Digital Commons Network^™

Prdm16 Enhances Osteoblastogenic Runx2 Via Canonical Wnt10b/Β-Catenin Pathway In Testosterone-Treated Hypogonadal Men, Siresha Bathina, Mia Prado, Virginia Fuenmayor Lopez, Georgia Colleluori, Lina Aguirre, Rui Chen, Dennis T Villareal, Reina Armamento-Villareal

Faculty, Staff and Students Publications

We previously reported that PRDM16 mediated the improvement in body composition in testosterone (T)-treated hypogonadal men by shifting adipogenesis to myogenesis. Previous preclinical studies suggest that Prdm16 regulates Runx2, an important osteoblastic transcription factor, expression and activity. However, the changes in PRDM16, and other genes/proteins involved in osteoblastogenesis with T therapy in hypogonadal men are unexplored. We investigated the role of PRDM16 in RUNX2 activation by measuring changes in gene expression in peripheral blood monocytes (PBMCs) and proteins in the serum of hypogonadal men after T therapy for 6 months. Likewise, we evaluated changes in the WNT10b—β-CATENIN signaling …

Toward Personalized Digital Experiences To Promote Diabetes Self-Management: Mixed Methods Social Computing Approach, Tavleen Singh, Kirk Roberts, Kayo Fujimoto, Jing Wang, Constance Johnson, Sahiti Myneni

Faculty, Staff and Student Publications

BACKGROUND: Type 2 diabetes affects nearly 34.2 million adults and is the seventh leading cause of death in the United States. Digital health communities have emerged as avenues to provide social support to individuals engaging in diabetes self-management (DSM). The analysis of digital peer interactions and social connections can improve our understanding of the factors underlying behavior change, which can inform the development of personalized DSM interventions.

OBJECTIVE: Our objective is to apply our methodology using a mixed methods approach to (1) characterize the role of context-specific social influence patterns in DSM and (2) derive interventional targets that enhance individual …

Evaluating The Effects Of High-Throughput Structural Neuroimaging Predictors On Whole-Brain Functional Connectome Outcomes Via Network-Based Matrix-On-Vector Regression, Tong Lu, Yuan Zhang, Vince Lyzinski, Chuan Bi, Peter Kochunov, Elliot Hong, Shuo Chen

Faculty, Staff and Student Publications

The joint analysis of multimodal neuroimaging data is vital in brain research, revealing complex interactions between brain structures and functions. Our study is motivated by the analysis of a vast dataset of brain functional connectivity (FC) and multimodal structural imaging (SI) features from the UK Biobank. Specifically, we aim to investigate the effects of SI features, such as white matter microstructure integrity (WMMI) and cortical thickness, on the whole-brain functional connectome network. This analysis is inherently challenging due to the extensive structural-functional associations and the intricate network patterns present in multimodal high-dimensional neuroimaging data. To bridge methodological gaps, we developed …

Organizational Readiness For Implementation: A Qualitative Assessment To Explain Survey Responses, Maria Mcclam, Lauren Workman, Timothy J Walker, Emanuelle M Dias, Derek W Craig, Joe R Padilla, Andrea E Lamont, Abraham Wandersman, Maria E Fernandez

Faculty, Staff and Student Publications

BACKGROUND: One factor considered essential to successful implementation is organizational readiness. The purpose of this study was to explore ways to improve the measurement of organizational readiness, and in particular to refine a preliminary measure based on the Readiness = Motivation x innovation Specific Capacity x General Capacity (R = MC2) heuristic. We assessed the experiences of staff in Federally Qualified Health Centers (FQHC) implementing evidence-based interventions (EBIs) designed to increase colorectal cancer screening (CRCS) who previously completed the survey and aimed to understand their perspectives on why our data were positively skewed.

METHODS: We conducted a series of qualitative …

Causal Models And Prediction In Cell Line Perturbation Experiments, James P Long, Yumeng Yang, Shohei Shimizu, Thong Pham, Kim-Anh Do

Faculty, Staff and Student Publications

In cell line perturbation experiments, a collection of cells is perturbed with external agents and responses such as protein expression measured. Due to cost constraints, only a small fraction of all possible perturbations can be tested in vitro. This has led to the development of computational models that can predict cellular responses to perturbations in silico. A central challenge for these models is to predict the effect of new, previously untested perturbations that were not used in the training data. Here we propose causal structural equations for modeling how perturbations effect cells. From this model, we derive two estimators for …

Sstr2-Targeted Theranostics In Hepatocellular Carcinoma, Majid Momeny, Solmaz Aghaamiri, Servando Hernandez Vargas, Belkacem Acidi, Sukhen C Ghosh, Tyler M Bateman, Jack T Adams, Vahid Khalaj, Ahmed O Kaseb, Hop S Tran Cao, Ali Azhdarinia

Faculty, Staff and Student Publications

Background: While the clinical use of radiolabeled somatostatin analogs is well established in neuroendocrine tumors, there is growing interest in expanding their application to other somatostatin receptor 2 (SSTR2)-expressing cancers. This study investigates the potential utility of SSTR2-targeted theranostics in hepatocellular carcinoma (HCC).

Methods: SSTR2 expression in HCC cell lines and clinical samples was evaluated using qRT-PCR, Western blot analysis, and a public dataset. 67Ga-DOTATATE uptake was measured, 177Lu-DOTATATE cytotoxicity was assessed, and 68Ga-DOTATATE tumor targeting was evaluated in HCC animal models and a patient via PET/CT imaging.

Results: SSTR2 expression was confirmed in HCC cell lines and clinical samples. …

Development Of Sacb-Based Counterselection For Efficient Allelic Exchange In Fusobacterium Nucleatum, Peng Zhou, Bibek G C, Bo Hu, Chenggang Wu

Faculty, Staff and Student Publications

Fusobacterium nucleatum, prevalent in the oral cavity, is significantly linked to overall human health. Our molecular comprehension of its role in oral biofilm formation and its interactions with the host under various pathological circumstances has seen considerable advancements in recent years, primarily due to the development of various genetic tools for DNA manipulation in this bacterium. Of these, counterselection-based unmarked in-frame mutation methods have proved notably effective. Under suitable growth conditions, cells carrying a counterselectable gene die, enabling efficient selection of rare, defined allelic exchange mutants. The sacB gene from Bacillus subtilis, encoding levansucrase, is a widely used …

The Gip Receptor Activates Futile Calcium Cycling In White Adipose Tissue To Increase Energy Expenditure And Drive Weight Loss In Mice, Xinxin Yu, Shiuhwei Chen, Jan-Bernd Funcke, Leon G Straub, Valentina Pirro, Margo P Emont, Brian A Droz, Kyla Ai Collins, Chanmin Joung, Mackenzie J Pearson, Corey M James, Gopal J Babu, Vissarion Efthymiou, Ashley Vernon, Mary Elizabeth Patti, Yu A An, Evan D Rosen, Matthew P Coghlan, Ricardo J Samms, Philipp E Scherer, Christine M Kusminski

Faculty, Staff and Student Publications

Obesity is a chronic disease that contributes to the development of insulin resistance, type 2 diabetes (T2D), and cardiovascular risk. Glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR) and glucagon-like peptide-1 (GLP-1) receptor (GLP-1R) co-agonism provide an improved therapeutic profile in individuals with T2D and obesity when compared with selective GLP-1R agonism. Although the metabolic benefits of GLP-1R agonism are established, whether GIPR activation impacts weight loss through peripheral mechanisms is yet to be fully defined. Here, we generated a mouse model of GIPR induction exclusively in the adipocyte. We show that GIPR induction in the fat cell protects mice from diet-induced …

A Regularized Bayesian Dirichlet-Multinomial Regression Model For Integrating Single-Cell-Level Omics And Patient-Level Clinical Study Data, Yanghong Guo, Lei Yu, Lei Guo, Lin Xu, Qiwei Li

Faculty, Staff and Student Publications

The abundance of various cell types can vary significantly among patients with varying phenotypes and even those with the same phenotype. Recent scientific advancements provide mounting evidence that other clinical variables, such as age, gender, and lifestyle habits, can also influence the abundance of certain cell types. However, current methods for integrating single-cell-level omics data with clinical variables are inadequate. In this study, we propose a regularized Bayesian Dirichlet-multinomial regression framework to investigate the relationship between single-cell RNA sequencing data and patient-level clinical data. Additionally, the model employs a novel hierarchical tree structure to identify such relationships at different cell-type …

Targeted Inhibition Of Aurora Kinase A Promotes Immune Checkpoint Inhibition Efficacy In Human Papillomavirus-Driven Cancers, Soma Ghosh, Madison P O'Hara, Pragya Sinha, Tuhina Mazumdar, Lacin Yapindi, Jagannadha K Sastry, Faye M Johnson

Faculty, Staff and Student Publications

Background: Human papillomavirus (HPV)-driven cancers include head and neck squamous cell carcinoma and cervical cancer and represent approximately 5% of all cancer cases worldwide. Standard-of-care chemotherapy, radiotherapy, and immune checkpoint inhibitors (ICIs) are associated with adverse effects and limited responses in patients with HPV-driven cancers. The integration of targeted therapies with ICIs may improve outcomes. In a previous study, we demonstrated that Aurora kinase A (AURKA, Aurora A) inhibitors lead to apoptosis of human HPV-positive cancer cells in vitro and in vivo. Here, we explored the potential of Aurora A inhibition to enhance response to ICIs in immune-competent …

Genetics And Biology Of Pancreatic Ductal Adenocarcinoma, Haoqiang Ying, Alec C Kimmelman, Nabeel Bardeesy, Raghu Kalluri, Anirban Maitra, Ronald A Depinho

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) poses a grim prognosis for patients. Recent multidisciplinary research efforts have provided critical insights into its genetics and tumor biology, creating the foundation for rational development of targeted and immune therapies. Here, we review the PDAC genomic landscape and the role of specific oncogenic events in tumor initiation and progression, as well as their contributions to shaping its tumor biology. We further summarize and synthesize breakthroughs in single-cell and metabolic profiling technologies that have illuminated the complex cellular composition and heterotypic interactions of the PDAC tumor microenvironment, with an emphasis on metabolic cross-talk across cancer and …

Rpa And Rad27 Limit Templated And Inverted Insertions At Dna Breaks, Yang Yu, Xin Wang, Jordan Fox, Qian Li, Yang Yu, P J Hastings, Kaifu Chen, Grzegorz Ira

Faculty, Staff and Students Publications

Formation of templated insertions at DNA double-strand breaks (DSBs) is very common in cancer cells. The mechanisms and enzymes regulating these events are largely unknown. Here, we investigated templated insertions in yeast at DSBs using amplicon sequencing across a repaired locus. We document very short (most ∼5-34 bp), templated inverted duplications at DSBs. They are generated through a foldback mechanism that utilizes microhomologies adjacent to the DSB. Enzymatic requirements suggest a hybrid mechanism wherein one end requires Polδ-mediated synthesis while the other end is captured by nonhomologous end joining (NHEJ) or by alternative end joining (Alt-EJ). This process is exacerbated …

Modulation Of Stemness And Differentiation Regulators By Valproic Acid In Medulloblastoma Neurospheres, Natália Hogetop Freire, Alice Laschuk Herlinger, Julia Vanini, Matheus Dalmolin, Marcelo A C Fernandes, Carolina Nör, Vijay Ramaswamy, Caroline Brunetto De Farias, André Tesainer Brunetto, Algemir Lunardi Brunetto, Lauro José Gregianin, Mariane Da Cunha Jaeger, Michael D Taylor, Rafael Roesler

Faculty, Staff and Students Publications

Changes in epigenetic processes such as histone acetylation are proposed as key events influencing cancer cell function and the initiation and progression of pediatric brain tumors. Valproic acid (VPA) is an antiepileptic drug that acts partially by inhibiting histone deacetylases (HDACs) and could be repurposed as an epigenetic anticancer therapy. Here, we show that VPA reduced medulloblastoma (MB) cell viability and led to cell cycle arrest. These effects were accompanied by enhanced H3K9 histone acetylation (H3K9ac) and decreased expression of the MYC oncogene. VPA impaired the expansion of MB neurospheres enriched in stemness markers and reduced MYC while increasing TP53 …

Advancing De Novo Lipogenesis: Genetic And Metabolic Insights, Sean M Hartig, Mark A Herman

Faculty, Staff and Students Publications

De novo lipogenesis (DNL) is the process whereby cells synthesize fatty acids from acetyl-CoA, contributing to steatosis in fatty liver disease. Two new studies, using genetic mouse models, metabolomics, and pharmacology, identified alternative pathways in DNL and unexpected physiological effects when targeting key enzymes in this pathway.

Yap Overcomes Mechanical Barriers To Induce Mitotic Rounding And Adult Cardiomyocyte Division, Yuka Morikawa, Jong H Kim, Rich Gang Li, Lin Liu, Shijie Liu, Vaibhav Deshmukh, Matthew C Hill, James F Martin

Faculty, Staff and Students Publications

Background: Many specialized cells in adult organs acquire a state of cell cycle arrest and quiescence through unknown mechanisms. Our limited understanding of mammalian cell cycle arrest is derived primarily from cell culture models. Adult mammalian cardiomyocytes, a classic example of cell cycle arrested cells, exit the cell cycle postnatally and remain in an arrested state for the life of the organism. Cardiomyocytes can be induced to re-enter the cell cycle by YAP5SA, an active form of the Hippo signaling pathway effector YAP.

Methods: We performed clonal analyses to determine the cell cycle kinetics of YAP5SA cardiomyocytes. We also performed …

Microtubules Sequester Acetylated Yap In The Cytoplasm And Inhibit Heart Regeneration, Shijie Liu, Vaibhav Deshmukh, Fansen Meng, Yidan Wang, Yuka Morikawa, Jeffrey D Steimle, Rich Gang Li, Jun Wang, James F Martin

Faculty, Staff and Students Publications

Background: The Hippo pathway effector YAP (Yes-associated protein) plays an essential role in cardiomyocyte proliferation and heart regeneration. In response to physiological changes, YAP moves in and out of the nucleus. The pathophysiological mechanisms regulating YAP subcellular localization after myocardial infarction remain poorly defined.

Methods: We identified YAP acetylation at site K265 by in vitro acetylation followed by mass spectrometry analysis. We used adeno-associated virus to express YAP-containing mutations that either abolished acetylation (YAP-K265R) or mimicked acetylation (YAP-K265Q) and studied how acetylation regulates YAP subcellular localization in mouse hearts. We generated a cell line with YAP-K265R mutation and investigated the …

A Caution Against Customized Ai In Healthcare, Kristin M Kostick-Quenet

Center for Medical Ethics and Health Policy Staff Publications

This article critiques the shift towards personalized AI in healthcare and other high-stakes domains, cautioning that without careful deliberation, customized AI systems can compromise the diversity and reach of human knowledge by restricting exposure to critical information that may conflict with users' preferences and biases. Customized AI should be applied with caution and intention where access to a wide and diverse range of perspectives is essential for impartial, informed decision making.

Cell Cycle Progression Of Under-Replicated Cells, Min Huang, Chang Yang, Litong Nie, Huimin Zhang, Dandan Zhu, Chao Wang, Jeong-Min Park, Mrinal Srivastava, Elina Mosa, Siting Li, Mengfan Tang, Xu Feng, Sarah J Keast, Fabio Stossi, Junjie Chen

Faculty, Staff and Student Publications

Cell cycle checkpoints are the regulatory mechanisms that secure the strict order of cellular events for cell division that ensure genome integrity. It has been proposed that mitosis initiation depends on the completion of DNA replication, which must be tightly controlled to guarantee genome duplication. Contrary to these conventional hypotheses, we showed here that cells were able to enter mitosis without completion of DNA replication. Although DNA replication was not completed in cells upon depletion of MCM2, CDC45 or GINS4, these under-replicated cells progressed into mitosis, which led to cell death. These unexpected results challenge current model and suggest the …

Circakb: A Comprehensive Knowledgebase Of Circadian Genes Across Multiple Species, Xingchen Zhu, Xiao Han, Zhijin Li, Xiaobo Zhou, Seung-Hee Yoo, Zheng Chen, Zhiwei Ji

Faculty, Staff and Student Publications

Circadian rhythms, which are the natural cycles that dictate various physiological processes over a 24-h period, have been increasingly recognized as important in the management and treatment of various human diseases. However, the lack of sufficient data and reliable analysis methods have been a major obstacle to understanding the bidirectional interaction between circadian variation and human health. We have developed CircaKB, a comprehensive knowledgebase of circadian genes across multiple species. CircaKB is the first knowledgebase that provides systematic annotations of the oscillatory patterns of gene expression at a genome-wide level for 15 representative species. Currently, CircaKB contains 226 time-course transcriptome …

Scproatlas: An Atlas Of Multiplexed Single-Cell Spatial Proteomics Imaging In Human Tissues, Tiangang Wang, Xuanmin Chen, Yujuan Han, Jiahao Yi, Xi Liu, Pora Kim, Liyu Huang, Kexin Huang, Xiaobo Zhou

Faculty, Staff and Student Publications

Spatial proteomics can visualize and quantify protein expression profiles within tissues at single-cell resolution. Although spatial proteomics can only detect a limited number of proteins compared to spatial transcriptomics, it provides comprehensive spatial information with single-cell resolution. By studying the spatial distribution of cells, we can clearly obtain the spatial context within tissues at multiple scales. Spatial context includes the spatial composition of cell types, the distribution of functional structures, and the spatial communication between functional regions, all of which are crucial for the patterns of cellular distribution. Here, we constructed a comprehensive spatial proteomics functional annotation knowledgebase, scProAtlas (https://relab.xidian.edu.cn/scProAtlas/#/), …

Cansar 2024-An Update To The Public Drug Discovery Knowledgebase, Phillip W Gingrich, Rezvan Chitsazi, Ansuman Biswas, Chunjie Jiang, Li Zhao, Joseph E Tym, Kevin M Brammer, Jun Li, Zhigang Shu, David S Maxwell, Jeffrey A Tacy, Ioan L Mica, Michael Darkoh, Patrizio Di Micco, Kaitlyn P Russell, Paul Workman, Bissan Al-Lazikani

Faculty, Staff and Student Publications

canSAR (https://cansar.ai) continues to serve as the largest publicly available platform for cancer-focused drug discovery and translational research. It integrates multidisciplinary data from disparate and otherwise siloed public data sources as well as data curated uniquely for canSAR. In addition, canSAR deploys a suite of curation and standardization tools together with AI algorithms to generate new knowledge from these integrated data to inform hypothesis generation. Here we report the latest updates to canSAR. As well as increasing available data, we provide enhancements to our algorithms to improve the offering to the user. Notably, our enhancements include a revised ligandability classifier …

Dimensionality Reduction For Visualizing Spatially Resolved Profiling Data Using Spasne, Yuansheng Zhou, Chen Tang, Xue Xiao, Xiaowei Zhan, Tao Wang, Guanghua Xiao, Lin Xu

Faculty, Staff and Student Publications

Background: Spatially resolved profiling technologies to quantify transcriptomes, epigenomes, and proteomes have been emerging as groundbreaking methods for comprehensive molecular characterizations. Dimensionality reduction and visualization is an essential step to analyze and interpret spatially resolved profiling data. However, state-of-the-art dimensionality reduction methods for single-cell sequencing data, such as the t-distributed stochastic neighbor embedding (t-SNE) and uniform manifold approximation and projection (UMAP), were not tailored for spatially resolved profiling data.

Results: Here we developed a spatially resolved t-SNE (SpaSNE) method to integrate both spatial and molecular information. We applied it to a variety of public spatially resolved profiling datasets that were …

Intrinsic Adaptive Plasticity In Mouse And Human Sensory Neurons, Lisa A Mcilvried, John Smith Del Rosario, Melanie Y Pullen, Andi Wangzhou, Tayler D Sheahan, Andrew J Shepherd, Richard A Slivicki, John A Lemen, Theodore J Price, Bryan A Copits, Robert W Gereau

Faculty, Staff and Student Publications

In response to changes in activity induced by environmental cues, neurons in the central nervous system undergo homeostatic plasticity to sustain overall network function during abrupt changes in synaptic strengths. Homeostatic plasticity involves changes in synaptic scaling and regulation of intrinsic excitability. Increases in spontaneous firing and excitability of sensory neurons are evident in some forms of chronic pain in animal models and human patients. However, whether mechanisms of homeostatic plasticity are engaged in sensory neurons of the peripheral nervous system (PNS) is unknown. Here, we show that sustained depolarization (induced by 24-h incubation in 30 mM KCl) induces compensatory …

Urban Sensing In The Era Of Large Language Models, Ce Hou, Fan Zhang, Yong Li, Haifeng Li, Gengchen Mai, Yuhao Kang, Ling Yao, Wenhao Yu, Yao Yao, Song Gao, Min Chen, Yu Liu

Faculty, Staff and Student Publications

Urban sensing has become increasingly important as cities evolve into the centers of human activities. Large language models (LLMs) offer new opportunities for urban sensing based on commonsense and worldview that emerged through their language-centric framework. This paper illustrates the transformative impact of LLMs, particularly in the potential of advancing next-generation urban sensing for exploring urban mechanisms. The discussion navigates through several key aspects, including enhancing knowledge transfer between humans and LLM, urban mechanisms awareness, and achieve automated decision-making with LLM agents. We emphasize the potential of LLMs to revolutionize urban sensing, offering a more comprehensive, efficient, and in-depth understanding …

Aspdb: An Integrative Knowledgebase Of Human Protein Isoforms From Experimental And Ai-Predicted Structures, Yuntao Yang, Himansu Kumar, Yuhan Xie, Zhao Li, Rongbin Li, Wenbo Chen, Chiamaka S Diala, Meer A Ali, Yi Xu, Albon Wu, Sayed-Rzgar Hosseini, Erfei Bi, Hongyu Zhao, Pora Kim, W Jim Zheng

Faculty, Staff and Student Publications

Alternative splicing is a crucial cellular process in eukaryotes, enabling the generation of multiple protein isoforms with diverse functions from a single gene. To better understand the impact of alternative splicing on protein structures, protein-protein interaction and human diseases, we developed ASpdb (https://biodataai.uth.edu/ASpdb/), a comprehensive database integrating experimentally determined structures and AlphaFold 2-predicted models for human protein isoforms. ASpdb includes over 3400 canonical isoforms, each represented by both experimentally resolved and predicted structures, and >7200 alternative isoforms with AlphaFold 2 predictions. In addition to detailed splicing events, 3D structures, sequence variations and functional annotations, ASpdb uniquely offers comparative analyses and …

Metsdb: A Knowledgebase Of Cancer Metastasis At Bulk, Single-Cell And Spatial Levels, Sijia Wu, Jiajin Zhang, Yanfei Wang, Xinyu Qin, Zhaocan Zhang, Zhennan Lu, Pora Kim, Xiaobo Zhou, Liyu Huang

Faculty, Staff and Student Publications

Cancer metastasis, the process by which tumour cells migrate and colonize distant organs from a primary site, is responsible for the majority of cancer-related deaths. Understanding the cellular and molecular mechanisms underlying this complex process is essential for developing effective metastasis prevention and therapy strategies. To this end, we systematically analysed 1786 bulk tissue samples from 13 cancer types, 988 463 single cells from 17 cancer types, and 40 252 spots from 45 spatial slides across 10 cancer types. The results of these analyses are compiled in the metsDB database, accessible at https://relab.xidian.edu.cn/metsDB/. This database provides insights into alterations in …

Crisprofft: Comprehensive Database Of Crispr/Cas Off-Targets, Grant Wang, Xiaona Liu, Aoqi Wang, Jianguo Wen, Pora Kim, Qianqian Song, Xiaona Liu, Xiaobo Zhou

Faculty, Staff and Student Publications

The CRISPR (clustered regularly interspaced short palindromic repeats)/Cas (CRISPR-associated protein) programmable nuclease system continues to evolve, with in vivo therapeutic gene editing increasingly applied in clinical settings. However, off-target effects remain a significant challenge, hindering its broader clinical application. To enhance the development of gene-editing therapies and the accuracy of prediction algorithms, we developed CRISPRoffT (https://ccsm.uth.edu/CRISPRoffT/). Users can access a comprehensive repository of off-target regions predicted and validated by a diverse range of technologies across various cell lines, Cas enzyme variants, engineered sgRNAs (single guide RNAs) and CRISPR editing systems. CRISPRoffT integrates results of off-target analysis from 74 studies, encompassing …

The Association Of The Chemotherapy Response Score And Homologous Recombination Deficiency In Patients Undergoing Interval Tumor Reductive Surgery Following Neoadjuvant Chemotherapy, Roni Nitecki Wilke, Jinsong Liu, Shannon Neville Westin, Bryan M Fellman, Travis T Sims, Melissa Pham, Kelly Rangel, Esther Sey, Jose Alejandro Rauh-Hain, Karen H Lu, Anil K Sood, Nicole D Fleming

Faculty, Staff and Student Publications

Objectives: In patients undergoing interval tumor reductive surgery, a good response to neoadjuvant chemotherapy may limit available tumor for homologous recombination deficiency testing. The objective of this study was to assess whether the chemotherapy response score predicts homologous recombination status.

Methods: We identified patients with advanced epithelial ovarian cancer (diagnosed January 2019 to 20 June 2023) who received neoadjuvant chemotherapy, underwent interval surgery, and for whom a chemotherapy response score was reported (1=no or minimal tumor response, 2=appreciable tumor response, 3=complete or near complete response with no residual tumor). Comparisons were made using ANOVAs or Kruskal-Wallis test for continuous variables …

Myo5b And The Polygenic Landscape Of Very Early-Onset Inflammatory Bowel Disease In An Ethnically Diverse Population, Ashleigh Watson, R Alan Harris, Amy C Engevik, Numan Oezguen, Maribeth R Nicholson, Sarah Dooley, Rachel Stubler, Lisa Forbes Satter, Lina B Karam, Richard Kellermayer

Faculty, Staff and Students Publications

Background: Genetic discovery in very early-onset inflammatory bowel disease (VEO-IBD) can elucidate not only the origins of VEO-IBD, but also later-onset inflammatory bowel disease. We aimed to investigate the polygenic origins of VEO-IBD in a cohort with a high proportion of Hispanic patients.

Methods: Patients with VEO-IBD who underwent whole exome sequencing at our center were included. Genes were categorized as genes of interest (GOIs) (129 genes previously described to be associated with VEO-IBD) or non-GOIs. VEO-IBD "susceptibility" single nucleotide variants (SNVs) were identified through enrichment compared with gnomAD (Genome Aggregation Database) and ALFA (Allele Frequency Aggregator) and were scored …

Foundation Model Of Electronic Medical Records For Adaptive Risk Estimation, Pawel Renc, Michal K Grzeszczyk, Nassim Oufattole, Deirdre Goode, Yugang Jia, Szymon Bieganski, Matthew B A Mcdermott, Jaroslaw Was, Anthony E Samir, Jonathan W Cunningham, David W Bates, Arkadiusz Sitek

Faculty, Staff and Students Publications

Background: Hospitals struggle to predict critical outcomes. Traditional early warning systems, like NEWS and MEWS, rely on static variables and fixed thresholds, limiting their adaptability, accuracy, and personalization.

Methods: We previously developed the Enhanced Transformer for Health Outcome Simulation (ETHOS), an artificial intelligence (AI) model that tokenizes patient health timelines (PHTs) from electronic health records and uses transformer-based architectures to predict future PHTs. ETHOS is a versatile framework for developing a wide range of applications. In this work, we develop the Adaptive Risk Estimation System (ARES) that leverages ETHOS to compute dynamic, personalized risk probabilities for clinician-defined critical events. ARES …