Digital Commons Network^™

Unveiling The Genetic Landscape Of Coronary Artery Disease Through Common And Rare Structural Variants, Kruthika R Iyer, Shoa L Clarke, Rodrigo Guarischi-Sousa, Ketrin Gjoni, Adam S Heath, Erica P Young, Nathan O Stitziel, Cecelia Laurie, Jai G Broome, Alyna T Khan, Joshua P Lewis, Huichun Xu, May E Montasser, Kellan E Ashley, Natalie R Hasbani, Eric Boerwinkle, Alanna C Morrison, Nathalie Chami, Ron Do, Ghislain Rocheleau, Donald M Lloyd-Jones, Rozenn N Lemaitre, Joshua C Bis, James S Floyd, Gregory L Kinney, Donald W Bowden, Nicholette D Palmer, Emelia J Benjamin, Matthew Nayor, Lisa R Yanek, Brian G Kral, Lewis C Becker, Sharon L R Kardia, Jennifer A Smith, Lawrence F Bielak, Arnita F Norwood, Yuan-I Min, April P Carson, Wendy S Post, Stephen S Rich, David Herrington, Xiuqing Guo, Kent D Taylor, Joann E Manson, Nora Franceschini, Katherine S Pollard, Braxton D Mitchell, Ruth J F Loos, Myriam Fornage, Lifang Hou, Bruce M Psaty, Kendra A Young, Elizabeth A Regan, Barry I Freedman, Ramachandran S Vasan, Daniel Levy, Rasika A Mathias, Patricia A Peyser, Laura M Raffield, Charles Kooperberg, Alex P Reiner, Jerome I Rotter, Goo Jun, Paul S De Vries, Themistocles L Assimes

Faculty, Staff and Student Publications

Background: Genome-wide association studies have identified several hundred susceptibility single nucleotide variants for coronary artery disease (CAD). Despite single nucleotide variant-based genome-wide association studies improving our understanding of the genetics of CAD, the contribution of structural variants (SVs) to the risk of CAD remains largely unclear.

Method and results: We leveraged SVs detected from high-coverage whole genome sequencing data in a diverse group of participants from the National Heart Lung and Blood Institute's Trans-Omics for Precision Medicine program. Single variant tests were performed on 58 706 SVs in a study sample of 11 556 CAD cases and 42 907 controls. …

Metabolic Effects Of Testosterone Added To Intensive Lifestyle Intervention In Older Men With Obesity And Hypogonadism, Adrian M Gonzalez-Gil, Yoann Barnouin, Alessandra Celli, Viola Viola, Marcos D Villarreal, Maria Liza Duremdes Nava, Adam Sciuk, Clifford Qualls, Reina Armamento-Villareal, Dennis T Villareal

Faculty, Staff and Students Publications

Background: Whether testosterone replacement therapy (TRT) conveys additional cardiometabolic benefit to an intensive lifestyle therapy (LT) in older men with obesity and hypogonadism remains unclear.

Objective: To determine whether TRT augments the effect of LT on metabolic outcomes in older men with obesity and hypogonadism.

Design: Secondary analysis of a randomized, double-blind, placebo-controlled trial.

Setting: Veterans Affairs Medical Center.

Participants: Eighty-three older (age ≥ 65 years) men with obesity (body mass index ≥ 30 kg/m2) and persistently low Am testosterone (< 10.4 nmol/L) associated with frailty.

Interventions: LT (weight management and exercise training) plus either testosterone (LT + TRT) or placebo (LT + Pbo) for …

The Potential Of Using Screening Tools For Bipolar Disorder To Predict Lithium Response, Delfina Janiri, Mario Pinto, Silvia Montanari, Ester Maria Marzo, Greta Sfratta, Guglielmo Donofrio, Alexia Koukopoulos, Giovanni Camardese, Alessio Simonetti, Lorenzo Moccia, Gianna Autullo, Gabriele Sani

Faculty, Staff and Students Publications

Background/Objectives: Lithium is the gold standard for treating Bipolar Disorder (BD), but its effectiveness varies widely. While clinical and environmental factors may influence response, it remains unclear if screening tools can reliably predict lithium response outcomes. This study explores this potential using two widely used screening instruments for BD.

Methods: A total of 146 patients with BD were evaluated. Lithium response was assessed using the Alda Scale, while hypomanic and manic symptoms were characterized through the Hypomania Checklist-32 (HCL-32) and the Mood Disorder Questionnaire (MDQ). Group differences in HCL-32 and MDQ scores were analyzed using ANOVA, and a multivariate model …

Biguanides Antithetically Regulate Tumor Properties By The Dose-Dependent Mitochondrial Reprogramming-Driven C-Src Pathway, Jun Hyoung Park, Kwang Hwa Jung, Dongya Jia, Sukjin Yang, Kuldeep S Attri, Songyeon Ahn, Divya Murthy, Tagari Samanta, Debasmita Dutta, Meron Ghidey, Somik Chatterjee, Seung Yeop Han, Diego A Pedroza, Abha Tiwari, Joyce V Lee, Caitlin Davis, Shuting Li, Vasanta Putluri, Chad J Creighton, Nagireddy Putluri, Lacey E Dobrolecki, Michael T Lewis, Jeffrey M Rosen, José N Onuchic, Andrei Goga, Benny Abraham Kaipparettu

Faculty, Staff and Students Publications

The biguanide metformin attenuates mitochondrial oxidation and is proposed as an anti-cancer therapy. However, recent clinical studies suggest increased proliferation and fatty acid β-oxidation (FAO) in a subgroup of patients with breast cancer (BC) after metformin therapy. Considering that FAO can activate Src kinase in aggressive triple-negative BC (TNBC), we postulate that low-dose biguanide-driven AMPK-ACC-FAO signaling may activate the Src pathway in TNBC. The low bioavailability of metformin in TNBC xenografts mimics metformin's in vitro low-dose effect. Pharmacological or genetic inhibition of FAO significantly enhances the anti-tumor properties of biguanides. Lower doses of biguanides induce and higher doses suppress Src …

Machine Learning-Enhanced Surface-Enhanced Spectroscopic Detection Of Polycyclic Aromatic Hydrocarbons In The Human Placenta, Oara Neumann, Yilong Ju, Andres B Sanchez-Alvarado, Guodong Zhou, Weiwu Jiang, Bhagavatula Moorthy, Melissa A Suter, Ankit Patel, Peter Nordlander, Naomi J Halas

Faculty, Staff and Students Publications

The detection and identification of polycyclic aromatic hydrocarbons (PAHs) and their derivatives, polycyclic aromatic compounds (PACs), are essential for environmental and health monitoring, for assessing toxicological exposure and their associated health risks. PAHs/PACs are the most dangerous chemicals found in tobacco smoke, and cigarette use during pregnancy can convey these molecules to the developing fetus through the placenta. This exposure is associated with many negative health outcomes, from premature birth to sudden infant death syndrome and adverse neurodevelopmental disorders. This study demonstrates the use of surface-enhanced Raman and surface-enhanced infrared absorption spectroscopies for direct detection of PAHs/PACs in human placental …

Development And Implementation Of A Personal Virtual Assistant For Patient Engagement And Communication In Postsurgical Cancer Care: Feasibility Cohort Study, Miguel Bargas-Ochoa, Alejandro Zulbaran-Rojas, M G Finco, Anthony B Costales, Areli Flores-Camargo, Rasha O Bara, Manuel Pacheco, Tina Phan, Aleena Khichi, Bijan Najafi

Faculty, Staff and Students Publications

BACKGROUND: Cancer-care complexity heightens communication challenges between health care providers and patients, impacting their treatment adherence. This is especially evident upon hospital discharge in patients undergoing surgical procedures. Digital health tools offer potential solutions to address communication challenges seen in current discharge protocols. We aim to explore the usability and acceptability of an interactive health platform among discharged patients who underwent oncology-related procedures.

METHODS: A 4-week exploratory cohort study was conducted. Following hospital discharge, a tablet equipped with an integrated Personal Virtual Assistant (PVA) system was provided to patients who underwent oncology-related procedures. The PVA encompasses automated features that provide …

Deep5mc: Predicting 5-Methylcytosine (5mc) Methylation Status Using A Deep Learning Transformer Approach, Evan Kinnear, Houssemeddine Derbel, Zhongming Zhao, Qian Liu

Faculty, Staff and Student Publications

DNA methylations, such as 5-methylcytosine (5mC), are crucial in biological processes, and aberrant methylations are strongly linked to various human diseases. Genomic 5mC is not randomly distributed but exhibits a strong association with genomic sequences. Thus, various computational methods were developed to predict 5mC status based on DNA sequences. These methods generated promising achievements and overcome the limitations of experimental approaches. However, few studies have comprehensively investigated the dependency of 5mC on genomic sequences, and most existing methods focus on specific genomic regions. In this work, we introduce Deep5mC, a deep learning transformer-based method designed to predict 5mC methylations. Deep5mC …

Mindfulness-Based Interventions And Stress, Jacqueline Parker

Doctor of Nursing Practice Final Project Abstract

Purpose: Stress within the nursing profession is a substantial issue. Staff shortages, poor leadership, and even COVID-19 have contributed to an increase in nursing stress. Stress can negatively impact a nurse’s ability to perform at an optimal level while at work. The purpose of this project is to reduce perceived stress by implementing mindfulness-based interventions (MBI).

Background: The project was implemented in a twenty-three-bed unit that cares for the post operative pediatric population in Houston, Texas.

Methodology: A series of in-person and virtual educational lessons (eight total) on MBIs (with flyers) were implemented throughout this project. The Perceived Stress Scale …

Next-Generation Sequencing-Based Msi Scoring Predicts Benefit In Mismatch Repair-Deficient Tumors Treated With Nivolumab: Follow-Up On Nci-Match Arm Z1d, Jonathan D Schoenfeld, Nilofer S Azad, Jacob Gross, Li Chen, Michael J Overman, Katrina Kao, Latifa Jackson, Donna Brunnquell, Xiangning Bu, Christina Coppola, Ping Guan, Jennifer Lee, David Sims, Rebecca Fuchs, Jason L Weirather, Kathleen L Pfaff, Lauren Gunasti, Srin Ranasinghe, Stanley R Hamilton, Victoria Wang, Peter J O'Dwyer, Catherine J Wu, Scott J Rodig, David R Patton, Lyndsay Harris

Faculty, Staff and Student Publications

Purpose: Mismatch repair-deficient (dMMR) tumors have demonstrated favorable responses to immune checkpoint inhibition targeting PD-1. However, more in-depth identification of predictors of response could further refine patient selection for immunotherapy treatment.

Patients and methods: We undertook integrated evaluation performed on samples collected from 28 of 42 patients enrolled on the NCI-Molecular Analysis for Therapy Choice arm Z1D trial that evaluated PD-1 inhibition treatment with nivolumab in patients with noncolorectal dMMR tumors. Genomic analyses were performed using next-generation sequencing (NGS), whole-exome sequencing, and RNA sequencing and supplemented by multiplex immunofluorescence performed on tissue samples.

Results: In this dMMR population, more extensive …

Markedly Elevated Blood Pressure, Tachycardia, And Altered Consciousness In Patients With Bacteremia During Transurethral Surgeries: Two Case Reports, Arisa Hotta, Momoka Nishimura, Daisuke Nakada, Riko Uchida, Hiroshi Matsuura, Naoko Torii, Naoko Fujita, Taku Hamada, Ai Nakamoto, Noriko Yoshikawa

Faculty, Staff and Students Publications

Background: Transurethral surgery is often accompanied by postoperative urinary tract infection. Although early detection and adequate treatment of bacteremia are required to prevent sepsis, it is usually undetectable during surgery. We report two cases with remarkable hypertension and tachycardia during transurethral surgery in which bacteremia was diagnosed by an intraoperative blood test.

Case presentation: An 80-year-old man (Case 1) underwent transurethral holmium laser prostate enucleation under spinal anesthesia, and an 88-year-old woman (Case 2) underwent transurethral resection of bladder tumor under general anesthesia. Altered consciousness (Case 1) and postoperative delirium (Case 2) were noted, in addition to remarkable intraoperative hypertension …

Rna Methyltransferase Spout1/Cenp-32 Links Mitotic Spindle Organization With The Neurodevelopmental Disorder Spadmiss, Avinash V Dharmadhikari, Maria Alba Abad, Sheraz Khan, Reza Maroofian, Tristan T Sands, Farid Ullah, Itaru Samejima, Yanwen Shen, Martin A Wear, Kiara E Moore, Elena Kondakova, Natalia Mitina, Theres Schaub, Grace K Lee, Christine H Umandap, Sara M Berger, Alejandro D Iglesias, Bernt Popp, Rami Abou Jamra, Heinz Gabriel, Stefan Rentas, Alyssa L Rippert, Christopher Gray, Kosuke Izumi, Laura K Conlin, Daniel C Koboldt, Theresa Mihalic Mosher, Scott E Hickey, Dara V F Albert, Haley Norwood, Amy Feldman Lewanda, Hongzheng Dai, Pengfei Liu, Tadahiro Mitani, Dana Marafi, Hatice Koçak Eker, Davut Pehlivan, Jennifer E Posey, Natalie C Lippa, Natalie Vena, Erin L Heinzen, David B Goldstein, Cyril Mignot, Jean-Madeleine De Sainte Agathe, Nouriya Abbas Al-Sannaa, Mina Zamani, Saeid Sadeghian, Reza Azizimalamiri, Tahere Seifia, Maha S Zaki, Ghada M H Abdel-Salam, Mohamed S Abdel-Hamid, Lama Alabdi, Fowzan Sami Alkuraya, Heba Dawoud, Aya Lofty, Peter Bauer, Giovanni Zifarelli, Erum Afzal, Faisal Zafar, Stephanie Efthymiou, Daniel Gossett, Meghan C Towne, Raey Yeneabat, Belen Perez-Duenas, Ana Cazurro-Gutierrez, Edgard Verdura, Veronica Cantarin-Extremera, Ana Do Vale Marques, Aleksandra Helwak, David Tollervey, Sandeep N Wontakal, Vimla S Aggarwal, Jill A Rosenfeld, Victor Tarabykin, Shinya Ohta, James R Lupski, Henry Houlden, William C Earnshaw, Erica E Davis, A Arockia Jeyaprakash, Jun Liao

Faculty, Staff and Students Publications

SPOUT1/CENP-32 encodes a putative SPOUT RNA methyltransferase previously identified as a mitotic chromosome associated protein. SPOUT1/CENP-32 depletion leads to centrosome detachment from the spindle poles and chromosome misalignment. Aided by gene matching platforms, here we identify 28 individuals with neurodevelopmental delays from 21 families with bi-allelic variants in SPOUT1/CENP-32 detected by exome/genome sequencing. Zebrafish spout1/cenp-32 mutants show reduction in larval head size with concomitant apoptosis likely associated with altered cell cycle progression. In vivo complementation assays in zebrafish indicate that SPOUT1/CENP-32 missense variants identified in humans are pathogenic. Crystal structure analysis of SPOUT1/CENP-32 reveals that most disease-associated missense variants are …

Framework, Design, And Baseline Data Of A Collective Impact Initiative To Strengthen The Community Health Worker Workforce Ecosystem In Texas, Shreela V Sharma, Heidi Hagen Mcpherson, Jemima John, Rosalia Guerrero, Sisan B Tennyson, Deborah Banerjee, Nadia Siddiqui, Sheila Savannah, Peter Durand, Amanda Gao, Sean A Haley, Elisa Garcia, Jennifer Cofer, Adrick Harris

Faculty, Staff and Student Publications

BACKGROUND: The Health Equity Collective (HEC), a multi-sector systems-level collective impact coalition in the Greater Houston region, partnered with the City of Houston Health Department (HHD) to launch a 2-year effort to implement a comprehensive approach towards strengthening the regional Community Health Workers (CHW) workforce infrastructure as a pathway to advancing health equity. Our paper presents the logic model, methods, and baseline qualitative and quantitative data from this initiative.

METHODS: In the fall of 2022, the Health Equity Collective brought together a Network of CHW-employing or training organizations in the Greater Houston region. This Network was the working group of …

Genetic And Environmental Contribution To Phenotypic Resemblance Between Iranian Couples: Tehran Cardiometabolic And Genetic Study (Tcgs), Parisa Riahi, Amir Hossein Saeidian, Albert Tenesa, Carolyn T Hogan, Michael March, Kamran Guity, Mahmoud Amiri Roudbar, Asieh Zahedi, Maryam Zarkesh, Farideh Neshati, Mehdi Hedayati, Fereidoun Azizi, Hakon Hakonarson, Maryam S Daneshpour, Mahdi Akbarzadeh

Faculty, Staff and Students Publications

Objective: To provide an applied framework for assessing the genetic contribution to assortative mating (AM) using height as a model trait and disclose the trace of certain pieces of evidence of AM in the form of the shared environmental effects from long-term cohabitation on spouses' anthropometric traits and lipid serum levels.

Methods: 2315 genotyped couples were extracted from the Tehran Cardiometabolic Genetic Study (TCGS). Pearson correlation analysis was used to assess the relationship between spouses' height. The GCTA-GREML was used to assess the SNP-based heritability of individual and spousal heights with AM adjustments. We used a recent GWAS meta-analysis of …

Outcomes Of Arteriovenous Malformation Patients With Multiple Versus Single Feeders: A Multicenter Retrospective Study With Propensity-Score Matching, Basel Musmar, Nimer Adeeb, Hammam Abdalrazeq, Joanna M Roy, Stavropoula I Tjoumakaris, Hamza Adel Salim, Douglas Kondziolka, Jason Sheehan, Christopher S Ogilvy, Howard Riina, Sandeep Kandregula, Adam A Dmytriw, Kareem El Naamani, Ahmed Abdelsalam, Natasha Ironside, Deepak Kumbhare, Cagdas Ataoglu, Muhammed Amir Essibayi, Abdullah Keles, Sandeep Muram, Daniel Sconzo, Arwin Rezai, Omar Alwakaa, Salem M Tos, Ufuk Erginoglu, Johannes Pöppe, Rajeev D Sen, Christoph J Griessenauer, Jan-Karl Burkhardt, Robert M Starke, Mustafa K Baskaya, Laligam N Sekhar, Michael R Levitt, David J Altschul, Malia Mcavoy, Assala Aslan, Abdallah Abushehab, Christian Swaid, Adib A Abla, Saman Sizdahkhani, Sravanthi Koduri, Elias Atallah, Spyridon Karadimas, M Reid Gooch, Robert H Rosenwasser, Christopher Stapleton, Matthew Koch, Visish M Srinivasan, Peng R Chen, Spiros Blackburn, Joseph Cochran, Omar Choudhri, Bryan Pukenas, Darren Orbach, Edward Smith, Pascal J Mosimann, Ali Alaraj, Mohammad A Aziz-Sultan, Aman B Patel, Hugo H Cuellar, Michael Lawton, Bharat Guthikonda, Jacques Morcos, Pascal Jabbour

Faculty, Staff and Student Publications

Introduction: The impact of multiple feeding arteries on clinical outcomes of cerebral arteriovenous malformations (AVMs) is not well understood. This study aims to compare outcomes between AVMs with multiple versus single feeding arteries.

Patients and methods: Data from the Multicenter International Study for Treatment of Brain AVMs (MISTA) consortium were analyzed. Propensity score matching (PSM) was used to balance cohorts. Subgroup analysis was conducted for ruptured and unruptured AVMs and different treatment options, and multivariable logistic regression was applied to assess the impact of feeding artery origin.

Results: Among 953 patients, 661(69.4%) had multiple feeding arteries, and 292 (30.6%) had …

Reassessing Estrogen Receptor Expression Thresholds For Breast Cancer Prognosis In Her2-Negative Patients Using Shape Restricted Modeling, Wenli Dong, Takeo Fujii, Jing Ning, Toshiaki Iwase, Jing Qin, Naoto T Ueno, Yu Shen

Faculty, Staff and Student Publications

We used a novel shape-restricted Cox model to determine the desirable ER expression cutoff to predict breast cancer prognoses. Our model treats ER as a continuous variable using a flexible monotone-shaped Cox regression to assess its association with survival outcomes holistically. The study included 3055 patients with stage II/III HER2-negative breast cancer. The primary outcomes were time to recurrence or death (TTR) and overall survival (OS). The shape-restricted Cox model identified 10% ER as the preferred cutoff to predict TTR. The finding was confirmed by the log-rank test and standard Cox model that patients with ER ≥ 10% had TTR …

Single-Cell Rna Sequencing Identifies Molecular Biomarkers Predicting Late Progression To Cdk4/6 Inhibition In Patients With Hr+/Her2- Metastatic Breast Cancer, Linjie Luo, Peng Yang, Sofia Mastoraki, Xiayu Rao, Yan Wang, Nicole M Kettner, Akshara Singareeka Raghavendra, Debasish Tripathy, Senthil Damodaran, Kelly K Hunt, Jing Wang, Ziyi Li, Khandan Keyomarsi

Faculty, Staff and Student Publications

Background: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6is) in combination with endocrine therapy are the standard treatment for patients with hormone receptor-positive, HER2-negative metastatic breast cancer (mBC). Despite the efficacy of CDK4/6is, intrinsic resistance occurs in approximately one-third of patients, highlighting the need for reliable predictive biomarkers.

Methods: Single-cell RNA sequencing analyzed metastatic tumors from HR+/HER2- mBC patients pre-CDK4/6i treatment at baseline (BL) and/or at disease progression. BL samples were from CDK4/6i responders (median progression-free survival [mPFS] = 25.5 months), while progressors were categorized as early-progressors (EP, mPFS = 3 months) and late-progressors (LP, mPFS = 11 months). Metastatic sites included liver, …

Inadequate Intensification Of Ldl-Cholesterol Lowering Therapy After Coronary Revascularization: Insights From The Gould Registry, Benjamin E Peterson, Deepak L Bhatt, Christie M Ballantyne, James A De Lemos, Robert S Rosenson, Mikhail N Kosiborod, Christopher P Cannon

Faculty, Staff and Students Publications

Background: Patients with a history of coronary revascularization are at a higher risk for subsequent cardiovascular events and all-cause mortality. Lowering LDL-cholesterol (LDL-C) levels post-revascularization significantly reduces these risks.

Methods: This analysis compared LDL-C-lowering therapies at baseline and over time among patients with and without prior coronary revascularization in the GOULD registry (a prospective multicenter cohort study). Baseline- and 24-month follow-up characteristics-including LDL-C levels and strategies for lipid-lowering therapy (LLT)-were evaluated.

Results: Out of 5006 patients, 2195 (43.8%) had prior coronary revascularization. At baseline, these patients had lower LDL-C (99.2 mg/dL vs. 102.5 mg/dL; p < 0.001) and were more likely to be on intensive LLT (52.8% vs. 42.7%; p < 0.001). At 24 months, they had small reductions in LDL-C (-15.6% vs. -13.7%; p = 0.145) and were more likely to be on intensive LLT (61.9% vs. 51.5%; p < 0.001). Similar LDL-C reductions were observed in the PCSK9i group regardless of revascularization status.

Conclusions: Despite slightly better baseline …

High-Output Cardiac Failure Caused By Large Coronary Artery Fistulas Treated With Coil Embolization, Nawal Mustafa, Blain Tafaesse, Hajra Nadeem, Muhammad Mustafa

The VAD Journal

There are many causes of high-output cardiac failure. We present a unique case of high-output cardiac failure caused by multiple coronary-to-pulmonary artery (PA) fistulas, which, to our knowledge, is a rare finding that has not been previously researched. The purpose of our case report is to highlight the importance of considering coronary-to-PA fistulas in the differential diagnosis of patients presenting with high-output cardiac failure. Our patient presented to the emergency department with shortness of breath and underwent nuclear stress testing, which, through cardiac catheterization, revealed coronary-to-PA fistulas as the cause of the high-output cardiac failure. These fistulas were successfully treated …

Single-Cell Analysis Identifies Ifi27l2a As A Gene Regulator Of Microglial Inflammation In The Context Of Aging And Stroke In Mice, Gab Seok Kim, Elisabeth Harmon, Manuel C Gutierrez, Sodam Kim, Lauren Vance, Haven Burrous, Jessica M Stephenson, Anjali Chauhan, Anik Banerjee, Zachary Wise, Andrea Doan, John Ahn, Ting Wu, Jesus Bautista-Garrido, Juneyoung Lee, Chunfeng Tan, Joo Eun Jung, Louise D Mccullough, Joshua D Wythe, Sean P Marrelli

Faculty, Staff and Student Publications

Inflammation is a significant driver of ischemic stroke pathology in the brain. To identify potential regulators of inflammation, we performed single-cell RNA sequencing (scRNA-seq) of young and aged mouse brains following stroke and found that interferon alpha-inducible protein 27 like 2 A (Ifi27l2a) was significantly up-regulated, particularly in microglia of aged brain. Ifi27l2a is induced by interferons for viral host defense and has been linked with pro-inflammatory cellular mechanisms. However, its potential role in neurodegeneration is unknown. Using a combination of cell culture, experimental stroke models in mice, and human autopsy brain samples, we demonstrated that induction of Ifi27l2a occurs …

Divergence In Cellular Markers Observed In Single-Cell Transcriptomics Datasets Between Cultured Primary Trabecular Meshwork Cells And Tissues, Alice Tian, Sangbae Kim, Hasna Baidouri, Jin Li, Xuesen Cheng, Janice Vranka, Yumei Li, Rui Chen, Vijaykrishna Raghunathan

Faculty, Staff and Students Publications

The trabecular meshwork within the outflow apparatus is critical in maintaining intraocular pressure homeostasis. In vitro studies employing primary cell cultures of the human trabecular meshwork (hTM) have conventionally served as surrogates for investigating the pathobiology of TM dysfunction. Despite its abundant use, translation of outcomes from in vitro studies to ex vivo and/or in vivo studies remains a challenge. Given the cell heterogeneity, performing single-cell RNA sequencing comparing primary hTM cell cultures to hTM tissue may provide important insights on cellular identity and translatability, as such an approach has not been reported before. In this study, we assembled a …

Multimodal Objective Assessment Of Impulsivity In Healthy And Mood Disorder Participants, Bishal Lamichhane, Nidal Moukaddam, Ramiro Salas, Wayne Goodman, Ashutosh Sabharwal

Faculty, Staff and Students Publications

Impulsivity represents an individual's tendency to act on urges without sufficient forethought. Heightened impulsivity is a hallmark of many mental health disorders. Objective impulsivity assessments could improve risk evaluation, diagnosis, and behavioral outcome monitoring in impulsivity-related health disorders. Towards objective impulsivity assessment, in this work, we identify impulsivity correlates in objective measurements, investigate their complementarity, and contrast impulsivity mechanisms across health conditions. We analyzed behavioral tests, heart rate variability (HRV), and fMRI-based brain connectivity in 227 healthy participants and 34 participants with mood disorders. Impulsivity dimensions had complementary correlates in objective measurements, with fMRI providing the strongest correlates. Multimodal assessment …

Mage-A4 Induces Non-Small Cell Lung Cancer And Tumor-Promoting Plasma Cell Accumulation, Dominique Armstrong, Cheng-Yen Chang, Monica J Hong, Linda Green, Yichao Shen, William Hudson, Kelsey E Mauk, Li-Zhen Song, Sheetal Jammi, Benjamin Casal, Brianna Burns, Chad J Creighton, Alexandre Carisey, Xiang H-F Zhang, Neil J Mckenna, Sung Wook Kang, Hyun-Sung Lee, William Decker, David B Corry, Farrah Kheradmand

Faculty, Staff and Students Publications

Adaptive immunity is critical in eliminating tumors, but cancer-intrinsic factors can subvert this function. Melanoma antigen-A4 (MAGE-A4), a cancer-testis antigen, is expressed in solid tumors and correlates with poor survival, but its role in tumorigenesis and antitumor immunity remains unclear. We found that expression of MAGE-A4 was highly associated with the loss of PTEN, a tumor suppressor, in human non–small cell lung cancers (NSCLC). Here, we show that constitutive expression of human MAGE-A4 with Pten loss in mouse airway epithelia results in metastatic adenocarcinoma. Tumors showed distinct enrichment in IgA+ CD138+ CXCR4+ plasma cells (PCs) and increased expression of …

Proxy Panels Enable Privacy-Aware Outsourcing Of Genotype Imputation, Degui Zhi, Xiaoqian Jiang, Arif Harmanci

Faculty, Staff and Student Publications

One of the major challenges in genomic data sharing is protecting participants' privacy in collaborative studies and in cases when genomic data are outsourced to perform analysis tasks, for example, genotype imputation services and federated collaborations genomic analysis. Although numerous cryptographic methods have been developed, these methods may not yet be practical for population-scale tasks in terms of computational requirements, rely on high-level expertise in security, and require each algorithm to be implemented from scratch. In this study, we focus on outsourcing of genotype imputation, a fundamental task that utilizes population-level reference panels, and develop protocols that rely on using …

Identification Of Distinct Stool Metabolites In Women With Endometriosis For Non-Invasive Diagnosis And Potential For Microbiota-Based Therapies, Chandni Talwar, Goutham Venkata Naga Davuluri, Abu Hena Mostafa Kamal, Cristian Coarfa, Sang Jun Han, Surabi Veeraragavan, Krishna Parsawar, Nagireddy Putluri, Kristi Hoffman, Patricia Jimenez, Scott Biest, Ramakrishna Kommagani

Faculty, Staff and Students Publications

Background: Endometriosis, a poorly studied gynecological condition, is characterized by the presence of ectopic endometrial lesions resulting in pelvic pain, inflammation, and infertility. These associated symptoms contribute to a significant burden, often exacerbated by delayed diagnosis. Current diagnostic methods involve invasive procedures, and existing treatments provide no cure.

Methods: Microbiome-metabolome signatures in stool samples from individuals with and without endometriosis were determined using unbiased metabolomics and 16S bacteria sequencing. Functional studies for selected microbiota-derived metabolites were conducted in vitro using patient-derived cells and in vivo by employing murine and human xenograft pre-clinical disease models.

Findings: We discovered a unique bacteria-derived …

Successful Posthospitalisation Oncology Workflow Implementing Lace+ Score To Stratify And Reduce Readmissions Within A Safety-Net Hospital, Cindy M Pabon, Janine Wong, Marcela Perez, Jessica Jimenez-Abarca, Lianchun Xiao, Lymesia Jackson, Anne Park, Anjali Lankford, Vinita Akula, Saumil Datar, Taylor Hopper, Yaser Alkhatib, Terri Earles, Tejal Patel

Faculty, Staff and Student Publications

Background: Patients with advanced cancers visit the emergency room and get hospitalised frequently, with potentially half of these visits being avoidable. Our institution provides comprehensive, low-cost cancer treatment to a safety-net population in Texas. We performed a retrospective review of hospital readmission patterns amongst our oncology patients and developed a posthospitalisation workflow to reduce readmissions.

Method: Following discharge, oncology patients were risk stratified based on their Length of stay, Acuity of admission, Charlson comorbidity index score and Emergency department visits+index in the past 6 months. The higher the score, the quicker the outpatient oncology follow-up. In addition to addressing acute …

Inhibition Of Histone Methyltransferase Ezh2 For Immune Interception Of Colorectal Cancer In Lynch Syndrome, Charles M Bowen, Fahriye Duzagac, Abel Martel-Martel, Laura Reyes-Uribe, Mahira Zaheer, Jacklyn Thompson, Nan Deng, Ria Sinha, Soham Mazumdar, Melissa W Taggart, Abhinav K Jain, Elena Tosti, Winfried Edelmann, Krishna M Sinha, Eduardo Vilar

Faculty, Staff and Student Publications

Colorectal precancers in Lynch syndrome (LS) exhibit a distinct immune profile, presenting unique opportunities for developing immune-interception strategies to prevent carcinogenesis. Epigenetic modulation by EZH2 of immune-related genes is implicated in the carcinogenesis of different cancer types, including colorectal cancer. This study utilizes a mouse model of LS and ex vivo colonic organoids to assess the effects of the EZH2 inhibitor GSK503 on immune regulatory pathways, tumorigenesis, and epigenetic reprogramming. Our findings revealed that GSK503 significantly increased CD4+ and CD8+ T cells in both splenocytes and colonic mucosa of treated mice compared with controls. Additionally, a preventive dose of GSK503 …

Structure-Activity Relationship Studies Of Dna Methyltransferase 1 Monovalent Degraders, Chao Qian, Youngeun Lee, Yulin Han, Yue Zhong, Jujun Zhou, Joel Hrit, Ling Xie, Qin Chen, H Ümit Kaniskan, Xian Chen, Scott Rothbart, Xiaodong Cheng, Yan Xiong, Jian Jin

Faculty, Staff and Student Publications

DNA methyltransferase 1 (DNMT1), which catalyzes maintenance methylation of hemimethylated DNA during DNA replication, is overexpressed in cancer. Recently, the first-in-class DNMT1-selective noncovalent small-molecule inhibitors, GSK3484862 and GSK3685032, were discovered. These inhibitors were also reported to degrade DNMT1. However, structure–activity relationship (SAR) studies of these monovalent DNMT1 degraders are lacking. Here, we report our SAR studies of this scaffold on degrading DNMT1, which led to the discovery of multiple lead degraders, including compound 4 (MS9024). Compound 4 potently and selectively degraded DNMT1 in multiple cancer cell lines in a concentration-, time-, and proteasome-dependent manner without altering DNMT1 transcription. Further mechanism-of-action …

Prediction Of Cognitive Conversion Within The Alzheimer’S Disease Continuum Using Deep Learning, Siyu Yang, Xintong Zhang, Xinyu Du, Peng Yan, Jing Zhang, Wei Wang, Jing Wang, Lei Zhang, Huaiqing Sun, Yin Liu, Xinran Xu, Yaxuan Di, Jin Zhong, Caiyun Wu, Jan D Reinhardt, Yu Zheng, Ting Wu

Faculty, Staff and Students Publications

Background: Early diagnosis and accurate prognosis of cognitive decline in Alzheimer's disease (AD) is important to timely assignment to optimal treatment modes. We aimed to develop a deep learning model to predict cognitive conversion to guide re-assignment decisions to more intensive therapies where needed.

Methods: Longitudinal data including five variable sets, i.e. demographics, medical history, neuropsychological outcomes, laboratory and neuroimaging results, from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort were analyzed. We first developed a deep learning model to predicted cognitive conversion using all five variable sets. We then gradually removed variable sets to obtained parsimonious models for four different …

Plasma Micrornas To Select Optimal Patients For Antibody Production From Anti-Addiction Vaccines, Thomas R Kosten, Amrit Koirala, David A Nielsen, Coreen B Domingo, Ynhi T Thomas, Preethi H Gunaratne, Cristian Coarfa

Faculty, Staff and Students Publications

Background: Cocaine and illicit amphetamines (disguised as “Adderall”) are being laced with fentanyl and producing accidental and intentional fatal overdoses. Vaccines can prevent these overdoses, but 33% of humans generate insufficient anti-drug antibody (AB) levels. Plasma microRNAs (miRs) can be used to predict non-responders. We have plasma stored from 152 cocaine vaccine trial participants following three vaccinations over 9 weeks and examined miRs as potential response biomarkers. Methods: We compared 2517 miRs before anti-cocaine vaccination in participants with the highest (n = 25) to the lowest (n = 23) antibody levels. False Discovery Rates (FDRs) were applied to identify differentially …

Navigating Epstein-Barr Virus (Ebv) And Post-Transplant Lymphoproliferative Disorder (Ptld) In Pediatric Liver Transplantation: Current Knowledge And Strategies For Treatment And Surveillance, Erin Y Chen, Natasha Dilwali, Krupa R Mysore, Sara Hassan, Sara Kathryn Smith, Wikrom Karnsakul

Faculty, Staff and Students Publications

Epstein-Barr virus (EBV) is strongly associated with the development of post-transplant lymphoproliferative disorder (PTLD) in pediatric liver transplant recipients. PTLD is one of the most common malignancies following liver transplantation and is associated with significant morbidity and mortality. Factors such as EBV-serostatus mismatch and prolonged or high levels of immunosuppression impact a patient's risk of developing PTLD. While pre-transplant EBV serological screening and post-transplant monitoring of EBV-DNA levels are strongly recommended, universal guidelines for its prevention and management are lacking. Due to a lack of robust prospective studies, current clinical practices vary widely. The treatment of PTLD typically involves reducing …