Medical Genetics Commons^™

Characterization Of Inflammatory Pseudotumors In A Large Animal Model Of Liver Cancer, Erik N K Cressman, Samantha Hicks, Natalie W Fowlkes, Danielle L Stolley, Maria Sophia Stenkamp

Faculty, Staff and Student Publications

Background: The development of relevant and robust large animal models of hepatocellular carcinoma is needed to test new therapeutic strategies for this disease. Transgenic approaches hold promise in addressing this complex problem. One such model, the Oncopig, has been reported to develop tumors of up to 4 cm in diameter within 7-14 days at sites of in situ vector inoculation. However, the resulting lesions reportedly contained an extensive inflammatory component that has not been evaluated in detail.

Methods: Herein, we describe our results from multiparametric characterization of the lesions generated using liver biopsy cores incubated in vector solution and replaced …

Defective Dna Damage Response Is A Targetable Therapeutic Vulnerability In Esr1 Mutant Breast Cancer, Sarah K Herzog, Jessica H Stevens, Guowei Gu, Sandra L Grimm, Kloma Cardoza, Autumn G M Hawkins, Hangqing Lin, Daniela Ramos, Amanda R Beyer, David G Edwards, Derek Dustin, Harry J Yang, Nicole Liang, Ashfia F Khan, Tasneem Bawa-Khalfe, Daniel J Mcgrail, Shiaw-Yih Lin, Cristian Coarfa, Suzanne A W Fuqua

Faculty, Staff and Student Publications

ESR1 mutations are the leading cause of endocrine therapy resistance and progression in ER-positive metastatic breast cancer. ESR1 mutations are detected in ~50% of metastatic breast cancer patients, and identification of effective targeted therapeutics are critically needed. Here, we identified enrichment of dysregulated replication stress and DNA damage responses in multiple ESR1 mutant models. Targeting the replication stress response utilizing checkpoint inhibition in combination with PARP inhibition synergistically suppressed growth, induced cell cycle arrest, and attenuated DNA replication. PARP inhibition blocked metastatic dissemination in vivo and reduced both PARP1 and ER-regulated protein expression. PARP trapping by olaparib treatment with or …

Modality-Agnostic, Patient-Specific Digital Twins Modeling Temporally Varying Digestive Motion, Jorge Tapias Gomez, Nishant Nadkarni, Lando S Bosma, Jue Jiang, Ergys D Subashi, William P Segars, James M Balter, Mert R Sabuncu, Neelam Tyagi, Harini Veeraraghavan

Faculty, Staff and Student Publications

No abstract provided.

Correction: Sadagopan Et Al Reduced Computed Tomography Scan Speed Improves Alignment Errors For Patients Undergoing Thoracic Stereotactic Body Radiation Therapy, Ramaswamy Sadagopan, Rachael M Martin-Paulpeter, Christopher R Peeler, Xiaochun Wang, Paige Nitsch, Julianne M Pollard-Larkin

Faculty, Staff and Student Publications

In the original publication [...].

Inhibition Of Gpx4 Induces The Death Of P53-Mutant Triple-Negative Breast Cancer Cells, William M Tahaney, Amanda Lanier, Jing Qian, Cassandra L Moyer, Nghi Nguyen, Yanxia Ma, Jamal Hill, Reid T Powell, Clifford C Stephan, Peter J A Davies, Abhijit Mazumdar, Powel H Brown

Faculty, Staff and Student Publications

Background: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer characterized by high rates of tumor protein 53 (TP53) mutation and with limited targeted therapies. Despite being clinically advantageous, direct targeting of mutant TP53 has been challenging. Therefore, we hypothesized that p53-mutant TNBC cells rely upon other potentially targetable survival pathways.

Methods: In vitro and in silico screens were used to identify drugs that induced preferential death in TP53-mutant cells. The effect of the ferroptosis inducer ML-162 was tested both in vitro and in vivo and the mechanism of cell death following ML-162 treatment or GPX4 knockout was …

Peripheral Nerve Injury Reduces Macrophage Efferocytosis To Facilitate Neuropathic Pain, Vipul K Pandey, Tusar K Acharya, Kendal F Willcox, Sandeep Dembla, Ajeena Ramanujan, Anamaria R Grieco, Younus A Zuberi, Rajasekaran Mahalingam, Andrew J Shepherd, Cobi J Heijnen, Peter M Grace

Faculty, Staff and Student Publications

For reasons not fully understood, proresolving immune processes sometimes fail to engage after peripheral nerve injury (PNI), leading to enhanced neuropathic pain and inflammation. Here, we implicate reduced efferocytosis due to proteolytic cleavage of surface MER tyrosine kinase (MERTK) from macrophages at the site of PNI. After PNI, the proportion of macrophages expressing MERTK progressively decreased, while soluble (cleaved) MER increased. Using male and female knock-in mice encoding cleavage-resistant Mertk, we demonstrated that cleavage of MERTK from macrophages at the PNI site led to exaggerated pain-related behaviors. PNI-induced hyperactivity of TRPV1+ sensory neurons and damage to myelin and myelinated …

International Guidelines On The Diagnosis And Treatment Of Nut Carcinoma, Yu Zhang, Qi Zhang, Yue Hao, Jia Luo, Yingshi Piao, Wenxian Wang, Zhengbo Song, Ziming Li, Luka Brcic, Aijun Liu, Jinpu Yu, Yasuhiro Tsutani, Wenzhao Zhong, Wenfeng Fang, Zhijie Wang, Shengxiang Ren, Athanasios G Papavassiliou, Yongchang Zhang, Jingjing Liu, Shirong Zhang, Xiuyu Cai, Ayten Kayi Cangir, Anwen Liu, Wen Li, Filippo Lococo, Ping Zhan, Hongbing Liu, Tangfeng Lv, Liyun Miao, Lingfeng Min, Helmut Popper, Yu Chen, Jingping Yuan, Feng Wang, Zhansheng Jiang, Gen Lin, Long Huang, Xingxiang Pu, Rongbo Lin, Kalevi Kairemo, Weifeng Liu, Chuangzhou Rao, Dongqing Lv, Zongyang Yu, Ashrafian Leanne, Xiaoyan Li, Chuanhao Tang, Hifzur R Siddique, Chengzhi Zhou, Junping Zhang, Junli Xue, Vishal Shelat, Hui Guo, Qian Chu, Rui Meng, Fatemeh Ardeshir, Jingxun Wu, Rui Zhang, Jin Zhou, Robert A Kratzke, Zhengfei Zhu, Yongheng Li, Hong Qiu, Fan Xia, Fiorella Calabrese, Yang Xia, Alessandro Wasum Mariani, Yuanyuan Lu, Xiaofeng Chen, Mark A Klein, Rui Ge, Enyong Dai, Axel H Schönthal, Yu Han, Zhenying Guo, Jian Zhang, Yinghua Ji, Xianbin Liang, Hongmei Zhang, Xuelei Ma, Marco Chiappetta, Xuewen Liu, Francoise Galateau Salle, Yu Yao, Malgorzata Szolkowska, Weiwei Pan, Fei Pang, Fan Wu, Stefan B Watzka, Liping Wang, Youcai Zhu, Li Lin, Aparna Sharma, Jianfei Tu, Xinqing Lin, Jing Cai, Ling Xu, Jisheng Li, Xiaodong Jiao, Kainan Li, Marjorie G Zauderer, Jia Wei, Huijing Feng, Lin Wang, Yingying Du, Wang Yao, Elizabeth Dudnik, Xuefei Shi, Xiaomin Niu, Dongmei Yuan, Yanwen Yao, Jianhui Huang, Yue Feng, Yinbin Zhang, Binbin Song, Wenfeng Li, Jianfei Fu, Marina K Baine, Pingli Sun, Hong Wang, Mingxiang Ye, Dong Wang, Zhaofeng Wang, Jing Wu, Yunyun Yang, Yuan Fang, Zhen Wang, Bin Wan, Donglai Lv, Huafei Chen, Shengjie Yang, Jing Kang, Jiatao Zhang, Chao Zhang, Lin Shi, Yina Wang, Mohamed Emam Sobeih, Bihui Li, Bin Lian, Lili Mao, Zhang Zhang, Ke Wang, Zhongwu Li, Zhefeng Liu, Nong Yang, Lin Wu, Xiaobing Chen, Gu Jin, Miao Li, Guansong Wang, Thomas U Marron, Jiandong Wang, Sanjay Popat, Meiyu Fang, Yong Fang, Daniel Mansilla, Yuan Li, Xiaojia Wang, Jing Chen, Yiping Zhang, Xixu Zhu, Yi Shen, Shenglin Ma, Aaron S Mansfield, Biyun Wang, Lu Si, Anja C Roden, Bjørn H Grønberg, Yong Song, Geoffrey I Shapiro, Christopher A French, Yuanzhi Lu, Qian Wang, Chunwei Xu

Faculty, Staff and Student Publications

Nuclear protein in testis (NUT) carcinoma (NC) represents a rare, clinically aggressive cancer defined by pathognomonic NUT Midline Carcinoma Family Member 1 (NUTM1) gene fusions, with bromodomain and extraterminal domain (BET) protein 4 (BRD4)-NUTM1 being the predominant oncogenic driver. Since its description in 1991, gradual advances have clarified the pathologic mechanisms of NC and its diagnostic methods; however, NC treatment remains a significant challenge. Moreover, diagnostic and treatment approaches for this cancer require further validation and standardization. These guidelines were developed by the Chinese Alliance of Research for NC (ChARN) based on current evidence in …

Precision Targeting Of Sting: Challenges, Innovations, And Clinical Outlook For Cancer Therapy, Jiaqi Shi, Yingying Zhang, Na Zhao, Ekihiro Seki, Li Ma, Gordana Kocic, Xiaobo Li, Janoš Terzić, Tongsen Zheng

Faculty, Staff and Student Publications

The stimulator of interferon genes (STING) pathway plays a crucial role in immune responses and has emerged as a compelling target in cancer therapy. Despite promising preclinical studies, clinical trials of STING agonists have largely failed to deliver durable efficacy, with no agents progressing to phase III trials. This review examines the biological, pharmacological, and clinical barriers limiting STING pathway activation in cancer treatment. We discuss the inherent limitations of STING agonists as well as host-related resistance driven by tumor heterogeneity, immune suppression, and chronic STING activation. Mechanisms of acquired resistance, such as immune checkpoint upregulation and suppression of effector …

A Prognostic Matrix Gene Expression Signature Defines Functional Glioblastoma Phenotypes And Niches, Monika Vishnoi, Zeynep Dereli, Zheng Yin, Elisabeth K Kong, Meric Kinali, Kisan Thapa, Ozgun Babur, Kyuson Yun, Nourhan Abdelfattah, Xubin Li, Behnaz Bozorgui, Mary C Farach-Carson, Robert C Rostomily, Anil Korkut

Faculty, Staff and Student Publications

Interactions among tumor, immune, and vascular niches play major roles in glioblastoma (GBM) malignancy and treatment responses. The composition and heterogeneity of extracellular core matrix proteins (CMPs) that mediate such interactions are not well understood. Here, we present an analysis of the clinical relevance of CMP expression in GBM at bulk, single-cell, and spatial anatomical resolution. We show that CMP enrichment is associated with worse patient survival, specific driver oncogenic alterations, mesenchymal state, pro-tumor immune infiltration, and immune checkpoint expression. Matrisome expression is enriched in vascular and leading edge/infiltrative niches that are known to harbor glioma stem cells. Finally, we …

Pathogenesis Of Polyglutamine Diseases: Piecing Together A Complex Molecular Puzzle, Esmeralda Villavicencio Gonzalez, Huda Y Zoghbi

Duncan NRI Faculty and Staff Publications

Polyglutamine (polyQ) diseases, caused by a CAG repeat expansion encoding a glutamine tract in nine distinct proteins, present a complex molecular puzzle in which each piece contributes to neurodegeneration. While each of the causative proteins has a distinct function, the downstream consequences of polyQ toxicity are often similar, including protein accumulation, transcriptional dysregulation, somatic CAG repeat instability, disrupted energy homeostasis, compromised synaptic function, and selective neuronal death. This review summarizes emerging insights into how proteins with an expanded polyQ tract disrupt distinct cellular functions, and we examine a multitude of discoveries that are inspiring and reshaping novel therapeutic strategies.

Stakeholder Perspectives On Humanistic Implementation Of Computer Perception In Health Care: Qualitative Study, Kristin M Kostick-Quenet, Meghan E Hurley, Syed Ayaz, John D Herrington, Casey J Zampella, Julia Parish-Morris, Birkan Tunç, Gabriel Lázaro-Muñoz, Jennifer Blumenthal-Barby, Eric A Storch

Center for Medical Ethics and Health Policy Staff Publications

Background: Computer perception (CP) technologies-including digital phenotyping, affective computing, and related passive sensing approaches-offer unprecedented opportunities to personalize health care, especially mental health care, yet they also provoke concerns about privacy, bias, and the erosion of empathic, relationship-centered practice. At present, it remains elusive what stakeholders who design, deploy, and experience these tools in real-world settings perceive as the risks and benefits of CP technologies.

Objective: This study aims to explore key stakeholder perspectives on the potential benefits, risks, and concerns associated with integrating CP technologies into patient care. A better understanding of these concerns is crucial for responding to …

Nf2 Loss Malignantly Transforms Human Pancreatic Acinar Cells And Enhances Cell Fitness Under Environmental Stress, Yi Xu, Michael H Nipper, Angel A Dominguez, Chenhui He, Francis E Sharkey, Sajid Khan, Han Xu, Daohong Zhou, Lei Zheng, Yu Luan, Jun Liu, Pei Wang

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) occurs as a complex, multifaceted event driven by the interplay of tumor-permissive genetic mutations, the nature of the cellular origin, and microenvironmental stress. In this study, using primary human pancreatic acinar 3D organoids, we performed a CRISPR-KO screen targeting 199 potential tumor suppressors curated from clinical PDAC samples. Our data revealed significant enrichment of a list of candidate genes, with neurofibromatosis type 2 associated gene (NF2) emerging as the top target. Functional validation confirmed that loss of NF2 promoted the transition of PDAC to an invasive state, potentially through extracellular matrix modulation. NF2 inactivation …

Public Support For Alcohol-Control Policies And Political Ideology In The Us, Joël Fokom Domgue, Robert Yu, Ernest Hawk, Sanjay Shete

Faculty, Staff and Student Publications

This cross-sectional study examines the role of US adults’ political affiliation, perception about alcohol use and cancer, and sociodemographic and behavioral factors in banning outdoor alcohol advertising and adding cancer warnings on alcohol containers.

Peroxisomal Integrity In Demyelination-Associated Microglia Enables Cellular Debris Clearance And Myelin Renewal In Mice, Joseph A Barnes-Vélez, Xiaohong Zhang, Yaren L Peña Señeriz, Kiersten A Scott, Yinglu Guan, Jian Hu

Faculty, Staff and Student Publications

Demyelination associated microglia (DMAM) orchestrate the regenerative response to demyelination by clearing myelin debris and promoting oligodendrocyte maturation. Peroxisomal metabolism has emerged as a candidate regulator of DMAMs, though the cell-intrinsic contribution in microglia remains undefined. Here we elucidate the role of peroxisome integrity in DMAMs, using cuprizone-mediated demyelination coupled with conditional KO of peroxisome biogenesis factor 5 (PEX5) in microglia. Absent demyelination, PEX5 conditional KO (PEX5cKO) had minimal impact on homeostatic microglia. However, during cuprizone-induced demyelination, the emergence of DMAMs unmasked a critical requirement for peroxisome integrity. At peak demyelination, PEX5cKO DMAMs exhibited increased lipid droplet burden and reduced …

Cholesterol Efflux Protein, Abca1, Supports Anticancer Functions Of Myeloid Immune Cells, Shruti V Bendre, Yu Wang, Basel Hajyousif, Rajendra K C, Shounak G Bhogale, Dhanya Pradeep, Natalia Krawczynska, Claire P Schane, Erin Weisser, Avni Singh, Simon Han, Hannah Kim, Lara Kockaya, Anasuya Das Gupta, Adam T Nelczyk, Hashni Epa Vidana Gamage, Yifan Fei, Desirée Rodríguez-Casiano, Xingyu Guo, Haoyun Li, Ryan J Deaton, Fei Mo, Maria Sverdlov, Peter H Gann, Saurabh Sinha, Sahil Sahni, Kun Wang, Kevin Van Bortle, Emad Tajkorshid, Wendy A Woodward, Wonhwa Cho, Erik R Nelson

Faculty, Staff and Student Publications

Breast and other solid tumors respond poorly to immune therapy. Myeloid cells (MCs) such as macrophages contribute to resistance. Established clinical evidence links cholesterol to cancer outcomes, with MC function being regulated by cholesterol metabolism. We screened MC-expressed regulators of cholesterol homeostasis linked to survival and identified the cholesterol efflux protein ABCA1. ABCA1 activity increases anticancer functions of macrophages: enhancing tumor infiltration, decreasing angiogenic potential, reducing efferocytosis, and improving support of CD8+ T cell activity. Mechanistically, different AKT isoforms are involved, through both PI3K-dependent and PI3K-independent mechanisms. Highlighting the clinical relevance of our findings are correlations between ABCA1 in macrophages …

Racial, Ethnic, And Socioeconomic Survival Disparities In Early-Onset Metastatic Colorectal Cancer, Jennifer S Wang, Benny Johnson, Caitlin C Murphy

Faculty, Staff and Student Publications

Importance: Rates of metastatic colorectal cancer (mCRC) are rising among young adults. Disparities by race and ethnicity and neighborhood-level socioeconomic status (SES) among this population are understudied.

Objective: To examine the association of race and ethnicity and neighborhood-level SES with mortality among a community-based sample of young adults with mCRC.

Design, setting, and participants: This cohort study used a large electronic health record-derived database of young adults with cancer treated at 280 community-based US clinics between 2013 and 2021. Eligible patients were young adults aged 18 to 49 years diagnosed with de novo or recurrent mCRC. Patients were followed up …

Reported Safety Practices Of Publicly Advertised Psychedelic Retreats, Amy L Mcguire, Logan Neitzke-Spruill, Jill O Robinson, Caroline S Beit, Nikita Singh, David S Mathai, Lynnette A Averill

Center for Medical Ethics and Health Policy Staff Publications

Importance: The availability of psychedelic retreats has grown to meet the demand for access to these substances. Despite centuries of use among Indigenous communities, psychedelics can pose serious risks for some users.

Objective: To determine safety precautions that retreat organizations that offer psychedelic substances currently use.

Design, setting, and participants: This qualitative study included structured interviews conducted by phone or email with representatives from 49 organizations publicly advertising psychedelic retreat offerings from July to October 2023. Organizations were eligible if they marketed their services in English, offered at least 1 psychedelic substance, and made contact information available online. Organizations were …

Test-Retest Apparent Diffusion Coefficient Reproducibility In Head And Neck Cancer Using A 15-T Mr-Linac, Brigid A Mcdonald, Dina El-Habashy, Renjie He, Sam Mulder, Sarah Mirbahaeddin, Abdallah S R Mohamed, Sara Ahmed, Yao Ding, Jihong Wang, Stephen Y Lai, Alex Dresner, John Christodouleas, Clifton D Fuller

Faculty, Staff and Student Publications

Purpose

To evaluate the reproducibility of apparent diffusion coefficient (ADC) measurements in head and neck squamous cell carcinoma (HNSCC) using a 1.5-T MR-linac (MRI-guided linear accelerator) system.

Materials and Methods

In this retrospective study, conducted between February 2021 and January 2024, patients with HNSCC lesions underwent echo-planar imaging diffusion-weighted MRI on a 1.5-T MR-linac system at two time points before the start of radiation therapy. Mean and median ADC values and volumes were measured for each lesion. Absolute and percent reproducibility coefficients (RCs) were calculated. Linear regression analyses and F tests were performed to determine whether the lesion volume or …

Putting The L In Elsi: Legal Methods For Bioethics Research, Anya E R Prince, Benjamin Berkman, Donald Ford, Dov Fox, Christi Guerrini, Amy Koopmann, Natalie Ram, Jessica L Roberts, Kayte Spector-Bagdady, Sonia Suter

Center for Medical Ethics and Health Policy Staff Publications

Lawyers and law professors are increasingly involved in interdisciplinary scientific teams and grant research to answer ethical, legal and policy questions related to biomedical topics. Yet, the methods that lawyers use to conduct legal research and analysis are not always familiar to scientists and social scientists conducting peer review of a proposed project with legal aims or a publication reporting a legal study. To better facilitate interdisciplinary ethical, legal, and social implications collaboration, there is a need to better explain how legal research methodologies can provide robust tools to address a range of nuanced biomedical questions. This paper explores …

Access To Digital Health Technologies: Personalized Framework And Global Perspectives, Sanjiv M Narayan, Mina K Chung, Demilade Adedinsewo, Luisa C C Brant, Leslie L Davis, David Duncker, Jennifer L Hall, Janet K Han, Carolyn S P Lam, Eldrin Lewis, Joseph Loscalzo, Manlio F Márquez, Vasiliki Rahimzadeh, Fatima Rodriguez, Prashanthan Sanders, Emma Svennberg, Kenneth Stein, Mintu Turakhia, Clyde Yancy, Antonis A Armoundas

Center for Medical Ethics and Health Policy Staff Publications

The emergence and rapid adoption of digital health technologies (DHT) present unprecedented opportunities to democratize and reduce disparities in health care by monitoring health and disease at the point of care in all patients. However, limited access to DHT is becoming a major obstacle to realizing these goals. Access to DHT is influenced not only by well-recognized social determinants of health, but also by digital determinants of health, such as digital literacy and the need for broad access to digital infrastructure, as well as commercial and economic factors. Addressing these challenges and designing unbiased systems of care are essential to …

Contralateral Breast Cancer After Radiotherapy And Hormone Therapy In Two Cohorts Of Us Breast Cancer Survivors, Lene H S Veiga, Gretchen L Gierach, Susan A Smith, Rebecca M Howell, Matthew M Mille, Monjoy Saha, Rochelle E Curtis, Cody Ramin, Clara Bodelon, Heather Spencer Feigelson, Erin J Aiello Bowles, Diana S M Buist, Sheila Weinmann, Jacqueline B Vo, Choonsik Lee, Amy Berrington De Gonzalez

Faculty, Staff and Student Publications

Background: Radiotherapy increases contralateral breast cancer risk, while hormone therapy reduces it; their combined effects are unclear.

Methods: Data from two US retrospective cohort studies of 5-year breast cancer survivors (stage I-III, ages 20-84), Kaiser Permanente (KP, 1990-2012) and SEER (1990-2013), were analysed. Contralateral breast radiation doses were estimated for the KP cohort. Multivariable Poisson regression estimated relative risks (RRs) and excess relative risks per Gray (ERR/Gy), stratified by hormone therapy use.

Results: KP cohort (n = 9053) included 353 contralateral breast cancer cases (73% ER+); SEER cohort (n = 244,834) included 10,470 cases (72% ER+). Among women with ER+ …

Alternative Polyadenylation Signatures Distinguish Maladaptive Right Ventricular Remodeling In Pulmonary Hypertension: Implications For Rna-Based Diagnostics And Therapeutics, Janani Subramaniam, Venkata Jonnakuti, Scott D Collum, Sandra Martineau, Kai-Lieh Huang, Sandra Breuils-Bonnet, Andrea L Frump, Bindu H Akkanti, Jayeshkumar A Patel, Manish K Patel, Ismael Salas De Armas, Isabella N Lefebvre, Rajko Radovancevic, Elvin Blanco, Eric J Wagner, Igor Gregoric, Sriram Nathan, Biswajit Kar, Steeve Provencher, Sebastien Bonnet, François Potus, Hari Krishna Yalamanchili, Harry Karmouty-Quintana

Faculty, Staff and Student Publications

Increased pulmonary vascular pressures due to vascular remodeling, elevated vascular resistance, and vasoconstriction characterize Pulmonary Arterial Hypertension (PAH). The narrowing of the pulmonary arteries and obstruction of blood flow increase the Right Ventricular (RV) afterload, forcing the RV to undergo structural and functional changes. While adaptive remodeling leads to RV compensation by maintaining function, maladaptive remodeling leads to RV decompensation, characterized by worsening function and eventual failure. At present, there is no effective treatment for these patients as therapies for left ventricular failure are ineffectual, and there are no therapies specifically targeting the RV. Therefore, there is a clear need …

Guadecitabine Improved Relapse-Free Survival In High-Risk Acute Myeloid Leukemia And Myelodysplastic Syndrome Patients After Transplant: Phase Ii Results From A Single Center, Betül Oran, Peter Thall, Amin Alousi, Gheath Al-Atrash, Rohtesh Mehta, David Marin, Partow Kebriaei, Uday Popat, Roland Bassett, Qaiser Bashir, Jin Im, Amanda Olson, Jessica Jewell, Portia Smallbone, Elizabeth Shpall, Richard Champlin

Faculty, Staff and Student Publications

This phase II, single-center clinical trial evaluated the efficacy and safety of guadecitabine, with or without donor lymphocyte infusion, following allogeneic stem cell transplantation in adult patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). The study had three treatment cohorts based on post-transplant disease status. Cohort 1 included patients with hematologic relapse after transplant (N=13). Cohort 2 consisted of patients with minimal residual disease (MRD) detected after transplant (N=18). Cohort 3 compromised patients in remission without MRD within 100 days after transplant (N=24). The primary objectives were achievement of morphological complete remission in cohort 1 and MRD eradication …

Endogenous Processes Underlying Clock-Like Mutational Signatures, Teresa Druck, Rami I Aqeilan, C Marcelo Aldaz, Nicola Zanesi, Kay Huebner

Faculty, Staff and Student Publications

Wellcome Trust scientists have shown that “mutational signatures” in specific nucleotide contexts accumulate in genomes of mammalian tissues, providing clues to underlying causes of specific signatures. Analysis of cancer genomes has identified more than 50 single‐base substitution (SBS) signatures, with SBS1, SBS5, and SBS40 linked to aging and present in normal tissues. SBS1 results from cytosine demethylation, whereas SBS5 and SBS40 arise from unknown endogenous mechanisms. We hypothesized that loss of fragile‐site genes drives these two signatures. FHIT, located at FRA3B, is frequently deleted in cancers, and Fhit‐deficient mouse tissues exhibit a mutation profile resembling human SBS5. Data mining of …

Preclinical Ischemic Stroke Multicenter Trials (Prism) Collective Statement: Opportunities, Challenges, And Recommendations For A New Era, Cenk Ayata, Philip M Bath, Anna M Planas, Stuart M Allan, Johannes Boltze, Ryan P Cabeen, Claire L Gibson, Marilyn J Cipolla, Marcio A Diniz, Stefano Fumagalli, Fahmeed Hyder, Raymond C Koehler, Arthur Liesz, Sarah K Mccann, Tim Magnus, Louise D Mccullough, Emily S Sena, Simone Beretta, Jaroslaw Aronowski, Francesca Bosetti, Clinton B Wright, Patrick D Lyden, Lauren H Sansing

Faculty, Staff and Student Publications

Preclinical stroke research faces a critical translational gap, with animal studies failing to reliably predict clinical efficacy. To address this, the field is moving toward rigorous, multicenter preclinical randomized controlled trials (mpRCTs) that mimic phase 3 clinical trials in several key components. This collective statement, derived from experts involved in mpRCTs, outlines considerations for designing and executing such trials. mpRCTs offer advantages such as increased sample sizes, robust statistical design, incorporation of heterogeneity, and standardized protocols, but they face challenges in finding the right balance between standardization and heterogeneity, appropriate stroke model selection, and outcome measures, as well as the …

Management Of Retropharyngeal Lymph Node Metastases In Thyroid Cancer, Isabelle Fournier, Ashwini Venkata Bandi, Sarah Hamidi, Priyanka Iyer, Naifa L Busaidy, Maria E Cabanillas, Ramona Dadu, Mimi I Hu, Steven G Waguespack, Ugur Nur Basmaci, Michelle D Williams, Mena Mansour, Maria Gule Monroe, Neil D Gross, Ryan P Goepfert, Nancy D Perrier, Victoria Banuchi, Jennifer R Wang, Anastasios Maniakas, Mark E Zafereo

Faculty, Staff and Student Publications

Background: Retropharyngeal lymph node (RPLN) metastases in thyroid cancer are rare, with optimal management underreported.

Methods: Retrospective study of consecutive thyroid cancer patients with RPLN metastases treated at MD Anderson Cancer Center between 2000 and 2024.

Results: One hundred and sixty-seven patients (75% differentiated, 21% medullary, 4% poorly differentiated thyroid cancer) were divided into three groups: active surveillance (AS) (13%), surgery (56%), and nonsurgical treatment (31%). In the AS group (median follow-up 2.3 years), RPLN metastases grew a median 3% (range: 0-56) or 0.02 cm (range: 0-0.7) per year. Surgical therapy included transcervical (73%), transoral robotic (14%), transoral (12%), and …

Knowledge Distillation And Dataset Distillation Of Large Language Models: Emerging Trends, Challenges, And Future Directions, Luyang Fang, Xiaowei Yu, Jiazhang Cai, Yongkai Chen, Shushan Wu, Zhengliang Liu, Zhenyuan Yang, Haoran Lu, Xilin Gong, Yufang Liu, Terry Ma, Wei Ruan, Ali Abbasi, Jing Zhang, Tao Wang, Ehsan Latif, Wei Liu, Wei Zhang, Soheil Kolouri, Xiaoming Zhai, Dajiang Zhu, Wenxuan Zhong, Tianming Liu, Ping Ma

Faculty, Staff and Student Publications

The exponential growth of Large Language Models (LLMs) continues to highlight the need for efficient strategies to meet ever-expanding computational and data demands. This survey provides a comprehensive analysis of two complementary paradigms: Knowledge Distillation (KD) and Dataset Distillation (DD), both aimed at compressing LLMs while preserving their advanced reasoning capabilities and linguistic diversity. We first examine key methodologies in KD, such as task-specific alignment, rationale-based training, and multi-teacher frameworks, alongside DD techniques that synthesize compact, high-impact datasets through optimization-based gradient matching, latent space regularization, and generative synthesis. Building on these foundations, we explore how integrating KD and DD can …

Blood Flow Regulates Metabolism In Hematopoietic Development, Pamela L Wenzel

Faculty, Staff and Student Publications

Blood flow modifies oxygen availability and biomechanical forces within the vasculature of the embryo as the hematopoietic system develops. The aorta-gonad-mesonephros (AGM) envelops the largest artery in the body and is a critical site for the emergence of hematopoietic stem cells (HSCs). Herein, I discuss the role of hypoxia-inducible factors (HIFs) and force as determinants of metabolism and fate determination. To address the effects of blood flow on hematopoietic development, I employ mouse embryo models and biomimetic culture. Real-time cell metabolic analyses show that oxygen consumption rates (OCR) and extracellular acidification rates (ECAR) are altered by flow in cultures of …

Host Modulation Therapy In Periodontitis: From Established Therapies To Emerging Technologies, Aonjittra Phanrungsuwan, Jiaqi Huang, Neeraja Dharmaraj, Alejandra Cobos Perez, Omid Veiseh, Simon Young, Chun-Teh Lee

Faculty, Staff and Student Publications

Periodontitis is a biofilm-induced chronic inflammatory disease, characterized by gingival inflammation and alveolar bone loss. According to a national survey, approximately half of the U.S. adults are affected by periodontal disease. To effectively prevent and treat periodontitis, it is essential to address its underlying causes. The primary etiological factors include polymicrobial synergy and dysbiosis of the oral microbiota, and a dysregulated immune response. The standard therapeutic approach, mechanical removal of biofilm through debridement, sometimes demonstrates limited efficacy, particularly in cases of severe periodontitis, which may require adjunctive or additional therapy. Emerging evidence indicates that periodontal tissue destruction is initiated by …

Applications And Challenges Of Utilizing Digital Pathology And Ai-Enabled Workflows In Clinical Trials, Manu Sebastian, Harsh Batra, Monika Lamba Saini, Staci Kearney, Lorcan Sherry, Serge Alexanian, Michael Cohen, William Weber, Joe Lennerz, Anil V Parwani

Faculty, Staff and Student Publications

This is a comprehensive review on current utilization and challenges of digital pathology adoption in clinical trials and aims to provide a broad view on its impact on pathology review processes in clinical trials. It provides an overview of current pathology review practices in clinical trials and unique advantages digital pathology adoption can offer. The key areas including existing workflows, use case scenarios in different disease areas in clinical trials, including but not limited to patient identification and pre-screening, and regulatory aspects have been described with relevance. In addition, the review delves into the integration of genomics, AI, image analysis, …