Medicine and Health Sciences Commons^™

The Past, Present, And Future Of A Human T-Cell Leukemia Virus Type 1 Vaccine, Joshua J Tu, Victoria Maksimova, Lee Ratner, Amanda R Panfil

2020-Current year OA Pubs

Human T-cell leukemia virus type 1 (HTLV-1) is an oncogenic human retrovirus which causes a lifelong infection. An estimated 5-10 million persons are infected with HTLV-1 worldwide - a number which is likely higher due to lack of reliable epidemiological data. Most infected individuals remain asymptomatic; however, a portion of HTLV-1-positive individuals will develop an aggressive CD4+ T-cell malignancy called adult T-cell leukemia/lymphoma (ATL), or a progressive neurodegenerative disease known as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Few treatment options exist for HAM/TSP outside of palliative care and ATL carries an especially poor prognosis given the heterogeneity of the disease and …

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.

Exploring The Role Of Low-Density Neutrophils During Mycobacterium Tuberculosis Infection, Ananda N Rankin, Skyler V Hendrix, Sumanta K Naik, Christina L Stallings

2020-Current year OA Pubs

Tuberculosis (TB) is caused by infection with the bacterium

It's About The Patients: Practical Antibiotic Stewardship In Outpatient Settings In The United States, Alpesh N Amin, E Patchen Dellinger, Glenn Harnett, Bryan D Kraft, Kerry L Laplante, Frank Lovecchio, James A Mckinnell, Glenn Tillotson, Salisia Valentine

2020-Current year OA Pubs

Antibiotic-resistant pathogens cause over 35,000 preventable deaths in the United States every year, and multiple strategies could decrease morbidity and mortality. As antibiotic stewardship requirements are being deployed for the outpatient setting, community providers are facing systematic challenges in implementing stewardship programs. Given that the vast majority of antibiotics are prescribed in the outpatient setting, there are endless opportunities to make a smart and informed choice when prescribing and to move the needle on antibiotic stewardship. Antibiotic stewardship in the community, or "smart prescribing" as we suggest, should factor in antibiotic efficacy, safety, local resistance rates, and overall cost, in …

Inferring The Dynamical Effects Of Stroke Lesions Through Whole-Brain Modeling, Sebastian Idesis, Chiara Favaretto, Nicholas V Metcalf, Joseph C Griffis, Gordon L Shulman, Maurizio Corbetta, Gustavo Deco

2020-Current year OA Pubs

Understanding the effect of focal lesions (stroke) on brain structure-function traditionally relies on behavioral analyses and correlation with neuroimaging data. Here we use structural disconnection maps from individual lesions to derive a causal mechanistic generative whole-brain model able to explain both functional connectivity alterations and behavioral deficits induced by stroke. As compared to other models that use only the local lesion information, the similarity to the empirical fMRI connectivity increases when the widespread structural disconnection information is considered. The presented model classifies behavioral impairment severity with higher accuracy than other types of information (e.g.: functional connectivity). We assessed topological measures …

Sepsis Prediction For The General Ward Setting, Sean C Yu, Aditi Gupta, Kevin D Betthauser, Patrick G Lyons, Albert M Lai, Marin H Kollef, Philip R O Payne, Andrew P Michelson

2020-Current year OA Pubs

OBJECTIVE: To develop and evaluate a sepsis prediction model for the general ward setting and extend the evaluation through a novel pseudo-prospective trial design.

DESIGN: Retrospective analysis of data extracted from electronic health records (EHR).

SETTING: Single, tertiary-care academic medical center in St. Louis, MO, USA.

PATIENTS: Adult, non-surgical inpatients admitted between January 1, 2012 and June 1, 2019.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: Of the 70,034 included patient encounters, 3.1% were septic based on the Sepsis-3 criteria. Features were generated from the EHR data and were used to develop a machine learning model to predict sepsis 6-h ahead …

Aging With Long-Term Physical Disability: Cohort Analysis Of Survey Sample In The U.S., Kerri A Morgan, Michelle Putnam, Sandra M Espin-Tello, Marian Keglovits, Margaret Campbell, Yan Yan, Aimee Wehmeier, Susan Stark

2020-Current year OA Pubs

BACKGROUND: Chronic health conditions, secondary conditions, and decreasing functional ability related to aging and/or changes in underlying impairment may influence participation for persons aging with long-term physical disability (AwD).

OBJECTIVE: To examine sample integrity and baseline findings through exploration of associations of sociodemographic, health, and disability factors with social participation for persons AwD.

METHODS: This is a longitudinal cohort study following persons AwD over three years, reporting baseline cohort study data. A convenience sample of 474 persons AwD aged 45-65 reporting physical disability of ≥5 years' duration was recruited through community organizations and social media. The cohort was majority female …

Preclinical Antibody-Pet Imaging Of Pd-L1, Emma L Brown, Rachel A Deweerd, Abbey Zidel, Patricia M R Pereira

2020-Current year OA Pubs

Programmed cell death protein-1/ligand-1 (PD-1/PD-L1) blockade, including antibody therapeutics, has transformed cancer treatment. However, a major challenge in the field relates to selecting patients who are likely to respond to immune checkpoint inhibitors. Indeed, biopsy-based diagnostic tests to determine immune checkpoint protein levels do not accurately capture the inherent spatial and temporal heterogeneity of PD-L1 tumor expression. As a result, not all PD-L1-positive tumors respond to immunotherapies, and some patients with PD-L1-negative tumors have shown clinical benefits. In 2018, a first-in-human study of the clinically-approved anti-PD-L1 antibody Atezolizumab labeled with the positron emitter zirconium-89 validated the ability of positron emission …

Il-1 Reprogramming Of Adult Neural Stem Cells Limits Neurocognitive Recovery After Viral Encephalitis By Maintaining A Proinflammatory State, Allison L Soung, Veronica A Davé, Charise Garber, Eric D Tycksen, Lauren L Vollmer, Robyn S Klein

2020-Current year OA Pubs

Innate immune responses to emerging RNA viruses are increasingly recognized as having significant contributions to neurologic sequelae, especially memory disorders. Using a recovery model of West Nile virus (WNV) encephalitis, we show that, while macrophages deliver the antiviral and anti-neurogenic cytokine IL-1β during acute infection; viral recovery is associated with continued astrocyte inflammasome-mediated production of inflammatory levels of IL-1β, which is maintained by hippocampal astrogenesis via IL-1R1 signaling in neural stem cells (NSC). Accordingly, aberrant astrogenesis is prevented in the absence of IL-1 signaling in NSC, indicating that only newly generated astrocytes exert neurotoxic effects, preventing synapse repair and promoting …

Reconstructing Neural Circuits Using Multiresolution Correlated Light And Electron Microscopy, Karl Friedrichsen, Pratyush Ramakrishna, Jen-Chun Hsiang, Katia Valkova, Daniel Kerschensteiner, Josh L Morgan

2020-Current year OA Pubs

Correlated light and electron microscopy (CLEM) can be used to combine functional and molecular characterizations of neurons with detailed anatomical maps of their synaptic organization. Here we describe a multiresolution approach to CLEM (mrCLEM) that efficiently targets electron microscopy (EM) imaging to optically characterized cells while maintaining optimal tissue preparation for high-throughput EM reconstruction. This approach hinges on the ease with which arrays of sections collected on a solid substrate can be repeatedly imaged at different scales using scanning electron microscopy. We match this multiresolution EM imaging with multiresolution confocal mapping of the aldehyde-fixed tissue. Features visible in lower resolution …

Yoga Therapy During Chemotherapy For Early-Stage And Locally Advanced Breast Cancer, Samantha K Greaney, Neha Amin, Bethany C Prudner, Maggie Compernolle, Linda J Sandell, Susan C Tebb, Katherine N Weilbaecher, Peri Abeln, Jingqin Luo, Yu Tao, Angela C Hirbe, Lindsay L Peterson

2020-Current year OA Pubs

BACKGROUND: Chemotherapy is associated with decreased quality of life (QOL), fatigue, depression, and weight gain in patients with breast cancer. Weight gain is associated with poorer prognosis. Yoga improves QOL, fatigue, and mood in women with breast cancer but its effect on treatment-related weight gain has not been studied. The aim of this trial was to determine the feasibility of personalized yoga therapy in women receiving treatment for early-stage or locally advanced breast cancer and assess its impact on weight gain.

METHODS: Thirty women were randomized 1:1 to receive yoga therapy by a certified yoga therapist during treatment or a …

Bridging The Technological Divide: Stigmas And Challenges With Technology In Digital Brain Health Studies Of Older Adults, Jessica Nicosia, Andrew J Aschenbrenner, Sarah L Adams, Marisol Tahan, Sarah H Stout, Hannah Wilks, Joyce E Balls-Berry, John C Morris, Jason Hassenstab

2020-Current year OA Pubs

The COVID-19 pandemic has increased adoption of remote assessments in clinical research. However, longstanding stereotypes persist regarding older adults' technology familiarity and their willingness to participate in technology-enabled remote studies. We examined the validity of these stereotypes using a novel technology familiarity assessment (

Association Of Pretreatment Hippocampal Volume With Neurocognitive Function In Patients Treated With Hippocampal Avoidance Whole Brain Radiation Therapy For Brain Metastases: Secondary Analysis Of Nrg Oncology/Rtog 0933, Christopher D. Abraham, Stephanie L. Pugh, Joseph A. Bovi, Vinai Gondi, Minesh P. Mehta, Tammie Benzinger, Christopher J. Owen, Simon S. Lo, Vijayananda Kundapur, Paul D. Brown, Alexander Y. Sun, Steven P. Howard, Albert S Denittis, Clifford G. Robinson, Lisa A. Kachnic

2020-Current year OA Pubs

PURPOSE: Hippocampal volume (HV) is an established predicting factor for neurocognitive function (NCF) in neurodegenerative disease. Whether the same phenomenon exists with hippocampal-avoidant whole brain radiation therapy is not known; therefore, we assessed the association of baseline HV with NCF among patients enrolled on RTOG 0933.

METHODS AND MATERIALS: Hippocampal volume and total brain volume were calculated from the radiation therapy plan. Hippocampal volume was correlated with baseline and 4-month NCF scores (Hopkins Verbal Learning Test-Revised [HVLT-R] Total Recall [TR], Immediate Recognition, and Delayed Recall [DR]) using Pearson correlation. Deterioration in NCF was defined per the primary endpoint of RTOG …

Variation In Ampicillin Dosing For Lower Respiratory Tract Infections And Neonatal Bacterial Infections In Us Children's Hospitals, Elizabeth A Daniels, Christopher C Mcpherson, Jason G Newland, Brian R Lee

2020-Current year OA Pubs

OBJECTIVE: We examined ampicillin dosing in pediatric patients across 3 conditions: (1) bacterial lower respiratory tract infections (LRTIs) in infants and children >3 months, (2) neonates with suspected or proven sepsis, and (3) neonates with suspected central nervous system (CNS) infections. We compared our findings to dosing guidance for these specific indications.

DESIGN: Retrospective cohort study.

SETTING: The study included data from 32 children's hospitals in the United States.

METHODS: We reviewed prescriptions from the SHARPS study of antimicrobials, a survey of antibiotic prescribing from July 2016 to December 2017. Prescriptions were analyzed for indication, total daily dose per kilogram, …

Leishmania Guyanensis Suppressed Inducible Nitric Oxide Synthase Provoked By Its Viral Endosymbiont, Dmitry Kopelyanskiy, Chantal Desponds, Florence Prevel, Matteo Rossi, Romain Migliorini, Tiia Snäkä, Remzi Onur Eren, Stéphanie Claudinot, Lon-Fye Lye, Manolis Pasparakis, Stephen M Beverley, Nicolas Fasel

2020-Current year OA Pubs

Inducible nitric oxide synthase (iNOS) is essential to the production of nitric oxide (NO), an efficient effector molecule against intracellular human pathogens such as

Combining Empirical Knowledge, In Silico Molecular Docking And Admet Profiling To Identify Therapeutic Phytochemicals From Brucea Antidysentrica For Acute Myeloid Leukemia, Lemessa Etana Bultum, Gemechu Bekele Tolossa, Doheon Lee

2020-Current year OA Pubs

Acute myeloid leukemia (AML) is one of the deadly cancers. Chemotherapy is the first-line treatment and the only curative intervention is stem cell transplantation which are intolerable for aged and comorbid patients. Therefore, finding complementary treatment is still an active research area. For this, empirical knowledge driven search for therapeutic agents have been carried out by long and arduous wet lab processes. Nonetheless, currently there is an accumulated bioinformatics data about natural products that enabled the use of efficient and cost effective in silico methods to find drug candidates. In this work, therefore, we set out to computationally investigate the …

Cognitive And Brain Reserve Predict Decline In Adverse Driving Behaviors Among Cognitively Normal Older Adults, Samantha A Murphy, Ling Chen, Jason M Doherty, Prerana Acharyya, Noah Riley, Ann M Johnson, Alexis Walker, Hailee Domash, Maren Jorgensen, Sayeh Bayat, David B Carr, Beau M Ances, Ganesh M Babulal

2020-Current year OA Pubs

Daily driving is a multi-faceted, real-world, behavioral measure of cognitive functioning requiring multiple cognitive domains working synergistically to complete this instrumental activity of daily living. As the global population of older adult continues to grow, motor vehicle crashes become more frequent among this demographic. Cognitive reserve (CR) is the brain's adaptability or functional robustness despite damage, while brain reserve (BR) refers the structural, neuroanatomical resources. This study examined whether CR and BR predicted changes in adverse driving behaviors in cognitively normal older adults. Cognitively normal older adults (Clinical Dementia Rating 0) were enrolled from longitudinal studies at the Knight Alzheimer's …

Infantile-Onset Pompe Disease Complicated By Sickle Cell Anemia: Case Report And Management Considerations, Rodrigo Tzovenos Starosta, Ying-Chen Claire Hou, Katelyn Leestma, Prapti Singh, Luke Viehl, Linda Manwaring, Jorge Luis Granadillo, Molly C Schroeder, Jamie N Colombo, Halana Whitehead, Patricia Irene Dickson, Monica L Hulbert, Hoanh Thi Nguyen

2020-Current year OA Pubs

Infantile-onset Pompe disease (IOPD) is a rare, severe disorder of lysosomal storage of glycogen that leads to progressive cardiac and skeletal myopathy. IOPD is a fatal disease in childhood unless treated with enzyme replacement therapy (ERT) from an early age. Sickle cell anemia (SCA) is a relatively common hemoglobinopathy caused by a specific variant in the hemoglobin beta-chain. Here we report a case of a male newborn of African ancestry diagnosed and treated for IOPD and SCA. Molecular testing confirmed two

Using Innovation-Corps (I-Corps™) Methods To Adapt A Mobile Health (Mhealth) Obesity Treatment For Community Mental Health Settings, Rita Haddad, Carolina Badke D'Andrea, Amanda Ricchio, Bradley Evanoff, Elaine H Morrato, Joseph Parks, John W Newcomer, Ginger E Nicol

2020-Current year OA Pubs

BACKGROUND: We employed Innovation Corps (I-Corps™) methods to adaptation of a mobile health (mHealth) short-message-system (SMS) -based interactive obesity treatment approach (iOTA) for adults with severe mentall illness receiving care in community settings.

METHODS: We hypothesized "jobs to be done" in three broad stakeholder groups: "decision makers" (DM = state and community clinic administrators), "clinician consumers" (CC = case managers, peer supports, nurses, prescribers) and "service consumers" (SC = patients, peers and family members). Semistructured interviews (

RESULTS: Four themes emerged across groups: education, inertia, resources and ownership. Sub-themes in education and ownership differed between DM and CC groups on …

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.

Clinical And Molecular Characteristics Of A Novel Rare De Novo Variant In Ppp2ca In A Patient With A Developmental Disorder, Autism, And Epilepsy, Iris Verbinnen, Sara S Procknow, Lisa Lenaerts, Sara Reynhout, Aujan Mehregan, Chris Ulens, Veerle Janssens, Katherine A King

2020-Current year OA Pubs

PP2A-related (neuro) developmental disorders are a family of genetic diseases caused by a heterozygous alteration in one of several genes encoding a subunit of type 2A protein phosphatases. Reported affected genes, so far, are

Expert Guidance On Prophylaxis And Treatment Of Dermatologic Adverse Events With Tumor Treating Fields (Ttfields) Therapy In The Thoracic Region, Milan J Anadkat, Mario Lacouture, Adam Friedman, Zachary D Horne, Jae Jung, Benjamin Kaffenberger, Sujith Kalmadi, Liza Ovington, Rupesh Kotecha, Huda Ismail Abdullah, Federica Grosso

2020-Current year OA Pubs

Tumor Treating Fields (TTFields) are electric fields, delivered via wearable arrays placed on or near the tumor site, that exert physical forces to disrupt cellular processes critical for cancer cell viability and tumor progression. As a first-in-class treatment, TTFields therapy is approved for use in newly diagnosed glioblastoma, recurrent glioblastoma, and pleural mesothelioma. Additionally, TTFields therapy is being investigated in non-small cell lung cancer (NSCLC), brain metastases from NSCLC, pancreatic cancer, ovarian cancer, hepatocellular carcinoma, and gastric adenocarcinoma. Because TTFields therapy is well tolerated and delivery is locoregional, there is low risk of additive systemic adverse events (AEs) when used …

Do The Expert Recommendations For Implementing Change (Eric) Strategies Adequately Address Sustainment?, Nicole Nathan, Byron J Powell, Rachel C Shelton, Celia V Laur, Luke Wolfenden, Maji Hailemariam, Sze Lin Yoong, Rachel Sutherland, Melanie Kingsland, Thomas J Waltz, Alix Hall

2020-Current year OA Pubs

BACKGROUND: Sustainability science is an emerging area within implementation science. There is limited evidence regarding strategies to best support the continued delivery and sustained impact of evidence-based interventions (EBIs). To build such evidence, clear definitions, and ways to operationalize strategies specific and/or relevant to sustainment are required. Taxonomies and compilations such as the Expert Recommendations for Implementing Change (ERIC) were developed to describe and organize implementation strategies. This study aimed to adapt, refine, and extend the ERIC compilation to incorporate an explicit focus on sustainment. We also sought to classify the specific phase(s) of implementation when the ERIC strategies could …

Protocol For The Ketamine For Postoperative Avoidance Of Depressive Symptoms (K-Pass) Feasibility Study: A Randomized Clinical Trial, Bradley A Fritz, Bethany R Tellor Pennington, Ben J A Palanca, Julie A Schweiger, Jon T Willie, Nuri B Farber

2020-Current year OA Pubs

No abstract provided.

Isotopically Nonstationary 13c Metabolic Flux Analysis In Resting And Activated Human Platelets, Cara L Sake, Alexander J Metcalf, Michelle Meagher, Jorge Di Paola, Keith B Neeves, Nanette R Boyle

2020-Current year OA Pubs

Platelet metabolism is linked to platelet hyper- and hypoactivity in numerous human diseases. Developing a detailed understanding of the link between metabolic shifts and platelet activation state is integral to improving human health. Here, we show the first application of isotopically nonstationary

Alopecia Areata After Mogamulizumab Treatment, Neel S Raval, Nora A Alexander, Karlee De Monnin, Christine C Yokoyama, Neha Mehta-Shah, Ilana S Rosman, Amy C Musiek

2020-Current year OA Pubs

No abstract provided.

3d Bi-Directional Transformer U-Net For Medical Image Segmentation, Xiyao Fu, Zhexian Sun, Haoteng Tang, Eric M Zou, Heng Huang, Yong Wang, Liang Zhan

2020-Current year OA Pubs

As one of the popular deep learning methods, deep convolutional neural networks (DCNNs) have been widely adopted in segmentation tasks and have received positive feedback. However, in segmentation tasks, DCNN-based frameworks are known for their incompetence in dealing with global relations within imaging features. Although several techniques have been proposed to enhance the global reasoning of DCNN, these models are either not able to gain satisfying performances compared with traditional fully-convolutional structures or not capable of utilizing the basic advantages of CNN-based networks (namely the ability of local reasoning). In this study, compared with current attempts to combine FCNs and …

Cardiac Immune Cell Infiltration Associates With Abnormal Lipid Metabolism, Vincenza Cifarelli, Ondrej Kuda, Kui Yang, Xinping Liu, Richard W Gross, Terri A Pietka, Gyu Seong Heo, Deborah Sultan, Hannah Luehmann, Josie Lesser, Morgan Ross, Ira J Goldberg, Robert J Gropler, Yongjian Liu, Nada A Abumrad

2020-Current year OA Pubs

CD36 mediates the uptake of long-chain fatty acids (FAs), a major energy substrate for the myocardium. Under excessive FA supply, CD36 can cause cardiac lipid accumulation and inflammation while its deletion reduces heart FA uptake and lipid content and increases glucose utilization. As a result, CD36 was proposed as a therapeutic target for obesity-associated heart disease. However, more recent reports have shown that CD36 deficiency suppresses myocardial flexibility in fuel preference between glucose and FAs, impairing tissue energy balance, while CD36 absence in tissue macrophages reduces efferocytosis and myocardial repair after injury. In line with the latter homeostatic functions, we …

Analysis Of Neuronal Injury Transcriptional Response Identifies Ctcf And Yy1 As Co-Operating Factors Regulating Axon Regeneration, Oshri Avraham, Jimmy Le, Kathleen Leahy, Tiandao Li, Guoyan Zhao, Valeria Cavalli

2020-Current year OA Pubs

Injured sensory neurons activate a transcriptional program necessary for robust axon regeneration and eventual target reinnervation. Understanding the transcriptional regulators that govern this axon regenerative response may guide therapeutic strategies to promote axon regeneration in the injured nervous system. Here, we used cultured dorsal root ganglia neurons to identify pro-regenerative transcription factors. Using RNA sequencing, we first characterized this neuronal culture and determined that embryonic day 13.5 DRG (eDRG) neurons cultured for 7 days are similar to e15.5 DRG neurons

Binary Acoustic Metasurfaces For Dynamic Focusing Of Transcranial Ultrasound, Zhongtao Hu, Yaoheng Yang, Lu Xu, Yao Hao, Hong Chen

2020-Current year OA Pubs

Transcranial focused ultrasound (tFUS) is a promising technique for non-invasive and spatially targeted neuromodulation and treatment of brain diseases. Acoustic lenses were designed to correct the skull-induced beam aberration, but these designs could only generate static focused ultrasound beams inside the brain. Here, we designed and 3D printed binary acoustic metasurfaces (BAMs) for skull aberration correction and dynamic ultrasound beam focusing. BAMs were designed by binarizing the phase distribution at the surface of the metasurfaces. The phase distribution was calculated based on time reversal to correct the skull-induced phase aberration. The binarization enabled the ultrasound beam to be dynamically steered …