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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 Arch.t.ctural 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 th.t.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 ph.t.acoustic tomography, we tracked dPLt trafficking to gut vasculature and an exclusive Kupffer cell-mediated dPLt clearance in the liver, a process th.t.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

Storylines of family medicine Ⅲ:core principles—primary care,systems and family

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Family Medicine and Community health 2024年第S3期12卷 23-32页

作者： William B Ventres Leslie A Stone timothy A Joslin john W Saultz Sommer Aldulaimi Paul R Gordon john C Lane Eric R Lee Jacob Prunuske Limor Gildenblatt Michael h Friedman Colleen t Fogarty Susan h McDaniel tessa Rohrberg Amy Odom Family and Preventive Medicine University of Arkansas for Medical Sciences College of MedicineLittle RockArkansasUSA Family Medicine Oregon Health&Science UniversityPortlandOregonUSA Family and Community Medicine University of Arizona Medical Center–South CampusTucsonArizonaUSA Family and Community Medicine University of Arizona Medical Center–University CampusTucsonArizonaUSA UAMS West Regional Campus Family Medicine Residency Program Fort SmithArkansasUSA Medical College of Wisconsin–Central Wisconsin Campus WausauWisconsinUSA Family and Community Medicine Medical College of Wisconsin–Central Wisconsin CampusWausauWisconsinUSA Family Medicine Advocate Illinois Masonic Medical CenterChicagoIllinoisUSA Family Medicine Presence Saints Mary and Elizabeth Medical CenterChicagoIllinoisUSA Family Medicine University of Rochester Medical CenterRochesterNew YorkUSA Psychiatry and Family Medicine University of Rochester Medical CenterRochesterNew YorkUSA Family and Community Medicine University of Kansas School of Medicine-WichitaWichitaKansasUSA Sparrow/Michigan State University Family Medicine Residency Program LansingMichiganUSA

Storylines of Family Medicine is a 12-part series of thematically linked mini-essays with accompanying illustrations th.t.explore the many dimensions of family medicine,as interpreted by individual family physicians and medical educators in the USA and elsewhere around the ***‘Ⅲ:core principles—primary care,systems,and family’,authors address the following themes:‘Continuity of care—building therapeutic relationships over time’,‘Comprehensiveness—combining breadth and depth of scope’,‘Coordination of care—managing multiple realities’,‘Access to care—intersectional,systemic,and personal’,‘Systems theory—a core value in patient-centered care’,‘Family-oriented practice—supporting patients’health and well-being’,‘Family physician as family member’and‘Family in the exam room’.May readers develop new understandings from these essays.

关键词： individual Storyline principles

Optimizing oncolytic virus design:a“Swiss army knife”approach.t. create a systemically delivered therapeutic

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Signal transduction and targeted therapy 2024年第5期9卷 1791-1792页

作者： Carolina S.Ilkow john Cameron Bell Ottawa hospital Research Institute 501 Smyth RoadOttawaONK1H 8L6Canada

In a recent paper published in Nature Biotechnology,Chen et al.1 describe a multiplex oncolytic virus platform th.t.coupled with adoptive t cell therapy could solve the problem of repeat,systemic delivery of virus based *** is widely accepted th.t.multi-targeted therapeutic approaches attacking several facets of cancer biology are necessary to effectively deal with.t.e tumor h.t.rogeneity th.t.exists within and between patients.

关键词： therapeutic al. targeted

Superior antibody and membrane protein‑specific t‑cell responses to CoronaVac by intradermal versus intramuscular routes in adolescents

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World Journal of Pediatrics 2024年第4期20卷 353-370页

作者： Jaime S.Rosa Duque Samuel M.S.Cheng Carolyn A.Cohen Daniel Leung Xiwei Wang Xiaofeng Mu Yuet Chung tsun Ming Lau Manni Wang Wenyue Zhang Yanmei Zhang howard h.W.Wong Leo C.h.t.ang Sara Chaothai tsz Chun Kwan john K.C.Li Karl C.K.Chan Leo L.h.Luk Jenson C.h.ho Wing Yan Li Amos M.t.Lee Jennifer h.Y.Lam Sau Man Chan Wilfred h.S.Wong Issan Y.S.tam Masashi Mori Sophie A.Valkenburg Malik Peiris Wenwei tu Yu Lung Lau Department of Paediatrics and Adolescent Medicine The University of Hong KongHong KongChina School of Public health The University of Hong KongHong KongChina hKU‑Pasteur Research Pole School of Public HealthThe University of Hong KongHong KongChina Research Institute for Bioresources and Biotechnology Ishikawa Prefectural UniversityNonoichiJapan Department of Microbiology and Immunology Peter Doherty Institute for Infectionand ImmunityUniversity of MelbourneMelbourneVICAustralia Center for Immunology and Infection C2i Hong KongChina

Background Optimising the immunogenicity of COVID-19 vaccines to improve their protection against disease is *** dosing by intradermal(ID)administration has been shown to be equally immunogenic as intramuscular(IM)administration for several vaccines,but the immunogenicity of ID inactivated whole severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)at the full dose is *** study(NCt04800133)investigated the superiority of antibody and t-cell responses of full-dose CoronaVac by ID over IM administration in *** Participants aged 11–17 years received two doses of IM or ID vaccine,followed by the 3rd dose 13–42 days *** and cellular immunogenicity outcomes were measured post-dose 2(IM-CC versus ID-CC)and post-dose 3(IMCCC versus ID-CCC).Doses 2 and 3 were administered to 173 and 104 adolescents,*** Spike protein(S)immunoglobulin G(IgG),S-receptor-binding domain(RBD)IgG,S IgG Fcγreceptor IIIa(FcγRIIIa)-binding,SNM[sum of individual(S),nucleocapsid protein(N),and membrane protein(M)peptide pool]-specific interleukin-2(IL-2)+CD4^(+),SNM-specific IL-2^(+)CD8^(+),S-specific IL-2^(+)CD8^(+),N-specific IL-2^(+)CD4^(+),N-specific IL-2^(+)CD8^(+)and M-specific IL-2^(+)CD4^(+)responses fulfilled the superior and non-inferior criteria for ID-CC compared to IM-CC,whereas IgG avidity was *** ID-CCC,S-RBD IgG,surrogate virus neutralisation test,90%plaque reduction neutralisation titre(PRNt90),PRNt50,S IgG avidity,S IgG FcγRIIIa-binding,M-specific IL-2^(+)CD4^(+),interferon-γ+CD8^(+)and IL-2^(+)CD8^(+)responses were superior and non-inferior to *** estimated vaccine efficacies were 49%,52%,66%and 79%for IM-CC,ID-CC,IM-CCC and ID-CCC,*** ID groups reported more local,mild adverse *** this is the first study to demonstrate superior antibody and M-specific t-cell responses by ID inactivated SARSCoV-2 vaccination and serves as the basis for future research.t. improve the

关键词： CoronaVac Coronavirus disease 2019 Immunity Intradermal Vaccine

C19MC miRNA-520G induces SP100 antiviral gene transcription and inhibits melanin production in skin cutaneous melanoma

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Genes & Diseases 2024年第1期11卷 60-63页

作者： Goodwin G.Jinesh Marian t.Smallin Nino Mtchedlidze Isha Godwin Marco Napoli Nicole hackel Manali S.Phadke Avani A.Deshpande Xiaobo Li john h.Lockhart Jaden R.Baldwin Suehelay Acevedo-Acevedo Yifeng Gao Michelle A.Reiser Keiran S.M.Smalley Elsa R.Flores Andrew S.Brohl Department of Molecular Oncology H.Lee Moffitt Cancer Center&Research InstituteTampaFL 33612USA Molecular Medicine Program H.Lee Moffitt Cancer Center&Research InstituteTampaFL 33612USA Saveetha Medical College ChennaiTamil Nadu 602105India tumor Biology Department H.Lee Moffitt Cancer Center&Research InstituteTampaFL 33612USA Sarcoma Department H.Lee Moffitt Cancer Center&Research InstituteTampaFL 33612USA

SP100 is an antiviral protein th.t.restricts the productive stage of human papillomavirus(hPV)and multiple other viruses,and viruses in turn block sUMO-1-mediated stabilization of SP100 and promotes its degradation(table S1).Interferon(IFN)signaling could still produce more SP100 through.t.anscription to counteract viruses.1 Viruses also disable the transcriptional up-regulation of SP100 to achieve persistent infection in hosts.

关键词： SP100 melanoma stabilization

Combining GLP-1 receptor agonists and SGLt-2 inhibitors for cardiovascular disease prevention in type 2 diabetes:A systematic review with multiple network meta-regressions

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World Journal of Diabetes 2024年第10期15卷 2135-2146页

作者： Jing-Jing Zhu john P h Wilding Xiao-Song Gu Department of Endocrinology and Metabolic Medicine The Second Affiliated Hospital of Soochow UniversitySuzhou 215004Jiangsu ProvinceChina Department of Cardiovascular and Metabolic Medicine University of LiverpoolLiverpool L697ZXUnited Kingdom Clinical Sciences Centre Liverpool University Hospitals NHS Foundation TrustLiverpool L97ALUnited Kingdom Department of Cardiovascular Medicine The Second Affiliated Hospital of Soochow UniversitySuzhou 215004Jiangsu ProvinceChina

BACKGROUND Glucagon-like peptide-1 receptor agonists(GLP-1RA)and sodium-glucose co-transporter-2 inhibitors(SGLt-2I)are associated with significant cardiovascular benefit in type 2 diabetes(t2D).however,GLP-1RA or SGLt-2I alone may not improve some cardiovascular outcomes in patients with prior cardiovascular *** to explore wh.t.er combining GLP-1RA and SGLt-2I can achieve additional benefit in preventing cardiovascular diseases in *** the systematic review was conducted according to PRISMA *** protocol was registered on PROSPERO(ID:42022385007).A total of 107049 participants from eligible cardiovascular outcomes trials of GLP-1RA and SGLt-2I were included in network meta-regressions to estimate cardiovascular benefit of the combination *** modification of prior myocardial infarction(MI)and heart failure(hF)was also explored to provide clinical insight as to when the INtRODUCtION the macro-and micro-vascular benefits of glucagon-like peptide-1 receptor agonists(GLP-1RA)and sodium-glucose co-transporter-2 inhibitors(SGLt-2I)are independent of their glucose-lowering effects[1].In patients with.t.pe 2 diabetes(t2D),the major cardiovascular outcome trials(CVOt)showed th.t.dipeptidyl peptidase-4 inhibitors(DPP-4I)did not improve cardiovascular outcomes[2],whereas cardiovascular benefit of GLP-1RA or SGLt-2I was significant[3,4].Further subgroup analyses indicated th.t.the background cardiovascular risk should be considered when examining the cardiovascular outcomes of these newer glucose-lowering *** instance,prevention of major adverse cardiovascular events(MACE)was only seen in those patients with baseline atherosclerotic cardiovascular disease[3,4].Moreover,a series of CVOt conducted in patients with heart failure(hF)have demonstrated th.t.compared with placebo)SGLt-2I significantly reduced risk of hospitalization for hF or cardiovascular death,irrespective of their history of t2D[5-8].however,similar car

关键词： type 2 diabetes Glucagon-like peptide-1 receptor agonist Sodium-glucose co-transporter-2 inhibitor Combination treatment Cardiovascular outcome Systematic review Network meta-regression

the first record of a Konservat-Lagerstätten in which early post-settlement stages of fossil archaeobalanids(Cirripedia:Balanomorpha)are preserved

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Integrative Zoology 2024年第2期19卷 200-223页

作者： tomáš KOCÍ Rok GAŠPARIC john BUCKERIDGE Martina KOCOVÁ VESELSKÁ Aleš ŠOStER Ivancická581 PragueCzech Republic Palaeontological Department Natural History MuseumNational MuseumPragueCzech Republic Oertijdmuseum Bosscheweg 80Boxtel5293 WBThe Netherlands Institute for Palaeobiology and Evolution Novi TrgKamnikSlovenia Earth and Oceanic Systems Group RMIT UniversityMelbourneAustralia Museums Victoria CarltonVictoriaAustralia Department of Paleobiology and Paleoecology Institute of Geology of the Czech Academy of SciencesPragueCzech Republic Institute of Geology and Palaeontology Charles UniversityPragueCzech Republic Faculty of Natural Sciences and Engineering University of LjubljanaLjubljanaSlovenia

A diverse sessile barnacle fauna from a Miocene shallow-water deposit at Dolnja Stara vas in Slovenia is *** includes the first descriptions of early post settlement juveniles of Actinobalanus sloveniensis attached to mangrove *** represent three distinct growth phases,the earliest being interpreted as being less than 24 h post settlement,the others being 1 to 2 days post *** assessment of their taphonomy is *** adult balanomorphs are attached to a variety of organic substrates,including mangrove leaves and branches,fragments of the conifers?taxodioxylon,Carapoxylon,pine cones,molluscs,and cetacean *** barnacles include ***,Amphibalanus venustus,and Perforatus perforatus—many with opercula retained within the *** retains some of the original shell *** is the second record of barnacle–plant associations from the Central Paratethys from Kamnik and *** paleoecology and paleogeography of the site are discussed.

关键词： acorn barnacles barnacle metamorphosis epibiont paleoecology taxonomy

hVOF-sprayed hAp/S53P4 BG composite coatings on an AZ31 alloy for potential applications in temporary implants

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Journal of Magnesium and Alloys 2024年第1期12卷 345-360页

作者： Carlos A.Poblano-Salas john henao Astrid L.Giraldo-Betancur Paola Forero-Sossa Diego German Espinosa-Arbelaez Jorge A.González-Sánchez Luis R.Dzib-Pérez Susana t.Estrada-Moo Idelfonso E.Pech-Pech CIAtEQ A.C. Av.Manantiales 23-AParque Industrial Bernardo QuintanaEl MarquésQuerétaro 76246Mexico CONAhCYt-CIAtEQ A.C. Av.Manantiales 23-AParque Industrial Bernardo QuintanaEl MarquésQuerétaro 76246Mexico CONAhCYt-Cinvestav Libramiento Norponiente#2000.Fraccionamiento Real de JuriquillaQuerétaro 76230Mexico Universidad tecnológica de Querétaro Av.Pie de la Cuesta N°2501Querétaro 76148Mexico CIDESI Av.Playa Pie de la Cuesta No 702Col.San PabloQuerétaro 76125Mexico Center for Corrosion Research Autonomous University of CampecheAv.Héroe de Nacozari No.480P.C.24070San Francisco de CampecheCam.Mexico

Bioactive thermal spray coatings produced via high-velocity oxygen fuel spray(hVOF)from hydroxyapatite(hAp)and bioactive glasses(BG)have the potential to be employed on temporary implants due to the ability of both hAp and BG to dissolve and promote osseointegration,considering th.t.both phases have different reaction and dissolution rates under in-vitro *** the present work,75%***-25%wt.S53P4 bioactive glass powders were hVOF-sprayed to obtain hAp/S53P4 BG composite coatings on a bioresorbable AZ31 *** study is focused on exploring the effect of the stand-off distance and fuel/oxygen ratio variation as hVOF parameters to obtain stable structural coatings and to establish.t.eir effect on the phases and microstructure produced in those *** characterization techniques,such as scanning electron microscopy,X-ray diffraction,and Fourier transform infrared spectroscopy,were employed to characterize relevant structural and microstructural properties of the composite *** results showed th.t.thermal gradients during coating deposition must be managed to avoid delamination due to the high.t.mperature achieved(max 550℃)and the differences in coefficients of thermal *** was also found th.t.both spraying distance and oxygen/fuel ratio allowed to keep the hydroxyapatite as the main phase in the *** addition,in-vitro electrochemical studies were performed on the obtained hAp/S53P4 BG composite coatings and compared against the uncoated AZ31 *** results showed a significant decrease in hydrogen evolution(at least 98%)when the bioactive coating was applied on the Mg alloy during evaluation in simulated body fluid(SBF).

关键词： Coatings Composites thermal spray temporary implants hydrogen evolution

Patients’experiences with‘sludge’(administrative burden)in the cancer screening process and its relationship with screening completion,experience and health system distrust

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Family Medicine and Community health 2024年第S2期12卷 8-17页

作者： Michelle S Rockwell Brianna Chang Vivian Zagarese Jamie K turner Ally Southworth YingXing Wu Paul Yeaton Li Li Jeffrey S Stein Sarah h Parker john W Epling Department of Family and Community Medicine Virginia Tech Carilion School of MedicineRoanokeVirginiaUSA Department of Family and Community Medicine Carilion ClinicRoanokeVirginiaUSA Virginia tech Carilion School of Medicine RoanokeVirginiaUSA Department of health Systems and Implementation Science Virginia Tech Carilion School of MedicineRoanokeVirginiaUSA Graduate Program in translational Biology Medicineand HealthVirginia TechRoanokeVirginiaUSA health Analytics Research.t.am Carilion ClinicRoanokeVirginiaUSA Division of Gastroenterology Department of Internal MedicineCarilion ClinicRoanokeVirginiaUSA Department of Family Medicine University of Virginia School of MedicineCharlottesvilleVirginiaUSA Center for health Behaviors Research Fralin Biomedical Research Institute at VTCRoanokeVirginiaUSA

Objective‘Sludge’refers to administrative burdens or frictions th.t.preclude people from getting wh.t.they want or need(eg,duplicative forms,complicated instructions,long waiting times).this mixed methods study evaluated patients’perceptions of sludge in the colorectal cancer(CRC)screening process and some impacts of this *** We employed an exploratory sequential mixed methods study design th.t.comprised patient interviews and a patient *** interviews informed final survey revisions and captured contextual data about patients’experiences with *** transcripts were inductively and deductively analysed to identify overarching *** survey quantified sludge,delayed or forgone screenings,screening experience(Net Promoter Score)and health system distrust(health System Distrust Scale).We usedχ2 or t-tests for univariable comparisons and logistic or linear regressions to evaluate the association between cumulative sludge score and delayed or forgone screenings,screening experience and health system *** were integrated for *** Southeastern United *** Patients who were 45–75 years of age,at average risk for CRC and had either completed or been referred for CRC screening(colonoscopy or stool-based test)within the previous 12 *** 22 interview participants and 255 survey participants completed the study.38(15%)survey participants rated their screening experience as poor(Net Promoter Score=0–7 out of 10).the mean(SD)health System Distrust Scale score was 22.4(6.3)out of 45 possible points(higher score=greater distrust).Perceptions of sludge in the CRC screening process varied,with long waiting times and burdensome communication being the most common sources(58%and 35%of participants,respectively).Sludge was positively associated with delayed or forgone screenings(OR=1.42,95%CI 1.28,1.57,phealth system distrust(β=0.47,p

关键词： sludge screening burden