Digital Commons Network^™

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

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 …

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 …

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 …

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 …

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 …

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 …

Task Modulation Of Single-Neuron Activity In The Human Amygdala And Hippocampus, Runnan Cao, Alexander Todorov, Nicholas Brandmeir, Shuo Wang

Open Access Publications

The human amygdala and hippocampus are critically involved in various processes in face perception. However, it remains unclear how task demands or evaluative contexts modulate processes underlying face perception. In this study, we employed two task instructions when participants viewed the same faces and recorded single-neuron activity from the human amygdala and hippocampus. We comprehensively analyzed task modulation for three key aspects of face processing and we found that neurons in the amygdala and hippocampus (1) encoded high-level social traits such as perceived facial trustworthiness and dominance and this response was modulated by task instructions; (2) encoded low-level facial features …

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

Open Access Publications

No abstract provided.

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 (

A Test Of The Pioneer Factor Hypothesis Using Ectopic Liver Gene Activation, Jeffrey L. Hansen, Kaiser J. Loell, Barak A. Cohen

Open Access Publications

The pioneer factor hypothesis (PFH) states that pioneer factors (PFs) are a subclass of transcription factors (TFs) that bind to and open inaccessible sites and then recruit non-pioneer factors (non-PFs) that activate batteries of silent genes. The PFH predicts that ectopic gene activation requires the sequential activity of qualitatively different TFs. We tested the PFH by expressing the endodermal PF FOXA1 and non-PF HNF4A in K562 lymphoblast cells. While co-expression of FOXA1 and HNF4A activated a burst of endoderm-specific gene expression, we found no evidence for a functional distinction between these two TFs. When expressed independently, both TFs bound and …

The Mutationathon Highlights The Importance Of Reaching Standardization In Estimates Of Pedigree-Based Germline Mutation Rates, Lucie A. Bergeron, Tychele Turner, Et Al

Open Access Publications

In the past decade, several studies have estimated the human per-generation germline mutation rate using large pedigrees. More recently, estimates for various nonhuman species have been published. However, methodological differences among studies in detecting germline mutations and estimating mutation rates make direct comparisons difficult. Here, we describe the many different steps involved in estimating pedigree-based mutation rates, including sampling, sequencing, mapping, variant calling, filtering, and appropriately accounting for false-positive and false-negative rates. For each step, we review the different methods and parameter choices that have been used in the recent literature. Additionally, we present the results from a 'Mutationathon,' a …

Intrinsic Mechanisms In The Gating Of Resurgent Na+ Currents, Joseph L. Ransdell, Jonathan D. Moreno, Druv Bhagavan, Jonathan R. Silva, Jeanne M. Nerbonne

Open Access Publications

The resurgent component of the voltage-gated sodium current (I

Tumor Lysis Syndrome In A Patient With Metastatic Endometrial Cancer Treated With Lattice Stereotactic Body Radiation Therapy, Joshua P Schiff, Matthew B Spraker, Sai Duriseti, Sana Shaikh, Haris F Murad, David G Mutch, Clifford G Robinson, James Kavanaugh, Alexander J Lin

Open Access Publications

No abstract provided.

Perceptions Of Risk Of Sars-Cov-2 Transmission In Social And Educational Activities By Infectious Diseases And General Pediatric Healthcare Providers, A Pre-Vaccine Risk Perception Cross-Sectional Survey, Andrew B. Janowski, Philip M. Polgreen, Susan E. Beekmann, Jason G. Newland

Open Access Publications

BACKGROUND: The perception of the transmission risks of SARS-CoV-2 in social and educational settings by US healthcare providers have not been previously quantified.

METHODS: Respondents completed an online survey between September and October 2020 to estimate the risk of SARS-CoV-2 transmission on a scale of 0-10 for different social and educational activities prior to the availability of the SARS-CoV-2 vaccines. Demographic information and experiences during the pandemic were also collected. The risk assessment was emailed to three listservs of healthcare providers, including national listservs of pediatric (PID) and adult infectious diseases (AID) providers, and a listserv of general pediatric practitioners …

Effect Of Early Treatment With Fluvoxamine On Risk Of Emergency Care And Hospitalisation Among Patients With Covid-19: The Together Randomised, Platform Clinical Trial, Gilmar Reis, Eric J Lenze, Angela M Reiersen, Et Al

Open Access Publications

BACKGROUND: Recent evidence indicates a potential therapeutic role of fluvoxamine for COVID-19. In the TOGETHER trial for acutely symptomatic patients with COVID-19, we aimed to assess the efficacy of fluvoxamine versus placebo in preventing hospitalisation defined as either retention in a COVID-19 emergency setting or transfer to a tertiary hospital due to COVID-19.

METHODS: This placebo-controlled, randomised, adaptive platform trial done among high-risk symptomatic Brazilian adults confirmed positive for SARS-CoV-2 included eligible patients from 11 clinical sites in Brazil with a known risk factor for progression to severe disease. Patients were randomly assigned (1:1) to either fluvoxamine (100 mg twice …

Loss Of Kmt2c Reprograms The Epigenomic Landscape In Hpscs Resulting In Nodal Overexpression And A Failure Of Hemogenic Endothelium Specification, Shailendra Maurya, Wei Yang, Minori Tamai, Qiang Zhang, Petra Erdmann-Gilmore, Amelia Bystry, Fernanda Martins Rodrigues, Mark C Valentine, Wing H Wong, Reid Townsend, Todd E Druley

Open Access Publications

Germline or somatic variation in the family of KMT2 lysine methyltransferases have been associated with a variety of congenital disorders and cancers. Notably,

What Can Brinley Plots Tell Us About Cognitive Aging? Exploring Simulated Data And Modified Brinley Plots, Jessica Nicosia, Emily R Cohen-Shikora, Michael J Strube

Open Access Publications

Cognitive aging researchers have been challenged with demonstrating age-related effects above and beyond global slowing ever since Cerella raised this issue in 1990. As the literature has made clear, this has indeed proved to be a difficult task and continues to plague the field. One way that researchers have attempted to test for disproportionate age differences across task conditions is by using Brinley plots, or plotting the mean response latencies of older adults against the mean latencies for younger adults. The simplicity and large proportion of variance accounted for by these models has led to the widespread use of Brinley …

Selected Histone Deacetylase Inhibitors Reverse The Frataxin Transcriptional Defect In A Novel Friedreich's Ataxia Induced Pluripotent Stem Cell-Derived Neuronal Reporter System, Anna M Schreiber, Yanjie Li, Yi-Hsien Chen, Jill S Napierala, Marek Napierala

Open Access Publications

Friedreich's ataxia (FRDA) is a neurodegenerative disorder caused by the expansion of guanine-adenine-adenine repeats within the first intron of the frataxin (

Isolation Of Sars-Cov-2 In Viral Cell Culture In Immunocompromised Patients With Persistently Positive Rt-Pcr Results, Abby Sung, Adam L Bailey, Henry B Stewart, David Mcdonald, Meghan A Wallace, Kate Peacock, Candace Miller, Kimberly A Reske, Caroline A O'Neil, Victoria J Fraser, Michael S Diamond, Carey-Ann D Burnham, Hilary M Babcock, Jennie H Kwon

Open Access Publications

Immunocompromised adults can have prolonged acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive RT-PCR results, long after the initial diagnosis of coronavirus disease 2019 (COVID-19). This study aimed to determine if SARS-CoV-2 virus can be recovered in viral cell culture from immunocompromised adults with persistently positive SARS-CoV-2 RT-PCR tests. We obtained 20 remnant SARS-CoV-2 PCR positive nasopharyngeal swabs from 20 immunocompromised adults with a positive RT-PCR test ≥14 days after the initial positive test. The patients' 2

De Novo Missense Variants In Fbxo11 Alter Its Protein Expression And Subcellular Localization, Anne Gregor, Marwan Shinawi, Et Al

Open Access Publications

Recently, others and we identified de novo FBXO11 (F-Box only protein 11) variants as causative for a variable neurodevelopmental disorder (NDD). We now assembled clinical and mutational information on 23 additional individuals. The phenotypic spectrum remains highly variable, with developmental delay and/or intellectual disability as the core feature and behavioral anomalies, hypotonia and various facial dysmorphism as frequent aspects. The mutational spectrum includes intragenic deletions, likely gene disrupting and missense variants distributed across the protein. To further characterize the functional consequences of FBXO11 missense variants, we analyzed their effects on protein expression and localization by overexpression of 17 different mutant …

An Overview Of Treatment Options For Patients With Relapsed/Refractory Multiple Myeloma And Renal Impairment, Meletios A Dimopoulos, Joseph Mikhael, Evangelos Terpos, Xavier Leleu, Philippe Moreau, Joan Bladé, Jin Seok Kim, Keith Stockerl-Goldstein, Paul G Richardson

Open Access Publications

Renal impairment (RI) is a relatively common complication of multiple myeloma, which increases in frequency as disease becomes more advanced and recovery of renal function becomes less likely as patients progress through lines of therapy. Clinical trials in the relapsed/refractory multiple myeloma (RRMM) setting have not uniformly included patients with RI or robustly reported their outcomes. Here, we review existing data among patients with RI and RRMM across drug classes (including immunomodulatory agents, proteasome inhibitors, monoclonal antibodies, antibody-drug conjugates, chimeric antigen receptor T-cell therapies, and exportin-1 inhibitor) to provide an improved understanding of available treatment options for this important population. …

Dysregulation Of The Leukocyte Signaling Landscape During Acute Covid-19, Isaiah R. Turnbull, Anja Fuchs, Kenneth E. Remy, Michael P. Kelly, Elfaridah P. Frazier, Sarbani Ghosh, Shin-Wen Chang, Monty B. Mazer, Annie Hess, Jennifer M. Leonard, Mark H. Hoofnagle, Marco Colonna, Richard S. Hotchkiss

Open Access Publications

The global COVID-19 pandemic has claimed the lives of more than 750,000 US citizens. Dysregulation of the immune system underlies the pathogenesis of COVID-19, with inflammation mediated tissue injury to the lung in the setting of suppressed systemic immune function. To define the molecular mechanisms of immune dysfunction in COVID-19 we utilized a systems immunology approach centered on the circulating leukocyte phosphoproteome measured by mass cytometry. We find that although COVID-19 is associated with wholesale activation of a broad set of signaling pathways across myeloid and lymphoid cell populations, STAT3 phosphorylation predominated in both monocytes and T cells. STAT3 phosphorylation …

Steroid Hormone Signaling Activates Thermal Nociception During Drosophila Peripheral Nervous System Development, Jacob S. Jaszczak, Laura Devault, Lily Yeh Jan, Yuh Nung Jan

Open Access Publications

Sensory neurons enable animals to detect environmental changes and avoid harm. An intriguing open question concerns how the various attributes of sensory neurons arise in development.

Association Between Hospital Private Equity Acquisition And Outcomes Of Acute Medical Conditions Among Medicare Beneficiaries, Marcelo Cerullo, Kelly Yang, Karen E. Joynt Maddox, Ryan C. Mcdevitt, James M. Roberts, Anaeze C. Offodile

Open Access Publications

Importance: As private equity (PE) acquisitions of short-term acute care hospitals (ACHs) continue, their impact on the care of medically vulnerable older adults remains largely unexplored.

Objective: To investigate the association between PE acquisition of ACHs and access to care, patient outcomes, and spending among Medicare beneficiaries hospitalized with acute medical conditions.

Design, Setting, and Participants: This cross-sectional study used a generalized difference-in-differences approach to compare 21 091 222 patients admitted to PE-acquired vs non-PE-acquired short-term ACHs between January 1, 2001, and December 31, 2018, at least 3 years before to 3 years after PE acquisition. The analysis was conducted …

Fracture Healing Is Delayed In The Absence Of Gasdermin-Interleukin-1 Signaling, Kai Sun, Chun Wang, Jianqiu Xiao, Michael D. Brodt, Luorongxin Yuan, Tong Yang, Yael Alippe, Huimin Hu, Dingjun Hao, Yousef Abu-Amer, Matthew J. Silva, Jie Shen, Gabriel Mbalaviele

Open Access Publications

Amino-terminal fragments from proteolytically cleaved gasdermins (GSDMs) form plasma membrane pores that enable the secretion of interleukin-1β (IL-1β) and IL-18. Excessive GSDM-mediated pore formation can compromise the integrity of the plasma membrane thereby causing the lytic inflammatory cell death, pyroptosis. We found that GSDMD and GSDME were the only GSDMs that were readily expressed in bone microenvironment. Therefore, we tested the hypothesis that GSDMD and GSDME are implicated in fracture healing owing to their role in the obligatory inflammatory response following injury. We found that bone callus volume and biomechanical properties of injured bones were significantly reduced in mice lacking …