Digital Commons Network^™

Causal Ai-Based Clinical And Radiomic Analysis For Optimizing Patient Selection In Combined Immunotherapy And Sabr In Early-Stage Nsclc: A Secondary Analysis Of The Phase Ii I-Sabr Trial, Maliazurina B Saad, Eman Showkatian, Vivek Verma, Qasem Al-Tashi, Muhammad Aminu, Xinyan Xu, Muhamed Qayati Mohamed, Morteza Salehjahromi, Sheeba J Sujit, Yuliya Kitsel, Steven H Lin, Zhongxing Liao, Saumil Gandhi, David Qian, David Jaffray, Caroline Chung, Natalie I Vokes, Jianjun Zhang, J Jack Lee, John V Heymach, Jia Wu, Joe Y Chang

Faculty, Staff and Student Publications

Background: The recent phase II randomized stereotactic ablative radiotherapy with and without immunotherapy (I-SABR) trial has shown improved event-free survival (EFS) when adding immunotherapy to stereotactic ablative radiotherapy (SABR) for early-stage inoperable non-small cell lung cancer (NSCLC). However, optimizing patient selection thereof is critical, because not every patient benefits from immunotherapy. Leveraging the powerful use of artificial intelligence, this secondary analysis of the I-SABR trial developed a modeling system (named "I-SABR-SELECT") based on clinical and radiomic factors to address which patients should receive additional immunotherapy.

Methods: The discovery/validation cohorts were from the I-SABR trial, with external validation from the single-arm …

Advancing Modified Barium Swallow Pre-Sorting With Deep Learning: A New Paradigm For The First Step Analysis In X-Ray Swallowing Study, Shitong Mao, Mohamed A Naser, Sheila Buoy, Kristy K Brock, Katherine A Hutcheson

Faculty, Staff and Student Publications

Purpose: Modified barium swallow (MBS) exams are pivotal for assessing swallowing function and include diagnostic video segments imaged in various planes, such as anteroposterior (AP or coronal plane) and lateral (or mid-sagittal plane), alongside non-diagnostic 'scout' image segments used for anatomic reference and image set-up that do not include bolus swallows. These variations in imaging files necessitate manual sorting and labeling, complicating the pre-analysis workflow.

Methods: Our study introduces a deep learning approach to automate the categorization of swallow videos in MBS exams, distinguishing between the different types of diagnostic videos and identifying non-diagnostic scout videos to streamline the MBS …

Male Hypogonadism: Recommendations From The Fifth International Consultation On Sexual Medicine (Icsm 2024), Mohit Khera, Luiz Otavio Torres, Ethan D Grober, Abraham Morgentaler, Martin Miner, Thomas Hugh Jones, Jesse N Mills, Andrea Salonia

Faculty, Staff and Students Publications

Introduction: Male hypogonadism is a clinical condition combining low circulating testosterone (T) and specific signs and symptoms associated with impaired hormone production.

Objectives: To provide the 5th International Consultation for Sexual Medicine consensus paper with recommendations concerning management strategies for hypogonadism.

Outcomes: A narrative review combined with expert opinions on major topics concerning diagnosis of male hypogonadism; treatment options; T impact toward cardiovascular, metabolic, sexual, and reproductive health; and prostate cancer (PCa).

Methods: A consensus panel was held with leading Sexual Medicine experts during the 5th ICSM. Relevant English-language peer-reviewed literature was reviewed with a focus on research from but …

Risk Markers For Sudden Unexpected Death In Epilepsy: An Observational, Prospective, Multicentre Cohort Study, Manuela Ochoa-Urrea, Xi Luo, Laura Vilella, Nuria Lacuey, Shirin Jamal Omidi, Norma J Hupp, Blanca Talavera, Johnson P Hampson, M R Sandhya Rani, Shiqiang Tao, Xiaojin Li, Christina Y Miyake, Licong Cui, Jaison S Hampson, Ganne Chaitanya, Yash Shashank Vakilna, Rup K Sainju, Daniel Friedman, Maromi Nei, Luke Allen, Catherine A Scott, Joana Oliveira, Brian Gehlbach, Stephan U Schuele, Jennifer A Ogren, Ronald M Harper, Beate Diehl, Lisa M Bateman, George B Richerson, Jose-Miguel Yamal, Guo-Qiang Zhang, Orrin Devinsky, Samden D Lhatoo

Faculty, Staff and Student Publications

Background: Sudden unexpected death in epilepsy (SUDEP) is the leading cause of epilepsy-related mortality. Generalised-particularly nocturnal-convulsive seizures, longstanding epilepsy, and solitary living have been identified retrospectively as risk factors. No definitive electroclinical biomarkers have been prospectively ascertained. This study aimed to identify SUDEP risk markers using multimodality data with long-term follow-up.

Methods: This prospective, multicentre, observational cohort study, conducted at nine centres (eight in the USA and one in the UK), recruited children and adults with epilepsy who were undergoing prolonged video-electroencephalographic (EEG) monitoring. Inclusion criteria were diagnosis of epilepsy by an epilepsy specialist, with or without drug resistance; age …

Vaccine Value Profile For Schistosomiasis, Gavin Yamey, Kaci Kennedy Mcdade, Roy M Anderson, Sarah M Bartsch, Maria Elena Bottazzi, David Diemert, Peter J Hotez, Bruce Y Lee, Donald Mcmanus, Adebayo J Molehin, Meta Roestenberg, David Rollinson, Afzal A Siddiqui, Miriam Tendler, Joanne P Webster, Hong You, Raphaël M Zellweger, Caroline Marshall

Faculty, Staff and Students Publications

Schistosomiasis is caused by parasitic flatworms (Schistosoma). The disease in humans can be caused by seven different species of Schistosoma: S. mansoni, S. japonicum, S. haematobium, S. malayensis, S. mekongi, S. guineensis and S. intercalatum, as well as by hybrids between species, including livestock schistosome species. People are infected when exposed to infested water and the parasite larvae penetrate the skin. Poor and rural communities are typically the most affected, and the general population who lives in affected areas and is exposed to contaminated water is at risk. Areas with poor access to safe water and adequate sanitation are also …

Household Dysfunction And Dating Violence Perpetration: The Moderating Effects Of Parental Monitoring And Closeness Among Middle School Adolescents In Southeast Texas, Sumaita Choudhury, Emily T Hébert, Timothy J Walker, Christine M Markham, Ross Shegog, Robert C Addy, Melissa F Peskin

Faculty, Staff and Student Publications

Background: Adolescent dating violence (DV) perpetration is a significant public health issue affecting millions of adolescents in the United States. Adverse childhood experiences such as household dysfunction (HD) have been exhibited to be risk factors for DV perpetration during adolescence and adulthood. Furthermore, the literature is scant regarding how positive parent-child relationships can mitigate these risk factors and decrease HD-related consequences among sixth-grade adolescents. Thus, our study examined the moderating effects of parental monitoring and closeness regarding the association between HD and DV perpetration among middle schoolers in Southeast Texas.

Methods: In our cross-sectional study, we used the baseline data …

The Great Escape: A Case Series On Ddx3x Craniofacial Phenotypes In Females, Ellen Wang, Kylie Swiekatowski, Danielle Sobol, Matthew Greives, Emily Hansen-Kiss

Faculty, Staff and Student Publications

Introduction

Case Description

Post-Rt Head And Neck Dce-Mri: Association Between Mandibular Dose And Ve, Brandon Reber, Renjie He, Moamen R Abdelaal, Abdallah S R Mohamed, Samuel L Mulder, Laia Humbert Vidan, Clifton D Fuller, Stephen Y Lai, Kristy K Brock

Faculty, Staff and Student Publications

Background: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a functional imaging modality that can quantify tissue permeability and blood flow. Due to vasculature changes resulting from radiation therapy (RT), DCE-MRI quantitative parameters should be significantly different in regions receiving a high radiation dose compared to regions receiving a low radiation dose. This study sought to determine whether a significant difference exists in post-head-and-neck-cancer (HNC)-RT DCE-MRI quantitative parameters (Ktrans and ve) between regions of the mandible receiving a high radiation dose and regions of the mandible receiving a low radiation dose.

Methods: DCE-MRI was acquired from HNC subjects post-RT. The DCE-MRI …

Assessing Spatial Variability In Observed Infectious Disease Spread In A Prospective Time-Space Series, Chih-Chieh Wu, Chien-Hsiun Chen, Shann-Rong Wang, Sanjay Shete

Faculty, Staff and Student Publications

Most of the growing prospective analytic methods in space-time disease surveillance and intended functions of disease surveillance systems focus on earlier detection of disease outbreaks, disease clusters, or increased incidence. The spread of the virus such as SARS-CoV-2 has not been spatially and temporally uniform in an outbreak. With the identification of an infectious disease outbreak, recognizing and evaluating anomalies (excess and decline) of disease incidence spread at the time of occurrence during the course of an outbreak is a logical next step. We propose and formulate a hypergeometric probability model that investigates anomalies of infectious disease incidence spread at …

All-Optical Voltage Interrogation For Probing Synaptic Plasticity In Vivo, Jacques Carolan, Michelle A Land, Xiaoyu Lu, Maxime Beau, Dimitar Kostadinov, François St-Pierre, Beverley A Clark, Michael Häusser

Faculty, Staff and Students Publications

Measuring synaptic efficacy and defining the rules for induction of synaptic plasticity at identified connections in the mammalian brain is essential for understanding how synapses contribute to learning and memory. This requires new approaches to selectively evoke presynaptic activity and measure postsynaptic responses with high spatiotemporal resolution and high sensitivity over long periods in vivo. Here we develop an all-optical approach to probe synaptic plasticity at identified cerebellar synapses in awake, behaving mice. We developed and applied JEDI-2Psub, a genetically encoded voltage indicator with increased sensitivity around resting membrane potentials, to record subthreshold and suprathreshold activity in Purkinje cell (PC) …

Ambient Fine Particulate Matter, Residential Greenness, And Childhood Cancer Risk By Trimester Of Exposure In Minnesota 2000 To 2014: A Case-Control Study, Cassandra J Clark, David Haynes, Zhanni Lu, Jeannette M Sample, Laura A Mcguinn, Thanh T Hoang, Philip J Lupo, Michael E Scheurer, Erin L Marcotte, Lindsay A Williams

Faculty, Staff and Students Publications

Background: Outdoor air pollution is a suspected risk factor for childhood cancer, and there is some evidence that greenness may reduce cancer risk. We examined relationships between prenatal exposure to ambient fine particle air pollution [particulate matter < 2.5 µg/m3 (PM2.5)], greenness, and childhood cancer risk in Minnesota.

Methods: Cases included individuals born in the state of Minnesota and reported to the Minnesota Cancer Reporting System between 2000 and 2014 (n = 1272, ages 0-14 years at diagnosis) and birth year-matched cancer-free controls (n = 5245). We used Network Common Data Form to estimate monthly PM2.5 exposure and the normalized difference vegetation index for census tract-level greenness. We estimated ORs and …

A Needed Nomenclature For Nucleosomes, Michael-Christopher Keogh, Genevieve Almouzni, Andrew J Andrews, Karim-Jean Armache, Cheryl H Arrowsmith, Sung Hee Baek, Mark T Bedford, Emily Bernstein, Jacques Côté, Yael David, John M Denu, Beat Fierz, Benjamin A Garcia, Karen C Glass, Or Gozani, Kristian Helin, Steven Henikoff, Ole N Jensen, Steven Z Josefowicz, Neil L Kelleher, Tatiana G Kutateladze, Herbert H Lindner, Chao Lu, Karolin Luger, Parag Mallick, Catherine A Musselman, Tom W Muir, Ljiljana Paša-Tolić, Robert Schneider, Xiaobing Shi, Yang Shi, Simone Sidoli, Lloyd M Smith, Jessica K Tyler, Cynthia Wolberger, Jerry L Workman, Brian D Strahl, Nicolas L Young

Faculty, Staff and Student Publications

Histone post-translational modifications (PTMs) are crucial to eukaryotic genome regulation, with a range of reported functions and mechanisms of action. Though often studied individually, it has long been recognized that the modifications function by combinatorial synergy or antagonism. Interplay may involve PTMs on the same histone, within the same nucleosome (containing a histone octamer), or between nucleosomes in higher-order chromatin. Given this, the field must distinguish ever greater complexity, and the context in which it is studied, with brevity and precision. The proteoform was introduced to define individual forms of a protein by sequence and PTMs, followed by the nucleoform …

A Mast Cell Receptor Mediates Post-Stroke Brain Inflammation Via A Dural-Brain Axis, Ruchita Kothari, Mostafa W Abdulrahim, Hyun Jong Oh, Daniel H Capuzzi, Collin B Kilgore, Sumil K Nair, Yaowu Zhang, Nathachit Limjunyawong, Sarbjit S Saini, Jennifer E Kim, Justin M Caplan, Fernanado L Gonzalez, Christopher M Jackson, Chetan Bettegowda, Judy Huang, Bhanu P Ganesh, Chunfeng Tan, Raymond C Koehler, Rafael J Tamargo, Louise D Mccullough, Risheng Xu, Xinzhong Dong

Faculty, Staff and Student Publications

The immune environment surrounding the brain plays a fundamental role in monitoring signs of injury. Insults, including ischemic stroke, can disrupt this balance and incite an exaggerated inflammatory response, yet the underlying mechanism remains unclear. Here, we show that the mast-cell-specific receptor Mrgprb2 regulates post-stroke brain inflammation from the meninges. Mrgprb2 causes meningeal mast cell degranulation after stroke, releasing immune mediators. This process recruits skull bone marrow neutrophils into the dura and further promotes neutrophil migration from the dura into the brain by cleaving the chemorepellent semaphorin 3a. We demonstrate that the human ortholog, MRGPRX2, is expressed in human meningeal …

Rare Variants In Prkci Cause Van Der Woude Syndrome And Other Features Of Peridermopathy, Kelsey Robinson, Sunil K Singh, Rachel B Walkup, Dorelle V Fawwal, Kendra M Vilfort, Amanda Koloskee, Azeez Fashina, Wasiu Lanre Adeyemo, Terri H Beaty, Azeez Butali, Carmen J Buxó, Wendy K Chung, David J Cutler, Michael P Epstein, Brooklynn Gasser, Lord J J Gowans, Jacqueline T Hecht, Anuj Mankad, Lina Moreno Uribe, Daryl A Scott, Gary M Shaw, Mary Ann Thomas, Seth M Weinberg, Eric C Liao, Harrison Brand, Mary L Marazita, Robert J Lipinski, Jeffrey C Murray, Robert A Cornell, Elizabeth J Leslie-Clarkson

Faculty, Staff and Student Publications

Van der Woude syndrome (VWS) is an autosomal dominant disorder characterized by lower lip pits and orofacial clefts (OFCs). With a prevalence of ∼1 in 35,000 live births, it is the most common form of syndromic clefting. Most VWS is attributed to variants in IRF6 (∼70%) or GRHL3 (∼5%), leaving up to 25% of individuals without a molecular diagnosis. Both IRF6 and GRHL3 function in a transcriptional regulatory network (TRN) governing differentiation of periderm, a single epithelial cell layer preventing pathological adhesions during palatogenesis. Periderm disruption can elicit a spectrum of phenotypes, including lip pits and OFCs, pterygia, and severe …

Preclinical Models Of Melanoma Leptomeningeal Disease To Assess Intrathecal Checkpoint Blockade, Renato A Guerrieri, Grant M Fischer, Jacob R Cortez, Barbara G Knighton, Debora A Ledesma, Courtney W Hudgens, Yimmy F Delcid, Qianghua Hu, Christian Y B Onana, Fernando C L Carapeto, Michael T Tezlaff, Jason T Huse, Patrick Hwu, Elizabeth M Burton, Isabella C Glitza Oliva, Michael A Davies, Sherise D Ferguson

Faculty, Staff and Student Publications

Leptomeningeal disease (LMD) is a subtype of central nervous system metastatic disease that is associated with poor patient outcomes and limited treatment options. There is an unmet need to develop preclinical models of LMD to expedite and improve the development of new therapeutics. Here, we describe the development of multiple orthotopic immunocompetent murine models of melanoma LMD, including their use to assess the efficacy of systemic and/or intrathecal immunotherapy. LMD was established by direct intrathecal injection of murine cell lines (B16-F10, BP, D4M, D4M-UV2, MC38-gp100, RMS, YUMM3.1, and YUMMER1.7) into the cisterna magna of C57BL/6 mice. Tumor take rate, distribution, …

Long-Term Outcomes In Flt3-Mutated Acute Myeloid Leukemia After Frontline Hypomethylating Agent, Venetoclax And A Flt3 Inhibitor, Nicholas J Short, Sanam Loghavi, Musa Yilmaz, Omer Karrar, Kunhwa Kim, Courtney D Dinardo, Tapan M Kadia, Manuel Maroun, Gautam Borthakur, Ghayas C Issa, Joseph Jabbour, Betul Oran, Elizabeth J Shpall, Uday Popat, Keyur P Patel, Mark Routbort, Marina Konopleva, Farhad Ravandi, Hagop Kantarjian, Naval Daver

Faculty, Staff and Student Publications

Triplet regimens with a hypomethylating agent, venetoclax and a FLT3 inhibitor yield high rates of response in newly diagnosed FLT3-mutated AML. However, the long-term outcomes and patterns of relapse with these triplet regimens are not well-established. In this retrospective analysis, 73 patients with newly diagnosed FLT3-mutated AML received a frontline FLT3 inhibitor-containing triplet regimen. The composite complete remission (CR) and CR with incomplete hematologic recovery (CRi) rate was 93%. Next-generation sequencing FLT3-ITD MRD negativity (sensitivity: 0.005%) was achieved in 60% of patients after cycle 2 and 90% after cycle 4. The estimated 3-year relapse-free survival (RFS) for FLT3-ITD-mutated and FLT3 …

Reversible Arginine Methylation Of Pi3kc2Α Controls Mitotic Spindle Dynamics, Yena Cho, Jee Won Hwang, Mark T Bedford, Dong Hee Na, Dae-Geun Song, Su-Nam Kim, Yong Kee Kim

Faculty, Staff and Student Publications

Microtubules, composed of αβ-tubulin dimers, undergo dynamic polymerization and are fundamental to cell structure and function. In the current study, we discovered that phosphatidylinositol 3-kinase class 2α (PI3KC2α) acts as a novel regulatory factor in microtubule dynamics. Specifically, asymmetric dimethylation of PI3KC2α at the R175 residue (R175me2a) by coactivator-associated arginine methyltransferase 1 (CARM1) enhances its interaction with α-tubulin, stabilizing microtubule assembly. Furthermore, lysine Demethylase 4 A (KDM4A) serves as an arginine demethylase for PI3KC2α R175me2a. During mitosis, protein kinase C (PKC)-mediated phosphorylation of KDM4A results in its dissociation from PI3KC2α, preventing demethylation and increasing R175me2a levels. This facilitates spindle formation …

Genome-Wide Analysis Of Dna Methylation Signatures Linking Prenatal Exposure To The Chinese Great Famine And Blood Lipids In Late Adulthood: The Genomic Research Of The Chinese Famine (Grecf) Study, Huan Wang, Luqi Shen, Tingting Liu, Ruiyuan Zhang, Zhenghe Wang, Jingkai Wei, Ye Shen, Jinzhen Guo, Toni Miles, Changwei Li, Zhiyong Zou

Faculty, Staff and Student Publications

Background/objectives: Prenatal exposure to famine can lead to lasting health effects through changes in DNA methylation. This study aims to evaluate the impact of prenatal exposure to the Chinses Great Famine (1959-1961) on human epigenome and the subsequent influence on blood lipids.

Methods: We conducted an epigenome-wide association study (EWAS) of peripheral blood-based DNA methylation and prenatal exposure to the Chinese Great Famine as well as blood lipids among eight participants exposed to famine and eight sex-matched participants (born ≤ 3 years after the famine). Genome-wide DNA methylation sites were profiled using the Illumina EPIC BeadChip, which covers 850K methylation …

Development Of A Polyvinyl Alcohol-Capped Copper Nanocluster-Integrated Electrochemical Sensor For Trace-Level Monitoring Of Anthraquinone, Saba A Memon, Huma Shaikh, Jamil A Buledi, Amber R Solangi, Saima Q Memon, Tania Ghumro

Faculty, Staff and Student Publications

In the current study, polyvinyl alcohol-capped copper nanoclusters (PVA-CuNCs) were synthesized via a chemical reduction method using PVA as a capping and stabilizing agent. The synthesized PVA-CuNCs were used for the fabrication of an ultra-sensitive electrochemical sensor to detect anthraquinone (AQ) at trace levels in an aqueous environment. The fabricated nanoclusters were thoroughly characterized using a wide range of analytical tools. FTIR analysis confirmed the functional properties of the PVA-CuNCs, while XRD investigation revealed a crystalline nature with an average size of 4.21 nm. Their elemental composition was assessed through EDX, indicating a clean copper-based matrix without any notable impurity. …

The 10-Year Functional Outcome Of Ponseti Treatment Of Idiopathic And Arthrogrypotic Clubfeet With An Age-Matched Control, Chris Church, Nicole Wang, Stephanie Butler, Jose J Salazar-Torres, John Henley, Freeman Miller, Nancy Carlin, Maureen Donohoe, L Reid Nichols

Faculty and Staff Publications

Background: The Ponseti method is accepted as an effective primary conservative treatment for idiopathic clubfoot (IC) using serial casting, percutaneous Achilles tenotomy, and prolonged bracing. The outcomes of its use in treating rigid clubfoot in arthrogryposis are unclear. This study assesses the outcomes of the Ponseti method in children with IC and arthrogrypotic clubfoot at an average age of 10 years.

Methods: Outcomes of the Ponseti method were retrospectively studied in ambulatory children ages 8.0 to 12.9 years in the gait lab between 2004 and 2024. Children were excluded due to the presence of nonidiopathic or nonarthrogryposis-related clubfoot and history …

Accreditation Standards Must Protect Trainees: Creating Ethical Fellowship Programs, Anna D Goff, Ryan J Dougherty, Joelle Robertson-Preidler

Faculty and Staff Publications

No abstract provided.

Indomethacin Versus Ketorolac For The Prevention Of Heterotopic Ossification In Hip Arthroscopy Patients, Christopher S Frey, Thomas M Spears, Daniel Puczko, Alicia M Hymel, Candler G Mathews, Patrick M Luchini, Katherine D Van Schaik, Jessica R Leschied, Jaron Sullivan

Faculty, Staff and Student Publications

Background: Nonsteroidal anti-inflammatory drugs are commonly utilized to reduce the risk of developing heterotopic ossification (HO) after hip arthroscopy. However, it is not known which regimen is optimal.

Purpose: The purpose of this study is to determine the rate of HO formation after hip arthroscopy in response to different NSAID protocols.

Methods: Consecutive cases of a single fellowship-trained surgeon at a tertiary referral center were retrospectively reviewed. Patients received a regimen of two medications, starting with four days of either Ketorolac or Indomethacin and ending with either Celecoxib, Meloxicam, Diclofenac, or Naproxen. Two reviewers assessed HO on postoperative radiographs.

Results: …

Escape Of Kdm6a From X Chromosome Is Detrimental To Ischemic Brains Via Irf5 Signaling, Conelius Ngwa, Afzal Misrani, Kanaka Valli Manyam, Yan Xu, Shaohua Qi, Romana Sharmeen, Juneyoung Lee, Long-Jun Wu, Louise Mccullough, Fudong Liu

The Brown Foundation: Institute of Molecular Medicine

The role of chromatin biology and epigenetics in disease progression is gaining increasing recognition. Genes that escape X chromosome inactivation (XCI) can impact neuroinflammation through epigenetic mechanisms. Our previous study has suggested that the X escapee genes Kdm6a and Kdm5c are involved in microglial activation after stroke in aged mice. However, the underlying mechanisms remain unclear. We hypothesized that Kdm6a/5c demethylate H3K27Me3/H3K4Me3 in microglia, respectively, and mediate the transcription of interferon regulatory factor 5 (IRF5) and IRF4, leading to microglial pro-inflammatory responses and exacerbated stroke injury. Aged (17–20 months) Kdm6a/5c microglial conditional knockout (CKO) female mice (one allele of the …

Treatment-Related Adverse Events And Associated Outcomes In Patients With Advanced Urothelial Carcinoma Treated With Enfortumab Vedotin: Analysis Of The Unite Study, Amanda Nizam, Charles B Nguyen, Jinju Li, Emily C Zabor, Pavlos Msaouel, Cindy Y Jiang, Omar Alhalabi, Eugene Oh, Matthew P Davidsohn, Ilana B Epstein, Dimitra Rafailia Bakaloudi, Rafee Talukder, Tanya Jindal, Amy K Taylor, Michael J Glover, Ali Raza Khaki, Emily Lemke, Hannah Mabey, Bashar Abuqayas, Albert Jang, Jason R Brown, Sean T Evans, Cameron Pywell, Arnab Basu, Mehmet A Bilen, Pedro C Barata, Yousef Zakharia, Matthew I Milowsky, Deepak Kilari, Christopher J Hoimes, Sumit A Shah, Hamid Emamekhoo, Nancy B Davis, Shilpa Gupta, Petros Grivas, Joaquim Bellmunt, Matthew T Campbell, Ajjai S Alva, Vadim S Koshkin

Faculty, Staff and Students Publications

Introduction: Enfortumab vedotin-ejfv (EV), an antibody-drug conjugate approved for advanced urothelial carcinoma (aUC), has limited real-world safety data and no validated predictive biomarkers. Retrospective studies suggest higher objective response rates (ORR) among patients developing EV-related dermatologic toxicities, but survival implications remain unclear. This analysis assessed the safety of EV monotherapy and the impact of dermatologic and neurologic toxicities on efficacy outcomes in a multi-institutional cohort.

Materials and methods: UNITE is a multicenter, retrospective study across 16 US sites of patients with aUC treated with targeted agents, including EV. Primary endpoints were the incidence of EV treatment-related adverse events (TRAEs, any …

Genetic Architecture Of Cerebral White Matter Hyperintensities In Diverse Hispanic/Latino Adults, Myriam Fornage, Rui Xia, Adriana Ordonez, Tamar Sofer, Carmen R Isasi, Richard B Lipton, Ariana M Stickel, Wassim Tarraf, Hector M Gonzalez, Charles S Decarli

Faculty, Staff and Student Publications

Background and objectives: Cerebral white matter hyperintensities (WMHs) on MRI are part of the spectrum of age-related brain vascular injury and are associated with increased risk of stroke and dementia. Genome-wide association studies (GWASs) conducted mostly in populations of European ancestry have identified several genetic loci. Although Hispanic/Latino adults have a greater burden of WMHs than their non-Hispanic White counterparts, they are vastly underrepresented in genetic studies. We sought to characterize the genetic architecture of WMHs in a Hispanic/Latino cohort by investigating the transferability of known WMH genetic loci and by leveraging Hispanic/Latino genetic diversity to map novel loci.

Methods: …

Concussion Knowledge, Attitudes, And Behaviors: A Comparison Study Of Youth Athletes And Their Parents, Summer D Ott, Sukhnandan K Cheema, Holden Axel, Seema S Aggarwal, Natalie R Parks, Nikhil Gattu, Philip Schatz

Faculty, Staff and Student Publications

Objective: Given the rising participation in high school athletics and the concerning trend of underreporting concussions, this study aims to identify and compare factors influencing sports-related concussion (SRC) awareness and reporting among youth athletes to their parents.'

Methods: Surveys were completed by 239 student-athletes (ages 13-19) and their parents, using a modified Rosenbaum Concussion Knowledge and Attitudes Survey-Student Version (RoCKAS-ST) and demographic questionnaires. Statistical analyses, including paired sample t-tests, ANOVAs, and Spearman's correlations, compared knowledge and attitudes between groups and examined demographic influences.

Results: Parents showed significantly higher concussion knowledge (CKI: t(230) = 5.18, p < .001) and safer attitudes (CAI: t(230) = 10.62, p < .001) than their children. Knowledge scores varied significantly by race and socioeconomic status, with White parents scoring higher than Hispanic and African American parents (F(3,224) = 8.97, p < .001). Child knowledge scores also differed by race (F(4,223) = 3.73, p = .006) …

Liver-Specific Expression Of Hiv-1 Viral Protein R Causes Hepatic Steatosis And Glucose Intolerance In Male Mice, Neeti Agarwal, Pradip Saha, Claudia E Ramirez Bustamante, Sean M Hartig, Mark A Herman, Ashok Balasubramanyam, Jordan E Lake

Faculty, Staff and Students Publications

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly recognized in people with HIV (PWH), with both HIV and antiretroviral therapy contributing to liver damage and glucose intolerance. However, the role of viral proteins derived from reservoirs in this process remains unclear.

Methods: Adeno-associated virus (AAV) constructs encoding a control protein or HIV-1 viral protein R (Vpr) driven by the thyroxine-binding globulin promoter were administered to male mice (n = 5 per group) fed regular chow or a high-fat diet (HFD). Young adult mice underwent intraperitoneal glucose tolerance testing and magnetic resonance imaging, followed by euthanasia. Liver and adipose tissues …

Inhibition Of Ros1 Activity With Lorlatinib Reversibly Suppresses Fertility In Male Mice, Yuki Oyama, Kentaro Shimada, Haruhiko Miyata, Rie Iida-Norita, Chihiro Emori, Maki Kamoshita, Seiya Oura, Ryohei Katayama, Martin M Matzuk, Masahito Ikawa

Faculty, Staff and Students Publications

Background: Inhibition of sperm maturation in the epididymis is a promising post-testicular strategy for short-acting male contraceptives. It has been shown that ROS1, a receptor tyrosine kinase expressed in the epididymis, is essential for epididymal differentiation, sperm maturation, and male fertility in mice. However, it is unknown if inhibition of ROS1 suppresses male fertility reversibly.

Objectives: Our study aimed to investigate the effects of ROS1 inhibitor administration in male mice on sperm function and fertility.

Materials and methods: We used lorlatinib, an anti-cancer drug that inhibits ROS1. We treated 10-week-old sexually mature male mice with lorlatinib for 3 weeks and …

Carbonic Anhydrase Inhibition Sensitizes Group 3 Medulloblastoma To Radiotherapy, Cory M Richman, Alexandra Rasnitsyn, Borja L Holgado, Maria Vladoiu, Namal Abeysundara, Sandra Majo, Sara Chabi, Lucie J Taunay, Hiromichi Suzuki, Ichiyo Shibahara, Joonas Haapasalo, Jonelle G Pallotta, Tajana Douglas, Kaitlin Kharas, Kyle Juraschka, Oliver Ocsenas, Sachin A Kumar, Kristiina Nordfors, Ana Guerreiro Stücklin, Raul A Suarez, Jiao Zhang, Xiaochong Wu, Craig Daniels, Livia Garzia, Jüri Reimand, Olivier Saulnier, Thomas E Merchant, Celio Pouponnot, David R Raleigh, Michael D Taylor, Pasqualino De Antonellis

Faculty, Staff and Students Publications

Group 3 (G3) medulloblastoma constitutes the most aggressive molecular subgroup, and nearly all patients present with metastases upon recurrence. Treatment for newly diagnosed medulloblastoma relies on a combination of maximal safe surgical resection, followed by chemotherapy and ionizing radiation, and no therapies have been shown to confer a survival benefit at the time of recurrence. Given the limited therapeutic options available for patients with medulloblastoma, especially at recurrence, and the incomplete understanding of the molecular mechanisms underlying resistance to treatment, we sought to uncover actionable targets and biomarkers that could help refine patient selection and treatment of newly diagnosed medulloblastoma …

Unravelling The Distinct Effects Of Vhl Mutations And Chromosome 3p Loss In Clear Cell Renal Cell Carcinoma: Implications For Prognosis And Treatment, Xiang Wang, Jian-Rong Li, Naail Raed Chowdhury, Lang Wu, Cheng Chao

Faculty, Staff and Students Publications

No abstract provided.