Genetic Phenomena Commons^™

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, Partow Kebriaei, 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 …

Functional, Pharmacogenomic, And Immune Landscapes Of Long Non-Coding Rnas In Cancer, Runhao Wang, Mei Luo, Yuan Liu, Jingwen Yang, Yamei Chen, Lifei Ma, James Wengler, Yong Zang, Bora Lim, Wenbo Li, Liuqing Yang, Chunru Lin, Lixia Diao, Leng Han

Faculty, Staff and Student Publications

Long non-coding RNAs (lncRNAs) are emerging as key regulators in cancer, with significant potential as diagnostic, prognostic, and therapeutic targets. Here, this work systematically analyzes lncRNA associations with targeted therapies and immunotherapies across 33 cancer types using The Cancer Genome Atlas (TCGA) and real-world datasets. This work identifies 53,173 lncRNA-pathway associations, millions of lncRNA-drug response associations (via CancerRxTissue and VAEN), and extensive correlations with immune checkpoints and infiltration. This work further identifies 69 lncRNAs associated with immunotherapy response and 2,611 differentially expressed lncRNAs between low and high objective response rate (ORR) groups. Additionally, two lncRNAs are correlated with immune-related adverse …

Initial Experience With Remote Mri Scanning Support In An Oncology Focused Practice: Opportunities For Expanded Access To Radiology Care, Christopher M Walker, Maria G Maldonado, Megan C Jacobsen, Suprateek Kundu, Michelle L Underwood, Brandy J Reed, R Jason Stafford, Marshall E Hicks, Caroline Chung, Aradhana M Venkatesan

Faculty, Staff and Student Publications

Background: As medical imaging demand grows, there is increasing stress on the currently available workforce to deliver consistent, high-quality imaging studies while ensuring rapid study turnaround times and round-the-clock radiology coverage. Advances in remote access technology facilitating remote scan assistance and control are now commercially available to address these pressing clinical needs.

Methods: This work evaluated an early clinical application of a virtual scanner operations system (syngo Virtual Cockpit (VA13A, Siemens Healthineers, Erlangen, Germany) for remote magnetic resonance imaging (MRI) monitoring and scan control at three geographically distant outpatient sites associated with our primary institution.

Results: The system facilitated execution …

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, Zhenyuan Yang, 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 …

Perspective: Radiotherapy And Body Composition: Unmet Needs In Low- And Middle-Income Countries, Alexia J Murphy-Alford, Aaron J Grossberg, Vickie E Baracos, Maha Barbar, Judy Bauer, Elena Fidarova, Anastassia Löser, Amy C Moreno, Anurima Patra, Deepa Puttaswamy, David I Rosenthal, Judy Schoeman, Yavuz Anacak

Faculty, Staff and Student Publications

Radiotherapy plays a vital role in cancer treatment, yet its effects on patients' nutritional status can precipitate muscle loss, with significant implications for treatment tolerance and outcomes. Evidence from high-income countries increasingly links radiation-induced muscle loss to adverse clinical outcomes. In contrast, low- and middle-income countries face a stark evidence gap, despite the heightened vulnerability of cancer patients in these settings due to delayed diagnosis, limited access to care, and high rates of co-morbidities. This paper highlights the critical gaps in nutritional care for radiotherapy patients in low- and middle-income countries.

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, Rochelle E Curtis, 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+ …

Prickle4 Drives Microenvironmental Remodeling And Resistance To Parp Inhibition In Idh-Mutant Glioma, Ju Yang, Hua Yang, Yifan Yuan, Chenyang Zhang, Ziwei Fu, Yinghong Xiong, Kexin Ling, Ying Liu, Jason T Huse, Bo Chen, Timothy A Chan, Zengxin Qi, Zhao Zhang, Xiuping Liu, Yuxiang Wang

Faculty, Staff and Student Publications

Mutations in isocitrate dehydrogenase (IDH) genes sensitize gliomas to PARP inhibition (PARPi) by inducing epigenetic reprogramming of DNA damage repair circuits. However, tumors treated with PARPi eventually relapse despite initial responsiveness. In this study, it is demonstrated that the anti-angiogenic agent lenvatinib synergizes effectively with PARPi, resulting in substantial tumor regression and significantly extended survival. Genomic analysis of tumors reveals that PARPi induces widespread transcriptomic changes that are predominantly pro-inflammatory, thereby promoting tumor angiogenesis. Prickle4, a planar cell polarity protein, is identified as a critical mediator of PARPi-induced neovascularization. Targeting Prickle4 effectively overcomes PARPi resistance in these tumors. Collectively, these …

Host Modulation Therapy In Periodontitis: From Established Therapies To Emerging Technologies, Aonjittra Phanrungsuwan, Jiaqi Huang, Neeraja Dharmaraj, Alejandra Cobos Perez, Omid Veiseh, 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 …

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 …

Wilson’S Disease Psychosis In A Young Man With Autism Spectrum Disorder: A Case Report And Focus On Management, Landon C. Sowell, Barbara L. Gracious

HCA Healthcare Journal of Medicine

Introduction

Wilson's disease is a rare autosomal recessive disorder, affecting approximately 1 in 30 000 individuals and is characterized by abnormal copper accumulation in the body, primarily affecting the liver and brain. Psychiatric manifestations as a first presentation, particularly psychosis, are less commonly recognized resulting in failure to begin treatment early in the course of the disease. This case report highlights a patient that presented to the hospital with psychosis, who was later diagnosed with Wilson’s disease. This case underscores the importance of considering organic causes in first-episode psychosis.

Case Presentation

An 18-year-old man with a history of autism spectrum …

Netrin-1 Promotes Pancreatic Tumorigenesis And Innervation Through Neo1, Hiroki Kobayashi, Yosuke Ochiai, Junya Arai, Masahiro Hata, Feijing Wu, Tadashi Iida, Ermanno Malagola, Takayuki Tanaka, Zhengyu Jiang, Ruth A White, Xiaofei Zhi, Jin Qian, Quin T Waterbury, Ruhong Tu, Biyun Zheng, Yi Zeng, Hualong Zheng, Puran Zhang, Shuang Li, Leah B Zamechek, Jonathan S Labella, Takahiro Sugie, Atsushi Enomoto, Holger K Eltzschig, Carmine F Palermo, Iok In Christine Chio, Kenneth P Olive, Timothy C Wang

Faculty, Staff and Student Publications

Nerves can regulate tumorigenesis and cancer progression. However, clarification of the role of axon guidance molecules in tumorigenesis, innervation, and metastasis is required to better understand the tumor-promoting functions of nerves. Using murine KrasG12D-mutant pancreatic organoids, we screened axon guidance molecules and identified netrin-1 upregulation. Netrin-1 was also upregulated in vivo during pancreatic tumorigenesis in humans and mice. Mutant KRAS and β-adrenergic signaling upregulated netrin-1 and its receptor NEO1 in epithelial cells in part through the MAPK pathway. Ex vivo culture of celiac ganglia showed that netrin-1 promoted the axonogenesis of sympathetic neurons through nerve NEO1. In the Pdx1-Cre;LSL-KrasG12D/+ model, …

Speeding Up Interval Estimation For R2-Based Mediation Effect Of High-Dimensional Mediators Via Cross-Fitting, Zhichao Xu, Chunlin Li, Sunyi Chi, Tianzhong Yang, Peng Wei

Faculty, Staff and Student Publications

Mediation analysis is a useful tool in investigating how molecular phenotypes such as gene expression mediate the effect of exposure on health outcomes. However, commonly used mean-based total mediation effect measures may suffer from cancellation of component-wise mediation effects in opposite directions in the presence of high-dimensional omics mediators. To overcome this limitation, we recently proposed a variance-based R-squared total mediation effect measure that relies on the computationally intensive nonparametric bootstrap for confidence interval estimation. In the work described herein, we formulated a more efficient two-stage, cross-fitted estimation procedure for the R2 measure. To avoid potential bias, we performed …

Black Bone Mri Morphometry For Mandibular Cortical Bone Measurement In Head And Neck Cancer Patients: Prospective Method Comparison With Ct, Lisanne V Van Dijk, Juan Ventura, Kareem A Wahid, Lin L Zhu, Brigid A Mcdonald, Keith L Sanders, Lance Mccoy, Christina S Sharafi, Kathryn E Preston, Natalie A West, Sarah Mirbahaeddin, Dina M El-Habashy, Travis Salzillo, Samuel Mulder, Joly Fahim, Aubryane Dearmas, Mona Arbab, Yao Ding, Jihong Wang, Bastien Rigaud, Anando Sen, Mark Chambers, Katherine A Hutcheson, Kristy K Brock, Abdallah S R Mohamed, Stephen Y Lai, Clifton D Fuller

Faculty, Staff and Student Publications

Objectives: Determine the utility of low-flip angle "black bone" magnetic resonance imaging (MRI) for cortical mandibular bone assessment compared to computed tomography (CT).

Methods: Quantification of cortical mandibular bone width was performed per Hamada et al. at 15 cross-sectional interdentium locations on pretreatment black bone MRI and CT for 15 oropharyngeal cancer patients, with interobserver analyses on a subset of three patients by 11 observers. CT and MRI measurements were compared using Bland-Altman analysis, Lin's concordance, and Deming regression; interobserver variability was assessed with absolute variance and intraclass correlation coefficient (ICC).

Results: Bland Altman and Deming regression analyses showed CT …

Batf2 Is A Glutamine-Responsive Tumour Suppressor Required For Type-I Interferon-Dependent Anti-Tumour Immunity, Wang Gong, Hülya F Taner, Yuesong Wu, Yumin He, Xingwu Zhou, Xin Hu, Kala Chand Debnath, Kohei Okuyama, Qiang Hu, Christopher R Donnelly, Felipe Nör, Chamila D Perera, Emily Bellile, Arash Yunesi, Zhiqian Zhai, Mei Zhao, Wanqing Cheng, Zackary R Fitzsimonds, Luke Broses, Jiaqian Li, Shadmehr Demehri, Deepak Nagrath, Gregory T Wolf, Andrew G Sikora, Yanbao Yu, Haitao Wen, Lei Wei, Steven B Chinn, Jeffrey N Myers, Shizuo Akira, Yuying Xie, James J Moon, Yu Leo Lei

Faculty, Staff and Student Publications

Recent evidence highlights the significance of a new type of tumour suppressors, which are not frequently mutated but inhibited by metabolic cues in cancers. Here, we identify BATF2 as a tumour suppressor whose expression is epigenetically silenced by glutamine in Head and Neck Squamous Cell Carcinomas (HNSCC). BATF2 correlates with type-I interferon and Th1 signatures in human HNSCC, with correlation coefficients even stronger than those of the positive control, STING. The phosphorylation of BATF2 at serine 227 promotes the oligomerization of STING. BATF2 deficiency or high glutamine levels result in higher oxygen consumption rates and metabolic profiles unfavorable for …

Sex Differences In Bile Acid Homeostasis And Excretion Underlie The Disparity In Liver Cancer Incidence Between Males And Females, Megan E Patton, Sherwin Kelekar, Lauren J Taylor, Angela E Dean, Qianying Zuo, Sung Hwan Lee, Morgan Panitchpakdi, Pieter Dorrestein, Yazen Alnouti, Zeynep Madak-Erdogan, Ju-Seog Lee, Milton J Finegold, Sayeepriyadarshini Anakk

Faculty, Staff and Student Publications

Hepatocellular carcinoma (HCC), the common liver cancer, exhibits higher incidence in males. Here, we report that mice lacking bile acid (BA) regulators, Farnesoid X Receptor (FXR also termed NR1H4) and Small Heterodimer Partner (SHP also termed NR0B2), recapitulate the sex difference in liver cancer risk. Since few therapeutic options are available, we focused on understanding the intrinsic protection afforded to female livers. Transcriptomic analysis in control and NR1H4 and NR0B2 double knockout livers identified female-specific changes in metabolism, including amino acids, lipids, and steroids. To assess translational relevance, we examined if transcriptomic signatures obtained from this murine HCC model correlate …

Loss Of The Maternal Effect Gene Nlrp2 Impairs Embryonic And Extra-Embryonic Development, Revealing A Novel Genetic Cause Of Congenital Anomalies†, Momal Sharif, Zahra Anvar, Imen Chakchouk, Sara H El-Dessouky, Roni Zemet, Eric C Kao, Wessam E Sharaf-Eldin, Ying-Wooi Wan, Zhandong Liu, Pengfei Liu, Michael Jochum, Ignatia B Van Den Veyver

Duncan NRI Faculty and Staff Publications

Maternal-effect genes (MEGs) play a crucial role in early mammalian development, and their dysfunction can lead to severe embryonic and extra-embryonic abnormalities. NLRP2, a MEG that encodes a subcortical maternal complex (SCMC) protein, has been implicated in preimplantation development, but its role after implantation remains underexplored. In this study, we investigated the developmental consequences of maternal Nlrp2 loss-of-function in a maternal knockout (KO) mouse model at embryonic day 11.5. Embryos derived from Nlrp2-KO females have abnormal yolk sac vasculature, increased embryonic resorption, craniofacial abnormalities, neural tube defects, and congenital heart defects. Placental architecture is disrupted with an altered junctional zone …

Anti-Saccade Error Rates Are Associated With Somatic Depressive Symptoms In Cocaine Use Disorder, Constanza De Dios, Heather E Webber, Margaret C Wardle, Jin H Yoon, Michelle A Patriquin, Joy M Schmitz

Faculty, Staff and Student Publications

Background: Inhibitory control deficits are associated with cocaine use disorder (CUD) development and maintenance. Additionally, drug use and inhibitory control can be negatively affected by depressive symptoms, including somatic factors like sleep disturbance and fatigue.

Aim: The current study assessed the relationship between inhibitory control and depressive symptoms among individuals initiating CUD treatment. We examined associations among anti-saccade response inhibition performance, total scores on the Beck Depression Inventory-II (BDI-II), and individual BDI-II items.

Methods: N = 101 patients enrolled in a clinical trial for CUD completed drug-specific anti-saccade and depression (BDI-II) measures prior to treatment. Generalized linear models tested the …

The Impact Of Targeting Traf2 And Nck-Interacting Protein Kinase On Antitumor Effect And Tumor Immune Environment In C-Myc-High Sclc, Azusa Tanimoto, Kavya Ramkumar, C Allison Stewart, Bingnan Zhang, Kyle Concannon, Li Shen, Jing Wang, Carl M Gay, Lauren Averett Byers

Faculty, Staff and Student Publications

Introduction: Wnt/β-catenin signaling pathway activation contributes to tumorigenesis and chemo-resistance in SCLC, yet clinical attempts to target this pathway have been unsuccessful. TRAF2 and NCK-interacting protein kinase (TNIK), an essential nuclear activator of Wnt/β-catenin target genes, has not yet been validated as a viable therapeutic target in SCLC. Here, we validated that TNIK inhibition is a promising approach for personalized anticancer therapy in SCLC.

Methods: We correlated the IC50 values of a TNIK inhibitor, NCB-0846, with proteomic profiling (reverse phase protein array) data across 28 SCLC cell lines. Cytokine array analysis was performed to quantify changes in 105 cytokines after …

Detection Of The Linac Jaw Face Angle Misalignment Using High Energy Electron Beam Symmetry, Song Gao, Andres Cibrian, Jared Ohrt, Peter Balter

Faculty, Staff and Student Publications

Purpose: To demonstrate the usage of a high energy electron beam symmetry measured at different collimator angles to detect jaws face angle misalignments on Varian TrueBeam linear accelerators (linac) during acceptance and commissioning processes.

Methods: During the linac acceptance, all beams were steered to a symmetric shape with the gantry and collimator at 0°. We noted that the symmetries of higher energies electrons (e.g., 16 MeV, 20 MeV) changed over 2% when measured with the collimator at 90° and/or 270° for two linacs commissioned within 5-months of each other. Misaligned applicators were ruled out as the cause of this issue. …

Intraventricular Iron Causes Severe Hydrocephalus – A Model Of Severe Neonatal Hydrocephalus, Kwang-Min Kim, Arokoruba Oboba Cheetham-West, Mohamed Rafiuddin Ahmed, Megan Phillips, Andrey V Malkovskiy, Kyle D Brewer, Jayakumar Rajadas, Kelly B Mahaney

Faculty, Staff and Student Publications

Background: Neonatal germinal matrix hemorrhage-intraventricular hemorrhage and subsequent post-hemorrhagic hydrocephalus (PHH) is a leading cause of neurologic morbidity and mortality in preterm infants. Preclinical models of PHH have implicated hemoglobin and iron-mediated cellular injury in the pathogenesis of PHH, but have typically demonstrated a phenotype characterized by mild to moderate ventriculomegaly – the equivalent of which may not even require intervention in the human condition. We sought to establish a preclinical model of severe IVH that recapitulates the severity of the hydrocephalus phenotype requiring neurosurgical intervention and to determine the causal blood degradation product resulting in severe hydrocephalus following preterm …