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Colonic ulcerations may predict steroid-refractory course in patients with ipilimumab-mediated enterocolitis

World Journal of gastroenterology 2017年第11期23卷 2023-2028页

作者： Animesh Jain Evan J Lipson William H Sharfman Steven R Brant mark g lazarev Division of gastroenterology and Hepatology Department of Internal MedicineUniversity of North Carolina Chapel Hill Department of Oncology Johns Hopkins University School of Medicine and Sidney Kimmel Comprehensive Cancer Center Division of gastroenterology and Hepatology Department of Internal MedicineJohns Hopkins University School of Medicine

AIM To investigate management of patients who develop ipilimumab-mediated enterocolitis, including association of endoscopic findings with steroid-refractory symptoms and utility of infliximab as second-line therapy.METHODS We retrospectively reviewed all patients at our centerwith metastatic melanoma who were treated with ipilimumab between March 2011 and May 2014. All patients received a standard regimen of intravenous ipilimumab 3 mg/kg every 3 wk for four doses or until therapy was stopped due to toxicity or disease progression. Basic demographic and clinical data were collected on all patients. For patients who developed grade 2 or worse diarrhea(increase of 4 bowel movements per day), additional data were collected regarding details of gastrointestinal symptoms, endoscopic findings and treatment course. Descriptive statistics were used.RESULTS A total of 114 patients were treated with ipilimumab during the study period and all were included. Sixteen patients(14%) developed ≥ grade 2 diarrhea. All patients were treated with high-dose corticosteroids(1-2 mg/kg prednisone daily or equivalent). Nine of 16 patients(56%) had ongoing diarrhea despite highdose steroids. Steroid-refractory patients received one dose of intravenous infliximab at 5 mg/kg, and all but one had brisk resolution of diarrhea. Fourteen of the patients underwent either colonoscopy or sigmoidoscopy with variable endoscopic findings, ranging from mild erythema to colonic ulcers. Among 8 patients with ulcers demonstrated by sigmoidoscopy or colonoscopy, 7 patients(88%) developed steroidrefractory symptoms requiring infliximab. With a median follow-up of 264 d, no major adverse events associated with prednisone or infliximab were reported.CONCLUSION In patients with ipilimumab-mediated enterocolitis, the presence of colonic ulcers on endoscopy was associated with a steroid-refractory course.

关键词： Ipilimumab Melanoma Enterocolitis Colitis Infliximab Corticosteroid Colonic ulcer

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Inflammatory bowel disease associated neoplasia:Asurgeon's perspective

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World Journal of gastroenterology 2016年第3期22卷 961-973页

作者： Azah A Althumairi mark g lazarev Susan L gearhart Division of Colorectal Surgery Department of SurgeryJohns Hopkins University School of MedicineBaltimoreMD 21287United States Division of gastroenterology Department of MedicineJohns Hopkins University School of MedicineBaltimoreMD 21287United States

Inflammatory bowel disease(IBD) is associated with increased risk of colorectal cancer(CRC). The risk is known to increase with longer duration of the disease, family history of CRC, and history of primary sclerosing cholangitis. The diagnosis of the neoplastic changes associated with IBD is difficult owing to the heterogeneous endoscopic appearance and interobserver variability of the pathological diagnosis. Screening and surveillance guidelines have been established which aim for early detection of neoplasia. Several surgical options are available for the treatment of IBD-associated neoplasia. Patients' morbidities, risk factors for CRC, degree and the extent of neoplasia must be considered in choosing the surgical treatment. A multidisciplinary team including the surgeon, gastroenterologist, pathologist, and the patient who has a clear understanding of the nature of their disease is needed to optimize outcomes.

关键词： Inflammatory bowel disease Dysplasia Colorectal cancer Endoscopy Surveillance Colectomy

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Optimizing perioperative Crohn's disease management: Role of coordinated medical and surgical care

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World Journal of gastroenterology 2015年第4期21卷 1182-1188页

作者： Jennifer L Bennett Christina Y Ha Jonathan E Efron Susan L gearhart mark g lazarev Elizabeth C Wick Department of Surgery The Johns Hopkins University School of MedicineBaltimoreMD 21287United States Division of gastroenterology the Johns Hopkins University School of MedicineBaltimoreMD 21287United States Division of Digestive Diseases the David Geffen School of Medicine at University of California Los AngelesLos AngelesCA 90095United States

AIM: To investigate rates of re-establishing gastroenterology care, colonoscopy, and/or initiating me-dical therapy after Crohn's disease(CD) surgery at a tertiary care referral center.METHODS: CD patients having small bowel or ileocolonic resections with a primary anastomosis between 2009-2012 were identified from a tertiary academic referral center. CD-specific features, medications, and surgical outcomes were abstracted from the medical record. The primary outcome measure was compliance rates with medical follow-up within 4 wk of hospital discharge and surveillance colonoscopy within 12 mo of surgery. RESULTS: Eighty-eight patients met study inclusion criteria with 92%(n = 81) of patients returning for surgical follow-up compared to only 41%(n = 36) of patients with documented gastroenterology follow-up within four-weeks of hospital discharge, P ger age, longer length of hospitalization, postoperative biologic use and academic center patients. In the study cohort, 75.0% of patients resumed medical therapy within 12 mo, whereas only 53.4% of patients underwent a colonoscopy within 12 mo of surgery.CONCLUSION: Our study highlights the need for coordinated CD multidisciplinary clinics and structured handoffs among providers to improve of quality of care in the postoperative setting.

关键词： Coordinated care Crohn’s disease Postoperative pro

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Dysregulated bidirectional epithelial-mesenchymal crosstalk:A core determinant of lung fibrosis progression

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Chinese Medical Journal Pulmonary and Critical Care Medicine 2024年第1期2卷 27-33页

作者： Liudi Yao Zijian Xu Donna E.Davies mark g.Jones Yihua Wang Biological Sciences Faculty of Environmental and Life SciencesUniversity of SouthamptonSouthampton SO171BJUK Clinical and Experimental Sciences Faculty of MedicineUniversity of SouthamptonSouthampton SO166YDUK Institute for Life Sciences University of SouthamptonSouthampton SO171BJUK NIHR Southampton Biomedical Research Centre University Hospital SouthamptonSouthampton SO166YDUK

Progressive lung fibrosis is characterized by dysregulated extracellular matrix(ECM)homeostasis.Understand-ing of disease pathogenesis remains limited and has prevented the development of effective treatments.While an abnormal wound-healing response is strongly implicated in lung fibrosis initiation,factors that determine why fi-brosis progresses rather than regular tissue repair occur are not fully explained.Within human lung fibrosis,there is evidence of altered epithelial and mesenchymal populations as well as cells undergoing epithelial-mesenchymal transition(EMT),a dynamic and reversible biological process by which epithelial cells lose their cell polarity and down-regulate cadherin-mediated cell-cell adhesion to gain migratory properties.This review will focus on the role of EMT and dysregulated epithelial-mesenchymal crosstalk in progressive lung fibrosis.

关键词： Lung fibrosis Epithelial-mesenchymal transition(EMT) Crosstalk

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The Wave Front Set Correspondence for Dual Pairs with One Member Compact

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Acta Mathematica Sinica,English Series 2024年第3期40卷 823-869页

作者： mark MCKEE Angela PASQUALE Tomasz PRZEBINDA Hammond Lane ProvidenceUT 84332USA Universite de Lorraine CNRSIECLF-57000 MetzFrance Department of Mathematics University of OklahomaNormanOK 73019USA

Let W be a real symplectic space and(g,g')an irreducible dual pair in Sp(W),in the sense of Howe,with g compact.Let g be the preimage of g in the metaplectic group Sp(W).given an irreducible unitary representation II of g that occurs in the restriction of the Weil representation to g,let On denote its character.We prove that,for a suitable embedding T of Sp(W)in the space of tempered distributions on W,the distribution T(On)admits an asymptotic limit,and the limit is a nilpotent orbital integral.As an application,we compute the wave front set of II',the representation of g dual to II,by elementary means.

关键词： Reductive dual pairs Howe duality Weil representation wave front set orbital integrals

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Is Deep Time geology Scientific?

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Journal of Earth Science 2024年第2期35卷 700-703页

作者： T.mark Harrison Department of Earth Planetary and Space SciencesUniversity of CaliforniaLos Angeles90095USA

We all know what car mechanics do.They maintain and repair our automobiles according to established engineering practices.We all know what physicians do.They maintain and repair our bodies according to established medical practices.But what is it that I do as a scientist?Indeed,am I a scientist?The answer to these questions depends on what we meant by“science”.

关键词： maintain Deep repair

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Monomeric C-reactive protein:a link between chronic inflammation and neurodegeneration?

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Neural Regeneration Research 2024年第8期19卷 1643-1644页

作者： Nicoleta Arnaut Ylenia Pastorello mark Slevin george Emil Palade University of Medicine PharmacyScience and TechnologyTârgu MuresRomania Department of Anatomy and Embryology George Emil Palade University of MedicinePharmacyScience and TechnologyTârgu MuresRomania Center for Advanced Medical and Pharmaceutical Research(CCAMF) George Emil Palade University of MedicinePharmacyScience and TechnologyTârgu MuresRomania

Pre-diabetic insulin resistance is associated with sub-clinical inflammation and concomitant increase in systemic C-reactive protein(CRP)levels.Type 2 diabetes mellitus(T2DM)patients register even higher chronic levels of inflammation,with excess circulating CRP originating from both typical hepatic synthesis,and also visceral white adipose tissue.

关键词： inflammation reactive clinical

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Normal Crossings Singularities for Symplectic Topology:Structures

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Acta Mathematica Sinica,English Series 2024年第1期40卷 107-160页

作者： Mohammad FARAJZADEH-TEHRANI mark MCLEAN Aleksey ZINgER The University of Iowa MacLean HallIowa CityIA 52241 Department of Mathematics Stony Brook UniversityStony BrookNY 11794

Our previous papers introduce topological notions of normal crossings symplectic divisor and variety,show that they are equivalent,in a suitable sense,to the corresponding geometric notions,and establish a topological smoothability criterion for normal crossings symplectic varieties.The present paper constructs a blowup,a complex line bundle,and a logarithmic tangent bundle naturally associated with a normal crossings symplectic divisor and determines the Chern class of the last bundle.These structures have applications in constructions and analysis of various moduli spaces.As a corollary of the Chern class formula for the logarithmic tangent bundle,we refine Aluffi’s formula for the Chern class of the tangent bundle of the blowup at a complete intersection to account for the torsion and extend it to the blowup at the deepest stratum of an arbitrary normal crossings divisor.

关键词： Normal crossings divisor Chern class Logarithmic tangent bundle

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LKB1 depletion-mediated epithelial-mesenchymal transition induces fibroblast activation in lung fibrosis

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genes & Diseases 2024年第3期11卷 417-426页

作者： Zijian Xu Elizabeth R.Davies Liudi Yao Yilu Zhou Juanjuan Li Aiman Alzetani Ben g.Marshall David Hancock Tim Wallis Julian Downward Rob M.Ewing Donna E.Davies mark g.Jones Yihua Wang Biological Sciences Faculty of Environmental and Life SciencesUniversity of SouthamptonSouthampton SO171BJUK clinical and Experimental Sciences Faculty of MedicineUniversity of SouthamptonSouthampton SO166YDUK Institute for Life Sciences University of SouthamptonSouthampton SO171BJUK NIHR Southampton Biomedical Research Centre University Hospital SouthamptonSouthampton SO166YDUK University Hospital Southampton Southampton SO166YDUK Oncogene Biology The Francis Crick InstituteLondon NW11ATUK

The factors that determine fibrosis progression or normal tissue repair are largely unknown.We previously demonstrated that autophagy inhibition-mediated epithelial-mesenchymal transition(EMT)in human alveolar epithelial type Il(ATIl)cells augments local myofibroblast differentiation in pulmonary fibrosis by paracrine signaling.Here,we report that liver kinase B1(LKB1)inactivation in ATIl cells inhibits autophagy and induces EMT as a conse-quence.In IPF lungs,this is caused by the down-regulation of CAB39L,a key subunit within the LKB1 complex.3D co-cultures of ATIl cells and MRC5 lung fibroblasts coupled with RNA sequencing(RNA-seq)confirmed that paracrine signaling between LKB1-depleted ATIl cells and fibroblasts augmented myofibroblast differentiation.Together,these data suggest that reduced autophagy caused by LKB1 inhibition can induce EMT in ATIl cells and contribute to fibrosis via aberrant epithelial-fibroblast crosstalk.

关键词： CAB39L Crosstalk EMT LKB1 Pulmonary fibrosis

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Electroactivity of the magnetotactic bacteria Magnetospirillum magneticum AMB-1 and Magnetospirillum gryphiswaldense MSR-1

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Frontiers of Environmental Science & Engineering 2024年第4期18卷 103-110页

作者： Mathias Fessler Qingxian Su Marlene mark Jensen Yifeng Zhang Department of Environmental and Resource Engineering Technical University of DenmarkCopenhagenDK-2800Denmark

Magnetotactic bacteria reside in sediments and stratified water columns.They are named after their ability to synthesize internal magnetic particles that allow them to align and swim along the Earth’s magnetic field lines.Here,we show that two magnetotactic species,Magnetospirillum magneticum strain AMB-1 and Magnetospirillum gryphiswaldense strain MSR-1,are electroactive.Both M.magneticum and M.gryphiswaldense were able to generate current in microbial fuel cells with maximum power densities of 27 and 11μW/m^(2),respectively.In the presence of the electron shuttle resazurin both species were able to reduce the crystalline iron oxide hematite(Fe_(2)O_(3)).In addition,M.magneticum could reduce poorly crystalline iron oxide(FeOOH).Our study adds M.magneticum and M.gryphiswaldense to the growing list of known electroactive bacteria,and implies that electroactivity might be common for bacteria within the Magnetospirillum genus.

关键词： Magnetotactic bacteria Magnetospirillum magneticum Magnetospirillum gryphiswaldense Extracellular electron transfer Microbial fuel cells

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