Medical Specialties Commons^™

Design And Rationale Of Myoflame-19 Randomised Controlled Trial: Myocardial Protection To Reduce Post-Covid Inflammatory Heart Disease Using Cardiovascular Magnetic Resonance Endpoints, Valentina O Puntmann, Dietrich Beitzke, Andreas Kammerlander, Inga Voges, Dominik D Gabbert, Marcus Doerr, Bishwas Chamling, Biykem Bozkurt, Juan Carlos Kaski, Erica Spatz, Eva Herrmann, Gernot Rohde, Philipp Deleuw, Lenka Taylor, Christine Windemuth-Kieselbach, Cornelia Harz, Marta Santiuste, Laura Schoeckel, Juliana Hirayama, Peter C Taylor, Colin Berry, Eike Nagel

Faculty, Staff and Students Publications

Background: Cardiac symptoms due to postacute inflammatory cardiac involvement affect a broad segment of previously well people with only mild acute coronavirus disease 2019 (COVID-19) illness and without overt structural heart disease. Cardiovascular magnetic resonance (CMR) imaging can identify the underlying subclinical disease process, which is associated with chronic cardiac symptoms. Specific therapy directed at reducing postacute cardiac inflammatory involvement before development of myocardial injury and impairment is missing.

Methods: Prospective multicenter randomized placebo-controlled study of myocardial protection therapy (combined immunosuppressive/antiremodeling) of low-dose prednisolone and losartan. Consecutive symptomatic individuals with a prior COVID-19 infection, no pre-existing significant comorbidities or structural …

Baroreflex Function In Cardiovascular Disease, Husam M Salah, Richa Gupta, Albert J Hicks, Kiran Mahmood, Nicholas A Haglund, Amarinder S Bindra, Steve M Antoine, Rachel Garcia, Amin Yehya, Dmitry M Yaranov, Pujan P Patel, Jason P Feliberti, Allman T Rollins, Vishal N Rao, Laurie Letarte, Vikram Raje, Amit H Alam, Patrick Mccann, Nirav Y Raval, Brian Howard, Marat Fudim

Faculty, Staff and Students Publications

The baroreflex system is involved in modulating several physiological functions of the cardiovascular system and can modulate cardiac output, blood pressure, and cardiac electrophysiology directly and indirectly. In addition, it is involved in regulating neurohormonal pathways involved in the cardiovascular function, such as the renin-angiotensin-aldosterone system and vasopressin release. Baroreflex dysfunction is characterized by sympathetic overactivation and parasympathetic withdrawal and is associated with several cardiovascular diseases, such as hypertension, heart failure, and coronary artery disease. Targeting the baroreflex system via invasive (eg, baroreflex activation therapy and endovascular baroreceptor amplification) and noninvasive approaches (eg, slow breathing exercises and exercise training) has …

Healthcare Utilization Unchanged In The Control Arm Of A Randomized Clinical Trial, Pratik Gongloor, Saad Nadeem, Xiaoying Yu, Mukaila Raji, Kristina D Mena, Elizabeth M Vaughan

Faculty, Staff and Students Publications

including among control groups. Increased access to care and heightened health awareness during trial enrollment could lead to altered behaviors, a phenomenon known as the Hawthorne effect, which may obscure true intervention impacts; however, this effect remains poorly studied in low-income environments.

Aim: To conduct a secondary exploratory analysis of healthcare utilization among control participants of a randomized clinical trial (RCT).

Methods: We retrospectively analyzed electronic medical records from the control arm (n = 26) of an RCT involving low-income Hispanic adults with type 2 diabetes receiving care at a community clinic. Before randomization to a 12-month diabetes education intervention …

Global Consensus On Optimal Exercise Recommendations For Enhancing Healthy Longevity In Older Adults (Icsfr), Mikel Izquierdo, Philipe De Souto Barreto, Hidenori Arai, Heike A Bischoff-Ferrari, Eduardo L Cadore, Matteo Cesari, Liang-Kung Chen, Paul M Coen, Kerry S Courneya, Gustavo Duque, Luigi Ferrucci, Roger A Fielding, Antonio García-Hermoso, Luis Miguel Gutiérrez-Robledo, Stephen D R Harridge, Ben Kirk, Stephen Kritchevsky, Francesco Landi, Norman Lazarus, Teresa Liu-Ambrose, Emanuele Marzetti, Reshma A Merchant, John E Morley, Kaisu H Pitkälä, Robinson Ramírez-Vélez, Leocadio Rodriguez-Mañas, Yves Rolland, Jorge G Ruiz, Mikel L Sáez De Asteasu, Dennis T Villareal, Debra L Waters, Chang Won Won, Bruno Vellas, Maria A Fiatarone Singh

Faculty, Staff and Students Publications

Aging, a universal and inevitable process, is characterized by a progressive accumulation of physiological alterations and functional decline over time, leading to increased vulnerability to diseases and ultimately mortality as age advances. Lifestyle factors, notably physical activity (PA) and exercise, significantly modulate aging phenotypes. Physical activity and exercise can prevent or ameliorate lifestyle-related diseases, extend health span, enhance physical function, and reduce the burden of non-communicable chronic diseases including cardiometabolic disease, cancer, musculoskeletal and neurological conditions, and chronic respiratory diseases as well as premature mortality. Physical activity influences the cellular and molecular drivers of biological aging, slowing aging rates-a foundational …

Circulating Tumor Hpv Dna, Antibodies To Hpv16 Early Proteins, And Oral Hpv16 Dna As Biomarkers For Hpv-Related Oropharyngeal Cancer Screening, Kristina R Dahlstrom, Andrew T Day, Victor M Alvarez, Samantha R Chirinos, Giselle Santillana, Ming Guo, Karen S Anderson, Erich M Sturgis

Faculty, Staff and Students Publications

Background: Oropharyngeal cancer rates continue to rise with no effective screening method. Persistent oral oncogenic human papillomavirus (HPV), antibodies to HPV16 early (E) oncoproteins, and circulating tumor HPV DNA (ctHPVDNA) are biomarkers that show promise for use in HPV-related cancer screening.

Objective: To assess the prevalence of biomarkers for HPV-related cancer and their agreement in middle-aged men.

Methods: Men aged 50–64 years from the general population provided oral rinse and blood samples as well as information about demographics, tobacco/alcohol exposure, sexual behavior, and HPV-related disease history. Oral rinse was tested for HPV16 DNA and plasma was tested for HPV16 E …

Genetic Newborn Screening For Retinoblastoma: A Belgian Initiative Baby Detect, Daniel A Rodriguez, Alex Song, Anshul Bhatnagar, Christina Y Weng

Faculty, Staff and Students Publications

Baby Detect Project, started in September 2022, aimed to create a newborn screening test using targeted next-generation sequencing for all early-onset, treatable, and serious conditions. The elaborated gene panel covers 405 genes, associated with 165 genetic conditions, and includes RB1, linked to retinoblastoma, the only oncological disease tested for. Germline RB1 mutations concern around 50% of all retinoblastoma cases and 100% of the most severe, bilateral cases. Ninety percent of them occur de novo, which delays the diagnosis by about a year with subsequent loss of vision and sometimes the eye itself. Detecting children with germline RB1 mutation at …

High Tumor Cd161 Expression Predicts A Survival Advantage And Marks A Th1-Skewed Microenvironment, Briana Amicarella Burns, Manasvi Chandra, Vanaja Konduri, William K Decker

Faculty, Staff and Students Publications

CD8+CD161+ T-cells exhibit augmented memory and cytolytic properties, mediating enhanced immunity in murine tumor models and improved survival in human non-small cell lung cancer. This T-cell subset might serve as a biomarker of positive response to therapy or even be isolated to augment current immunotherapeutic approaches yet limited knowledge of CD161 expression in human cancers restricts practical application. Here we bioinformatically tested the hypothesis that CD161 expression may be associated with positive outcomes in human cancers and investigated mechanisms underlying any observed advantages. Using TCGA-PANCAN dataset, we analyzed expression of CD161 in over 10,000 human tumors, correlating expression levels with …

The Reprogramming Factor Klf4 In Normal And Malignant Blood Cells, H Daniel Lacorazza

Faculty, Staff and Students Publications

The Krüppel-like factor 4 (KLF4) is an evolutionarily conserved zinc finger transcription factor that regulates cellular processes in stem cells, epithelial cells, and immune blood cells by controlling gene expression through genetic, epigenetic, and chromatin remodeling. The landmark 2006 publication identified KLF4 as one of the factors involved in reprogramming differentiated cells into pluripotent stem cells, sparking increased interest in KLF4 research a decade after its discovery, particularly in the fields of stem cell research, epithelial cell biology, endothelial cell function, and tumorigenesis. Over the years, KLF4 has emerged as a key transcription factor in modulating innate and adaptive immunity, …

Multidisciplinary Approach To Treating Complex Immune Dysregulation Disorders: An Adaptive Model For Institutional Implementation, Lauren A Henderson, Roshini S Abraham, Aisha Ahmed, Lindsey Blount, Scott W Canna, Natalia S Chaimowitz, Shanmuganathan Chandrakasan, Bria Coates, James A Connelly, Megan A Cooper, Christine N Duncan, Anthony French, Melissa Hazen, Michelle L Hermiston, Brian Nolan, Anish Ray, Melissa J Rose, Lisa Forbes Satter, Grant Schulert, Sara Kristen Sexson Tejtel, Tiphanie Vogel, Kelly Walkovich, Matt S Zinter, Edward M Behrens

Faculty, Staff and Students Publications

Patients with immune dysregulation may present with varying combinations of autoimmunity, autoinflammation, immunodeficiency, atopy, lymphoproliferation, and/or malignancy, often with multisystem involvement. Recognizing specific patterns of immune dysregulation, coordinating and interpreting complex diagnostic testing, and choosing initial (often empiric) treatment can be challenging. Centers are increasingly assembling multidisciplinary teams (MDTs) to standardize evaluation and optimize treatment of patients with complex immune dysregulation (immune dysregulation MDTs [immMDTs]). However, published information on the composition and function of immMDTs is sparse, and there is little guidance for those seeking to establish or optimize an immMDT. To inform this review, we assembled a panel of …

Application Of A Digital Quality Measure For Cancer Diagnosis In Epic Cosmos, Andrew J Zimolzak, Sundas P Khan, Hardeep Singh, Jessica A Davila

Faculty, Staff and Students Publications

Objectives: Missed and delayed cancer diagnoses are common, harmful, and often preventable. We previously validated a digital quality measure (dQM) of emergency presentation (EP) of lung cancer in 2 US health systems. This study aimed to apply the dQM to a new national electronic health record (EHR) database and examine demographic associations.

Materials and methods: We applied the dQM (emergency encounter followed by new lung cancer diagnosis within 30 days) to Epic Cosmos, a deidentified database covering 184 million US patients. We examined dQM associations with sociodemographic factors.

Results: The overall EP rate was 19.6%. EP rate was higher in …

A Pipeline For Rapid, High-Throughput Imaging And Quantitative Analysis Of Human Intestinal Organoids, Faith M Sawyer, Fabio Stossi, Erika Nachman, Robert A Britton, Michael J Bolt, Michael A Mancini, Mary K Estes, Sarah E Blutt

Faculty, Staff and Students Publications

Human intestinal organoids (HIOs) are a model system for studying human intestinal epithelium. Utilizing HIOs for high-throughput studies remains inefficient, as analyzing their cellular composition and responses to varying experimental conditions requires extensive time and labor. We describe a 96-well plate-based automated pipeline for rapidly imaging and quantifying fluorescent labeling in HIOs using a high-throughput confocal microscope and image analysis software. The pipeline was leveraged to quantify varying levels of cell proliferation among donor HIO lines in response to microbial products. Cytoplasmic fluorescence via antibody labeling was also quantified with the pipeline, enabling measurement of the prevalence of specific cell …

Long-Term Anti-Sars-Cov-2 Antibody Trajectories After Neutralizing Monoclonal Antibody Treatment, Elizabeth S Munroe, Greg A Grandits, Robert C Hyzy, Hallie C Prescott, Thomas W Barrett, Robin L Dewar, Nicole Engen, Anna L Goodman, Timothy J Hatlen, Helene Highbarger, Thomas L Holland, Gareth Hughes, Tomas O Jensen, Muhammad A Khan, Ioannis Kalomenidis, Nayon Kang, Sylvain Laverdure, Prasad Manian, Vidya Menon, Ravi Patel, Srikanth Ramachandruni, Tauseef Rehman, Kathryn Shaw-Saliba, Birgit Thorup Røge, David M Vock, Amy C Weintrob, Barnaby E Young, Anne P Frosch, Strive Network And Therapeutics For Inpatients With Covid-19 (Tico) Study Groups

Faculty, Staff and Students Publications

Background: Neutralizing monoclonal antibodies (nMAbs) have been used to treat COVID-19 and are increasingly being used to treat other infections. However, there is concern that by neutralizing the SARS-CoV-2 virus, nMAbs may decrease the availability of antigens to the immune system, potentially impairing the endogenous polyclonal immune response and decreasing long-term immune protection.

Methods: We compared 28 and 90-day anti-SARS-CoV-2 spike protein neutralization activity and anti-SARS-CoV-2 nucleocapsid response for patients hospitalized with COVID-19 infection randomized to receive nMAbs or placebo in the large platform ACTIV-3/TICO trials. We pooled results from four trials of anti-spike nMAbs. For most tested agents, measurements …

B-Cell Immune Repertoire Sequencing In Tobacco Cigarette Smoking, Vaping, And Chronic Obstructive Pulmonary Disease In The Copdgene Cohort, Matthew Moll, Zhonghui Xu, Adel Boueiz, Min Hyung Ryu, Edwin K Silverman, Michael H Cho, Craig P Hersh, Maor Sauler, Francesca Polverino, Gregory L Kinney, Jeffrey L Curtis, Laura E Crotty-Alexander, Christopher Vollmers, Peter J Castaldi

Faculty, Staff and Students Publications

Rationale: Cigarette smoking (CS) impairs B-cell function and antibody production, increasing infection risk. The impact of e-cigarette use ('vaping') and combined CS and vaping ('dual-use') on B-cell activity is unclear.

Objective: To examine B-cell receptor sequencing (BCR-seq) profiles associated with CS, vaping, and dual-use.

Methods: BCR-seq was performed on blood RNA samples from 234 participants in the COPDGene study. We assessed multivariable associations of B-cell function measures (immunoglobulin heavy chain (IGH) subclass expression and usage, class-switching, V allele usage, and clonal expansion) with CS, vaping, and dual-use. We adjusted for multiple comparisons using the Benjamini-Hochberg method, identifying significant associations at …

Mice With Lymphatic Dysfunction Develop Pathogenic Lung Tertiary Lymphoid Organs That Model An Autoimmune Emphysema Phenotype Of Copd, Barbara Summers, Kihwan Kim, Anjali Trivedi, Tyler M Lu, Sean Houghton, Jade Palmer-Johnson, Joselyn Rojas-Quintero, Juan Cala-Garcia, Tania Pannellini, Francesca Polverino, Raphaël Lis, Hasina Outtz Reed

Faculty, Staff and Students Publications

We have previously shown that mice with a loss of C-type lectin-like type II (CLEC2), which have lymphatic dysfunction due to the role of CLEC2 in platelets for maintaining separation between the venous and lymphatic system, develop lung tertiary lymphoid organ (TLO) formation and lung injury that resembles an emphysema phenotype of chronic obstructive pulmonary disease (COPD). We now sought to investigate whether and how TLOs in these mice may play a pathogenic role in lung injury that is relevant to human disease. We found that inhibiting TLO formation using an anti-CD20 antibody in CLEC2-deficient mice partially blocked the development …

Promotion Of Hiv Clearance By Sensitization Of Hiv Reservoirs To Cell Death, Min Li, Baichao Sun, Jing Dong, Jian-Rong Li, Laurie J Minze, Min Chen, Chao Cheng, Jin Wang

Faculty, Staff and Students Publications

Introduction: HIV integrates its proviral DNA into the host genome to establish persistent infection. To promote HIV clearance, we have designed an approach for selective elimination of host cells harboring replication-competent HIV (SECH), through inhibition of autophagy and anti-apoptotic molecules during viral reactivation. SECH approach can clear HIV-infected cells in approximately 50% humanized mice. However, the mechanisms for the resistance of reservoirs to depletion in mice with failure in HIV clearance are unclear.

Methods: We have performed single cell transcriptome analyses of HIV-infected T cells that escaped the treatments, in order to identify cellular pathways that could be targeted to …

Relationships Of Personality Traits With The Taxonomic Composition Of The Gut Microbiome Among Psychiatric Inpatients, William Orme, Sandra L Grimm, Divya S N Vella, J Christopher Fowler, B Christopher Frueh, Benjamin L Weinstein, Joseph Petrosino, Cristian Coarfa, Alok Madan

Faculty, Staff and Students Publications

Objective: Through the brain-gut-microbiome axis, myriad psychological functions that affect behavior share a dynamic, bidirectional relationship with the intestinal microbiome. Little is known about the relationship between personality-a stable construct that influences social- and health-related behaviors-and the bacterial ecosystem. The authors of this exploratory study examined the relationship between general and maladaptive personality traits and the composition of the gut microbiome.

Methods: In total, 105 psychiatric inpatients provided clinical data and fecal samples. Personality traits were measured with the five-factor model of personality, the Structured Clinical Interview for DSM-IV Axis II Personality Disorders, and the Personality Inventory for DSM-5; 16S …

Heterologous Prime-Pull Mucosal Vaccination With An Adjuvanted Rbd Vaccine Elicits Robust Iga Production And Protects Against Sars-Cov-2, Allyson H Hirsch, Calder R Ellsworth, William A Lewis, Ryan Craig, Amy E Meyer, Jonatan Maldonado, Frania Ramirez Lopez, Syamala Rani Thimmiraju, James B Mclachlan, Xuebin Qin, Nicholas J Maness, Jeroen Pollet, Ulrich Strych, Maria Elena Bottazzi, Peter J Hotez, Lisa A Morici

Faculty, Staff and Students Publications

Despite the efficacy of approved severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in preventing severe disease and death, breakthrough infections continue to occur in vaccinated individuals, contributing to further viral mutation and spread. These limitations may be attributable to the poor induction of mucosal immunity by parenteral vaccination. Mucosal adjuvants, such as T-vant, can enhance vaccine-induced immune responses through the generation of antigen-specific antibodies and T cells in the respiratory tract. In this study, we evaluated the protective efficacy of adjuvanted SARS-CoV-2 receptor binding domain (RBD) subunit vaccines administered by homologous and heterologous routes. Immunized mice were challenged with …

Mixed-Methods Evaluation And Behavior Change Interventions To Improve Hand Hygiene Resources And Practices Among Healthcare Workers In Polyclinics And Health Centers In Belize, 2023, Anh N Ly, Kelsey Mcdavid, Christina Craig, Rosalva Blanco, Vickie Romero, Melissa Diaz-Musa, Francis Morey, Russell Manzanero, Gerhaldine Morazan, Makenzie Towery, Anna Impellitteri, Matthew Lozier, Kristy O Murray

Faculty, Staff and Students Publications

Background: Hand hygiene (HH) is an effective public health measure to prevent the spread of infections in healthcare settings. A previous study in Belize showed gaps in HH practices in hospitals and large polyclinics; however, there are limited national data assessing access to and use of HH resources in smaller outpatient primary care facilities, especially in rural areas.

Methods: In February 2023, facility assessments were conducted at 26 health centers and polyclinics in Belize to assess the availability of HH resources. Of these, 12 pilot healthcare facilities (HCF) were selected for additional evaluation, which included observation of HH practices, hand …

Real-World Experiences With Vmat2 Inhibitors In Pediatric Hyperkinetic Movement Disorders, Sujal Manohar, Jennifer Jacobe, Rebecca Berger, Joseph Jankovic, Mariam Hull

Faculty, Staff and Students Publications

Background: Vesicular monoamine transporter 2 (VMAT2) inhibitors are often prescribed for the treatment of hyperkinetic movement disorders such as tics, stereotypy, tardive dyskinesia and chorea. These dopamine depleters have been FDA approved in adults for the treatment of chorea in Huntington's disease and tardive dyskinesia. Use of VMAT2 inhibitors in pediatric hyperkinetic movement disorders, however, is limited due to lack of pediatric FDA approval. We review the real-world prescribing practices and patient experiences with VMAT2 inhibitors in children.

Methods: We performed a retrospective chart review of patients treated with VMAT2 inhibitors at a pediatric movement disorders clinic from 2011 to …

Predictive Equation Derived From 6,497 Doubly Labelled Water Measurements Enables The Detection Of Erroneous Self-Reported Energy Intake, Rania Bajunaid, Chaoqun Niu, Catherine Hambly, Zongfang Liu, Yosuke Yamada, Heliodoro Aleman-Mateo, Liam J Anderson, Lenore Arab, Issad Baddou, Linda Bandini, Kweku Bedu-Addo, Ellen E Blaak, Carlijn V C Bouten, Soren Brage, Maciej S Buchowski, Nancy F Butte, Stefan G J A Camps, Regina Casper, Graeme L Close, Jamie A Cooper, Richard Cooper, Sai Krupa Das, Peter S W Davies, Prasangi Dabare, Lara R Dugas, Simon Eaton, Ulf Ekelund, Sonja Entringer, Terrence Forrester, Barry W Fudge, Melanie Gillingham, Annelies H Goris, Michael Gurven, Asmaa El Hamdouchi, Hinke H Haisma, Daniel Hoffman, Marije B Hoos, Sumei Hu, Noorjehan Joonas, Annemiek M Joosen, Peter Katzmarzyk, Misaka Kimura, William E Kraus, Wantanee Kriengsinyos, Rebecca Kuriyan, Robert F Kushner, Estelle V Lambert, Pulani Lanerolle, Christel L Larsson, William R Leonard, Nader Lessan, Marie Löf, Corby K Martin, Eric Matsiko, Anine C Medin, James C Morehen, James P Morton, Aviva Must, Marian L Neuhouser, Theresa A Nicklas, Christine D Nyström, Robert M Ojiambo, Kirsi H Pietiläinen, Yannis P Pitsiladis, Jacob Plange-Rhule, Guy Plasqui, Ross L Prentice, Susan B Racette, David A Raichlen, Eric Ravussin, Leanne M Redman, John J Reilly, Rebecca Reynolds, Susan B Roberts, Dulani Samaranayakem, Luis B Sardinha, Analiza M Silva, Anders M Sjödin, Marina Stamatiou, Eric Stice, Samuel S Urlacher, Ludo M Van Etten, Edgar G A H Van Mil, George Wilson, Jack A Yanovski, Tsukasa Yoshida, Xueying Zhang, Alexia J Murphy-Alford, Srishti Sinha, Cornelia U Loechl, Amy H Luke, Herman Pontzer, Jennifer Rood, Hiroyuki Sagayama, Dale A Schoeller, Klaas R Westerterp, William W Wong, John R Speakman

Faculty, Staff and Students Publications

Nutritional epidemiology aims to link dietary exposures to chronic disease, but the instruments for evaluating dietary intake are inaccurate. One way to identify unreliable data and the sources of errors is to compare estimated intakes with the total energy expenditure (TEE). In this study, we used the International Atomic Energy Agency Doubly Labeled Water Database to derive a predictive equation for TEE using 6,497 measures of TEE in individuals aged 4 to 96 years. The resultant regression equation predicts expected TEE from easily acquired variables, such as body weight, age and sex, with 95% predictive limits that can be used …

Comparing Guillain-Barré Syndrome Outcomes Between Rural And Urban Hospitals In The United States: A Retrospective Cohort Study, Anudeep Surendranath, Rahul Damani, Anushareddy Muddasani, Anupam Kumar Gupta

Faculty, Staff and Students Publications

Background and purpose: Rural-urban disparities in neurological care have been well documented, but limited data exist regarding Guillain-Barré Syndrome (GBS). This study examines differences in patient demographics, hospital characteristics, and outcomes among GBS admissions to rural versus urban hospitals in the United States.

Methods: Using the 2021 National Inpatient Sample, we conducted a retrospective cohort study of adult hospitalizations with a principal diagnosis of GBS. Hospitals were classified as rural or urban based on U.S. census designations. Multivariate logistic and linear regression models were used to assess associations between hospital location and outcomes, adjusting for demographic, clinical, and hospital-level factors. …

Predictive Equation Derived From 6,497 Doubly Labelled Water Measurements Enables The Detection Of Erroneous Self-Reported Energy Intake, Rania Bajunaid, Chaoqun Niu, Catherine Hambly, Zongfang Liu, Yosuke Yamada, Heliodoro Aleman-Mateo, Liam J Anderson, Lenore Arab, Issad Baddou, Linda Bandini, Kweku Bedu-Addo, Ellen E Blaak, Carlijn V C Bouten, Soren Brage, Maciej S Buchowski, Nancy F Butte, Stefan G J A Camps, Regina Casper, Graeme L Close, Jamie A Cooper, Richard Cooper, Sai Krupa Das, Peter S W Davies, Prasangi Dabare, Lara R Dugas, Simon Eaton, Ulf Ekelund, Sonja Entringer, Terrence Forrester, Barry W Fudge, Melanie Gillingham, Annelies H Goris, Michael Gurven, Asmaa El Hamdouchi, Hinke H Haisma, Daniel Hoffman, Marije B Hoos, Sumei Hu, Noorjehan Joonas, Annemiek M Joosen, Peter Katzmarzyk, Misaka Kimura, William E Kraus, Wantanee Kriengsinyos, Rebecca Kuriyan, Robert F Kushner, Estelle V Lambert, Pulani Lanerolle, Christel L Larsson, William R Leonard, Nader Lessan, Marie Löf, Corby K Martin, Eric Matsiko, Anine C Medin, James C Morehen, James P Morton, Aviva Must, Marian L Neuhouser, Theresa A Nicklas, Christine D Nyström, Robert M Ojiambo, Kirsi H Pietiläinen, Yannis P Pitsiladis, Jacob Plange-Rhule, Guy Plasqui, Ross L Prentice, Susan B Racette, David A Raichlen, Eric Ravussin, Leanne M Redman, John J Reilly, Rebecca Reynolds, Susan B Roberts, Dulani Samaranayakem, Luis B Sardinha, Analiza M Silva, Anders M Sjödin, Marina Stamatiou, Eric Stice, Samuel S Urlacher, Ludo M Van Etten, Edgar G A H Van Mil, George Wilson, Jack A Yanovski, Tsukasa Yoshida, Xueying Zhang, Alexia J Murphy-Alford, Srishti Sinha, Cornelia U Loechl, Amy H Luke, Herman Pontzer, Jennifer Rood, Hiroyuki Sagayama, Dale A Schoeller, Klaas R Westerterp, William W Wong, John R Speakman

Faculty, Staff and Students Publications

Nutritional epidemiology aims to link dietary exposures to chronic disease, but the instruments for evaluating dietary intake are inaccurate. One way to identify unreliable data and the sources of errors is to compare estimated intakes with the total energy expenditure (TEE). In this study, we used the International Atomic Energy Agency Doubly Labeled Water Database to derive a predictive equation for TEE using 6,497 measures of TEE in individuals aged 4 to 96 years. The resultant regression equation predicts expected TEE from easily acquired variables, such as body weight, age and sex, with 95% predictive limits that can be used …

Interleukin-15-Armoured Gpc3 Car T Cells For Patients With Solid Cancers, David Steffin, Nisha Ghatwai, Antonino Montalbano, Purva Rathi, Amy N Courtney, Azlann B Arnett, Julien Fleurence, Ramy Sweidan, Tao Wang, Huimin Zhang, Prakash Masand, John M Maris, Daniel Martinez, Jennifer Pogoriler, Navin Varadarajan, Sachin G Thakkar, Deborah Lyon, Natalia Lapteva, Mei Zhuyong, Kalyani Patel, Dolores Lopez-Terrada, Carlos A Ramos, Premal Lulla, Tannaz Armaghany, Bambi J Grilley, Stephen Gottschalk, Gianpietro Dotti, Leonid S Metelitsa, Helen E Heslop, Malcolm K Brenner, Pavel Sumazin, Andras Heczey

Faculty, Staff and Students Publications

Interleukin-15 (IL15) promotes the survival of T lymphocytes and enhances the antitumor properties of CAR T cells in preclinical models of solid neoplasms in which CAR T cells have limited efficacy1-4. Glypican-3 (GPC3) is expressed in a group of solid cancers5-10, and here we report the first evaluation in humans of the effects of IL15 co-expression on GPC3-CAR T cells. Cohort 1 patients (NCT02905188/NCT02932956) received GPC3-CAR T cells, which were safe but produced no objective antitumor responses and reached peak expansion at two weeks. Cohort 2 patients ( …

A Multifunctional Theranostic Ultrasound Platform For Remote Magnetogenetics And Expanded Blood-Brain Barrier Opening, Alec J Batts, Fotios N Tsitsos, Jeannette Ingabire, Guillaume Duret, Samantha L Gorman, Deny Tsakri, Rebecca L Noel, Robin Ji, Nancy Kwon, Quoc-Khanh Pham, Linlin Zhang, Gang Bao, Jacob T Robinson, Elisa E Konofagou

Faculty, Staff and Students Publications

Introduction: Brain stimulation techniques are critical for unraveling the innerworkings of complex neuronal pathways governing both normal physiological function and pathologic states in neurological disorders. Focused ultrasound (FUS) is an emerging technique poised to significantly alter central nervous system (CNS) drug delivery and neuroscience research through non-invasive means. Magnetogenetics is a brain stimulation technique which may benefit from FUS technology in that alternating magnetic fields (AMF), like FUS, can pass through the skull without requiring surgery.

Methodology: Magnetogenetics involves the deposition of superparamagnetic iron-oxide nanoparticles (SPIONs) and overexpression of thermoreceptor transmembrane proteins (e.g. TRPV1 and TRPA1) in the brain. When …

Delayed Excretion Of High-Dose Methotrexate In Pediatric Acute Leukemia Correlates With Laxative And Constipation Management, Jennifer A Belsky, Ashley Chavana, Ankona Banerjee, Mark Zobeck, Eric S Schafer, Karen R Rabin, Monica Gramatges, Alex Sim, Audrey Leisinger, Trisha Reddy, Megan J Parod, Philip Lupo, Michael Scheurer, Austin L Brown, M Brooke Bernhardt

Faculty, Staff and Students Publications

Background: Delayed excretion of high-dose methotrexate (HD-MTX) in pediatric acute lymphoblastic leukemia (ALL) can result in significant morbidity. While methotrexate is primarily renally excreted, HD-MTX may overwhelm renal excretion and increase reliance on fecal elimination. This study evaluated the association between laxative use for constipation and delayed excretion of HD-MTX.

Methods: This multisite chart review included pediatric patients with ALL (2010-2020) who received HD-MTX (5 g/m2). Delayed excretion was defined as a serum MTX concentration greater than 0.4 µM at Hour 48. We identified use of laxative medications after each HD-MTX infusion, with receipt of two or more doses considered …

Exercise Mitigates High-Fat Diet-Induced Cardiac Dysfunction Via Apoe Genotype- And Immune-Dependent Mechanisms: A Photon-Counting Ct Study In Adult Mice, Rohan Nadkarni, Alex J Allphin, Darin P Clark, Yi Qi, Zay Yar Han, Ketan B Ghaghada, Alexandra Badea, Cristian T Badea

Faculty, Staff and Students Publications

Background: Cardiovascular dysfunction frequently accompanies aging and is often worsened by adverse lifestyle factors and genetic susceptibility. The apolipoprotein E (APOE) gene modulates susceptibility to cardiovascular disease, but how exercise and diet interact with APOE genotype remains insufficiently understood. We investigate the cardioprotective potential of exercise in humanized APOE-targeted replacement mice on control and high-fat diet, using photon-counting computed tomography (PCCT) and deep learning-based image segmentation.

Methods: This study included 251 male and female mice in mid-to-late life of APOE2, APOE3, and APOE4 genotypes with variation in humanized NOS2 (HN) mediated innate immune response, exercise status (exercised vs. sedentary) and …

Averting Collapse: Reimagining The Ntds Ecosystem Through G20 Health Diplomacy And Science Innovation, Maple Goh, Peter J Hotez

Faculty, Staff and Students Publications

The recent termination of the U.S. Government's neglected topical diseases (NTD) mass treatment program, following similar cuts by the UK, threatens decades of progress. Without a strategic reset, NTDs may re-emerge, exacerbating poverty across Africa and beyond. We call for a broadened donor base and reframing NTD control as a shared global interest, especially as NTDs rise in G20 nations due to climate change and urbanization. This moment demands investment in sustainable tools, like NextGen vaccines and biologics, and greater leadership from G20 countries. While USAID's exit is a setback, opportunities arise for decolonizing global health and fostering new partnerships.

Maintenance Therapy With A P2y12 Receptor Inhibitor After Cangrelor In Patients With Acute Coronary Syndrome The Electra-Sirio 2 Investigators’ Viewpoint, Jacek Kubica, Piotr Adamski, Robert Gajda, Aldona Kubica, Małgorzata Ostrowska, Gavino Casu, Diana A Gorog, Paul A Gurbel, Tomasz Hajdukiewicz, Miłosz Jaguszewski, Young-Hoon Jeong, Agata Kosobucka-Ozdoba, Zuzana Motovska, Piotr Niezgoda, Maciej Piasecki, Przemysław Podhajski, Paolo Raggi, Uzeyir Rahimov, Jolanta M Siller-Matula, Grzegorz Skonieczny, Łukasz Szarpak, Paweł Szymański, Udaya Tantry, Eliano P Navarese

Faculty, Staff and Students Publications

According to the ESC guidelines, cangrelor may be considered in P2Y12-inhibitor-naïve acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). The aim of this review is to summarize available evidence on the optimal maintenance therapy with P2Y12 receptor inhibitor after cangrelor. Transitioning from cangrelor to a thienopyridine, but not ticagrelor, can be associated with a drug-drug interaction (DDI); therefore, a ticagrelor loading dose (LD) can be given any time before, during, or at the end of a cangrelor infusion, while a LD of clopidogrel or prasugrel should be administered at the time the infusion of cangrelor ends or within …

Early Structural Valve Deterioration And Cusp Tear Leading To Acute Heart Failure In A Second-Generation Trifecta Glide Technology Heart Valve, Akiyoshi Yamamoto, Kenji Kuwaki, Hidekazu Furuya, Yasunori Cho

The Texas Heart Institute Journal

This report highlights a case of early structural valve deterioration with a cusp tear in a second-generation Abbott Trifecta Glide Technology bioprosthetic heart valve. A 70-year-old man had undergone aortic valve replacement with a Trifecta Glide Technology valve 30 months earlier for severe bicuspid aortic valve stenosis. He suddenly developed acute heart failure with dyspnea resulting from severe aortic valve regurgitation, with a cusp tear in the Trifecta Glide Technology valve, as demonstrated by transthoracic echocardiography. The patient was successfully treated with urgent repeat aortic valve replacement.

Lyme Carditis And Inflammation-Driven Plaque Erosion Presenting As Sudden Cardiac Arrest, Marco Kaldas, Moneal Shah, Diana Pashaieva, Georgios Lygouris, Anita Radhakrishnan

The Texas Heart Institute Journal

Lyme carditis represents a rare cardiac complication of Borrelia burgdorferi infection, often causing conduction disturbances but rarely causing malignant arrhythmias. Inflammatory acute coronary syndrome, driven by immune-mediated plaque erosion rather than rupture, represents a nontraditional ischemic mechanism. This case highlights their overlap. The case of a previously healthy man with Lyme disease who experienced cardiac arrest because of ventricular tachycardia is reported. Imaging showed myocardial inflammation together with coronary plaque erosion instead of plaque rupture. The patient underwent advanced diagnostic testing and received multidisciplinary medical care, which led to complete cardiac recovery and implantable cardioverter-defibrillator placement.