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Perspectives And Experiences With Covid-19 Vaccines In People With Ms, John R Ciotti, Dana C Perantie, Brandon P Moss, Kathryn C Fitzgerald, Jeffrey A Cohen, Ellen M Mowry, Robert T Naismith, Salim Chahin

Open Access Publications

Background: People with MS may have unique perspectives on COVID-19 vaccines due to their condition and/or medications.

Objective: Assess perspectives and experiences with COVID-19 vaccination, and quantify variables impacting COVID-19 vaccine willingness in people with MS.

Methods: A survey captured demographics, MS characteristics, and COVID-19 infection and exposures data; opinions on COVID-19 vaccine safety, side effects, and efficacy; and experiences following vaccination. Chi-square tests and a logistic regression model were used to denote between-group differences and variables predicting vaccine willingness, respectively.

Results: Most (87.8%) of the 237 participants were willing to receive the vaccine. Fifteen percent held or delayed a …

Patients With Serious Injection Drug Use-Related Infections Who Experience Patient-Directed Discharges On Oral Antibiotics Have High Rates Of Antibiotic Adherence But Require Multidisciplinary Outpatient Support For Retention In Care, Sophia Lewis, Stephen Y. Liang, Evan S. Schwarz, David B. Liss, Rachel P. Winograd, Nathanial S. Nolan, Michael J. Durkin, Laura R. Marks

Open Access Publications

Background: Persons who inject drugs (PWID) are frequently admitted for serious injection-related infections (SIRIs). Outcomes and adherence to oral antibiotics for PWID with patient-directed discharge (PDD) remain understudied.

Methods: We conducted a prospective multicenter bundled quality improvement project of PWID with SIRI at 3 hospitals in Missouri. All PWID with SIRI were offered multidisciplinary care while inpatient, including the option of addiction medicine consultation and medications for opioid use disorder (MOUD). All patients were offered oral antibiotics in the event of a PDD either at discharge or immediately after discharge through an infectious diseases telemedicine clinic. Additional support services included …

Multicenter, Prospective Validation Of A Phenotypic Algorithm To Guide Carbapenemase Testing In Carbapenem-Resistant Pseudomonas Aeruginosa Using The Erace-Pa Global Surveillance Program, Christian M. Gill, Carey-Ann D. Burnham, Et Al

Open Access Publications

Background: Carbapenemase-producing, carbapenem-resistant

Methods: CRPA isolates were collected during the Enhancing Rational Antimicrobials for

Results: A total of 807 CRPA were assessed, and 464 isolates met the algorithm criteria described above. Overall, testing was reduced by 43% compared with testing all CRPA. Carbapenemase-positive isolates missed by the algorithm were largely driven by Guiana extended spectrum (GES). Addition of the criterion of imipenem- or meropenem-resistant plus ceftolozane/tazobactam-nonsusceptible decreased the number of CP-CRPA missed by the algorithm (21 vs 40 isolates, respectively), reducing number of isolates tested by 39%.

Conclusions: Application of the initial algorithm (imipenem- or meropenem-resistant plus ceftazidime-nonsusceptible plus cefepime-nonsusceptible) …

Essential Functions Of Mll1 And Mll2 In Retinal Development And Cone Cell Maintenance, Chi Sun, Xiaodong Zhang, Philip A Ruzycki, Shiming Chen

Open Access Publications

MLL1 (KMT2A) and MLL2 (KMT2B) are homologous members of the mixed-lineage leukemia (MLL) family of histone methyltransferases involved in epigenomic transcriptional regulation. Their sequence variants have been associated with neurological and psychological disorders, but little is known about their roles and mechanism of action in CNS development. Using mouse retina as a model, we previously reported MLL1's role in retinal neurogenesis and horizontal cell maintenance. Here we determine roles of MLL2 and MLL1/MLL2 together in retinal development using conditional knockout (CKO) mice. Deleting

Assessing The Relationship Of Patient Reported Outcome Measures With Functional Status In Dysferlinopathy: A Rasch Analysis Approach, Anna G Mayhew, Catherine Siener, Alan Pestronk, Et Al

Open Access Publications

Dysferlinopathy is a muscular dystrophy with a highly variable functional disease progression in which the relationship of function to some patient reported outcome measures (PROMs) has not been previously reported. This analysis aims to identify the suitability of PROMs and their association with motor performance.Two-hundred and four patients with dysferlinopathy were identified in the Jain Foundation's Clinical Outcome Study in Dysferlinopathy from 14 sites in 8 countries. All patients completed the following PROMs: Individualized Neuromuscular Quality of Life Questionnaire (INQoL), International Physical Activity Questionnaire (IPAQ), and activity limitations for patients with upper and/or lower limb impairments (ACTIVLIMs). In addition, nonambulant …

It's Getting Complicated-A Fresh Look At P53-Mdm2-Arf Triangle In Tumorigenesis And Cancer Therapy, Che-Pei Kung, Jason D Weber

Open Access Publications

Anti-tumorigenic mechanisms mediated by the tumor suppressor p53, upon oncogenic stresses, are our bodies' greatest weapons to battle against cancer onset and development. Consequently, factors that possess significant p53-regulating activities have been subjects of serious interest from the cancer research community. Among them, MDM2 and ARF are considered the most influential p53 regulators due to their abilities to inhibit and activate p53 functions, respectively. MDM2 inhibits p53 by promoting ubiquitination and proteasome-mediated degradation of p53, while ARF activates p53 by physically interacting with MDM2 to block its access to p53. This conventional understanding of p53-MDM2-ARF functional triangle have guided the …

A Novel Computer Adaptive Word List Memory Test Optimized For Remote Assessment: Psychometric Properties And Associations With Neurodegenerative Biomarkers In Older Women Without Dementia, Nikki H Stricker, John L Stricker, Aimee J Karstens, Jennifer R Geske, Julie A Fields, Jason Hassenstab, Christopher G Schwarz, Nirubol Tosakulwong, Heather J Wiste, Clifford R Jack, Kejal Kantarci, Michelle M Mielke

Open Access Publications

Introduction: This study established the psychometric properties and preliminary validity of the Stricker Learning Span (SLS), a novel computer adaptive word list memory test designed for remote assessment and optimized for smartphone use.

Methods: Women enrolled in the Mayo Clinic Specialized Center of Research Excellence (SCORE) were recruited via e-mail or phone to complete two remote cognitive testing sessions. Convergent validity was assessed through correlation with previously administered in-person neuropsychological tests (n = 96, ages 55-79) and criterion validity through associations with magnetic resonance imaging measures of neurodegeneration sensitive to Alzheimer's disease (n = 47).

Results: SLS performance significantly correlated …

Wormbase In 2022-Data, Processes, And Tools For Analyzing Caenorhabditis Elegans, Paul Davis, Tim Schedl, Et Al

Open Access Publications

WormBase (www.wormbase.org) is the central repository for the genetics and genomics of the nematode Caenorhabditis elegans. We provide the research community with data and tools to facilitate the use of C. elegans and related nematodes as model organisms for studying human health, development, and many aspects of fundamental biology. Throughout our 22-year history, we have continued to evolve to reflect progress and innovation in the science and technologies involved in the study of C. elegans. We strive to incorporate new data types and richer data sets, and to provide integrated displays and services that avail the knowledge generated by the …

Low Knowledge Of Hiv Prep Within A Midwestern Us Cohort Of Persons Who Inject Drugs, Sena Sayood, Laura R. Marks, Rupa Patel, Nathanial S. Nolan, Stephen Y. Liang, Michael J. Durkin

Open Access Publications

We interviewed persons who inject drugs (PWID) to understand perceptions of pre-exposure prophylaxis (PrEP) to prevent HIV infection. Knowledge of PrEP was poor. Patients felt that PrEP was for sexual intercourse rather than injection drug use, and PWID managed on medications for opioid use disorder felt that they had no need for PrEP.

Prospective Nasal Screening For Methicillin-Resistant Staphylococcus Aureus In Critically Ill Patients With Suspected Pneumonia, Nicholas Raush, Kevin D. Betthauser, Karen Shen, Tamara Krekel, Marin H. Kollef

Open Access Publications

We carried out a prospective de-escalation study based on methicillin-resistant

Understanding And Application Of Daptomycin-Susceptible Dose-Dependent Category For Enterococcus: A Mixed-Methods Study, Jennifer L. Adema, Laurel N. Lake, Ryan W. Stevens, Breann M. Hogan, Audrey N. Schuetz, Aaron J. Tande, Kristin C. Mara, Allison R. Eberly, Christina G. Rivera

Open Access Publications

Background: In 2018, the Clinical Microbiology Laboratory at our institution adopted updated daptomycin

Methods: This mixed-methods study combined a clinician survey with a retrospective pre-post prescribing analysis. An 8-question survey was distributed to infectious diseases (ID) and internal medicine (IM) clinicians. A retrospective chart review of hospitalized adults with infections due to

Results: Survey response rates were 40 of 98 (41%) for IM and 22 of 34 (65%) for ID clinicians. ID clinicians scored significantly higher than IM clinicians in knowledge of SDD. Chart review of 474 patients (225 pre- vs 249 post-SDD) showed that daptomycin dosage following susceptibility testing …

Outcomes Of Sars-Cov-2-Positive Youths Tested In Emergency Departments: The Global Pern-Covid-19 Study, Anna L. Funk, Fahd A. Ahmad, Et Al

Open Access Publications

Importance: Severe outcomes among youths with SARS-CoV-2 infections are poorly characterized.

Objective: To estimate the proportion of children with severe outcomes within 14 days of testing positive for SARS-CoV-2 in an emergency department (ED).

Design, Setting, and Participants: This prospective cohort study with 14-day follow-up enrolled participants between March 2020 and June 2021. Participants were youths aged younger than 18 years who were tested for SARS-CoV-2 infection at one of 41 EDs across 10 countries including Argentina, Australia, Canada, Costa Rica, Italy, New Zealand, Paraguay, Singapore, Spain, and the United States. Statistical analysis was performed from September to October 2021. …

Cost-Effectiveness Of Total Neoadjuvant Therapy With Short-Course Radiotherapy For Resectable Locally Advanced Rectal Cancer, Re-I Chin, Ebunoluwa E. Otegbeye, Kylie H. Kang, Su-Hsin Chang, Scott Mchenry, Amit Roy, William C. Chapman, Lauren E. Henke, Shahed N. Badiyan, Katrina Pedersen, Benjamin R. Tan, Sean C. Glasgow, Matthew G. Mutch, Pamela P. Samson, Hyun Kim

Open Access Publications

Importance: Short-course radiotherapy and total neoadjuvant therapy (SCRT-TNT) followed by total mesorectal excision (TME) has emerged as a new treatment paradigm for patients with locally advanced rectal adenocarcinoma. However, the economic implication of this treatment strategy has not been compared with that of conventional long-course chemoradiotherapy (LCCRT) followed by TME with adjuvant chemotherapy.

Objective: To perform a cost-effectiveness analysis of SCRT-TNT vs LCCRT in conjunction with TME for patients with locally advanced rectal cancer.

Design, Setting, and Participants: A decision analytical model with a 5-year time horizon was constructed for patients with biopsy-proven, newly diagnosed, primary locally advanced rectal adenocarcinoma …

Understanding Contributors To Racial And Ethnic Inequities In Covid-19 Incidence And Mortality Rates, Karen E. Joynt Maddox, Mat Reidhead, Joshua Grotzinger, Timothy Mcbride, Aaloke Mody, Elna Nagasako, Will Ross, Joseph T. Steensma, Abigail R. Barker

Open Access Publications

BACKGROUND: Racial inequities in Coronavirus 2019 (COVID-19) have been reported over the course of the pandemic, with Black, Hispanic/Latinx, and Native American individuals suffering higher case rates and more fatalities than their White counterparts.

METHODS: We used a unique statewide dataset of confirmed COVID-19 cases across Missouri, linked with historical statewide hospital data. We examined differences by race and ethnicity in raw population-based case and mortality rates. We used patient-level regression analyses to calculate the odds of mortality based on race and ethnicity, controlling for comorbidities and other risk factors.

RESULTS: As of September 10, 2020 there were 73,635 confirmed …

High Temporal Resolution Measurements Of Movement Reveal Novel Early-Life Physiological Decline In C. Elegans, Drew Benjamin Sinha, Zachary Scott Pincus

Open Access Publications

Age-related physiological changes are most notable and best-studied late in life, while the nature of aging in early- or middle-aged individuals has not been explored as thoroughly. In C. elegans, many studies of movement vs. age generally focus on three distinct phases: sustained, youthful movement; onset of rapidly progressing impairment; and gross immobility. We investigated whether this first period of early-life adult movement is a sustained "healthy" level of high function followed by a discrete "movement catastrophe"-or whether there are early-life changes in movement that precede future physiological declines. To determine how movement varies during early adult life, we followed …

Estimated Population Access To Acute Stroke And Telestroke Centers In The Us, 2019, Kori S. Zachrison, Rebecca E. Cash, Opeolu Adeoye, Krislyn M. Boggs, Lee H. Schwamm, Ateev Mehrotra, Carlos A. Camargo

Open Access Publications

No abstract provided.

Advances And Gaps In Sars-Cov-2 Infection Models, César Muñoz-Fontela, Michael S. Diamond, Et Al

Open Access Publications

The global response to Coronavirus Disease 2019 (COVID-19) is now facing new challenges such as vaccine inequity and the emergence of SARS-CoV-2 variants of concern (VOCs). Preclinical models of disease, in particular animal models, are essential to investigate VOC pathogenesis, vaccine correlates of protection and postexposure therapies. Here, we provide an update from the World Health Organization (WHO) COVID-19 modeling expert group (WHO-COM) assembled by WHO, regarding advances in preclinical models. In particular, we discuss how animal model research is playing a key role to evaluate VOC virulence, transmission and immune escape, and how animal models are being refined to …

Gastric Organoids: Progress And Remaining Challenges, Min-Jiao Pang, Joseph R Burclaff, Ramon Jin, Mahliyah Adkins-Threats, Luciana H Osaki, Yunan Han, Jason C Mills, Zhi-Feng Miao, Zhen-Ning Wang

Open Access Publications

The stomach is a complex and physiologically necessary organ, yet large differences in physiology between mouse and human stomachs have impeded translation of physiological discoveries and drug screens performed using murine gastric tissues. Gastric cancer (GC) is a global health threat, with a high mortality rate and limited treatment options. The heterogeneous nature of GC makes it poorly suited for current "one size fits all" standard treatments. In this review, we discuss the rapidly evolving field of gastric organoids, with a focus on studies expanding cultures from primary human tissues and describing the benefits of mouse organoid models. We introduce …

Integrating The Ohif Viewer Into Xnat: Achievements, Challenges And Prospects For Quantitative Imaging Studies, Simon J. Doran, Woonchan Cho, Dan Marcus, Et Al

Open Access Publications

No abstract provided.

Sonobiopsy For Minimally Invasive, Spatiotemporally-Controlled, And Sensitive Detection Of Glioblastoma-Derived Circulating Tumor Dna, Christopher Pacia, Jinyun Yuan, Yimei Yue, Lu Xu, Arash Nazeri, Rupen Desai, H. Michael Gach, Xiaowei Wang, Michael Talcott, Aadel Chaudhuri, Gavin Dunn, Eric Leuthardt, Hong Chen

Open Access Publications

No abstract provided.

Clinical And Kidney Structural Characteristics Of Living Kidney Donors With Nephrolithiasis And Their Long-Term Outcomes, Matthew R D'Costa, Massini A Merzkani, Aleksandar Denic, Aidan F Mullan, Joseph J Larson, Walter K Kremers, Walter D Park, Mariam P Alexander, Harini A Chakkera, Sandra J Taler, Stephen J Erickson, Mark D Stegall, Naim Issa, Andrew D Rule

Open Access Publications

Background: Nephrolithiasis in living kidney donors is concerning due to the potential impact on long-term postdonation kidney function.

Methods: We performed a cohort study of living kidney donors from 2 centers with a baseline computed tomography scan and implantation renal biopsy. Donors (>5 y since donation) completed a follow-up survey or underwent chart review to assess eGFR and incident hypertension. Stone formers were classified as symptomatic if they had a past symptomatic episode or asymptomatic if only incidental radiographic kidney stones were identified during donor evaluation. We compared baseline clinical, imaging, and biopsy characteristics by stone former status including …

Sarm1 Activation Produces Cadpr To Increase Intra-Axonal Ca++ And Promote Axon Degeneration In Pipn, Yihang Li, Maria F. Pazyra-Murphy, Daina Avizonis, Mariana De Sá Tavares Russo, Sophia Tang, Chiung-Ya Chen, Yi-Ping Hsueh, Johann S. Bergholz, Tao Jiang, Jean J. Zhao, Jian Zhu, Kwang Woo Ko, Jeffrey Milbrandt, Aaron Diantonio, Rosalind A. Segal

Open Access Publications

Cancer patients frequently develop chemotherapy-induced peripheral neuropathy (CIPN), a painful and long-lasting disorder with profound somatosensory deficits. There are no effective therapies to prevent or treat this disorder. Pathologically, CIPN is characterized by a "dying-back" axonopathy that begins at intra-epidermal nerve terminals of sensory neurons and progresses in a retrograde fashion. Calcium dysregulation constitutes a critical event in CIPN, but it is not known how chemotherapies such as paclitaxel alter intra-axonal calcium and cause degeneration. Here, we demonstrate that paclitaxel triggers Sarm1-dependent cADPR production in distal axons, promoting intra-axonal calcium flux from both intracellular and extracellular calcium stores. Genetic or …

The 2021 Faseb Science Research Conference On Nad Metabolism And Signaling, Vera Gorbunova, Shin-Ichiro Imai, Et Al

Open Access Publications

No abstract provided.

Dopamine D4 Receptor Is A Regulator Of Morphine-Induced Plasticity In The Rat Dorsal Striatum, Alicia Rivera, Diana Suarez-Boomgard, Cristina Miguelez, Alejandra Valderrama-Carvajal, Jerome Baufreton, Kirill Shumilov, Anne Taupignon, Belen Gago, M.Angeles Real

Open Access Publications

No abstract provided.

Utility Of Using Electrocardiogram Measures Of Heart Rate Variability As A Measure Of Cardiovascular Autonomic Neuropathy In Type 1 Diabetes Patients, Rodica Pop-Busui, Jye-Yu C Backlund, Ionut Bebu, Barbara H Braffett, Gayle Lorenzi, Neil H White, John M Lachin, Elsayed Z Soliman, Dcct/Edic Research Group

Open Access Publications

AIMS/INTRODUCTION: Cardiovascular autonomic neuropathy (CAN) is a predictor of cardiovascular disease and mortality. Cardiovascular reflex tests (CARTs) are the gold standard for the diagnosis of CAN, but might not be feasible in large research cohorts or in clinical care. We investigated whether measures of heart rate variability obtained from standard electrocardiogram (ECG) recordings provide a reliable measure of CAN.

MATERIALS AND METHODS: Standardized CARTs (R-R response to paced breathing, Valsalva, postural changes) and digitized 12-lead resting ECGs were obtained concomitantly in Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications participants (n = 311). Standard deviation of normally conducted …

Differences In Shoulder Internal Rotation Strength Between Baseball Players With Ulnar Collateral Ligament Reconstruction And Healthy Controls, Sean Kennedy, Philip Sheedy, Brooks Klein, Mason Gist, Joseph Hannon, John Conway, Kalyssa Creed, J. Craig Garrison

Open Access Publications

Background: Studies have indicated decreased shoulder internal rotation (IR) and external rotation (ER) strength in the throwing limb of baseball players after ulnar collateral ligament injury. There is limited evidence on the recovery of shoulder rotation strength after primary ulnar collateral ligament reconstruction (UCLR).

Hypothesis: At the time of return to throwing, baseball players who underwent UCLR would demonstrate decreased IR and ER shoulder strength in the throwing arm as compared with healthy baseball players.

Study Design: Cross-sectional study; Level of evidence, 3.

Methods: Male competitive high school and collegiate baseball athletes participated in this study. Athletes who underwent UCLR …

Mitigating The Effects Of Covid-19 On Hiv Treatment And Care In Lusaka, Zambia: A Before-After Cohort Study Using Mixed Effects Regression, Jake Pry, Kombatende Sikombe, Aaloke Mody, Shilpa Iyer, Jacob Mutale, Natalie Vlahakis, Theodora Savory, Mwanza Wa Mwanza, Keith Mweebo, Annie Mwila, Consity Mwale, Mpande Mukumbwa-Mwenechanya, Andrew Kerkhoff, Izukanji Sikazwe, Carolyn Bolton Moore, Daniel Mwamba, Elvin Geng, Michael Herce

Open Access Publications

INTRODUCTION: The Zambian Ministry of Health (MoH) issued COVID-19 mitigation guidance for HIV care immediately after the first COVID-19 case was confirmed in Zambia on 18 March 2020. The Centre for Infectious Disease Research in Zambia implemented MoH guidance by: 1) extending antiretroviral therapy (ART) refill duration to 6 multi-month dispensation (6MMD) and 2) task-shifting communication and mobilisation of those in HIV care to collect their next ART refill early. We assessed the impact of COVID-19 mitigation guidance on HIV care 3 months before and after guidance implementation.

METHODS: We reviewed all ART pharmacy visit data in the national HIV …

Severe Ocrelizumab-Induced Enterocolitis Treated Successfully With Ustekinumab, Janaki Shah, Ahmad Al-Taaee, Parakkal Deepak, Anas Gremida

Open Access Publications

No abstract provided.

Transition From Cmyc To L-Myc During Dendritic Cell Development Coordinated By Rising Levels Of Irf8, David A. Anderson, Feiya Ou, Sunkyung Kim, Theresa L. Murphy, Kenneth M. Murphy

Open Access Publications

During dendritic cell (DC) development, Myc expression in progenitors is replaced by Mycl in mature DCs, but when and how this transition occurs is unknown. We evaluated DC development using reporters for MYC, MYCL, and cell cycle proteins Geminin and CDT1 in wild-type and various mutant mice. For classical type 1 dendritic cells (cDC1s) and plasmacytoid DCs (pDCs), the transition occurred upon their initial specification from common dendritic cell progenitors (CDPs) or common lymphoid progenitors (CLPs), respectively. This transition required high levels of IRF8 and interaction with PU.1, suggesting the use of EICEs within Mycl enhancers. In pDCs, maximal MYCL …

M6a Modifications Regulate Intestinal Immunity And Rotavirus Infection, Anmin Wang, Gaopeng Hou, Siyuan Ding, Et Al

Open Access Publications

N6-methyladenosine (m6A) is an abundant mRNA modification and affects many biological processes. However, how m6A levels are regulated during physiological or pathological processes such as virus infections, and the in vivo function of m6A in the intestinal immune defense against virus infections are largely unknown. Here, we uncover a novel antiviral function of m6A modification during rotavirus (RV) infection in small bowel intestinal epithelial cells (IECs). We found that rotavirus infection induced global m6A modifications on mRNA transcripts by down-regulating the m6a eraser ALKBH5. Mice lacking the m6A writer enzymes METTL3 in IECs (