Medicine and Health Sciences Commons^™

Emg-Guided Human-Machine Interaction Training Develops New Intermuscular Coordination Patterns In Stroke: A Pilot Study, Gang Seo, Manuel Portilla-Jiménez, Michael Houston, Jeong-Ho Park, Hangil Lee, Sheng Li, Yingchun Zhang, Hyung-Soon Park, Jinsook Roh

Faculty, Staff and Student Publications

Background: Stroke survivors often experience impaired upper extremity motor function due to abnormal muscle synergies. This pilot study evaluated the feasibility and preliminary effectiveness of electromyography-guided human-machine interaction training designed to expand the repertoire of intermuscular coordination patterns and improve upper extremity motor function in chronic stroke survivors.

Methods: Four chronic stroke survivors with mild-to-moderate upper extremity motor impairment and three age-matched healthy controls participated in a six-week electromyography-guided training intervention. Participants practiced selectively activating one elbow flexor muscle while suppressing another (brachioradialis or biceps brachii). Throughout the course of the intervention, the effect of the training on intermuscular coordination, …

First-In-Child Phase I Trial Of P-Stat3 Inhibitor Wp1066 In Pediatric Brain Tumor Patients, Robert C Castellino, Hope L Mumme, Andrea T Franson, Bing Yu, M Hope Robinson, Kavita Dhodapkar, Dolly Aguilera, Matthew J Schniederjan, Rohali Keesari, Zhulin He, Manoj Bhasin, Waldemar Priebe, Amy B Heimberger, Tobey J Macdonald

Faculty, Staff and Student Publications

Background: WP1066 is an orally bioavailable, small molecule inhibitor of activated p-STAT3 that has demonstrated preclinical efficacy in pediatric brain tumor models.

Methods: In a first-in-child, single-center, single-arm 3+3 design Phase I clinical trial, ten patients were treated with WP1066 twice daily, Monday-Wednesday-Friday, for 14 days of each 28-day cycle to determine the maximum tolerated dose (MTD)/maximum feasible dose (MFD) of WP1066. Compassionate use treatment with WP1066 in three pediatric patients with H3.3 G34R/V-mutant high-grade glioma (HGG) is also described.

Results: There was no significant toxicity and the MFD was determined to be 8 mg/kg. Treatment-related adverse events were Grade …

Structural Birth Defects And Leukemia Risk In Children With Down Syndrome, Ching-Ju Hsu, Jeremy M Schraw, Sonja A Rasmussen, Tiffany M Chambers, Tania A Desrosiers, Chad D Huff, Amanda E Janitz, Russell S Kirby, Eirini Nestoridi, Wendy N Nembhard, Jason L Salemi, Charles Shumate, Jean Paul Tanner, Mahsa M Yazdy, Michael E Scheurer, Karen R Rabin, Philip J Lupo

Faculty, Staff and Students Publications

Birth defects are associated with increased cancer risk in the general pediatric population, yet their impact on leukemia risk in children with Down syndrome (DS) remains uncertain. We assessed this using data from 26,660 children with DS in the Genetic Overlap Between Anomalies and Cancer in Kids Registry Linkage Study. Among them, 71.9% had at least one major birth defect, predominantly involving the cardiac (64.2%), musculoskeletal (21%), and gastrointestinal systems (6.8%). The cumulative incidence of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) was comparable in children with and without co-occurring defects. Adjusted hazard ratios (aHR) for ALL and …

Psychiatric Comorbidities And Treatment Modalities In Children With Osteogenesis Imperfecta: A Systematic Review Of Mental Health, Julia M Morales, Camille F Villar, Beatriz Varman, Gianna M Colombo, Danqi Li, Sarah J Sadek, Marie-Eve Robinson, Chaya N Murali, Kara Ayers, Jocelyn Gomez, Brendan Lee, V Reid Sutton, Eric A Storch, Andrew D Wiese

Library Staff Publications

To evaluate the prevalence of psychiatric signs and symptoms and describe psychotherapeutic and psychopharmacological interventions among children with osteogenesis imperfecta (OI). PRISMA guidelines were followed, and the study was registered in PROSPERO (CRD42024588284). Studies (n = 1419) were identified across five databases. Eligible studies, identified by independent reviewers, included peer-reviewed research on psychiatric comorbidities or interventions in children with OI. Data extraction included study design, population characteristics, mental health outcomes, and treatment effectiveness, with all studies assessed for quality and bias. Findings were synthesized to evaluate the prevalence of psychiatric comorbidities and intervention effectiveness. Five articles met inclusion criteria after …

Implementing An Ehr Handoff Tool To Improve Care Transitions For Patients Requiring Inpatient Dialysis, Jolly Mathews

Doctor of Nursing Practice Final Project Abstract

Purpose

The Quality Improvement (QI) project aimed to implement an electronic health record (EHR)-based SMART phrase handoff tool to improve patient safety outcomes, such as reducing Clinical Emergency Response Team (CERT) activations by 20% during dialysis treatments, minimizing treatment delays, and decreasing communication errors during care transitions. 

Background

The lack of a standardized handoff process led to adverse patient events and prolonged hospital stay. Joint Commission identifies communication failures as a leading cause of sentinel events and recommends using structured handoff tools.

Methodology

The project was implemented at a dialysis unit at Texas Medical Center, Houston. A SBAR (Situation, Background, …

Retrospective Review Of Metastatic Hormone Receptor-Positive Inflammatory Breast Cancer Patients Reveals Poor Responses To Cyclin Dependent Kinase 4/6 Inhibition, Azadeh Nasrazadani, Rebecca S Tidwell, Megumi Kai, Bora Lim, Vicente Valero, Debu Tripathy, Sadia Saleem, Bisrat G Debeb, Anthony Lucci, Wendy A Woodward, Rachel M Layman

Faculty, Staff and Student Publications

Background: Patients with inflammatory breast cancer (IBC) have aggressive biology and relatively inferior responses to standard-of-care (SOC) therapies. Understanding the efficacy of SOC therapies in IBC is critical to optimize outcomes. Our objective was to assess the progression-free survival (PFS) of metastatic hormone receptor-positive HER2-negative/low (HR+HER2-) IBC patients treated with CDK4/6 inhibitors (CDKIs) and hormonal therapy (HT).

Methods: Data from 58 IBC patients with metastatic HR + /HER2- IBC from a single institution were reviewed. The medians (95% confidence intervals) of overall survival (OS), PFS, and time on treatment (ToT) from the time of CDKI initiation were reported via the …

Seed Amplification Of Msa Alpha-Synuclein Aggregates Preserves The Biological And Structural Properties Of Brain-Derived Aggregates, Fei Wang, Victor Banerjee, Carla Barria, Santiago Ramirez, Tyler Allison, Damian Gorski, Haley Evans, Quynh Nguyen, Danielle Harrison, Rabab Al-Lahham, Nicole De Gregorio Carbonell, Michelle Pinho, Sanne Kaalund, Jonas Folke, Susana Aznar, Luis Concha-Marambio, Mohd Ishtikhar, Venkata Kps Mallampalli, Sandra Pritzkow, Mohammad Shahnawaz, Matthew L Baker, Irina Serysheva, Claudio Soto

Faculty, Staff and Student Publications

Parkinson's disease (PD), Dementia with Lewy bodies (DLB), and multiple system atrophy (MSA), are characterized by the misfolding and aggregation of alpha-synuclein (αSyn). Compelling evidence showed that αSyn aggregates exist as distinct conformational strains in different synucleinopathies. Recently, we reported that the αSyn Seed Amplification Assay (αSyn-SAA) can amplify and distinguish αSyn strains from PD and MSA. In this study, we investigate whether MSA-seeded, SAA-amplified αSyn fibrils retain the biological and structural properties of the αSyn seeds present in MSA brains. We study the biological activities of both brain-derived and SAA-amplified αSyn aggregates using an αSyn "biosensor" cell model and …

Circulating Tumor Dna Refines Risk Stratification Of Neoadjuvant Therapy-Resistant Breast Tumors, Mark Jesus M Magbanua, Nayelis A Manon, Denise M Wolf, Samuel Rivero-Hinojosa, Ziad Ahmed, Rosalyn W Sayaman, Antony Tin, Derrick Renner, Ekaterina Kalashnikova, Lamorna Brown-Swigart, Gillian L Hirst, Christina Yau, Wen Li, Claudine Isaacs, Rebecca A Shatsky, Amy S Clark, Alexandra Zimmer, Amy L Delson, Angel Rodriguez, Minetta C Liu, Paula R Pohlmann, Laura J Esserman, Hope S Rugo, Angela Demichele, Laura Van 'T Veer

Faculty, Staff and Student Publications

Early-stage breast cancers resistant to neoadjuvant therapy (NAT), characterized by high residual cancer burden (RCB) after treatment, have an increased risk of metastatic recurrence. Here, we show that circulating tumor DNA (ctDNA) detected using a tumor-informed test (1) can improve risk stratification of patients with NAT-resistant tumors (RCB-II/RCB-III) and (2) predict response to NAT. Stratification using ctDNA status at pretreatment or post-NAT and ctDNA dynamics identified NAT-resistant tumors with a significantly decreased risk of metastatic recurrence. ctDNA clearance as early as week 3 across receptor subtypes predicted favorable responses to NAT, including immunotherapies. Interestingly, less than a fifth of patients …

Single Cell Spatial Profiling Of The Matrisome Identifies Region-Specific Adhesion And Signaling Networks In Glioblastoma, Arpan De, Santiago A Forero, Ali Pirani, John E Morales, Marisol De La Fuente-Granada, Sumod Sebastian, Jason T Huse, Leomar Y Ballester, Jeffrey S Weinberg, Frederick F Lang, Kadir C Akdemir, Joseph H Mccarty

Faculty, Staff and Student Publications

The human brain contains a milieu of extracellular matrix (ECM) components that promote normal development and physiology. ECM signaling pathways are often dysregulated in brain pathologies including the malignant cancer glioblastoma (GBM). Here, we used single-cell spatial transcriptomic platforms to map the expression of nearly 400 ECM genes in matching non-cancerous brain and GBM samples. At least four different GBM cell populations have been identified that show unique ECM expression profiles and spatial enrichment in distinct intratumor regions. Spatial mapping demonstrates largely non-overlapping expression signatures of ECM components in GBM stromal cell types, particularly in vascular endothelial cells and microglia/macrophages. …

To Jump Or Not To Jump: Comparing Effects Of Phenotypic Plasticity On The Visual Responses And Escape Behavior Of Locusts And Grasshoppers, Soumi Mitra, Saina Namazifard, David Mario Bellini, Alexis Leigh Sarne, Bidisha Halder, Margaret Ruth Eisenbrandt, Aliya Macknojia, Jiayi Luo, Samme Xie, Hojun Song, Chenghang Zong, Fabrizio Gabbiani, Richard Burkett Dewell

Faculty, Staff and Students Publications

Locusts exhibit remarkable phenotypic plasticity changing their appearance and behavior from solitary to gregarious when population density increases. These changes include morphological differences in the size and shape of brain regions, but little is known about plasticity within individual neurons and alterations in behavior not directly related to aggregation or swarming. We investigated looming escape behavior and the properties of a well-studied collision-detection neuron in gregarious and solitarious animals of three closely related species, the desert locust (Schistocerca gregaria), the Central American locust (S. piceifrons) and the American bird grasshopper (S. americana). For this neuron, the lobula giant movement detector …

Implementing The Nyu Electronic Patient Visit Assessment (Epva), Janet H Van Cleave, Abraham A Brody, Dena Schulman-Green, Kenneth S Hu, Zujun Li, Stephen B Johnson, Vincent J Major, Christopher E Lominska, Jessica R Bauman, Alexander N Hanania, Ghia V Tatlonghari, Marcely Tsikis, Brian L Egleston

Faculty, Staff and Students Publications

Background: Aggressive treatment with multimodal therapies such as surgery, chemotherapy, and radiation therapy has improved survival in head and neck cancer (HNC) but at a human cost of a substantial symptom burden and impact on quality of life. We developed the NYU Electronic Patient Visit Assessment (ePVA)© for HNC as a digital patient-reported symptom monitoring system that enables early symptom detection and real-time interventions at the point of care. With this study protocol, we aim to test the effectiveness of the ePVA in improving HNC outcomes in real-world settings and to identify implementation strategies optimizing its effectiveness.

Methods: We will …

Tgfbr2 Coordinates The Endometrial Response To Estrogen, Regulating Endometrial Hyperplasia And Fertility, Sydney E Parks, Suni Tang, Anna Catherine Unser, Ananya L Bhonsley, Eunbi M Chung, Peixin Jiang, Audrey Savolainen, Vanessa J Joseph, Dominique I Cope, Ramya P Masand, Renata Prunskaite-Hyyryläinen, Diana Monsivais

Faculty, Staff and Students Publications

Proper endometrial function is critical for establishing and maintaining healthy pregnancies, as well as preventing the pathogenesis of conditions such as endometrial hyperplasia and endometrial cancer. The TGFβ signaling pathway regulates key aspects of endometrial biology, although the direct effects of many individual receptors remain unstudied. In this study, we characterize the role of TGFβR2 within the endometrium using a progesterone receptor-cre conditional knock-out mouse model (Tgfbr2flox/flox;Pgrcre/+; “Tgfbr2 cKO”). We found that conditional deletion of TGFβR2 resulted in female infertility, endometrial hyperplasia, altered estrogen and progesterone response, and, only in bred females, reproductive tract …

International Consensus Guidelines For The Conduct And Reporting Of Car T-Cell Clinical Trials In Aml, Swati Naik, Richard Aplenc, Susanne H C Baumeister, Marco Becilli, Anand S Bhagwat, Challice L Bonifant, Lihua E Budde, Christopher D Chien, Kevin J Curran, Anthony F Daniyan, Alexandra Dreyzin, Rebecca A Gardner, Sara Ghorashian, Stephen Gottschalk, Laquisa C Hill, M Eric Kohler, Adam Lamble, Franco Locatelli, Maksim Mamonkin, Bilal Omer, Jae H Park, Concetta Quintarelli, Benedetta Rambaldi, Rebecca M Richards, David A Sallman, Tim Sauer, Nirali N Shah, Marion Subklewe, Corinne Summers, Sarah K Tasian, Naomi Taylor, Sarah Tettamanti, Michael R Verneris, M Paulina Velasquez, Saar I Gill

Faculty, Staff and Students Publications

Early clinical experience with the use of chimeric antigen receptor (CAR) T-cell therapies for patients with acute myeloid leukemia (AML) has been beset by high rates of toxicities and low rates of response. We convened an international workshop with the goal of bringing investigators in the field of AML-directed CAR T-cell therapy together to facilitate discussion of challenges and to brainstorm potential solutions. Based on discussions at the workshop, it was evident that (1) treating and targeting AML with CAR T cells is associated with unique clinical challenges, and (2) variability in clinical trial design, definitions of toxicities, correlative data …

Rare Epigenetic Alterations Are Conserved Across Hematopoietic Differentiation Stages After Mycobacterial Infection, Brandon T Tran, Pamela N Luna, Ruoqiong Cao, Duy T Le, Apoorva Thatavarty, Laure Maneix, Bailee N Kain, Scott Koh, Andre Catic, Katherine Y King

Faculty, Staff and Students Publications

Infection leads to durable cell-autonomous changes in hematopoietic stem and progenitor cells (HSPCs), resulting in production of innate immune cells with heightened immunity. The mechanisms underlying this phenomenon, termed central trained immunity, remain poorly understood. We hypothesized that infection induces histone modifications leading to changes in chromatin accessibility that are conserved during differentiation from HSPCs to myeloid progenitors and monocytes. We conducted genome-wide surveillance of histone marks H3K27ac and H3K4me3 and chromatin accessibility in hematopoietic stem cells, multipotent progenitor 3, granulocyte-monocyte progenitors, monocytes and macrophages of naïve and Mycobacterium avium infected mice. Interferon signaling pathways and related transcription factor binding …

Exploring Mediated Psychosocial Effects On Dating Violence Perpetration And Victimization In The Me & You Building Healthy Relationships Program For Middle School Students, Mike Henson-Garcia, Elizabeth R Baumler, Christine M Markham, Robert C Addy, Ross Shegog, Belinda Hernandez, Paula Cuccaro, Jeffery Temple, Susan Tortolero Emery, Melissa F Peskin

Faculty, Staff and Student Publications

Teen dating violence (TDV) is a prevalent and injurious public health threat affecting adolescent populations across the globe. In response, a plethora of interventions have been developed and implemented with various effects emerging from evaluation studies of these prevention initiatives. The purpose of this study was to investigate whether attitudes toward sexting, gender-based norms toward violence, and constructive conflict resolution skills mediate the main effects of a TDV intervention. Specifically, this study leverages data from the original efficacy trial of the

Imaging Reactive Oxygen Species With L-012 Reveals Neutrophil Extracellular Trap Formation In Pancreatic Ductal Adenocarcinoma, Angisha Basnet, Kaitlyn M Landreth, Michael Sestito, Kristen Ranson, Seth T Gammon, David Piwnica-Worms, Brian A Boone, Tracy W Liu

Faculty, Staff and Student Publications

Neutrophils, key effector cells of the innate immune system, combat pathogens through mechanisms including the production of reactive oxygen species (ROS) and the release of neutrophil extracellular traps (NETs). While these responses are critical for host defense, prolonged elevation of ROS and dysregulated NETosis mediated by neutrophils have been implicated in autoimmune diseases, chronic inflammation, and cancer. In pancreatic ductal adenocarcinoma (PDAC), a highly aggressive and inflammatory malignancy, an increase in neutrophils infiltrating the tumor microenvironment promotes cancer progression and metastasis through increased ROS production and NET release. Using bioluminescence imaging with the reporter L-012 and NET assays, we assessed …

Precise Diagnosis Of Small Invasive Pulmonary Nodules Driven By Single-Cell Immune Signatures In Peripheral Blood, Yang Xia, Yin Zhu, Sai Zhang, Mo Zhou, Jiaqi Zhou, Guanxin Xu, Baiqin Zhao, Guofei Zhang, Qiyuan Wang, Bin Wang, Zexin Chen, Hongyu Shi, Xiuning Le, Tony Mok, Wei Chen, Junqiang Fan, Weiwei Yin, Wen Li

Faculty, Staff and Student Publications

Early detection of lung cancer is crucial for improving patient outcomes. However, accurately diagnosing invasive pulmonary nodules and predicting tumor invasiveness remain major clinical challenges. Given the established role of immune dysfunction in cancer development, we hypothesize that peripheral immune profiling could provide a strategy for managing pulmonary nodules. In this multi-center, prospective study, we combine peripheral immune profiling via mass cytometry with machine learning algorithms to develop an integrated pulmonary nodule management platform. This platform accurately distinguishes invasive from non-invasive pulmonary nodules (AUC = 0.952), outperforming established clinical and radiomics-based models. Furthermore, it effectively predicts tumor invasiveness, differentiating minimally …

Comprehensive Cmr Evaluation Including 4d Flow-Derived E/A Vorticity Ratio In Overweight Adults With And Without Type 2 Diabetes Mellitus, Sungho Park, Erin K Englund, Takashi Fujiwara, Daniel Enge, Michal Schäfer, Jochen Gerstner Saucedo, Ethan W Clark, Layla A Abushamat, Rebecca L Scalzo, Brian Fonseca, Kendall S Hunter, Mary D Sammel, Judith G Regensteiner, Jane E B Reusch, Alex J Barker

Faculty, Staff and Students Publications

Aims: This study aimed to assess the impacts of overweight and type 2 diabetes (T2D) on early hemodynamic and left ventricular (LV) changes using comprehensive cardiovascular magnetic resonance imaging (CMR) in three age- and sex-similar groups: lean individuals (LI group), BMI-similar overweight controls without T2D (CWO group) and overweight individuals with uncomplicated T2D (T2D group).

Methods: Middle-aged participants included 13 in the LI group, 37 in the CWO group, and 28 in the T2D group. Baseline assessments included cardiac and vascular function measured by CMR, thoracic echocardiography, insulin sensitivity, clinical measures, and cardiorespiratory fitness. 4D flow CMR was used to …

Improving Breastfeeding Confidence And Initiation Rates Through Flyer-Based Education In A Labor And Delivery Setting, Janet Rebollar-Trejo

Doctor of Nursing Practice Final Project Abstract

PURPOSE

This quality improvement project aimed to increase breastfeeding initiation within one hour of birth among eligible mothers and improve maternal confidence during the first feed.

BACKGROUND

Breastfeeding provides significant benefits for infants and mothers; however, many mothers receive limited education prior to delivery, contributing to low initiation rates. Early labor breastfeeding education has been shown to improve knowledge, confidence, and initiation outcomes.

METHODOLOGY

A pre-post quality improvement design using the Plan-Do-Study-Act framework was implemented in a Level IV maternal care unit. The intervention included a standardized breastfeeding education flyer with graphics and a QR code video provided during early …

Early Peripheral Blood Gene Expression Predicts 90-Day Outcomes Following Subarachnoid Hemorrhage, Bodie Knepp, Garreck H Lenz, Frank R Sharp, Fernando Rodriguez, Huimahn Alex Choi, Aaron M Gusdon, Glen Jickling, Lara L Zimmermann, Ryan Martin, Jeffrey Vitt, Ben Waldau, Brandon J Cord, Alan Yee, Kwan Ng, Nerissa U Ko, Heather Hull, Bradley P Ander, Boryana Stamova

Faculty, Staff and Student Publications

BACKGROUND: Previous clinical, radiological and machine learning studies have predicted 90-day outcomes following subarachnoid hemorrhage (SAH). The present study was designed to determine whether early changes in mRNA expression of immune, clotting and other genes expressed in peripheral blood can predict patient outcomes at 90 days after SAH and possibly provide insights into the molecular factors that promote good versus poor outcomes.

METHODS: Peripheral blood was drawn after SAH and from vascular risk factor controls (VRFC) and RNAseq performed to measure mRNA expression. A mixed effects regression model identified potential predictors and machine learning algorithms derived the best predictors of …

Bayesian Learning To Reduce Cardiac Risk Of Patients With Locally Advanced Non-Small Cell Lung Cancer Based On Personalized Radiation Therapy Prescription, Ruitao Lin, Mei Chen, Xiaodong Zhang, Tianlin Xu, Ting Xu, Rachel C Maguire, Kelsey L Corrigan, Efstratios Koutroumpakis, Joe Y Chang, Steven H Lin, Aileen B Chen, Quynh-Nhu Nguyen, Saumil J Gandhi, Matthew S Ning, Julianna Bronk, Stephen Chun, Ali Ajdari, Joshua S Niedzielski, Jinzhong Yang, Xinru Chen, Tinsu Pan, Qing H Meng, Anne S Tsao, Anita Deswal, Radhe Mohan, Zhongxing Liao

Faculty, Staff and Student Publications

Purpose: Radiation-induced heart damage is a significant concern in the treatment of non-small cell lung cancer (NSCLC) that can have debilitating or life-threatening consequences. Current strategies focus on minimizing heart exposure, but individual susceptibility varies. Existing evidence also suggests that a uniform "one-size-fits-all" dosimetric constraint for the heart may not be optimal for all patients.

Methods and materials: We developed a prospective study using Bayesian continuous learning and adaptation to develop a framework for personalized adaptive radiation treatment (PART) to reduce cardiovascular adverse events among patients with locally advanced NSCLC. The trial includes a Bayesian personalized risk prediction model to …

Health-Related Quality Of Life In The Era Of Immune Checkpoint Blockade: What Do Patient-Reported Outcomes Reveal?, Alexandra M Dunker, Neha Malik, Kathryn J Krause, Emily Z Keung, Jason B Liu, Elise F Nassif Haddad, Neeta Somaiah, Heather G Lyu, Christina L Roland

Faculty, Staff and Student Publications

Background: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment by providing durable survival gains, but understanding their effects on patient health-related quality of life (HRQL) is critical.

Methods: We performed a narrative review of cross-sectional surveys, early-phase trials, and large-scale phase II and III randomized controlled clinical trials assessing FDA-approved ICIs, including programmed cell death protein 1 (PD-1) inhibitors, programmed death ligand 1 (PD-L1) inhibitors, and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) inhibitors, with emphasis on patient-reported HRQL. Validated HRQL instruments were summarized, and for pivotal trials, the positioning of HRQL outcomes as primary, secondary, or exploratory endpoints was taken …

Proteome-Wide Association Study Of Prostate Cancer Risk Across Populations, Hua Zhong, Jingjing Zhu, Shuai Liu, Chong Wu, Liang Wang, Seamus P Whelton, Catherine H Marshall, Michael J Blaha, Peter Durda, Xiuqing Guo, Craig W Johnson, Henry J Lin, Kent D Taylor, Russell P Tracy, Ronit I Yarden, Ani W Manichaikul, Stephen S Rich, Jerome I Rotter, Rajat Deo, Ruth F Dubin, Peter Ganz, Lang Wu

Faculty, Staff and Student Publications

There is insufficient understanding of the molecular basis of prostate cancer (PCa) across different populations. We perform a large-scale proteome-wide association study (PWAS) to identify proteins with genetically regulated expression in plasma to be associated with PCa risk across populations. We develop genetic prediction models for expression of 1578, 1993, 1218, and 1390 proteins for African (n = 450), European (n = 758), Asian (n = 289), and Hispanic/Latino (n = 474) males, respectively, and evaluate associations of genetically regulated protein expression with PCa risk in 19,391 PCa cases and 61,608 controls of African population, 122,188 cases and 604,640 controls …

Actin Dysregulation Induces Neuroendocrine Plasticity And Immune Evasion: A Vulnerability Of Small Cell Lung Cancer, Yoojeong Seo, Shengzhe Zhang, Jinho Jang, Kyung-Pil Ko, Kee-Beom Kim, Yuanjian Huang, Dong-Wook Kim, Bongjun Kim, Gengyi Zou, Jie Zhang, Sohee Jun, Wonhong Chu, Nicole A Kirk, Ye Eun Hwang, Young Ho Ban, Shilpa S Dhar, Joseph M Chan, Min Gyu Lee, Charles M Rudin, Kwon-Sik Park, Jae-Il Park

Faculty, Staff and Student Publications

Small cell lung cancer (SCLC) is an aggressive malignancy with limited therapeutic options. Capping protein inhibiting regulator of actin dynamics (CRACD) that promotes actin polymerization, is frequently inactivated in SCLC. However, the role of CRACD loss in SCLC is unknown. Here we show that CRACD depletion drives neuroendocrine (NE) cell plasticity and immune evasion in SCLC. Mechanistically, CRACD inactivation disrupts actin organization, leading to suppression of Yap1-NOTCH signaling and subsequent NE gene upregulation. Simultaneously, CRACD loss drives EZH2-mediated histone methylation via nuclear actin disruption, leading to repression of MHC-I genes and depletion of CD8⁺ T cells. Consequently, CRACD-downregulated tumors exhibit …

Sex Hormones Influence Ormdl3 Expression: Implications For Sex-Associated Asthma Phenotype, Elisabetta Granato, Ida Cerqua, Antonietta Rossi, Maria Antonietta Riemma, Maria Chiara Monti, Giusy Ferraro, Barbara Romano, Maria Francesca Nanì, Danilo D'Avino, Martina Simonelli, Joshua Malo, Francesca Polverino, Bruno D'Agostino, Giuseppe Cirino, Fiorentina Roviezzo

Faculty, Staff and Students Publications

Background: Genetic polymorphisms in sphingolipid metabolism, particularly involving the orosomucoid-like 3 (ORMDL3) gene, have been associated with asthma risk. Notably, asthma prevalence and severity exhibit pronounced sex differences, emerging in childhood and persisting into adulthood. However, the molecular mechanisms underlying this sexual dimorphism remain incompletely elucidated.

Objective: We investigated whether ORMDL3 contributes to sex differences in airway function and asthma-like features.

Methods: ORMDL3 expression was measured in lung tissues from healthy male and female human donors and in human bronchial epithelial cells (BEAS-2B) after exposure to 17β-estradiol (E2), Dermatophagoides pteronyssinus 1 (Der p 1), or both. A murine preparation of …

Limits On Wimp Dark Matter With Nai(Tl) Crystals In Three Years Of Cosine-100 Data, G H Yu, N Carlin, J Y Cho, J J Choi, S Choi, A C Ezeribe, L E França, C Ha, I S Hahn, S J Hollick, E J Jeon, H W Joo, W G Kang, M Kauer, B H Kim, H J Kim, J Kim, K W Kim, S H Kim, S K Kim, W K Kim, Y D Kim, Y H Kim, Y J Ko, D H Lee, E K Lee, H Lee, H S Lee, H Y Lee, I S Lee, J Lee, J Y Lee, M H Lee, S H Lee, S M Lee, Y J Lee, D S Leonard, N T Luan, V H A Machado, B B Manzato, R H Maruyama, R J Neal, S L Olsen, B J Park, H K Park, H S Park, J C Park, K S Park, S D Park, R L C Pitta, H Prihtiadi, S J Ra, C Rott, K A Shin, D F F S Cavalcante, M K Son, N J C Spooner, L T Truc, L Yang, Cosine-100 Collaboration

Faculty and Staff Publications

We report limits on weakly interacting massive particle (WIMP) dark matter derived from three years of data collected by the COSINE-100 experiment with NaI(Tl) crystals, achieving an improved energy threshold of 0.7 keV. This lowered threshold enhances sensitivity in the sub-GeV mass range, extending the reach for direct detection of low-mass dark matter. Although no excess of WIMP-like events was observed, the increased sensitivity enabled a model-insensitive comparison between the expected WIMP signal rate-based on mass limits from our data-and DAMA's reported modulation amplitude. Our findings strongly disfavor the DAMA signal as originating from WIMP interactions, fully excluding DAMA/LIBRA 3σ …

Timely Transfusions In Trauma: Instituting A Transfusion Guideline For Trauma Nurses, Lauren Standiford

Doctor of Nursing Practice Final Project Abstract

PURPOSE This project aims to reduce delays in the blood transfusion process in three non-monitored trauma units at a large academic Level I Trauma Center by decreasing the mean "RN transfusion process times" (RN-TPT) by 20 minutes. The project focuses on optimizing transfusion rates, nursing practices, and electronic documentation integration to enhance transfusion timeliness and improve overall patient care.

BACKGROUND Delays in the blood transfusion process can negatively affect patient outcomes and increase healthcare costs. In three non-monitored trauma units at a Level I Trauma Center, inefficiencies in transfusion rates, nursing practices, and electronic documentation were identified. Barriers included concerns …

Racial And Ethnic Disparities In Neoadjuvant Chemotherapy Patterns And Outcomes In Early-Stage Her2-Positive Breast Cancer, Inimfon Jackson, Xiudong Lei, Hui Zhao, Rashmi Murthy, Sharon H Giordano, Mariana Chavez-Macgregor

Faculty, Staff and Student Publications

We examined neoadjuvant chemotherapy (NACT) use, pathological complete response (pCR) and the association with overall survival (OS) among patients with early-stage HER2-positive breast cancer (BC). Patients ≥18 years with stage I-III HER2-positive BC from 2010-2022 who had surgery and chemotherapy were identified. Of 195,023 patients treated with chemotherapy, 37.7% received NACT. NACT use increased from 18.6% in 2010 to 63.4% in 2022 (p <  0.001) and pCR rates rose from 21% to 47.6% (p <  0.001). Black patients were less likely to receive NACT (aOR = 0.96;95%CI 0.93-0.99) or achieve pCR (aOR = 0.86;95%CI 0.82-0.90) than White patients. pCR was associated with a reduction in the risk of death (aHR = 0.45;95%CI 0.42-0.48). 3-year OS increased from 91% in 2010 to 95% in 2019 for patients without a pCR (p <  0.001), and from 97% to 99% for patients with pCR (p = 0.002). Further research is needed to understand and address racial and ethnic disparities in treatment access and outcomes.

Fgf13 Regulates Vgsc-Independent Cardiomyocyte Impulse Propagation Via Cx43 Trafficking, Lala Tanmoy Das, Mattia Malvezzi, Aravind R Gade, Maiko Matsui, Margaret Mckay, Eric Q Wei, Matea J Zelich, Keon Mazdisnian, Jared Kushner, Bi-Xing Chen, Isabella Distefano, Daniel Roybal, Lin Yang, Lisa Stoll, James C Lo, Marian Kalocsay, Fadi G Akar, Steven O Marx, Geoffrey S Pitt

Faculty, Staff and Student Publications

Background: FHF (fibroblast growth factor homologous factor) variants associate with arrhythmias. Although FHFs are best characterized as regulators of voltage-gated sodium channel (VGSC) gating, recent studies suggest broader, non-VGSC-related functions, including regulation of Cx43 (connexin 43) gap junctions and hemichannels, mechanisms that have generally been understudied or disregarded.

Methods: We assessed cardiac conduction and cardiomyocyte action potentials in mice with constitutive cardiac-specific Fgf13 ablation (cFgf13KO) while targeting Cx43 gap junctions and hemichannels pharmacologically. We characterized FGF13 regulation of Cx43 abundance and subcellular distribution. With proximity labeling proteomics, we investigated novel candidate mechanisms underlying FGF13 regulation of Cx43. …

Yap-Induced Glycolysis Drives Fibroinflammation And Disrupts Fibroblast Fidelity, Chang-Ru Tsai, Lin Liu, Yi Zhao, Jong H Kim, Paulo Czarnewski, Rich Gang Li, Fansen Meng, Mingjie Zheng, Jeffrey Steimle, Xiaolei Zhao, Francisco Grisanti, Zheng Sun, Jun Wang, Md Abul Hassan Samee, Xiao Li, James F Martin

Faculty, Staff and Students Publications

Background: Separation of the pulmonic and systemic circulation is essential for terrestrial life, and mammals have evolved distinct cardiac chambers with specialized structures and functions. Transcriptomics profiling revealed cellular heterogeneity between heart chambers. However, the mechanisms underlying chamber-specific transcriptomic and metabolic differences-and their functional significance-remain poorly understood. The Hippo/YAP (yes-associated protein) pathway is a conserved signaling network that regulates diverse cellular processes. The Hippo kinases inhibit YAP in cardiac fibroblasts (CF) to restrict fibrosis and inflammation. Nonetheless, how YAP regulates the metabolic microenvironment during homeostasis and fibroinflammation remains unclear.

Methods: We investigated YAP and glycolysis activity in the 4 cardiac …