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Monogenic deficiency in murine intestinal Cdc42 leads to mucosal inflammation that induces crypt dysplasia

Genes & Diseases 2024年第1期11卷 413-429页

作者： Dongsheng Zhang Wenjuan Tang Haitao Niu william Tse Hai-Bin Ruan Helmut Dolznig thomas Knosel Friedrich Karl-Heinz Madeleine Themanns Jiang Wang Mingquan Song Lee Denson Lukas Kenner Richard Moriggl Yi Zheng Xiaonan Han Division of Hematology and Oncology Division of Cancer BiologyDepartment of MedicineMetroHealth Medical Center(MHMC)Case Western Reserve University(CWRU)School of MedicineClevelandOH 44109USA Cancer Genomics and Epigenomics Program Case Comprehensive Cancer CenterCase Western Reserve University(CWRU)ClevelandOH 44106USA Division of Gastroenterology Hepatology and NutritionCincinnati Children’s Hospital Medical Center(CCHMC)CincinnatiOH 45229USA Children’s Hospital of Fudan University Shanghai 201102China School of Medicine Jinan UniversityGuangzhouGuangdong 510632China Laboratory Animal Science(ILAS) Chinese Academy of Medical Science(CAMS)and Peking Union Medical College(PUMC)Beijing 100006China Department of Integrative Biology and Physiology University of Minnesota Medical SchoolMinneapolisMI 55455USA Institute of Medical Genetics Medical University of ViennaVienna 1040Austria Institute of Pathology Ludwig-Maximilians-University MunichMunich 80539Germany Institute of Biochemistry II University Hospital JenaJena 07743Germany Laboratory Animal Pathology University of Veterinary Medicine ViennaVienna 1210Austria Department of Pathology University of CincinnatiCincinnatiOH 45221USA Department of Gastroenterology The Affiliated Hospital of Qingdao UniversityQingdaoShandong 266005China Department of Pathology Medical University of ViennaVienna 1040Austria Ludwig Boltzmann Institute for Cancer Research Vienna 1090Austria Medical University of Vienna Vienna 1040Austria Institute of Animal Breeding and Genetics University of Veterinary Medicine ViennaVienna 1210Austria Division of Experimental Hematology CCHMCCincinnatiOH 45229USA

CDC42 controls intestinal epithelial(IEC)stem cell(IESC)*** aberrant CDC42 initiates intestinal inflammation or neoplasia is *** utilized models of inflam-matory bowel diseases(IBD),colorectal cancer,aging,and IESC injury to determine the loss of intestinal Cdc42 upon inflammation and *** specimens were collected to determine the levels of CDC42 in IBD or colorectal ***42 floxed mice were crossed with Villin-Cre,Villin-CreERT2 and/or Lgr5-eGFP-IRES-CreERT2,or Bmi1-CreERT2 mice to generate Cdc42 deficient ***,colitis,aging,and intestinal organoid were used to evaluate CDC42 upon mucosal inflammation,IESC/progenitor regenerative capacity,and IEC *** studies revealed that increased CDC42 in colorectal cancer correlated with lower survival;in contrast,lower levels of CDC42 were found in the inflamed IBD *** Cdc42 depletion significantly reduced Lgr5+IEsCs,increased progenitors'hyperplasia,and induced mucosal inflammation,which led to crypt *** Cdc42 depletion markedly enhanced irra-diation-or chemical-induced *** or inhibition of Cdc42 reduced colonic Lgr5+IESC *** conclusion,depletion of Cdc42 reduces the IESC regeneration and IEC repair,leading to prolonged mucosal *** monogenic loss of Cdc42 in-duces mucosal inflammation,which could result in intestinal neoplasia in the context of aging.

关键词： Cell divisioncycle 42(CDC42) Colitis Colorectal cancer(CRC) Inflammatory bowel diseases(IBD) Intestinal epithelial cell(IEC) Intestinal epithelial stem cell(IESC) Irradiation

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Two-step exhumation of Caucasian intraplate rifts:A proxy of sequential plate-margin collisional orogenies

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Geoscience Frontiers 2024年第2期15卷 68-84页

作者： william Cavazza thomas Gusmeo Massimiliano Zattin Victor Alania Onise Enukidze Sveva Corrado Andrea Schito Department of Biological Geologicaland Environmental SciencesUniv.of BolognaItaly Department of Geosciences Univ.of PaduaItaly Institute of Geophysics I.Javakhishvili State UniversityTbilisiGeorgia Department of Sciences Roma Tre UniversityRomeItaly Department of Geology and Geophysics Univ.of AberdeenUnited Kingdom

Intraplate structural deformation is diagnostic of tectonic stress regime changes linked to plate interactions and can result from superposed tectonic events whose single contributions are hardly *** this paper,we present a set of integrated thermochronologic inverse models along a 140 km-long transect across the central Greater Caucasus and the adjacent Adjara-Trialeti fold-and-thrust belt of Georgia,two intraplate orogens produced by structural inversion of parallel continental rift zones located on the Eurasian *** dataset allows to distinguish discrete and superposed deformation episodes and quantify their respective contributions to orogenic *** integration of(U-Th)/He analysis on apatite and zircon,fission-track analysis on apatite,and peak-temperature determinations(clay mineralogy,organic matter petrography,Raman spectroscopy)shows that structural inversion was punctuated by two incremental steps starting respectively in the latest Cretaceous and the *** Cretaceous partial inversion of the Greater Caucasus is documented here for the first time and placed in a geographically wider context of coeval *** two episodes of intraplate structural inversion,exhumation,and sediment generation are chronologically and physically correlated with docking of(i)the Anatolide-Tauride-Armenian terrane(Late Cretaceous-Paleocene)and(ii)Arabia(Miocene hard collision)against the southern Eurasian plate *** deformation in the Caucasian domain was triggered by far-field propagation of plate-margin collisional stress which focused preferentially along rheologically weak rift zones.

关键词： Intraplate deformation Far-field tectonics Greater Caucasus Structural reactivation Terrane accretion

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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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An analysis of Great Salt Lake Winogradsky columns

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Journal of Oceanology and Limnology 2023年第4期41卷 1352-1368页

作者： Sierra A.DE LEON Anna E.JACKSON william black.william thomas Matt KRUBACK June BAXTER Bonnie K.BAXTER Great Salt Lake Institute Westminster UniversitySalt Lake City 84105USA Department of Visual Arts Westminster UniversitySalt Lake City 84105USA Natural History Museum of Utah University of UtahSalt Lake City 84112USA

Sergei Winogradsky illuminated revolutionary concepts and produced a tool to visualize complex microbial communities and their metabolisms over time:columns displaying aquatic consortia with variety of *** worked with museums in Utah to create Winogradsky columns that would highlight aesthetic properties of the Great Salt Lake(GSL)ecosystem,which has a salinity gradient from the freshwater wetlands to salt *** column,constructed using haloarchaea-rich hypersaline brine and oolitic sand of the lake’s north arm,was enriched with nutrients,and resulted in the desired pink hue over *** a seven-year maturation period,we examined the microbial taxa present in the water through 16 S/18 S rRNA and Internal Transcribed Spacer(ITS)gene sequencing.A pigment analysis revealed an abundance of bacteriochlorophyll *** presence of this pigment coupled with the DNA sequencing results,suggest that the haloarchaea that dominate the GSL brine,were not responsible for the pink coloration,but instead Gammaproteobacteria,especially Halorhodospira *** the eukaryotes,the lack of phytoplankton and the abundance of fungi were noteworthy *** data likely relate to the reduction of oxygen in a non-aerated sealed system over *** second exhibit had the goal of educating museum goers about the varying salinities of Great Salt *** we employed three distinct columns of water and sediment from this salinity *** of these columns overtime gave us information about invertebrate communities in addition to the microbial *** installations taught us about comparing an artificial environment in a museum setting to the natural *** together,we present the data collected and lessons learned from using Winogradsky columns in public spaces for teaching about an important saline lake.

关键词： Great Salt Lake Winogradsky halophiles extreme environment museum exhibit

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Calling for a Hero:The Displacement of the Nezha Archetypal Image from Chinese Animated Film Nezha Naohai(1979)to New Gods:Nezha Reborn(2021)

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Fudan Journal of the Humanities and Social Sciences 2022年第3期15卷 389-409页

作者： thomas william Whyke Joaquin Lopez Mugica Zhejiang University International Business School Institute of China StudiesZhejiang University718 East Haizhou RdHaining 314400ZhejiangPeople’s Republic of China Department of Liberal Arts University of Wenzhou-Kean in ChinaWenzhouPeople’s Republic of China

From the classical Chinese literary masterpiece Investiture of the Gods to contemporary flm animation,Nezha’s image is *** the portrayals of Nezha,namely in those most celebrated animated flms,we argue that his role as the epitome of a‘god like fgure’is in constant displacement and *** the framework of archetype and displacement as advanced by Northrop Frye,with a more pluralistic myth analysis extension found in the myth critique of Gilbert Durand,this article examines the multi-layered mythical mini structures within Nezha’s displacement and return in Chinese animation,to explore the themes,images,and archetype represented by the character from the perspective of Chinese history and *** argue that Nezha’s displacement and return in Chinese animation expresses the need and call for a traditional heroic image in a particular *** such,Nezha’s intertextuality exposes the profound inner patterns that form and refashion the Chinese collective unconscious,performing as a recurring mirror that symbolically inform and transform human experiences in China.

关键词： Chinese animation Nezha Archetype Displacement Return

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Calcium pyrophosphate dihydrate crystals in a 9-year-old with osteomyelitis of the knee:A case report

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World Journal of Orthopedics 2022年第9期13卷 870-875页

作者： william Pavlis David S Constantinescu Rajan Murgai Spencer Barnhill Brian black Department of Orthopaedics University of MiamiMiami33136United States

BACKGROUND Calcium pyrophosphate dihydrate deposition disease(CPPD),or pseudogout,is an inflammatory arthritis common among elderly patients,but rarely seen in patients under the age of *** the rare cases presented of young patients with CPPD,genetic predisposition or related metabolic conditions were almost always *** SUMMARY The authors report the case of a 9-year-old boy with no past medical history who presented with acute knee pain and swelling after a cat scratch injury 5 d *** fluid analysis identified calcium pyrophosphate dihydrate *** MRI analysis identified osteomyelitis and a small soft tissue *** This case presents the extremely rare diagnostic finding of calcium pyrophosphate dihydrate crystals in a previously healthy pediatric *** presence of osteomyelitis presents a unique insight into the pathogenesis of these crystals in pediatric *** research needs to be done on the role of CPPD in pediatric arthritis and joint infection.

关键词： Calcium pyrophosphate Pseudogout Pediatrics Crystals Osteomyelitis Case report

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Double Consciousness of Chinese Modernity:in the Cosmopolitan Ruins of Shanghai

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Fudan Journal of the Humanities and Social Sciences 2022年第3期15卷 411-435页

作者： Joaquin Lopez-Mugica thomas william Whyke University of Wenzhou-Kean WenzhouChina University of Nottingham NingboChina School of International Communications University of Nottingham Ningbo ChinaNingboZhejiangChina

This paper examines the inextricable relationship between the uncanny effects of knocking down Shanghai’s central district and their traumatic post-colonial *** value of the Chinese ruin,with its apocalyptic and contemporary imagery,begs to be discussed from a western perspective of ruin admiration as a metaphor for decadence and *** points to a new consciousness of globalization as means of conceptualizing well-established post-colonial orders at the heart of the urban deterioration of *** a potential concept to spark a dialogue of cosmopolitanism between China and the west,urban ruins can be analyzed as a transnational,creative ethos that reimagines the Chinese city as never *** the work of the Canadian photographer Greg Girard(born 1955),this article examines how his photograph book presents a cosmopolitan image of Shanghai’s derelict‘community lanes’(longtang or lilong)built in the city’s International Concessions(1842–1949),in which the past,present,and future are interwoven and *** authors argue that his ruin photography not only retriggers material knowledge of the city but also repurposes transcultural and creative expressions of mutually spectral moments of destruction and production between the east and the west,in which a myriad of potential features are discovered.

关键词： Post-colonial spaces Material ruins Hospitality Cosmopolitanism Hauntology

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Prostate magnetic resonance imaging and the value of experience:An intrareader variability study

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Asian Journal of Urology 2023年第4期10卷 488-493页

作者： thomas Whish-Wilson Jo-Lynn Tan william Cross Lih-Ming Wong Tom Sutherland Department of Surgery St Vincent's Hospital Melbourne41 Victoria PdeFitzroy VICAustralia Department of Surgery The University of MelbourneMelbourne VICAustralia Faculty of Medicine The University of MelbourneMelbourne VICAustralia Medical Imaging Department St Vincent's Hospital Melbourne41 Victoria PdeFitzroy VICAustralia

Objective To measure the intraobserver concordance of an experienced genitourinary radiologist reporting of multiparametric magnetic resonance imaging of the prostate(mpMRIp)scans over *** An experienced genitourinary radiologist re-reported his original 100 consecutive mpMRIp scans using Prostate Imaging-Reporting and Data System version 2(PI-RADS v2)after 5 years of further experience comprising>1000 *** agreement was measured using Cohen's ***,specificity,negative predictive value(NPV),positive predictive value(PPV),and accuracy were calculated,and comparison of sensitivity was performed using McNemar's *** Ninety-six mpMRIp scans were included in our final *** the 96 patients,53(55.2%)patients underwent subsequent biopsy(n=43)or prostatectomy(n=15),with 73 lesions *** agreement(Cohen's kappa 0.55)was seen in the number of lesions identified at initial reporting and on re-reading(81 vs.39 total lesions;and 71 vs.37 number of PI-RADS≥3 lesions).For clinically significant prostate cancer,re-reading demonstrated an increase in specificity(from 43%to 89%)and PPV(from 62%to 87%),but a decrease in sensitivity(from 94%to 72%,p=0.01)and NPV(from 89%to 77%).Conclusion The intraobserver agreement for a novice to experienced radiologist reporting mpMRIp using PI-RADS v2 is *** sensitivity is off-set by improved specificity and PPV,which validate mpMRIp as a gold standard for prebiopsy screening.

关键词： Prostate cancer Magneticresonance imaging Prostate Imaging-Reporting and Data System Intrareader Prostate biopsy

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Can preoperative planning using IRIS™three-dimensional anatomical virtual models predict operative findings during robot-assisted partial nephrectomy?

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Asian Journal of Urology 2023年第4期10卷 431-439页

作者： Ahmed Ghazi Nitin Sharma Ahmed Radwan Hani Rashid thomas Osinski thomas Frye william Tabayoyong Jonathan Bloom Jean Joseph University of Rochester Urology DepartmentRochesterNYUSA Ain Shams University Urology DepartmentCairoEgypt

Objective To evaluate the predictive validity of IRIS™(Intuitive Surgical®,Sunnyvale,CA,USA)as a planning tool for robot-assisted partial nephrectomy(RAPN)by assessing the degree of overlap with intraoperative *** Thirty-one patients scheduled for RAPN by four experienced urologists were enrolled in a prospective *** to surgery,urologists reviewed the IRIS™three-dimensional model on an iphone Operating System(iOS)app and completed a questionnaire outlining their surgical plan including surgical approach,and ischemia technique as well as confidence in executing this ***,questionnaires assessing the procedural approach,clinical utility,efficiency,and effectiveness of IRIS™were *** degree of overlap between the preoperative and intraoperative questionnaires and between the planned approach and actual execution of the procedure was *** were answered on a 5-point Likert scale and scores of 4 or greater were considered *** Mean age was 65.1 years with a mean tumor size of 27.7 mm(interquartile range 17.5-44.0 mm).Hilar tumors consisted of 32.3%;48.4%of patients had *** scores of *** preoperative questionnaires,the surgeons reported that in 67.7%cases they were confident that they can perform the procedure successfully,and on intraoperative questionnaires,the surgeons reported that in 96.8%cases IRIS™helped achieve good spatial sensation of the *** was a high degree of overlap between preoperative and intraoperative questionnaires for the surgical approach,interpreting anatomical details and clinical *** comparing plans for selective or off-clamp,the preoperative plan was executed in 90.0%of cases *** A high degree of overlap between the preoperative surgical approach and intraoperative RAPN execution was found using IRIS™.This is the first study to evaluate the predictive accuracy of IRIS™during RAPN by comparing preoperative pl

关键词： Renal cancer Patient-specific Three-dimensional virtual model Imaging Partial nephrectomy Robotics

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Low-intensity extracorporeal shock wave therapy for Peyronie’s disease:a single-center experience

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Asian Journal of Andrology 2022年第1期24卷 45-49页

作者： Maher Abdessater william Akakpo Anthony Kanbar Jérome Parra thomas Seisen Emmanuel Chartier-Kastler Sarah J Drouin Morgan Roupret APHP-Sorbonne University PitiéSalpêtrièreAcademic Urology Unit83 bvd HopitalParis 75013France

The aim of this article is to assess the outcomes of a low-intensity extracorporeal shock wave therapy(LiESWT)protocol for the treatment of Peyronie’s disease(PD).Patients treated for PD were prospectively recorded,and data were retrospectively ***,characteristics of fibrous plaques,concomitant treatments,International Index of Erectile Function(IIEF-5),Lue score,and pain score on Likert scale were *** in acute phase of PD and an angulation of<40°were *** protocol consisted of 6 weekly sessions of 4000 pulses each,applied from different directions,with a maximal power of 20 W and 8 Hz *** included 39 patients(median age:56.8 years,interquartile range[IQR]:35.8–62.2 years).The median number of sessions received per patient was *** treatment,the median Lue score decreased from 6.8 initially to 3.3(P=0.003),the median Likert pain score dropped from 1.8 to 0.7(P=0.004),the median plaque size was reduced from 2 cm to 1.2 cm(P=0.08),and the median penile curvature diminished from 31°to 17°(P=0.07).On univariate and multivariate analysis,the only predictors of success were younger age(odds ratio[OR]=0.95,P=0.03 and OR=0.91,P=0.04,respectively)and concomitant use of phosphodiesterase-5 inhibitors(PDE5i;OR=0.92,P=0.02 and OR=0.93,P=0.01,respectively).LiESWT had a favorable impact on Lue score and notably penile pain,curvature,plaque size,and erectile function in patients treated for PD during the early inflammatory phase,with no side *** age and concomitant use of PDE5i were the only success predictors.

关键词： erectile dysfunction extracorporeal shock wave therapy Peyronie’s disease piezoelectric waves

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