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Safety,immunogenicity,and protection provided by unadjuvanted and adjuvanted formulations of a recombinant plant-derived virus-like particle vaccine candidate for COVId-19 in nonhuman primates

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Cellular & Molecular Immunology 2022年第2期19卷 222-233页

作者： Stéphane Pillet Prabhu SArunachalam Guadalupe Andreani Nadia Golden Jane Fontenot Pyone Pyone Aye Katharina Röltgen Gabrielle Lehmicke Philipe Gobeil Charlotte dubé Sonia Trépanier Nathalie Charland Marc-Andréd’Aoust Kasi Russell-Lodrigue Christopher Monjure Robert V.Blair scott d.boyd Rudolf P.Bohm Jay Rappaport François Villinger Nathalie Landry Bali Pulendran Brian J.Ward Medicago Inc. QuébecQCCanada. Institute for Immunity Transplantation and InfectionStanford University School of MedicineStanford UniversityStanfordCAUSA. Tulane National Primate Research Center CovingtonLAUSA. New Iberia Research Center University of Louisiana at LafayetteNew IberiaLAUSA. department of Pathology Stanford University School of MedicineStanford UniversityStanfordCAUSA. department of Microbiology and Immunology Tulane University School of MedicineNew OrleansLAUSA. department of Microbiology and Immunology Stanford University School of MedicineStanford UniversityStanfordCAUSA. Institute for Immunity Transplantation&InfectionStanford University School of MedicineStanford UniversityStanfordCAUSA Research Institute of the McGill University Health Centre MontrealQCCanada.

Although antivirals are important tools to control severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection,effective vaccines are essential to control the current coronavirus disease 2019(COVId-19)***-derived virus-like particle(VLP)vaccine candidates have previously demonstrated immunogenicity and efficacy against ***,we report the immunogenicity and protection induced in rhesus macaques by intramuscular injections of a VLP bearing a SARS-CoV-2 spike protein(CoVLP)vaccine candidate formulated with or without Adjuvant System 03(AS03)or cytidine-phospho-guanosine(CpG)*** a single dose of the unadjuvanted CoVLP vaccine candidate stimulated humoral and cell-mediated immune responses,booster immunization(at 28 days after priming)and adjuvant administration significantly improved both responses,with higher immunogenicity and protection provided by the AS03-adjuvanted *** micrograms of CoVLP adjuvanted with AS03 induced a polyfunctional interleukin-2(IL-2)-driven response and IL-4 expression in Cd4 T *** were challenged by multiple routes(i.e.,intratracheal,intranasal,and ocular)with a total viral dose of 106 plaque-forming units of *** viral replication in nasal swabs and bronchoalveolar lavage fluid(BALF)as well as fewer SARS-CoV-2-infected cells and immune cell infiltrates in the lungs concomitant with reduced levels of proinflammatory cytokines and chemotactic factors in the BALF were observed in animals immunized with the CoVLP adjuvanted with *** clinical,pathologic,or virologic evidence of vaccineassociated enhanced disease was observed in vaccinated *** CoVLP adjuvanted with AS03 was therefore selected for vaccine development and clinical trials.

关键词： SARS-CoV-2 Virus-like particles Non-humane primates AS03 CpG1018

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Exploring the effects of coronary artery disease as a preexisting comorbidity on mortality in hospitalized septic patients:a retrospective observation study

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Emergency and Critical Care Medicine 2024年第2期4卷 47-51页

作者： Anmol Multani Greg Stahl Kerry Johnson scott Goade Robert d.Arnce College of Osteopathic Medicine Kansas City UniversityJoplinMOUSA department of data Improvement Freeman Health SystemJoplinMOUSA department of Mathematics Missouri Southern State UniversityJoplinMOUSA department of Pharmacy Freeman Health SystemJoplinMOUSA

Background:Sepsis has high prevalence and mortality rate,and it is imperative to identify populations at risk of poor sepsis *** patients with preexisting chronic comorbidities are shown to have worse sepsis *** identifying comorbidities with greater influence on sepsis progression,we can direct limited resources to septic patients with comorbidities and reduce health care *** comorbidities can impact the risk of developing sepsis and having worse *** artery disease(CAd)is a common comorbidity,especially in the elderly,and a leading cause of death *** wished to investigate the influence of CAd as a comorbidity on sepsis and hypothesized that preexisting CAd would increase mortality in hospitalized septic ***:We conducted retrospective observational study using patient data from Freeman Health System in Joplin,*** analyzed patient records from Freeman Health System database from January 1,2019,to June 30,*** patients were identified using the International Classification of diseases,Tenth Revision sepsis *** identify septic patients with preexisting CAd,we used International Classification of diseases,Tenth Revision codes for *** compared mortality rates for septic patients with and without ***:Two-sample proportion test was conducted to test the difference in mortality between septic patients with and without preexisting *** difference in mortality for the total population was−0.016(P=0.553).In the male and female subgroups,the differences in mortality were 0.0122(P=0.739)and−0.0511(P=0.208),*** differences in mortality in patients aged 40 to 64 years and 65 years and older were−0.0077(P=0.870)and 0.0007(P=0.983),*** statistical tests failed to find significant differences when comparing septic patients with and without preexisting *** was no significant difference in the age and sex ***:Our study showed that CAd alone was n

关键词： Comorbidity Coronary artery disease Inflammation Mortality rate in sepsis prognosis Sepsis

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2024 Wheelchair Compendium of Physical Activities:An update of activity codes and energy expenditure values

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Journal of Sport and Health Science 2024年第1期13卷 18-23页

作者： scott A.Conger Stephen d.Herrmann Erik A.Willis Tom E.Nightingale Joseph R.Sherman Barbara E.Ainsworth department of Kinesiology Boise State UniversityBoiseID 83725USA Kansas Center for Metabolism and Obesity Research The University of Kansas Medical CenterKansas CityKS 66160USA Center for Health Promotion and disease Prevention University of North Carolina at Chapel HillChapel HillNC 27599USA School of Sport Exercise and Rehabilitation SciencesUniversity of BirminghamBirmingham AL B152TTUK Centre for Trauma Sciences Research University of BirminghamEdgbastonBirmingham AL B152TTUK College of Health Solutions Arizona State UniversityPhoenixAZ 85003USA School of Exercise and Health Shanghai University of SportShanghai 200438China

Purpose:This paper presents an update of the 2011 Wheelchair Compendium of Physical Activities designed for wheelchair users and is referred to as the 2024 Wheelchair *** Wheelchair Compendium aims to curate existing knowledge of the energy expenditure for wheelchair physical activities(PAs).Methods:A systematic review of the published energy expenditure of PA for wheelchair users was completed between 2011 and May *** added these data to the 2011 Wheelchair Compendium data that was compiled previously in a systematic review through ***:A total of 47 studies were included,and 124 different wheelchair PA reported energy expenditure values ranging from 0.8 metabolic equivalents for wheelchair users(filing papers,light effort)to 11.8 metabolic equivalents for wheelchair users(Nordic sit skiing).Conclusion:In introducing the updated 2024 Wheelchair Compendium,we hope to bridge the resource gap and challenge the prevailing narratives that inadvertently exclude wheelchair users from physical fitness and health PAs.

关键词： disability Exercise MET Mobility

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Promoting public health through the 2024 Compendium of Physical Activities:Strategies for adults,older adults,and wheelchair users

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Journal of Sport and Health Science 2024年第6期13卷 739-742页

作者： Stephen d.Herrmann scott A.Conger Erik A.Willis Barbara E.Ainsworth Kansas Center for Metabolism and Obesity Research University of Kansas Medical CenterKansas CityKS 66160USA division of Physical Activity and Weight Management Department of Internal MedicineUniversity of Kansas Medical CenterKansas CityKS 66160USA department of Kinesiology Boise State UniversityBoiseID 83725USA Prevention Research Center University of North Carolina at Chapel HillChapel HillNC 27599USA College of Health Solutions Arizona State UniversityPhoenixAZ 85003USA School of Exercise and Health Shanghai University of SportShanghai 200438China

Physical activity(PA)is fundamentally linked to public health,^(1)providing benefits including chronic disease prevention and treatment,^(2)mental health,^(3)musculoskeletal health,^(4)and healthy aging,^(5)along with socioeconomic advantages.^(6)These benefits highlight the importance of promoting PA for all *** recent publication of the Compendium of Physical Activities(Compendium)serves as a valuable resource,^(7)offering an updated and expanded guide for adults(ages 19-59)with tailored energy cost values for diverse populations.

关键词： Activities prevention offering

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Adaptation in brain structure and respiratory and olfactory structures across environmental gradients in African and North American muroid rodents

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Integrative Zoology 2024年第1期19卷 165-181页

作者： Peter J.TAYLOR Aluwani NENGOVHELA Christiane dENYS Graham R.scott Catherine M.IVY department of Zoology School of Natural and Mathematical SciencesUniversity of VendaThohoyandouSouth Africa Afromontane Unit Department of Zoology and EntomologyUniversity of the Free StatePhuthaditjhabaSouth Africa department of Mammalogy National MuseumBloemfonteinSouth Africa Institut de Systématique EvolutionBiodiversité(ISYEB)Muséum National d’Histoire NaturelleCNRSSorbonne UniversitéEPHEUniversitéDes AntillesParisFrance department of Biology McMaster UniversityHamiltonOntarioCanada Guglielmo and Shoemaker Labs Advanced Facility for Avian ResearchUniversity of Western OntarioLondonOntarioCanada

Morphometric studies of 3d micro CT-scanned images can provide insights into the evolution of the brain and sensory structures but such data are still scarce for the most diverse mammalian order of *** reviewed and new data,we tested for convergence to extreme aridity and high elevation in the sensory and brain morphology of rodents,from morphometric data from micro-CT X-ray scans of 174 crania of 16 species of three distantly re-lated African murid(soft-furred mice,Praomyini,laminate-toothed rats,Otomyini,and gerbils,Gerbillinae)clades and one North American cricetid(deer mice and white-footed mice,Peromyscus)*** studies demon-strated convergent evolution acting on the oval window area of the cochlea(enlarged in extremely arid-adapted species of Otomyini and Gerbillinae)and on endocranial volume(reduced in high elevation taxa of Otomyini and Peromyscus).However,contrary to our predictions,we did notfind evidence of convergence in brain struc-ture to aridity,or in the olfactory/respiratory system(turbinate bones)to high *** structure differed,particularly in the petrosal lobules of the cerebellum and the olfactory bulbs,between Otomyini and Gerbillinae,with extreme arid-adapted species in each clade being highly divergent(not convergent)from other species in the same *** observed greater“packing”of the maxillary turbinate bones,which have important respiratory functions,in Peromyscus mice from high and low elevations compared to the high-elevation African Praomyini,but more complex patterns within Peromyscus,probably related to trade-offs in respiratory physiology and heat exchange in the nasal epithelium associated with high-elevation adaptation.

关键词： 3d morphometrics Africa brain size North America Rodentia sensory evolution

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Older Adult Compendium of Physical Activities:Energy costs of human activities in adults aged 60 and older

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Journal of Sport and Health Science 2024年第1期13卷 13-17,F0003页

作者： Erik A.Willis Stephen d.Herrmann Mary Hastert Chelsea L.Kracht Tiago V.Barreira John M.Schuna Jr. Zhenghua Cai Minghui Quan scott A.Conger Wendy J.Brown Barbara E.Ainsworth Center for Health Promotion and disease Prevention University of North Carolina at Chapel HillChapel HillNC 27599USA Kansas Center for Metabolism and Obesity Research The University of Kansas Medical CenterKansas CityKS 66160USA division of Physical Activity and Weight Management Department of Internal MedicineUniversity of Kansas Medical CenterKansas CityKS 66160USA Clinical Science division Pennington Biomedical Research CenterBaton RougeLA 70808USA Exercise Science department Syracuse UniversitySyracuseNY 13244USA School of Exercise&Sport Science Oregon State UniversityCorvallisOR 97331USA School of Exercise and Health Shanghai University of SportShanghai 200438China department of Kinesiology Boise State UniversityBoiseID 83725USA School of Human Movement and Nutrition Sciences The University of QueenslandSt.LuciaQLD 4072Australia Faculty of Health Sciences and Medicine Bond UniversityGold CoastQLD 4229Australia College of Health Solutions Arizona State UniversityPhoenixAZ 85003USA

Purpose:To describe the development of a Compendium for estimating the energy costs of activities in adults>60 years(OA Compendium).Methods:Physical activities(PAs)and their metabolic equivalent of task(MET)values were obtained from a systematic search of studies published in 4 sport and exercise databases(PubMed,Embase,SPORTdiscus(EBSCOhost),and Scopus)and a review of articles included in the 2011 Adult Compendium that measured PA in older *** values were computed as the oxygen cost(VO_(2),mL/kg/min)during PA divided by 2.7 m L/kg/min(MET_(60+))to account for the lower resting metabolic rate in older ***:We identified 68 articles and extracted energy expenditure data on 427 *** these,we derived 99 unique Specific Activity codes with corresponding MET_(60+)values for older *** developed a website to present the OA Compendium MET_(60+)values:https://***:The OA Compendium uses data collected from adults>60 years for more accurate estimation of the energy cost of PAs in older *** is an accessible resource that will allow researchers,educators,and practitioners to find MET_(60+)values for older adults for use in PA research and practice.

关键词： Energy expenditure Exercise MET Older adults

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Randomised study of bailout intracranial angioplasty following thrombectomy for acute large vessel occlusion(ANGEL-REBOOT):protocol of a multicentre randomised controlled trial

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Stroke & Vascular Neurology 2024年第2期9卷 181-188页

作者： Feng Gao Xu Tong Baixue Jia Ming Yang Yuesong Pan Zeguang Ren William scott Burgin Liping Liu Xingquan Zhao Yilong Wang Yongjun Wang Zhongrong Miao Interventional Neuroradiology Department of NeurologyBeijing Tiantan HospitalBeijingChina China National Clinical Research Center for Neurological diseases Beijing Tiantan HospitalBeijingChina department of Neurosurgery University of South FloridaTampaFloridaUSA department of Neurology Morsani College of MedicineUniversity of South FloridaTampaFloridaUSA Comprehensive Stroke Center Tampa General HospitalTampaFloridaUSA department of Neurology Beijing Tiantan HospitalBeijingChina

Rationale Unsuccessful thrombectomy of acute large vessel occlusions(LVOs)has been associated with unfavourable *** randomised controlled trials(RCTs)have reported a failure rate of 12%–41%for thrombectomy *** factors contribute to failed thrombectomy,including technical difficulties in accessing the occlusion,unsuccessful thrombus retrieval,thrombotic reocclusion and pre-existing intracranial atherosclerotic *** some studies have explored balloon dilation or permanent stenting as rescue intracranial angioplasty for failed thrombectomy in individual cases,there is currently no evidence from RCTs on this specific *** To evaluate the potential superiority of bailout angioplasty over standard treatment in cases of unsuccessful recanalisation(eTICI 0 to 2a)or residual severe stenosis(>70%)after thrombectomy in acute LVO patients within 24 hours of stroke *** This study is a multicentre,prospective,randomised,controlled clinical trial designed by *** compares bailout angioplasty with standard therapy and follows an open-label treatment approach while maintaining a blinded outcome assessment(PROBE design).Our objective is to allocate 348 patients in a 1:1 ratio to either receive bailout angioplasty as an intervention or standard therapy as a control,following unsuccessful *** The main measure of interest is the modified Rankin Scale(mRS)Score,which will be assessed in a blinded manner at 90(±14)days following *** primary effect size will be determined using ordered logistic regression to calculate the common OR,representing the shift on the six-category mRS Scale at the 90-day ***,the safety outcomes will be evaluated,including symptomatic intracranial haemorrhage within 18–36hours,severe procedure-related complications and mortality within 90(±14)days,among *** The ANGEL-REBOOT study aims to generate substantial evidence regarding the efficacy

关键词： angioplasty throm intracranial

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APIR:Aggregating Universal Proteomics database Search Algorithms for Peptide Identification with FdR Control

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Genomics, Proteomics & Bioinformatics 2024年第2期22卷 171-187页

作者： Yiling Elaine Chen Xinzhou Ge Kyla Woyshner MeiLu Mcdermott Antigoni Manousopoulou scott B.Ficarro Jarrod A.Marto Kexin Li Leo david Wang Jingyi Jessica Li department of Statistics and data Science University of CaliforniaLos AngelesCA 90095USA department of Immuno-Oncology Beckman Research InstituteCity of Hope National Medical CenterDuarteCA 91010USA department of Quantitative and Computational Biology University of Southern CaliforniaLos AngelesCA 90089USA department of Cancer Biology and Blais Proteomics Center Dana-Farber Cancer InstituteDepartment of PathologyBrigham and Women’s Hospital and Harvard Medical SchoolBostonMA 02215USA department of Pediatrics City of Hope National Medical CenterDuarteCA 91010USA Bioinformatics Interdepartmental Program University of CaliforniaLos AngelesCA 90095USA department of Human Genetics University of CaliforniaLos AngelesCA 90095USA department of Computational Medicine University of CaliforniaLos AngelesCA 90095USA department of Biostatistics University of CaliforniaLos AngelesCA 90095USA

Advances in mass spectrometry(MS)have enabled high-throughput analysis of proteomes in biological *** state-of-the-art MS data analysis relies on database search algorithms to quantify proteins by identifying peptide–spectrum matches(PSMs),which convert mass spectra to peptide *** database search algorithms use distinct search strategies and thus may identify unique ***,no existing approaches can aggregate all user-specified database search algorithms with a guaranteed increase in the number of identified peptides and a control on the false discovery rate(FdR).To fill in this gap,we proposed a statistical framework,Aggregation of Peptide Identification Results(APIR),that is universally compatible with all database search ***,under an FdR threshold,APIR is guaranteed to identify at least as many,if not more,peptides as individual database search algorithms *** of APIR on a complex proteomics standard dataset showed that APIR outpowers individual database search algorithms and empirically controls the *** data studies showed that APIR can identify disease-related proteins and post-translational modifications missed by some individual database search *** APIR framework is easily extendable to aggregating discoveries made by multiple algorithms in other high-throughput biomedical data analysis,e.g.,differential gene expression analysis on RNA sequencing *** APIR R package is available at https://***/yiling0210/APIR.

关键词： Shotgun proteomics Peptide–spectrum match Peptide identification Aggregation of lists FdR control

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EZH2 inhibitors promote β-like cell regeneration in young and adult type 1 diabetes donors

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Signal Transduction and Targeted Therapy 2024年第2期9卷 679-692页

作者： Keith Al-Hasani Safiya Naina Marikar Harikrishnan Kaipananickal scott Maxwell Jun Okabe Ishant Khurana Thomas Karagiannis Julia J.Liang Lina Mariana Thomas Loudovaris Thomas Kay Assam El-Osta Epigenetics in Human Health and disease Program Baker Heart and Diabetes Institute75 Commercial RoadMelbourne 3004 VICAustralia department of diabetes Central Clinical SchoolMonash UniversityMelbourne 3004 VICAustralia Epigenetics in Human Health and disease Laboratory Central Clinical SchoolMonash UniversityMelbourne 3004 VICAustralia School of Science STEM CollegeRMIT UniversityMelbourne 3001 VICAustralia Immunology and diabetes Unit St Vincent’s Institute of Medical ResearchFitzroy 3065 VICAustralia department of Medicine and Therapeutics The Chinese University of Hong KongSha TinHong Kong SAR Hong Kong Institute of diabetes and Obesity Prince of Wales HospitalThe Chinese University of Hong Kong3/F Lui Che Woo Clinical Sciences Building30-32-Ngan Shing StreetSha TinHong Kong SAR Li Ka Shing Institute of Health Sciences The Chinese University of Hong KongSha TinHong Kong SAR Biomedical Laboratory Science Department of TechnologyFaculty of HealthUniversity College CopenhagenCopenhagenDenmark

β-cells are a type of endocrine cell found in pancreatic islets that synthesize,store and release *** type 1 diabetes(T1d),T-cells of the immune system selectively destroy the insulin-producingβ-*** of these cells leads to a lifelong dependence on exogenous insulin administration for ***,there is an urgent need to identify novel therapies that stimulateβ-cell growth and induceβ-cell *** and others have shown that pancreatic ductal progenitor cells are a promising source for regeneratingβ-cells for T1d owing to their inherent differentiation *** transcriptional suppression is refractory to exocrine reaction and tightly controls the regenerative potential by the EZH2 *** the present study,we show that transient stimulation of exocrine cells,derived from juvenile and adult T1d donors to the FdAapproved EZH2 inhibitors GSK126 and Tazemetostat(Taz)influence a phenotypic shift towards aβ-like cell *** transition from repressed to permissive chromatin states are dependent on bivalent H3K27me3 and H3K4me3 chromatin *** EZH2 is fundamental toβ-cell regenerative *** pancreatic ductal cells exhibit insulin production and secretion in response to a physiological glucose challenge ex *** pre-clinical studies underscore the potential of small molecule inhibitors as novel modulators of ductal progenitor differentiation and a promising new approach for the restoration ofβ-like cell function.

关键词： EZH2 struction inhibitors

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Effect of Planting date on Yield and Yield Components of Grain Sorghum Hybrids

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American Journal of Plant Sciences 2024年第5期15卷 387-402页

作者： Bandiougou diawara Sory diallo Brahima Traore scott Staggenbord Vara Prasad Institut d’ Economie Rurale (IER) Bamako Mali Manhattan KS USA

In Kansas, productivity of grain sorghum [Sorghum bicolor (L.) Moench] is affected by weather conditions at planting and during pollination. Planting date management and selection of hybrid maturity group can help to avoid severe environmental stresses during these sensitive stages. The hypothesis of the study was that late May planting improves grain sorghum yield and yield components compared with late June planting. The objectives of this research were to investigate the influence of planting dates yield and yield components of different grain sorghum hybrids, and to determine the optimal planting date and hybrid combination for maximum biomass and grains production. Three sorghum hybrids (early, medium, and late maturing) were planted in late May and late June without irrigation in Kansas at Manhattan/Ashland Bottom Research Station, and Hutchinson in 2010;and at Manhattan/North Farm and Hutchinson in 2011. data on dry matter production, yield and yield components were collected. Grain yield and yield components were influenced by planting date depending on environmental conditions. At Manhattan (2010), greater grain yield, number of heads per plant, were obtained with late-June planting compared with late May planting, while at Hutchinson (2010) greater yield was obtained with late May planting for all hybrids. The yield component most affected at Hutchinson was the number of kernels∙panicle−1 and plant density. Late-May planting was favorable for late maturing hybrid (P84G62) in all locations. However, the yield of early maturing hybrid (dKS 28-05) and medium maturing hybrid (dKS 37-07) was less affected by delayed planting. The effects of planting dates on yield and yield components of grain sorghum hybrids were found to be variable among hybrid maturity groups and locations.

关键词： Sorghum [Sorghum bicolor (L.) Moench] Grain Yield Yield Components

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