Digital Commons Network^™

Phase I Study Of Vemurafenib In Children With Recurrent Or Progressive Brafv600e Mutant Brain Tumors: Pacific Pediatric Neuro-Oncology Consortium Study (Pnoc-002), Theodore Nicolaides, Karen Gauvain, Et Al

Open Access Publications

No abstract provided.

Deconstructing Tumor Heterogeneity: The Stromal Perspective, Renee E. Vickman, Douglas V. Faget, Sheila A. Stewart, Et Al

Open Access Publications

Significant advances have been made towards understanding the role of immune cell-tumor interplay in either suppressing or promoting tumor growth, progression, and recurrence, however, the roles of additional stromal elements, cell types and/or cell states remain ill-defined. The overarching goal of this NCI-sponsored workshop was to highlight and integrate the critical functions of non-immune stromal components in regulating tumor heterogeneity and its impact on tumor initiation, progression, and resistance to therapy. The workshop explored the opposing roles of tumor supportive

Orsay Virus Cp-Δ Adopts A Novel Β-Bracelet Structural Fold And Incorporates Into Virions As A Head Fiber, Yusong R. Guo, Yanlin Fan, Ying Zhou, Miao Jin, Jim L. Zhang, Hongbing Jiang, Matthew V. Holt, Tao Wang, Nicolas L. Young, David Wang, Weiwei Zhong, Yizhi J. Tao

Open Access Publications

Fiber proteins are commonly found in eukaryotic and prokaryotic viruses, where they play important roles in mediating viral attachment and host cell entry. They typically form trimeric structures and are incorporated into virions via noncovalent interactions. Orsay virus, a small RNA virus which specifically infects the laboratory model nematode

Cadmium Activates Ampa And Nmda Receptors With M3 Helix Cysteine Substitutions, Timothy J. Wilding, James E. Huettner

Open Access Publications

AMPA and NMDA receptors are ligand-gated ion channels that depolarize postsynaptic neurons when activated by the neurotransmitter L-glutamate. Changes in the distribution and activity of these receptors underlie learning and memory, but excessive change is associated with an array of neurological disorders, including cognitive impairment, developmental delay, and epilepsy. All of the ionotropic glutamate receptors (iGluRs) exhibit similar tetrameric architecture, transmembrane topology, and basic framework for activation; conformational changes induced by extracellular agonist binding deform and splay open the inner helix bundle crossing that occludes ion flux through the channel. NMDA receptors require agonist binding to all four subunits, whereas …

Tourette Syndrome Research Highlights From 2019, Andreas Hartmann, Yulia Worbe, Kevin J Black

Open Access Publications

This is the sixth yearly article in the Tourette Syndrome Research Highlights series, summarizing research from 2019 relevant to Tourette syndrome and other tic disorders. The highlights from 2020 is being drafted on the Authorea online authoring platform; readers are encouraged to add references or give feedback on our selections comments feature on this page. After the calendar year ends, this article is submitted as the annual update for the Tics collection F1000Research.

Tictimer Web: Software For Measuring Tic Suppression Remotely, Jonathan K Black, Jonathan M Koller, Kevin J. Black

Open Access Publications

Woods and Himle developed a standardized tic suppression paradigm (TSP) for the experimental setting, to quantify the effects of intentional tic suppression in Tourette syndrome. We previously provided a computer program to facilitate recording tic occurrence and to automate reward delivery during the several experimental conditions of the TSP. The present article describes a web-based program that performs the same functions. Implementing this program on the web allows research sessions to be performed remotely, in tandem with a video calling program. Relevant data for each session, such as the timing of tics and dispensed rewards, are stored in plain text …

Sex Differences In Population Dynamics During Formation Of Kidney Bacterial Communities By Uropathogenic Escherichia Coli, Lisa K. Mclellan, Allyssa L. Daugherty, David A. Hunstad

Open Access Publications

No abstract provided.

Identification Of New Helicobacter Pylori Subpopulations In Native Americans And Mestizos From Peru, Andrés Julián Gutiérrez-Escobar, Douglas E Berg, Et Al

Open Access Publications

Region-specific

Campylobacter Colonization, Environmental Enteric Dysfunction, Stunting, And Associated Risk Factors Among Young Children In Rural Ethiopia: A Cross-Sectional Study From The Campylobacter Genomics And Environmental Enteric Dysfunction (Caged) Project, Dehao Chen, Mark J Manary, Et Al

Open Access Publications

Livestock farming provides a possible mechanism by which smallholder farmers can meet their household need for animal source foods (ASF), which may reduce the risk of stunting. However, direct/indirect contacts with domestic animals may increase colonization by

Insights From Genetic Studies Of Cerebral Palsy, Sara A Lewis, Sheetal Shetty, Bryce A Wilson, Aris J Huang, Sheng Chih Jin, Hayley Smithers-Sheedy, Michael C Fahey, Michael C Kruer

Open Access Publications

Cohort-based whole exome and whole genome sequencing and copy number variant (CNV) studies have identified genetic etiologies for a sizable proportion of patients with cerebral palsy (CP). These findings indicate that genetic mutations collectively comprise an important cause of CP. We review findings in CP genomics and propose criteria for CP-associated genes at the level of gene discovery, research study, and clinical application. We review the published literature and report 18 genes and 5 CNVs from genomics studies with strong evidence of for the pathophysiology of CP. CP-associated genes often disrupt early brain developmental programming or predispose individuals to known …

Assessment Of Potential Risk Factors For The Development Of Persistent Postural-Perceptual Dizziness: A Case-Control Pilot Study, Aaron Trinidade, Paula Harman, Jon Stone, Jeffrey P Staab, Joel A Goebel

Open Access Publications

No abstract provided.

Nonmicrobial Activation Of Tlrs Controls Intestinal Growth, Wound Repair, And Radioprotection, William F Stenson, Matthew A Ciorba

Open Access Publications

TLRs, key components of the innate immune system, recognize microbial molecules. However, TLRs also recognize some nonmicrobial molecules. In particular, TLR2 and TLR4 recognize hyaluronic acid, a glycosaminoglycan in the extracellular matrix. In neonatal mice endogenous hyaluronic acid binding to TLR4 drives normal intestinal growth. Hyaluronic acid binding to TLR4 in pericryptal macrophages results in cyclooxygenase2- dependent PGE

Mental Distress And Human Rights Violations During Covid-19: A Rapid Review Of The Evidence Informing Rights, Mental Health Needs, And Public Policy Around Vulnerable Populations, Muhammad Rahman, Rabab Ahmed, Ross Brownson, Mary Mckay, Et Al

Open Access Publications

No abstract provided.

Apurinic/Apyrimidinic Endonuclease 1 Restricts The Internalization Of Bacteria Into Human Intestinal Epithelial Cells Through The Inhibition Of Rac1, Gerco Den Hartog, Lindsay D Butcher, Amber L Ablack, Laura A Pace, Jailal N G Ablack, Richard Xiong, Soumita Das, Thaddeus S Stappenbeck, Lars Eckmann, Peter B Ernst, Sheila E Crowe

Open Access Publications

Pathogenic intestinal bacteria lead to significant disease in humans. Here we investigated the role of the multifunctional protein, Apurinic/apyrimidinic endonuclease 1 (APE1), in regulating the internalization of bacteria into the intestinal epithelium. Intestinal tumor-cell lines and primary human epithelial cells were infected with

Regulatory T Cells Developing Peri-Weaning Are Continually Required To Restrain Th2 Systemic Responses Later In Life, Kathryn A. Knoop, Keely G Mcdonald, Chyi-Song Hsieh, Phillip I Tarr, Rodney D Newberry

Open Access Publications

Atopic disorders including allergic rhinitis, asthma, food allergy, and dermatitis, are increasingly prevalent in Western societies. These disorders are largely characterized by T helper type 2 (Th2) immune responses to environmental triggers, particularly inhaled and dietary allergens. Exposure to such stimuli during early childhood reduces the frequency of allergies in at-risk children. These allergic responses can be restrained by regulatory T cells (Tregs), particularly Tregs arising in the gut. The unique attributes of how early life exposure to diet and microbes shape the intestinal Treg population is a topic of significant interest. While imprinting during early life promotes the development …

Rna Based Approaches To Profile Oncogenic Pathways From Low Quantity Samples To Drive Precision Oncology Strategies, Anja Van De Stolpe, Wim Verhaegh, Jean-Yves Blay, Cynthia X Ma, Patrick Pauwels, Mark Pegram, Hans Prenen, Dirk De Ruysscher, Nabil F Saba, Susan F Slovin, Karen Willard-Gallo, Hatim Husain

Open Access Publications

Precision treatment of cancer requires knowledge on active tumor driving signal transduction pathways to select the optimal effective targeted treatment. Currently only a subset of patients derive clinical benefit from mutation based targeted treatment, due to intrinsic and acquired drug resistance mechanisms. Phenotypic assays to identify the tumor driving pathway based on protein analysis are difficult to multiplex on routine pathology samples. In contrast, the transcriptome contains information on signaling pathway activity and can complement genomic analyses. Here we present the validation and clinical application of a new knowledge-based mRNA-based diagnostic assay platform (OncoSignal) for measuring activity of relevant signaling …

Using The Zebrafish Lateral Line To Understand The Roles Of Mitochondria In Sensorineural Hearing Loss, Melanie Holmgren, Lavinia Sheets

Open Access Publications

Hair cells are the mechanosensory receptors of the inner ear and can be damaged by noise, aging, and ototoxic drugs. This damage often results in permanent sensorineural hearing loss. Hair cells have high energy demands and rely on mitochondria to produce ATP as well as contribute to intracellular calcium homeostasis. In addition to generating ATP, mitochondria produce reactive oxygen species, which can lead to oxidative stress, and regulate cell death pathways. Zebrafish lateral-line hair cells are structurally and functionally analogous to cochlear hair cells but are optically and pharmacologically accessible within an intact specimen, making the zebrafish a good model …

Advances In Modeling The Immune Microenvironment Of Colorectal Cancer, Paul Sukwoo Yoon, Nuala Del Piccolo, Venktesh S Shirure, Yushuan Peng, Amanda Kirane, Robert J Canter, Ryan C Fields, Steven C George, Sepideh Gholami

Open Access Publications

Colorectal cancer (CRC) is the third most common cancer and second leading cause of cancer-related death in the US. CRC frequently metastasizes to the liver and these patients have a particularly poor prognosis. The infiltration of immune cells into CRC tumors and liver metastases accurately predicts disease progression and patient survival. Despite the evident influence of immune cells in the CRC tumor microenvironment (TME), efforts to identify immunotherapies for CRC patients have been limited. Here, we argue that preclinical model systems that recapitulate key features of the tumor microenvironment-including tumor, stromal, and immune cells; the extracellular matrix; and the vasculature-are …

Ige And T Cell Reactivity To A Comprehensive Panel Of Cockroach Allergens In Relation To Disease, Anna Pomés, Véronique Schulten, Jill Glesner, Ricardo Da Silva Antunes, Aaron Sutherland, Leonard B Bacharier, Avraham Beigelman, Paula Busse, April Frazier, Alessandro Sette

Open Access Publications

IgE sensitization to cockroach allergens is associated with development of allergic diseases, such as asthma. To understand the relevance of different cockroach allergens for diagnosis and immunotherapy, a comprehensive analysis of IgE antibody levels and T cell reactivity to an expanded set of cockroach allergens and their relationship to disease was performed in a cohort of USA cockroach sensitized patients. IgE antibody levels to recombinant chitinase and hemocyanin were measured for 23 subjects by custom-made ImmunoCAPs and compared with IgE levels to eight cockroach allergens we previously reported for the same cohort.

Nab-Paclitaxel Plus Durvalumab In Patients With Previously Treated Advanced Stage Non-Small Cell Lung Cancer (Abound.2l+), Daniel Morgensztern, Manuel Cobo Dols, Santiago Ponce Aix, Pieter E Postmus, Jaafar Bennouna, Jürgen R Fischer, Oscar Juan-Vidal, David J Stewart, Andrea Ardizzoni, Rafia Bhore, Marianne Wolfsteiner, Martin Reck, Denis Talbot, Ramaswamy Govindan, Teng Jin Ong

Open Access Publications

No abstract provided.

Treatment-Emergent Neuroendocrine Prostate Cancer: A Clinicopathological And Immunohistochemical Analysis Of 94 Cases, Qingfu Zhang, Yunan Han, Yao Zhang, Dan Liu, Jian Ming, Bo Huang, Xueshan Qiu

Open Access Publications

Purpose: This study aimed to evaluate the pathological characteristics, immunophenotype, and prognosis of treatment-emergent neuroendocrine prostate cancer (T-NEPC).

Materials and Methods: We collected 231 repeated biopsy specimens of castration-resistant prostate cancer (CRPC) cases between 2008 and 2019. We used histopathological and immunohistochemical evaluations of Synaptophysin (SYN), ChromograninA (CgA), CD56, androgen receptor (AR), and prostate

Results: Among the 231 CRPC cases, 94 (40.7%) cases were T-NEPC. T-NEPC were more likely to present with negative immunohistochemistry for AR (30.9%) and PSA (47.9%) than that of CRPC (8.8% and 17.5%, respectively). Kaplan-Meier analysis revealed that patients with T-NEPC (median overall survival [OS]: 17.6 …

Toxic Effects Of Endoplasmic Reticulum Stress Transducer Bbf2h7-Derived Small Peptide Fragments On Neuronal Cells, Koji Matsuhisa, Longjie Cai, Atsushi Saito, Fumika Sakaue, Yasunao Kamikawa, Sachiko Fujiwara, Rie Asada, Yukitsuka Kudo, Kazunori Imaizumi

Open Access Publications

No abstract provided.

Sirt1 Mediates Hypoxic Preconditioning Induced Attenuation Of Neurovascular Dysfunction Following Subarachnoid Hemorrhage, Ananth K. Vellimana, Diane J. Aum, Deepti Diwan, Julian V. Clarke, James W. Nelson, Molly Lawrence, Byung Hee Han, Jeffrey M. Gidday, Gregory J. Zipfel

Open Access Publications

No abstract provided.

Randomized Controlled Crossover Trials Of The Pharmacokinetics Of Prc-063, A Novel Multilayer Extended-Release Formulation Of Methylphenidate, In Healthy Adults, Martin A. Katzman, Greg Mattingly, Larry J. Klassen, Marc J. Cataldo, Graeme A. E. Donnelly

Open Access Publications

No abstract provided.

Dementia Research In The Caribbean Hispanic Islands: Present Findings And Future Trends, Daisy Acosta, Jorge J Llibre-Guerra, Ivonne Z Jiménez-Velázquez, Juan J Llibre-Rodríguez

Open Access Publications

During the last decade, the Caribbean Hispanic islands experienced accelerated demographic aging, representing the fastest aging region within Latin America. Age-related non-communicable diseases, including dementia, are now reported at high prevalence. The Caribbean islands share similar genetic ancestry, culture, migration patterns, and risk profiles, providing a unique setting to understand dementia in the Caribbean-Hispanics. This perspective article aimed to describe the impact of dementia in the Caribbean, at a local and regional level and reflect on research strategies to address dementia. We report on 10/66 project findings, described research projects and regional plans for the region. According to our results, …

Intensive Teenage Activity Is Associated With Greater Muscle Hyperintensity On T1w Magnetic Resonance Imaging In Adults With Dysferlinopathy, Ursula Moore, Alan Pestronk, Et Al

Open Access Publications

Practice of sports during childhood or adolescence correlates with an earlier onset and more rapidly progressing phenotype in dysferlinopathies. To determine if this correlation relates to greater muscle pathology that persists into adulthood, we investigated the effect of exercise on the degree of muscle fatty replacement measured using muscle MRI. We reviewed pelvic, thigh and leg T1W MRI scans from 160 patients with genetically confirmed dysferlinopathy from the Jain Foundation International clinical outcomes study in dysferlinopathy. Two independent assessors used the Lamminen-Mercuri visual scale to score degree of fat replacement in each muscle. Exercise intensity for each individual was defined …

The Impact Of Sars-Cov-2 In Dementia Across Latin America: A Call For An Urgent Regional Plan And Coordinated Response, Agustin Ibanez, Jorge Llibre-Guerra, Et Al

Open Access Publications

The SARS-CoV-2 global pandemic will disproportionately impact countries with weak economies and vulnerable populations including people with dementia. Latin American and Caribbean countries (LACs) are burdened with unstable economic development, fragile health systems, massive economic disparities, and a high prevalence of dementia. Here, we underscore the selective impact of SARS-CoV-2 on dementia among LACs, the specific strain on health systems devoted to dementia, and the subsequent effect of increasing inequalities among those with dementia in the region. Implementation of best practices for mitigation and containment faces particularly steep challenges in LACs. Based upon our consideration of these issues, we urgently …

Prospective Trial Of Sacroiliac Joint Fusion Using 3d-Printed Triangular Titanium Implants, Vikas Patel, Don Kovalsky, S Craig Meyer, Abhineet Chowdhary, Harry Lockstadt, Fernando Techy, Casey Langel, Robert Limoni, Philip S Yuan, Andy Kranenburg, Daniel Cher, Gabriel Tender, Travis J Hillen

Open Access Publications

Background: Prior trials provide strong evidence supporting minimally invasive sacroiliac joint (SIJ) fusion using triangular titanium implants (TTI) for chronic SIJ dysfunction.

Objective: To assess the safety and effectiveness of SIJF using a 3D-printed TTI.

Methods: Fifty-one subjects with carefully diagnosed SIJ dysfunction underwent SIJF with 3D TTI. Subjects completed pain, disability and quality of life questionnaires at baseline and 3, 6 and 12 months postoperatively. Functional tests were performed in the clinic at each visit. Pelvic CT scans were independently evaluated for radiolucency, bridging bone and other endpoints.

Results: Ninety percent had 12-month follow-up. Dysfunction due to pain (Oswestry …

Essential But Undefined — Reimagining How Policymakers Identify Safety-Net Hospitals, Paula Chatterjee, Benjamin D. Sommers, Karen E. Joynt Maddox

Open Access Publications

No abstract provided.

Effects Of Diet Versus Gastric Bypass On Metabolic Function In Diabetes, Mihoko Yoshino, Brandon D. Kayser, Jun Yoshino, Richard I. Stein, Dominic Reeds, J. Christopher Eagon, Shaina R. Eckhouse, Jeramie D. Watrous, Mohit Jain, Rob Knight, Kenneth Schechtman, Bruce W. Patterson, Samuel Klein

Open Access Publications

No abstract provided.