Digital Commons Network^™

Plasma Neurofilament Light Chain Levels Are Elevated In Children And Young Adults With Wolfram Syndrome, Sarah A Eisenstein, Raveena S Boodram, Courtney L Sutphen, Heather M Lugar, Brian A Gordon, Bess A Marshall, Fumihiko Urano, Anne M Fagan, Tamara Hershey

2020-Current year OA Pubs

Wolfram syndrome is a rare disease caused by pathogenic variants in the

Differential Sphingosine-1-Phosphate Receptor-1 Protein Expression In The Dorsolateral Prefrontal Cortex Between Schizophrenia Type 1 And Type 2, Ganesh B Chand, Hao Jiang, J Philip Miller, C Harker Rhodes, Zhude Tu, Dean Foster Wong

2020-Current year OA Pubs

Understanding the etiology and treatment approaches in schizophrenia is challenged in part by the heterogeneity of this disorder. One encouraging progress is the growing evidence that there are subtypes of schizophrenia. Recent

Is It Possible To Separate The Graft-Versus-Leukemia (Gvl) Effect Against B Cell Acute Lymphoblastic Leukemia From Graft-Versus-Host Disease (Gvhd) After Hematopoietic Cell Transplant?, Jacob Rozmus, Sima T Bhatt, Nataliya Prokopenko Buxbaum, Geoffrey D E Cuvelier, Amanda M Li, Carrie L Kitko, Kirk R Schultz

2020-Current year OA Pubs

Hematopoietic cell transplant is a curative therapy for many pediatric patients with high risk acute lymphoblastic leukemia. Its therapeutic mechanism is primarily based on the generation of an alloreactive graft-versus-leukemia effect that can eliminate residual leukemia cells thus preventing relapse. However its efficacy is diminished by the concurrent emergence of harmful graft-versus-host disease disease which affects healthly tissue leading to significant morbidity and mortality. The purpose of this review is to describe the interventions that have been trialed in order to augment the beneficial graft-versus leukemia effect post-hematopoietic cell transplant while limiting the harmful consequences of graft-versus-host disease. This includes …

Case Report: "Primary Immunodeficiency"-Severe Autoimmune Enteropathy In A Pediatric Heart Transplant Recipient Treated With Abatacept And Alemtuzumab, Elizaveta Kalaidina, Elizabeth C Utterson, Deepa Mokshagundam, Mai He, Shalini Shenoy, Megan A Cooper

2020-Current year OA Pubs

Disorders of immune dysregulation following heart transplantation in children have been reported; however, the management of such disorders remains uncertain and challenging. In this case report, we describe a clinical course of a child with severe autoimmune enteropathy after a heart transplant in infancy and detail a treatment approach with abatacept and alemtuzumab. A 21-month-old girl with a medical history of congenital dilated cardiomyopathy and heart transplantation at 2 months was evaluated for chronic hematochezia. The patient underwent an extensive workup, including endoscopic biopsy which showed crypt apoptosis, similar to that seen with graft-versus-host disease (GVHD). Results of her immune …

Low Cancer Incidence In Naked Mole-Rats May Be Related To Their Inability To Express The Warburg Effect, Pedro Freire Jorge, Matthew L Goodwin, Maurits H Renes, Maarten W Nijsten, Matthew Pamenter

2020-Current year OA Pubs

Metabolic flexibility in mammals enables stressed tissues to generate additional ATP by converting large amounts of glucose into lactic acid; however, this process can cause transient local or systemic acidosis. Certain mammals are adapted to extreme environments and are capable of enhanced metabolic flexibility as a specialized adaptation to challenging habitat niches. For example, naked mole-rats (NMRs) are a fossorial and hypoxia-tolerant mammal whose metabolic responses to environmental stressors markedly differ from most other mammals. When exposed to hypoxia, NMRs exhibit robust hypometabolism but develop minimal acidosis. Furthermore, and despite a very long lifespan relative to other rodents, NMRs have …

Combination Laser Interstitial Thermal Therapy Plus Stereotactic Radiotherapy Increases Time To Progression For Biopsy-Proven Recurrent Brain Metastases, Matthew M Grabowski, Alex Scott, Michael Olufawo, Albert H Kim, Eric C Leuthardt, Et Al.

2020-Current year OA Pubs

BACKGROUND: Improved survival for patients with brain metastases has been accompanied by a rise in tumor recurrence after stereotactic radiotherapy (SRT). Laser interstitial thermal therapy (LITT) has emerged as an effective treatment for SRT failures as an alternative to open resection or repeat SRT. We aimed to evaluate the efficacy of LITT followed by SRT (LITT+SRT) in recurrent brain metastases.

METHODS: A multicenter, retrospective study was performed of patients who underwent treatment for biopsy-proven brain metastasis recurrence after SRT at an academic medical center. Patients were stratified by "planned LITT+SRT" versus "LITT alone" versus "repeat SRT alone." Index lesion progression …

Prospective Biomarker Study In Newly Diagnosed Glioblastoma: Cyto-C Clinical Trial, Corinne E Griguer, Milan G Chheda, Et Al.

2020-Current year OA Pubs

BACKGROUND: Glioblastoma (GBM) has a 5-year survival rate of 3%-5%. GBM treatment includes maximal resection followed by radiotherapy with concomitant and adjuvant temozolomide (TMZ). Cytochrome C oxidase (CcO) is a mitochondrial enzyme involved in the mechanism of resistance to TMZ. In a prior retrospective trial, CcO activity in GBMs inversely correlated with clinical outcome. The current Cyto-C study was designed to prospectively evaluate and validate the prognostic value of tumor CcO activity in patients with newly diagnosed primary GBM, and compared to the known prognostic value of

METHODS: This multi-institutional, blinded, prospective biomarker study enrolled 152 patients with newly diagnosed …

Immune Deconvolution And Temporal Mapping Identifies Stromal Targets And Developmental Intervals For Abrogating Murine Low-Grade Optic Glioma Formation, Amanda De Andrade Costa, Jit Chatterjee, Olivia Cobb, Elizabeth Cordell, Astoria Chao, Suzanne Schaeffer, Andrea Goldstein, Sonika Dahiya, David H Gutmann

2020-Current year OA Pubs

BACKGROUND: Brain tumor formation and progression are dictated by cooperative interactions between neoplastic and non-neoplastic cells. This stromal dependence is nicely illustrated by tumors arising in the Neurofibromatosis type 1 (NF1) cancer predisposition syndrome, where children develop low-grade optic pathway gliomas (OPGs). Using several authenticated

METHODS: A combination of bulk and single-cell RNA mouse optic nerve sequencing, immunohistochemistry, T cell assays, and pharmacologic and antibody-mediated inhibition methods were used in these experiments.

RESULTS: We show that T cells and microglia are the main non-neoplastic immune cell populations in both murine and human LGGs. Moreover, we demonstrate that CD8

CONCLUSIONS: Collectively, …

What Does It Mean To Be Affiliated With Care?: Delphi Consensus On The Definition Of "Unaffiliation" And "Specialist" In Sickle Cell Disease, Andrea E. Lamont, Lewis L. Hsu, Sara Jacobs, Robert Gibson, Marsha Treadwell, Yumei Chen, Richard Lottenberg, Kathleen Axelrod, Taniya Varughese, Cathy Melvin, Sharon Smith, Ifeanyi Beverly Chukwudozie, Julie Kanter, Sickle Cell Disease Implementation Consortium

2020-Current year OA Pubs

Accruing evidence reveals best practices for how to help individuals living with Sickle Cell Disease (SCD); yet, the implementation of these evidence-based practices in healthcare settings is lacking. The Sickle Cell Disease Implementation Consortium (SCDIC) is a national consortium that uses implementation science to identify and address barriers to care in SCD. The SCDIC seeks to understand how and why patients become unaffiliated from care and determine strategies to identify and connect patients to care. A challenge, however, is the lack of agreed-upon definition for what it means to be unaffiliated and what it means to be a "SCD expert …

Association Between Recent Overdose And Chronic Pain Among Individuals In Treatment For Opioid Use Disorder, Sarah M. Hartz, Robert C. Culverhouse, Carrie M. Mintz, Matthew S. Ellis, Zachary A. Kasper, Patricia Cavazos-Rehg, Richard A. Grucza, Laura J. Bierut, Theodore J. Cicero

2020-Current year OA Pubs

Chronic pain increases risk for opioid overdose among individuals with opioid use disorder. The purpose of this study is to evaluate the relationship between recent overdose and whether or not chronic pain is active. 3,577 individuals in treatment for opioid use disorder in 2017 or 2018 were surveyed regarding recent overdoses and chronic pain. Demographics from the 2017 Treatment Episode Data Set, which includes all U.S. facilities licensed or certified to provide substance use care, were used to evaluate the generalizability of the sample. χ2 tests and logistic regression models were used to compare associations between recent overdoses and chronic …

Barriers And Facilitators To Diabetes Screening And Prevention After A Pregnancy Complicated By Gestational Diabetes, Drishti D. Sinha, Roxann C. Williams, Laura N. Hollar, Hannah R. Lucas, Bethany Johnson-Javois, Heidi B. Miller, Amanda Stoermer, Graham A. Colditz, Aimee S. James, Cynthia J. Herrick

2020-Current year OA Pubs

OBJECTIVE: Gestational diabetes mellitus (GDM) is increasing in the United States, with higher rates among minoritized racial and ethnic populations and lower income populations. GDM increases risk for type 2 diabetes (T2DM), and postpartum diabetes screening and prevention are imperative. This qualitative study examines barriers and facilitators to postpartum T2DM screening and prevention among non-privately insured individuals with a history of GDM in a state prior to Medicaid expansion.

METHODS: Thirty-six non-privately insured women with a history of GDM completed semi-structured interviews. Four focus groups and seven interviews were conducted with 30 nurse practitioners, physicians, physician assistants, nurses and registered …

Children With Supratentorial Midline Pilocytic Astrocytomas Exhibit Multiple Progressions And Acquisition Of Neurologic Deficits Over Time, Nicole M Brossier, Jennifer M Strahle, Samuel J Cler, Michael Wallendorf, David H Gutmann

2020-Current year OA Pubs

No abstract provided.

The Impact Of A Virtual Orthopaedic Surgery Symposium On Medical Students: Increasing Awareness And Knowledge Of The Field, Theodore Quan, Alex Gu, Amil R. Agarwal, Simone A. Bernstein, Alisa Malyavko, William N. Levine, Lisa K. Cannada, Medical Student Orthopedic Society

2020-Current year OA Pubs

UNLABELLED: Orthopaedic surgery has become an increasingly popular field of residency training for medical students. Many institutions offer elective time to explore areas of interest through clinical rotations and research; however, most of these opportunities are reserved for senior medical students. The purpose of this study was to evaluate the impact of a dedicated medical student orthopaedic surgery symposium to increase awareness about the field and to assess students' interest and knowledge of orthopaedic surgery before and after the symposium.

METHODS: Medical students were invited to submit orthopaedic surgery-related research to a free, 1-day virtual symposium held in April 2022. …

Neurofibromatosis-1 Gene Mutational Profiles Differ Between Syndromic Disease And Sporadic Cancers, Alice F. Bewley, Titilope M. Akinwe, Tychele N. Turner, David H. Gutmann

2020-Current year OA Pubs

No abstract provided.

Prescribing Unproven Cancer Drugs: Physician Perspectives On Expanded Access And Right To Try, Haley Manley, Bryan A Sisk, Zubin Master, Christopher Thomas Scott

2020-Current year OA Pubs

BACKGROUND: For gravely ill patients who have no treatment options and who are ineligible for clinical trials, the US Food and Drug Administration (FDA) established the Expanded Access Program (EAP). Motivated by efforts to weaken FDA regulation and sold as providing greater access to experimental drugs, the federal Right to Try Act (RTT) was passed in 2017. It reduces FDA oversight by not requiring physicians to report safety data and foregoes approval of protocols by local institutional review boards.

METHODS: This study explored the views of 17 neuro-oncologists from 15 different academic medical centers with varying experience with EAP and …

A Comparison Of 64cu-Labeled Bi-Terminally Pegylated A20fmdv2 Peptides Targeting Integrin Ανβ6, Truc T Huynh, Sreeja Sreekumar, Cedric Mpoy, Buck E Rogers

2020-Current year OA Pubs

Expression of epithelial-specific integrin α

Predicting At-Risk Opioid Use Three Months After Ed Visit For Trauma: Results From The Aurora Study, Brittany E. Punches, Stacey L. House, Et Al

2020-Current year OA Pubs

OBJECTIVE: Whether short-term, low-potency opioid prescriptions for acute pain lead to future at-risk opioid use remains controversial and inadequately characterized. Our objective was to measure the association between emergency department (ED) opioid analgesic exposure after a physical, trauma-related event and subsequent opioid use. We hypothesized ED opioid analgesic exposure is associated with subsequent at-risk opioid use.

METHODS: Participants were enrolled in AURORA, a prospective cohort study of adult patients in 29 U.S., urban EDs receiving care for a traumatic event. Exclusion criteria were hospital admission, persons reporting any non-medical opioid use (e.g., opioids without prescription or taking more than prescribed …

Metal Coordinating Inhibitors Of Rift Valley Fever Virus Replication, Elizabeth Geerling, Mohamed Elagawany, Bahaa Elgendy, Et Al

2020-Current year OA Pubs

Rift Valley fever virus (RVFV) is a veterinary and human pathogen and is an agent of bioterrorism concern. Currently, RVFV treatment is limited to supportive care, so new drugs to control RVFV infection are urgently needed. RVFV is a member of the order Bunyavirales, whose replication depends on the enzymatic activity of the viral L protein. Screening for RVFV inhibitors among compounds with divalent cation-coordinating motifs similar to known viral nuclease inhibitors identified 47 novel RVFV inhibitors with selective indexes from 1.1-103 and 50% effective concentrations of 1.2-56 μM in Vero cells, primarily α-Hydroxytropolones and N-Hydroxypyridinediones. Inhibitor activity and selective …

Hydroxychloroquine/Chloroquine For The Treatment Of Hospitalized Patients With Covid-19: An Individual Participant Data Meta-Analysis, Leon Di Stefano, Jane A. O'Halloran, Adriana M. Rauseo, Et Al

2020-Current year OA Pubs

BACKGROUND: Results from observational studies and randomized clinical trials (RCTs) have led to the consensus that hydroxychloroquine (HCQ) and chloroquine (CQ) are not effective for COVID-19 prevention or treatment. Pooling individual participant data, including unanalyzed data from trials terminated early, enables more detailed investigation of the efficacy and safety of HCQ/CQ among subgroups of hospitalized patients.

METHODS: We searched ClinicalTrials.gov in May and June 2020 for US-based RCTs evaluating HCQ/CQ in hospitalized COVID-19 patients in which the outcomes defined in this study were recorded or could be extrapolated. The primary outcome was a 7-point ordinal scale measured between day 28 …

Self-Esteem And Weight Status Of Young Adults: Findings From A Pilot Study, Echu Liu, Su-Hsin Chang

2020-Current year OA Pubs

BACKGROUND: Researchers have examined the association between self-esteem and obesity in past studies. However, most studies have focused on pediatric or adolescent populations. In this pilot study, we aim to explore the association of self-esteem with weight status in young adults, a group of individuals in a significant and pivotal period of their lives whose needs and challenges have received little attention in previous studies.

MATERIALS AND METHODS: Exactly 127 college juniors and seniors in the Midwest participated in late 2017. For our survey, we collected the following information: body weight, height, self-esteem score from the state self-esteem scale, grade …

Epidermolysis Bullosa With Congenital Absence Of Skin: Congenital Corneal Cloudiness And Esophagogastric Obstruction Including Extended Genotypic Spectrum Of Plec, Lamc2, Itgb4 And Col7a1, Pharuhad Pongmee, Sanchawan Wittayakornrerk, Ramrada Lekwuttikarn, Sasikarn Pakdeeto, Piangor Watcharakuldilok, Chatchay Prempunpong, Thipwimol Tim-Aroon, Chawintee Puttanapitak, Piyawan Wattanasoontornsakul, Thitiporn Junhasavasdikul, Parith Wongkittichote, Saisuda Noojarern, Duangrurdee Wattanasirichaigoon

2020-Current year OA Pubs

Epidermolysis bullosa (EB) is a rare and genetically heterogeneous disorder characterized by skin fragility and blister formation occurring spontaneously or after minor trauma. EB is accompanied by congenital absence of skin (EB with CAS) in some patients. Pathogenic variants of

Phase 1 Clinical Trial Evaluating The Safety And Anti-Tumor Activity Of Adp-A2m10 Spear T-Cells In Patients With Mage-A10+ Head And Neck, Melanoma, Or Urothelial Tumors, David S Hong, Russell K Pachynski, Armin Ghobadi, Et Al.

2020-Current year OA Pubs

BACKGROUND: ADP-A2M10 specific peptide enhanced affinity receptor (SPEAR) T-cells are genetically engineered autologous T-cells that express a high-affinity melanoma-associated antigen (MAGE)-A10-specific T-cell receptor (TCR) targeting MAGE-A10-positive tumors in the context of human leukocyte antigen (HLA)-A*02. ADP-0022-004 is a phase 1, dose-escalation trial to evaluate the safety and anti-tumor activity of ADP-A2M10 in three malignancies (https://clinicaltrials.gov: NCT02989064).

METHODS: Eligible patients were HLA-A*02 positive with advanced head and neck squamous cell carcinoma (HNSCC), melanoma, or urothelial carcinoma (UC) expressing MAGE-A10. Patients underwent apheresis; T-cells were isolated, transduced with a lentiviral vector containing the MAGE-A10 TCR, and expanded. Patients underwent lymphodepletion with fludarabine …

Hand Transplants, Daily Functioning, And The Human Capacity For Limb Regeneration, Susan M Fitzpatrick, David Brogan, Prateek Grover

2020-Current year OA Pubs

Unlike some of our invertebrate and vertebrate cousins with the capacity to regenerate limbs after traumatic loss, humans do not have the ability to regrow arms or legs lost to injury or disease. For the millions of people worldwide who have lost a limb after birth, the primary route to regaining function and minimizing future complications is

Relief Of Chronic Pain Associated With Increase In Midline Frontal Theta Power, Nabi Rustamov, Elizabeth A. Wilson, Alexandra E. Fogarty, Lara W. Crock, Eric C. Leuthardt, Simon Haroutounian

2020-Current year OA Pubs

INTRODUCTION: There is a need to identify objective cortical electrophysiological correlates for pain relief that could potentially contribute to a better pain management. However, the field of developing brain biomarkers for pain relief is still largely underexplored.

OBJECTIVES: The objective of this study was to investigate cortical electrophysiological correlates associated with relief from chronic pain. Those features of pain relief could serve as potential targets for novel therapeutic interventions to treat pain.

METHODS: In 12 patients with chronic pain in the upper or lower extremity undergoing a clinically indicated nerve block procedure, brain activity was recorded by means of electroencephalogram …

Investing In Late-Life Brain Capital, Walter D Dawson, Eric J Lenze, Et Al.

2020-Current year OA Pubs

Within many societies and cultures around the world, older adults are too often undervalued and underappreciated. This exacerbates many key challenges that older adults may face. It also undermines the many positive aspects of late life that are of tremendous value at both an individual and societal level. We propose a new approach to elevate health and well-being in late life by optimizing late-life Brain Capital. This form of capital prioritizes brain skills and brain health in a brain economy, which the challenges and opportunities of the 21st-century demands. This approach incorporates investing in late-life Brain Capital, developing initiatives focused …

Covariance And Correlation Analysis Of Resting State Functional Magnetic Resonance Imaging Data Acquired In A Clinical Trial Of Mindfulness-Based Stress Reduction And Exercise In Older Individuals, Abraham Z Snyder, Tomoyuki Nishino, Joshua S Shimony, Eric J Lenze, Julie Loebach Wetherell, Michelle Voegtle, J Philip Miller, Michael D Yingling, Daniel Marcus, Jenny Gurney, Jerrel Rutlin, Drew Scott, Lisa Eyler, Deanna Barch

2020-Current year OA Pubs

We describe and apply novel methodology for whole-brain analysis of resting state fMRI functional connectivity data, combining conventional multi-channel Pearson correlation with covariance analysis. Unlike correlation, covariance analysis preserves signal amplitude information, which feature of fMRI time series may carry physiological significance. Additionally, we demonstrate that dimensionality reduction of the fMRI data offers several computational advantages including projection onto a space of manageable dimension, enabling linear operations on functional connectivity measures and exclusion of variance unrelated to resting state network structure. We show that group-averaged, dimensionality reduced, covariance and correlation matrices are related, to reasonable approximation, by a single scalar …

The Enantiomer Of Allopregnanolone Prevents Pressure-Mediated Retinal Degeneration Via Autophagy, Makoto Ishikawa, Toru Nakazawa, Hiroshi Kunikata, Kota Sato, Takeshi Yoshitomi, Kathiresan Krishnan, Douglas F Covey, Charles F Zorumski, Yukitoshi Izumi

2020-Current year OA Pubs

In an

The Burden Of Critical Illness In Hospitalized Children In Low- And Middle-Income Countries: Protocol For A Systematic Review And Meta-Analysis, Teresa B Kortz, Kenneth E Remy, Et Al.

2020-Current year OA Pubs

BACKGROUND: The majority of childhood deaths occur in low- and middle-income countries (LMICs). Many of these deaths are avoidable with basic critical care interventions. Quantifying the burden of pediatric critical illness in LMICs is essential for targeting interventions to reduce childhood mortality.

OBJECTIVE: To determine the burden of hospitalization and mortality associated with acute pediatric critical illness in LMICs through a systematic review and meta-analysis of the literature.

DATA SOURCES AND SEARCH STRATEGY: We will identify eligible studies by searching MEDLINE, EMBASE, CINAHL, and LILACS using MeSH terms and keywords. Results will be limited to infants or children (ages >28 …

Epithelial Abnormalities In The Small Intestine Of Zambian Children With Stunting, Chola Mulenga, Sanja Sviben, Kanta Chandwe, Beatrice Amadi, Violet Kayamba, James A J Fitzpatrick, Victor Mudenda, Paul Kelly

2020-Current year OA Pubs

BACKGROUND: Environmental enteropathy (EE) contributes to impaired linear growth (stunting), in millions of children worldwide. We have previously reported that confocal laser endomicroscopy (CLE) shows fluorescein leaking from blood to gut lumen

METHODS: We performed confocal laser endomicroscopy (CLE) in 75 children and collected intestinal biopsies for histology in 91 children. CLE videos were evaluated, employing the Watson score to determine severity of leakiness. Morphometry was carried out on well-orientated mucosa and 3 biopsies were examined by electron microscopy.

RESULTS: Confocal laser endomicroscopy demonstrated substantial leakage from circulation to gut lumen in 73 (97%) children. Histology consistently showed characteristic changes …

Loss Of Function Of Wfs1 Causes Er Stress-Mediated Inflammation In Pancreatic Β-Cells, Shuntaro Morikawa, Lindsey Blacher, Chinyere Onwumere, Fumihiko Urano

2020-Current year OA Pubs

Wolfram syndrome is a rare genetic disorder characterized by juvenile-onset diabetes mellitus, optic nerve atrophy, hearing loss, diabetes insipidus, and progressive neurodegeneration. Pathogenic variants in the