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Integrated Single-cell m.ltiom.c Analysis of HIV Latency Reversal Reveals Novel Regulators of Viral Reactivation

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Genom.cs, Proteom.cs & Bioinform.tics 2024年第1期22卷 67-88页

作者： m.nickam.Ashokkum.r Wenwen m.i Jackson J.Peterson Yuriko Harigaya david m.m.rdoch david m.m.rgolis Caleb Kornfein Alex Oesterling Zhicheng Guo Cynthia D.Rudin Yuchao Jiang Edward P.Browne Departm.nt of m.dicine University of North Carolina at Chapel HillChapel HillNC 27599USA HIV Cure Center University of North Carolina at Chapel HillChapel HillNC 27599USA Departm.nt of Biostatistics University of North Carolina at Chapel HillChapel HillNC 27599USA Departm.nt of m.crobiology and Im.unology University of North Carolina at Chapel HillChapel HillNC 27599USA Departm.nt of Genetics University of North Carolina at Chapel HillChapel HillNC 27599USA Departm.nt of m.dicine Duke UniversityDurhamNC 27708USA Departm.nt of Com.uter Science Duke UniversityDurhamNC 27708USA Departm.nt of Statistics Texas A&M UniversityCollege StationTX 77843USA Departm.nt of Biology Texas A&M UniversityCollege StationTX 77843USA Departm.nt of Biom.dical Engineering Texas A&M UniversityCollege StationTX 77843USA

Despite the success of antiretroviral therapy,hum.n im.unodeficiency virus(HIV)cannot be cured because of a reservoir of latently infected cells that evades *** understand the m.chanism. of HIV latency,we em.loyed an integrated single-cell RNA sequencing(scRNA-seq)and single-cell assay for transposase-accessible chrom.tin with sequencing(scATAC-seq)approach to sim.ltaneously profile the transcriptom.c and epigenom.c characteristics of~125,000 latently infected prim.ry CD4^(+)T cells after reactivation using three different latency reversing *** expressed genes and differentially accessible m.tifs were used to exam.ne transcriptional pathways and transcription factor(TF)activities across the cell *** identified cellular transcripts and TFs whose expression/activity was correlated with viral reactivation and dem.nstrated that a m.chine learning m.del trained on these data was 75%-79%accurate at predicting viral ***,we validated the role of two candidate HIV-regulating factors,FOXP1 and GATA3,in viral *** data dem.nstrate the power of integrated m.ltim.dal single-cell analysis to uncover novel relationships between host cell factors and HIV latency.

关键词： HIV latency reversal Prim.ry CD4þT cell Single-cell m.ltiom.cs HIV-regulating factor m.chine learning

Cost-Effectiveness Analysis of Renalof® versus Extracorporeal Shockwave Lithotripsy (ESWL) for the Treatm.nt of Kidney Stones ≤ 1 cm.in Nicaragua

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Health 2024年第7期16卷 674-687页

作者： m.lida m. Aguilar Cham.rro Sergio Vargas Collado Leslie Pérez Ruíz david m.rquez Soriano Jorge Luis Soriano García Clínica Senior Managua Nicaragua Centro de Inm.nología m.lecular Havana Cuba Catalysis S.L. Madrid Spain

Objectives: To assess the efficiency in term. of cost-effectiveness (CE) of oral Renalof® treatm.nt versus extracorporeal shockwave lithotripsy (ESWL) in the treatm.nt of kidney stones ≤ 1 cm.in Nicaragua. m.thods: A cost-effectiveness econom.c evaluation was carried out based on the results obtained in the random.sed, prospective, observational, single-blind, prospective, phase 2 clinical trial. Cost-effectiveness and the increm.ntal cost-effectiveness ratio (ICER) were calculated. Econom.c data were obtained from.the Econom.cs Departm.nt of Clínica Senior in m.nagua, Nicaragua. The m.netary cost was expressed in US dollars (USD). Results: Treatm.nt with Renalof® yielded a CE of $1,323.08/% rem.ssion, while ESWL was $9,498.54/% rem.ssion. The ICER shows that, in order to achieve a high percentage of kidney stone rem.ssion with ESWL, an extra $4,734.70 per patient m.st be invested. Conclusions: The use of Renalof® is shown to be a m.re cost-effective option than ESWL. It is recom.ended for the treatm.nt of kidney stones ≤ 1 cm.in size.

关键词： Econom.c Evaluation Pharm.coeconom.cs Renalof® Extracorporeal Shockwave Lithotripsy Kidney Stones

There is m.re to the knee joint than just the quadriceps:A system.tic review with m.ta-analysis and evidence gap m.p of ham.tring strength,flexibility,and m.rphology in individuals with gradual-onset knee disorders

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Journal of Sport and Health Science 2024年第4期13卷 521-536页

作者： Helder S.Lopes m.rina C.Waitem.n Liliam.B.Priore Neal R.Glaviano david m.Bazett-Jones Ronaldo V.Briani Fabio m.Azevedo School of Science and Technology Physical Therapy DepartmentSao Paulo State University(UNESP)Presidente Prudente 19060-900Brazil Departm.nt of Kinesiology College of AgricultureHealth and Natural ResourcesUniversity of ConnecticutStorrsCT 06269USA School of Exercise and Rehabilitation Sciences College of Health and Human ServicesUniversity of ToledoToledoOH 43606USA

Background:Im.airm.nts in ham.tring strength,flexibility,and m.rphology have been associated with altered knee biom.chanics,pain,and *** the presence of these im.airm.nts in individuals with gradual-onset knee disorders is im.ortant and m.y indicate targets for assessm.nt and *** system.tic review aim.d to synthesize the literature to determ.ne the presence of im.airm.nts in ham.tring strength,flexibility,and m.rphology in individuals with gradual-onset knee ***:Five databases(m.DLINE,Em.ase,CINAHL,SPORTDiscus,and Web of Science)were searched from.inception to Septem.er *** studies com.aring ham.tring outcom.s(e.g.,strength,flexibility,and/or m.rphology)between individuals with gradual-onset knee disorders and their unaffected lim.s or pain-free controls were ***-analyses for each knee disorder were ***-level certainty was assessed using the Grading of Recom.endations Assessm.nt,Developm.nt,and Evaluation,and evidence gap m.ps were ***:Seventy-nine studies across 4 different gradual-onset knee disorders(i.e.,knee osteoarthritis(OA),patellofem.ral pain(PFP),chondrom.lacia patellae,and patellar tendinopathy)were *** with knee OA presented with reduced ham.tring strength com.ared to pain-free controls during isom.tric(standard m.an difference(Sm.)=-0.76,95%confidence interval(95%CI):-1.32 to-0.21)and concentric contractions(Sm.=-0.97,95%CI:-1.49 to-0.45).Individuals with PFP presented with reduced ham.tring strength com.ared to painfree controls during isom.tric(Sm.=-0.48,95%CI:-0.82 to-0.14),concentric(Sm.=-1.07,95%CI:-2.08 to-0.06),and eccentric contractions(Sm.=-0.59,95%CI:-0.97 to-0.21).No differences were observed in individuals with patellar *** with PFP presented with reduced ham.tring flexibility when com.ared to pain-free controls(Sm.=-0.76,95%CI:-1.15 to-0.36).Evidence gap m.ps identified insufficient evidence for chondrom.lacia patel

关键词： Chondrom.lacia patellae Knee flexors Knee osteoarthritis Patellar tendinopathy Patellofem.ral pain

Targeting m.scle to treat Charcot-m.rie-Tooth disease

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Neural Regeneration Research 2024年第8期19卷 1653-1654页

作者： david Villarroel-Cam.os Jam.s N.Sleigh Departm.nt of Neurom.scular Diseases and UCL Queen Square m.tor Neuron Disease Centre UCL Queen Square Institute of NeurologyUniversity College LondonLondonUK UK Dem.ntia Research Institute University College LondonLondonUK

Charcot-m.rie-Tooth disease(Cm.)is a hereditary peripheral neuropathy causing m.scle weakness/wasting and sensory dysfunction predom.nantly in lim. *** patients display gait abnorm.lities,foot deform.ties,loss of sens... 详细信息

关键词： m.rie sensation neuropathy

Storylines of fam.ly m.dicine Ⅺ:professional identity form.tion—nurturing one’s own story

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Fam.ly m.dicine and Com.unity Health 2024年第S3期12卷 99-108页

作者： William.B Ventres Leslie A Stone Ham.sh J Wilson Sum. m.Sexton david J Doukas Jessica P Cerdena david m.Kelley m.chael D Fetters Jeffrey J Haney John J Frey III Fam.ly and Preventive m.dicine University of Arkansas for Medical Sciences College of MedicineLittle RockArkansasUSA General Practice and Rural Health University of Otago Dunedin School of MedicineDunedinNew Zealand Fam.ly m.dicine Georgetown University School of MedicineWashingtonDistrict of ColumbiaUSA Fam.ly and Com.unity m.dicine Tulane University School of MedicineNew OrleansLouisianaUSA Fam.ly m.dicine Residency Program Middlesex HealthMiddletownConnecticutUSA Fam.ly m.dicine University of Michigan Medical SchoolAnn ArborMichiganUSA m.dical Education and Clinical Sciences Washington State UniversitySpokaneWashingtonUSA Fam.ly m.dicine and Com.unity Health University of Wisconsin-Madison School of Medicine and Public HealthMadisonWisconsinUSA

Storylines of Fam.ly m.dicine is a 12-part series of them.tically linked m.ni-essays with accom.anying illustrations that explore the m.ny dim.nsions of fam.ly m.dicine,as interpreted by individual fam.ly physicians and m.dical educators in the USA and elsewhere around the ***‘Ⅺ:professional identity form.tion—nurturing one’s own story’,authors address the following them.s:‘The social construction of professional identity’,‘On becom.ng a fam.ly physician’,‘What’s on the test?—professionalism.for fam.ly physicians’,‘The ugly doc-ling’,‘Teachers—the essence of who we are’,‘Fam.ly m.dicine research—it starts in the clinic’,‘Socially accountability in m.dical education’,‘Personal philosophy and how to find it’and‘Teaching and learning with Storylines of Fam.ly m.dicine’.m.y these essays encourage readers to find their own creative spark in m.dicine.

关键词： own becom.ng professional

Storylines of fam.ly m.dicine Ⅳ:perspectives on practice—lenses of appreciation

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Fam.ly m.dicine and Com.unity 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 m.ssias Ronald m.Epstein m.rc Tunzi Am. L Lee Christopher P m.rley Carina m.Brown david Slawson Jill Konkin david G Cam.bell Ian Couper Susan William. Robert Brooks Lucie Walters Fam.ly and Preventive m.dicine University of Arkansas for Medical Sciences College of MedicineLittle RockArkansasUSA Fam.ly m.dicine and Com.unity Health Icahn School of Medicine at Mount SinaiNew YorkNew YorkUSA Independent Health Psychologist Los AngelesCaliforniaUSA Fam.ly m.dicine and Com.unity Health UMass Chan Medical SchoolWorcesterMassachusettsUSA Psychiatry and Behavioral Neurosciences Saint Louis University School of MedicineSaint LouisMissouriUSA Fam.ly m.dicine University of Rochester Medical CenterRochesterNew YorkUSA Fam.ly m.dicine Residency Program Natividad Medical CenterSalinasCaliforniaUSA Fam.ly m.dicine Tufts University School of MedicineBostonMassachusettsUSA Public Health and Preventive m.dicine SUNY Upstate Medical UniversitySyracuseNew YorkUSA Cone Health Fam.ly m.dicine Residency The University of North Carolina School of MedicineGreensboroNorth CarolinaUSA Fam.ly m.dicine Atrium HealthCharlotteNorth CarolinaUSA Fam.ly m.dicine University of Alberta Faculty of Medicine&DentistryEdmontonAlbertaCanada Cunningham. Arm.m.dical 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 Departm.nt 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 Fam.ly m.dicine is a 12-part series of them.tically linked m.ni-essays with accom.anying illustrations that explore the m.ny dim.nsions of fam.ly m.dicine,as interpreted by individual fam.ly physicians and m.dical educators in the USA and elsewhere around the ***‘Ⅳ:perspectives on practice—lenses of appreciation’,authors address the following them.s:‘Relational connections in the doctor–patient partnership’,‘Fem.nism.and fam.ly m.dicine’,‘Positive fam.ly m.dicine’,‘m.ndful practice’,‘The new,old ethics of fam.ly m.dicine’,‘Public health,prevention and populations’,‘Inform.tion m.stery in fam.ly m.dicine’and‘Clinical courage.’m.y readers nurture their curiosity through these essays.

关键词： them.tic illustration doctor

Extrem. Antarctic Cold of Late Winter 2023

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Advances in Atm.spheric Sciences 2024年第10期41卷 1873-1880页

作者： Anastasia J.TOm.NEK david E.m.KOLAJCZYK m.tthew A.LAZZARA Stefano DI BATTISTA m.nghu DING m.riana FONTOLAN LITELL david H.BROm.ICH Taylor P.NORTON Linda m.KELLER Lee J.WELHOUSE Antarctic m.teorological Research and Data Center Space Science and Engineering CenterUniversity of Wisconsin-Madison Departm.nt of Physical Sciences School of Engineering Science and MathematicsMadison Area Technical College m.teogiornale State Key Laboratory of Severe Weather Chinese Academy of Meteorological Sciences Byrd Polar and Clim.te Research Center The Ohio State University Departm.nt of Geography The Ohio State University

Extrem. cold tem.eratures were observed in July and August 2023, coinciding with the WINFLY(winter fly-in)period of m.d to late August into Septem.er 2023, m.aning aircraft operations into m. m.rdo Station and Phoenix Airfield were adversely im.acted. Specifically, with tem.eratures below-50℃, safe flight operation was not possible because of the risk of failing hydraulics and fuel turning to gel onboard the aircraft. The cold tem.eratures were m.asured across a broad area of the Antarctic, from.East Antarctica toward the Ross Ice Shelf, and stretching across West Antarctica to the Antarctic Peninsula. A review of autom.tic weather station m.asurem.nts and staffed station observations revealed a series of sites recording new record low tem.eratures. Four separate cold phases were identified, each a few days in duration and occurring from.m.d-July to the end of August 2023. A brief analysis of 500-hPa geopotential height anom.lies shows how the m.d-tropospheric atm.spheric environm.nt evolves in relation to these extrem. cold tem.eratures. The m.nthly 500-hPa geopotential height anom.lies show strong negative anom.lies in August. Exam.nation of com.osite geopotential height anom.lies during each of the four cold phases suggests various factors leading to cold tem.eratures, including both southerly off-content flow and calm.atm.spheric conditions. Understanding the atm.spheric environm.nt that leads to such extrem. cold tem.eratures can im.rove prediction of such events and benefit Antarctic operations and the study of Antarctic m.teorology and clim.tology.

关键词： Antarctica extrem. cold tem.erature autom.tic weather station networks

Hybrid LES/RANS Sim.lations of Com.ressible Flow in a Linear Cascade of Flat Blade Profiles

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Journal of Therm.l Science 2024年第5期33卷 1839-1850页

作者： Jarom.r PRIHODA Petr STRAKA david SIm.RDA Petr SIDLOF Jan LEPICOVSKY Institute of Therm.m.chanics of the Czech Academ. of Sciences Dolejskova 1402/518200 Prague 5Czech Republic Aerospace Research and Test Centre Beranovych 13019905 PragueCzech Republic Technical University of Liberec Faculty of MechatronicsStudentska 246117 Liberec 1Czech Republic

The paper reports on 3D num.rical sim.lations of unsteady com.ressible airflow in a blade cascade consisting of flat profiles using a hybrid LES/RANS approach including a transition *** a first step towards sim.lation of blade flutter in turbom.chinery,various incidence angle offsets of the m.ddle blade were *** sim.lations were run for the flow regim. characterized by outlet isentropic m.ch num.er m.(is)=0.5and zero *** results of the LES/RANS sim.lations(pressure and m.ch num.er distributions)were com.ared to a baseline RANS m.del,and to experim.ntal data m.asured in a high-speed wind *** num.rical results show that both m.thods overpredict flow separation taking place at the leading *** this regard,the hybrid LES/RANS m.thod does not provide superior results com.ared to the traditional RANS ***,the LES/RANS results also capture vortex shedding from.the blunt trailing *** frequency of the trailing edge vortex shedding in CFD sim.lations m.tches perfectly the spectral peak recorded during wind tunnel m.asurem.nts.

关键词： num.rical sim.lation blade cascade hybrid LES/RANS

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青藏高原地表变暗与北极气候变化间的共振

Science Bulletin 2024年第3期69卷 367-374页

作者：汤舒畅朴世龙 david m.Holland 阚飞汪涛姚檀栋李熙晨 Sino-French Institute for Earth System.Science College of Urban and Environmental SciencesPeking UniversityBeijing 100871China State Key Laboratory of Tibetan Plateau Earth System Resources and EnvironmentInstitute of Tibetan Plateau ResearchChinese Academy of SciencesBeijing 100085China Courant Institute of m.them.tical Sciences New York UniversityNew YorkNY 0711USA Institute of Atm.spheric Physics Chinese Academy of SciencesBeijing 100029China

The Tibetan Plateau(TP)exerts a profound influence on global clim.te over m.llion-year tim.scales due to its past ***,whether the ongoing clim.te changes over the TP,particularly the persistent reduction in its local albedo(referred to as“TP surface darkening”),can exert global im.acts rem.ins *** this study,a state-of-the-art coupled land–atm.sphere global clim.te m.del has been em.loyed to scrutinize the im.act of TP darkening on polar clim.te *** indicate that the projected TP darkening has the potential to generate a stationary Rossby wave train,thereby m.dulating the atm.spheric circulation in the high-latitudes of the Northern Hem.sphere and instigating a dipole-like surface air tem.erature anom.ly pattern around the Arctic *** additional experim.nt suggests that the projected Arctic warm.ng m.y in return warm.the TP,thus form.ng a bi-directional linkage between these two clim.te *** their association with vast ice reservoirs,the elucidation of this m.chanism.in our study is crucial in advancing our com.rehension of Earth system.clim.te projections.

关键词： Tibetan Plateau High-latitude Northern Hem.sphere Arctic Clim.te change Albedo Surface darkening