Medicine and Health Sciences Commons^™

A Single-Center Experience Comparing First- Versus Second-Generation Insertable Cardiac Monitors In Pediatric Patients, Nathan Miller, Lisa Roelle, Dean Lorimer Jr, Aarti S Dalal, William B Orr, George F Van Hare, Jennifer N Avari Silva

2020-Current year OA Pubs

Insertable cardiac monitors (ICMs) have undergone advancements in size and functionality over the past decade, resulting in the introduction of small, easily insertable devices capable of long-term remote monitoring. We define first-generation ICMs as implantable cardiac monitoring devices that require an incision and surgical creation of a subcutaneous pocket and second-generation ICMs as devices implanted using a custom-made tool for subcutaneous insertion, respectively. The aim of this study was to understand the differences between first- and second-generation pediatric ICM implants, implant indications, and time to diagnosis. We performed a retrospective, single-center chart review of patients who underwent ICM implantation from …

Translating Data Analytics Into Improved Spine Surgery Outcomes: A Roadmap For Biomedical Informatics Research In 2021, Jacob K. Greenberg, Ayodamola Otun, Zoher Ghogawala, Po-Yin Yen, Camilo A. Molina, David D. Limbrick, Randi E. Foraker, Michael P. Kelly, Wilson Z. Ray

2020-Current year OA Pubs

STUDY DESIGN: Narrative review.

OBJECTIVES: There is growing interest in the use of biomedical informatics and data analytics tools in spine surgery. Yet despite the rapid growth in research on these topics, few analytic tools have been implemented in routine spine practice. The purpose of this review is to provide a health information technology (HIT) roadmap to help translate data assets and analytics tools into measurable advances in spine surgical care.

METHODS: We conducted a narrative review of PubMed and Google Scholar to identify publications discussing data assets, analytical approaches, and implementation strategies relevant to spine surgery practice.

RESULTS: A …

Raising Anesthesiology Diversity And Antiracism: Launching A National Initiative, Matthew C. Wixson, Allison D. Mitchell, Scott D. Markowitz, Kate M. Malicke, Michael S. Avidan, George A. Mashour

2020-Current year OA Pubs

No abstract provided.

Serum Cholesterol Efflux Capacity In Age-Related Macular Degeneration And Polypoidal Choroidal Vasculopathy, Yasuo Yanagi, Richard M C Yu, Waseem Ahamed, Marco Yu, Kelvin Yi Chong Teo, Anna C S Tan, Ching-Yu Cheng, Tien Yin Wong, Rajendra S Apte, Chui Ming Gemmy Cheung

2020-Current year OA Pubs

PURPOSE: To investigate serum cholesterol efflux capacity (the ability of the serum to accept cholesterol) and factors that regulate it using nuclear magnetic resonance-quantified measures of lipoprotein particle composition and size and apolipoproteins metrics in patients with age-related macular degeneration (AMD).

DESIGN: Case-control study.

PARTICIPANTS: Four hundred two serum samples from 80 patients with early AMD (eAMD), and 212 patients with neovascular AMD (nAMD), including 80 with typical nAMD (tAMD) and 132 with polypoidal choroidal vasculopathy (PCV), and 110 age- and gender matched control participants.

METHODS: Serum from participants showed cholesterol efflux capacity measured using in vitro cell assays and …

Ultrapotent And Broad Neutralization Of Sars-Cov-2 Variants By Modular, Tetravalent, Bi-Paratopic Antibodies, Shane Miersch, Nitin Sharma, Reza Saberianfar, Chao Chen, Francesca Caccuri, Alberto Zani, Arnaldo Caruso, James Brett Case, Michael S Diamond, Gaya K Amarasinghe, Giuseppe Novelli, Sachdev S Sidhu

2020-Current year OA Pubs

Neutralizing antibodies (nAbs) that target the SARS-CoV-2 spike protein have received emergency use approval for treatment of COVID-19. However, with the emergence of variants of concern, there is a need for new treatment options. We report a format that enables modular assembly of bi-paratopic tetravalent nAbs with antigen-binding sites from two distinct nAbs. The tetravalent nAb purifies in high yield and exhibits biophysical characteristics that are comparable to those of clinically used therapeutic antibodies. The tetravalent nAb binds to the spike protein trimer at least 100-fold more tightly than bivalent IgGs (apparent K

Wireless Implantable Optical Probe For Continuous Monitoring Of Oxygen Saturation In Flaps And Organ Grafts, Hexia Guo, Yameng Xu, Lauren Jacobson, Amanda M Westman, Matthew R Macewan, Mitchell A Pet, Et Al.

2020-Current year OA Pubs

Continuous, real-time monitoring of perfusion after microsurgical free tissue transfer or solid organ allotransplantation procedures can facilitate early diagnosis of and intervention for anastomotic thrombosis. Current technologies including Doppler systems, cutaneous O

The H3k27m Mutation Alters Stem Cell Growth, Epigenetic Regulation, And Differentiation Potential, N Kfoury-Beaumont, R Prakasam, S Pondugula, J S Lagas, S Matkovich, P Gontarz, L Yang, H Yano, A H Kim, J B Rubin, K L Kroll

2020-Current year OA Pubs

BACKGROUND: Neurodevelopmental disorders increase brain tumor risk, suggesting that normal brain development may have protective properties. Mutations in epigenetic regulators are common in pediatric brain tumors, highlighting a potentially central role for disrupted epigenetic regulation of normal brain development in tumorigenesis. For example, lysine 27 to methionine mutation (H3K27M) in the H3F3A gene occurs frequently in Diffuse Intrinsic Pontine Gliomas (DIPGs), the most aggressive pediatric glioma. As H3K27M mutation is necessary but insufficient to cause DIPGs, it is accompanied by additional mutations in tumors. However, how H3K27M alone increases vulnerability to DIPG tumorigenesis remains unclear.

RESULTS: Here, we used human …

Beyond Inhibition: A Novel Strategy Of Targeting Hiv-1 Protease To Eliminate Viral Reservoirs, Josh G Kim, Liang Shan

2020-Current year OA Pubs

HIV-1 protease (PR) is a viral enzyme that cleaves the Gag and Gag-Pol polyprotein precursors to convert them into their functional forms, a process which is essential to generate infectious viral particles. Due to its broad substrate specificity, HIV-1 PR can also cleave certain host cell proteins. Several studies have identified host cell substrates of HIV-1 PR and described the potential impact of their cleavage on HIV-1-infected cells. Of particular interest is the interaction between PR and the caspase recruitment domain-containing protein 8 (CARD8) inflammasome. A recent study demonstrated that CARD8 can sense HIV-1 PR activity and induce cell death. …

The Differences In The Susceptibility Patterns To Triclabendazole Sulfoxide In Field Isolates Of Fasciola Hepatica Are Associated With Geographic, Seasonal, And Morphometric Variations, Martha V Fernandez-Baca, Cristian Hoban, Rodrigo A Ore, Pedro Ortiz, Young-Jun Choi, César Murga-Moreno, Makedonka Mitreva, Miguel M Cabada

2020-Current year OA Pubs

Triclabendazole (TCBZ) resistance is an emerging problem in fascioliasis that is not well understood. Studies including small numbers of parasites fail to capture the complexity of susceptibility variations between and within

Multisystem Proteinopathy Due To Vcp Mutations: A Review Of Clinical Heterogeneity And Genetic Diagnosis, Gerald Pfeffer, Grace Lee, Carly S Pontifex, Roberto D Fanganiello, Allison Peck, Conrad C Weihl, Virginia Kimonis

2020-Current year OA Pubs

In this work, we review clinical features and genetic diagnosis of diseases caused by mutations in the gene encoding valosin-containing protein (VCP/p97), the functionally diverse AAA-ATPase. VCP is crucial to a multitude of cellular functions including protein quality control, stress granule formation and clearance, and genomic integrity functions, among others. Pathogenic mutations in

Shiny Gatom: Omics-Based Identification Of Regulated Metabolic Modules In Atom Transition Networks, Mariia Emelianova, Anastasiia Gainullina, Nikolay Poperechnyi, Alexander Loboda, Maxim Artyomov, Alexey Sergushichev

2020-Current year OA Pubs

Multiple high-throughput omics techniques provide different angles on systematically quantifying and studying metabolic regulation of cellular processes. However, an unbiased analysis of such data and, in particular, integration of multiple types of data remains a challenge. Previously, for this purpose we developed GAM web-service for integrative metabolic network analysis. Here we describe an updated pipeline GATOM and the corresponding web-service Shiny GATOM, which takes as input transcriptional and/or metabolomic data and finds a metabolic subnetwork most regulated between the two conditions of interest. GATOM features a new metabolic network topology based on atom transition, which significantly improves interpretability of the …

Cardiovascular Tropism And Sequelae Of Sars-Cov-2 Infection, Oleksandr Dmytrenko, Kory J Lavine

2020-Current year OA Pubs

The extrapulmonary manifestation of coronavirus disease-19 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), became apparent early in the ongoing pandemic. It is now recognized that cells of the cardiovascular system are targets of SARS-CoV-2 infection and associated disease pathogenesis. While some details are emerging, much remains to be understood pertaining to the mechanistic basis by which SARS-CoV-2 contributes to acute and chronic manifestations of COVID-19. This knowledge has the potential to improve clinical management for the growing populations of patients impacted by COVID-19. Here, we review the epidemiology and pathophysiology of cardiovascular sequelae of COVID-19 and outline …

A Genetically Distinct Pediatric Subtype Of Primary Cns Large B-Cell Lymphoma Is Associated With Favorable Clinical Outcome, Ekin Güney, Sonika Dahiya, Et Al.

2020-Current year OA Pubs

No abstract provided.

Surprise And Recency In Novelty Detection In The Primate Brain, Kaining Zhang, Ethan S Bromberg-Martin, Fatih Sogukpinar, Kim Kocher, Ilya E Monosov

2020-Current year OA Pubs

Primates and other animals must detect novel objects. However, the neuronal mechanisms of novelty detection remain unclear. Prominent theories propose that visual object novelty is either derived from the computation of recency (how long ago a stimulus was experienced) or is a form of sensory surprise (stimulus unpredictability). Here, we use high-channel electrophysiology in primates to show that in many primate prefrontal, temporal, and subcortical brain areas, object novelty detection is intertwined with the computations of recency and sensory surprise. Also, distinct circuits could be engaged by expected versus unexpected sensory surprise. Finally, we studied neuronal novelty-to-familiarity transformations during learning …

Adherence And Engagement With A Cognitive Behavioral Therapy-Based Conversational Agent (Wysa For Chronic Pain) Among Adults With Chronic Pain: Survival Analysis, Chaitali Sinha, Abby L Cheng, Madhura Kadaba

2020-Current year OA Pubs

BACKGROUND: Digital applications are commonly used to support mental health and well-being. However, successfully retaining and engaging users to complete digital interventions is challenging, and comorbidities such as chronic pain further reduce user engagement. Digital conversational agents (CAs) may improve user engagement by applying engagement principles that have been implemented within in-person care settings.

OBJECTIVE: To evaluate user retention and engagement with an artificial intelligence-led digital mental health app (Wysa for Chronic Pain) that is customized for individuals managing mental health symptoms and coexisting chronic pain.

METHODS: In this ancillary survival analysis of a clinical trial, participants included 51 adults …

Development And Testing Of An Instrument To Measure Contextual Factors Influencing Self-Care Decisions Among Adults With Chronic Illness, Shayleigh Dickson Page, Christopher Lee, Subhash Aryal, Kenneth Freedland, Anna Stromberg, Ercole Vellone, Heleen Westland, Douglas J Wiebe, Tiny Jaarsma, Barbara Riegel

2020-Current year OA Pubs

BACKGROUND: Decisions about how to manage bothersome symptoms of chronic illness are complex and influenced by factors related to the patient, their illness, and their environment. Naturalistic decision-making describes decision-making when conditions are dynamically evolving, and the decision maker may be uncertain because the situation is ambiguous and missing information. Contextual factors, including time stress, the perception of high stakes, and input from others may facilitate or complicate decisions about the self-care of symptoms. There is no valid instrument to measure these contextual factors. The purpose of this study was to develop and test a self-report instrument measuring the contextual …

Integrative Genomic Analysis Reveals Low T-Cell Infiltration As The Primary Feature Of Tobacco Use In Hpv-Positive Oropharyngeal Cancer, Benjamin M Wahle, Paul Zolkind, Ricardo J Ramirez, Zachary L Skidmore, Sydney R Anderson, Angela Mazul, D Neil Hayes, Vlad C Sandulache, Wade L Thorstad, Douglas Adkins, Obi L Griffith, Malachi Griffith, Jose P Zevallos

2020-Current year OA Pubs

Although tobacco use is an independent adverse prognostic feature in HPV(+) oropharyngeal squamous cell carcinoma (OPSCC), the biologic features associated with tobacco use have not been systematically investigated. We characterized genomic and immunologic features associated with tobacco use through whole exome sequencing, mRNA hybridization, and immunohistochemical staining in 47 HPV(+) OPSCC tumors. Low expression of transcripts in a T cell-inflamed gene expression profile (TGEP) was associated with tobacco use at diagnosis and lower overall and disease-free survival. Tobacco use was associated with an increased proportion of T > C substitutions and a lower proportion of expected mutational signatures, but not with …

Measurement Error Affecting Web- And Paper-Based Dietary Assessment Instruments: Insights From The Multi-Cohort Eating And Activity Study For Understanding Reporting Error, Sharon I Kirkpatrick, Yikyung Park, Et Al.

2020-Current year OA Pubs

Few biomarker-based validation studies have examined error in online self-report dietary assessment instruments, and food records (FRs) have been considered less than food frequency questionnaires (FFQs) and 24-hour recalls (24HRs). We investigated measurement error in online and paper-based FFQs, online 24HRs, and paper-based FRs in 3 samples drawn primarily from 3 cohorts, comprising 1,393 women and 1,455 men aged 45-86 years. Data collection occurred from January 2011 to October 2013. Attenuation factors and correlation coefficients between reported and true usual intake for energy, protein, sodium, potassium, and respective densities were estimated using recovery biomarkers. Across studies, average attenuation factors for …

Poly(Gr) And Poly(Ga) In Cerebrospinal Fluid As Potential Biomarkers For C9orf72-Als/Ftd, Gopinath Krishnan, Timothy M Miller, Et Al

2020-Current year OA Pubs

GGGGCC repeat expansion in C9ORF72, which can be translated in both sense and antisense directions into five dipeptide repeat (DPR) proteins, including poly(GP), poly(GR), and poly(GA), is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Here we developed sensitive assays that can detect poly(GA) and poly(GR) in the cerebrospinal fluid (CSF) of patients with C9ORF72 mutations. CSF poly(GA) and poly(GR) levels did not correlate with age at disease onset, disease duration, or rate of decline of ALS Functional Rating Scale, and the average levels of these DPR proteins were similar in symptomatic and pre-symptomatic …

Belimumab For Systemic Lupus Erythematosus - Focus On Lupus Nephritis, Marlene Plüß, Silvia Piantoni, Björn Tampe, Alfred H J Kim, Peter Korsten

2020-Current year OA Pubs

In recent years, advances in the treatment and management of patients with systemic lupus erythematosus (SLE) have improved their life expectancy and quality of life. However, lupus nephritis (LN) still represents a major life-threatening complication of the disease. Belimumab (BEL), a fully human monoclonal IgG1λ antibody neutralizing soluble B cell activating factor, was approved more than ten years ago as add-on therapy in adults and pediatric patients with a highly active, autoantibody-positive disease despite standard of care (SoC). Recently, the superiority of the addition of BEL to SoC was also demonstrated in LN. In this review, we provide a comprehensive …

The Plasmodium Falciparum Abc Transporter Abci3 Confers Parasite Strain-Dependent Pleiotropic Antimalarial Drug Resistance, James M Murithi, Eva S Istvan, Daniel E Goldberg, Et Al.

2020-Current year OA Pubs

Widespread Plasmodium falciparum resistance to first-line antimalarials underscores the vital need to develop compounds with novel modes of action and identify new druggable targets. Here, we profile five compounds that potently inhibit P. falciparum asexual blood stages. Resistance selection studies with three carboxamide-containing compounds, confirmed by gene editing and conditional knockdowns, identify point mutations in the parasite transporter ABCI3 as the primary mediator of resistance. Selection studies with imidazopyridine or quinoline-carboxamide compounds also yield changes in ABCI3, this time through gene amplification. Imidazopyridine mode of action is attributed to inhibition of heme detoxification, as evidenced by cellular accumulation and heme …

Fmrp Regulates Gabaa Receptor Channel Activity To Control Signal Integration In Hippocampal Granule Cells, Pan-Yue Deng, Ajeet Kumar, Valeria Cavalli, Vitaly A Klyachko

2020-Current year OA Pubs

Fragile X syndrome, the most common inherited form of intellectual disability, is caused by loss of fragile X mental retardation protein (FMRP). GABAergic system dysfunction is one of the hallmarks of FXS, yet the underlying mechanisms remain poorly understood. Here, we report that FMRP interacts with GABA

Effectiveness Of Mrna Vaccines Against Covid-19 Hospitalization By Age And Chronic Medical Conditions Burden Among Immunocompetent Us Adults, March-August 2021, Nathaniel M Lewis, Hilary M Babcock, Jennie H Kwon, Et Al.

2020-Current year OA Pubs

Vaccine effectiveness (VE) against COVID-19 hospitalization was evaluated among immunocompetent adults (≥18 years) during March-August 2021 using a case-control design. Among 1669 hospitalized COVID-19 cases (11% fully vaccinated) and 1950 RT-PCR-negative controls (54% fully vaccinated), VE was 96% (95% confidence interval [CI], 93%-98%) among patients with no chronic medical conditions and 83% (95% CI, 76%-88%) among patients with ≥ 3 categories of conditions. VE was similar between those aged 18-64 years versus ≥65 years (P > .05). VE against severe COVID-19 was very high among adults without chronic conditions and lessened with increasing comorbidity burden.

Reliability And Stability Challenges In Abcd Task Fmri Data, James T. Kennedy, Michael P. Harms, Ozlem Korucuoglu, Serguei V. Astafiev, Deanna M. Barch, Wesley K. Thompson, James M. Bjork, Andrey P. Anokhin

2020-Current year OA Pubs

Trait stability of measures is an essential requirement for individual differences research. Functional MRI has been increasingly used in studies that rely on the assumption of trait stability, such as attempts to relate task related brain activation to individual differences in behavior and psychopathology. However, recent research using adult samples has questioned the trait stability of task-fMRI measures, as assessed by test-retest correlations. To date, little is known about trait stability of task fMRI in children. Here, we examined within-session reliability and long-term stability of individual differences in task-fMRI measures using fMRI measures of brain activation provided by the adolescent …

Anxiety-Like Behavior And Anxiolytic Treatment In The Rett Syndrome Natural History Study, Caroline B Buchanan, Robin C Ryther, Et Al.

2020-Current year OA Pubs

BACKGROUND: Rett syndrome (RTT) is a neurodevelopmental disorder most often related to a pathogenic variant in the X-linked MECP2 gene. Internalizing behaviors appear to be common, but standard methods of diagnosing anxiety are not readily applied in this population which typically has cognitive impairment and limited expressive language. This study aims to describe the frequency of anxiety-like behavior and anxiolytic treatments along with associated clinical features in individuals with RTT.

METHODS: Parental reports and medication logs provided data from 1380 females with RTT participating in two iterations of the multicenter U.S. RTT Natural History Study (RNHS) from 2006 to 2019. …

Metasquare: An Integrated Metadatabase Of 16s Rrna Gene Amplicon For Microbiome Taxonomic Classification, Chun-Chieh Liao, Po-Ying Fu, Chih-Wei Huang, Chia-Hsien Chuang, Yun Yen, Chung-Yen Lin, Shu-Hwa Chen

2020-Current year OA Pubs

MOTIVATION: Taxonomic classification of 16S ribosomal RNA gene amplicon is an efficient and economic approach in microbiome analysis. 16S rRNA sequence databases like SILVA, RDP, EzBioCloud and HOMD used in downstream bioinformatic pipelines have limitations on either the sequence redundancy or the delay on new sequence recruitment. To improve the 16S rRNA gene-based taxonomic classification, we merged these widely used databases and a collection of novel sequences systemically into an integrated resource.

RESULTS: MetaSquare version 1.0 is an integrated 16S rRNA sequence database. It is composed of more than 6 million sequences and improves taxonomic classification resolution on both long-read …

"I Expected Little, Although I Learned A Lot": Perceived Benefits Of Participating In Hiv Risk Reduction Sessions Among Women Engaged In Sex Work In Uganda, Ozge Sensoy Bahar, Proscovia Nabunya, Josephine Nabayinda, Susan S Witte, Joshua Kiyingi, Larissa Jennings Mayo-Wilson, Prema Filippone, Lyla Sunyoung Yang, Janet Nakigudde, Yesim Tozan, Fred M Ssewamala

2020-Current year OA Pubs

BACKGROUND: The global HIV burden remains a public health concern. Women engaged in sex work (WESW) are at higher risk of acquiring HIV compared to the general adult population. Uganda reports high rates of HIV prevalence among WESW. While WESW in Uganda have long been the subject of surveillance studies, they have not been targeted by theory-informed HIV prevention intervention approaches. In this study, we explored the perceived benefits of an evidence-based HIV risk reduction intervention that was implemented as part of a combination intervention tested in a clinical trial in Uganda.

METHODS: As part of a larger randomized clinical …

Aging With Disability Symptoms And Ability To Participate In, And Satisfaction With, Social Participation Among Persons Aged 45-64, Michelle Putnam, Kerri A. Morgan, Rachel Heeb, Yan Yan, Szu-Wei Chen, Susan L Stark

Open Access Publications

Pain, fatigue, and depression, considered aging with disability (AwD) symptoms, are known to be substantially higher among middle-aged adults with long-term disability compared to their age peers. Participation has been recognized as an important component of health. This cohort survey study reports findings on the relationship between AwD symptoms and ability to participate in, and satisfaction with participation in, social roles and activities using PROMIS measures. Data were collected at three time points from individuals aged 45-64 with an average of two decades of disability duration and primarily living in the state of Missouri, USA. This study reports on Time …

Treatment For Mild Chronic Hypertension During Pregnancy, Alan T Tita, Methodius Tuuli, Et Al.

2020-Current year OA Pubs

BACKGROUND: The benefits and safety of the treatment of mild chronic hypertension (blood pressure, <160/100 mm Hg) during pregnancy are uncertain. Data are needed on whether a strategy of targeting a blood pressure of less than 140/90 mm Hg reduces the incidence of adverse pregnancy outcomes without compromising fetal growth.

METHODS: In this open-label, multicenter, randomized trial, we assigned pregnant women with mild chronic hypertension and singleton fetuses at a gestational age of less than 23 weeks to receive antihypertensive medications recommended for use in pregnancy (active-treatment group) or to receive no such treatment unless severe hypertension (systolic pressure, ≥160 mm Hg; or diastolic pressure, ≥105 mm Hg) developed (control group). The primary outcome was a composite of preeclampsia with severe features, medically indicated preterm birth at less than 35 weeks' gestation, placental abruption, or fetal …

Upregulated Influenza A Viral Entry Factors And Enhanced Interferon-Alpha Response In The Nasal Epithelium Of Pregnant Rats, Tusar Giri, Santosh Panda, Jeannie C Kelly, Carlo Pancaro, Arvind Palanisamy

2020-Current year OA Pubs

Despite the increased severity of influenza A infection in pregnancy, knowledge about the expression of cell entry factors for influenza A virus (IAV) and the innate immune response in the nasal epithelium, the primary portal of viral entry, is limited. Here, we compared the expression of IAV cell entry factors and the status of the innate immune response in the nasal epithelium of pregnant