Medicine and Health Sciences Commons^™

Prevention Is Political: Political Party Affiliation Predicts Perceived Risk And Prevention Behaviors For Covid-19, Marc T Kiviniemi, Heather Orom, Jennifer L Hay, Erika A Waters

2020-Current year OA Pubs

BACKGROUND: Many US politicians have provided mixed messages about the risks posed by SARS-CoV-2/COVID-19 and whether and to what extent prevention practices should be put in place to prevent transmission. This politicization of the virus and pandemic may affect individuals' risk perceptions and willingness to take precautions. We examined how political party affiliation relates to risk perception for one's own and other people's likelihood of SARS-CoV-2 infection/COVID-19 illness.

METHODS: We surveyed members of a nationally-representative, probability-sampling based survey panel (N = 410) to examine their risk perceptions, precautionary behaviors, and political party affiliation.

RESULTS: The more strongly one identified as …

Intracranial Internal Carotid Artery Calcification Is Not Predictive Of Future Cognitive Decline, Farzaneh Rahmani, Marina Nguyen, Charles D Chen, Nicole Mckay, Aylin Dincer, Nelly Joseph-Mathurin, Gengsheng Chen, Jingxia Liu, Hilary L P Orlowski, John C Morris, Tammie L S Benzinger

2020-Current year OA Pubs

BACKGROUND: Intracranial internal carotid artery (ICA) calcification is a common incidental finding in non-contrast head CT. We evaluated the predictive value of ICAC (ICAC) for future risk of cognitive decline and compared the results with conventional imaging biomarkers of dementia.

METHODS: In a retrospective observational cohort, we included 230 participants with a PET-CT scan within 18 months of a baseline clinical assessment and longitudinal imaging assessments. Intracranial ICAC was quantified on baseline CT scans using the Agatson calcium score, and the association between baseline ICA calcium scores and the risk of conversion from a CDR of zero in baseline to …

Community-Level Factors Associated With Geographic Access To Food Retailers Offering Nutrition Incentives In Chicago, Illinois, Chelsea R Singleton, Fikriyah Winata, Alexandra M Roehll, Isa Adamu, Gabriella M Mcloughlin

2020-Current year OA Pubs

INTRODUCTION: Nutrition incentive programs provide low-income populations with a monetary resource to make healthy foods affordable and accessible. This study aimed to use geospatial analysis to evaluate availability of the Link Match nutrition incentive program in Chicago, Illinois, to determine whether underresourced communities have access.

METHODS: We obtained 2018 spatial data on census tract-level sociodemographic characteristics in Chicago. Fifty-seven retailers (eg, farmers markets, food cooperatives) offered Link Match across the city's 801 census tracts. We examined ordinary least squares and spatial lag regression models to identify census tract-level variables associated with distance (in miles) from the nearest Link Match retailer. …

Single-Agent Mosunetuzumab Shows Durable Complete Responses In Patients With Relapsed Or Refractory B-Cell Lymphomas: Phase I Dose-Escalation Study, Lihua E Budde, Nancy L Bartlett, Et Al

2020-Current year OA Pubs

PURPOSE: Mosunetuzumab is a bispecific antibody targeting CD20 and CD3 that redirects T cells to engage and eliminate malignant B cells and is being developed for relapsed or refractory (R/R) B-cell non-Hodgkin lymphomas (B-NHLs).

METHODS: This first-in-human trial (ClinicalTrials.gov identifier: NCT02500407) evaluated the safety and tolerability and efficacy of mosunetuzumab in patients with R/R B-NHL and established the recommended phase II dose. Data from dose escalation are presented. Single-agent mosunetuzumab was administered intravenously in 3-week cycles, at full dose in cycle 1 day 1 (group A) or with ascending (step-up) doses during cycle 1 on days 1, 8, and 15 …

Bridging The Gap To Advance The Care Of Individuals With Cancer: Collaboration And Partnership In The Cardiology Oncology Innovation Network (Coin), Sherry-Ann Brown, Craig Beavers, Hugo R Martinez, Catherine H Marshall, Iredia M Olaye, Avirup Guha, David Cho, Alison Bailey, Carmen Bergom, Neha Bansal, Brenton Bauer, Richard K Cheng

2020-Current year OA Pubs

Cardiovascular diseases and cancer continue to be the two leading causes of death in the United States. While innovations in artificial intelligence, digital health, and telemedicine may revolutionize cardio-oncology clinical practice, barriers to widespread adoption continue to exist. The most effective way to advance these technologies is through a broad range of stakeholders sharing a common vision. Additionally, as we enter the digital era in healthcare, we must help lead this charge for the benefit of our cardiology and oncology patients. Bolstering collaborations in cardiology and oncology is key, in partnership with technology firms, industry, academia, and private practice, with …

Disseminated Infection Due To Neocosmospora (Fusarium) Falciformis In A Patient With Acute Myelogenous Leukemia, Ra'ed Jabr, Rachael M Liesman, Venkata Rakesh Sethapati, D Matthew Shoemaker, Andrej Spec, Wissam El Atrouni

2020-Current year OA Pubs

No abstract provided.

Regulation Of The Double-Stranded Rna Response Through Adar1 Licenses Metaplastic Reprogramming In Gastric Epithelium, José B. Sáenz, Nancy Vargas, Charles J. Cho, Jason C. Mills

2020-Current year OA Pubs

Cells recognize both foreign and host-derived double-stranded RNA (dsRNA) via a signaling pathway that is usually studied in the context of viral infection. It has become increasingly clear that the sensing and handling of endogenous dsRNA is also critical for cellular differentiation and development. The adenosine RNA deaminase, ADAR1, has been implicated as a central regulator of the dsRNA response, but how regulation of the dsRNA response might mediate cell fate during injury and whether such signaling is cell intrinsic remain unclear. Here, we show that the ADAR1-mediated response to dsRNA was dramatically induced in 2 distinct injury models of …

Videos Of Sipuleucel-T Programmed T Cells Lysing Cells That Express Prostate Cancer Target Antigens, Adam S Kibel, Brant A Inman, Russell K Pachynski, Tuyen Vu, Nadeem A Sheikh, Daniel P Petrylak

2020-Current year OA Pubs

Sipuleucel-T, an autologous cellular immunotherapy, was approved to treat metastatic castration-resistant prostate cancer in 2010 in the United States. Treatment with sipuleucel-T primes the immune system to target prostate acid phosphatase, which is expressed by prostate cancer cells, potentially leading to lysis of cancer cells. Expanding on previously reported indirect evidence of cell killing with sipuleucel-T treatment, we sought to provide direct evidence of cell lysis through visualization. We used advanced video technology and available samples of peripheral blood mononuclear cells from subjects enrolled in the STAMP trial (NCT01487863). Isolated CD8+ T cells were used as effector cells and cocultured …

Highly Reliable Creation Of Floxed Alleles By Electroporating Single-Cell Embryos, Monica F Sentmanat, J Michael White, Evguenia Kouranova, Xiaoxia Cui

2020-Current year OA Pubs

BACKGROUND: Floxed (flanked by loxP) alleles are a crucial portion of conditional knockout mouse models. However, an efficient and reliable strategy to flox genomic regions of any desired size is still lacking.

RESULTS: Here, we demonstrate that the method combining electroporation of fertilized eggs with gRNA/Cas9 complexes and single-stranded oligodeoxynucleotides (ssODNs), assessing phasing of loxP insertions in founders using an in vitro Cre assay and an optional, highly specific and efficient second-round targeting ensures the generation of floxed F1 animals in roughly five months for a wide range of sequence lengths (448 bp to 160 kb reported here).

CONCLUSIONS: Floxed …

Single Circulating-Tumor-Cell-Targeted Sequencing To Identify Somatic Variants In Liquid Biopsies In Non-Small-Cell Lung Cancer Patients, Mouadh Barbirou, Amanda Miller, Yariswamy Manjunath, Arturo B Ramirez, Nolan G Ericson, Kevin F Staveley-O'Carroll, Jonathan B Mitchem, Wesley C Warren, Aadel A Chaudhuri, Yi Huang, Guangfu Li, Peter J Tonellato, Jussuf T Kaifi

2020-Current year OA Pubs

Non-small-cell lung cancer (NSCLC) accounts for most cancer-related deaths worldwide. Liquid biopsy by a blood draw to detect circulating tumor cells (CTCs) is a tool for molecular profiling of cancer using single-cell and next-generation sequencing (NGS) technologies. The aim of the study was to identify somatic variants in single CTCs isolated from NSCLC patients by targeted NGS. Thirty-one subjects (20 NSCLC patients, 11 smokers without cancer) were enrolled for blood draws (7.5 mL). CTCs were identified by immunofluorescence, individually retrieved, and DNA-extracted. Targeted NGS was performed to detect somatic variants (single-nucleotide variants (SNVs) and insertions/deletions (Indels)) across 65 oncogenes and …

Selective Reduction Of Astrocyte Apoe3 And Apoe4 Strongly Reduces Aβ Accumulation And Plaque-Related Pathology In A Mouse Model Of Amyloidosis, Thomas E Mahan, Chao Wang, Xin Bao, Ankit Choudhury, Jason D Ulrich, David M Holtzman

2020-Current year OA Pubs

BACKGROUND: One of the key pathological hallmarks of Alzheimer disease (AD) is the accumulation of the amyloid-β (Aβ) peptide into amyloid plaques. The apolipoprotein E (APOE) gene is the strongest genetic risk factor for late-onset AD and has been shown to influence the accumulation of Aβ in the brain in an isoform-dependent manner. ApoE can be produced by different cell types in the brain, with astrocytes being the largest producer of apoE, although reactive microglia also express high levels of apoE. While studies have shown that altering apoE levels in the brain can influence the development of Aβ plaque pathology, …

Protein Phosphatase 2a Restrains Dlk Signaling To Promote Proper Drosophila Synaptic Development And Mammalian Cortical Neuron Survival, Margaret Hayne, Aaron Diantonio

2020-Current year OA Pubs

Protein phosphatase 2A (PP2A) is a major cellular phosphatase with many protein substrates. As expected for a signaling molecule with many targets, inhibition of PP2A disrupts fundamental aspects of cellular physiology including cell division and survival. In post-mitotic neurons, the microtubule associated protein Tau is a particularly well-studied PP2A substrate as hyperphosphorylation of Tau is a hallmark of Alzheimer's disease. Although many cellular targets are likely altered by loss of PP2A, here we find that activation of a single pathway can explain important aspects of the PP2A loss-of-function phenotype in neurons. We demonstrate that PP2A inhibits activation of the neuronal …

A Prospective Multicenter Evaluation Of Initial Treatment Choice In Metastatic Renal Cell Carcinoma Prior To The Immunotherapy Era: The Marcc Registry Experience, Brian A. Costello, Russell K. Pachynski, Et Al.

2020-Current year OA Pubs

INTRODUCTION: The Metastatic Renal Cell Carcinoma (MaRCC) Registry provides prospective data on real-world treatment patterns and outcomes in patients with metastatic renal cell carcinoma (mRCC).

METHODS AND MATERIALS: Patients with mRCC and no prior systemic therapy were enrolled at academic and community sites. End of study data collection was in March 2019. Outcomes included overall survival (OS). A survey of treating physicians assessed reasons for treatment initiations and discontinuations.

RESULTS: Overall, 376 patients with mRCC initiated first-line therapy; 171 (45.5%) received pazopanib, 75 (19.9%) sunitinib, and 74 (19.7%) participated in a clinical trial. Median (95% confidence interval) OS was longest …

Brain Stimulation Treatments In Epilepsy: Basic Mechanisms And Clinical Advances, Thomas J. Foutz, Michael Wong

2020-Current year OA Pubs

Drug-resistant epilepsy, characterized by ongoing seizures despite appropriate trials of anti-seizure medications, affects approximately one-third of people with epilepsy. Brain stimulation has recently become available as an alternative treatment option to reduce symptomatic seizures in short and long-term follow-up studies. Several questions remain on how to optimally develop patient-specific treatments and manage therapy over the long term. This review aims to discuss the clinical use and mechanisms of action of Responsive Neural Stimulation and Deep Brain Stimulation in the treatment of epilepsy and highlight recent advances that may both improve outcomes and present new challenges. Finally, a rational approach to …

Host Cell-Intrinsic Innate Immune Recognition Of Sars-Cov-2, Emily A Madden, Michael S Diamond

2020-Current year OA Pubs

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emerged at the end of 2019 and caused the pandemic of coronavirus disease 2019 (COVID-19). Basic and clinical investigations indicate that severe forms of COVID-19 are due in part to dysregulated immune responses to virus infection. The innate immune system is the first line of host defense against most virus infections, with pathogen recognition receptors detecting SARS-CoV-2 RNA and protein components and initiating pro-inflammatory and antiviral responses. Notwithstanding this response, SARS-CoV-2 proteins evade, inhibit, and skew innate immune signaling early in infection. In this review, we highlight the components of cell-based recognition of SARS-CoV-2 …

No Difference In Radiologic Outcomes For Natalizumab Patients Treated With Extended Interval Dosing Compared With Standard Interval Dosing: Real-World Evidence From Ms Paths, Lana Zhovtis Ryerson, Robert T. Naismith, Lauren B. Krupp, Leigh E. Charvet, Shirley Liao, Elizabeth Fisher, Carl De Moor, James R. Williams, Nolan Campbell

2020-Current year OA Pubs

BACKGROUND: Extended interval dosing (EID; average dosing interval approximately every 6 weeks) of natalizumab is associated with significantly lower risk of progressive multifocal leukoencephalopathy than standard interval dosing (SID; every 4 weeks) in patients with relapsing-remitting multiple sclerosis (MS). Real-world studies, though limited, suggest that natalizumab effectiveness is generally maintained in patients who switch to EID after initiation of stable treatment with SID. MS PATHS (Multiple Sclerosis Partners Advancing Technology and Health Solutions) is a collaborative, multicenter learning health system that generates real-world clinical and MRI data using highly standardized acquisition protocols. We compared MRI outcomes in MS PATHS patients …

Validation Of Actigraphy For Sleep Measurement In Children With Cerebral Palsy, Bing Xue, Amy Licis, Jill Boyd, Catherine R Hoyt, Yo-El S Ju

2020-Current year OA Pubs

OBJECTIVES: Sleep issues are common in children with cerebral palsy (CP), although there are challenges in obtaining objective data about their sleep patterns. Actigraphs measure movement to quantify sleep but their accuracy in children with CP is unknown. Our goals were to validate actigraphy for sleep assessment in children with CP and to study their sleep patterns in a cross-sectional cohort study.

METHODS: We recruited children with (N = 13) and without (N = 13) CP aged 2-17 years (mean age 9 y 11mo [SD 4 y 10mo] range 4-17 y; 17 males, 9 females; 54% spastic quadriplegic, 23% spastic …

Fractality Of Tics As A Quantitative Assessment Tool For Tourette Syndrome, Payton Beeler, Nicholas O Jensen, Soyoung Kim, Amy Robichaux-Viehoever, Bradley L Schlaggar, Deanna J Greene, Kevin J. Black, Rajan K Chakrabarty

2020-Current year OA Pubs

Tics manifest as brief, purposeless and unintentional movements or noises that, for many individuals, can be suppressed temporarily with effort. Previous work has hypothesized that the chaotic temporal nature of tics could possess an inherent fractality, that is, have neighbour-to-neighbour correlation at all levels of timescale. However, demonstrating this phenomenon has eluded researchers for more than two decades, primarily because of the challenges associated with estimating the scale-invariant, power law exponent-called the fractal dimension

Importance Of The Intersection Of Age And Sex To Understand Variation In Incidence And Survival For Primary Malignant Gliomas, Gi-Ming Wang, Gino Cioffi, Nirav Patil, Kristin A Waite, Robert Lanese, Quinn T Ostrom, Carol Kruchko, Michael E Berens, James R Connor, Justin D Lathia, Joshua B Rubin, Jill S Barnholtz-Sloan

2020-Current year OA Pubs

BACKGROUND: Gliomas are the most common type of malignant brain and other CNS tumors, accounting for 80.8% of malignant primary brain and CNS tumors. They cause significant morbidity and mortality. This study investigates the intersection between age and sex to better understand variation of incidence and survival for glioma in the United States.

METHODS: Incidence data from 2000 to 2017 were obtained from CBTRUS, which obtains data from the NPCR and SEER, and survival data from the CDC's NPCR. Age-adjusted incidence rate ratios (IRR) per 100 000 were generated to compare male-to-female incidence by age group. Cox proportional hazard models …

Rpop: Robust Pet-Only Processing Of Community Acquired Heterogeneous Amyloid-Pet Data, Leonardo Iaccarino, Renaud La Joie, Robert Koeppe, Barry A Siegel, Bruce E Hillner, Constantine Gatsonis, Rachel A Whitmer, Maria C Carrillo, Charles Apgar, Monica R Camacho, Rachel Nosheny, Gil D Rabinovici, Alzheimer's Disease Neuroimaging Initiative

2020-Current year OA Pubs

The reference standard for amyloid-PET quantification requires structural MRI (sMRI) for preprocessing in both multi-site research studies and clinical trials. Here we describe rPOP (robust PET-Only Processing), a MATLAB-based MRI-free pipeline implementing non-linear warping and differential smoothing of amyloid-PET scans performed with any of the FDA-approved radiotracers (

A Unique Sarcopenic Progression In The Mouse Rotator Cuff, Gretchen A Meyer, Karen C Shen

2020-Current year OA Pubs

BACKGROUND: In response to chronic injury, the muscles of the rotator cuff (RC) experience a unique degeneration characterized by extensive fatty infiltration and loss of contractile function. Human studies suggest this degeneration is also a feature of RC sarcopenia and may precede RC injury. In this study, we investigated whether RC muscles exhibit a similar unique sarcopenia in the mouse.

METHODS: Male and female mice were subdivided into four age groups: 3, 9, 18, and 24 months. The supraspinatus (SS) and infraspinatus muscles of the RC and the tibialis anterior (TA) muscle of the hindlimb were assessed. Muscle mass, contractile …

Clinical Image: Calcinosis Cutis Universalis In A Patient With Polymyositis/Scleroderma Overlap Syndrome, Katie Carbonell, Nicole Droz

2020-Current year OA Pubs

No abstract provided.

Mental Health In The Uk Biobank: A Roadmap To Self-Report Measures And Neuroimaging Correlates, Rosie K Dutt, Kayla Hannon, Ty O Easley, Joseph C Griffis, Wei Zhang, Janine D Bijsterbosch

2020-Current year OA Pubs

The UK Biobank (UKB) is a highly promising dataset for brain biomarker research into population mental health due to its unprecedented sample size and extensive phenotypic, imaging, and biological measurements. In this study, we aimed to provide a shared foundation for UKB neuroimaging research into mental health with a focus on anxiety and depression. We compared UKB self-report measures and revealed important timing effects between scan acquisition and separate online acquisition of some mental health measures. To overcome these timing effects, we introduced and validated the Recent Depressive Symptoms (RDS-4) score which we recommend for state-dependent and longitudinal research in …

Echocardiographic And Clinical Predictors Of Cardiac Amyloidosis: Limitations Of Apical Sparing, Douglas Kyrouac, Walter Schiffer, Brandon Lennep, Nicole Fergestrom, Kathleen W Zhang, John Gorcsan Iii, Daniel J Lenihan, Joshua D Mitchell

2020-Current year OA Pubs

AIMS: The accuracy of an apical-sparing strain pattern on transthoracic echocardiography (TTE) for predicting cardiac amyloidosis (CA) has varied in prior studies depending on the underlying cohort. We sought to evaluate the performance of apical sparing and other TTE strain findings to screen for CA in an unselected population and determine the frequency that patients with echocardiographic concern for CA undergo evaluation for amyloidosis in clinical practice.

METHODS AND RESULTS: As strain is routinely performed at our institution on all clinical TTEs, we identified all TTEs performed from 2016 through 2019 with reported concern for CA or apical sparing. We …

Significant Variations In Surgical Construct And Return To Sport Protocols With Syndesmotic Injuries: An Isakos Global Perspective, Kenneth J. Hunt, Jonathan Bartolomei, Shanthan C. Challa, Jeremy J. Mccormick, Pieter D'Hooghe, Michael Tuffiash, Annunziato Amendola, Isakos Leg, Ankle Foot Committee

2020-Current year OA Pubs

No abstract provided.

Utility Of Covid-19 Antigen Testing In The Emergency Department, W Frank Peacock, Stacey L House, Et Al.

2020-Current year OA Pubs

BACKGROUND: The BinaxNOW coronavirus disease 2019 (COVID-19) Ag Card test (Abbott Diagnostics Scarborough, Inc.) is a lateral flow immunochromatographic point-of-care test for the qualitative detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid protein antigen. It provides results from nasal swabs in 15 minutes. Our purpose was to determine its sensitivity and specificity for a COVID-19 diagnosis.

METHODS: Eligible patients had symptoms of COVID-19 or suspected exposure. After consent, 2 nasal swabs were collected; 1 was tested using the Abbott RealTime SARS-CoV-2 (ie, the gold standard polymerase chain reaction test) and the second run on the BinaxNOW point of …

Gene Expression Predicts Dormant Metastatic Breast Cancer Cell Phenotype, Qihao Ren, Weng Hua Khoo, Alexander P Corr, Tri Giang Phan, Peter I Croucher, Sheila A Stewart

2020-Current year OA Pubs

BACKGROUND: Breast cancer can recur months to decades after an initial diagnosis and treatment. The mechanisms that control tumor cell dormancy remain poorly understood, making it difficult to predict which patients will recur and thus benefit from more rigorous screening and treatments. Unfortunately, the extreme rarity of dormant DTCs has been a major obstacle to their study.

METHODS: To overcome this challenge, we developed an efficient system to isolate and study rare dormant breast cancer cells from metastatic organs including bones, which represent a major site of metastasis. After isolation of cells from the long bones, we used single cell …

Development Of A Standard Of Care For Patients With Valosin-Containing Protein Associated Multisystem Proteinopathy, Manisha Korb, Nupur Ghoshal, Conrad Weihl, Et Al.

2020-Current year OA Pubs

Valosin-containing protein (VCP) associated multisystem proteinopathy (MSP) is a rare inherited disorder that may result in multisystem involvement of varying phenotypes including inclusion body myopathy, Paget's disease of bone (PDB), frontotemporal dementia (FTD), parkinsonism, and amyotrophic lateral sclerosis (ALS), among others. An international multidisciplinary consortium of 40+ experts in neuromuscular disease, dementia, movement disorders, psychology, cardiology, pulmonology, physical therapy, occupational therapy, speech and language pathology, nutrition, genetics, integrative medicine, and endocrinology were convened by the patient advocacy organization, Cure VCP Disease, in December 2020 to develop a standard of care for this heterogeneous and under-diagnosed disease. To achieve this goal, …

Acute Minocycline Administration Reduces Brain Injury And Improves Long-Term Functional Outcomes After Delayed Hypoxemia Following Traumatic Brain Injury, Marta Celorrio, Kirill Shumilov, Camryn Payne, Sangeetha Vadivelu, Stuart H Friess

2020-Current year OA Pubs

Clinical trials of therapeutics for traumatic brain injury (TBI) demonstrating preclinical efficacy for TBI have failed to replicate these results in humans, in part due to the absence of clinically feasible therapeutic windows for administration. Minocycline, an inhibitor of microglial activation, has been shown to be neuroprotective when administered early after experimental TBI but detrimental when administered chronically to human TBI survivors. Rather than focusing on the rescue of primary injury with early administration of therapeutics which may not be clinically feasible, we hypothesized that minocycline administered at a clinically feasible time point (24 h after injury) would be neuroprotective …

Analysis Of Non-Relapsed And Relapsed Adult Type Granulosa Cell Tumors Suggests Stable Transcriptomes During Tumor Progression, Noora Andersson, Ulla-Maija Haltia, Anniina Färkkilä, Swee Chong Wong, Katja Eloranta, David B Wilson, Leila Unkila-Kallio, Marjut Pihlajoki, Antti Kyrönlahti, Markku Heikinheimo

2020-Current year OA Pubs

Adult-type granulosa cell tumor (AGCT) is a rare ovarian malignancy characterized by slow growth and hormonal activity. The prognosis of AGCT is generally favorable, but one-third of patients with low-stage disease experience a late relapse, and over half of them die of AGCT. To identify markers that would distinguish patients at risk for relapse, we performed Lexogen QuantSeq 3' mRNA sequencing on formalin-fixed paraffin-embedded, archival AGCT tissue samples tested positive for the pathognomonic Forkhead Box L2 (