Digital Commons Network^™

Mechanical Overstimulation Causes Acute Injury And Synapse Loss Followed By Fast Recovery In Lateral-Line Neuromasts Of Larval Zebrafish, Melanie Holmgren, Michael E. Ravicz, Kenneth E. Hancock, Olga Strelkova, Dorina Kallogjeri, Artur A. Indzhykulian, Mark E. Warchol, Lavinia Sheets

Open Access Publications

Excess noise damages sensory hair cells, resulting in loss of synaptic connections with auditory nerves and, in some cases, hair-cell death. The cellular mechanisms underlying mechanically induced hair-cell damage and subsequent repair are not completely understood. Hair cells in neuromasts of larval zebrafish are structurally and functionally comparable to mammalian hair cells but undergo robust regeneration following ototoxic damage. We therefore developed a model for mechanically induced hair-cell damage in this highly tractable system. Free swimming larvae exposed to strong water wave stimulus for 2 hr displayed mechanical injury to neuromasts, including afferent neurite retraction, damaged hair bundles, and reduced …

Inflammatory Pathophysiology As A Contributor To Myeloproliferative Neoplasms, Daniel Arthur Corpuz Fisher, Jared Scott Fowles, Amy Zhou, Stephen Tracy Oh

Open Access Publications

Myeloid neoplasms, including acute myeloid leukemia (AML), myeloproliferative neoplasms (MPNs), and myelodysplastic syndromes (MDS), feature clonal dominance and remodeling of the bone marrow niche in a manner that promotes malignant over non-malignant hematopoiesis. This take-over of hematopoiesis by the malignant clone is hypothesized to include hyperactivation of inflammatory signaling and overproduction of inflammatory cytokines. In the

Tissue Biodistribution And Tumor Targeting Of Near-Infrared Labelled Anti-Cd38 Antibody-Drug Conjugate In Preclinical Multiple Myeloma, Nicholas Cho, Sooah Ko, Monica Shokeen

Open Access Publications

Daratumumab (DARA) is an FDA-approved high-affinity monoclonal antibody targeting CD38 that has shown promising therapeutic efficacy in double refractory multiple myeloma (MM) patients. Despite the well-established clinical efficacy of DARA, not all heavily pretreated patients respond to single-agent DARA, and the majority of patients who initially respond eventually progress. Antibody-drug conjugates (ADCs) combine the highly targeted tumor antigen recognition of antibodies with the cell killing properties of chemotherapy for effective internalization and processing of the drug. In this study, we evaluated the anti-tumor efficacy of DARA conjugated to the maytansine derivative, mertansine (DM1), linked via a non-cleavable bifunctional linker. The …

The Valproate Mediates Radio-Bidirectional Regulation Through Rfwd3-Dependent Ubiquitination On Rad51, Guochao Liu, David Lim, Zuchao Cai, Wenwen Ding, Zhujun Tian, Chao Dong, Fengmei Zhang, Gongshe Guo, Xiaowei Wang, Pingkun Zhou, Zhihui Feng

Open Access Publications

Ionizing radiation (IR) can induce DNA double-strand breaks (DSBs) in tumor cells during radiotherapy (RT), but the efficiency of RT is limited because of the toxicity to normal cells. Locating an adjuvant treatment to alleviate damage in normal cells while sensitizing tumor cells to IR has attracted much attention. Here, using the 7,12-dimethylbenz[α]anthracene (DMBA)-induced malignant transformed MCF10A cells, we found that valproate (VPA), a histone deacetylase inhibitor (HDACi), radiosensitized transformed cells while alleviated IR-induced damage in normal cells at a safe dose (0.5 mM). We further demonstrated the decrease of homologous recombination (HR)-associated Rad51 in the transformed cells was related …

Corynebacterium Species Inhibit Streptococcus Pneumoniae Colonization And Infection Of The Mouse Airway, Kadi J Horn, Alexander C Jaberi Vivar, Vera Arenas, Sameer Andani, Edward N Janoff, Sarah E Clark

Open Access Publications

The stability and composition of the airway microbiome is an important determinant of respiratory health. Some airway bacteria are considered to be beneficial due to their potential to impede the acquisition and persistence of opportunistic bacterial pathogens such as

Green Nanotechnology Of Mgf‑Aunps For Immunomodulatory Intervention In Prostate Cancer Therapy, Menka Khoobchandani, Aslam Khan, Kavita K. Katti, Velaphi C. Thipe, Amal Y. Al-Yasiri, Darsha K. D. Mohandoss, Michael B. Nicholl, Ademar B. Lugão, Chetan P. Hans, Kattesh V. Katti

Open Access Publications

No abstract provided.

Cancer-Associated Mesothelial Cells Promote Ovarian Cancer Chemoresistance Through Paracrine Osteopontin Signaling, Jin Qian, Bauer L Lesavage, Kelsea M Hubka, Chenkai Ma, Suchitra Natarajan, Joshua T Eggold, Yiren Xiao, Katherine C Fuh, Venkatesh Krishnan, Annika Enejder, Sarah C Heilshorn, Oliver Dorigo, Erinn B Rankin

Open Access Publications

Ovarian cancer is the leading cause of gynecological malignancy-related deaths, due to its widespread intraperitoneal metastases and acquired chemoresistance. Mesothelial cells are an important cellular component of the ovarian cancer microenvironment that promote metastasis. However, their role in chemoresistance is unclear. Here, we investigated whether cancer-associated mesothelial cells promote ovarian cancer chemoresistance and stemness in vitro and in vivo. We found that osteopontin is a key secreted factor that drives mesothelial-mediated ovarian cancer chemoresistance and stemness. Osteopontin is a secreted glycoprotein that is clinically associated with poor prognosis and chemoresistance in ovarian cancer. Mechanistically, ovarian cancer cells induced osteopontin expression …

The Sarm1 Tir Nadase: Mechanistic Similarities To Bacterial Phage Defense And Toxin-Antitoxin Systems, Aaron Diantonio, Jeffrey Milbrandt, Matthew D Figley

Open Access Publications

The Toll/interleukin-1 receptor (TIR) domain is the signature signalling motif of innate immunity, with essential roles in innate immune signalling in bacteria, plants, and animals. TIR domains canonically function as scaffolds, with stimulus-dependent multimerization generating binding sites for signalling molecules such as kinases and ligases that activate downstream immune mechanisms. Recent studies have dramatically expanded our understanding of the TIR domain, demonstrating that the primordial function of the TIR domain is to metabolize NAD

Predicting Mortality Among Patients With Liver Cirrhosis In Electronic Health Records With Machine Learning, Aixia Guo, Nikhilesh R. Mazumder, Daniela P. Ladner, Randi E. Foraker

Open Access Publications

OBJECTIVE: Liver cirrhosis is a leading cause of death and effects millions of people in the United States. Early mortality prediction among patients with cirrhosis might give healthcare providers more opportunity to effectively treat the condition. We hypothesized that laboratory test results and other related diagnoses would be associated with mortality in this population. Our another assumption was that a deep learning model could outperform the current Model for End Stage Liver disease (MELD) score in predicting mortality.

MATERIALS AND METHODS: We utilized electronic health record data from 34,575 patients with a diagnosis of cirrhosis from a large medical center …

Pharmacokinetics Of Single Domain Antibodies And Conjugated Nanoparticles Using A Hybrid Near Infrared Method, Shiran Su, Thomas J Esparza, Duong Nguyen, Simone Mastrogiacomo, Joong H Kim, David L Brody

Open Access Publications

Iron oxide nanoparticles and single domain antibodies from camelids (VHHs) have been increasingly recognized for their potential uses for medical diagnosis and treatment. However, there have been relatively few detailed characterizations of their pharmacokinetics (PK). The aim of this study was to develop imaging methods and pharmacokinetic models to aid the future development of a novel family of brain MRI molecular contrast agents. An efficient near-infrared (NIR) imaging method was established to monitor VHH and VHH conjugated nanoparticle kinetics in mice using a hybrid approach: kinetics in blood were assessed by direct sampling, and kinetics in kidney, liver, and brain …

Emerging Nanotechnology For Treatment Of Alzheimer's And Parkinson's Disease, Amanda Li, Joel Tyson, Shivni Patel, Meer Patel, Sruthi Katakam, Xiaobo Mao, Weiwei He

Open Access Publications

The prevalence of the two most common neurodegenerative diseases, Parkinson's disease (PD) and Alzheimer's Disease (AD), are expected to rise alongside the progressive aging of society. Both PD and AD are classified as proteinopathies with misfolded proteins α-synuclein, amyloid-β, and tau. Emerging evidence suggests that these misfolded aggregates are prion-like proteins that induce pathological cell-to-cell spreading, which is a major driver in pathogenesis. Additional factors that can further affect pathology spreading include oxidative stress, mitochondrial damage, inflammation, and cell death. Nanomaterials present advantages over traditional chemical or biological therapeutic approaches at targeting these specific mechanisms. They can have intrinsic properties …

Familial History Of Autoimmune Disorders Among Patients With Pediatric Multiple Sclerosis, Benjamin M. Greenberg, Soe S. Mar, Shannon Liang, Manu Goyal, Et Al

Open Access Publications

No abstract provided.

Glucose-Mediated De Novo Lipogenesis In Photoreceptors Drives Early Diabetic Retinopathy, Rithwick Rajagopal, Beau Sylvester, Sheng Zhang, Sangeeta Adak, Xiaochao Wei, Megan Bowers, Sebastian Jessberger, Fong-Fu Hsu, Clay F. Semenkovich

Open Access Publications

No abstract provided.

Bromodomain Protein Brd4 Directs And Sustains Cd8 T Cell Differentiation During Infection, J. Justin Milner, Takeshi Egawa, Et Al

Open Access Publications

In response to infection, pathogen-specific CD8 T cells differentiate into functionally diverse effector and memory T cell populations critical for resolving disease and providing durable immunity. Through small-molecule inhibition, RNAi studies, and induced genetic deletion, we reveal an essential role for the chromatin modifier and BET family member BRD4 in supporting the differentiation and maintenance of terminally fated effector CD8 T cells during infection. BRD4 bound diverse regulatory regions critical to effector T cell differentiation and controlled transcriptional activity of terminal effector-specific super-enhancers in vivo. Consequentially, induced deletion of Brd4 or small molecule-mediated BET inhibition impaired maintenance of a terminal …

Unexpected Role Of Sterol Synthesis In Rna Stability And Translation In Leishmania, Zemfira N Karamysheva, Samrat Moitra, Andrea Perez, Sumit Mukherjee, Elena B Tikhonova, Andrey L Karamyshev, Kai Zhang

Open Access Publications

No abstract provided.

Development And External Validation Of Deep-Learning-Based Tumor Grading Models In Soft-Tissue Sarcoma Patients Using Mr Imaging, Fernando Navarro, Matthew B Spraker, Et Al

Open Access Publications

BACKGROUND: In patients with soft-tissue sarcomas, tumor grading constitutes a decisive factor to determine the best treatment decision. Tumor grading is obtained by pathological work-up after focal biopsies. Deep learning (DL)-based imaging analysis may pose an alternative way to characterize STS tissue. In this work, we sought to non-invasively differentiate tumor grading into low-grade (G1) and high-grade (G2/G3) STS using DL techniques based on MR-imaging.

METHODS: Contrast-enhanced T1-weighted fat-saturated (T1FSGd) MRI sequences and fat-saturated T2-weighted (T2FS) sequences were collected from two independent retrospective cohorts (training: 148 patients, testing: 158 patients). Tumor grading was determined following the French Federation of Cancer …

Combined Effect Of Lead Exposure And Allostatic Load On Cardiovascular Disease Mortality-A Preliminary Study, Emmanuel Obeng-Gyasi, Alesia C Ferguson, Katherine A Stamatakis, Michael A Province

Open Access Publications

This study explores the combined effect of lead (Pb) exposure and an index of chronic physiological stress on cardiovascular disease mortality using data from the National Health and Nutrition Examination Survey (NHANES) 1999-2008 linked to 1999-2014 National Death Index data. Chronic physiological stress was measured using the allostatic load (AL) index, which was formed by analyzing markers from the cardiovascular, inflammatory, and metabolic systems, with Pb levels, assessed using blood lead levels (BLL). The dataset was analyzed with statistical techniques to explore (a) the relationship between Pb exposure and AL, and (b) the combined role of Pb and AL on …

A Microfluidic-Based Filtration System To Enrich For Bone Marrow Disseminated Tumor Cells From Breast Cancer Patients, Sreeraj G. Pillai, Chidananda M. Siddappa, Cynthia Ma, Jackie Snider, Madhurima Kaushal, Mark A. Watson, Rebecca Aft

Open Access Publications

Disseminated tumors cells (DTCs) present in the bone marrow (BM) are believed to be the progenitors of distant metastatic spread, a major cause of mortality in breast cancer patients. To better understand the behavior and therapeutic vulnerabilities of these rare cell populations, unbiased methods for selective cell enrichment are required. In this study, we have evaluated a microfluidic-based filtration system (ParsortixR, Angle PLC), previously demonstrated for use in circulating tumor cell (CTC) capture, to capture BM DTCs. Performance using BM samples was also compared directly to enrichment of CTCs in the peripheral blood (PB) from both metastatic and non-metastatic breast …

Evaluation Of A Clinical Decision Support Strategy To Increase Seasonal Influenza Vaccination Among Hospitalized Children Before Inpatient Discharge, Evan W. Orenstein, Omar Elsayed-Ali, Swaminathan Kandaswamy, Erin Masterson, Reena Blanco, Pareen Shah, Patricia Lantis, Amy Kolwaite, Thomas E. Dawson, Edwin Ray, Christy Bryant, Srikant Iyer, Andi L. Shane, Stephanie Jernigan

Open Access Publications

Importance: Hospitalized children are at increased risk of influenza-related complications, yet influenza vaccine coverage remains low among this group. Evidence-based strategies about vaccination of vulnerable children during all health care visits are especially important during the COVID-19 pandemic.

Objective: To design and evaluate a clinical decision support (CDS) strategy to increase the proportion of eligible hospitalized children who receive a seasonal influenza vaccine prior to inpatient discharge.

Design, Setting, and Participants: This quality improvement study was conducted among children eligible for the seasonal influenza vaccine who were hospitalized in a tertiary pediatric health system providing care to more than half …

Cd16+Cd163+ Monocytes Traffic To Sites Of Inflammation During Necrotizing Enterocolitis In Premature Infants, Oluwabunmi O. Olaloye, Misty Good, Et Al

Open Access Publications

Necrotizing enterocolitis (NEC) is a severe gastrointestinal complication of prematurity. Using suspension and imaging mass cytometry coupled with single-cell RNA sequencing, we demonstrate severe inflammation in patients with NEC. NEC mucosa could be subtyped by an influx of three distinct neutrophil phenotypes (immature, newly emigrated, and aged). Furthermore, CD16+CD163+ monocytes/Mϕ, correlated with newly emigrated neutrophils, were specifically enriched in NEC mucosa, found adjacent to the blood vessels, and increased in circulation of infants with surgical NEC, suggesting trafficking from the periphery to areas of inflammation. NEC-specific monocytes/Mϕ transcribed inflammatory genes, including TREM1, IL1A, IL1B, and calprotectin, and neutrophil recruitment genes …

Targeting Angiogenesis For Fracture Nonunion Treatment In Inflammatory Disease, Cuicui Wang, Jun Ying, Xiaolei Nie, Tianhong Zhou, Ding Xiao, Guarav Swarnkar, Yousef Abu-Amer, Jianjun Guan, Jie Shen

Open Access Publications

No abstract provided.

Lesion Quantification Toolkit: A Matlab Software Tool For Estimating Grey Matter Damage And White Matter Disconnections In Patients With Focal Brain Lesions, Joseph C Griffis, Nicholas V Metcalf, Maurizio Corbetta, Gordon L Shulman

Open Access Publications

Lesion studies are an important tool for cognitive neuroscientists and neurologists. However, while brain lesion studies have traditionally aimed to localize neurological symptoms to specific anatomical loci, a growing body of evidence indicates that neurological diseases such as stroke are best conceptualized as brain network disorders. While researchers in the fields of neuroscience and neurology are therefore increasingly interested in quantifying the effects of focal brain lesions on the white matter connections that form the brain's structural connectome, few dedicated tools exist to facilitate this endeavor. Here, we present the Lesion Quantification Toolkit, a publicly available MATLAB software package for …

Brain/Minds Beyond Human Brain Mri Project: A Protocol For Multi-Level Harmonization Across Brain Disorders Throughout The Lifespan, Shinsuke Koike, Matthew F Glasser, David C Van Essen, Et Al

Open Access Publications

Psychiatric and neurological disorders are afflictions of the brain that can affect individuals throughout their lifespan. Many brain magnetic resonance imaging (MRI) studies have been conducted; however, imaging-based biomarkers are not yet well established for diagnostic and therapeutic use. This article describes an outline of the planned study, the Brain/MINDS Beyond human brain MRI project (BMB-HBM, FY2018 ~ FY2023), which aims to establish clinically-relevant imaging biomarkers with multi-site harmonization by collecting data from healthy traveling subjects (TS) at 13 research sites. Collection of data in psychiatric and neurological disorders across the lifespan is also scheduled at 13 sites, whereas designing …

Phase 3 Randomized Trial Of Chemotherapy With Or Without Oblimersen In Older Aml Patients: Calgb 10201 (Alliance), Alison R. Walker, Ravi Vij, Et Al.

Open Access Publications

No abstract provided.

The Extensive And Functionally Uncharacterized Mitochondrial Phosphoproteome, Natalie M. Niemi, David J. Pagliarini

Open Access Publications

No abstract provided.

Oasis/Creb3l1 Is A Factor That Responds To Nuclear Envelope Stress, Yasunao Kamikawa, Atsushi Saito, Koji Matsuhisa, Masayuki Kaneko, Rie Asada, Yasunori Horikoshi, Satoshi Tashiro, Kazunori Imaizumi

Open Access Publications

No abstract provided.

Genetic Association Study Of Childhood Aggression Across Raters, Instruments, And Age, Hill F. Ip, Andrew C. Heath, Pamela Madden, Et Al.

Open Access Publications

No abstract provided.

Report From The 6th International Meeting On Bone Marrow Adiposity (Bma2020), Erica L Scheller, Meghan E Mcgee-Lawrence, Beata Lecka-Czernik

Open Access Publications

The 6

Strategies And Tools For Studying Microglial-Mediated Synapse Elimination And Refinement, Raffaella Morini, Matteo Bizzotto, Fabio Perrucci, Fabia Filipello, Michela Matteoli

Open Access Publications

The role of microglia in controlling synapse homeostasis is becoming increasingly recognized by the scientific community. In particular, the microglia-mediated elimination of supernumerary synapses during development lays the basis for the correct formation of neuronal circuits in adulthood, while the possible reactivation of this process in pathological conditions, such as schizophrenia or Alzheimer's Disease, provides a promising target for future therapeutic strategies. The methodological approaches to investigate microglial synaptic engulfment include different

Ablative Five-Fraction Stereotactic Body Radiation Therapy For Inoperable Pancreatic Cancer Using Online Mr-Guided Adaptation, Comron Hassanzadeh, Soumon Rudra, Ani Bommireddy, William G Hawkins, Andrea Wang-Gillam, Ryan C Fields, Bin Cai, Justin Park, Olga Green, Michael Roach, Lauren Henke, Hyun Kim

Open Access Publications

Purpose: Patients with inoperable pancreatic adenocarcinoma have limited options, with traditional chemoradiation providing modest clinical benefit and an otherwise poor prognosis. Stereotactic body radiation therapy for pancreatic cancer is limited by proximity to organs-at-risk (OAR). However, stereotactic magnetic resonance-guided adaptive radiation therapy (SMART) has shown promise in delivering ablative doses safely. We sought to demonstrate the benefits of SMART using a 5-fraction approach with daily on-table adaptation.

Methods and Materials: Patients with locally advanced, nonmetastatic pancreatic adenocarcinoma were treated with 50 Gy in 5 fractions (biologically effective dose

Results: Forty-four patients were treated with SMART at our institution from 2014 …