Digital Commons Network^™

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 …

Multiplexed Plasmon-Enhanced Lateral Flow Assay For Early Diagnosis Of Acute Kidney Injury, Heng Guo, Yuxiong Liu, Ravi Jada, Ying Liu, Carissa Ng, Aquiles Payte, Jiaying Xu, Connor Malone, Jie Zhao, Kedhareswara Sairam Pasupuleti, Arda Aidan Arikan, Sameer Thadani, Srikanth Singamaneni, Ayse Akcan Arikan, Limei Tian

Faculty, Staff and Students Publications

Early diagnosis of acute kidney injury (AKI) remains a major clinical challenge due to the delayed and insensitive nature of conventional markers such as serum creatinine. Urinary protein biomarkers, including neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C (CysC), provide earlier and complementary information on kidney injury, but their clinical translation is limited by the lack of rapid, quantitative, and multiplexed point-of-care (POC) diagnostic tests. Here, we report a multiplexed plasmonic-fluor-based lateral flow assay (p-LFA) that enables sensitive, quantitative, and simultaneous detection of NGAL and CysC. By harnessing ultrabright plasmonic-fluor nanolabels and ratiometric fluorescence analysis, the p-LFA achieves picogram-per-milliliter analytical sensitivity …

Elective Genomic Sequencing For Adults In Research, Clinical And Commercial Contexts, Michael D Linderman, Sophia M Adelson, Tala M Berro, Jennifer L Anderson, Scott D Crawford, Tshaka J Cunningham, Edward D Esplin, Altovise T Ewing-Crawford, Daiva E Nielsen, Stacey Pereira, Tara Schmidlen, Heather Andrighetti, Steven B Bleyl, George M Church, Eden V Haverfield, Madhuri Hegde, Lazaridis N Konstantinos, Paul Kruszka, Debra Leonard, Thomas May, Molly Mcginniss, Vaibhav Pandya, Eric E Schadt, Bastian Greshake Tzovaras, Bethany Zettler, Amy L Mcguire, Robert C Green

Center for Medical Ethics and Health Policy Staff Publications

Purpose: Elective genomic sequencing (EGS) returns monogenic disease findings in multiple genes, including potentially novel variants, and may also provide participants with carrier status, pharmacogenomic and other health-related information. The PeopleSeq Study assessed participants' motivations for and concerns about EGS and the associated clinical and psychosocial outcomes across diverse EGS providers.

Methods: We administered a shared questionnaire to participants who chose to undergo EGS via 18 academic, clinical, or commercial EGS platforms.

Results: We enrolled 1575 participants, of whom 1147 (72.8%) completed a questionnaire after receiving their EGS results. A majority (60.3%) of the participants who completed a post-result questionnaire …

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 …

Antibody-Oligonucleotide Conjugates: An Emerging Modality For Precision Rna Therapeutics, Chen-Hsu Yu, Summer Y Y Ha, Zhiqiang An, Kyoji Tsuchikama, Wenbo Li

The Brown Foundation: Institute of Molecular Medicine

RNA-targeting therapeutics have enormous potential to precisely target disease-causing RNAs, extending beyond the traditional limits of "druggability" for small molecules, antibodies, and protein-targeting cell therapies. However, one crucial limitation is that RNA-targeting drug modalities (such as oligonucleotides) cannot effectively reach diseased tissue or cell types. Antibody-oligonucleotide conjugates (AOCs) emerge as a promising frontier in aiding RNA therapeutics by harnessing antibodies to deliver drug modalities to target specific RNAs in desired tissues or cells. In this Review, we summarize the critical components of AOCs, key considerations for their design and manufacturing, ongoing AOCs in preclinical/clinical development, and disease indications. We discuss …

Implementing A Professional Wellness Session To Foster Improvement In Oncology Nurse Retention And Well-Being, Connie Tran

Doctor of Nursing Practice Final Project Abstract

Purpose

The purpose of this quality improvement (QI) project was to implement chaplain-led professional wellness sessions to improve the well-being of nurses on an oncology pilot unit.  Aims were to increase nurse retention by 5%, decrease staff absenteeism by 3%, and improve Perceived Stress Scale (PSS) scores by 10%, and Professional Quality of Life (ProQOL) scores by 10% from baseline.

Background

The emotionally taxing nature of oncology patient care creates a high-pressure environment, which can lead to turnover. Literature has shown that allowing staff to pray, debrief and engage in peer support groups to discuss work-related stressful encounters reduces stress …

Improving Physiologic Monitoring Adherence During Behavioral Emergencty Sedation In A Prehospital Ems System, Jared Aucoin

Doctor of Nursing Practice Final Project Abstract

Abstract

Purpose:

This quality improvement (QI) project evaluated whether provider education and standardized documentation improved adherence to evidence-based physiologic monitoring during behavioral emergency sedation in a prehospital EMS setting.

Background:

Behavioral emergencies are common and often require rapid chemical sedation, with risks of hypoxia, hypercapnia, and cardiovascular instability. At baseline, inconsistent adherence to recommended monitoring and documentation of end-tidal carbon dioxide (EtCO₂) and pulse oximetry (SpO₂) presented an opportunity to improve patient safety.

Methodology:

This QI project educated current adult behavioral emergency protocol in a prehospital EMS setting, re-emphasizing standardized documentation and evidence-based monitoring practices. Utilizing Plan-Do-Study-Act (PDSA) through pre- …

Enhancing Care Coordination Between The Same Day Clinic (Sdc) And Primary Care Group (Pcg) By Facilitating Care Establishment With A Primary Care Provider (Pcp), Saba Zabarah

Doctor of Nursing Practice Final Project Abstract

PURPOSE

The purpose of this Quality Improvement (QI) project was to connect patients to a Primary Care Provider (PCP). The specific aim was to increase by 25% the percentage of patients without a PCP who established care with a PCP within 30 days of visiting the Same Day Clinic (SDC).

BACKGROUND

The SDC provides episodic care for acute illness, making it difficult to coordinate care for patients who do not have a PCP and require follow-up. The project was implemented in an outpatient clinic that is connected to a larger primary care group in Houston, Texas.

METHODOLOGY

The intervention included …

Reducing Over-Isolation: Baseline Evaluation Of Isolation Precaution Reassessment In Hospitalized Children, Laura Brambilla, Wan-Hsuan Chen

Summer Research Program Abstracts

No abstract provided.

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 …

Antibody-Oligonucleotide Conjugates: An Emerging Modality For Precision Rna Therapeutics, Chen-Hsu Yu, Summer Y Y Ha, Zhiqiang An, Kyoji Tsuchikama, Wenbo Li

The Brown Foundation: Institute of Molecular Medicine

RNA-targeting therapeutics have enormous potential to precisely target disease-causing RNAs, extending beyond the traditional limits of "druggability" for small molecules, antibodies, and protein-targeting cell therapies. However, one crucial limitation is that RNA-targeting drug modalities (such as oligonucleotides) cannot effectively reach diseased tissue or cell types. Antibody-oligonucleotide conjugates (AOCs) emerge as a promising frontier in aiding RNA therapeutics by harnessing antibodies to deliver drug modalities to target specific RNAs in desired tissues or cells. In this Review, we summarize the critical components of AOCs, key considerations for their design and manufacturing, ongoing AOCs in preclinical/clinical development, and disease indications. We discuss …

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 …

Quantitative Analysis Of Peri-Implant Collagen Fiber Orientation Around External Hexagon And Morse Taper Implant Connections: A Dog Model Study, Daniel Sartorelli Marques De Castro, Jefferson David Melo De Matos, Jozely Francisca Mello Lima, Maria Angelica Rehder De Araujo, Mário Alexandre Coelho Sinhoreti, Daher Antonio Queiroz, Adriano Piattelli, Carlos Dos Reis Pereira De Araújo

Faculty, Staff and Student Publications

Background: Peri-implant soft tissue stability depends on the implant-abutment interface and collagen fiber organization. Unlike natural teeth, peri-implant fibers exhibit a less favorable orientation, potentially weakening the biological seal. Implant connection design may influence this collagen arrangement and tissue integrity.

Materials and methods: Eighteen immediately loaded implants (n = 9 per group) were placed in nine mongrel dogs. Group I received external hexagon implants, while Group II received Morse taper implants. After a 4-month healing period, animals were euthanized and specimens were processed for histological evaluation. Collagen fiber orientation was analyzed using polarized light microscopy and quantified with ImageJ software. …

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 …

Using The Consolidated Framework For Implementation Research (Cfir) To Evaluate Complex School Settings, Carlie P. Coerver, Tricia A Zucker

Summer Research Program Abstracts

No abstract provided.

Hpv Vaccination Status And Associated Factors Among Postpartum Patients, Morgan L. Malonson, Sandhya B. Avula, Mary B. Rysavy

Summer Research Program Abstracts

No abstract provided.

Long-Term Quality Of Life For Patients With Merkel Cell Carcinoma Receiving Standard-Of-Care Adjuvant Radiation Therapy, Christian Paul D. Denolan, Kelsey N. Nordlund, Aya F. Salem, Devarati Mitra

Summer Research Program Abstracts

No abstract provided.

Anesthetic Considerations In Geriatric Oncological Patients: A Case Series, Allison Chen, Edward H. Tsai

Summer Research Program Abstracts

No abstract provided.

Optimizing Biomechanical Conditioning For Human Intestinal Organoids With An Enteric Nervous System, Cash L. Davis, Rachel Bordelon, Madushani Herath, Younus A Zuberi, Allison L. Speer

Summer Research Program Abstracts

No abstract provided.

Clinical Observation Of Glp-1ra And Substance Use (Cogs) Study Preliminary Data Outcomes, Akshara S. Narahari, Nzingha Johnson

Summer Research Program Abstracts

No abstract provided.

Neuroinflammatory Profiles In The Hippocampus Of Cognitively Resilient Alzheimer's Disease Patients, William H. Otte, Avery Matthews, Hongyu Wu, Ashlee Arizmendez, Michael E. Maniskas, Xinhai (Robert) Zhang, Chunfeng (Sheryl) Tan

Summer Research Program Abstracts

No abstract provided.

Caregiver Health Literacy Is Associated With Pediatric Burn Recovery Outcomes, Ananya Sampathkumar, Anna Sabukurian, Erin M. Morris, Alyssa M. Griffith, Nicholas A. Long, Alexa Cumming, Macie Boden, Christina G. Morris, Lauren K. Mayon, Thian H. Nguyen, Allison L. Speer, Natalie A. Drucker

Summer Research Program Abstracts

No abstract provided.

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 …

Sex Differences In The Protective Effect Of Brain Volume: Age Attenuates Protection In Women, Javier Gomez-Farias, Ngoc Mai Le, Joseph N Samaha, Bruna Kfoury, Hussain M Azeem, Ritesh Bajaj, Mahnoor Khalid, Freya Kanakhara, Shikha Tripathi, Shayan Shams, Luca Giancardo, Eunyoung A Lee, Robert W Regenhardt, Louise D Mccullough, Sunil A Sheth

Faculty, Staff and Student Publications

Background: Sex differences in outcomes after acute ischemic stroke are well recognized, but mechanisms remain unclear. This study evaluates whether parenchymal brain volume (PBV), age, and final infarct volume explain sex-specific differences in poststroke disability.

Methods: We analyzed a prospectively collected multicenter registry of acute ischemic stroke patients treated between 2015 and 2024. Automated pipelines quantified PBV from noncontrast computed tomography and diffusion-weighted imaging-derived final infarct volume from 24- to 48-hour magnetic resonance imaging. With the primary outcome being 90-day functional independence (modified Rankin Scale score 0-2), sex-stratified logistic regression models evaluated its association with PBV. Stratified logistic and linear …