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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 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

A parsimonious Bayesian predictive model for forecasting new reported cases of west Nile disease

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Infectious Disease Modelling 2024年第4期9卷 1175-1197页

作者： Saman Hosseini Lee w.Cohnstaedt john M.Humphreys Caterina Scoglio Department of Electrical and Computer Engineering Kansas State UniversityManhattanKSUSA Foreign Arthropod-Borne Animal Diseases Research Unit National Bio-and Agro-defense Facility USDA ARSManhattanKSUSA Foreign Animal Disease Research Unit National Bio-and Agro-defense FacilityUSDA ARSManhattanKSUSA

Upon researching predictive models related towest Nile virus disease,it is discovered that there are numerous parameters and extensive information in most models,thus contributing to unnecessary *** challenge frequently encountered is the lead time,which refers to the period for which predictions are made and often is too *** paper addresses these issues by introducing a parsimonious method based on ICC curves,offering a logistic distribution model derived from the vector-borne SEIR *** existing models relying on diverse environmental data,our approach exclusively utilizes historical and present infected human cases(number of new cases).with a yearlong lead time,the predictions extend throughout the 12 months,gaining precision as new data *** conditions are derived to minimize Bayesian loss,enhancing predictive *** construct a Bayesian forecasting probability density function using carefully selected prior *** these functions,we predict monthspecific infections nationwide,rigorously evaluating accuracy with probabilistic ***,HPD credible intervals at 90%,95%,and 99%levels is *** assessment is conducted for HPD intervals,measuring the proportion of intervals that does not include actual reported cases for 2020e2022.

关键词： west nile virus ICC curve Bayesian model Logistic distribution HPD credible interval

Telomeric DNA breaks in human induced pluripotent stem cells trigger ATR-mediated arrest and telomerase-independent telomere damage repair

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Journal of Molecular Cell Biology 2024年第3期16卷 46-60页

作者： Katrina N.Estep john w.Tobias Rafael J.Fernandez Brinley M.Beveridge F.Brad johnson Department of Pathology and Laboratory Medicine University of PennsylvaniaPhiladelphiaPA 19104USA Quantiative Biosciences Merck&Co.Inc.West PointPA 19486USA Penn Genomic Analysis Core University of PennsylvaniaPhiladelphiaPA 19104USA

Although mechanisms of telomere protection are well-defined in differentiated cells,how stem cells sense and respond to telomere dysfunction,in particular telomeric double-strand breaks(DSBs),is poorly ***,we report the DNA damage signaling,cell cycle,and transcriptome changes in human induced pluripotent stem cells(iPSCs)in response to telomere-internal *** engineer human iPSCs with an inducible TRF1-FokI fusion protein to acutely induce DSBs at *** this model,we demonstrate that TRF1-FokI DSBs activate an ATR-dependent DNA damage response,which leads to p53-independent cell cycle arrest in *** CRISPR–Cas9 to cripple the catalytic domain of telomerase reverse transcriptase,we show that telomerase is largely dispensable for survival and lengthening of TRF1-FokI-cleaved telomeres,which instead are effectively repaired by robust homologous recombination(HR).In contrast to HR-based telomere maintenance in mouse embryonic stem cells,where HR causes ZSCAN4-dependent extension of telomeres beyond their initial lengths,HR-based repair of telomeric breaks is sufficient to maintain iPSC telomeres at a normal length,which is compatible with sustained survival of the cells over several days of TRF1-FokI *** findings suggest a previously unappreciated role for HR in telomere maintenance in telomerase-positive iPSCs and reveal distinct iPSC-specific responses to targeted telomeric DNA damage.

关键词： telomeres telomerase alternative lengthening of telomeres pluripotent stem cells DNA damage double-strand breaks

The risk of prostate cancer on incidental finding of an avid prostate uptake on 2-deoxy-2-[^(18)F]fluoro-D-glucose positron emission tomography/computed tomography for non-prostate cancer-related pathology:A single centre retrospective study

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Asian Journal of Urology 2024年第1期11卷 33-41页

作者： Anthony Franklin Troy Gianduzzo Boon Kua David wong Louise McEwan James walters Rachel Esler Matthew J.Roberts Geoff Coughlina john w.Yaxley Department of Urology The Wesley HospitalBrisbaneQLDAustralia wesley Medical Research BrisbaneQLDAustralia School of Medicine The University of QueenslandBrisbaneQLDAustralia Department of Radiology Wesley Medical ImagingBrisbaneQLDAustralia Department of Urology Royal Brisbane and Women's HospitalBrisbaneQLDAustralia

Objective:To review the risk of prostate cancer(PCa)in men with incidentally reported increased intraprostatic uptake at 2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography/computed tomography(18F-FDG PET/CT)ordered at Department of Urology,The wesley Hospital,Brisbane,QLD,Australia for non-PCa related ***:Retrospective analysis of consecutive men between August 2014 and August 2019 presenting to a single institution for 18F-FDG PET/CT for non-prostate related conditions was *** were classified as benign,indeterminate,or malignant depending of the results of prostate-specific antigen(PSA),PSA velocity,biopsy histopathology,and three-Tesla(3 T)multiparametric MRI(mpMRI)Prostate Imaging Reporting and Data System score,or gallium-68-prostate-specific membrane antigen(68Ga-PSMA)PET/CT ***:Three percent(273/9122)of men demonstrated 18F-FDG avidity within the ***-five percent(231/273)were further investigated,including with PSA tests(227/231,98.3%),3 T mpMRI(68/231,29.4%),68Ga-PSMA PET/CT(33/231,14.3%),and prostate biopsy(57/231,24.7%).Results were considered benign in 130/231(56.3%),indeterminate in 31/231(13.4%),and malignant in 70/231(30.3%).PCa was identified in 51/57(89.5%)of the men who proceeded to biopsy,including 26/27(96.3%)men with Prostate Imaging Reporting and Data System scores 4-5 mpMRI and six men with a positive 68Ga-PSMA PET/*** most common Gleason score on biopsy was greater than or equal to 4+5(14/51,27.5%).68Ga-PSMA PET/CT was concordant with the 18F-FDG findings in 26/33(78.8%).All 13 men with a positive concordant 18F-FDG,3 T mpMRI,and 68Ga-PSMA PET/CT had PCa on *** was no statistically significant difference in the 18F-FDG maximum standardized uptake value between the benign or malignant groups(5.7 vs.6.1;p=0.580).Conclusion:In this study,after an incidental finding of an avid intraprostatic lesion on 18F-FDG PET/CT,70 of the 231 cases(30.3%;0.8%of the entire cohort)had results c

关键词： Prostatecancer Positionemission tomography Multiparametric magneticresonance imaging Prostatebiopsy

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 that 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

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 Team 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 that preclude people from getting what 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 that 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,p<0.001),poor screening experience(OR=1.15,95%CI 1.04,1.28,p=0.009)and health system distrust(β=0.47,p

关键词： sludge screening burden

Two-photon polymerization lithography for imaging optics

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International Journal of Extreme Manufacturing 2024年第4期6卷 21-60页

作者： Hao wang Cheng-Feng Pan Chi Li Kishan S Menghrajani Markus A Schmidt Aoling Li Fu Fan Yu Zhou wang Zhang Hongtao wang Parvathi Nair Suseela Nair john You En Chan Tomohiro Mori Yueqiang Hu Guangwei Hu Stefan A Maier Haoran Ren Huigao Duan Joel K w Yang College of Mechanical and Vehicle Engineering Hunan UniversityChangsha 410082People's Republic of China Engineering Product Development Singapore University of Technology and DesignSingapore 487372Singapore Greater Bay Area Institute for Innovation Hunan UniversityGuangzhou 511300People's Republic of China Department of Electrical and Computer Engineering National University of Singapore4 Engineering Drive 3Singapore 117576Singapore School of Physics and Astronomy Faculty of ScienceMonash UniversityMelbourneVictoria 3800Australia Leibniz Institute of Photonic Technology 07745 JenaGermany Abbe Center of Photonics and Faculty of Physics FSU Jena07745 JenaGermany Otto Schott Institute of Material Research FSU Jena07745 JenaGermany Institute of Materials Research and Engineering A*STAR(Agency for Science Technology and Research)Singapore 138634Singapore Industrial Technology Center of wakayama Prefecture Wakayama 6496261Japan School of Electrical and Electronic Engineering Nanyang Technological UniversitySingapore639798Singapore Department of Physics Imperial College LondonLondon SW72AZUnited Kingdom

Optical imaging systems have greatly extended human visual capabilities,enabling the observation and understanding of diverse *** technologies span a broad spectrum of wavelengths from x-ray to radio frequencies and impact research activities and our daily *** glass lenses are fabricated through a series of complex processes,while polymers offer versatility and ease of ***,modern applications often require complex lens assemblies,driving the need for miniaturization and advanced designs with micro-and nanoscale features to surpass the capabilities of traditional fabrication ***-dimensional(3D)printing,or additive manufacturing,presents a solution to these challenges with benefits of rapid prototyping,customized geometries,and efficient production,particularly suited for miniaturized optical imaging *** 3D printing methods have demonstrated advantages over traditional counterparts,yet challenges remain in achieving nanoscale ***-photon polymerization lithography(TPL),a nanoscale 3D printing technique,enables the fabrication of intricate structures beyond the optical diffraction limit via the nonlinear process of two-photon absorption within liquid *** offers unprecedented abilities,***-free fabrication,micro-and nanoscale capabilities,and rapid prototyping of almost arbitrary complex 3D *** this review,we emphasize the importance of the criteria for optical performance evaluation of imaging devices,discuss material properties relevant to TPL,fabrication techniques,and highlight the application of TPL in optical *** the first panoramic review on this topic,it will equip researchers with foundational knowledge and recent advancements of TPL for imaging optics,promoting a deeper understanding of the *** leveraging on its high-resolution capability,extensive material range,and true 3D processing,alongside advances in materials,fabrication,and design,we en

关键词： two-photon polymerization lithography 3D printing additive manufacturing imaging optics and nanophotonics

Imaging approach for jaw and maxillofacial bone tumors with updates from the 2022 world Health Organization classification

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world Journal of Radiology 2024年第8期16卷 294-316页

作者： woongsoon john Choi Peggy Lee Penelope C Thomas Tanya J Rath Monique A Mogensen Roberta w Dalley Pattana wangaryattawanich Division of Neuroradiology Department of RadiologyUniversity of Washington School of MedicineSeattleWA 98195United States Department of Radiology M&S Radiology AssociatesSan AntonioTX 78217United States Division of Oral Radiology University of Washington School of DentistrySeattleWA 98195United States Division of Neuroradiology Department of RadiologyMayo ClinicPhoenixAZ 85054United States

Jaw and maxillofacial bone lesions encompass a wide variety of both neoplastic and non-neoplastic *** lesions can arise from various tissues,including bone,cartilage,and soft tissue,each presenting distinct challenges in diagnosis and *** some pathologies exhibit characteristic imaging features that aid in diagnosis,many others are *** overlap often necessitates a multimodal imaging approach,combining techniques such as radiographs,computed tomography,and magnetic resonance imaging to achieve a diagnosis or narrow the diagnostic *** article provides a comprehensive review of the imaging approach to jaw and maxillofacial bone tumors,including updates on the 2022 world Health Organization classification of these *** relevant anatomy of the jaw and dental structures that is important for accurate imaging interpretation is discussed.

关键词： Mandible Maxilla Maxillofacial Jaw Tumor Neoplasm

Dynamic knowledge graph approach for modelling the decarbonisation of power

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Energy and AI

Energy and AI 2024年第3期17卷 48-64页

作者： wanni Xie Feroz Farazi john Atherton Jiaru Bai Sebastian Mosbach Jethro Akroyd Markus Kraft Department of Chemical Engineering and Biotechnology University of CambridgePhilippa Fawcett DriveCambridge CB30ASUK CARES Cambridge Centre for Advanced Research and Education in Singapore1 Create WayCREATE Tower#05-05Singapore138602Singapore School of Chemical and Biomedical Engineering Nanyang Technological University62 Nanyang DriveSingapore637459Singapore The Alan Turing Institute LondonNW12DBUK

This paper presents a dynamic knowledge graph approach that offers a reusable,interoperable,and extensible framework for modelling power *** ontologies have been developed to support a linked data representation of infrastructure data,socio-demographic data,areal attributes like demand,and models describing power *** knowledge graph links the data with a hierarchical representation of administrative regions,supporting geospatial queries to retrieve information about the population within the vicinity of a power plant,the number of power plants,total generation capacity,and demand within specific *** agents were developed to operate on the knowledge *** agents performed tasks including data uploading,updating,retrieval,processing,model construction and scenario analysis.A derived information framework was used to track the provenance of information calculated by agents involved in each *** knowledge graph was populated with data describing the UK power *** alternative models of the transmission grid with different levels of structural resolution were instantiated,providing the foundation for the power system simulation and optimisation tasks performed by the *** application of the dynamic knowledge graph was demonstrated via a case study that investigates clean energy transition trajectories based on the deployment of Small Modular Reactors in the UK.

关键词： Power system modelling Decarboni sation Dynanic knowledge graph Ontology and Semantic web