Digital Commons Network^™

Exploring The International Terminology Associated With Nurses Caring For Neonates, Infants, Children, Young People And Their Families., Matt Carey, Jane Coad, Imelda Coyne, Suja Somanadhan, Sarah Neill

School of Nursing and Midwifery

The terminology used for Registered Nurses specializing in caring for neonates, infants, children, young people (CYP), and their families varies globally. While many countries’ nursing students qualify as “Registered Nurses” upon completion of undergraduate education, specialist titles like “Children’s Nurses” in the United Kingdom or “Pediatric Nurses” in Italy denote expertise in CYP care. In countries like the United States and Canada, neonatal and pediatric nursing specialization typically requires postgraduate study. However, there is limited evidence on the range of international terms for nurses in this field. This expert opinion paper presents the results from a scoping survey designed to …

Covid-19 Infection History As A Risk Factor For Early Pregnancy Loss: Results From The Electronic Health Record-Based Southeast Texas Covid And Pregnancy Cohort Study, Micaela N Sandoval, Michelle R Klawans, Mackinsey A Bach, Jennifer Mikhail, Edward A Graviss, Tru Cao, Jacqueline G Parchem, Junaid Husain, Eric Boerwinkle

Faculty, Staff and Student Publications

Background: The effects of SARS-CoV-2 infection before or during pregnancy on pregnancy outcomes are still largely unknown. We hypothesized that COVID-19 in early pregnancy is a risk factor for adverse pregnancy outcomes, particularly miscarriage.

Methods: We examined the relationship between COVID-19 and adverse pregnancy outcomes, including spontaneous abortion, ectopic pregnancy, and preterm delivery in a large, retrospective, electronic health record (EHR)-based cohort, from 2019 to 2023. Generalized estimating equation modeling was performed to identify risk factors for adverse pregnancy outcomes. Study exposures included COVID-19 before pregnancy, COVID-19 during pregnancy, age, race/ethnicity, comorbidity burden, and neighborhood-level social vulnerability.

Results: In the …

Intracellular Inclusions Induced By Patient-Derived And Amplified Α-Synuclein Aggregates Are Morphologically Indistinguishable, Rabab Al-Lahham, Mark E Corkins, Mohd Ishtikhar, Prakruti Rabadia, Santiago Ramirez, Victor Banerjee, Mohammad Shahnawaz

Faculty, Staff and Student Publications

Lewy Body Disease (LBD) and Multiple System Atrophy (MSA) are synucleinopathies with distinct prognoses and neuropathologies, however, with overlapping clinical symptoms. Different disease characteristics are proposed to be determined by distinct conformations of alpha-synuclein (α-Syn) aggregates, which can self-propagate and spread between cells via a prion-like mechanism. The goal of this study is to investigate whether α-syn aggregates amplified from brain and CSF samples of LBD and MSA patients using the Seed Amplification Assay (SAA) maintain α-Syn seeding properties similar to those of α-syn aggregates derived from patients' brains. To address this, SAA-amplified and un-amplified α-Syn aggregates from LBD and …

Increased Fatty Acid Delivery By Tumor Endothelium Promotes Metastatic Outgrowth, Deanna N Edwards, Shan Wang, Kelby Kane, Wenqiang Song, Laura C Kim, Verra M Ngwa, Yoonha Hwang, Kevin Ess, Mark R Boothby, Jin Chen

Faculty, Staff and Students Publications

Metastatic outgrowth in distant microscopic niches requires sufficient nutrients, including fatty acids (FAs), to support tumor growth and to generate an immunosuppressive tumor microenvironment (TME). However, despite the important role of FAs in metastasis, the regulation of FA supply in metastatic niches has not been defined. In this report, we show that tumor endothelium actively promotes outgrowth and restricts antitumor cytolysis by transferring FAs into developing metastatic tumors. We describe a process of transendothelial FA delivery via endosomes that requires mTORC1 activity. Thus, endothelial cell-specific targeted deletion of Raptor (RptorECKO), a unique component of the mTORC1 complex, significantly reduced metastatic …

Human Genetic Variation Determines 24-Hour Rhythmic Gene Expression And Disease Risk, Ying Chen, Panpan Liu, Aniko Sabo, Dongyin Guan

Faculty, Staff and Students Publications

24-hour biological rhythms are essential to maintain physiological homeostasis. Disruption of these rhythms increases the risks of multiple diseases. Biological rhythms are known to have a genetic basis formed by core clock genes, but how individual genetic variation shapes the oscillating transcriptome and contributes to human chronophysiology and disease risk is largely unknown. Here, we mapped interactions between temporal gene expression and genotype to identify quantitative trait loci (QTLs) contributing to rhythmic gene expression. These newly identified QTLs were termed as rhythmic QTLs (rhyQTLs), which determine previously unappreciated rhythmic genes in human subpopulations with specific genotypes. Functionally, rhyQTLs and their …

Investigating Social Network Peer Effects On Hiv Care Engagement Using A Fuzzy-Like Matching Approach: Cross-Sectional Secondary Analysis Of The N2 Cohort Study, Cho-Hee Shrader, Dustin T Duncan, Redd Driver, Juan G Arroyo-Flores, Makella S Coudray, Raymond Moody, Yen-Tyng Chen, Britt Skaathun, Lindsay Young, Natascha Del Vecchio, Kayo Fujimoto, Justin R Knox, Mariano Kanamori, John A Schneider

Faculty, Staff and Student Publications

BACKGROUND: Social network data are essential and informative for public health research and implementation as they provide details on individuals and their social context. For example, health information and behaviors, such as HIV-related prevention and care, may disseminate within a network or across society. By harmonizing egocentric and digital networks, researchers may construct a sociocentric-like "fuzzy" network based on a subgroup of the population.

OBJECTIVE: We aimed to generate a more complete sociocentric-like "fuzzy" network by harmonizing alternative sources of egocentric and digital network data to examine relationships between participants in the Neighborhoods and Networks (N2) cohort study. Further, we …

Development Of A Risk Score To Aid With The Diagnosis Of Infections After Spinal Cord Injury: Protocol For A Retrospective Cohort Study, Felicia Skelton, Larissa Grigoryan, Joann Pan, Ashley Collazo, Barbara Trautner

Faculty, Staff and Students Publications

Background: Patients with spinal cord injury (SCI) who develop urinary tract infection (UTI) present differently than the non-SCI population. UTIs can cause loss of quality of life and even lead to life-threatening complications including urosepsis. Challenges in SCI management include distinguishing symptomatic UTI from asymptomatic bacteriuria (ASB), which occurs often in patients with SCI, and the lack of standardization in UTI diagnosis in SCI.

Objective: This study aims to set the foundation for the development of a risk score to improve diagnostic accuracy of UTI after SCI.

Methods: This study will use data from the Veterans Health Administration Corporate Data …

Empathy And Psychological Outcomes In Informal Caregivers Of Community-Dwelling Older Adults: A Systematic Review And Meta-Analysis, Meng Huo, Thi Vu, Tomiko Yoneda, Jingkai Wei, Bruce Abbott, Joan K Monin

Faculty, Staff and Student Publications

Objectives: Scholars have increasingly recognized the crucial role that empathy plays as informal caregivers provide unpaid care to their older family and friends (i.e., care recipients). Yet, the existing literature exhibits substantial variability in study approaches and results, which limits the extent to which this literature can inform interventions intended to benefit informal caregivers. We sought to address this critical gap by synthesizing research that examined how caregivers' and care recipients' empathy were associated with caregivers' psychological health.

Methods: We conducted a literature search using PubMed, PsycInfo, CINAHL (Cumulative Index to Nursing and Allied Health Literature), EMBASE, and Scopus databases …

Overconfidence And Financial Risk Tolerance In Older Age, Colleen C Frank, Gary R Mottola, Meiru Chen, Lei Yu, Patricia A Boyle, Gregory R Samanez-Larkin, Kendra L Seaman

Faculty, Staff and Student Publications

Objectives: Excessive financial risk-taking in older age can have harmful consequences as opportunities to recover lost wealth are limited. Understanding financial risk-taking in older age is important for identifying vulnerabilities and developing interventions to empower aging investors to make wise financial choices. In this paper, we explore how overconfidence in financial knowledge affects financial risk-taking among older adults.

Methods: We examine this research question in older adults aged 58-101 (N = 1,242) using data from the Rush Memory and Aging Project (MAP).

Results: After controlling for demographics, overconfidence was associated with self-reported financial risk tolerance such that those who were …

The Association Of Resistin With Metabolic Health And Obesity In A Mexican-American Population, Reem Al-Dallal, Keziah Thomas, Minjae Lee, Aysha Chaudhri, Eleanor Davis, Priyanka Vaidya, Miryoung Lee, Joseph B Mccormick, Susan P Fisher-Hoch, Absalon D Gutierrez

Faculty, Staff and Student Publications

Research on the relationship between resistin levels, metabolic health, and obesity has produced inconsistent findings across different ethnic groups, making it unclear whether lower resistin levels are associated with these conditions in Mexican-Americans. This cross-sectional study investigated the relationship between resistin, metabolic health, and obesity in an adult Mexican-American cohort (n = 1511) using multivariable linear regression analysis. Related adipokines (leptin and adiponectin) were measured simultaneously. Participants were categorized into four groups by metabolic health (healthy/unhealthy) and obesity (obese/non-obese) status. “Metabolically unhealthy” was defined as ≥2 cardiometabolic abnormalities. Obesity was defined as a BMI ≥ 30 kg/m2. We also …

Characterising Acute And Chronic Care Needs: Insights From The Global Burden Of Disease Study 2019, A. A. Asadi-Pooya

Department of Neurology Faculty Papers

Chronic care manages long-term, progressive conditions, while acute care addresses short-term conditions. Chronic conditions increasingly strain health systems, which are often unprepared for these demands. This study examines the burden of conditions requiring acute versus chronic care, including sequelae. Conditions and sequelae from the Global Burden of Diseases Study 2019 were classified into acute or chronic care categories. Data were analysed by age, sex, and socio-demographic index, presenting total numbers and contributions to burden metrics such as Disability-Adjusted Life Years (DALYs), Years Lived with Disability (YLD), and Years of Life Lost (YLL). Approximately 68% of DALYs were attributed to chronic …

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 …

Residential Proximity, Duration, And Health-Related Quality Of Life: Insights From The Fernald Cohort, Sara Burcham, Wei-Wen Hsu, Sharon L. Larson, Phd, Jack Rubinstein, Susan M. Pinney

College of Population Health Faculty Papers

The impact of living near environmental contamination on the health-related quality of life (HRQoL) is not well understood. This study examined the impacts of the residential proximity (RP) and time spent near a former Department of Energy uranium processing facility (located in Fernald, Ohio) on the surrounding community’s HRQoL outcomes. A cross-sectional analysis was conducted using the data collected from participants using the Short Form-36 survey at the time of the enrollment in the Fernald Medical Monitoring Program (n = 7957). Mental and physical component summary scores (MCS and PCS, respectively) were computed for each participant. The scores were compared …

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 …

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 …

Multilevel Factors Influencing Perceived Barriers To Adjuvant Endocrine Therapy Among Breast Cancer Patients At Medication Onset, Timothy Cocozza, Rita Smith, Ana Maria Lopez, Shari Rudoler, Rachel Slamon, Tingting Zhan, Jazmarie L. Vega, Minal Dhamankar, Aruna Padmanabhan, Suzanne M. Miller, Kuang-Yi Wen

Department of Medical Oncology Faculty Papers

Purpose: Adjuvant endocrine therapy (AET) significantly diminishes recurrence and mortality risks in hormone receptor-positive breast cancer (BCa) patients. Nonetheless, suboptimal adherence and premature discontinuation during the initial year of treatment undermine these positive outcomes. This study aims to understand the potential diverse factors associated with perceived barriers to AET compliance at the onset of medication. Methods: We assessed perceived barriers to AET using the ASK-20 instrument for BCa patients initiating AET within 3 months. Our survey also included demographic variables (e.g., musculoskeletal symptoms) and clinical traits (e.g., medication type). Stepwise regression analyses were employed to elucidate the links between multilevel …

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. …

Relationship Between Maternal Iron Indices In The Second Trimester With Cord Blood Iron Indices And Pregnancy Outcomes: A Prospective Cohort Study, J.P. Akshaykirthan, Manjunath S. Somannavar, M.S. Deepthy, Umesh Charantimath, S. Yogeshkumar, Amaresh Patil, Mrutyunjaya B. Bellad, Richard Derman, Shivaprasad S. Goudar

Global Health Articles

Background/Objectives: Iron deficiency anemia in pregnancy poses risks to mothers and infants. This study aimed to correlate maternal iron indices in the second trimester with cord blood indices and pregnancy outcomes.

Methods: This prospective cohort study was nested within the RAPIDIRON Trial (Reducing Anaemia in Pregnancy in India) at Jawaharlal Nehru Medical College, Karnataka, India. A total of 292 pregnant women with moderate anemia who received oral iron supplementation were enrolled from April 2021 to May 2023. Maternal iron indices were measured at multiple time points and correlated with cord blood indices and pregnancy outcomes.

Results: Increased hemoglobin levels were …

Rescue Of The First Mitochondrial Membrane Carrier, The Mpic, By Tat-Mediated Protein Replacement Treatment, Samar Zabit, Orly Melloul, Michal Lichtenstein, Erin L. Seifert, Haya Lorberboum-Galski

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The mitochondrial phosphate carrier (mPiC), encoded by the nuclear gene SLC25A3, is synthesized with an N-terminus mitochondrial targeting sequence (MTS), enabling its import into the mitochondria. mPiC imports inorganic phosphate (P_i) into the mitochondrial matrix for ATP production and other matrix phosphorylation reactions, as well as regulates mitochondrial Ca²⁺ uptake and buffering of matrix Ca²⁺. PiC also imports copper (Cu), crucial to COX subunit holoenzyme assembly. Variants in SLC25A3 exist and lead to mPiC deficiency (MPCD), cause a rare autosomal recessive disease with no current cure; patients with MPCD usually die within the first …

What Are The Effects Of Time-Restricted Eating Upon Metabolic Health Outcomes In Individuals With Metabolic Syndrome: A Scoping Review, Rory J Heath, Jessie Welbourne, Daniel Martin

Peninsula Medical School

The primary objective of this scoping review (ScR) was to assess the breadth and type of evidence related to time-restricted eating (TRE) as an intervention to modify metabolic health outcomes in individuals with diagnosed metabolic syndrome (MetS), a major health challenge due to increasing prevalence and association with other chronic diseases. MetS comprises three or more of hypertension, hypercholesterolaemia, dyslipidaemia, dysregulated glucose homeostasis, and abdominal obesity. TRE, also known as time-restricted feeding (TRF), restricts food intake to specific time windows within a day, for example, a 10-h eating period between 10:00 and 20:00. Via multiple mechanisms, TRE interventions may provide …

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 …

Crispr/Ncas9-Edited Cd34+ Cells Rescue Mucopolysaccharidosis Iva Fibroblasts Phenotype, Angélica María Herreno-Pachón, Andrés Felipe Leal, Shaukat Khan, Carlos Javier Alméciga-Díaz, Shunji Tomatsu

Department of Pediatrics Faculty Papers

Mucopolysaccharidosis (MPS) IVA is a bone-affecting lysosomal storage disease (LSD) caused by impaired degradation of the glycosaminoglycans (GAGs) keratan sulfate (KS) and chondroitin 6-sulfate (C6S) due to deficient N-acetylgalactosamine-6-sulfatase (GALNS) enzyme activity. Previously, we successfully developed and validated a CRISPR/nCas9-based gene therapy (GT) to insert an expression cassette at the AAVS1 and ROSA26 loci in human MPS IVA fibroblasts and MPS IVA mice, respectively. In this study, we have extended our approach to evaluate the effectiveness of our CRISPR/nCas9-based GT in editing human CD34+ cells to mediate cross-correction of MPS IVA fibroblasts. CD34+ cells were electroporated with the CRISPR/nCas9 system, …

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) …

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 …

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 …

Kinasefusiondb: An Integrative Knowledge Of Kinase Fusion Proteins In Multi-Scales, Himansu Kumar, Zikang Chen, Abayomi Adegunlehin, Loren Trowbridge, Leonardo Aguilar, Pora Kim

Faculty, Staff and Student Publications

Kinase fusion genes were the most targeted fusion gene group among multiple major cellular gene groups. Kinase inhibitors disrupt aberrant signaling cascades and inhibit tumor progression, yet the specific mechanisms of action of the U.S. Food and Drug Administration (FDA)-approved inhibitors in the context of kinase fusion oncoproteins remain largely unknown. This gap limits our ability to develop personalized therapies and next-generation kinase inhibitors. To address this, we developed a novel in silico pipeline for predicting 3D structures of kinase fusion proteins and performing structure-based virtual screening. This approach enables large-scale structural annotation and drug screening across pan-cancer kinase fusions. …

Bmal1-Hif2a Heterodimer Modulates Circadian Variations Of Myocardial Injury, Wei Ruan, Tao Li, In Hyuk Bang, Jaewoong Lee, Wankun Deng, Xinxin Ma, Cong Luo, Fang Du, Seung-Hee Yoo, Boyun Kim, Jiwen Li, Xiaoyi Yuan, Katherine Figarella, Yu A An, Yin-Ying Wang, Yafen Liang, Matthew Deberge, Dongze Zhang, Zhen Zhou, Yanyu Wang, Joshua M Gorham, Jonathan G Seidman, Christine E Seidman, Sary F Aranki, Ragini Nair, Lei Li, Jagat Narula, Zhongming Zhao, Alemayehu A Gorfe, Jochen D Muehlschlegel, Kuang-Lei Tsai, Holger K Eltzschig

Faculty, Staff and Student Publications

Acute myocardial infarction is a leading cause of morbidity and mortality worldwide1. Clinical studies have shown that the severity of cardiac injury after myocardial infarction exhibits a circadian pattern, with larger infarcts and poorer outcomes in patients experiencing morning-onset events2–7. However, the molecular mechanisms underlying these diurnal variations remain unclear. Here we show that the core circadian transcription factor BMAL17–11 regulates circadian-dependent myocardial injury by forming a transcriptionally active heterodimer with a non-canonical partner—hypoxia-inducible factor 2 alpha (HIF2A)12–16—in a diurnal manner. To substantiate this finding, we determined …

Robust Privacy Amidst Innovation With Large Language Models Through A Critical Assessment Of The Risks, Yao-Shun Chuang, Atiquer Rahman Sarkar, Yu-Chun Hsu, Noman Mohammed, Xiaoqian Jiang

Faculty, Staff and Student Publications

Objective: This study evaluates the integration of electronic health records (EHRs) and natural language processing (NLP) with large language models (LLMs) to enhance healthcare data management and patient care, focusing on using advanced language models to create secure, Health Insurance Portability and Accountability Act-compliant synthetic patient notes for global biomedical research.

Materials and methods: The study used de-identified and re-identified versions of the MIMIC III dataset with GPT-3.5, GPT-4, and Mistral 7B to generate synthetic clinical notes. Text generation employed templates and keyword extraction for contextually relevant notes, with One-shot generation for comparison. Privacy was assessed by analyzing protected health …

Fentanyl Test Strip Use And Overdose Risk Reduction Behaviors Among People Who Use Drugs, Rachel A Vickers-Smith, Kitty H Gelberg, Janet E Childerhose, Denise C Babineau, Redonna Chandler, James L David, Lauren D'Costa, Megan Dzurec, Barry Eggleston, Amanda Fallin-Bennett, Laura C Fanucchi, Soledad Fernandez, Jace Gilbert, Louisa Gilbert, Megan E Hall, Brooke E Hiltz, Michael W Konstan, Kathryn E Lancaster, Beth Linas, Katherine R Marks, Nichole Michaels, Jennifer Miles, Fernando Montero, Haley J Ramsey Harden, Carter Roeber, Mary R Russo, Rachel Taylor, Melissa A Theis

Epidemiology and Environmental Health Faculty Publications

IMPORTANCE: Illegal fentanyl is driving overdose mortality, and fentanyl test strips (FTS) can be used to test drugs for fentanyl at the point of consumption. Evidence on whether FTS use is associated with overdose risk reduction behaviors is encouraging, but largely limited to smaller, single-site studies.

OBJECTIVE: To determine whether self-reported baseline FTS use among people who use drugs (PWUD) was associated with overdose risk reduction behaviors and nonfatal overdose over a 28-day follow-up.

DESIGN, SETTING, AND PARTICIPANTS: Multisite, observational cohort study of PWUD conducted from May to December 2023 as an ancillary study of the HEALing Communities Study, which …