Digital Commons Network^™

Procedural Outcomes After Percutaneous Coronary Interventions In Focal And Diffuse Coronary Artery Disease, Takuya Mizukami, Jeroen Sonck, Koshiro Sakai, Brian Ko, Michael Maeng, Hiromasa Otake, Bon-Kwon Koo, Sakura Nagumo, Bjarne L Nørgaard, Jonathon Leipsic, Toshiro Shinke, Daniel Munhoz, Niya Mileva, Marta Belmonte, Hirofumi Ohashi, Emanuele Barbato, Nils P Johnson, Bernard De Bruyne, Carlos Collet

Faculty, Staff and Student Publications

Background

Coronary artery disease (CAD) patterns play an essential role in the decision‐making process about revascularization. The pullback pressure gradient (PPG) quantifies CAD patterns as either focal or diffuse based on fractional flow reserve (FFR) pullbacks. The objective of this study was to evaluate the impact of CAD patterns on acute percutaneous coronary intervention (PCI) results considered surrogates of clinical outcomes.

Methods and Results

This was a prospective, multicenter study of patients with hemodynamically significant CAD undergoing PCI. Motorized FFR pullbacks and optical coherence tomography (OCT) were performed before and after PCI. Post‐PCI FFR >0.90 was considered an optimal result. …

Plasma Growth Hormone Is A Potential Biomarker Of Response To Atezolizumab And Bevacizumab In Advanced Hepatocellular Carcinoma Patients, Yehia I Mohamed, Dan G Duda, Muhammad O Awiwi, Sunyoung S Lee, Lina Altameemi, Lianchun Xiao, Jeffrey S Morris, Robert A Wolff, Khaled M Elsayes, Rikita I Hatia, Aliya Qayyum, Shadi M Chamseddine, Asif Rashid, James C Yao, Armeen Mahvash, Manal M Hassan, Hesham M Amin, Ahmed Omar Kaseb

Faculty, Staff and Student Publications

INTRODUCTION: Hepatocellular carcinoma (HCC) has limited systemic therapy options when discovered at an advanced stage. Thus, there is a need for accessible and minimally invasive biomarkers of response to guide the selection of patients for treatment. This study investigated the biomarker value of plasma growth hormone (GH) level as a potential biomarker to predict outcome in unresectable HCC patients treated with current standard therapy, atezolizumab plus bevacizumab (Atezo/Bev).

MATERIALS AND METHODS: Study included unresectable HCC patients scheduled to receive Atezo/Bev. Patients were followed to determine progression-free survival (PFS) and overall survival (OS). Plasma GH levels were measured by ELISA and …

Open-Source Benchmarking Of Ibd Segment Detection Methods For Biobank-Scale Cohorts, Kecong Tang, Ardalan Naseri, Yuan Wei, Shaojie Zhang, Degui Zhi

Faculty, Staff and Student Publications

In the recent biobank era of genetics, the problem of identical-by-descent (IBD) segment detection received renewed interest, as IBD segments in large cohorts offer unprecedented opportunities in the study of population and genealogical history, as well as genetic association of long haplotypes. While a new generation of efficient methods for IBD segment detection becomes available, direct comparison of these methods is difficult: existing benchmarks were often evaluated in different datasets, with some not openly accessible; methods benchmarked were run under suboptimal parameters; and benchmark performance metrics were not defined consistently. Here, we developed a comprehensive and completely open-source evaluation of …

Tele-Medicine Based And Self-Administered Interactive Exercise Program (Tele-Exergame) To Improve Cognition In Older Adults With Mild Cognitive Impairment Or Dementia: A Feasibility, Acceptability, And Proof-Of-Concept Study, Catherine Park, Ram Kinker Mishra, Michele K York, Ana Enriquez, Abigail Lindsay, Gregory Barchard, Ashkan Vaziri, Bijan Najafi

Center on Aging Staff Publications

Improved life expectancy is increasing the number of older adults who suffer from motor-cognitive decline. Unfortunately, conventional balance exercise programs are not tailored to patients with cognitive impairments, and exercise adherence is often poor due to unsupervised settings. This study describes the acceptability and feasibility of a sensor-based in-home interactive exercise system, called tele-Exergame, used by older adults with mild cognitive impairment (MCI) or dementia. Our tele-Exergame is specifically designed to improve balance and cognition during distractive conditioning while a telemedicine interface remotely supervises the exercise, and its exercises are gamified balance tasks with explicit augmented visual feedback. Fourteen adults …

Federated Learning Enables Big Data For Rare Cancer Boundary Detection, Sarthak Pati, Ujjwal Baid, Brandon Edwards, Micah Sheller, Shih-Han Wang, G. Anthony Reina, Patrick Foley, Alexey Gruzdev, Deepthi Karkada, Christos Davatzikos, Chiharu Sako, Satyam Ghodasara, Michel Bilello, Suyash Mohan, Philipp Vollmuth, Gianluca Brugnara, Chandrakanth J. Preetha, Felix Sahm, Klaus Maier-Hein, Maximilian Zenk, Martin Bendszus, Wolfgang Wick, Evan Calabrese, Jeffrey Rudie, Javier Villanueva-Meyer, Soonmee Cha, Madhura Ingalhalikar, Manali Jadhav, Umang Pandey, Jitender Saini, John Garrett, Matthew Larson, Robert Jeraj, Stuart Currie, Russell Frood, Kavi Fatania, Raymond Y. Huang, Ken Chang, Carmen Balaña, Jaume Capellades, Josep Puig, Johannes Trenkler, Josef Pichler, Georg Necker, Andreas Haunschmidt, Stephan Meckel, Gaurav Shukla, Spencer Liem, Gregory S Alexander, Joseph Lombardo, Joshua D. Palmer, Adam E. Flanders, Adam P. Dicker, Haris I. Sair, Craig K. Jones, Archana Venkataraman, Meirui Jiang, Tiffany Y. So, Cheng Chen, Pheng Ann Heng, Qi Dou, Michal Kozubek, Filip Lux, Jan Michálek, Petr Matula, Miloš Keřkovský, Tereza Kopřivová, Marek Dostál, Václav Vybíhal, Michael A. Vogelbaum, J. Ross Mitchell, Joaquim Farinhas, Joseph A. Maldjian, Chandan Ganesh Bangalore Yogananda, Marco C. Pinho, Divya Reddy, James Holcomb, Benjamin C. Wagner, Benjamin M. Ellingson, Timothy F. Cloughesy, Catalina Raymond, Talia Oughourlian, Akifumi Hagiwara, Chencai Wang, Minh-Son To, Sargam Bhardwaj, Chee Chong, Marc Agzarian, Alexandre Xavier Falcão, Samuel B. Martins, Bernardo C. A. Teixeira, Flávia Sprenger, David Menotti, Diego R. Lucio, Pamela Lamontagne, Daniel Marcus, Benedikt Wiestler, Florian Kofler, Ivan Ezhov, Marie Metz, Rajan Jain, Matthew Lee, Yvonne W. Lui, Richard Mckinley, Johannes Slotboom, Piotr Radojewski, Raphael Meier, Roland Wiest, Derrick Murcia, Eric Fu, Rourke Haas, John Thompson, David Ryan Ormond, Chaitra Badve, Andrew E. Sloan, Vachan Vadmal, Kristin Waite, Rivka R. Colen, Linmin Pei, Murat Ak, Ashok Srinivasan, J. Rajiv Bapuraj, Arvind Rao, Nicholas Wang, Ota Yoshiaki, Toshio Moritani, Sevcan Turk, Joonsang Lee, Snehal Prabhudesai, Fanny Morón, Jacob Mandel, Konstantinos Kamnitsas, Ben Glocker, Luke V. M. Dixon, Matthew Williams, Peter Zampakis, Vasileios Panagiotopoulos, Panagiotis Tsiganos, Sotiris Alexiou, Ilias Haliassos, Evangelia I Zacharaki, Konstantinos Moustakas, Christina Kalogeropoulou, Dimitrios M. Kardamakis, Yoon Seong Choi, Seung-Koo Lee, Jong Hee Chang, Sung Soo Ahn, Bing Luo, Laila Poisson, Ning Wen, Pallavi Tiwari, Ruchika Verma, Rohan Bareja, Ipsa Yadav, Jonathan Chen, Neeraj Kumar, Marion Smits, Sebastian R. Van Der Voort, Ahmed Alafandi, Fatih Incekara, Maarten M. J. Wijnenga, Georgios Kapsas, Renske Gahrmann, Joost W Schouten, Hendrikus J. Dubbink, Arnaud J. P. E. Vincent, Martin J. Van Den Bent, Pim J. French, Stefan Klein, Yading Yuan, Sonam Sharma, Tzu-Chi Tseng, Saba Adabi, Simone P. Niclou, Olivier Keunen, Ann-Christin Hau, Martin Vallières, David Fortin, Martin Lepage, Bennett Landman, Karthik Ramadass, Kaiwen Xu, Silky Chotai, Lola B. Chambless, Akshitkumar Mistry, Reid C. Thompson, Yuriy Gusev, Krithika Bhuvaneshwar, Anousheh Sayah, Camelia Bencheqroun, Anas Belouali, Subha Madhavan, Thomas C. Booth, Alysha Chelliah, Marc Modat, Haris Shuaib, Carmen Dragos, Aly Abayazeed, Kenneth Kolodziej, Michael Hill, Ahmed Abbassy, Shady Gamal, Mahmoud Mekhaimar, Mohamed Qayati, Mauricio Reyes, Ji Eun Park, Jihye Yun, Ho Sung Kim, Abhishek Mahajan, Mark Muzi, Sean Benson, Regina G. H. Beets-Tan, Jonas Teuwen, Alejandro Herrera-Trujillo, Maria Trujillo, William Escobar, Ana Abello, Jose Bernal, Jhon Gómez, Joseph Choi, Stephen Baek, Yusung Kim, Heba Ismael, Bryan Allen, John M. Buatti, Aikaterini Kotrotsou, Hongwei Li, Tobias Weiss, Michael Weller, Andrea Bink, Bertrand Pouymayou, Hassan F. Shaykh, Joel Saltz, Prateek Prasanna, Sampurna Shrestha, Kartik M. Mani, David Payne, Tahsin Kurc, Enrique Pelaez, Heydy Franco-Maldonado, Francis Loayza, Sebastian Quevedo, Pamela Guevara, Esteban Torche, Cristobal Mendoza, Franco Vera, Elvis Ríos, Eduardo López, Sergio A. Velastin, Godwin Ogbole, Mayowa Soneye, Dotun Oyekunle, Olubunmi Odafe-Oyibotha, Babatunde Osobu, Mustapha Shu'aibu, Adeleye Dorcas, Farouk Dako, Amber L. Simpson, Mohammad Hamghalam, Jacob J. Peoples, Ricky Hu, Anh Tran, Danielle Cutler, Fabio Y. Moraes, Michael A. Boss, James Gimpel, Deepak Kattil Veettil, Kendall Schmidt, Brian Bialecki, Sailaja Marella, Cynthia Price, Lisa Cimino, Charles Apgar, Prashant Shah, Bjoern Menze, Jill S. Barnholtz-Sloan, Jason Martin, Spyridon Bakas

Department of Radiation Oncology Faculty Papers

Although machine learning (ML) has shown promise across disciplines, out-of-sample generalizability is concerning. This is currently addressed by sharing multi-site data, but such centralization is challenging/infeasible to scale due to various limitations. Federated ML (FL) provides an alternative paradigm for accurate and generalizable ML, by only sharing numerical model updates. Here we present the largest FL study to-date, involving data from 71 sites across 6 continents, to generate an automatic tumor boundary detector for the rare disease of glioblastoma, reporting the largest such dataset in the literature (n = 6, 314). We demonstrate a 33% delineation improvement for the surgically …

Complexity Of Progranulin Mechanisms Of Action In Mesothelioma, Elisa Ventura, Christopher Xie, Simone Buraschi, Antonino Belfiore, Renato V. Iozzo, Antonio Giordano, Andrea Morrione

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background: Mesothelioma is an aggressive disease with limited therapeutic options. The growth factor progranulin plays a critical role in several cancer models, where it regulates tumor initiation and progression. Recent data from our laboratories have demonstrated that progranulin and its receptor, EphA2, constitute an oncogenic pathway in bladder cancer by promoting motility, invasion and in vivo tumor formation. Progranulin and EphA2 are expressed in mesothelioma cells but their mechanisms of action are not well defined. In addition, there are no data establishing whether the progranulin/EphA2 axis is tumorigenic for mesothelioma cells.

Methods: The expression of progranulin in various mesothelioma cell …

A Cross-Sectional Study Of The Prevalence Of Anal Dysplasia Among Women With High-Grade Cervical, Vaginal, And Vulvar Dysplasia Or Cancer: The Panda Study, Samantha Batman, Craig A Messick, Andrea Milbourne, Ming Guo, Mark F Munsell, Joel Fokom-Domgue, Mila Salcedo, Ashish Deshmukh, Kristina R Dahlstrom, Mallory Ogburn, Anthony Price, Nicole D Fleming, Jolyn Taylor, Aaron Shafer, Lauren Cobb, Keith Sigel, Erich M Sturgis, Elizabeth Y Chiao, Kathleen M Schmeler

Faculty, Staff and Students Publications

BACKGROUND: High-risk human papillomavirus (HR-HPV) infection is a risk factor for anal cancer, yet no anal cancer screening guidelines exist for women with lower genital tract HPV-related disease. We sought to describe the prevalence of anal HR-HPV or cytologic abnormalities in such women.

METHODS: This cross-sectional study was performed between October 2018 and December 2021. Inclusion criteria were ≥21 years of age and a prior diagnosis of high-grade dysplasia/cancer of the cervix, vagina, or vulva. Participants underwent anal cytology and anal/cervicovaginal HR-HPV testing. Women with abnormal anal cytology were referred for high-resolution anoscopy (HRA).

RESULTS: 324 evaluable women were enrolled. …

Efficacy And Safety Of Pacritinib Vs Placebo For Patients With Severe Covid-19: A Phase 2 Randomized Clinical Trial, John Cafardi, Carole Miller, Howard Terebelo, Chad Tewell, Sadia Benzaquen, David Park, Pamela Egan, Daniel Lebovic, Kristen Pettit, Eric Whitman, Douglas Tremblay, Jonathan Feld, Sarah Buckley, Karisse Roman-Torres, Jennifer Smith, Adam Craig, John Mascarenhas

Einstein Health Papers

IMPORTANCE: The morbidity and mortality associated with COVID-19 remain high despite advances in standard of care therapy, and the role of anti-inflammatory agents that inhibit the interleukin 6/JAK2 pathway is still being elucidated.

OBJECTIVE: To evaluate the efficacy and safety of the oral JAK2/IRAK1 inhibitor pacritinib vs placebo in the treatment of adults with severe COVID-19.

DESIGN, SETTING, AND PARTICIPANTS: This phase 2, double-blind, placebo-controlled, randomized clinical trial enrolled hospitalized adult patients with severe COVID-19 at 21 centers across the US between June 2020 and February 2021, with approximately 1.5 months of safety follow-up per patient. Data analysis was performed …

Impact Of International Travel And Diarrhea On Gut Microbiome And Resistome Dynamics, Manish Boolchandani, Kevin S Blake, Drake H Tilley, Miguel M Cabada, Drew J Schwartz, Sanket Patel, Maria Luisa Morales, Rina Meza, Giselle Soto, Sandra D Isidean, Chad K Porter, Mark P Simons, Gautam Dantas

2020-Current year OA Pubs

International travel contributes to the global spread of antimicrobial resistance. Travelers' diarrhea exacerbates the risk of acquiring multidrug-resistant organisms and can lead to persistent gastrointestinal disturbance post-travel. However, little is known about the impact of diarrhea on travelers' gut microbiomes, and the dynamics of these changes throughout travel. Here, we assembled a cohort of 159 international students visiting the Andean city of Cusco, Peru and applied next-generation sequencing techniques to 718 longitudinally-collected stool samples. We find that gut microbiome composition changed significantly throughout travel, but taxonomic diversity remained stable. However, diarrhea disrupted this stability and resulted in an increased abundance …

How I Approach Leishmaniasis: Diagnosis And Treatment In The United States, Tara E Ness, Rachel Martin-Blais, Jill E Weatherhead

Faculty, Staff and Students Publications

Leishmaniasis is a vector-borne disease caused by over 20 species of obligate intracellular protozoa belonging to the genus Leishmania. Leishmaniasis has a global distribution, including in the United States, and can cause a spectrum of clinical syndromes, including cutaneous, mucosal, and visceral diseases depending on host factors and the infecting Leishmania spp. Accurate diagnosis, including Leishmania species identification, is an important step to guide the most appropriate therapeutic intervention. Antileishmanial therapy is dependent on the Leishmania spp. identified, the clinical syndrome, and the child's immune system. However, many treatment regimens for children have been extrapolated from adult clinical trials, which …

Human Papillomavirus Vaccine Administration Trends Among Commercially Insured Us Adults Aged 27-45 Years Before And After Advisory Committee On Immunization Practices Recommendation Change, 2007-2020, Ryan Suk, Kaiping Liao, Cici X Bauer, Catherine Basil, Meng Li

Faculty, Staff and Student Publications

IMPORTANCE: In 2019, the Advisory Committee on Immunization Practices (ACIP) recommended patient-clinician shared decision-making for human papillomavirus (HPV) vaccination in adults aged 27 to 45 years. Less is known about the HPV vaccine administration trends in this age group before and after this recommendation update.

OBJECTIVE: to examine the association between the ACIP recommendation update and the HPV vaccine administration among US adults aged 27 to 45 years.

DESIGN, SETTING, AND PARTICIPANTS: This large commercial claim-based retrospective cohort study used the Optum Clinformatics database for validated claims from January 1, 2007, through December 31, 2020. A total of 22 600 …

Hyperkalemia And Electrocardiogram Manifestations In End-Stage Renal Disease, Zubaid Rafique, Bryan Hoang, Heba Mesbah, Ryan Pappal, Frank W Peacock, Raul Juarez-Vela, Lukasz Szarpak, Dick C Kuo

Faculty, Staff and Students Publications

Hyperkalemia is one of the more common acute life-threatening metabolic emergencies. The aim of our study is to determine the correlation and accuracy of abnormal ECG parameters as a function of serum potassium concentration in the end-stage renal disease (ESRD) population. We performed a retrospective chart review of emergency department patients presenting with ESRD and receiving emergent hemodialysis treatment. A total of 96 patients, each with five independent ED visits, provided 480 sets of ECGs and electrolytes. Of these, four ECGs were excluded for inability to interpret, leaving a total of 476 patient encounters that met all inclusion criteria. Linear …

Active Dna Demethylation Promotes Cell Fate Specification And The Dna Damage Response, Dongpeng Wang, Wei Wu, Elsa Callen, Raphael Pavani, Nicholas Zolnerowich, Srikanth Kodali, Dali Zong, Nancy Wong, Santiago Noriega, William J Nathan, Gabriel Matos-Rodrigues, Raj Chari, Michael J Kruhlak, Ferenc Livak, Michael Ward, Keith Caldecott, Bruno Di Stefano, André Nussenzweig

Faculty, Staff and Students Publications

Neurons harbor high levels of single-strand DNA breaks (SSBs) that are targeted to neuronal enhancers, but the source of this endogenous damage remains unclear. Using two systems of postmitotic lineage specification-induced pluripotent stem cell-derived neurons and transdifferentiated macrophages-we show that thymidine DNA glycosylase (TDG)-driven excision of methylcytosines oxidized with ten-eleven translocation enzymes (TET) is a source of SSBs. Although macrophage differentiation favors short-patch base excision repair to fill in single-nucleotide gaps, neurons also frequently use the long-patch subpathway. Disrupting this gap-filling process using anti-neoplastic cytosine analogs triggers a DNA damage response and neuronal cell death, which is dependent on TDG. …

Myocardial Infarction With Nonobstructive Coronary Arteries In New-Onset Inflammatory Bowel Disease, Benjamin B. Claxton, George Sun, Ritu Nahar, Christopher Henry

Division of Gastroenterology and Hepatology Faculty Papers

No abstract provided.

Intraoperative Localization And Preservation Of Reading In Ventral Occipitotemporal Cortex, Oscar Woolnough, Kathryn M Snyder, Cale W Morse, Meredith J Mccarty, Samden D Lhatoo, Nitin Tandon

Faculty, Staff and Student Publications

OBJECTIVE: Resective surgery in language-dominant ventral occipitotemporal cortex (vOTC) carries the risk of causing impairment to reading. Because it is not on the lateral surface, it is not easily accessible for intraoperative mapping, and extensive stimulation mapping can be time-consuming. Here the authors assess the feasibility of using task-based electrocorticography (ECoG) recordings intraoperatively to help guide stimulation mapping of reading in vOTC.

METHODS: In 11 patients undergoing extraoperative, intracranial seizure mapping, the authors recorded induced broadband gamma activation (70-150 Hz) during a visual category localizer. In 2 additional patients, whose pathologies necessitated resections in language-dominant vOTC, task-based functional mapping was …

Heavy Metals As Risk Factors For Human Diseases - A Bayesian Network Approach, M Perrelli, R Wu, D J Liu, R G Lucchini, L Del Bosque-Plata, Michael Vergare, M P Akhter, J Ott, Claudia Gragnoli

Division of Endocrinology, Diabetes and Metabolic Diseases Faculty Papers

Modern industrial agricultural processes expose human beings to multifactorial environmental pollution including heightened levels of heavy metals. The effects of acute heavy metal exposures at toxic levels are usually known; they are tested for and treated promptly. The effects of low/moderate-level chronic heavy metal exposures are less known as they may be subclinical, and pathogenic effects may only manifest clinically over time under the disguise of a diagnosable disease or miscellaneous symptoms attributed to aging. Consequently, the health impact of low-moderate heavy metal exposure is unlikely to be identified. Furthermore, established heavy metal safety levels often fail to recognize the …

Comparing The Outcomes Of Face-To-Face And Synchronous Online Research Mentor Training Using Propensity Score Matching, Jenna Rogers, Xue Gong, Angela Byars-Winston, Melissa Mcdaniels, Nancy Thayer-Hart, Philip Cheng, Kelly Diggs-Andrews, Kermin J. Martínez-Hernández, Christine Pfund

Sleep Medicine Articles

In this study, propensity score matching (PSM) was conducted to examine differences in the effectiveness of research mentor training (RMT) implemented using two modes-face-to-face or synchronous online training. This study investigated each training mode and assessed participants' perceived gains in mentoring skills, ability to meet mentees' expectations, and overall quality of mentoring, as well as intention to make changes to their mentoring practices. Additional factors that may contribute to participant outcomes were also examined. In total, 152 mentors trained using a synchronous online platform and 655 mentors trained in in-person workshops were analyzed using the PSM method. Mentors were matched …

Social Networks, High-Risk Anal Hpv And Coinfection With Hiv In Young Sexual Minority Men, Kayo Fujimoto, Alan G Nyitray, Jacky Kuo, Jing Zhao, Lu-Yu Hwang, Elizabeth Chiao, Anna R Giuliano, John A Schneider, Aditya Khanna

Faculty, Staff and Student Publications

OBJECTIVES: Young sexual minority men (SMM) exhibit a high prevalence and incidence of high-risk genotypes of human papillomavirus (hrHPV) anal infections and a confluence of a high prevalence of HIV and rectal STIs. Social determinants of health (SDOHs) are linked to social network contexts that generate and maintain racial disparities in HIV and STIs. A network perspective was provided to advance our knowledge of drivers of genotype-specific hrHPV infection and coinfection with HIV. The study also examined whether socially connected men are infected with the same high-risk HPV genotypes and, if so, whether this tendency is conditioned on coinfection with …

Perceived Efficacy, Reduced Prescription Drug Use, And Minimal Side Effects Of Cannabis In Patients With Chronic Orthopedic Pain, Ari Greis, Eric Larsen, Conan Liu, Bryan Renslo, Anjithaa Radakrishnan, Adrianne R Wilson-Poe

Rothman Institute Papers

Introduction: Although cannabis is widely used for the treatment of chronic pain, most research relies on patient self-report and few studies have objectively quantified its efficacy and side effects. Extant inventories for measuring cannabis use were not designed to capture the medically relevant features of cannabis use, but rather were designed to detect problematic use or cannabis use disorder. Thus, we sought to capture the medically relevant features of cannabis use in a population of patients with orthopedic pain and pair these data with objective measures of pain and prescription drug use. Materials and Methods: In this prospective observational study, …

Technology-Enhanced In Vivo Exposures In Prolonged Exposure For Ptsd: A Pilot Randomized Controlled Trial, Tanya C Saraiya, Amber M Jarnecke, Alex O Rothbaum, Bethany Wangelin, Lisa M Mcteague, Ron Acierno, Delisa G Brown, Emily Bristol, Hayley Feigl, Mclain Reese, Adam R Cobb, Bill Harley, Robert J Adams, Sudie E Back

Faculty, Staff and Student Publications

In vivo exposures (IVEs) are a key component of exposure-based treatments, during which patients approach fear-provoking, yet safe, situations in "real life." This pilot study assessed the use of a wearable technology (Bio Ware) during IVEs to enhance Prolonged Exposure (PE) therapy for PTSD. Bio Ware provides a clinician dashboard with real-time physiological and subjective data for clinicians to use for virtually guided IVEs. Participants (N = 40) were randomized to a Guided group that received standard PE and virtual, clinician-guided IVEs with the Bio Ware device, or a Non-Guided group that received standard PE and used the Bio Ware …

Low-Dose Aspirin For Venous Thromboembolism Prophylaxis Is Associated With Lower Rates Of Periprosthetic Joint Infection After Total Joint Arthroplasty, Farideh Najafi, Joseph K. Kendal, Nicholas V. Peterson, Kerri-Anne Ciesielka, Camilo Restrepo, Javad Parvizi, Nicholas M. Bernthal

Department of Orthopaedic Surgery Faculty Papers

BACKGROUND: Aspirin as a venous thromboembolism (VTE) prophylactic agent has been shown to have antistaphylococcal and antibiofilm roles. Optimal acetylsalicylic acid (ASA) dosage would facilitate antimicrobial effects while avoiding over-aggressive inhibition of platelet antimicrobial function. Our purpose was to determine the periprosthetic joint infection (PJI) rate after total joint arthroplasty in patients receiving low-dose ASA (81 mg twice a day), in comparison to high-dose ASA (325 mg twice a day).

METHODS: We conducted a retrospective cohort study between 2008 and 2020. Eligible patients were older than 18 years, underwent primary total joint arthroplasty, both total knee arthroplasty and total hip …

A Minimal Role For Synonymous Variation In Human Disease, Ryan S Dhindsa, Quanli Wang, Dimitrios Vitsios, Oliver S Burren, Fengyuan Hu, James E Dicarlo, Leonid Kruglyak, Daniel G Macarthur, Matthew E Hurles, Slavé Petrovski

Duncan NRI Faculty and Staff Publications

Synonymous mutations change the DNA sequence of a gene without affecting the amino acid sequence of the encoded protein. Although some synonymous mutations can affect RNA splicing, translational efficiency, and mRNA stability, studies in human genetics, mutagenesis screens, and other experiments and evolutionary analyses have repeatedly shown that most synonymous variants are neutral or only weakly deleterious, with some notable exceptions. Based on a recent study in yeast, there have been claims that synonymous mutations could be as important as nonsynonymous mutations in causing disease, assuming the yeast findings hold up and translate to humans. Here, we argue that there …

A Framework For Detecting Noncoding Rare-Variant Associations Of Large-Scale Whole-Genome Sequencing Studies, Zilin Li, Xihao Li, Hufeng Zhou, Sheila M Gaynor, Margaret Sunitha Selvaraj, Theodore Arapoglou, Corbin Quick, Yaowu Liu, Han Chen, Ryan Sun, Rounak Dey, Donna K Arnett, Paul L Auer, Lawrence F Bielak, Joshua C Bis, Thomas W Blackwell, John Blangero, Eric Boerwinkle, Donald W Bowden, Jennifer A Brody, Brian E Cade, Matthew P Conomos, Adolfo Correa, L Adrienne Cupples, Joanne E Curran, Paul S De Vries, Ravindranath Duggirala, Nora Franceschini, Barry I Freedman, Harald H H Göring, Xiuqing Guo, Rita R Kalyani, Charles Kooperberg, Brian G Kral, Leslie A Lange, Bridget M Lin, Ani Manichaikul, Alisa K Manning, Lisa W Martin, Rasika A Mathias, James B Meigs, Braxton D Mitchell, May E Montasser, Alanna C Morrison, Take Naseri, Jeffrey R O'Connell, Nicholette D Palmer, Patricia A Peyser, Bruce M Psaty, Laura M Raffield, Susan Redline, Alexander P Reiner, Muagututi'a Sefuiva Reupena, Kenneth M Rice, Stephen S Rich, Jennifer A Smith, Kent D Taylor, Margaret A Taub, Ramachandran S Vasan, Daniel E Weeks, James G Wilson, Lisa R Yanek, Wei Zhao, Jerome I Rotter, Cristen J Willer, Pradeep Natarajan, Gina M Peloso, Xihong Lin

Faculty, Staff and Student Publications

Large-scale whole-genome sequencing studies have enabled analysis of noncoding rare-variant (RV) associations with complex human diseases and traits. Variant-set analysis is a powerful approach to study RV association. However, existing methods have limited ability in analyzing the noncoding genome. We propose a computationally efficient and robust noncoding RV association detection framework, STAARpipeline, to automatically annotate a whole-genome sequencing study and perform flexible noncoding RV association analysis, including gene-centric analysis and fixed window-based and dynamic window-based non-gene-centric analysis by incorporating variant functional annotations. In gene-centric analysis, STAARpipeline uses STAAR to group noncoding variants based on functional categories of genes and incorporate …

Human Loss-Of-Function Variants In The Serotonin 2c Receptor Associated With Obesity And Maladaptive Behavior, Yang He, Bas Brouwers, Hesong Liu, Hailan Liu, Katherine Lawler, Edson Mendes De Oliveira, Dong-Kee Lee, Yongjie Yang, Aaron R Cox, Julia M Keogh, Elana Henning, Rebecca Bounds, Aliki Perdikari, Vikram Ayinampudi, Chunmei Wang, Meng Yu, Longlong Tu, Nan Zhang, Na Yin, Junying Han, Nikolas A Scarcelli, Zili Yan, Kristine M Conde, Camille Potts, Jonathan C Bean, Mengjie Wang, Sean M Hartig, Lan Liao, Jianming Xu, Inês Barroso, Jacek Mokrosinski, Yong Xu, I Sadaf Farooqi

Children’s Nutrition Research Center Staff Publications

Serotonin reuptake inhibitors and receptor agonists are used to treat obesity, anxiety and depression. Here we studied the role of the serotonin 2C receptor (5-HT2CR) in weight regulation and behavior. Using exome sequencing of 2,548 people with severe obesity and 1,117 control individuals without obesity, we identified 13 rare variants in the gene encoding 5-HT2CR (HTR2C) in 19 unrelated people (3 males and 16 females). Eleven variants caused a loss of function in HEK293 cells. All people who carried variants had hyperphagia and some degree of maladaptive behavior. Knock-in male mice harboring a human loss-of-function HTR2C variant developed …

Fulminant Lung Fibrosis In Non-Resolvable Covid-19 Requiring Transplantation, Soma S K Jyothula, Andrew Peters, Yafen Liang, Weizhen Bi, Pooja Shivshankar, Simon Yau, Puneet S Garcha, Xiaoyi Yuan, Bindu Akkanti, Scott Collum, Nancy Wareing, Rajarajan A Thandavarayan, Fernando Poli De Frias, Ivan O Rosas, Bihong Zhao, L Maximilian Buja, Holger K Eltzschig, Howard J Huang, Harry Karmouty-Quintana

Faculty, Staff and Student Publications

BACKGROUND: Coronavirus Disease 2019 (COVID-19) can lead to the development of acute respiratory distress syndrome (ARDS). In some patients with non-resolvable (NR) COVID-19, lung injury can progress rapidly to the point that lung transplantation is the only viable option for survival. This fatal progression of lung injury involves a rapid fibroproliferative response and takes on average 15 weeks from initial symptom presentation. Little is known about the mechanisms that lead to this fulminant lung fibrosis (FLF) in NR-COVID-19.

METHODS: Using a pre-designed unbiased PCR array for fibrotic markers, we analyzed the fibrotic signature in a subset of NR-COVID-19 lungs. We …

Dietary And Complementary Feeding Practices Of Us Infants, 6 To 12 Months: A Narrative Review Of The Federal Nutrition Monitoring Data, Regan L Bailey, Jaime S Stang, Teresa A Davis, Timothy S Naimi, Barbara O Schneeman, Kathryn G Dewey, Sharon M Donovan, Rachel Novotny, Ronald E Kleinman, Elsie M Taveras, Lydia Bazzano, Linda G Snetselaar, Janet De Jesus, Kellie O Casavale, Eve E Stoody, Joseph D Goldman, Alanna J Moshfegh, Donna G Rhodes, Kirsten A Herrick, Kristin Koegel, Cria G Perrine, Tusarebecca Pannucci

Children’s Nutrition Research Center Staff Publications

Complementary foods and beverages (CFBs) are key components of an infant’s diet in the second 6 months of life. This article summarizes nutrition and feeding practices examined by the 2020 Dietary Guidelines Advisory Committees during the CFB life stage. Breastfeeding initiation is high (84%), but exclusive breastfeeding at 6 months (26%) is below the Healthy People 2030 goal (42%). Most infants (51%) are introduced to CFBs sometime before 6 months. The primary mode of feeding (ie, human milk fed [HMF]; infant formula or mixed formula and human milk fed [FMF]) at the initiation of CFBs is associated with the timing …

International Pooled Patient-Level Meta-Analysis Of Ketamine Infusion For Depression: In Search Of Clinical Moderators, Rebecca B Price, Nicholas Kissel, Andrew Baumeister, Rebecca Rohac, Mary L Woody, Elizabeth D Ballard, Carlos A Zarate, William Deakin, Chadi G Abdallah, Adriana Feder, Dennis S Charney, Michael F Grunebaum, J John Mann, Sanjay J Mathew, Bronagh Gallagher, Declan M Mcloughlin, James W Murrough, Suresh Muthukumaraswamy, Rebecca Mcmillan, Rachael Sumner, George Papakostas, Maurizio Fava, Rebecca Hock, Jennifer L Phillips, Pierre Blier, Paulo Shiroma, Peter Šóš, Tung-Ping Su, Mu-Hong Chen, Mikael Tiger, Johan Lundberg, Samuel T Wilkinson, Meredith L Wallace

Children’s Nutrition Research Center Staff Publications

Depression is disabling and highly prevalent. Intravenous (IV) ketamine displays rapid-onset antidepressant properties, but little is known regarding which patients are most likely to benefit, limiting personalized prescriptions. We identified randomized controlled trials of IV ketamine that recruited individuals with a relevant psychiatric diagnosis (e.g., unipolar or bipolar depression; post-traumatic stress disorder), included one or more control arms, did not provide any other study-administered treatment in conjunction with ketamine (although clinically prescribed concurrent treatments were allowable), and assessed outcome using either the Montgomery-Åsberg Depression Rating Scale or the Hamilton Rating Scale for Depression (HRSD-17). Individual patient-level data for at least …

Association Of Initial Sars-Cov-2 Test Positivity With Patient-Reported Well-Being 3 Months After A Symptomatic Illness., Lauren E Wisk, Michael A Gottlieb, Erica S Spatz, Huihui Yu, Ralph C Wang, B. H. Slovis, Sharon Saydah, Ian D Plumb, Kelli N O'Laughlin, Juan Carlos C Montoy, Samuel A Mcdonald, Zhenqiu Lin, Jin-Mann S Lin, Katherine Koo, Ahamed H Idris, Ryan M Huebinger, Mandy J Hill, Nicole L Gentile, Anna Marie Chang, Jill Anderson, Bala Hota, Arjun K Venkatesh, Robert A Weinstein, Joann G Elmore, Graham Nichol

Department of Emergency Medicine Faculty Papers

IMPORTANCE: Long-term sequelae after symptomatic SARS-CoV-2 infection may impact well-being, yet existing data primarily focus on discrete symptoms and/or health care use.

OBJECTIVE: To compare patient-reported outcomes of physical, mental, and social well-being among adults with symptomatic illness who received a positive vs negative test result for SARS-CoV-2 infection.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study was a planned interim analysis of an ongoing multicenter prospective longitudinal registry study (the Innovative Support for Patients With SARS-CoV-2 Infections Registry [INSPIRE]). Participants were enrolled from December 11, 2020, to September 10, 2021, and comprised adults (aged ≥18 years) with acute symptoms suggestive …

Covid-19 Vaccine Equity: Codesigning Public Health Interventions With Community Partners, Eva Varotsis, Lauren Schlegel, B. H. Slovis, Patricia C. Henwood, Sandra E Brooks, Robert S. Pugliese, Bon Ku, Morgan Hutchinson

Department of Emergency Medicine Faculty Papers

No abstract provided.

Clinical And Economic Evaluation Of A Proteomic Biomarker Preterm Birth Risk Predictor: Cost-Effectiveness Modeling Of Prenatal Interventions Applied To Predicted Higher-Risk Pregnancies Within A Large And Diverse Cohort, Julja Burchard, Glenn R Markenson, George R Saade, Louise C Laurent, Kent D Heyborne, Dean V Coonrod, Corina N Schoen, Jason K. Baxter, David M Haas, Sherri A Longo, Scott A Sullivan, Sarahn M Wheeler, Leonardo M Pereira, Kim A Boggess, Angela F Hawk, Amy H Crockett, Ryan Treacy, Angela C Fox, Ashoka D Polpitiya, Tracey C Fleischer, Thomas J Garite, J Jay Boniface, John A F Zupancic, Gregory C Critchfield, Paul E Kearney

Department of Obstetrics and Gynecology Faculty Papers

Objectives: Preterm birth occurs in more than 10% of U.S. births and is the leading cause of U.S. neonatal deaths, with estimated annual costs exceeding $25 billion USD. Using real-world data, we modeled the potential clinical and economic utility of a prematurity-reduction program comprising screening in a racially and ethnically diverse population with a validated proteomic biomarker risk predictor, followed by case management with or without pharmacological treatment.

Methods: The ACCORDANT microsimulation model used individual patient data from a prespecified, randomly selected sub-cohort (N = 847) of a multicenter, observational study of U.S. subjects receiving standard obstetric care with …