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Multiple Event Segmentation Mechanisms In The Human Brain, Tan T Nguyen, Joset A Etzel, Matthew A Bezdek, Jeffrey M Zacks

2020-Current year OA Pubs

The human brain segments continuous experience into discrete events, with theoretical accounts proposing two distinct mechanisms: creating boundaries at points of high

Feasibility Evaluation Of Tumor Treating Fields For Brainstem Gliomas, Anthony Chen, Ryan Shah, William Shi, Noa Urman, Nadav Shapira, Nicholas Avgeropoulos, Patrick Conlon, Neil Mookerjee, Wenyin Shi

Department of Radiation Oncology Faculty Papers

PURPOSE: Tumor treating fields (TTFields) are FDA-approved for supratentorial glioblastoma, but feasibility in infratentorial tumors remains poorly defined. This simulation study evaluated TTFields dose in brainstem gliomas using patient-specific modeling with scalp-only transducer arrays.

METHODS: MRI and CT imaging from seven patients with brainstem gliomas were used for TTFields planning with MAXPOINT® (Novocure, Switzerland). Clinical target volume (CTV) was defined as enhancing tumor on T1 post-contrast MRI (Gross tumor volume, GTV) plus a 3 mm peritumoral expansion. The platform optimized scalp-only array layouts, and finite element calculations generated maps of local minimum field intensity (LMiFI, V/cm) and local minimum power …

High-Order Brain Interactions During Ketamine-Induced State Changes: A Functional Marker Of Response In Late-Life Treatment-Resistant Depression?, Krisha Shah, Rubén Herzog, Alan C Swann, Brittany O'Brien, Rahul Balakrishnan, Sanjay J Mathew, Nicholas Murphy

Faculty, Staff and Students Publications

Ketamine is a fast-acting intervention for treatment-resistant depression (TRD), yet only a subset of patients show robust clinical response, and the underlying neural mechanisms remain unclear. High-order interactions (HOI) derived from multivariate information theory provide a framework for examining nonlinear dependencies among brain regions beyond pairwise connectivity. One such metric, the O-information, captures the balance between synergistic and redundant interactions across three or more variables. In this secondary analysis of a randomized, double-blind, midazolam-controlled trial (NCT02556606), we examined EEG-derived HOI in 30 late-life veterans with TRD following a single 40-minute intravenous infusion of ketamine (0.1, 0.25, 0.5 mg/kg; n = …

Tranexamic Acid In High-Risk Shoulder Arthroplasty Patients: Safety Across Thromboembolic, Cardiac, Renal, And Neurologic Risk Profiles, Tarishi Parmar, Akin Adio, Asim Handy, Mohammad Daher, Alec Kellish, Adam Khan, Joseph A. Abboud

Rothman Institute Papers

INTRODUCTION: Tranexamic acid (TXA) effectively reduces blood loss and transfusion requirements in shoulder arthroplasty. However, concerns regarding thromboembolic, neurologic, cardiac, and renal complications have limited its use in medically high-risk patients. This study evaluated temporal trends and the safety of TXA in high-risk patients undergoing total shoulder arthroplasty (TSA).

METHODS: A retrospective cohort study was conducted using TriNetX, identifying patients who underwent shoulder arthroplasty (2012-2025). Patients were stratified by preexisting high-risk conditions, including prior thromboembolism, renal failure, atrial fibrillation, seizure disorders, and visual disturbances. Within each subgroup, patients receiving TXA were propensity score-matched to those who did not. Perioperative TXA …

Advancing Bioinformatics With Language Models: Components, Applications, And Perspectives, Jiajia Liu, Mengyuan Yang, Yankai Yu, Haixia Xu, Tiangang Wang, Kang Li, Xiaobo Zhou

Faculty, Staff and Student Publications

Large language models (LLMs) are deep learning-based artificial intelligence models that have achieved remarkable success in natural language processing. Typically composed of neural networks with billions of parameters, they are trained on massive unlabeled datasets using self-supervised or semi-supervised learning. Beyond language, LLMs hold immense potential for addressing complex bioinformatics challenges. This review provides a comprehensive overview of transformer-based model applications in genomics, transcriptomics, proteomics, drug discovery, and single-cell analysis. We discuss critical components, including tokenization strategies for diverse biological data, transformer architectures, attention mechanisms, and pretraining approaches. We also survey currently available foundation models and their downstream applications across …

Bi-Allelic Loss-Of-Function Variants In Tmem63b Cause Syndromic Surfactant Dysfunction Disorder, Sock Hoai Chan, Audra N Iness, Jill A Rosenfeld, Mir Reza Bekheirnia, Lindsay C Burrage, Matthew Hoi Kin Chau, Chaerish Eint Myet Chae Htoo, Eric C Kao, Shamika Ketkar, Wan Wan Lim, Xi Luo, Rifhan Mazlan, Elizabeth Mizerik, Kein Seong Mun, Kalyani R Patel, Lorraine Potocki, Christina K Rapp, Xavier Roca, Ana Saianda, Ignacio Iglesias-Serrano, Everlyn C Siew, Donald Yuhui Sim, David R Spielberg, Sok-Kun Tae, Jing Xian Teo, Julian Warfsmann, Fan Xia, Child-Eu Registry, Saumya S Jamuar, Ee Shien Tan, Matthias Griese, Weng Khong Lim, Meow-Keong Thong, Keren Machol

Faculty, Staff and Students Publications

Transmembrane protein 63B gene (TMEM63B) encodes a mechanosensitive ion channel expressed in alveolar type II epithelial cells, where it mediates stretch-induced surfactant secretion. While heterozygous gain-of-function variants in TMEM63B have been associated with developmental and epileptic encephalopathy, no human disorder has previously been linked to bi-allelic loss-of-function variants. Here, we report five individuals from four unrelated families with childhood interstitial lung disease and bi-allelic predicted loss-of-function variants in TMEM63B. Affected individuals presented with early-onset respiratory distress, chronic hypoxemia, and diffuse parenchymal lung abnormalities on chest imaging. One individual died in infancy, two underwent bilateral lung transplantation, and two require oxygen …

In Vivo Evidence Of Blood Flow Slippage: Failure Of The No-Slip Boundary Condition Assumption, Alena Jarolímová, Jaroslav Hron, Karel Tůma, Radomír Chabiniok, Josef Málek, Keshava Rajagopal

Division of Cardiology Faculty Papers

The assumption that blood adheres to vessel walls with zero tangential velocity component, the so-called "no-slip" boundary condition, is a foundational premise of cardiovascular fluid dynamics. Whether the no-slip condition holds in vivo, however, remains unknown. Seven healthy adult volunteers underwent cardiovascular magnetic resonance imaging. With four-dimensional flow magnetic resonance imaging of the descending thoracic aorta and modeling blood as a Navier-Stokes fluid, near-wall blood velocities were quantified, and wall shear stress was calculated based on the measured velocity fields. Within the Navier-Stokes data assimilation framework, tangential wall velocities of ∼30-80% of the mean luminal velocity were consistently obtained. These …

Insurance Type And Menopausal Hormone Therapy Use Among Us Women, Arina Chesnokova, Sunni Mumford, Allison Schachter, Rebecca Hamm, Scott Lorch, Matthew Klebanoff, Sarah Lindley, Erika Harness, Makeba Williams, Marilyn Schapira

Student Papers, Posters & Projects

IMPORTANCE: Access to menopausal hormone therapy (MHT) in the US remains low. Understanding whether insurance type is associated with MHT underuse and racial disparities in menopausal care is critical for designing interventions that increase evidence-based and equitable menopause care.

OBJECTIVE: To examine whether Medicaid compared with private insurance is associated with lower MHT use among US women. A secondary objective explored the degree that payer type is associated with observed racial differences in MHT use.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used the 2013-2014, 2015-2016, and 2017-2020 cycles of the National Health and Nutrition Examination Survey (NHANES) to identify …

Fluoroquinolone Use And Risk Of Pneumothorax In Adults Hospitalized With Community Acquired Pneumonia: A Retrospective Cohort Study, Steven Yi B. S., Saurav Sumughan B.S., Jessica Cobb M. D., Erika J. Yoo

Department of Medicine Faculty Papers

Objectives: The objective of this study is to examine the relationship between fluoroquinolone exposure and pneumothorax risk in patients hospitalized with pneumonia.

Methods: This retrospective cohort study used the TriNetX US Collaborative Network. We defined two mutually exclusive cohorts of hospitalized adults based on exposure to antibiotic classes commonly used to treat community acquired pneumonia: fluoroquinolone (ciprofloxacin, moxifloxacin, levofloxacin, and ofloxacin) versus nonfluoroquinolone (amoxicillin, azithromycin, ceftriaxone, and doxycycline). Patients with connective tissue disorders were excluded. The primary outcome was the occurrence of pneumothorax within 60 days. We used Cox proportional hazards regression to estimate hazard ratios (HRs) adjusted for demographics, …

Factors Associated With Pre-Donation Health-Related Quality-Of-Life Among Pediatric Sibling Hematopoietic Cell Donors: A Donorkids Ql Study., Galen E. Switzer, Jessica G. Bruce, Bronwen E. Shaw, Vidya Kuniyil, James W. Varni, Brandan J. Butler, Connor Erickson, Alisha Mussetter, Allison Neutzling, Hisham Abdel-Azim, Paibel Aguayo-Hiraldo, Eric J. Anderson, Victor M. Aquino, Karlie Boone, Farid Boulad, Joseph H. Chewning, Jessica Cooper, Ann Dahlberg, Christopher C. Dvorak, Jorge Galvez-Silva, Ann E. Haight, Jennifer A. Hoag, Michelle Hudspeth, David Jacobsohn, Kimberly A. Kasow, Carrie L. Kitko, Lakshmanan Krishnamurti, Lisa Madden, Holly K. Miller, Erin Morales, Timothy S. Olson, Anna B. Pawlowska, Vinod K. Prasad, Troy C. Quigg, Andromachi Scaradavou, Niketa C. Shah, Shalini Shenoy, Nancy Terwilliger, Lori Wiener, Gregory A. Yanik, Lolie C. Yu, Michael A. Pulsipher

Manuscripts, Articles, Book Chapters and Other Papers

Due to limited published data assessing pediatric hematopoietic cell donor experiences, we previously conducted one of the largest quantitative investigations of pediatric donor experiences and health-related quality-of-life (HRQoL) at the time (RDSafe). Findings from RDSafe demonstrated that a subset of pediatric HC donors experienced very poor HRQoL; unfortunately, that dataset addressed only a limited number of factors, and key associations explaining this poor HRQoL were not found. In this study, our goal was to address that deficit by describing pre-donation donor HRQoL in detail and identifying factors across five key domains that were associated with donor HRQoL. We conducted a …

Clinical Ethics Training Needs Among Pediatricians And Pediatric Residents In Ethiopia: Conference-Based Cross-Sectional Survey., Betelehem Kassa, Addishiwot Melesse, Eyob Kebede Etissa, Bitseat W. Haile, Atnafu Mekonnen Tekleab, Stephanie Kukora

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Pediatricians encounter ethically challenging cases in clinical practice throughout the world. In Ethiopia, ethically distressing pediatric cases are heightened by limited resources, lack of ethical frameworks to guide clinical care and withdrawal of supportive therapies, absence of child protection laws, and dearth of trained ethics consultants or institutional ethics committees providing clinical ethics consultation. Ethics training remains limited in undergraduate medical programs and absent in the resident curriculum at most institutions.

METHODS: A survey of Pediatric Residents and Pediatricians attending the Ethiopian Pediatric Society's 24th Annual Conference on March 2023 was conducted using a self-administered, clinical ethics needs assessment. …

Acute Intermittent Hypoxia And Acute Intermittent Hypercapnic Hypoxia Elicit Cortico-Diaphragmatic Plasticity In People With Chronic Spinal Cord Injury, Alysha Bogard, Michela Mir, Tommy Sutor, Jessica Dunn, Kathryn Cavka, Arian Vistamehr, Hannah Snyder, Joseph Welch, Jayakrishnan Nair, Gina Brunetti, Gordon Mitchell, Emily Fox

Department of Physical Therapy Faculty Papers

Respiratory impairment is a leading cause of morbidity and mortality after spinal cord injury (SCI), highlighting the need for interventions that improve breathing function. In people with SCI, acute intermittent hypoxia (AIH) elicits respiratory motor plasticity and improves inspiratory function. However, in uninjured people facilitation of corticospinal diaphragm motor evoked potential (MEP) amplitude occurs only when AIH is combined with mild hypercapnia (acute intermittent hypercapnic hypoxia; AIHH). It remains unclear whether AIHH similarly enhances diaphragm corticospinal excitability after SCI. We tested the hypothesis that AIHH increases diaphragm MEP amplitude and reduces MEP onset latency in individuals with chronic SCI, whereas …

Cerebrovascular Risk With Calcitonin Gene-Related Peptide Monoclonal Antibodies Versus Onabotulinumtoxina In Patients With Migraine: A Real-World Pharmacoepidemiologic Study In The National Institutes Of Health All Of Us Research Program, Sedat Gül, Bradley Ong, Stephen Trudeau, Nicolas Thompson, Hsiangkuo Yuan

Department of Jefferson Headache Center Papers and Presentations

AimTo evaluate whether initiation of calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) was non-inferior to initiation of onabotulinumtoxinA with respect to the hazard of ischemic stroke or transient ischemic attack (IS + TIA) in a real-world cohort of adults with migraine.MethodsWe conducted a retrospective, active-comparator, new-user pharmacoepidemiology study using the NIH All of Us Research Program Registered Tier Dataset (v8). Adults with migraine initiating CGRP mAbs (erenumab, fremanezumab, galcanezumab, eptinezumab) were compared with initiators of onabotulinumtoxinA from January 2018 through September 2023. The primary outcome was IS + TIA occurring more than 90 days after treatment initiation. Inverse probability of …

Current State And Needs Of Clinical Laboratories In Latin America: A Cross-Country Assessment., Alejandro R. Molinelli, Elizabeth L. Palavecino, José C. Jara-Aguirre, Kerry Cosby, Allison Targowski, Barbara Goldsmith, Rosa Sierra-Amor, Juan D. García, Alicia Algeciras-Schimnich, Eugenio H. Zabaleta, Veronica I. Luzzi, Jessica M. Colón-Franco

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The Association for Diagnostics & Laboratory Medicine (ADLM) aims to improve health by providing education to laboratory scientists worldwide. Different regions of the world face unique challenges shaped by their national and regional contexts. However, the needs of clinical laboratories worldwide remain largely understudied. To address this gap, we conducted a comprehensive needs assessment survey among laboratory professionals in the Latin American region. The survey was distributed to over 2708 individuals across Latin American countries and yielded 148 responses. Most respondents were from urban areas (74%) and worked in private hospital laboratories (45%), with microbiology (25%) and chemistry (23%) identified …

Cefepime Pharmacokinetics In Critically Ill Children With Multiple Organ Dysfunction Syndrome Using Volumetric Absorptive Microsampling, Victor Amajor, Amanda Bwint, Steven Shein, Janet Hume, Courtney Rowan, Leeanne Flygt, Matthew Malone, Erin Stenson, Scott Weiss, Matt Zinter, Sujatha Kannan, Mary Dahmer, Ryan Nofziger, Manjunath Pai, Athena Zuppa, Nathaniel Rhodes, Mark Hall, Marc Scheetz, Kevin Downes

Department of Pediatrics Faculty Papers

Up to half of critically ill children experience multiple organ dysfunction syndrome (MODS), which worsens outcomes and increases mortality risk. Cefepime is a broad-spectrum antibiotic commonly used in pediatric sepsis, but its pharmacokinetics during MODS has not been evaluated. We performed a prospective, observational study of critically ill children with MODS who were administered cefepime and collected up to 15 whole blood samples over 3 days using volumetric absorptive microsampling (VAMS). We performed nonlinear mixed-effects modeling to develop a population PK model for cefepime in children with MODS. We then reran our final population PK model using estimated plasma concentrations …

Risk Of Fracture Following Androgen Receptor Pathway Inhibitors In Men With Advanced Prostate Cancer, Grace Lu-Yao, Nikita Nikita, Scott W. Keith, Krupa Gandhi, Amy L. Shaver, Swapnil Sharma, Christina Steinbock-Malfer, Hushan Yang, Christopher Yang, Kevin K. Zarrabi, Stephen J. Freedland, William K. Kelly

Kimmel Cancer Center Faculty Papers

BACKGROUND: This population-based study aimed to quantify fracture risk after androgen receptor pathway inhibitors in advanced prostate cancer patients by preexisting health conditions.

METHODS: Patients were identified from the Surveillance, Epidemiology, and End Results-Medicare files who received abiraterone acetate with prednisone or enzalutamide between January 1, 2013, and December 31, 2020. Health and fracture history were based on claims 1 year before androgen receptor pathway inhibitor with follow-up through December 31, 2020. The main outcome of the study was the cumulative fracture risk after first date of androgen receptor pathway inhibitor. Fine and Gray subdistribution hazard model was used to …

Neighbourhood Social Vulnerability And Preterm Birth Risk Among Infants With Trisomy 21: A Statewide Analysis, Fatima R Sheriff, Renata H Benjamin, Qian Xiao, Jenil Patel, Charles Shumate, Alejandra Fernandez, A J Agopian

Faculty, Staff and Student Publications

Background: Residing in socioeconomically vulnerable areas is known to be associated with increased preterm birth (PTB) risk in the general population. However, the relationship between social vulnerability and PTB remains unexplored among infants with trisomy 21, who experience more than twice the PTB rate of the general population.

Objectives: The primary objective was to examine the association between maternal socioeconomic vulnerability, as measured by the SVI, and PTB among infants with trisomy 21.

Methods: We conducted a retrospective cohort study among infants with trisomy 21 born in Texas (1999-2018). We examined the association between neighbourhood vulnerability, measured by Social Vulnerability …

Pangenome Analysis Of Proteus Mirabilis Reveals Lineage-Specific Antimicrobial Resistance Profiles And Discordant Genotype-Phenotype Correlations, Namrata Deka, Aimee L Brauer, Katherine Connerton, Blake M Hanson, Jennifer N Walker, Chelsie E Armbruster

Faculty, Staff and Student Publications

Urinary tract infections (UTIs) impose a large healthcare burden, with escalating antimicrobial resistance (AMR), and treatment failure. Proteus mirabilis is an undercharacterized and challenging UTI pathogen due to intrinsic resistance and biofilm formation. To understand P. mirabilis population genomics, we combined pangenome analysis, in silico AMR prediction, and phenotypic antimicrobial susceptibility testing (AST) across 1,027 P. mirabilis genomes derived from human urine specimens. This revealed a mosaic pangenome driven by extensive accessory genome plasticity. Multilocus sequence typing (MLST) identified 213 MLSTs, with only 7% having ≥10 genomes, highlighting strain diversity. AMR gene profiles were largely lineage-specific, with 25% of genomes …

Nano-Bio Interfacial Effects Modulating Protein Adsorption In Dialdehyde Lentinan-Crosslinked Polysaccharide Sponges Reinforced With Zein Nanoflowers, Dorota Chelminiak-Dudkiewicz, Miloslav Machacek, Hana Janová, Klara Konecna, Ondrej Jandourek, Jana Kejmarová, Kinga Mylkie, Aleksander Smolarkiewicz-Wyczachowski, Marta Ziegler-Borowska

The Brown Foundation: Institute of Molecular Medicine

The interfacial organization of porous biomaterials critically influences protein adsorption and subsequent cell-material interactions at hydrated biointerfaces relevant to wound-contacting environments. Herein, hybrid sponges were developed by rationally assembling chitosan, lentinan, levan, and fucoidan into a covalently defined macromolecular network featuring nano-bio interfacial effects. The materials were designed to modulate interfacial biological performance via engineered pore-wall structures, with protein-layer formation at sponge interfaces associated with downstream cell-material responses. A dialdehyde lentinan was deliberately employed to establish a chemically defined pore-wall interface via dense Schiff-base junctions with chitosan. The incorporation of zein nanoflowers introduced additional nanoscale structure features, providing additional anchoring …

Cost Utility Analysis Of Fluticasone Exhalation Delivery System Versus Budesonide Nasal Irrigation For Chronic Rhinosinusitis With Nasal Polyps, Daniel Xiao, Martin J Citardi, William C Yao, Amber U Luong

The Brown Foundation: Institute of Molecular Medicine

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is managed after sinus surgery with topical corticosteroids. Given limited distribution of nasal steroid sprays, patients have the option of either steroid nasal irrigation (SNI) or exhalation delivery system with fluticasone (EDS-FLU). This study evaluates the cost-effectiveness of EDS-FLU compared to SNI for CRSwNP.

Methods: A cohort-style Markov decision-tree economic model with a 33-year time horizon was developed in TreeAgePro. Because EDS-FLU is not currently covered by Medicare, costs of medications were estimated using retail pricing. A willingness-to-pay threshold of $50,000/quality adjusted life year (QALY) was used to determine cost-effectiveness. One-way and probabilistic …

Functional Characterization Of Uhrf1 Variants In Facilitating Dna Methylation, Bigang Liu, Kaila Nayvelt, Swanand Hardikar, Kimie Kondo, Marcos R Estecio, Xiaodong Cheng, Taiping Chen

The Brown Foundation: Institute of Molecular Medicine

Ubiquitin-like with plant homeodomain (PHD) and really interesting new gene (RING) finger domains 1 (UHRF1) is essential for DNA methylation inheritance. However, the functional impacts of several natural and engineered UHRF1 variants are either insufficiently characterized or obscured by conflicting results, with some discrepancies likely stemming from cellular toxicity and adaptive responses induced by DNA methylation changes. In this study, we utilized mouse embryonic stem cells (mESCs)-which uniquely tolerate the complete loss of DNA methylation-to evaluate the functional consequences of clinical mutations, isoform variation, and epitope tagging. Using rescue experiments in Uhrf1-deficient mESCs, we characterized two UHRF1 mutations identified in …

Mosaic Loss Of Y Chromosome Associates With Lung Function, Emphysema, And Epigenetic Aging, Woei-Yuh Saw, Kangjin Kim, Yichen Huang, Jeong H Yun, Xiaolong Ma, Jason Bacon, Yash Pershad, Daniel Levy, George T O'Connor, Eric Boerwinkle, R Graham Barr, Stephen S Rich, Jerome I Rotter, April P Carson, Laura M Raffield, Sina A Gharib, Traci M Bartz, Bruce M Psaty, Tamar Sofer, Kari E North, Robert C Kaplan, Elizabeth C Oelsner, Ani Manichaikul, Alexander G Bick, Paul Scheet, Alexander P Reiner, Nhlbi Trans-Omics For Precision Medicine Consortium, Yasminka A Jakubek, Paul L Auer, Michael H Cho, Dawn L Demeo

Faculty, Staff and Student Publications

Rationale: As the global population ages, identifying risk factors for age-related diseases, such as COPD, is crucial for public health. Mosaic loss of Y chromosome (mLOY) in blood cells is an age-related somatic mosaicism event, but its relationship with pulmonary health remains undercharacterized.

Objectives: To examine the association between mLOY and pulmonary outcomes in men.

Methods: Leveraging mLOY assessment (cell fraction ≥ 5%) in over 12 000 men, including 5097 from the COPDGene Study and 7235 from six additional cohorts in the Trans-Omics for Precision Medicine program, we investigated mLOY associations with respiratory outcomes and epigenetic aging using multivariable cross-sectional, …

Current Adoption Of The Prosthodontic Diagnostic Index For Clinical Care-A Cross-Sectional Survey Study, Esther O Kuyinu, Joseph B Breitman, Arthur Nimmo, Jay S Patel

Faculty, Staff and Student Publications

Purpose: To assess current utilization of the Prosthodontic Diagnostic Index (PDI), identify perceived benefits and limitations, and evaluate support for future updates.

Materials and methods: A survey regarding the use of the PDI was made available through email invitations to 68 US dental school prosthodontic/restorative department chairs (PD), 48 graduate prosthodontic program directors (GP), and 1834 private practice prosthodontists (PP) from the American College of Prosthodontists (ACP) member database. The results of this initial survey were inconclusive due to low response rates. The survey was also administered during the 2024 ACP Annual Session with an improved response rate for educators. …

Kras G12c And Kras G12d Respond To Lipid Metabolism In An Allele-Specific Manner, Neha Arora, Hong Liang, Walaa Kattan, Wantong Yao, Haoqiang Ying, Junchen Liu, Yong Zhou

Faculty, Staff and Student Publications

KRAS mutated at hotspots G12, G13, and Q61 possess profound allele-specific oncogenesis. Signaling of KRAS mutants is mostly compartmentalized to the proteolipid nanoclusters on the plasma membrane (PM), illustrating critical roles of spatiotemporal organization in KRAS cancer signaling. The activated GTP-bound KRAS molecules, including the wild type and mutants, have been traditionally thought to favor similar lipids. We recently reported distinct lipid sensing capabilities of different KRAS mutants, especially with KRASG12D favoring unsaturated lipids and KRASG12C gaining additional enrichment of saturated lipids. As such, KRAS mutants may respond to lipid acyl chain remodeling in an allele-specific manner. Lysophosphatidylcholine acyltransferase 1 …

Erk-Mediated Phosphorylation Of Yap Defines A Noncanonical Fgf Signaling Mechanism In Stem Cells, Xiaolei Zhao, Shannon Erhardt, Li Tang, Xiaotong Chen, Stephen M Farmer, Zixiu Cheng, Wen Chen, Ella Ziyuan Lu, Kihan Sung, Chang-Ru Tsai, Mingjie Zheng, Sheng Zhang, Yang Liu, Jianxin Wang, Min Li, James F Martin, Jun Wang

Faculty, Staff and Student Publications

While Fgf and Hippo-Yap signaling are fundamental for proper development, homeostasis, and disease, their crosstalk remains largely unknown. Here, we identified that Yap and Taz, canonical Hippo effectors, function as noncanonical effectors of Fgf signaling to maintain the proper function of neural crest (NC) lineages. NC cells are a multipotent stem cell population during vertebrate embryogenesis that contribute to numerous structures and diverse cell lineages, including craniofacial and cardiac tissues, neurons, and suture mesenchymal cells (SMCs), a specified cell population required for cranial bone growth and repair. We observed that activation of Fgf signaling in NC cells and NC-derived SMCs …

Immediate Postoperative Pacing Dependency Is Not Associated With Worse Mid-Term Survival In Redo Mitral Valve Surgery, Devon Kelley, Joyce Ho, Andrew Belec, Takahiro Tashima, Victoria Li, James Lao, Varun Kathawate, Kazuhiro Ueno, Amit Iyengar, Jessica Dominic, Pavan Atluri

Division of Cardiology Faculty Papers

Risk factors (RF) for permanent pacemaker (PPM) placement in cardiac surgery include valvular operations and redo operations. We aim to identify RF for PPM placement prior to discharge (DC) specifically among redo mitral valvular operations, and to analyze outcomes in this population. Our retrospective review considered 943 patients undergoing redo MV operations between 01/2002 and 12/2021, excluding patients experiencing in-hospital death within 48 hours of their operation and patients with existing PPM or implanted cardiac defibrillator (ICD). Patients (n = 742) were categorized based on whether they received a PPM before DC or not. Of the 742 patients analyzed, 47 …

Standardization Of Objectives And Response Criteria For Neoadjuvant Immunotherapy In Resectable Squamous Cell Carcinoma Of The Head And Neck, Carlo Resteghini, Athanassios Argiris, Pierre Blanchard, Irene Braña, Anna Maria Camarda, Anthony T. C. Chan, Robert Ferris, Vincent Gregoire, Kevin J. Harrington, Ingeborg Tinhofer, Senada Koljenović, Nancy Y. Lee, C. René Leemans, Jean-Pascal Machiels, Hisham Mehanna, Robert Metcalf, Brian O'Sullivan, Sjoukje Oosting, Ester Orlandi, Vinidh Paleri, Amanda Psyrri, Nabil F F. Saba, Sandra Schmitz, Christian Simon, Makoto Tahara, Vincent Vander Poorten, Milan Vošmik, Paolo Bossi

Department of Medical Oncology Faculty Papers

The management of locally-advanced, resectable head and neck squamous cell carcinoma (HNSCC) is undergoing a major shift driven by the integration of neoadjuvant immunotherapy (nIO). The rationale for nIO lies in its administration within an immunologically active, treatment-naïve microenvironment that enhances immune priming and anti-tumor response. Despite encouraging clinical data, including the pivotal KEYNOTE-689 trial and multiple phase II studies, methodological heterogeneity in trial design, endpoint definitions, and response criteria currently hampers data comparability and the establishment of new standards of care. This expert narrative review proposes a structured framework for standardizing clinical, pathologic, imaging, and translational endpoints in HNSCC …

Clinical Document Metadata Extraction: A Scoping Review, Kurt Miller, Qiuhao Lu, William Hersh, Kirk Roberts, Steven Bedrick, Andrew Wen, Hongfang Liu

Faculty, Staff and Student Publications

Objectives: Clinical document metadata, such as document type, structure, author role, medical specialty, and encounter setting, is essential for accurate interpretation of information captured in clinical documents. However, vast documentation heterogeneity and drift over time challenge harmonization of document metadata. Automated extraction methods have emerged to coalesce metadata from disparate practices into target schema. This scoping review aims to catalog research on clinical document metadata extraction, identify methodological trends and applications, and highlight gaps warranting further investigation.

Methods: We followed the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) guidelines to identify articles from Ovid …

Medadl: High-Throughput Information Extraction Of Functional Status From Electronic Health Records To Advance Frailty Assessment In Older Adults, Sunyang Fu, Zhiyi Yue, Jennyly T Nguyen, Huipeng Liu, Jaerong Ahn, Vanessa Ramirez, Jude Des Bordes, Hongfang Liu, Min Ji Kwak, Nahid J Rianon

Faculty, Staff and Student Publications

Background: Functional status is essential for assessing frailty and planning care in older adults but is often under-documented in the structured fields of electronic health records. Manual chart review can capture functional status information but is labor-intensive and time-consuming. In this study, we developed and validated a scalable natural language processing (NLP) model to extract functional status information from unstructured electronic health record (EHR) notes.

Methods: This retrospective cohort study included 110 older adults seen at a geriatric osteoporosis clinic. A large language model-augmented symbolic NLP pipeline (MedADL) was developed to extract activities of daily living (ADL) and instrumental activities …

Implementation And Evaluation Of The Owll Intervention To Improve The Quality And Safety Of Pediatric Dental Sedation: A Mixed-Methods Approach, Kawtar Zouaidi, Jan Yeager, Sayali Tungare, Suhasini Bangar, Janelle Urata, Alfa-Ibrahim Yansane, Jungsoo Kim, Emily Sedlock, Krishna K Kookal, Yan Xiao, Oluwabunmi Tokede, Heiko Spallek, Amy Franklin, Gregory Olson, Joel White, Elsbeth Kalenderian, Muhammad F Walji

Faculty, Staff and Student Publications

Background: The OWLL (Open-Wide Learning Lab) intervention was developed using Human-Centered Design to improve the quality and safety of pediatric dental sedation. The intervention includes a patient-facing informational sedation brochure and video, and an enhanced set of clinical sedation records. Here, we report on the process evaluation 6 months after implementation in daily clinical practice.

Methods: This study was conducted at the outpatient pediatric dental clinics of 2 large US academic dental institutions. We used a mixed-methods design to assess the fidelity, acceptability, appropriateness, and feasibility of the OWLL intervention. Quantitative data were gathered through chart reviews, while qualitative data …