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2020

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Case Report: Dsm-5 Misses An Edge Case In Tic Disorders Nosology, Kevin J. Black Jan 2020

Case Report: Dsm-5 Misses An Edge Case In Tic Disorders Nosology, Kevin J. Black

Open Access Publications

A boy with multiple phonic tics, one lifetime motor tic, and no impairment or marked distress does not meet criteria for any DSM-5 tic disorder diagnosis. The next version of the Diagnostic and Statistical Manual should adjust the criteria for Tourette's Disorder and/or for "other specified tic disorder" and "unspecified tic disorder."


A Phase Ii Study Of Glembatumumab Vedotin For Metastatic Uveal Melanoma, Merve Hasanov, Matthew J Rioth, Kari Kendra, Leonel Hernandez-Aya, Richard W Joseph, Stephen Williamson, Sunandana Chandra, Keisuke Shirai, Christopher D Turner, Karl Lewis, Elizabeth Crowley, Jeffrey Moscow, Brett Carter, Sapna Patel Jan 2020

A Phase Ii Study Of Glembatumumab Vedotin For Metastatic Uveal Melanoma, Merve Hasanov, Matthew J Rioth, Kari Kendra, Leonel Hernandez-Aya, Richard W Joseph, Stephen Williamson, Sunandana Chandra, Keisuke Shirai, Christopher D Turner, Karl Lewis, Elizabeth Crowley, Jeffrey Moscow, Brett Carter, Sapna Patel

Open Access Publications

Glembatumumab vedotin (CDX-011, GV) is a fully human Immunoglobulin G2 monoclonal antibody directed against glycoprotein NMB coupled via a peptide linker to monomethyl auristatin E (MMAE), a potent cytotoxic microtubule inhibitor. This phase II study evaluated the overall response rate and safety of GV, glycoprotein NMB (GPNMB) expression, and survival in patients with metastatic uveal melanoma. Eligible patients with metastatic uveal melanoma who had not previously been treated with chemotherapy received GV 1.9 mg/kg every three weeks. The primary endpoint was the objective response rate (ORR). Secondary endpoints included GPNMB expression, progression-free survival (PFS), overall survival (OS), and toxicity analysis. …


Krabbe Disease Successfully Treated Via Monotherapy Of Intrathecal Gene Therapy, Allison M Bradbury, Xuntian Jiang, Mark S Sands, Daniel S Ory, Et Al Jan 2020

Krabbe Disease Successfully Treated Via Monotherapy Of Intrathecal Gene Therapy, Allison M Bradbury, Xuntian Jiang, Mark S Sands, Daniel S Ory, Et Al

Open Access Publications

Globoid cell leukodystrophy (GLD; Krabbe disease) is a progressive, incurable neurodegenerative disease caused by deficient activity of the hydrolytic enzyme galactosylceramidase (GALC). The ensuing cytotoxic accumulation of psychosine results in diffuse central and peripheral nervous system (CNS, PNS) demyelination. Presymptomatic hematopoietic stem cell transplantation (HSCT) is the only treatment for infantile-onset GLD; however, clinical outcomes of HSCT recipients often remain poor, and procedure-related morbidity is high. There are no effective therapies for symptomatic patients. Herein, we demonstrate in the naturally occurring canine model of GLD that presymptomatic monotherapy with intrathecal AAV9 encoding canine GALC administered into the cisterna magna increased …


Client Processing Is Altered By Novel Myopathy-Causing Mutations In The Hsp40 J Domain, Melanie Y. Pullen, Conrad C. Weihl, Heather L. True Jan 2020

Client Processing Is Altered By Novel Myopathy-Causing Mutations In The Hsp40 J Domain, Melanie Y. Pullen, Conrad C. Weihl, Heather L. True

Open Access Publications

The misfolding and aggregation of proteins is often implicated in the development and progression of degenerative diseases. Heat shock proteins (HSPs), such as the ubiquitously expressed Type II Hsp40 molecular chaperone, DNAJB6, assist in protein folding and disaggregation. Historically, mutations within the DNAJB6 G/F domain have been associated with Limb-Girdle Muscular Dystrophy type 1D, now referred to as LGMDD1, a dominantly inherited degenerative disease. Recently, novel mutations within the J domain of DNAJB6 have been reported in patients with LGMDD1. Since novel myopathy-causing mutations in the Hsp40 J domain have yet to be characterized and both the function of DNAJB6 …


Obesity Is A Risk Factor For Acute Promyelocytic Leukemia: Evidence From Population And Cross-Sectional Studies And Correlation With Flt3 Mutations And Polyunsaturated Fatty Acid Metabolism, Luca Mazzarella, Timothy J. Ley, Et Al. Jan 2020

Obesity Is A Risk Factor For Acute Promyelocytic Leukemia: Evidence From Population And Cross-Sectional Studies And Correlation With Flt3 Mutations And Polyunsaturated Fatty Acid Metabolism, Luca Mazzarella, Timothy J. Ley, Et Al.

Open Access Publications

No abstract provided.


Macrophage Secretion Of Mir-106b-5p Causes Renin-Dependent Hypertension, J. Oh, S. J. Matkovich, A. E. Riek, S. M. Bindom, J. S. Shao, R.D. Head, R. A. Barve, M. S. Sands, G. Carmeliet, P. Osei-Owusu, R.H. Knutsen, H. Zhang, K. J. Blumer, C. G. Nichols, R. P. Mecham, Á Baldán, B. A. Benitez, M. L. Sequeira-Lopez, R. A. Gomez, C. Bernal-Mizrachi Jan 2020

Macrophage Secretion Of Mir-106b-5p Causes Renin-Dependent Hypertension, J. Oh, S. J. Matkovich, A. E. Riek, S. M. Bindom, J. S. Shao, R.D. Head, R. A. Barve, M. S. Sands, G. Carmeliet, P. Osei-Owusu, R.H. Knutsen, H. Zhang, K. J. Blumer, C. G. Nichols, R. P. Mecham, Á Baldán, B. A. Benitez, M. L. Sequeira-Lopez, R. A. Gomez, C. Bernal-Mizrachi

Open Access Publications

No abstract provided.


Spatial Mapping Of The Collagen Distribution In Human And Mouse Tissues By Force Volume Atomic Force Microscopy, Annalisa Calò, Yevgeniy Romin, Rami Srouji, Constantinos P. Zambirinis, Ning Fan, Anthony Santella, Elvin Feng, Sho Fujisawa, Mesruh Turkekul, Sharon Huang, Amber L. Simpson, Michael D'Angelica, William R. Jarnagin, Katia Manova-Todorova Jan 2020

Spatial Mapping Of The Collagen Distribution In Human And Mouse Tissues By Force Volume Atomic Force Microscopy, Annalisa Calò, Yevgeniy Romin, Rami Srouji, Constantinos P. Zambirinis, Ning Fan, Anthony Santella, Elvin Feng, Sho Fujisawa, Mesruh Turkekul, Sharon Huang, Amber L. Simpson, Michael D'Angelica, William R. Jarnagin, Katia Manova-Todorova

Open Access Publications

No abstract provided.


The Nemp Family Supports Metazoan Fertility And Nuclear Envelope Stiffness, Yonit Tsatskis, Ariz Mohammad, Karen Krchma, Jun Wu, Didier Hodzic, Daniel Potter, Tim Schedl, Kyunghee Choi, Helen Mcneill, Et Al Jan 2020

The Nemp Family Supports Metazoan Fertility And Nuclear Envelope Stiffness, Yonit Tsatskis, Ariz Mohammad, Karen Krchma, Jun Wu, Didier Hodzic, Daniel Potter, Tim Schedl, Kyunghee Choi, Helen Mcneill, Et Al

Open Access Publications

Human genome-wide association studies have linked single-nucleotide polymorphisms (SNPs) in


Deeph&M: Estimating Single-Cpg Hydroxymethylation And Methylation Levels From Enrichment And Restriction Enzyme Sequencing Methods, Yu He, Hyo Sik Jang, Xiaoyun Xing, Daofeng Li, Michael J Vasek, Joseph D Dougherty, Ting Wang Jan 2020

Deeph&M: Estimating Single-Cpg Hydroxymethylation And Methylation Levels From Enrichment And Restriction Enzyme Sequencing Methods, Yu He, Hyo Sik Jang, Xiaoyun Xing, Daofeng Li, Michael J Vasek, Joseph D Dougherty, Ting Wang

Open Access Publications

Increased appreciation of 5-hydroxymethylcytosine (5hmC) as a stable epigenetic mark, which defines cell identity and disease progress, has engendered a need for cost-effective, but high-resolution, 5hmC mapping technology. Current enrichment-based technologies provide cheap but low-resolution and relative enrichment of 5hmC levels, while single-base resolution methods can be prohibitively expensive to scale up to large experiments. To address this problem, we developed a deep learning-based method, "DeepH&M," which integrates enrichment and restriction enzyme sequencing methods to simultaneously estimate absolute hydroxymethylation and methylation levels at single-CpG resolution. Using 7-week-old mouse cerebellum data for training the DeepH&M model, we demonstrated that the 5hmC …


Affording Autism An Early Brain Development Re-Definition, Ami Klin, Megan Micheletti, Cheryl Klaiman, Sarah Shultz, John N Constantino, Warren Jones Jan 2020

Affording Autism An Early Brain Development Re-Definition, Ami Klin, Megan Micheletti, Cheryl Klaiman, Sarah Shultz, John N Constantino, Warren Jones

Open Access Publications

The national priority to advance early detection and intervention for children with autism spectrum disorder (ASD) has not reduced the late age of ASD diagnosis in the US over several consecutive Centers for Disease Control and Prevention (CDC) surveillance cohorts, with traditionally under-served populations accessing diagnosis later still. In this review, we explore a potential perceptual barrier to this enterprise which views ASD in terms that are contradicted by current science, and which may have its origins in the current definition of the condition and in its historical associations. To address this perceptual barrier, we propose a re-definition of ASD …


Targeting Cxcr4 In Aml And All, Daniel Cancilla, Michael P Rettig, John F Dipersio Jan 2020

Targeting Cxcr4 In Aml And All, Daniel Cancilla, Michael P Rettig, John F Dipersio

Open Access Publications

The interaction of acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) blasts with the bone marrow microenvironment regulates self-renewal, growth signaling, as well as chemotherapy resistance. The chemokine receptor, CXC receptor 4 (CXCR4), with its ligand chemokine ligand 12 (CXCL12), plays a key role in the survival and migration of normal and malignant stem cells to the bone marrow. High expression of CXCR4 on AML and ALL blasts has been shown to be a predictor of poor prognosis for these diseases. Several small molecule inhibitors, short peptides, antibodies, and antibody drug conjugates have been developed for the purposes of …


The Pathway To Secondary Prevention Of Alzheimer's Disease, Eric Mcdade, Martin M Bednar, H Robert Brashear, David S Miller, Paul Maruff, Christopher Randolph, Zahinoor Ismail, Maria C Carrillo, Christopher J Weber, Lisa J Bain, Ann Marie Hake Jan 2020

The Pathway To Secondary Prevention Of Alzheimer's Disease, Eric Mcdade, Martin M Bednar, H Robert Brashear, David S Miller, Paul Maruff, Christopher Randolph, Zahinoor Ismail, Maria C Carrillo, Christopher J Weber, Lisa J Bain, Ann Marie Hake

Open Access Publications

Alzheimer's disease (AD) is a continuum consisting of a preclinical stage that occurs decades before symptoms appear. As researchers make advances in investigating the continuum, the importance of developing drugs for secondary prevention is garnering increased discussion. For efficacious drug development for secondary prevention it is important to define what are the earliest biological stages of AD. The Alzheimer's Association Research Roundtable convened November 27 to 28, 2018 to focus on pre-clinical AD. This review will address the biological approach to defining pre-clinical AD, detection, identification of at-risk individuals, and lessons learned from trials such as A4 and TOMMORROW.


Lactate-Protechypoglycemia (Lph), Matthew L Goodwin, L Bruce Gladden, Maarten W N Nijsten Jan 2020

Lactate-Protechypoglycemia (Lph), Matthew L Goodwin, L Bruce Gladden, Maarten W N Nijsten

Open Access Publications

Here, we provide an overview of the concept of a lactate-protected hypoglycemia ("LPH"), originally proposed as lowering glucose while simultaneously increasing lactate concentration as a method by which tumors might be targeted. Central to this hypothesis is that lactate can act as a critical salvage fuel for the central nervous system, allowing for wide perturbations in whole body and central nervous system glucose concentrations. Further, many tumors exhibit "the Warburg" effect, consuming glucose and producing and exporting lactate despite adequate oxygenation. While some recent data have provided evidence for a "reverse-Warburg," where some tumors may preferentially consume lactate, many of …


Harnessing Real-World Data To Inform Decision-Making: Multiple Sclerosis Partners Advancing Technology And Health Solutions (Ms Paths), Ellen M Mowry, Tammie L S Benzinger, Robert T Naismith, Et Al Jan 2020

Harnessing Real-World Data To Inform Decision-Making: Multiple Sclerosis Partners Advancing Technology And Health Solutions (Ms Paths), Ellen M Mowry, Tammie L S Benzinger, Robert T Naismith, Et Al

Open Access Publications

No abstract provided.


Inhibition Of Pikfyve Kinase Prevents Infection By Zaire Ebolavirus And Sars-Cov-2, Yuan-Lin Kang, Yi-Ying Chou, Paul W. Rothlauf, Zhuoming Liu, Timothy K. Soh, David Cureton, James Brett Case, Rita E. Chen, Michael S. Diamond, Sean P.J. Whelan, Tom Kirchhausen Jan 2020

Inhibition Of Pikfyve Kinase Prevents Infection By Zaire Ebolavirus And Sars-Cov-2, Yuan-Lin Kang, Yi-Ying Chou, Paul W. Rothlauf, Zhuoming Liu, Timothy K. Soh, David Cureton, James Brett Case, Rita E. Chen, Michael S. Diamond, Sean P.J. Whelan, Tom Kirchhausen

Open Access Publications

No abstract provided.


The Membrane-Associated Form Of Cyclin D1 Enhances Cellular Invasion, Ke Chen, Xuanmao Jiao, Anthony Ashton, Agnese Di Rocco, Timothy G. Pestell, Yunguang Sun, Jun Zhao, Mathew C. Casimiro, Zhiping Li, Michael P. Lisanti, Peter A. Mccue, Duanwen Shen, Samuel Achilefu, Hallgeir Rui, Richard G. Pestell Jan 2020

The Membrane-Associated Form Of Cyclin D1 Enhances Cellular Invasion, Ke Chen, Xuanmao Jiao, Anthony Ashton, Agnese Di Rocco, Timothy G. Pestell, Yunguang Sun, Jun Zhao, Mathew C. Casimiro, Zhiping Li, Michael P. Lisanti, Peter A. Mccue, Duanwen Shen, Samuel Achilefu, Hallgeir Rui, Richard G. Pestell

Open Access Publications

No abstract provided.


Hypoxia Protects Rat Bone Marrow Mesenchymal Stem Cells Against Compression-Induced Apoptosis In The Degenerative Disc Microenvironment Through Activation Of The Hif-1a/Yap Signaling Pathway, Zhe Wang, Min Cui, Yanji Qu, Ruijun He, Wei Wu, Hui Lin, Zengwu Shao Jan 2020

Hypoxia Protects Rat Bone Marrow Mesenchymal Stem Cells Against Compression-Induced Apoptosis In The Degenerative Disc Microenvironment Through Activation Of The Hif-1a/Yap Signaling Pathway, Zhe Wang, Min Cui, Yanji Qu, Ruijun He, Wei Wu, Hui Lin, Zengwu Shao

Open Access Publications

No abstract provided.


Tert, A Promoter Of Cns Malignancies, Bhuvic Patel, Rukayat Taiwo, Albert H. Kim, Gavin P. Dunn Jan 2020

Tert, A Promoter Of Cns Malignancies, Bhuvic Patel, Rukayat Taiwo, Albert H. Kim, Gavin P. Dunn

Open Access Publications

As cells replicate their DNA during mitosis, telomeres are shortened due to the inherent limitations of the DNA replication process. Maintenance of telomere length is critical for cancer cells to overcome cellular senescence induced by telomere shortening. Telomerase reverse transcriptase (TERT) is the rate-limiting catalytic subunit of telomerase, an RNA-dependent DNA polymerase that lengthens telomeric DNA to maintain telomere homeostasis.


Huntingtin-Interacting Protein Family Members Have A Conserved Pro-Viral Function From Caenorhabditis Elegans To Humans, Hongbing Jiang, Luis Enrique Sandoval Del Prado, Christian Leung, David Wang Jan 2020

Huntingtin-Interacting Protein Family Members Have A Conserved Pro-Viral Function From Caenorhabditis Elegans To Humans, Hongbing Jiang, Luis Enrique Sandoval Del Prado, Christian Leung, David Wang

Open Access Publications

No abstract provided.


Association Of Sex And Apoe Ε4 With Brain Tau Deposition And Atrophy In Older Adults With Alzheimer’S Disease, Shaozhen Yan, Chaojie Zheng, Manish D. Paranjpe, Jian Li, Tammie L.S. Benzinger, Jie Lu, Yun Zhou Jan 2020

Association Of Sex And Apoe Ε4 With Brain Tau Deposition And Atrophy In Older Adults With Alzheimer’S Disease, Shaozhen Yan, Chaojie Zheng, Manish D. Paranjpe, Jian Li, Tammie L.S. Benzinger, Jie Lu, Yun Zhou

Open Access Publications

No abstract provided.


Increased Aqueous Humor Gdf15 Is Associated With Worse Visual Field Loss In Pseudoexfoliative Glaucoma Patients, Jonathan B. Lin, Arsham Sheybani, Andrea Santeford, Alicia De Maria, Rajendra S. Apte Jan 2020

Increased Aqueous Humor Gdf15 Is Associated With Worse Visual Field Loss In Pseudoexfoliative Glaucoma Patients, Jonathan B. Lin, Arsham Sheybani, Andrea Santeford, Alicia De Maria, Rajendra S. Apte

Open Access Publications

No abstract provided.


Functional Analysis Of Rare Genetic Variants In Complement Factor I (Cfi) Using A Serum-Based Assay In Advanced Age-Related Macular Degeneration, Anuja Java, Peter Baciu, Rafael Widjajahakim, Yun Ju Sung, Jae Yang, David Kavanagh, John Atkinson, Johanna Seddon Jan 2020

Functional Analysis Of Rare Genetic Variants In Complement Factor I (Cfi) Using A Serum-Based Assay In Advanced Age-Related Macular Degeneration, Anuja Java, Peter Baciu, Rafael Widjajahakim, Yun Ju Sung, Jae Yang, David Kavanagh, John Atkinson, Johanna Seddon

Open Access Publications

No abstract provided.


Discovery Of A Novel Simian Pegivirus In Common Marmosets (Callithrix Jacchus) With Lymphocytic Enterocolitis, Anna S. Heffron, Michael Lauck, Elizabeth D. Somsen, Elizabeth C. Townsend, Adam L. Bailey, Megan Sosa, Jens Eickhoff, Saverio Capuano Iii, Christina M. Newman, Jens H. Kuhn, Andres Mejia, Heather A. Simmons, David H. O'Connor Jan 2020

Discovery Of A Novel Simian Pegivirus In Common Marmosets (Callithrix Jacchus) With Lymphocytic Enterocolitis, Anna S. Heffron, Michael Lauck, Elizabeth D. Somsen, Elizabeth C. Townsend, Adam L. Bailey, Megan Sosa, Jens Eickhoff, Saverio Capuano Iii, Christina M. Newman, Jens H. Kuhn, Andres Mejia, Heather A. Simmons, David H. O'Connor

Open Access Publications

No abstract provided.


Human Ferroportin Mediates Proton-Coupled Active Transport Of Iron, Shuang Li, Yihu Yang, Weikai Li Jan 2020

Human Ferroportin Mediates Proton-Coupled Active Transport Of Iron, Shuang Li, Yihu Yang, Weikai Li

Open Access Publications

No abstract provided.


Acvr1/Jak1/Jak2 Inhibitor Momelotinib Reverses Transfusion Dependency And Suppresses Hepcidin In Myelofibrosis Phase 2 Trial, Stephen T. Oh, Et Al. Jan 2020

Acvr1/Jak1/Jak2 Inhibitor Momelotinib Reverses Transfusion Dependency And Suppresses Hepcidin In Myelofibrosis Phase 2 Trial, Stephen T. Oh, Et Al.

Open Access Publications

No abstract provided.


Mitochondrial Calcium Uniporter (Mcu) Defciency Reveals An Alternate Path For ­Ca2+ Uptake In Photoreceptor Mitochondria, Celia M. Bisbach, Rachel A. Hutto, Deepak Poria, Whitney M. Cleghorn, Fatima Abbas, Frans Vinberg, Vladimir J. Kefalov, James B. Hurley, Susan E. Brockerhoff Jan 2020

Mitochondrial Calcium Uniporter (Mcu) Defciency Reveals An Alternate Path For ­Ca2+ Uptake In Photoreceptor Mitochondria, Celia M. Bisbach, Rachel A. Hutto, Deepak Poria, Whitney M. Cleghorn, Fatima Abbas, Frans Vinberg, Vladimir J. Kefalov, James B. Hurley, Susan E. Brockerhoff

Open Access Publications

No abstract provided.


Six-Year Follow-Up Of A Trial Of Antenatal Vitamin D For Asthma Reduction, Augusto A. Litonjua, Vincent J. Carey, Nancy Laranjo, Benjamin J. Stubbs, Hooman Mirzakhani, George T. O'Connor, Megan Sandel, Avraham Beigelman, Leonard B. Bacharier, Robert S. Zeiger, Michael Schatz, Bruce W. Hollis, Scott T. Weiss Jan 2020

Six-Year Follow-Up Of A Trial Of Antenatal Vitamin D For Asthma Reduction, Augusto A. Litonjua, Vincent J. Carey, Nancy Laranjo, Benjamin J. Stubbs, Hooman Mirzakhani, George T. O'Connor, Megan Sandel, Avraham Beigelman, Leonard B. Bacharier, Robert S. Zeiger, Michael Schatz, Bruce W. Hollis, Scott T. Weiss

Open Access Publications

No abstract provided.


Self-Reported Sleep Disturbance In Crohn’S Disease Is Not Confrmed By Objective Sleep Measures, Heba N. Iskandar, Emily E. Linan, Ami Patel, Renee Moore, Yi Lasanajak, C. Prakash Gyawali, Gregory S. Sayuk, Matthew A. Ciorba Jan 2020

Self-Reported Sleep Disturbance In Crohn’S Disease Is Not Confrmed By Objective Sleep Measures, Heba N. Iskandar, Emily E. Linan, Ami Patel, Renee Moore, Yi Lasanajak, C. Prakash Gyawali, Gregory S. Sayuk, Matthew A. Ciorba

Open Access Publications

No abstract provided.


Heavy Metals Contaminating The Environment Of A Progressive Supranuclear Palsy Cluster Induce Tau Accumulation And Cell Death In Cultured Neurons, Carolina Alquezar, Jessica B. Felix, Elizabeth Mccandlish, Brian T. Buckley, Dominique Caparros-Lefebvre, Celeste M. Karch, Lawrence I. Golbe, Aimee W. Kao Jan 2020

Heavy Metals Contaminating The Environment Of A Progressive Supranuclear Palsy Cluster Induce Tau Accumulation And Cell Death In Cultured Neurons, Carolina Alquezar, Jessica B. Felix, Elizabeth Mccandlish, Brian T. Buckley, Dominique Caparros-Lefebvre, Celeste M. Karch, Lawrence I. Golbe, Aimee W. Kao

Open Access Publications

No abstract provided.


Generation Of Light-Producing Somatic-Transgenic Mice Using Adeno-Associated Virus Vectors, Rajvinder Karda, Jonathan D. Cooper, Et Al. Jan 2020

Generation Of Light-Producing Somatic-Transgenic Mice Using Adeno-Associated Virus Vectors, Rajvinder Karda, Jonathan D. Cooper, Et Al.

Open Access Publications

No abstract provided.