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Predictors of survival in autoimmune liver disease overlap syndromes

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World Journal of Hepatology 2024年第9期16卷 1269-1277页

作者： Dujinthan Jayabalan Yi Huang Luis Calzadilla-Bertot Malik Janjua Bastiaan de Boer John Joseph Wendy Cheng simon Hazeldine Briohny W smith Gerry C MacQuillan Michael C Wallace George Garas Leon A Adams Gary P Jeffrey Medical School University of Western AustraliaNed-lands 6009Western AustraliaAustralia Department of Hepatology Sir Charles Gairdner HospitalNedlands 6009Western AustraliaAustralia Department of Anatomical Pathology PathWest Laboratory MedicineNedlands 6009Western AustraliaAustralia Department of Gastroenterology and Hepatology Royal Perth HospitalPerth 6000Western AustraliaAustralia Department of Gastroenterology and Hepatology Fiona Stanley HospitalMurdoch 6150Western AustraliaAustralia Medical School University of Western AustraliaNedl-ands 6009Western AustraliaAustralia

BACKGROUND Survival in patients with autoimmune liver disease overlap syndromes(AILDOS)compared to those with single autoimmune liver disease is *** To investigate the survival of patients with AILDOS and assess the accuracy of non-invasive serum models for predicting liver-related *** Patients with AILDOS were defined as either autoimmune hepatitis and primary biliary cholangitis overlap(AIH-PBC)or autoimmune hepatitis and primary sclerosing cholangitis overlap(AIH-PSC)and were identified from three tertiary centres for this cohort ***-related death or transplantation(liver-related mortality)was determined using a population-based data linkage *** scores for liver-related death were compared for accuracy[including liver outcome score(LOS),Hepascore,Mayo Score,model for end-stage liver disease(MELD)score and MELD incorporated with serum sodium(MELD-Na)score].RESULTS Twenty-two AILDOS patients were followed for a median of 3.1 years(range,0.35-7.7).Fourteen were female,the median age was 46.7 years(range,17.8 to 82.1)and median Hepascore was 1(range,0.07-1).At five years post enrolment,57%of patients remained free from liver-related mortality(74%AIH-PBC,27%AIH-PSC).There was no significant difference in survival between AIH-PBC and *** was a significant predictor of liver-related mortality(P<0.05)in patients with AIH-PBC(n=14)but not AIH-PSC(n=8).A LOS cut-point of 6 discriminated liver-related mortality in AIH-PBC patients(P=0.012,log-rank test,100%sensitivity,77.8%specificity)(Harrell's C-statistic 0.867).The MELD score,MELD-Na score and Mayo Score were not predictive of liver-related mortality in any *** Survival in the rare,AILDOS is *** current study supports the LOS as a predictor of liver-related mortality in AIH-PBC *** trials investigating predictors of survival in AILDOS are required.

关键词： Autoimmune liver disease overlap syndromes Liver outcome score Liver-related death Hepascore Autoimmune hepatitis Primary biliary cholangitis Primary sclerosing cholangitis

Utilization of RNA sequencing to investigate olfactory dysfunction in chronic rhinosinusitis without nasal polyps:A pilot study

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World Journal of Otorhinolaryngology-Head and Neck Surgery 2024年第1期10卷 29-36页

作者： Jorge A.Gutierrez III jeremy L.Barth Rodney J.Schlosser Thomas S.Edwards Timothy L.smith Zachary M.Soler Department of Otolaryngology-Head and Neck Surgery Medical University of South CarolinaCharlestonSouth CarolinaUSA Department of Regenerative Medicine&Cell Biology Medical University of South CarolinaCharlestonSouth CarolinaUSA Department of Otolaryngology-Head and Neck Surgery Oregon Health&Science UniversityPortlandOregonUSA

Objectives:Prior research on olfactory dysfunction in chronic rhinosinusitis(CRS)has focused on patients with polyps and suggests that direct inflammation of the olfactory cleft mucosa plays a contributory *** purpose of this study was to evaluate gene expression in superior turbinate mucosal specimens,comparing normosmic and dysosmic CRS patients without polyps(CRSsNP).Methods:Tissue samples were obtained from the superior turbinates of patients with CRSsNP at the time of endoscopic sinus *** subsequently underwent RNA sequencing and functional analysis to investigate biological pathways associated with differentially expressed genes between dysosmic(n=7)and normosmic(n=4)***:Differential gene expression analysis comparing dysosmic and normosmic CRSsNP patients showed upregulation of 563 genes and downregulation of 327 *** stringent criteria for multiple comparisons,one upregulated gene(Immediate Early Response 3[IER3])had an false discovery rate(FDR)correction adjustedP value considered statistically significant(P<0.001,fold change 2.69).Reactome functional analysis revealed eight biological pathways significantly different between dysosmic and normosmic patients(P<0.05,FDR correction)including IL-4 and IL-13 signaling,IL-10 signaling,and rhodopsin-like ***:RNA sequencing of the superior turbinates in patients with CRSsNP can provide valuable information regarding biological pathways and genes involved in olfactory *** study supports literature suggesting that Type 2 inflammation may play a role in olfactory dysfunction in at least some patients with *** study also prompts questions regarding the role of IL-10,rhodopsin-like receptors,andIER3 in the pathogenesis of olfactory dysfunction.

关键词： chronic rhinosinusitis without nasal polyps olfactory dysfunction RNA sequencing

Overview of Activities:ARES-III and LEARN Analog Missions in the LunAres Hab

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Space(Science & Technology) 2022年第1期2022卷 64-82页

作者： simon Bouriat Matej Poliaček Jacob smith SpaceAble France Aerospace Industry Professional and Independent Reseacher Slovakia UK Students for the Exploration and Development of Space(UKSEDS) UK

Progress is being made on human Lunar and Martian missions by space agencies and private organisations around the world,with the aims of establishing reliable long-duration *** this,research is being carried out under controlled and isolated conditions within simulated space habitats,to gain insights into the effects of such conditions on the research subjects and their impacts on crews’wellbeing and *** paper provides an overview of the experiments conducted during two separate 15-day missions—one Martian and one Lunar—conducted in the LunAres Research Base in Piła,Poland,in *** activities were common between the two crews;others were only carried out by *** the same methodology,both collected cognitive function,environmental,physiological,and inventory data,resulting in a larger dataset allowing comparisons between the two missions in terms of varying human *** conducted by the Lunar crew included the following:effects of consuming lyophilised food on oral health and saliva production,influence of isolation on hearing capability,feelings on security in the isolated habitat,and research into earthworm growth in different soil *** Mars mission analysed physical performances of the crew and compared them to performances realised during similar activities in Mars Research Desert Station missions and the impact of confinement on their efficiency performing a remote operation of a *** each piece of research,an overview of the background,methodology,results,and conclusions is given,referencing the resulting *** addition,nonresearch activities are included for completeness and context.

关键词： Desert habitat consuming

Genetic interactions between polycystin-1 and Wwtr1 in osteoblasts define a novel mechanosensing mechanism regulating bone formation in mice

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Bone Research 2023年第4期11卷 772-783页

作者： Zhousheng Xiao Li Cao Micholas Dean smith Hanxuan Li Wei Li jeremy C.smith Leigh Darryl Quarles Department of Medicine University of Tennessee Health Science CenterMemphisTN 38163USA UT/ORNL Center for Molecular Biophysics Oak Ridge National LaboratoryOak RidgeTN 37830USA Department of Biochemistry and Cellular and Molecular Biology The University of Tennessee-KnoxvilleKnoxvilleTN 37996-1939USA Department of Pharmaceutical Sciences University of Tennessee Health Science CenterMemphisTN 38163USA

Molecular mechanisms transducing physical forces in the bone microenvironment to regulate bone mass are poorly ***,we used mouse genetics,mechanical loading,and pharmacological approaches to test the possibility that polycystin-1 and Wwtr1 have interdependent mechanosensing functions in *** created and compared the skeletal phenotypes of control Pkd1^(flox/)+;Wwtr1^(flox/)+,Pkd1^(Oc-cKO),Wwtr1^(Oc-cKO),and Pkd1/Wwtr1^(Oc-cKO)mice to investigate genetic *** with an interaction between polycystins and Wwtr1 in bone in vivo,Pkd1/Wwtr1^(Oc-cKO)mice exhibited greater reductions of BMD and periosteal MAR than either Wwtr1Oc-cKOor Pkd1^(Oc-cKO)***-CT 3D image analysis indicated that the reduction in bone mass was due to greater loss in both trabecular bone volume and cortical bone thickness in Pkd1/Wwtr1Oc-cKO mice compared to either Pkd1Oc-cKOor Wwtr1^(Oc-cKO)***1/Wwtr1^(Oc-cKO)mice also displayed additive reductions in mechanosensing and osteogenic gene expression profiles in bone compared to Pkd1Oc-cKOor Wwtr1^(Oc-cKO)***,we found that Pkd1/Wwtr1^(Oc-cKO)mice exhibited impaired responses to tibia mechanical loading in vivo and attenuation of loadinduced mechanosensing gene expression compared to control ***,control mice treated with a small molecule mechanomimetic,MS2 that activates the polycystin complex resulted in marked increases in femoral BMD and periosteal MAR compared to vehicle *** contrast,Pkd1/Wwtr1^(Oc-cKO)mice were resistant to the anabolic effects of *** findings suggest that PC1 and Wwtr1 form an anabolic mechanotransduction signaling complex that mediates mechanical loading responses and serves as a potential novel therapeutic target for treating osteoporosis.

关键词： mec impaired additive

Current and future applications of in vitro magnetic resonance spectroscopy in hepatobiliary disease

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World Journal of Gastroenterology 2006年第30期12卷 4773-4783页

作者： I Jane Cox Amar Sharif jeremy FL Cobbold Howard C Thomas simon D Taylor-Robinson Imaging Sciences Department Division of Clinical Sciences Imperial College London Hammersmith Hospital Campus Du Cane Road London W12 OHS United Kingdom Department of Medicine Division of Medi-cine Imperial College London St Mary's Campus London W2 United Kingdom

Nuclear magnetic resonance spectroscopy allows the study of cellular biochemistry and metabolism, both in the whole body in vivo and at higher magnetic field strengths in vitro. Since the technique is non-invasive and non-selective, magnetic resonance spectroscopy methodologies have been widely applied in biochemistry and medicine. In vitro magnetic resonance spectroscopy studies of cells, body fluids and tissues have been used in medical biochemistry to investigate pathophysiologi- cal processes and more recently, the technique has been used by physicians to determine disease abnormalities in vivo. This highlighted topic illustrates the potential of in vitro magnetic resonance spectroscopy in studying the hepatobiliary system. The role of in vitro proton and phosphorus magnetic resonance spectroscopy in the study of malignant and non-malignant liver disease and bile composition studies are discussed, particularly with reference to correlative in vivo whole-body magnetic resonance spectroscopy applications. In summary, magnetic resonance spectroscopy techniques can provide non-invasive biochemical information on disease severity and pointers to underlying pathophysiological processes. Magnetic resonance spectroscopy holds potential promise as a screening tool for disease biomarkers, as well as assessing therapeutic response.

关键词： Magnetic resonance spectroscopy Liver Hepatobiliary disease Membrane metabolism

Taking FAIR on the ChIN:The Chemistry Implementation Network

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Data Intelligence 2020年第1期2卷 131-138,310页

作者： simon J.Coles jeremy G.Frey Egon L.Willighagen Stuart J.Chalk School of Chemistry Faculty of Engineering and Physical SciencesUniversity of SouthamptonSouthampton SO171BJUK Department of Bioinformatics Maastricht UniversityMaastrichtLimburg 6200 MDThe Netherlands Department of Chemistry University of North FloridaJacksonvilleFL 32224-7699USA

The Chemistry Implementation Network(ChIN)is focused on supporting the FAIR Data needs of the research community regarding chemical related *** Implementation Network is a consortium drawn from a community,in this case the chemistry discipline,committed to defining and constructing standards,materials and software in the spirit of the FAIR data principles and under the structure of the GO FAIR ***,as a core science the ChIN has to reach beyond the chemistry community and support the use of chemical information in other *** will be facilitated through connections in the GO FAIR ecosystem of Implementation *** of the FAIR chemical concepts that need to be supported include molecular and materials structures,chemical reactions,nomenclature and other chemical terminology and *** ChIN aims to drive forward the application of the FAIR Data Principles relating to the full range of chemistry concepts that are key to the transparent and efficient communication of chemical *** the goal of FAIR chemistry data will require a culture change across the *** this is best addressed once a critical mass of tools and approaches has been developed.

关键词： Chemistry Chemical information Chemistry data Chemical data standards Infrastructure Nomenclature Molecular structure Materials structure Chemical reactions Education Community engagement Endorsement and governance

Expanding plant genome-editing scope by an engineered iSpyMacCas9 system that targets A-rich PAM sequences

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Plant Communications 2021年第2期2卷 78-88页

作者： simon Sretenovic Desuo Yin Adam Levav jeremy D.Selengut Stephen M.Mount Yiping Qi Department of Plant Science and Landscape Architecture University of MarylandCollege ParkMD 20742USA Hubei Academy of Agricultural Sciences Wuhan 430064China Montgomery Blair High School Silver SpringMD 20901USA Center for Bioinformatics and Computational Biology University of MarylandCollege ParkMD 20742USA Department of Cell Biology and Molecular Genetics University of MarylandCollege ParkMD 20742USA Institute for Bioscience and Biotechnology Research University of MarylandRockvilleMD 20850USA

The most popular CRISPR-SpCas9 systemrecognizes canonical NGG protospacer adjacent motifs(PAMs).Previously engineered SpCas9 variants,such as Cas9-NG,favor G-rich PAMs in genome *** this manuscript,we describe a new plant genome-editing system based on a hybrid iSpyMacCas9 platform that allows for targeted mutagenesis,C to T base editing,and A to G base editing at A-rich *** study fills amajor technology gap in the CRISPR-Cas9 system for editing NAAR PAMs in plants,which greatly expands the targeting scope of ***,our vector systems are fully compatible with Gateway cloning and will work with all existing single-guide RNA expression systems,facilitating easy adoption of the systems by *** anticipate that more tools,such as prime editing,homology-directed repair,CRISPR interference,and CRISPR activation,will be further developed based on our promising iSpyMac-Cas9 platform.

关键词： plant genome editing iSpyMacCas9 PAM cytosine base editing adenine base editing

DIY Corpora for Vocabulary Learning

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语言与文化论坛 2020年第2期 3-26页

作者： simon smith Humanities and Research Associate Centre for Global Learning:Education and Attainment

INTRODUCTION One of the principal applications of corpora in English language teaching and learning has been the compilation of vocabulary lists for student ***’s General Service List(GSL;1953)was based on a painstaking(manual)corpus analysis of frequency and range(Gilner,2011),and almost all subsequent lists,whether of general English(College Entrance Examination Center,2002),academic English(Coxhead,2000)or specialist domains have been derived directly or indirectly from *** need to acquire words that are both frequent in the language and occur across a range of texts,and the use of corpora can furnish lists that satisfy these frequency and distributional requirements.

关键词： lists teaching has

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Angola’s Awakening

ChinAfrica 2011年第7期3卷 30-32页

作者： simon Freemantle jeremy Stevens the Standard Bank

BRIC is dominant in Angola’s economic awakening,with China a special and prominent partner Since the end of the civil war in 2002, Angola has moved from the fringe to the center of African economic ***,Angola accounts for 6 percent of Africa’s GDP,10 percent of its trade and 5 percent of continental-wide investment flows. Importantly,Angola’s economic awakening has occurred in tandem with the resurgence of BRIC(Brazil,Russia,India and China) commercial interest in *** such,Angola is,

关键词： Angola’s Awakening CITIC