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Survival after inflammatory bowel disease-associated colorectal cancer in the Colon Cancer Family Registry

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World Journal of Gastroenterology 2013年第21期19卷 3241-3248页

作者： Scott V Adams dennis J Ahnen john A Baron Peter T Campbell Steven Gallinger William M Grady Loic LeMarchand Noralane M Lindor john d potter Polly A Newcomb Cancer Prevention Public Health SciencesFred Hutchinson Cancer Research CenterSeattleWA 98109United States department of Medicine Denver VA Medical Center and University of Colorado School of MedicineDenverCO 80045United States department of Medicine University of North CarolinaChapel HillNC 27599United States Epidemiology Research Program Department of Intramural ResearchAmerican Cancer SocietyAtlantaGA 30303United States division of General Surgery University of TorontoTorontoON M5G2C4Canada Cancer Research Center of Hawaii University of HawaiiHonoluluHI 96813United States department of Health Science Research Mayo Clinic ArizonaScottsdaleAZ 85259United States

AIM: To investigate the survival of individuals with colorectal cancer (CRC) with inflammatory bowel disease (IBd-associated CRC) compared to that of individuals without IBd diagnosed with CRC. METHOdS: Epidemiologic, clinical, and follow-up data were obtained from the Colon Cancer Family Registry (Colon CFR). IBd-associated cases were identified from self-report of physician diagnosis. For a subset of participants, medical records were examined to confirm self-report of IBd. Cox proportional hazards regression was applied to estimate adjusted hazard ratios (aHR) and 95%CI of mortality, comparing IBd-associated to non-IBd-associated CRC, adjusted for age at CRC diagnosis, sex, Colon CFR phase, and number of prior endoscopies. Following imputation to complete CRC stage information, adjustment for CRC stage was examined. RESULTS: A total of 7202 CRC cases, including 250 cases of IBd-associated CRC, were analyzed. Over a twelve year follow-up period following CRC diagnosis, 2013 and 74 deaths occurred among non-IBd associated CRC and IBd-associated CRC patients, respectively. The difference in survival between IBd-associated and non-IBd CRC cases was not statistically significant (aHR = 1.08; 95%CI: 0.85-1.36). However, the assumption of proportional hazards necessary for valid inference from Cox regression was not met over the entire follow-up period, and we therefore limited analyses to within five years after CRC diagnosis when the assumption of proportional hazards was met. Over this period, there was evidence of worse prognosis for IBd-associated CRC (aHR = 1.36; 95%CI: 1.05-1.76). Results were similar when adjusted for CRC stage, or restricted to IBd confirmed in medical records. CONCLUSION: These results support the hypothesis that IBd-associated CRC has a worse prognosis than non-IBd-associated CRC.

关键词： Colorectal cancer Inflammatory bowel disease Outcomes research Cancer survival Inflammation

红肉和加工肉及其与人类和地球的健康当代的肉类消费有害于人类健康，也不利于地球

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英国医学杂志中文版 2018年第5期21卷 246-247页

作者：童钰玲(译) 宋震亚(校) 浙江大学医学院附属第二医院全科医学科

美国国立健康研究院（the National Institutes of Health，NIH）先前的分析AARP研究发现，肉类摄人多的研究参与者病死率较高。Etemadi及其团队通过对超过750万人年的观察和进一步分析（doi：10．1136／bmj．j1957）发现，红肉和加工... 详细信息

美国国立健康研究院（the National Institutes of Health，NIH）先前的分析AARP研究发现，肉类摄人多的研究参与者病死率较高。Etemadi及其团队通过对超过750万人年的观察和进一步分析（doi：10．1136／bmj．j1957）发现，红肉和加工肉的高摄人与总病死率和主因病死率（心血管疾病、糖尿病、癌症和肝、肾、呼吸道疾病）升高相关。

关键词：红肉加工肉

Aerodynamics of a Tandem-Bladed Axial Compressor Rotor under Circumferential distortion at different Rotational Speeds

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Journal of Thermal Science 2024年第4期33卷 1340-1356页

作者： Amit KUMAR Jerry T.john A.M.PRAdEEP R.A.dAKKERMANS dragan KOZULOVIC department of Aerospace Engineering Indian Institute of Technology BombayMumbai400076India department of Automotive and Aeronautical Engineering Hamburg University of Applied Sciences20099HamburgGermany Institute of Jet Propulsion Bundeswehr University Munich85577NeubibergGermany

For most aircraft engines,inflow distortion is *** distortion is known to degrade the aerodynamic performance and stable operating limits of a *** rotor configuration is an arrangement that effectively controls the growth of the boundary layer over the suction surface of the ***,a higher total pressure rise can be achieved through this unconventional design approach involving the splitting of the blade into forward and aft *** is expected that the effect of inlet flow distortion would be more severe for a tandem-rotor design due to the greater flow turning inherent in such ***,this aspect needs to be thoroughly *** present study discusses the effect of circumferential distortion on the tandem-rotor at different rotational ***-annulus RANS simulations using ANSYS CFX are used in the present *** performance of the rotor at a particular flow coefficient and different rotational speeds is *** total pressure and efficiency are observed to drop at lower mass flow rates under the influence of circumferential *** loss region in each blade passage is mainly associated with the blade wake,tip leakage vortex,secondary flow,and boundary ***,their contribution varies from passage to passage,particularly in the distorted *** the lower span,the wake width is found to be higher than that at a higher *** to the redistribution of the mass flow,the circumferential extent reduces at a higher *** the undistorted sector,the strength of the tip leakage vortex is significantly higher at the design rotational speed than at lower *** distortion near the tip region promotes an early vortex breakdown even at the design operating *** adversely affects the total pressure,efficiency,and stall *** clean flow conditions,this phenomenon is only observed near the stall *** the design operating condition,the breakdown of the forward rotor tip l

关键词： tandem rotor circumferential distortion loss tip leakage vortex vortex breakdown diffusion factor aerodynamics of compressor blade

Challenges and Opportunities in Preserving Key Structural Features of 3d-Printed Metal/Covalent Organic Framework

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Nano-Micro Letters 2024年第8期16卷 362-381页

作者： Ximeng Liu dan Zhao john Wang department of Materials Science and Engineering National University of SingaporeSingapore 117574Singapore department of Chemical and Biomolecular Engineering National University of SingaporeSingapore 117585Singapore National University of Singapore(Chongqing)Research Institute Chongqing 401123People’s Republic of China

Metal-organic framework(MOF)and covalent organic framework(COF)are a huge group of advanced porous materials exhibiting attractive and tunable microstructural features,such as large surface area,tunable pore size,and functional surfaces,which have significant values in various application *** emerging 3d printing technology further provides MOF and COFs(M/COFs)with higher designability of their macrostructure and demonstrates large achievements in their performance by shaping them into advanced 3d ***,the currently available 3d printing M/COFs strategy faces a major challenge of severe destruction of M/COFs’microstructural features,both during and after 3d *** is envisioned that preserving the microstructure of M/COFs in the 3d-printed monolith will bring a great improvement to the related *** this overview,the 3d-printed M/COFs are categorized into M/COF-mixed monoliths and M/COF-covered *** differences in the properties,applications,and current research states are *** up-to-date advancements in paste/scaffold composition and printing/covering methods to preserve the superior M/COF microstructure during 3d printing are further discussed for the two types of 3d-printed M/*** the analysis of the current states of 3d-printed M/COFs,the expected future research direction to achieve a highly preserved microstructure in the 3d monolith is proposed.

关键词： Metal-organic frameworks Covalent organic frameworks 3d printing Microstructure Monolith

Aging impairs the osteocytic regulation of collagen integrity and bone quality

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Bone Research 2024年第1期12卷 78-94页

作者： Charles A.Schurman Serra Kaya Neha dole Nadja M.Maldonado Luna Natalia Castillo Ryan potter Jacob P.Rose Joanna Bons Christina d.King Jordan B.Burton Birgit Schilling Simon Melov Simon Tang Eric Schaible Tamara Alliston department of Orthopaedic Surgery University of CaliforniaSan FranciscoCA 94143USA UC Berkeley/UCSF Graduate Program in Bioengineering San FranciscoCA 94143USA Buck Institute for Research on Aging NovatoCA 94945USA Washington University in St Louis Department of OrthopedicsSt.LouisMO 63130USA Advanced Light Source Lawrence Berkeley National LaboratoryBerkeleyCA 94720USA

Poor bone quality is a major factor in skeletal fragility in elderly *** molecular mechanisms that establish and maintain bone quality,independent of bone mass,are unknown but are thought to be primarily determined by *** hypothesize that the age-related decline in bone quality results from the suppression of osteocyte perilacunar/canalicular remodeling(PLR),which maintains bone material *** examined bones from young and aged mice with osteocyte-intrinsic repression of TGFβsignaling(TβRII^(ocy−/−))that suppresses *** control aged bone displayed decreased TGFβsignaling and PLR,but aging did not worsen the existing PLR suppression in male TβRII^(ocy−/−)*** relationship impacted the behavior of collagen material at the nanoscale and tissue scale in macromechanical *** effects of age on bone mass,density,and mineral material behavior were independent of osteocytic TGFβ.We determined that the decline in bone quality with age arises from the loss of osteocyte function and the loss of TGFβ-dependent maintenance of collagen integrity.

关键词： maintain primarily integrity

Prehospital transdermal glyceryl trinitrate for ultra- acute ischaemic stroke: data from the RIGHT- 2 randomised sham- controlled ambulance trial

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Stroke & Vascular Neurology 2024年第1期9卷 38-49,I0035-I0046页

作者： Jason Philip Appleton Lisa J Woodhouse Craig S Anderson Sandeep Ankolekar Lesley Cala Mark dixon Timothy J England Kailash Krishnan Grant Mair Keith W Muir john potter Christopher I Price Marc Randall Thompson G Robinson Christine Roffe Else C Sandset Jeffrey L Saver Angela Shone Aloysius Niroshan Siriwardena Joanna M Wardlaw Nikola Sprigg Philip M Bath Stroke University Hospitals Birmingham NHS Foundation TrustBirminghamUK Institute of Applied HealthResearch University of Birmingham College of Medical and Dental SciencesBirminghamUK Stroke Trials Unit Mental Health and Clinical NeurosciencesUniversity of NottinghamNottinghamUK Faculty of Medicine The George Institute for Global HealthSydneyNew South WalesAustralia The George Institute China at Peking University Health Science Center BeijingChina Neurology Royal Prince Alfred HospitalSydney Health PartnersSydneyNew South WalesAustralia department of Neurology King's College Hospital NHS Foundation TrustLondonUK Faculty of Health and Medical Sciences University of Western AustraliaCrawleyWestern AustraliaAustralia East Midlands Ambulance Service NHS Trust NottinghamUK Stroke Queen's Medical CentreNottingham University Hospitals NHS TrustNottinghamUK Centre for Clinical Brain Sciences Dementia Research InstituteUniveristy of EdinburghEdinburghUK Institute of Neurology and Psychology University of GlasgowGlasgowUK Bob Champion Research and Education Building University of East AngliaNorwichUK Institute of Neuroscience Newcastle UniversityNewcastle upon TyneUK department of Neurology Leeds Teaching Hospitals NHS TrustLeedsUK department of Cardiovascular Sciences and NIHR Leicester Biomedical Research Centre University of LeicesterLeicesterUK Stroke Research in Stoke Institute for Science and Technology in MedicineKeele UniversityStoke-on TrentUK department of Neurology Oslo University HospitalOsloNorway Research and development Norwegian Air Ambulance FoundationOsloNorway department of Neurology and Comprehensive Stroke Center David Geffen School of MedicineUCLALos AngelesCaliforniaUSA Research and Graduate Services University of NottinghamNottinghamUK Community and Health Research Unit University of LincolnLincolnUK

Background The effect of transdermal glyceryl trinitrate(GTN,a nitrovasodilator)on clinical outcome when administered before hospital admission in suspected stroke patients is ***,we assess the safety and efficacy of GTN in the prespecified subgroup of patients who had an ischaemic stroke within the Rapid Intervention with Glyceryl trinitrate in Hypertensive stroke Trial-2(RIGHT-2).Methods RIGHT-2 was an ambulance-based multicentre sham-controlled blinded-endpoint study with patients randomised within 4hours of *** primary outcome was a shift in scores on the modified Rankin scale(mRS)at day *** outcomes included death;a global analysis(Wei-Lachin test)containing Barthel Index,EuroQol-5d,mRS,telephone interview for cognitive status-modified and Zung depression scale;and neuroimaging-determined‘brain frailty’*** were reported as n(%),mean(Sd),median[IQR],adjusted common OR(acOR),mean difference or Mann-Whitney difference(MWd)with 95%*** 597 of 1149(52%)patients had a final diagnosis of ischaemic stroke;age 75(12)years,premorbid mRS>2107(18%),Glasgow Coma Scale 14(2)and time from onset to randomisation 67[45,108]***‘brain frailty’was common:median score 2[2,3](range 0–3).At day 90,GTN did not influence the primary outcome(acOR for increased disability 1.15,95%CI 0.85 to 1.54),death or global analysis(MWd 0.00,95%CI-0.10 to 0.09).In subgroup analyses,there were non-significant interactions suggesting GTN may be associated with more death and dependency in participants randomised within 1hour of symptom onset and in those with more severe *** In patients who had an ischaemic stroke,ultra-acute administration of transdermal GTN in the ambulance did not improve clinical outcomes in a population with more clinical and radiological frailty than seen in previous in-hospital *** IS ALREAdY KNOWN ON THIS TOPIC⇒Transdermal glyceryl trinitrate(GTN)was associat-ed with less death and dependency in those w

关键词： Glasgow nitrate random

Hepatic angiotensin-converting enzyme 2 expression in metabolic dysfunction-associated steatotic liver disease and in patients with fatal COVId-19

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World Journal of Gastroenterology 2024年第31期30卷 3705-3716页

作者： Angus K Jacobs Steven d Morley Kay Samuel Katie Morgan Lyndsey Boswell Timothy J Kendall david A dorward Jonathan A Fallowfield Peter C Hayes john N Plevris Hepatology Laboratory University of EdinburghEdinburgh EH164SBUnited Kingdom Scottish National Blood Transfusion Service Jack Copland CentreEdinburgh EH144BEUnited Kingdom Institute for Regeneration and Repair University of EdinburghEdinburgh EH164UUUnited Kingdom Edinburgh Pathology University of EdinburghEdinburgh EH164SBUnited Kingdom

BACKGROUNd Metabolic dysfunction-associated steatotic liver disease(MASLd),characterised by hepatic lipid accumulation,causes inflammation and oxidative stress accompanied by cell damage and *** injury(LI)is also frequently reported in patients hospitalised with coronavirus disease 2019(COVId-19),while preexisting MASLd increases the risk of LI and the development of COVId-19-associated *** of injury at the cellular level remain unclear,but it may be significant that severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)which causes COVId-19,uses angiotensin-converting expression enzyme 2(ACE2),a key regulator of the‘anti-inflammatory’arm of the renin-angiotensin system,for viral attachment and host cell *** To determine if hepatic ACE2 levels are altered during progression of MASLd and in patients who died with severe *** ACE2 protein levels and localisation,and histological fibrosis and lipid droplet accumulation as markers of MASLd were determined in formalin-fixed liver tissue sections across the MASLd pathological spectrum(isolated hepatocellular steatosis,metabolic dysfunction-associated steatohepatitis(MASH)+/-fibrosis,end-stage cirrhosis)and in post-mortem tissues from patients who had died with severe COVId-19,using ACE2 immunohistochemistry and haematoxylin and eosin and picrosirius red staining of total collagen and lipid droplet areas,followed by quantification using machine learning-based image pixel *** ACE2 staining is primarily intracellular and concentrated in the cytoplasm of centrilobular hepatocytes and apical membranes of bile duct ***,ACE2 protein levels are elevated in non-fibrotic MASH compared to healthy controls but not in the progression to MASH with fibrosis and in ***2 protein levels and histological fibrosis are not associated,but ACE2 and liver lipid droplet content are significantly correlated across the MASLd *** A

关键词： Metabolic dysfunction-associated steatotic liver disease Angiotensin-converting enzyme 2 Immunohistochemistry COVId-19 COVId-19-associated cholangiopathy

desialylated Platelet Clearance in the Liver is a Novel Mechanism of Systemic Immunosuppression

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Research 2024年第3期2023卷 35-50页

作者： June Li danielle Karakas Feng Xue Yingyu Chen Guangheng Zhu Yeni H.Yucel Sonya A.MacParland Haibo Zhang john W.Semple john Freedman Qizhen Shi Heyu Ni department of Laboratory Medicine and Pathobiology University of TorontoTorontoONCanada Toronto Platelet Immunobiology Group TorontoONCanada Keenan Research Centre for Biomedical Science of St.Michael's Hospital TorontoONCanada Canadian Blood Services Centre for Innovation TorontoONCanada departments of Pediatrics Medical College of WisconsinMilwaukeeWIUSA Blood Research Institute Versiti WisconsinMilwaukeeWIUSA departments of Ophthalmology and Vision Sciences Medicine University of TorontoTorontoONCanada Faculty of Engineering and Architectural Science Ryerson UniversityTorontoONCanada Multi-Organ Transplant Program Toronto General Hospital Research InstituteTorontoONCanada department of Immunology University of TorontoTorontoONCanada Critical Care Medicine Department ofAnesthesiology and PainUniversity of TorontoTorontoONCanada department of Physiology University of TorontoTorontoONCanada department of Pharmacology University of TorontoTorontoONCanada. division of Hematology and Transfusion Medicine Lund UniversityLundSweden clinical Immunology and Transfusion Medicine Ofice of Medical ServicesRegion SkaneLundSweden department of Medicine University of TorontoTorontoONCanada Children's Research Institute Children's WisconsinWauwatosaWIUSA Midwest Athletes Against Childhood Cancer Fund Research Center MilwaukeeWIUSA.

Platelets are small, versatile blood cells that are critical for hemostasis/thrombosis. Local platelet accumulation is a known contributor to proinflammation in various disease states. However, the anti-inflammatory/immunosuppressive potential of platelets has been poorly explored. Here, we uncovered, unexpectedly, desialylated platelets (dPLTs) down-regulated immune responses against both platelet-associated and -independent antigen challenges. Utilizing multispectral photoacoustic tomography, we tracked dPLT trafficking to gut vasculature and an exclusive Kupffer cell-mediated dPLT clearance in the liver, a process that we identified to be synergistically dependent on platelet glycoprotein Ibα and hepatic Ashwell–Morell receptor. Mechanistically, Kupffer cell clearance of dPLT potentiated a systemic immunosuppressive state with increased anti-inflammatory cytokines and circulating Cd4+ regulatory T cells, abolishable by Kupffer cell depletion. Last, in a clinically relevant model of hemophilia A, presensitization with dPLT attenuated anti-factor VIII antibody production after factor VIII ( infusion. As platelet desialylation commonly occurs in daily-aged and activated platelets, these findings open new avenues toward understanding immune homeostasis and potentiate the therapeutic potential of dPLT and engineered dPLT transfusions in controlling autoimmune and alloimmune diseases.

关键词： Platelet transfusion homeostasis

damage evolution of rock-encased-backfill structure under stepwise cyclic triaxial loading

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Journal of Rock Mechanics and Geotechnical Engineering 2024年第2期16卷 597-615页

作者： Xin Yu Yuye Tan Weidong Song john Kemeny Shengwen Qi Bowen Zheng Songfeng Guo Key Laboratory of Shale Gas and Geoengineering Institute of Geology and GeophysicsChinese Academy of SciencesBeijing100089China Innovation Academy for Earth Science Chinese Academy of SciencesBeijing100089China University of Chinese Academy of Sciences Beijing100049China School of Civil and Resources Engineering University of Science and Technology BeijingBeijing100083China Key Laboratory of High-Efficient Mining and Safety of Metal Mines(Ministry of Education of China) University of Science and Technology BeijingBeijing100083China department of Mining and Geological Engineering University of ArizonaTucsonAZ86721USA

Rock-encased-backfill(RB)structures are common in underground mining,for example in the cut-andfill and stoping *** understand the effects of cyclic excavation and blasting activities on the damage of these RB structures,a series of triaxial stepwise-increasing-amplitude cyclic loading experiments was conducted with cylindrical RB specimens(rock on outside,backfill on inside)with different volume fractions of rock(VF=0.48,0.61,0.73,and 0.84),confining pressures(0,6,9,and 12 MPa),and cyclic loading rates(200,300,400,and 500 N/s).The damage evolution and meso-crack formation during the cyclic tests were analyzed with results from stress-strain hysteresis loops,acoustic emission events,and post-failure X-ray 3d fracture *** results showed significant differences between cyclic and monotonic loadings of RB specimens,particularly with regard to the generation of shear microcracks,the development of stress memory and strain hardening,and the contact forces and associated friction that develops along the rock-backfill *** important finding is that as a function of the number of cycles,the elastic strain increases linearly and the dissipated energy increases ***,compared with monotonic loading,the cyclic strain hardening characteristics are more sensitive to rising confining pressures during the initial compaction *** finding is that compared with monotonic loading,more shear microcracks are generated during every reloading stage,but these microcracks tend to be dispersed and lessen the likelihood of large shear fracture *** transition from elastic to plastic behavior varies depending on the parameters of each test(confinement,volume fraction,and cyclic rate),and an interesting finding was that the transformation to plastic behavior is significantly lower under the conditions of 0.73 rock volume fraction,400 N/s cyclic loading rate,and 9 MPa *** the findings have important practical implications on t

关键词： Rock and backfill Triaxial cyclic loading Volume fraction damage evolution 3d visualization