Medical Specialties Commons^™

Role And Use Of Race In Artificial Intelligence And Machine Learning Models Related To Health, Martin C Were, Ang Li, Bradley A Malin, Zhijun Yin, Joseph R Coco, Benjamin X Collins, Ellen Wright Clayton, Laurie L Novak, Rachele Hendricks-Sturrup, Abiodun O Oluyomi, Shilo Anders, Chao Yan

Faculty, Staff and Students Publications

The role and use of race within health-related artificial intelligence (AI) and machine learning (ML) models have sparked increasing attention and controversy. Despite the complexity and breadth of related issues, a robust and holistic framework to guide stakeholders in their examination and resolution remains lacking. This perspective provides a broad-based, systematic, and crosscutting landscape analysis of race-related challenges, structured around the AI and ML life cycle and framed through "points to consider" to support inquiry and decision-making.

Retrotransposon Methylation Profiles And Survival In Black Women With High-Grade Serous Ovarian Carcinoma, Christelle Colin-Leitzinger, Katherine A Lawson-Michod, Courtney E Johnson, Irma M Vlasac, Sean Yoder, Tania Mesa, Dana Roeber, Chad Huff, Michelle A T Hildebrandt, Kristin Haller, Anthony J Alberg, Elisa V Bandera, Melissa Bondy, Michele L Cote, Theresa Hastert, Edward S Peters, Paul D Terry, Andrew B Lawson, Andrew Berchuck, Brooke L Fridley, Jing-Yi Chern, Jennifer A Doherty, Jeffrey R Marks, Joellen M Schildkraut, Brock C Christensen, Lucas A Salas, Lauren C Peres

Faculty, Staff and Student Publications

Introduction: Retrotransposons (REs) constitute nearly half of the genome and include long terminal repeat (LTR) elements, Long INterspersed Elements (LINE), and Short INterspersed Elements (SINE). REs are typically silenced in somatic tissues via DNA methylation but can be reactivated through DNA hypomethylation, potentially impacting gene regulation. Here, we investigate genome-scale profiles of RE methylation in high-grade serous ovarian carcinoma (HGSOC) and associations with survival among Black women.

Methods: Methylation levels of LTR, LINE-1, and Alu (type of SINE) in 200 HGSOC tumors were predicted using a random forest approach and clustered using multiple consensus algorithms. Associations between RE methylation clusters …

Integrating Circulating Tumor Dna Into Clinical Management Of Colorectal Cancer: Practical Implications And Therapeutic Challenges, Nikhil Vojjala, Viktoriya Gibatova, Raj N Shah, Sakshi Singal, Rishab Prabhu, Geetha Krishnamoorthy, Karen Riggins, Nagaishwarya Moka

Faculty, Staff and Students Publications

The American Cancer Society estimates that over 152,000 new cases of colorectal cancer (CRC) were diagnosed in 2024, with more than 105,000 cases affecting the colon and 46,000 involving the rectum. CRC remains the second leading cause of cancer-related deaths in the United States, with an estimated 53,010 deaths in 2024. In the era of precision medicine, which incorporates molecular and environmental information into clinical decision-making, identifying patients harboring a deficiency in Deoxyribonucleic acid (DNA) repair allowed for targeted immunotherapies and significantly reduced CRC-related mortality. A significant advancement in this domain is the application of liquid biopsy, which has emerged …

Long-Term Testosterone Pellet Insertion In Women With Low Libido Shows No Evidence Of Erythrocytosis And A Minimal Side Effect Profile, Beatriz S Hernandez, Gal Saffati, Katherine A Lowrey, Amit Reddy, Bridget S Park, Jeffrey J Song, Gabrielle Lyon, Mohit Khera

Faculty, Staff and Students Publications

Background: Testosterone therapy for low libido in women has become increasingly prevalent in recent years. While numerous testosterone formulations exist and have been studied in women, there has been little data assessing the safety and efficacy of subcutaneous testosterone pellet use in this population. The primary objective of this study is to understand the biochemical effects and side effect profile of female patients who underwent testosterone pellet insertion in a clinical practice.

Methods: A retrospective chart review of female patients who underwent testosterone pellet insertion from 2009 to 2022 was undertaken. Women taking 75 and 100 mg testosterone pellets were …

Unveiling Spatial Heterogeneity In Medulloblastoma: A Multi-Omics Analysis Of Cellular State And Geographical Organization, Jiankang Li, Hailong Liu, Ziwei Wang, Jiao Zhang, Xuan Chen, Craig Daniels, Xiaochong Wu, Olivier Saulnier, Hiromichi Suzuki, Pasqualino De Antonellis, Alexandra Rasnitsyn, Winnie Ong, Evan Y Wang, Liam D Hendrikse, Yu Su, Yu Tian, Dongming Han, Ruohan Wang, Jialin Mo, Fei Liu, Kaiwen Deng, Dongyang Wang, Zhaoyang Feng, Yifei Jiang, Yanong Li, Yuting Ma, Zijia Liu, Meiyu Li, Peiyi Tian, Yanfeng Shi, Yong Jiang, Tao Yang, Shouwei Li, Jianfeng Liang, Jingchuan Wu, Ying Wang, Wanjing Zou, Yina Jiang, Lusheng Wang, Fang Chen, Xin Jin, Shuaicheng Li, Xiaoguang Qiu, Chunde Li, Ya Gao, Yujie Tang, Michael D Taylor, Tao Jiang

Faculty, Staff and Students Publications

Background: Despite numerous studies on medulloblastoma (MB) cell heterogeneity, the spatial characteristics of cellular states remain unclear.

Methods: We analyze single-nucleus and spatial transcriptomes and chromatin accessibility from human MB spanning four subgroups, to identify malignant cell populations and describe the spatial evolutionary trajectories. The spatial copy number variations (CNVs) patterns and niches were analyzed to investigate the cellular interactions.

Results: Three main malignant cell populations were identified, including progenitor-like, cycling, and differentiated populations. Gene signatures of cell populations strongly correlate to clinical outcomes. These tumor cell populations are geographically organized as stem-like and mature regions, highlighting their spatially heterogeneous …

Systematic Review Of Parkinsonism In Cerebrotendinous Xanthomatosis, Jennifer Hanson, Penelope E Bonnen

Faculty, Staff and Students Publications

Background: Cerebrotendinous Xanthomatosis (CTX) is a rare, inherited metabolic disease caused by pathogenic variants in CYP27A1. The clinical presentation of this progressive disease includes cognitive deficits, ataxia, peripheral neuropathy, and pyramidal signs, as well as bilateral cataracts and tendon xanthomas. In some cases, CTX also includes parkinsonism. The goals of this study are to develop a data source that provides improved characterization and awareness of parkinsonism in CTX.

Methods: We conducted a systematic review of the literature according to PRISMA guidelines to identify all published individuals diagnosed with CTX and parkinsonism. Clinical signs, imaging findings and treatment response to …

Lessons In Longevity From Blood Stem Cells Under Protein Stress, André Catic

Center on Aging Staff Publications

Blood stem cells are among the body's longest-living cells despite being highly vulnerable to proteotoxic damage, which accelerates their aging. To maintain protein homeostasis (proteostasis), hematopoietic stem cells (HSCs) employ mechanisms such as reduced translation rates, high chaperone activity, autophagy, and selective protein degradation. These strategies mitigate protein misfolding, maintain quiescence, and preserve regenerative potential. Disruptions in proteostasis can lead to the elimination of impaired HSCs through differentiation or apoptosis, ensuring the integrity of the stem cell pool. Due to the systemic impact of the blood on aging and its experimental and clinical accessibility, investigating HSC proteostasis provides insights into …

A Phase I Trial Of Evorpacept, Lenalidomide And Rituximab For Patients With B-Cell Non-Hodgkin Lymphoma, Paolo Strati, Lei Feng, Andrey Tyshevich, Darya Shavronskaya, Julia Alesse, Noel English, Elizabeth Sheehan, Nikita Syzrantsev, Alexander Nesmelov, Tony Z Zhuang, Dai Chihara, Jason R Westin, Sairah Ahmed, Luis E Fayad, Jared Henderson, Kylie Dent, Elizabeth Mcchesney, Sattva S Neelapu, Christopher R Flowers

Faculty, Staff and Student Publications

Introduction: SIRPα+ macrophages can mediate resistance to lenalidomide and rituximab (R2) in patients with B-cell non-Hodgkin lymphoma (B-NHL). Evorpacept (ALX148) is a novel CD47 blocker that abrogates interactions between lymphoma cells and SIRPα+ macrophages.

Methods: Adult patients with B-NHL who had received at least 2 prior lines of systemic therapy were included in this single arm phase I study (NCT05025800). Evorpacept was administered intravenously (IV), in a 28-day cycle, until progression, at two dose levels (DL): 30 mg/Kg on day (D) 1 and D15 (DL1), or 60 mg/Kg on day 1 (DL2); rituximab 375 mg/m2 IV was given …

Cell Type-Specific Purifying Selection Of Synonymous Mitochondrial Dna Variation, Caleb A Lareau, Patrick Maschmeyer, Yajie Yin, Jacob C Gutierrez, Ryan S Dhindsa, Anne-Sophie Gribling-Burrer, Sebastian Zielinski, Yu-Hsin Hsieh, Lena Nitsch, Veronika Dimitrova, Benan Nalbant, Frank A Buquicchio, Tsion Abay, Robert R Stickels, Jacob C Ulirsch, Patrick Yan, Fangyi Wang, Zhuang Miao, Katalin Sandor, Bence Daniel, Vincent Liu, Paul L Mendez, Petra Knaus, Manpreet Meyer, William J Greenleaf, Anshul Kundaje, Redmond P Smyth, Mathias Munschauer, Leif S Ludwig, Ansuman T Satpathy

Duncan NRI Faculty and Staff Publications

While somatic variants are well-characterized drivers of tumor evolution, their influence on cellular fitness in nonmalignant contexts remains understudied. We identified a mosaic synonymous variant (m.7076A > G) in the mitochondrial DNA (mtDNA)-encoded cytochrome c-oxidase subunit 1 (MT-CO1, p.Gly391=), present at homoplasmy in 47% of immune cells from a healthy donor. Single-cell multiomics revealed strong, lineage-specific selection against the m.7076G allele in CD8+ effector memory T cells, but not other T cell subsets, mirroring patterns of purifying selection of pathogenic mtDNA alleles. The limited anticodon diversity of mitochondrial tRNAs forces m.7076G translation to rely on wobble pairing, unlike the Watson-Crick-Franklin pairing …

Sleep Drive, Not Total Sleep Amount, Increases Seizure Risk, Vishnu Anand Cuddapah, Cynthia T Hsu, Fernanda Valle Sirias, Yongjun Li, Hrishit M Shah, Christopher Saul, Samantha Killiany, Camilo Guevara, Joy Shon, Zhifeng Yue, Gabrielle L Gionet, Mary E Putt, Amita Sehgal

Duncan NRI Faculty and Staff Publications

Sleep loss has been associated with increased seizure risk since antiquity. Using automated video detection of spontaneous seizures in Drosophila epilepsy models, we show that seizures worsen only when sleep restriction raises homeostatic "sleep drive," not simply when total sleep amount falls. This is supported by the paradoxical finding that acute activation of sleep-promoting circuits worsens seizures, because it increases sleep drive without changing sleep amount. Sleep-promoting circuits become hyperactive after sleep loss and are associated with increased whole-brain activity. During sleep restriction, optogenetic inhibition of sleep-promoting circuits to reduce sleep drive protects against seizures. Downregulation of the 5HT1A serotonin …

A Data Assimilation Framework For Predicting The Spatiotemporal Response Of High-Grade Gliomas To Chemoradiation, Hugo J M Miniere, David A Hormuth, Ernesto A B F Lima, Maguy Farhat, Bikash Panthi, Holly Langshaw, Mihir D Shanker, Wasif Talpur, Sara Thrower, Jodi Goldman, Sophia Ty, Caroline Chung, Thomas E Yankeelov

Faculty, Staff and Student Publications

Background: High-grade gliomas are highly invasive and respond variably to chemoradiation. Accurate, patient-specific predictions of tumor response could enhance treatment planning. We present a novel computational platform that assimilates MRI data to continually predict spatiotemporal tumor changes during chemoradiotherapy.

Methods: Tumor growth and response to chemoradiation was described using a two-species reaction-diffusion model of enhancing and non-enhancing regions of the tumor. Two evaluation scenarios were used to test the predictive accuracy of this model. In scenario 1, the model was calibrated on a patient-specific basis (n = 21) to weekly MRI data during the course of chemoradiotherapy. A data assimilation …

Structural Variants: Mechanisms, Mapping, And Interpretation In Human Genetics, Shruti Pande, Moez Dawood, Christopher M Grochowski

Faculty, Staff and Students Publications

Structural variations (SVs) represent genomic variations that involve breakage and rejoining of DNA segments. SVs can alter normal gene dosage, lead to rearrangements of genes and regulatory elements within a topologically associated domain, and potentially contribute to physical traits, genomic disorders, or complex traits. Recent advances in sequencing technologies and bioinformatics have greatly improved SV detection and interpretation at unprecedented resolution and scale. Despite these advances, the functional impact of SVs, the underlying SV mechanism(s) contributing to complex traits, and the technical challenges associated with SV detection and annotation remain active areas of research. This review aims to provide an …

Xpert Mtb/Rif Ultra Assay For Pulmonary Tuberculosis And Rifampicin Resistance In Adults And Adolescents, David J Horne, Jerry S Zifodya, Adrienne E Shapiro, Elizabeth Chandler Church, Jonah S Kreniske, Alexander W Kay, Katie Scandrett, Karen R Steingart, Yemisi Takwoingi

Faculty, Staff and Students Publications

Background: Xpert MTB/RIF Ultra (Xpert Ultra) is a molecular World Health Organization (WHO)-recommended rapid diagnostic test that simultaneously detects tuberculosis and rifampicin resistance. This review updates a comparative accuracy Cochrane review of Xpert MTB/RIF and Xpert Ultra as Xpert Ultra has replaced Xpert MTB/RIF.

Objectives: To determine the diagnostic accuracy of Xpert MTB/RIF Ultra (Xpert Ultra) for detecting pulmonary tuberculosis and rifampicin resistance in adults and adolescents with presumptive tuberculosis based on signs or symptoms or with an abnormal chest x-ray suggestive of tuberculosis.

Search methods: We searched seven databases including CENTRAL, MEDLINE, and Embase, plus two trial registers (ClinicalTrials.gov …

A Novel Microdosimetry-Based Formalism For Cell Survival Modelling Applicable To Hypofractionated Radiotherapy, Oleg N Vassiliev, Radhe Mohan

Faculty, Staff and Student Publications

Objectives

Hypofractionated radiotherapy requires reliable cell survival models for doses much higher than the standard 2 Gy, for which the linear-quadratic (LQ) model is not applicable. We developed an alternative approach applicable to both low doses and high doses used in hypofractionated treatments and radiobiological experiments.

Approach.

We combined a standard microdosimetric technique with a recently introduced non-LQ cell survival model. Our formulation accounts for cell damage by multi-track events involving any number of particles. This is necessary for modelling cell survival at therapeutic doses. We characterise each cell type by the size �� of the sensitive volume (SV) and …

Use Of Cholic Acid In Smith-Lemli-Opitz Syndrome (Slos): Real-World Patient Outcomes, Edwin Ferren, Paul R Hillman, Amy Kritzer, Joseph Ray, Alvaro Serrano, Hope Northrup, Paige Roberts, Rana Dutta, Tiziano Pramparo, Pamela Vig, Robert D Steiner

Faculty, Staff and Student Publications

Background: Smith-Lemli-Opitz Syndrome (SLOS) is an autosomal recessive disorder of cholesterol biosynthesis caused by biallelic pathogenic variants in DHCR7, which encodes the enzyme 7-dehydrocholesterol reductase (DHCR7). SLOS is a multisystemic disorder affecting various aspects of health, including growth, development, behavior, and quality of life, underscoring the need for safe, efficacious interventions that limit disease burden. DHCR7 enzyme deficiency leads to a "metabolic block" resulting in decreased cholesterol production and accumulation of its precursor 7-dehydrocholesterol and the secondary isomer 8-dehydrocholesterol. Reduced cholesterol synthesis, in turn, leads to decreased levels of cholic acid (CA), an endogenous bile acid synthesized from cholesterol and …

Melanoma Antigens In Pediatric Medulloblastoma Contribute To Tumor Heterogeneity And Species-Specificity Of Group 3 Tumors, Rebecca R J Collins, Rebecca R Florke Gee, Sima Tozandehjani, Tara Bayat, Maria Camila Hoyos Sanchez, Juan Sebastian Solano Gutierrez, Barbara Breznik, Anna K Lee, Samuel T Peters, Jon P Connelly, Shondra M Pruett-Miller, Martine F Roussel, Dinesh Rakheja, Heather S Tillman, Patrick Ryan Potts, Klementina Fon Tacer

Faculty, Staff and Student Publications

Medulloblastoma (MB) is the most malignant childhood brain cancer. Group 3 MB (G3 MB) subtype accounts for about 25% of MB and is associated with the worst outcomes. Herein, we report that more than half of G3 MB tumors express melanoma antigens (MAGEs), which are potential prognostic and therapeutic markers. MAGEs are cancer-testis antigens, aberrantly expressed in several adult cancers, and associated with poorer prognosis and therapy resistance; however, their role in pediatric cancers is mostly unknown. This study aimed to determine whether MAGEs are activated and important in pediatric MB. We obtained formalin-fixed paraffin-embedded tumor samples of 34 patients, …

Phosphoglycerate Mutase Regulates Treg Differentiation Through Control Of Serine Synthesis And One-Carbon Metabolism, Wesley H Godfrey, Judy J Lee, Shruthi Shanmukha, Kaho Cho, Xiaojing Deng, Chandra Shekar R Ambati, Vasanta Putluri, Abu Hena Mostafa Kamal, Paul M Kim, Nagireddy Putluri, Michael D Kornberg

Faculty, Staff and Students Publications

The differentiation and suppressive functions of regulatory CD4 T cells (Tregs) are supported by a broad array of metabolic changes, providing potential therapeutic targets for immune modulation. In this study, we focused on the regulatory role of glycolytic enzymes in Tregs and identified phosphoglycerate mutase (PGAM) as being differentially overexpressed in Tregs and associated with a highly suppressive phenotype. Pharmacologic or genetic inhibition of PGAM reduced Treg differentiation and suppressive function while reciprocally inducing markers of a pro-inflammatory, T helper 17 (Th17)-like state. The regulatory role of PGAM was dependent on the contribution of 3-phosphoglycerate (3 PG), the PGAM substrate, …

Dietary Lipids Induce Ppard And Bcl6 To Repress Macrophage Il-23 Induction After Intestinal Injury And Lps Exposure, Ashleigh M Gil, Daniel F Zegarra-Ruiz, Wan-Jung Wu, Kendra Norwood, Adrien Assie, Buck S Samuel, Angela M Major, Gretchen E Diehl, Andrea A Hill Mcalester

Faculty, Staff and Students Publications

Unresolved tissue damage is a common feature of Inflammatory Bowel Disease (IBD) that facilitates disease progression. Here, we showed that high animal fat diets (HFD), an environmental risk factor associated with IBD pathogenesis, suppress intestinal macrophage production of critical tissue repair responses after damage. This includes reduced IL-23 production, which drives downstream production of IL-22, which is needed for barrier repair. Indicating that dietary lipids interfere with responses to microbial molecules needed to induce barrier protective functions, we found oleic acid could directly suppress macrophage Il23a induction after lipopolysaccharide (LPS) treatment. Deleting the lipid transporter CD36 on macrophages restored the …

Adaptive Bayesian Clinical Trials: The Past, Present, And Future Of Clinical Research, Donald A Berry

Faculty, Staff and Student Publications

Background/Objectives: Decision-analytic Bayesian approaches are ideally suited for designing clinical trials. They have been used increasingly over the last 30 years in developing medical devices and drugs. A prototype trial is a bandit problem in which treating participants is as important as treating patients in clinical practice after the trial.

Methods: This article chronicles the use of the Bayesian approach in clinical trials motivated by bandit problems. It provides a comprehensive historical and practical review of Bayesian adaptive trials, with a focus on bandit-inspired designs.

Results: The 20th century saw advances in Bayesian methodology involving computer simulation. In the …

Distinct Clinicogenomic Features And Immunotherapy Associations In Pulmonary Sarcomatoid Carcinoma: A Multicenter Retrospective Study, Lingzhi Hong, Alessandro Di Federico, Bolun Liu, Alissa J Cooper, Joao V Alessi, Phoebe Clark, Waree Rinsurongkawong, Chingyi Young, Hui Li, Kang Qin, Muhammad Aminu, Valentina Santo, Yasir Elamin, Boris Sepesi, Jeff Lewis, Don L Gibbons, Ara A Vaporciyan, J Jack Lee, Xiuning Le, Jia Wu, Sinchita Roy-Chowdhuri, Mark J Routbort, P Andrew Futreal, John V Heymach, Mark M Awad, Adam J Schoenfeld, Jianjun Zhang, Biagio Ricciuti, Lei Deng, Natalie I Vokes

Faculty, Staff and Student Publications

Introduction: Pulmonary sarcomatoid carcinoma (PSC) is a rare NSCLC subtype with poor prognosis. Outcomes to immune checkpoint inhibitors (ICIs) and genomic features in PSC remain underexplored compared with other NSCLC subtypes.

Methods: Patients from three institutions and the National Cancer Database (NCDB) with metastatic NSCLC treated with ICI alone or with chemotherapy were identified. Clinicogenomics and treatment outcomes were compared across PSC, lung adenocarcinoma (LUAD), and lung squamous cell carcinoma (LUSC).

Results: We analyzed 4841 patients including 165 PSC cases treated with ICI-based therapy from three institutions and 201 PSC from NCDB. In MDACC, 65 (4.3%) were PSC, 1138 (75.1%) …

Human Ipsc-Based Breast Cancer Model Identifies S100p-Dependent Cancer Stemness Induced By Brca1 Mutation, Jingxin Liu, Cai Zhao, Jiahao Chen, Pengguihang Zeng, Qingjian Li, Ranran Dai, Xingqiang Lai, Wenqian Song, Jianing Chen, Xixi Zhu, Xinyi Liu, Jun Sun, Jia Wang, Peihang Fang, Tengfei Wang, Wenjie Chen, Diana Guallar, Nan Cao, Jianli Zhao, Shicheng Su, Andy Peng Xiang, Yi Arial Zeng, Jie Li, Junchao Cai, Dung-Fang Lee, Jinxin Bei, Yongliang Huo, Hai Hu, Shengbao Suo, Dong-Feng Huang, Jin Bai, Junjun Ding

Faculty, Staff and Student Publications

Breast cancer is the most common malignancy in females and remains the leading cause of cancer-related deaths for women worldwide. The cellular and molecular basis of breast tumorigenesis is not completely understood partly due to the lack of human research models which simulate the development of breast cancer. Here, we developed a method for generating functional mammary-like cells (MCs) from human-induced pluripotent stem cells (iPSCs). The iPSC-MCs closely resemble human primary MCs at cellular, transcriptional, and functional levels. Using this method, a breast cancer model was generated using patient-derived iPSCs harboring germline

Il-6 Predicts Cdk4/6 Inhibitor Resistance, Identifying Stat3 As A Target In Hr + /Her2-Negative Metastatic Breast Cancer, Nicole M Kettner, Tuyen N Bui, Juliana Navarro-Yepes, Sanaz Ghotbaldini, Bethanie Quintela, Catherine K Luo, Nghi Lam, Xiayu Rao, Akshara Singareeka Raghavendra, Yan Wang, Nancy Azizian, T Kris Eckols, Moses Makokha Kasembeli, Kurt Evans, Min Yi, Hannah Wingate, Jing Wang, Aysegul A Sahin, Funda Meric-Bernstam, Kelly K Hunt, Senthil Damodaran, David J Tweardy, Debu Tripathy, Khandan Keyomarsi

Faculty, Staff and Student Publications

Resistance to CDK4/6 inhibitors (CDK4/6i) is a major challenge in treating hormone receptor-positive, HER2-negative metastatic breast cancer. This study aimed to identify a biomarker predictive of resistance that could also serve as a therapeutic target. Circulating IL-6 levels in 166 patients significantly increased at progression, making IL-6 a non-invasive biomarker to predict CDK4/6i resistance. Knockdown of IL-6 re-sensitized resistant cells to palbociclib and endocrine therapy, underscoring IL-6's critical role in maintaining resistance. Patient-derived xenograft models from patients who progressed within 3 months versus ≥6 months of palbociclib therapy revealed distinct transcriptomic profiles, with later progressors exhibiting IL-6/STAT3 activation, epithelial-to-mesenchymal transition, …

Assessment Of Dnase Activity By Ratiometric Fluorescence Resonance Energy Transfer, Candace L Minchew, Vladimir V Didenko

Faculty, Staff and Students Publications

The present protocol describes a simple and sensitive ratiometric Förster resonance energy transfer (FRET) assay for the detection and quantitative assessment of DNase activity. Ratiometric FRET measurements make use of the ratio of donor and acceptor emission signals. The assay detects single-stranded DNA breaks using a staple-shaped, dual-tagged 38-mer FRET oligoprobe, employed as a real-time DNA cleavage sensor. The main application of the described approach is the quantitative assessment of the effects of reaction conditions, such as pH, temperature, and buffer composition, on DNase activity. Due to its ability to detect even minor and slow DNA cleavage, the assay is …

Adhd In Youth With Major Depressive Disorder In The Texas Youth Depression And Suicide Research Network (Tx-Ydsrn): Clinical Correlates And Moderators, Blake M Upshaw, Samuel D Spencer, Caitlin M Pinciotti, Vadym Zhyrov, Abu Minhajuddin, Ace A Castillo, Allyssa Abacan, Holli Slater, Rachel A Walker, Joseph C Blader, Sarah L Martin, Jeffrey D Shahidullah, Jair C Soares, Robert Andrew Harper, Madelyn Guerra, Lynnel C Goodman, Wayne K Goodman, Sarah M Wakefield, Madhukar H Trivedi, Eric A Storch

Faculty, Staff and Student Publications

Objective: Depression is a major public health concern with a 19% lifetime prevalence in youth, often precipitating other concerns, including suicidal behavior, poor school performance, and worsened peer relationships. ADHD is also common among youth and frequently presents alongside major depressive disorder (MDD), with this comorbidity associated with increased impairment. More research is needed to elucidate the clinical characteristics of this comorbidity (MDD + ADHD), especially as it relates to youth with MDD and no ADHD (MDD - ADHD). The present study examined the clinical correlates of MDD + ADHD in youth and the presence of an ADHD diagnosis as …

Imaging Efficacy And Safety Of Low Dose Intraventricular Tissue Plasminogen Activator In Aneurysmal Subarachnoid Hemorrhage: Case Series, Collin Liu, William W Wroe, Hussein A Zeineddine, Bryden Dawes, Michael Giordano, Aaron Mccabe, Ching-Jen Chen, Devin W Mcbride, Aaron M Gusdon, Huimahn A Choi, Spiros L Blackburn

Faculty, Staff and Student Publications

Introduction: Free hemoglobin's release into CSF from blood breakdown is a primary instigator of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH). Early clearance of subarachnoid blood with intrathecal (IT) fibrinolytics has shown potential to decrease incidence of DCI. However, the dosage of fibrinolytic needed is not known. We investigated the ability of low dose tissue plasminogen activator (tPA) to rapidly remove subarachnoid clot.

Material and methods: We performed a single center retrospective review of aSAH patients who received IT tPA. Dosing consistent with the CLEAR III trial for IVH was utilized-tPA (1 mg) administered every 8 h via …

Cancer Screening Uptake And Usual Source Of Care Among Hispanic Survivors Of Adolescent And Young Adult Cancer, Eunju Choi, Amy M Berkman, Clark R Andersen, John M Salsman, Andrea C Betts, Joel Milam, Kimberly A Miller, Susan K Peterson, Qian Lu, Christabel K Cheung, Lauren V Ghazal, J A Livingston, Michelle A T Hildebrandt, Susan K Parsons, David R Freyer, Michael E Roth

Faculty, Staff and Student Publications

Purpose: This study examines cancer screening rates and the usual source of care among Hispanic survivors of adolescent and young adult (AYA, aged 15-39) cancer, a group at increased risk for poor health outcomes, including secondary cancers.

Methods: National Health Interview Survey data were analyzed to identify Hispanic survivors of AYA cancer and Hispanic age- and sex-matched non-cancer controls. Breast, cervical, and colorectal screening (ever screened and up-to-date according to the U.S. Preventive Services Task Force recommendations) as well as reporting a usual source of care were compared among survivors and controls eligible for screening using multivariable logistic regressions.

Results: …

Minimal Ablative Margin Quantification Using Hepatic Arterial Versus Portal Venous Phase Ct For Colorectal Metastases Segmentation: A Dual-Center, Retrospective Analysis, Noreen S Siddiqi, Yuan-Mao Lin, Jessica Albuquerque Marques Silva, Gregor Laimer, Peter Schullian, Yannick Scharll, Alexandra M Dunker, Caleb S O'Connor, Kyle A Jones, Kristy K Brock, Reto Bale, Bruno C Odisio, Iwan Paolucci

Faculty, Staff and Student Publications

Objective: To compare the predictive value of minimal ablative margin (MAM) quantification using tumor segmentation on intraprocedural contrast-enhanced hepatic arterial (HAP) versus portal venous phase (PVP) CT on local outcomes following percutaneous thermal ablation of colorectal liver metastases (CRLM).

Methods: This dual-center retrospective study included patients undergoing thermal ablation of CRLM with intraprocedural preablation and postablation contrast-enhanced CT imaging between 2009 and 2021. Tumors were segmented in both HAP and PVP CT phases using an artificial intelligence-based auto-segmentation model and reviewed by a trained radiologist. The MAM was quantified using a biomechanical deformable image registration process. The area under the …

Survival-Inferred Fragility Of Statistical Significance In Phase Iii Oncology Trials, Alexander D Sherry, Yufei Liu, Pavlos Msaouel, Timothy A Lin, Alex Koong, Christine Lin, Joseph Abi Jaoude, Roshal R Patel, Ramez Kouzy, Molly B El-Alam, Avital M Miller, Mohannad Owiwi, Jonathan Ofer, David Bomze, Zachary R Mccaw, Tomer Meirson, Ethan B Ludmir

Faculty, Staff and Student Publications

In phase III oncology trials, superiority is defined by statistical significance using P thresholds. However, this approach has been criticized because P is continuous. Here, we reconstruct patient-level data for 230 phase III oncology trials to model the robustness of statistical significance by estimating the survival-inferred fragility index (SIFI), defined as the smallest number of patients changing arms that alters the statistical significance interpretation. The median SIFI was 8 patients (IQR 4-19), representing 1.4% of enrollments (IQR 0.7%-3%). As a continuous statistic, P-but not the significance interpretation-was correlated with SIFI. Moreover, overall survival endpoints were more fragile than surrogate endpoints. …

Feasibility Of Manufacturing And Antitumor Activity Of Til For Advanced Endometrial Cancers, Yongliang Zhang, Kathleen N Moore, Amir A Jazaeri, Judy Fang, Ilabahen Patel, Andrew Yuhas, Patrick Innamarato, Nathan Gilbert, Joseph W Dean, Behzad Damirchi, Joe Yglesias, Rongsu Qi, Michelle R Simpson-Abelson, Erwin Cammaart, Sean R R Hall, Hequn Yin

Faculty, Staff and Student Publications

Lifileucel, a tumor-infiltrating lymphocyte (TIL) cell therapy approved for advanced melanoma, demonstrates promise for treating other solid tumors, including endometrial cancer (EC). The current study evaluates the feasibility of manufacturing TILs from EC tumors using Iovance’s proprietary 22-day Gen2 manufacturing process. Key parameters, including TIL yield, viability, immune phenotype, T-cell receptor clonality, and cytotoxic activity, were assessed. Of the 11 EC tumor samples processed at research scale, 10 (91%) successfully generated >1 × 109 viable TIL cells, with a median yield of 1.1 × 1010 cells and a median viability of 82.8%. Of the four EC tumor samples processed at …

Machine-Learning Driven Strategies For Adapting Immunotherapy In Metastatic Nsclc, Maliazurina B Saad, Qasem Al-Tashi, Lingzhi Hong, Vivek Verma, Wentao Li, Daniel Boiarsky, Shenduo Li, Milena Petranovic, Carol C Wu, Brett W Carter, Girish S Shroff, Tina Cascone, Xiuning Le, Yasir Y Elamin, Mehmet Altan, Simon Heeke, Ajay Sheshadri, Joe Y Chang, Percy P Lee, Zhongxing Liao, Don L Gibbons, Ara A Vaporciyan, J Jack Lee, Ignacio I Wistuba, Cara Haymaker, Seyedali Mirjalili, David Jaffray, Justin F Gainor, Yanyan Lou, Alessandro Di Federico, Federica Pecci, Mark Awad, Biagio Ricciuti, John V Heymach, Natalie I Vokes, Jianjun Zhang, Jia Wu

Faculty, Staff and Student Publications

Immune checkpoint inhibitors (ICIs), either as monotherapy (ICI-Mono) or combined with chemotherapy (ICI-Chemo), improves survival in advanced non-small cell lung cancer (NSCLC). However, prospective guidance for choosing between these options remains limited, and single-feature biomarkers like PD-L1 prove inadequate. We develop a machine learning model using clinicogenomic data from four cohorts (MD Anderson n = 750; Mayo Clinic n = 80; Dana-Farber n = 1077; Stand Up To Cancer n = 393) to predict individual benefit from adding chemotherapy. Benefit scores are calculated using five distinct functions derived from 28 genomic and 6 clinical features. Our integrated model, A-STEP (Attention-based …