Digital Commons Network^™

Exploration Of Sensory And Spinal Neurons Expressing Gastrin-Releasing Peptide In Itch And Pain Related Behaviors, Devin M. Barry, Xue-Ting Liu, Benlong Liu, Xian-Yu Liu, Fang Gao, Xiansi Zeng, Juan Liu, Qianyi Yang, Steven Wilhelm, Jun Yin, Ailin Tao, Zhou-Feng Chen

Open Access Publications

No abstract provided.

Advances In Vaporisation: A Narrative Review, Pankaj Kundra, Shreya Goswami, Aruna Parameswari

Open Access Publications

No abstract provided.

Structural Basis For Adhesion G Protein-Coupled Receptor Gpr126 Function, Katherine Leon, Rebecca L. Cunningham, Joshua A. Riback, Ezra Feldman, Jingxian Li, Tobin R. Sosnick, Minglei Zhao, Kelly R. Monk, Demet Araç

Open Access Publications

No abstract provided.

Dill Extract Induces Elastic Fiber Neosynthesis And Functional Improvement In The Ascending Aorta Of Aged Mice With Reversal Of Age-Dependent Cardiac Hypertrophy And Involvement Of Lysyl Oxidase-Like-1, Wassim Fhayli, Quentin Boëté, Nadjib Kihal, Valérie Cenizo, Pascal Sommer, Walter A Boyle, Marie-Paule Jacob, Gilles Faury

Open Access Publications

Elastic fibers (90% elastin, 10% fibrillin-rich microfibrils) are synthesized only in early life and adolescence mainly by the vascular smooth muscle cells through the cross-linking of its soluble precursor, tropoelastin. Elastic fibers endow the large elastic arteries with resilience and elasticity. Normal vascular aging is associated with arterial remodeling and stiffening, especially due to the end of production and degradation of elastic fibers, leading to altered cardiovascular function. Several pharmacological treatments stimulate the production of elastin and elastic fibers. In particular, dill extract (DE) has been demonstrated to stimulate elastin production in vitro in dermal equivalent models and in skin …

Induction Of Wnt16 Via Peptide-Mrna Nanoparticle-Based Delivery Maintains Cartilage Homeostasis, Huimin Yan, Ying Hu, Antonina Akk, Muhammad Farooq Rai, Hua Pan, Samuel A Wickline, Christine T N Pham

Open Access Publications

Osteoarthritis (OA) is a progressive joint disease that causes significant disability and pain and for which there are limited treatment options. We posit that delivery of anabolic factors that protect and maintain cartilage homeostasis will halt or retard OA progression. We employ a peptide-based nanoplatform to deliver Wingless and the name Int-1 (WNT) 16 messenger RNA (mRNA) to human cartilage explants. The peptide forms a self-assembled nanocomplex of approximately 65 nm in size when incubated with WNT16 mRNA. The complex is further stabilized with hyaluronic acid (HA) for enhanced cellular uptake. Delivery of peptide-WNT16 mRNA nanocomplex to human cartilage explants …

The Non-Coding Rna Landscape Of Plasma Cell Dyscrasias, Eugenio Morelli, Roberta Rocca, Kareem A Azab, Et Al

Open Access Publications

Despite substantial advancements have been done in the understanding of the pathogenesis of plasma cell (PC) disorders, these malignancies remain hard-to-treat. The discovery and subsequent characterization of non-coding transcripts, which include several members with diverse length and mode of action, has unraveled novel mechanisms of gene expression regulation often malfunctioning in cancer. Increasing evidence indicates that such non-coding molecules also feature in the pathobiology of PC dyscrasias, where they are endowed with strong therapeutic and/or prognostic potential. In this review, we aim to summarize the most relevant findings on the biological and clinical features of the non-coding RNA landscape of …

Roles Of Reconstituted High-Density Lipoprotein Nanoparticles In Cardiovascular Disease: A New Paradigm For Drug Discovery, Jiansheng Huang, Dongdong Wang, Li-Hao Huang, Hui Huang

Open Access Publications

Epidemiological results revealed that there is an inverse correlation between high-density lipoprotein (HDL) cholesterol levels and risks of atherosclerotic cardiovascular disease (ASCVD). Mounting evidence supports that HDLs are atheroprotective, therefore, many therapeutic approaches have been developed to increase HDL cholesterol (HDL-C) levels. Nevertheless, HDL-raising therapies, such as cholesteryl ester transfer protein (CETP) inhibitors, failed to ameliorate cardiovascular outcomes in clinical trials, thereby casting doubt on the treatment of cardiovascular disease (CVD) by increasing HDL-C levels. Therefore, HDL-targeted interventional studies were shifted to increasing the number of HDL particles capable of promoting ATP-binding cassette transporter A1 (ABCA1)-mediated cholesterol efflux. One such …

Patient-Controlled Intravenous Morphine Analgesia Combined With Transcranial Direct Current Stimulation For Post-Thoracotomy Pain: A Cost-Effectiveness Study And A Feasibility For Its Future Implementation, Nemanja Rancic, Katarina Mladenovic, Nela V Ilic, Viktorija Dragojevic-Simic, Menelaos Karanikolas, Tihomir V Ilic, Dusica M Stamenkovic

Open Access Publications

This prospective randomized study aims to evaluate the feasibility and cost-effectiveness of combining transcranial direct current stimulation (tDCS) with patient controlled intravenous morphine analgesia (PCA-IV) as part of multimodal analgesia after thoracotomy. Patients assigned to the active treatment group (a-tDCS,

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

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.

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 …

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.

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 …

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 …

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.

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.

Investigating The Ferric Ion Binding Site Of Magnetite Biomineralisation Protein Mms6, Andrea E. Rawlings, Panah Liravi, Sybilla Corbett, Alex S. Holehouse, Sarah S. Staniland

Open Access Publications

The biomineralization protein Mms6 has been shown to be a major player in the formation of magnetic nanoparticles both within the magnetosomes of magnetotactic bacteria and as an additive in synthetic magnetite precipitation assays. Previous studies have highlighted the ferric iron binding capability of the protein and this activity is thought to be crucial to its mineralizing properties. To understand how this protein binds ferric ions we have prepared a series of single amino acid substitutions within the C-terminal binding region of Mms6 and have used a ferric binding assay to probe the binding site at the level of individual …

High Prevalence Of Radiographic Outliers And Revisions With Unicompartmental Knee Arthroplasty, Gregory S Kazarian, Toby N Barrack, Louis Okafor, Robert L Barrack, Ryan M Nunley, Charles M Lawrie

Open Access Publications

BACKGROUND: Alignment outcomes and their impact on implant survival following unicompartmental knee arthroplasty (UKA) are unclear. The purpose of this study was to assess the implant survival and radiographic outcomes after UKA as well as the impact of component alignment and overhang on implant survival.

METHODS: We performed a retrospective analysis of 253 primary fixed-bearing and mobile-bearing medial UKAs from a single academic center. All UKAs were performed by 2 high-volume fellowship-trained arthroplasty surgeons. UKAs comprised <10% of their knee arthroplasty practices, with an average of 14.2 medial UKAs per surgeon per year. Implant survival was assessed. Femoral coronal (FCA), femoral sagittal (FSA), tibial coronal (TCA), and tibial sagittal (TSA) angles as well as implant overhang were radiographically measured. Outliers were defined for FCA (>±10° deviation from neutral), FSA (>15° of flexion), TCA (>±5° deviation from neutral), and TSA (>±5° deviation from 7°). "Far outliers" …

Orbitofrontal-Striatal Potentiation Underlies Cocaine-Induced Hyperactivity, Sebastiano Bariselli, Nanami L. Miyazaki, Meaghan C. Creed, Alexxai V. Kravitz

Open Access Publications

No abstract provided.

Contribution Of Aberrant Toll Like Receptor Signaling To The Pathogenesis Of Myelodysplastic Syndromes, Luana Chiquetto Paracatu, Laura G Schuettpelz

Open Access Publications

Toll like receptors (TLRs) are a family of pattern recognition receptors that play a central role in the innate immune response. These receptors are expressed on a wide variety of immune and non-immune cells, and they help shape the immune response to infection and injury through the recognition of pathogen-associated molecular patterns (PAMPs) as well as endogenous damage-associated molecular patterns (DAMPs). Accumulating evidence suggests that, in addition to regulating mature effector immune cells, TLRs can influence the immune response from the level of the hematopoietic stem cell (HSC). HSCs express TLRs, and exposure to TLR ligands influences the cycling, differentiation, …

The Road To Recovery: A Pilot Study Of Driving Behaviors Following Antibody-Mediated Encephalitis, Gregory S. Day, Ganesh M. Babulal, Ganesh Rajasekar, Sarah Stout, Catherine M. Roe

Open Access Publications

No abstract provided.

Outcome Of Everolimus-Based Therapy In Hormone-Receptor-Positive Metastatic Breast Cancer Patients After Progression On Palbociclib, Ajay Dhakal, Roby Antony Thomas, Ellis G. Levine, Adam Brufsky, Kazuaki Takabe, Matthew G. Hanna, Kristopher Attwood, Austin Miller, Thaer Khoury, Amy P. Early, Saif Soniwala, Tracy O'Connor, Matuesz Opyrchal

Open Access Publications

No abstract provided.