Medical Sciences Commons^™

Population-Scale Sequencing Resolves Determinants Of Persistent Ebv Dna, Sherry S Nyeo, Erin M Cumming, Oliver S Burren, Meghana S Pagadala, Jacob C Gutierrez, Thahmina A Ali, Laura C Kida, Yifan Chen, Hoyin Chu, Fengyuan Hu, Xueqing Zoe Zou, Benjamin Hollis, Margarete A Fabre, Stewart Macarthur, Quanli Wang, Leif S Ludwig, Kushal K Dey, Slavé Petrovski, Ryan S Dhindsa, Caleb A Lareau

Duncan NRI Faculty and Staff Publications

Epstein–Barr virus (EBV) is an endemic herpesvirus implicated in autoimmunity, cancer and neurological disorders. Although primary infection is often subclinical, persistent EBV infection can drive immune dysregulation and long-term complications. Despite the ubiquity of infection, the determinants of EBV persistence following primary exposure remain poorly understood, although human genetic variation partially contributes to this phenotypic spectrum1–3. Here we demonstrate that existing whole genome sequencing (WGS) data of human populations can be used to quantify persistent EBV DNA. Using WGS and health record data from the UK Biobank (n = 490,560) and All of Us ( …

Rare Heterozygous Missense Variants In Vsx2 Are Associated With Retinal Detachment, Daniel C Brock, Justin S Dhindsa, Yifan Chen, Vida Ravanmehr, Jonathan Mitchell, Fengyuan Hu, Xiaoyin Li, Likhita Nandigam, Quanli Wang, Kevin Wu, Jessica C Butts, Hardeep S Dhindsa, Benjamin J Frankfort, Nicholas M Tran, Slavé Petrovski, Ryan S Dhindsa

Duncan NRI Faculty and Staff Publications

Retinal detachment (RD) is a sight-threatening emergency requiring urgent intervention to prevent permanent vision loss. While both environmental and genetic risk factors contribute to RD, its complete genetic architecture remains unknown. Here, we performed the largest whole genome sequencing-based case-control study in RD to date, including data from 7,276 RD cases and 236,741 controls in the UK Biobank. Through variant- and gene-level association analyses, we identified VSX2 as a genetic determinant of RD risk while confirming established associations including FAT3, RDH5, and COL2A1. Gene-level collapsing analysis revealed that rare heterozygous missense variants in VSX2 confer a 2.8-fold …

Humanity Is Evolving Its Consciousness: The Role Of Archetypal Energies As Guides During An Unfolding Weeding Out And Alignment Process, Carroy U. Ferguson

Psychology Faculty Publication Series

Humanity is evolving its consciousness at individual and collective levels.  Given these seemingly tumultuous times, as of this writing (January 2026), to make such a statement may sound like a strange thing to say.  However, I suggest that if you are alive today and if you are reading these words, these are the very times for which you were born—to assist Humanity as it evolves its consciousness with your unique gifts, whatever they may be.  That is, this period of our individual and collective human being-ness may be characterized as an unfolding period of weeding out and alignment with the …

Preoperative Malnutrition Is Associated With Increased Postoperative Complications Following Lumbar Fusion: A Propensity-Matched Analysis, Ali Mehaidli, Muaaz Wajahath, Jad Lawand, Omar Abdalla, Lorenzo Deveza, Noah Hodson, Ryan J Berger, Kevin Taliaferro

Faculty, Staff and Students Publications

Background: Lumbar fusion (LF) is a common surgical intervention for degenerative spinal conditions but carries significant short- and long-term risks. Preoperative malnutrition, characterized by low serum albumin or leukocyte counts, impairs wound healing and increases susceptibility to infection, yet its influence on LF outcomes remains underexplored. This study evaluates the association between preoperative malnutrition and long-term postoperative outcomes following LF.

Methods: Adult patients undergoing LF between 2003 and 2023 were identified in the TriNetX US Collaborative Network. Malnutrition was defined as serum albumin < 3.5 g/dL or leukocyte count < 1,500/mm3 within 1 year preoperatively. A 1:1 propensity score match was performed for demographics, comorbidities, surgical approach, and body mass index (BMI), yielding two cohorts (n=20,693 each). Ninety-day and 5‑year postoperative outcomes were compared using hazard ratios (HRs) with 95% confidence intervals (CIs).

Results: Malnourished patients experienced significantly higher 90‑day rates of transfusion (8.4% vs. 4.5%; HR 1.87, 95% CI: …

Global Dose Prescription Variances Exemplified Through Oropharynx Cancer: When Is 70 Gray 70 Gray?, Christian Rønn Hansen, Tony Tadic, Manju Sharma, Gareth Price, Jens Petersen, Mohamed A Naser, Ying Xiao, Nataliya Kovalchuk, Pernille Lassen, Jens Overgaard, Lachlan Mcdowell, Prabhakar Ramachandran, Jun Won Kim, Clifton David Fuller, David J Thomson, Jørgen Johansen, Jeppe Friborg, Sue S Yom, Andrew Hope

Faculty, Staff and Student Publications

Purpose/objectives: Radiation therapy treatment planning hinges on a critical factor: the prescribed dose. Surprisingly, there is no consistent, standardized global approach to evaluating the dosimetry of this prescription across different centers treating head and neck cancer (HNC). This study aimed to quantify global dose variations for identical prescriptions across international centers treating oropharyngeal cancer, to establish the foundation for future outcome-based studies and improve consistency of interpretation worldwide.

Materials and methods: The study included patients with oropharyngeal cancer who were consecutively treated from 2017 onward with intensity-modulated radiation therapy or volumetric modulated arc therapy at 8 globally recognized radiation therapy …

Unlocking Hope: Mirtazapine's Promise In Obsessive-Compulsive Disorder Treatment, Rebecca K. Hicks, Iram Kingson, Jordan Gaal, Suzanne Holroyd

Marshall Journal of Medicine

Obsessive-compulsive disorder (OCD) is a chronic and debilitating psychiatric condition characterized by intrusive thoughts (obsessions) and repetitive behaviors (compulsions). While selective serotonin reuptake inhibitors (SSRIs) and cognitive-behavioral therapy (CBT) are first-line treatments for OCD, a significant proportion of patients remain refractory to these interventions. Mirtazapine, an atypical antidepressant with unique pharmacological properties, has emerged as a potential adjunctive therapy for treatment-resistant OCD. This review synthesizes existing evidence regarding the efficacy and safety profile of mirtazapine in OCD management. We analyze clinical trials, observational studies, and case reports, distinguishing high- vs. low-quality evidence, and discuss mechanisms underlying mirtazapine's therapeutic effects. Additionally, …

Perceived Neighborhood Safety And Firearm Secure Storage: Findings From The 2024 Behavioral Risk Factor Surveillance System, Alexander Testa, Karyn Fu, Muhammed Ahmed, Daniel C Semenza, Dylan B Jackson, Sandra Mckay, Kyle T Ganson, Jason M Nagata

Faculty, Staff and Student Publications

Background: Secure firearm storage (i.e., keeping firearms locked and ammunition stored separately) is a means of reducing risks of suicide, unintentional injury, and homicide. While prior research has examined demographic and household factors associated with storage practices, less is known about how contextual factors, such as perceived neighborhood safety from crime, influence firearm storage behavior.

Methods: Data were from the 2024 Behavioral Risk Factor Surveillance System (BRFSS), a nationally coordinated, state-based survey administered by state health departments with technical and methodological support from the Centers for Disease Control and Prevention. Analyses were restricted to respondents in firearm-owning households from ten …

Functional Genomic Analysis Of Non-Canonical Dna Regulatory Elements Of The Aryl Hydrocarbon Receptor, Shayan Shahriar, Tajhal D Patel, Manjula Nakka, Sandra L Grimm, Cristian Coarfa, Daniel A Gorelick

Faculty, Staff and Students Publications

The aryl hydrocarbon receptor (AHR) is a ligand-dependent transcription factor activated by environmental toxicants like halogenated and polycyclic aromatic hydrocarbons, which then binds to DNA and regulates gene expression. AHR is implicated in numerous physiological processes, including liver and immune function, cell cycle control, oncogenesis, and metabolism. Traditionally, AHR binds a consensus DNA sequence (GCGTG), the xenobiotic response element (XRE), recruits coregulators, and modulates gene expression. Yet, recent evidence suggests AHR can also regulate gene expression via a non-consensus sequence (GGGA), termed the non-consensus XRE (NC-XRE). The prevalence and functional significance of NC-XRE motifs in the genome have remained unclear. …

Beyond Bile Acids Synthesis: Metabolomics Profiling Highlights Extensive Metabolic Dysregulation And Treatment Response In Ctx, Monte A Del Monte, Jennifer Hanson, Penelope E Bonnen

Faculty, Staff and Students Publications

Background: Cerebrotendinous xanthomatosis (CTX) is an inherited metabolic disorder caused by variants in CYP27A1 leading to loss of sterol-27-hydroxylase activity. Sterol-27-hydroxylase generates two classes of bioactive signaling molecules: bile acids and oxysterols. The broader metabolic consequences resulting from perturbations in bile acid and oxysterol signaling and their reversibility with FDA-approved treatment chenodeoxycholic acid (CDCA), are not fully described.

Methods: To establish a comprehensive map of metabolic consequences of CTX, we performed large-scale, untargeted plasma metabolomics in a single subject with CTX, both before and after 6 months of CDCA therapy, and compared results with a reference cohort of over 1100 …

Supercharging-Enhanced Ndia-Ms Enables Global Profiling Of Drug-Induced Proteome Solubility Shifts, Yun Xiong, Huimin Zhang, Lin Tan, Bo Wei, John N Weinstein, Philip L Lorenzi

Faculty, Staff and Student Publications

Mass spectrometry (MS) is indispensable for high-throughput quantitation of protein expression. But protein function is regulated by factors beyond abundance alone. Here, we evaluate two supercharging reagents, dimethyl sulfoxide (DMSO) and m-nitrobenzyl alcohol (mNBA), in narrow-window data-independent acquisition (nDIA)-MS. DMSO markedly enhances MS signal and protein identification, whereas mNBA primarily increases peptide identifications. Optimizating nDIA-MS with 3% DMSO boosts signal intensity by up to 56%, enabling identification of ~9,600 proteins from 1 µg HeLa digest in 15 min. Using this methodology, we quantify solubility and abundance changes in 8,694 proteins across three cell lines following short-term treatment with the proteasome …

High-Throughput Proteomic Profiling To Evaluate Differentiation Syndrome With Menin Inhibition, Miriam B Garcia, Bofei Wang, Irtiza Sheikh, Georgina El Hajjar, David Mccall, Cesar Nunez, Amber Gibson, Philip L Lorenzi, Ghayas C Issa, Branko Cuglievan, Hussein A Abbas

Faculty, Staff and Student Publications

High-throughput proteomic profiling provides a comprehensive analysis of systemic cancer effects and tumor microenvironment interactions. Characterizing soluble proteins driving inflammation in acute myeloid leukemia (AML) offers insight into inflammatory diseases like differentiation syndrome (DS) related to AML therapies like menin inhibitors. We present our application of NUcleic acid-Linked Immuno-Sandwich Assay (NULISA), a novel technology leveraging next-generation sequencing (NGS) for high-throughput, ultra-sensitive characterization of secreted inflammatory proteins in plasma or serum. Here we report its use to identify dynamic soluble protein changes during treatment and at the time of suspected DS in pediatric AML patients treated with the menin inhibitor revumenib …

Two Lysosomal Genes Atp13a2 And Gba1 Interact To Drive Neurodegeneration, Mingxue Gu, Jinghan Zhao, Mingxi Deng, Guang Lin, Xueyang Pan, Wenwen Lin, Mengqi Ma, Jinyong Kim, Seul Kee Byeon, Akhilesh Pandey, Lara M Lange, Chad A Shaw, Jonggeol Kim, Joanne Trinh, Christine Klein, Oguz Kanca, Joshua M Shulman, Hugo J Bellen

Duncan NRI Faculty and Staff Publications

Background: Parkinson’s disease (PD) is a genetically complex disorder in which combinations of heterozygous risk variants may contribute to pathogenesis. Many PD risk loci encode lysosomal genes, such as GBA1, a common and potent risk factor, conferring at least a 5-fold increase. However, the mechanisms of GBA1 penetrance remain poorly understood.

Methods: Using Drosophila melanogaster, we performed a genetic interaction screen of lysosomal storage disorder (LSD) genes to identify dominant modifiers of Gba1b (fly homolog of GBA1). Age-dependent locomotor assessments, electroretinograms (ERG), transmission electron microscopy (TEM) analyses and quantification of dopaminergic (DA) neurons were used to assess …

Comparing Educational Pathways For Denturists To Become Maxillofacial Prosthetic Specialists In The Us And The Uk, Minseok Kim

Oral Health

Abstract

In the absence of formal training, licensure, and professionalism, this scientific literature review will seek to include denturists in the American maxillofacial prosthetics industry. Denturists are oral health professionals who perform oral examination, design, manufacture, and place removable oral prostheses. In other regions of the world, they are also known as clinical dental technologists and dental prosthetists. This practice is not widespread in the US. The review can also be assessed on the model mediated by PRISMA, which is concentrated on the experiences of international education in the United Kingdom, Canada, and Australia, where the concentration further revolves around …

Comparative Outcomes Of Abdominal, Laparoscopic, And Vaginal Sacral Colpopexy: A National Analysis Of Apical Suspension Procedures (2014–2022), Smit Bharat Solanki, Apurva B Pancholy, Vishal Pancholy

Faculty, Staff and Student Publications

Objective: Sacral colpopexy is a well-established procedure for apical suspension, but the relative outcomes of abdominal, laparoscopic, and vaginal approaches remain debated. This study compared perioperative outcomes across these surgical routes using a national database and evaluated trends in robotic assistance.

Materials and methods: We analyzed sacral colpopexy cases from the American College of Surgeons National Surgical Quality Improvement Program between 2014 and 2022. Patient demographics, complication rates, and surgical outcomes were compared among abdominal, laparoscopic, and vaginal procedures. Relative risks (RR) were adjusted for confounders. The utilization of robotic systems in laparoscopic procedures was examined.

Results: Among 61,524 cases, …

Dhodh Links Mitochondrial Bioenergetics, One-Carbon Metabolism, And Dna Repair To Sustain Aggressive Prostate Adenocarcinoma, Saiswaroop Rajaratnam, Danthasinghe Waduge Badrajee Piyarathna, Ranjit K Mehta, Venugopalareddy Mekala, Jun Hyoung Park, Uttam Rasaily, Vani Venkatappa, Karthik Reddy Kami Reddy, Vasanta Putluri, Kaveri Goel, Sandra L Grimm, Sai Manohar Thota, Taylor Morrison, Cristian Coarfa, Benny Abraham Kaipparettu, Chao Cheng, Nagireddy Putluri, Jeffrey A Jones, Mukesh K Nyati, Michael Ittmann, Natalie R Gassman, Arun Sreekumar

Faculty, Staff and Students Publications

Background

Dihydroorotate dehydrogenase (DHODH) is a mitochondrial enzyme that connects de novo pyrimidine biosynthesis with the electron transport chain (ETC) function. However, its broader role in prostate cancer (PCa) signaling and response to therapy remains unclear.

Methods

We combined transcriptomic, metabolomic, epigenomic, and functional analyses with clinical outcome data to explore the effects of DHODH depletion in ancestry-annotated European American (EA) and African American (AA) prostate cancer cell line models.

Results

DHODH was markedly overexpressed in malignant prostate epithelial cells and was abundant in tumors. Its knockdown hindered cell proliferation by causing pyrimidine depletion, while unexpectedly increasing oxidative phosphorylation, ETC …

Seipin Expression In Hepatocytes Impairs The Assembly Of Vldls And Exacerbates Steatohepatitis, Qianqian Dong, Yidan Ma, Xin Chen, Xiaowei Wang, Ziwei Liu, Chenxi Liang, Liwen Qiu, Jinye Tang, Jin Wu, Yang Liu, Xiaoqin Wu, Yaru Zhou, Mingming Gao, Hongyuan Yang

Faculty, Staff and Student Publications

VLDLs are crucial for maintaining liver and whole-body lipid homeostasis. Limited knowledge exists regarding the lipidation process of VLDL. Endoplasmic reticulum (ER) luminal lipid droplets (LLDs) have been suggested to provide lipids for VLDL lipidation and maturation. Seipin, an integral membrane protein of the ER, plays key roles in the formation of cytoplasmic LDs (CLDs) and adipocyte differentiation. Surprisingly, seipin is hardly detectable in hepatocytes. Given the critical contribution of seipin in forming CLDs, we hypothesize that the absence of seipin in hepatocytes might ensure the proper formation of LLDs and the lipidation and assembly of VLDLs. To explore the …

Downregulation Of Slc40a1 Leads To Iron Accumulation In Fibrotic Lung Fibroblasts, Quanjin Dang, Chaoqun Huang, Yurong Liang, Akshaya Surendran, Dharanya Muthiah, Kishore Vaddadi, Sankha Hewawasam, Tingting W Mills, Lin Liu

Faculty, Staff and Student Publications

Iron is an essential nutrient for almost all organisms. However, excess iron generates reactive oxygen species and causes tissue injuries. Iron is implicated in idiopathic pulmonary fibrosis (IPF). In this study, we examined iron accumulation in fibrotic lung fibroblasts and the underlying mechanisms. We hypothesize that the downregulation of Solute Carrier Family 40 Member 1 (SLC40A1) results in iron accumulation in lung fibroblasts of IPF patients. Using a Prussian Blue iron staining, we found that iron accumulated in the fibrotic region of the lungs from IPF patients and bleomycin- and asbestos-induced lung fibrosis mice. Iron was partially co-localized with the …

The Origin Of Hepatocellular Carcinoma Depends On Metabolic Zonation, Jason Guo, Roger Liang, Andrew Chung, Zhijie Li, Boyuan Li, Eric Chen, Lin Li, Jingjing Wang, Meng-Hsiung Hsieh, Ivy Xiangyi Fang, Benjamin Kroger, Yunguan Wang, Min Zhu, Xiongzhao Ren, Greg Mannino, Yuemeng Jia, Yonglong Wei, Stephen Moore, Daniel J Siegwart, Stephen S Chung, Zixi Wang, Tripti Sharma, Suman Komjeti, Yi Han, Purva Gopal, Guanghua Xiao, Tao Wang, Hao Zhu

Faculty, Staff and Student Publications

The origin of cancer is poorly understood because premalignant cells are rarely followed in their native environments. Although the spatial compartmentalization of metabolic functions is critical for proper liver function, it is unknown whether cancers arise from some zones but not others and whether there are metabolic determinants of cancer risk. Zone-specific, mosaic introduction of Ctnnb1 (catenin beta 1) and Arid2 (AT-rich interaction domain 2) mutations, commonly co-mutated genes in hepatocellular carcinoma (HCC), in mouse models showed that position and metabolic context determine clone fates. Ctnnb1/Arid2-driven cancers were much more likely to arise in zone 3. The …

A Comparison Of The Effectiveness Of Salmonella-Shigella (Ss) Agar And Xylose Lysine Deoxycholate (Xld) Agar In Supporting The Growth Of Salmonella Sp. And Shigella Sp., Ika Ningsih, Kharisma Winnie Chryssantium Tiro

Indonesian Journal of Medical Chemistry and Bioinformatics

Diarrheal diseases caused by Salmonella sp. and Shigella sp. are among the most significant public health challenges worldwide, especially among children. To identify these bacteria, Salmonella-Shigella (SS) and Xylose Lysine Deoxycholate (XLD) agar media are used, which are selective and differential for Salmonella sp. and Shigella sp. Although these media share similar properties and functions for growing Salmonella sp. and Shigella sp., results from previous studies differ from those obtained in tests conducted by the Department of Microbiology, Faculty of Medicine, University of Indonesia. This laboratory-based experimental study used serial dilution with three replicates (triplicate). Based on SNI 2897 of …

A Robust Convnext-Based Framework For Efficient, Generalizable, And Explainable Brain Tumor Classification On Mri, Kirti Pant, Pijush Kanti Dutta Pramanik, Zhongming Zhao

Faculty, Staff and Student Publications

Background: Accurate and dependable brain tumor classification from magnetic resonance imaging (MRI) is essential for clinical decision support, yet remains challenging due to inter-dataset variability, heterogeneous tumor appearances, and limited generalization of many deep learning models. Existing studies often rely on single-dataset evaluation, insufficient statistical validation, or lack interpretability, which restricts their clinical reliability and real-world deployment.

Methods: This study proposes a robust brain tumor classification framework based on the ConvNeXt Base architecture. The model is evaluated across three independent MRI datasets comprising four classes-glioma, meningioma, pituitary tumor, and no tumor. Performance is assessed using class-wise and aggregate metrics, including …

Translating Cardiovascular Ion Channel And Ca2+ Signalling Mechanisms Into Therapeutic Insights, Silvia Marchianò, Miguel Martín-Aragón Baudel, Charlotte E R Smith, Gonzalo Hernandez Hernandez, Donald M Bers, Patrick M Boyle, Dobromir Dobrev, Shanna Hamilton, Osama F Harraz, Na Li, Thomas A Longden, William E Louch, Madeline Nieves-Cintron, Matthew A Nystoriak, Walter Lee Murfee, Przemysław B Radwański, Swapnil K Sonkusare, Manuel F Navedo, Eleonora Grandi

Faculty, Staff and Students Publications

Cardiovascular diseases remain the leading cause of mortality worldwide, driven by complex, multi-scale mechanisms that span molecular, cellular, and organ-level dysfunction. Effective therapeutic strategies therefore require integrative approaches that link fundamental biology to translational applications. The 8th UC Davis CardioVascular Symposium gathered experts in ion channel biophysics, Ca2+ signaling, arrhythmia mechanisms, and cardiovascular physiology to discuss recent advances and define emerging priorities. This white paper synthesizes the key themes and consensus points that emerged, highlighting progress in two core domains: (1) advances in cardiovascular electrophysiology and arrhythmia mechanisms, and (2) spatiotemporal dynamics of Ca2+ signaling in cardiac and vascular function …

Designing Inclusive Newborn Sequencing Research: Insights From Parents In Underrepresented Communities, Maya C Del Rosario, Sheyenne A Walmsley, Barbara W Harrison, Crystal T Stephens, Bethany Zettler, Greysha Rivera-Cruz, Priyal Agrawal, Amy Brower, Stephanie Chigbu, Kurt D Christensen, Casie A Genetti, Richetta Givens, Nina B Gold, Inez V Reeves, Isabella Schichter, Habib Shariat, Sandra Simon, Hadley Stevens Smith, Melissa Uveges, Robert C Green, Ingrid A Holm, Stacey Pereira

Center for Medical Ethics and Health Policy Staff Publications

Background: It is essential that studies of genomic sequencing (GS) in newborns and children include individuals from under-represented racial and ethnic groups (URG) to ensure future applications are equitably implemented. We conducted interviews with parents from URG to better understand their perspectives on GS research, develop strategies to reduce barriers to enrollment, and facilitate research participation.

Methods: Semi-structured interviews with 50 parents from URG.

Results: Nearly all parents said they would be interested in participating in an infant GS study. Parents were interested in participating in GS research for reasons including clinical utility, personal utility, and/or family health benefits. Deterrents …

Kdm4a Promotes Nepc Progression Through Regulation Of Myc Expression, Celia Sze Ling Mak, Ming Zhu, Jie Fu, Xin Liang, Xiaoxuan Wang, Fei Yuan, Feng Wang, Anh G Hoang, Xingzhi Song, Peter Shepherd, Derek Liang, Jessica Suh, Jordan Contreras, Thisawin Dang, Cindy Yan, Brandon Figueroa, Mathias Mazzocco, Athena Luo, Bijeta Pradhan, Jiwon Park, Mirrah Bashir, Miao Zhang, Eric Metzger, Roland Schüle, Abhinav K Jain, Ellen Karasik, Daniel Frigo, Barbara A Foster, Min Gyu Lee, Paul Corn, Christopher J Logothetis, Ana Aparicio, Nora Navone, Patricia Troncoso, Zhi Tan, Jianhua Zhang, Sue-Hwa Lin, Guocan Wang

Faculty, Staff and Students Publications

Neuroendocrine prostate cancer (NEPC) is a highly aggressive and lethal subtype of prostate cancer (PCa) that often emerges in response to androgen receptor pathway inhibitors (ARPIs), which are widely used in treating metastatic castration-resistant and hormone-sensitive prostate cancer. The incidence of NEPC is increasing, yet effective therapeutic strategies remain limited due to an incomplete understanding of its molecular drivers. Through transcriptomic analyses of human prostate tumor samples, we identified the histone lysine demethylase KDM4A as uniquely overexpressed in human and mouse NEPC compared to prostate adenocarcinoma. Functional validation demonstrated that KDM4A is a key regulator of NEPC progression and a …

The Cortico-Cortical And Subcortical Circuits Of The Human Brain Language Centers Including The Dual Limbic And Language Functioning Fiber Tracts, Arash Kamali, Nithya P Narayana, Anastasia Loiko, Anusha Gandhi, Paul E Schulz, Nitin Tandon, Manish N Shah, Vinodh A Kumar, Larry A Kramer, Jay-Jiguang Zhu, Haris Sair, Roy F Riascos, Khader M Hasan

Faculty, Staff and Student Publications

Background/Objectives: In recent years, MRI-based diffusion-weighted tractography techniques have uncovered additional white matter pathways that have significant roles in language processing and production. In this review, we aim to outline the major language centers of the brain and major language pathways along with association tracts that serve dual roles in both the language and limbic systems. According to the current dual-stream model of language processing, the brain's language network is organized into a dorsal stream, responsible for mapping sound to articulation, and a ventral stream, which maps sound to meaning.

Materials and Methods: The literature cited in this …

Payload Diversification Overcomes Resistance And Guides Sequential Antibody-Drug Conjugate Therapy In Breast Cancer, Dileep Reddy Rampa, Minji Seo, Nanae Ogata, Zhaoxuan Yang, Nithya Sridhar, Fujii Takeo, Chalothorn Wannaphut, Jennifer A Maynard, Kyoji Tsuchikama, George W Sledge, Naoto T Ueno, Jangsoon Lee

Faculty, Staff and Student Publications

Purpose: Antibody-drug conjugates (ADCs) have transformed the treatment of breast cancer. FDA-approved ADCs such as trastuzumab deruxtecan (T-DXd), sacituzumab govitecan (SG), and datopotamab deruxtecan (Dato-DXd) have demonstrated clinical benefit; however, drug resistance will almost inevitably emerge in the metastatic setting, and there is no established strategy for selecting subsequent ADCs after disease progression to the first exposure to the ADC. This study aimed to define mechanisms of acquired resistance and evaluate rational sequencing approaches.

Experimental design: We generated breast cancer cell lines resistant to T-DXd (TDXd-R) and SG (SG-R). We assessed antigen expression, internalization, and resistance pathways, including efflux transporter …

Cabozantinib And Thromboembolism In Patients With Cancer: A Systematic Review, Meta-Analysis, And Retrospective Study, Harish Eswaran, Rohan R Kasthuri, Pavan K Bendapudi, Alok A Khorana, Raj S Kasthuri, Nick Van Es, Steven P Grover

Faculty, Staff and Student Publications

Antiangiogenic agents, including vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs), represent an important class of treatments for a range of solid tumors. However, concerns have arisen over potential associations between antiangiogenic agents and thromboembolic events. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) that compared a frequently used VEGFR TKI, cabozantinib, with placebo or usual care. The primary outcome was the risk of any thromboembolism. Secondary outcomes included the risk of venous thromboembolism (VTE), risk of arterial thromboembolism (ATE) and progression-free survival. 14 RCTs were included with a combined total of 4204 patients, …

Expression Spectrum Of Te-Driven Transcripts In Human Adult Tissues, Benpeng Miao, Xinlong Luo, Amina Ademovic, Yushan Yang, Tao P Wu, Bo A Zhang

Faculty, Staff and Students Publications

Background

Transposable elements (TEs) are vital components of eukaryotic genomes and have played a critical role in genome evolution. Although most TEs are silenced in the mammalian genome, increasing evidence suggests that certain TEs are actively involved in gene regulation during early developmental stages. However, the extent to which human TEs drive gene transcription in adult tissues remains largely unexplored.

Results

In this study, we systematically analyze 17,329 human transcriptomes to investigate how TEs influence gene transcription across 47 adult tissues. Our findings reveal that TE-driven transcripts are broadly expressed in human tissues, contributing to both housekeeping functions and tissue-specific …

Integrated Proteomics To Understand The Role Of Neuritin-1 (Nrn1) As A Molecular Mediator Of Synaptic Resilience In Alzheimer’S Disease, Derian Pugh

ETDs from 2020-2029

Alzheimer’s disease (AD) is the leading cause of dementia in adults over the age of 65, and currently affects approximately 6.9 million people in the United States. By 2060, the number of people age 65 and older with AD is projected to reach 13.8 million, barring the development of disease-altering therapies to prevent, slow or cure AD. Thus, there is a need for progress in the understanding of AD pathophysiology, as well as in the development of diagnostic and therapeutic interventions. Approximately one-third of individuals without dementia at the time of death are found to harbor high levels of amyloid-beta …

Targeting Interleukin-6 Trans-Signaling To Improve Post-Stroke Inflammation: A Precision Immunotherapy Perspective, Kate Mendoza, Dustin T Nguyen, Anjali Chauhan

Faculty, Staff and Student Publications

No abstract provided.

Differentiation In The Human Urothelia Is Defined By Distinct Alternative Polyadenylation, Ninh B Le, Surbhi Sona, Briana Santo, Yi Zhang, Rosie Ou, R Allen Schweickart, Veena Kochat, William I Padron, Kunal Rai, Shih-Han Lee, Joo Mi Yi, Oliver Wessely, Byron H Lee, Angela H Ting

Faculty, Staff and Student Publications

Distinct epithelial cell states arise during differentiation, but mechanisms generating transcriptomic diversity among them remain poorly defined. The human ureter urothelium contains basal progenitor, intermediate cells, and terminally differentiated umbrella cells. Prior single-cell RNA sequencing revealed similar global gene expression profiles across these states, raising the question of how distinct identities emerge. Here, we show that alternative cleavage and polyadenylation (APA) introduces a major layer of transcriptomic diversity during urothelial differentiation, largely independent of changes in mRNA levels. Analysis of 13,544 urothelial cells identified hundreds of differentiation-associated APA events. Single-cell imaging revealed spatially specific APA patterns, and reporter assays demonstrated …