Medicine and Health Sciences Commons^™

Building A Pre-Surgical Multiparametric-Mri-Based Morphologic, Qualitative, Semiquantitative, First And High-Order Radiomic Predictive Treatment Response Model For Undifferentiated Pleomorphic Sarcoma To Replace Recist, Raul F Valenzuela, Elvis Duran-Sierra, Mathew Antony, Behrang Amini, Sam Lo, Keila E Torres, Robert S Benjamin, Jingfei Ma, Ken-Pin Hwang, R Jason Stafford, Dejka Araujo, Andrew J Bishop, Ravin Ratan, Wei-Lien Wang, Jossue Espinoza, Pia V Valenzuela, Chengyue Wu, John E Madewell, William A Murphy, Colleen M Costelloe

Faculty, Staff and Student Publications

Background: Undifferentiated pleomorphic sarcoma (UPS) is the largest subgroup of soft-tissue sarcomas. It demonstrates post-therapeutic hemosiderin deposition, granulation tissue formation, fibrosis, and calcification. Our research aims to establish the multiparametric MRI (mp-MRI) value for predicting UPS treatment response.

Methods: An IRB-approved retrospective study included 33 extremity UPS patients with pre-operative mp-MRI, including diffusion-weighted imaging (DWI), contrast-enhanced susceptibility-weighted imaging (CE-SWI), and perfusion-weighted imaging with dynamic contrast-enhancement (PWI/DCE), and surgical resection between February 2021 and May 2023. Lesions were visually classified on CE-SWI into one of 6 morphology patterns. On PWI/DCE, lesions were classified into one of 6 patterns, and time-intensity curves …

Correction: A Mapping Review And Critique Of The Literature On Translation, Dissemination, And Implementation Capacity Building Initiatives For Different Audiences, Ana A Baumann, Danielle R Adams, Laura-Mae Baldwin, Rachel G Tabak, Sara Malone, Maura M Kepper, Anita D Misra-Hebert, Kathleen R Stevens, Maria E Fernandez, Sunil Kripalani

Faculty, Staff and Student Publications

This corrects the article "A mapping review and critique of the literature on translation, dissemination, and implementation capacity building initiatives for different audiences", 34.

The Dynamic Immune Behavior Of Primary And Metastatic Ovarian Carcinoma, Elaine Stur, Fuduan Peng, Pang-Ning Teng, Emine Bayraktar, Min Hu, Sara Corvigno, David J Brown, Sanghoon Lee, Kathleen N Moore, Nicholas W Bateman, Kathleen M Darcy, George L Maxwell, Thomas P Conrads, Nidhi Sahni, Ignacio Vázquez-García, Sohrab P Shah, Joseph Celestino, Nicole D Fleming, Nicholas E Navin, Linghua Wang, Anil K Sood

Faculty, Staff and Student Publications

Patients with high-grade serous ovarian carcinoma (HGSC) are usually diagnosed with advanced-stage disease, and the tumors often have immunosuppressive characteristics. Together, these factors are important for disease progression, drug resistance, and mortality. In this study, we used a combination of single-cell sequencing and spatial transcriptomics to identify the molecular mechanisms that lead to immunosuppression in HGSC. Primary tumors consistently showed a more active immune microenvironment than did omental tumors. In addition, we found that untreated primary tumors were mostly populated by dysfunctional CD4 and CD8 T cells in later stages of differentiation; this, in turn, was correlated with expression changes …

Tfcp2 Fusion-Positive Rhabdomyosarcomas: A Report Of 10 Cases And A Review Of The Literature, Madison P Ginn, Ryan A Denu, Davis R Ingram, Khalida M Wani, Alexander J Lazar, Douglas J Harrison, Michael S Nakazawa, Anthony P Conley, Shreyaskumar Patel, John Andrew Livingston

Faculty, Staff and Student Publications

Background/Objectives: The fusion of the TFCP2 gene with either EWSR1 or FUS typically results in a spindle cell and/or epithelioid variant of rhabdomyosarcoma. This is an ultra-rare type of sarcoma, with most of our knowledge about these coming from case reports and small case series. Herein, we describe the clinical characteristics and treatment course of 10 patients with TFCP2 fusion sarcomas.

Methods: We identified 10 patients in our hospital system with TFCP2 fusion sarcomas and 43 previously reported cases in the literature. We assessed primary tumor characteristics, treatment regimens, and survival rates among all cases.

Results: We find that …

Acute Brcaness Induction And Ar Pathway Blockage Through Cdk12/7/9 Degradation Enhances Parp Inhibitor Sensitivity In Prostate Cancer, Fu Gui, Baishan Jiang, Jie Jiang, Zhixiang He, Takuya Tsujino, Tomoaki Takai, Seiji Arai, Celine Pana, Jens Köllermann, Gary Andrew Bradshaw, Robyn Eisert, Marian Kalocsay, Anne Fassl, Steven P Balk, Adam S Kibel, Li Jia

Faculty, Staff and Student Publications

Current treatments for advanced prostate cancer (PCa) primarily target the androgen receptor (AR) pathway. However, the emergence of castration-resistant prostate cancer (CRPC) and resistance to AR pathway inhibitors (APPIs) remains ongoing challenges. Here, we present BSJ-5-63, a proteolysis-targeting chimera (PROTAC) targeting cyclin-dependent kinases (CDKs) CDK12, CDK7, and CDK9, offering a multipronged approach to CRPC therapy. BSJ-5-63 degrades CDK12, diminishing BRCA1 and BRCA2 expression and inducing a sustained "BRCAness" state. This sensitizes cancer cells to PARP inhibitors (PARPis) regardless of their homologous recombination repair (HRR) status. Furthermore, CDK7 and CDK9 degradation attenuates AR signaling, enhancing its therapeutic efficacy. Preclinical studies, including …

A Pioneering Artificial Intelligence Tool To Predict Treatment Outcomes In Ovarian Cancer Via Diagnostic Laparoscopy, Xiaotian Ma, Yu-Chun Hsu, Amma Asare, Kai Zhang, Deanna Glassman, Katelyn F Handley, Katherine Foster, Khwahish Sharma, Shannon Westin, Amir Jazaeri, Nicole D Fleming, Pratip K Bhattacharya, Xiaoqian Jiang, Anil K Sood, Shayan Shams

Faculty, Staff and Student Publications

Ovarian cancer is associated with high rates of patient mortality and morbidity. Laparoscopic assessment of tumor localization can be used for treatment planning in newly diagnosed high-grade serous ovarian carcinoma (HGSOC). While spread to multiple intra-abdominal areas is correlated with worse outcomes, whether other morphological tumor differences are also associated with patient outcomes is unknown. Given the large volume of visual information in laparoscopic videos, we investigated whether deep-learning models can capture implicit features and predict treatment outcomes. We developed a novel deep-learning framework using pre-treatment laparoscopic images to assess clinical outcomes following upfront standard treatment, defined as short progression-free …

High-Grade Astrocytoma With Piloid Features: A Single-Institution Case Series And Literature Review, Eric A Goethe, Subhiksha Srinivasan, Swaminathan Kumar, Sujit S Prabhu, Maria A Gubbiotti, Sherise D Ferguson

Faculty, Staff and Student Publications

High-grade astrocytoma with piloid features (HGAP) is a recently described primary brain tumor and the first requiring a specific methylation pattern for diagnosis, as its histologic features are often compatible with other tumors such as glioblastoma (GBM). Characterized by molecular alterations in CDKN2A/B, NF1, BRAF, FGFR1, and ATRX, they may be located anywhere in the CNS but show a predilection for the posterior fossa. Reports are limited to retrospective case series, and the standard of care is not yet established. We performed a retrospective review of electronic medical records of all patients with HGAP at our institution. Records were queried …

Dual Targeting Of Ezh2 And Ezh1 Drives Exit Of Leukemia Stem Cells From Quiescence And Potentiates Chemotherapy In Acute Myeloid Leukemia, Hiroki Akiyama, Yuki Nishida, Kyung Hee Chang, Andrea D Bedoy, Muharrem Muftuoglu, Wencai Ma, Mahesh Basyal, Zoe Hirschi, Daisuke Honma, Shinji Tsutsumi, Jing Wang, Weiguo Zhang, Xuelin Huang, Raajit K Rampal, Olalekan O Oluwole, Dale Lee Bixby, Naval G Daver, Michael Andreeff

Faculty, Staff and Student Publications

No abstract provided.

Idh Status Dictates Ohsv Mediated Metabolic Reprogramming Affecting Anti-Tumor Immunity, Upasana Sahu, Matthew P Mullarkey, Sara A Murphy, Joshua C Anderson, Vasanta Putluri, Abu Hena Mostafa Kamal, Jun Hyoung Park, Tae Jin Lee, Alexander L Ling, Benny A Kaipparettu, Ashok Sharma, Nagireddy Putluri, Pamela L Wenzel, Christopher D Willey, E Antonio Chiocca, James M Markert, Balveen Kaur

Faculty, Staff and Student Publications

Identification of isocitrate dehydrogenase (IDH) mutations has uncovered the crucial role of metabolism in gliomagenesis. Oncolytic herpes virus (oHSV) initiates direct tumor debulking by tumor lysis and activates anti-tumor immunity, however, little is known about the role of glioma metabolism in determining oHSV efficacy. Here we identify that oHSV rewires central carbon metabolism increasing glucose utilization towards oxidative phosphorylation and shuttling glutamine towards reductive carboxylation in IDH wildtype glioma. The switch in metabolism results in increased lipid synthesis and cellular ROS. PKC induces ACSL4 in oHSV treated cells leading to lipid peroxidation and ferroptosis. Ferroptosis is critical to launch an …

Impact Of Antidiabetic Medication Type On A New Episode Of Depression: A Retrospective Cohort Study In Texas, Usa, Lin-Na Chou, Mukaila A Raji, Holly M Holmes, Yong-Fang Kuo

Faculty, Staff and Student Publications

Objectives: To examine the associations between antidiabetic medication type and a new episode of depression using 100% Texas Medicare database during 2009 and 2018.

Design: A retrospective cohort study.

Setting: A population-based study using the Texas Medicare data.

Interventions: 11 common antihyperglycaemic medication types, alone and in combinations: metformin-only, five non-metformin-containing regimens (dipeptidyl peptidase-4 inhibitor (DPP4i) only, sulfonylureas (SU) only, thiazolidinediones (TZD) only, SU/DPP4i and SU/TZD) and five metformin-containing combination treatments (metformin/DPP4i, metformin/SU, metformin/TZD, metformin/SU/DPP4i and metformin/SU/TZD).

Participants: This study included 59 057 type 2 diabetes (T2D) patients from a cohort of Texas Medicare beneficiaries who were aged ≥66 years, …

Dual Implants For Geriatric Distal Femur Fractures Results In Greater Healthy Days At Home, Makoa Mau, Tyler Thorne, Cole Payne, Kaleb Roach, Reese Svetgoff, Patrick J Kellam, Graham J Dekeyser, Stephen J Warner, Lucas S Marchand, Justin Haller

Faculty, Staff and Student Publications

Objectives: To compare Healthy Days At Home (HDAH90) within 90 days of hospital discharge after single implant (SI) or dual implant (DI) fixation in geriatric distal femur fractures.

Methods: Design: Retrospective Review.

Setting: Three Level I Trauma Centers.

Patient selection criteria: Geriatric (age ≥ 60 years) distal femur fracture patients (OTA/AO 33 A, C) operatively treated with SI (lateral plate or retrograde intramedullary nail (IMN)) or DI (two plates or plate and IMN) between January 2018-January 2024 were included.

Outcome measures and comparisons: The primary outcome was HDAH90, which was calculated from date of surgery to 90 days follow-up and …

Retrospective Analysis Of Cement Extravasation Rates In Vertebroplasty, Kyphoplasty, And Bone Tumor Radiofrequency Ablation, Soun Sheen, Prit Hasan, Xiaowen Sun, Jian Wang, Claudio Tatsui, Kent Nouri, Saba Javed

Faculty, Staff and Student Publications

Background: Percutaneous vertebral augmentation techniques, including vertebroplasty, kyphoplasty, and bone tumor radiofrequency ablation (BT-RFA), are commonly used to treat painful vertebral compression fractures (VCFs). While generally safe and effective, they carry risks, including cement extravasation, which can lead to pulmonary embolism or spinal cord compression. This study aims to compare the rate of cement extravasation across different vertebral augmentation techniques and identify potential risk factors.

Methods: A retrospective cohort study was conducted at a comprehensive cancer center on 1002 procedure encounters in 888 patients who underwent vertebral augmentation for painful VCFs. Data were collected on patient demographics, fracture pathology, procedure …

Development And Validation Of A Dynamic Real-Time Risk Prediction Model For Intensive Care Units Patients Based On Longitudinal Irregular Data: Multicenter Retrospective Study, Zhuo Zheng, Jiawei Luo, Yingchao Zhu, Lei Du, Lan Lan, Xiaobo Zhou, Xiaoyan Yang, Shixin Huang

Faculty, Staff and Student Publications

Background: Timely and accurate prediction of short-term mortality is critical in intensive care units (ICUs), where patients' conditions change rapidly. Traditional scoring systems, such as the Simplified Acute Physiology Score and Acute Physiology and Chronic Health Evaluation, rely on static variables collected within the first 24 hours of admission and do not account for continuously evolving clinical states. These systems lack real-time adaptability, interpretability, and generalizability. With the increasing availability of high-frequency electronic medical record (EMR) data, machine learning (ML) approaches have emerged as powerful tools to model complex temporal patterns and support dynamic clinical decision-making. However, existing models are …

Ensemble Learning With Explainable Ai For Improved Heart Disease Prediction Based On Multiple Datasets, Shahid Mohammad Ganie, Pijush Kanti Dutta Pramanik, Zhongming Zhao

Faculty, Staff and Student Publications

Heart disease is one of the leading causes of death worldwide. Predicting and detecting heart disease early is crucial, as it allows medical professionals to take appropriate and necessary actions at earlier stages. Healthcare professionals can diagnose cardiac conditions more accurately by applying machine learning technology. This study aimed to enhance heart disease prediction using stacking and voting ensemble methods. Fifteen base models were trained on two different heart disease datasets. After evaluating various combinations, six base models were pipelined to develop ensemble models employing a meta-model (stacking) and a majority vote (voting). The performance of the stacking and voting …

Vaccination Schedules Recommended By The Centers For Disease Control And Prevention: From Human-Readable To Machine-Processable, Xia Jing, Hua Min, Yang Gong, Mytchell A Ernst, Aneesa Weaver, Chloe Crozier, David Robinson, Dean F Sittig, Paul G Biondich, Samuil Orlioglu, Akash Shanmugan Boobalan, Kojo Abanyie, Richard D Boyce, Adam Wright, Christian Nøhr, Timothy D Law, Arild Faxvaag, Lior Rennert, Ronald W Gimbel

Faculty, Staff and Student Publications

Background: Reusable, machine-processable clinical decision support system (CDSS) rules have not been widely achieved in the medical informatics field. This study introduces the process, results, challenges faced, and lessons learned while converting the United States of America Centers for Disease Control and Prevention (CDC)-recommended immunization schedules (2022) to machine-processable CDSS rules.

Methods: We converted the vaccination schedules into tabular, charts, MS Excel, and clinical quality language (CQL) formats. The CQL format can be automatically converted to a machine-processable format using existing tools. Therefore, it was regarded as a machine-processable format. The results were reviewed, verified, and tested.

Results: We have …

Tobacco Smoking Functional Networks: A Whole-Brain Connectome Analysis In 24 539 Individuals, Yezhi Pan, Chuan Bi, Zhenyao Ye, Hwiyoung Lee, Jiaao Yu, Luba Yammine, Tianzhou Ma, Peter Kochunov, L Elliot Hong, Shuo Chen

Faculty, Staff and Student Publications

Introduction: Nicotine addiction, a multifaceted neuropsychiatric disorder, profoundly impacts brain functions through interactions with neural pathways. Despite its significance, the impact of tobacco smoking on the whole-brain functional connectome remains largely unexplored.

Aims and methods: We conducted a whole-brain analysis on 24 539 adults aged 40 and above from the United Kingdom Biobank cohort. Subjects were categorized into individuals who use nicotine and those who do not use nicotine based on current and chronic tobacco smoking information. Functional connectivity was assessed using resting-state functional magnetic resonance imaging. We employed a network analysis method to assess the systematic effects of tobacco …

Can The Discovery Of High-Impact Diagnostics Be Improved By Matching The Sampling Rate Of Clinical Diagnostics To The Frequency Domain Of Diagnostic Information?, Steven W Millward, Peng Wei, David Piwnica-Worms, Seth T Gammon

Faculty, Staff and Student Publications

Over the past 30 years, academic and industrial research investigators have developed molecular reporters to visualize cell death in complex biological systems. In parallel, clinical researchers, chemists, biochemists, and molecular biologists have endeavored to translate these molecular tools into clinical imaging agents. Despite these efforts, there are no clinically approved imaging methodologies with which to image cell death consistently and quantitatively. One reason may reside in the intrinsic mismatch between the sampling frequency of translational molecular imaging and the biochemical kinetics that define cell death. Beyond cell death imaging, many active research programs are now attempting to create translational diagnostic …

Swi/Snf Complex-Mediated Znf410 Cooperative Binding Maintains Chromatin Accessibility And Enhancer Activity, Siyuan Xu, Chuxuan Peng, Ren Ren, Haowen Lu, Han Zhao, Sijian Xia, Yijie Shen, Bin Xu, Haoyue Zhang, Xiaodong Cheng, Gerd A Blobel, Xianjiang Lan

Faculty, Staff and Student Publications

The clustering of multiple transcription factor binding sites (TFBSs) for the same TF has proved to be a pervasive feature of cis-regulatory elements in the eukaryotic genome. However, the contribution of binding sites within the homotypic clusters of TFBSs (HCTs) to TF binding and target gene expression remains to be understood. Here, we characterize the CHD4 enhancers that harbor unique functional ZNF410 HCTs genome wide. We uncover that ZNF410 controls chromatin accessibility and activity of the CHD4 enhancer regions. We demonstrate that ZNF410 binds to the HCTs in a collaborative fashion, further conferring transcriptional activation. In particular, three ZNF410 motifs …

Mandibular Condylar Cartilage In Development And Diseases: A Pthrp-Centric View, Chiaki Tsutsumi-Arai, Amy Tran, Yuki Arai, Wanida Ono, Noriaki Ono

Faculty, Staff and Student Publications

The mandibular condylar cartilage (MCC) is a dual-function component of the temporomandibular joint (TMJ), acting as both articular cartilage for jaw movement and growth cartilage for vertical growth of the mandibular condyle. Parathyroid hormone-related protein (PTHrP) plays a critical role in orchestrating chondrogenesis in the long bone, and its importance is also highlighted in both MCC development and TMJ function. Here, we discuss the role of PTHrP in the development, growth and diseases of the MCC. PTHrP is a key morphogen in the MCC that regulates chondrogenesis by promoting chondrocyte proliferation and preventing premature hypertrophic differentiation. Exclusively expressed in the …

Trends In Celecoxib Prescribing: A Single Institution 16-Month Review, Ivo H Cerda, Helen Jung, Maria C Guerrero, Rodrigo Diez Tafur, Robert Jason Yong, Christopher L Robinson, Jamal J Hasoon

Faculty, Staff and Student Publications

Background/Objectives: Celecoxib, a COX-2 selective nonsteroidal anti-inflammatory drug (NSAID), is widely prescribed for pain management due to its efficacy and improved gastrointestinal safety profile compared to traditional NSAIDs. Understanding prescription trends and their comparison to other NSAIDs provides valuable insight into prescribing behaviors in clinical settings.

Methods: This retrospective study analyzed celecoxib prescriptions written by three pain management physicians in a single institution over a 16-month period from 1 January 2023 to 30 April 2024. Prescription data were collected and grouped into four 4-month intervals to assess temporal trends. Additionally, we compared celecoxib prescriptions to other commonly prescribed NSAIDs, including …

Changes Of Eeg Beta Band Power And Functional Connectivity During Spaceflight: A Retrospective Study, Adrián Quivira-Lopesino, María Sevilla-García, Pablo Cuesta, Sandra Pusil, Ricardo Bruña, Patrique Fiedler, Ana Maria Cebolla, Guy Cheron, Michael Funke, Fernando Maestu

Faculty, Staff and Student Publications

Spaceflight exposes astronauts to unique conditions like microgravity, which may affect brain function, though it remains underexplored compared to other physiological systems. Astronauts often report temporary neurological symptoms, such as disorientation, visual disturbances, and motor issues, potentially linked to structural and electrophysiological brain changes. To investigate this, electroencephalography (EEG) is a reliable tool to study brain activity in space, measuring oscillatory activity and functional connectivity (FC). This study analyzed EEG data from five male astronauts during three stages: pre-flight, during low Earth orbit (LEO), and post-flight in a 2-min task-free eyes-closed (EC) condition followed by another 2-min of eyes-open (EO) …

Incident Hearing Loss And Subsequent Risk Of Dementia: The Health And Retirement Study 2010-2018, Jingkai Wei, Youngran Kim, Yike Li, Donglan Zhang, Casey Crump

Faculty, Staff and Student Publications

Background and Objectives

Research Design and Methods

Correction: 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

No abstract provided.

Rnase1-Driven Alk-Activation Is An Oncogenic Driver And Therapeutic Target In Non-Small Cell Lung Cancer, Zhengyu Zha, Chunxiao Liu, Meisi Yan, Cong Chen, Cheng Yu, Yaohui Chen, Chenhao Zhou, Lu Li, Yi-Chuan Li, Hiro Yamaguchi, Leiguang Ye, Tong Liu, Ying-Nai Wang, Heng-Huan Lee, Wen-Hao Yang, Li-Chuan Chan, Baozhen Ke, Jennifer L Hsu, Lieming Ding, Dong Ji, Peng Pan, Yiran Meng, Yue Pu, Lunxu Liu, Mien-Chie Hung

Faculty, Staff and Student Publications

Targeted therapy has achieved significant success in the treatment of non-small cell lung cancer (NSCLC), particularly in patients harboring common oncogenic driver mutations such as EGFR, KRAS, and ALK rearrangement. However, ~35-50% of NSCLC patients without tyrosine kinase mutation or rearrangement (non-mutated) cannot benefit from these targeted treatments, highlighting the urgent need for novel therapeutic strategies for this patient population. In this study, we report a non-canonical role of human secretory ribonuclease 1 (RNase1), which binds to and activates wild-type ALK in lung cancer cells, thereby triggering its downstream signaling pathway. RNase1-driven ALK-activation (RDAA) cells exhibit enhanced cell proliferation, migration, …

Association Between B-Cell Marker Expression And Runx1 Lesions In Acute Myeloid Leukemia, Beyond Runx1::Runx1t1 Fusion: Diagnostic Pitfalls With Mixed-Phenotype Acute Leukemia—B/Myeloid, Giby V George, Malgorzata Kajstura, Audrey N Jajosky, Hong Fang, Fatima Zahra Jelloul, Andrew G Evans, W Richard Burack, John M Bennett, L Jeffrey Medeiros, Wei Wang, Siba El Hussein

Faculty, Staff and Student Publications

Acute myeloid leukemia (AML) with RUNX1::RUNX1T1 fusion is well known to often demonstrate aberrant upregulation of CD19 expression. We studied the clinicopathologic and genetic features of 16 cases of AML with various RUNX1 lesions, including mutations, copy number gains, and translocations other than fusions with RUNX1T1. Most of these cases were classified as AML-myelodysplasia-related or AML-post-cytotoxic therapy based on the cytogenetic and molecular work-up. These neoplasms showed partial expression of one or more B-cell antigens by flow cytometry and/or immunohistochemistry, fulfilling the criteria for mixed-phenotype acute leukemia (MPAL)-B/myeloid (i.e., ≥20% blasts expressing B and myeloid lineage antigens) …

Enriched Pathways In Gut Microbiome Predict Response To Immune Checkpoint Inhibitor Treatment Across Demographic Regions And Various Cancer Types, Xunhui Cai, Jennifer Y Cho, Lijun Chen, Yufeng Liu, Fenghu Ji, Katia Salgado, Siyi Ge, Dehua Yang, Hui Yu, Jianbo Shao, P Andrew Futreal, Boris Sepesi, Don Gibbons, Yaobing Chen, Guoping Wang, Chao Cheng, Meng Wu, Jianjun Zhang, Ansel Hsiao, Tian Xia

Faculty, Staff and Student Publications

Understanding the effect of gut microbiota function on immune checkpoint inhibitor (ICI) responses is urgently needed. Here, we integrated 821 fecal metagenomes from 12 datasets to identify differentially abundant genes and construct random forest models to predict ICI response. Gene markers demonstrated excellent predictive performance, with an average area under the curve (AUC) of 0.810. Pathway analyses revealed that quorum sensing (QS), ABC transporters, flagellar assembly, and amino acid biosynthesis pathways were enriched between responders (R) and non-responders (NRs) across 12 datasets. Furthermore,

Primary Care Telehealth In A Dynamic Healthcare Environment From Digital Divide To Healthcare Outcomes, Yunxi Zhang, Lincy S Lal, Saurabh Chandra, John Michael Swint

Faculty, Staff and Student Publications

With expanded telehealth availability in primary care, its impact on quality of care and associated costs remains debated. Analyzing 199,829 Medicare beneficiaries in Mississippi (2019-2021), we found telehealth utilization associated with significant sociodemographic disparities, reduced inpatient admissions, and lower 30-day readmissions. By accounting for primary care utilization, our findings suggest that the higher absolute costs observed among telehealth users may reflect underlying healthcare needs rather than telehealth utilization.

Reduced Venetoclax Exposure To 7 Days Vs Standard Exposure With Hypomethylating Agents In Newly Diagnosed Aml Patients, Christophe Willekens, Alexandre Bazinet, Samy Chraibi, Alex Bataller, Justine Decroocq, Naszrin Arani, Benjamin Carpentier, Caitlin Rausch, Delphine Lebon, Abhishek Maiti, Nicolas Gauthier, Nicholas Short, Sarah Bonnet, Koji Sasaki, Sabine Khalife-Hachem, Mahesh Swaminathan, Jean-Baptiste Micol, Florence Pasquier, Christophe Marzac, Damien Roos-Weil, Laurent Pascal, Naval Daver, Tapan Kadia, Didier Bouscary, Farhad Ravandi, Arnaud Pages, Hagop Kantarjian, Stéphane De Botton, Courtney Dinardo

Faculty, Staff and Student Publications

Hypomethylating agent (HMA) plus venetoclax (VEN) regimens are standard of care in patients with acute myeloid leukemia (AML) ineligible for intensive chemotherapy. While the VEN label recommends continuous 28-day cycles, shortened VEN durations may induce similar response rates and improve tolerability. It is unknown how a VEN exposure reduced to 7 days during cycles compares to standard HMA + VEN. We retrospectively compared newly diagnosed AML patients treated with azacitidine (AZA) x 7 days plus VEN x 7 days ("7 + 7" regimen) from the first cycle (n = 82) vs patients treated with standard dose HMA + VEN (std-HMA/VEN) …

Humanized Saccharomyces Cerevisiae Provides A Facile And Effective Tool To Identify Damaging Human Variants That Cause Exosomopathies, Khondakar Sayef Ahammed, Milo B Fasken, Anita H Corbett, Ambro Van Hoof

Faculty, Staff and Student Publications

The RNA exosome is an evolutionarily conserved, multiprotein complex that is the major RNase in 3' processing and degradation of a wide range of RNAs in eukaryotes. Single amino acid changes in RNA exosome subunits cause rare genetic diseases collectively called exosomopathies. However, distinguishing disease-causing variants from nonpathogenic ones remains challenging, and the mechanism by which these variants cause disease is largely unknown. Previous studies have employed a budding yeast model of RNA exosome-linked diseases that relies on mutating the orthologous yeast genes. Here, we develop a humanized yeast model of exosomopathies that allows us to unambiguously assess damaging effects …

Kras Mutation Detection By Liquid Biopsy For Pancreatic Ductal Adenocarcinoma, Mahmoud Yousef, Abdelrahman Yousef, Mark W Hurd, Ashwathy Pillai, Saikat Chowdhury, Rebecca Snyder, Mark Knafl, Ryan L Lewis, Paul M Roy, Mohammad Fanaeian, Sali Albarouki, Luca F Castelnovo, Jennifer Peterson, Brandon G Smaglo, Robert A Wolff, Shubham Pant, Jason Willis, Ryan Huey, Michael Overman, Ching-Wei Tzeng, Michael P Kim, Naruhiko Ikoma, Jess E Maxwell, Matthew H G Katz, Huamin Wang, Anirban Maitra, Eugene Koay, Ethan B Ludmir, Anthony Chen, Camila Lopez, Haoqiang Ying, John Paul Shen, Dan Zhao

Faculty, Staff and Student Publications

The clinical utility of liquid biopsy (LB) for pancreatic ductal adenocarcinoma (PDAC) remain understudied. Our single-institution cohort of 311 PDAC patients with non-tumor tissues informed LB found 81.2% positivity (N = 186) in metastatic cases and in 52.4% (N = 43) of localized disease. KRAS mutations were detected in 64.6% (N = 148) of metastatic cases and 16% (N = 13) for localized disease. Positive LB, especially KRAS mutation detection, is associated with worse overall survival (OS) in metastatic PDAC (median 14.5 vs. 31.3 months, HR = 2.7, 95%CI = 1.7-4.3, P <  0.0001). The positive concordance rates of KRAS and TP53 mutations were 63% and 68% in metastatic disease but only 7% (KRAS) and 33% (TP53) in localized disease, respectively. Among the 41 patients who underwent serial liquid biopsy testing, 25% tested positive after an initial negative result. LB detects therapeutically targetable mutations in 58.5% of PDAC patients and is associated with OS.