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Engineering hyaluronic acid-based nanoassemblies for monoclonal antibody delivery-design,characterization,and biological insights

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Nano Research 2024年第10期17卷 9111-9125页

作者： Ana m.lópez-Estévez Y.Zhang maría medel Iker Arriaga lucía Sanjurjo Cristian Huck-Iriart Nicola G.A.Abrescia maría J.Vicent Defang Ouyang Dolores Torres maría José Alonso Center for Research in molecular medicine and Chronic Diseases(CimUS) University of Santiago de CompostelaSantiago de Compostela 15782Spain Department of Pharmacology Pharmacy and Pharmaceutical TechnologySchool of PharmacyUniversity of Santiago de CompostelaSantiago de Compostela 15782Spain Health Research Institute of Santiago de Compostela(IDIS) Santiago de Compostela 15782Spain State Key laboratory of Quality Research in Chinese medicine Institute of Chinese Medical Sciences(ICMS)University of MacaoMacao 999078China Polymer Therapeutics laboratory and CIBERONC Prince Felipe Research Centre Valencia E-46012Spain Structure and Cell Biology of Viruses lab CIC bioGUNEBasque Research and Technology Alliance(BRTA)Derio 48160Spain AlBA Synchrotron light Source Experiments DivisionCerdanyola del VallèsBarcelona 08290Spain IKERBASQUE Basque Foundation for ScienceBilbao 48009Spain

The current spotlight of cancer therapeutics is shifting towards personalized medicine with the widespread use of monoclonal antibodies(mAbs).Despite their increasing potential,mAbs have an intrinsic limitation related to their inability to cross cell membranes and reach intracellular *** offers promising solutions to overcome this limitation,however,formulation challenges *** challenges are the limited loading capacity(often insufficient to achieve clinical dosing),the complex formulation methods,and the insufficient characterization of mAb-loaded ***,we present a new nanocarrier consisting of hyaluronic acid-based nanoassemblies(HANAs)specifically designed to entrap mAbs with a high efficiency and an outstanding loading capacity(50%,w/w).HANAs composed by an mAb,modified HA and phosphatidylcholine(PC)resulted in sizes of~100 nm and neutral surface *** modeling identified the principal factors governing the high affinity of mAbs with the amphiphilic HA and *** composition and structural configuration were analyzed using the orthogonal techniques cryogenic transmission electron microscopy(cryo-TEm),asymmetrical flow field-flow fractionation(AF4),and small-angle X-ray scattering(SAXS).These techniques provided evidence of the formation of core-shell nanostructures comprising an aqueous core surrounded by a bilayer consisting of phospholipids and amphiphilic *** vitro experiments in cancer cell lines and macrophages confirmed HANAs’low toxicity and ability to transport mAbs to the intracellular *** reproducibility of this assembling process at industrial-scale batch sizes and the long-term stability was *** conclusion,these results underscore the suitability of HANAs technology to load and deliver biologicals,which holds promise for future clinical translation.

关键词： monoclonal antibody nanoparticles hyaluronic acid characterization particle size computational modeling

Three-dimensional analysis of age and sex differences in femoral head asphericity in asymptomatic hips in the United States

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World Journal of Orthopedics 2024年第8期15卷 754-763页

作者： mahad m Hassan Aliya G Feroe Brenton W Douglass Andrew E Jimenez Benjamin Kuhns Charles F mitchell Robert l Parisien Daniel A maranho Eduardo N Novais Young-Jo Kim Ata m Kiapour Department of Orthopedic Surgery University of MinnesotaMinneapolisMN 55454United States Department of Orthopedic Surgery TRIA Orthopaedic CenterBloomingtonMN 55122United States Department of Orthopedic Surgery Boston Children’s HospitalBostonMA 02115United States Department of Orthopedic Surgery Mayo ClinicRochesterMN 55901United States Department of Orthopaedics and Rehabilitation Yale School of MedicineNew HavenCT 06510United States Department of Orthopedic Surgery American Hip Institute Research FoundationDes PlainesIL 60018United States Department of Orthopedic Surgery Mount SinaiNew YorkNY 10029United States Department of Biomechanics Medicineand Rehabilitation of the Locomotor SystemRibeirao Preto Medical SchoolUniversity of São PauloRibeirao Preto 14048-900São PauloBrazil

BACKGROUND The sphericity of the femoral head is a metric used to evaluate hip pathologies and is associated with the development of osteoarthritis and femoral-acetabular *** To analyze the three-dimensional asphericity of the femoral head of asymptomatic pediatric *** hypothesized that femoral head asphericity will vary significantly between male and female pediatric hips and increase with age in both *** Computed tomography scans were obtained on 158 children and adolescents from a single institution in the United States(8-18 years;50%male)without hip *** femoral measurements including the femoral head diameter,femoral head volume,residual volume,asphericity index,and local diameter difference were used to evaluate femoral head *** In both sexes,the residual volume increased by age(Ply smaller femoral head size in older ages(>13 years)in females,there were no sex-differences in residual volume and aspherity *** were no age-related changes in mean diameter difference in both sexes(P=0.07)with no significant sex-differences across different age groups(P=0.06).In contrast,there were significant increases in local aspherity(maximum diameter difference)across whole surface of the femoral head and all quadrants except the inferior regions in males(P=0.03).There were no sex-differences in maximum diameter difference at any regions and age group(P>0.05).Increased alpha angle was only correlated to increased mean diameter difference across overall surface of the femoral head(P=0.024).CONClUSION There is a substantial localized asphericity in asymptomatic hips which increases with age *** 2D measured alpha angle can capture overall asphericity of the femoral head,it may not be sensitive enough to represent regional asphericity patterns.

关键词： Hip Femoral head Sphericity Skeletal growth Sex differences

Comparing material wastage levels between conventional in-situ and prefabrication construction in Hong Kong

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Journal of Harbin Institute of Technology(New Series) 2004年第5期11卷 548-551页

作者： Vivian W Ytam C m tam l Y Shen Dept. of Building and Construction City University of Hong Kong Hong Kong ChinaDept. of Building and Construction City University of Hong Kong Hong Kong ChinaDept. of Building and Construction City University of Hong Kong Hong Kong China

Generation of construction wastes constitutes a major impact to the environment. Studies have been directed toward reducing wastes of the various construction processes. However, contractors in Hong Kong are rather conservative and lack motivation to develop new technology for waste minimization. This paper examines the benefits of using prefabrication in reducing material wastage levels for some traditional in-situ trades such as concreting, rebar fixing, bricklaying, drywall, plastering, screeding and tiling in Hong Kong. By measuring thirty construction projects, it is been found that waste levels of all major construction trades can be effectively reduced. This is particularly significant in the trade of plastering where 100% saving can be achieved after adopting prefabrication. The standardized design of the building can also be useful in the adoption of prefabrication for private housing projects.

关键词： prefabrication conventional in-situ trades material wastage environment

Storylines of family medicine Ⅳ:perspectives on practice—lenses of appreciation

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Family medicine and Community Health 2024年第S3期12卷 33-42页

作者： William B Ventres leslie A Stone Radeeb Akhtar Jeffrey m Ring lucy m Candib Erick messias Ronald m Epstein marc Tunzi Amy l lee Christopher P morley Carina m Brown David Slawson Jill Konkin David G Campbell Ian Couper Susan Williams Robert Brooks lucie Walters Family and Preventive medicine University of Arkansas for Medical Sciences College of MedicineLittle RockArkansasUSA Family medicine and Community Health Icahn School of Medicine at Mount SinaiNew YorkNew YorkUSA Independent Health Psychologist Los AngelesCaliforniaUSA Family medicine and Community Health UMass Chan Medical SchoolWorcesterMassachusettsUSA Psychiatry and Behavioral Neurosciences Saint Louis University School of MedicineSaint LouisMissouriUSA Family medicine University of Rochester Medical CenterRochesterNew YorkUSA Family medicine Residency Program Natividad Medical CenterSalinasCaliforniaUSA Family medicine Tufts University School of MedicineBostonMassachusettsUSA Public Health and Preventive medicine SUNY Upstate Medical UniversitySyracuseNew YorkUSA Cone Health Family medicine Residency The University of North Carolina School of MedicineGreensboroNorth CarolinaUSA Family medicine Atrium HealthCharlotteNorth CarolinaUSA Family medicine University of Alberta Faculty of Medicine&DentistryEdmontonAlbertaCanada Cunninghame Arm medical Centre Australian College of Rural and Remote MedicineLakes EntranceQueenslandAustralia Ukwanda Centre for Rural Health Stellenbosch University Faculty of Medicine and Health SciencesCape TownWestern CapeSouth Africa Adelaide Rural Clinical School The University of AdelaideAdelaideSouth AustraliaAustralia Department of Rural Health Broken Hill UniversityBroken HillNew South WalesAustralia Adelaide Rural Clinical School The University of Adelaide Faculty of Health and Medical SciencesMount GambierSouth AustraliaAustralia

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 ***‘Ⅳ:perspectives on practice—lenses of appreciation’,authors address the following themes:‘Relational connections in the doctor–patient partnership’,‘Feminism and family medicine’,‘Positive family medicine’,‘mindful practice’,‘The new,old ethics of family medicine’,‘Public health,prevention and populations’,‘Information mastery in family medicine’and‘Clinical courage.’may readers nurture their curiosity through these essays.

关键词： thematic illustration doctor

COVID-19 vaccination produces exercise-responsive SARS-CoV-2 specific T-cells regardless of infection history

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Journal of Sport and Health Science 2024年第1期13卷 99-107页

作者： Kyle A.Smith Tiffany m.Zúñiga Forrest l.Baker Helena Batatinha Charles R.Pedlar Shane C.Burgess michael P.Gustafson Emmanuel Katsanis Richard J.Simpson School of Nutritional Sciences and Wellness The University of ArizonaTucsonAZ 85721USA Department of Pediatrics The University of ArizonaTucsonAZ 85724USA Faculty of Sport Allied Health and Performance ScienceSt.Mary's UniversityTwickenham TW14SXUK Institute of Sport Exercise and Health University College LondonLondon WC1E 7HUUK Department of Animal and Comparative Biomedical Sciences The University of ArizonaTucsonAZ 85721USA The University of Arizona Cancer Center The University of ArizonaTucsonAZ 85719USA laboratory medicine and Pathology Mayo Clinic ArizonaPhoenixAZ 85054USA Department of Immunobiology The University of ArizonaTucsonAZ 85724USA Department of medicine The University of ArizonaTucsonAZ 85724USA Department of Pathology The University of ArizonaTucsonAZ 85724USA

Background:The mobilization and redistribution of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)specific T-cells and neutralizing antibodies(nAbs)during exercise is purported to increase immune surveillance and protect against severe coronavirus disease 2019(COVID-19).We sought to determine if COVID-19 vaccination would elicit exercise-responsive SARS-CoV-2 T-cells and transiently alter nAb ***:Eighteen healthy participants completed a 20-min bout of graded cycling exercise before and/or after receiving a COVID-19 *** major leukocyte subtypes were enumerated before,during,and after exercise by flow cytometry,and immune responses to SARS-CoV-2 were determined using whole blood peptide stimulation assays,T-cell receptor(TCR)-βsequencing,and SARS-CoV-2 nAb ***:COVID-19 vaccination had no effect on the mobilization or egress of major leukocyte subsets in response to intensity-controlled graded ***,non-infected participants had a significantly reduced mobilization of CD4+and CD8+naive T-cells,as well as CD4+central memory T-cells,after vaccination(synthetic immunity group);this was not seen after vaccination in those with prior SARS-CoV-2 infection(hybrid immunity group).Acute exercise after vaccination robustly mobilized SARS-CoV-2 specific T-cells to blood in an intensity-dependent *** groups mobilized T-cells that reacted to spike protein;however,only the hybrid immunity group mobilized T-cells that reacted to membrane and nucleocapsid *** increased significantly during exercise only in the hybrid immunity ***:These data indicate that acute exercise mobilizes SARS-CoV-2 specific T-cells that recognize spike protein and increases the redistribution of nAbs in individuals with hybrid immunity.

关键词： Anti-viral COVID-19 Exercise immunology SARS-CoV-2 T-Cells Vaccine

Increasing the maximum Capacity Path in a Network and Its Application for Improving the Connection Between Two Routers

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Tsinghua Science and Technology 2024年第3期29卷 753-765页

作者： Adrian m.Deaconu Javad Tayyebi Department of mathematics and Computer Science Transilvania University of BrasovBrasov 500036Romania Department of Industrial Engineering Birjand University of TechnologyBirjand 000097Iran

Abstract:This paper addresses the problem of improving the optimal value of the maximum Capacity Path(mCP)through expansion in a flexible network,and minimizing the involved *** only condition applied to the cost functions is to be non-decreasing *** is a non-restrictive condition,reflecting the reality in practice,and is considered for the first time in the ***,the total cost of expansion is a combination of max-type cost(e.g.,for supervision)and sum-type cost(*** building infrastructures,price of materials,price of labor,etc.).For this purpose,two types of strategies are combined:(l)increasing the capacity of the existing arcs,and(l)adding potential new *** different problems are introduced and *** the problems have immediate applications in Internet routing *** first one is to extend the network,so that the capacity of an mcP in the modified network becomes equal to a prescribed value,therefore the cost of modifications is minimized.A strongly polynomial-time algorithm is deduced to solve this *** second problem is a network expansion under a budget constraint,so that the capacity of an mcP is maximized.A weakly polynomial-time algorithm is presented to deal with *** the special case when all the costs are linear,a meggido's parametric search technique is used to develop an algorithm for solving the problem in strongly polynomial *** new approach has a time complexity of O(n^(4)),which is better than the time complexity of O(n4 log(n)of the previously known method from literature.

关键词： maximum Capacity Path(mCP) network expansion Internet routing polynomial-time algorithms

Estimating geographic variation of infection fatality ratios during epidemics

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Infectious Disease modelling 2024年第2期9卷 634-643页

作者： Joshua ladau Eoin l.Brodie Nicola Falco Ishan Bansal Elijah B.Hoffman marcin P.Joachimiak Ana m.mora Angelica m.Walker Haruko m.Wainwright Yulun Wu mirko Pavicic Daniel Jacobson matthias Hess James B.Brown Katrina Abuabara Departments of Computational Precision Health and Dermatology University of CaliforniaSan FranciscoCA94115USA Arva Intelligence Inc.Salt Lake CityUT84101USA Computational Biosciences Group Lawrence Berkeley National LaboratoryBerkeleyCA94720USA Earth and Environmental Sciences Area Lawrence Berkeley National LaboratoryBerkeleyCA94720USA Graduate Group in Biostatistics University of CaliforniaBerkeleyCA94720USA Biosystems Data Science Environmental Genomics and Systems BiologyLawrence Berkeley National LaboratoryBerkeleyCA94720USA Center for Environmental Research and Community Health(CERCH) School of Public HealthUniversity of CaliforniaBerkeleyCA94720USA Bredesen Center for Interdisciplinary Research and Graduate Education University of TennesseeKnoxvilleTN37996USA Department of Nuclear Science and Engineering Massachusetts Institute of TechnologyBostonMA02139USA Biosciences Oak Ridge National LaboratoryOak RidgeTN37830USA University of California DavisCA95616USA Statistics Department University of CaliforniaBerkeleyCA94720USA Division of Epidemiology and Biostatistics University of California Berkeley School of Public Health2121 Berkeley WayBerkeleyCA94720USA

Objectives We aim to estimate geographic variability in total numbers of infections and infection fatality ratios(IFR;the number of deaths caused by an infection per 1,000 infected people)when the availability and quality of data on disease burden are limited during an *** We develop a noncentral hypergeometric framework that accounts for differential probabilities of positive tests and reflects the fact that symptomatic people are more likely to seek *** demonstrate the robustness,accuracy,and precision of this framework,and apply it to the United States(U.S.)COVID-19 pandemic to estimate county-level SARS-CoV-2 *** The estimators for the numbers of infections and IFRs showed high accuracy and precision;for instance,when applied to simulated validation data sets,across counties,Pearson correlation coefficients between estimator means and true values were 0.996 and 0.928,respectively,and they showed strong robustness to model *** the county-level estimators to the real,unsimulated COVID-19 data spanning April 1,2020 to September 30,2020 from across the U.S.,we found that IFRs varied from 0 to 44.69,with a standard deviation of 3.55 and a median of *** The proposed estimation framework can be used to identify geographic variation in IFRs across settings.

关键词： Infection fatality ratio Infection fatality rate Noncentral hypergeometric distribution COVID-19 SARS-CoV-2

Prompt neutron emission in ^(250)No spontaneous fission associated with ground and isomeric state decays

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Chinese Physics C 2024年第6期48卷 112-117页

作者： R.S.mukhin A.V.Isaev A.V.Andreev m.l.Chelnokov V.I.Chepigin H.m.Devaraja I.N.Izosimov A.A.Kuznetsova O.N.malyshev A.G.Popeko Yu.A.Popov A.Rahmatinejad B.Sailaubekov T.m.Shneidman E.A.Sokol A.I.Svirikhin m.S.Tezekbayeva m.A.Bychkov A.V.Yeremin O.Dorvaux B.Gall K.Kessaci K.Hauschild A.lopez-martens Joint Institute for Nuclear Research Dubna141980Russia Dubna State University Dubna141982Russia Institute of Nuclear Physics Almaty050032Kazakhstan l.N.Gumilyov Eurasian National University Astana010008Kazakhstan Kazan Federal University Kazan420008Russia Universitéde Strasbourg CNRSStrasbourg67000France IJClab IN2P3-CNRSUniversitéParis-SaclayOrsay91400France

The complete-fusion reaction^(204)Pb(^(48)Ca,2n)^(250)No was used to study two activities of^(250)No with distinct half-lives.A total of 1357 events were observed in the SFiNx neutron detection *** average number of neutrons emitted per spontaneous fission of^(250)No was determined to be(4.1±0.1).The unusually symmetrical shape of the prompt neutron multiplicity distribution was restored and presented for the first *** tests were performed to compare the prompt neutron multiplicity distributions associated with the ground state and K-isomer state decays.

关键词： spontaneous fission prompt neutrons actinide

The Iberian Roma Population Variant Server(IRPVS)

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Journal of Genetics and Genomics 2024年第7期51卷 769-773页

作者： Fabiola mavillard Javier Perez-Florido Francisco m.Ortuño Amador Valladares miren l.Álvarez-Villegas Gema Roldán Rosario Carmona manuel Soriano Santiago Susarte Pilar Fuentes Daniel lópez-lópez Ana maría Nuñez-Negrillo Alejandra Carvajal Yolanda morgado Daniel Arteaga Rosa Ufano Pablo mir Juan F.Gamella Joaquín Dopazo Carmen Paradas macarena Cabrera-Serrano Instituto de Biomedicina de Sevilla(IBiS) Hospital Universitario Virgen del Rocío/CSIC/Universidad de SevillaSevillaSpain Centro Investigación Biomédica en Red Enfermedades Neurodegenerativas(CIBERNED) Instituto de Salud CarlosⅢSevillaSpain Plataforma Andaluza de medicina Computacional Fundación Progreso y Salud(FPS)Hospital Virgen del RocíoSevillaSpain Grupo de medicina computacional de sistemas Instituto de Biomedicina de Sevilla(IBiS)Hospital Virgen del RocíoSevillaSpain Nodo de Genómica Funcional (INB-ELIXIR-es)Fundación Progreso y Salud(FPS)Hospital Virgen del RocíoSevilla 41013Spain Bioinformática en Enfermedades raras(BiER) Centro de Investigación Biomédica en Red de Enfermedades Raras(CIBERER)Instituto de salud CarlosⅢSevillaSpain Departamento de Ingeniería de Computadores Automática y RobóticaUniversidad de GranadaGranadaSpain Servicio de Urgencias de Atención Primaria Distrito SevillaSevillaSpain Centro de Servicios Sociales Negociado de Servicios EspecializadosAyuntamiento de SevillaSevillaSpain Departamento de Enfermería Facultad de Ciencias de la SaludUniversidad de GranadaGranadaSpain Departamento de Neurología Hospital Virgen de las NievesGranadaSpain Departamento de Neurología Hospital Virgen de ValmeSevillaSpain Centro de Salud Utrera Sur SevillaSpain Centro de Salud Polígono Sur SevillaSpain Unidad de Trastornos del movimiento Servicio de Neurología y Neurofisiología ClínicaHospital Universitario Virgen del RocíoSevillaSpain Departamento de medicina Facultad de MedicinaUniversidad de SevillaSevilleSpain Departamento de Antropología Social Universidad de GranadaSpain Unidad Enfermedades Neuromusculares Servicio de Neurología y Neurofisiología ClínicaHospital Universitario Virgen del RocíoSevillaSpain

In recent years,the number of known disease genes has exponentially grown due to the widespread adoption of cost-effective massive parallel *** identify new disease variants,especially in monogenic disorders,a frequen... 详细信息

关键词： Server filtering massive