“Entropy, mutual information, and systematic measures of structured spiking neural networks” (2020) Journal of Theoretical Biology
Entropy, mutual information, and systematic measures of structured spiking neural networks
(2020) Journal of Theoretical Biology, 501, art. no. 110310, .
Li, W.a , Li, Y.b
a Department of Mathematics and Statistics, Washington University, St. Louis, MO 63130, United States
b Department of Mathematics and Statistics, University of Massachusetts Amherst, Amherst, MA 01002, United States
Abstract
The aim of this paper is to investigate various information-theoretic measures, including entropy, mutual information, and some systematic measures that are based on mutual information, for a class of structured spiking neuronal networks. In order to analyze and compute these information-theoretic measures for large networks, we coarse-grained the data by ignoring the order of spikes that fall into the same small time bin. The resultant coarse-grained entropy mainly captures the information contained in the rhythm produced by a local population of the network. We first show that these information theoretical measures are well-defined and computable by proving stochastic stability and the law of large numbers. Then we use three neuronal network examples, from simple to complex, to investigate these information-theoretic measures. Several analytical and computational results about properties of these information-theoretic measures are given. © 2020 Elsevier Ltd
Author Keywords
Complexity; Degeneracy; Entropy; Mutual information; Neural field models
Document Type: Article
Publication Stage: Final
Source: Scopus
“Densitometric Profiles of Optic Disc Hemorrhages in the Ocular Hypertension Treatment Study” (2020) American Journal of Ophthalmology
Densitometric Profiles of Optic Disc Hemorrhages in the Ocular Hypertension Treatment Study
(2020) American Journal of Ophthalmology, 217, pp. 10-19.
Cousins, C.C.a , Pan, B.X.a , Chou, J.C.a , Shen, L.Q.a , Gordon, M.O.b , Kass, M.A.b , Ritch, R.c , Pasquale, L.R.c
a Department of Ophthalmology, Massachusetts Eye and Ear, Boston, MA, United States
b Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO, United States
c Einhorn Clinical Research Center, New York Eye and Ear Infirmary of Mount Sinai, New York, NY, United States
Abstract
Purpose: The origin of blood in glaucoma-related disc hemorrhages (DH) remains unknown. A prior clinic-based study of primary open-angle glaucoma (POAG)-related DH showed that they had grayscale pixel intensities more similar to blood from retinal macroaneurysms and adjacent retinal arterioles than to blood from retinal vein occlusions or adjacent retinal venules, suggesting an arterial source. Here we assessed the densitometric profile of DH from fundus photographs in the Ocular Hypertension Treatment Study (OHTS). Design: Retrospective cross-sectional study of prospectively collected images. Methods: Stereo disc photographs of 161 DH events from 83 OHTS participants (mean age [standard deviation (SD)]: 65.6 [9.2] years; 46.6% female; 13.0% black race) were imported into ImageJ to measure densitometry differences (adjacent arterioles minus DH [ΔA] or venules minus DH [ΔV]). Their size as percentage of disc area, ratio of length to midpoint width, and location relative to the disc margin were also analyzed. We performed t tests to compare ΔA and ΔV, analysis of variance to compare ΔA and ΔV across DH recurrent events, and multivariable linear regression to identify determinants of ΔA and ΔV. Results: Mean (SD) ΔA and ΔV were −2.2 (8.7) and −11.4 (9.7) pixel intensity units, respectively (P <.001). ΔA and ΔV each did not differ significantly across recurrence of DH (P ≥.92) or between DH events with and without POAG (P ≥.26). Conclusions: OHTS DH had densitometric measurements more similar in magnitude to adjacent arterioles than venules, supporting an arterial origin for DH. Vascular dysregulation may contribute to disc hemorrhage formation in ocular hypertension. © 2020 Elsevier Inc.
Document Type: Article
Publication Stage: Final
Source: Scopus
“Searching for autoimmune encephalitis: Beware of normal CSF” (2020) Journal of Neuroimmunology
Searching for autoimmune encephalitis: Beware of normal CSF
(2020) Journal of Neuroimmunology, 345, art. no. 577285, .
Hébert, J.a , Gros, P.a , Lapointe, S.a b , Amtashar, F.S.c , Steriade, C.d , Maurice, C.a b , Wennberg, R.A.a b , Day, G.S.e , Tang-Wai, D.F.a b
a University of Toronto, Division of Neurology, Canada
b University Health Network, Toronto, Canada
c Washington University School of Medicine, Dept of NeurologyMO, United States
d New York University Langone Comprehensive Epilepsy CenterNY, United States
e Mayo Clinic Florida, Department of Neurology, Jacksonville, FL, United States
Abstract
Objective: To determine the prevalence of cerebrospinal fluid (CSF) markers associated with inflammation (i.e., elevated white blood cell count, protein concentration, and CSF-specific oligoclonal bands) in patients with early active autoimmune encephalitis (AE). Methods: CSF characteristics, including WBC count, protein concentration, and oligoclonal banding, were analyzed in patients diagnosed with AE at two tertiary care centers. Results: Ninety-five patients were included in the study. CSF white blood cell counts and protein levels were within normal limits for 27% (CI95%: 19–37) of patients with AE. When results of oligoclonal banding were added, 14% (CI95%: 6–16) of patients with AE had “normal” CSF. The median CSF white blood cell count was 8 cells/mm3 (range: 0–544) and the median CSF protein concentration was 0.42 g/L (range: 0.15–3.92). Conclusions: White blood cell counts and protein levels were within normal limits in the CSF of a substantial proportion of patients with early active AE. Inclusion of CSF oligoclonal banding identified a higher proportion of patients with an inflammatory CSF profile, especially when CSF was sampled early in the disease process. © 2020 Elsevier B.V.
Author Keywords
Autoimmune diseases; Autoimmune encephalitis; Cerebrospinal fluid; Diagnostic studies; Encephalitis
Document Type: Article
Publication Stage: Final
Source: Scopus
“Serum neurofilament light chain levels are associated with white matter integrity in autosomal dominant Alzheimer’s disease” (2020) Neurobiology of Disease
Serum neurofilament light chain levels are associated with white matter integrity in autosomal dominant Alzheimer’s disease
(2020) Neurobiology of Disease, 142, art. no. 104960, .
Schultz, S.A.a , Strain, J.F.a , Adedokun, A.a , Wang, Q.a , Preische, O.b c , Kuhle, J.d , Flores, S.a , Keefe, S.a , Dincer, A.a , Ances, B.M.a , Berman, S.B.e , Brickman, A.M.f , Cash, D.M.g , Chhatwal, J.h , Cruchaga, C.a , Ewers, M.i , Fox, N.N.j , Ghetti, B.k , Goate, A.l , Graff-Radford, N.R.m x , Hassenstab, J.J.a , Hornbeck, R.a , Jack, C., Jrn , Johnson, K.h , Joseph-Mathurin, N.a , Karch, C.M.a , Koeppe, R.A.o , Lee, A.K.W.p , Levin, J.q y z , Masters, C.r , McDade, E.a , Perrin, R.J.a , Rowe, C.C.s , Salloway, S.t , Saykin, A.J.u , Sperling, R.h , Su, Y.v , Villemagne, V.L.s , Vöglein, J.q y z , Weiner, M.w , Xiong, C.a , Fagan, A.M.a , Morris, J.C.a , Bateman, R.J.a , Benzinger, T.L.S.a , Jucker, M.b c , Gordon, B.A.a , for the Dominantly Inherited Alzheimer Networkaa
a Department of Radiology, Department of Neurology, Department of Pathology & Immunology, Department of Psychiatry, Division of Biostatistics, Washington University in St. Louis School of Medicine, Saint Louis, MO, United States
b DZNE-German Center for Neurodegenerative Diseases, Tübingen, D-72076, Germany
c Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, D-72076, Germany
d Neurologic Clinic and Policlinic, Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Basel, CH-4031, Switzerland
e Alzheimer Disease Research Center and Pittsburgh Institute for Neurodegenerative Diseases, University of Pittsburgh School of Medicine, 4-West Montefiore University Hospital, 200 Lothrop Street, Pittsburgh, PA, United States
f Department of Neurology, Columbia University Medical Center, New York, NY, United States
g Dementia Research Centre, UCL Queen Square Institute of Neurology, London, United Kingdom
h Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
i Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität LMU, Munich, Germany
j Department of Neurodegenerative Disease, Dementia Research Centre, UCL Institute of Neurology, London, United Kingdom
k Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, United States
l Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, United States
m Department of Neuroscience, Mayo Clinic, Jacksonville, FL, United States
n Department of Radiology, Mayo Clinic, Rochester, MN, United States
o Department of Radiology, University of Michigan, Ann Arbor, United States
p Department of Psychiatry and Human Behavior, Butler Hospital, Warren Alpert Medical School, Brown University, Providence, RI, United States
q German Center for Neurodegenerative Diseases (DZNE), Munich, Germany
r The Florey Institute, University of Melbourne, Parkville, VIC, Australia
s Department of Molecular Imaging & Therapy, Austin Health, Melbourne, Australia
t Department of Neurology, Butler Hospital, Warren Alpert Medical School, Brown University, Providence, RI, United States
u Department of Neurology, Department of Radiology, Indiana University School of Medicine, Indianapolis, IN, United States
v Banner Alzheimer’s Institute, Phoenix, AZ, United States
w Departments of Psychiatry, Radiology, Medicine, and Neurology, University of California at San Francisco, San Francisco, CA, United States
x Department of Neurology, Mayo Clinic, Jacksonville, FL, United States
y Department of Neurology, Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany
z Munich Cluster for Systems Neurology (SyNergy), Germany
Abstract
Neurofilament light chain (NfL) is a protein that is selectively expressed in neurons. Increased levels of NfL measured in either cerebrospinal fluid or blood is thought to be a biomarker of neuronal damage in neurodegenerative diseases. However, there have been limited investigations relating NfL to the concurrent measures of white matter (WM) decline that it should reflect. White matter damage is a common feature of Alzheimer’s disease. We hypothesized that serum levels of NfL would associate with WM lesion volume and diffusion tensor imaging (DTI) metrics cross-sectionally in 117 autosomal dominant mutation carriers (MC) compared to 84 non-carrier (NC) familial controls as well as in a subset (N = 41) of MC with longitudinal NfL and MRI data. In MC, elevated cross-sectional NfL was positively associated with WM hyperintensity lesion volume, mean diffusivity, radial diffusivity, and axial diffusivity and negatively with fractional anisotropy. Greater change in NfL levels in MC was associated with larger changes in fractional anisotropy, mean diffusivity, and radial diffusivity, all indicative of reduced WM integrity. There were no relationships with NfL in NC. Our results demonstrate that blood-based NfL levels reflect WM integrity and supports the view that blood levels of NfL are predictive of WM damage in the brain. This is a critical result in improving the interpretability of NfL as a marker of brain integrity, and for validating this emerging biomarker for future use in clinical and research settings across multiple neurodegenerative diseases. © 2020
Author Keywords
Alzheimer’s disease; Blood-based biomarkers; Neurodegeneration; Neurofilament; Neuroimaging; White matter
Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“Prospects of Photo- and Thermoacoustic Imaging in Neurosurgery” (2020) Neurosurgery
Prospects of Photo- and Thermoacoustic Imaging in Neurosurgery
(2020) Neurosurgery, 87 (1), pp. 11-24.
Ravina, K.a , Lin, L.b c , Liu, C.Y.a d e f , Thomas, D.g , Hasson, D.h , Wang, L.V.b , Russin, J.J.a d
a Neurorestoration Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, Mexico
b Caltech Optical Imaging Laboratory, rew and Peggy Cherng Department of Medical Engineering, Department of Electrical Engineering, California Institute of Technology, Pasadena, CA, United States
c Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO, United States
d Department of Neurological Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, Mexico
e Department of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, United States
f Tianqiao and Chrissy Chen Brain-machine Interface Center, California Institute of Technology, Pasadena, CA, United States
g Department of Surgery, University of California Davis, Davis, CA, United States
h Division of Critical Care Medicine, Cincinnati Children’s Hospital, Cincinnati, OH, United States
Abstract
The evolution of neurosurgery has been, and continues to be, closely associated with innovations in technology. Modern neurosurgery is wed to imaging technology and the future promises even more dependence on anatomic and, perhaps more importantly, functional imaging. The photoacoustic phenomenon was described nearly 140 yr ago; however, biomedical applications for this technology have only recently received significant attention. Light-based photoacoustic and microwave-based thermoacoustic technologies represent novel biomedical imaging modalities with broad application potential within and beyond neurosurgery. These technologies offer excellent imaging resolution while generally considered safer, more portable, versatile, and convenient than current imaging technologies. In this review, we summarize the current state of knowledge regarding photoacoustic and thermoacoustic imaging and their potential impact on the field of neurosurgery. Copyright © 2019 by the Congress of Neurological Surgeons.
Author Keywords
Functional imaging; Molecular imaging; Neurosurgical imaging; Photoacoustics; Theranostics; Thermoacoustics
Document Type: Article
Publication Stage: Final
Source: Scopus
“PTSD improvement and incident cardiovascular disease in more than 1000 veterans” (2020) Journal of Psychosomatic Research
PTSD improvement and incident cardiovascular disease in more than 1000 veterans
(2020) Journal of Psychosomatic Research, 134, p. 110128.
Scherrer, J.F.a , Salas, J.a , Schneider, F.D.b , Friedman, M.J.c , van den Berk-Clark, C.d , Chard, K.M.e , Norman, S.B.f , Lustman, P.J.g , Tuerk, P.h , Schnurr, P.P.c , Cohen, B.E.i
a Department of Family and Community Medicine, Saint Louis University School of Medicine, St. Louis, MO 63104, United States of America; Harry S. Truman Veterans Administration Medical Center, Columbia, MO, United States of America
b Department of Family and Community Medicine, University of Texas Southwestern, TX, Dallas, United States
c National Center for PTSD and Department of Psychiatry, Geisel School of Medicine at Dartmouth, NHHanover, United States
d Department of Family and Community Medicine, Saint Louis University School of Medicine, St. Louis, MO 63104, United States of America
e University of Cincinnati, Trauma Recovery Center Cincinnati VAMC and Department of Psychiatry and Behavioral Neuroscience, OH, United States
f National Center for PTSD and Department of Psychiatry, University of California San Diego, United States
g Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States of America; The Bell Street Clinic Opioid Addiction Treatment Program, VA St. Louis Health Care System, St. Louis, MO, United States of America
h Department of Human Services, University of Virginia, VA, Sheila C. Johnson Center for Clinical Services, Charlottesville, United States
i Department of Medicine, University of California San Francisco School of Medicine and San Francisco VAMC, CA, United States
Abstract
BACKGROUND: Posttraumatic stress disorder (PTSD) is associated with increased risk for cardiovascular disease (CVD). Whether clinically meaningful PTSD improvement is associated with lowering CVD risk is unknown. METHODS: Eligible patients (n = 1079), were 30-70 years old, diagnosed with PTSD and used Veterans Health Affairs PTSD specialty clinics. Patients had a PTSD Checklist score (PCL) ≥ 50 between Fiscal Year (FY) 2008 and FY2012 and a second PCL score within 12 months and at least 8 weeks after the first PCL ≥ 50. Clinically meaningful PTSD improvement was defined by ≥20 point PCL decrease between the first and second PCL score. Patients were free of CVD diagnoses for 1 year prior to index. Index date was 12 months following the first PCL. Follow-up continued to FY2015. Cox proportional hazard models estimated the association between clinically meaningful PTSD improvement and incident CVD and incident ischemic heart disease (IHD). Sensitivity analysis stratified by age group (30-49 vs. 50-70 years) and depression. Confounding was controlled using propensity scores and inverse probability of exposure weighting. RESULTS: Patients were 48.9 ± 10.9 years of age on average, 83.3% male, 60.1% white, and 29.5% black. After controlling for confounding, patients with vs. without PTSD improvement did not differ in CVD risk (HR = 1.08; 95%CI: 0.72-1.63). Results did not change after stratifying by age group or depression status. Results were similar for incident IHD. CONCLUSIONS: Over a 2-7 year follow-up, we did not find an association between clinically meaningful PTSD improvement and incident CVD. Additional research is needed using longer follow-up. Copyright © 2020 Elsevier Inc. All rights reserved.
Author Keywords
Cardiovascular disease; Epidemiology; Posttraumatic stress disorder; Psychotherapy; Veterans
Document Type: Article
Publication Stage: Final
Source: Scopus
“Neurofibromatosis type 1-related tumours in paediatrics: an evolving treatment landscape” (2020) The Lancet Child and Adolescent Health
Neurofibromatosis type 1-related tumours in paediatrics: an evolving treatment landscape
(2020) The Lancet Child and Adolescent Health, 4 (7), pp. 488-490.
Armstrong, A.E.a , Brossier, N.M.a , Hirbe, A.C.b
a Division of Hematology and Oncology, Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110, United States
b Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, United States
Document Type: Note
Publication Stage: Final
Source: Scopus
“Overseeing Memory Circuits by NFIA: New Face In Astrocytes” (2020) Neuron
Overseeing Memory Circuits by NFIA: New Face In Astrocytes
(2020) Neuron, 106 (6), pp. 878-880.
Li, Q.a b c
a Department of Neuroscience, Washington University School of Medicine, St. Louis, MO 63110, United States
b Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110, United States
c Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO 63110, United States
Abstract
Astrocytes are heterogeneous controlling numerous aspects of brain function. In this issue of Neuron, Huang et al. (2020) uncover a novel role of NFIA, which regulates unique properties of adult hippocampal astrocytes via region-specific DNA binding, thereby modulating the plasticity of local circuits. Astrocytes are heterogeneous controlling numerous aspects of brain function. In this issue of Neuron, Huang et al. (2020) uncover a novel role of NFIA, which regulates unique properties of adult hippocampal astrocytes via region-specific DNA binding, thereby modulating the plasticity of local circuits. © 2020 Elsevier Inc.
Document Type: Article
Publication Stage: Final
Source: Scopus
“The neurons that mistook a hat for a face” (2020) eLife
The neurons that mistook a hat for a face
(2020) eLife, 9, .
Arcaro, M.J.a , Ponce, C.b , Livingstone, M.c
a Department of Psychology, University of Pennsylvania, Philadelphia, United States
b Department of Neuroscience, Washington University in St. Louis, St. Louis, United States
c Department of Neurobiology, Harvard Medical School, Boston, United States
Abstract
Despite evidence that context promotes the visual recognition of objects, decades of research have led to the pervasive notion that the object processing pathway in primate cortex consists of multiple areas that each process the intrinsic features of a few particular categories (e.g. faces, bodies, hands, objects, and scenes). Here we report that such category-selective neurons do not in fact code individual categories in isolation but are also sensitive to object relationships that reflect statistical regularities of the experienced environment. We show by direct neuronal recording that face-selective neurons respond not just to an image of a face, but also to parts of an image where contextual cues-for example a body-indicate a face ought to be, even if what is there is not a face. © 2020, Arcaro et al.
Author Keywords
bodies; faces; inferotemporal cortex; macaques; neuroscience; object relationships; regularities; rhesus macaque
Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“Hemolytic anemia associated with dapsone PCP prophylaxis in GBM patients with normal G6PD activity” (2020) Neuro-Oncology
Hemolytic anemia associated with dapsone PCP prophylaxis in GBM patients with normal G6PD activity
(2020) Neuro-Oncology, 22 (6), pp. 892-893.
Rogers, L.R.a , Oppelt, P.b , Nayak, L.c
a Department of Neurology, University Hospitals Cleveland Medical Center, Cleveland, OH, United States
b Washington University, St Louis Siteman Cancer Center, St PetersMO
c Seidman Cancer Center, University Hospitals Cleveland Medical Center, Cleveland, OH, United States
Author Keywords
dapsone; glioblastoma; hemolytic anemia
Document Type: Article
Publication Stage: Final
Source: Scopus
“AI-based prognostic imaging biomarkers for precision neuro-oncology: the ReSPOND consortium” (2020) Neuro-Oncology
AI-based prognostic imaging biomarkers for precision neuro-oncology: the ReSPOND consortium
(2020) Neuro-Oncology, 22 (6), pp. 886-888.
Davatzikos, C.a b , Barnholtz-Sloan, J.S.c , Bakas, S.a b d , Colen, R.e , Mahajan, A.f , Quintero, C.B.g , Capellades Font, J.h , Puig, J.i , Jain, R.j , Sloan, A.E.k , Badve, C.l , Marcus, D.S.m , Seong Choi, Y.n o , Lee, S.-K.n , Chang, J.H.p , Poisson, L.M.q , Griffith, B.r , Dicker, A.P.s , Flanders, A.E.t , Booth, T.C.u , Rathore, S.a b , Akbari, H.a b , Sako, C.a b , Bilello, M.a b , Shukla, G.a b v , Fathi Kazerooni, A.a b , Brem, S.d , Lustig, R.v , Mohan, S.b , Bagley, S.w , Nasrallah, M.x , O’Rourke, D.M.d
a Center for Biomedical Image Computing and Analytics, University of Pennsylvania, Philadelphia, PA, United States
b Department of Radiology, University of Pennsylvania, Philadelphia, PA, United States
c Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, United States
d Department of Neurosurgery, University of Pennsylvania, Philadelphia, PA, United States
e Department of Radiology, University of Pittsburgh, Pittsburgh, PA, United States
f Department of Radiodiagnosis & Imaging, Tata Memorial Hospital
g Catalan Institute of Oncology, Barcelona, Spain
h Hospital del Mar, Barcelona, Spain
i Department of Radiology, University of Manitoba WinnipegMB, Canada
j Department of Radiology, New York University
k Department of Neurosurgery, Case Western Reserve University, Cleveland, OH, United States
l Department of Radiology, Case Western Reserve University, Cleveland, OH, United States
m Department of Radiology, Washington University, St. Louis, MO, United States
n Department of Radiology and Research Institute of Radiological Science, Yonsei University College of MedicineSeoul, South Korea
o Department of Diagnostic Radiology, Singapore General Hospital, Singapore
p Department of Neurosurgery, Yonsei University CollegeSeoul, South Korea
q Department of Public Health Sciences, Henry Ford Health System, Detroit, MI, United States
r Department of Radiology, Henry Ford Health System, Detroit, MI, United States
s Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, PA, United States
t Department of Radiology, Thomas Jefferson University, Philadelphia, PA, United States
u School of Biomedical Engineering & Imaging Sciences, King’s College London, London, United Kingdom
v Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA, United States
w Department of Medicine, University of Pennsylvania, Philadelphia, PA, United States
x Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, United States
Document Type: Article
Publication Stage: Final
Source: Scopus
“Implications of new understandings of gliomas in children and adults with NF1: report of a consensus conference” (2020) Neuro-Oncology
Implications of new understandings of gliomas in children and adults with NF1: report of a consensus conference
(2020) Neuro-Oncology, 22 (6), pp. 773-784. Cited 2 times.
Packer, R.J.a b , Iavarone, A.c , Jones, D.T.W.d , Blakeley, J.O.e , Bouffet, E.f , Fisher, M.J.g , Hwang, E.b , Hawkins, C.f , Kilburn, L.b , MacDonald, T.h , Pfister, S.M.d , Rood, B.b , Rodriguez, F.J.i , Tabori, U.f , Ramaswamy, V.f , Zhu, Y.b , Fangusaro, J.h , Johnston, S.A.j , Gutmann, D.H.k
a Center for Neuroscience and Behavioral Medicine, DCWA, United States
b Gilbert Family Neurofibromatosis Institute, Brain Tumor Institute, Children’s National Hospital, DCWA, United States
c Departments of Neurology and Pathology Institute for Cancer Genetics Columbia University Medical CenterNY, United States
d Division of Pediatric Neuro-Oncology German Cancer Research Center Hopp Children’s Cancer Center Heidelberg, Germany
e Departments of Neurology; Oncology; Neurosurgery, Baltimore, Maryland, USA
f Pediatric Neuro-Oncology Program; Research Institute; and The Arthur and Sonia Labatt; Brain Tumor Research Centre, Hospital for Sick Children, Toronto, Canada
g Department of Pediatric Oncology; Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
h Department of Pediatrics; Emory University School of Medicine, Atlanta, Georgia, USA
i Pathology; The Johns Hopkins School of Medicine, Baltimore, Maryland, USA
j Center for Innovations in Medicine; Biodesign Institute; Arizona State University, Tempe, Arizona, USA
k Department of Neurology; Washington University, St Louis, Missouri, USA
Abstract
Gliomas are the most common primary central nervous system tumors occurring in children and adults with neurofibromatosis type 1 (NF1). Over the past decade, discoveries of the molecular basis of low-grade gliomas (LGGs) have led to new approaches for diagnosis and treatments. However, these new understandings have not been fully applied to the management of NF1-associated gliomas. A consensus panel consisting of experts in NF1 and gliomas was convened to review the current molecular knowledge of NF1-associated low-grade “transformed” and high-grade gliomas; insights gained from mouse models of NF1-LGGs; challenges in diagnosing and treating older patients with NF1-associated gliomas; and advances in molecularly targeted treatment and potential immunologic treatment of these tumors. Next steps are recommended to advance the management and outcomes for NF1-associated gliomas. © The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.
Author Keywords
gliomas; immunotherapy; molecular-targeted therapy; neurofibromatosis type 1; pilocytic astrocytomas
Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“Fractures in the prodromal period of Parkinson disease” (2020) Neurology
Fractures in the prodromal period of Parkinson disease
(2020) Neurology, 94 (23), pp. e2448-e2456.
Camacho-Soto, A., Gross, A., Searles Nielsen, S., Miller, A.N., Warden, M.N., Salter, A., Racette, B.A.
From the Departments of Neurology (A.C.-S., A.G., S.S.N., M.N.W., B.A.R.) and Orthopedic Surgery (A.N.M.) and Division of Biostatistics (A.S.), Washington University School of Medicine, St. Louis, MO; and School of Public Health, Faculty of Health Sciences (B.A.R.), University of the Witwatersrand, Johannesburg, South Africa
Abstract
OBJECTIVE: To examine the association between fractures and Parkinson disease (PD) during the 5-year prodromal phase as compared to controls. METHODS: We performed a population-based case-control study of Medicare beneficiaries in the United States from 2004 to 2009. We identified 89,632 incident PD cases and 117,760 comparable controls 66-90 years of age in 2009. PD case status was the outcome, and noncranial fracture the independent variable. We used logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for association between fracture and PD in yearly time intervals prior to PD diagnosis/control reference date, after adjusting for covariates. RESULTS: There were 39,606 total fractures (25.4% cases, 14.3% controls) over the 5 years prior to the PD diagnosis/control reference date. PD was positively associated with fractures even after adjusting for age, sex, race/ethnicity, Charlson comorbidity index, alcohol use, tobacco use, and osteoporosis. The association between PD and fracture was evident at yearly time windows prior to PD diagnosis/control reference date. The association between PD and each type of fracture strengthened as the PD diagnosis/control reference date approached (all time interaction p values ≤0.02). Among beneficiaries with a mechanism of injury, the majority were attributed to falls (74.6% cases, 72.8% controls). CONCLUSION: Fractures occur more commonly during the prodromal period of PD compared to controls, especially as diagnosis date approached, suggesting that patients with PD may experience unrecognized motor and nonmotor symptoms. © 2020 American Academy of Neurology.
Document Type: Article
Publication Stage: Final
Source: Scopus
“Cell Type-Specific In Vitro Gene Expression Profiling of Stem Cell-Derived Neural Models” (2020) Cells
Cell Type-Specific In Vitro Gene Expression Profiling of Stem Cell-Derived Neural Models
(2020) Cells, 9 (6), .
Gregory, J.A.a , Hoelzli, E.a , Abdelaal, R.a , Braine, C.b , Cuevas, M.b , Halpern, M.c , Barretto, N.c , Schrode, N.c , Akbalik, G.a , Kang, K.a , Cheng, E.c , Bowles, K.d , Lotz, S.e , Goderie, S.e , Karch, C.M.f , Temple, S.e , Goate, A.d , Brennand, K.J.c , Phatnani, H.a b
a Center for Genomics of Neurodegenerative Disease, New York Genome Center, NY, NY 10013, United States
b Department of Neurology, Columbia University Medical Center, NY, NY 10068, United States
c Pamela Sklar Division of Psychiatric Genomics, Department of Genetics and Genomics, Icahn School of Medicine at Mount Sinai, NY, NY 10029, United States
d Ronald M. Loeb Center for Alzheimer’s Disease, Department of Neuroscience, Icahn School of Medicine at Mount Sinai, NY, NY 10029, United States
e Neural Stem Cell Institute, One Discovery Drive, Rensselaer, NY 12144, USA
f Department of Psychiatry, Washington University in St. Louis, St. Louis, MO 63110, USA
Abstract
Genetic and genomic studies of brain disease increasingly demonstrate disease-associated interactions between the cell types of the brain. Increasingly complex and more physiologically relevant human-induced pluripotent stem cell (hiPSC)-based models better explore the molecular mechanisms underlying disease but also challenge our ability to resolve cell type-specific perturbations. Here, we report an extension of the RiboTag system, first developed to achieve cell type-restricted expression of epitope-tagged ribosomal protein (RPL22) in mouse tissue, to a variety of in vitro applications, including immortalized cell lines, primary mouse astrocytes, and hiPSC-derived neurons. RiboTag expression enables depletion of up to 87 percent of off-target RNA in mixed species co-cultures. Nonetheless, depletion efficiency varies across independent experimental replicates, particularly for hiPSC-derived motor neurons. The challenges and potential of implementing RiboTags in complex in vitro cultures are discussed.
Author Keywords
bacTRAP; genomics; glia; hiPSC; neuron; RiboTag; RNA-seq
Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“Wave of single-impulse-stimulated fast initial dip in single vessels of mouse brains imaged by high-speed functional photoacoustic microscopy” (2020) Journal of Biomedical Optics
Wave of single-impulse-stimulated fast initial dip in single vessels of mouse brains imaged by high-speed functional photoacoustic microscopy
(2020) Journal of Biomedical Optics, 25 (6), pp. 1-11.
He, Y.a b , Shi, J.b , Maslov, K.I.b , Cao, R.b , Wang, L.V.b c
a Washington University in St. Louis, Department of Biomedical Engineering, St. Louis, MO, United States
b California Institute of Technology, Caltech Optical Imaging Laboratory, United States
c California Institute of Technology, Caltech Optical Imaging Laboratory, Department of Electrical Eng, United States
Abstract
SIGNIFICANCE: The initial dip in hemoglobin-oxygenation response to stimulations is a spatially confined endogenous indicator that is faster than the blood flow response, making it a desired label-free contrast to map the neural activity. A fundamental question is whether a single-impulse stimulus, much shorter than the response delay, could produce an observable initial dip without repeated stimulation. AIM: To answer this question, we report high-speed functional photoacoustic (PA) microscopy to investigate the initial dip in mouse brains. APPROACH: We developed a Raman-laser-based dual-wavelength functional PA microscope that can image capillary-level blood oxygenation at a 1-MHz one-dimensional imaging rate. This technology was applied to monitor the hemodynamics of mouse cerebral vasculature after applying an impulse stimulus to the forepaw. RESULTS: We observed a transient initial dip in cerebral microvessels starting as early as 0.13 s after the onset of the stimulus. The initial dip and the subsequent overshoot manifested a wave pattern propagating across different microvascular compartments. CONCLUSIONS: We quantified both spatially and temporally the single-impulse-stimulated microvascular hemodynamics in mouse brains at single-vessel resolution. Fast label-free imaging of single-impulse response holds promise for real-time brain-computer interfaces.
Author Keywords
blood oxygen saturation; hemodynamics; photoacoustic microscopy
Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“Animal Wrongs and Animal Rights: Why Nonhuman Primate Research Is Essential for Children’s Eye Health” (2020) American Journal of Ophthalmology
Animal Wrongs and Animal Rights: Why Nonhuman Primate Research Is Essential for Children’s Eye Health
(2020) American Journal of Ophthalmology, .
Tychsen, L.
John F. Hardesty MD Department of Ophthalmology and Visual Sciences, Pediatrics, and Neuroscience, St Louis Children’s Hospital at Washington University Medical Center, St Louis, MO, United States
Document Type: Editorial
Publication Stage: Article in Press
Source: Scopus
“Mislocalization of cone nuclei impairs cone function in mice” (2020) FASEB Journal
Mislocalization of cone nuclei impairs cone function in mice
(2020) FASEB Journal, .
Xue, Y.a b , Razafsky, D.c , Hodzic, D.c , Kefalov, V.J.c
a Department of Genetics, Harvard Medical School, Boston, MA, United States
b Department of Ophthalmology, Harvard Medical School, Boston, MA, United States
c Department of Ophthalmology & Visual Sciences, Washington University School of Medicine, St. Louis, MO, United States
Abstract
The nuclei of cone photoreceptors are located on the apical side of the outer nuclear layer (ONL) in vertebrate retinas. However, the functional role of this evolutionarily conserved localization of cone nuclei is unknown. We previously showed that Linkers of the Nucleoskeleton to the Cytoskeleton (LINC complexes) are essential for the apical migration of cone nuclei during development. Here, we developed an efficient genetic strategy to disrupt cone LINC complexes in mice. Experiments with animals from both sexes revealed that disrupting cone LINC complexes resulted in mislocalization of cone nuclei to the basal side of ONL in mouse retina. This, in turn, disrupted cone pedicle morphology, and appeared to reduce the efficiency of synaptic transmission from cones to bipolar cells. Although we did not observe other developmental or phototransduction defects in cones with mislocalized nuclei, their dark adaptation was impaired, consistent with a deficiency in chromophore recycling. These findings demonstrate that the apical localization of cone nuclei in the ONL is required for the timely dark adaptation and efficient synaptic transmission in cone photoreceptors. © 2020 Federation of American Societies for Experimental Biology
Author Keywords
cone photoreceptor; dark adaptation; LINC complex; nucleus migration; retina electrophysiology; retinal degeneration
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Heterogeneity in the dynamic change of cognitive function among older Chinese people: A growth mixture model” (2020) International Journal of Geriatric Psychiatry
Heterogeneity in the dynamic change of cognitive function among older Chinese people: A growth mixture model
(2020) International Journal of Geriatric Psychiatry, .
Qiu, P.a b c d , Zeng, M.a , Kuang, W.e , Meng, S.S.d , Cai, Y.a , Wang, H.f g , Wan, Y.a
a West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China
b West China Research Center for Rural Health Development, Sichuan University, Chengdu, China
c Social System Design Lab, George Warren Brown School of Social Work, Washington University in St. Louis, St. Louis, MO, United States
d Department of Psychiatry, University of Rochester Medical Center, Rochester, NY, United States
e West China Hospital, Sichuan University, Chengdu, China
f Dementia Care & Research Center, Peking University Institute of Mental Health (Sixth Hospital), Beijing, China
g Beijing Dementia Key Lab, National Clinical Research Center for Mental Disorders, Key Laboratory for Mental Health, National Health Commission, Beijing, China
Abstract
Objectives: Our aim is to distinguish different trajectories of cognitive change in Chinese geriatric population and identify risk factors for cognitive decline in each subpopulation. Methods: We obtained data from five waves (2002, 2005, 2008, 2011, 2014) of the Chinese Longitudinal Health Longevity Survey, using the Chinese Mini-Mental State Examination (C-MMSE) as a proxy for cognitive function. We applied growth mixture modeling (GMM) to identify heterogeneous subpopulations and potential risk factors. Results: Our sample included 3859 older adults, 1387 (48.7%) male and 1974 (51.2%) female with age range of 62 to 108 (average of 74.5) at initial survey. Using GMM and best fit statistics, we identified two distinct subgroups in respect to their longitudinal cognitive function: (a) cognitively stable (87.8%) group with 0.49 C-MMSE points decline per 3 years, and (b) cognitively declining (12.2%) group with 6.03 C-MMSE points decline per 3 years. Of note, cognitive activities were protective, and hearing and visual impairments were risk factors in both groups. Diabetes, hypertension, stroke and cardiovascular disease were associated with cognitive decline in the cognitively declining group. Physical activities, and intake of fresh vegetables, fruits, and fish products were protective in the cognitively stable group. Conclusions: Using GMM, we identified heterogeneity in trajectories of cognitive change in older Chinese people. Moreover, we found risk factors specific to each subgroup, which should be considered in future studies. © 2020 John Wiley & Sons Ltd
Author Keywords
China; cognitive function; growth mixture model; hearing and vision impairments; heterogeneity; older adults
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Myelin and Lipid Composition of the Corpus Callosum in Mucopolysaccharidosis Type I Mice” (2020) Lipids
Myelin and Lipid Composition of the Corpus Callosum in Mucopolysaccharidosis Type I Mice
(2020) Lipids, .
Le, S.Q.a b , Nestrasil, I.c , Kan, S.-H.a d , Egeland, M.a , Cooper, J.D.a b , Elashoff, D.e , Guo, R.e , Tolar, J.c f , Yee, J.K.a , Dickson, P.I.a b
a Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, 1124 W. Carson Street, Torrance, CA 90502, United States
b Department of Pediatrics, Washington University School of Medicine, 660 S. Euclid, Saint Louis, MO 63110, United States
c Department of Pediatrics, University of Minnesota, 2450 Riverside Avenue, Minneapolis, MN 55454, United States
d CHOC Children’s Research Institute, 2450 Riverside Avenue, Orange, CA 55454, United States
e Department of Medicine Statistics Core, University of California, 100 Medical Plaza Driveway, Los Angeles, CA 90095, United States
f Stem Cell Institute, University of Minnesota, 2001 6th Street SE, Minneapolis, MN 55455, United States
Abstract
Mucopolysaccharidosis type I (MPS I) is a lysosomal disease with progressive central nervous system involvement. This study examined the lipid, cholesterol, and myelin basic protein composition of white matter in the corpus callosum of MPS I mice. We studied 50 week-old, male MPS I mice and littermate, heterozygote controls (n = 12 per group). Male MPS I mice showed lower phosphatidylcholine and ether-linked phosphatidylcholine quantities than controls (p < 0.05). Twenty-two phospholipid or ceramide species showed significant differences in percent of total. Regarding specific lipid species, MPS I mice exhibited lower quantities of sphingomyelin 18:1, phosphatidylserine 38:3, and hexosylceramide d18:1(22:1) mH2O than controls. Principal components analyses of polar, ceramide, and hexosylceramide lipids, respectively, showed some separation of MPS I and control mice. We found no significant differences in myelin gene expression, myelin basic protein, or total cholesterol in the MPS I mice versus heterozygous controls. There was a trend toward lower proteolipid protein-1 levels in MPS I mice (p = 0.06). MPS I mice show subtle changes in white matter composition, with an unknown impact on pathogenesis in this model. © 2020 AOCS
Author Keywords
Glycosaminoglycans; Hurler syndrome; Inborn errors of metabolism; Lipidomics; Lysosomal storage disease
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Models of Axon Degeneration in Drosophila Larvae” (2020) Methods in Molecular Biology (Clifton, N.J.)
Models of Axon Degeneration in Drosophila Larvae
(2020) Methods in Molecular Biology (Clifton, N.J.), 2143, pp. 311-320.
Brace, E.J., DiAntonio, A.
Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO, USA
Abstract
The fruit fly Drosophila melanogaster has been a powerful model to study axonal biology including axon degeneration and regeneration (Brace et al., J Neurosci 34:8398-8410, 2014; Valakh et al. J Neurosci 33:17863-17,873, 2013; Xiong and Collins J Neurosci 32:610-615, 2012; Xiong et al. 191:211-223, 2010). Both adult and larval injury models have been developed in the fruit fly. This chapter focuses on in vivo and ex vivo methods developed for studying axon degeneration in Drosophila larvae. Additional models have been developed in the adult fly including injury models of olfactory receptor neurons in the brain and a model of axonal degeneration of sensory axons in the wing (Fang and Bonini, Annu Rev. Cell Dev Biol 28:575-597, 2012; Hoopfer et al. Neuron 50:883-895, 2006; Neukomm et al. Proc Natl Acad Sci U S A 111:9965-9970, 2014).
Author Keywords
Axon degeneration; Axon injury; Axon regeneration; Drosophila; Wallerian degeneration
Document Type: Article
Publication Stage: Final
Source: Scopus
“Viral Transduction of DRG Neurons” (2020) Methods in Molecular Biology (Clifton, N.J.)
Viral Transduction of DRG Neurons
(2020) Methods in Molecular Biology (Clifton, N.J.), 2143, pp. 55-62.
Sasaki, Y.
Department of Genetics, Washington University in St. Louis, Couch Biomedical Research Building, St. Louis, MO, USA
Abstract
The manipulation of gene expression is an essential tool to study the function of genes or signaling pathways. Uniform and robust gene manipulation is crucial for successful assays. However, neuronal cells are generally difficult-to-transfect cells with conventional DNA/RNA transfection reagents. Therefore, virus-mediated gene delivery is a primary choice for the studies of gene functions in neurons. In this chapter, we will describe the methods for lentivirus-mediated gene expression or knockdown in DRG neurons.
Author Keywords
Axon degeneration; DRG; Lentivirus; Neurodegeneration; Wallerian degeneration
Document Type: Article
Publication Stage: Final
Source: Scopus
“Cockayne syndrome: The many challenges and approaches to understand a multifaceted disease” (2020) Genetics and Molecular Biology
Cockayne syndrome: The many challenges and approaches to understand a multifaceted disease
(2020) Genetics and Molecular Biology, 43 (1), art. no. e20190085, .
Vessoni, A.T.a , Guerra, C.C.C.b , Kajitani, G.S.b c , Nascimento, L.L.S.c , Garcia, C.C.M.b
a Washington University, School of Medicine, Saint Louis, MO, United States
b Universidade Federal de Ouro Preto, Instituto de Ciências Exatas e Biológicas, Núcleo de Pesquisa em Ciências Biológicas, Departamento de Ciências Biológicas, Ouro Preto, MG, Brazil
c Universidade de São Paulo, Instituto de Ciências Biomédicas, Departamento de Microbiologia, São Paulo, SP, Brazil
Abstract
The striking and complex phenotype of Cockayne syndrome (CS) patients combines progeria-like features with developmental deficits. Since the establishment of the in vitro culture of skin fibroblasts derived from patients with CS in the 1970s, significant progress has been made in the understanding of the genetic alterations associated with the disease and their impact on molecular, cellular, and organismal functions. In this review, we provide a historic perspective on the research into CS by revisiting seminal papers in this field. We highlighted the great contributions of several researchers in the last decades, ranging from the cloning and characterization of CS genes to the molecular dissection of their roles in DNA repair, transcription, redox processes and metabolism control. We also provide a detailed description of all pathological mutations in genes ERCC6 and ERCC8 reported to date and their impact on CS-related proteins. Finally, we review the contributions (and limitations) of many genetic animal models to the study of CS and how cutting-edge technologies, such as cell reprogramming and state-of-the-art genome editing, are helping us to address unanswered questions. © 2020, Sociedade Brasileira de Genética.
Author Keywords
Cockayne syndrome; DNA repair; Neurodegeneration; Progeroid syndrome; Transcription-coupled nucleotide excision repair
Document Type: Review
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“Long-term super-resolution imaging of amyloid structures using transient binding of thioflavin T” (2019) Optical Molecular Probes, Imaging and Drug Delivery – Proceedings Biophotonics Congress: Optics in the Life Sciences Congress 2019 (BODA, BRAIN, NTM, OMA, OMP)
Long-term super-resolution imaging of amyloid structures using transient binding of thioflavin T
(2019) Optical Molecular Probes, Imaging and Drug Delivery – Proceedings Biophotonics Congress: Optics in the Life Sciences Congress 2019 (BODA, BRAIN, NTM, OMA, OMP), .
Spehar, K.a , Ding, T.b , Sun, Y.c , Kedia, N.a , Lu, J.b , Nahass, G.R.a , Lew, M.D.b , Bieschke, J.a c
a Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO 63130, United States
b Department of Electrical and Systems Engineering, Washington University in St. Louis, St. Louis, MO 63130, United States
c MRC Prion Unit, UCL Institute of Prion Diseases, Gower Street, London, WC1E 6BT, United Kingdom
Abstract
Amyloids are implicated in Alzheimer’s disease but cannot be well resolved by standard light microscopy. We developed a tool to directly image native amyloid structures and dynamics at nanometer resolution over minutes to days. © 2019 The Author(s).
Document Type: Conference Paper
Publication Stage: Final
Source: Scopus
“Patterns of intrinsic neural and hemodynamic activity recover uniquely following stroke” (2019) Optics and the Brain – Proceedings Biophotonics Congress: Optics in the Life Sciences Congress 2019 (BODA, BRAIN, NTM, OMA, OMP)
Patterns of intrinsic neural and hemodynamic activity recover uniquely following stroke
(2019) Optics and the Brain – Proceedings Biophotonics Congress: Optics in the Life Sciences Congress 2019 (BODA, BRAIN, NTM, OMA, OMP), .
Kim, B.a , Rosenthal, Z.b , Culver, J.P.a c d , Lee, J.-M.a d e , Bauer, A.Q.a d
a Departments of Radiology, Washington University School of Medicine, Saint Louis, MO 63110, United States
b Departments of Neuroscience, Washington University School of Medicine, Saint Louis, MO 63110, United States
c Departments of Physics, Washington University School of Medicine, Saint Louis, MO 63110, United States
d Departments of Biomedical Engineering, Washington University School of Medicine, Saint Louis, MO 63110, United States
e Departments of Neurology Washington University School of Medicine, Saint Louis, MO 63110, United States
Abstract
Longitudinal functional imaging of intrinsic and stimulus-evoked neural and hemodynamic activity was performed in mice pre- A nd post-stroke. Hemodynamic connectivity is restored by 8 weeks while neural activity patterns are permanently affected. © 2019 The Authors.
Document Type: Conference Paper
Publication Stage: Final
Source: Scopus
“Anesthesia affects forepaw motor output and movement complexity during light-based motor mapping” (2019) Optics and the Brain – Proceedings Biophotonics Congress: Optics in the Life Sciences Congress 2019 (BODA, BRAIN, NTM, OMA, OMP)
Anesthesia affects forepaw motor output and movement complexity during light-based motor mapping
(2019) Optics and the Brain – Proceedings Biophotonics Congress: Optics in the Life Sciences Congress 2019 (BODA, BRAIN, NTM, OMA, OMP), .
Voss, T.R.C.a , Bice, A.R.a , Lee, J.-M.a b c , Bauer, A.Q.a b
a Department of Radiology, Washington University School of Medicine, Saint Louis, MO 63110, United States
b Department of Biomedical Engineering, Washington University School of Medicine, Saint Louis, MO 63110, United States
c Department of Neurology, Washington University School of Medicine, Saint Louis, MO 63110, United States
Abstract
We used automated, light-based optogenetic mapping in Thy1-ChR2 mice to map forepaw motor movements under titrated levels of ketamine anesthesia. Anesthesia dose affected the amplitude, direction, and complexity of photostimulus-evoked movement types. © 2019 The Authors.
Document Type: Conference Paper
Publication Stage: Final
Source: Scopus
“Detecting inflammatory responses in live animal models with near-infrared ROS probes” (2019) Optical Molecular Probes, Imaging and Drug Delivery – Proceedings Biophotonics Congress: Optics in the Life Sciences Congress 2019 (BODA, BRAIN, NTM, OMA, OMP)
Detecting inflammatory responses in live animal models with near-infrared ROS probes
(2019) Optical Molecular Probes, Imaging and Drug Delivery – Proceedings Biophotonics Congress: Optics in the Life Sciences Congress 2019 (BODA, BRAIN, NTM, OMA, OMP), .
Zhou, H.a , Akers, W.b , Brody, S.a , Wood, M.a , Berezin, M.Y.a
a Washington University in St. Louis School of Medicine, 4115 McKinley Ave, St. Louis, MO 63110, United States
b St. Jude Children’s Research Hospital, 262 Danny Thomas Pl, Memphis, TN 38105, United States
Abstract
Near-infrared contrast agents and optical methods are useful in detection of reactive oxygen species in vivo in the small animal models of acute lung injury, angiogenesis and peripheral neuropathies. © 2019 The Author(s).
Document Type: Conference Paper
Publication Stage: Final
Source: Scopus
“Excitatory and inhibitory circuits differentially regulate local and distant cerebral hemodynamics” (2019) Optics and the Brain – Proceedings Biophotonics Congress: Optics in the Life Sciences Congress 2019 (BODA, BRAIN, NTM, OMA, OMP)
Excitatory and inhibitory circuits differentially regulate local and distant cerebral hemodynamics
(2019) Optics and the Brain – Proceedings Biophotonics Congress: Optics in the Life Sciences Congress 2019 (BODA, BRAIN, NTM, OMA, OMP), .
Lee, J.a , Bice, A.R.a , Rosenthal, Z.P.a b c , Lee, J.-M.a b c , Bauer, A.Q.a
a Department of Radiology, Washington University School of Medicine, Saint Louis, MO 63110, United States
b Department of Neurology, Washington University School of Medicine, Saint Louis, MO 63110, United States
c Department of Biomedical Engineering, Washington University School of Medicine, Saint Louis, MO 63110, United States
Abstract
Optogenetic photostimulation of excitatory or inhibitory circuits differentially regulated local cerebral blood volume and flow in awake, transgenic mice. Each neural subclass also uniquely influenced distant cortical hemodynamic activity. © 2019 The Authors.
Document Type: Conference Paper
Publication Stage: Final
Source: Scopus
“Outcomes of BRAF V600E pediatric gliomas treated with targeted BRAF inhibition” (2019) JCO Precision Oncology
Outcomes of BRAF V600E pediatric gliomas treated with targeted BRAF inhibition
(2019) JCO Precision Oncology, 3, pp. 561-571.
Nobre, L.a , Zapotocky, M.a b , Ramaswamy, V.a d e , Ryall, S.a , Bennett, J.a , Alderete, D.f , Guill, J.B.g , Baroni, L.f , Bartels, U.a , Bavle, A.h , Bornhorst, M.i , Boue, D.R.j , Canete, A.g , Chintagumpala, M.k , Coven, S.L.l , Cruz, O.m , Dahiya, S.n , Dirks, P.d o , Dunkel, I.J.p , Eisenstat, D.q , Conter, C.F.r , Finch, E.s , Finlay, J.L.j , Frappaz, D.r , Garre, M.L.t , Gauvain, K.n , Bechensteen, A.G.u , Hansford, J.R.v , Harting, I.w , Hauser, P.x , Hazrati, L.-N.y , Huang, A.a d , Injac, S.G.k , Iurilli, V.t , Karajannis, M.p , Kaur, G.p , Kyncl, M.b , Krskova, L.b , Laperriere, N.a , Larouche, V.z , Lassaletta, A.aa , Leary, S.ab , Lin, F.k , Mascelli, S.t , McKeown, T.a , Milde, T.w , la Madrid, A.M.m , Morana, G.t , Morse, H.ac , Mushtaq, N.ad , Osorio, D.S.j am , Packer, R.i am , Pavelka, Z.ae , Quiroga-Cantero, E.af , Rutka, J.d o , Sabel, M.ag , Salgado, D.ah , Solano, P.af , Sterba, J.ae , Su, J.k , Sumerauer, D.b , Taylor, M.D.c d o y ai aj , Toledano, H.ak , Tsang, D.S.a , Fernandes, M.V.ah , van Landeghem, F.q , van Tilburg, C.M.w , Wilson, B.q , Witt, O.w , Zamecnik, J.b , Bouffet, E.a , Hawkins, C.d y al am , Tabori, U.a d
a Department of Hematology and Oncology, Hospital for Sick Children, Toronto, ON, Canada
b Second Faculty of Medicine, Charles University, University Hospital Motol, Prague, Czech Republic
c Developmental and Stem Cell Biology Program, Hospital for Sick Children, Toronto, ON, Canada
d Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, ON, Canada
e Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada
f Hospital of Pediatrics, SAMIC Prof. Dr Juan P. Garrahan, Buenos Aires, Argentina
g Hospital Universitario y Politecnico La Fe, University of Valencia, Valencia, Spain
h Jimmy Everest Section of Pediatric Heamatology/Oncology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States
i Children’s National Health System, Washington, DC, United States
j Nationwide Children’s Hospital, Ohio State University, Columbus, OH, United States
k Texas Children’s Cancer Center, Houston, TX, United States
l Division of Pediatric Hematology and Oncology, Department of Pediatrics, Indiana University, Indianapolis, IN, United States
m Hospital Sant Joan de Déu, Barcelona, Spain
n Washington University School of Medicine, St Louis, MO, United States
o Division of Neurosurgery, Hospital for Sick Children, Toronto, ON, Canada
p Memorial Sloan Kettering Cancer Center, New York, NY, United States
q Stollery Children’s Hospital, University of Alberta, Edmonton, AB, Canada
r Institute d’Hémato-Oncologie Pédiatrique, Centre Leon Berard, Lyon, France
s University of North Carolina at Chapel Hill, Chapel Hill, NC, United States
t G. Gaslini Children’s Hospital, Genoa, Italy
u Oslo University Hospital, Oslo, Norway
v Royal Children’s Hospital, Murdoch Children’s Research Institute, University of Melbourne, Melbourne, VIC, Australia
w Hopp Children’s Cancer Center Heidelberg, Heidelberg, Germany
x Semmelweis University, Budapest, Hungary
y Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
z Universite Laval, Quebec City, QC, Canada
aa Hospital Infantil Universitario Niño Jesús, Madrid, Spain
ab Seattle Children’s Hospital, Seattle, WA, United States
ac Lund University, Lund, Sweden
ad Aga Khan University Hospital, Karachi, Pakistan
ae University Hospital Brno, Masaryk University, ICRC Brno, Brno, Czech Republic
af Hospital Infantil Virgen del Rocío, Sevilla, Spain
ag Sahlgrenska University Hospital, University of Gothenburg, Gothenburg, Sweden
ah Portuguese Oncology Institute, Lisbon, Portugal
ai Department of Surgery, University of Ontario, Toronto, ON, Canada
aj Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada
ak Schneiders Children’s Medical Center of Israel, Petah Tikva, Israel
al Department of Pediatric Laboratory Medicine, Hospital for Sick Children, Toronto, ON, Canada
am Hospital for Sick Children, 555 University Ave, Toronto, ON M5G 1X8, Canada
Abstract
PURPOSE Children with pediatric gliomas harboring a BRAF V600E mutation have poor outcomes with current chemoradiotherapy strategies. Our aim was to study the role of targeted BRAF inhibition in these tumors. PATIENTS AND METHODS We collected clinical, imaging, molecular, and outcome information from patients with BRAF V600E–mutated glioma treated with BRAF inhibition across 29 centers from multiple countries. RESULTS Sixty-seven patients were treated with BRAF inhibition (pediatric low-grade gliomas [PLGGs], n = 56; pediatric high-grade gliomas [PHGGs], n = 11) for up to 5.6 years. Objective responses were observed in 80% of PLGGs, compared with 28% observed with conventional chemotherapy (P, .001). These responses were rapid (median, 4 months) and sustained in 86% of tumors up to 5 years while receiving therapy. After discontinuation of BRAF inhibition, 76.5% (13 of 17) of patients with PLGG experienced rapid progression (median, 2.3 months). However, upon rechallenge with BRAF inhibition, 90% achieved an objective response. Poor prognostic factors in conventional therapies, such as concomitant homozygous deletion of CDKN2A, were not associated with lack of response to BRAF inhibition. In contrast, only 36% of those with PHGG responded to BRAF inhibition, with all but one tumor progressing within 18 months. In PLGG, responses translated to 3-year progression-free survival of 49.6% (95% CI, 35.3% to 69.5%) versus 29.8% (95% CI, 20% to 44.4%) for BRAF inhibition versus chemotherapy, respectively (P = .02). CONCLUSION Use of BRAF inhibition results in robust and durable responses in BRAF V600E–mutated PLGG. Prospective studies are required to determine long-term survival and functional outcomes with BRAF inhibitor therapy in childhood gliomas. © 2020 by American Society of Clinical Oncology
Document Type: Conference Paper
Publication Stage: Final
Source: Scopus