Biomedical Informatics Commons^™

Evaluation Of Quantum Contouring Algorithms For Treatment Planning On Mr Abdominal Images, Rachel Glenn, Tucker Netherton, Adrian Celaya, Mohamed Eltaher, Beatrice Riviere, Eugene J Koay, David Fuentes

Faculty, Staff and Student Publications

Introduction: Quantum computing is increasingly being investigated for integration into medical radiology and healthcare applications worldwide. Given its potential to enhance clinical care and medical research, there is growing interest in evaluating its practical applications in clinical workflows.

Methods: We developed an evaluation of quantum computing-based auto-contouring methods to introduce medical physicists to this emerging technology. We implemented existing quantum algorithms as prototypes tailored for specific quantum hardware, focusing on their application to auto-contouring in medical imaging. The evaluation was performed using a medical resonance imaging (MRI) abdominal dataset, comprising 102 patient scans.

Results: The quantum algorithms were applied to …

Novel Use And Value Of Contrast-Enhanced Susceptibility-Weighted Imaging Morphologic And Radiomic Features In Predicting Extremity Soft Tissue Undifferentiated Pleomorphic Sarcoma Treatment Response, Raul F Valenzuela, Elvis De Jesus Duran Sierra, Mathew A Canjirathinkal, Behrang Amini, Ken-Pin Hwang, Jingfei Ma, Keila E Torres, R Jason Stafford, Wei-Lien Wang, Robert S Benjamin, Andrew J Bishop, John E Madewell, William A Murphy, Colleen M Costelloe

Faculty, Staff and Student Publications

Purpose: Undifferentiated pleomorphic sarcomas (UPSs) demonstrate therapy-induced hemosiderin deposition, granulation tissue formation, fibrosis, and calcification. We aimed to determine the treatment-assessment value of morphologic tumoral hemorrhage patterns and first- and high-order radiomic features extracted from contrast-enhanced susceptibility-weighted imaging (CE-SWI).

Materials and methods: This retrospective institutional review board-authorized study included 33 patients with extremity UPS with magnetic resonance imaging and resection performed from February 2021 to May 2023. Volumetric tumor segmentation was obtained at baseline, postsystemic chemotherapy (PC), and postradiation therapy (PRT). The pathology-assessed treatment effect (PATE) in surgical specimens separated patients into responders (R; ≥90%, n = 16), partial responders …

Quantile Regression Based Method For Characterizing Risk-Specific Behavioral Patterns In Relation To Longitudinal Left-Censored Biomarker Data Collected From Heterogeneous Populations, Minjae Lee, Belinda M Reininger, Kelley Pettee Gabriel, Nalini Ranjit, Larkin L Strong

Faculty, Staff and Student Publications

There are many studies aimed at promoting positive lifestyle behaviors to reduce lifetime risk of cancer and related diseases. However, assessing these modifiable behaviors through statistical modeling is challenging because of the multidimensionality of interrelated measurements that may dramatically differ between at-risk individuals. Taking into account this heterogeneity while considering the multidimensionality of behavior changes is fundamental to tailoring interventions to their needs. Biomarkers that identify high-risk individuals may help validate proximal measures, but the number of validated methods that link biomarkers to multiple behavioral measurements by determining their dynamic relations with disease risks is limited to just a few, …

Prrx1 Has Functional Roles In Pancreatic Acinar To Ductal Metaplasia And Carcinogenesis, Noriyuki Nishiwaki, Kensuke Sugiura, Kensuke Suzuki, Alina L Li, Constanza Tapia Contreras, Gizem Efe, Alice E Shin, Dorsay Sadeghian, Jun Zhao, Anirban Maitra, Jason R Pitarresi, Peter A Sims, Rohit Chandwani, Anil K Rustgi

Faculty, Staff and Student Publications

No abstract provided.

Building Boundary-Crossers In Clinical-Translational Research: An Exploratory Study Of A Novel Communication Intervention, Carrie Cameron, Irene Rull-Garcia, Laura G Meyer, Jose-Armando Fernandez-Guerrero, Erin K Dahlstrom, Christine Bell, Christine Pribbenow

Faculty, Staff and Student Publications

INTRODUCTION: Integrating scientific research across multiple disciplines to advance breakthroughs is at the heart of clinical-translational science (CTS); among competencies that have been identified as essential for progress, skillful communication is critical. Few tools are available to address the social dynamics of the multidimensional diversity characteristics of CTS. We created the "Building a Diverse Biomedical Workforce Through Communication Across Difference (CAD)" workshop intervention. Based on principles of intercultural communication, CAD taught novel situationally-based communication skills to dyads of near-peer mentors and their undergraduate mentees. This study reports on the effectiveness of the operative mechanisms employed in CAD workshops for helping …

Tissue And Imaging Biomarkers Of Response To Neoadjuvant Nivolumab Or Nivolumab Plus Ipilimumab In Patients With Resectable Hepatocellular Carcinoma, Michael Lapelusa, Shadi Chamseddine, Hop Sanderson Tran Cao, Lianchun Xiao, Elshad Hasanov, Priya Bhosale, Hesham M Amin, Yehia I Mohamed, Betul Gok Yavuz, Yara Sakr, Li Xu, Ian Hu, Sunyoung S Lee, Divya Sakamuri, Sonali Jindal, Van Nguyen, Michael A Curran, Ryan Sun, Asif Rashid, Dan Gabriel Duda, Padmanee Sharma, Aliya Qayyum, Ahmed Omar Kaseb

Faculty, Staff and Student Publications

Introduction: Perioperative immunotherapy has shown promise in some patients with early-stage hepatocellular carcinoma (HCC). This study examined tissue and imaging biomarkers associated with pathologic response in a phase II clinical trial in patients with resectable HCC.

Methods: Analysis included 18 patients with biopsy-proven resectable HCC treated with neoadjuvant nivolumab plus ipilimumab or nivolumab alone in a phase II clinical trial at MD Anderson Cancer Center (NCT03222076). Liver MRE (to measure tissue fibrosis) and biopsies (to evaluate immune activation markers) were obtained serially pretreatment and after completing neoadjuvant immunotherapy. A major pathologic response (MPR) was defined as tumor necrosis …

Knowledge-Based Planning For Fully Automated Radiation Therapy Treatment Planning Of 10 Different Cancer Sites, Christine V Chung, Meena S Khan, Adenike Olanrewaju, Mary Pham, Quyen T Nguyen, Tina Patel, Prajnan Das, Michael S O'Reilly, Valerie K Reed, Anuja Jhingran, Hannah Simonds, Ethan B Ludmir, Karen E Hoffman, Komeela Naidoo, Jeannette Parkes, Ajay Aggarwal, Lauren L Mayo, Shalin J Shah, Chad Tang, Beth M Beadle, Julie Wetter, Gary Walker, Simon Hughes, Vinod Mullassery, Stephen Skett, Christopher Thomas, Lifei Zhang, Son Nguyen, Raymond P Mumme, Raphael J Douglas, Hana Baroudi, Laurence E Court

Faculty, Staff and Student Publications

Purpose: Radiation treatment planning is highly complex and can have significant inter- and intra-planner inconsistency, as well as variability in planning time and plan quality. Knowledge-based planning (KBP) is a tool that can be used to efficiently produce high-quality, consistent, clinically acceptable plans, independent of planner skills and experience. In this study, we created and validated multiple clinically acceptable and fully automatable KBP models, with the goal of creating VMAT plans without user intervention.

Methods: Ten KBP models were configured using high quality clinical plans from a single institution. They were then honed to be part of a fully automatable …

Characterizing Spatial Immune Architecture In Metastatic Melanoma Using High-Dimensional Multiplex Imaging, Joel Eliason, Santhoshi Krishnan, Yasunari Fukuda, Matias A Bustos, Dan Winkowski, Sungnam Cho, Akshay Basi, Regan Baird, Elizabeth A Grimm, Michael A Davies, Dave S B Hoon, Arvind Rao, Jared K Burks, Suhendan Ekmekcioglu

Faculty, Staff and Student Publications

Introduction: Immune checkpoint inhibitors (ICIs) have significantly improved survival for patients with metastatic melanoma, yet many experienceresistance due to immunosuppressive mechanisms within the tumor immune microenvironment (TIME). Understanding how the spatial architecture of immune and inflammatory components changes across disease stages may reveal novel prognostic biomarkers and therapeutic targets.

Methods: We performed high-dimensional spatial profiling of two melanoma tissue microarrays (TMAs), representing Stage III (n = 157) and Stage IV (n = 248) metastatic tumors. Using imaging mass cytometry (IMC) and multiplex immunofluorescence (mIF), we characterized the phenotypic, functional, and spatial properties of the TIME. Cellular neighborhoods were …

Case Report: Durable Remission After Abscopal Effect Following Transcatheter Hepatic Arterial Embolization In A Patient With Mucosal Melanoma Refractory To Immunotherapy, Lynsey M Claus, Hannah E Kostan, Marshall E Hicks, Rony Avritscher, Michael A Davies

Faculty, Staff and Student Publications

Mucosal melanoma, a rare subtype of melanoma affecting mucosal surfaces, presents significant challenges in diagnosis and treatment, particularly due to its low programmed death-ligand 1 (PD-L1) expression and reduced response to immune checkpoint inhibitors (ICIs). This case report describes a 58-year-old woman with metastatic nasal mucosal melanoma initially resistant to neoadjuvant ipilimumab and nivolumab. After undergoing hepatic transcatheter arterial embolization, she experienced an unexpected abscopal effect, where distant metastases showed near-complete resolution despite prior lack of response to immunotherapy. The patient's disease initially progressed despite two cycles of ICI treatment, and further immunotherapy with nivolumab and relatimab did not improve …

Editorial: Molecular Mechanisms And Targeted Therapies For Colorectal Cancer Vol Ii, Alessandro Passardi, David Gibbons, Antonio Mario Scanu, Shilpa S Dhar

Faculty, Staff and Student Publications

No abstract provided.

Cord Blood-Derived Ink T Cells As A Platform For Allogeneic Car T Cell Therapy, Maison Grefe, Abel Trujillo-Ocampo, Jelita Clinton, Hong He, Ling Yu, Dan Li, Qing Ma, Elizabeth J Shpall, Jeffrey J Molldrem, Jin S Im

Faculty, Staff and Student Publications

CD1d-restricted invariant Natural Killer (iNK) T cells are a suitable candidate for allogeneic Chimeric Antigen Receptor (CAR) T cell therapy as they do not cause graft-versus-host disease (GvHD) due to the monomorphic nature of CD1d proteins. However, the phenotypic and functional heterogeneity of iNK T cells from adult donors (AD) may lead to the inconstant CAR-iNK T cell products. Cord blood-derived (CB) iNK T cells, in contrast, exhibit inter-donor homogeneity in phenotype including uniform CD4 expression and are enriched in memory iNK T cell populations. Thus, we evaluated the preclinical therapeutic potential of iNK T cells derived from cord blood …

Molecular Alterations In Idh-Mutant Astrocytoma: A Multi-Institutional Retrospective Study, Keng Lam, Hanim I Ozkizilkaya, Denái R Milton, Antonio Dono, Yajie Liu, Suprateek Kundu, Vinodh A Kumar, Jason M Johnson, Yoshua Esquenazi, Chirag B Patel, Leomar Y Ballester

Faculty, Staff and Student Publications

Background: Several molecular alterations have been identified to provide prognosis for patients with isocitrate dehydrogenase (IDH)-mutant astrocytoma. However, contemporary baseline survival data with respect to their molecular alterations are lacking. The prognostic value of histologic grading remains controversial.

Methods: This was a retrospective multi-site study of adult IDH-mutant diffuse astrocytoma patients. Overall survival (OS) was estimated using the Kaplan-Meier method. Associations between OS and measures of interest were evaluated using Cox proportional hazards regression models.

Results: We identified 241 eligible patients. The most frequent mutations were IDH1 (98%), TP53 (91%), ATRX (70%), ARID1A (8%), BRCA2 (6%), TSC2 (6%), CDKN2A (6%), …

The Impact Of Post-Remission Granulocyte Colony-Stimulating Factor Use In The Phase 3 Studies Of Venetoclax Combination Treatments In Patients With Newly Diagnosed Acute Myeloid Leukemia, Courtney D Dinardo, Keith W Pratz, Panayiotis Panayiotidis, Xudong Wei, Vladimir Vorobyev, Árpád Illés, Inho Kim, Vladimir Ivanov, Grace Ku, Catherine L Miller, Meng Zhang, Fernando Tatsch, Jalaja Potluri, Xenia Schmidt, Christian Récher

Faculty, Staff and Student Publications

No abstract provided.

Il-7: A Potential Next-Generation Adjuvant For Immune Cell Therapies, Richard S Hotchkiss, John F Dipersio, Cassian Yee, Russell K Pachynski, Marcel R M Van Den Brink

Faculty, Staff and Student Publications

Cell-based immune therapies ranging from CAR-T cells to tumor infiltrating lymphocytes (TILs) and endogenous T-cell products, have produced unprecedented clinical responses in hematologic malignancies and are currently under active investigation for solid tumors. Nevertheless, several key challenges continue to limit the durability and breadth of clinical benefit. IL-7 is a pleiotropic cytokine that increases both the number and function of lymphocytes. Although not yet clinically approved, IL-7 has been used in over 620 adult and pediatric patients for a variety of reasons including, for example, to hasten bone marrow recovery after allogenic stem cell transplantation, to reverse lymphopenia due to …

Ganglioside Gd2 Contributes To A Stem-Like Phenotype In Intrahepatic Cholangiocarcinoma, Antonella Mannini, Mirella Pastore, Alessia Giachi, Margherita Correnti, Elena Spínola Lasso, Tiziano Lottini, Benedetta Piombanti, Ignazia Tusa, Elisabetta Rovida, Cédric Coulouarn, Jesper B Andersen, Monika Lewinska, Claudia Campani, V Lokesh Battula, Bin Yuan, Massimo Aureli, Emma V Carsana, Caterina Peraldo Neia, Paola Ostano, Alessia Tani, Daniele Nosi, Anna Vanni, Laura Maggi, Luca Di Tommaso, Giuseppina Comito, Stefania Madiai, Annarosa Arcangeli, Fabio Marra, Chiara Raggi

Faculty, Staff and Student Publications

BACKGROUND & AIMS: GD2, a member of the ganglioside (GS) family (sialic acid-containing glycosphingolipids), is a potential biomarker of cancer stem cells (CSC) in several tumours. However, the possible role of GD2 and its biosynthetic enzyme, GD3 synthase (GD3S), in intrahepatic cholangiocarcinoma (iCCA) has not been explored.

METHODS: The stem-like subset of two iCCA cell lines was enriched by sphere culture (SPH) and compared to monolayer parental cells (MON). GS profiles were evaluated by chromatography, after feeding with radioactive sphingosine. Membrane GD2 expression was evaluated by FACS, and the expression of enzymes of GS biosynthesis was analysed by RT-qPCR. The …

Ft538, Ipsc-Derived Nk Cells, Enhance Aml Cell Killing When Combined With Chemotherapy, Amanda Eckstrom, Anudishi Tyagi, Sajid Mahmood, Lilly Wong, Bahram Valamehr, Adishwar Rao, Akriti Agrawal, Maryam Siddiqui, V Lokesh Battula

Faculty, Staff and Student Publications

Induced pluripotent stem cell (iPSC)-derived natural killer (NK) cells offer an opportunity for a standardized, off-the-shelf treatment with the potential to treat a wider population of acute myeloid leukaemia (AML) patients than the current standard of care. FT538 iPSC-NKs express a high-affinity, noncleavable CD16 to maximize antibody dependent cellular cytotoxicity, a CD38 knockout to improve metabolic fitness, and an IL-15/IL-15 receptor fusion preventing the need for cytokine administration, the main source of adverse effects in NK cell-based therapies. Here, we sought to evaluate the potential of FT538 iPSC-NKs as a therapy for AML through their effect on AML cell lines …

18 Kda Translocator Protein (Tspo) Is Upregulated In Rat Brain After Peripheral Nerve Injury And Downregulated By Diroximel Fumarate, Rafael A Cazuza, Sever M Zagrai, Anamaria R Grieco, Thomas D Avery, Andrew D Abell, Hsiao-Ying Wey, Marco L Loggia, Peter M Grace

Faculty, Staff and Student Publications

Neuroimmune signaling is a key process underlying neuropathic pain. Clinical studies have demonstrated that 18 kDa translocator protein (TSPO), a putative marker of neuroinflammation, is upregulated in discrete brain regions of patients with chronic pain. However, no preclinical studies have investigated TSPO dynamics in the brain in the context of neuropathic pain and in response to analgesic treatments. We used positron emission tomography-computed tomography (PET-CT) and [18F]-PBR06 radioligand to measure TSPO levels in the brain across time after chronic constriction injury (CCI) of the sciatic nerve in both male and female rats. Up to 10 weeks post-CCI, TSPO expression was …

High-Grade B-Cell Lymphoma Not Otherwise Specified, With Diffuse Large B-Cell Lymphoma Gene Expression Signatures: Genomic Analysis And Potential Therapeutics, Waseem Lone, Alyssa Bouska, Tyler A Herek, Catalina Amador, Joo Song, Alexander M Xu, Dylan Jochum, Issa Ismail Issa, Dennis D Weisenburger, Xuan Zhang, Sharath Kumar Bhagavathi, Tayla B Heavican-Foral, Sunandini Sharma, Ab Rauf Shah, Abdul Rouf Mir, Aisha Ahmad Alkhinji, Dalia El-Gamal, Bhavana J Dave, Keenan Hartert, Jiayu Yu, Mallick Saumyaranjan, Timothy C Greiner, Julie Vose, Timothy W Mckeithan, Kai Fu, Michael Green, Chengfeng Bi, Akil Merchant, Wing C Chan, Javeed Iqbal

Faculty, Staff and Student Publications

High-grade B-cell lymphoma not otherwise specified (HGBCL, NOS) has overlapping morphological and genetic features with diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL), leading to uncertainty in its diagnosis and clinical management. Using functional genomic approaches, we previously characterized HGBCL and NOS, that demonstrate gene expression profiling (GEP), and genetic signatures similar to BL. Herein, we characterize distinct HGBCL, NOS, cohort (n = 55) in adults (n = 45) and in children (n = 10), and compared the GEP, genomic DNA copy number (CN), and mutational spectrum with de novo DLBCL (n = 85) and BL (n = 52). …

Plasma Dna Methylation-Based Biomarkers For Mpnst Detection In Patients With Neurofibromatosis Type 1, Katarzyna Tomczak, Manishkumar S Patel, Angela D Bhalla, Christine B Peterson, Sharon M Landers, S Carson Callahan, Di Zhang, Justin Wong, Jace P Landry, Alexander J Lazar, J Andrew Livingston, B Ashleigh Guadagnolo, Heather G Lyu, Heather Lillemoe, Christina L Roland, Emily Z Keung, Christopher P Scally, Kelly K Hunt, Ian E Mccutcheon, John M Slopis, Jian Gu, Paul Scheet, Liang Wang, Kunal Rai, Keila E Torres

Faculty, Staff and Student Publications

Malignant peripheral nerve sheath tumor (MPNST) development is characterized by an altered DNA methylation landscape, which presents a promising area for developing MPNST-specific biomarkers for screening patients with NF1. Genome-wide DNA methylation profiling of a cohort of 13 patients with MPNST (29 samples of tumor and adjacent neurofibroma tissues) and of NF1-MPNST cell lines was performed to identify and validate candidate MPNST-specific CpG sites (CpGs). A logistic regression prediction model was constructed to select MPNST-specific CpGs distinct from adjacent neurofibromas and normal tissues. To test if hypermethylation at selected CpGs can also be detected in plasma from patients with MPNST, …

Approach To Determining Etiology Of Hypophosphatemia In A Patient With Coexisting Phosphaturic Mesenchymal Tumor And Fibrous Dysplasia, Madhuri D Patil, Sintawat Wangsiricharoen, Alexander J Lazar, Bryan Moon, John E Madewell, Michael T Collins, Theresa A Guise

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Dysregulated FGF23 production is a demonstrated cause of hypophosphatemia and osteomalacia. Diseases associated with these conditions include phosphaturic mesenchymal tumor (PMT) causing tumor induced osteomalacia, various forms of rickets, and fibrous dysplasia (FD). Coexistence of 2 conditions that can increase FGF23 concentrations is rare. We report a case of a 79-yr-old man who presented with rib and right flank pain. Imaging revealed bone lesions in the right iliac wing, left supra-acetabular area, and L4 vertebral body. Biopsies showed a right iliac PMT and left supra-acetabular FD. Cryoablation of both lesions resolved the phosphaturia with normalization of phosphorus level. Coexistence of …

Ntrk Fusion-Positive Thyroid Carcinoma: From Diagnosis To Targeted Therapy, Vicente R Marczyk, Sasan Fazeli, Ramona Dadu, Naifa L Busaidy, Priyanka Iyer, Mimi I Hu, Steven I Sherman, Sarah Hamidi, Sayed Mohsen Hosseini, Michelle D Williams, Salmaan Ahmed, Mark J Routbort, Raja Luthra, Sinchita Roy-Chowdhuri, Francis Anthony San Lucas, Keyur P Patel, David S Hong, Mark Zafereo, Jennifer R Wang, Anastasios Maniakas, Steven G Waguespack, Maria E Cabanillas

Faculty, Staff and Student Publications

Purpose: Neurotrophic tropomyosin receptor kinase (NTRK) fusions may act as an oncogenic driver in thyroid carcinomas. Given their low frequency, clinical, pathological, and molecular data on these patients and their responses to targeted therapies are limited.

Methods: This is an observational retrospective study conducted at a single high-volume cancer center in the United States. Data were retrospectively collected from medical records.

Results: We included 65 patients (37 adult, 28 pediatric) with an NTRK fusion-positive thyroid carcinoma (24 NTRK1, 41 NTRK3), of which 54 were papillary thyroid carcinomas (PTC), four poorly differentiated thyroid carcinomas (PDTC), and seven …

Mmrt: Multimut Recursive Tree For Predicting Functional Effects Of High-Order Protein Variants From Low-Order Variants, Bryce Forrest, Houssemeddine Derbel, Zhongming Zhao, Qian Liu

Faculty, Staff and Student Publications

Protein sequences primarily determine their stability and functions. Mutations may occur at one, two, or three positions at the same time (low-order variants) or at multiple positions simultaneously (high-order variants), which affect protein functions. So far, low-order variants, such as single variants, double variants, and triple variants, have been well-studied through high-throughput experimental scanning techniques and computational prediction methods. However, research on high-order variants remains limited because of the difficulty of scanning an exponentially large number of potential variant combinations. Nonetheless, studying higher-order variants is crucial for understanding the pathogenesis of complex diseases, advancing protein engineering, and driving precision medicine. …

Enhancing The Utility Of Polygenic Scores In Alzheimer’S Disease Through Systematic Curation And Annotation, Savannah Mwesigwa, Yulin Dai, Nitesh Enduru, Zhongming Zhao

Faculty, Staff and Student Publications

Introduction: Polygenic Scores (PGSs) assess cumulative genetic risk variants that contribute to the association with complex diseases like Alzheimer's Disease (AD). The PGS Catalog is a valuable repository of PGSs of various complex diseases, but it lacks standardized annotations and harmonization, making the information difficult to integrate for a specific disease.

Methods: In this study, we curated 44 PGS datasets for AD from the PGS Catalog, categorized them into five methodological groups, and annotated 813,257 variants to nearby genes. We aligned the scores based on the "GWAS significant variants" (GWAS-SV) method with the GWAS Catalog and flagged redundant files and …

Lp-118 Is A Novel B-Cell Lymphoma 2 / Extra-Large Inhibitor That Demonstrates Efficacy In Models Of Venetoclaxresistant Chronic Lymphocytic Leukemia, Janani Ravikrishnan, Daisy Y Diaz-Rohena, Elizabeth Muhowski, Xiaokui Mo, Tzung-Huei Lai, Shrilekha Misra, Charmelle D Williams, John Sanchez, Andrew Mitchell, Suresh Satpati, Elizabeth Perry, Tierney Kaufman, Chaomei Liu, Arletta Lozanski, Gerard Lozanski, Kerrya Rogers, Adam S Kittai, Seema A Bhat, Mary C Collins, Matthew S Davids, Nitin Jain, William G Wierda, Rosa Lapalombella, John C Byrd, Fenlai Tan, Yi Chen, Yu Chen, Yue Shen, Stephen P Anthony, Jennifer A Woyach, Deepa Sampath

Faculty, Staff and Student Publications

Patients with chronic lymphocytic leukemia (CLL) respond well to initial treatment with the B-cell lymphoma 2 (BCL2) inhibitor venetoclax. Upon relapse, they often retain sensitivity to BCL2 targeting, but durability of response remains a concern. We hypothesize that targeting both BCL2 and B-cell lymphoma-extra large (BCLXL) will be a successful strategy to treat CLL, including for patients who relapse on venetoclax. To test this hypothesis, we conducted a pre-clinical investigation of LP-118, a highly potent inhibitor of BCL2 with moderate BCLXL inhibition to minimize platelet toxicity. This study demonstrated that LP-118 induces efficient BAK activation, cytochrome C release, and apoptosis …

Optimal Timing Of Organs-At-Risk-Sparing Adaptive Radiation Therapy For Head-And-Neck Cancer Under Re-Planning Resource Constraints, Fatemeh Nosrat, Cem Dede, Lucas B Mccullum, Raul Garcia, Abdallah S R Mohamed, Jacob G Scott, James E Bates, Brigid A Mcdonald, Kareem A Wahid, Mohamed A Naser, Renjie He, Aysenur Karagoz, Amy C Moreno, Lisanne V Van Dijk, Kristy K Brock, Jolien Heukelom, Seyedmohammadhossein Hosseinian, Mehdi Hemmati, Andrew J Schaefer, Clifton D Fuller

Faculty, Staff and Student Publications

Background and purpose: Prior work on adaptive organ-at-risk (OAR)-sparing radiation therapy has typically reported outcomes based on fixed-number or fixed-interval re-planning, which represent one-size-fits-all approaches and do not account for the variable progression of individual patients' toxicities. The purpose of this study was to determine the personalized optimal timing of re-planning in adaptive OAR-sparing radiation therapy, considering limited re-planning resources, for patients with head and neck cancer (HNC).

Materials and methods: A novel Markov decision process (MDP) model was developed to determine optimal timing of re-planning based on the patient's expected toxicity, characterized by normal tissue complication probability (NTCP), for …

Association Of Cardiovascular Disease With Dementia: A Longitudinal Analysis Using National Alzheimer’S Coordinating Center Data, Diana Summanwar, Hyena Kim, Jingkai Wei, Malaz Boustani, Alvaro Alonso, Ambar Kulshreshtha

Faculty, Staff and Student Publications

We analyzed how cardiovascular disease subtypes influence the prevalence and incidence of dementia among 30,582 individuals aged 50 and older in the National Alzheimer's Coordinating Center cohort. We calculated prevalence ratios (aPR) and hazard ratios (aHR), using models adjusted for age, sex, race, years of education, hypertension, diabetes, and dyslipidemia. Stroke (aPR: 1.26; 95% CI: 1.20-1.32) and history of arrhythmias (aPR: 1.17; 95% CI: 1.09-1.24) were associated with higher dementia prevalence. In survival analysis, stroke was associated with a 55% increased risk of incident dementia (aHR: 1.55; 95% CI: 1.36-1.77).

Daily Movement Activities Are Associated With Within-Person Instability Of Cognitive Function In Older Adults: Evidence From An Ambulatory Assessment Study, Chih-Hsiang Yang, Donald Hedeker, Jongwon Lee, Halle Prine, Donna Coffman, Jingkai Wei, Jonathan George Hakun

Faculty, Staff and Student Publications

Background and objectives: Physical inactivity and excessive sedentary time (ST) are associated with poor cognitive health in older adults. However, current literature largely relies on cross-sectional designs or in-lab cognitive assessments, which do not adequately reflect cognitive function in naturalistic settings. Further, existing studies have largely overlooked the variability or the instability in daily cognitive function, which represents a critical marker of cognitive decline. This ambulatory assessment study examined the temporal associations of daily movement behaviors with the mean levels and the variability of cognition among older adults at risk of dementia.

Research design and methods: 96 older adults from …

Limitations Of The Radiotheranostic Concept In Neuroendocrine Tumors Due To Lineage-Dependent Somatostatin Receptor Expression On Hematopoietic Stem And Progenitor Cells, Nghia Nguyen, Yu Min, Jennifer Rivière, Mark Van Der Garde, Sukhen Ghosh, Laura M Bartos, Matthias Brendel, Florian Bassermann, Ali Azhdarinia, Wolfgang A Weber, Katharina S Götze, Susanne Kossatz

Faculty, Staff and Student Publications

Rationale: Radiopharmaceutical therapy (RPT) has become an effective treatment option for neuroendocrine tumors (NETs) and castration-resistant prostate cancer and is in clinical development for many indications. One of the major advantages of theranostic RPT is that the distribution of radiopharmaceuticals in the human body can be imaged, and radiation doses to the patient's organs can be calculated. However, accurate dosimetry may be fundamentally limited by microscopic heterogeneity of radiopharmaceutical distribution.

Methods: We developed fluorescent analogs of somatostatin-receptor-subtype 2 (SSTR2) targeting Lutetium-177 labeled radiopharmaceuticals that are clinically used in patients with NETs and studied their uptake by hematopoietic stem and progenitor …

New Insights Into Liver Injury And Regeneration From Single-Cell Transcriptomics, Yankai Wen, Cynthia Ju

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Recent advancements in single-cell transcriptomics have significantly enhanced our understanding of acute liver injury (ALI) and regeneration. These technologies enable high-resolution profiling of individual cells, uncovering the diverse and dynamic responses of liver cells to injury. By integrating single-cell RNA sequencing (scRNA-seq) with spatial transcriptomics, researchers have elucidated the complex cellular and molecular mechanisms driving ALI and regeneration processes. This review summarises the platforms and analytical methods of single-cell transcriptomics in liver research and discusses liver sample processing considerations for scRNA-seq, including the comparison between in vivo enzymatic perfusion and ex vivo digestion. It highlights the transformative impact of single-cell …

Three-Dimensional Deep Learning Normal Tissue Complication Probability Model To Predict Late Xerostomia In Patients With Head And Neck Cancer, Hung Chu, Suzanne P M De Vette, Hendrike Neh, Nanna M Sijtsema, Roel J H M Steenbakkers, Amy Moreno, Johannes A Langendijk, Peter M A Van Ooijen, Clifton D Fuller, Lisanne V Van Dijk

Faculty, Staff and Student Publications

Purpose: Conventional normal tissue complication probability (NTCP) models for patients with head and neck cancer are typically based on single-value variables, which, for radiation-induced xerostomia, are baseline xerostomia and mean salivary gland doses. This study aimed to improve the prediction of late xerostomia by using 3-dimensional information from radiation dose distributions, computed tomography imaging, organ-at-risk segmentations, and clinical variables with deep learning (DL).

Methods and materials: An international cohort of 1208 patients with head and neck cancer from 2 institutes was used to train and twice validate DL models (deep convolutional neural network, EfficientNet-v2, and ResNet) with 3-dimensional dose distribution, …