Digital Commons Network^™

Cathepsin S And Protease-Activated Receptor-2 Drive Alloimmunity And Immune Regulation In Kidney Allograft Rejection, Yutian Lei, Benjamin Ehle, Santhosh V Kumar, Susanne Müller, Solange Moll, Andrew F Malone, Benjamin D Humphreys, Joachim Andrassy, Hans-Joachim Anders

Open Access Publications

Alloantigen presentation is an essential process in acute allorejection. In this context, we speculated on a pathogenic role of cathepsin S (Cat-S), a cysteine protease known to promote antigenic peptide loading into MHC class II and to activate protease-activated receptor (PAR)-2 on intrarenal microvascular endothelial and tubular epithelial cells. Single-cell RNA sequencing and immunostaining of human kidney allografts confirmed Cat-S expression in intrarenal mononuclear phagocytes.

Come Together: Protein Assemblies, Aggregates And The Sarcostat At The Heart Of Cardiac Myocyte Homeostasis, Moydul Islam, Abhinav Diwan, Kartik Mani

Open Access Publications

Homeostasis in vertebrate systems is contingent on normal cardiac function. This, in turn, depends on intricate protein-based cellular machinery, both for contractile function, as well as, durability of cardiac myocytes. The cardiac small heat shock protein (csHsp) chaperone system, highlighted by αB-crystallin (CRYAB), a small heat shock protein (sHsp) that forms ∼3-5% of total cardiac mass, plays critical roles in maintaining proteostatic function via formation of self-assembled multimeric chaperones. In this work, we review these ancient proteins, from the evolutionarily preserved role of homologs in protists, fungi and invertebrate systems, as well as, the role of sHsps and chaperones in …

Prostate Cancer Theranostics - An Overview, Diane Abou, Nadia Benabdallah, Wen Jiang, Lu Peng, Hanwen Zhang, Alexandria Villmer, Mark S Longtine, Daniel L J Thorek

Open Access Publications

Metastatic prostate cancer is incurable, and novel methods to detect the disease earlier and to direct definitive treatment are needed. Molecularly specific tools to localize diagnostic and cytotoxic radionuclide payloads to cancer cells and the surrounding microenvironment are recognized as a critical component of new approaches to combat this disease. The implementation of theranostic approaches to characterize and personalize patient management is beginning to be realized for prostate cancer patients. This review article summarized clinically translated approaches to detect, characterize, and treat disease in this rapidly expanding field.

Harnessing Activin A Adjuvanticity To Promote Antibody Responses To Bg505 Hiv Envelope Trimers, Diane G Carnathan, Kirti Kaushik, Ali H Ellebedy, Chiamaka A Enemuo, Etse H Gebru, Pallavi Dhadvai, Mohammed Ata Ur Rasheed, Matthias G Pauthner, Gabriel Ozorowski, Rafi Ahmed, Dennis R Burton, Andrew B Ward, Guido Silvestri, Shane Crotty, Michela Locci

Open Access Publications

T follicular helper (T

Formation Of Lung Inducible Bronchus Associated Lymphoid Tissue Is Regulated By Mycobacterium Tuberculosis Expressed Determinants, Micah D Dunlap, Oliver A Prince, Javier Rangel-Moreno, Kimberly A Thomas, Julia M Scordo, Jordi B Torrelles, Jeffery Cox, Adrie J C Steyn, Joaquín Zúñiga, Deepak Kaushal, Shabaana A Khader

Open Access Publications

No abstract provided.

Evidence-Based Guidelines For Managing Patients With Primary Er+ Her2− Breast Cancer Deferred From Surgery Due To The Covid-19 Pandemic, Mitch Dowsett, Cynthia X. Ma, Et Al.

Open Access Publications

No abstract provided.

Landscape Of Somatic Single Nucleotide Variants And Indels In Colorectal Cancer And Impact On Survival, Syed H. Zaidi, Yin Cao, Et Al.

Open Access Publications

No abstract provided.

Effects Of Early Life Exposure To Traffic-Related Air Pollution On Brain Development In Juvenile Sprague-Dawley Rats, Kelley T. Patten, Eduardo A. González, Anthony Valenzuela, Elizabeth Berg, Christopher Wallis, Joel R. Garbow, Jill L. Silverman, Keith J. Bein, Anthony S. Wexler, Pamela J. Lein

Open Access Publications

No abstract provided.

Evolution And Structure Of Clinically Relevant Gene Fusions In Multiple Myeloma, Steven M. Foltz, Qingsong Gao, Christopher J. Yoon, Hua Sun, Lijun Yao, Yize Li, Reyka G. Jayasinghe, Song Cao, Justin King, Daniel R. Kohnen, Mark A. Fiala, Li Ding, Ravi Vij

Open Access Publications

No abstract provided.

Experiences From The Missouri Antimicrobial Stewardship Collaborative: A Mixed Methods Study, Sena J Sayood, Chinmayi Venkatram, Jason G Newland, Hilary M Babcock, David K Warren, George Turabelidze, Virginia R Mckay, Erin C Rachmiel, Kate Peacock, Tracey Habrock-Bach, Kevin Hsueh, Michael J Durkin

Open Access Publications

We performed a mixed-methods study to evaluate antimicrobial stewardship program (ASP) uptake and to assess variability of program implementation in Missouri hospitals. Despite increasing uptake of ASPs in Missouri, there is wide variability in both the scope and sophistication of these programs.

The Current State Of Antifungal Stewardship Among Pediatric Antimicrobial Stewardship Programs, Lourdes Eguiguren, Jason G Newland, Matthew P Kronman, Adam L Hersh, Jeffrey S Gerber, Grace M Lee, Hayden T Schwenk

Open Access Publications

OBJECTIVE: To characterize the current state of antifungal stewardship practices and perceptions of antifungal use among pediatric antimicrobial stewardship programs (ASPs).

DESIGN: We developed and distributed an electronic survey, which included 17 closed-ended questions about institutional antifungal stewardship practices and perceptions, among pediatric ASPs.

PARTICIPANTS: ASP physicians and pharmacists of 74 hospitals participating in the multicenter Sharing Antimicrobial Reports for Pediatric Stewardship (SHARPS) Collaborative.

RESULTS: We sent surveys to 74 hospitals and received 68 unique responses, for a response rate of 92%. Overall, 63 of 68 the respondent ASPs (93%) reported that they conduct 1 or more antifungal stewardship activities. …

Using A Developmental Perspective To Examine The Moderating Effects Of Marriage On Heavy Episodic Drinking In A Young Adult Sample Enriched For Risk, Seung Bin Cho, Rebecca L Smith, Kathleen Bucholz, Grace Chan, Howard J Edenberg, Victor Hesselbrock, John Kramer, Vivia V Mccutcheon, John Nurnberger, Marc Schuckit, Yong Zang, Danielle M Dick, Jessica E Salvatore

Open Access Publications

Many studies demonstrate that marriage protects against risky alcohol use and moderates genetic influences on alcohol outcomes; however, previous work has not considered these effects from a developmental perspective or in high-risk individuals. These represent important gaps, as it cannot be assumed that marriage has uniform effects across development or in high-risk samples. We took a longitudinal developmental approach to examine whether marital status was associated with heavy episodic drinking (HED), and whether marital status moderated polygenic influences on HED. Our sample included 937 individuals (53.25% female) from the Collaborative Study on the Genetics of Alcoholism who reported their HED …

Postdischarge Antibiotic Use For Prophylaxis Following Spinal Fusion, David K Warren, Katelin B Nickel, Jennifer H Han, Pam Tolomeo, Christopher J Hostler, Katherine Foy, Ian R Banks, Victoria J Fraser, Margaret A Olsen, Cdc Prevention Epicenter Program

Open Access Publications

OBJECTIVE: Despite recommendations to discontinue prophylactic antibiotics after incision closure or <24 hours after surgery, prophylactic antibiotics are continued after discharge by some clinicians. The objective of this study was to determine the prevalence and factors associated with postdischarge prophylactic antibiotic use after spinal fusion.

DESIGN: Multicenter retrospective cohort study.

PATIENTS: This study included patients aged ≥18 years undergoing spinal fusion or refusion between July 2011 and June 2015 at 3 sites. Patients with an infection during the surgical admission were excluded.

METHODS: Prophylactic antibiotics were identified at discharge. Factors associated with postdischarge prophylactic antibiotic use were identified using hierarchical generalized linear models.

RESULTS: In total, 8,652 spinal fusion admissions were included. Antibiotics were prescribed at discharge in 289 admissions (3.3%). The most commonly prescribed antibiotics were trimethoprim/sulfamethoxazole (22.1%), cephalexin (18.8%), and ciprofloxacin (17.1%). …

Policies And Practices Of Shea Research Network Hospitals During The Covid-19 Pandemic, Michael S Calderwood, Valerie M Deloney, Deverick J Anderson, Vincent Chi-Chung Cheng, Shruti Gohil, Jennie H Kwon, Lona Mody, Elizabeth Monsees, Valerie M Vaughn, Timothy L Wiemken, Matthew J Ziegler, Eric Lofgren

Open Access Publications

To understand hospital policies and practices as the COVID-19 pandemic accelerated, the Society for Healthcare Epidemiology of America (SHEA) conducted a survey through the SHEA Research Network (SRN). The survey assessed policies and practices around the optimization of personal protection equipment (PPE), testing, healthcare personnel policies, visitors of COVID-19 patients in relation to procedures, and types of patients. Overall, 69 individual healthcare facilities responded in the United States and internationally, for a 73% response rate.

Reduced Intensity Conditioning For Acute Myeloid Leukemia Using Melphalan- Vs Busulfan-Based Regimens: A Cibmtr Report, Zheng Zhou, Geoffrey L. Uy, Et Al.

Open Access Publications

No abstract provided.

Residual Endotoxin Induces Primary Graft Dysfunction Through Ischemia/Reperfusion-Primed Alveolar Macrophages, Mahzad Akbarpour, Daniel Kreisel, Wenjun Li, Et Al

Open Access Publications

Despite the widespread use of antibiotics, bacterial pneumonias in donors strongly predispose to the fatal syndrome of primary graft dysfunction (PGD) following lung transplantation. We report that bacterial endotoxin persists in human donor lungs after pathogen is cleared with antibiotics and is associated with neutrophil infiltration and PGD. In mouse models, depletion of tissue-resident alveolar macrophages (TRAMs) attenuated neutrophil recruitment in response to endotoxin as shown by compartmental staining and intravital imaging. Bone marrow chimeric mice revealed that neutrophils were recruited by TRAM through activation of TLR4 in a MyD88-dependent manner. Intriguingly, low levels of endotoxin, insufficient to cause donor …

Interleukin-15 Superagonist (N-803) Treatment Of Pml And Jcv In A Post–Allogeneic Hematopoietic Stem Cell Transplant Patient, Aabha Oza, Michael P. Rettig, Phil Powell, Kathryn O'Brien, David B. Clifford, Julie Ritchey, Leah Gehrs, Julia Hollaway, Eugene Major, Todd A. Fehniger, Christopher A. Miller, Patrick Soon-Shiong, Amy Rock, John F. Dipersio

Open Access Publications

No abstract provided.

Incipient Alcohol Use In Childhood: Early Alcohol Sipping And Its Relations With Psychopathology And Personality, Ashley L Watts, Phillip K Wood, Kristina M Jackson, Krista M Lisdahl, Mary M Heitzeg, Raul Gonzalez, Susan F Tapert, Deanna M Barch, Kenneth J Sher

Open Access Publications

Prior research has shown that sipping of alcohol begins to emerge during childhood and is potentially etiologically significant for later substance use problems. Using a large, community sample of 9- and 10-year-olds (N = 11,872; 53% female), we examined individual differences in precocious alcohol use in the form of alcohol sipping. We focused explicitly on features that are robust and well-demonstrated correlates of, and antecedents to, alcohol excess and related problems later in the lifespan, including youth- and parent-reported externalizing traits (i.e., impulsivity, behavioral inhibition and activation) and psychopathology. Seventeen percent of the sample reported sipping alcohol outside of a …

Preclinical Single Photon Emission Computed Tomography Of Alpha Particle-Emitting Radium-223, Diane S. Abou, Andrew Rittenbach, Ryan E. Tomlinson, Paige A. Finley, Benjamin Tsui, Brian W. Simons, Abhinav K. Jha, David Ulmert, Ryan C. Riddle, Daniel L. J. Thorek

Open Access Publications

No abstract provided.

Induced Remission Of Metastatic Squamous Cell Carcinoma With An Immune Checkpoint Inhibitor In A Patient With Recessive Dystrophic Epidermolysis Bullosa, Karam Khaddour, Emily S. Gorell, Farrokh Dehdashti, Jean Y. Tang, George Ansstas

Open Access Publications

No abstract provided.

Top Ten Tips Palliative Care Clinicians Should Know About Amyotrophic Lateral Sclerosis, Elyse A. Everett, Elizabeth Pedowitz, Samuel Maiser, Joss Cohen, Jessica Besbris, Ambereen K. Mehta, Luqi Chi, Christopher A. Jones

Open Access Publications

No abstract provided.

Improving Hba1c With Glucose Self-Monitoring In Diabetic Patients With Epxdiabetes, A Phone Call And Text Message-Based Telemedicine Platform: A Randomized Controlled Trial, Ran Xu, Maggie Xing, Kavon Javaherian, Robert Peters, Will Ross, Carlos Bernal-Mizrachi

Open Access Publications

No abstract provided.

Work-Related And Personal Factors Associated With Mental Well-Being During The Covid-19 Response: Survey Of Health Care And Other Workers, Bradley A Evanoff, Jaime R Strickland, Ann Marie Dale, Lisa Hayibor, Emily Page, Jennifer G Duncan, Thomas Kannampallil, Diana L Gray

Open Access Publications

BACKGROUND: The response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has created an unprecedented disruption in work conditions. This study describes the mental health and well-being of workers both with and without clinical exposure to patients with coronavirus disease (COVID-19).

OBJECTIVE: The aim of this study is to measure the prevalence of stress, anxiety, depression, work exhaustion, burnout, and decreased well-being among faculty and staff at a university and academic medical center during the SARS-CoV-2 pandemic and describe work-related and personal factors associated with their mental health and well-being.

METHODS: All faculty, staff, and postdoctoral fellows of …

Cellular Diversity Of The Regenerating Caudal Fin, Yiran Hou, Hyung Joo Lee, Yujie Chen, Jiaxin Ge, Fujr Osman Ibrahim Osman, Anthony R Mcadow, Mayssa H Mokalled, Stephen L Johnson, Guoyan Zhao, Ting Wang

Open Access Publications

Zebrafish faithfully regenerate their caudal fin after amputation. During this process, both differentiated cells and resident progenitors migrate to the wound site and undergo lineage-restricted, programmed cellular state transitions to populate the new regenerate. Until now, systematic characterizations of cells comprising the new regenerate and molecular definitions of their state transitions have been lacking. We hereby characterize the dynamics of gene regulatory programs during fin regeneration by creating single-cell transcriptome maps of both preinjury and regenerating fin tissues at 1/2/4 days post-amputation. We consistently identified epithelial, mesenchymal, and hematopoietic populations across all stages. We found common and cell type-specific cell …

Single-Cell Transcriptomic Analysis Identifies The Conversion Of Zebrafish Etv2-Deficient Vascular Progenitors Into Skeletal Muscle, Brendan Chestnut, Satish Casie Chetty, Andrew L. Koenig, Saulius Sumanas

Open Access Publications

No abstract provided.

Alcohol Drinking And Head And Neck Cancer Risk: The Joint Effect Of Intensity And Duration, Gioia Di Credico, Jose P Zevallos, Et Al

Open Access Publications

BACKGROUND: Alcohol is a well-established risk factor for head and neck cancer (HNC). This study aims to explore the effect of alcohol intensity and duration, as joint continuous exposures, on HNC risk.

METHODS: Data from 26 case-control studies in the INHANCE Consortium were used, including never and current drinkers who drunk ≤10 drinks/day for ≤54 years (24234 controls, 4085 oral cavity, 3359 oropharyngeal, 983 hypopharyngeal and 3340 laryngeal cancers). The dose-response relationship between the risk and the joint exposure to drinking intensity and duration was investigated through bivariate regression spline models, adjusting for potential confounders, including tobacco smoking.

RESULTS: For …

Both Unmedicated And Medicated Individuals With Schizophrenia Show Impairments Across A Wide Array Of Cognitive And Reinforcement Learning Tasks, Erin K Moran, James M Gold, Cameron S Carter, Angus W Macdonald, J Daniel Ragland, Steven M Silverstein, Steven J Luck, Deanna M Barch

Open Access Publications

BACKGROUND: Schizophrenia is a disorder characterized by pervasive deficits in cognitive functioning. However, few well-powered studies have examined the degree to which cognitive performance is impaired even among individuals with schizophrenia not currently on antipsychotic medications using a wide range of cognitive and reinforcement learning measures derived from cognitive neuroscience. Such research is particularly needed in the domain of reinforcement learning, given the central role of dopamine in reinforcement learning, and the potential impact of antipsychotic medications on dopamine function.

METHODS: The present study sought to fill this gap by examining healthy controls (N = 75), unmedicated (N = 48) …

Promoting Undetectable Equals Untransmittable In Sub-Saharan Africa: Implication For Clinical Practice And Art Adherence, Nicholas Ekow Thomford, Doreen Mhandire, Collet Dandara, George B Kyei

Open Access Publications

In the last decade, reliable scientific evidence has emerged to support the concept that undetectable viral loads prevent human immunodeficiency virus (HIV). Undetectable equals untransmissible (U = U) is a simple message that everyone can understand. The success of this concept depends on strict adherence to antiretroviral therapy (ART) and the attainment of suppressed viral loads (VLs). To achieve U = U in sub-Saharan Africa (SSA), poor adherence to ART, persistent low-level viremia, and the emergence of drug-resistant mutants are challenges that cannot be overlooked. Short of a cure for HIV, U = U can substantially reduce the burden and …

Ancestral Roles Of Atypical Cadherins In Planar Cell Polarity, Maria Brooun, Alexander Klimovich, Mikhail Bashkurov, Bret J. Pearson, Robert E. Steele, Helen Mcneill

Open Access Publications

No abstract provided.

A Retrospective Analysis Of The Efficacy Of Immunotherapy In Metastatic Soft-Tissue Sarcomas, Varun Monga, Hilary Dietz, Angela C Hirbe, Brian A Van Tine, Peter Oppelt, Et Al

Open Access Publications

Although checkpoint inhibitors have been approved in multiple cancers, they are still under investigation in soft tissue sarcoma (STS). We conducted a retrospective review to report the safety, efficacy, and prognostic factors related to checkpoint inhibitors in STS. A sequential cohort of metastatic STS patients from four institutions treated with checkpoint inhibitors was assembled. Logistic and Cox regression models were applied to determine the effect of patient characteristics, prior treatment, and baseline factors on achieving the best overall response of complete response (CR), partial response (PR), or stable disease (SD) as determined by the treating physician. Eighty-eight patients with two …