-lobe techniques(Group 2).We performed a retrospective review of patients undergoing EEP for benign prostaticenlargement in 12 centers between January 2020 and January *** were presented as median and interquartile range(IQR).Univariable and multivariable logistic regression analysis was performed to evaluate factors associated with stress urinary incontinence(SUI)and mixed urinary incontinence(MUI).There were 1711 patients in Group 1 and 3357 patients in Group *** in Group 2were significantly younger(68[62–73]years vs 69[63–74]years,P=0.002).Median(interquartile range)prostate volume(PV)wassimilar between the groups(70[52–92]ml in Group 1 vs 70[54–90]ml in Group 2,P=0.774).There was no difference in preoperativeInternational Prostate Symptom Score,quality of life,or maximum flow ***,morcellation,and total surgical time weresignificantly shorter in Group *** 1 month,overall incontinence rate was 6.3%in Group 1 versus 5.3%in Group 2(P=0.12),and urge incontinence was significantly higher in Group 1(55.1%vs 37.3%in Group 2,P<0.001).After 3 months,the overall rate ofincontinence was 1.7%in Group 1 versus 2.3%in Group 2(P=0.06),and SUI was significantly higher in Group 2(55.6%vs 24.1%in Group 1,P=0.002).At multivariable analysis,PV and IPSS were factors significantly associated with higher odds of transient SUI/***,surgical time,and no early apical release technique were factors associated with higher odds of persistent SUI/MUI.

关键词： benign prostatic hyperplasia en-bloc enucleation endoscopic enucleation of the prostate laser therapy stress urinaryincontinence urge urinary incontinence

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