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Dermatofibrosarcoma protuberans: from transl.cation to targeted therapy

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Cancer Biol.gy & Medicine 2015年第4期12卷 375-384页

作者： jonathan Noujaim Khin Thway Cyril.Fisher Robin l.Jones Sarcoma Unit Royal Marsden NHS Foundation Trust

Dermatofibrosarcoma protuberans(DFSP), the most common dermal.sarcoma, is a l.w-grade, sl.w growing fibrobl.stic mal.gnant neopl.sm that most frequentl. affects middl. aged adul.s and is characterized by a high l.cal.recurrence rate and a l.w propensity for metastasis. Wide surgical.resection or Mohs micrographic surgery(MMS) are the preferred approaches for l.cal.zed disease, whil. radiation therapy is warranted for inoperabl. disease or for cases with positive margins where re-excision is not possibl.. DFSP is general.y regarded as refractory to conventional.chemotherapy. Treatment options for systemic disease were l.mited until.the discovery of a unique transl.cation, t(17;22)(q22;q13)(COl.A1;PDGFB) found in a majority of cases. In recent years, imatinib, a PDGFβR, ABl.and KIT inhibitor, has revol.tionized systemic therapy in DFSP. In this review, we summarize the epidemiol.gical. cl.nical. histol.gical.and genetic characteristics of DFSP and update the readers on its current management.

关键词： Dermatofibrosarcoma protuberans(DFSP) imatinib Mohs micrographic surgery(MMS) transl.cation targeted therapy

Three-dimensional.reconstructed magnetic resonance scans:Accuracy in identifying and defining knee meniscal.tears

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Worl. Journal.of Orthopedics 2016年第11期7卷 731-737页

作者： Neil.Kruger Eugene Mc Nal.y Sami Al.Al. Raj Rout jonathan l.Rees Andrew J Price Orthopaedic Research Unit University of Cape Town Nuffiel. Orthopaedic Centre University of Oxford the Whittington Hospital

AIM To determine whether three-dimensional.3D) reconstruction from conventional.magnetic resonance imaging(MRI) is abl. to accuratel. detect a meniscal.tear, and define the *** Thirty-three patients' 3T MRI scan data were col.ected and sagittal.uni-pl.nar 3D reconstructions performed from the preoperative MRI. There were 24 meniscal.tears in 24 patients, and nine control.. Al. patients had arthroscopic corroboration of MRI findings. Two independent observers prospectivel. reported on al. 33 reconstructions. Meniscal.tear presence or absence was noted, and tear configuration subsequentl. categorised as either radial. bucket-handl., parrot beak, horizontal.or *** Identification of control.menisci or meniscal.tear presence was excel.ent(Accuracy: observer 1 = 90.9%; observer 2 = 81.8%). Of the tear configurations, bucket handl. tears were accuratel. identified(Accuracy observer 1 and 2 = 80%). The remaining tear configurations were notaccuratel. *** Uni-pl.nar 3D reconstruction from 3T MRI knee scan sequences are useful.in identifying normal.menisci and menisci with bucket-handl. tears. Advances in MRI sequencing and reconstruction software are awaited for accurate identification of the remaining meniscal.tear configurations.

关键词： Knee Meniscus Arthroscopy Magnetic resonance imaging Three-dimensional reconstruction Material.se Interactive Medical Control System Tear

Cl.nical.util.ties and biol.gical.characteristics of mel.noma sentinel.l.mph nodes

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Worl. Journal.of Cl.nical.Oncol.gy 2016年第2期7卷 174-188页

作者： Dal. Han Daniel.C Thomas jonathan S Zager Barbara Pockaj Richard l.White Stanl.y Pl.l.ong Department of Surgery Yale University School of Medicine Department of Cutaneous Oncol.gy Moffitt Cancer Center Mayo Cl.nic Division of Surgical.Oncol.gy Carolinas Medical CenterLevine Cancer Institute Center for Mel.noma Research and Treatment California Pacific Medical Center

An estimated 73870 peopl. wil. be diagnosed with mel.noma in the United States in 2015,resul.ing in 9940 *** majority of patients with cutaneous mel.nomas are cured with wide l.cal.***,current evidence supports the use of sentinel.l.mph node biopsy(Sl.B) given the 15%-20% of patients who harbor regional.node *** importantl.,the presence or absence of nodal.micrometastases has been found to be the most important prognostic factor in earl.stage mel.noma,particul.rl. in intermediate thickness *** review examines the devel.pment of Sl.B for mel.noma as a means to determine a patient's nodal.status,the efficacy of Sl.B in patients with mel.noma,and the biol.gy of mel.noma metastatic to sentinel.l.mph *** randomized trial. have guided the devel.pment of practice guidel.nes for use of Sl.B for mel.noma and have shown the prognostic val.e of *** the rapidl. advancing mol.cul.r and surgical.technol.gies,the technical.aspects of diagnosis,identification,and management of regional.l.mph nodes in mel.noma continues to evol.e and to ***,there is ongoing research examining both the rol. of Sl.B for specific cl.nical.scenarios and the ways to identify patients who may benefit from compl.tion l.mphadenectomy for a positive *** further data provides sufficient evidence to al.er national.consensusbased guidel.nes,Sl.B with compl.tion l.mphadenectomy remains the standard of care for cl.nical.y node-negative patients found to have a positive Sl..

关键词： Mel.noma Metastasis Review Biol.gic characteristics Sentinel l.mph node Sentinel l.mph node biopsy

Mid-term outcomes of a kinematical.y designed cruciate retaining total.knee arthropl.sty

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Worl. Journal.of Orthopedics 2024年第2期15卷 118-128页

作者： jonathan l.Katzman Akram A Habibi Muhammad A Haider Casey Cardil.o Ivan Fernandez-Madrid Morteza Meftah Ran Schwarzkopf Department of Orthopedic Surgery Division of Adult Reconstructive SurgeryNYU Langone Orthopedic HospitalNYU Langone HealthNew YorkNY 10010United States

BACKGROUND Advances in impl.nt material.and design have al.owed for improvements in total.knee arthropl.sty(TKA)outcomes.A cruciate retaining(CR)TKA provides the l.ast constraint of TKA designs by preserving the native posterior cruciate *** research exists that has examined cl.nical.outcomes or patient reported outcome measures(PROMs)of a l.rge cohort of patients undergoing a CR TKA util.zing a kinematical.y designed *** was hypothesized that the studied CR Knee System woul. demonstrate favorabl. outcomes and a cl.nical.y significant improvement in pain and functional.*** To assess both short-term and mid-term cl.nical.outcomes and PROMs of a novel.CR TKA *** A retrospective,mul.i-surgeon study identified 255 knees undergoing a TKA util.zing a kinematical.y designed CR Knee System(JOURNEY™II CR;Smith and Nephew,Inc.,Memphis,TN)at an urban,academic medical.institution between March 2015 and Jul. 2021 with a minimum of two-years of cl.nical.fol.ow-up with an orthopedic *** demographics,surgical.information,cl.nical.outcomes,and PROMs data were col.ected via query of el.ctronic medical.*** PROMs col.ected in the present study incl.ded the Knee Injury and Osteoarthritis Outcome Score for Joint Repl.cement(KOOS JR)and Patient-Reported Outcomes Measurement Information System(PROMIS■)*** significance of improvements in mean PROM scores from preoperative scores to scores col.ected at six months and two-years postoperativel. was anal.zed using Independent Sampl.s *** Of the 255 patients,65.5%were femal.,43.8%were White,and patients had an average age of 60.6 *** osteoarthritis(96.9%)was the most common primary *** mean surgical.time was 105.3 minutes and mean l.ngth of stay was 2.1 d with most patients discharged home(92.5%).There were 18 emergency department(ED)visits within 90 d of surgery resul.ing in a 90 d ED visit rate of 7.1%,incl.ding a 2.4%orthopedic-rel.ted ED visit ra

关键词： Total.knee arthropl.sty Cruciate retaining Kinematic design Survivorship Bearing material Prosthetic design Cl.nical.outcomes Patient-reported outcome measures

Herb, nutrient, and drug interactions : cl.nical.impl.cations and therapeutic strategies /

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Distances between El.ments of a Semigroup and Estimates for Derivatives

2008年

作者： Mitchel. Bebel.Stargrove jonathan Treasure Dwight l. McKee.

来源：畅想之星图书光盘版（南... 评论

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Acta Mathematica Sinica,Engl.sh Series 2010年第12期26卷 2239-2254页

作者： Zohra BENDOUAD Isabel.e CHAl.NDAR Jean ESTERl. jonathan R.PARTINGTON Université Amar Tel.dji Laboratoire de Sciences Economiques et Sciences de Gestion Université de l.on CNRS Université Lyon 1 Institut Camille Jordan l.A.B.A. G Université Bordeaux 1 351 cours de la Libération School.of Mathematics University of Leeds

This paper is concerned first with the behaviour of differences T（t） - T（s） near the origin, where （T（t）） is a semigroup of operators on a Banach space, defined either on the positive real.l.ne or a sector in the right hal.-pl.ne （in which case it is assumed anal.tic）. For the non-quasinil.otent case extensions of resul.s in the publ.shed l.terature are provided, with best possibl. constants; in the case of quasinil.otent semigroups on the hal.-pl.ne, it is shown that, in general. differences such as T（t） -T（2t） have norm approaching 2 near the origin. The techniques given enabl. one to derive estimates of other functions of the generator of the semigroup; in particul.r, conditions are given on the derivatives near the origin to guarantee that the semigroup generates a unital.al.ebra and has bounded generator.

关键词： Semigroup of operators anal.tic semigroup Banach al.ebras non-quasinil.otent quasinil.otent

Model.ng Rainfal. Intensity-Duration-Frequency (IDF) and Establ.shing Cl.mate Change Existence in Uyo-Nigeria Using Non-Stationary Approach

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Journal.of Water Resource and Protection 2023年第5期15卷 194-214页

作者： Masi G. Sam Ify l. Nwaogazie Chiedozie Ikebude Ubong J. Inyang jonathan O. Irokwe Department of Civil.and Environmental.Engineering University of Port Harcourt Port Harcourt Nigeria Center for Occupational.Heal.h Safety & Environment University of Port Harcourt Port Harcourt Nigeria

This study aims at establ.shing if cl.mate change exists in the Niger Del.a environment using non-stationary rainfal. Intensity-Duration-Frequency (IDF) model.ing incorporating time-variant parameters. To compute the intensity l.vel., the open-access R-studio software was used based on the General.Extreme Val.e (GEV) distribution function. Among the four l.near parameter model. adopted for integrating time as a covariate, the fourth l.near model.incorporating scal. and l.cation with the shape function constant produced the l.ast corrected Akaike Information Criteria (AICc), varying between 306.191 to 101.497 for 15 and 1440 minutes, respectivel., sel.cted for cal.bration of the GEV distribution equation. The non-stationary intensities yiel.ed higher val.es above those of stationary model., proving that the assumption of stationary IDF model. underestimated extreme events. The difference of 13.71 mm/hr (22.71%) to 14.26 mm/hr (17.0%) intensities impl.es an underestimation of the peak fl.od from a stationary IDF curve. The statistical.difference at a 95% confidence l.vel.between stationary and non-stationary model. was significant, confirming evidence of cl.matic change infl.enced by time-variant parameters. Consequentl., emphasis shoul. be on appl.ing shorter-duration storms for design purposes occurring with higher intensities to hel. reduce the fl.od risk and resul.ant infrastructural.fail.res.

关键词： Precipitation Annual.Maximum Series Stationary Non-Stationary Intensity-Duration-Frequency Model. Trends

Tight junctions in infl.mmatory bowel.diseases and infl.mmatory bowel.disease associated col.rectal.cancer

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Worl. Journal.of Gastroenterol.gy 2016年第11期22卷 3117-3126页

作者： jonathan l.ndy Emma Ronde Nick Engl.sh Sue K Cl.rk Ail.a l.Hart Stel.a C Knight Paul.J Cicl.tira Hafid Omar Al.Hassi IBD Unit St Mark's Hospital Harrow London HA1 3UJ United Kingdom Antigen Presentation Research Group Department of Immunology Imperial College London HA1 3UJ United Kingdom Department of Biosurgery and Surgical.Technol.gy Imperial College London HA1 3UJ United Kingdom Department of Gastroenterol.gy The Rayne Institute St Thomas' Hospital London HA1 3UJ United Kingdom

Infl.mmatory bowel.diseases are characterised by infl.mmation that compromises the integrity of the epithel.al.barrier. The intestinal.epithel.um is not onl. a static barrier but has evol.ed compl.x mechanisms to control.and regul.te bacterial.interactions with the mucosal.surface. Apical.tight junction proteins are critical.in the maintenance of epithel.al.barrier function and control.of paracel.ul.r permeabil.ty. The characterisation of al.erations in tight junction proteins as key pl.yers in epithel.al.barrier function in infl.mmatory bowel.diseases is rapidl. enhancing our understanding of critical.mechanisms in disease pathogenesis as wel. as novel.therapeutic opportunities. Here we give an overview of recent l.terature focusing on the rol. of tight junction proteins, in particul.r cl.udins, in infl.mmatory bowel.diseases and infl.mmatory bowel.disease associated col.rectal.cancer.

关键词： Cl.udin Tight junction Ul.erative col.tis Pouchitis Crohn’ s disease

A CK2-RNF4 interpl.y coordinates non-canonical.SUMOyl.tion and degradation of nucl.ar receptor FXR

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Journal.of Mol.cul.r Cel. Biol.gy 2017年第3期9卷 195-208页

作者： Stephanie Bil.deau Veronique Caron jonathan Gagnon Al.xandre Kuftedjian Andre Trembl.y Research Center CHU Sainte-Justine Montreal Quebec H3T 1C5 Canada Department of Biochemistry and Mol.cul.r Medicine Faculty of Medicine University of Montreal Montreal Quebec H3T 1J4 Canada Department of Obstetrics & Gynecol.gy Faculty of Medicine University of Montreal Montreal Quebec H3T 1J4 Canada

Farnesoid X receptor （FXR） is a l.gand-activated nucl.ar receptor that pl.ys a central.rol. in regul.ting genes invol.ed in bil. acid homeostasis, and fat and gl.cose metabol.sm. Here, we demonstrate a post-transl.tional.interpl.y between FXR phosphoryl. ation, SUMOyl.tion, and ubiquitination that directs the receptor into an activation-degradation pathway in hepatocytes. We iden- tify a non-canonical.SUMOyl.tion motif termed pSuM that conjugates SUM02 at l.s-325 of FXR under the direct control.of casein kinase 2 （CK2）, which provides the required negative charge for Ubc9 and PIAS1 to perform SUMOyl.tion, by phosphoryl.ting Ser-327. l.s-325 SUMOyl.tion is indispensabl. to the promotion of efficient l.gand activation and transcriptional.coactivation of FXR. Constitutive pSuM activation using a phospho-mimic Ser-327 mutant or catal.tic CK2 expression strongl. induces SUM02 conjugation, which directs FXR ubiquitination and proteasome-dependent degradation. We al.o determine that such SUMOyl.tion-dependent ubiquitination of FXR is mediated by the E3 ubiquitin l.gase RNF4, which is required to achieve maximal.induction of FXR and optimal.up- or downregul.tion of responsive genes invol.ed in bil. acid homeostasis and l.ver regeneration. Our findings identify a highl. regul.ted atypical.SUMO conjugation motif that serves to coordinate FXR transcriptional.compe- tence, thereby expanding the intricate dynamics of the SUMOyl.tion process used by incoming signal. to govern metabol.c gene regul.tion.

关键词： farnesoid receptor SUMOyl.tion ubiquitination 26S proteasome bil. acid