Digital Commons Network^™

A Multimodal Non-Invasive Approach For Intracranial Pressure Assessment: A Single-Center Study, Dana Klavansky, Helaina Lehrer, Aris Desai, Gabriela Keeton, Neha Dangayach, Alexandra Reynolds, Spyridoula Tsetsou

Faculty, Staff and Students Publications

Background: Intracranial pressure (ICP) monitoring is an integral part of acute brain injury management. While invasive ICP monitoring is the gold standard, there are several medical conditions that preclude its placement. The aim of the present study is to validate a multimodal approach for increasing ICP detection.

Material and methods: In this retrospective study, patients with acute brain injury who had an external ventricular drain (EVD) placement were included. We measured bilateral optic nerve sheath diameter (ONSD) and assessed for optic nerve disk elevation (ONDE) by using ocular ultrasound, bilateral middle cerebral artery pulsatility index (PI) by using transcranial Doppler, …

Exploration Of Zileuton Protective Mechanisms Against Vancomycin-Associated Nephrotoxicity, Cole S Hudson, James E Smith, Rongjin Sun, Linh T Vuong, Luan D Truong, David Sheikh-Hamad, Masayuki Nigo, Ming Hu, Vincent H Tam

Faculty, Staff and Students Publications

Vancomycin is one of the most commonly used parenteral antibiotics for treating drug-resistant bacterial infections, however, it is hindered by nephrotoxicity. We previously demonstrated that zileuton could delay the onset of vancomycin-associated nephrotoxicity in rats. Here, we sought to understand the mechanism(s) of zileuton renal protection. Sprague-Dawley rats were administered vancomycin (200 mg/kg) and zileuton (1 and 4 mg/kg) daily for 10 days. After 3 days, kidneys were collected from select animals for histopathological analysis of renal injury. Single-dose vancomycin serum pharmacokinetics and renal tissue spatial distribution with adjuvant zileuton were evaluated. In vitro, proximal tubular cells were exposed …

Sleep-Disordered Breathing Subtypes And Future Diet Quality In The Multi-Ethnic Study Of Atherosclerosis, Kaitlin S Potts, Cecilia Castro-Diehl, Tianyi Huang, Alexis C Wood, Jerome I Rotter, Stephen S Rich, Tamar Sofer, Susan Redline, Heming Wang

Children’s Nutrition Research Center Staff Publications

Objectives: Sleep-disordered breathing (SDB) and diet quality impact cardiometabolic disease, but few studies have examined if SDB influences diet quality. This study estimated the association between SDB subtypes (with and without sleepiness) and future diet quality in the Multi-Ethnic Study of Atherosclerosis.

Methods: Probable SDB was characterized by self-reported physician-diagnosed sleep apnea (PDSA) or habitual snoring and subtyped by presence or absence of sleepiness. A food frequency questionnaire measured diet 1.6 years before, and 7.8 years after SDB assessment. Diet quality was measured with the Alternate Healthy Eating Index-2010 (AHEI). Mean differences in AHEI at follow-up by SDB subtypes were …

A Class Of Benzofuranoindoline-Bearing Heptacyclic Fungal Ripps With Anticancer Activities, Qiuyue Nie, Fanglong Zhao, Xuerong Yu, Mithun C Madhusudhanan, Caleb Chang, Siting Li, Sandipan Roy Chowdhury, Bryce Kille, Andy Xu, Rory Sharkey, Chunxiao Sun, Hongzhi Zeng, Shuai Liu, Dishu Zhou, Xin Yu, Kevin Yang, Sandra A C Figueiredo, Maria Zotova, Zichen Hu, Alan Y Du, Dongyin Guan, Rui Tang, Todd Treangen, Jin Wang, Pedro N Leão, Yang Gao, Junjie Chen, Peng Liu, Hans Renata, Xue Gao

Children’s Nutrition Research Center Staff Publications

Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a promising source of new pharmaceuticals, yet the therapeutic potential of fungal RiPPs remains largely underexplored. Here, we report asperigimycins as a distinct class of fungal RiPPs, featuring a unique heptacyclic scaffold consisting of a benzofuranoindoline core and three additional macrocycles, primarily assembled by six distinct fungi-specific DUF3328 oxidases. Inspired by the enhancement of anticancer activity through the N-terminal pyroglutamate in naturally occurring asperigimycins C and D, we chemically modify the inactive asperigimycin B with a series of lipid substitutions at its N-terminus. A derivative with a C-11 linear fatty …

Middle Meningeal Artery Embolization Of Septated Chronic Subdural Hematomas, Juan Carlos Martinez-Gutierrez, Salvatore A D'Amato, Hussein A Zeineddine, Michael I Nahhas, Matthew J Kole, Hyun Woo Kim, Youngran Kim, Bryden H Dawes, Peng Roc Chen, Spiros L Blackburn, Sunil A Sheth, Gary Spiegel, Ching-Jen Chen, Ashutosh Mahapatra, Ryan S Kitagawa, Mark J Dannenbaum

Faculty, Staff and Student Publications

Introduction

Middle meningeal artery embolization (MMAE) has emerged as a promising new treatment for patients with chronic subdural hematomas (cSDH). Its efficacy, however, upon the subtype with a high rate of recurrence—septated cSDH—remains undetermined.

Methods

From our prospective registry of patients with cSDH treated with MMAE, we classified patients based on the presence or absence of septations. The primary outcome was the rate of recurrence of cSDH. Secondary outcomes included a reduction in cSDH thickness, midline shift, and rate of reoperation.

Results

Among 80 patients with 99 cSDHs, the median age was 68 years (IQR 59–77) with 20% females. Twenty-eight …

Healthcare Professionals’ Awareness Of And Barriers To Shared-Clinical-Decision-Making For Hpv Vaccination Among Adults 27–45 Years, Manali Desai, Shreela V Sharma, Joel Fokom Domgue, Onyema Chido-Amajuoyi, Robert Yu, Wenyaw Chan, Charles Darkoh, Sanjay Shete

Faculty, Staff and Student Publications

The Advisory Committee on Immunization Practices recommends human papillomavirus (HPV) vaccination for inadequately vaccinated adults aged 27–45 based on shared clinical decision-making (SCDM). However, little is known about awareness and barriers to SCDM among US healthcare providers (HCPs), especially in Texas, where HPV vaccination rates are below the national average. Between January and April 2021, we conducted a population-based cross-sectional survey (12% response rate) of HCPs licensed in Texas to assess the prevalence and factors associated with awareness of the SCDM recommendation. HCPs were asked if they were aware and if they foresaw any barriers in implementing SCDM for HPV …

Metabolomic Signatures Of Prediabetes In Mexican Americans: The Role Of Genetics And Macronutrients, Shinhye Chung, Charles Evans, Charles F Burant, Han Chen, Bing Yu, David Aguilar, Eric L Brown, Craig L Hanis, Goo Jun

Faculty, Staff and Student Publications

Prediabetes is one of the main health concerns in public health, and various etiological factors contribute to its onset. This study aimed to evaluate genetic associations and gene‐macronutrient interaction with prediabetes‐related metabolites to understand how genetic variation and dietary intake contribute to dysglycemia. We analyzed a total of 482 self‐identified Mexican American participants recruited from Starr County, Texas in 2018‐2019. Untargeted metabolomic profiling was performed using LC‐MS. Nutrient densities of six macronutrients were derived from a 106‐item food frequency questionnaire. Genetic associations for each metabolite were tested using Generalized linear Mixed Model Association Tests (GMMAT). Gene‐macronutrient interactions on prediabetes‐associated metabolites …

Clinical And Genomic Characterization Of Serratia Bloodstream Infections, Roberta Monardo, Lawrence P Park, Felicia Ruffin, Phillip Cox, An Q Dinh, Rachel E Korn, Parisa Farahani, Marco Ripa, Antonella Castagna, Blake M Hanson, Vance G Fowler, Joshua T Thaden, Stacey A Maskarinec

Faculty, Staff and Student Publications

Background: Previously considered a rare opportunistic pathogen, Serratia is now an emerging cause of bacteremia. We compared the risk factors and outcomes of patients with Serratia bacteremia relative to other Enterobacterales in a cohort of hospitalized patients.

Methods: Patients were prospectively enrolled from 2002-2021 at Duke University. Characteristics and outcomes were compared among bacteremic patients due to Serratia and other Enterobacterales. Regression models were used to determine features associated with outcomes. Whole genome sequencing (WGS) was performed to characterize the phylogenetic diversity of Serratia isolates associated with device infections.

Results: Of 2676 patients, 173 (6.5%) had Serratia bacteremia. Among patients …

A Qualitative Study Of Health Priorities Of People With Dementia And Care Partners In Emergency Department And Hospital Care In A Public Safety-Net Setting, Anita Chary, Sumin Yoon, Victor Lara, Annika Bhananker, Michelle Suh, Kei Ouchi, Maura Kennedy, Aanand D Naik

Faculty, Staff and Student Publications

Background: Over half of the people with dementia visit the emergency department (ED) each year. Little is known about how people with dementia and their care partners conceptualize or communicate about health outcome goals or care preferences during acute care episodes.

Participants and setting: We conducted interviews with 14 Hispanic people with dementia and 19 care partners recruited from a public safety net hospital system in the southeastern United States. Participants were community-dwelling and had recently visited the ED.

Methods: We used a qualitative study design informed by phenomenology and guided by the patient priorities care (PPC) framework. Interviews elicited …

The "Woundosome" Concept And Its Impact On Procedural Outcomes In Patients With Chronic Limb-Threatening Ischemia, Lorenzo Patrone, Edoardo Pasqui, Michael S Conte, Alik Farber, Roberto Ferraresi, Matthew Menard, Joseph L Mills, John Rundback, Peter Schneider, August Ysa, Kumar Abhishek, George L Adams, Naseer Ahmad, Irfan Ahmed, Vlad A Alexandrescu, Max Amor, David Alper, Martin Andrassy, Christopher Attinger, Andy Baadh, Hashem Barakat, Lukla Biasi, Theodosios Bisdas, Zagum Bhatti, Erwin Blessing, Marc P Bonaca, Stefano Bonvini, Michel Bosiers, Andrew W Bradbury, Robert Beasley, Christian-Alexander Behrendt, Marianne Brodmann, Gonzalo Cabral, Roberto Cancellieri, Andrea Casini, Venita Chandra, Emiliano Chisci, Omar Chohan, Edward T C Choke, Patrick F S Chong, Giacomo Clerici, Raphael Coscas, Mary Costantino, Luca Dalla Paola, Sabeen Dand, Robert S M Davies, Mario D'Oria, Athanasios Diamantopoulos, Sebastian Debus, Koen Deloose, Costantino Del Giudice, Gianmarco De Donato, Brian De Rubertis, Jean Paul De Vries, Nuno V Dias, Larry Diaz-Sandoval, Florian Dick, Konstantinos Donas, Anahita Dua, Fabrizio Fanelli, Stefano Fazzini, Mazin Foteh, Roberto Gandini, Mauro Gargiulo, Luca Garriboli, Elizabeth A Genovese, Edward Gifford, Yann Goueffic, Peter Goverde, Prem Chand Gupta, Robert Hinchliffe, Andrew Holden, Kim C Houlind, Dominic Pj Howard, Bella Huasen, Giacomo Isernia, Konstantinos Katsanos, Barry Katzen, Philippe Kolh, Igor Koncar, Grigorios Korosoglou, Prakash Krishnan, Thomas Kroencke, Miltiadis Krokidis, Arun Kumarasamy, Paul Hayes, Osamu Iida, Enrique Alejandre Lafont, Ralf Langhoff, Alexandre Lecis, Mark Lessne, Hady Lichaa, Michael Lichtenberg, Marta Lobato, Alice Lopes, Giorgio Loreni, Pierleone Lucatelli, Sreekumar Madassery, Lieven Maene, Marco Manzi, Martin Maresch, Jay Santhosh Mathews, James Mccaslin, Antonio Micari, Stefano Michelagnoli, Bruno Migliara, Robert Morgan, Luis Morelli, Daniele Morosetti, Nicolas Mouawad, Paul Moxey, Stefan Müller-Hülsbeck, Jihad Mustapha, Tatsuya Nakama, Bahaa Nasr, Zola N'Dandu, Richard Neville, Elias Noory, Joakim Nordanstig, Katariina Noronen, Luis Mariano Palena, Gianbattista Parlani, Ashish S Patel, Parag Patel, Rafiuddin Patel, Sanjay Patel, Costantino Pena, Drazen Perkov, Mark Portou, Giovanni Pratesi, Christos Rammos, Jim Reekers, Vicente Riambau, Trisha Roy, Kenneth Rosenfield, Maria Antonella Ruffino, Fadi Saab, Athanasios Saratzis, Paolo Sbarzaglia, Andrej Schmidt, Eric Secemsky, Michael Siah, Henrik Sillesen, Gioele Simonte, Marc Sirvent, Jill Sommerset, Sabine Steiner, Ahmed Sakr, Dierk Scheinert, Mehdi Shishebor, Stavros Spiliopoulos, Alessio Spinelli, Konstantinos Stravoulakis, Gergana Taneva, Desarom Teso, Joerg Tessarek, Selva Theivacumar, Anish Thomas, Shannon Thomas, Narayan Thulasidasan, Giovanni Torsello, Ramesh Tripathi, Nicola Troisi, Srini Tummala, Venkat Tummala, Christopher Twine, Raman Uberoi, Alessandro Ucci, Domenico Valenti, Jos Van Den Berg, Daniel Van Den Heuvel, Isabelle Van Herzeele, Ramon Varcoe, Melina Vega De Ceniga, Frank J Veith, Maarit Venermo, Badri Vijaynagar, Sanjiv Virdee, Conrad Von Stempel, Michiel T Voûte, Kak Khee Yeung, Thomas Zeller, Hany Zayed, Miguel Montero Baker

Faculty, Staff and Student Publications

No abstract provided.

Context Dependent Regulation Of Dicer Function During Oocyte-To-Embryo Transition, Nick A. Newkirk

Dissertations and Theses (Open Access)

Over two decades ago, Dicer was discovered as the primary enzyme responsible for the generation of small RNAs known as the microRNAs (miRNAs) and short interfering RNAs (siRNAs). Spatiotemporal regulation of Dicer-dependent small-RNA biogenesis affects many aspects of biology, including aging, disease progression, fertility, and cancer. Interestingly, a distinct population of Dicer-dependent small RNAs, known as the endogenous siRNAs (endo-siRNAs), are uniquely abundant in the germ cells and gametes, and are critical for normal fertility. Despite their function regulating new life, the mechanisms controlling their biogenesis and subsequent germ cell functions remain poorly defined. Work to parse these mechanisms in …

Neural Dynamics Supporting Flexible Cognition, Meredith J. Mccarty

Dissertations and Theses (Open Access)

Flexible cognition enables humans to adapt their behavior to changing circumstances by prioritizing relevant information and filtering out distractions. This process is thought to be supported by the integration of ongoing behavioral goals with incoming sensory information, but how this integration is realized in the human brain remains unclear. It is unknown how high-order sensory cortices can balance specialized processing with flexible integration of changing behavioral goals. In the following investigations, we use intracranial EEG (iEEG) recordings in humans to study the neural dynamics of flexible cognition during high-order sensory processing. First, we validated assumptions about the locality of iEEG …

Orthogonal Comparison Of Nuclear And Mitochondrial Clonal Architectures In Hematologic Malignancies, Nehali Shah

Dissertations and Theses (Open Access)

Acute myeloid leukemia (AML) is a hematologic malignancy characterized by accumulation of mutations that disrupt hematopoietic differentiation and promote clonal expansion. Understanding how these mutations arise and evolve is essential for improving diagnosis, prognosis, and treatment stratification. Current methods are limited by either restricted genomic coverage (targeted panels) or low throughput and high cost (in single-cell whole genome sequencing, scWGS). An emerging alternative is the use of mitochondrial DNA (mtDNA) mutations as clonal markers.

This study aims to determine whether mitochondrial-derived clonal architectures correlate with nuclear-derived clonal architectures in AML, thereby evaluating mtDNA as a scalable orthogonal tool for lineage …

Maternal Folic Acid Supplement Use, Folate Intake, And Preterm Birth Among Infants With Spina Bifida, Renata H Benjamin, Katherine L Ludorf, Rachel P Allred, Jenil R Patel, Wendy N Nembhard, Gary M Shaw, Suzan L Carmichael, Tania A Desrosiers, Eirini Nestoridi, Eva M Williford, A J Agopian

Faculty, Staff and Student Publications

Background: We sought to assess the extent to which folic acid supplementation and dietary folate intake are associated with preterm delivery among infants with spina bifida.

Methods: We conducted a retrospective population-based study using the National Birth Defects Prevention Study (NBDPS; 1999-2011) and the Birth Defects Study To Evaluate Pregnancy exposureS (BD-STEPS; 2014-2019). We utilized robust Poisson regression to calculate the risk ratio (RR) and 95% confidence interval (CI) for the associations between preterm birth (< 37 weeks) and maternal use of folic acid-containing supplements, dietary folate intake quartile, and a combined variable accounting for supplementation and dietary folate status.

Results: Among 1199 infants with spina bifida (1011 in NBDPS, 188 in BD-STEPS), 217 (18.1%) were born preterm. There were no statistically significant associations …

Ddt Exposure Induces Microglial Activation And Disease-Associated Microglial Signatures: Relevance To Mechanisms Of Alzheimer’S Disease, Isha Mhatre-Winters, Aseel Eid, Nicole Blum, Yoonhee Han, Ferass M Sammoura, Long-Jun Wu, Jason R Richardson

The Brown Foundation: Institute of Molecular Medicine

Background: Alzheimer's disease (AD) is characterized by the presence of amyloid-β plaques, neurofibrillary tangles, and neuroinflammation. Previously, we reported that serum levels of dichlorodiphenyldichloroethylene (DDE), the primary metabolite of the pesticide dichlorodiphenyltrichloroethane (DDT), were significantly higher in AD patients compared to age-matched controls and that DDT exposure worsened AD pathology in animal models.

Objective: Here, we investigated the effect of DDT on neuroinflammation in primary mouse microglia (PMG) and C57BL/6J mice.

Methods: DDT-induced inflammatory and disease-associated microglial (DAM) gene expression were determined in PMG by qPCR and immunocytochemistry, with and without pretreatment with the sodium channel antagonist tetrodotoxin (TTX). Furthermore, …

Understanding Dental Hygienists’ Knowledge, Attitudes, And Practices Regarding Hpv Vaccination, Paula M Cuccaro, Jihye Choi, Kawtar Zouaidi, Efrat K Gabay, Michael Mackert, Josefine Ortiz Wolfe

Faculty, Staff and Student Publications

The American Dental Association and American Academy of Pediatric Dentistry encourage oral health professionals to strongly recommend human papillomavirus (HPV) vaccination to prevent HPV-associated oropharyngeal cancer. This study examined oral health professionals' knowledge, attitudes, and practices regarding HPV vaccination. We used purposive sampling to recruit participants through state and national oral health societies and social media platforms. Flyers outlining eligibility criteria were distributed, and eligible participants completed an online survey. Primary measures included participants' HPV-related knowledge, attitudes, and practices, and willingness to receive HPV-related training and recommend HPV vaccination to patients, including parents of adolescents. Only responses from dental hygienists …

Combine Ebis: A Novel Collaborative Method For Building Interventions From Existing Evidence-Based Interventions, Justin Knox, Kara Portier, Christopher Magana, Maggie Denning, Christopher M Ferraris, Emily Dove-Medows, Cho-Hee Shrader, Ohemaa Poku, Phil Kreniske, Robert Remien, Efrat Aharonovich, Jennifer C Elliott, Denis Nash, Kathryn Lancaster, Till Baernighausen, Kayo Fujimoto, Adam Carrico, John A Schneider, Alida Bouris, D Scott Batey, Sheree R Schwartz, Jose Bauermeister, Patrick S Sullivan, Joseph G Rosen, Gina Wingood, Milton Wainberg, Deborah Hasin, Elvin Geng, Patrick A Wilson, Stefan D Baral

Faculty, Staff and Student Publications

Purpose: Combining evidence-based interventions (EBIs) is a discrete process from adapting EBIs, and specific guidance for how to combine EBIs could be helpful amidst the proliferation of frameworks that combine and stage EBIs and calls for services to be combined or bundled. To address this gap, we developed and applied the COllaborative Method for Building INterventions from Existing Evidence-Based Interventions (COMBINE-EBIs) approach, a five-step process for combining EBIs.

Methods: The five steps of COMBINE-EBIs are: (1) Identify and Select EBIs, (2) Develop a Shared Conceptual Model, (3) Evaluate the Conceptual Model, (4) Create a Single Combined Protocol, and (5) Refine …

Proteogenomics In Cerebrospinal Fluid And Plasma Reveals New Biological Fingerprint Of Cerebral Small Vessel Disease, Ilana Caro, Daniel Western, Shinichi Namba, Na Sun, Shuji Kawaguchi, Yunye He, Masashi Fujita, Gennady Roshchupkin, Tim D'Aoust, Marie-Gabrielle Duperron, Muralidharan Sargurupremraj, Ami Tsuchida, Masaru Koido, Marziehsadat Ahmadi, Chengran Yang, Jigyasha Timsina, Laura Ibanez, Koichi Matsuda, Yutaka Suzuki, Yoshiya Oda, Akinori Kanai, Pouria Jandaghi, Markus Munter, Daniel Auld, Iana Astafeva, Raquel Puerta, Jerome I Rotter, Bruce M Psaty, Joshua C Bis, W T Longstreth, Thierry Couffinhal, Pablo García-González, Vanesa Pytel, Marta Marquié, Amanda Cano, Mercè Boada, Marc Joliot, Mark Lathrop, Quentin Le Grand, Lenore J Launer, Joanna M Wardlaw, Myriam Heiman, Agustin Ruiz, Paul M Matthews, Sudha Seshadri, Myriam Fornage, Hieab Adams, Aniket Mishra, David-Alexandre Trégouët, Yukinori Okada, Manolis Kellis, Philip L De Jager, Christophe Tzourio, Yoichiro Kamatani, Fumihiko Matsuda, Carlos Cruchaga, Stéphanie Debette

Faculty, Staff and Student Publications

Cerebral small vessel disease (cSVD) is a leading cause of stroke and dementia with no specific treatment, of which molecular mechanisms remain poorly understood. To identify potential biomarkers and therapeutic targets, we applied Mendelian randomization to examine over 2,500 proteins measured in plasma and, uniquely, cerebrospinal fluid, in relation to magnetic resonance imaging (MRI) markers of cSVD in more than 40,000 individuals. Here we show that 49 proteins are associated with MRI markers of cSVD, most prominently in cerebrospinal fluid. We highlight associations that are consistent across platforms and ancestries, and supported by complementary observational analyses, and we explore differences …

Effect Of Material And Processing Lag Time On Radiant Energy Penetration And Modulus Of 3d-Printed Indirect Bonding Jig Materials, Megan Meyer, Kamal Awad, Baylie Subjeck, Joe C Ontiveros, Venu G Varanasi, F Kurtis Kasper

Faculty, Staff and Student Publications

Objective: To investigate the effect of the time between 3D printing and post-print processing (lag time) on the modulus and radiant energy penetration of 3D-printed indirect bonding jig materials.

Materials and methods: Three 3D-printed resins (Formlabs IBT Resin, SprintRay IDB 2, Pro3dure GR-18.1 IB) were tested for three lag times (0, 16 and 64 h; n = 10 per group). Radiant energy penetration was measured using a power meter, and Vickers hardness was assessed for composites cured through the samples. Mechanical properties were evaluated using uniaxial testing and three-point bending.

Results: Both the resin type and lag time significantly affected …

High-Risk Medications In Pediatric Dentistry: Patterns, Outcomes, And Clinical Implications, Yilei Liu, Kawtar Zouaidi, Colin C Hubbard, Muhammad F Walji, Matthew R Cooke, Donald B Rindal, Kristin N Ray, Elsbeth Kalenderian, Katie J Suda

Faculty, Staff and Student Publications

Background: High-risk medications such as opioids and benzodiazepines are frequently prescribed in pediatric dental care, yet their prescribing patterns and associated adverse outcomes remain poorly understood. The aim of this study was to determine the extent of such prescribing to pediatric patients and factors associated with adverse outcomes.

Methods: MarketScan data for patients younger than 18 years with a dental visit from 2014 through 2019 were analyzed. High-risk medications included benzodiazepines, barbiturates, and opioids. Composite outcomes included hospitalization, emergency department visit, or urgent care visit within 7 days after the dental visit. Opioid-attributable outcomes included opioid-related overdose within 7 days …

Does Reducing Videofluoroscopy Frame Rate Affect Dige/St Grades In Modified Barium Swallow Studies?, Shitong Mao, Carla L Warneke, Sheila N Buoy, Ariana J Sahli, Brinda Rao Korivi, Carly E A Barbon, Kristy K Brock, Katherine A Hutcheson

Faculty, Staff and Student Publications

Understanding the effects of reduced frame rates on the reliability of Modified Barium Swallow (MBS) ratings for swallowing safety and efficiency is essential for clinical practice. While previous research has examined frame rate (simulated pulse rates) implications concerning penetration, aspiration, and residue ratings, the impact on summary grading systems like the Dynamic Imaging Grade of Swallowing Toxicity (DIGEST) remains unclear. This study analyzed a total of 315 full MBS videos collected from 278 patients, and 76.25% of patients were diagnosed with head and neck cancer (mean age 62.51 years, SD 8.53; 12.23% female). We performed pairwise comparisons of DIGEST grades …

Tumor Intrinsic Mettl5 Modulates Atf4 Translation To Prevent T Cell-Induced Ferroptosis In Ovarian Cancer, Jiakai Hou, Cheng-Wei Ju, Nicholas A Egan, Yanjun Wei, Yunfei Wang, Minghao Dang, Tianyi Zhou, Leilei Shi, Ningbo Zheng, Si Chen, Ashley M Guerrero, Xiaofang Liang, Wanfu Wu, Areej Akhtar, Chitra Dhiman, Debanwita Roy Burman, Andro E Gerges, Mason D Flores, Han Li, Li-Sheng Zhang, Marleen Kok, Xiaobo Mao, Linghua Wang, Qin Feng, Yiwen Chen, Sanghoon Lee, Daniel J Mcgrail, Nidhi Sahni, Chuan He, Amir A Jazaeri, Weiyi Peng

Faculty, Staff and Student Publications

Poor clinical responses to immune checkpoint blockade (ICB) observed in ovarian cancer (OC) highlight an unmet need to understand the mechanisms driving immune evasion in this disease. To address this, an integrative analysis is conducted by combining in vitro genome‐wide immune screens, in vivo ICB screens, and clinical data mining, and METTL5 is identified as a crucial OC‐intrinsic factor that promotes immune resistance. Immunologically “cold” OC tumors and poor responders to ICB exhibit elevated METTL5 expression. Mechanistically, knocking out (KO) METTL5 in OC disrupts ATF4 translation by altering 18S rRNA m6A levels, leading to the downregulation of SLC7A11 and SLC3A2 …

Perceived Utility Of Genetic Carrier Screening In A Diverse Patient Population, Jack A Colleran, Meagan Choates, Syed Hashmi, Brittanie Shelton, Aranza Gonzalez Cendejas, Angela Haynes Burgess, Blair K Stevens

Faculty, Staff and Student Publications

Current reproductive guidelines call for offering expanded carrier screening (ECS) for genetic conditions. Currently available panels can include screening for carrier status of tens to hundreds of autosomal recessive and/or X-linked conditions. Clinical utility is based on alterations to reproductive decision-making, but study cohorts supporting the utility of ECS largely consist of individuals of European ancestry who are highly educated, of high income, and who often receive preconception counseling. There is a lack of research on the views of patients from diverse backgrounds. Therefore, we aimed to assess and compare perceptions of the utility of ECS and targeted carrier screening …

Kras Inhibition Activates An Actionable Cd24 "Do Not Eat Me" Signal In Pancreatic Cancer, Yongkun Wei, Minghui Liu, Er-Yen Yen, Jun Yao, Zhenzhen Xun, Phuoc T Nguyen, Xiaofei Wang, Zecheng Yang, Abdelrahman Yousef, Dean Pan, Yanqing Jin, Ching-Fei Li, Madelaine S Theardy, Jangho Park, Yiming Cai, Mitsunobu Takeda, Matthew Vasquez, Elizabeth M Park, David H Peng, Yong Zhou, Hong Zhao, Timothy P Heffernan, Andrea Viale, Huamin Wang, Stephanie S Watowich, Han Liang, Dan Zhao, Ronald A Depinho, Wantong Yao, Haoqiang Ying

Faculty, Staff and Student Publications

KRASG12C inhibitors (G12Ci) have produced encouraging, albeit modest and transient, clinical benefit in pancreatic ductal adenocarcinoma (PDAC). Identifying and targeting resistance mechanisms to G12Ci treatment is therefore crucial. To better understand the function of KRASG12C and possible G12Ci bypass mechanisms, we developed an autochthonous KRASG12C-driven PDAC model. Compared to the classical KRASG12D PDAC model, the G12C model exhibits slower tumor growth, yet similar histopathological and molecular features. Aligned with clinical experience, G12Ci treatment of KRASG12C tumors produced modest impact despite stimulating a ‘hot’ tumor immune microenvironment. Immunoprofiling revealed that CD24, a ‘don’t eat me’ signal, is significantly upregulated on cancer …

Clinical Outcomes Of Adult Patients With Newly Diagnosed Mixed Phenotype Acute Leukemia, Hannah Goulart, Farhad Ravandi, Nicholas J Short, Nitin Jain, Naval Daver, Tapan M Kadia, Courtney Dinardo, Gautam Borthakur, Koichi Takahashi, Naveen Pemmaraju, Fadi G Haddad, Guillermo Montalban Bravo, Yesid Alvarado, Ghayas C Issa, Alex Bataller, Sherry Pierce, Sanam Loghavi, Guilin Tang, Sa A Wang, Beenu Thakral, Elizabeth Shpall, Richard Champlin, Issa Khouri, Partow Kebriaei, Guillermo Garcia-Manero, Koji Sasaki, Elias J Jabbour, Jayastu Senapati

Faculty, Staff and Student Publications

Purpose: Mixed phenotype acute leukemia (MPAL) is a rare clinical entity with historically poor outcomes.

Methods: We conducted a retrospective analysis of adults 18 years and older with newly diagnosed B-cell (B/M) or T-cell/myeloid (T/M) MPAL treated at our institution between 2017 and 2024.

Results: We identified 42 patients (median age 70 years); 20 (48%) had B/M MPAL, and 22 (52%) had T/M MPAL; 57% of patients had adverse risk cytogenetics, and 41% had a TP53 mutation. Sixty-two percent of patients were treated with a hybrid regimen, and 45% of patients received intensive therapy. A composite complete remission (CRc; CR …

Mecom Fusion Partner And Bone Marrow Blast Percentage Influence Outcomes Of Patients With Mecom Rearranged Acute Myeloid Leukaemia, Wei-Ying Jen, Guilin Tang, Eitan Kugler, Jennifer Croden, Koji Sasaki, Alexandre Bazinet, Alex Bataller, Guillermo Montalban-Bravo, Gautam Borthakur, Gokce A Toruner, Sanam Loghavi, Nicholas J Short, Ghayas C Issa, Ian M Bouligny, Sherry Pierce, Uday Popat, Naveen Pemmaraju, Elias Jabbour, Guillermo Garcia-Manero, Kapil Bhalla, Farhad Ravandi, Naval G Daver, Courtney D Dinardo, Hagop M Kantarjian, Tapan M Kadia

Faculty, Staff and Student Publications

MECOM rearrangements (MECOM-r) are acute myeloid leukaemia (AML)-defining, regardless of blast percentage or MECOM fusion partner. We sought to investigate if blast percentage or MECOM-r partner was associated with overall survival (OS). We included 152 adult patients with newly diagnosed MECOM-r and classified blast percentage into < 20% or ≥20% and MECOM-r partner into classic (GATA2::MECOM) or variant (others). Thirty-one per cent had < 20% blasts, with 69% having ≥20%; 57% had classic and 43% variant MECOM-r. Treatment was with intensive chemotherapy (IC) in 41% and low-intensity therapy (LIT) in 59%. Composite complete remission rates were similar between IC (50%) and LIT (48%, p = 0.99). The median OS was 17 months (95% confidence interval [CI], 12-not estimable [NE]) for < 20% blasts, compared with 9 months (95% CI, 6-10) for ≥20% blasts (p <  0.01). On multivariate analysis, ≥20% blasts were associated with worse OS (hazard ratio [HR] 1.9, [95% CI, 1.2-3.2], p <  0.01), independent of age, MECOM-r partner, additional cytogenetic abnormalities, treatment intensity, addition of venetoclax and stem cell transplant (SCT). HR for IC was 2.0 (95% CI, 1.1-3.7, p = 0.03). In < 20% blasts, variant MECOM-r was independently associated with a reduced hazard of death (HR 0.2 [95% CI, 0.1-0.8], p <  0.01). MECOM-r AML is a heterogenous entity; consideration should be given to LIT approaches.

Periostin Promotes Sarcoma Growth By Promoting Tumor-Associated Macrophage Migration And Differentiation, Jin-Fen Xiao, Kristin Ishaya, Emily Y Ko, Annaliese Fowler, Marina T Broz, Jlenia Guarnerio

Faculty, Staff and Student Publications

Soft-tissue sarcomas (STS) are characterized by abundant extracellular matrix (ECM) deposition, yet the functional contribution of specific ECM components remains poorly understood. In this study, we identify periostin (POSTN), a matricellular protein, as a regulator of sarcoma progression and the tumor immune microenvironment. Analysis of human sarcoma datasets revealed that high POSTN expression correlates with poor prognosis and elevated expression of ECM-related and myeloid cell–associated genes. In murine genetic models of sarcoma, tumors expressing high levels of Postn displayed enhanced expression of ECM genes and monocyte-recruiting cytokines. Functional silencing of Postnin vivo reduced tumor growth without altering tumor cell …

Impact Of Postpartum Diagnosis On Survival Of Women With Inflammatory Breast Cancer, Jennifer H Chen, Rebecca S Slack Tidwell, Megumi Kai, Anthony Lucci, Wendy A Woodward, Helen M Johnson

Faculty, Staff and Student Publications

Background: Postpartum diagnosis of breast cancer confers increased risk of metastasis and death, possibly because of protumorigenic pathways that occur after weaning. We sought to evaluate the impact of postpartum diagnosis on survival in patients with inflammatory breast cancer (IBC).

Methods: We performed a retrospective analysis of patients with nonmetastatic IBC enrolled in a prospective registry (2007-2023). Kruskal-Wallis, χ2, and Fisher exact tests were used to compare between postpartum groups. The Kaplan-Meier method and log-rank tests were used for survival estimates.

Results: Among 320 patients with IBC, 25 (7.8%) were nulliparous, 31 (9.7%) were 0 to 5 years postpartum, 26 …

Individualizing Nsaid Therapy In Axial Spondyloarthritis: N-Of-1 Trials With Bayesian Analysis, Mark C Hwang, Seokhun Kim, Shervin Assassi, Reyna Chavez, Joyce Samuel, Charles Green, Jon Tyson, John Reveille

Faculty, Staff and Student Publications

Objective: Axial spondyloarthritis (axSpA) is a chronic inflammatory disease predominantly affecting the spine and sacroiliac joints. NSAIDs are first-line therapy, but individual responses vary widely. We evaluated the efficacy and patient preference of three NSAIDs (celecoxib, meloxicam and naproxen) through Bayesian N-of-1 clinical trials to optimize axSpA management.

Methods: We conducted N-of-1 trials with 42 patients meeting ASAS criteria for axSpA. Each patient was asked to complete two cycles of randomized double-blind crossover comparisons of the three NSAIDs, each for 4 weeks. The primary end point was the change in the Ankylosing Spondylitis Disease Activity Score (ASDAS). Bayesian analysis assessed …

Personalized Risk Prediction For Cancer Survivors: A Generalized Bayesian Semi-Parametric Model Of Recurrent Events With Competing Outcomes, Nam Hoai Nguyen, Seung Jun Shin, Elissa Dodd-Eaton, Jing Ning, Wenyi Wang

Faculty, Staff and Student Publications

Multiple primary cancers are increasingly more frequent due to improved survival of cancer patients. Characteristics of the first primary cancer largely impact the risk of developing subsequent primary cancers. Hence, model-based risk characterization of cancer survivors that captures patient-specific variables is needed for healthcare policy making. We propose a Bayesian semi-parametric framework, where the occurrence processes of the competing cancer types follow independent non-homogeneous Poisson processes and adjust for covariates including the type and age at diagnosis of the first primary. Applying this framework to a historically collected cohort with families presenting a highly enriched history of multiple primary tumors …