Medicine and Health Sciences Commons^™

Systematic Review Of Parkinsonism In Cerebrotendinous Xanthomatosis, Jennifer Hanson, Penelope E Bonnen

Faculty, Staff and Students Publications

Background: Cerebrotendinous Xanthomatosis (CTX) is a rare, inherited metabolic disease caused by pathogenic variants in CYP27A1. The clinical presentation of this progressive disease includes cognitive deficits, ataxia, peripheral neuropathy, and pyramidal signs, as well as bilateral cataracts and tendon xanthomas. In some cases, CTX also includes parkinsonism. The goals of this study are to develop a data source that provides improved characterization and awareness of parkinsonism in CTX.

Methods: We conducted a systematic review of the literature according to PRISMA guidelines to identify all published individuals diagnosed with CTX and parkinsonism. Clinical signs, imaging findings and treatment response to …

Structural Variants: Mechanisms, Mapping, And Interpretation In Human Genetics, Shruti Pande, Moez Dawood, Christopher M Grochowski

Faculty, Staff and Students Publications

Structural variations (SVs) represent genomic variations that involve breakage and rejoining of DNA segments. SVs can alter normal gene dosage, lead to rearrangements of genes and regulatory elements within a topologically associated domain, and potentially contribute to physical traits, genomic disorders, or complex traits. Recent advances in sequencing technologies and bioinformatics have greatly improved SV detection and interpretation at unprecedented resolution and scale. Despite these advances, the functional impact of SVs, the underlying SV mechanism(s) contributing to complex traits, and the technical challenges associated with SV detection and annotation remain active areas of research. This review aims to provide an …

Xpert Mtb/Rif Ultra Assay For Pulmonary Tuberculosis And Rifampicin Resistance In Adults And Adolescents, David J Horne, Jerry S Zifodya, Adrienne E Shapiro, Elizabeth Chandler Church, Jonah S Kreniske, Alexander W Kay, Katie Scandrett, Karen R Steingart, Yemisi Takwoingi

Faculty, Staff and Students Publications

Background: Xpert MTB/RIF Ultra (Xpert Ultra) is a molecular World Health Organization (WHO)-recommended rapid diagnostic test that simultaneously detects tuberculosis and rifampicin resistance. This review updates a comparative accuracy Cochrane review of Xpert MTB/RIF and Xpert Ultra as Xpert Ultra has replaced Xpert MTB/RIF.

Objectives: To determine the diagnostic accuracy of Xpert MTB/RIF Ultra (Xpert Ultra) for detecting pulmonary tuberculosis and rifampicin resistance in adults and adolescents with presumptive tuberculosis based on signs or symptoms or with an abnormal chest x-ray suggestive of tuberculosis.

Search methods: We searched seven databases including CENTRAL, MEDLINE, and Embase, plus two trial registers (ClinicalTrials.gov …

Phosphoglycerate Mutase Regulates Treg Differentiation Through Control Of Serine Synthesis And One-Carbon Metabolism, Wesley H Godfrey, Judy J Lee, Shruthi Shanmukha, Kaho Cho, Xiaojing Deng, Chandra Shekar R Ambati, Vasanta Putluri, Abu Hena Mostafa Kamal, Paul M Kim, Nagireddy Putluri, Michael D Kornberg

Faculty, Staff and Students Publications

The differentiation and suppressive functions of regulatory CD4 T cells (Tregs) are supported by a broad array of metabolic changes, providing potential therapeutic targets for immune modulation. In this study, we focused on the regulatory role of glycolytic enzymes in Tregs and identified phosphoglycerate mutase (PGAM) as being differentially overexpressed in Tregs and associated with a highly suppressive phenotype. Pharmacologic or genetic inhibition of PGAM reduced Treg differentiation and suppressive function while reciprocally inducing markers of a pro-inflammatory, T helper 17 (Th17)-like state. The regulatory role of PGAM was dependent on the contribution of 3-phosphoglycerate (3 PG), the PGAM substrate, …

Dietary Lipids Induce Ppard And Bcl6 To Repress Macrophage Il-23 Induction After Intestinal Injury And Lps Exposure, Ashleigh M Gil, Daniel F Zegarra-Ruiz, Wan-Jung Wu, Kendra Norwood, Adrien Assie, Buck S Samuel, Angela M Major, Gretchen E Diehl, Andrea A Hill Mcalester

Faculty, Staff and Students Publications

Unresolved tissue damage is a common feature of Inflammatory Bowel Disease (IBD) that facilitates disease progression. Here, we showed that high animal fat diets (HFD), an environmental risk factor associated with IBD pathogenesis, suppress intestinal macrophage production of critical tissue repair responses after damage. This includes reduced IL-23 production, which drives downstream production of IL-22, which is needed for barrier repair. Indicating that dietary lipids interfere with responses to microbial molecules needed to induce barrier protective functions, we found oleic acid could directly suppress macrophage Il23a induction after lipopolysaccharide (LPS) treatment. Deleting the lipid transporter CD36 on macrophages restored the …

Assessment Of Dnase Activity By Ratiometric Fluorescence Resonance Energy Transfer, Candace L Minchew, Vladimir V Didenko

Faculty, Staff and Students Publications

The present protocol describes a simple and sensitive ratiometric Förster resonance energy transfer (FRET) assay for the detection and quantitative assessment of DNase activity. Ratiometric FRET measurements make use of the ratio of donor and acceptor emission signals. The assay detects single-stranded DNA breaks using a staple-shaped, dual-tagged 38-mer FRET oligoprobe, employed as a real-time DNA cleavage sensor. The main application of the described approach is the quantitative assessment of the effects of reaction conditions, such as pH, temperature, and buffer composition, on DNase activity. Due to its ability to detect even minor and slow DNA cleavage, the assay is …

U-Rich Elements Drive Pervasive Cryptic Splicing In 3′ Utr Massively Parallel Reporter Assays, Khoa Dao, Courtney F Jungers, Sergej Djuranovic, Anthony M Mustoe

Faculty, Staff and Students Publications

Untranslated RNA sequences play essential roles in orchestrating gene expression. However, the sequence codes and mechanisms underpinning post-transcriptional regulation remain incompletely understood. Here, we revisit the finding from a prior massively parallel reporter assay (MPRA) that AU-rich elements in 3' untranslated regions (3' UTRs) can drive upregulation or downregulation of mRNA expression depending on 3' UTR context. We unexpectedly discover that this variable regulation arises from widespread cryptic splicing, predominately from an unannotated splice donor in the coding sequence of GFP to diverse acceptor sites in reporter 3' UTRs. Splicing is activated by U-rich sequences, which function as potent position-dependent …

A Multi-Modal Pelvic Mri Dataset For Deep Learning-Based Pelvic Organ Segmentation In Endometriosis, Xiaomin Liang, Linda A Alpuing Radilla, Kamand Khalaj, Haaniya Dawoodally, Chinmay Mokashi, Xiaoming Guan, Kirk E Roberts, Sunil A Sheth, Varaha S Tammisetti, Luca Giancardo

Faculty, Staff and Students Publications

Endometriosis affects approximately 190 million females of reproductive age worldwide. Magnetic Resonance Imaging (MRI) has been recommended as the primary non-invasive diagnostic method for endometriosis. This study presents new female pelvic MRI multicenter datasets for endometriosis and shows the baseline segmentation performance of two auto-segmentation pipelines: the self-configuring nnU-Net and RAovSeg, a custom network. The multi-sequence endometriosis MRI scans from two clinical institutions were collected. A multicenter dataset of 51 subjects with manual labels for multiple pelvic structures from three raters was used to assess interrater agreement. A second single-center dataset of 81 subjects with labels for multiple pelvic structures …

Anxious Traits Intensify The Impact Of Depressive Symptoms On Stigma In People Living With Hiv, Alexia Koukopoulos, Antonio Maria D'Onofrio, Alessio Simonetti, Delfina Janiri, Flavio Cherubini, Paolo Vassalini, Letizia Santinelli, Gabriella D'Ettorre, Gabriele Sani, Giovanni Camardese

Faculty, Staff and Students Publications

Background/Objectives: Despite medical advances, stigma remains a major challenge for people living with HIV (PLWH). This study examined clinical, sociodemographic, and psychological predictors of HIV-related stigma, and explored whether affective temperament moderates the impact of depression on stigma.

Methods: This cross-sectional observational study included 97 PLWH attending a tertiary infectious disease unit in Rome, Italy. Participants completed a battery of validated psychometric instruments assessing depressive symptoms, anxiety, manic symptoms, mixed affective states, general psychopathology, impulsivity, and affective temperament. HIV-related stigma was evaluated using the Berger HIV Stigma Scale, which measures personalized stigma, disclosure concerns, negative self-image, and concerns …

Project Evolve: An International Analysis Of Postimmunotherapy Lineage Switch, An Emergent Form Of Relapse In Leukemia, Sara K Silbert, Alexander W Rankin, Chloe N Hoang, Alexandra Semchenkova, Regina M Myers, Elena Zerkalenkova, Hao-Wei Wang, Alexandra E Kovach, Constance M Yuan, Dana Delgado Colon, Loïc Vasseur, Alex Bataller, Samuel John, Kaylyn Utley Lyons, Barbara Friedes, Anna Alonso-Saladrigues, Hisham Abdel-Azim, Estelle Balducci, Ahmed Assim Aljudi, Marie Balsat, D Nathan Biery, Aghiad Chamdin, Bill H Chang, Raymund S Cuevo, Barbara De Moerloose, David S Dickens, Ulrich Duffner, Nicolas Duployez, Firas El Chaer, Michelle Ann Elliott, Gabriele Escherich, Sneha Fernandes, Mandi R Fitzjohn, Zhubin Gahvari, Stephan A Grupp, Rui Rochelle He, Cynthia Harrison, Christopher B Hergott, Emily M Hsieh, Annette S Kim, Dennis J Kuo, Daniel P Larson, Benjamin J Lee, Thibaut Leguay, R Coleman Lindsley, Abhishek A Mangaonkar, Kerstin Mezger, Holly L Pacenta, Jing Pan, Marlie Provost, Latika Puri, Sunil S Raikar, Armando Martinez, Isabella Bristol, Kyle Murphy, Lauren Reiman, Michele Redell, Kelly Reed, Gabrielle Roth-Guepin, Jeremy Rubinstein, Süreyya Savaşan, Kristian Schafernak, Alexandra Stevens, Aimee Talleur, Naomi Torres Carapia, Jacques Vargaftig, Anant Vatsayan, Matthias Wölfl, Liping Zhao, Susana Rives, Vanessa A Fabrizio, Koji Sasaki, Ibrahim Aldoss, Nicolas Boissel, Susan R Rheingold, Kara L Davis, Sara Ghorashian, Elad Jacoby, Alexander Popov, Adam J Lamble, Nirali N Shah

Faculty, Staff and Students Publications

Lineage switch (LS), defined as the immunophenotypic transformation of acute leukemia, has emerged as a mechanism of relapse after antigen-targeted immunotherapy, which is associated with dismal outcomes. Through an international collaborative effort, we identified cases of LS after a host of antigen-targeted therapies (eg, CD19, CD22, CD38, and CD7), described how LS was diagnosed, reviewed treatment approaches, and analyzed overall outcomes for this form of postimmunotherapy relapse. Collectively, 75 cases of LS were evaluated, including 53 (70.7%) cases of B-cell acute lymphoblastic leukemia (B-ALL) transforming to acute myeloid leukemia (AML), 17 (22.7%) cases of B-ALL transforming to mixed phenotypic acute …

Improving Door-In-Door-Out Times For Stemi Transfer Patients: Impact Of A Protocolized Autolaunch Process, Hashim Zaidi, Waleed Kayani, Eric Power, Hei Kit Chan, Sini Eapen, Benjamin Karfunkle

Faculty, Staff and Students Publications

Background: The timely transfer of patients with ST-segment elevation myocardial infarction (STEMI) to percutaneous coronary intervention-capable centers is critical for improving outcomes. Although the American Heart Association recommends a door-in-door-out (DIDO) time of ≤30 minutes, national compliance remains low.

Project rationale: At Harris Health, no patients with STEMI met this benchmark before 2022. We implemented a quality improvement (QI) initiative, including an "Autolaunch" process, to expedite STEMI transfers.

Project summary: During 2022-2023, we introduced QI initiatives, including the Autolaunch protocol, for patients with unequivocal STEMI. This process included rapid emergency medical services activation, direct catheterization laboratory transfer, and prearrival cardiologist …

Understanding The Health And Social Determinants Of Health Needs Of Resettled Afghan Refugees In Houston, Texas, Karissa Chesky, Angelica Garcia, Aaron Pathak, Imran Humza Hanif, Srijana Shrestha, Sophia Banu

Faculty, Staff and Students Publications

Purpose

Methods

Constitutive Il-7 Signaling Promotes Car-Nk Cell Survival In The Solid Tumor Microenvironment But Impairs Tumor Control, Matthew Dysthe, Ishwar Navin, Dayenne Van Leeuwen, Josue Pineda, Corrine Baumgartner, Cliona M Rooney, Robin Parihar

Faculty, Staff and Students Publications

Background: Adoptive transfer of chimeric antigen receptor (CAR)-expressing natural killer (NK) cells has demonstrated success against hematological malignancies. Efficacy against solid tumors has been limited by poor NK cell survival and function in the suppressive tumor microenvironment (TME). To enhance efficacy against solid tumors, stimulatory cytokines have been incorporated into CAR-NK cell therapeutic approaches. However, current cytokine strategies have limitations, including systemic toxicities, exogenous dependencies, and unwanted TME bystander effects. Here, we aimed to overcome these limitations by modifying CAR-NK cells to express a constitutively active interleukin (IL)-7 receptor, termed C7R, capable of providing intrinsic CAR-NK cell activation that does …

A Whole-Brain Voxel-Based Analysis Of Structural Abnormalities In Ptsd: An Enigma-Pgc Study, Cheryl R Z See, Shuqing Si, C Lexi Baird, Courtney C Haswell, Ahmed Hussain, Miranda Olff, Dick J Veltman, Jessie L Frijling, Mirjam Van Zuiden, Saskia B J Koch, Laura Nawijn, Li Wang, Ye Zhu, Gen Li, Yuval Neria, Xi Zhu, Benjamin Suarez-Jimenez, Sigal Zilcha-Mano, Amit Lazarov, Jennifer S Stevens, Kerry Ressler, Negar Fani, Tanja Jovanovic, Sanne J H Van Rooij, Milissa L Kaufman, Lauren A M Lebois, Isabelle M Rosso, Elizabeth A Olson, Justin T Baker, Scott R Sponheim, Seth G Disner, Nicholas D Davenport, Amit Etkin, Adi Maron-Katz, Murray B Stein, Martha E Shenton, Dan J Stein, Jonathan Ipser, Sheri-Michelle Koopowitz, Soraya Seedat, Stefan Du Plessis, Leigh L Van Den Heuvel, Shmuel Lissek, Hannah Berg, Thomas Straube, David Hofman, Lee A Baugh, Gina L Forster, Raluca M Simons, Jeffrey S Simons, Vincent A Magnotta, Kelene A Fercho, Xin Wang, Andrew S Cotton, Erin N O'Leary, Hong Xie, Daniel W Grupe, Jack B Nitschke, Richard J Davidson, Christine L Larson, Terri A Deroon-Cassini, Carissa W Tomas, Jacklynn M Fitzgerald, Jennifer Urbano Blackford, Bunmi O Olatunji, Evan M Gordon, Geoffrey May, Steven M Nelson, Ruth Lanius, Jean Théberge, Maria Densmore, Richard W J Neufeld, Chadi G Abdallah, Christopher L Averill, Ilan Harpaz-Rotem, Ifat Levy, John H Krystal, Elbert Geuze, Remko Van Lutterveld, Emily L Dennis, David F Tate, David X Cifu, William C Walker, Elisabeth A Wilde, Nic J A Van Der Wee, Robert R J M Vermeiren, Steven J A Van Der Werff, Katie Mclaughlin, Kelly Sambrook, Matthew Peverill, Joaquim Radua, Lauren E Salminen, Neda Jahanshad, Sophia I Thomopoulos, Anthony James, Lucia Valmaggia, Paul M Thompson, Rajendra A Morey, Matthew J Kempton

Faculty, Staff and Students Publications

Background: Patients with posttraumatic stress disorder (PTSD) exhibit smaller regional brain volumes in commonly reported regions including the amygdala and hippocampus, regions associated with fear and memory processing. In the current study, we have conducted a voxel-based morphometry (VBM) meta-analysis using whole-brain statistical maps with neuroimaging data from the ENIGMA-PGC PTSD working group.

Methods: T1-weighted structural neuroimaging scans from 36 cohorts (PTSD n = 1309; controls n = 2198) were processed using a standardized VBM pipeline (ENIGMA-VBM tool). We meta-analyzed the resulting statistical maps for voxel-wise differences in gray matter (GM) and white matter (WM) volumes between PTSD patients and …

Fractional Flow Reserve From Coronary Ct: Evidence, Applications, And Future Directions, Arta Kasaeian, Mohadese Ahmadzade, Taylor Hoffman, Mohammad Ghasemi-Rad, Anoop Padoor Ayyappan

Faculty, Staff and Students Publications

Coronary computed tomography angiography (CCTA) has emerged as the leading noninvasive imaging modality for the assessment of coronary artery disease (CAD), offering high-resolution visualization of the coronary anatomy and plaque characterization. The development of fractional flow reserve derived from CCTA (FFR-CT) has further transformed the diagnostic landscape by enabling the simultaneous evaluation of both anatomical stenosis and lesion-specific ischemia. FFR-CT has demonstrated diagnostic accuracy comparable to invasive FFR. The combined use of CCTA and FFR-CT is now pivotal in a broad range of clinical scenarios, including the evaluation of stable and acute chest pain, assessment of high-risk and complex plaque …

No Evidence Of Pitavastatin Effect On Muscle Area Or Density Among People With Hiv, Kristine M Erlandson, Triin Umbleja, Heather J Ribaudo, Michael T Lu, Jana Taron, Marissa R Diggs, Pamela S Douglas, Kathleen V Fitch, Carl J Fichtenbaum, Markella V Zanni, Judith A Aberg, Maria C Rodriguez-Barradas, Katharine Breaux, Rosalba Gomez Morones, Craig A Sponseller, Judith S Currier, Gerald S Bloomfield, Sarah M Chu, Alex B Lu, Carlos D Malvestutto, Steven K Grinspoon, Todd T Brown

Faculty, Staff and Students Publications

Background: Skeletal muscle area (MA) and muscle density (MD) are key determinants of physical function and typically decline with increasing age. Statins have well-known musculoskeletal effects but whether statins impact MA or MD is not well established, especially in the setting of randomized treatment.

Methods: REPRIEVE is a double-blind randomized trial evaluating the effect of pitavastatin for primary prevention of major adverse cardiovascular events in people with HIV (PWH). Thoracic paraspinal, pectoralis, and infraspinatus MA and MD were assessed among Mechanistic Substudy participants with CT at baseline and month 24.

Results: Of 804 substudy participants, 510 remained on study treatment …

No Evidence Of Pitavastatin Effect On Muscle Area Or Density Among People With Hiv, Kristine M Erlandson, Triin Umbleja, Heather J Ribaudo, Michael T Lu, Jana Taron, Marissa R Diggs, Pamela S Douglas, Kathleen V Fitch, Carl J Fichtenbaum, Markella V Zanni, Judith A Aberg, Maria C Rodriguez-Barradas, Katharine Breaux, Rosalba Gomez Morones, Craig A Sponseller, Judith S Currier, Gerald S Bloomfield, Sarah M Chu, Alex B Lu, Carlos D Malvestutto, Steven K Grinspoon, Todd T Brown

Faculty, Staff and Students Publications

Background: Skeletal muscle area (MA) and muscle density (MD) are key determinants of physical function and typically decline with increasing age. Statins have well-known musculoskeletal effects but whether statins impact MA or MD is not well established, especially in the setting of randomized treatment.

Methods: REPRIEVE is a double-blind randomized trial evaluating the effect of pitavastatin for primary prevention of major adverse cardiovascular events in people with HIV (PWH). Thoracic paraspinal, pectoralis, and infraspinatus MA and MD were assessed among Mechanistic Substudy participants with CT at baseline and month 24.

Results: Of 804 substudy participants, 510 remained on study treatment …

No Evidence Of Pitavastatin Effect On Muscle Area Or Density Among People With Hiv, Kristine M Erlandson, Triin Umbleja, Heather J Ribaudo, Michael T Lu, Jana Taron, Marissa R Diggs, Pamela S Douglas, Kathleen V Fitch, Carl J Fichtenbaum, Markella V Zanni, Judith A Aberg, Maria C Rodriguez-Barradas, Katharine Breaux, Rosalba Gomez Morones, Craig A Sponseller, Judith S Currier, Gerald S Bloomfield, Sarah M Chu, Alex B Lu, Carlos D Malvestutto, Steven K Grinspoon, Todd T Brown

Faculty, Staff and Students Publications

Background: Rapid initiation of antiretroviral therapy (Rapid ART) is a key strategy for the Ending the HIV Epidemic inititative. In Harris County, Texas, a priority Ending the HIV Epidemic jurisdiction, 57% of persons with HIV receive care at 1 of 5 public agencies that receive funding from the Ryan White HIV/AIDS Program. The Ryan White HIV/AIDS Program is administered by the US Department of Health and Human Services, Health Resources and Services Administration, and HIV/AIDS Bureau. This program administers grants to clinics and local/state programs to deliver medical and support services (Part A) for low-income persons with HIV. In 2019, …

Injury And Illness: An Analysis Of Team Usa Athletes At The 2024 Winter Youth Olympic Games, Ashley N Triplett, Eric G Post, Travis Anderson, Olivia Samson, Alexis D Gidley, Francisco Silva, Lea Thomann, Amber T Donaldson, Jonathan T Finnoff, Eric L Dugan, Jeffrey S Shilt, William M Adams

Faculty, Staff and Students Publications

Background: Injury and illness surveillance is essential for understanding the relative risks of sports participation to develop effective strategies to optimize athlete health, wellness, and performance. Epidemiological studies examining injuries and illnesses among Team USA youth athletes are limited, particularly among athletes competing in Winter sports. The purpose of this study was to characterize the injury and illness incidence rate among Team USA athletes participating in the 2024 Winter Youth Olympic Games (YOG).

Methods: Injuries and illnesses among 101 Team USA youth athletes (40.6% female; age, 17 ± 1 years) were prospectively documented. Injury and illness prevalence, and incidence rate …

Potential Biological And Genetic Links Between Dementia And Osteoporosis: A Scoping Review, Abayomi N Ogunwale, Paul E Schulz, Jude K Des Bordes, Florent Elefteriou, Nahid J Rianon

Faculty, Staff and Students Publications

Background: The biological mediators for the epidemiologic overlap between osteoporosis and dementia are unclear. We undertook a scoping review of clinical studies to identify genetic and biological factors linked with these degenerative conditions, exploring the mechanisms and pathways connecting both conditions.

Methods: Studies selected (1) involved clinical research investigating genetic factors or biomarkers associated with dementia or osteoporosis, and (2) were published in English in a peer-reviewed journal between July 1993 and March 2025. We searched Medline Ovid, Embase, PsycINFO, the Cochrane Library, the Web of Science databases, Google Scholar, and the reference lists of studies following the guidelines for …

Genes Encoding Multiple Modulators Of The Immune Response Are Methylated In The Prostate Tumor Microenvironment Of African Americans, Vinay Kumar, Tara Sinta Kartika Jennings, Lucas Ueta, James Nguyen, Liankun Song, Michael Mcclelland, Weiping Chu, Michael Lilly, Michael Ittmann, Patricia Castro, Arash Rezazadeh Kalebasty, Dan Mercola, Omid Yazdanpanah, Xiaolin Zi, Farah Rahmatpanah

Faculty, Staff and Students Publications

Background/Objectives: Prostate cancer (PCa) is diagnosed at an earlier median age, more advanced stage, and has worse clinical outcomes in African American (AA) men compared to European Americans (EA).

Methods: To investigate the role of aberrant DNA methylation in tumor-adjacent stroma (TAS), methyl binding domain sequencing (MBD-seq) was performed on AA (n = 17) and EA (n = 15) PCa patients. This was independently confirmed using the long interspersed nuclear element-1 (LINE-1) assay. Pathway analysis was performed on statistically significantly differentially methylated genes for AA and EA TAS. DNA methylation profiles of primary cultured AA and …

Mouse Metastable Epialleles Are Extremely Rare, Chathura J Gunasekara, Uditha Maduranga, Taylor Zhang, Jonathan N Wells, Maria S Baker, Eleonora Laritsky, Yumei Li, Cristian Coarfa, Yi Zhu, Robert A Waterland

Faculty, Staff and Students Publications

Metastable epialleles (MEs) are genomic loci at which epigenetic marks are established stochastically during early embryonic development and maintained during subsequent differentiation and throughout life, leading to stable epigenetic and phenotypic variation among genetically identical individuals. Although MEs were first described in mice over 20 years ago, the extent of epigenetic metastability in the mouse genome remains unknown. We present the first unbiased genome-wide screen for MEs in mice. Using deep whole-genome bisulfite sequencing across tissues derived from the three embryonic germ layers in isogenic C57BL/6J mice, we identified only 29 MEs, precisely localizing them and documenting their rarity. Consistent …

Integration Of A Pedometer-Based Physical Activity Intervention With Cognitive Behavioral Therapy For Adults With Chronic Obstructive Lung Disease, Patricia M Bamonti, Marilyn L Moy, Grace A Rose, Amy K Silberbogen, Jeffrey A Cully, Erica R Checko, David Coultas, Brent R Schell, Jennifer Moye

Faculty, Staff and Students Publications

Physical activity interventions effectively improve physical activity (i.e., daily step count) and reduce the risk of adverse health outcomes in persons with chronic obstructive pulmonary disease (COPD), but effects on depression and anxiety are poorly understood. Behavioral interventions concurrently targeting both physical activity and mood symptoms are needed in this population. This paper describes acceptability testing and refinement of Step-CBT, a synchronous, video-delivered, pedometer-based physical activity intervention integrated with cognitive behavioral therapy (CBT) to improve step count in individuals with COPD; physical disability and depression and anxiety symptoms are secondary outcomes. Adults (N = 5) with COPD and clinically significant …

Machine Learning Assisted Immune Profiling Of Copd Identifies A Unique Emphysema Subtype Independent Of Gold Stage, Natalie Bordag, Katharina Jandl, Ayu Hutami Syarif, Jürgen Gindlhuber, Diana Schnoegl, Ayse Ceren Mutgan, Vasile Foris, Konrad Hoetzenecker, Panja Maria Boehm, Robab Breyer-Kohansal, Katarina Zeder, Gregor Gorkiewicz, Francesca Polverino, Slaven Crnkovic, Grazyna Kwapiszewska, Leigh Matthew Marsh

Faculty, Staff and Students Publications

Chronic obstructive pulmonary disease (COPD) is a severe, progressive, and heterogeneous disease with a poor outcome. Inflammation plays a central role in disease pathogenesis; however, the interplay between immune changes and disease heterogeneity has been difficult to unravel. We performed a multilevel immunoinflammatory characterization of patients with COPD using flow cytometry, cytokine profiling, single-cell, or spatial transcriptomics in combination with machine learning algorithms. Our cross-cohort analysis demonstrated shared skewing of immune profiles in COPD lungs toward adaptive immune cells. We furthermore identified a subgroup of patients with COPD with a distinct immune profile, characterized by increased antigen-presenting cells, mast cells, …

Multi-Ancestry Genome-Wide Meta-Analysis Of 56,241 Individuals Identifies Known And Novel Cross-Population And Ancestry-Specific Associations As Novel Risk Loci For Alzheimer’S Disease, Farid Rajabli, Penelope Benchek, Giuseppe Tosto, Nicholas Kushch, Jin Sha, Katrina Bazemore, Congcong Zhu, Wan-Ping Lee, Jacob Haut, Kara L Hamilton-Nelson, Nicholas R Wheeler, Yi Zhao, John J Farrell, Michelle A Grunin, Yuk Yee Leung, Pavel P Kuksa, Donghe Li, Eder Lucio Da Fonseca, Jesse B Mez, Ellen L Palmer, Jagan Pillai, Richard M Sherva, Yeunjoo E Song, Xiaoling Zhang, Takeshi Ikeuchi, Taha Iqbal, Omkar Pathak, Otto Valladares, Dolly Reyes-Dumeyer, Amanda B Kuzma, Erin Abner, Larry D Adams, Perrie M Adams, Alyssa Aguirre, Marilyn S Albert, Roger L Albin, Mariet Allen, Lisa Alvarez, Liana G Apostolova, Steven E Arnold, Sanjay Asthana, Craig S Atwood, Sanford Auerbach, Gayle Ayres, Clinton T Baldwin, Robert C Barber, Lisa L Barnes, Sandra Barral, Thomas G Beach, James T Becker, Gary W Beecham, Duane Beekly, Bruno A Benitez, David Bennett, John Bertelson, Thomas D Bird, Deborah Blacker, Bradley F Boeve, James D Bowen, Adam Boxer, James Brewer, James R Burke, Jeffrey M Burns, Joseph D Buxbaum, Nigel J Cairns, Laura B Cantwell, Chuanhai Cao, Christopher S Carlson, Cynthia M Carlsson, Regina M Carney, Minerva M Carrasquillo, Scott Chasse, Marie-Francoise Chesselet, Nathaniel A Chin, Helena C Chui, Jaeyoon Chung, Suzanne Craft, Paul K Crane, David H Cribbs, Elizabeth A Crocco, Carlos Cruchaga, Michael L Cuccaro, Munro Cullum, Eveleen Darby, Barbara Davis, Philip L De Jager, Charles Decarli, John Detoledo, Malcolm Dick, Dennis W Dickson, Beth A Dombroski, Rachelle S Doody, Ranjan Duara, Nilüfer Ertekin-Taner, Denis A Evans, Kelley M Faber, Thomas J Fairchild, Kenneth B Fallon, David W Fardo, Martin R Farlow, Victoria Fernandez-Hernandez, Steven Ferris, Robert P Friedland, Tatiana M Foroud, Matthew P Frosch, Brian Fulton-Howard, Douglas R Galasko, Adriana Gamboa, Marla Gearing, Daniel H Geschwind, Bernardino Ghetti, John R Gilbert, Rodney C P Go, Alison M Goate, Thomas J Grabowski, Neill R Graff-Radford, Robert C Green, John H Growdon, Hakon Hakonarson, James Hall, Ronald L Hamilton, Oscar Harari, John Hardy, Lindy E Harrell, Elizabeth Head, Victor W Henderson, Michelle Hernandez, Timothy Hohman, Lawrence S Honig, Ryan M Huebinger, Matthew J Huentelman, Christine M Hulette, Bradley T Hyman, Linda S Hynan, Laura Ibanez, Gail P Jarvik, Suman Jayadev, Lee-Way Jin, Kim Johnson, Leigh Johnson, M Ilyas Kamboh, Anna M Karydas, Mindy J Katz, John S Kauwe, Jeffrey A Kaye, C Dirk Keene, Aisha Khaleeq, Masataka Kikuchi, Ronald Kim, Janice Knebl, Neil W Kowall, Joel H Kramer, Walter A Kukull, Frank M Laferla, James J Lah, Eric B Larson, Alan Lerner, James B Leverenz, Allan I Levey, Andrew P Lieberman, Richard B Lipton, Mark Logue, Oscar L Lopez, Kathryn L Lunetta, Constantine G Lyketsos, Douglas Mains, Flanagan E Margaret, Daniel C Marson, Eden Rr Martin, Frank Martiniuk, Deborah C Mash, Eliezer Masliah, Paul Massman, Arjun Masurkar, Wayne C Mccormick, Susan M Mccurry, Andrew N Mcdavid, Stefan Mcdonough, Ann C Mckee, Marsel Mesulam, Bruce L Miller, Carol A Miller, Joshua W Miller, Thomas J Montine, Edwin S Monuki, John C Morris, Shubhabrata Mukherjee, Amanda J Myers, Trung Nguyen, Thomas Obisesan, Sid O'Bryant, John M Olichney, Marcia Ory, Raymond Palmer, Joseph E Parisi, Henry L Paulson, Valory Pavlik, David Paydarfar, Victoria Perez, Elaine Peskind, Ronald C Petersen, Helen Petrovitch, Aimee Pierce, Marsha Polk, Wayne W Poon, Huntington Potter, Liming Qu, Mary Quiceno, Joseph F Quinn, Ashok Raj, Murray Raskind, Eric M Reiman, Barry Reisberg, Joan S Reisch, John M Ringman, Erik D Roberson, Monica Rodriguear, Ekaterina Rogaeva, Howard J Rosen, Roger N Rosenberg, Donald R Royall, Marwan Sabbagh, A Dessa Sadovnick, Mark A Sager, Mary Sano, Andrew J Saykin, Julie A Schneider, Lon S Schneider, William W Seeley, Susan H Slifer, Scott Small, Amanda G Smith, Janet P Smith, Joshua A Sonnen, Salvatore Spina, Peter St George-Hyslop, Takiyah D Starks, Robert A Stern, Alan B Stevens, Stephen M Strittmatter, David Sultzer, Russell H Swerdlow, Rudolph E Tanzi, Jeffrey L Tilson, John Q Trojanowski, Juan C Troncoso, Magda Tsolaki, Debby W Tsuang, Vivianna M Van Deerlin, Linda J Van Eldik, Jeffery M Vance, Badri N Vardarajan, Robert Vassar, Harry V Vinters, Jean-Paul Vonsattel, Sandra Weintraub, Kathleen A Welsh-Bohmer, Patrice L Whitehead, Ellen M Wijsman, Kirk C Wilhelmsen, Benjamin Williams, Jennifer Williamson, Henrik Wilms, Thomas S Wingo, Thomas Wisniewski, Randall L Woltjer, Martin Woon, Clinton B Wright, Chuang-Kuo Wu, Steven G Younkin, Chang-En Yu, Lei Yu, Xiongwei Zhu, Brian W Kunkle, William S Bush, Akinori Miyashita, Goldie S Byrd, Li-San Wang, Lindsay A Farrer, Jonathan L Haines, Richard Mayeux, Margaret A Pericak-Vance, Gerard D Schellenberg, Gyungah R Jun, Christiane Reitz, Adam C Naj, Alzheimer’S Disease Genetics Consortium (Adgc)

Faculty, Staff and Students Publications

Background: Limited ancestral diversity has impaired our ability to detect risk variants more prevalent in ancestry groups of predominantly non-European ancestral background in genome-wide association studies (GWAS). We construct and analyze a multi-ancestry GWAS dataset in the Alzheimer's Disease Genetics Consortium (ADGC) to test for novel shared and population-specific late-onset Alzheimer's disease (LOAD) susceptibility loci and evaluate underlying genetic architecture in 37,382 non-Hispanic White (NHW), 6728 African American, 8899 Hispanic (HIS), and 3232 East Asian individuals, performing within ancestry fixed-effects meta-analysis followed by a cross-ancestry random-effects meta-analysis.

Results: We identify 13 loci with cross-population associations including known loci at/near CR1, …

Prognostic Gene Expression And Microrna Profiling Signatures And Genetic Alterations In Primary Testicular Diffuse Large B-Cell Lymphoma, Wenyu Shi, Zijun Y Xu-Monette, Youchao Jia, Alexandar Tzankov, Heounjeong Go, Ling Li, Maurilio Ponzoni, Yafei Wang, Qiongli Zhai, Anamarija M Perry, Shi Wang, Xiaoxiao Wang, April Chiu, Mina L Xu, Carlo Visco, Karen Dybkaer, Henry Withers, Mark Long, Alyssa F Yuan, Yi Miao, Everardo Macias, Dehong Wu, Wen Shuai, Bangchen Wang, Jianyong Li, Govind Bhagat, Youli Zu, Zenggang Pan, William Choi, Santiago Montes-Moreno, Weina Chen, J Han Van Krieken, Michael B Møller, Xinfang Yu, Benjamin M Parsons, Shanxiang Zhang, Eric D Hsi, Aliyah R Sohani, Jeremy S Abramson, Andrés J M Ferreri, Bing Xu, Yong Li, Ken H Young

Faculty, Staff and Students Publications

Primary testicular (PT) diffuse large B-cell lymphoma (DLBCL) is a rare and aggressive lymphoma with distinct clinical and molecular characteristics. To identify prognostic biomarkers in PT-DLBCL, in this study we analyzed DNA and RNA samples of PT-DLBCL tumors from 206 patients using next-generation sequencing platforms and assays. Genetic alteration analysis found that multiple chromosomal copy number variations (CNVs), TP53 transcript mutations with high variant allele frequency, and MCD subtype had significantly adverse prognostic effects, whereas elevated microsatellite instability had a significantly favorable prognostic effect in PT-DLBCL. Targeted RNA-seq analysis identified a PTL gene expression signature by comparing PT-DLBCL with systemic …

Publisher Correction: Comprehensive Evaluation Of Phosphoproteomic-Based Kinase Activity Inference, Sophia Müller-Dott, Eric J Jaehnig, Khoi Pham Munchic, Wen Jiang, Tomer M Yaron-Barir, Sara R Savage, Martin Garrido-Rodriguez, Jared L Johnson, Alessandro Lussana, Evangelia Petsalaki, Jonathan T Lei, Aurelien Dugourd, Karsten Krug, Lewis C Cantley, D R Mani, Bing Zhang, Julio Saez-Rodriguez

Faculty, Staff and Students Publications

No abstract provided.

Sensing The Stiffness: Cellular Mechano-Sensing At The Implant Interface, Patricia S Pardo, Delia Danila, Raja Devesh Kumar Misra, Aladin M Boriek

Faculty, Staff and Students Publications

In this perspective, we highlight the relevance of the FA-Hippo signaling pathway and its regulation of the Yes-associated protein (YAP) and the transcriptional coactivator with a PDZ-binding domain (TAZ) as main players in the process of implants integration. The modulation and responses of YAP/TAZ triggered by substrate and ECM stiffness are of particular interest in the construction of materials used for medical implants. YAP/TAZ nuclear localization and activity respond to the substrate stiffness by several mechanisms that involve the canonical and non-canonical Hippo signaling and independently of the Hippo cascade. YAP/TAZ regulate the expression of genes involved in several mechanisms …

Development And Validation Of Risk Models For Hospital-Acquired Bleeding In Medical Inpatients: The Medical Inpatients Thrombosis And Hemostasis (Mith) Study, Neil A Zakai, Katherine Wilkinson, Andrew D Sparks, Ryan T Packer, Nicholas S Roetker, Allen B Repp, Mansour Gergi, Chris Holmes, Mary Cushman, Timothy B Plante, Hanny Al-Samkari, Allyson M Pishko, William A Wood, Camila Masias, Radhika Gangaraju, Ang Li, David Garcia, Kerri L Wiggins, Jordan K Schaefer, Nicholas L Smith, Augusto Ferraris, Karlyn A Martin, Deirdra R Terrell, Leslie A Mcclure

Faculty, Staff and Students Publications

Background: Hospital-acquired (HA) bleeding in medical inpatients is a serious complication with limited tools to predict risk.

Objectives: This study aimed to develop and validate risk assessment models (RAMs) for anatomic location-specific HA bleeding in medical inpatients using objective and routinely available risk factors.

Methods: Patients aged ≥18 years admitted to medical hospital services from 6 health systems and 15 hospitals in the United States between 2016 and 2020 for at least 1 midnight and without bleeding at admission were eligible for inclusion. Two health systems (10 hospitals) formed the development cohort, and 4 systems (5 hospitals) constituted the validation …

Elimination Of Hiv Reservoirs Harboring Intact Proviruses, Min Li, Khanghy Truong, Suman Sharma, Baichao Sun, Min Chen, Jason T Kimata, Jin Wang

Faculty, Staff and Students Publications

Background: Human immunodeficiency virus (HIV) establishes persistent infection by integrating its proviral DNA into the host genome. While most integrated proviruses are defective, a small portion of proviruses are intact that represent a major obstacle to achieving an HIV cure. 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. However, the effects of SECH on the dynamics of intact and defective HIV provirus remain unclear.

Methods: We isolated DNA from HIV-infected samples after SECH treatments. We analyzed HIV-1 proviruses in these samples by intact …