Digital Commons Network^™

Human Pain Neuroscience And The Next Generation Of Pain Therapeutics, Bryan A Copits, Michele Curatolo, Patrick M Dougherty, Robert W Gereau, Wenqin Luo, Maryann Martone, Hakan Olausson, Theodore J Price, William Renthal, Clifford J Woolf, Guoyan Zhao

Faculty, Staff and Student Publications

The recent approval of suzetrigine for acute pain treatment highlights both the success of targeting peripheral sensory neurons for pain management and the potential of developing new pain therapies primarily in human-based systems. To realize this transformative potential, further research into somatosensation and pain neuroimmunology in human systems is essential.

The Seroprevalence And Risk Factors For Spotted Fever Group And Typhus Group Rickettsia Along The Texas-Mexico Border, Frederick M Cramer, Lauren M Leining, Timothy A Erickson, Josephine Tolan, Craig L Hanis, Eric L Brown, Sarah M Gunter

Faculty, Staff and Students Publications

Rickettsial pathogens are an endemic and emergent source of disease in Texas, with a historically high rate of transmission along the United States-Mexico border. To better understand the prevalence and risk factors for spotted fever group Rickettsia (SFGR) and typhus group Rickettsia (TGR) along the Texas-Mexico border, we conducted a seroprevalence study of adults residing in Starr County, Texas (N = 616). Plasma samples were screened for IgG reactivity to SFGR and TGR using commercially available ELISA. ELISA-positive samples were confirmed using a dual spot IgG indirect immunofluorescent assay. Seropositivity was defined as having a ≥1:128 titer. Analysis was conducted …

A Honduran Prevalence Study On Soil-Transmitted Helminths Highlights Serological Antibodies To Tm-Wap49 As A Diagnostic Marker For Exposure To Human Trichuriasis, Neima Briggs, Leroy Versteeg, Rojelio Mejia, Jeroen Pollet, Maria Jose Villar, Bin Zhan, Graeme Segal, Stephanie Novak, Patricia Lenihan, Paul Musgrave, Viviana Ellis, Carol Florencia Coello, K Jagannadha Sastry, Joe Craft, Peter J Hotez, Maria Elena Bottazzi

Faculty, Staff and Student Publications

Soil-transmitted helminth (STH) infections rank among the most prevalent communicable diseases of humans, yet detection of these parasites is mostly restricted to identifying active infection through fecal examinations. Currently, there are no commercial diagnostic tools to identify a prior whipworm or hookworm exposure, and the few serological assays for roundworm infection have not been well validated for crossreactivity or infections in humans. Such diagnostic restrictions limit the range of scientific and clinical questions that surround STH exposures and their implicated relationship to chronic diseases, such as autoimmunity, allergy, and cancer. The goal of this investigation was to evaluate the diagnostic …

A Quality Improvement Project On Implementing A Nurse-Driven Foley Catheter Removal Protocol Using Modified Houdini Criteria For Oncology Patients To Reduce The Catheter-Associated Urinary Tract Infection (Cauti) And Catheter Days In The Intensive Care Unit (Icu), Rittu K. Justin

Doctor of Nursing Practice Final Project Abstract

Purpose: This scholarly project aimed to develop modified criteria for oncology patients regarding Foley catheter removal guidance and implement a nurse initiative in the ICU to reduce CAUTI and catheter days.

Background: CAUTIs are considered preventable nosocomial infections; hence, a nurse-driven Foley catheter removal protocol has become an essential strategy in healthcare to reduce CAUTIs. The project was implemented in a 43-bed ICU in an academic hospital at the Texas Medical Center. The 12-week pilot project included adult patients with a primary diagnosis of cancer.

Methodology: A quantitative design with a PDSA framework was employed. The institutional infection control trend …

Implementation Of A Standardized Pain Assessment Tool To Drive Opioid Management In End-Of-Life Patients In A Medical Intensive Care Unit, Sonia Carrizales

Doctor of Nursing Practice Final Project Abstract

Purpose

This quality improvement project implemented a standardized pain assessment tool, the Multidimensional Observational Pain Assessment Tool (MOPAT), to drive opioid administration for end-of-life (EOL) patients. This project intended to increase opioid administration to EOL patients through increased confidence levels noted in bedside staff with the use of a standardized pain assessment tool.

Background

The project was implemented in a thirty-two-bed adult medical intensive care unit in Round Rock, Texas. The patients focused on in this project were those transitioned to EOL care.

Methodology

A pre-and post-survey was sent to bedside staff to gauge confidence levels. The MOPAT was then …

Simplified Control Of Neuromuscular Stimulation Systems For Restoration Of Reach With Limb Stiffness As A Modifiable Degree Of Freedom, Tyler R Johnson, Chase A Haddix, A Bolu Ajiboye, Dawn M Taylor

Faculty, Staff and Student Publications

Objective. Brain-controlled functional electrical stimulation (FES) of the upper limb has been used to restore arm function to paralyzed individuals in the lab. Able-bodied individuals naturally modulate limb stiffness throughout movements and in anticipation of perturbations. Our goal is to develop, via simulation, a framework for incorporating stiffness modulation into the currently-used ‘lookup-table-based’ FES control systems while addressing several practical issues: (1) optimizing stimulation across muscles with overlap in function, (2) coordinating stimulation across joints, and (3) minimizing errors due to fatigue. Our calibration process also needs to account for when current spread causes additional muscles to become activated. Approach. …

Progressive Multifocal Leukoencephalopathy In Chimeric Antigen Receptor T-Cell Therapy Recipients: A Case Study, Michelly Abreu, Chirag B Patel, Krina Patel, Fareed Khawaja, Sudhakar Tummala

Faculty, Staff and Student Publications

Chimeric antigen receptor (CAR) T-cell therapy is a novel immunotherapy modality that has shown remarkable response rates in refractory hematologic malignancies, including multiple myeloma (MM). Cytokine release syndrome (CRS) and neurotoxicity are well-described side effects of this therapy. CAR T-cell therapy recipients are also at increased risk for infections due to immune dysfunction, history of multiple lines of therapy, history of lymphodepleting chemotherapy prior to cell infusion, and prolonged B-cell aplasia. Progressive multifocal leukoencephalopathy (PML) is an opportunistic disease of the central nervous system caused by the reactivation of JC virus (JCV) in the setting of immunosuppression, which leads to …

Lifespan Reference Curves For Harmonizing Multi-Site Regional Brain White Matter Metrics From Diffusion Mri, Alyssa H Zhu, Talia M Nir, Shayan Javid, Julio E Villalón-Reina, Amanda L Rodrigue, Lachlan T Strike, Greig I De Zubicaray, Katie L Mcmahon, Margaret J Wright, Sarah E Medland, John Blangero, David C Glahn, Peter Kochunov, Douglas E Williamson, Asta K Håberg, Paul M Thompson, Neda Jahanshad

Faculty, Staff and Student Publications

Age-related white matter (WM) microstructure maturation and decline occur throughout the human lifespan, complementing the process of gray matter development and degeneration. Here, we create normative lifespan reference curves for global and regional WM microstructure by harmonizing diffusion MRI (dMRI)-derived data from ten public datasets (N = 40,898 subjects; age: 3-95 years; 47.6% male). We tested three harmonization methods on regional diffusion tensor imaging (DTI) based fractional anisotropy (FA), a metric of WM microstructure, extracted using the ENIGMA-DTI pipeline. ComBat-GAM harmonization provided multi-study trajectories most consistent with known WM maturation peaks. Lifespan FA reference curves were validated with test-retest data …

Axl Promotes Inflammatory Breast Cancer Progression By Regulating Immunosuppressive Macrophage Polarization, Lan T H Phi, Yating Cheng, Yohei Funakoshi, Francois Bertucci, Pascal Finetti, Steven J Van Laere, Fang Zou, James P Long, Suguru Ogata, Savitri Krishnamurthy, James M Reuben, Jason M Foulks, Steven L Warner, Jennifer M Rosenbluth, Anil K Sood, Debu Tripathy, Naoto T Ueno, Xiaoping Wang

Faculty, Staff and Student Publications

Background: Tumor-associated macrophages (TAMs) are key promoters of inflammatory breast cancer (IBC), the most aggressive form of breast cancer. The receptor tyrosine kinase AXL is highly expressed in various cancer types, including IBC, but its role in TAMs remains unexplored.

Methods: We examined the effects of AXL inhibitor TP-0903 on tumor growth and tumor microenvironment (TME) component M2 macrophages (CD206+) in IBC and triple-negative breast cancer mouse models using flow cytometry and immunohistochemical staining. Additionally, we knocked out AXL expression in human THP-1 monocytes and evaluated the effect of AXL signaling on immunosuppressive M2 macrophage polarization and IBC cell growth …

Anti-Csf-1r Therapy With Combined Immuno- Chemotherapy Coordinate An Adaptive Immune Response To Eliminate Macrophage Enriched Triple Negative Breast Cancers, Diego A Pedroza, Xueying Yuan, Fengshuo Liu, Hilda L Chan, Christina Zhang, William Bowie, Alex J Smith, Sebastian J Calderon, Nadia Lieu, Weiguo Wu, Paul Porter, Poonam Sarkar, Na Zhao, Constanze V Oehler, Ondrej Peller, M Waleed Gaber, Qian Zhu, Charles M Perou, Xiang H-F Zhang, Jeffrey M Rosen

Faculty, Staff and Students Publications

Patients diagnosed with metastatic triple negative breast cancer (mTNBC) have limited treatment options, are more prone to develop resistance and are associated with high mortality. A cold tumor immune microenvironment (TIME) characterized by low T cells and high tumor associated macrophages (TAMs) in mTNBC is associated with the failure of standard-of-care chemotherapy and immune checkpoint blockade (ICB) treatment. We demonstrate that the combination of immunomodulatory metronomic Cyclophosphamide (CTX) coupled with anti-CSF-1R antibody targeted therapy (SNDX-ms6352) and anti-PD-1 (ICB), was highly effective against aggressive metastatic syngeneic

Decreasing Incidence Of Intramuscular Emergency Psychiatry Medications In Psychiatric Adult Patients Through The Acute Violent Assessment Tool (Avat), Edidiong G. Ebong

Doctor of Nursing Practice Final Project Abstract

Purpose The purpose of this QI project was to reduce emergency IM psychiatric medication usage by implementing the Acute Violent Assessment Tool (AVAT) to improve early aggression management. Background The frequent use of emergency intramuscular (IM) psychiatric medications in inpatient psychiatric settings raises concerns regarding patient safety, autonomy, and staff burden. This quality improvement (QI) project aimed to reduce emergency IM medication administration by 20% over three months by implementing the AVAT to improve early identification, prediction, and management of aggression and violence. Methodology A Plan-Do-Study-Act (PDSA) framework guided the AVAT implementation in an adult psychiatric unit. Three weeks of …

A Cluster Randomized Trial Of A Multicomponent Clinical Care Pathway (Mccp) To Improve Masld Diagnosis And Management In Primary Care: Study Protocol, Kyler M Godwin, Larissa Grigoryan, Aaron P Thrift, Hao Duong, Fasiha Kanwal, Traber Giardina, Himabindu Kadiyala, Andrew Zimolzak, Kavish R Patidar, Hashem B El-Serag

Faculty, Staff and Students Publications

Background: Metabolic dysfunction associated steatotic liver disease (MASLD) is the most common chronic liver disorder in the world. Most patients with MASLD are undiagnosed, untreated and unreferred. Treatment depends on diagnosis and accurate staging of fibrosis risk, and therefore screening at the primary care setting coupled with consistent, timely, evidence-based, widely accessible, and testable management processes is critical. Randomized controlled trials of methods for screening, diagnosis, severity stratification, and referral are lacking. We previously validated the MASLD clinical care pathway (MCCP), a multistep algorithmic process geared to support primary care settings in screening, diagnosis, risk stratification, and suggested referral and …

Language Mapping During Awake Brain Surgery In A Deaf Patient With A Brain Tumor: Illustrative Case, Ene Chibawanye I, Elizabeth Silva, Kyle Noll, Mariana Bradshaw, Katherine Connelly, Ho-Ling Liu, Ravi Tummala, David Ferson, Frederick F Lang, Vinodh A Kumar

Faculty, Staff and Student Publications

Background: Signed language integrates complex sensorimotor processes involving visual and motor networks. The contribution of language regions such as Broca's and Wernicke's areas during signing is not well established. Here, the authors report the case of a 45-year-old right-handed male with congenital deafness, who communicates using American Sign Language (ASL) and Signed English, presenting with focal seizures. Imaging showed a diffuse infiltrative glioma in the right cerebral hemisphere.

Observations: Remarkably, preoperative functional MRI language activations were bihemispheric and overlapped for both traditional language paradigms and sign paradigms, suggesting that the same cortical regions of the brain are used for language …

Dynamic Vertebral Artery Recanalization As A Cause For Recurrent Posterior Circulation Thromboembolic Stroke: Illustrative Case, Hussein A Zeineddine, Gabriel Galan Castro, Antonio Dono, William W Wroe, Salvatore A D'Amato, Duncan Trimble, Nimer Adeeb, Andrew Barreto, Spiros L Blackburn

Faculty, Staff and Student Publications

Background: Posterior circulation strokes comprise one-fourth of ischemic strokes and can arise from many causes. One rare etiology is transient occlusion of the vertebral artery (VA) with head rotation due to an osteophyte, termed bow hunter's syndrome. The authors present the case of recurrent thromboembolic posterior strokes secondary to transient reopening of an osteophyte-occluded VA.

Observations: A 71-year-old man presented with dizziness and visual changes with a history of prior cervical fusion and myocardial ischemia, controlled with Plavix and aspirin. CT angiography of the neck revealed osteophyte occlusion of the right VA at C4, and MRI revealed a right posterior …

Catecholaminergic Polymorphic Ventricular Tachycardia-Linked Ryanodine Receptor Variants Exhibit Domain-Specific Calcium Leak And Calmodulin Affinity Properties, Hitoshi Uchinoumi, Xiaoqiong Dong, Ivanita Stefanon, Yi Yang, Eduardo Hertel Ribeiro, Bengt Svensson, Xander H T Wehrens, Takeshi Yamamoto, Razvan L Cornea, Robyn T Rebbeck, Masafumi Yano, Donald M Bers

Faculty, Staff and Students Publications

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited stress-induced arrhythmogenic disease often caused by point variants in the cardiac ryanodine receptor (RyR2) that enhance diastolic sarcoplasmic reticulum (SR) Ca2+ leak. These RyR2 variants cluster in three hot-spots (N-terminal, central and C-terminal domains). We previously demonstrated a pathologic diastolic RyR2 conformation in heart failure, oxidative stress and CaMKII phosphorylation exhibiting a trilogy of effects: (1) reduced calmodulin (CaM)-RyR2 affinity, (2) enhanced unzipping peptide (DPc10) binding and (3) elevated diastolic SR Ca2+ leak that are dantrolene-sensitive. Here we test whether this pathological trilogy occurs in CPVT knock-in (KI) mice bearing N-terminal (R176Q/+), …

Gut Dysbiosis Patterns In Cvid Patients With Noninfectious Complications Observed In A Germ-Free Mouse Model Through Fecal Microbiota Transplantation, Joud Hajjar, Anita Y Voigt, Margaret E Conner, Alton G Swennes, Stephanie Fowler, Chadi Calarge, Danielle D Mendonca, Dominique Armstrong, Chen-Yen Chang, Jolan E Walter, Manish J Butte, Tor Savidge, Julia Oh, Farrah Kheradmand, Joseph F Petrosino

Faculty, Staff and Students Publications

Patients with common variable immunodeficiency (CVID) who develop noninfectious complications (NIC) have worse clinical outcomes than those with infections only (INF). While gut microbiome aberrations have been linked to NIC, reductionist animal models that accurately recapitulate CVID are lacking. Our aim in this study was to uncover potential microbiome roles in the development of NIC in CVID. We performed whole-genome shotgun sequencing on fecal samples from CVID patients with NIC, INF, and their household controls. We also performed fecal microbiota transplants from CVID patients to germ-free mice. We found potentially pathogenic microbes

Improving Therapeutic Communication Between Patients And Nurses Using The Commit To Sit Method In The Obgyn/Postpartum/Mother-Baby Unit, Simisola A. Shodunke

Doctor of Nursing Practice Final Project Abstract

Purpose

To improve patients’ perceptions of nurses by listening to their needs, helping nurses to engage with their patients therapeutically in the OBGYN/Postpartum/Mother-Baby unit. Aiming to increase patient satisfaction scores from 62.5% to 70% by December 2024 using the "Commit to Sit" method.

Background

The project was implemented in an OBGYN/Postpartum/Mother-Baby Unit, addressing the concerns of the patient’s perception of nurses not listening and addressing their needs which has contributed to a decline in patient satisfaction scores.

Methodology

The Plan-Do-Study-Act (PDSA) model was used. Nurses were trained to sit at eye level with patients for 3–5 minutes per shift. Data …

Protocol For A Randomized Controlled Trial To Determine If Biomarkers Predict Response To A Pediatric Chronic Pain Symptom Management Program, Rona L Levy, Tasha B Murphy, Margaret M Heitkemper, Miranda A L Van Tilburg, Ann R Mcmeans, Jocelyn Chang, Cynthia Boutte, Katherine Lamparyk, Bruno P Chumpitazi, Robert J Shulman

Faculty, Staff and Students Publications

Background/Objectives: Disorders of gut-brain interaction (DGBI), characterized by chronic abdominal pain and significant disability, affect 15-20% of children and adults and continue into adulthood in ~60% of cases. Costs for adults reach USD 30 billion per year, yet effective management strategies are elusive. Studies support using cognitive behavioral therapy (CBT), but abdominal pain only improves in ~40% of patients. Dietary management (low FODMAP diet; LFD) has also shown promise but it is effective in only a similar percentage of patients. Studies suggest that biologic factors (biomarkers) contribute to CBT response. Similarly, gut microbiome composition appears to influence abdominal pain …

Protocol For A Randomized Controlled Trial To Determine If Biomarkers Predict Response To A Pediatric Chronic Pain Symptom Management Program, Rona L Levy, Tasha B Murphy, Margaret M Heitkemper, Miranda A L Van Tilburg, Ann R Mcmeans, Jocelyn Chang, Cynthia Boutte, Katherine Lamparyk, Bruno P Chumpitazi, Robert J Shulman

Children’s Nutrition Research Center Staff Publications

Background/Objectives: Disorders of gut-brain interaction (DGBI), characterized by chronic abdominal pain and significant disability, affect 15-20% of children and adults and continue into adulthood in ~60% of cases. Costs for adults reach USD 30 billion per year, yet effective management strategies are elusive. Studies support using cognitive behavioral therapy (CBT), but abdominal pain only improves in ~40% of patients. Dietary management (low FODMAP diet; LFD) has also shown promise but it is effective in only a similar percentage of patients. Studies suggest that biologic factors (biomarkers) contribute to CBT response. Similarly, gut microbiome composition appears to influence abdominal pain …

Prognostic Value Of Serum And Bronchoalveolar Lavage Fluid Galactomannan Levels In Invasive Aspergillosis: An 8-Year Experience At A Tertiary Cancer Center, Saliba Wehbe, Anne-Marie Chaftari, Ray Hachem, Hiba Dagher, Andrea Haddad, Ann Philip, Ying Jiang, Ramia Zakhour, Peter Bakht, Jishna Shrestha, Peter Lamie, Robin Sherchan, Jennifer Makhoul, Patrick Chaftari, Issam I Raad

Faculty, Staff and Student Publications

Background: Invasive aspergillosis (IA) is a life-threatening fungal infection that primarily affects immunocompromised individuals and has high morbidity and mortality rates, necessitating timely diagnosis and treatment. This study aimed to evaluate the prognostic utility of serum and bronchoalveolar lavage (BAL) fluid galactomannan levels, as well as galactomannan kinetics, in patients with IA.

Methods: We retrospectively reviewed the medical records of patients who were diagnosed with proven or probable IA from March 2016 to April 2024 at a tertiary cancer center. The collected data included patient characteristics, baseline and peak galactomannan levels in serum and BAL fluid, galactomannan trends, and …

Alzheimer’S Disease Protective Allele Of Clusterin Modulates Neuronal Excitability Through Lipid-Droplet-Mediated Neuron-Glia Communication, Xiaojie Zhao, Yan Li, Siwei Zhang, Ari Sudwarts, Hanwen Zhang, Alena Kozlova, Matthew J Moulton, Lindsey D Goodman, Zhiping P Pang, Alan R Sanders, Hugo J Bellen, Gopal Thinakaran, Jubao Duan

Duncan NRI Faculty and Staff Publications

Background: Genome-wide association studies (GWAS) of Alzheimer's disease (AD) have identified a plethora of risk loci. However, the disease variants/genes and the underlying mechanisms have not been extensively studied.

Methods: Bulk ATAC-seq was performed in induced pluripotent stem cells (iPSCs) differentiated various brain cell types to identify allele-specific open chromatin (ASoC) SNPs. CRISPR-Cas9 editing generated isogenic pairs, which were then differentiated into glutamatergic neurons (iGlut). Transcriptomic analysis and functional studies of iGlut co-cultured with mouse astrocytes assessed neuronal excitability and lipid droplet formation.

Results: We identified a putative causal SNP of CLU that impacted neuronal chromatin accessibility to transcription-factor(s), with …

Implementing Lean Methodology To Decrease Wait Times In A Psychiatric Emergency Department, Kristina S. Baxter

Doctor of Nursing Practice Final Project Abstract

Purpose

This quality improvement project aimed to implement Lean strategies to optimize the intake process in a psychiatric emergency department, thereby reducing patient wait times, minimizing left-without-being-seen (LWBS) occurrences, and improving access to timely psychiatric care.

Background

The project was conducted in a hospital-based psychiatric emergency department in Southeast Texas, serving adults and children six years and older.

Methodology

Lean methodology and PDSA cycles were employed to refine the intake process and eliminate inefficiencies. Key interventions included patient transport by technicians to minimize delays, using tele-clinicians for assessments to reduce staff burden, and restructuring nursing assessments to prioritize telehealth consultations …

Artificial Intelligence-Based Virtual Staining Platform For Identifying Tumor-Associated Macrophages From Hematoxylin And Eosin-Stained Images, Arpit Aggarwal, Mayukhmala Jana, Amritpal Singh, Tanmoy Dam, Himanshu Maurya, Tilak Pathak, Sandra Orsulic, Kailin Yang, Deborah Chute, Justin A Bishop, Farhoud Faraji, Wade M Thorstad, Shlomo Koyfman, Scott Steward, Qiuying Shi, Vlad Sandulache, Nabil F Saba, James S Lewis, Germán Corredor, Anant Madabhushi

Faculty, Staff and Students Publications

Background: Virtual staining is an artificial intelligence-based approach that transforms pathology images between stain types, such as hematoxylin and eosin (H&E) to immunohistochemistry (IHC), providing a tissue-preserving and efficient alternative to traditional IHC staining. However, existing methods for translating H&E to virtual IHC often fail to generate images of sufficient quality for accurately delineating cell nuclei and IHC+ regions. To address these limitations, we introduce VISTA, an artificial intelligence-based virtual staining platform designed to translate H&E into virtual IHC.

Methods: We applied VISTA to identify M2-subtype tumor-associated macrophages (M2-TAMs) in H&E images from 968 patients with HPV+ oropharyngeal squamous cell …

Examining Demographic, Geographic, And Temporal Patterns Of Melanoma Incidence In Texas From 2000 To 2018: Retrospective Study, Kehe Zhang, Madison M Taylor, Jocelyn Hunyadi, Hung Q Doan, Adewole S Adamson, Paige Miller, Kelly C Nelson, Cici Bauer

Faculty, Staff and Student Publications

Background: Melanoma currently ranks as the fifth leading cancer diagnosis and is projected to become the second most common cancer in the United States by 2040. Melanoma detected at earlier stages may be treated with less-risky and less-costly therapeutic options.

Objective: This study aims to analyze temporal and spatial trends in melanoma incidence by stage at diagnosis (overall, early, and late) in Texas from 2000 to 2018, focusing on demographic and geographic variations to identify high-risk populations and regions for targeted prevention efforts.

Methods: We used melanoma incidence data from all 254 Texas counties from the Texas Cancer Registry (TCR) …

Longitudinal Profiling Of Circulating Tumor Dna Reveals The Evolutionary Dynamics Of Metastatic Prostate Cancer During Serial Therapy, Yuehui Zhao, Naveen Ramesh, Ping Xu, Emi Sei, Min Hu, Shanshan Bai, Patricia Troncoso, Ana M Aparicio, Christopher J Logothetis, Paul G Corn, Nicholas E Navin, Amado J Zurita

Faculty, Staff and Student Publications

Treatment decisions in metastatic castration-resistant prostate cancer are mostly guided by clinical variables, but efforts to molecularly monitor the disease remain hampered by challenges in acquiring tumor tissue repeatedly. In this study, we simultaneously profiled the genome copy number and exome in longitudinal plasma circulating tumor DNA (ctDNA) acquired before, during, and upon progression to serial treatments with androgen signaling inhibitors and taxane chemotherapy from 60 patients with metastatic castration-resistant prostate cancer (2-10 samples per patient). The genomic data were used to delineate the clonal substructure and evolutionary dynamics of each patient, and an evolutionary dynamic index was developed to …

Efficacy And Safety Of Larotrectinib In Patients With Trk Fusion Gastrointestinal Cancer, Changsong Qi, Lin Shen, Thierry Andre, Hyun Cheol Chung, Timothy L Cannon, Elena Garralda, Antoine Italiano, Damian T Rieke, Tianshu Liu, Domnita-Ileana Burcoveanu, Natascha Neu, Chiara E Mussi, Rui-Hua Xu, David S Hong, Alexander Drilon, Jordan Berlin

Faculty, Staff and Student Publications

Background: Larotrectinib is the first-in-class, highly selective TRK inhibitor with demonstrated efficacy in various TRK fusion solid tumours. We report the efficacy and safety of larotrectinib in patients with TRK fusion gastrointestinal (GI) cancer.

Methods: Patients with TRK fusion GI cancer from NAVIGATE (NCT02576431) were included. Response was independent review committee (IRC)-assessed per RECIST v1.1.

Results: As of July 2023, 44 patients were enrolled. Tumour types included colorectal (CRC; n = 26), pancreatic (n = 7), cholangiocarcinoma (n = 4), gastric (n = 3), and one each of appendiceal, duodenal, oesophageal and hepatic cancers. Of the 26 patients …

Genomic Characterization Of High-Grade Serous Ovarian Carcinoma Reveals Distinct Somatic Features In Black Individuals, Katherine A Lawson-Michod, Jeffrey R Marks, Lindsay J Collin, David A Nix, Natalie R Davidson, Chad D Huff, Yao Yu, Aaron Atkinson, Courtney E Johnson, Lucas A Salas, Lauren C Peres, Casey S Greene, Joellen M Schildkraut, Jennifer A Doherty

Faculty, Staff and Student Publications

Black individuals experience worse survival after a diagnosis of high-grade serous ovarian carcinoma (HGSC) than White individuals and are underrepresented in ovarian cancer research. To date, the understanding of the molecular and genomic heterogeneity of HGSC is based primarily on the evaluation of tumors from White individuals. In the present study, we performed whole-exome sequencing on HGSC samples from 211 Black patients to identify significantly mutated genes and characterize mutational signatures, assessing their distributions by gene expression subtypes. The occurrence and frequency of somatic mutations and signatures by self-reported race were compared with historic data from The Cancer Genome Atlas …

Reexploring The Stress Trial: Subgroup Postoperative Outcomes Following Methylprednisolone For Infant Heart Surgery, Sudeep D Sunthankar, Kevin D Hill, Jeffrey P Jacobs, H Scott Baldwin, Marshall L Jacobs, Jennifer S Li, Eric M Graham, Ashraf M Resheidat, Venugopal Amula, Mark S Bleiweis, Eric L Wald, Pirooz Eghtesady, John P Scott, Brett R Anderson, Michael F Swartz, Alexis Benscoter, William Ravekes, Prince J Kannankeril

Faculty, Staff and Students Publications

Objective Assess the association between intraoperative methylprednisolone and specific postoperative outcomes among subgroups undergoing infant heart surgery.

Design: Subpopulation analyses of The Steroids to Reduce Systemic Inflammation after Infant Heart Surgery trial, a double-blind randomized placebo-controlled trial.

Setting: 24 congenital heart centers.

Patients: Infants (< 1 year old) undergoing heart surgery with cardiopulmonary bypass. Patients stratified by Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery Congenital Heart Surgery (STAT) Mortality Category, age, gestational age, and presence of chromosomal or syndromic diagnosis (CSD).

Interventions: Methylprednisolone (30 mg/kg) versus placebo administered into cardiopulmonary bypass pump-priming fluid.

Measurements and main results: Outcomes included death, heart transplantation, mechanical circulatory support, reinterventions, and hospital length of stay. Ranked composite outcome (death, transplant, or one of 13 major complications) was compared between placebo and methylprednisolone for each subgroup using the win ratio. Methylprednisolone …

The Association Of Discrimination, Inflammation, And Coping Style On Self-Rated Health Among South Asian Individuals In The Masala Study, Raji Pillai, Sahiti Myneni, Constance M Johnson, Nilay S Shah, Alka M Kanaya, Jennifer E S Beauchamp

Faculty, Staff and Student Publications

Objectives: South Asian individuals (SAs) may have heightened levels of inflammatory markers, such as C reactive protein (CRP), Tumor Necrosis Factor-α (TNF-α), leptin, and resistin, and decreased levels of anti-inflammatory adiponectin, contributing to higher cardiovascular disease (CVD) incidence. Social determinants of health, like discrimination, are also associated with risks for CVD in SAs. This study examined the associations between discrimination and inflammation and whether coping styles moderated the association between discrimination and self-rated health (SRH) among SAs in the United States.

Design: Secondary analysis of data obtained from 1164 SAs (mean age = 57 years, SD = 9.4, 48% women) …

Modeling Buprenorphine Treatment Discontinuation In Opioid Use Disorder – Predictors And Disparities Using Statistical And Machine Learning Approaches, Wanru Guo

Dissertations and Theses (Open Access)

Background: Opioid Use Disorder (OUD) remains a major public health crisis in the U.S., and while buprenorphine is an effective treatment, early discontinuation undermines its impact. Existing statistical and machine learning (ML) models often overlook key social and healthcare-related predictors and fail to capture subgroup disparities, limiting their utility for equitable intervention design. This study addresses these gaps using a nationwide, longitudinal dataset and a two-stage modeling approach focused on disparity identification. Methods: We analyzed buprenorphine treatment episodes for OUD from the IQVIA Pharmetrics Plus database (2006–2023), defining discontinuation as episodes lasting under 180 days. A Cox proportional hazards model …