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2022

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Full-Text Articles in Medical Specialties

Machine Learning To Predict Sports-Related Concussion Recovery Using Clinical Data, Yan Chu, Gregory Knell, Riley P. Brayton, Scott O. Burkhart, Xiaoqian Jiang, Shayan Shams Feb 2022

Machine Learning To Predict Sports-Related Concussion Recovery Using Clinical Data, Yan Chu, Gregory Knell, Riley P. Brayton, Scott O. Burkhart, Xiaoqian Jiang, Shayan Shams

Faculty Research, Scholarly, and Creative Activity

Objectives
Sport-related concussions (SRCs) are a concern for high school athletes. Understanding factors contributing to SRC recovery time may improve clinical management. However, the complexity of the many clinical measures of concussion data precludes many traditional methods. This study aimed to answer the question, what is the utility of modeling clinical concussion data using machine-learning algorithms for predicting SRC recovery time and protracted recovery?
Methods
This was a retrospective case series of participants aged 8 to 18 years with a diagnosis of SRC. A 6-part measure was administered to assess pre-injury risk factors, initial injury severity, and post-concussion symptoms, including …


Prevalence And Types Of Drugs Used Among Hepatitis A Patients During Outbreaks Associated With Person-To-Person Transmission, Kentucky, Michigan, And West Virginia, 2016–2019, Megan G. Hofmeister, Alice Asher, Christopher M. Jones, Ryan J. Augustine, Cole Burkholder, Jim Collins, Monique A. Foster, Shannon Mcbee, Erica D. Thomasson, Doug Thoroughman, Mark K. Weng, Philip R. Spradling Feb 2022

Prevalence And Types Of Drugs Used Among Hepatitis A Patients During Outbreaks Associated With Person-To-Person Transmission, Kentucky, Michigan, And West Virginia, 2016–2019, Megan G. Hofmeister, Alice Asher, Christopher M. Jones, Ryan J. Augustine, Cole Burkholder, Jim Collins, Monique A. Foster, Shannon Mcbee, Erica D. Thomasson, Doug Thoroughman, Mark K. Weng, Philip R. Spradling

Journal of Appalachian Health

Background: People who use drugs are at increased risk for hepatitis A virus infection. Since 1996, the Advisory Committee on Immunization Practices has recommended hepatitis A vaccination for people who use drugs. Since 2016, the U.S. has experienced widespread hepatitis A outbreaks associated with person-to-person transmission.

Purpose: To describe the prevalence of drug use, route of use, and drugs used among hepatitis A outbreak-associated patients.

Methods: State outbreak and medical records were reviewed to describe the prevalence, type, and route of drug use among a random sample of 812 adult outbreak-associated hepatitis A patients from Kentucky, Michigan, and West Virginia …


The Aoc In The Age Of Covid—Pandemic Preparedness Planning In The Federal Courts, Zoe Niesel Feb 2022

The Aoc In The Age Of Covid—Pandemic Preparedness Planning In The Federal Courts, Zoe Niesel

St. Mary's Law Journal

The 2020 COVID-19 pandemic created a crisis for American society—and the federal courts were not exempt. Court facilities came to a grinding halt, cases were postponed, and judiciary employees adopted work-from-home practices. Having court operations impacted by a pandemic was not a new phenomenon, but the size, scope, and technological lift of the COVID-19 pandemic was certainly unique.

Against this background, this Article examines the history and future of pandemic preparedness planning in the federal court system and seeks to capture some of the lessons learned from initial federal court transitions to pandemic operations in 2020. The Article begins by …


Left Ventricular Outflow Tract Endocarditis As A Sequela Of Pneumonia In A Patient Without Valvular Abnormalities, Mohd Asyiq Raffali, Prapatricca Shanmugam, Muhammad Ishamuddin Ismail, Suria Hayati Pauzi, Hamat Hamdi Che Hassan Feb 2022

Left Ventricular Outflow Tract Endocarditis As A Sequela Of Pneumonia In A Patient Without Valvular Abnormalities, Mohd Asyiq Raffali, Prapatricca Shanmugam, Muhammad Ishamuddin Ismail, Suria Hayati Pauzi, Hamat Hamdi Che Hassan

Journal of the Saudi Heart Association

A 50-year-old woman with underlying end stage renal disease on hemodialysis developed large isolated staphylococcal infective endocarditis over the left ventricular outflow tract when she had pneumonia, without apparent valvular involvement. She subsequently had successful surgery for excision of vegetation.


Noncoding-Rna-Based Therapeutics With An Emphasis On Prostatic Carcinoma-Progress And Challenges., Victor E. Nava, Pin-Yu Perera, Nirbhay Kumar, Maneesh Jain Feb 2022

Noncoding-Rna-Based Therapeutics With An Emphasis On Prostatic Carcinoma-Progress And Challenges., Victor E. Nava, Pin-Yu Perera, Nirbhay Kumar, Maneesh Jain

Pathology Faculty Publications

Noncoding RNAs (ncRNAs) defy the central dogma by representing a family of RNA molecules that are not translated into protein but can convey information encoded in their DNA. Elucidating the exact function of ncRNA has been a focus of discovery in the last decade and remains challenging. Nevertheless, the importance of understanding ncRNA is apparent since these molecules regulate gene expression at the transcriptional and post-transcriptional level exerting pleiotropic effects critical in development, oncogenesis, and immunity. NcRNAs have been referred to as "the dark matter of the nucleus", and unraveling their role in physiologic and pathologic processes will provide vast …


The Effects Of Rosiglitazone On Task Specific Anxiety-Like Behavior And Novelty Seeking In A Model Of Chronic Adolescent Unpredictable Stress, Hannah Sexton, Nathan A. Olszewski, Mary-Louise Risher Feb 2022

The Effects Of Rosiglitazone On Task Specific Anxiety-Like Behavior And Novelty Seeking In A Model Of Chronic Adolescent Unpredictable Stress, Hannah Sexton, Nathan A. Olszewski, Mary-Louise Risher

Biomedical Sciences

Adolescence is characterized as a period of increased social behavior, risk taking, and novelty seeking, partly due to ongoing maturation in critical brain areas and the hypothalamic-pituitary-adrenal (HPA) negative-feedback system. During this period there is heightened vulnerability to stress that can drive neuro-immune-endocrine remodeling, resulting in the emergence of maladaptive behaviors that increase susceptibility to alcohol and substance abuse. Here we used a rat model to investigate the impact of chronic adolescent unpredictable stress on a battery of behavioral measures to assess anxiety, novelty seeking, risk taking, depression, and voluntary ethanol consumption while determining whether the PPARγ agonist rosiglitazone can …


Food Parenting Practices And Feeding Styles And Their Relations With Weight Status In Children In Latin America And The Caribbean, Luisa Pérez, Marcela Vizcarra, Sheryl O Hughes, Maria A Papaioannou Feb 2022

Food Parenting Practices And Feeding Styles And Their Relations With Weight Status In Children In Latin America And The Caribbean, Luisa Pérez, Marcela Vizcarra, Sheryl O Hughes, Maria A Papaioannou

Children’s Nutrition Research Center Staff Publications

While a growing body of literature looks at the associations between food parenting practices, and feeding styles, and child's weight status in developed countries, little is known for less developed countries, in general, and the Latin America and the Caribbean (LAC) region, in particular. This study systemically reviews and synthesizes existing evidence on the associations between child caregivers' food parenting practices and feeding styles and 2 to 12-year-old child weight status. Keywords were used to search in PubMed, Web of Science, PsycINFO, and Cumulative Index to Nursing and Allied Health Literature. Among the ten eligible articles, all of them reported …


Gap Junction-Dependent And -Independent Functions Of Connexin43 In Biology, Yi Zhu Feb 2022

Gap Junction-Dependent And -Independent Functions Of Connexin43 In Biology, Yi Zhu

Children’s Nutrition Research Center Staff Publications

Simple Summary

Connexin43 is one of the 21 members of a large protein family that forms intercellular gap junction complexes. It plays a critical role in development by allowing two adjacent cells to exchange cellular content. Mouse deletion studies have demonstrated its critical roles in many organs, including cardiac muscle, blood vessels, bone, adipose tissue and more. However, as the most expressed and most studied connexin in the family, Connexin43 surprisingly shows many gap-junction-independent roles, spanning from the forming of hemichannels, to regulating membrane trafficking, to regulating mitochondrial function. Connexin43 is also unique in the family by forming many smaller …


Treatment Of Nonsurgical Refractory Back Pain With High-Frequency Spinal Cord Stimulation At 10 Khz: 12-Month Results Of A Pragmatic, Multicenter, Randomized Controlled Trial., Leonardo Kapural, Jessica Jameson, Curtis Johnson, Daniel Kloster, Aaron Calodney, Peter Kosek, Julie Pilitsis, Markus Bendel, Erika Petersen, Chengyuan Wu, Taissa Cherry, Shivanand P Lad, Cong Yu, Dawood Sayed, Johnathan Goree, Mark K Lyons, Andrew Sack, Diana Bruce, Frances Rubenstein, Rose Province-Azalde, David Caraway, Naresh P Patel Feb 2022

Treatment Of Nonsurgical Refractory Back Pain With High-Frequency Spinal Cord Stimulation At 10 Khz: 12-Month Results Of A Pragmatic, Multicenter, Randomized Controlled Trial., Leonardo Kapural, Jessica Jameson, Curtis Johnson, Daniel Kloster, Aaron Calodney, Peter Kosek, Julie Pilitsis, Markus Bendel, Erika Petersen, Chengyuan Wu, Taissa Cherry, Shivanand P Lad, Cong Yu, Dawood Sayed, Johnathan Goree, Mark K Lyons, Andrew Sack, Diana Bruce, Frances Rubenstein, Rose Province-Azalde, David Caraway, Naresh P Patel

Department of Neurosurgery Faculty Papers

Objective: Spinal cord stimulation (SCS) at 10 kHz (10-kHz SCS) is a safe and effective therapy for treatment of chronic low-back pain. However, it is unclear from existing evidence whether these findings can be generalized to patients with chronic back pain that is refractory to conventional medical management (CMM) and who have no history of spine surgery and are not acceptable candidates for spine surgery. The authors have termed this condition "nonsurgical refractory back pain" (NSRBP) and conducted a multicenter, randomized controlled trial to compare CMM with and without 10-kHz SCS in this population.

Methods: Patients with NSRBP, as defined …


The Frequency Of Pathogenic Variation In The All Of Us Cohort Reveals Ancestry-Driven Disparities, Oi-Wa Chan, Wan-Hsuan Chen, Jainn-Jim Lin, Ming-Chou Chiang, Shao-Hsuan Hsia, Huei-Shyong Wang, En-Pei Lee, Yi-Shan Wang, Cheng-Yen Kuo, Kuang-Lin Lin, Icns Group Feb 2022

The Frequency Of Pathogenic Variation In The All Of Us Cohort Reveals Ancestry-Driven Disparities, Oi-Wa Chan, Wan-Hsuan Chen, Jainn-Jim Lin, Ming-Chou Chiang, Shao-Hsuan Hsia, Huei-Shyong Wang, En-Pei Lee, Yi-Shan Wang, Cheng-Yen Kuo, Kuang-Lin Lin, Icns Group

Faculty, Staff and Student Publications

BACKGROUND: In general clinical practice, neonatal seizures are identified visually by direct clinical observation. The study aimed to examine the frequency of clinical seizures in paroxysmal events in a neonatal intensive care unit.

METHODS: We conducted a prospective study of continuous video-EEG monitoring in a neonatal intensive care unit between January 2017 and December 2020. The demographic data were also reviewed.

RESULTS: Sixty-four neonates were enrolled. The median total video-EEG monitoring duration was 24.1 h (IQR 17.5-44.8 h). There were 309 clinically suspected seizure episodes, of which 181 (58.6%) were the motor type and 128 (41.4%) were the non-motor type. …


Sensitivity Enhancement Of An Experimental Benchtop X-Ray Fluorescence Imaging System By Deploying A Single Crystal Cadmium Telluride Detector System Optimized For High Flux X-Ray Operations, Hem Moktan, Sandun Jayarathna, Sang Hyun Cho Feb 2022

Sensitivity Enhancement Of An Experimental Benchtop X-Ray Fluorescence Imaging System By Deploying A Single Crystal Cadmium Telluride Detector System Optimized For High Flux X-Ray Operations, Hem Moktan, Sandun Jayarathna, Sang Hyun Cho

Faculty, Staff and Student Publications

In this work, an energy-resolving thermoelectrically cooled single crystal cadmium telluride (CdTe) detector system upgraded with the latest firmware was optimized for high x-ray flux operations using high bias voltage and fast peaking time. This detector system was deployed into an experimental benchtop x-ray fluorescence (XRF) imaging/computed tomography (XFCT) system developed for quantitative imaging of metal nanoprobes such as gold nanoparticles (GNPs). Using the firmware-upgraded and existing/old CdTe detector systems, the Compton/XRF spectra from small (8 mm diameter) GNP-containing phantoms were acquired. The phantoms were irradiated with 1.8 mm Sn-filtered 125 kVp cone beam x-rays at 24 mA. The firmware-upgraded …


Combination Of Tipifarnib And Sunitinib Overcomes Renal Cell Carcinoma Resistance To Tyrosine Kinase Inhibitors Via Tumor-Derived Exosome And T Cell Modulation, Jacob W. Greenberg, Hogyoung Kim, Miae Ahn, Ahmed A. Moustafa, He Zhou, Pedro C. Barata, A. Hamid Boulares, Asim B. Abdel-Mageed, Louis S. Krane Feb 2022

Combination Of Tipifarnib And Sunitinib Overcomes Renal Cell Carcinoma Resistance To Tyrosine Kinase Inhibitors Via Tumor-Derived Exosome And T Cell Modulation, Jacob W. Greenberg, Hogyoung Kim, Miae Ahn, Ahmed A. Moustafa, He Zhou, Pedro C. Barata, A. Hamid Boulares, Asim B. Abdel-Mageed, Louis S. Krane

School of Graduate Studies Faculty Publications

Background: Tyrosine kinase inhibitors (TKI) were initially demonstrated as an efficacious treatment for renal cell carcinoma (RCC). However, after a median treatment length of 14 months, a vast majority of patients develop resistance. This study analyzed a combination therapy of tipifarnib (Tipi) + sunitinib that targeted exosome-conferred drug resistance. Methods: 786-O, 786-O-SR (sunitinib resistant), A498, A498-SR, Caki-2, Caki-2-SR, and 293T cells were cultured. Ex-osomes were collected using differential ultracentrifugation. Cell proliferation, Jurkat T cell immune assay, and immunoblot analysis were used for downstream analysis. Results: SR exosomes treatment displayed a cytotoxic effect on immune cells. This cytotoxic effect was associated …


Sars-Cov-2 Infection Increases Risk Of Acute Kidney Injury In A Bimodal Age Distribution, Erica C Bjornstad, Gary Cutter, Pramod Guru, Shina Menon, Isabella Aldana, Scott House, Nancy M Tofil, Catherine A St Hill, Yasir Tarabichi, Valerie M Banner-Goodspeed, Amy B Christie, Surapaneni Krishna Mohan, Devang Sanghavi, Jarrod M Mosier, Girish Vadgaonkar, Allan J Walkey, Rahul Kashyap, Vishakha K Kumar, Vikas Bansal, Karen Boman, Mayank Sharma, Marija Bogojevic, Neha Deo, Lynn Retford, Ognjen Gajic, Katja M Gist, Sccm Discovery Virus Investigators Group Feb 2022

Sars-Cov-2 Infection Increases Risk Of Acute Kidney Injury In A Bimodal Age Distribution, Erica C Bjornstad, Gary Cutter, Pramod Guru, Shina Menon, Isabella Aldana, Scott House, Nancy M Tofil, Catherine A St Hill, Yasir Tarabichi, Valerie M Banner-Goodspeed, Amy B Christie, Surapaneni Krishna Mohan, Devang Sanghavi, Jarrod M Mosier, Girish Vadgaonkar, Allan J Walkey, Rahul Kashyap, Vishakha K Kumar, Vikas Bansal, Karen Boman, Mayank Sharma, Marija Bogojevic, Neha Deo, Lynn Retford, Ognjen Gajic, Katja M Gist, Sccm Discovery Virus Investigators Group

Faculty, Staff and Students Publications

BACKGROUND: Hospitalized patients with SARS-CoV2 develop acute kidney injury (AKI) frequently, yet gaps remain in understanding why adults seem to have higher rates compared to children. Our objectives were to evaluate the epidemiology of SARS-CoV2-related AKI across the age spectrum and determine if known risk factors such as illness severity contribute to its pattern.

METHODS: Secondary analysis of ongoing prospective international cohort registry. AKI was defined by KDIGO-creatinine only criteria. Log-linear, logistic and generalized estimating equations assessed odds ratios (OR), risk differences (RD), and 95% confidence intervals (CIs) for AKI and mortality adjusting for sex, pre-existing comorbidities, race/ethnicity, illness severity, …


Reducing Influenza Virus Transmission: The Potential Value Of Antiviral Treatment, Frederick G Hayden, Jason Asher, Benjamin J Cowling, Aeron C Hurt, Hideyuki Ikematsu, Klaus Kuhlbusch, Annabelle Lemenuel-Diot, Zhanwei Du, Lauren Ancel Meyers, Pedro A Piedra, Takahiro Takazono, Hui-Ling Yen, Arnold S Monto Feb 2022

Reducing Influenza Virus Transmission: The Potential Value Of Antiviral Treatment, Frederick G Hayden, Jason Asher, Benjamin J Cowling, Aeron C Hurt, Hideyuki Ikematsu, Klaus Kuhlbusch, Annabelle Lemenuel-Diot, Zhanwei Du, Lauren Ancel Meyers, Pedro A Piedra, Takahiro Takazono, Hui-Ling Yen, Arnold S Monto

Faculty, Staff and Students Publications

Prompt antiviral treatment has the potential to reduce influenza virus transmission to close contacts, but rigorous data on the magnitude of treatment effects on transmission are limited. Animal model data indicate that rapid reductions in viral replication after antiviral treatment reduce the risk of transmission. Observational and clinical trial data with oseltamivir and other neuraminidase inhibitors indicate that prompt treatment of household index patients seems to reduce the risk of illness in contacts, although the magnitude of the reported effects has varied widely across studies. In addition, the potential risk of transmitting drug-resistant variants exists with all approved classes of …


Second Heart Field–Derived Cells Contribute To Angiotensin Ii–Mediated Ascending Aortopathies, Hisashi Sawada, Yuriko Katsumata, Hideyuki Higashi, Chen Zhang, Yanming Li, Stephanie Morgan, Lang H. Lee, Sasha A. Singh, Jeff Z. Chen, Michael K. Franklin, Jessica J. Moorleghen, Deborah A. Howatt, Debra L. Rateri, Ying H. Shen, Scott A. Lemaire, Masanori Aikawa, Mark W. Majesky, Hong S. Lu, Alan Daugherty Feb 2022

Second Heart Field–Derived Cells Contribute To Angiotensin Ii–Mediated Ascending Aortopathies, Hisashi Sawada, Yuriko Katsumata, Hideyuki Higashi, Chen Zhang, Yanming Li, Stephanie Morgan, Lang H. Lee, Sasha A. Singh, Jeff Z. Chen, Michael K. Franklin, Jessica J. Moorleghen, Deborah A. Howatt, Debra L. Rateri, Ying H. Shen, Scott A. Lemaire, Masanori Aikawa, Mark W. Majesky, Hong S. Lu, Alan Daugherty

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: The ascending aorta is a common location for aneurysm and dissection. This aortic region is populated by a mosaic of medial and adventitial cells that are embryonically derived from either the second heart field (SHF) or the cardiac neural crest. SHF-derived cells populate areas that coincide with the spatial specificity of thoracic aortopathies. The purpose of this study was to determine whether and how SHF-derived cells contribute to ascending aortopathies.

METHODS: Ascending aortic pathologies were examined in patients with sporadic thoracic aortopathies and angiotensin II (AngII)–infused mice. Ascending aortas without overt pathology from AngII-infused mice were subjected …


Antibody Response To Sars-Cov-2 Infection And Vaccination In Covid-19-Naive And Experienced Individuals, Susan L. Uprichard, Amornrat O'Brien, Monika Evdokimova, Cynthia L. Rowe, Cara Joyce, Matthew Hackbart, Yazmin Edith Cruz Pulido, Courtney A. Cohen, Michelle L. Rock, John M. Dye, Paul Kuehnert, Keersten M. Ricks, Marybeth Casper, Lori Linhart, Katrina Anderson, Laura Kirk, Jack A. Maggiore, Andrew S. Herbert, Nina M. Clark, Gail E. Reid, Susan C. Baker Feb 2022

Antibody Response To Sars-Cov-2 Infection And Vaccination In Covid-19-Naive And Experienced Individuals, Susan L. Uprichard, Amornrat O'Brien, Monika Evdokimova, Cynthia L. Rowe, Cara Joyce, Matthew Hackbart, Yazmin Edith Cruz Pulido, Courtney A. Cohen, Michelle L. Rock, John M. Dye, Paul Kuehnert, Keersten M. Ricks, Marybeth Casper, Lori Linhart, Katrina Anderson, Laura Kirk, Jack A. Maggiore, Andrew S. Herbert, Nina M. Clark, Gail E. Reid, Susan C. Baker

Biostatistics Collaborative Core: Faculty Publications and Other Works

Understanding the magnitude of responses to vaccination during the ongoing SARS-CoV-2 pandemic is essential for ultimate mitigation of the disease. Here, we describe a cohort of 102 subjects (70 COVID-19-naïve, 32 COVID-19-experienced) who received two doses of one of the mRNA vaccines (BNT162b2 (Pfizer–BioNTech) and mRNA-1273 (Moderna)). We document that a single exposure to antigen via infection or vaccination induces a variable antibody response which is affected by age, gender, race, and co-morbidities. In response to a second antigen dose, both COVID-19-naïve and experienced subjects exhibited elevated levels of anti-spike and SARS-CoV-2 neutralizing activity; however, COVID-19-experienced individuals achieved higher antibody …


Friend Of The Devil: Negative Social Influences Driving Substance Use Disorders, Matthew B. Pomrenze, Franciely Paliarin, Rajani Maiya Feb 2022

Friend Of The Devil: Negative Social Influences Driving Substance Use Disorders, Matthew B. Pomrenze, Franciely Paliarin, Rajani Maiya

School of Medicine Faculty Publications

Substance use disorders in humans have significant social influences, both positive and negative. While prosocial behaviors promote group cooperation and are naturally rewarding, distressing social encounters, such as aggression exhibited by a conspecific, are aversive and can enhance the sensitivity to rewarding substances, promote the acquisition of drug-taking, and reinstate drug-seeking. On the other hand, withdrawal and prolonged abstinence from drugs of abuse can promote social avoidance and suppress social motivation, accentuating drug cravings and facilitating relapse. Understanding how complex social states and experiences modulate drug-seeking behaviors as well as the underlying circuit dynamics, such as those interacting with mesolimbic …


Implementation Of A Drive-Through Covid-19 Mass Vaccination Site: Experiences From Louvax–Broadbent In Louisville, Kentucky, Ruth Carrico, Sarah Beth Hartlage, Valenchia Brown Msn, Aprn, Fnp-C, Sarah M. Bishop, Luanne Didelot, William Hayden, Beverly Williams Coleman, Sarah Tan, Delanor Manson, Kellie Kane, Dawn Balcom, Paul Kern Feb 2022

Implementation Of A Drive-Through Covid-19 Mass Vaccination Site: Experiences From Louvax–Broadbent In Louisville, Kentucky, Ruth Carrico, Sarah Beth Hartlage, Valenchia Brown Msn, Aprn, Fnp-C, Sarah M. Bishop, Luanne Didelot, William Hayden, Beverly Williams Coleman, Sarah Tan, Delanor Manson, Kellie Kane, Dawn Balcom, Paul Kern

The University of Louisville Journal of Respiratory Infections

Background: Response to the COVID-19 pandemic has required innovative approaches to vaccination, including methods to rapidly and safely immunize communities. A major challenge to such a response involved access to untapped healthcare worker resources. The Louisville, Kentucky, response involved the use of a large volunteer workforce to supplement local public health employees in planning and implementing a large-scale drive-through vaccination event. The objective of this manuscript was to outline processes involved in training a mass immunization workforce and implementating a large-scale COVID-19 community vaccination.

Approach: Competency-based and standardized training was provided for every volunteer before working their shift. Volunteers worked …


Effective Therapy For Aml With Runx1 Mutation By Cotreatment With Inhibitors Of Protein Translation And Bcl2, Christopher P Mill, Warren Fiskus, Courtney D Dinardo, Christine Birdwell, John A Davis, Tapan M Kadia, Koichi Takahashi, Nicholas Short, Naval Daver, Maro Ohanian, Gautam Borthakur, Steven M Kornblau, Michael R Green, Yuan Qi, Xiaoping Su, Joseph D Khoury, Kapil N Bhalla Feb 2022

Effective Therapy For Aml With Runx1 Mutation By Cotreatment With Inhibitors Of Protein Translation And Bcl2, Christopher P Mill, Warren Fiskus, Courtney D Dinardo, Christine Birdwell, John A Davis, Tapan M Kadia, Koichi Takahashi, Nicholas Short, Naval Daver, Maro Ohanian, Gautam Borthakur, Steven M Kornblau, Michael R Green, Yuan Qi, Xiaoping Su, Joseph D Khoury, Kapil N Bhalla

Faculty, Staff and Student Publications

The majority of RUNX1 mutations in acute myeloid leukemia (AML) are missense or deletion-truncation and behave as loss-of-function mutations. Following standard therapy, AML patients expressing mtRUNX1 exhibit inferior clinical outcome than those without mutant RUNX1. Studies presented here demonstrate that as compared with AML cells lacking mtRUNX1, their isogenic counterparts harboring mtRUNX1 display impaired ribosomal biogenesis and differentiation, as well as exhibit reduced levels of wild-type RUNX1, PU.1, and c-Myc. Compared with AML cells with only wild-type RUNX1, AML cells expressing mtRUNX1 were also more sensitive to the protein translation inhibitor homoharringtonine (omacetaxine) and BCL2 inhibitor venetoclax. Homoharringtonine treatment repressed …


Differences In Clinical And Functional Outcomes Between Osteochondral Allograft Transplantation And Autologous Chondrocyte Implantation For The Treatment Of Focal Articular Cartilage Defects, John R Matthews, Joseph Brutico, Daniel Abraham, Jeremy Heard, Bradford Tucker, Fotios Tjoumakaris, Kevin Freedman Feb 2022

Differences In Clinical And Functional Outcomes Between Osteochondral Allograft Transplantation And Autologous Chondrocyte Implantation For The Treatment Of Focal Articular Cartilage Defects, John R Matthews, Joseph Brutico, Daniel Abraham, Jeremy Heard, Bradford Tucker, Fotios Tjoumakaris, Kevin Freedman

Rothman Institute Papers

Background: Articular cartilage pathology can result from a spectrum of origins, including trauma, osteochondritis dissecans, avascular necrosis, or degenerative joint disease.

Purpose: To compare the differences in clinical and patient-reported outcomes after autologous chondrocyte implantation (ACI) versus osteochondral allograft transplantation (OCA) in patients with focal articular cartilage defects without underlying bone loss.

Study design: Cohort study; Level of evidence, 3.

Methods: A retrospective review identified patients who underwent ACI or OCA between 2008 and 2016 for isolated grades 3 and 4 articular cartilage defects without underlying bone loss. Outcome measures included the Knee injury and Osteoarthritis Outcome Score for Joint …


Lymphoma With Tuberculous Granulomas, Jyoti Mohan Lal, Anila Rashid Feb 2022

Lymphoma With Tuberculous Granulomas, Jyoti Mohan Lal, Anila Rashid

Department of Pathology and Laboratory Medicine

Chronic granulomatous inflammation is a common finding in lymphoproliferative disorders (LPDs), but it is important to exclude coexisting mycobacterium tuberculosis (MTB) especially in patients from areas of high endemicity. This case emphasizes the relevance of performing MTB culture on bone marrow exhibiting LPD and concomitant granulomas


Hpg80 (Circulating Progastrin), A Novel Blood-Based Biomarker For Detection Of Poorly Differentiated Neuroendocrine Carcinoma And Well Differentiated Neuroendocrine Tumors, Aman Chauhan, Alexandre Prieur, Jill Kolesar, Susanne Arnold, Léa Payen, Younes Mahi, Berengere Vire, Madison Sands, B. Mark Evers, Dominique Joubert, Lowell Anthony Feb 2022

Hpg80 (Circulating Progastrin), A Novel Blood-Based Biomarker For Detection Of Poorly Differentiated Neuroendocrine Carcinoma And Well Differentiated Neuroendocrine Tumors, Aman Chauhan, Alexandre Prieur, Jill Kolesar, Susanne Arnold, Léa Payen, Younes Mahi, Berengere Vire, Madison Sands, B. Mark Evers, Dominique Joubert, Lowell Anthony

Markey Cancer Center Faculty Publications

Current blood-based biomarkers for neuroendocrine neoplasms (NENs) lack both sensitivity and specificity. Human circulating progastrin (hPG80) is a novel biomarker that can be easily measured in plasma by ELISA. This study is the first to examine hPG80 in NENs. Plasma hPG80 was quantified from 95 stage IV NEN patients, using DxPG80 technology (ECS Progastrin, Switzerland) and compared with hPG80 concentrations in two cohorts of healthy donor controls aged 50–80 (n = 252) and 18–25 (n = 137). Median hPG80 in NENs patients was 5.54 pM compared to 1.5 pM for the …


Glomerular Biomechanical Stress And Lipid Mediators During Cellular Changes Leading To Chronic Kidney Disease., Mukut Sharma, Vikas Singh, Ram Sharma, Arnav Koul, Ellen T. Mccarthy, Virginia J. Savin, Trupti Joshi, Tarak Srivastava Feb 2022

Glomerular Biomechanical Stress And Lipid Mediators During Cellular Changes Leading To Chronic Kidney Disease., Mukut Sharma, Vikas Singh, Ram Sharma, Arnav Koul, Ellen T. Mccarthy, Virginia J. Savin, Trupti Joshi, Tarak Srivastava

Manuscripts, Articles, Book Chapters and Other Papers

Hyperfiltration is an important underlying cause of glomerular dysfunction associated with several systemic and intrinsic glomerular conditions leading to chronic kidney disease (CKD). These include obesity, diabetes, hypertension, focal segmental glomerulosclerosis (FSGS), congenital abnormalities and reduced renal mass (low nephron number). Hyperfiltration-associated biomechanical forces directly impact the cell membrane, generating tensile and fluid flow shear stresses in multiple segments of the nephron. Ongoing research suggests these biomechanical forces as the initial mediators of hyperfiltration-induced deterioration of podocyte structure and function leading to their detachment and irreplaceable loss from the glomerular filtration barrier. Membrane lipid-derived polyunsaturated fatty acids (PUFA) and their …


Depletion Of The Apical Endosome In Response To Viruses And Bacterial Toxins Provides Cell-Autonomous Host Defense At Mucosal Surfaces, Keiko Maeda, Nicholas C Zachos, Megan H Orzalli, Stefanie S Schmieder, Denis Chang, Katlynn Bugda Gwilt, Michele Doucet, Nicholas W Baetz, Sun Lee, Sue E Crawford, Mary K Estes, Jonathan C Kagan, Jerrold R Turner, Wayne I Lencer Feb 2022

Depletion Of The Apical Endosome In Response To Viruses And Bacterial Toxins Provides Cell-Autonomous Host Defense At Mucosal Surfaces, Keiko Maeda, Nicholas C Zachos, Megan H Orzalli, Stefanie S Schmieder, Denis Chang, Katlynn Bugda Gwilt, Michele Doucet, Nicholas W Baetz, Sun Lee, Sue E Crawford, Mary K Estes, Jonathan C Kagan, Jerrold R Turner, Wayne I Lencer

Faculty, Staff and Students Publications

Polarized epithelial cells form an essential barrier against infection at mucosal surfaces. Many pathogens breach this barrier to cause disease, often by co-opting cellular endocytosis mechanisms to enter the cell through the lumenal (apical) cell surface. We recently discovered that the loss of the cell polarity gene PARD6B selectively diminishes apical endosome function. Here, we find that in response to the entry of certain viruses and bacterial toxins into the epithelial cells via the apical membrane, PARD6B and aPKC, two components of the PARD6B-aPKC-Cdc42 apical polarity complex, undergo rapid proteasome-dependent degradation. The perturbation of apical membrane glycosphingolipids by toxin- or …


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 Feb 2022

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

Faculty, Staff and Students Publications

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 …


Myocardial Rev-Erb-Mediated Diurnal Metabolic Rhythm And Obesity Paradox, Shiyang Song, Chih-Liang Tien, Hao Cui, Paul Basil, Ningxia Zhu, Yingyun Gong, Wenbo Li, Hui Li, Qiying Fan, Jong Min Choi, Weijia Luo, Yanfeng Xue, Rui Cao, Wenjun Zhou, Andrea R Ortiz, Brittany Stork, Vatsala Mundra, Nagireddy Putluri, Brian York, Maoping Chu, Jiang Chang, Sung Yun Jung, Liang Xie, Jiangping Song, Lilei Zhang, Zheng Sun Feb 2022

Myocardial Rev-Erb-Mediated Diurnal Metabolic Rhythm And Obesity Paradox, Shiyang Song, Chih-Liang Tien, Hao Cui, Paul Basil, Ningxia Zhu, Yingyun Gong, Wenbo Li, Hui Li, Qiying Fan, Jong Min Choi, Weijia Luo, Yanfeng Xue, Rui Cao, Wenjun Zhou, Andrea R Ortiz, Brittany Stork, Vatsala Mundra, Nagireddy Putluri, Brian York, Maoping Chu, Jiang Chang, Sung Yun Jung, Liang Xie, Jiangping Song, Lilei Zhang, Zheng Sun

Faculty, Staff and Students Publications

BACKGROUND: The nuclear receptor Rev-erbα/β, a key component of the circadian clock, emerges as a drug target for heart diseases, but the function of cardiac Rev-erb has not been studied in vivo. Circadian disruption is implicated in heart diseases, but it is unknown whether cardiac molecular clock dysfunction is associated with the progression of any naturally occurring human heart diseases. Obesity paradox refers to the seemingly protective role of obesity for heart failure, but the mechanism is unclear.

METHODS: We generated mouse lines with cardiac-specific Rev-erbα/β knockout (KO), characterized cardiac phenotype, conducted multi-omics (RNA-sequencing, chromatin immunoprecipitation sequencing, proteomics, and metabolomics) …


Cryo-Et Of Toxoplasma Parasites Gives Subnanometer Insight Into Tubulin-Based Structures, Stella Y Sun, Li-Av Segev-Zarko, Muyuan Chen, Grigore D Pintilie, Michael F Schmid, Steven J Ludtke, John C Boothroyd, Wah Chiu Feb 2022

Cryo-Et Of Toxoplasma Parasites Gives Subnanometer Insight Into Tubulin-Based Structures, Stella Y Sun, Li-Av Segev-Zarko, Muyuan Chen, Grigore D Pintilie, Michael F Schmid, Steven J Ludtke, John C Boothroyd, Wah Chiu

Faculty, Staff and Students Publications

Tubulin is a conserved protein that polymerizes into different forms of filamentous structures in Toxoplasma gondii, an obligate intracellular parasite in the phylum Apicomplexa. Two key tubulin-containing cytoskeletal components are subpellicular microtubules (SPMTs) and conoid fibrils (CFs). The SPMTs help maintain shape and gliding motility, while the CFs are implicated in invasion. Here, we use cryogenic electron tomography to determine the molecular structures of the SPMTs and CFs in vitrified intact and detergent-extracted parasites. Subvolume densities from detergent-extracted parasites yielded averaged density maps at subnanometer resolutions, and these were related back to their architecture in situ. An intralumenal spiral …


Incorporation Of Surgical Cadaver Lab Training In A Physician Assistant Fellowship Program, Jacqueline Guarino, Jordan Rodriguez, Ming Zhang Phd, Ryan Krasnosky, Kristina Marsack Feb 2022

Incorporation Of Surgical Cadaver Lab Training In A Physician Assistant Fellowship Program, Jacqueline Guarino, Jordan Rodriguez, Ming Zhang Phd, Ryan Krasnosky, Kristina Marsack

Journal of Nursing & Interprofessional Leadership in Quality & Safety

Physician Assistants (PAs) are licensed medical professionals who provide health care under the supervision of and in collaboration with physicians. PAs can specialize in any field of medicine or surgery with additional on-the-job training while some PAs participate in a postgraduate training program in order to increase their knowledge in a certain subspecialty area. This paper describes the incorporation of a cadaver lab curriculum into a postgraduate PA surgical training program. The description of the development, implementation, and evaluation of the cadaver lab experience can assist other programs to implement this hands-on educational experience for a variety of medical providers, …


Feasibility Of Using Ring-Mounted Halcyon Linac For Single-Isocenter/Two-Lesion Lung Stereotactic Body Radiation Therapy, Damodar Pokhrel, Aaron Webster, Richard Mallory, Justin Visak, Mark E. Bernard, Ronald C. Mcgarry, Mahesh Kudrimoti Feb 2022

Feasibility Of Using Ring-Mounted Halcyon Linac For Single-Isocenter/Two-Lesion Lung Stereotactic Body Radiation Therapy, Damodar Pokhrel, Aaron Webster, Richard Mallory, Justin Visak, Mark E. Bernard, Ronald C. Mcgarry, Mahesh Kudrimoti

Radiation Medicine Faculty Publications

PURPOSE: To demonstrate the plan quality and delivery efficiency of volumetric-modulated arc therapy (VMAT) with the Halcyon Linac ring delivery system (RDS) in the treatment of single-isocenter/two-lesion lung stereotactic body radiation therapy (SBRT).

MATERIALS/METHODS: Sixteen previously treated non-coplanar VMAT single-isocenter/two-lesion lung SBRT plans delivered with SBRT-dedicated C-arm TrueBeam Linac were selected. Prescribed dose was 50 Gy to each lesion over five fractions with treatment delivery every other day and AcurosXB algorithm as the final dose calculation algorithm. TrueBeam single-isocenter plans were reoptimized for Halcyon Linac with coplanar geometry. Both TrueBeam and Halcyon plans were normalized for identical combined target coverage …


The Remote Assessment And Dynamic Response Program: Development Of An In-Home Dementia-Related Care Needs Assessment To Improve Well-Being, Lindsey M. Miller, Diane N. Solomon, Carol J. Whitlatch, Shirin O, Hiatt, Chao-Yi Wu, Christina Reynolds, Wan-Tai Michael Au-Yueng, Jeffrey Kaye, Joel Steele Feb 2022

The Remote Assessment And Dynamic Response Program: Development Of An In-Home Dementia-Related Care Needs Assessment To Improve Well-Being, Lindsey M. Miller, Diane N. Solomon, Carol J. Whitlatch, Shirin O, Hiatt, Chao-Yi Wu, Christina Reynolds, Wan-Tai Michael Au-Yueng, Jeffrey Kaye, Joel Steele

Psychology Faculty Publications and Presentations

Background and Objectives

The Remote Assessment and Dynamic Response (READyR) Program was developed in order to address the current lack of early-stage dementia care planning programs that assess the care needs of persons with dementia. The goal was to create a program informed by care values and ongoing ecologically valid data. The objectives of this study are to describe the development and design process of the READyR Program, and to evaluate the utility of the READyR Program for identifying dementia-related care needs.

Research Design and Methods

A prototype of the web-based READyR Program tool was first created using digital activity …