Digital Commons Network^™

Etv6 Germline Mutations Cause Hdac3/Ncor2 Mislocalization And Upregulation Of Interferon Response Genes., Marlie H. Fisher, Gregory D. Kirkpatrick, Brett Stevens, Courtney Jones, Michael Callaghan, Madhvi Rajpurkar, Joy M. Fulbright, Megan A. Cooper, Jesse Rowley, Christopher C. Porter, Arthur Gutierrez-Hartmann, Kenneth Jones, Craig Jordan, Eric M. Pietras, Jorge Di Paola

Manuscripts, Articles, Book Chapters and Other Papers

ETV6 is an ETS family transcription factor that plays a key role in hematopoiesis and megakaryocyte development. Our group and others have identified germline mutations in ETV6 resulting in autosomal dominant thrombocytopenia and predisposition to malignancy; however, molecular mechanisms defining the role of ETV6 in megakaryocyte development have not been well established. Using a combination of molecular, biochemical, and sequencing approaches in patient-derived PBMCs, we demonstrate abnormal cytoplasmic localization of ETV6 and the HDAC3/NCOR2 repressor complex that led to overexpression of HDAC3-regulated interferon response genes. This transcriptional dysregulation was also reflected in patient-derived platelet transcripts and drove aberrant proplatelet formation …

A Sonographer’S Step-By-Step Approach For Preventing Transmission Of Covid-19, Corinne Wessner, Joann Nelson, Sarah Mott, Maria Francesco, Laurence Needleman

Department of Radiology Faculty Papers

The 2019 novel coronavirus, known as COVID-19, has greatly affected the way sonographers care for their patients. Sonography can be a useful imaging tool for surveillance and diagnosis of various conditions associated with COVID-19 patients or patients under investigation (PUIs). Currently, there are limited resources and protocols for preventing the transmission of COVID-19 from ultrasound equipment. Our institution has created a detailed protocol for scanning COVID-19 patients or PUIs to address this important issue.

Supporting Coordination Of Children With Asd Using Neurological Music Therapy: A Pilot Randomized Control Trial Comparing An Elastic Touch-Display With Tambourines, Franceli L. Cibrian, Melisa Madrigal, Marina Avelais, Monica Tentori

Engineering Faculty Articles and Research

Aim

To evaluate the efficacy of Neurologic Music Therapy (NMT) using a traditional and a technological intervention (elastic touch-display) in improving the coordination of children with Autism Spectrum Disorder (ASD), as a primary outcome, and the timing and strength control of their movements as secondary outcomes.

Methods

Twenty-two children with ASD completed 8 NMT sessions, as a part of a 2-month intervention. Participants were randomly assigned to either use an elastic touch-display (experimental group) or tambourines (control group). We conducted pre- and post- assessment evaluations, including the Developmental Coordination Disorder Questionnaire (DCDQ) and motor assessments related to the control of …

Ier5, A Dna Damage Response Gene, Is Required For Notch-Mediated Induction Of Squamous Cell Differentiation, Li Pan, Madeleine E Lemieux, Tom Thomas, Julia M Rogers, Colin H Lipper, Winston Lee, Carl Johnson, Lynette M Sholl, Andrew P. South, Jarrod A Marto, Guillaume O Adelmant, Stephen C Blacklow, Jon C Aster

Department of Dermatology and Cutaneous Biology Faculty Papers

Notch signaling regulates squamous cell proliferation and differentiation and is frequently disrupted in squamous cell carcinomas, in which Notch is tumor suppressive. Here, we show that conditional activation of Notch in squamous cells activates a context-specific gene expression program through lineage-specific regulatory elements. Among direct Notch target genes are multiple DNA damage response genes, including IER5, which we show is required for Notch-induced differentiation of squamous carcinoma cells and TERT-immortalized keratinocytes. IER5 is epistatic to PPP2R2A, a gene that encodes the PP2A B55α subunit, which we show interacts with IER5 in cells and in purified systems. Thus, Notch and DNA-damage …

Parent Responses To Pediatric Pain: The Differential Effects Of Ethnicity On Opioid Consumption, Candice D. Donaldson, Brooke N. Jenkins, Michelle A. Fortier, Michael T. Phan, Daniel M. Tomaszewski, Sun Yang, Zeev N. Kain

Psychology Faculty Articles and Research

Objective

Within the context of the United States opioid epidemic, some parents often fear the use of opioids to help manage their children's postoperative pain. As a possible consequence, parents often do not dispense optimal analgesic medications to their children after surgery, putting their children at risk of suffering from postsurgical pain. The objective of this research was to assess ethnicity as a predictor of both pain and opioid consumption, and to examine how Hispanic/Latinx and Non-Hispanic White parents alter their child's opioid consumption in response to significant postsurgical pain.

Methods

Participants were 254 children undergoing outpatient tonsillectomy and/or adenoidectomy …

Prophylactic Mesh Placement For The Prevention Of Incisional Hernia In High-Risk Patients After Abdominal Surgery: A Systematic Review And Meta-Analysis, Jawad Ahmed, Nimra Hasnain, Iayla Fatima, Farheen Malik, Muhammad A. Chaudhary, Junaid Ahmad, Mehreen Malik, Laraib Malik, Muhammad Osama, Mirza Zain Baig, Faisal Khosa, Faiz Bhora

Department of Anaesthesia

Background and objectives: In high-risk populations, the efficacy of mesh placement in incisional hernia (IH) prevention after elective abdominal surgeries has been supported by many published studies. This meta-analysis aimed at providing comprehensive and updated clinical implications of prophylactic mesh placement (PMP) for the prevention of IH as compared to primary suture closure (PSC).
Materials and methods: PubMed, Science Direct, Cochrane, and Google Scholar were systematically searched until March 3, 2020, for studies comparing the efficacy of PMP to PSC in abdominal surgeries. The main outcome of interest was the incidence of IH at different follow-up durations. All statistical analyses …

Cells From Discarded Dressings Differentiate Chronic From Acute Wounds In Patients With Epidermolysis Bullosa, Ignacia Fuentes, Christina Guttmann-Gruber, Birgit Tockner, Anja Diem, Alfred Klausegger, Glenda Cofré-Araneda, Olga Figuera, Yessia Hidalgo, Pilar Morandé, Francis Palisson, Boris Rebolledo-Jaramillo, María Joao Yubero, Raymond J Cho, Heather I Rishel, M Peter Marinkovich, Joyce M C Teng, Timothy G. Webster, Marco Prisco, Luis H. Eraso, Josefina Piñon Hofbauer, Andrew P. South

Department of Dermatology and Cutaneous Biology Faculty Papers

Impaired wound healing complicates a wide range of diseases and represents a major cost to healthcare systems. Here we describe the use of discarded wound dressings as a novel, cost effective, accessible, and non-invasive method of isolating viable human cells present at the site of skin wounds. By analyzing 133 discarded wound dressings from 51 patients with the inherited skin-blistering disease epidermolysis bullosa (EB), we show that large numbers of cells, often in excess of 100 million per day, continually infiltrate wound dressings. We show, that the method is able to differentiate chronic from acute wounds, identifying significant increases in …

Role Of Extracellular Vesicles In Substance Abuse And Hiv-Related Neurological Pathologies, Katherine E. Odegaard, Subhash Chand, Sydney Wheeler, Sneham Tiwari, Adrian Flores, Jordan Hernandez, Mason Savine, Austin Gowen, Gurudutt Pendyala, Sowmya V. Yelamanchili

Journal Articles: Anesthesiology

Extracellular vesicles (EVs) are a broad, heterogeneous class of membranous lipid-bilayer vesicles that facilitate intercellular communication throughout the body. As important carriers of various types of cargo, including proteins, lipids, DNA fragments, and a variety of small noncoding RNAs, including miRNAs, mRNAs, and siRNAs, EVs may play an important role in the development of addiction and other neurological pathologies, particularly those related to HIV. In this review, we summarize the findings of EV studies in the context of methamphetamine (METH), cocaine, nicotine, opioid, and alcohol use disorders, highlighting important EV cargoes that may contribute to addiction. Additionally, as HIV and …

Endogenous Cyclin D1 Promotes The Rate Of Onset And Magnitude Of Mitogenic Signaling Via Akt1 Ser473 Phosphorylation., Ke Chen, Xuanmao Jiao, Agnese Di Rocco, Duanwen Shen, Shaohua Xu, Adam Ertel, Zuoren Yu, Gabriele Di Sante, Min Wang, Zhiping Li, Timothy G Pestell, Mathew C Casimiro, Emmanuel Skordalakes, Samuel Achilefu, Richard G Pestell

Department of Cancer Biology Faculty Papers

Cyclin D1 encodes the regulatory subunit of a holoenzyme that phosphorylates RB and functions as a collaborative nuclear oncogene. The serine threonine kinase Akt plays a pivotal role in the control of cellular metabolism, survival, and mitogenic signaling. Herein, Akt1-mediated phosphorylation of downstream substrates in the mammary gland is reduced by cyclin D1 genetic deletion and is induced by mammary-gland-targeted cyclin D1 overexpression. Cyclin D1 is associated with Akt1 and augments the rate of onset and maximal cellular Akt1 activity induced by mitogens. Cyclin D1 is identified in a cytoplasmic-membrane-associated pool, and cytoplasmic-membrane-localized cyclin D1-but not nuclear-localized cyclin D1-recapitulates Akt1 …

Structural Characterization Of A Clinically Described Heparin-Like Substance In Plasma Causing Bleeding, Lisa Hensch, Shiu-Ki Hui, Fakiha Siddiqui, Amber Farooqui, Ahmed Kouta, Fuming Zhang, Jawed Fareed, Jun Teruya, Robert J Linhardt

Faculty, Staff and Students Publications

Heparin-like substances (HLS) have been described in various clinical situations, including in settings of liver disease associated with infection, transplant, and metastasis. HLS are generally attributed to circulating glycosaminoglycans. Initial results for this patient showed coagulopathy due to liver disease without HLS. Two weeks after liver transplantation, a 10 year-old female with liver failure patient began to bleed from catheter insertion sites, mouth, and nares and HLS was suspected. The patient subsequently died and these clinical samples resulted in the isolation of a single heparan sulfate (HS) present at high concentrations in the plasma. Analysis of this HS showed it …

Atom Identifiers Generated By A Neighborhood-Specific Graph Coloring Method Enable Compound Harmonization Across Metabolic Databases, Huan Jin, Joshua M. Mitchell, Hunter N. B. Moseley

Molecular and Cellular Biochemistry Faculty Publications

Metabolic flux analysis requires both a reliable metabolic model and reliable metabolic profiles in characterizing metabolic reprogramming. Advances in analytic methodologies enable production of high-quality metabolomics datasets capturing isotopic flux. However, useful metabolic models can be difficult to derive due to the lack of relatively complete atom-resolved metabolic networks for a variety of organisms, including human. Here, we developed a neighborhood-specific graph coloring method that creates unique identifiers for each atom in a compound facilitating construction of an atom-resolved metabolic network. What is more, this method is guaranteed to generate the same identifier for symmetric atoms, enabling automatic identification of …

Increased Epicardial Adipose Tissue Is Associated With The Extent Of Aortic Dissection, Ahmet S. Yõlmaz

Journal of the Saudi Heart Association

Background: Epicardial adipose tissue (EAT) is a biologically active organ that has endocrine and paracrine functions. Endothelial dysfunction, systemic, and local inflammatory response, due to bio-active molecules produced by EAT, may affect aortic dissection propagation and extent. We investigated the association between EAT thickness and the extent of aortic dissection.

Methods: We retrospectively enrolled 78 patients with aortic dissection diagnosed by thoracoabdominal Computerized Tomography (CT). EAT was measured from the thickest part of the perpendicular plane between the pericardium and free wall of the right ventricle using CT. Aortic dissection length was measured from the beginning to the end of …

Develop A High-Throughput Screening Method To Identify C-P4h1 (Collagen Prolyl 4-Hydroxylase 1) Inhibitors From Fda-Approved Chemicals, Shike Wang, Kuo-Hao Lee, Nathália Victoria Araujo, Chang-Guo Zhan, Vivek M. Rangnekar, Ren Xu

Pharmaceutical Sciences Faculty Publications

Collagen prolyl 4-hydroxylase 1 (C-P4H1) is an α-ketoglutarate (α-KG)-dependent dioxygenase that catalyzes 4-hydroxylation of proline on collagen. C-P4H1-induced prolyl hydroxylation is required for proper collagen deposition and cancer metastasis. Therefore, targeting C-P4H1 is considered a potential therapeutic strategy for collagen-related cancer progression and metastasis. However, no C-P4H1 inhibitors are available for clinical testing, and the high content assay is currently not available for C-P4H1 inhibitor screening. In the present study, we developed a high-throughput screening assay by quantifying succinate, a byproduct of C-P4H-catalyzed hydroxylation. C-P4H1 is the major isoform of collagen prolyl 4-hydroxylases (CP4Hs) that contributes the majority prolyl 4-hydroxylase …

Upregulation Of Cpt1a Is Essential For The Tumor-Promoting Effect Of Adipocytes In Colon Cancer, Xiaopeng Xiong, Yang-An Wen, Rachelle Fairchild, Yekaterina Y. Zaytseva, Heidi L. Weiss, B. Mark Evers, Tianyan Gao

Markey Cancer Center Faculty Publications

Colon tumors grow in an adipose tissue-enriched microenvironment. Locally advanced colon cancers often invade into surrounding adipose tissue with a direct contact with adipocytes. We have previously shown that adipocytes promote tumor growth by modulating cellular metabolism. Here we demonstrate that carnitine palmitoyltransferase I (CPT1A), a key enzyme controlling fatty acid oxidation (FAO), was upregulated in colon cancer cells upon exposure to adipocytes or fatty acids. In addition, CPT1A expression was increased in invasive tumor cells within the adipose tissue compared to tumors without direct contact with adipocytes. Silencing CPT1A abolished the protective effect provided by fatty acids against nutrient …

Translocase Of The Outer Mitochondrial Membrane Complex Subunit 20 (Tomm20) Facilitates Cancer Aggressiveness And Therapeutic Resistance In Chondrosarcoma., Megan E Roche, Zhao Lin, Diana Whitaker-Menezes, Tingting Zhan, Karoly Szuhai, Judith V M G Bovee, John A Abraham, Wei Jiang, Ubaldo Martinez-Outschoorn, Atrayee Basu-Mallick

Department of Medical Oncology Faculty Papers

Chondrosarcoma is the second most common primary bone malignancy, representing one fourth of all primary bone sarcomas. It is typically resistant to radiation and chemotherapy treatments. However, the molecular mechanisms that contribute to cancer aggressiveness in chondrosarcomas remain poorly characterized. Here, we studied the role of mitochondrial transporters in chondrosarcoma aggressiveness including chemotherapy resistance. Histological grade along with stage are the most important prognostic biomarkers in chondrosarcoma. We found that high-grade human chondrosarcoma tumors have higher expression of the mitochondrial protein, translocase of the outer mitochondrial membrane complex subunit 20 (TOMM20), compared to low-grade tumors. TOMM20 overexpression in human chondrosarcoma …

Perinatal Palliative Care Birth Planning As Advance Care Planning., Donnamaria E. Cortezzo, Kelstan Ellis, Amy Schlegel

Manuscripts, Articles, Book Chapters and Other Papers

Purpose of Review: A significant number of pregnancies are complicated by a fetus with a life-limiting diagnosis. As diagnoses are made earlier in the pregnancy, families experience anticipatory grief and are faced with navigating goals of care for a baby that has yet to be born. With the support of the care team, families can begin to grieve, plan, and make meaningful memories during the duration of the pregnancy, the birth of their baby, and life of the child. Creating a palliative care birth plan, which expands beyond the traditional concept for delivery planning to include prenatal, perinatal, and neonatal …

Perspectives In Melanoma: Meeting Report From The "Melanoma Bridge" (December 5th-7th, 2019, Naples, Italy)., Paolo A Ascierto, Igor Puzanov, Sanjiv S Agarwala, Christian Blank, Richard D Carvajal, Sandra Demaria, Reinhard Dummer, Marc Ernstoff, Soldano Ferrone, Bernard A Fox, Thomas F Gajewski, Claus Garbe, Patrick Hwu, Roger S Lo, Georgina V Long, Jason J Luke, Iman Osman, Michael A Postow, Ryan J Sullivan, Janis M Taube, Giorgio Trinchieri, Hassane M Zarour, Corrado Caracò, Magdalena Thurin

Articles, Abstracts, and Reports

The melanoma treatment landscape changed in 2011 with the approval of the first anti-cytotoxic T-lymphocyte-associated protein (CTLA)-4 checkpoint inhibitor and of the first BRAF-targeted monoclonal antibody, both of which significantly improved overall survival (OS). Since then, improved understanding of the tumor microenvironment (TME) and tumor immune-evasion mechanisms has resulted in new approaches to targeting and harnessing the host immune response. The approval of new immune and targeted therapies has further improved outcomes for patients with advanced melanoma and other combination modalities are also being explored such as chemotherapy, radiotherapy, electrochemotherapy and surgery. In addition, different strategies of drugs administration including …

Estimating Partial Body Ionizing Radiation Exposure By Automated Cytogenetic Biodosimetry, Peter Rogan

Biochemistry Publications

Purpose: Inhomogeneous exposures to ionizing radiation can be detected and quantified with the Dicentric Chromosome Assay (DCA) of metaphase cells. Complete automation of interpretation of the DCA for whole body irradiation has significantly improved throughput without compromising accuracy, however low levels of residual false positive dicentric chromosomes (DCs) have confounded its application for partial body exposure determination.

Materials and Methods: We describe a method of estimating and correcting for false positive DCs in digitally processed images of metaphase cells. Nearly all DCs detected in unirradiated calibration samples are introduced by digital image processing. DC frequencies of irradiated calibration …

Prosthetic Temporomandibular Joint Reconstruction In A Cohort Of Adolescent Females With Juvenile Idiopathic Arthritis., Michael Lypka, Karina Shah, Jordan T. Jones

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Temporomandibular joint (TMJ) arthritis and involvement is commonly seen in Juvenile Idiopathic Arthritis (JIA). Therapy includes conservative measures, but also includes intraarticular corticosteroid injections (IASI) and systemic immunosuppressive therapy. Despite aggressive medical therapy, some patients develop arthritic changes and frank TMJ ankylosis that can result in persistent pain and limitation in range of motion (ROM). A surgical option is prosthetic TMJ replacement with concurrent correction of dentofacial deformities, which can be performed simultaneously. The objective of this study was to evaluate the outcomes of prosthetic TMJ replacement in a cohort of adolescent females with JIA and severe TMJ involvement. …

Sequential Complications Of Hypercalcemia, Necrotizing Granulomatous Vasculitis, And Aplastic Anemia Occurring In One Patient With Angioimmunoblastic T-Cell Lymphoma., Sriman Swarup, Jonathan Kopel, Kyaw Zin Thein, Kaiser Tarafdar, Khatrina Swarup, Seshadri Thirumala, Donald P Quick

Articles, Abstracts, and Reports

In this case report of a patient with angioimmunoblastic T-cell lymphoma (AITL), we describe the occurrence of three sequential complications that have been reported uncommonly in this disease subtype. Firstly, the patient developed hypercalcemia due to elevated 1,25-didydroxyvitamin D. Although hypercalcemia in AITL is not rare (1-2% incidence), this case was unusual in that the complication developed when disease appeared stable and symptomatically, he was doing well otherwise. Hypercalcemia surprisingly resolved a few months later at a time when his disease appeared to be progressing. A year later, the patient presented with digital ischemia necessitating partial amputation of a finger. …

Structural Insights Of Transcriptionally Active, Full-Length Androgen Receptor Coactivator Complexes, Hong Shen, Muyuan Chen, Charles E Foulds, Michael A Mancini, Steven J Ludtke, Zhao Wang, Bert W O'Malley

Faculty, Staff and Students Publications

Steroid receptors activate gene transcription by recruiting coactivators to initiate transcription of their target genes. For most nuclear receptors, the ligand-dependent activation function domain-2 (AF-2) is a primary contributor to the nuclear receptor (NR) transcriptional activity. In contrast to other steroid receptors, such as ERα, the activation function of androgen receptor (AR) is largely dependent on its ligand-independent AF-1 located in its N-terminal domain (NTD). It remains unclear why AR utilizes a different AF domain from other receptors despite that NRs share similar domain organizations. Here, we present cryoelectron microscopy (cryo-EM) structures of DNA-bound full-length AR and its complex structure …

African League Against Rheumatism (Aflar) Preliminary Recommendations On The Management Of Rheumatic Diseases During The Covid-19 Pandemic, Richard Oluyinka Akintayo, Rachid Bahiri, Yasser El Miedany, Hakeem Olaosebikan, Asgar Ali Kalla, Adewale Olukayode Adebajo, Angela Migowa, Samy Slimani, Ouma Devi Koussougbo, Ben Abdelghani Kawther

Paediatrics and Child Health, East Africa

Objectives: To develop recommendations for the management of rheumatic and musculoskeletal diseases (RMDs) during the COVID-19 pandemic.

Method: A task force comprising of 25 rheumatologists from the 5 regions of the continent was formed and operated through a hub-and-spoke model with a central working committee (CWC) and 4 subgroups. The subgroups championed separate scopes of the clinical questions and formulated preliminary statements of recommendations which were processed centrally in the CWC. The CWC and each subgroup met by several virtual meetings, and two rounds of voting were conducted on the drafted statements of recommendations. Votes were online-delivered and …

Mitochondrial Oxidative And Nitrosative Stress And Alzheimer Disease, D. Allan Butterfield, Debra Boyd-Kimball

Chemistry Faculty Publications

Oxidative and nitrosative stress are widely recognized as critical factors in the pathogenesis and progression of Alzheimer disease (AD) and its earlier stage, amnestic mild cognitive impairment (MCI). A major source of free radicals that lead to oxidative and nitrosative damage is mitochondria. This review paper discusses oxidative and nitrosative stress and markers thereof in the brain, along with redox proteomics, which are techniques that have been pioneered in the Butterfield laboratory. Selected biological alterations in—and oxidative and nitrosative modifications of—mitochondria in AD and MCI and systems of relevance thereof also are presented. The review article concludes with a section …

Caring For Aml Patients During The Covid-19 Crisis: An American And Italian Experience., Lindsay Wilde, Md, Alessandro Isidori, Gina Keiffer, Md, Neil D. Palmisiano, Md, Margaret Kasner

Department of Medical Oncology Faculty Papers

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the subsequent pandemic have impacted every aspect of oncology care worldwide. Healthcare systems have been forced to rapidly change practices in order to maximize the safety of patients and healthcare providers and preserve scare resources. Patients with acute myeloid leukemia are at increased risk of complications from SARS-CoV-2 not only due to immune compromise related to the malignancy but also due to the acuity of the disease and intensity of treatment. These issues have created unique challenges during this difficult time. In this article, we present the approaches taken …

Musculoskeletal Tumours Throughout History And Beyond: Clinical Features, Imaging, Staging And Biopsy, Akbar Jaleel Zubairi, Obada Hussein Hasan, Mohammad Mustafa, Masood Umer

Section of Orthopaedic Surgery

Background: Over the last century, there has been a remarkable development in the study of bone and soft tissue sarcomas. This is primarily due to the improved knowledge of the nature of these lesions and the improved imaging technology. In literature there are many protocols that are being used and all of them have reported various advantages and disadvantages of each technique used. However, there is no set guideline and whatever has been proposed has been developed on the basis of the experience of different centres and different surgeons.
Objective: The current systematic review was planned to thoroughly evaluate the …

Efficacy And Safety Of First-Line Avelumab In Patients With Advanced Non-Small Cell Lung Cancer: Results From A Phase Ib Cohort Of The Javelin Solid Tumor Study., Claire F Verschraegen, Guy Jerusalem, Edward F Mcclay, Nicholas Iannotti, Charles H Redfern, Jaafar Bennouna, Franklin L Chen, Karen Kelly, Janice Mehnert, John C Morris, Matthew H Taylor, David Spigel, Ding Wang, Hans Juergen Grote, Dongli Zhou, Neru Munshi, Marcis Bajars, James L Gulley

Articles, Abstracts, and Reports

INTRODUCTION: Avelumab, an antiprogrammed death ligand-1 antibody, is approved as a monotherapy for treatment of metastatic Merkel cell carcinoma and advanced urothelial carcinoma, and in combination with axitinib for advanced renal cell carcinoma. We report the efficacy and safety of first-line avelumab in advanced non-small cell lung cancer (NSCLC).

METHODS: In a phase I expansion cohort of the JAVELIN Solid Tumor trial, patients with treatment-naive, metastatic, or recurrent NSCLC received 10 mg/kg avelumab intravenously every 2 weeks. Endpoints included best overall response, duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.

RESULTS: Overall, 156 patients were enrolled …

Defining The Proteolytic Landscape During Enterovirus Infection., Mohsan Saeed, Sebastian Kapell, Nicholas T Hertz, Xianfang Wu, Kierstin Bell, Alison W Ashbrook, Milica Tesic Mark, Henry A Zebroski, Maxwell L Neal, Malin Flodström-Tullberg, Margaret R Macdonald, John D Aitchison, Henrik Molina, Charles M Rice

Articles, Abstracts, and Reports

Viruses cleave cellular proteins to remodel the host proteome. The study of these cleavages has revealed mechanisms of immune evasion, resource exploitation, and pathogenesis. However, the full extent of virus-induced proteolysis in infected cells is unknown, mainly because until recently the technology for a global view of proteolysis within cells was lacking. Here, we report the first comprehensive catalog of proteins cleaved upon enterovirus infection and identify the sites within proteins where the cleavages occur. We employed multiple strategies to confirm protein cleavages and assigned them to one of the two enteroviral proteases. Detailed characterization of one substrate, LSM14A, a …

Biomanufacturing Organized Collagen-Based Microfibers As A Tissue Engineered Device (Tend) For Tendon Regeneration, Yas Maghdouri-White, Nardos Sori, Stella Petrova, Hilary Wriggers, Nathan Kemper, Amrita Dasgupta, Kelly Coughenour, Seth Polk, Nick Thayer, Mario Rodriguez, Bill Simon, Anna Bulysheva, Kevin Bonner,, Steven Arnoczky, Samuel Adams, Michael Francis

Bioelectrics Publications

Approximately 800,000 surgical repairs are performed annually in the U.S. for debilitating injuries to ligaments and tendons of the foot, ankle, knee, wrist, elbow and shoulder, presenting a significant healthcare burden. To overcome current treatment shortcomings and advance the treatment of tendon and ligament injuries, we have developed a novel electrospun Tissue ENgineered Device (TEND), comprised of type I collagen and poly(D,L-lactide) (PDLLA) solubilized in a benign solvent, dimethyl sulfoxide (DMSO). TEND fiber alignment, diameter and porosity were engineered to enhance cell infiltration leading to promote tissue integration and functional remodeling while providing biomechanical stability. TEND rapidly adsorbs …

Pregnancy Cohorts And Biobanking In Sub-Saharan Africa: A Systematic Review, Jeffrey N. Bone, Kelly Pickerill, Mai-Lei Woo Kinshella, Marianne Vidler, Rachel Craik, Lucilla Poston, William Stones, Esperanca Sevene, Marleen Temmerman, Angela Koech

Obstetrics and Gynaecology, East Africa

Background: Technological advances and high throughput biological assays can facilitate discovery science in biobanks from population cohorts, including pregnant women. Biological pathways associated with health outcomes differ depending on geography, and high-income country data may not generalise to low-resource settings. We conducted a systematic review to identify prospective pregnancy cohorts in sub-Saharan Africa (SSA) that include biobanked samples with potential to enhance discovery science opportunity.

Methods: Inclusion criteria were prospective data collection during pregnancy, with associated biobanking in SSA. Data sources included: scientific databases (with comprehensive search terms), grey literature, hand searching applicable reference lists and expert input. Results were …

Covid-19 Pathways For Brain And Heart Injury In Comorbidity Patients: A Role Of Medical Imaging And Artificial Intelligence-Based Covid Severity Classification: A Review., Jasjit S Suri, Anudeep Puvvula, Mainak Biswas, Misha Majhail, Luca Saba, Gavino Faa, Inder M Singh, Ronald Oberleitner, Monika Turk, Paramjit S Chadha, Amer M Johri, J Miguel Sanches, Narendra N Khanna, Klaudija Viskovic, Sophie Mavrogeni, John R Laird, Gyan Pareek, Martin Miner, David W Sobel, Antonella Balestrieri, Petros P Sfikakis, George Tsoulfas, Athanasios Protogerou, Durga Prasanna Misra, Vikas Agarwal, George D Kitas, Puneet Ahluwalia, Raghu Kolluri, Jagjit Teji, Mustafa Al Maini, Ann Agbakoba, Surinder K Dhanjil, Meyypan Sockalingam, Ajit Saxena, Andrew Nicolaides, Aditya Sharma, Vijay Rathore, Janet N A Ajuluchukwu, Mostafa Fatemi, Azra Alizad, Vijay Viswanathan, Pudukode R Krishnan, Subbaram Naidu

Trauma and Acute Care Articles

Artificial intelligence (AI) has penetrated the field of medicine, particularly the field of radiology. Since its emergence, the highly virulent coronavirus disease 2019 (COVID-19) has infected over 10 million people, leading to over 500,000 deaths as of July 1st, 2020. Since the outbreak began, almost 28,000 articles about COVID-19 have been published (https://pubmed.ncbi.nlm.nih.gov); however, few have explored the role of imaging and artificial intelligence in COVID-19 patients-specifically, those with comorbidities. This paper begins by presenting the four pathways that can lead to heart and brain injuries following a COVID-19 infection. Our survey also offers insights into the role that imaging …