Digital Commons Network^™

Validation Of Ad8-Philippines (Ad8-P): A Brief Informant-Based Questionnaire For Dementia Screening In The Philippines, Jacqueline C Dominguez, John C Morris, Et Al

Open Access Publications

Aim: This study was aimed at validating the Filipino version of AD8 (AD8-P).

Methods: Community-dwelling Filipino older persons aged ≥60 years, together with their informants, participated in this study. Psychologists independently interviewed the informants with AD8-P and administered the Filipino-validated Mini-Mental State Examination (MMSE-P) and Montreal Cognitive Assessment (MoCA-P) to the older persons. Neurologists and geriatrician conducted physical and neurological examination and Clinical Dementia Rating™ (CDR™) to determine cognitive diagnosis and were blinded with the results of AD8-P. Dementia was diagnosed based on DSM-IV-TR criteria. AD8-P discriminatory ability to screen for dementia was evaluated according to DSM-IV-TR diagnostic criteria for …

Motor Improvements Enabled By Spinal Cord Stimulation Combined With Physical Training After Spinal Cord Injury: Review Of Experimental Evidence In Animals And Humans, Ismael Seáñez, Marco Capogrosso

Open Access Publications

Electrical spinal cord stimulation (SCS) has been gaining momentum as a potential therapy for motor paralysis in consequence of spinal cord injury (SCI). Specifically, recent studies combining SCS with activity-based training have reported unprecedented improvements in motor function in people with chronic SCI that persist even without stimulation. In this work, we first provide an overview of the critical scientific advancements that have led to the current uses of SCS in neurorehabilitation: e.g. the understanding that SCS activates dormant spinal circuits below the lesion by recruiting large-to-medium diameter sensory afferents within the posterior roots. We discuss how this led to …

The Application Of Exercise Training For Diabetic Peripheral Neuropathy, Clifton J. Holmes, Mary K. Hastings

Open Access Publications

Diabetic peripheral neuropathy (DPN) is the presence of symptoms and/or signs of peripheral nerve dysfunction in people with diabetes after the exclusion of other causes. It is associated with pain, paresthesia, sensory loss, muscle atrophy with fat infiltration, and muscular dysfunction typically starting distally in the feet and progressing proximally. Muscle deterioration within the leg and foot can lead to muscle dysfunction, reduced mobility, and increases the risk of disability, ulceration, and amputation. Exercise training is an established method for increasing the different components of physical fitness, including enhancing body composition and improving neuromuscular strength. A number of experimental studies …

High Seropositivity Rate Of Neutralizing Antibodies To Astrovirus Va1 In Human Populations, Andrew B Janowski, Macee C Owen, Holly Dudley, Tomás López, Rafaela Espinosa, Memory Elvin-Lewis, Alejandro Colichon, Carlos F Arias, Peter D Burbelo, David Wang

Open Access Publications

Astroviruses are common pathogens of the human gastrointestinal tract, but they have been recently identified from cases of fatal meningoencephalitis. Astrovirus VA1 is the most frequently detected astrovirus genotype from cases of human encephalitis, but the prevalence of neutralizing antibodies to VA1 in human sera is unknown. We developed a focus reduction neutralization assay (FRNT) for VA1 and measured the seroprevalence of neutralizing antibodies from two cohorts of adult and pediatric serum samples: (i) an age-stratified cohort from St. Louis, MO, collected from 2007 to 2008 and (ii) a cohort from the Peruvian Amazonian River Basin collected in the late …

American Society Of Hematology Living Guidelines On The Use Of Anticoagulation For Thromboprophylaxis In Patients With Covid-19: May 2021 Update On The Use Of Intermediate-Intensity Anticoagulation In Critically Ill Patients, Adam Cuker, Kristen M Sanfilippo, Et Al

Open Access Publications

BACKGROUND: COVID-19-related critical illness is associated with an increased risk of venous thromboembolism (VTE).

OBJECTIVE: These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in making decisions about the use of anticoagulation for thromboprophylaxis in patients with COVID-19-related critical illness who do not have confirmed or suspected VTE.

METHODS: ASH formed a multidisciplinary guideline panel that included 3 patient representatives and applied strategies to minimize potential bias from conflicts of interest. The McMaster University Grading of Recommendations Assessment, Development and Evaluation (GRADE) Centre supported the guideline development process …

Comparative Genomics Of Mycobacterium Avium Complex Reveals Signatures Of Environment-Specific Adaptation And Community Acquisition, Eric C Keen, Joohee Choi, Meghan A Wallace, Michelle Azar, Carlos R Mejia-Chew, Shail B Mehta, Thomas C Bailey, Lindsay J Caverly, Carey-Ann D Burnham, Gautam Dantas

Open Access Publications

Nontuberculous mycobacteria, including those in the Mycobacterium avium complex (MAC), constitute an increasingly urgent threat to global public health. Ubiquitous in soil and water worldwide, MAC members cause a diverse array of infections in humans and animals that are often multidrug resistant, intractable, and deadly. MAC lung disease is of particular concern and is now more prevalent than tuberculosis in many countries, including the United States. Although the clinical importance of these microorganisms continues to expand, our understanding of their genomic diversity is limited, hampering basic and translational studies alike. Here, we leveraged a unique collection of genomes to characterize …

Neutralizing Monoclonal Antibodies That Target The Spike Receptor Binding Domain Confer Fc Receptor-Independent Protection Against Sars-Cov-2 Infection In Syrian Hamsters, Wen Su, Sin Fun Sia, Aaron J Schmitz, Traci L Bricker, Tyler N Starr, Allison J Greaney, Jackson S Turner, Bassem M Mohammed, Zhuoming Liu, Ka Tim Choy, Tamarand L Darling, Astha Joshi, Ka Man Cheng, Alvina Y L Wong, Houda H Harastani, John M Nicholls, Sean P J Whelan, Jesse D Bloom, Hui-Ling Yen, Ali H Ellebedy, Adrianus C M Boon

Open Access Publications

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein is the main target for neutralizing antibodies. These antibodies can be elicited through immunization or passively transferred as therapeutics in the form of convalescent-phase sera or monoclonal antibodies (MAbs). Potently neutralizing antibodies are expected to confer protection; however, it is unclear whether weakly neutralizing antibodies contribute to protection. Also, their mechanism of action

Human Monoclonal Antibodies Against Ns1 Protein Protect Against Lethal West Nile Virus Infection, Alex W Wessel, Michael P Doyle, Taylor B Engdahl, Jessica Rodriguez, James E Crowe, Michael S Diamond

Open Access Publications

Envelope protein-targeted vaccines for flaviviruses are limited by concerns of antibody-dependent enhancement (ADE) of infections. Nonstructural protein 1 (NS1) provides an alternative vaccine target that avoids this risk since this protein is absent from the virion. Beyond its intracellular role in virus replication, extracellular forms of NS1 function in immune modulation and are recognized by host-derived antibodies. The rational design of NS1-based vaccines requires an extensive understanding of the antigenic sites on NS1, especially those targeted by protective antibodies. Here, we isolated human monoclonal antibodies (MAbs) from individuals previously naturally infected with WNV, mapped their epitopes using structure-guided mutagenesis, and …

Discovering Disease-Disease Associations Using Electronic Health Records In The Guideline Advantage (Tga) Dataset, Aixia Guo, Yosef M Khan, James R Langabeer 2nd, Randi E Foraker

Open Access Publications

Certain diseases have strong comorbidity and co-occurrence with others. Understanding disease-disease associations can potentially increase awareness among healthcare providers of co-occurring conditions and facilitate earlier diagnosis, prevention and treatment of patients. In this study, we utilized the valuable and large The Guideline Advantage (TGA) longitudinal electronic health record dataset from 70 outpatient clinics across the United States to investigate potential disease-disease associations. Specifically, the most prevalent 50 disease diagnoses were manually identified from 165,732 unique patients. To investigate the co-occurrence or dependency associations among the 50 diseases, the categorical disease terms were first mapped into numerical vectors based on disease …

Excellent Response To Very-Low-Dose Radiation (4 Gy) For Indolent B-Cell Lymphomas: Is 4 Gy Suitable For Curable Patients?, Brandon S. Imber, Joanna C. Yang, Et Al

Open Access Publications

No abstract provided.

6-Thioguanine Blocks Sars-Cov-2 Replication By Inhibition Of Plpro, Caleb D Swaim, Varun Dwivedi, Yi-Chieh Perng, Xu Zhao, Larissa A Canadeo, Houda H Harastani, Tamarand L Darling, Adrianus C M Boon, Deborah J Lenschow, Viraj Kulkarni, Jon M Huibregtse

Open Access Publications

The emergence of SARS-CoV-2 has led to a global health crisis that, in addition to vaccines and immunomodulatory therapies, calls for the identification of antiviral therapeutics. The papain-like protease (PLpro) activity of nsp3 is an attractive drug target as it is essential for viral polyprotein cleavage and for deconjugation of ISG15, an antiviral ubiquitin-like protein. We show here that 6-Thioguanine (6-TG), an orally available and widely available generic drug, inhibits SARS-CoV-2 replication in Vero-E6 cells with an EC50 of approximately 2 μM. 6-TG also inhibited PLpro-catalyzed polyprotein cleavage and de-ISGylation in cells and inhibited proteolytic activity of the purified PLpro …

Comparison Of 2-Year Outcomes With Car T Cells (Zuma-1) Vs Salvage Chemotherapy In Refractory Large B-Cell Lymphoma, Sattva S. Neelapu, Nancy L. Bartlett, Et Al

Open Access Publications

No abstract provided.

Surgical Strategy For The Management Of Cervical Deformity Is Based On Type Of Cervical Deformity, Han Jo Kim, Munish Gupta, Et Al

Open Access Publications

OBJECTIVES: Cervical deformity morphotypes based on type and location of deformity have previously been described. This study aimed to examine the surgical strategies implemented to treat these deformity types and identify if differences in treatment strategies impact surgical outcomes. Our hypothesis was that surgical strategies will differ based on different morphologies of cervical deformity.

METHODS: Adult patients enrolled in a prospective cervical deformity database were classified into four deformity types (Flatneck (FN), Focal kyphosis (FK), Cervicothoracic kyphosis (CTK) and Coronal (C)), as previously described. We analyzed group differences in demographics, preoperative symptoms, health-related quality of life scores (HRQOLs), and surgical …

Syndrome Of Reversible Cardiogenic Shock And Left Ventricular Ballooning In Obstructive Hypertrophic Cardiomyopathy, Mark V Sherrid, Daniel G Swistel, Iacopo Olivotto, Maurizio Pieroni, Omar Wever-Pinzon, Katherine Riedy, Richard G Bach, Mustafa Husaini, Sharon Cresci, Alex Reyentovich, Daniele Massera, Martin S Maron, Barry J Maron, Bette Kim

Open Access Publications

Background Cardiogenic shock from most causes has unfavorable prognosis. Hypertrophic cardiomyopathy (HCM) can uncommonly present with apical ballooning and shock in association with sudden development of severe and unrelenting left ventricular (LV) outflow obstruction. Typical HCM phenotypic features of mild septal thickening, outflow gradients, and distinctive mitral abnormalities differentiate these patients from others with Takotsubo syndrome, who have normal mitral valves and no outflow obstruction. Methods and Results We analyzed 8 patients from our 4 HCM centers with obstructive HCM and abrupt presentation of cardiogenic shock with LV ballooning, and 6 cases reported in literature. Of 14 patients, 10 (71%) …

Sirtuin 1 Mediates Protection Against Delayed Cerebral Ischemia In Subarachnoid Hemorrhage In Response To Hypoxic Postconditioning, Deepti Diwan, Ananth K Vellimana, Diane J Aum, Julian Clarke, James W Nelson, Molly Lawrence, Byung Hee Han, Jeffrey M Gidday, Gregory J Zipfel

Open Access Publications

Background Many therapies designed to prevent delayed cerebral ischemia (DCI) and improve neurological outcome in aneurysmal subarachnoid hemorrhage (SAH) have failed, likely because of targeting only one element of what has proven to be a multifactorial disease. We previously demonstrated that initiating hypoxic conditioning before SAH (hypoxic preconditioning) provides powerful protection against DCI. Here, we expanded upon these findings to determine whether hypoxic conditioning delivered at clinically relevant time points after SAH (hypoxic postconditioning) provides similarly robust DCI protection. Methods and Results In this study, we found that hypoxic postconditioning (8% O

The Content And Quality Of Publicly Available Information About Congenital Diaphragmatic Hernia: Descriptive Study, Frank Coyle Soltys, Kimi Spilo, Mary C Politi

Open Access Publications

BACKGROUND: Congenital diaphragmatic hernia (CDH) diagnosis in an infant is distressing for parents. Parents often feel unable to absorb the complexities of CDH during prenatal consultations and use the internet to supplement their knowledge and decision making.

OBJECTIVE: We aimed to examine the content and quality of publicly available, internet-based CDH information.

METHODS: We conducted internet searches across 2 popular search engines (Google and Bing). Websites were included if they contained CDH information and were publicly available. We developed a coding instrument to evaluate websites. Two coders (FS and KS) were trained, achieved interrater reliability, and rated remaining websites independently. …

Relationship Between Quality Of Life Indicators And Cardiac Status Indicators In Chemotherapy Patients, Blaž Matija Geršak, Andreja Kukec, Henning Steen, Moritz Montenbruck, Maja Šoštarič, Arne Kristian Schwarz, Sebastian Esch, Sebastian Kelle, Sorin Giusca, Grigorios Korosoglou, Pia Wülfing, Susan Dent, Daniel Lenihan

Open Access Publications

AIM: With the aim of improving personalized treatment of patients on chemotherapy, the objective of the study was to assess the degree of association between selected Quality of life (QoL) indicators and both clinical and imaging cardiac status indicators when detecting deterioration in QoL of these patients.

METHODS: In a cohort clinical study in Hamburg, from August 2017 through October 2020, 59 cancer patients, aged 18-80 years, were evaluated before chemotherapy, and at several follow-ups, using EQ-5D and SF-36 QoL questionnaires, fast strain-encoded (fast-SENC) cardiac magnetic resonance (CMR), conventional CMR, and echocardiography, and further received a clinical and biomarker examination. …

Elevated Mics Of Susceptible Antipseudomonal Cephalosporins In Non-Carbapenemase-Producing, Carbapenem-Resistant Pseudomonas Aeruginosa: Implications For Dose Optimization, Christian M Gill, Carey-Ann D Burnham, Et Al

Open Access Publications

The present study evaluated the

Alternative Pre-Mrna Splicing Of The Mu Opioid Receptor Gene, Oprm1: Insight Into Complex Mu Opioid Actions, Shan Liu, Wen-Jia Kang, Anna Abrimian, Jin Xu, Luca Cartegni, Susruta Majumdar, Patrick Hesketh, Alex Bekker, Ying-Xian Pan

Open Access Publications

Most opioid analgesics used clinically, including morphine and fentanyl, as well as the recreational drug heroin, act primarily through the mu opioid receptor, a class A Rhodopsin-like G protein-coupled receptor (GPCR). The single-copy mu opioid receptor gene,

Aducanumab For Alzheimer Disease: The Amyloid Hypothesis Moves From Bench To Bedside, Erik S. Musiek, Teresa Gomez-Isla, David M Holtzman

Open Access Publications

No abstract provided.

Cullin4 E3 Ubiquitin Ligases Regulate Male Gonocyte Migration, Proliferation And Blood-Testis Barrier Homeostasis, Yan Yin, Liming Zhu, Qiufang Li, Pengbo Zhou, Liang Ma

Open Access Publications

Ubiquitination, an essential posttranslational modification, plays fundamental roles during mammalian spermatogenesis. We previously reported the requirement of two Cullin 4 ubiquitin ligase family genes, Cullin 4a (

Plasmid-Encoded H-Ns Controls Extracellular Matrix Composition In A Modern Acinetobacter Baumannii Urinary Isolate, Saida Benomar, Gisela Di Venanzio, Mario F Feldman

Open Access Publications

Acinetobacter baumannii is emerging as a multidrug-resistant (MDR) nosocomial pathogen of increasing threat to human health worldwide. The recent MDR urinary isolate UPAB1 carries the plasmid pAB5, a member of a family of large conjugative plasmids (LCPs). LCPs encode several antibiotic resistance genes and repress the type VI secretion system (T6SS) to enable their dissemination, employing two TetR transcriptional regulators. Furthermore, pAB5 controls the expression of additional chromosomally encoded genes, impacting UPAB1 virulence. Here, we show that a pAB5-encoded H-NS transcriptional regulator represses the synthesis of the exopolysaccharide PNAG and the expression of a previously uncharacterized three-gene cluster that encodes …

Inhibition Of The Nlrp3 Inflammasome Improves Lifespan In Animal Murine Model Of Hutchinson-Gilford Progeria, Alvaro González-Dominguez, Raúl Montañez, Beatriz Castejón-Vega, Jéssica Nuñez-Vasco, Débora Lendines-Cordero, Chun Wang, Gabriel Mbalaviele, José M Navarro-Pando, Elísabet Alcocer-Gómez, Mario D Cordero

Open Access Publications

Inflammation is a hallmark of aging and accelerated aging syndromes such as Hutchinson-Gilford progeria syndrome (HGPS). In this study, we present evidence of increased expression of the components of the NLRP3 inflammasome pathway in HGPS skin fibroblasts, an outcome that was associated with morphological changes of the nuclei of the cells. Lymphoblasts from HGPS patients also showed increased basal levels of NLRP3 and caspase 1. Consistent with these results, the expression of caspase 1 and Nlrp3, but not of the other inflammasome receptors was higher in the heart and liver of Zmpste24

Coronary Artery Calcification And Plaque Characteristics In People Living With Hiv: A Systematic Review And Meta-Analysis, Cullen Soares, Amjad Samara, Matthew F Yuyun, Justin B Echouffo-Tcheugui, Ahmad Masri, Ahmad Samara, Alan R Morrison, Nina Lin, Wen-Chih Wu, Sebhat Erqou

Open Access Publications

Background Studies have reported that people living with HIV have higher burden of subclinical cardiovascular disease, but the data are not adequately synthesized. We performed meta-analyses of studies of coronary artery calcium and coronary plaque in people living with HIV. Methods and Results We performed systematic search in electronic databases, and data were abstracted in standardized forms. Study-specific estimates were pooled using meta-analysis. 43 reports representing 27 unique studies and involving 10 867 participants (6699 HIV positive, 4168 HIV negative, mean age 52 years, 86% men, 32% Black) were included. The HIV-positive participants were younger (mean age 49 versus 57 …

Disparities In Treatment Decisions For Abnormal Uterine Bleeding, Lulu Yu, Bhavana Janga, Rebecca Mcalister, Donna B Jeffe, Tammy Sonn

Open Access Publications

No abstract provided.

Structure Of Venezuelan Equine Encephalitis Virus In Complex With The Ldlrad3 Receptor, Katherine Basore, Hongming Ma, Natasha M Kafai, Samantha Mackin, Arthur S Kim, Christopher A Nelson, Michael S Diamond, Daved H Fremont

Open Access Publications

LDLRAD3 is a recently defined attachment and entry receptor for Venezuelan equine encephalitis virus (VEEV)

Novel Variants In Kat6b Spectrum Of Disorders Expand Our Knowledge Of Clinical Manifestations And Molecular Mechanisms, Megan Yabumoto, Catherine Gooch, Et Al

Open Access Publications

The phenotypic variability associated with pathogenic variants in Lysine Acetyltransferase 6B (KAT6B, a.k.a. MORF, MYST4) results in several interrelated syndromes including Say-Barber-Biesecker-Young-Simpson Syndrome and Genitopatellar Syndrome. Here we present 20 new cases representing 10 novel KAT6B variants. These patients exhibit a range of clinical phenotypes including intellectual disability, mobility and language difficulties, craniofacial dysmorphology, and skeletal anomalies. Given the range of features previously described for KAT6B-related syndromes, we have identified additional phenotypes including concern for keratoconus, sensitivity to light or noise, recurring infections, and fractures in greater numbers than previously reported. We surveyed clinicians to qualitatively assess the ways families …

Data-Driven Clustering Identifies Features Distinguishing Multisystem Inflammatory Syndrome From Acute Covid-19 In Children And Adolescents, Alon Geva, Philip C Spinella, Et Al

Open Access Publications

Background: Multisystem inflammatory syndrome in children (MIS-C) consensus criteria were designed for maximal sensitivity and therefore capture patients with acute COVID-19 pneumonia.

Methods: We performed unsupervised clustering on data from 1,526 patients (684 labeled MIS-C by clinicians) <21 years old hospitalized with COVID-19-related illness admitted between 15 March 2020 and 31 December 2020. We compared prevalence of assigned MIS-C labels and clinical features among clusters, followed by recursive feature elimination to identify characteristics of potentially misclassified MIS-C-labeled patients.

Findings: Of 94 clinical features tested, 46 were retained for clustering. Cluster 1 patients (

Interpretation: Using a data driven, unsupervised approach, we identified features that cluster patients into a group with high likelihood of having MIS-C. Other features identified a cluster of patients more likely to have acute severe COVID-19 pulmonary disease, and patients in this cluster labeled by clinicians as MIS-C …

Deep Learning-Based Method To Accurately Estimate Breast Tissue Optical Properties In The Presence Of The Chest Wall, Menghao Zhang, Shuying Li, Yun Zou, Quing Zhu

Open Access Publications

SIGNIFICANCE: In general, image reconstruction methods used in diffuse optical tomography (DOT) are based on diffusion approximation, and they consider the breast tissue as a homogenous, semi-infinite medium. However, the semi-infinite medium assumption used in DOT reconstruction is not valid when the chest wall is underneath the breast tissue.

AIM: We aim to reduce the chest wall's effect on the estimated average optical properties of breast tissue and obtain accurate forward model for DOT reconstruction.

APPROACH: We propose a deep learning-based neural network approach where a convolution neural network (CNN) is trained to simultaneously obtain accurate optical property values for …

Protocol For Draup: A Deimplementation Programme To Decrease Routine Chest Radiographs After Central Venous Catheter Insertion, Enyo Ablordeppey, Byron Powell, Virginia Mckay, Shannon Keating, Aimee James, Christopher Carpenter, Marin Kollef, Richard Griffey

Open Access Publications

INTRODUCTION: Avoiding low value medical practices is an important focus in current healthcare utilisation. Despite advantages of point-of-care ultrasound (POCUS) over chest X-ray including improved workflow and timeliness of results, POCUS-guided central venous catheter (CVC) position confirmation has slow rate of adoption. This demonstrates a gap that is ripe for the development of an intervention.

METHODS: The intervention is a deimplementation programme called DRAUP (

ETHICS AND DISSEMINATION: Approval of the study by the Human Research Protection Office has been obtained. This work will be disseminated by publication of peer-reviewed manuscripts, presentation in abstract form at scientific meetings and data …