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Adeno-associated virus as a delivery vector for gene therapy of human diseases

Signal Transduction and Targeted Therapy 2024年第5期9卷 1808-1840页

作者： Jiang-Hui Wang Dominic J.Gessler Wei Zhan thomas L.Gallagher Guangping Gao Horae Gene Therapy Center University of Massachusetts Chan Medical SchoolWorcesterMA01605USA Department of Microbiology and Physiological Systems University of Massachusetts Chan Medical SchoolWorcesterMA01605USA Centre for Eye Research Australia Royal Victorian Eye and Ear HospitalEast MelbourneVIC3002Australia Ophthalmology Department of SurgeryUniversity of MelbourneEast MelbourneVIC3002Australia Department of Neurological Surgery University of Massachusetts Chan Medical SchoolWorcesterMA01605USA Department of Neurosurgery University of MinnesotaMinneapolisMN55455USA Department of Medicine University of Massachusetts Chan Medical SchoolWorcesterMA01605USA Li Weibo Institute for Rare Diseases Research University of Massachusetts Chan Medical SchoolWorcesterMA01605USA

Adeno-associated virus(AAV)has emerged as a pivotal delivery tool in clinical gene therapy owing to its minimal pathogenicity and ability to establish long-term gene expression in different *** AAV(rAAV)has been engineered for enhanced specificity and developed as a tool for treating various ***,as rAAV is being more widely used as a therapy,the increased demand has created challenges for the existing manufacturing *** rAAV-based gene therapy products have received regulatory approval,but there continue to be concerns about safely using high-dose viral therapies in humans,including immune responses and adverse effects such as genotoxicity,hepatotoxicity,thrombotic microangiopathy,and *** this review,we explore AAV biology with an emphasis on current vector engineering strategies and manufacturing *** discuss how rAAVs are being employed in ongoing clinical trials for ocular,neurological,metabolic,hematological,neuromuscular,and cardiovascular diseases as well as *** outline immune responses triggered by rAAV,address associated side effects,and discuss strategies to mitigate these *** hope that discussing recent advancements and current challenges in the field will be a helpful guide for researchers and clinicians navigating the ever-evolving landscape of rAAV-based gene therapy.

关键词： diseases specificity approval

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Spatiotemporal dynamics of the social structure of Indo-Pacific humpback dolphins(Sousa chinensis)in Xiamen waters from 2007 to 2019

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Zoological Research 2024年第2期45卷 439-450页

作者： Yi Lu Xin-Rong Xu Bing-Yao Chen thomas A Jefferson Holly Fearnbach Guang Yang Jiangsu Key Laboratory for Biodiversity and Biotechnology College of Life SciencesNanjing Normal UniversityNanjingJiangsu 210023China Clymene Enterprises LakesideCalifornia 92040USA Marine Mammal Research SR3SeaLife ResponseRehabilitation and ResearchWA 98275USA Southern Marine Science and Engineering Guangdong Laboratory(Guangzhou) No.1119Haibin RoadNansha DistrictGuangzhouGuangdong 511458China

As highly social animals,Indo-Pacific humpback dolphins(Sousa chinensis)exhibit community ***,our understanding of the external and internal factors influencing these dynamics,as well as their spatiotemporal variations,is still *** the present study,variations in the social structure of an endangered Indo-Pacific humpback dolphin population in Xiamen Bay,China,were monitored over two distinct periods(2007–2010 and 2017–2019)to analyze the effects of habitat utilization and the composition of individuals within the *** both periods,the population demonstrated a strikingly similar pattern of social differentiation,characterized by the division of individuals into two main clusters and one small ***,the two primary clusters occupied the eastern and western waters,respectively,although the core distribution area of the eastern cluster shifted further eastward between the two *** this distribution shift,the temporal stability of the social structure and inter-associations within the eastern cluster remained unaffected.A subset of 16individuals observed in both periods,comprising 51.6%and 43.2%of the population in each respective period,emerged as a foundational element of the social structure and may be responsible for sustaining social structure stability,especially during the 2007–2010 *** observations suggest that the composition of dominant individuals,an internal factor,had a more substantial influence on the formation of the social network than changes in habitat use,an external ***,the study proposes distinct conservation measures tailored to each of the two main clusters.

关键词： Social differentiation Social structure Sousa chinensis Dynamics Conservation

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Examining the“revisability”benefit of hip resurfacing arthroplasty

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World Journal of Orthopedics 2024年第6期15卷 554-559页

作者： Jose George Adam J Taylor thomas P Schmalzried Department of Orthopedics Harbor UCLA Medical CenterTorranceCA 90509United States

BACKGROUND Hip resurfacing arthroplasty(HRA)is an alternative to total hip arthroplasty(THA)that is typically reserved for young active patients because it preserves ***,the benefits of HRA only hold true if conversion THA after failed HRA provides acceptable *** To compare patient reported outcomes for conversion THA after HRA failure to primary *** A retrospective review of 36 patients(37 hips)that underwent conversion THA for failed HRA between October 2006 and May 2019 by a single surgeon was *** reported outcomes[modified Harris Hip Score(mHHS),University of California Los Angeles(UCLA)activity score]were obtained via an email-based responder-anonymous *** were compared to normative data of a primary THA cohort with similar *** analysis was performed comparing outcomes of conversion THA for adverse local tissue reaction(ALTR)vs all other causes for *** The study group had a lower mHHS than the control group(81.7±13.8 vs 90.2±11.6,P<0.01);however,both groups had similar UCLA activity levels(7.5±2.3 vs 7.2±1.6,P=0.51).Patients that underwent conversion for non-ATLR causes had similar mHHS(85.2±11.5 vs 90.2±11.6,P=0.11)and higher UCLA activity levels(8.5±1.8 vs 7.2±1.6,P<0.01)compared to the control *** that underwent conversion for ATLR had worse mHHS(77.1±14.5 vs 90.2±11.6,P<0.01)and UCLA activity levels(6.1±2.3 vs 7.2±1.6,P=0.05)when compared to the control *** Patient outcomes equivalent to primary THA can be achieved following HRA conversion to ***,inferior outcomes were demonstrated for ALTR-related HRA *** selection and perhaps further studies examining alternative HRA bearing surfaces should be considered.

关键词： Total hip arthroplasty Hip resurfacing arthroplasty Conversion total hip arthroplasty Adverse local tissue reaction Patient reported outcome measures

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A simulation study for a cost-effective PET-like detector system intended to track particles in granular assemblies

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Particuology 2024年第1期84卷 117-125页

作者： Josephine Oppotsch Antonios Athanassiadis Miriam Fritsch Fritz-Herbert Heinsius thomas Held Nikoline Hilse Viktor Scherer Matthias Steinke Ulrich Wiedner Ruhr-Universität Bochum Institut für Experimentalphysik I44801 BochumGermany Ruhr-Universität Bochum Lehrstuhl für Energieanlagen und Energieprozesstechnik44801 BochumGermany

Since many industrial applications rely on the processing of densely packed and moving granular ma-terial,obtaining bulk internal information on the particle movement inside the reactors is of great *** information can be delivered by Positron Emission Particle Tracking(PEPT).By marking pellets with a positron-emitting radioisotope,the position of these tracer particles can be determined via the time-of-flight differences of the emitted gamma-ray *** current paper proposes a PET-like detector system based on cost-effective organic plastic scintillators instead of the more common but expensive inorganic *** system is currently under construction and was tested for its resolution and efficiency in this simulation *** Monte Carlo simulations and the software toolkit Geant4,three different geometries(an empty glass box,a generic grate system,and a cubic box of 1 m3 completely filled with pellets)were investigated,leading to a spatial resolution in the millimeter range and an efficiency,defined as the ratio of reconstructed decay locations to simulated decays,of 2.7%,1.4%,and 0.3%.

关键词： Positron emission particle tracking Geant4 Monte Carlo method Time-of-flight Plastic scintillators Silicon photomultipliers(SiPMs)

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Tuning beneficial calcineurin phosphatase activation to counterα-synuclein toxicity in a yeast model of Parkinson’s disease

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Neural Regeneration Research 2025年第1期20卷 199-200页

作者： Srishti Chawla Mikael Molin thomas Nystrom Institute for Biomedicine Sahlgrenska AcademyCentre for Ageing and Health-AgeCapUniversity of GothenburgGothenburgSweden Department of Life Sciences Chalmers University of TechnologyGothenburgSweden

Calcineurin(CN)is a calcium-and calmodulindependent serine/threonine that has been studied in many model organisms including yeast,filamentous fungi,plants,and *** biological functions range from ion homeostasis and virulence in lower eukaryotes to T-cell activation in humans by human nuclear factors of activated *** is a heterodimeric protein consisting of a catalytic subunit,calcineurin A(Cna1p),which contains an active site with a dinuclear metal center,and a regulatory Ca^(2+) binding subunit called calcineurin B(Cnb1p)required to activate *** calcineurin B subunit has been highly conserved through evolution:For example,the mammalian calcineurin B shows 54%identity with calcineurin B from Saccharomyces cerevisiae.

关键词： activation dinuclear conserved

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Bacterial plant pathogens affect the locomotor behavior of the insect vector:a case study of Citrus volkameriana-Triozae erytreae-Candidatus Liberibacter asiaticus system

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Insect Science 2024年第3期31卷 901-910页

作者： Arnaud Ameline Alain Karkach thomas Denoirjean Martial Grondin Florencia Molinari Patrick Turpin Helene Delatte Bernard Reynaud UMR CNRS 7058 EDYSAN(Ecologie et Dynamique des Systemes Anthropises) Universite de Picardie Jules VerneAmiensCedexFrance UMR PVBMT(Peuplements végétaux et bioagresseurs en milieu tropical) Universitéde la RéunionSaint PierreLa RéunionFrance

Plant pathogens can alter the behavior of their insect vectors as well as their survival and *** African psyllid,Trioza erytreae,is one of the vectors of Huanglongbing,a citrus disease caused mainly by"Candidatus Liberibacter asiaticus"(CLas).The purpose of this study was to characterize the effects of CLas on the psyllid,*** using Citrus volkamerina plants as the study *** study focused more specifically on the CLas effects prior to and after its acquisition by the psyllid *** results did not support the hypothesis that CLas effects psyllid probing behavior prior to acquisition;few differences were observed between uninfected *** feeding on CLas-infected versus control *** the other hand,compared to psyllids that had completed their development on control plants,the ones that had completed their development on a CLas-infected plant exhibited changes in their behavior(greater velocity),physiology(smaller mass)and biochemistry(lower water and lipid content).Altogether,our results confirm the existence of a marked postacquisition effect on the vector locomotor behavior and a minor preacquisition effect of CLas on the vector behavior,which can be partially explained by physiological and biochemical changes.

关键词： electrical penetration graph Huanglongbing locomotory behavior lipid biomass probing behavior vector manipulation

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Femoral Access with Ultrasound-Guided Puncture and Z-Stitch Hemostasis for Adults with Congenital Heart Diseases Undergoing Electrophysiological Procedures

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Congenital Heart Disease 2024年第1期19卷 85-92页

作者： Fu Guan Matthias Gass Florian Berger Heiko Schneider Firat Duru thomas Wolber Arrhythmia and Electrophysiology Division Department of CardiologyUniversity Heart Center ZurichZurichSwitzerland Children’s Research Center Zurich University Children’s HospitalZurichSwitzerland Center for Integrative Human Physiology University of ZurichZurichSwitzerland

Aims:Although the application of ultrasound-guided vascular puncture and Z-stitch hemostasis to manage femoral access has been widely utilized,there is limited data on this combined application in adult congenital heart disease(ACHD)patients undergoing electrophysiological(EP)*** sought to evaluate the safety and efﬁcacy of ultrasound-guided puncture and postprocedural Z-stitch hemostasis for ACHD patients under-going EP *** and Results:The population of ACHD patients undergoing transfemoral EP pro-cedures at the University of Zurich Heart Center between January 2019 and December 2022 was observed and *** the study period,femoral access(left/right,arterial/venous)was performed under real-time ultrasound *** the end of the procedure,a single Z-stitch was performed at the puncture *** eval-uated the incidence of in-hospital complications associated with femoral access puncture in this *** 101 patients who had a total of 147 previous ipsilateral vascular punctures(mean 1.5 per person),100 patients underwent successful femoral vascular access for EP *** median age of the patients was 47±15 years and 34(34%)were male.Z-stitches were performed after the procedure in 100 patients with 303 femoral vascular accesses(mean 3 punctures per person).No patient developed vascular puncture relevant inguinal hematoma,pseudo aneurysm,arteriovenousﬁstula,venous or arterial ***:In ACHD patients undergoing EP procedures,optimal femoral access management can be achieved with ultra-sound-guided puncture and postprocedural Z-stitch hemostasis.

关键词： Congenital heart disease cardiac electrophysiology cardiac catheterization femoral access hemostasis

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Tribological behavior of shape-specific microplate-enriched synovial fluids on a linear two-axis tribometer

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Friction 2024年第3期12卷 539-553页

作者： Agnese FRAGASSI Antonietta GRECO Martina DI FRANCESCO Luca CESERACCIU Aiman ABU AMMAR Israel DVIR thomas Lee MOORE Haytam KASEM Paolo DECUZZI Laboratory of Nanotechnology for Precision Medicine Fondazione Istituto Italiano di TecnologiaGenova 16163Italy Department of Chemistry and Industrial Chemistry University of GenovaGenoa 16146Italy Materials Characterization Facility Istituto Italiano di TecnologiaGenova 16163Italy Department of Pharmaceutical Engineering Azrieli College of Engineering JerusalemJerusalem 9103501Israel Department of Mechanical Engineering Azrieli College of Engineering JerusalemJerusalem 9103501Israel

Nano-and micro-particles are being increasingly used to tune interfacial frictional properties in diverse applications,from friction modifiers in industrial lubrication to enhanced biological fluids in human osteoarthritic ***,we assessed the tribological properties of a simulated synovial fluid enriched with non-spherical,poly lactic-co-glycolic acid(PLGA)microparticles(μPL)that have been previously demonstrated for the pharmacological management of osteoarthritis(OA).Three different μPL configurations were fabricated presenting a 20μm×20μm square base and a thickness of 5μm(thin,5H μPL),10μm(10H μPL),and 20μm(cubical,20H μPL).After extensive morphological and physicochemical characterizations,the apparent Young’s modulus of the μPL was quantified under compressive loading returning an average value of~6 kPa,independently of the particle ***,using a linear two-axis tribometer,the static(μ_(s))and dynamic(μ_(d))friction coefficients of the μPL-enriched simulated synovial fluid were determined in terms of particle configuration and concentration,varying from 0(fluid only)to 6×10^(5) μPL/*** particle morphology had a modest influence on friction,possibly because the μPL were fully squeezed between two mating surfaces by a 5.8 N normal load realizing boundary-like lubrication ***,friction was observed to depend on the dimensionless parameterW,defined as the ratio between the total volume of the μPL enriching the simulated synovial fluid and the volume of the fluid *** coefficients of friction were documented to grow withWreaching a plateau of μ_(s)~0.4 and μ_(d)~0.15,already at Ω~2×10^(-3).Future investigations will have to systematically analyze the effect of sliding velocity,normal load,and rigidity of the mating surfaces to elucidate in full the tribological behavior of μPL in the context of osteoarthritis.

关键词： osteoarthritis microparticles tribology synovial fluid pin on plate

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Characteristics of patients with Wilson disease in the United States: An insurance claims database study

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World Journal of Hepatology 2024年第5期16卷 791-799页

作者： thomas Daniel-Robin Pradeep Kumar Bernard Benichou Jean-Philippe Combal Vivet Therapeutics Paris 75008France Clarivate Noida 201301Uttar PradeshIndia

BACKGROUND Wilson disease(WD)is a progressive,potentially fatal degenerative disease affecting the liver and central nervous *** its low prevalence,collecting data on large cohorts of patients with WD is *** insur-ance claims databases provide powerful tools to collect retrospective data on large numbers of patients with rare *** To describe patients with WD in the United States,their treatment and clinical outcome,using a large insurance claims *** This retrospective,longitudinal study was performed in the Clarivate Real-World Data Product *** patients with≥2 claims associated with an Interna-tional Classification of Diseases 10(ICD-10)diagnostic code for WD(E83.01)between 2016 and 2021 were included and followed until death or study *** were divided into two groups by whether or not they were documented to have received a specific treatment for *** manifestations,hospital-isations,liver transplantation and death were *** Overall,5376 patients with an ICD-10 diagnostic code for WD were *** mean age at inclusion was 41.2 years and 52.0%were men.A specific WD treatment was documented for 885 patients(15.1%),although the number of patients taking zinc salts may be underestimated due to over the counter *** inclusion,the mean age of patients with a documented treatment was 36.6±17.8 years vs 42.2±19.6 years in those without a documented *** follow-up,273 patients(5.1%)*** with the American general population,the standardised mortality ratio was *** proportion of patients with a documented WD-specific treatment who died during follow-up was 4.0%and the mean age at death 52.7 *** Patients treated for WD in the United States had an excess early mortality compared with the American *** findings indicate that there is a significant unmet need for effective treatment for WD in the United States.

关键词： Wilson disease Mortality Treatment Copper chelators Zinc acetate United States

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Federated Learning on Internet of Things:Extensive and Systematic Review

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Computers, Materials & Continua 2024年第5期79卷 1795-1834页

作者： Meenakshi Aggarwal Vikas Khullar Sunita Rani thomas AndréProla Shyama Barna Bhattacharjee Sarowar Morshed Shawon Nitin Goyal Chitkara University Institute of Engineering and Technology Chitkara UniversityRajpuraPunjab140401India Department of CSE&IT BPS Mahila VishwavidyalayaKhanpur KalanSonipatHaryana131305India Engineering Research&Innovation Group Universidad Europea del AtlánticoC/Isabel Torres 21Santander39011Spain Department of Project Management Universidad Internacional IberoamericanaAreciboPR00613USA Department of Project Management Universidade Internacional do CuanzaEstrada Nacional 250Bairro KaluapandaCuito-BiéAngola Department of Computer Science and Engineering University of Science and Technology Chittagong(USTC)Chattogram4202Bangladesh Deptartment of EEE University of Science and Technology Chittagong(USTC)Chattogram4202Bangladesh Department of Computer Science and Engineering School of Engineering and TechnologyCentral University of HaryanaMahendragarhHaryana123031India

The proliferation of IoT devices requires innovative approaches to gaining insights while preserving privacy and resources amid unprecedented data ***,FL development for IoT is still in its infancy and needs to be explored in various areas to understand the key challenges for deployment in real-world *** paper systematically reviewed the available literature using the PRISMA guiding *** study aims to provide a detailed overview of the increasing use of FL in IoT networks,including the architecture and challenges.A systematic review approach is used to collect,categorize and analyze FL-IoT-based *** was performed in the IEEE,Elsevier,Arxiv,ACM,and WOS databases and 92 articles were finally *** measures were published in English and with the keywords“FL”and“IoT”.The methodology begins with an overview of recent advances in FL and the IoT,followed by a discussion of how these two technologies can be *** be more specific,we examine and evaluate the capabilities of FL by talking about communication protocols,frameworks and *** then present a comprehensive analysis of the use of FL in a number of key IoT applications,including smart healthcare,smart transportation,smart cities,smart industry,smart finance,and smart *** key findings from this analysis of FL IoT services and applications are also ***,we performed a comparative analysis with FL IID(independent and identical data)and non-ID,traditional centralized deep learning(DL)*** concluded that FL has better performance,especially in terms of privacy protection and resource *** is excellent for preserving privacy becausemodel training takes place on individual devices or edge nodes,eliminating the need for centralized data aggregation,which poses significant privacy *** facilitate development in this rapidly evolving field,the insights presented are intended to help practitioners and re

关键词： Internet of Things federated learning PRISMA framework of FL applications of FL data privacy communication

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