Digital Commons Network^™

Tracking Regional Brain Growth Up To Age 13 In Children Born Term And Very Preterm, Deanne K. Thompson, Lilian G. Matthews, Bonnie Alexander, Katherine J. Lee, Claire E. Kelly, Chris L. Adamson, Rod W. Hunt, Jeanie L.Y. Cheong, Megan Spencer-Smith, Jeffrey J. Neil, Marc L. Seal, Terrie E. Inder, Lex W. Doyle, Peter J. Anderson

Open Access Publications

No abstract provided.

Interpreting Pathways To Discover Cancer Driver Genes With Moonlight, Antonio Colaprico, Matthew H. Bailey, Et Al.

Open Access Publications

No abstract provided.

Trial Of Sodium Phenylbutyrate–Taurursodiol For Amyotrophic Lateral Sclerosis, Sabrina Paganoni, Timothy M. Miller, Et Al

Open Access Publications

No abstract provided.

To “Heed The Call” Amidst The Covid-19 Pandemic, Andrew W. Kuhn, Francesca R. Coxe, Kyle N. Kunze, David N. Bernstein

Open Access Publications

No abstract provided.

Marrowquant Across Aging And Aplasia: A Digital Pathology Workflow For Quantification Of Bone Marrow Compartments In Histological Sections, Josefine Tratwal, Erica L Scheller, Et Al

Open Access Publications

The bone marrow (BM) exists heterogeneously as hematopoietic/red or adipocytic/yellow marrow depending on skeletal location, age, and physiological condition. Mouse models and patients undergoing radio/chemotherapy or suffering acute BM failure endure rapid adipocytic conversion of the marrow microenvironment, the so-called "red-to-yellow" transition. Following hematopoietic recovery, such as upon BM transplantation, a "yellow-to-red" transition occurs and functional hematopoiesis is restored. Gold Standards to estimate BM cellular composition are pathologists' assessment of hematopoietic cellularity in hematoxylin and eosin (H&E) stained histological sections as well as volumetric measurements of marrow adiposity with contrast-enhanced micro-computerized tomography (CE-μCT) upon osmium-tetroxide lipid staining. Due to user-dependent …

The Probable, Possible, And Novel Functions Of Erp29, Margaret Brecker, Svetlana Khakhina, Tyler J Schubert, Zachary Thompson, Ronald C Rubenstein

Open Access Publications

The luminal endoplasmic reticulum (ER) protein of 29 kDa (ERp29) is a ubiquitously expressed cellular agent with multiple critical roles. ERp29 regulates the biosynthesis and trafficking of several transmembrane and secretory proteins, including the cystic fibrosis transmembrane conductance regulator (CFTR), the epithelial sodium channel (ENaC), thyroglobulin, connexin 43 hemichannels, and proinsulin. ERp29 is hypothesized to promote ER to

Vitamin D Receptor Protects Against Dysbiosis And Tumorigenesis Via The Jak/Stat Pathway In Intestine, Yong-Guo Zhang, Rong Lu, Shaoping Wu, Ishita Chatterjee, David Zhou, Yinglin Xia, Jun Sun

Open Access Publications

BACKGROUND & AIMS: Vitamin D exerts regulatory roles via vitamin D receptor (VDR) in mucosal immunity, host defense, and inflammation involving host factors and microbiome. Human Vdr gene variation shapes the microbiome and VDR deletion leads to dysbiosis. Low VDR expression and diminished vitamin D/VDR signaling are observed in colon cancer. Nevertheless, how intestinal epithelial VDR is involved in tumorigenesis through gut microbiota remains unknown. We hypothesized that intestinal VDR protects mice against dysbiosis via modulating the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway in tumorigenesis.

METHODS: To test our hypothesis, we used an azoxymethane/dextran sulfate sodium-induced …

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.

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 …

A Regulatory Science Initiative To Harmonize And Standardize Digital Pathology And Machine Learning Processes To Speed Up Clinical Innovation To Patients, Hetal Desai Marble, Mike Isaacs, Et Al.

Open Access Publications

No abstract provided.

Dangerous Liaisons: Interactions Of Cryptococcus Neoformans With Host Phagocytes, Elizabeth A Gaylord, Hau Lam Choy, Tamara L Doering

Open Access Publications

No abstract provided.

Leukocyte Telomere Length Is Unrelated To Cognitive Performance Among Non-Demented And Demented Persons: An Examination Of Long Life Family Study Participants, Adiba Ashrafi, Stephanie Cosentino, Min S Kang, Joseph H Lee, Nicole Schupf, Stacy L Andersen, Kaare Christensen, Michael A Province, Bharat Thyagarajan, Joseph M Zmuda, Lawrence S Honig

Open Access Publications

OBJECTIVE: Leukocyte telomere length (LTL) is a widely hypothesized biomarker of biological aging. Persons with shorter LTL may have a greater likelihood of developing dementia. We investigate whether LTL is associated with cognitive function, differently for individuals without cognitive impairment versus individuals with dementia or incipient dementia.

METHOD: Enrolled subjects belong to the Long Life Family Study (LLFS), a multi-generational cohort study, where enrollment was predicated upon exceptional family longevity. Included subjects had valid cognitive and telomere data at baseline. Exclusion criteria were age ≤ 60 years, outlying LTL, and missing sociodemographic/clinical information. Analyses were performed using linear regression with …

Metabolic Effects Of Selective Deletion Of Group Via Phospholipase A2 From Macrophages Or Pancreatic Islet Beta-Cells, John Turk, Haowei Song, Mary Wohltmann, Cheryl Frankfater, Xiaoyong Lei, Sasanka Ramanadham

Open Access Publications

To examine the role of group VIA phospholipase A

Characterization Of A High-Resolution Breath Acetone Meter For Ketosis Monitoring, Donald J Suntrup Iii, Timothy V Ratto, Matt Ratto, James P Mccarter

Open Access Publications

Background: The ketone bodies beta-hydroxybutyrate (BHB) and acetone are endogenous products of fatty acid metabolism. Although ketone levels can be monitored by measuring either blood BHB or breath acetone, determining the precise correlation between these two measurement methods has been challenging. The purpose of this study is to characterize the performance of a novel portable breath acetone meter (PBAM) developed by Readout, Inc., to compare single versus multiple daily ketone measurements, and to compare breath acetone (BrAce) and blood BHB measurements.

Methods: We conducted a 14-day prospective observational cohort study of 21 subjects attempting to follow either a low-carbohydrate/ketogenic or …

Quality Of Anticoagulation With Warfarin In Rural Chhattisgarh, India, Puja Chebrolu, Sushil Patil, Timothy S. Laux, Noor Al-Hammadi, Yogesh Jain, Brian Gage

Open Access Publications

No abstract provided.

Chemical Effects Of Dicect Staining Protocols On Fluid-Preserved Avian Specimens, Catherine M. Early, Ashley C. Morhardt, Timothy P. Cleland, Christopher M. Milensky, Gwénaëlle M. Kavich, Helen F. James

Open Access Publications

Diffusible iodine-based contrast-enhanced computed tomography (diceCT) techniques allow visualization of soft tissues of fluid-preserved specimens in three dimensions without dissection or histology. Two popular diceCT stains, iodine-potassium iodide (I2KI) dissolved in water and elemental iodine (I2) dissolved in 100% ethanol (EtOH), yield striking results. Despite the widespread use of these stains in clinical and biological fields, the molecular mechanisms that result in color change and radiopacity attributed to iodine staining are poorly understood. Requests to apply these stains to anatomical specimens preserved in natural history museums are increasing, yet curators have little information about the potential for degradation of treated …

Effects Of Cyp46a1 Inhibition On Long-Term-Depression In Hippocampal Slices Ex Vivo And 24s-Hydroxycholesterol Levels In Mice In Vivo, Michael Popiolek, Yukitoshi Izumi, Allen T Hopper, Jing Dai, Silke Miller, Hong-Jin Shu, Charles F Zorumski, Steven Mennerick

Open Access Publications

The manipulation of cholesterol and its metabolites has been hypothesized to be therapeutically beneficial for mood disorders, neurodegenerative disorders, and epilepsies. A major regulator of cholesterol clearance and turnover in the central nervous system is CYP46A1, a brain enriched enzyme responsible for metabolism of cholesterol into 24S-hydroxycholesterol. Inhibition of this enzyme may negatively modulate NMDARs as 24S-hydroxycholesterol was shown to enhance NMDAR function. In addition, alterations of local cholesterol or other changes mediated by CYP46A1 activity could have important influences on central nervous system function. Here we demonstrate that humans and mice display brain region specific and similar CYP46A1 and …

A Pilot Study Of Cardiac Mri In Breast Cancer Survivors After Cardiotoxic Chemotherapy And Three-Dimensional Conformal Radiotherapy, Carmen Bergom, Jason Rubenstein, J Frank Wilson, Aimee Welsh, El-Sayed H Ibrahim, Phillip Prior, Aronne M Schottstaedt, Daniel Eastwood, Mei-Jie Zhang, Adam Currey, Lindsay Puckett, Jennifer L Strande, Julie A Bradley, Julia White

Open Access Publications

Purpose/Objectives: Node-positive breast cancer patients often receive chemotherapy and regional nodal irradiation. The cardiotoxic effects of these treatments, however, may offset some of the survival benefit. Cardiac magnetic resonance (CMR) is an emerging modality to assess cardiac injury. This is a pilot trial assessing cardiac damage using CMR in patients who received anthracycline-based chemotherapy and three-dimensional conformal radiotherapy (3DCRT) regional nodal irradiation using heart constraints.

Materials and Methods: Node-positive breast cancer patients (2000-2008) treated with anthracycline-based chemotherapy and 3DCRT regional nodal irradiation (including the internal mammary chain nodes) with heart ventricular constraints (V25 < 10%) were invited to participate. Cardiac tissues were contoured and analyzed separately for whole heart (pericardium) and for combined ventricles and left atrium (myocardium). CMR obtained ventricular function/dimensions, late gadolinium enhancement (LGE), global longitudinal strain (GLS), and extracellular volume fraction (ECV) as measures of cardiac injury and/or early fibrosis. CMR parameters were correlated with dose-volume constraints using Spearman correlations.

Results: Fifteen left-sided and five right-sided patients …

Mapping Geographical Inequalities In Access To Drinking Water And Sanitation Facilities In Low-Income And Middle-Income Countries, 2000-17, Aniruddha Deshpande, Ziyad Al-Aly, Local Burden Of Disease Wash Collaborators, Et Al

Open Access Publications

No abstract provided.

Discovery Of Driver Non-Coding Splice-Site-Creating Mutations In Cancer, Song Cao, Daniel Cui Zhou, Clara Oh, Reyka G. Jayasinghe, Yanyan Zhao, Christopher J. Yoon, Matthew A. Wyczalkowski, Matthew H. Bailey, Terrence Tsou, Qingsong Gao, Andrew Malone, Sheila Reynolds, Ilya Shmulevich, Michael C. Wendl, Feng Chen, Li Ding

Open Access Publications

No abstract provided.

Primary Cilia As The Nexus Of Biophysical And Hedgehog Signaling At The Tendon Enthesis, Fei Fang, Andrea G Schwartz, Emily R Moore, Mckenzie E Sup, Stavros Thomopoulos

Open Access Publications

The tendon enthesis is a fibrocartilaginous tissue critical for transfer of muscle forces to bone. Enthesis pathologies are common, and surgical repair of tendon to bone is plagued by high failure rates. At the root of these failures is a gap in knowledge of how the tendon enthesis is formed and maintained. We tested the hypothesis that the primary cilium is a hub for transducing biophysical and hedgehog (Hh) signals to regulate tendon enthesis formation and adaptation to loading. Primary cilia were necessary for enthesis development, and cilia assembly was coincident with Hh signaling and enthesis mineralization. Cilia responded inversely …

Portal Dosimetry Scripting Application Programming Interface (Pdsapi) For Winston-Lutz Test Employing Ceramic Balls, Yao Hao, Matthew C Schmidt, Yu Wu, Nels C Knutson

Open Access Publications

PURPOSE: Stereotactic radiosurgery (SRS) and stereotactic body radiation therapy (SBRT) treatments require a high degree of accuracy. Mechanical, imaging, and radiation isocenter coincidence is especially important. As a common method, the Winston-Lutz (WL) test plays an important role. However, weekly or daily WL test can be very time consuming. We developed novel methods using Portal Dosimetry Scripting Application Programming Interface (PDSAPI) to facilitate the test as well as documentation.

METHODS: Winston-Lutz PDSAPI was developed and tested on our routine weekly WL imaging. The results were compared against two commercially available software RIT (Radiological Imaging Technology, Colorado Springs, CO) and DoseLab …

Bidirectional Pathways Between Psychosocial Risk Factors And Paranoid Ideation In A General Nonclinical Population, Aino Saarinen, Niklas Granö, Mirka Hintsanen, Terho Lehtimäki, C Robert Cloninger, Liisa Keltikangas-Järvinen

Open Access Publications

We investigated (a) whether psychosocial factors (experienced stress, anticipatory worry, social detachment, sleeping disturbances, alcohol use) predict the course of paranoid ideation between the ages of 24 to 50 years and (b) whether the predictive relationships are more likely to proceed from the psychosocial factors to paranoid ideation, or vice versa. The participants (N = 1534-1553) came from the population-based Young Finns study. Paranoid ideation and psychosocial factors were assessed by reliable self-report questionnaires in 2001, 2007, and 2011/2012. The data were analyzed using growth curve and structural equation models. High experienced stress, anticipatory worry, social detachment, frequent sleeping disturbances, …

Immunotherapy And Radiation Therapy For Gastrointestinal Malignancies: Hope Or Hype?, Shahed Badiyan, Adeel Kaiser, Bory Eastman, Matthew Forsthoefel, Jing Zeng, Keith Unger, Michael Chuong

Open Access Publications

Immunotherapy represents the newest pillar in cancer care. Although there are increasing data showing the efficacy of immunotherapy there is a spectrum of response across unselected populations of cancer patients. In fact, response rates can be poor even among patients with immunogenic tumors for reasons that remain poorly understood. A promising clinical strategy to improve outcomes, which is supported by an abundance of preclinical data, is combining immunotherapy with radiation therapy. Here we review the existing evidence and future directions for combining immunotherapy and radiation therapy for patients with gastrointestinal cancers.

Determining The Recommended Dose Of Pacritinib: Results From The Pac203 Dose-Finding Trial In Advanced Myelofibrosis, Aaron T. Gerds, Stephen T. Oh, Et Al.

Open Access Publications

No abstract provided.

Genetic Loci Associated With Prevalent And Incident Myocardial Infarction And Coronary Heart Disease In The Cohorts For Heart And Aging Research In Genomic Epidemiology (Charge) Consortium, Julie Hahn, Mary F. Feitosa, Et Al.

Open Access Publications

BACKGROUND: Genome-wide association studies have identified multiple genomic loci associated with coronary artery disease, but most are common variants in non-coding regions that provide limited information on causal genes and etiology of the disease. To overcome the limited scope that common variants provide, we focused our investigation on low-frequency and rare sequence variations primarily residing in coding regions of the genome.

METHODS AND RESULTS: Using samples of individuals of European ancestry from ten cohorts within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, both cross-sectional and prospective analyses were conducted to examine associations between genetic variants …

Core Warming Of Coronavirus Disease 2019 (Covid-19) Patients Undergoing Mechanical Ventilation-A Protocol For A Randomized Controlled Pilot Study, Nathaniel Bonfanti, Emily Gundert, Anne M. Drewry, Kristina Goff, Roger Bedimo, Erik Kulstad

Open Access Publications

BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by the virus SARS-CoV-2, is spreading rapidly across the globe, with little proven effective therapy. Fever is seen in most cases of COVID-19, at least at the initial stages of illness. Although fever is typically treated (with antipyretics or directly with ice or other mechanical means), increasing data suggest that fever is a protective adaptive response that facilitates recovery from infectious illness.

OBJECTIVE: To describe a randomized controlled pilot study of core warming patients with COVID-19 undergoing mechanical ventilation.

METHODS: This prospective single-site randomized controlled pilot study will enroll 20 patients undergoing mechanical ventilation …

E Proteins Orchestrate Dynamic Transcriptional Cascades Implicated In The Suppression Of The Differentiation Of Group 2 Innate Lymphoid Cells, Vincent Peng, Constantin Georgescu, Anna Bakowska, Aneta Pankow, Liangyue Qian, Jonathan D. Wren, Xiao-Hong Sun

Open Access Publications

No abstract provided.

American Thyroid Association Sonographic Risk And Afirma Gene Expression Classifier Alone And In Combination For The Diagnosis Of Thyroid Nodules With Bethesda Category Iii Cytology, Marilyn Arosemena, Anu Thekkumkattil, Maria Linares Valderrama, Russ Kuker, Rosa Patricia Castillo, Charif Sidani, Manuel Lora Gonzalez, Sabina Casula, Atil Yilmaz Kargi

Open Access Publications

No abstract provided.

Cockayne Syndrome: The Many Challenges And Approaches To Understand A Multifaceted Disease, Alexandre Teixeira Vessoni, Camila Chaves Coelho Guerra, Gustavo Satoru Kajitani, Livia Luz Souza Nascimento, Camila Carrião Machado Garcia

Open Access Publications

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 …