Medical Sciences Commons^™

Pd-L1 Positivity Predicts A Unique Hyperaggressive Tumor Group Within Meng C Meningiomas, Vijay Nitturi, Shervin Hosseingholi Nouri, Collin English, Hsiang-Chih Lu, Elizabeth Ledbetter, Diego Rojas, Sean Lau, Malcolm Mcdonald, Jacob J Mandel, Abdul Basit Khan, Arif O Harmanci, Akdes S Harmanci, Tiemo Klisch, Akash J Patel

Duncan NRI Faculty and Staff Publications

Molecular profiling has identified 3 groups of meningiomas, with MenG C tumors exhibiting the vast majority of recurrences. Efforts to find effective treatments for recurrent meningiomas have remained elusive. Higher WHO-grade meningiomas have exhibited greater Programmed Death Ligand 1 (PD-L1) expression through various methods, but the prognostic value of PD-L1 expression has not been described in the context of molecular profiling. Additionally, trials investigating PD-1/PD-L1-targeted immunotherapies have produced disappointing results. Here, we find that PD-L1 positivity, while prevalent in MenG C tumors, does not predict recurrence in the benign MenG A and B tumors. PD-L1 positivity also occurs independently of …

Mechanometabolism Instructs Hematopoietic Stem Cell Specification, Paulina D Horton, Alina Syed, Michelle Winkler, Abishek B Vaidya, Michael Rariden, Neha Arora, Yong Zhou, Michihiro Kobayashi, Momoko Yoshimoto, Hyun Jung Lee, Hyun-Eui Kim, John P Hagan, Catherine Denicourt, Travis I Moore, Pamela L Wenzel

Faculty, Staff and Student Publications

Mechanical force generated by blood flow stimulates emergence of the first hematopoietic stem cells (HSCs) that populate the blood system. Force drives the transition of HSC precursors from an endothelial to hematopoietic identity, yet the molecular regulation of this fate switch remains poorly understood. We report that shear stress triggers adaptation in mitochondrial composition, ultrastructure, and function, which are essential for hematopoietic fate and engraftment potential. Shear stress remodels mitochondria in hemogenic endothelium by promoting mitochondrial gene transcription and protein synthesis. Laminar flow selectively initiates translation of 5' terminal polypyrimidine (5'TOP) motif-containing transcripts, which commonly encode ribosome and translation machinery. …

Ectopic B Lymphocyte Follicles Exacerbate Ischemic Brain Damage Via Mif-Cd74/Cxcr4 And Interferon Signaling, Sheng Yang, Hang Zhang, Lu-Lu Xu, Luo-Qi Zhou, Yun-Hui Chu, Lian Chen, Xiao-Wei Pang, Lu-Yang Zhang, Li-Fang Zhu, Ming-Hao Dong, Ke Shang, Jun Xiao, Long-Jun Wu, Wei Wang, Dai-Shi Tian, Chuan Qin

Faculty, Staff and Student Publications

Neuroinflammation, encompassing both innate and adaptive immune responses, plays a crucial role in ischemic stroke. Although B lymphocytes are central to adaptive immunity, their contributions to ischemic stroke remain poorly understood. Here, we demonstrated that B lymphocytes accumulate in ischemic lesions, forming germinal center-like structures at the later stage after stroke, which mainly depended on in situ proliferation. This accumulation correlated with worsened neuroinflammation and ischemic injury, whereas B cell depletion reduced chronic brain damage during stroke. Mechanistically, microglia recruited B cells into ischemic lesions through MIF-CD74/CXCR4 signaling during the early phase of stroke, while IFN-related pathways in B cells …

Dna Methylation Is Associated With Von Willebrand Factor And Coagulation Factor Viii Plasma Levels: The Atherosclerosis Risk In Communities Study, Julie Hahn, Jan Bressler, Myriam Fornage, Eric Boerwinkle, Nicholas L Smith, Alanna C Morrison, Paul S De Vries

Faculty, Staff and Student Publications

Background: Limited information is available on how DNA methylation of cytosine-phosphate-guanine (CpG) sites across the genome regulate circulating von Willebrand Factor (VWF) and factor VIII (FVIII) levels.

Methods: We performed an epigenome-wide association study to examine the association of leukocyte DNA methylation levels at 483,735 CpG sites with VWF antigen plasma levels and FVIII activity in 2,597 Black and 1,011 White participants from the Atherosclerosis Risk in Communities (ARIC) study. VWF antigen levels and FVIII activity were measured at the baseline exam, while DNA methylation was measured with the Infinium HumanMethylation450 BeadChip array at visit 2 or 3. Discovery analysis …

Poly(Adp-Ribose) Glycohydrolase Enforces P21 Degradation Via Deparylation To Promote Gastric Cancer Progression, Yangchan Hu, Qimei Bao, Yixing Huang, Yan Wang, Xin Zhao, Junjun Nan, Yuxin Meng, Mingcong Deng, Yuancong Li, Zirui Zhuang, Hanyi He, Dan Zu, Yuke Zhong, Chunkai Zhang, Bing Wang, Ran Li, Yanhua He, Qihan Wang, Min Liu, John A Tainer, Yin Shi, Xiangdong Cheng, Ji Jing, Zu Ye

Faculty, Staff and Student Publications

Dysregulation of cell cycle checkpoints is a cancer hallmark, with ubiquitination-controlled protein stability playing a pivotal role. Although p21, a key cyclin-dependent kinase inhibitor, is tightly regulated by ubiquitin-mediated degradation, the key upstream modulators of its ubiquitination remain incompletely defined. Here, we identify poly(ADP-ribose) glycohydrolase (PARG) as a regulator of p21 stability in gastric cancer (GC) cells. We show that PARG expression is markedly upregulated in GC tissues and correlates with poor patient prognosis. Functional assays revealed that genetic depletion of PARG triggers G2/M phase arrest and impairs GC cell proliferation. Mechanistically, we demonstrate that PARG loss enhances p21 PARylation, …

Selective Deletion Of Fgfr1 In Agrp Neurons Impairs Energy Homeostasis Under High-Fat Diet In Mice, Daniel Shookster, Shea O'Connell, Patel Darshan, Taylor Landry, Wyatt Bunner, Zhiying Jiang, Qingchun Tong, Hu Huang

Faculty, Staff and Student Publications

Background: The global obesity crisis and the limited success of current treatments underscore the need to identify novel regulatory pathways. While central administration of α-Klotho exerts anti-obesity effects in rodents through AgRP neurons, the intracellular signaling mechanisms that mediate this process remain undefined.

Methods: To define the role of FGFR1 within the α-Klotho signaling pathway in AgRP neurons, we performed a targeted deletion of the receptor in adult mice using an AAV-mediated CRISPR/Cas9 system alongside transgenic models.

Results: Deletion of FGFR1 in AgRP neurons disrupted energy homeostasis, promoting weight gain induced by a high-fat diet. Electrophysiological recordings revealed that FGFR1 …

Cd44v9 As A Therapeutic Target For Antibody-Drug Conjugate In Advanced Breast Cancer, Dileep R Reddy, Mckenna E Flynn, Yasuaki Anami, Zhaoxuan Yang, Jayden Aleman, Minji Seo, Kyoji Tsuchikama, Jennifer A Maynard, Naoto T Ueno, Jangsoon Lee

Faculty, Staff and Student Publications

Antibody-drug conjugates (ADCs) have revolutionized breast cancer therapy. HER2 is the only validated biomarker guiding ADC therapy in breast cancer. However, their clinical benefit remains confined to HER2- and TROP2-targeted therapies. Tumor heterogeneity and acquired resistance often limit durable responses, underscoring the need for novel, tumor-specific ADC targets. CD44 variant isoform 9 (CD44v9), a splice variant of the CD44 family, is largely absent in normal tissues but enriched in aggressive breast cancers, where it contributes to stemness, redox regulation, and therapy resistance. In this study, we developed a chimeric monoclonal antibody against CD44v9 (clone SUM24.1, IgG1) and conjugated it to …

The Filamentous Ultrastructure Of The Popz Condensate Is Required For Its Cellular Function, Daniel Scholl, Tumara Boyd, Andrew P Latham, Alexandra Salazar, Asma M A M Khan, Steven Boeynaems, Alex S Holehouse, Gabriel C Lander, Andrej Sali, Donghyun Park, Ashok A Deniz, Keren Lasker

Duncan NRI Faculty and Staff Publications

Biomolecular condensates have key roles in regulating cellular processes. Yet, the relationship between atomic features and condensate function remains poorly understood. We studied this relationship using the polar organizing protein Z (PopZ). Here, we revealed hierarchical assembly of PopZ into a filamentous condensate by integrating cryo-electron tomography, biochemistry, single-molecule techniques and molecular dynamics simulations. The PopZ helical domain drives filamentation and condensation, while the disordered region inhibits them. Phase-dependent conformational changes prevent interfilament contacts in the dilute phase and expose client-binding sites in the dense phase. Perturbing filament formation in vitro alters the dynamics of scaffold and client proteins and …

Intraoperative Ultrasound Imaging Features Guiding Surgical Strategy In Spinal Cord Ependymoma Resection, Esteban Ramirez-Ferrer, Ian E Mccutcheon, Gil Kimchi, Behrang Amini, Romulo Andrade Almeida, Francisco Call-Orellana, Juan Pablo Zuluaga-Garcia, Robert Y North, Christopher A Alvarez-Breckenridge, Jeffrey S Weinberg, Laurence D Rhines, Claudio E Tatsui

Faculty, Staff and Student Publications

Background and objectives: Preoperative imaging provides surgeons with an initial estimate of tumor infiltration and the likelihood of achieving an en-bloc resection in spinal cord ependymomas, yet the definitive decision is made intraoperatively. This study characterizes the intraoperative ultrasound (iUS) features that guide real-time surgical strategy and are associated with successful en-bloc removal.

Methods: A retrospective review of iUS images obtained during resection of spinal cord ependymomas was performed. The presence of a peritumoral halo representing the transition zone between the tumor and the spinal cord, the dorsal sagittal area of the spinal cord overlying the tumoral poles, the presence …

Alpha 7 Nicotinic Acetylcholine Receptor Contributes To Long-Term Cognitive Recovery Following Ischemic Stroke, Dustin T Nguyen, Kate Mendoza, Cassandra Hall, Chunfeng Tan, Anjali Chauhan

Faculty, Staff and Student Publications

Stroke is associated with autonomic dysfunction and reduced acetylcholine (ACh), a neurotransmitter critical for cognition. ACh signals in part through the alpha-7 nicotinic acetylcholine receptor (α7nAChR), a ligand-gated ion channel involved in synaptic plasticity, learning, and memory. Impaired α7nAChR signaling has been linked to heightened neuroinflammation and poor acute stroke recovery. Here, we investigated whether α7nAChR contributes to post-stroke cognitive recovery in young male mice. Wild-type (WT) and α7nAChR knockout (α7n0KO) mice underwent 60-min middle cerebral artery occlusion (MCAO). In a pharmacology cohort, the α7nAChR agonist GTS-21 was administered immediately after reperfusion and then daily for 20 days. Cognitive performance …

Barriers To Occupational And Physical Therapy Utilization For Children With Cancer, Maria C Swartz, Shiming Zhang, Donna Kelly, Clark R Andersen, Keri Schadler, Alakh P Rajan, Eduardo Gonzalez Villarreal, Stephanie J Wells, Amy Heaton, Karen Moody

Faculty, Staff and Student Publications

Introduction: Occupational and physical therapy (OT/PT) referrals and utilization barriers for childhood cancer patients have not been adequately examined. The current study investigated factors influencing referrals to and utilization of OT/PT services among children with cancer at an NIH-designated cancer center.

Methods: This retrospective cohort study included pediatric cancer patients (up to 18.99 years) presenting to the center over a 33.5-month period. Variables that could influence referrals to OT/PT were extracted from the electronic medical record (EMR) including OT and PT referrals (inpatient and outpatient), OT and PT consult completion, age at diagnosis, cancer type, sex, race/ethnicity, insurance, cancer treatment, …

Clinicopathologic And Molecular Characteristics Of High-Grade Appendiceal Mucinous Neoplasms, Ashlee N Seldomridge, Michael G White, Christopher Scally, Richard E Royal, Mark Routbort, Jbryan Iorgulescu, Michael J Overman, Sun Mi Lee, Wai Chin Foo, Melissa W Taggart, Yun Song, Paul F Mansfield, Keith F Fournier, John Paul Shen, Beth A Helmink

Faculty, Staff and Student Publications

Background: Although 2016 consensus guidelines defined high-grade appendiceal mucinous neoplasms (HAMNs) as a distinct histologic entity, their clinical course and optimal management remain poorly characterized. Comparative data with low-grade appendiceal mucinous neoplasms (LAMNs) are limited. This study aims to detail the clinical management and outcomes of patients with HAMN and those with LAMN.

Methods: This retrospective cohort study was conducted at a large academic cancer center. An internal database was queried to identify patients with LAMN or HAMN who underwent appendectomy between 2016 and 2024. Kaplan-Meier survival analyses were used to assess the impact of primary tumor type and peritoneal …

Impact Of Mutational Landscape And Burden On Rbc Transfusion Response In Patients With Lower-Risk Myelodysplastic Syndromes (Lr-Mds) In The Commands Study, Rami S Komrokji, Sheida Hayati, Manuel Ugidos, Guillermo Garcia-Manero, Matteo Giovanni Della Porta, Amer M Zeidan, Valeria Santini, Uwe Platzbecker, Anita K Gandhi, Rajasekhar N V S Suragani

Faculty, Staff and Student Publications

The COMMANDS trial established luspatercept as a first‐line treatment for anemia in transfusion‐dependent lower‐risk (LR) myelodysplastic syndromes (MDS). Here we report red blood cell (RBC) transfusion response analysis based on somatic mutations profile and disease risk for patients treated with luspatercept or epoetin alfa in the COMMANDS trial. Of 350 evaluable patients, 238 (68.0%) had MDS with multiple lineage dysplasia and ring sideroblasts (RS) according to World Health Organization 2016 criteria, and 320 (91.4%) had somatic mutations in ≥ 1 gene (median, 2) with median variant allele frequencies (VAF) of 2%–59%. Mutation profiles were similar in the treatment groups. Luspatercept …

Shiny-Magec: A Bayesian R Shiny Application For Meta-Analysis Of Censored Adverse Events, Zihan Zhou, Zizhong Tian, Christine Peterson, Le Bao, Shouhao Zhou

Faculty, Staff and Student Publications

Accurate assessment of adverse event (AE) incidence is critical in clinical research for drug safety. While meta-analysis serves as an essential tool to comprehensively synthesize the evidence across multiple studies, incomplete AE reporting in clinical trials remains a persistent challenge. In particular, AEs occurring below study-specific reporting thresholds are often omitted from publications, leading to left-censored data. Failure to account for these censored AE counts can result in biased AE incidence estimates. We present an R Shiny application that implements a Bayesian meta-analysis model specifically designed to incorporate censored AE data into the estimation process. This interactive tool provides a …

Fgl2-Knockout Tumor Cells Serve As A Vaccine Inducing Long-Duration Brain-Resident Memory T Cells That Reject Subsequent Intracranial Tumor Cell Challenges, Sheng Zhang, Yining Jin, Zhiliang Jia, Xueqing Xia, Yang Li, Qi Wang, Jing Wang, Jian Wang, Joya Chandra, Gregory K Friedman, Shulin Li

Faculty, Staff and Student Publications

The failure to prevent brain tumors, including both recurrent primary and metastatic brain tumors, is the primary cause of patients' mortality. We developed a novel whole tumor-cell vaccine to rapidly induce long-duration brain-resident memory T (TRM) cells that prevent brain tumor progression. Ten Fgl2-KO primary and metastatic tumor cell lines, generated via CRISPR/Cas9, were used to vaccinate mice and for intracranial challenges with the WT tumor cells. Not only did vaccinated mice reject these tumor cell challenges, but also more than half of these mice became long-duration survivors. Transplanting brain immune cells from vaccinated mice into naïve mice enabled this …

Spatial Profiling Reveals Distinct Molecular And Immune Evolution Of Mouse Lung Adenocarcinoma Precancers With Or Without Carcinogen Exposure, Bo Zhu, Muhammad Aminu, Pingjun Chen, Jian-Rong Li, Chuanpeng Dong, Chenyang Li, Yanhua Tian, Shao-Wei Lu, Hong Chen, Chenxi Ma, Xin Hu, Jie Ye, Andrew Y Liu, Beibei Huang, Frank R Rojas, Parra Cuentas Edwin Roger, Ou Shi, Monique B Nilsson, Alissa Poteete, Khaja B Khan, Wei Lu, Luisa M Solis Soto, Junya Fujimoto, Cara Haymaker, Ignacio I Wistuba, Zhubo Wei, Linghua Wang, Don L Gibbons, Ken Chen, Alexandre Reuben, Jason M Schenkel, John V Heymach, Chao Cheng, Jia Wu, Jianjun Zhang

Faculty, Staff and Student Publications

Tumor evolution involves genetic, transcriptional, and phenotypic alterations that shape cancer cell behavior and interactions with the microenvironment. While single‐cell technologies have advanced our understanding of this process, spatial dynamics remain incompletely characterized. Here, whole‐exome sequencing (WES), imaging mass cytometry (IMC), and spatial transcriptomics (ST) were integrated to study molecular evolution and immune responses in two lung adenocarcinoma (LUAD) mouse models: a genetically engineered model (129S4/Sv‐KrasLSL‐G12D, termed 129S4 K) and a carcinogen‐induced precancer model (129S4 U). Compared to 129S4 K, 129S4 U tumors exhibited higher mutational, neoantigen but lower copy number variation (CNV) burdens at matched developmental timepoints, consistent with …

Segmental Tracheal Resection For Thyroid Cancer: Perioperative Morbidity, Locoregional Control, And Survival, Anastasios Maniakas, David C Wilde, Isabelle Fournier, Emily K Hyde, Li Xu, Jennifer R Wang, Neil D Gross, Erich M Sturgis, Victoria Banuchi, Naifa L Busaidy, Maria E Cabanillas, Priyanka Iyer, Ramona Dadu, Steven G Waguespack, Mimi I Hu, G Brandon Gunn, Michael Kwon, Salmaan Ahmed, Michelle D Williams, Mark E Zafereo

Faculty, Staff and Student Publications

Background: Segmental tracheal resection is rarely needed for advanced thyroid cancer but is among the most complex, high-risk thyroid surgeries.

Methods: Retrospective study of patients undergoing segmental tracheal resection for thyroid cancer at MD Anderson Cancer Center (2005-2024).

Results: We identified 120 patients with a median follow-up of 4.6 years (range 0.02-16.38). Papillary thyroid cancer was most common (68%). The median number of tracheal rings resected was 4 (range 1-9). Seventeen (14%) patients had a new tracheostomy placed at the time of surgery, with 11 (9%) remaining trach-dependent at last follow-up. Twenty-six (22%) patients had a return to the operating …

Sexual Toxicity After Chemoradiation For Anal Cancer Among Men Who Have Sex With Men: A Mixed-Methods Analysis, Beck O Gold, Angie Arzola, Benjamin R Schrank, Van K Morris, Christophe Marques, Jaime Gilliland, Thomas M Atkinson, Emma B Holliday

Faculty, Staff and Student Publications

Purpose: Chemoradiation (CRT) is the standard of treatment for localized anal squamous cell carcinoma (SCCA). Although cure rates are high, acute and late toxicities are common. There are increasing published data regarding vaginal stenosis and erectile dysfunction; however, the nature and impact of holistic sexual dysfunction after pelvic radiation, particularly among men who have sex with men (MSM), remains poorly characterized. This study aimed to: (1) explore patient-reported sexual health outcomes among MSM as measured by existing patient-reported outcome tools, and (2) assess the applicability of these existing tools for this population.

Methods and materials: MSM who are at least …

Physical Activity In Osteosarcoma Patients During And Post Therapy: A Single Site Prospective Observational Study, Elysia R Cohen, Clark Andersen, Karen Moody, Maria C Swartz, Michael C Robertson, Alakh Rajan, Theresa Honey, Sandra Lugo, Grace Waterman, Keri Schadler

Faculty, Staff and Student Publications

PURPOSE: Osteosarcoma is the most common primary bone tumor in childhood and adolescence. Many patients face long-term impairments in their mobility and function after treatment, leading to a decrease in their quality of life. Exercise has been shown to improve functional recovery and improve quality of life in patients with cancer, though data specific to children with osteosarcoma are sparse. Exercise has also been shown to be feasible in patients undergoing chemotherapy, with numerous potential benefits to health and quality of life. To design the most effective exercise interventions for children and adolescents with osteosarcoma, we must first understand the …

Clemastine Ameliorates Cognitive Deficits In An Experimental Rat Model Of Chronic Cerebral Hypoperfusion, Xuemei Zong, Zhihai Huang, Fanfei Kong, Yu Feng, Yulan Zhang, Peibin Zou, Hung Wen Lin, David C Hess, Quanguang Zhang

Faculty, Staff and Student Publications

Chronic cerebral hypoperfusion (CCH) profoundly affects patient well-being and has been proposed as a risk factor for cognitive impairment and dementia. However, due to the limited understanding of the pathophysiology of CCH, there are currently no effective preventive or therapeutic approaches for CCH-associated cognitive impairment. Therefore, identifying new targets for CCH is essential to bridge this knowledge gap. In this study, we sought to determine whether enhanced myelination could prevent cognitive impairment associated with CCH. Experimental CCH was induced via bilateral common carotid artery occlusion (BCCAO) in rats, and clemastine, a well-established pro-myelinating agent, was administered to boost myelin renewal. …

Optimizing Feasibility And Acceptability Of An Online Expressive Writing Intervention For Survivors Of Adolescent And Young Adult Cancer: A Pilot Randomized Trial Of Iterative Modifications And Outcomes, Eunju Choi, Yusi Aveva Xu, Celia Cy Wong-Meli, Michael E Roth, Yisheng Li, Qian Lu

Faculty, Staff and Student Publications

Objective: To evaluate the feasibility of an online expressive writing (EW) intervention for survivors of adolescent and young adult (AYA) cancer and determine whether iterative, theory-driven modifications can enhance response, adherence, and completion rates.

Methods: In this randomized pilot trial, survivors of AYA cancer were recruited through a hospital-based AYA oncology clinic and an online community. Forty participants were randomly assigned to the EW intervention or control group. To improve on lower-than-expected adherence and completion rates in a previous cohort, the protocol was iteratively revised using the Framework for Reporting Adaptations and Modifications to Evidence-based Implementation Strategies (FRAME-IS). Modifications included …

Large Language Models For Bioinformatics, Wei Ruan, Yanjun Lyu, Jing Zhang, Jiazhang Cai, Peng Shu, Yang Ge, Yao Lu, Shang Gao, Yue Wang, Peilong Wang, Lin Zhao, Tao Wang, Yufang Liu, Luyang Fang, Ziyu Liu, Zhengliang Liu, Yiwei Li, Zihao Wu, Junhao Chen, Hanqi Jiang, Yi Pan, Zhenyuan Yang, Jingyuan Chen, Shizhe Liang, Wei Zhang, Terry Ma, Yuan Dou, Jianli Zhang, Xinyu Gong, Qi Gan, Yusong Zou, Zebang Chen, Yuanxin Qian, Shuo Yu, Jin Lu, Kenan Song, Xianqiao Wang, Andrea Sikora, Gang Li, Xiang Li, Quanzheng Li, Yingfeng Wang, Lu Zhang, Yohannes Abate, Lifang He, Wenxuan Zhong, Rongjie Liu, Chao Huang, Wei Liu, Ye Shen, Ping Ma, Hongtu Zhu, Yajun Yan, Dajiang Zhu, Tianming Liu

Faculty, Staff and Student Publications

With the rapid advancements in large language model technology and the emergence of bioinformatics-specific language models (BioLMs), there is a growing need for a comprehensive analysis of the current landscape, computational characteristics, and diverse applications. This survey aims to address this need by providing a thorough review of BioLMs, focusing on their evolution, classification, and distinguishing features, alongside a detailed examination of training methodologies, datasets, and evaluation frameworks. We explore the wide-ranging applications of BioLMs in critical areas such as disease diagnosis, drug discovery, and vaccine development, highlighting their impact and transformative potential in bioinformatics. We identify key challenges and …

Beyond Short Microhomologies: Mismatch-Compatible Pol Θ-Mediated Dna Damage Repair, Yuzhen Li, Richard D Wood

Faculty, Staff and Student Publications

DNA polymerase θ (Pol θ)-mediated end-joining (TMEJ), one of several pathways for repairing DNA double-strand breaks, is traditionally thought to initiate via anchoring at short, consecutive, and perfectly matched microhomologies (MHs). Emerging evidence indicates that Pol θ can utilize MHs containing mismatches both in vitro and in vivo. This revised definition of MH provides a mechanistic explanation for a broader spectrum of Pol θ-dependent repair outcomes. Here, we summarize recent findings on the revised definition of MHs utilized by Pol θ, assess the applicability of this concept across species, and compare TMEJ with other (micro)hom(e)ology-mediated repair pathways. We explore how …

Tuscan: Tumor Segmentation And Classification Analysis In Spatial Transcriptomics, Chenxuan Zang, Charles C Guo, Yaohong Wang, Peng Wei, Ziyi Li

Faculty, Staff and Student Publications

The identification of tumor cells is pivotal for understanding tumor heterogeneity and the tumor microenvironment. Recent advances in spatially resolved transcriptomics (SRT) have revolutionized the way that transcriptomic profiles are characterized and have enabled the simultaneous quantification of transcript locations in intact tissue samples. SRT is a promising alternative method to study gene expression patterns in spatial domains. Nevertheless, the precise detection of tumor regions within intact tissue remains a great challenge. A common strategy for identifying tumor cells is via tumor-specific marker gene expression signatures, which are highly dependent on marker accuracy. Another effective approach is through aneuploid copy …

Impact Of Intra- And Interfractional Motion On The Dose Distribution And Urinary Adverse Events For Magnetic Resonance-Guided Prostate Cancer Radiotherapy, Shu Xing, Sarah Burleson, Xiao Tan, Qijie Huang, Nima Hassan-Razein, Chengcheng Gui, Ergys Subashi, Himanshu Nagar, Victoria Brennan, Neelam Tyagi

Faculty, Staff and Student Publications

Purpose: To evaluate the impact of intra- and interfractional motion on dose distribution and clinical outcome in prostate magnetic resonance (MR)-guided adaptive radiotherapy.

Methods: Seventy-six patients were treated with five-fraction stereotactic radiotherapy on a 1.5 T MR linear accelerator. Cine MR images were acquired during treatment and exported to a motion monitoring research package, to generate motion traces in the anterior-posterior (AP), superior-inferior (SI) and left-right (LR) directions. Planned dose distributions were shifted according to motion trace to reconstruct intrafraction motion-blurred dose. Intrafraction motion-blurred doses were deformably registered to fraction one motion-blurred dose to obtain interfraction accumulated dose. The impact …

Classification Of Major Depressive Disorder Using Vertex-Wise Brain Sulcal Depth, Curvature, And Thickness With A Deep And A Shallow Learning Model, Roberto Goya-Maldonado, Tracy Erwin-Grabner, Ling-Li Zeng, Christopher R K Ching, Andre Aleman, Alyssa R Amod, Zeynep Basgoze, Francesco Benedetti, Bianca Besteher, Katharina Brosch, Robin Bülow, Romain Colle, Colm G Connolly, Emmanuelle Corruble, Baptiste Couvy-Duchesne, Kathryn Cullen, Udo Dannlowski, Christopher G Davey, Annemiek Dols, Jan Ernsting, Jennifer W Evans, Lukas Fisch, Paola Fuentes-Claramonte, Ali Saffet Gonul, Ian H Gotlib, Hans J Grabe, Nynke A Groenewold, Dominik Grotegerd, Tim Hahn, J Paul Hamilton, Laura K M Han, Ben J Harrison, Tiffany C Ho, Neda Jahanshad, Alec J Jamieson, Andriana Karuk, Tilo Kircher, Bonnie Klimes-Dougan, Sheri-Michelle Koopowitz, Thomas Lancaster, Ramona Leenings, Meng Li, David E J Linden, Frank P Macmaster, David M A Mehler, Susanne Meinert, Elisa Melloni, Bryon A Mueller, Benson Mwangi, Igor Nenadić, Amar Ojha, Yasumasa Okamoto, Mardien L Oudega, Brenda W J H Penninx, Sara Poletti, Edith Pomarol-Clotet, Maria J Portella, Joaquim Radua, Elena Rodríguez-Cano, Matthew D Sacchet, Raymond Salvador, Anouk Schrantee, Kang Sim, Jair C Soares, Aleix Solanes, Dan J Stein, Frederike Stein, Aleks Stolicyn, Sophia I Thomopoulos, Yara J Toenders, Aslihan Uyar-Demir, Eduard Vieta, Yolanda Vives-Gilabert, Henry Völzke, Martin Walter, Heather C Whalley, Sarah Whittle, Nils Winter, Katharina Wittfeld, Margaret J Wright, Mon-Ju Wu, Tony T Yang, Carlos Zarate, Dick J Veltman, Lianne Schmaal, Paul M Thompson, Enigma Major Depressive Disorder Working Group

Faculty, Staff and Student Publications

Major depressive disorder (MDD) is a complex psychiatric disorder that affects the lives of hundreds of millions of individuals around the globe. Even today, researchers debate if morphological alterations in the brain are linked to MDD, likely due to the heterogeneity of this disorder. The application of deep learning tools to neuroimaging data, capable of capturing complex non-linear patterns, has the potential to provide diagnostic and predictive biomarkers for MDD. However, previous attempts to demarcate MDD patients and healthy controls (HC) based on segmented cortical features via linear machine learning approaches have reported low accuracies. In this study, we used …

Trends And Challenges: A 15-Year Review Of Imaging And Radiation Oncology Core Anthropomorphic Phantom Audits For Proton Therapy, Lian Duan, Hunter S Mehrens, Stephen F Kry, Jessica R L Lowenstein, Nadia Hernandez, Lucas B Acuna Scafati, Paige A Taylor

Faculty, Staff and Student Publications

Purpose: This study aims to analyze the trends in institutional performance on Imaging and Radiation Oncology Core (IROC) proton phantoms and to investigate the impact of treatment parameters on proton therapy delivery accuracy.

Materials and methods: We analyzed 402 IROC anthropomorphic phantom audits performed by 57 institutions worldwide between 2009 and 2024, including brain, head and neck (H&N), spine, prostate, lung, and liver phantoms. Dosimetric assessments included thermoluminescent dosimeters (TLDs) for dose comparison and gamma analysis of radiochromic film. The lung and liver phantoms were irradiated with simulated motion. Univariate analysis was performed to evaluate the relationships between treatment parameters …

An Adp Getaway Service, Not An Atp Tank: Insights Into The Phosphagen System In Neurons, Madeline P Marques, Kartik Venkatachalam

Faculty, Staff and Student Publications

No abstract provided.

Pharmacokinetic Modeling Strategies For Dynamic Hyperpolarized Urea Imaging, Keith A Michel, Collin J Harlan, Christopher M Walker, Matthew E Merritt, Yunyun Chen, Stephen Y Lai, James A Bankson

Faculty, Staff and Student Publications

Purpose: To evaluate pharmacokinetic modeling methods for quantification of tissue perfusion/permeability with hyperpolarized 13C urea.

Methods: Three models for quantitative analysis of dynamic HP urea imaging data were proposed and evaluated in numerical simulations and a thyroid cancer mouse model. A multicompartment model resembling the extended Tofts model for DCE-MRI (Model I) and two simplified models were used. The simplified models each eliminate a volume parameter representing vascular (Model II) or impermeable cellular space (Model III). Signal curves were generated from Model I, and models were fit to these synthetic data to quantify the effects of acquisition settings, bias in …

Quantifying Rate-Limiting Genetic Variation In Breast And Ovarian Tumourigenesis, Kathleen E Houlahan, Mahad Bihie, Yves Greatti, Julián Grandvallet Contreras, Daniel J Fulop, Gonzalo Lopez, Marc Williams, Hsin-Hsiung Huang, Peter Van Loo, Paul C Boutros, Kuan-Lin Huang

Faculty, Staff and Student Publications

Background: The number and type of genetic alterations required to initiate breast and ovarian cancer remain unclear. While germline BRCA1/2 carriers show markedly elevated cancer risk, it is uncertain whether point mutations or copy number alterations constitute the rate-limiting events of tumourigenesis.

Methods: We developed a statistical framework extending prior incidence-mutation models to estimate the minimal number and type of driver events required for cancer initiation. Somatic mutation and copy-number data from >3000 breast and ovarian cancers in TCGA and METABRIC were compared between germline BRCA1/2 carriers and non-carriers matched on subtypes. Results were validated through analyses of evolutionary timing …