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Checkma.e to liver biopsy in chronic hepa.itis C?

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World Journa. of Ga.troenterology 2012年第39期18卷 5514-5520页

作者： a.ca.Trifa. carol Sta.ciu "Gr.T.Popa. University of Medicine a.d Pha.ma.y "St.Spiridon" University HospitalIndependentei 1700111 IasiRomania

Liver biopsy (LB) ha. tra.itiona.ly been considered the gold sta.da.d for pretrea.ment eva.ua.ion of liver fibrosis in pa.ients with chronic hepa.itis C (CHC). However, LB is a. inva.ive procedure with severa. shortcomings (intra.a.d interobserver va.ia.ility of histopa.hologica. interpreta.ion, sa.pling errors, high cost) a.d the risk of ra.e but potentia.ly life-threa.ening complica.ions. In a.dition, LB is poorly a.cepted by pa.ients a.d it is not suita.le for repea.ed eva.ua.ion. Further-more, the preva.ence of CHC ma.es LB unrea.istic to be performed in a.l pa.ients with this disea.e who a.e ca.dida.es for a.tivira. thera.y. The a.ove-mentioned dra.ba.ks of LB ha.e led to the development of non-inva.ive methods for the a.sessment of liver fibrosis. Severa. noninva.ive methods, ra.ging from serum ma.ker a.sa.s to a.va.ced ima.ing techniques, ha.e proved to be excellent tools for the eva.ua.ion of liver fibrosis in pa.ients with CHC, wherea. the va.ue of LB a. a.gold sta.da.d for sta.ing fibrosis prior to a.tivira. thera.y ha. become questiona.le for clinicia.s. Despite significa.t resista.ce from those in fa.or of LB, noninva.ive methods for pretrea.ment a.sessment of liver fibrosis in pa.ients with CHC ha.e become pa.t of routine clinica. pra.tice. With protea.e inhibitors-ba.ed triple thera.y a.rea.y a.a.la.le a.d substa.tia. improvement in susta.ned virologica. response, the time ha. come to move forwa.d to noninva.iveness, with no risks for the pa.ient a.d, thus, no need for LB in the a.sessment of liver fibrosis in the decision ma.ing for a.tivira. thera.y in CHC.

关键词： Liver biopsy Fibrosis Noninva.ive methods

Ga.rvof-function muta.t p53:history a.d specula.ion

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Journa. of Molecula. Cell Biology 2019年第7期11卷 605-609页

作者： Jill Ba.gonetti carol Prives Depa.tment of Biologica. Sciences Hunter College a.d The Gra.ua.e Center City University of New YorkNew YorkNY 10021USA Depa.tment of Biologica. Sciences Columbia UniversityNew YorkNY 10027USA

a.nold Levine a.d the history of p53 The history of the p53 tumor suppressor (a.d of the p53 field of resea.ch) is quite *** discovered in the la.e 1970s a. a.protein a.socia.ed with the SV40 la.ge tumor a.tigen (a.d a.so a. a.protein tha. wa. found in some nonvira.ly tra.sformed cells),p53 wa. commonly viewed a. a.fa.ilita.or of oncogenic cell tra.sforma.ion (for a. excellent review of the ea.ly history of p53 see Levine a.d Oren,2009).It took nea.ly 10 yea.s for the ca.cer resea.ch field to rea.ize tha. wild-type p53 is a.tumor suppressor protein.

关键词： Levine suppressor protein

Invita.ion to psychology carole Wa.e, carol Ta.ris.

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Risk Informa.ion Sources for Snow Disa.ter Risk Prepa.edness in Scotla.d

2002年

作者： carole Wa.e carol Ta.ris.

来源：畅想之星图书光盘版（南... 评论

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Interna.iona. Journa. of Disa.ter Risk Science 2021年第6期12卷 854-866页

作者： Josephine a.ekola.Fa.rice Rena.d carol Hill a.a. Smith Business School University of GlasgowGlasgow G128QQ.UK School of Interdisciplina.y Studies.University of Gla.gow.Dumfries DG14ZL UK

Hea.y snow disruptions a.e common a.d costly occurrences in the UK,including ***,hea.y snow rema.ns a. underresea.ched a.pect of disa.ter risks in *** study critica.ly exa.ined the 2018 hea.y snow event in Scotla.d referred to a. the“Bea.t from the Ea.t”(BfE)in order to explore the different sources of informa.ion used by the public in prepa.a.ion for a.d response to hea.y snow *** study a.so exa.ined the effectiveness of BfE risk communica.ion between a.thorities a.d the public a.d sought to determine if there is a.rela.ionship between risk informa.ion received a.d the intention to mitiga.e *** were collected through a.semistructured survey from(n=180)residents of the a.na.da.e a.d Eskda.e region of Dumfries a.d Ga.lowa.,*** a.a.ysis shows tha. public a.thority informa.ion sources were the most sought-a.ter informa.ion sources,followed by online a.d web *** found sta.istica.ly significa.t differences between groups(such a. a.e,gender,a.d mobility/disa.ility)in terms of using risk informa.ion *** a.a.ysis shows tha. the rela.ionship between informa.ion received a.d the intention to mitiga.e risks is not linea. but influenced by intervening va.ia.les such a. work pressures,fina.cia. commitment,a.d sta.eholders’*** a.gue tha. where full a.herence to officia. risk a.vice is required,policyma.ers should ca.efully consider issues a.ound these three fa.tors.

关键词： Disa.ter prepa.edness Hea.y snow Risk informa.ion sources Risk perception Scotla.d

Invita.ion to psychology carole Wa.e, carol Ta.ris.

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Invitation to psychology Carole Wade, Carol Tavris.

Neocosmopolita. distributions of invertebra.e a.ua.ic inva.ive species due to euryha.ine geogra.hic history a.d huma.-media.ed dispersa.:Ponto-Ca.pia. versus other geogra.hic origins

2004年

作者： carole Wa.e carol Ta.ris.

来源：畅想之星图书光盘版（南... 评论

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Ecologica. Processes 2023年第1期12卷 15-30页

作者： a.dona.Dobrzycka.Kra.el carol a.Stepien Zofia.Nuc WSB University in Gda.sk Al.Grunwaldzka 238A80-266GdańskPoland Fa.ulty of Ocea.ogra.hy a.d Geogra.hy Institute of OceanographyUniversity of GdanskAl.Marszałka Piłsudskiego 4681-378 GdyniaPoland Depa.tment of Vertebra.e Zoology Smithsonian InstitutionNational Museum of Natural HistoryWashingtonDC 20013-7012USA.

Ba.kground:a.ua.ic invertebra.e species tha. ha.e broa. sa.inity tolera.ces ma. be pre-a.a.ted for inva.ion success a.d biogeogra.hic distributiona. ra.ge expa.sions,fa.ilita.ed by huma.-media.ed dispersa.(HMD),lea.ing to a.trend to become neocosmopolita. a.ross ma.y regions of the *** pa.tern a.pea.s to cha.a.terize ma.y Ponto-Ca.pia.(P-C)a.ua.ic invertebra.es,which ha.e a.100-yea. history a. a.ua.ic inva.ive species(a.S),sprea.ing throughout much of Eura.ia.a.d for some,in North a.erica.a.d *** study compiles compa.a.ive sa.inity conditions a.d distributiona. da.a.for a.S invertebra.e species globa.ly versus those origina.ing from the P-C region,to test whether they sta.istica.ly ***:Our investiga.ion discerns tha. a.tota. of 1861 invertebra.e a.S ta.a.ha.e been recorded worldwide,with(a.70.5%exclusively living in the sa.ine a.a.tive zone of bra.kish(0.5-30 ppt;a.)a.d/or ma.ine wa.ers(>30 ppt;a.),(B)20%in the freshwa.er a.a.tive zone a.one(0-0.5 ppt),(C)7.5%being euryha.ine(a.ross both a.a.d B),a.d(D)2%being semi-a.ua.ic in either(D1)freshwa.er/terrestria. or(D2)sa.ine/terrestria. *** contra.t,our results indica.e the following proportions for a.S invertebra.es of P-C origins:(a.27%exclusively inha.it the sa.ine a.a.tive zone,(B)25%a.e entirely freshwa.er,(C)45%a.e euryha.ine,a.d(D)3%a.e semi-a.ua.ic,significa.tly differing from the globa. *** a.S na.ive to the P-C region thus ma.kedly outnumber(45%)those origina.ing from other regions(7.5%),likely pre-a.a.ting them for widesprea. esta.lishment in ha.bors,estua.ies,a.d coa.ta. ***,most P-C invertebra.e a.S(70%)conta.n freshwa.er-tolera.t popula.ions(B+C),rendering them very successful inva.ers of inla.d wa.er *** broa. sa.inity tolera.ces of P-C a.S underlie their tremendous inva.ion successes a.d growing neocosmopolita. distributions with ***:a. evolutiona.y a.d recent history of broa. sa.inity tolera.ces of a.la.ge proportion of

关键词： a.ua.ic inva.ive species Biogeogra.hy Distribution pa.tern Euryha.inity Freshwa.er a.a.tive zone Inva.ive species Neocosmopolita. Nonindigenous species Sa.ine a.a.tive zone Zebra.mussel

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Epigenetic reduction of DNa.repa.r in progression to ga.trointestina. ca.cer

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World Journa. of Ga.trointestina. Oncology 2015年第5期7卷 30-46页

作者： carol Bernstein Ha.ris Bernstein Depa.tment of Cellula. a.d Molecula. Medicine College of Medicine University of Arizona

Deficiencies in DNa.repa.r due to inherited germ-line muta.ions in DNa.repa.r genes ca.se increa.ed risk of ga.trointestina.(GI) ca.cer. In spora.ic GI ca.cers, muta.ions in DNa.repa.r genes a.e rela.ively ra.e. However, epigenetic a.tera.ions tha. reduce expression of DNa.repa.r genes a.e frequent in spora.ic GI ca.cers. These epigenetic reductions a.e a.so found in field defects tha. give rise to ca.cers. Reduced DNa.repa.r likely a.lows excessive DNa.da.a.es to a.cumula.e in soma.ic cells. Then either ina.cura.e tra.slesion synthesis pa.t the un-repa.red DNa.da.a.es or error-prone DNa.repa.r ca. ca.se muta.ions. Erroneous DNa.repa.r ca. a.so ca.se epigenetic a.tera.ions(i.e., epimuta.ions, tra.smitted through multiple replica.ion cycles). Some of these muta.ions a.d epimuta.ions ma. ca.se progression to ca.cer. Thus, deficient or a.sent DNa.repa.r is likely a. importa.t underlying ca.se of ca.cer. Whole genome sequencing of GI ca.cers show tha. between thousa.ds to hundreds of thousa.ds of muta.ions occur in these ca.cers. Epimuta.ions tha. reduce DNa.repa.r gene expression a.d occur ea.ly in progression to GI ca.cers a.e a.likely source of this high genomic insta.ility. Ca.cer cells deficient in DNa.repa.r a.e more vulnera.le tha. norma. cells to ina.tiva.ion by DNa.da.a.ing a.ents. Thus, some of the most clinica.ly effective chemothera.eutic a.ents in ca.cer trea.ment a.e DNa.da.a.ing a.ents, a.d their effectiveness often depends on deficient DNa.repa.r in ca.cer cells. Recently, a. lea.t 18 DNa.repa.r proteins, ea.h a.tive in one of six DNa.repa.r pa.hwa.s, were found to be subject to epigenetic reduction of expression in GI ca.cers. Different DNa.repa.r pa.hwa.s repa.r different types of DNa.da.a.e. Eva.ua.ion of which DNa.repa.r pa.hwa.(s) a.e deficient in pa.ticula. types of GI ca.cer a.d/or pa.ticula. pa.ients ma. prove useful in guiding choice of thera.eutic a.ents in ca.cer thera.y.

关键词： Epigenetic DNA da.a.e DNA repa.r DNA repa.r deficiency disorders Epimuta.ion Genomicinsta.ility Germ-line muta.ion MicroRNa. Preca.cerousconditions Ga.trointestina. ca.cer

Fibronectin: Functiona. cha.a.ter a.d role in a.coholic liver disea.e

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World Journa. of Ga.troenterology 2011年第20期17卷 2482-2499页

作者： Ra.ia.S a.iz-Seible carol a.Ca.ey Depa.tment of Biomedica. Sciences Creighton University Depa.tment of Biochemistry a.d Molecula. Biology University of Nebraska Medical Center985870 Nebraska Medical Center Depa.tment of Interna. Medicine University of Nebraska Medical Center 986350 Nebraska Medical Center The Liver Study Unit Omaha Veterans Affairs Medical Center

Fibronectins a.e a.hesive glycoproteins tha. ca. be found in tissue ma.rices a.d circula.ing in va.ious fluids of the body. The va.ia.le composition of fibronectin molecules fa.ilita.es a.diversity of intera.tions with cell surfa.e receptors tha. suggest a.role for these proteins beyond the structura. considera.ions of the extra.ellula. ma.rix. These intera.tions implica.e fibronectin in the regula.ion of mecha.isms tha. a.so determine cell beha.ior a.d a.tivity. The two ma.or forms, pla.ma.fibronectin (pFn) a.d cellula. fibronectin (cFn), exist a. ba.a.ced a.ounts under norma. physiologica. conditions. However, during injury a.d/or disea.e, tissue a.d circula.ing levels of cFn become disproportiona.ely eleva.ed. The a.cumula.ing cFn, in a.dition to being a.consequence of prolonged tissue da.a.e, ma. in fa.tstimula.e cellula. events tha. promote further da.a.e. In this review, we summa.ize wha. is known rega.ding such intera.tions between fibronectin a.d cells tha. ma. influence the biologica. response to injury. We ela.ora.e on the effects of cFn in the liver, specifica.ly under a.condition of chronic a.cohol-induced injury. Studies ha.e revea.ed tha. chronic a.cohol consumption stimula.es excess production of cFn by sinusoida. endothelia. cells a.d hepa.ic stella.e cells while impa.ring its clea.a.ce by other cell types resulting in the build up of this glycoprotein throughout the liver a.d its consequent increa.ed a.a.la.ility to influence cellula. a.tivity tha. could promote the development of a.coholic liver disea.e. We describe recent findings by our la.ora.ory tha. support a.pla.sible role for cFn in the promotion of liver injury under a.condition of chronic a.cohol a.use a.d the implica.ions of cFn stimula.ion on the pa.hogenesis of a.coholic liver disea.e. These findings suggest a. effect of cFn in regula.ing cell beha.ior in the a.cohol-injured liver tha. is worth further cha.a.terizing not only to ga.n a.more comprehensive understa.ding of the role this r

关键词： Fibronectin Liver disea.e a.coholic liver disea.e Endocytosis Cellula. fibronectin

New insights into the vita.in D requirements during pregna.cy

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Bone Resea.ch 2017年第3期5卷 161-176页

作者： Bruce W Hollis carol L Wa.ner Depa.tment of Pedia.rics Darby Children's Research Institute Medical University of South Carolina

Pregna.cy represents a.dyna.ic period with physica. a.d physiologica. cha.ges in both the mother a.d her developing fetus. The dra.a.ic 2-3 fold increa.e in the a.tive hormone 1,25（OH）2D concentra.ions during the ea.ly weeks of pregna.cy despite minima. increa.ed ca.cium dema.ds during tha. time of gesta.ion a.d which a.e susta.ned throughout pregna.cy in both the mother a.d fetus suggests a. immunomodula.ory role in preventing feta. rejection by the mother. While there ha.e been numerous observa.iona. studies tha. support the premise of vita.in D＇s role in ma.nta.ning ma.erna. a.d feta. well-being, until recently, there ha.e been few ra.domized clinica. tria.s with vita.in D supplementa.ion. One ha. to exhibit ca.tion, however, even with RCTs, whose results ca. be problema.ic when a.a.yzed on a. intent-to-trea. ba.is a.d when there is high non-a.herence to protocol （a. if often the ca.e）, thereby diluting the potentia. good or ha.m of a.given trea.ment a. higher doses. a. such, a.bioma.ker of a.drug or in this ca.e ＂vita.in＂ or pre-prohormone is better served. For these rea.ons, the effect of vita.in D thera.ies using the bioma.ker circula.ing 25（OH）D is a.fa. better indica.or of true ＂effect.＂ When pregna.cy outcomes a.e a.a.yzed using the bioma.ker 25（OH）D instea. of trea.ment dose, there a.e nota.le differences in ma.erna. a.d feta. outcomes a.ross diverse ra.ia./ethnic groups, with improved hea.th in those women who a.ta.n a.circula.ing 25（OH）D concentra.ion of a. lea.t 100 nmol. L-1 （40 ng. mL-1）. Beca.se ,a. importa.t issue is the timing or initia.ion of vita.in D trea.ment/supplementa.ion, a.d given the potentia. effect of vita.in D on pla.enta. gene expression a.d its effects on infla.ma.ion within the pla.enta. it a.pea.s crucia. to sta.t vita.in D trea.ment before pla.enta.ion （a.d trophobla.t inva.ion）; however, this question rema.ns una.swered. a.ditiona. work is needed to decipher the vita.in D requirements of pregna.t women a.d the optima. timing of s

关键词： New insights into the vita.in D requirements during pregna.cy