Digital Commons Network^™

Birthing While Black: The Color Of Care And Black Women’S Lived Experiences Giving Birth In The United States, Portia Cowlings

Theses and Dissertations

Black women in the United States face disproportionate maternal health outcomes during pregnancy, childbirth, and postpartum compared to other racial and ethnic groups. Despite advancements in healthcare, the United States continues to report the highest maternal mortality rates among high-income developed nations, with Black women experiencing rates up to three times higher than their White counterparts. This phenomenological study explores the lived experiences of Black women in the United States to understand how they navigate the continuum of maternal healthcare, from preconception through postpartum. Guided by the social determinants of health (SDOH) theoretical framework, childbirth was examined through four interconnected …

Structural Heart Imaging Using 3-Dimensional Intracardiac Echocardiography: Jacc: Cardiovascular Imaging Position Statement, Gilbert H L Tang, Syed Zaid, Rebecca T Hahn, Vratika Aggarwal, Mohamad Alkhouli, Edris Aman, Sergio Berti, Y S Chandrashekhar, Scott M Chadderdon, Andreina D'Agostino, Neil P Fam, Edwin C Ho, Chad Kliger, Susheel K Kodali, Parasuram Krishnamoorthy, Azeem Latib, Stamatios Lerakis, D Scott Lim, Vaikom S Mahadevan, Devi G Nair, Jagat Narula, Patrick T O'Gara, Douglas L Packer, Fabien Praz, Jason H Rogers, Tobias F Ruf, Carlos E Sanchez, Alok Sharma, Gagan D Singh, Nicolas M Van Mieghem, Mani A Vannan, Pradeep K Yadav, Lina Ya'qoub, Firas E Zahr, Ralph Stephan Von Bardeleben

Faculty, Staff and Students Publications

3-dimensional (3D) intracardiac echocardiography (ICE) is emerging as a promising complement and potential alternative to transesophageal echocardiography for imaging guidance in structural heart interventions. To establish standardized practices, our multidisciplinary expert position statement serves as a comprehensive guide for the appropriate indications and utilization of 3D-ICE in various structural heart procedures. The paper covers essential aspects such as the fundamentals of 3D-ICE imaging, basic views, and workflow recommendations specifically tailored for ICE-guided structural heart procedures, such as transeptal puncture, device closure of intracardiac structures, and transcatheter mitral and tricuspid valve interventions. Current challenges, future directions, and training requirements to ensure …

Anxiety And Body-Focused Repetitive Behaviors: A Systematic Review And Meta-Analysis Of Comorbidity Rates And Symptom Associations, Kathryn E. Barber, Isabella F. Cram, Elyse C. Smith, Leila K. Capel, Ivar Snorrason, Douglas W. Woods

Psychology Faculty Research and Publications

Body-focused repetitive behavior (BFRB) disorders, including hair pulling disorder (trichotillomania [TTM]) and skin picking disorder (SPD), frequently co-occur with anxiety disorders, but reported comorbidity rates vary widely. Additionally, research on the relationship between anxiety and BFRB symptoms has yielded inconsistent findings. This meta-analysis and systematic review examined (1) the prevalence of comorbid anxiety disorders in individuals with BFRB disorders and (2) correlations between anxiety and BFRB symptom measures. The study protocol was pre-registered on PROSPERO. A systematic search of PsycInfo, PubMed, and Web of Science identified 119 studies (N=15,902) reporting anxiety prevalence rates in BFRB disorders and/or correlations between anxiety …

Proactive Distributed Emergency Response With Heterogeneous Tasks Allocation, Justice Darko, Hyoshin Park

Engineering Management & Systems Engineering Faculty Publications

Traditionally, traffic incident management (TIM) programs coordinate the deployment of emergency resources to immediate incident requests without accommodating the interdependencies on incident evolutions in the environment. However, ignoring these inherent interdependencies while making current deployment decisions is shortsighted, and the resulting naive deployment strategy can significantly worsen the overall incident delay impact on the network. The interdependencies on incident evolution in the environment, including those between incident occurrences and those between resource availability in near-future requests and the anticipated duration of the immediate incident request, should be considered through a look-ahead model when making current-stage deployment decisions. This study develops …

Quantifying Multidimensional Effects Of Physicochemical Parameters On Pfas Adsorption Using A Hybrid Response Surface Methodology-Machine Learning Approach, Harsh V. Patel, Jazmin Green, John Park, Stephanie Luster-Teasley Pass, Renzun Zhao

Engineering Management & Systems Engineering Faculty Publications

Per- and polyfluoroalkyl substances (PFAS) contamination has posed a significant environmental and public health challenge due to their ubiquitous nature. Adsorption has emerged as a promising remediation technique, yet optimizing adsorption efficiency remains complex due to the diverse physicochemical properties of PFAS and the wide range of adsorbent materials. Traditional modeling approaches, such as response surface methodology (RSM), struggled to capture nonlinear interactions, while standalone machine learning (ML) models required extensive datasets. This study addressed these limitations by developing hybrid RSM-ML models to improve the prediction and optimization of PFAS adsorption. A comprehensive dataset was constructed using experimental adsorption data, …

Zero Trust Architecture As A Risk Countermeasure In Small-Medium Enterprises And Advanced Technology Systems, Ahmed M. Abdelmagid, Rafael Diaz

Engineering Management & Systems Engineering Faculty Publications

The growing sophistication of cyberattacks exposes small- and medium-sized businesses (SMBs) to a widening range of security risks. As these threats evolve in complexity, the need for advanced security measures becomes increasingly pressing. This necessitates a proactive approach to defending against potential cyber intrusions. Emerging technologies, such as blockchain, artificial intelligence, and Zero Trust security framework, offer crucial tools for strengthening the digital infrastructure of SMBs. The Zero Trust architecture (ZTA) holds significant promise as a critical strategy for protecting SMBs. While existing literature explores the implementation of ZTA in various business settings, discussions specifically addressing the financial, human resource, …

Nanoparticle Contrast Agents For Photon-Counting Computed Tomography: Recent Developments And Future Opportunities, Laxman Devkota, Rohan Bhavane, Cristian T Badea, Eric A Tanifum, Ananth V Annapragada, Ketan B Ghaghada

Faculty, Staff and Students Publications

The clinical availability of photon-counting computed tomography (PCCT) has ushered in a new era of CT imaging. Spectral imaging coupled with superior contrast resolution, and ultrahigh spatial resolution (200 μm) offered by PCCT has the potential to revolutionize value-driven imaging. The potential of multicolor PCCT has generated excitement, and renewed interest, in novel contrast agent development for comprehensive disease interrogation, prediction and monitoring of treatment outcomes. Nanoparticles provide a versatile and powerful platform for the development of next generation contrast agents for spectral PCCT. In this article, we review recent developments and use of nanoparticle contrast agents for PCCT. We …

Mutations In Retinal Cyclic Nucleotide-Gated Channels Identified In Familial Cases Of Inherited Retinal Dystrophies From Pakistan, Zainab Akhtar, Kiran Afshan, Yumei Li, Sumaira Altaf, Aleesha Asghar, Ume Sughra, Wajid Ali Khan, Haiba Kaul, Rui Chen, Sabika Firasat

Faculty, Staff and Students Publications

Purpose: Cyclic nucleotide-gated (CNG) channels are ligand-gated ion channels that transduce light signals into electrical signals in the retinal photoreceptors. Pathogenic variants in CNG channel genes are reported to cause inherited retinal dystrophies (IRDs). The current study used targeted panel sequencing to describe the mutational spectrum of CNG channel genes in familial cases of IRDs from eight consanguineous Pakistani families.

Methods: The current study included consanguineous Pakistani families with at least two affected members. DNA was extracted from whole blood samples by the phenol-chloroform method. Two affected members from each family were initially analyzed using targeted panel sequencing of 344 …

Assessing The Cardioprotective Effects Of Exercise In Apoe Mouse Models Using Deep Learning And Photon-Counting Micro-Ct, Alex J Allphin, Rohan Nadkarni, Zay Y Han, Darin P Clark, Ketan B Ghaghada, Alexandra Badea, Cristian T Badea

Faculty, Staff and Students Publications

Background: The allelic variations of the apolipoprotein E (APOE) gene play a critical role in regulating lipid metabolism and significantly impact cardiovascular disease risk (CVD). This study aimed to evaluate the impact of exercise on cardiac structure and function in mouse models expressing different APOE genotypes using photon-counting computed tomography (PCCT) and deep learning-based segmentation.

Methods: A total of 140 mice were grouped based on APOE genotype (APOE2, APOE3, APOE4), sex, and exercise regimen. All mice were maintained on a controlled diet to isolate the effects of exercise. Low dose cardiac photon counting micro-CT imaging with intrinsic gating was performed …

Exercise Mitigates High-Fat Diet-Induced Cardiac Dysfunction Via Apoe Genotype- And Immune-Dependent Mechanisms: A Photon-Counting Ct Study In Adult Mice, Rohan Nadkarni, Alex J Allphin, Darin P Clark, Yi Qi, Zay Yar Han, Ketan B Ghaghada, Alexandra Badea, Cristian T Badea

Faculty, Staff and Students Publications

Background: Cardiovascular dysfunction frequently accompanies aging and is often worsened by adverse lifestyle factors and genetic susceptibility. The apolipoprotein E (APOE) gene modulates susceptibility to cardiovascular disease, but how exercise and diet interact with APOE genotype remains insufficiently understood. We investigate the cardioprotective potential of exercise in humanized APOE-targeted replacement mice on control and high-fat diet, using photon-counting computed tomography (PCCT) and deep learning-based image segmentation.

Methods: This study included 251 male and female mice in mid-to-late life of APOE2, APOE3, and APOE4 genotypes with variation in humanized NOS2 (HN) mediated innate immune response, exercise status (exercised vs. sedentary) and …

Structural Dynamics And Binding Of Caenorhabditis Elegans Lifespan-Extending Lipid Binding Protein-3 To Polyunsaturated Fatty Acids, André R Cuevas, Matthew C Tillman, Meng C Wang, Eric A Ortlund

Faculty, Staff and Students Publications

Intracellular lipid binding proteins (iLBPs) play crucial roles in lipid transport and cellular metabolism across the animal kingdom. Recently, a fat‐to‐neuron axis was described in Caenorhabditis elegans, in which lysosomal activity in the fat liberates polyunsaturated fatty acids (PUFAs) that signal to neurons and extend lifespan with durable fecundity. In this study, we investigate the structure and binding mechanisms of a lifespan‐extending lipid chaperone, lipid binding protein‐3 (LBP‐3), which shuttles dihomo‐γ‐linolenic (DGLA) acid from intestinal fat to neurons. We present the first high‐resolution crystal structure of LBP‐3, which reveals a classic iLBP fold with an unexpected and unique homodimeric …

Primary Cardiac Osteosarcoma: Epidemiology, Diagnosis, And Management - A Narrative Review, Tommy Li, Eric Nguyen, Jamal Hasoon, Ali Khalifa, Anvinh Nguyen

Faculty, Staff and Students Publications

Primary cardiac sarcomas are exceedingly rare, with a very low incidence in the general population. A variety of sarcoma subtypes can originate in the heart, including angiosarcoma, rhabdomyosarcoma, leiomyosarcoma, fibrosarcoma, and osteosarcoma. These tumors are typically classified based on histological characteristics, most often determined following surgical excision or biopsy. Among them, primary cardiac osteosarcoma is one of the rarest forms, with fewer than 60 cases reported in the literature to date. This narrative review aims to provide an overview of primary cardiac osteosarcoma, including its epidemiology, clinical presentation, and current management strategies. Additionally, we highlight several remarkable case reports to …

Recognition And Management Of Persistent Chylomicronemia: A Joint Expert Clinical Consensus By The National Lipid Association And The American Society For Preventive Cardiology, Seyedmohammad Saadatagah, Miriam Larouche, Mohammadreza Naderian, Vijay Nambi, Diane Brisson, Iftikhar J Kullo, P Barton Duell, Erin D Michos, Michael D Shapiro, Gerald F Watts, Daniel Gaudet, Christie M Ballantyne

Faculty, Staff and Students Publications

Extreme hypertriglyceridemia, defined as triglyceride (TG) levels ≥1000 mg/dL, is almost always indicative of chylomicronemia. The current diagnostic approach categorizes individuals with chylomicronemia into familial chylomicronemia syndrome (FCS; prevalence 1-10 per million), caused by the biallelic combination of pathogenic variants that impair the lipolytic action of lipoprotein lipase (LPL), or multifactorial chylomicronemia syndrome (MCS, 1 in 500). A pragmatic framework should emphasize the severity of the phenotype and the risk of complications. Therefore, we endorse the term "persistent chylomicronemia (PC)" defined as TG ≥1000 mg/dL in more than half of the measurements to encompass patients with the highest risk for …

Tb And Diabetes In Eswatini: Addressing Suboptimal Treatment Outcomes Through Integrated Services, Yael Hirsch-Moverman, Dana Bezuidenhout, Sakthi Senthilvelan, Lobsang Palmo, Debrah Vambe, Ntombifuthi Ginindza, Nonhlanhla Dlamini, Andrea A Howard, Joanne E Mantell

Faculty, Staff and Students Publications

Tuberculosis (TB) remains a significant public health challenge in Eswatini, a country with the highest global HIV prevalence. Diabetes mellitus (DM) is increasingly common among people newly diagnosed with TB, contributing to suboptimal TB treatment outcomes, including relapse and death. The DETECT study employed a multi-method approach to assess the prevalence and DM impact on TB treatment outcomes among adults with TB in 10 Ministry of Health facilities in Eswatini, and explore barriers and facilitators to integrating TB/DM services. DM screening was conducted using laboratory-based glycated hemoglobin (A1c) testing, with DM defined as A1c ≥ 6.5% and preDM as A1c …

Occult Abdominal Trauma Screening In The Evaluation Of Suspected Child Physical Abuse, Tagrid M Ruiz-Maldonado, Joanne N Wood, Antoinette L Laskey, Christopher S Greeley, Angela Bachim, Daniel M Lindberg, James Anderst, John Melville, Carmen Coombs, Nancy S Harper, Lori Frasier, Farah W Brink, Caitlin E Crumm, Kristine A Campbell

Faculty, Staff and Students Publications

Background and objectives: Occult abdominal trauma (OAT) screening with transaminases, followed by abdominal computed tomography (CT) for transaminase values greater than 80 IU/L, has been recommended in cases of suspected physical abuse. This study aimed to evaluate case characteristics associated with OAT evaluation and determine OAT prevalence in these children.

Methods: Injured children aged younger than 60 months undergoing Child Abuse Pediatrics (CAP) consultation for suspected physical abuse from February 2021 to May 2023 were identified in CAPNET, a multicenter research network. Children with symptoms or signs of intra-abdominal injury were excluded. We identified case characteristics associated with transaminase screening …

Recessive Loss-Of-Function Variants In Dph1 Identified As The Molecular Cause In A Sibling Pair Previously Diagnosed With Fine-Lubinsky Syndrome, Emily R Waskow, Lisa T Emrick, Jill A Rosenfeld, Shamika Ketkar, Lindsay C Burrage, Daryl A Scott

Faculty, Staff and Students Publications

Fine-Lubinsky syndrome is a rare clinically defined syndrome sometimes referred to as brachycephaly, deafness, cataract, microstomia, and impaired intellectual development syndrome. Here we provide a clinical and molecular update for a sibling pair diagnosed with Fine-Lubinsky syndrome. An extensive genetic work-up, including chromosomal microarray analysis and quad exome sequencing, was nondiagnostic. However, a research reanalysis of their exome sequencing data revealed that both were homozygous for an intronic c.749+39G>A [NM_001383.6] variant in DPH1. RNAseq analysis performed on RNA from fibroblasts revealed significantly reduced expression of DPH1 transcripts suggestive of abnormal splicing followed by nonsense mediated mRNA decay. Since the …

Increasing Surgical Healthcare Utilization For Infants With Congenital Anomalies In Texas, Bea B Jeon, Sarah Peiffer, Shannon M Larabee, Kathleen Hosek, Dailen Alonso, Timothy C Lee, Sundeep G Keswani, Alice King

Faculty, Staff and Students Publications

Introduction: Congenital anomalies (CAs) impact 3% of live births and account for disproportionately high healthcare costs. While many CAs require multidisciplinary care and surgical intervention, the overall financial impact of infants diagnosed with CA with surgical needs is unknown. We aim to evaluate and characterize the charges of care in infants with CA and surgical needs in Texas.

Methods: A database study using the Texas Inpatient Public Use Data File was performed to query infants (< 365 days) statewide from 1/2021 to 12/2021 for admissions with CA and involved organ system by ICD-10 codes. Encounters transferred to an outside hospital were excluded to avoid systematic double-counting. Descriptive statistics were performed.

Results: Of 376,215 total admissions, 81,666 had surgical needs with OR charges. While non-CA represent the majority of surgical admissions (63,895/81,666; 78.24%), CA-surgical admissions …

Toward Precision Longevity: Aging Interventions In The Single-Cell Atlas Era, Jason B Chen, Miranda C Wang, Shangyu Gong, Hongjie Li

Faculty, Staff and Students Publications

With growing global interest in extending not only lifespan but also healthspan, healthy aging has emerged as a central goal in biomedical research. This review provides an overview of current longevity interventions, including genetic manipulations, dietary restriction, exercise, pharmacological treatments, targeting senescence and cellular reprogramming strategies, as studied in key model organisms such as Caenorhabditis elegans, Drosophila melanogaster, and Mus musculus. We examine the limitations and challenges associated with these approaches, particularly their variability across tissues and cell types. Furthermore, we emphasize the critical role of single-cell aging atlas technologies in uncovering cell-type–specific aging patterns and molecular …

Interleukin-15-Armoured Gpc3 Car T Cells For Patients With Solid Cancers, David Steffin, Nisha Ghatwai, Antonino Montalbano, Purva Rathi, Amy N Courtney, Azlann B Arnett, Julien Fleurence, Ramy Sweidan, Tao Wang, Huimin Zhang, Prakash Masand, John M Maris, Daniel Martinez, Jennifer Pogoriler, Navin Varadarajan, Sachin G Thakkar, Deborah Lyon, Natalia Lapteva, Mei Zhuyong, Kalyani Patel, Dolores Lopez-Terrada, Carlos A Ramos, Premal Lulla, Tannaz Armaghany, Bambi J Grilley, Stephen Gottschalk, Gianpietro Dotti, Leonid S Metelitsa, Helen E Heslop, Malcolm K Brenner, Pavel Sumazin, Andras Heczey

Faculty, Staff and Students Publications

Interleukin-15 (IL15) promotes the survival of T lymphocytes and enhances the antitumor properties of CAR T cells in preclinical models of solid neoplasms in which CAR T cells have limited efficacy1-4. Glypican-3 (GPC3) is expressed in a group of solid cancers5-10, and here we report the first evaluation in humans of the effects of IL15 co-expression on GPC3-CAR T cells. Cohort 1 patients (NCT02905188/NCT02932956) received GPC3-CAR T cells, which were safe but produced no objective antitumor responses and reached peak expansion at two weeks. Cohort 2 patients ( …

Defining Dysphoric Milk Ejection Reflex: Using Premenstrual Dysphoric Disorder As A Framework For Proposing Preliminary Diagnostic Criteria, Megan Howard, Teni Davoudian, Nicole H Cirino

Faculty, Staff and Students Publications

Dysphoric Milk Ejection Reflex (D-MER) is a distinct neurobiological condition characterized by negative alterations in mental state in response to milk letdown during lactation. Symptoms vary by patient and can include feelings of sadness, anxiety or agitation. Importantly, the symptoms are brief, typically lasting no more than 5 minutes. Prevalence has been found between 6 and 27% of lactating women, but studies show heterogeneity, due in part to inconsistent definition. D-MER is not currently classified in the Diagnostic and Statistical Manual of Mental Disorders (DSM) or the International Classification of Diseases (ICD), which presents a challenge for researchers of the …

Finite Element Modeling In Obstetrics And Gynecology: Advances, Applications, And Challenges, Taylor Moseley, Ashley J Hicks, Elizabeth M Cosgriff-Hernandez, Manuel Karl Rausch, Julie Hakim

Faculty, Staff and Students Publications

Finite element modeling (FEM) is a critical tool in biomechanics and biomedical engineering, offering valuable insights where in vivo or ex vivo investigations are not possible. This review specifically highlights the diverse applications of FEM within obstetrics and gynecology through a comprehensive analysis of the literature. We explore the past use of FEM in analyzing complications affecting pelvic floor structures, urinary continence, and reproduction. The potential contributions of FEM in addressing these challenges are summarized and future directions for its application in obstetrics and gynecology are highlighted.

A Natural Small Molecule Isoginkgetin Alleviates Hypercholesterolemia And Atherosclerosis By Targeting Acly, Zhidan Zhang, Meijie Chen, Yitong Xu, Zhihua Wang, Zhenghong Liu, Chenyang He, Fanshun Zhang, Xiaojun Feng, Xiayun Ni, Yuanli Chen, Jixia Wang, Xinmiao Liang, Zhifu Xie, Jingya Li, Maciej Banach, Jaroslav Pelisek, Yuqing Huo, Yunhui Hu, Paul C Evans, Li Wang, Xiao-Yu Tian, Jianbo Xiao, Yuhua Shang, Yijun Zheng, Xunde Xian, Jianping Weng, Suowen Xu

Faculty, Staff and Students Publications

Rationale: Atherosclerotic cardiovascular disease (ASCVD) represents the predominant cause of mortality and morbidity globally. Given the established role of hypercholesterolemia as a significant risk factor for ASCVD, the discovery of new lipid-lowering medications is of paramount importance. ATP citrate lyase (ACLY) is a crucial enzyme in cellular metabolism, providing acetyl-CoA as the building block for the biosynthesis of fatty acids and cholesterol. Consequently, it has emerged as a promising drug target for innovative treatments of lipid metabolic disorders.

Methods: Virtual screening of a natural product library was performed to identify small-molecule ACLY inhibitors, leading to the discovery of isoginkgetin (ISOGK). …

Mutations In Retinal Cyclic Nucleotide-Gated Channels Identified In Familial Cases Of Inherited Retinal Dystrophies From Pakistan, Zainab Akhtar, Kiran Afshan, Yumei Li, Sumaira Altaf, Aleesha Asghar, Ume Sughra, Wajid Ali Khan, Haiba Kaul, Rui Chen, Sabika Firasat

Faculty, Staff and Students Publications

Purpose: Cyclic nucleotide-gated (CNG) channels are ligand-gated ion channels that transduce light signals into electrical signals in the retinal photoreceptors. Pathogenic variants in CNG channel genes are reported to cause inherited retinal dystrophies (IRDs). The current study used targeted panel sequencing to describe the mutational spectrum of CNG channel genes in familial cases of IRDs from eight consanguineous Pakistani families.

Methods: The current study included consanguineous Pakistani families with at least two affected members. DNA was extracted from whole blood samples by the phenol-chloroform method. Two affected members from each family were initially analyzed using targeted panel sequencing of 344 …

Testosterone Plus Lifestyle Therapy Improves Skeletal Muscle Glycolysis In Older Men With Obesity And Hypogonadism, Viola Viola, Marlene Aguilar, Maria Liza Duremdes Nava, Alessandra Celli, Reina Armamento-Villareal, Yoann Barnouin, Nicola Napoli, Nagireeddy Putluri, Clifford Qualls, Dennis T Villareal

Faculty, Staff and Students Publications

Objective: Weight loss in older men with obesity and hypogonadism accelerates musculoskeletal decline, yet the underlying metabolic mechanisms remain unclear. Testosterone replacement therapy (TRT), when added to lifestyle therapy (LT), mitigates this decline, but its metabolic basis has not been defined. We examined skeletal muscle metabolomic adaptations to LT with or without TRT, focusing on glycolysis, the pentose phosphate pathway (PPP), the tricarboxylic acid (TCA) cycle, and carnitine metabolism to identify dominant pathways of metabolic adaptation.

Design: Randomized, double-blind, placebo-controlled trial (LITROS).

Methods: Eighty-three men aged 65 years or older with obesity (BMI ≥30 kg/m2), hypogonadism (testosterone < 10.4 nmol/L), and frailty (Physical Performance Test score ≤31) were randomized to 26 weeks of LT plus TRT (LT+TRT) or LT plus placebo (LT+Pbo). A metabolomic substudy was performed in 44 participants, who underwent serial biopsies of the vastus lateralis for targeted LC-MS/MS analysis of intermediates in glycolysis, PPP, TCA cycle, and carnitine metabolism.

Results: Among the …

Clues To Transcription/Replication Collision-Induced Dna Damage: It Was Rnap, In The Chromosome, With The Fork, Matthew B Cooke, Christophe Herman, Priya Sivaramakrishnan

Faculty, Staff and Students Publications

DNA replication and RNA transcription processes compete for the same DNA template and, thus, frequently collide. These transcription-replication collisions are thought to lead to genomic instability, which places a selective pressure on organisms to avoid them. Here, we review the predisposing causes, molecular mechanisms, and downstream consequences of transcription-replication collisions (TRCs) with a strong emphasis on prokaryotic model systems, before contrasting prokaryotic findings with cases in eukaryotic systems. Current research points to genomic structure as the primary determinant of steady-state TRC levels and RNA polymerase regulation as the primary inducer of excess TRCs. We review the proposed mechanisms of TRC-induced …

Folate Receptor Β Performs An Immune Checkpoint Function In Activated Macrophages, Fenghua Zhang, Md Yusuf Al-Amin, Sagar Utturkar, Rina Jiang, Gregory Cresswell, Rami Alfar, Ian Ophaug-Johansen, Gabriel Bachman, Madduri Srinivasarao, Richard Finnell, Amaya Puig-Kröger, Timothy Ratliff, Philip S Low

Faculty, Staff and Students Publications

Monocytes and macrophages are sentinels of the immune system that distinguish themselves from other cells by expressing the beta isoform of the folate receptor (FRβ). Because FRβ does not bind folate until the monocyte/macrophage is exposed to immunosuppressive cytokines, the question naturally arose whether FRβ might also perform an immune-related function. To examine this matter, we compared the properties of wild type (WT) and FRβ knockout mice. We observe that FRβ knockout (KO) mice display autoimmune symptoms that can include alopecia, enlarged spleens, and dermatitis, despite having normal cellular folate levels. We further demonstrate that syngeneic tumors (TRAMP C2, MC38) …

A Multifunctional Theranostic Ultrasound Platform For Remote Magnetogenetics And Expanded Blood-Brain Barrier Opening, Alec J Batts, Fotios N Tsitsos, Jeannette Ingabire, Guillaume Duret, Samantha L Gorman, Deny Tsakri, Rebecca L Noel, Robin Ji, Nancy Kwon, Quoc-Khanh Pham, Linlin Zhang, Gang Bao, Jacob T Robinson, Elisa E Konofagou

Faculty, Staff and Students Publications

Introduction: Brain stimulation techniques are critical for unraveling the innerworkings of complex neuronal pathways governing both normal physiological function and pathologic states in neurological disorders. Focused ultrasound (FUS) is an emerging technique poised to significantly alter central nervous system (CNS) drug delivery and neuroscience research through non-invasive means. Magnetogenetics is a brain stimulation technique which may benefit from FUS technology in that alternating magnetic fields (AMF), like FUS, can pass through the skull without requiring surgery.

Methodology: Magnetogenetics involves the deposition of superparamagnetic iron-oxide nanoparticles (SPIONs) and overexpression of thermoreceptor transmembrane proteins (e.g. TRPV1 and TRPA1) in the brain. When …

Delayed Excretion Of High-Dose Methotrexate In Pediatric Acute Leukemia Correlates With Laxative And Constipation Management, Jennifer A Belsky, Ashley Chavana, Ankona Banerjee, Mark Zobeck, Eric S Schafer, Karen R Rabin, Monica Gramatges, Alex Sim, Audrey Leisinger, Trisha Reddy, Megan J Parod, Philip Lupo, Michael Scheurer, Austin L Brown, M Brooke Bernhardt

Faculty, Staff and Students Publications

Background: Delayed excretion of high-dose methotrexate (HD-MTX) in pediatric acute lymphoblastic leukemia (ALL) can result in significant morbidity. While methotrexate is primarily renally excreted, HD-MTX may overwhelm renal excretion and increase reliance on fecal elimination. This study evaluated the association between laxative use for constipation and delayed excretion of HD-MTX.

Methods: This multisite chart review included pediatric patients with ALL (2010-2020) who received HD-MTX (5 g/m2). Delayed excretion was defined as a serum MTX concentration greater than 0.4 µM at Hour 48. We identified use of laxative medications after each HD-MTX infusion, with receipt of two or more doses considered …

Association Between Parathyroid Hormone Concentration And Incident Atrial Fibrillation In Older Persons With Kidney Failure Initiating Dialysis, Pascale Khairallah, Sai Liu, Maria E Montez-Rath, Kevin F Erickson, Tara I Chang, Wolfgang C Winkelmayer

Faculty, Staff and Students Publications

Introduction: Atrial fibrillation (AF) is common in persons with kidney failure on hemodialysis. In the general population, higher intact parathyroid hormone (iPTH) levels were found to be associated with presence of AF. Whether iPTH associates with AF in patients on hemodialysis is unknown.

Methods: Using merged USRDS-DaVita data (2006-2011), we selected persons aged 67+ years who initiated hemodialysis and survived 120 days. Eligible persons had continuous Medicare A + B coverage from 2 years prior to kidney failure and no diagnosis of AF. Sociodemographic, comorbidity, and clinical information were abstracted from Medicare forms, billing claims, and electronic health records. iPTH …

Association Of Insulin Resistance With Radiographic Lung Abnormalities And Incident Lung Disease: The Framingham Offspring Study, Sarath Raju, Paula Sierra, Vickram Tejwani, Kristen A Staggers, Meredith Mccormack, Dennis T Villareal, Ivan O Rosas, Nicola A Hanania, Tianshi David Wu

Faculty, Staff and Students Publications

Objective: Insulin resistance (IR) may be a risk factor for lung disease, but objective evidence is limited. We sought to define the relationship of longitudinal IR with radiographic imaging outcomes and examiner-identified incident lung disease in the Framingham Offspring Study.

Research design and methods: Participants without baseline lung disease underwent repeated measurements of fasting insulin and glucose levels over an average period of 13.6 years, from which time-weighted average HOMA-IR was calculated. Each participant then underwent a cardiac gated whole-lung computed tomography scan, which was analyzed for the presence of emphysema, interstitial lung abnormalities (ILAs), and quantitative airway features. Incident …