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PP 8.2 – 00015 Retargeting cytomegalovirus-specific CD8+ cytotoxic T lymphocytes to kill HIV/SIV-infected cells via peptide-MHC Iantibody fusion proteins

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Journal of Virus Eradication 2022年 8卷

作者： B.C. Rosen M.J. Ricciardi J.J. Louw T.B. Voigt F.D. Laurino A. Yrizarry-Medina C. Panayiotou F. Zhao J. Woolf S.P. Fuchs M.A. Martins M. Farzan D.R. Burton D. Sok E.G. Rakasz R.C. Desrosiers D.I. Watkins Medical Scientist Training Program University of Miami Miller School of Medicine Miami FL USA Department of Pathology University of Miami Miller School of Medicine Miami FL USA Department of Pathology George Washington University School of Medicine Washington DC USA Department of Immunology and Microbiology The Scripps Research Institute La Jolla CA USA Department of Immunology and Microbiology UF Scripps Biomedical Research Jupiter FL USA International AIDS Vaccine Initiative (IAVI) Neutralizing Antibody Center The Scripps Research Institute La Jolla CA USA Consortium for HIV/AIDS Vaccine Development (CHAVD) The Scripps Research Institute La Jolla CA USA Ragon Institute of Massachusetts General Hospital Massachusetts Institute of Technology and Harvard University Cambridge MA USA Wisconsin National Primate Research Center University of Wisconsin-Madison Madison WI USA

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Task-Sharing for Emergency Neurosurgery: A Retrospective Cohort Study in the Philippines

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World Neurosurgery: X 2020年 6卷 100058页

作者： Robertson, Faith C. Briones, Richard Mekary, Rania A. Baticulon, Ronnie E. Jimenez, Miguel A. Leather, Andrew J.M. Broekman, Marike L.D. Park, Kee B. Gormley, William B. Lucena, Lynne L. Harvard Medical School Boston MA United States Computational Neuroscience Outcomes Center Brigham and Women's Hospital Boston MA United States Department of Surgery Bicol Medical Center Naga City Philippines MCPHS University Department of Pharmaceutical Business and Administrative Sciences School of Pharmacy Boston MA United States Departments of Anatomy and Neurosciences University of the Philippines–Philippines General Hospital Manila Philippines King's Centre for Global Health & Health Partnerships School of Population Health and Environmental Sciences Faculty of Life Sciences & Medicine King's College London London United Kingdom Leiden University Medical Center Neurosurgery Leiden Netherlands Department of Neurosurgery Haaglanden Medical Center The Hague Netherlands Global Neurosurgery Initiative Program in Global Surgery and Social Change Department of Global Health and Social Medicine Harvard Medical School Boston MA United States Department of Neurological Surgery Brigham and Women's Hospital Harvard Medical School Boston MA United States Bicol Regional Teaching and Training Hospital Legazpi Bicol Philippines

Objective: The safety and effectiveness of task-sharing (TS) in neurosurgery, delegating clinical roles to non-neurosurgeons, is not well understood. This study evaluated an ongoing TS model in the Philippines, where neurosurgical workforce deficits are compounded with a large neurotrauma burden. Methods: medical records from emergency neurosurgical admissions to 2 hospitals were reviewed (January 2015–June 2018): Bicol medical Center (BMC), a government hospital in which emergency neurosurgery is chiefly performed by general surgery residents (TS providers), and Mother Seton Hospital, an adjacent private hospital where neurosurgery consultants are the primary surgeons. Univariable and multivariable linear and logistic regression compared provider-associated outcomes. Results: Of 214 emergency neurosurgery operations, TS providers performed 95 and neurosurgeons, 119. TS patients were more often male (88.4% vs. 73.1%;P = 0.007), younger (mean age, 27.6 vs. 50.5 years;P < 0.001), and had experienced road traffic accidents (69.1% vs. 31.4%;P < 0.001). There were no significant differences between Glasgow Coma Scale (GCS) scores on admission. Provider type was not associated with mortality (neurosurgeons, 20.2%;TS, 17.9%;P = 0.68), reoperation, or pneumonia. No significant differences were observed for GCS improvement between admission and discharge or in-hospital GCS improvement, including or excluding inpatient deaths. TS patients had shorter lengths of stay (17.3 days vs. 24.4 days;coefficient, −6.67;95% confidence interval, −13.01 to −0.34;P < 0.05) and were more likely to undergo tracheostomy (odds ratio, 3.1;95% confidence interval, 1.30–7.40;P = 0.01). Conclusions: This study, one of the first to examine outcomes of neurosurgical TS, shows that a strategic TS model for emergency neurosurgery produces comparable outcomes to the local neurosurgeons. © 2019 The Authors

关键词： Global health Global neurosurgery LMIC Neurotrauma Task-sharing Task-shifting Workforce

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Corrigendum to: Local Perturbations of Cortical Excitability Propagate Differentially Through Large-Scale Functional Networks

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Cerebral cortex (New York, N.Y. : 1991) 2020年第5期30卷 3431页

作者： Zachary P Rosenthal Ryan V Raut Ping Yan Deima Koko Andrew W Kraft Leah Czerniewski Benjamin Acland Anish Mitra Lawrence H Snyder Adam Q Bauer Abraham Z Snyder Joseph P Culver Marcus E Raichle Jin-Moo Lee Medical Scientist Training Program Washington University School of Medicine St. Louis MO 63110 USA. Graduate Program of Neuroscience Washington University School of Medicine St. Louis MO 63110 USA. Department of Neurology Washington University School of Medicine St. Louis MO 63110 USA. Department of Radiology Washington University School of Medicine St. Louis MO 63110 USA. Department of Medicine Brigham and Women's Hospital Harvard Medical School Boston MA 02115 USA. Department of Biomedical Engineering Washington University School of Medicine St. Louis MO 63110 USA. Department of Neuroscience Washington University School of Medicine St. Louis MO 63110 USA. Department of Physics Washington University School of Medicine St. Louis MO 63110 USA.

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Engineering Oncolytic Vaccinia Virus to redirect Macrophages to Tumor Cells

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Advances in cell and gene therapy 2021年第2期4卷 e99-e99页

作者： Felicia Cao Phuong Nguyen Bangxing Hong Christopher DeRenzo Nino C Rainusso Tania Rodriguez Cruz Meng-Fen Wu Hao Liu Xiao-Tong Song Masataka Suzuki Lisa L Wang Jason T Yustein Stephen Gottschalk Center for Cell and Gene Therapy Texas Children's Hospital Houston Methodist Hospital Baylor College of Medicine Houston TX USA. Interdepartmental Program in Translational Biology and Molecular Medicine Baylor College of Medicine Houston TX USA. Medical Scientist Training Program Baylor College of Medicine Houston Texas USA. Texas Children's Cancer and Hematology Centers Texas Children's Hospital Baylor College of Medicine Houston TX USA. Department of Pediatrics Baylor College of Medicine Houston Texas USA. Department of Bone Marrow Transplantation and Cellular Therapy St. Jude Children's Research Hospital Memphis Tennessee USA. Biostatistics Shared Resource Dan L Duncan Cancer Center Baylor College of Medicine Houston Texas USA. Department of Biostatistics Indiana University School of Medicine Indianapolis Indiana USA.

Oncolytic virotherapy has been tested in numerous early phase clinical studies. However, the antitumor activity of oncolytic viruses thus far has been limited. Numerous strategies are being explored to enhance their antitumor activity by activating the adaptive arm of the immune system. We reasoned that it might also be possible to engineer oncolytic viruses to redirect tumor-associated macrophages to tumor cells for therapeutic benefit. We engineered an oncolytic vaccinia virus (VV) to disrupt the CD47/SIRPα interaction by expressing a chimeric molecule that consists of the ectodomain of SIRPα and the Fc domain of IgG4 (SIRPα-Fc-VV). SIRPα-Fc-VV readily replicated in tumor cells and redirected M1 as well as M2 macrophages to tumor cells . In contrast, control VVs that either encoded YFP (YFP-VV) or SIRPα (SIRPα-VV) did not. , SIRPα-Fc-VV had greater antitumor activity than YFP-VV and SIRPα-VV in an immune competent osteosarcoma model resulting in a significant survival advantage. Pretreatment with cytoxan further augmented the antitumor activity of SIRPα-Fc-VV. Thus, arming oncolytic viruses with SIRPα-Fc may present a promising strategy to enhance their antitumor activity for the virotherapy of solid tumors.

关键词： CD47 SIRPα Vaccinia virus immunotherapy osteosarcoma pediatric cancer

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Correction: Combining treatments for migraine prophylaxis: the state‑of‑the‑art

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The journal of headache and pain 2025年第1期26卷 66页

作者： Lanfranco Pellesi David Garcia-Azorin Eloisa Rubio-Beltrán Wook-Seok Ha Roberta Messina Raffaele Ornello Igor Petrusic Bianca Raffaelli Alejandro Labastida-Ramirez Ruth Ruscheweyh Claudio Tana Doga Vuralli Marta Waliszewska-Prosół Wei Wang William Wells-Gatnik Department of Public Health Clinical Pharmacology Pharmacy and Environmental Medicine University of Southern Denmark Campusvej 55 Odense 5230 Denmark. lpellesi@health.sdu.dk. Department of Medicine Toxicology and Dermatology Faculty of Medicine University of Valladolid Valladolid Spain. Department of Neurology Hospital Universitario Río Hortega Valladolid Spain. Headache Group Wolfson Sensory Pain and Regeneration Centre Institute of Psychiatry Psychology and Neuroscience King's College London London UK. Department of Neurology Yonsei University College of Medicine Seoul Korea. Neuroimaging Research Unit and Neurology Unit IRCCS San Raffaele Scientific Institute Milan Italy. Vita-Salute San Raffaele University Milan Italy. Department of Biotechnological and Applied Clinical Sciences University of L'Aquila L'Aquila Italy. Laboratory for Advanced Analysis of Neuroimages Faculty of Physical Chemistry University of Belgrade Belgrade Serbia. Department of Neurology Charité - Universitätsmedizin Berlin corporate member of Freie Universität Berlin and Humboldt-Universität Zu Berlin Berlin Germany. Clinician Scientist Program Berlin Institute of Health (BIH) at Charité - Universitätsmedizin Berlin Berlin Germany. Division of Neuroscience Faculty of Biology Medicine and Health University of Manchester Manchester UK. Department of Neurology LMU University Hospital LMU Munich Munich Germany. Center of Excellence On Headache Geriatrics Clinic Ss. Annunziata of Chieti Italy. Department of Neurology and Algology Faculty of Medicine Gazi University Ankara Türkiye. Neuropsychiatry Center Gazi University Ankara Türkiye. Neuroscience and Neurotechnology Center of Excellence (NÖROM) Gazi University Ankara Türkiye. Department of Neurology Wroclaw Medical University Wroclaw Poland. Department of Neurology Sir Run Run Shaw Hospital School of Medicine Zhejiang University Hangzhou China. Department of Neurology Headache Center Beijing Tiantan Hospital Capital

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Contrasting alterations between cortical and subcortical myelin across age, AD diagnosis, and amyloid and tau pathology as assessed by quantitative R1 mapping

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Alzheimer's & Dementia 2020年第S5期16卷

作者： Akshay Kohli Steven Kecskemeti Nagesh Adluru Erin M Jonaitis Sanjay Asthana Kaj Blennow Henrik Zetterberg Cynthia M Carlsson Andrew L Alexander Sterling C Johnson Barbara B Bendlin Wisconsin Alzheimer's Disease Research Center Madison WI USA Neuroscience Training Program University of Wisconsin School of Medicine and Public Health Madison WI USA Department of Medical Physics University of Wisconsin - Madison Madison WI USA The Wisconsin Alzheimer's Institute University of Wisconsin Madison WI USA The Sahlgrenska Academy at the University of Gothenburg Mölndal Sweden

Background Accumulation of pathology in cortical tissue are early pathological hallmarks of Alzheimer’s disease. High resolution T1w/T2w ratio maps from structural MRI may reflect tissue microstructure with sensitivity to myelin, iron, and dendritic density. Few studies have investigated this in AD with conflicting reports of directionality of T1w/T2w ratios in individuals with AD diagnosis and pathology. However, these ratios will be sensitive to pulse sequences, protocols and bias field inhomogeneities, limiting their utility in clinical and research contexts. Here we employ R1 (=1/T1) relaxometry mapping, a quantitative imaging measure that is sensitive to myelin, to investigate relationships between cortical and subcortical tissue microstructure, age, AD diagnosis, and amyloid and tau pathology. Method Participants from the Wisconsin Alzheimer’s Disease Research Center and Wisconsin Registry for Alzheimer’s Prevention underwent 3T MRI with whole-brain, 1mm isotropic MPnRAGE T1 relaxometry with motion correction (Kecskemeti et al., 2016) (N=605/CN, 39/AD; age = 65.49 +/- 7.89 yrs) with a subset undergoing lumbar puncture for CSF Aß42/Tau biomarker classification (N = 141/A-T-, 26/A+T-, 22/A-T+, 18/A+T+). T1-weighted images were processed using ANTS and CAT12, and transformation warps were applied to produce subcortical R1 maps in MNI space (6mm smoothing) and cortical R1 surface meshes (164k mesh, 5mm smoothing). Vertex-wise (GM) and voxel-wise (WM) ANCOVA were performed (p<0.05 FWE corrected). Covariates included age, sex, study protocol, and AD diagnosis in model 1, and age, sex, years between CSF collection and MRI, study protocol, and A/T biomarker group in model 2. Result Significant associations between R1 and age, clinical AD diagnosis, and A/T pathology were found (Figure 1A-C). Post-hoc tests revealed increased R1 due to A/T pathology driven by A+T+ individuals. In contrast, significant widespread decreases in subcortical R1 were found with age and AD di

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Evolutionary optimization of nondiffracting helicon beams

Evolutionary optimization of nondiffracting helicon beams

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Frontiers in Optics, FiO 2017

作者： Schroeder, Bryce Zhu, Zhen H. Guo, Changliang Jia, Shu Department of Biomedical Engineering Stony Brook University Stony BrookNY11794 United States Medical Scientist Training Program Stony Brook University Stony BrookNY11794 United States

We optimized helicon-like beams in a high resolution imaging sytem with an evolutionary algorithm, achieving a tight intensity profile while largely maintaining self-rotation and nondiffraction. The method promises wi... 详细信息

ISBN: (纸本)9781943580330

关键词： Optimization

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Dynamic transcriptomic m6A decoration: writers, erasers, readers and functions in RNA metabolism

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细胞研究（英文版） 2018年第6期28卷 616-624页

作者： Ying Yang Phillip J.Hsu Yu-Sheng Chen Yun-Gui Yang CAS Key Laboratory of Genomic and Precision Medicine Collaborative Innovation Center of Genetics and Development College of Future Technology Beijing Institute of Genomics Chinese Academy of Sciences Beijing 100101 China University of Chinese Academy of Sciences Beijing 100049 China Institute of Stem Cell and Regeneration Chinese Academy of Sciences Beijing 100101 China Department of Chemistry and Institute for Biophysical Dynamics Howard Hughes Medical Institute The University of Chicago Chicago IL 60637 USA Medical Scientist Training Program/Committee on Immunology The University of Chicago Chicago IL 60637 USA CAS Key Laboratory of Genomic and Precision Medicine Collaborative Innovation Center of Genetics and Development College of Future Technology Beijing Institute of Genomics Chinese Academy of Sciences Beijing 100101 China University of Chinese Academy of Sciences Beijing 100049 China

N6-methyladenosine (m6A) is a chemical modification present in multiple RNA species,being most abundant in *** on enzymes or factors that catalyze,recognize,and remove m6A have revealed its comprehensive roles in almost every aspect of mRNA metabolism,as well as in a variety of physiological *** review describes the current understanding of the m6A modification,particularly the functions of its writers,erasers,readers in RNA metabolism,with an emphasis on its role in regulating the isoform dosage of mRNAs.

关键词： Methylation analysis RNA modification

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Embracing Monogenic Parkinson's Disease: The MJFF Global Genetic PD Cohort

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Movement disorders : official journal of the Movement Disorder Society 2023年第2期38卷 286-303页

作者： Eva-Juliane Vollstedt Susen Schaake Katja Lohmann Shalini Padmanabhan Alexis Brice Suzanne Lesage Christelle Tesson Marie Vidailhet Isabel Wurster Faycel Hentati Anat Mirelman Nir Giladi Karen Marder Cheryl Waters Stanley Fahn Meike Kasten Norbert Brüggemann Max Borsche Tatiana Foroud Eduardo Tolosa Alicia Garrido Grazia Annesi Monica Gagliardi Maria Bozi Leonidas Stefanis Joaquim J Ferreira Leonor Correia Guedes Micol Avenali Simona Petrucci Lorraine Clark Ekaterina Y Fedotova Natalya Y Abramycheva Victoria Alvarez Manuel Menéndez-González Silvia Jesús Maestre Pilar Gómez-Garre Pablo Mir Andrea Carmine Belin Caroline Ran Chin-Hsien Lin Ming-Che Kuo David Crosiers Zbigniew K Wszolek Owen A Ross Joseph Jankovic Kenya Nishioka Manabu Funayama Jordi Clarimon Caroline H Williams-Gray Marta Camacho Mario Cornejo-Olivas Luis Torres-Ramirez Yih-Ru Wu Guey-Jen Lee-Chen Ana Morgadinho Teeratorn Pulkes Pichet Termsarasab Daniela Berg Gregor Kuhlenbäumer Andrea A Kühn Friederike Borngräber Giuseppe de Michele Anna De Rosa Alexander Zimprich Andreas Puschmann George D Mellick Jolanta Dorszewska Jonathan Carr Rosangela Ferese Stefano Gambardella Bruce Chase Katerina Markopoulou Wataru Satake Tatsushi Toda Malco Rossi Marcelo Merello Timothy Lynch Diana A Olszewska Shen-Yang Lim Azlina Ahmad-Annuar Ai Huey Tan Bashayer Al-Mubarak Hasmet Hanagasi Dariusz Koziorowski Sibel Ertan Gençer Genç Patricia de Carvalho Aguiar Melinda Barkhuizen Marcia M G Pimentel Rachel Saunders-Pullman Bart van de Warrenburg Susan Bressman Mathias Toft Silke Appel-Cresswell Anthony E Lang Matej Skorvanek Agnita J W Boon Rejko Krüger Esther M Sammler Vitor Tumas Bao-Rong Zhang Gaetan Garraux Sun Ju Chung Yun Joong Kim Juliane Winkelmann Carolyn M Sue Eng-King Tan Joana Damásio Péter Klivényi Vladimir S Kostic David Arkadir Mika Martikainen Vanderci Borges Jens Michael Hertz Laura Brighina Mariana Spitz Oksana Suchowersky Olaf Riess Parimal Das Brit Mollenhauer Emilia M Gatto Maria Skaalum Petersen Nobutaka Hattori Ruey-Meei Wu Sergey N Illarioshkin Enz Institute of Neurogenetics University of Lübeck Lübeck Germany. Research Programs The Michael J. Fox Foundation for Parkinson's Research New York New York USA. Department of Neurology Sorbonne University Paris Brain Institute - ICM Inserm CNRS Assistance Publique Hôpitaux de Paris Pitié-Salpêtrière Hospital Paris France. Sorbonne University Paris Brain Institute - ICM Inserm CNRS Paris France. Department of Neurodegenerative Diseases University of Tuebingen Tuebingen Baden Wuerttemberg Germany Hertie Institute for Clinical Brain Research and German Centre for Neurodegenerative Diseases Tuebingen Germany. Mongi Ben Hmida National Institute of Neurology Tunis Tunisia. Laboratory of Early Markers of Neurodegeneration Neurological Institute Tel-Aviv Medical Center Tel-Aviv Israel Sackler School of Medicine Tel-Aviv University Tel-Aviv Israel Sagol School of Neuroscience Tel-Aviv University Tel-Aviv Israel. Neurological Institute Tel-Aviv Medical Center Tel-Aviv Israel Sackler School of Medicine Sagol School of Neuroscience Tel-Aviv University Tel-Aviv Israel. Department of Neurology Taub Institute for Alzheimer's Disease and the Aging Brain Columbia University New York New York USA. Department of Neurology Columbia University New York New York USA. Department of Psychiatry and Psychotherapy and Institute of Neurogenetics University of Lübeck Lübeck Germany. Department of Neurology and Institute of Neurogenetics University of Lübeck Lübeck Germany. Department of Medical and Molecular Genetics Indiana University School of Medicine Indianapolis Indiana USA. Parkinson Disease and Movement Disorders Unit Neurology Service Hospital Clínic de Barcelona Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) University of Barcelona (UB) Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED:CB06/05/0018-ISCIII) Barcelona Spain. Institute of Biomedical Research and Innovation National Research Council Cosenza

BACKGROUND:As gene-targeted therapies are increasingly being developed for Parkinson's disease (PD), identifying and characterizing carriers of specific genetic pathogenic variants is imperative. Only a small fraction of the estimated number of subjects with monogenic PD worldwide are currently represented in the literature and availability of clinical data and clinical trial-ready cohorts is limited. OBJECTIVE:The objectives are to (1) establish an international cohort of affected and unaffected individuals with PD-linked variants; (2) provide harmonized and quality-controlled clinical characterization data for each included individual; and (3) further promote collaboration of researchers in the field of monogenic PD. METHODS:We conducted a worldwide, systematic online survey to collect individual-level data on individuals with PD-linked variants in SNCA, LRRK2, VPS35, PRKN, PINK1, DJ-1, as well as selected pathogenic and risk variants in GBA and corresponding demographic, clinical, and genetic data. All registered cases underwent thorough quality checks, and pathogenicity scoring of the variants and genotype-phenotype relationships were analyzed. RESULTS:We collected 3888 variant carriers for our analyses, reported by 92 centers (42 countries) worldwide. Of the included individuals, 3185 had a diagnosis of PD (ie, 1306 LRRK2, 115 SNCA, 23 VPS35, 429 PRKN, 75 PINK1, 13 DJ-1, and 1224 GBA) and 703 were unaffected (ie, 328 LRRK2, 32 SNCA, 3 VPS35, 1 PRKN, 1 PINK1, and 338 GBA). In total, we identified 269 different pathogenic variants; 1322 individuals in our cohort (34%) were indicated as not previously published. CONCLUSIONS:Within the MJFF Global Genetic PD Study Group, we (1) established the largest international cohort of affected and unaffected individuals carrying PD-linked variants; (2) provide harmonized and quality-controlled clinical and genetic data for each included individual; (3) promote collaboration in the field of genetic PD with a view toward clini

关键词： Parkinson's disease monogenic PD

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TMEM106B PROTECTIVE VARIANT ASSOCIATED WITH INCREASED NEURONAL PROPORTION

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Alzheimer's & Dementia 2019年第7期15卷 P974-P975页

作者： Zeran Li Fabiana H.G. Farias Umber Dube Jorge L. Del-Aguila Victoria Fernandez Laura Ibanez John P. Budde Fengxian Wang Allison M. Lake Yuetiva Robles James Perez Chengran Yang Kathie A. Mihindukulasuriya Joseph Bradley Richard Davenport Kristy Bergmann Joseph D. Dougherty Oscar Harari Carlos Cruchaga Washington University School of Medicine St Louis MO USA Hope Center for Neurological Disorders St Louis MO USA Medical Scientist Training Program Washington University School of Medicine Saint Louis MO USA Vanderbilt University Medical Scientist Training Program Nashville TN USA University of Wisconsin-Madison Madison WI USA Hope Center for Neurological Disorders Washington University School of Medicine St. Louis MO USA Washington University School of Medicine St. Louis MO USA

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