Digital Commons Network^™

Clinical Utility Of Plasma Microbial Cell-Free Dna Sequencing In Determining Microbiologic Etiology Of Infectious Syndromes In Solid Organ Transplant Recipients, Jesal R Shah, Muhammad Rizwan Sohail, Todd Lasco, John A Goss, Mayar Al Mohajer, Sarwat Khalil

Faculty, Staff and Students Publications

BACKGROUND: Metagenomic next-generation sequencing (mNGS) is increasingly being used for microbial detection in various infectious syndromes. However, data regarding the use of mNGS in solid organ transplant recipients (SOTR) are lacking.

OBJECTIVES: To describe and analyze real-world clinical impact of mNGS using plasma microbial cell-free DNA (mcfDNA) in SOTR.Design: Retrospectively reviewed all adult SOTR who underwent mNGS testing using plasma mcfDNA at Baylor St Luke's Medical Center from March 2017 to February 2023.

METHODS: Clinical impact (positive, neutral, and negative) was assessed using standardized objective criteria. Three Infectious Diseases physicians independently performed clinical adjudication to determine the correlation of mcfDNA …

The Impact Of The Filmarray Meningitis/Encephalitis Panel On Empiric Antibiotic Prescriptions In Patients With Suspected Community-Acquired Meningitis, Aaron Pathak, Caitlynn Pham, Sabra Shay, Todd Lasco, Mayar Al Mohajer

Faculty, Staff and Students Publications

The BioFire® FilmArray® meningitis/encephalitis (FA/ME) panel provides rapid testing for common cerebrospinal fluid pathogens. We compared empiric antibiotic utilization between patients with suspected community-acquired meningitis with and without an FA/ME panel ordered. No significant differences in antibiotic use were found.

Comparison Of Complication Types In Patients Receiving Vesicant Intravenous Antimicrobials Or Vasopressors Via Midlines And Peripherally Inserted Central Catheters, Bryan Grigg, Nishant Varghese, Christi Knapp, Sabra L Shay, Geraldine Jones, James P Herlihy, Prasad Manian, Bradley Lembcke, Mayar Al Mohajer

Faculty, Staff and Students Publications

We assessed adverse events in hospitalized patients receiving selected vesicant antibiotics or vasopressors administered through midline catheters or peripherally inserted central catheters (PICC). The rates of catheter-related bloodstream infections, thrombosis, and overall events were similar across the two groups, while occlusion was higher in the PICC group.

Detection Of Invasive Bartonella Infections With Next-Generation Sequencing Of Microbial Cell-Free Dna, Fernando H Centeno, Ahmed M Hamdi, Todd M Lasco, Mayar Al Mohajer

Faculty, Staff and Students Publications

We report 9 patients with invasive Bartonella infections, including 5 with endocarditis, who were diagnosed with microbial cell-free DNA next-generation sequencing and Bartonella serology studies. Diagnosis with plasma mcfDNA NGS enabled a faster clinical and laboratory diagnosis in 8 patients. Prompt diagnosis impacted antibiotic management in all 9 patients.

Creating A Plasma Coordination Center To Support Covid-19 Outpatient Trials Across A National Network Of Hospital Blood Banks, Anusha Yarava, Christi Marshall, David E Reichert, Aaron Ye, Preeti Khanal, Sanford H Robbins, Bruce S Sachais, David Oh, Ryan A Metcalf, Kathleen Conry-Cantilena, Karen King, Meredith Reyes, Jill Adamski, Marisa B Marques, Minh-Ha Tran, Elizabeth S Allen, Daniel Pach, Neil Blumberg, Rhonda Hobbs, Tammon Nash, Aarthi G Shenoy, Giselle S Mosnaim, Yuriko Fukuta, Bela Patel, Sonya L Heath, Adam C Levine, Barry R Meisenberg, Shweta Anjan, Moises A Huaman, Janis E Blair, Judith S Currier, James H Paxton, William Rausch, Kevin Oei, Matthew Abinante, Donald N Forthal, Martin S Zand, Seble G Kassaye, Edward R Cachay, Kelly A Gebo, Shmuel Shoham, Arturo Casadevall, Nichol A Mcbee, Daniel Amirault, Ying Wang, Erica Hopkins, David M Shade, Oliver Layendecker, Sabra L Klein, Han-Sol Park, John S Lee, Patrizio Caturegli, Jay S Raval, Daniel Cruser, Alyssa F Ziman, Jonathan Gerber, Thomas J Gniadek, Evan M Bloch, Aaron A R Tobian, Daniel F Hanley, David J Sullivan, Karen Lane

Faculty, Staff and Students Publications

INTRODUCTION: In response to the COVID-19 pandemic, we rapidly implemented a plasma coordination center, within two months, to support transfusion for two outpatient randomized controlled trials. The center design was based on an investigational drug services model and a Food and Drug Administration-compliant database to manage blood product inventory and trial safety.

METHODS: A core investigational team adapted a cloud-based platform to randomize patient assignments and track inventory distribution of control plasma and high-titer COVID-19 convalescent plasma of different blood groups from 29 donor collection centers directly to blood banks serving 26 transfusion sites.

RESULTS: We performed 1,351 transfusions in …

Bridging The Gap: Assessing Cmv Dnaemia In Kidney Transplant Recipients With Previous Solid Organ Transplants, Goni Katz-Greenberg, Julie M Steinbrink, Krishna Shah, Jennifer S Byrns

Faculty, Staff and Students Publications

Cytomegalovirus (CMV) infection poses a significant threat to solid organ transplant (SOT) recipients and can lead to various complications and adverse outcomes. In an effort to prevent CMV infection, it is common to utilize prophylactic strategies, including antiviral medications such as valganciclovir, especially for high-risk patients. Risk factors for CMV infection in kidney transplant recipients (KTRs) include CMV mismatch between donor and recipient (i.e., donor positive, recipient negative), and intensity of immunosuppression, such as the use of T-cell depleting agents. However, little attention has been given to KTRs with a history of prior SOTs, despite their prolonged exposure to immunosuppressive …

Ibrutinib-Associated Cutaneous Mucormycosis Due To An Apophysomyces Species: Report Of A Case And Review Of The Literature, Trung Minh Nguyen, Eva Amenta, Lynne Chapman, Sarvari Yellapragada, Bhuvaneswari Krishnan, Jonathan Lim, Richard J Hamill

Faculty, Staff and Students Publications

The use of ibrutinib, a Bruton tyrosine kinase inhibitor, has been associated with invasive fungal infections (IFIs). We describe a case of Apophysomyces infection associated with long-term use of ibrutinib for the treatment of chronic lymphocytic leukemia as well as perform a literature review of Mucormycosis infections in patients on ibrutinib. Our review found that the onset of IFI can occur within months to years of starting tyrosine kinase inhibitors. These reports provide a more complete picture of the risk of IFI while patients are on ibrutinib. Our case also demonstrates the utility of molecular techniques in the diagnosis of …

Human Plcg2 Haploinsufficiency Results In A Novel Natural Killer Cell Immunodeficiency, Joshua B Alinger, Emily M Mace, Justin R Porter, Annelise Y Mah-Som, Allyssa L Daugherty, Stephanie Li, Allison A Throm, Jeanette T Pingel, Nermina Saucier, Albert Yao, Ivan K Chinn, James R Lupski, Mohammad Ehlayel, Michael Keller, Greg R Bowman, Megan A Cooper, Jordan S Orange, Anthony R French

Faculty, Staff and Students Publications

Background:

Although most individuals effectively control herpesvirus infections, some suffer from severe and/or recurrent infections. A subset of these patients possess defects in NK cells, lymphocytes which recognize and lyse herpesvirus-infected cells; however, the genetic etiology is rarely diagnosed. PLCG2 encodes a signaling protein in NK cell and B cell signaling. Dominant-negative or gain-of-function variants in PLCG2 cause cold urticaria, antibody deficiency, and autoinflammation. However, loss-of-function variants and haploinsufficiency have not been reported to date.

Objective:

We aimed to identify the genetic cause of NK cell immunodeficiency in two families, and herein describe the functional consequences of two novel loss-of-function …

Development, Implementation, And Evaluation Of Three Outreach Events To Improve Covid-19 Vaccine Uptake Among Racial And Ethnic Minority Communities In Houston, Texas, 2022, Carmin Munoz-Lavanderos, Abiodun Oluyomi, Omar Rosales, Norvin Hernandez, Nana Mensah-Bonsu, Hoda Badr

Faculty, Staff and Students Publications

OBJECTIVES: Lack of access to timely, accurate, and linguistically appropriate COVID-19 information has complicated the dissemination of evidence-based information and contributed to vaccine hesitancy among racial and ethnic minority groups in the United States. We developed community events that provided outreach, education, and access to COVID-19 vaccination to overcome vaccine hesitancy in these communities.

METHODS: Using spatial analysis techniques, we identified 3 communities with low vaccine uptake in Houston, Texas, in fall 2021; engaged 20 stakeholders from these communities via 4 focus groups to understand barriers to vaccination; and developed and implemented 3 COVID-19 vaccine education and outreach events tailored …

Clinical Evaluation Of A Fully Electronic Microfluidic White Blood Cell Analyzer, Jianye Sui, Zhongtian Lin, Shahriar Azizpour, Fei Chen, Sunanda Gaur, Kelly Keene, Farzad Soleimani, Tanaya Bhowmick, Zubaid Rafique, Mehdi Javanmard

Faculty, Staff and Students Publications

The White Blood Cell (WBC) count is one of the key parameters signaling the health of the immune system. Abnormal WBC counts often signal a systemic insult to the body such as an underlying infection or an adverse side effect to medication. Typically, the blood collected is sent to a central lab for testing, and results come back within hours, which is often inconvenient and may delay time-sensitive diagnosis or treatment. Here, we present the CytoTracker, a fully electronic, microfluidic based instant WBC analyzer with the potential to be used at point-of-care. The CytoTracker is a lightweight, portable, affordable platform …

Posttransplantation Late Complications Increase Over Time For Patients With Scid: A Primary Immune Deficiency Treatment Consortium (Pidtc) Landmark Study, Hesham Eissa, Monica S Thakar, Ami J Shah, Brent R Logan, Linda M Griffith, Huaying Dong, Roberta E Parrott, Richard J O'Reilly, Jasmeen Dara, Neena Kapoor, Lisa Forbes Satter, Sharat Chandra, Malika Kapadia, Shanmuganathan Chandrakasan, Alan Knutsen, Soma C Jyonouchi, Lyndsay Molinari, Ahmad Rayes, Christen L Ebens, Pierre Teira, Blachy J Dávila Saldaña, Lauri M Burroughs, Sonali Chaudhury, Deepak Chellapandian, Alfred P Gillio, Fredrick Goldman, Harry L Malech, Kenneth Desantes, Geoff D E Cuvelier, Jacob Rozmus, Ralph Quinones, Lolie C Yu, Larisa Broglie, Victor Aquino, Evan Shereck, Theodore B Moore, Mark T Vander Lugt, Talal I Mousallem, Joeseph H Oved, Morna Dorsey, Hisham Abdel-Azim, Caridad Martinez, Jacob H Bleesing, Susan Prockop, Donald B Kohn, Jeffrey J Bednarski, Jennifer Leiding, Rebecca A Marsh, Troy Torgerson, Luigi D Notarangelo, Sung-Yun Pai, Michael A Pulsipher, Jennifer M Puck, Christopher C Dvorak, Elie Haddad, Rebecca H Buckley, Morton J Cowan, Jennifer Heimall

Faculty, Staff and Students Publications

Background: The Primary Immune Deficiency Treatment Consortium (PIDTC) enrolled children in the United States and Canada onto a retrospective multicenter natural history study of hematopoietic cell transplantation (HCT).

Objective: We investigated outcomes of HCT for severe combined immunodeficiency (SCID).

Methods: We evaluated the chronic and late effects (CLE) after HCT for SCID in 399 patients transplanted from 1982 to 2012 at 32 PIDTC centers. Eligibility criteria included survival to at least 2 years after HCT without need for subsequent cellular therapy. CLE were defined as either conditions present at any time before 2 years from HCT that remained unresolved (chronic), …

A Transcriptomic Biomarker Predicting Linezolid-Associated Neuropathy During Treatment Of Drug-Resistant Tuberculosis, Nika Zielinski, Dragos Baiceanu, Antonela Dragomir, Jan Heyckendorf, Elmira Ibraim, Niklas Köhler, Christoph Leschczyk, Cristina Popa, Andrea Rachow, Jens Sachsenweger, Patricia Sanchez Carballo, Dagmar Schaub, Hajo Zeeb, Begna Tulu, Andrew R Dinardo, Christoph Lange, Maja Reimann

Faculty, Staff and Students Publications

BACKGROUND: Neuropathic adverse events occur frequently in linezolid-containing regimens, some of which remain irreversible after drug discontinuation.

OBJECTIVE: We aimed to identify and validate a host RNA-based biomarker that can predict linezolid-associated neuropathy before multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) treatment initiation and to identify genes and pathways that are associated with linezolid-associated neuropathy.

METHODS: Adult patients initiating MDR/RR-TB treatment including linezolid were prospectively enrolled in 3 independent cohorts in Germany. Clinical data and whole blood RNA for transcriptomic analysis were collected. The primary outcome was linezolid-associated optic and/or peripheral neuropathy. A random forest algorithm was used for biomarker identification. The biomarker was …

Divergent Responses Of Human Intestinal Organoid Monolayers Using Commercial In Vitro Cytotoxicity Assays, Miranda A Lewis, Ketki Patil, Khalil Ettayebi, Mary K Estes, Robert L Atmar, Sasirekha Ramani

Faculty, Staff and Students Publications

In vitro models, such as primary cells and continuous cell lines routinely used for evaluating drug candidates, have limitations in their translational relevance to human diseases. Organotypic cultures are increasingly being used to assess therapeutics for various cancers and infectious diseases. Monitoring drug cytotoxicity in cell cultures is crucial in drug development, and several commercially available kits for cytotoxicity assessment offer distinct advantages and limitations. Given the complexity of organoid cultures, including donor-driven variability, we investigated drug-treated, tissue stem cell-derived human intestinal organoid responses with commonly used cell cytotoxicity assay kits. Using seven different compounds, we compared the cytotoxicity assay …

Inference Of Phylogenetic Trees Directly From Raw Sequencing Reads Using Read2tree, David Dylus, Adrian Altenhoff, Sina Majidian, Fritz J Sedlazeck, Christophe Dessimoz

Faculty, Staff and Students Publications

Current methods for inference of phylogenetic trees require running complex pipelines at substantial computational and labor costs, with additional constraints in sequencing coverage, assembly and annotation quality, especially for large datasets. To overcome these challenges, we present Read2Tree, which directly processes raw sequencing reads into groups of corresponding genes and bypasses traditional steps in phylogeny inference, such as genome assembly, annotation and all-versus-all sequence comparisons, while retaining accuracy. In a benchmark encompassing a broad variety of datasets, Read2Tree is 10-100 times faster than assembly-based approaches and in most cases more accurate-the exception being when sequencing coverage is high and reference …

Case Report: P40phox Deficiency Underlying Pediatric-Onset Systemic Lupus Erythematosus, Alejandro Nieto-Patlán, Natalia S Fernández Dávila, Yuqing Wang, Michelle Zelnick, Eyal Muscal, Martha Curry, James R Lupski, Steven M Holland, Bo Yuan, Douglas B Kuhns, Tiphanie P Vogel, Ivan K Chinn

Faculty, Staff and Students Publications

Introduction

Systemic lupus erythematosus is a multi-faceted autoimmune disorder of complex etiology. Pre-pubertal onset of pediatric systemic lupus erythematosus (pSLE) is uncommon and should raise suspicion for a genetic driver of disease. Autosomal recessive p40^phox deficiency is a rare immunologic disorder characterized by defective but not abolished NADPH oxidase activity with residual production of reactive oxygen species (ROS) by phagocytic cells.

Case presentation

We report the case of a now 18-year-old female with pSLE onset at 7 years of age. She presented with recurrent fever and malar rash. Aspects of her immune dysregulation over time have included typical pSLE …

Translational And Oncologic Significance Of Tertiary Lymphoid Structures In Pancreatic Adenocarcinoma, Zachary Gao, Joseph Azar, Huili Zhu, Sophia Williams-Perez, Sung Wook Kang, Celia Marginean, Mark P Rubinstein, Shalini Makawita, Hyun-Sung Lee, E Ramsay Camp

Faculty, Staff and Students Publications

Pancreatic adenocarcinoma (PDAC) is an aggressive tumor with poor survival and limited treatment options. PDAC resistance to immunotherapeutic strategies is multifactorial, but partially owed to an immunosuppressive tumor immune microenvironment (TiME). However, the PDAC TiME is heterogeneous and harbors favorable tumor-infiltrating lymphocyte (TIL) populations. Tertiary lymphoid structures (TLS) are organized aggregates of immune cells that develop within non-lymphoid tissue under chronic inflammation in multiple contexts, including cancers. Our current understanding of their role within the PDAC TiME remains limited; TLS are complex structures with multiple anatomic features such as location, density, and maturity that may impact clinical outcomes such as …

Structure And Funding Of Clinical Informatics Fellowships: A National Survey Of Program Directors, Tushar N Patel, Aaron J Chaise, John J Hanna, Kunal P Patel, Karl M Kochendorfer, Richard J Medford, Dara E Mize, Edward R Melnick, Jonathan D Hron, Kenneth Youens, Deepti Pandita, Michael G Leu, Gregory A Ator, Feliciano Yu, Nicholas Genes, Carrie K Baker, Douglas S Bell, Joshua M Pevnick, Steven A Conrad, Aarti R Chandawarkar, Kendall M Rogers, David C Kaelber, Ila R Singh, Bruce P Levy, John T Finnell, Joseph Kannry, Natalie M Pageler, Vishnu Mohan, Christoph U Lehmann

Faculty, Staff and Students Publications

BACKGROUND: In 2011, the American Board of Medical Specialties established clinical informatics (CI) as a subspecialty in medicine, jointly administered by the American Board of Pathology and the American Board of Preventive Medicine. Subsequently, many institutions created CI fellowship training programs to meet the growing need for informaticists. Although many programs share similar features, there is considerable variation in program funding and administrative structures.

OBJECTIVES: The aim of our study was to characterize CI fellowship program features, including governance structures, funding sources, and expenses.

METHODS: We created a cross-sectional online REDCap survey with 44 items requesting information on program administration, …

Targeting Sars-Cov-2 Nonstructural Protein 3: Function, Structure, Inhibition, And Perspective In Drug Discovery, Xin Li, Yongcheng Song

Faculty, Staff and Students Publications

As a highly contagious human pathogen, severe acute respiratory syndrome-associated coronavirus-2 (SARS-CoV-2) has infected billions of people worldwide with more than 6 million deaths. With several effective vaccines and antiviral drugs now available, the SARS-CoV-2 pandemic been brought under control. However, a new pathogenic coronavirus could emerge in the future, given the zoonotic nature of this virus. Natural evolution and drug-induced mutations of SARS-CoV-2 also require continued efforts for new anti-coronavirus drugs. Nonstructural protein (nsp) 3 of CoVs is a large, multifunctional protein, containing a papain-like protease (PLpro) and a macrodomain (Mac1), which are essential for viral replication. Here, we …

Advances In Nanoprobes For Molecular Mri Of Alzheimer’S Disease, Parag Parekh, Andrew A Badachhape, Eric A Tanifum, Ananth V Annapragada, Ketan B Ghaghada

Faculty, Staff and Students Publications

Alzheimer's disease is the most common cause of dementia and a leading cause of mortality in the elderly population. Diagnosis of Alzheimer's disease has traditionally relied on evaluation of clinical symptoms for cognitive impairment with a definitive diagnosis requiring post-mortem demonstration of neuropathology. However, advances in disease pathogenesis have revealed that patients exhibit Alzheimer's disease pathology several decades before the manifestation of clinical symptoms. Magnetic resonance imaging (MRI) plays an important role in the management of patients with Alzheimer's disease. The clinical availability of molecular MRI (mMRI) contrast agents can revolutionize the diagnosis of Alzheimer's disease. In this article, we …

Etiology Of Hospital Mortality In Children Living In Low- And Middle-Income Countries: A Systematic Review And Meta-Analysis, Teresa B Kortz, Rishi P Mediratta, Audrey M Smith, Katie R Nielsen, Asya Agulnik, Stephanie Gordon Rivera, Hailey Reeves, Nicole F O'Brien, Jan Hau Lee, Qalab Abbas, Jonah E Attebery, Tigist Bacha, Emaan G Bhutta, Carter J Biewen, Jhon Camacho-Cruz, Alvaro Coronado Muñoz, Mary L Dealmeida, Larko Domeryo Owusu, Yudy Fonseca, Shubhada Hooli, Hunter Wynkoop, Mara Leimanis-Laurens, Deogratius Nicholaus Mally, Amanda M Mccarthy, Andrew Mutekanga, Carol Pineda, Kenneth E Remy, Sara C Sanders, Erica Tabor, Adriana Teixeira Rodrigues, Justin Qi Yuee Wang, Niranjan Kissoon, Yemisi Takwoingi, Matthew O Wiens, Adnan Bhutta

Faculty, Staff and Students Publications

In 2019, 80% of the 7.4 million global child deaths occurred in low- and middle-income countries (LMICs). Global and regional estimates of cause of hospital death and admission in LMIC children are needed to guide global and local priority setting and resource allocation but are currently lacking. The study objective was to estimate global and regional prevalence for common causes of pediatric hospital mortality and admission in LMICs. We performed a systematic review and meta-analysis to identify LMIC observational studies published January 1, 2005-February 26, 2021. Eligible studies included: a general pediatric admission population, a cause of admission or death, …

Colonic Malakoplakia In A Pediatric Renal Transplant Recipient Case Report, Kristen G Valencia Deray, Richard Kellermayer, Alexis C Gomez, Kalyani R Patel, Peace Imani, Seiji Kitagawa, Claire E Bocchini, Alvaro Orjuela

Faculty, Staff and Students Publications

Malakoplakia is a rare, chronic granulomatous disease that mainly affects the genitourinary system of immunocompromised adults. It is caused by a bactericidal deficit in macrophages and, therefore, the treatment includes antimicrobials that reach high concentrations in macrophages. To our knowledge, we present the first case of malakoplakia in a pediatric solid organ transplant recipient. Our patient is a 15-year-old male renal transplant recipient who presented with recurrent diarrhea. Blood, urine, and gastrointestinal pathogen panel testing were positive for enteroaggregative Escherichia coli. A colonoscopy revealed diffuse malakoplakia. He had a complete resolution of symptoms with trimethoprim-sulfamethoxazole therapy. Unfortunately, his malakoplakia recurred …

Pseudoviruses, A Safer Toolbox For Vaccine Development Against Enveloped Viruses, Syamala R Thimmiraju, Jason T Kimata, Jeroen Pollet

Faculty, Staff and Students Publications

Introduction: Pseudoviruses are recombinant, replication-incompetent, viral particles designed to mimic the surface characteristics of native enveloped viruses. They are a safer, and cost-effective research alternative to live viruses. With the potential emergence of the next major infectious disease, more vaccine scientists must become familiar with the pseudovirus platform as a vaccine development tool to mitigate future outbreaks.

Areas covered: This review aims at vaccine developers to provide a basic understanding of pseudoviruses, list their production methods, and discuss their utility to assess vaccine efficacy against enveloped viral pathogens. We further illustrate their usefulness as wet-lab simulators for emerging mutant variants, …

Researching Covid To Enhance Recovery (Recover) Pediatric Study Protocol: Rationale, Objectives And Design, Rachel S Gross, Tanayott Thaweethai, Erika B Rosenzweig, James Chan, Lori B Chibnik, Mine S Cicek, Amy J Elliott, Valerie J Flaherman, Andrea S Foulkes, Margot Gage Witvliet, Richard Gallagher, Maria Laura Gennaro, Terry L Jernigan, Elizabeth W Karlson, Stuart D Katz, Patricia A Kinser, Lawrence C Kleinman, Michelle F Lamendola-Essel, Joshua D Milner, Sindhu Mohandas, Praveen C Mudumbi, Jane W Newburger, Kyung E Rhee, Amy L Salisbury, Jessica N Snowden, Cheryl R Stein, Melissa S Stockwell, Kelan G Tantisira, Moriah E Thomason, Dongngan T Truong, David Warburton, John C Wood, Shifa Ahmed, Almary Akerlundh, Akram N Alshawabkeh, Brett R Anderson, Judy L Aschner, Andrew M Atz, Robin L Aupperle, Fiona C Baker, Venkataraman Balaraman, Dithi Banerjee, Deanna M Barch, Arielle Baskin-Sommers, Sultana Bhuiyan, Marie-Abele C Bind, Amanda L Bogie, Tamara Bradford, Natalie C Buchbinder, Elliott Bueler, Hülya Bükülmez, B J Casey, Linda Chang, Maryanne Chrisant, Duncan B Clark, Rebecca G Clifton, Katharine N Clouser, Lesley Cottrell, Kelly Cowan, Viren D'Sa, Mirella Dapretto, Soham Dasgupta, Walter Dehority, Audrey Dionne, Kirsten B Dummer, Matthew D Elias, Shari Esquenazi-Karonika, Danielle N Evans, E Vincent S Faustino, Alexander G Fiks, Daniel Forsha, John J Foxe, Naomi P Friedman, Greta Fry, Sunanda Gaur, Dylan G Gee, Kevin M Gray, Stephanie Handler, Ashraf S Harahsheh, Keren Hasbani, Andrew C Heath, Camden Hebson, Mary M Heitzeg, Christina M Hester, Sophia Hill, Laura Hobart-Porter, Travis K F Hong, Carol R Horowitz, Daniel S Hsia, Matthew Huentelman, Kathy D Hummel, Katherine Irby, Joanna Jacobus, Vanessa L Jacoby, Pei-Ni Jone, David C Kaelber, Tyler J Kasmarcak, Matthew J Kluko, Jessica S Kosut, Angela R Laird, Jeremy Landeo-Gutierrez, Sean M Lang, Christine L Larson, Peter Paul C Lim, Krista M Lisdahl, Brian W Mccrindle, Russell J Mcculloh, Kimberly Mchugh, Alan L Mendelsohn, Torri D Metz, Julie Miller, Elizabeth C Mitchell, Lerraughn M Morgan, Eva M Müller-Oehring, Erica R Nahin, Michael C Neale, Manette Ness-Cochinwala, Sheila M Nolan, Carlos R Oliveira, Onyekachukwu Osakwe, Matthew E Oster, R Mark Payne, Michael A Portman, Hengameh Raissy, Isabelle G Randall, Suchitra Rao, Harrison T Reeder, Johana M Rosas, Mark W Russell, Arash A Sabati, Yamuna Sanil, Alice I Sato, Michael S Schechter, Rangaraj Selvarangan, S Kristen Sexson Tejtel, Divya Shakti, Kavita Sharma, Lindsay M Squeglia, Shubika Srivastava, Michelle D Stevenson, Jacqueline Szmuszkovicz, Maria M Talavera-Barber, Ronald J Teufel, Deepika Thacker, Felicia Trachtenberg, Mmekom M Udosen, Megan R Warner, Sara E Watson, Alan Werzberger, Jordan C Weyer, Marion J Wood, H Shonna Yin, William T Zempsky, Emily Zimmerman, Benard P Dreyer, Recover-Pediatric Consortium

Faculty, Staff and Students Publications

IMPORTANCE: The prevalence, pathophysiology, and long-term outcomes of COVID-19 (post-acute sequelae of SARS-CoV-2 [PASC] or "Long COVID") in children and young adults remain unknown. Studies must address the urgent need to define PASC, its mechanisms, and potential treatment targets in children and young adults.

OBSERVATIONS: We describe the protocol for the Pediatric Observational Cohort Study of the NIH's REsearching COVID to Enhance Recovery (RECOVER) Initiative. RECOVER-Pediatrics is an observational meta-cohort study of caregiver-child pairs (birth through 17 years) and young adults (18 through 25 years), recruited from more than 100 sites across the US. This report focuses on two of …

The Seroprevalence Of Sars-Cov-2-Specific Antibodies In Australian Children: A Cross-Sectional Study, Archana Koirala, Jocelynne Mcrae, Philip N Britton, Marnie Downes, Shayal A Prasad, Suellen Nicholson, Noni E Winkler, Matthew V N O'Sullivan, Fatima Gondalwala, Cecile Castellano, Emma Carey, Alexandra Hendry, Nigel Crawford, Ushma Wadia, Peter Richmond, Helen S Marshall, Julia E Clark, Joshua R Francis, Jeremy Carr, Adam Bartlett, Brendan Mcmullan, Justin Skowno, Donald Hannah, Andrew Davidson, Britta S Von Ungern-Sternberg, Paul Lee-Archer, Laura L Burgoyne, Edith B Waugh, John B Carlin, Zin Naing, Nicole Kerly, Alissa Mcminn, Guillian Hunter, Christine Heath, Natascha D'Angelo, Carolyn Finucane, Laura A Francis, Sonia Dougherty, William Rawlinson, Theo Karapanagiotidis, Natalie Cain, Rianne Brizuela, Christopher C Blyth, Nicholas Wood, Kristine Macartney

Staff and Researcher Publications

Background: Following reduction of public health and social measures concurrent with SARS-CoV-2 Omicron emergence in late 2021 in Australia, COVID-19 case notification rates rose rapidly. As rates of direct viral testing and reporting dropped, true infection rates were most likely to be underestimated.

Objective: To better understand infection rates and immunity in this population, we aimed to estimate SARS-CoV-2 seroprevalence in Australians aged 0-19 years.

Methods: We conducted a national cross sectional serosurvey from June 1, 2022, to August 31, 2022, in children aged 0-19 years undergoing an anesthetic procedure at eight tertiary pediatric hospitals. Participant questionnaires were administered, and …

Comparing The Effects Of Two Initial Specimen Diversion Techniques On Blood Culture Contamination Rates And Clinical Outcomes-A Multicenter Study, Anthony Febres-Aldana, Patrycja Ashley, Eva Amenta, Megan Duffey, Theresa Sepulveda, Corina Lopez, Sabra Shay, Miriam Barrett, Todd Lasco, Takei Pipkins, Margaret Reed, Bradley Lembcke, Mayar Al Mohajer

Faculty, Staff and Students Publications

Although the initial specimen diversion device (ISDD) has been shown to reduce blood culture contamination (BCC) rates, its impact on clinical outcomes remains unclear. This multicenter study showed that ISDD significantly decreased BCC. However, there was no reduction in length of stay, days of therapy, or central line-associated bloodstream infections.

Advances In The Clinical Application Of High-Throughput Proteomics, Miao Cui, Fei Deng, Mary L Disis, Chao Cheng, Lanjing Zhang

Faculty, Staff and Students Publications

High-throughput proteomics has become an exciting field and a potential frontier of modern medicine since the early 2000s. While significant progress has been made in the technical aspects of the field, translating proteomics to clinical applications has been challenging. This review summarizes recent advances in clinical applications of high-throughput proteomics and discusses the associated challenges, advantages, and future directions. We focus on research progress and clinical applications of high-throughput proteomics in breast cancer, bladder cancer, laryngeal squamous cell carcinoma, gastric cancer, colorectal cancer, and coronavirus disease 2019. The future application of high-throughput proteomics will face challenges such as varying protein …

The Tb27 Transcriptomic Model For Predicting Mycobacterium Tuberculosis Culture Conversion, Maja Reimann, Korkut Avsar, Andrew R Dinardo, Torsten Goldmann, Gunar Günther, Michael Hoelscher, Elmira Ibraim, Barbara Kalsdorf, Stefan H E Kaufmann, Niklas Köhler, Anna M Mandalakas, Florian P Maurer, Marius Müller, Dörte Nitschkowski, Ioana D Olaru, Cristina Popa, Andrea Rachow, Thierry Rolling, Helmut J F Salzer, Patricia Sanchez-Carballo, Maren Schuhmann, Dagmar Schaub, Victor Spinu, Elena Terhalle, Markus Unnewehr, Nika J Zielinski, Jan Heyckendorf, Christoph Lange

Faculty, Staff and Students Publications

RATIONALE: Treatment monitoring of tuberculosis patients is complicated by a slow growth rate of Mycobacterium tuberculosis. Recently, host RNA signatures have been used to monitor the response to tuberculosis treatment.

OBJECTIVE: Identifying and validating a whole blood-based RNA signature model to predict microbiological treatment responses in patients on tuberculosis therapy.

METHODS: Using a multi-step machine learning algorithm to identify an RNA-based algorithm to predict the remaining time to culture conversion at flexible time points during anti-tuberculosis therapy.

RESULTS: The identification cohort included 149 patients split into a training and a test cohort, to develop a multistep algorithm consisting of …

Faslpr Gene Dosage Tunes The Extent Of Lymphoproliferation And T Cell Differentiation In Lupus, Ritu Bohat, Xiaofang Liang, Yanping Chen, Chunyu Xu, Ningbo Zheng, Ashley Guerrero, Jiakai Hou, Roshni Jaffery, Nicholas A Egan, Yaxi Li, Yitao Tang, Esra Unsal, Adolfo Robles, Si Chen, Angela M Major, Hadil Elldakli, Sang-Hyuk Chung, Han Liang, M John Hicks, Yong Du, Jamie S Lin, Xiqun Chen, Chandra Mohan, Weiyi Peng

Faculty, Staff and Student Publications

Sle1 and Fas^lpr are two lupus susceptibility loci that lead to manifestations of systemic lupus erythematosus. To evaluate the dosage effects of Fas^lpr in determining cellular and serological phenotypes associated with lupus, we developed a new C57BL/6 (B6) congenic lupus strain, B6.Sle1/Sle1.Fas^lpr/+ (Sle1homo.lprhet) and compared it with B6.Fas^lpr/lpr (lprhomo), B6.Sle1/Sle1 (Sle1homo), and B6.Sle1/Sle1.Fas^lpr/lpr (Sle1homo.lprhomo) strains. Whereas Sle1homo.lprhomo mice exhibited profound lymphoproliferation and early mortality, Sle1homo.lprhet mice had a lifespan comparable to B6 mice, with no evidence of splenomegaly or lymphadenopathy. Compared to B6 monogenic lupus strains, Sle1homo.lprhet mice exhibited significantly …

The Maternal Gut Microbiome In Pregnancy: Implications For The Developing Immune System, Omry Koren, Liza Konnikova, Petter Brodin, Indira U Mysorekar, Maria Carmen Collado

Faculty, Staff and Students Publications

The gut microbiome has important roles in host metabolism and immunity, and microbial dysbiosis affects human physiology and health. Maternal immunity and microbial metabolites during pregnancy, microbial transfer during birth, and transfer of immune factors, microorganisms and metabolites via breastfeeding provide critical sources of early-life microbial and immune training, with important consequences for human health. Only a few studies have directly examined the interactions between the gut microbiome and the immune system during pregnancy, and the subsequent effect on offspring development. In this Review, we aim to describe how the maternal microbiome shapes overall pregnancy-associated maternal, fetal and early neonatal …

Autophagy Determines Distinct Cell Fates In Human Amnion And Chorion Cells, Mary Elise L Severino, Lauren Richardson, Ananth Kumar Kammala, Enkhtuya Radnaa, Kamil Khanipov, Leslie Michelle M Dalmacio, Indira U Mysorekar, Marian Kacerovsky, Ramkumar Menon

Faculty, Staff and Students Publications

Human fetal membranes (amniochorion) that line the intrauterine cavity consist of two distinct cell layers; single-layer amnion epithelial cells (AEC) and multilayer chorion trophoblast cells (CTC). These layers are connected through a collagen-rich extracellular matrix. Cellular remodeling helps support membrane growth and integrity during gestation and helps to maintain pregnancy. Preterm prelabor rupture of the human amniochorionic (fetal) membrane (pPROM) is antecedent to 40% of all spontaneous preterm birth. Oxidative stress (OS) induced activation of the p38 MAPK due to various maternal risk exposures and the amniochorion cells' senescence are reported pathological features of pPROM. Our transcriptomics analysis implicated dysregulated …