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Screpertoire 2: Enhanced And Efficient Toolkit For Single-Cell Immune Profiling, Qile Yang, Ksenia R. Safina, Kieu Diem Quynh Nguyen, Zewen Kelvin Tuong, Nicholas Borcherding

2020-Current year OA Pubs

Single-cell adaptive immune receptor repertoire sequencing (scAIRR-seq) and single-cell RNA sequencing (scRNA-seq) provide a transformative approach to profiling immune responses at unprecedented resolution across diverse pathophysiologic contexts. This work presents scRepertoire 2, a substantial update to our R package for analyzing and visualizing single-cell immune receptor data. This new version introduces an array of features designed to enhance both the depth and breadth of immune receptor analysis, including improved workflows for clonotype tracking, repertoire diversity metrics, and novel visualization modules that facilitate longitudinal and comparative studies. Additionally, scRepertoire 2 offers seamless integration with contemporary single-cell analysis frameworks like Seurat and …

Cysteine Depletion Triggers Adipose Tissue Thermogenesis And Weight Loss, Aileen H Lee, Irina Shchukina, Prabhakar Sairam Andhey, Maxim N Artyomov, Et Al.

2020-Current year OA Pubs

Caloric restriction and methionine restriction-driven enhanced lifespan and healthspan induces 'browning' of white adipose tissue, a metabolic response that increases heat production to defend core body temperature. However, how specific dietary amino acids control adipose thermogenesis is unknown. Here, we identified that weight loss induced by caloric restriction in humans reduces thiol-containing sulfur amino acid cysteine in white adipose tissue. Systemic cysteine depletion in mice causes lethal weight loss with increased fat utilization and browning of adipocytes that is rescued upon restoration of cysteine in diet. Mechanistically, cysteine-restriction-induced adipose browning and weight loss requires sympathetic nervous system-derived noradrenaline signalling via …

A Systematic Review And Meta-Analysis Of Social Cognition Among People Living With Hiv: Implications For Non-Social Cognition And Social Everyday Functioning, David E Vance, Rebecca Billings, Crystal Chapman Lambert, Pariya L Fazeli, Burel R Goodin, Mirjam-Colette Kempf, Leah H Rubin, Bulent Turan, Jenni Wise, Gerhard Hellemann, Junghee Lee

2020-Current year OA Pubs

Social cognition-the complex mental ability to perceive social stimuli and negotiate the social environment-has emerged as an important cognitive ability needed for social functioning, everyday functioning, and quality of life. Deficits in social cognition have been well documented in those with severe mental illness including schizophrenia and depression, those along the autism spectrum, and those with other brain disorders where such deficits profoundly impact everyday life. Moreover, subtle deficits in social cognition have been observed in other clinical populations, especially those that may have compromised non-social cognition (i.e., fluid intelligence such as memory). Among people living with HIV (PLHIV), 44% …

Phase 2 Open-Label Study Of Sacituzumab Govitecan As Second-Line Therapy In Patients With Extensive-Stage Sclc: Results From Tropics-03, Afshin Dowlati, Anne C Chiang, Andrés Cervantes, Sunil Babu, Erika Hamilton, Shu Fen Wong, Andrea Tazbirkova, Ivana Gabriela Sullivan, Cédric Van Marcke, Antoine Italiano, Jilpa Patel, Sabeen Mekan, Tia Wu, Saiama N Waqar

2020-Current year OA Pubs

INTRODUCTION: The phase 2 TROPiCS-03 study evaluated the efficacy/safety of sacituzumab govitecan (SG) as second-line treatment in patients with previously treated extensive-stage SCLC (ES-SCLC).

METHODS: TROPiCS-03 (NCT03964727) is a multicohort, open-label, phase 2 basket study of solid tumors, including ES-SCLC. Adults with ES-SCLC that progressed after one previous line of platinum-based chemotherapy and anti-programmed death-(ligand) 1 (PD-[L]1) therapy received SG 10 mg/kg on days 1 and 8 of a 21-day cycle. The primary end point was the investigator-assessed objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors version 1.1. Key secondary end points included investigator-assessed duration of …

Plasma Mtbr-Tau243 Biomarker Identifies Tau Tangle Pathology In Alzheimer's Disease, Kanta Horie, Rama K Koppisetti, Nicolas R Barthélemy, Yingxin He, Chihiro Sato, Brian A Gordon, Hong Jiang, Tammie L S Benzinger, David M Holtzman, John C Morris, Suzanne E Schindler, Randall J Bateman, Et Al.

2020-Current year OA Pubs

Insoluble tau aggregates within neurofibrillary tangles are a defining neuropathological feature of Alzheimer's disease (AD) and closely correlate with clinical symptoms. Although tau pathology can be assessed using tau positron emission tomography, a more accessible biomarker is needed for diagnosis, prognosis and tracking treatment effects. Here we present a new plasma tau species, the endogenously cleaved, microtubule-binding region containing residue 243 (eMTBR-tau243), which specifically reflects tau tangle pathology. Across the AD spectrum in three different cohorts (n = 108, 55 and 739), plasma eMTBR-tau243 levels were significantly elevated at the mild cognitive impairment stage and increased further in dementia. Plasma …

Perceptions Of Smoking Stigma Among African Americans: A Qualitative Study, Denine R. Crittendon, Alison C. Brecher, Samantha Okere, Richard Hass, Rosemary Frasso, Rickie Brawer, Mph, Phd, Charnita Zeigler-Johnson

College of Population Health Faculty Papers

INTRODUCTION: African Americans/Blacks (AAB) are at increased risk for morbidity and mortality from smoking-related diseases including lung cancer (LC). Smoking stigma is believed to be a primary barrier to health care-seeking for people who smoke. Previous studies illustrate that perceptions of smoking vary across populations. However, little is known about the prevalence of smoking stigmas among AAB. The purpose of this study was to increase understanding of the perception of cigarette smoking by AAB.

AIMS AND METHODS: We conducted free-listing interviews in which individuals listed all-thoughts and feelings regarding smoking and health-related questions with a convenience sample of eligible AAB …

Clinical Trial Readiness In Limb Girdle Muscular Dystrophy R1 (Lgmdr1): A Grasp Consortium Study, Stephanie M Hunn, Amanda Clause, Conrad C Weihl, Et Al.

2020-Current year OA Pubs

OBJECTIVE: Identifying functional measures that are both valid and reliable in the limb girdle muscular dystrophy (LGMD) population is critical for quantifying the level of functional impairment related to disease progression in order to establish clinical trial readiness in the context of anticipated therapeutic trials.

METHODS: Through the Genetic Resolution and Assessments Solving Phenotypes in LGMD (GRASP-LGMD) Consortium, 42 subjects with LGMDR1 were enrolled in a 12-month natural history study across 11 international sites. Each subject completed a battery of clinical outcome assessments (COA), including the North Star Assessment for Limb Girdle-Type Dystrophies (NSAD), 10-m walk/run, and Performance of the …

Burst Steroid Therapy And Quality Of Life In Patients With Acute Heart Failure: Insights From The Cortahf Trial, Matteo Pagnesi, Douglas L Mann, Et Al.

2020-Current year OA Pubs

AIMS: Patients hospitalized with acute heart failure (AHF) treated with a 7 day prednisone course in the CORTAHF pilot trial had a greater improvement in health-related quality of life (QoL) at Day 7 in both the overall population and in patients with baseline interleukin 6 > 13 pg/mL. This post-hoc analysis examines the specific QoL domains and the relationship between clinical signs of congestion and QoL.

METHODS: In the CORTAHF pilot trial, patients with AHF and high-sensitivity C-reactive protein (hsCRP) > 20 mg/L were randomized 1:1 to once-daily oral 40 mg prednisone for 7 days plus usual care or usual care alone. …

Barriers To Clinical Cosmetic And Laser Dermatology Research In The Academic Setting By Source Of Funding: A Systematic Review, Bianca Y. Kang, Saranya P. Wyles, Yakir Levin, Rawaa Almukhtar, Stephanie R. Jackson Cullison, Jayne S. Joo, Sami K. Saikaly, Shalinie Mahadeo, Michael Ong, Sophia Salingaros, Maria Hordinsky, Sarah A. Ibrahim, Devina Mehta, Shoko Mori, Edit B. Olasz Harken, Diana Bolotin, Kira Minkis, Murad Alam

Department of Dermatology and Cutaneous Biology Faculty Papers

Clinical research is a cornerstone of academic dermatology, including research in cosmetic and laser procedures. However, numerous barriers exist to conducting clinical research in an academic setting as compared to private practice. The objective of this study was to describe the barriers to clinical research in cosmetic and laser dermatology in the academic setting under three common funding scenarios: (1) industry sponsored, (2) unfunded, investigator-initiated, and (3) publicly funded, investigator-initiated. A systematic review of the literature was conducted to identify 17 publications regarding funding of clinical dermatology research. Inductive content analysis was used to extract, categorize, and understand the barriers …

Anti-Viral Cd8 Central Memory Veto Cells As A New Platform For Car T Cell Therapy, Wei-Hsin Liu, Anat Globerson Levin, Assaf Lask, Galit Horn, Tova Waks, Bar Nathansohn Levi, Irit Milman Krentsis, Einav Shoshan, Xiaohua Su, Maksim Mamonkin, Richard E Champlin, Yair Reisner, Esther Bachar Lustig

Faculty, Staff and Student Publications

Central memory CD8 T cells exhibit marked veto activity enhancing engraftment in several mouse models of T cell-depleted bone marrow (TDBM) allografting. Graft-versus-host disease (GVHD) can be prevented by stimulation of mouse or human memory CD8 T cells against their cognate antigens under cytokine deprivation, in the early phase of culture followed by further expansion with IL21, IL15, and IL7. Thus, human anti-viral CD8 central memory veto T cells generated from CMV and EBV-positive donors are currently evaluated in a clinical trial at MD Anderson Cancer Centre (MDACC). Results in 15 patients indicate a low risk of GVHD. Considering that …

Icam-1 Autoantibodies Detected In Healthy Individuals And Cross-React With Functional Epitopes., Marc L. Herman, Eric S. Geanes, Rebecca Mclennan, Gage Greening, Heather Mwitanti, Todd Bradley

Manuscripts, Articles, Book Chapters and Other Papers

Intracellular adhesion molecule 1 (ICAM-1) is a cell surface glycoprotein that regulates cell-cell interactions, signaling, and immune processes. ICAM-1 expression has been shown to be elevated in many types of infections and inflammatory diseases. Strategies to block ICAM-1 function, including monoclonal anti-ICAM-1 antibodies, have been successful in treating the effects of chronic respiratory, autoimmune, and cardiovascular diseases. Naturally occurring autoantibodies targeting cytokines, endothelial cells, and other host receptors have been identified, and have been found to play a role in immunoregulation in health and disease. In this study, we determined the presence and levels of ICAM-1 autoantibodies across different age …

Colorectal Cancer And The Risk Of Mortality Among Individuals With Suicidal Ideation, Srikanta Banerjee, Jagdish Khubchandani, Stanley Nkemjika

Department of Psychiatry and Human Behavior Faculty Papers

Suicide is a major public health problem that has grown at alarming rates in the last two decades. Colorectal cancer (CRC) is one of the most common causes of cancer deaths in the United States in both males and females. However, the influence of suicidal ideation (SI) on the association between CRC and risk of mortality has not been well examined.

METHODS: For this study, the 2005-2018 National Health and Nutrition Examination Survey (NHANES), a nationally representative survey of United States adults aged 20 years or older, was utilized. CRC survivorship was determined from self-reported data on CRC, and mortality …

Neovascular Pruning By Ido1 Inhibitors Can Potentiate Immunogenic Cytotoxicity Of Ischemia-Targeted Agents To Synergistically Enhance Anti-Pd-1 Responsiveness, Shih-Chun Shen, Souvik Dey, James B. Duhadaway, Erika Sutanto-Ward, Maurice T. Hampton, Serguei V. Kozlov, George C. Prendergast, Alexander J. Muller

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Strategies for deploying indoleamine 2,3-dioxygenase 1 (IDO1)-targeted therapies for use against cancer have focused on IDO1's role in promoting peripheral immune tolerance that shields tumors from effector T cells. However, preclinical investigation of both primary and metastatic tumor development in the lungs has uncovered a previously unappreciated role for IDO1 in directing a counterregulatory response to interferon (IFN)-γ that realigns the local inflammatory environment to promote tumor neovascularization. Understanding how to therapeutically leverage the ability of IDO1 inhibitors to subvert inflammatory neovascularization within the tumor microenvironment has potential ramifications for future clinical development of these compounds.

METHODS: Pulmonary metastases …

Development And Validation Of The Immune Profile Score (Ips), A Novel Multiomic Algorithmic Assay For Stratifying Outcomes In A Real-World Cohort Of Patients With Advanced Solid Cancer Treated With Immune Checkpoint Inhibitors, Alia D Zander, Douglas Adkins, Et Al.

2020-Current year OA Pubs

BACKGROUND: Immune checkpoint inhibitors (ICIs) have transformed the oncology treatment landscape. Despite substantial improvements for some patients, the majority do not benefit from ICIs, indicating a need for predictive biomarkers to better inform treatment decisions.

METHODS: A de-identified pan-cancer cohort from the Tempus multimodal real-world database was used for the development and validation of the Immune Profile Score (IPS) algorithm leveraging Tempus xT (648 gene DNA panel) and xR (RNA sequencing) (N=1,707 development cohort; N=1,600 validation cohort). The cohort consisted of patients with advanced stage cancer with solid tumor carcinomas across 16 cancer types treated with any ICI-containing regimen as …

Mechanisms Of Change Of A Multifaceted Implementation Strategy On Fidelity To A Guideline For The Prevention Of Mental Health Problems At The Workplace: A Mechanism Analysis Within A Cluster-Randomized Controlled Trial, Andreas Rödlund, Anna Toropova, Rebecca Lengnick-Hall, Byron J Powell, Liselotte Schäfer Elinder, Christina Björklund, Lydia Kwak

2020-Current year OA Pubs

BACKGROUND: Occupational guidelines exist to support workplaces with the prevention of mental health problems (MHP) among their staff. However, knowledge of effective implementation strategies to support their implementation is limited. This study experimentally tested whether a multifaceted implementation strategy - comprising an educational meeting, five workshops, implementation teams, small cyclical tests of change, and facilitation - improves fidelity to a guideline for preventing MHP in a school setting through the pathway of change of the Capability Opportunity Motivation-Behavior (COM-B)-model. To gain a more granular understanding of the mechanisms of change, the Theoretical Domains Framework (TDF) was used to specify mediators …

Artificial Intelligence Use In Medical Education: Best Practices And Future Directions, Rasheed A. M. Thompson, Yash B. Shah, Francisco Aguirre, Courtney Stewart, Costas D. Lallas, Mihir S. Shah

Department of Urology Faculty Papers

PURPOSEOF REVIEW: This review examines the various ways artificial intelligence (AI) has been utilized in medical education (MedEd)and presents ideas that will ethically and effectively leverage AI in enhancing the learning experience of medical trainees.

RECENT FINDINGS: AI has improved accessibility to learning material in a manner that engages the wider population. It has utility as a reference tool and can assist academic writing by generating outlines, summaries and identifying relevant reference articles. As AI is increasingly integrated into MedEd and practice, its regulation should become a priority to prevent drawbacks to the education of trainees. By involving physicians in …

Development Of An Age-Appropriate Household Dysfunction Measure And Its Concurrent Validity With Multiple Outcomes Among Middle School Adolescents In Southeast Texas, Sumaita Choudhury, Timothy J Walker, Emily T Hébert, Christine M Markham, Ross Shegog, Robert C Addy, Melissa F Peskin

Faculty, Staff and Student Publications

Existing adverse childhood experience (ACE) measures include a limited number of household dysfunction (HD) items and the use of adult-oriented language that is not always appropriate for middle schoolers. We developed an age-appropriate 10-item HD measure informed by previously validated ACE measures and tested its concurrent validity with dating violence (DV) perpetration, lifetime substance use, and mental health outcomes among middle schoolers in Southeast Texas. This cross-sectional study used the baseline data from a DV prevention intervention program for sixth graders (N = 126), Me & You Tech. Baseline data were collected from March 2023 to April 2023. To …

Biallelic Loss-Of-Function Variant In Minpp1 Causes Pontocerebellar Hypoplasia With Characteristic Severe Neurodevelopmental Disorder, Aljazi Al-Maraghi, Rulan Shaath, Katherine Ford, Waleed Aamer, Jehan Alrayahi, Sura Hussein, Elbay Aliyev, Nourhen Agrebi, Muhammad Kohailan, Satanay Z Hubrack, Sasirekha Palaniswamy, Adam D Kennedy, Karen L Debalsi, Sarah H Elsea, Ruba Benini, Tawfeg Ben-Omran, Bernice Lo, Ammira S A Akil, Khalid A Fakhro

Faculty, Staff and Students Publications

Pontocerebellar hypoplasia (PCH) encompasses a group of autosomal recessive neurodegenerative disorders marked by cerebellar and pontine atrophy. Multiple subtypes of PCH have been identified, among which the rare subtype PCH type 16 is caused by MINPP1 genetic variants. MINPPI encodes an enzyme essential for inositol polyphosphate dephosphorylation, regulating calcium and iron homeostasis. We conducted genome sequencing on a proband from the consanguineous family, who presented with a severe neurodegenerative disorder, to identify the underlying cause of disease. A comprehensive clinical assessment in addition to neuroradiological findings are described. We performed the functional validation of the identified variant and conducted untargeted …

Spatiotemporal Calcium Signaling Patterns Underlying Opposing Effects Of Histamine And Tas2r Agonists In Airway Smooth Muscle, Stanley Conaway, Joshua Richard, Deepak A. Deshpande

Center for Translational Medicine Faculty Papers

Intracellular calcium (Ca²⁺) release via phospholipase C (PLC) following G-protein-coupled receptor (GPCR) activation is typically linked to membrane depolarization and airway smooth muscle (ASM) contraction. However, recent findings show that bitter taste receptor agonists, such as chloroquine (CQ), induce a paradoxical and potent relaxation response despite activating the Ca²⁺ signaling pathway. This relaxation has been hypothesized to be driven by a distinct compartmentalization of calcium ions toward the cellular periphery, subsequently leading to membrane hyperpolarization, in contrast to the contractile effects of histamine. In this study, we further investigate the spatiotemporal dynamics of Ca²⁺ signaling in …

Comparison Of Thrombectomy Alone Versus Bridging Thrombolysis In A Us Population Using Regression Discontinuity Analysis, Youngran Kim, Sergio Salazar-Marioni, Rania Abdelkhaleq, Ananya Iyyangar, Diogo Haussen, Jonathan Grossberg, Jaydevsinh Dolia, Aqueel Pabaney, Mahmoud Mohammaden, Ameer Hassan, Wondwossen Tekle, Hamzah Saei, Mohamad Abdalkader, Piers Klein, Taha Nisar, Adeel Saleemi, Shahram Majidi, Johanna Fifi, Gabrielle Valestin, Guillermo Linares, Kara Christopher, David S Liebeskind, Mouhammad Jumaa, Syed Zaidi, Raul Nogueira, Brijesh Mehta, Joy Sessa, Juan Vivanco-Suarez, Aaron Rodriguez-Calienes, Milagros Galecio-Castillo, Santiago Ortega-Gutierrez, James Siegler, Mary Penckofer, Italo Linfante, Sunil A Sheth, Svin Registry Consortium

Faculty, Staff and Student Publications

The role of intravenous thrombolysis (IVT) in combination with endovascular thrombectomy (EVT) for the treatment of large vessel occlusion acute ischemic stroke has been evaluated exclusively outside the US, in randomized clinical trials which failed to demonstrate non-inferiority of skipping IVT. Because practice patterns and IVT dosing differ within the US, and prior observational US-based cohorts suggested improved clinical outcomes in patients who received IVT before EVT, a US-based evaluation is needed. This is a quasi-experimental study of a large US cohort using a regression discontinuity design (RDD) that enables the estimation of causal effects when randomization is not feasible. …

Methylation Risk Score Of C-Reactive Protein Associates Sleep Health With Related Health Outcomes, Ziqing Wang, Danielle A Wallace, Brian W Spitzer, Tianyi Huang, Kent D Taylor, Jerome I Rotter, Stephen S Rich, Peter Y Liu, Martha L Daviglus, Lifang Hou, Alberto R Ramos, Sonya Kaur, J Peter Durda, Hector M González, Myriam Fornage, Susan Redline, Carmen R Isasi, Tamar Sofer

Faculty, Staff and Student Publications

C-reactive protein (CRP) reflects inflammation status and is linked to poor sleep, metabolic and cardiovascular health. Methylation (MRS) and polygenic risk scores (PRS) reflect long-term systemic inflammation, and genetically-determined CRP, respectively. To refine understanding of inflammation-linked sleep and health outcomes, we construct PRS-CRPs using GWAS summary statistics and a previously-developed MRS-CRP in the Hispanic Community Health Study/Study of Latinos. Via survey-weighted linear regression, we estimate associations between blood-, PRS-, and MRS-CRP, with multiple sleep and health outcomes (n = 2217). MRS-CRP and PRS-CRPs are associated with increasing blood-CRP level by 43% and 23% per standard deviation. MRS-CRP is associated with …

Stathmin-2 Enhances Motor Axon Regeneration After Injury Independent Of Its Binding To Tubulin., Melinda S Beccari, Olatz Arnold-Garcia, Michael W Baughn, Jonathan W Artates, Melissa Mcalonis-Downes, Jaisen Lim, Dulce Fernanda Leyva-Cázares, Hugo Isaac Rubio-Lara, Andrea Ramirez-Rodriguez, Carol N Bernal-Buenrostro, Brian Murgia-Bay, Carolina K Rangel, Dong Hyun Kim, Ze'ev Melamed, Cathleen Lutz, Clotilde Lagier-Tourenne, Kevin D Corbett, Jone López-Erauskin, Don W Cleveland

Faculty Research 2025

Stathmin-2 (also known as SCG10) is encoded by the STMN2 gene, whose mRNA is one of the most abundantly expressed in human motor neurons. In almost all instances of ALS and other TDP-43 proteinopathies, stathmin-2 encoding mRNAs are cryptically spliced and polyadenylated in motor neurons, a pathogenic consequence of nuclear loss of function of the RNA binding protein TDP-43. While stathmin-2 has been shown to enhance regeneration after axonal injury to axons of cultured motor neurons, here, we show that after crush injury within the adult murine nervous system of wild-type or stathmin-2-null mice, the presence of stathmin-2 reduces …

The Impact Of Breast Radiotherapy On The Tumor Genome And Immune Ecosystem, Aislyn Schalck, Tuan Tran, Jianzhuo Li, Emi Sei, Shanshan Bai, Min Hu, Jerome Lin, Scott J Bright, Samuel Reddick, Fei Yang, Harsh Batra, Alejandro Contreras, Maria Gabriela Raso, Michael C Stauder, Karen E Hoffman, Jay P Reddy, Kevin T Nead, Benjamin D Smith, Gabriel O Sawakuchi, Wendy A Woodward, Stephanie S Watowich, Jennifer K Litton, Isabelle Bedrosian, Elizabeth A Mittendorf, Huong Le-Petross, Nicholas E Navin, Simona F Shaitelman

Faculty, Staff and Student Publications

Radiotherapy is a pillar of breast cancer treatment; however, it remains unclear how radiotherapy modulates the tumor microenvironment. We investigated this question in a cohort of 20 patients with estrogen-receptor positive (ER+) breast tumors who received neoadjuvant radiotherapy. Tumor biopsies were collected before and 7 days postradiation. Single-cell DNA sequencing (scDNA-seq) and scRNA-seq were conducted on 8 and 11 patients, respectively, at these two time points. The scRNA data showed increased infiltration of naive-like CD4 T cells and an early, activated CD8 T cell population following radiotherapy. Radiotherapy also eliminated existing cytotoxic T cells and resulted in myeloid cell increases. …

Heterozygous Kmt2d Loss Diminishes Enhancers To Render Medulloblastoma Cells Vulnerable To Combinatory Inhibition Of Lsd1 And Oxphos, Shilpa S Dhar, Calena Brown, Ali Rizvi, Lauren Reed, Sivareddy Kotla, Constantin Zod, Janak Abraham, Jun-Ichi Abe, Veena Rajaram, Kaifu Chen, Min Gyu Lee

Faculty, Staff and Student Publications

The histone H3 lysine 4 (H3K4) methyltransferase KMT2D (also called MLL4) is one of the most frequently mutated epigenetic modifiers in many cancers, including medulloblastoma (MB). Notably, heterozygous KMT2D loss frequently occurs in MB and other cancers. However, its oncogenic role remains largely uncharacterized. Here, we show that heterozygous Kmt2d loss in murine cerebellar regions promotes MB genesis driven by heterozygous loss of the MB-suppressor gene Ptch via the upregulation of tumor-promoting programs (e.g., oxidative phosphorylation [OXPHOS]). Downregulation of the transcription-repressive tumor suppressor NCOR2 by heterozygous Kmt2d loss, along with Ptch

Candidate Interventions For Integrating Hypertension And Cardiovascular-Kidney-Metabolic Care In Primary Health Settings: Hearts 2.0 Phase 1, Andres Rosende, Mark D Huffman, Et Al.

2020-Current year OA Pubs

BACKGROUND: HEARTS in the Americas is the regional adaptation of the WHO Global HEARTS Initiative, aimed at helping countries enhance hypertension and cardiovascular disease (CVD) risk management in primary care settings. Its core implementation tool, the HEARTS Clinical Pathway, has been adopted by 28 countries. To improve the care of hypertension, diabetes, and chronic kidney disease (CKD), HEARTS 2.0 was developed as a three-phase process to integrate evidence-based interventions into a unified care pathway, ensuring consistency across fragmented guidelines. This paper focuses on Phase 1, highlighting targeted interventions to improve and update the HEARTS Clinical Pathway.

METHODS: First, the coordinating …

Overcoming Nk-Mediated Rejection By Anti-3rd-Party Central Memory Veto Cd8 T Cells Through Downregulation Of Dnam-1 On Alloreactive Nk Cells, Wei-Hsin Liu, Aloukick Kumar Singh, Christa Blagdon, Sandeep Kumar Yadav, Einav Shoshan, Esther Bachar-Lustig, Yair Reisner

Faculty, Staff and Student Publications

Anti-3rd-party central memory veto CD8 T (veto Tcm) cells can overcome T cell-mediated graft rejection under mild conditioning without causing significant graft versus host disease (GVHD). We previously demonstrated that these veto Tcm cells can effectively delete anti-donor T cell clones through a Fas-FasL mechanism, whereas their ability to neutralize alloreactive natural killer (NK) cells and the mechanism of such potential activity remained unknown. Using “nude” mice as recipients of allogeneic T cell-depleted hematopoietic stem cell transplantation (HSCT), we demonstrate effective inhibition of NK-mediated rejection by Tcm cells. Ex vivo studies revealed that Tcm cells express high levels of CD155, …

Broadening Inclusion Of Primary Care: Trainee Insights And Commentary On Diversity, Equity, And Inclusion., K Taylor Bosworth, Meghan Gilfoyle, Kimberley Norman, Kimberley Norman, Ashley Chisholm, Ione Locher, Naod F Belay, Bryce Ringwald, Chloe Warpinski, Geetika Gupta, Minika Ohioma, Macee Boyle

Medical Education Articles

We, as the current and immediate-past NAPCRG Trainee Committee, share our perspectives as an international and diverse group of primary care research trainees. In this essay, we discuss the challenges and opportunities for achieving a more diverse, equitable, and inclusive primary care workforce by reflecting on 2 main challenges: (1) insufficient support for underrepresented identities in medicine, and (2) inadequate integration within existing primary care teams. Within each of these challenges, we pose potential opportunities for improvement using a trainee lens.

Methods For Joint Modeling Of Longitudinal Omics Data And Time-To-Event Outcomes: Applications To Lysophosphatidylcholines In Connection To Aging And Mortality In The Long Life Family Study, Konstantin G Arbeev, Olivia Bagley, Svetlana V Ukraintseva, Alexander Kulminski, Eric Stallard, Michaela Schwaiger-Haber, Gary J Patti, Yian Gu, Anatoliy I Yashin, Michael A Province

2020-Current year OA Pubs

Studying the relationships between longitudinal changes in omics variables and event risks requires specific methodologies for joint analyses of longitudinal and time-to-event outcomes. We applied two such approaches (joint models [JM], stochastic process models [SPM]) to longitudinal metabolomics data from the Long Life Family Study, focusing on the understudied associations of longitudinal changes in lysophosphatidylcholines (LPCs) with mortality and aging-related outcomes. We analyzed 23 LPC species, with 5,066 measurements of each in 3,462 participants, 1,245 of whom died during follow-up. JM analyses found that higher levels of the majority of LPC species were associated with lower mortality risks, with the …

The Impact Of Narratives And Active Video Games Among Black And Hispanic Children With Overweight And Obesity: A Randomized Controlled Trial, Amy S Lu, Tom Baranowski, Tiago V Barreira, Amy Fleischman, Melanie C Green, Shirley Y Huang, I-Min Lee, Lynne L Levitsky, Farzad Noubary, Debbe Thompson

Children’s Nutrition Research Center Staff Publications

Background: Overweight and obesity disproportionately affect Black and Hispanic children who also play more video games. Narratives, coupled with home-based active video games (AVGs), may enhance PA and mitigate these disparities. This study tested the effect of narrative-enhanced home-based AVGs among predominantly Black and Hispanic children with overweight and obesity.

Methods: This 6-month three-group RCT recruited 135 children aged 7-14 from pediatric clinics in Boston, MA (January 2020 - May 2022) during the COVID-19 pandemic. Participants were randomized into: [Narrative + AVG], receiving an Xbox/Kinect with six AVGs interspersed with a narrative animation Ataraxia (72 episodes over six months), which …

Dna Repair And The Contribution To Chemotherapy Resistance, Ksenija Nesic, Phoebe Parker, Elizabeth M Swisher, John J Krais

2020-Current year OA Pubs

The DNA damage response comprises a set of imperfect pathways that maintain cell survival following exposure to DNA damaging agents. Cancers frequently exhibit DNA repair pathway alterations that contribute to their intrinsic genome instability. This, in part, facilitates a therapeutic window for many chemotherapeutic agents whose mechanisms of action often converge at the generation of a double-strand DNA break. The development of therapy resistance occurs through countless molecular mechanisms that promote tolerance to DNA damage, often by preventing break formation or increasing repair capacity. This review broadly discusses the DNA damaging mechanisms of action for different classes of chemotherapeutics, how …