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Relative carcinogenicity of tacrolimus vs mycophenolate after solid organ transplantation and its implications for liver transplant care

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World Journal of Hepatology 2024年第4期16卷 650-660页

作者： dorothy Liu mark m Youssef Josephine A Grace marie Sinclair Department of Gastroenterology Austin HealthMelbourne 3084VictoriaAustralia Victorian Liver Transplant Unit Austin HealthMelbourne 3084VictoriaAustralia Department of medicine University of MelbourneMelbourne 3084VictoriaAustralia

BACKGROUND De novo malignancy is a leading cause of late morbidity and mortality in liver transplant *** immunosuppression has been shown to contribute to post-transplant malignancy(PTm)*** is emerging evidence on the differential carcinogenic risk profile of individual immunosuppressive drugs,independent of the net effect of *** inhibitors such as tacrolimus may promote tumourigenesis,whereas mycophenolic acid(mPA),the active metabolite of mycophenolate mofetil,may limit tumour *** transplantation(LT)is relatively unique among solid organ transplantation in that immunosuppression monotherapy with either tacrolimus or mPA is often achievable,which makes careful consideration of the risk-benefit profile of these immunosuppression agents particularly relevant for this ***,there is limited clinical data on this subject in both LT and other solid organ transplant *** To investigate the relative carcinogenicity of tacrolimus and mPA in solid organ *** A literature search was conducted using mEDLINE and Embase databases using the key terms“solid organ transplantation”,“tacrolimus”,“mycophenolic acid”,and“carcinogenicity”,in order to identify relevant articles published in English between 1st January 2002 to 11th August *** terms,synonyms and explosion of meSH terms,Boolean operators and truncations were also utilised in the *** lists of retrieved articles were also reviewed to identify any additional *** duplicates,abstracts from 1230 records were screened by a single reviewer,whereby 31 records were reviewed in ***-text articles were assessed for eligibility based on pre-specified inclusion and exclusion *** A total of 6 studies were included in this *** studies were large population registries or cohort studies,which varied in transplant era,type of organ transplanted and immunosuppression protocol us

关键词： Immunosuppression Solid organ transplantation Liver transplantation Carcinogenicity Tacrolimus mycophenolate

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Serum outperforms plasma in small extracellular vesicle microRNA biomarker studies of adenocarcinoma of the esophagus

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World Journal of Gastroenterology 2020年第20期26卷 2570-2583页

作者： Karen Chiam George C mayne Tingting Wang David I Watson Tanya S Irvine Tim Bright Lorelle T Smith Imogen A Ball Joanne m Bowen dorothy m keefe Sarah K Thompson Damian J Hussey Discipline of Surgery College of Medicine and Public HealthFlinders University of South AustraliaAdelaideSA 5042Australia Flinders Health and medical Research Institute Cancer Program College of Medicine and Public HealthFlinders UniversityAdelaideSA 5042Australia Discipline of Surgery The University of AdelaideAdelaideSA 5005Australia Adelaide medical School The University of AdelaideAdelaideSA 5005Australia Faculty of Health Sciences The University of AdelaideAdelaideSA 5005Australia

BACKGROUND Circulating microRNAs(miRNAs)are potential biomarkers for many ***,they can originate from non-disease specific sources,such as blood cells,and compromise the investigations for miRNA *** small extracellular vesicles(sEVs)have been suggested to provide a purer source of circulating miRNAs for biomarkers discovery,the most suitable blood sample for sEV miRNA biomarker studies has not been *** To compare the mi RNA profiles between matched serum and plasma s EV preparations to determine their suitability for biomarker *** matched serum and plasma samples were obtained from 10 healthy controls and10 patients with esophageal adenocarcinoma.s EV isolates were prepared from serum and plasma using Exo Quick Tm and quantified using Nano *** was extracted from s EV preparations with the mi RNeasy Serum/Plasma kit and profiled using the Taqman Openarray q *** overall mi RNA content and theexpression of specific mi RNAs of reported vesicular and non-vesicular origins were compared between serum and plasma s EV *** diagnostic performance of a previously identified multi-mi RNA biomarker panel for esophageal adenocarcinoma was also *** The overall mi RNA content was higher in plasma s EV preparations(480 mi RNAs)and contained 97.5%of the mi RNAs found in the serum s EV preparations(412 mi RNAs).The expression of commonly expressed mi RNAs was highly correlated(Spearman’s R=0.87,Pma and serum s EV preparations,but was consistently higher in the plasma s EV *** blood-cell mi RNAs(hsa-mi R-223-3 p,hsa-mi R-451 a,mi R-19 b-3 p,hsa-mi R-17-5 p,hsa-mi R-30 b-5 p,hsa-mi R-106 a-5 p,hsa-mi R-150-5 p and hsa-mi R-92 a-3 p)were expressed at 2.7 to 9.6 fold higher levels in the plasma s EV preparations compared to serum s EV preparations(Pma s EV preparations,the percentage of protein-associated mi RNAs expressed at relatively higher levels(Ct

关键词： Biomarkers Exosomes Extracellular vesicles Circulating microRNA microRNAs Plasma Serum Blood cells Real-time polymerase chain reaction Adenocarcinoma of esophagus

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Additive manufacturing(3D printing)of electrically conductive polymers and polymer nanocomposites and their applications

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eScience 2022年第4期2卷 365-381页

作者： Kirstie R.Ryan michael P.Down Nicholas J.Hurst Edmund m.keefe Craig E.Banks Faculty of Science and Engineering Manchester Metropolitan UniversityChester StreetManchesterM15GDUK

Additive manufacturing,or three-dimensional(3D)printing,offers a unique solution for fabricating complex geometries with high ***,many commercial additive manufacturing machines focus on the printing of polymers with limited ***,conductive polymers(CPs)can be processed to enable the additive manufacturing of conductive,low-density,and low-cost parts for a myriad of *** review summarizes the relevant achievements in the additive manufacturing of conductive polymers(CPs)and conductive polymer nanocomposites,with a discussion of the advantages and limitations of processing and printing these materials compared with alternative traditional manufacturing methods and their ***,the prospective applications of these additive manufacturing printed conductive materials are explored.

关键词： Conducting polymers Additive manufacturing Electrochemcial applications Supercapacitors Batteries

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Discourse Intonation in L2. From theory and research to practice.

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丛书名： Language Learning & Language Teaching

2002年

作者： dorothy m. Chun

ISBN: (数字)9789027297525

ISBN: (纸本)9789027216915

Intonation, rhythm, and general “melody” of language are among the first aspects of speech that infants attend to and produce themselves. Yet, these same features are among the last to be mastered by adult L2 learners. Why is this, and how can L2 learners be helped? This book first presents the latest linguistic theories of intonation, in particular, how intonation functions in discourse not only to signal sentence types and attitudinal meanings but also to provide turn-taking and other conversational cues. The second part of the book examines the research in applied linguistics on the acquisition of L2 phonology and intonation. The third section offers practical applications of how to incorporate the teaching of intonation into L2 instruction, with a focus on using new speech technologies. The accompanying CD-ROm makes a unique addition in allowing for simultaneous audio playback and visual display of the pitch contours of utterances contained in the book. Users can start or stop the playback at any point in the utterance and can observe first-hand how such visual and audio representations could be useful for L2 learners.

关键词： language learn practice research intonation theory discourseWords & Language Education & Reference

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Impacts and challenges of United States medical students during the COVID-19 pandemic

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World Journal of Clinical Cases 2020年第15期8卷 3136-3141页

作者： Stacey Rolak Alexis m keefe Emily L Davidson Prabesh Aryal Sandesh Parajuli Department of medicine University of Wisconsin School of Medicine and Public HealthMadisonWI 53705United States College of medicine Nepalese Army Institute of Health SciencesKathmandu 44600Nepal Division of Nephrology Department of Internal MedicineUniversity of Wisconsin School of Medicine and Public HealthMadisonWI 53705United States

The delivery of medical student education has changed rapidly during the coronavirus disease 2019(COVID-19)*** in their pre-clinical years have transitioned to online courses and *** in their clinical years are not permitted on clinical rotations,and face uncertainties in career exploration and the residency application *** students in all stages of training are volunteering and helping their *** future presence of COVID-19 throughout the United States is unknown,and medical students are eager to return to their *** paper outlines current challenges in medical student education and the various responses that have been *** also discuss possible future directions for students through involvement in telemedicine,outpatient clinic visits,and non-respiratory inpatient care tasks as adequate personal protective equipment,COVID-19 testing,and resources become more widely available.

关键词： COVID-19 Education medical students Telemedicine Healthcare delivery Schools

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Determinants and rates of land degradation： Application of stationary time-series model to data from a semi-arid environment in Kenya

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Journal of Arid Land 2018年第1期10卷 1-11页

作者： kevin z mganga dickson m nyariki nashon k r musimba dorothy a amwata department of range and wildlife sciences south eastern kenya university170-90200 KituiKenya department of agricultural economics and agribusiness south eastern kenya university170-90200 KituiKenya school of business and economics murangáuniversity of technology75-10200 MurangaKenya

The causes of land degradation in the African drylands have been shown to vary. Some researchers consider climate to be the major contributor to degradation, with anthropogenic factors playing a minor role. Others reverse the significance of these two factors. A third group attributes land degradation to climate and anthropogenic factors equally. This study was undertaken to establish the factors influencing land degradation in a semi-arid environment in southeastern Kenya and the rate of change in vegetation types for a period of 35 years （1973-2007）. The reduction in grassland cover was used as an indicator of land degradation. Causes of land degradation were determined by a multiple regression analysis. A log-linear regression analysis was used to establish the rate of vegetation change. The multiple and log-linear regression analyses showed：（1） woody vegetation, livestock population and cultivated area to be the main contributors of reduction in grassland cover in the area, and （2） an increase in undesirable woody species, livestock population and cultivated area had a significant （P〈0.05） negative effect on grassland vegetation. Increased human population, low amounts of rainfall and drought showed no significant negative effect on grassland vegetation cover. In conclusion, human and livestock population growth and increased agricultural land have contributed to intensive crop cultivation and overgrazing in the semi-arid lands. This overuse of the semi-arid rangelands has worsened the deterioration of the natural grassland vegetation.

关键词： regression analysis land degradation grassland cover semi-arid Kenya Sub-Saharan Africa

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Partial epithelial-mesenchymal transition in keloid scars: regulation of keloid keratinocyte gene expression by transforming growth factor-β1

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Burns & Trauma 2016年第3期4卷 199-215页

作者： Jennifer m.Hahn Kevin L.mcFarland Kelly A.Combs dorothy m.Supp Research Department Shriners Hospitals for Children-CincinnatiCincinnatiOHUSA Research Department Shriners Hospitals for Children-CincinnatiCincinnatiOHUSA Department of Surgery University of Cincinnati College of MedicineCincinnatiOHUSA

Background:Keloids are an extreme form of abnormal scarring that result from a pathological fibroproliferative wound healing *** molecular mechanisms driving keloid pathology remain incompletely understood,hindering development of targeted,effective *** studies in our laboratory demonstrated that keloid keratinocytes exhibit adhesion abnormalities and display a transcriptional signature reminiscent of cells undergoing epithelial-mesenchymal transition(EmT),suggesting a role for EmT in keloid *** the current study,we further define the EmT-like phenotype of keloid scars and investigate regulation of EmT-related genes in ***:Primary keratinocytes from keloid scar and normal skin were cultured in the presence or absence of transforming growth factor beta 1(TGF-β1)+/-inhibitors of TGF-β1 and downstream signaling *** expression was measured using quantitative polymerase chain *** was analyzed using an in vitro wound healing *** in keloid scar and normal skin sections were localized by *** analyses utilized SigmaPlot(SyStat Software,San Jose,CA)or SAS?(SAS Institute,Cary,NC).Results:In keloid and normal keratinocytes,TGF-β1 regulated expression of EmT-related genes,including hyaluronan synthase 2,vimentin,cadherin-11,wingless-type mmTV integration site family,member 5A,frizzled 7,ADAm metallopeptidase domain 19,and *** of canonical TGF-β1 signaling in keloid keratinocytes significantly inhibited expression of these genes,and TGF-β1 stimulation of normal keratinocytes increased their *** inhibition of the extracellular signal-regulated kinase 1/2(ERK1/2)signaling pathway or the p38 mitogen-activated protein kinase pathway attenuated TGF-β1-induced expression of subsets of these *** of keloid keratinocytes,previously shown to be increased compared with normal keratinocytes,was significantly reduced by inhibition of TGF-β1 or E

关键词： Keloid Keratinocyte Epithelial-mesenchymal transition Wound healing Scar Fibrosis

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Quantifying the early snowmelt event of 2015 in the Cascade mountains,USA by developing and validating mODIS-based snowmelt timing maps

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Frontiers of Earth Science 2018年第4期12卷 693-710页

作者： Donal O'LEARY III dorothy HALL michael mEDLER Aquila FLOWER University of maryland Department of Geographical SciencesCollege ParkMD 20740USA Westem Washington University Department of Environmental StudiesBellinghamWA 98225USA National Aeronautics and Space Administration Goddard Space Flight CenterGreenbeltMD 20771USA Earth System Science Interdisciplinary Center University of MarylandCollege ParkMD 20740USA

Spring snowmelt serves as the major hydrological contribution to many watersheds of the US West. Since the 1970s the conterminous western USA has seen an earlier arrival of spring snowmelt. The extremely low snowpack and early melt of 2015 in the Cascade mountains may be a harbinger of winters to come, underscoring the interest in advancements in spring snowmelt monitoring. Target-of-opportunity and point measurements of snowmelt using meteorological stations or stream gauges are common sources of these data, however, there have been few attempts to identify snowmelt timing using remote sensing. In this study, we describe the creation of snowmelt timing maps (STms) which identify the day of year that each pixel of a remotely sensed image transitions from “snow-covered” to “no snow” during the spring melt season, controlling for cloud coverage and ephemeral spring snow storms. Derived from the 500 m mODerate-resolution Imaging Spectroradiometer (mODIS) standard snow map, mOD10A2, this new dataset provides annual maps of snowmelt timing, with corresponding maps of cloud interference and interannual variability in snow coverage from 2001–2015. We first show that the STms agree strongly with in-situ snow telemetry (SNOTEL) meteorological station measurements in terms of snowmelt timing. We then use the STms to investigate the early snowmelt event of 2015 in the Cascade mountains, USA, highlighting the protected areas of mt. Rainier, Crater Lake, and Lassen Volcanic National Parks. In 2015 the Cascade mountains experienced snowmelt 41 days earlier than the 2001–2015 average, with 25% of its land area melting>65 days earlier than average. The upper elevations of the Cascade mountains experienced the greatest snowmelt anomaly. Our results are relevant to land managers and biologists as they plan adaptation strategies for mitigating the effects of climate change throughout temperate mountains.

关键词： Cascade mountains snowmelt spring phenology mODIS remote sensing

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Phone skills for the Information Age / 3rd ed.

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2006年

作者： dorothy maxwell.

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Gm604 regulates developmental neurogenesis pathways and the expression of genes associated with amyotrophic lateral sclerosis

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Translational Neurodegeneration 2018年第1期7卷 322-345页

作者： William R.Swindell Krzysztof Bojanowski mark S.Kindy Raymond m.W.Chau dorothy Ko Heritage College of Osteopathic medicine Ohio UniversityAthensOHUSA Sunny BioDiscovery IncSanta PaulaCAUSA Department of Pharmaceutical Sciences College of PharmacyUniversity of South FloridaTampaFLUSA James A.Haley VAmC TampaFLUSA Genervon Biopharmaceuticals LLC PasadenaCAUSA

Background:Amyotrophic lateral sclerosis(ALS)is currently an incurable disease without highly effective pharmacological *** peptide drug Gm604(Gm6 or Alirinetide)was developed as a candidate ALS therapy,which has demonstrated safety and good drug-like properties with a favorable pharmacokinetic ***6 is hypothesized to bolster neuron survival through the multi-target regulation of developmental pathways,but mechanisms of action are not fully ***:This study used RNA-seq to evaluate transcriptome responses in SH-SY5Y neuroblastoma cells following Gm6 treatment(6,24 and 48 h).Results:We identified 2867 protein-coding genes with expression significantly altered by Gm6(FDRmponents,with increased expression of developmental genes mediating neurogenesis and axon *** Gm6 treatment(24 and 48 h)altered the expression of genes contributing to cell adhesion and the extracellular ***6 further down-regulated the expression of genes associated with mitochondria,inflammatory responses,mRNA processing and chromatin ***6-increased genes were located near GC-rich motifs interacting with C2H2 zinc finger transcription factors,whereas Gm6-decreased genes were located near AT-rich motifs associated with helix-turn-helix homeodomain *** motifs interacted with a diverse network of transcription factors encoded by Gm6-regulated genes(STAT3,HOXD11,HES7,GLI1).We identified 77 ALS-associated genes with expression significantly altered by Gm6 treatment(FDRm6 acts through developmental-stage pathways to influence neuron *** expression responses were consistent with neurotrophic effects,ECm modulation,and activation of the Notch and hedgehog neurodevelopmental *** multif

关键词： Alzheimer’s disease Amyotrophic lateral sclerosis Extracellular matrix,Hedgehog Huntington’s disease Neurodegenerative disease Notch,Parkinson’s disease RNA-seq Transcriptome

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