Medical Genetics Commons^™

The Pandemic Effect: Secondary Impact On The Diagnosis Of Clinically Significant Congenital Heart Disease And Role Of Deprivation Index, Cassandra Campbell, Kristin Wyckoff, Ronak Naik, Nithya Swaminathan, Salima Ahmed Bhimani, Jason Johnson, Vijaya Joshi, Ranjit Philip

Faculty, Staff and Student Publications

We sought to determine the impact of the COVID-19 on prenatal diagnosis (PND) of clinically significant congenital heart disease (CHD) and the role of socioeconomic status (SES), complexity of diagnosis, and proximity to advance testing. This single-center retrospective study evaluated 2 eras of infants (COVID (born July 1, 2020–July 31, 2023) and pre-COVID (born June 1, 2017–July 1, 2020) who had cardiac surgery in the first year of life. 512 infants, 292 in pre-COVID era and 220 in COVID era with no significant difference in the rate of prenatal care (PNC) or PND in the COVID era (88%/42%) versus pre-COVID …

Cardiometabolic Indicators Of Cognitive Impairment In The Cameron County Hispanic Cohort, Fadi I Musfee, Seema Agarwal, Vahed Maroufy, Chelsea Liu, Joseph B Mccormick, Susan Fisher-Hoch, Sean I Savitz

Faculty, Staff and Student Publications

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Objective

Methods

Venous Thromboembolism In Aggressive B-Cell Lymphoma Patients Treated With Cd19 Car-T Therapy: Single-Institution Study, Neha Venkatesh, Kevin Milligan, Julia Parrish, Yun Qing, Ryan Sun, Paolo Strati, Jeremy Ramdial, Amy Ayers, Sairah Ahmed, Cristhiam Rojas Hernandez

Faculty, Staff and Student Publications

Background: Large B-cell lymphomas (LBCLs) are a common subtype of non-Hodgkin lymphomas. CD19 chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized LBCL treatment, with high remission rates but also significant toxicities, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Venous thromboembolism (VTE) in CAR-T therapy patients is understudied.

Objective: This study aims to determine the incidence and characteristics of acute VTE in LBCL patients treated with CAR-T therapy and identify baseline clinical features associated with VTE. Methods: We retrospectively reviewed 172 adult LBCL patients treated with CAR-T therapy from January 2018 to November 2019 at MD …

A Guide To Transcriptomic Deconvolution In Cancer, Yaoyi Dai, Shuai Guo, Yidan Pan, Carla Castignani, Matthew D Montierth, Peter Van Loo, Wenyi Wang

Faculty, Staff and Student Publications

Cancer tissues are heterogeneous mixtures of tumour, stromal and immune cells, where each component comprises multiple distinct cell types and/or states. Mapping this heterogeneity and understanding the unique contributions of each cell type to the tumour transcriptome is crucial for advancing cancer biology, yet high-throughput expression profiles from tumour tissues only represent combined signals from all cellular sources. Computational deconvolution of these mixed signals has emerged as a powerful approach to dissect both cellular composition and cell-type-specific expression patterns. Here, we provide a comprehensive guide to transcriptomic deconvolution, specifically tailored for cancer researchers, presenting a systematic framework for selecting and …

Leveraging Large Language Models For Heuristic Usability Assessment Of Medical Software: Insights With The Radiation Planning Assistant, Laurence E Court, Jacobus Smit, Lourens Strauss, William Shaw, Andrea Marais, Christoph Trauernicht, Nanette Joubert, Elaine Smith, Shona Badre, Graeme L Lazarus, Thekiso Khotle, Lauren Netherton, Wanda Van Heerden, Carlos Cardenas, Monica Serban, Jan Seuntjens, Christine V Chung, Pavel Govyadinov, Meena Khan, Saurabh Nair, Tucker Netherton, Lifei Zhang

Faculty, Staff and Student Publications

Background: Usability engineering is essential for ensuring the safety and effectiveness of medical software, as design-related issues are a leading cause of use errors in clinical settings. Heuristic evaluation provides a practical approach to identifying usability problems, but its outcomes depend heavily on expert interpretation. Large Language Models (LLMs), such as ChatGPT, offer a potential means to augment heuristic evaluation by generating structured, context-aware usability feedback. This study explored the use of ChatGPT to support heuristic assessment of the Radiation Planning Assistant (RPA), a web-based radiotherapy planning tool designed to support clinical teams in low- and middle-income countries.

Methods: ChatGPT …

The American College Of Radiology Diagnostic Fluoroscopy Dose Index Registry Pilot: Dosimetric Performance And Benchmarking Challenges, Steve D Mann, Donald L Miller, Grant Fong, Allen R Goode, Emily L Marshall, Thomas Nishino, Pavlina Boxx, Liqiang Ren, Celalettin Topbas, Alan H Schoenfeld, Vivek Singh, Jie Zhang

Faculty, Staff and Student Publications

Background: The ACR Diagnostic Fluoroscopy Dose Index Registry (DIR-Fluoro) is expanding to include diagnostic fluoroscopy. Variations in dose reference points and overhead radiography events may introduce unique challenges for benchmarking.

Purpose: To survey the technological status and dosimetric performance of fluoroscopes participating in the DIR-Fluoro pilot project, focusing on longitudinal stability and variability of fluoroscopic dose reporting accuracy across multiple institutions and vendors.

Methods: Sixty-six fluoroscopic systems from nine institutions (24 facilities) were surveyed for facility type, fluoroscope type, image receptor type, age, dose reporting capabilities, and other key features. Of these, 56 were evaluable. Semi-annual measurements assessed reference air …

Convolutional Neural Networks For Automatic Tuber Segmentation And Quantification Of Tuber Burden In Tuberous Sclerosis Complex, Iván Sánchez Fernández, Matheus D Soldatelli, Gillian N Miller, Catharina F Gout, Ellen C Broekhuizen, Iris C J Den Hertog, Daan A Pijs, Errol Apostolopoulos, Prabhjot Kaur, Abdelhakim Ouaalam, Martina E Bebin, Hope Northrup, Darcy A Krueger, Joyce Y Wu, Alexander L Cohen, Mustafa Sahin, Davood Karimi, Simon K Warfield, Jurriaan M Peters

Faculty, Staff and Student Publications

Objective: This study was undertaken to develop a fully automated algorithm for tuber segmentation and quantification of tuber volume that performs similarly to the gold standard human neuroradiologist.

Methods: We used brain magnetic resonance imaging (MRI) from patients with tuberous sclerosis complex (TSC) to train and validate a convolutional neural network (CNN), which was evaluated on segmentation with the Dice-Sørensen similarity coefficient (DSSC) and on tuber burden quantification with Spearman correlation coefficient against a neuroradiologist's gold standard in the test set.

Results: We collected 263 MRIs from 196 patients (57% males) with median (25th percentile-75th percentile) age of 4.3 (3.0-10.1) …

Retrospective Analysis Of Cutaneous Immune-Related Adverse Events Following Checkpoint Inhibitor Therapy In Melanoma Patients Reveals Increased Risk Associated With The Hla-B*51:01 Allele, Mckenzie Dileo, Samantha Oglesby, Cheuk Hong Leung, Kristen E Pauken, Sahira Farooq, Lauren E Haydu, Shelby L Kubicki, Rebeca Martinez, Macartney Welborn, Sana Zahiruddin, Jun Zou, Kai Cao, Anisha B Patel

Faculty, Staff and Student Publications

Background: While immune checkpoint inhibitors (ICIs) have shown significant efficacy, a common side effect is cutaneous immune-related adverse events (irAEs). This study focuses on exploring the association between specific human leukocyte antigen (HLA) alleles and the development of cutaneous irAEs in melanoma patients undergoing ICI monotherapy and combination therapy. As certain HLA types are indicative of susceptibility to autoimmune diseases, it was hypothesized that HLA typing could serve as a potential screening tool for identifying patients at increased risk for developing irAEs.

Methods: A retrospective chart review was performed of 515 patients with melanoma who underwent ICI therapy, either as …

Presenilin L166p Mutation, A Model Of Familial Alzheimer's Disease, Leads To Early Onset Bone Loss, Vidyani Suryadevara, Connor J Krehbial, Anuradha K Valiya, Melinda Vang, Julian Balanta-Melo, Pierre P Eleniste, Sumana Posritong, Jung Min Hong, Katie Chester, Gabriel M Pagnotti, Teresita Bellido, Monte S Willis, Angela Bruzzaniti

Faculty, Staff and Student Publications

Accelerated bone loss has been reported in the early stages of Alzheimer's disease (AD) as indicated by reduced bone mineral density and increased fracture risk in these patients, compared to healthy individuals. In the present study, we investigated bone loss in mouse models of familial Alzheimer's disease harboring the Presenilin 1 (L166P) knock-in mutation (PSEN1 KI), with or without the human amyloid precursor protein transgene (hAPP Tg+) known to induce brain amyloid pathology by 6 months. Female and not male 12-month PSEN1/hAPP Tg+ mice exhibited reduced whole-body bone mineral density and bone mineral content, compared to sex-matched controls. Consistent with …

Can Patients With Recurrent Or Primary Squamous Cell Carcinoma Of The Anus In A Previously Irradiated Pelvis Receive Definitive Reirradiation, Jordan Mcdonald, Ethan P Damron, Prajnan Das, Eugene J Koay, Ethan B Ludmir, Bruce D Minsky, Sonal S Noticewala, Grace L Smith, Craig Messick, Van K Morris, Emma B Holliday

Faculty, Staff and Student Publications

Purpose: Although salvage surgery is the standard of care for locoregionally recurrent anal cancer, few local options exist for inoperable pelvic recurrences. Newly diagnosed anal cancer arising in a previously irradiated field also provides a unique treatment challenge, as delivery of standard doses would result in unsafe cumulative dose to pelvic structures. We aimed to evaluate efficacy and toxicity of a hyperfractionated accelerated reirradiation (reRT) regimen for such patients.

Methods and materials: Patients treated with hyperfractionated accelerated reRT at a single institution between 2005 and 2024 for nonmetastatic inoperable locoregionally recurrent anal cancer or primary anal cancer in a previously …

Decellularized Extracellular Matrix Scaffolds To Engineer The Dormant Landscape Of Microscopic Colorectal Cancer Liver Metastasis, Sabrina N Vandenheuvel, Lucia L Nash, Abigail J Clevenger, Claudia A Collier, Oscar R Benavides, Sanjana Roy, Brinlee Goggans, Aelita Salikhova, Anvitha Tharakesh, Svasti Haricharan, Amber N Stratman, Scott Kopetz, Alex J Walsh, Shreya A Raghavan

Faculty, Staff and Student Publications

Recurrent liver-metastatic colorectal cancer contributes to high mortality. Recurrence occurs when dormant, microscopic residual disease survives initial treatment to escape dormancy. In their dormant, microscopic state within the liver, these metastatic lesions are undetectable by clinical diagnostic imaging until they form overt, chemoresistant metastases. Therefore, understanding the molecular mechanisms underlying dormancy in colorectal cancer liver metastases is a significant knowledge gap, motivating the engineering of nuanced in vitro models of disease. The current work presents an engineered model of liver-metastatic colorectal cancer dormancy. Decellularized extracellular matrix (dECM) scaffolds are used to provide microscopic colorectal cancer cell clusters with a biomimetic, …

Local Delivery Of Mir-27a* Using Ultrasound-Targeted Microbubble Cavitation Inhibits Squamous Cell Carcinoma Growth, Nikhil S Chari, Cheng Chen, Thiruganesh Ramasamy, Xucai Chen, Geetika Wadhwa, Anurag N Paranjape, Stephen Y Lai, Flordeliza S Villanueva

Faculty, Staff and Student Publications

Objective: Ultrasound-targeted microbubble (MB) cavitation (UTMC) is an image-guided therapeutic oligonucleotide delivery platform utilizing intravenously injected gas-filled ultrasound contrast agents, which carry the therapeutic on the MB shell. During transit of MBs in the microcirculation of target tissue, ultrasound causes MB oscillation, facilitating endocytosis-independent payload uptake within insonified cells. Here, we tested the hypothesis that UTMC-mediated miR-27a* delivery will reduce tumor growth rate and result in accumulation of miR-27a* within tumor cells and the tumor microenvironment.

Methods: We used UTMC to deliver miR-27a* to SCC-VII cells in vitro and in SCC-VII mouse tumor models. Pulsed ultrasound was delivered during intravenous …

Who Classification Of Skin Tumours: Key Updates In The Fifth Edition, Gabrielle Goldman-Lévy, Raymond Barnhill, Boris C Bastian, Werner Kempf, David Elder, Pedram Gerami, Wayne Grayson, Dmitry Kazakov, Daniela Massi, Jane Messina, Arnaud De La Fouchardière, Alexander J Lazar, Thomas Brenn, Brian Rous, Andrew Field, Anthony Gill, Jennelle C Hodge, Joseph D Khoury, Katia Leite, Shahin Sayed, Puay Hoon Tan, Rosalie Elenitsas, Eduardo Calonje, Lyn M Duncan, Liang Zhiyong, Holger Moch, Rajendra Singh, Harshima Wijesinghe, Ian Cree, Dilani Lokuhetty

Faculty, Staff and Student Publications

The 5th edition of the World Health Organization Classification of Tumours (WCT) serves as a foundation for global diagnostic standards in tumour pathology. Similar to other volumes in this series, the Skin Tumours (Skin5) edition follows a standardized approach. This edition introduces two new chapters: 'Tumours of the nail unit' and 'Metastases to skin', along with new entities across relevant chapters. This review article provides an overview of the updates in Skin5 based on currently published evidence, with emphasis on newly introduced chapters and newly described entities that involve the skin, in particular, epidermal, melanocytic and appendageal tumours.

A Comparative Study Of Statistical Methods For Identifying Differentially Expressed Genes In Spatial Transcriptomics, Yishan Wang, Chenxuan Zang, Ziyi Li, Charles C Guo, Dejian Lai, Peng Wei

Faculty, Staff and Student Publications

Spatial transcriptomics (ST) provides unprecedented insights into gene expression patterns while retaining spatial context, making it a valuable tool for understanding complex tissue architectures, such as those found in cancers. Seurat, by far the most popular tool for analyzing ST data, uses the Wilcoxon rank-sum test by default for differential expression analysis. However, as a nonparametric method that disregards spatial correlations, the Wilcoxon test can lead to inflated false positive rates and misleading findings. This limitation highlights the need for a more robust statistical approach that effectively incorporates spatial correlations. To this end, we propose a Generalized Estimating Equations (GEE) …

Investigating The Oxygen Dependence Of Flash-Rt Using Electron Paramagnetic Resonance Imaging, Trey Waldrop, Grace Murley, Brett Velasquez, Elise Konradsson, Denae Neill, Luke Connell, Alan Lopez Hernandez, Abagail Delahoussaye, F William Schuler, Jorge De La Cerda, Ziyi Li, Mark D Pagel, Emil Schüler

Faculty, Staff and Student Publications

Purpose: The FLASH effect occurs when radiation given at ultra-high dose rates spares healthy tissue while achieving isoeffective tumor control relative to conventional (CONV) dose rate irradiation. Limited data has implicated oxygen in the FLASH effect. This study investigated the effect of tissue oxygen tension (pO2) on gastrointestinal (GI) FLASH sparing in mice.

Methods: pO2 was quantified in vivo by electron paramagnetic resonance imaging (EPRI)- noninvasive oximetry through spin probe injection and magnetic resonance co-registration- and a phosphorescent quenching microsensor. B6(Cg)-Tyrc-2 J/J female mice were imaged while breathing 10%, 21%, and 95% oxygen. C57BL/6 mice of both sexes underwent microsensor …

Tbr2-Dependent Parallel Pathways Regulate The Development Of Distinct Iprgc Subtypes, Takae Kiyama, Ching-Kang Chen, Halit Y Altay, Yu-Jiun Chen, Leviette Sigala, Dan Su, Steven Eliason, Brad A Amendt, Chai-An Mao

Faculty, Staff and Student Publications

The intrinsically photosensitive retinal ganglion cells (ipRGC) are the conduit between the retina and brain regions responsible for non-image-forming and image-forming vision. In mice, six ipRGC subtypes have been discovered based on morphological characteristics, functions, and molecular profiles. All ipRGCs arise from Tbr2-expressing RGCs during developmental stages and subsequently diverge and differentiate into the six mature, distinct subtypes in adult retinas. However, the cellular and molecular mechanisms controlling the formation and maturation of the six ipRGC subtypes remain elusive. Here, we demonstrate that two Tbr2-dependent transcription factors, Iroquois‑related homeobox 1 (Irx1) and T-box containing factor 20 (Tbx20), are key downstream …

Acta2 Pathogenic Variants Activating Heat Shock Factor 1 And Increasing Cholesterol Biosynthesis In Smooth Muscle Cells Predispose To Early Onset Atherosclerosis, Maura L Boerio, Abhijnan Chattopadhyay, Xue-Yan Duan, Aamuktha Karla, Ernesto Calderon Martinez, Amelie Pinard, Andrew K Morse, Darshan Reddy, Sree Dharma, Walter Velasco-Torrez, Julien Marcadier, Siddharth K Prakash, Sherene Shalhub, Julie De Backer, Richmond Jeremy, Shaine A Morris, Anji T Yetman, Alan C Braverman, Dianna M Milewicz

Faculty, Staff and Student Publications

Background: ACTA2 pathogenic variants predispose to thoracic aortic disease, and a subset of variants lead to early onset atherosclerotic cardiovascular disease (ASCVD). The molecular pathway linking misfolded SMA (α-smooth muscle actin) monomers to augmented atherosclerosis-associated smooth muscle cell phenotypic modulation can be modeled in vitro by stably expressing the ACTA2 p.R149C variant in Acta2-/- smooth muscle cells.

Methods: The Montalcino Aortic Consortium patient registry was used to identify cases with ACTA2 pathogenic/likely pathogenic missense variants. These patients were surveyed, and medical records were reviewed, to identify cases with early onset ASCVD. The variants for these cases, as well as …

Quantitative Analysis Of Robustness-Based Versus Let-Based Optimization In Intensity-Modulated Proton Therapy For Pediatric Brain Tumors, Fariha Kabir Torsha, Gino Lim, Hadis Moazami Goudarzi, Radhe Mohan, David Grosshans, Wenhua Cao

Faculty, Staff and Student Publications

Purpose: To perform a quantitative analysis of the trade-off between robustness-based and linear energy transfer (LET)-based optimization of intensity-modulated proton therapy for anatomically challenging pediatric brain tumor cases.

Methods: Three pediatric brain tumor patients were included in this study. Three plans were generated for each case based on: (1) nominal optimization, without considering uncertainties and LET; (2) robust optimization, including proton range and patient setup uncertainties; and (3) LET optimization, considering increasing LET in the target and reducing LET in normal tissues. All plans were optimized with individually fine-tuned objective weighing to obtain highest achievable target coverage and meet dose …

Composite Mantle Cell Lymphoma And Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: A Diagnostic And Therapeutic Challenge, Matthew T Ye, Yaling Yang, M James You

Faculty, Staff and Student Publications

No abstract provided.

50k4life: A Smart Study Protocol To Improve Walking Engagement In Public School Employees On The Us-Mexico Border, Jennifer J Salinas, Susan W Buchholz, Zenong Yin, Jennifer L Gay, Jing Wang, Janani Rajbhandari-Thapa, Mark G Wilson, Erin Finley, Zuber Mulla, Elizabeth Ramirez, Deborah Parra Medina

Faculty, Staff and Student Publications

Introduction: Mexican Americans living in the U.S.-Mexico border region suffer disproportionately from preventable cardiometabolic and cancer diseases. Workplace health promotion programs that include physical activity promotion are promising strategies to address this public health problem to improve physical activity engagement. Workplace-based programs can increase moderate to vigorous physical activity (MVPA) engagement while addressing barriers associated with inactivity.

Methods: We plan to conduct a clustered Sequential Multiple Assignment Randomized Trial (SMART) to determine the effectiveness of a workplace walking challenge intervention - 50,000 for Life (50K4Life) - in improving brisk walking engagement (at least 7000 steps/day, representing approximately 50,000 steps/week) for …

Partial Laryngectomy For Thyroid Cancer: A Single Institution Case Series With Operative Techniques, Ella E Hawes, Victoria E Banuchi, Anastasios Maniakas, Jennifer R Wang, Paul H Graham, Julia D Diersing, Naifa L Busaidy, Maria E Cabanillas, Ramona Dadu, Sarah Hamidi, Priyanka Iyer, Steven G Waguespack, Salmaan Ahmed, Sahar Alizada, Alexandra Belcastro, Ranim Alsharif, Mimi I Hu, Mark E Zafereo

Faculty, Staff and Student Publications

Background: Partial laryngectomy has been well described as a management option for T1-3 laryngeal squamous cell cancers. However, there are a few case reports of partial laryngeal surgery for locally advanced thyroid carcinoma.

Methods: This is a case series of five patients with thyroid carcinoma (one primary and four recurrent) with laryngeal involvement who underwent partial laryngectomy.

Results: All patients had complete surgical resection without perioperative complications or postoperative speech or swallowing deficits, and none required a feeding tube or tracheostomy tube. No patients had postoperative radiation therapy or started systemic therapy within 2 years of surgery, while two patients …

Phase 1b Pilot Study Of Itacitinib With Alemtuzumab In Patients With T-Cell Prolymphocytic Leukemia, Tapan M Kadia, Akhil Jain, Caitlin R Rausch, Alex Bataller, Farhad Ravandi, Elias Jabbour, Wei Qiao, Gautam Borthakur, Nicholas Short, Guillermo Montalban-Bravo, Andres E Quesada, Jan Burger, Alessandra Ferrajoli, William Wierda, Chitra Hosing, Hagop Kantarjian

Faculty, Staff and Student Publications

T-cell prolymphocytic leukemia (T-PLL) is a mature T-cell neoplasm with an aggressive clinical course. Overall prognosis is poor, and treatment relies on alemtuzumab because of inadequate response to conventional chemotherapy. Three-quarters of cases harbor activating mutations in the JAK-STAT pathway (JAK1, JAK3, STAT5B, IL2RG). We report safety and efficacy from a phase 1B study evaluating the combination of the JAK1 inhibitor itacitinib with alemtuzumab. Patients (N = 15) were aged >18 years, with treatment-naïve (n = 8) or relapsed/refractory (n = 7) T-PLL with adequate organ function, European Cooperative Oncology Group Performance Status ≤2, and …

First Report Of Response To Tarlatamab In A Patient With Histologic-Transformed Sclc From Alk-Rearranged Nsclc: Case Report, Kaiwen Wang, Ceylan Altintas Taslic, Patricia De Groot, Mitchell A Parma, Alvaro Guimaraes Paula, Melody Caranto, Komal Shah, Mukulika Bose, Cole Ruoff, Loukia G Karacosta, Lauren A Byers, Carl M Gay, Jianjun Zhang, John V Heymach, Bingnan Zhang

Faculty, Staff and Student Publications

Small cell transformation has been described as a resistance mechanism to targeted therapy treated in patients with EGFR-mutated NSCLC and less often reported with those with other actionable oncogenic alterations, including ALK-rearranged NSCLC. Given lack of standard-of-care treatments for patients with actionable oncogenic alteration NSCLC transformed to SCLC, this remains a challenge and unmet need for treating these patients.

Here, we present a case of a patient with ALK-rearranged NSCLC with transformation to SCLC, who has progressed on several lines of therapies and successfully treated with tarlatamab to elicit and maintain clinical benefit, including intracranial response.

Fireproof: Intricacies Of Microglial Biology, Wei Cao

Faculty, Staff and Student Publications

No abstract provided.

Bet Inhibitor-Based Combinations Targeting Novel Dependencies In Mecom-Rearranged (R) Aml, Christine E Birdwell, Warren Fiskus, Christopher P Mill, Tapan M Kadia, Naval Daver, Courtney D Dinardo, Koji Sasaki, John A Davis, Kaberi Das, Hanxi Hou, Antrix Jain, Anna Malovannaya, Lauren B Flores, Rasoul Pourebrahim, Selina Yuan, Xiaoping Su, Michele Ceribelli, Kapil N Bhalla

Faculty, Staff and Student Publications

MECOM rearrangement in AML involves either inv(3)(q21;q26.2) or t(3;3)(q21;q26.2), where the dislocated GATA2 enhancer drives overexpression of the transcriptional regulator EVI1, causes concomitant GATA2 repression, and promotes AML progression, aggressive phenotype and therapy refractoriness. Treatment with BET protein inhibitor (BETi) induces in vitro and in vivo efficacy in MECOM-r AML cells. Utilizing an unbiased, high-throughput drug screen, focused on mechanistically-annotated drugs, we identified BRD4, PIK3CA, mTOR, BCL-xL and XIAP as dependencies in the MECOM-r AML cells. Monotherapy with mivebresib (BETi), dactolisib (PI3K/mTORi) and LCL161 (IAPi) dose-dependently induced greater lethality in PD MECOM-r versus non-MECOM-r AML cells. RNA-Seq and/or mass spectrometry …

Outcomes Of Therapy-Related Non-Core Binding Factor Acute Myeloid Leukemia With Venetoclax-Based Therapies, Jayastu Senapati, Jennifer Croden, Guillermo Garcia-Manero, Koichi Takahashi, Naval G Daver, Tapan M Kadia, Gautam Borthakur, Nicholas James Short, Elias Jabbour, Fadi Haddad, Jennifer Marvin-Peek, Hussein A Abbas, Prithviraj Bose, Guilin Tang, Sanam Loghavi, Elizabeth J Shpall, Jeremy Ramdial, Uday R Popat, Richard E Champlin, Farhad Ravandi, Hagop M Kantarjian, Courtney D Dinardo

Faculty, Staff and Student Publications

Prognosis in therapy‐related acute myeloid leukemia (T‐AML) remains poor, but understanding outcomes with venetoclax (VEN)‐based therapy is relevant. We retrospectively analyzed 317 adult patients with newly diagnosed T‐AML focusing on lower intensity therapy (LIT) VEN‐containing regimens. Patients with an antecedent myeloid disorder before AML diagnosis were excluded. The median age was 69 years (range 21–92); 50% evaluated patients had a complex karyotype, and 40% evaluated patients had a TP53 mutation. Composite complete response rates were higher with LIT + VEN compared to LIT (58% vs. 40%, P = 0.003) but were similar in intensive chemotherapy (IC) + VEN versus IC …

Neurological Recovery After Ich Is Mediated By The Aryl Hydrocarbon Receptor-Bilirubin Interplay Through Improved Erythrophagocytosis, Xiurong Zhao, Shun-Ming Ting, Guanghua Sun, Jaroslaw Aronowski

Faculty, Staff and Student Publications

Hematoma clearance after ICH is a pro-hemostatic process aiming at repair/recovery and is achieved through microglia/macrophages (MMΦ)-mediated erythrophagocytosis. Upon the engulfment of masses of erythrocytes and toxic hemolysis products, hemoglobin and heme, phagocytes convert them to bilirubin (BrB). Bilirubin is essentially not soluble in water and when overproduced, it precipitates within the cell causing injury. Thus, keeping bilirubin soluble and at a low intracellular level is needed for proper function of MMΦ. Here, using cultured microglia (MG), we found that intracellular formation of BrB in microglia during erythrophagocytosis coincides with the activation of transcription factor AhR, and AhR target genes …

Investigation Of Teratogenic Concerns In The Coronavirus Disease Of 2019 Era, Kate Richardson, Emily C Daykin, Kathleen Shields, S Shahrukh Hashmi, Lorrie Harris-Sagaribay, Molly Daniels, Myla Ashfaq

Faculty, Staff and Student Publications

Background: MotherToBaby (MTB) is a teratogen information service that provides information about exposures during pregnancy and breastfeeding to the public and healthcare providers. During the Coronavirus Disease of 2019 (COVID-19) pandemic, MTB received an influx of queries regarding the teratogenicity of the virus and the vaccine. The purpose of this study was to assess the frequency and type of exposures asked about prior to the onset of the COVID-19 pandemic through March 2022 and to evaluate the demographics of individuals who made inquiries.

Methods: Data from MTB contacts (2018-2022) were accessed through a data-sharing agreement. The data were cleaned and …

Development And Implementation Of An Mri-Only Simulation, Planning, And Treatment Workflow For Prostate Radiotherapy Using Synthetic Ct On Mr-Linac, Reza Reiazi, Yao Ding, Sarath Vijayan, Jinzhong Yang, Ergys Subashi, Yao Zhao, Belinda M Lee, Hunter L Emory, Vi T Dinh, Greg L Swiedom, Jie Deng, Mu-Han Lin, Peter Balter, Rajat J Kudchadker, Elaine E Cha, Seungtaek Choi, Yusung Kim, Eun Young Han, Surendra Prajapati

Faculty, Staff and Student Publications

Purpose: We evaluated the feasibility of a magnetic resonance (MR)-only simulation, planning, and treatment (MROSPT) workflow for prostate cancer patients using synthetic computed tomography (sCT) generated from magnetic resonance imaging (MRI) data. By validating sCT-based dose calculations, we aimed to streamline radiotherapy workflows, eliminate the need for CT simulation, and enable reliable clinical implementation of MR-based radiotherapy for MR-linac (MRL).

Methods: We developed a comprehensive workflow encompassing the entire process from initial consultation to treatment delivery. After developing the workflow, a retrospective dosimetric validation study was performed on nine men with prostate cancer. They underwent CT and MRI simulations, and …

Validation Of The French Translation Of The Movement Disorder Society Non-Motor Symptoms Scale (Mds-Nms) In Parkinson's Disease, Clément Desjardins, Stéphan Grimaldi, Sheng Luo, Luowen Yu, Christopher G Goetz, Glenn T Stebbins, Pablo Martinez-Martin, Monica M Kurtis, Tiago A Mestre, Alvaro Sanchez-Ferro, Michelle H S Tosin, Roberta Balestrino, Chi-Ying R Lin, Carmen Gasca-Salas, Tatiana Witjas, Olivier Colin, David Maltete, Luc Defebvre, Caroline Giordana, Mahmoud Charif, Claire Thiriez, Chloé Laurencin, Mélissa Tir, Gwendoline Dupont, Philippe Remy, Christine Tranchant, Sophie Drapier, Alexandra Samier, Isabelle Benatru, Sara Sambin, Jean-Christophe Corvol, Fatma Khelifi, Margherita Fabbri, Olivier Rascol, Ns‐Part Cohort Study Group And The Mds Coa Translation Steering Committee

Faculty, Staff and Students Publications

No abstract provided.