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Skeletal muscle-directed gene therapy: hijacking the fusogenic properties of muscle cells

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Signal Transduction and Targeted Therapy 2023年第10期8卷 4428-4430页

作者： Hildegard Buning michael morgan Axel Schambach Institute of Experimental Hematology Hannover Medical SchoolHannover30625Germany REBIRTH Research Center for Translational Regenerative Medicine Hannover Medical SchoolHannover30625Germany Division of Hematology/Oncology Boston Children’s HospitalHarvard Medical SchoolBostonMA02115USA

A recent study published in Cell by the Millay lab reports on an elegant strategy to expand the repertoire of lentiviral(LV)vectors from being the main delivery tool for ex vivo gene therapy to an in vivo applicable viral vector that specifically transduces skeletal muscle.1 This very significant advance may result in novel therapeutics for patients suffering from various skeletal muscle diseases.

关键词： skeletal directed muscle

Base editing: a novel cure for severe combined immunodeficiency

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Signal Transduction and Targeted Therapy 2023年第10期8卷 4433-4435页

作者： Teng-Cheong Ha michael morgan Axel Schambach Institute of Experimental Hematology Hannover Medical SchoolHannover30625Germany REBIRTH Research Center for Translational Regenerative Medicine Hannover Medical SchoolHannover30625Germany Division of Hematology/Oncology Boston Children’s HospitalHarvard Medical SchoolBostonMA02115USA

In a recent Cell article,McAuley,Kohn et *** proof-of-principle of a promising gene therapy(GT)approach to correct the underlying genetic defect responsible for CD3δ-deficient severe combined immunodeficiency(SCID)using a CRISPR-Cas9-derived adenine-base-editor(ABE).1 This ground-breaking and important study could impact future GTs for monogenic diseases by providing novel tailored therapeutic options(Fig.1).

关键词： immunodeficiency al. diseases

Targeted cytokine delivery:cell therapy to remodel the pre-metastatic niche

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Signal Transduction and Targeted Therapy 2021年第8期6卷 2278-2279页

作者： michael A.morgan Lucas Lange Axel Schambach Institute of Experimental Hematology Hannover Medical SchoolHannoverGermany REBIRTH Research Center for Translational Regenerative Medicine Hannover Medical SchoolHannoverGermany Division of Hematology/Oncology Boston Children’s HospitalHarvard Medical SchoolBostonMAUSA

Tumor metastases present an often difficult to treat therapeutic challenge for cancer patients and their *** recent paper by the Kaplan group(Kaczanowska et al.)exploited the natural capacity of monocytes or a subset of monocytes to migrate to tumor sites and pre-metastatic niches to deliver IL-12 in a novel anticancer approach designed to stimulate local immune responses.1 This raises the possibility to simultaneously fight cancer on at least two critical fronts,(1)elimination of the primary tumor and(2)inhibition of newly developing pre-metastatic lesions.

关键词： metastatic cytokine migrate

Prime time for base editing in the mitochondria

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Signal Transduction and Targeted Therapy 2022年第8期7卷 2630-2631页

作者： michael A.morgan Lucas Lange Axel Schambach Institute of Experimental Hematology Hannover Medical SchoolHannover 30625Germany REBIRTH Research Center for Translational Regenerative Medicine Hannover Medical SchoolHannover 30625Germany Division of Hematology/Oncology Boston Children’s HospitalHarvard Medical SchoolBostonMA 02115USA

A recent study published in Cell by the Kim lab represents a great advance towards expanding DNA editing possibilities to mitochondrial DNA(mtDNA)as they show reasonable targeted A-to-G conversions in human mtDNA using base editors to broaden the arsenal of available tools.1 Mutations in mitochondrial DNA(mtDNA)are linked to several diseases(Fig.1),thus,development of gene therapy and editing approaches could lead to curative options for patients suffering from these *** this direction,gene editing tools such as zinc-finger nucleases(mitoZFN),transcription activator-like effector nucleases(mitoTALENs)and meganucleases(mitoARCUS)were shown to eliminate mutant mtDNA and shift heteroplasmy.

关键词： diseases base curative

COVID-19 vaccine-associated myocarditis

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World Journal of Cardiology 2022年第7期14卷 382-391页

作者： michael C morgan Lavannya Atri Sean Harrell Wael Al-Jaroudi Adam Berman Division of Cardiology Medical College of GeorgiaAugustaGA 30912United States Baptist Heart Baptist Medical CenterJacksonMS 39202United States Department of Population Health Sciences Medical College of GeorgiaAugustaGA 30912United States

Myocarditis is now recognized as a rare complication of coronavirus disease 2019(COVID-19)mRNA vaccination,particularly in adolescent and young adult *** the authorization of the Pfizer-BioNTech^(TM)and Moderna^(TM)mRNA vaccines targeting the severe acute respiratory syndrome coronavirus-2(SARSCoV-2)spike protein,the Centers for Disease Control and Prevention(CDC)has reported 1175 confirmed cases of myocarditis after COVID-19 vaccination in individuals ages 30 years and younger as of January *** to CDC data in June 2021,the incidence of vaccine-mediated myocarditis in males ages 12-29 years old was estimated to be 40.6 cases per million second doses of COVID-19 mRNA vaccination *** with cases of COVID-19 vaccinemediated myocarditis typically present with acute chest pain and elevated serum troponin levels,often within one week of receiving the second dose of mRNA COVID-19 *** cases follow a benign clinical course with prompt resolution of *** mechanisms of COVID-19 vaccine myocarditis include molecular mimicry between SARS-CoV-2 spike protein and self-antigens and the triggering of preexisting dysregulated immune pathways in predisposed *** higher incidence of COVID-19 vaccine myocarditis in young males may be explained by testosterone and its role in modulating the immune response in *** is limited data on long-term outcomes in these cases given the recency of their *** CDC continues to recommend COVID-19 vaccination for everyone 5 years of age and older given the greater risk of serious complications related to natural COVID-19 infection including hospitalization,multisystem organ dysfunction,and *** study is needed to better understand the immunopathology and long-term outcomes behind COVID-19 mRNA vaccine-mediated myocarditis.

关键词： COVID-19 SARS-CoV-2 mRNA vaccine Myocarditis Pericarditis

Role of cardiac magnetic resonance imaging in the diagnosis and management of COVID-19 related myocarditis: Clinical and imaging considerations

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World Journal of Radiology 2021年第9期13卷 283-293页

作者： Lavannya Atri michael morgan Sean Harrell Wael AlJaroudi Adam E Berman Division of Cardiology Medical College of GeorgiaAugusta UniversityAugustaGA 30912United States Division of Health Policy Medical College of GeorgiaAugusta UniversityAugustaGA 30912United States Division of Health Economics and Modeling Medical College of GeorgiaAugusta UniversityAugustaGA 30912United States

There is a growing evidence of cardiovascular complications in coronavirusdisease 2019 (COVID-19) patients. As evidence accumulated of COVID-19 mediatedinflammatory effects on the myocardium, substantial attention has beendirected towards cardiovascular imaging modalities that facilitate this *** magnetic resonance imaging (CMRI) is the gold standard for thedetection of structural and functional myocardial alterations and its role inidentifying patients with COVID-19 mediated cardiac injury is growing. Despiteits utility in the diagnosis of myocardial injury in this population, CMRI’s impacton patient management is still evolving. This review provides a framework for theuse of CMRI in diagnosis and management of COVID-19 patients from theperspective of a cardiologist. We review the role of CMRI in the management ofboth the acutely and remotely COVID-19 infected patient. We discuss patientselection for this imaging modality;T1, T2, and late gadolinium enhancementimaging techniques;and previously described CMRI findings in other cardiomyopathieswith potential implications in COVID-19 recovered patients.

关键词： Cardiac magnetic resonance imaging COVID-19 Cardiovascular magnetic resonance Myocarditis Coronavirus Cardiovascular complications

Severe acute respiratory syndrome coronavirus-2-related and imputable deaths in children:results from the French pediatric national registry

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World Journal of Pediatrics 2024年第6期20卷 611-620页

作者： Marguerite Lockhart-Bouron Noemie Vanel michael Levy Anais R.Briant Etienne Javouhey Sophie Breinig Julia Dina Marion Caseris Francois Angoulvant Stephane Leteurtre morgan Recher David W.Brossier Univ.Lille CHU LilleULR 2694-METRICS:Evaluation Des Technologies de Sante Et Des Pratiques Medicales59000LilleFrance Pediatric Intensive Care Unit CHU de MarseilleMarseilleFrance Pediatric Intensive Care Unit CHU Robert-DebreAssistance Publique Hopitaux de ParisParisFrance UniversitéParis-Cite ParisFrance Biostatistics and Clinical Research Unit CHU de Caen Normandie14000CaenFrance Pediatric Intensive Care Hospices Civils de LyonLyonFrance Neonatal andPediatric IntensiveCare Unit Children's HospitalToulouseFrance Virology Department INSERM U1311 DynamicureUniv CAEN NormandieCHU de Caen14000 CaenFrance Medical School Universite Caen Normandie14000 CaenFrance Department of Pediatrics CHU Robert-DebréAssistance Publique Hopitaux de ParisParisFrance Department Women-Mother-Child Service of PediatricsLausanne University Hospital(CHUV)LausanneSwitzerland Pediatric Intensive Care Unit Réanimation Et Soins Intensifs PéediatriquesCHU de CAENAvenue de La Cote de Nacre14000 CaenFrance CHU Sainte Justine Research Center MontréalCanada

Background Severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)is responsible for an important mortality rate *** aimed to evaluate the actual imputability of SARS-CoV-2 on the mortality rate associated with SARS-CoV-2-related illnesses in the pediatric intensive care unit(PICU).Secondary objectives were to identify risk factors for *** This national multicenter comparative study comprised all patients under 18 years old with positive SARS-CoV-2 polymerase chain reactions(PCRs)[acute corona virus disease 2019(COVID-19)or incidental SARS-CoV-2 infection]and/or pediatric inflammatory multisystem syndrome(PIMS)recorded in the French PICU registry(PICURe)between September 1,2021,and August 31,*** patients were classified and compared according to their living status at the end of their PICU *** patients were evaluated by four experts in the field of pediatric infectiology and/or pediatric intensive *** imputability of SARS-CoV-2 as the cause of death was classified into four categories:certain,very probable,possible,or unlikely,and was defined by any of the first three *** There were 948 patients included of which 43 died(4.5%).From this,26 deaths(67%)could be attributed to SARS-CoV-2 infection,with an overall mortality rate of 2.8%.The imputability of death to SARS-CoV-2 was considered certain in only one case(O.1%).Deceased patients suffered more often from comorbidities,especially heart disease,neurological disorders,hematological disease,cancer,and *** of the deceased patients were admitted for pediatric inflam-matory multisystem syndrome(PIMS).Mortality risk factors were male gender,cardiac comorbidities,cancer,and acute respiratorydistress *** SARS-CoV-2 mortality in the French pediatric population was *** though the imputability of SARS-Cov-2 on mortality was considered in almost two-thirds of cases,this imputability was considered certain in only one case.

关键词： Death Pediatric intensive care unit SARS-CoV-2

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振动光整介质和工件运动轨迹的测试与分析

噪声与振动控制 2018年第A2期38卷 431-434页

作者：张超刘志国王书文刘晓晓 michael morgan 上海理工大学机械工程学院上海200093 利物浦约翰摩尔斯大学通用工程研究所

在振动光整加工工艺中,介质和工件的运动轨迹是决定工件加工效果的重要因素。为了确定介质和工件的运动轨迹,通过X射线检测设备对介质和工件进行运动轨迹检测,再利用高速摄像机拍摄表面介质的运动。利用MATLAB处理软件对X射线检测录像... 详细信息

在振动光整加工工艺中,介质和工件的运动轨迹是决定工件加工效果的重要因素。为了确定介质和工件的运动轨迹,通过X射线检测设备对介质和工件进行运动轨迹检测,再利用高速摄像机拍摄表面介质的运动。利用MATLAB处理软件对X射线检测录像进行图像处理。检测图像显示,介质和工件的运动既有围绕滚动中心旋转的径向运动和围绕振动桶中轴旋转的周向运动,又有自身的翻转运动。结论是:利用X射线检测可以较准确地得到介质和工件的二维轨迹,结合高速摄像机对表面介质和工件的测试,能够较准确地建立介质和工件的三维运动方程,对深入研究振动光整加工机理具有重要意义。

关键词：振动与波振动光整运动轨迹 X射线测试介质工件

Improving sorghum digestion in broilers by targeting fermentation of xylan

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Animal Nutrition 2022年第3期10卷 198-206页

作者： Natalie K.morgan Andrew Wallace michael R.Bedford University of New England School of Environmental and Rural ScienceArmidaleNew South WalesAustralia AB Vista Woodstock CourtBlenheim RoadMarlborough Business ParkMarlboroughWiltshireEnglandUnited Kingdom Curtin University Kent StreetBentleyWestern AustraliaAustralia

This study was to examine if it is possible to accelerate sorghum digestion in broiler chickens by targeting fermentation of the *** 500 broilers(n=960,80 birds per treatment)were fed 12 sorghumsoybean meal-based dietary treatments fed as 3 phases(starter d 0 to 12,grower d 13 to 23,finisher d 24 to 35),with 8 replicate pens of 10 birds per *** half of the treatments(n=6),10%of the sorghum in the diet was directly replaced with 10%wheat bran,as a source of fermentable *** diets were supplemented with either 0,50 or 2,000 mg/kg xylo-oligosaccharides(XOS),with or without xylanase *** weight gain(BWG),feed intake(FI)and feed conversion corrected for mortality(cFCR)was determined at d 0 to 35,and male and female body weight were measured on d *** d 35,ileum and caeca samples were collected from 2 birds per pen,for determination of caecal cellulase and xylanase activity,microbiota composition and short chain fatty acid(SCFA)concentration,and ileal XOS *** with 2,000 mg/kg XOS caused increased BWG at d 0 to 35(P=0.007)and enhanced caecal propionic,valeric and succinic acid concentration(P<0.05).Wheat bran increased FI(P=0.018)and BWG(P=0.016),as well as caecal Bifidobacteria concentration(P<0.001).Ileal XOS concentration was greatest when feeding combined wheat bran,2,000 mg/kg XOS,and xylanase,resulting in increased caecal total SCFA,acetic acid and butyric acid concentration,and xylanase and cellulase activity(P<0.05).Results from this study present that feed efficiency in birds fed sorghum-based diets is improved as a consequence of supplementing with fermentable fibre,xylanase and XOS.

关键词： Xylanase Sorghum Oligosaccharides Broiler