Digital Commons Network^™

Exploring The Relationship Between Phonological Awareness And Adhd Symptoms In School-Aged Children, Nihal Hisham Abdelhamid, Mona Abdel-Fattah Hegazi, Dina Ahmed Elsayed Elrefaie

Journal of Medicine in Scientific Research

Attention deficit hyperactivity disorder is one of the neurodevelopmental disorders which characterized by: inattention and impulsivity as well as apparent deficits in executive functioning and impulse control. Auditory-linguistic areas and primary reading skills as early literacy skills were found to be lower than normal in ADHD. Other researches considered that the reading difficulties are in the areas of fluency, comprehension, and sustained attention during reading tasks. The aim of the study is to evaluate the phonological awareness abilities skills in children with attention deficit hyperactive disorder (ADHD), being contributors for early reading acquisition. Phonological awareness (PA) is the precise recognition …

Perioperative Dexmedetomidine Improve Outcomes After Cabg Surgery., Reham Salah, Ismail Rafik Barada, Mazen Isam Eldein Ali

Journal of Medicine in Scientific Research

Background Dexmedetomidine, is used in cardiac surgeries for its sedation, anxiolysis, and analgesic properties, with minimal respiratory depression. It may improve clinical outcomes in CABG surgery by reducing inflammatory responses, providing neuroprotection, and enhancing hemodynamic stability. Aim To assess the efficacy and safety of perioperative dexmedetomidine in improving clinical outcomes in CABG surgery. Methods This prospective, randomized controlled trial involved 160 patients undergoing elective on-pump CABG surgery. Participants were divided into two groups: 80 received dexmedetomidine, and 80 received a placebo. Key outcomes measured included the incidence of postoperative complications, duration of mechanical ventilation, and ICU stay. Results The dexmedetomidine …

Pediatric Cardiac Surgery After Pulmonary Arterial Interventions: Short-Term Outcomes, Rania Abushokka, Hanan Mohammed Hassan, Rasha Hosni, Amal Younan, Ahmed Algebaly

Journal of Medicine in Scientific Research

Background: Congenital cardiac interventions are progressing at a rapid pace. In the last few years, techniques such as stent placement for pulmonary artery stenosis, right ventricle outflow tract and ductal stenting showed great advances. Surgery over stents are increasing in complexity. Left pulmonary artery and right ventricle outflow tract sites account for more than half of stent handling. Percutaneous devices are not an ‘‘enemy’’ for the surgeon, but a tool for continuing the development of our surgical strategies. In this study, we describe the short-term outcome of patients who underwent surgical repair after pulmonary interventions for congenital heart diseases at …

Frequency Of Autoimmune Primary Adrenal Insufficiency In Children And Adolescents With Type 1 Diabetes Mellitus, Randa Mohamed Darwish, Ayat Ibrahim Ghanem, Lamis Safwat Mubarak

Journal of Medicine in Scientific Research

Background Type 1 diabetes mellitus (T1DM) is a chronic endocrine disorder of autoimmune origin with a predisposition to the development of further autoimmune diseases, including autoimmune adrenal insufficiency (Addison’s disease). Although uncommon and frequently underdiagnosed, it can coexist with T1DM, causing life-threatening complications if undiagnosed. Aim To assess the frequency of autoimmune adrenal insufficiency in children with T1DM and its association with other autoimmune diseases. Methods A cross-sectional study was conducted on 110 children with type 1 diabetes mellitus (T1DM) and 100 age- and sex-matched healthy controls. All participants underwent a full clinical evaluation and laboratory testing, including serum cortisol, …

Evaluating The Efficacy Of Conventional Crystalloid Cardioplegia Versus Modified Del Nido Cardioplegia In Patients With Multivessel Coronary Artery Disease For Cabg Surgery, Reham Salah, Ismail Rafik Barada, Mazen Isam Eldein Ali

Journal of Medicine in Scientific Research

Background: Cardioplegia is crucial in cardiac surgery for myocardial protection. Modified del Nido cardioplegia, initially used in paediatric patients, is now employed in adult cardiac surgeries for its prolonged protection with a single dose. Aim: To compare the efficacy of conventional crystalloid cardioplegia and modified del Nido cardioplegia in patients undergoing coronary artery bypass graft surgery (CABG) for multivessel coronary artery disease (CAD). Methods: A randomized controlled trial included 94 adult patients undergoing elective CABG. Patients were randomly assigned to receive either conventional crystalloid cardioplegia or modified Del Nido cardioplegia. Data collected included CPB and cross-clamp times, cardioplegia volume, postoperative …

Effectiveness Of Myoinositol Versus Metformin As Adjuvant Treatment On Infertile Pcos Women Undergoing Ovulation Induction Cycles Prospective Cohort Study, Ahmed M. Salman, Fatma M. Sayed, Hesham Mohammed Hamad

Journal of Medicine in Scientific Research

Background In anovulatory infertility Polycystic ovary syndrome (PCOS) plays a leading role, characterized by endocrine and metabolic disturbances. While metformin is usually used to decrease insulin resistance and restore ovulation, myoinositol has emerged as a promising alternative with fewer side effects. This study aimed to evaluate and compare the effectiveness of metformin and myoinositol as adjuvant treatments in infertile women with PCOS in ovulation induction cycles. Patient and methods This prospective cohort study included 192 women diagnosed with PCOS-related infertility, divided into two groups (n = 96 each) receiving either metformin or myoinositol for 3 months prior to ovulation induction. …

Glycolic Acid (Ga) Peel Versus Dermapen In Management Of Acne Scars Among Egyptian Patients: A Comparative Study, Rania Emam Elbanna

Journal of Medicine in Scientific Research

Aim of the work: To assess and contrast dermapen, glycolic acid (GA) peel, and a combination of the two therapys' safety and effectiveness in treating acne scars. Cases and methods: Thirty cases with acne scars participated in this trial. Ten cases each were divided into three cohorts at random; cohort I had dermapen therapy, whereas cohort II received glycolic peel therapy. Both procedures were administered to Cohort III. Six sessions were given to each case at intervals of two weeks. The quartile grading scale, the degree of case satisfaction, and the qualitative global scar grading system before and after therapy …

Clinical And Dosimetric Dataset Of Time-To-Event Normal Tissue Complication Probability For Osteoradionecrosis, Natalie A West, Serageldin Kamel, Andrew Wentzel, Zaphanlene Kaffey, Moamen Abdelaal, G Elisabeta Marai, Guadalupe Canahuate, Xinhua Zhang, Melissa M Chen, Kareem A Wahid, Jillian Rigert, Kristy K Brock, Mark Chambers, Adegbenga O Otun, Ruth Aponte-Wesson, Renjie He, Mohamed A Naser, Katherine A Hutcheson, Abdallah S R Mohamed, Lisanne V Van Dijk, Amy C Moreno, Stephen Y Lai, Clifton D Fuller, Laia Humbert-Vidan

Faculty, Staff and Student Publications

Osteoradionecrosis of the jaw (ORNJ) is a radiation-induced late toxicity that can dramatically decrease patients' quality of life. Recent increases in survival rates of head and neck cancers associated with human papillomavirus (HPV) infection have resulted in a higher frequency of radiation-induced toxicities, particularly ORNJ. Recent work with Normal Tissue Complication Probability (NTCP) models and a Weibull Accelerated Failure Time (WAFT) model have further developed our understanding of ORNJ clinical/dosimetric risk factors and longitudinal features, respectively. In this data descriptor, 1129 head and neck cancer (HNC) patients received curative intent radiotherapy (RT) at MD Anderson Cancer Center and were followed …

An Integrated Single-Cell And Spatial Transcriptomic Atlas Of Thyroid Cancer Progression Identifies Prognostic Fibroblast Subpopulations, Matthew A Loberg, George J Xu, Sheau-Chiann Chen, Hua-Chang Chen, Claudia C Wahoski, Kailey P Caroland, Megan L Tigue, Heather A Hartmann, Jean-Nicolas Gallant, Courtney J Phifer, Andres A Ocampo, Dayle K Wang, Reilly G Fankhauser, Kirti A Karunakaran, Chia-Chin Wu, Maxime Tarabichi, Sophia M Shaddy, James L Netterville, Sarah L Rohde, Carmen C Solórzano, Lindsay A Bischoff, Naira Baregamian, Barbara A Murphy, Jennifer H Choe, Jennifer R Wang, Eric C Huang, Quanhu Sheng, Luciane T Kagohara, Elizabeth M Jaffee, Ryan H Belcher, Ken S Lau, Fei Ye, Ethan Lee, Vivian L Weiss

Faculty, Staff and Student Publications

Although well-differentiated thyroid carcinoma (WDTC) is characterized by a robust treatment response, aggressive subtypes, such as anaplastic thyroid carcinoma (ATC), remain highly lethal. To understand thyroid cancer evolution in both children and adults, we analyzed single-cell transcriptomes of 423,733 cells from 81 samples and spatially resolved key tumor and microenvironment populations across 28 tumors with spatial transcriptomics, including rare and unique composite WDTC/ATC tumors and pediatric diffuse sclerosing thyroid carcinomas. Additionally, we identified gene signatures of stromal cell populations in 5 large thyroid cancer bulk RNA-sequencing cohorts. Through this multi-institutional effort, we defined a population of POSTN+ myofibroblast cancer-associated fibroblasts …

Prognostic Value Of Baseline Qfr In Single-Vessel Intermediate Coronary Stenosis, Yanfeng Lu, Abdulrahman Alqazzaz, Jasmine Bao, Gary S. Mintz, Jiahao Feng, Yong Zhang, Shanshan Gao, Qiang Song, Feifei Ning, Xin Huang, Ning Guo

Student Papers, Posters & Projects

BACKGROUND AND OBJECTIVES: The prognostic value of baseline Quantitative Flow Ratio (QFR) in real-world patients remains unclear. This study aimed to evaluate the prognostic value of baseline QFR and its three-tier model-low, grey-zone, and high QFR-in patients with single-vessel intermediate stenosis.

METHODS: This retrospective study included 478 patients with QFR between 0.70 and 0.90 who underwent coronary angiography between May and June 2023. Patients were stratified into Low (0.70-0.74), Grey-Zone (0.75-0.85), and High (0.86-0.90) QFR groups. The primary endpoint was major adverse cardiac events (MACE); the key secondary endpoint was target vessel failure (TVF). Kaplan-Meier and Cox proportional hazards models …

Primary Cortical Neurons Precipitate And Extrude Large Mitochondria-Associated Calcium-Phosphate Sheets With A Bone-Precursor-Like Ultrastructure, Erik D Anderson, Christopher A Cronkite, Philip R Baldwin, Carlota P Abella, Joseph G Duman, Ashleigh N Simmonds, M Neal Waxham, Kimberley F Tolias, Steven J Ludtke

Faculty, Staff and Students Publications

Calcium-phosphate (CaP) is a ubiquitous inorganic compound that plays an important structural role in healthy bone and teeth formation, but its pathologic buildup can occur in dyshomeostatic calcium disorders like Alzheimer's disease and Leigh syndrome. The nexus of pathologic extracellular CaP in the nervous system is not well understood, but prior evidence suggests mitochondria could be a source. We have observed mitochondria-sized sheet-like CaP aggregates within functional wild type cortical neuron cultures at 1 and 20 days in vitro. Neurons were extracted from embryonic day 18 (E18) rat embryos following standard protocols to study neuronal structure and function. We have …

Maternal Immunization With Vp8* Mrna Vaccine Yields Superior Passive Transfer Of Rotavirus-Neutralizing Antibodies To Foals, Karin E R Borba, Rebecca M Legere, Nathan M Canaday, Jill W Skrobarczyk, Zachary W T Arnold, Elena Cotton-Betteridge, Cristina Poveda, Michael F Criscitiello, Angela I Bordin, Luc R Berghman, Jeroen B K Pollet, Noah D Cohen

Faculty, Staff and Students Publications

Background: Despite the availability of a killed whole-virus (KV) vaccine, diarrhea caused by equine rotavirus group A (ERVA) remains a significant health concern for foals in the United States. The vaccine is administered to pregnant mares, with foals protected by passive transfer of colostral antibodies. However, KV-induced immunity is only partially protective and maternal antibody levels in foals are often low and wane rapidly. To address these limitations, we developed a mRNA-based ERVA vaccine encoding the highly conserved VP8* protein to evaluate whether it can provide improved immune protection.

Methods: Pregnant mares (n = 12 per group) were …

Developing A Multidisciplinary Approach To Complex Pediatric Areodigestive Care- Where We've Been, Where We're Going, And What We've Learned Along The Way, Jason R. Brown

Grand Rounds

1. Enhance competence and expand expertise in pediatric surgical conditions prevalent in our geographical area and nationally.
2. Develop strategies to enhance communication and collaboration among interdisciplinary team members addressing pediatric surgical conditions.
3. List barriers to multidisciplinary care.

Regional Anesthesia Utilizing Liposomal Bupivacaine, With Or Without Dexamethasone, Provides Excellent Pain Control And Minimizes Opioid Consumption Following Anterior Cruciate Ligament Reconstruction, William L. Johns, Armen Voskeridjian, Benjamin Miltenberg, Rahul Muchintala, Christopher C. Dodson, Steven B. Cohen, John Salvo, Matthew Sherman, Michael G. Ciccotti, Sommer Hammoud

Rothman Institute Papers

BACKGROUND: Perioperative nerve blocks are commonly used for regional analgesia with anterior cruciate ligament (ACL) reconstruction (ACLR). Liposomal bupivacaine (LB) is a long-acting anesthetic agent providing up to 72 hours of nerve blockade. It is theorized that the addition of dexamethasone to LB (LB+dex) may prolong the analgesic duration.

PURPOSE: To characterize pain control and opioid consumption with adductor canal block (ACB), interspace between the popliteal artery and capsule of the posterior knee (iPACK), and suprasartorial infiltration (SSI) regional anesthetic techniques utilizing LB after ACLR and to compare LB versus LB+dex.

STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. …

End Point–Based Threshold For The Ambulatory Arterial Stiffness Index, Yi-Bang Cheng, De-Wei An, Dong-Yan Zhang, Yu-Ling Yu, Jesus D. Melgarejo, José Boggia, Dries S. Martens, Tine W. Hansen, Kei Asayama, Gladys E. Maestre

School of Medicine Publications

Background: The ambulatory arterial stiffness index (AASI) is increasingly used in clinical research and practice. This individual-participant meta-analysis aims to consolidate the prognostic accuracy of AASI in the general population and to derive an end point-based AASI risk threshold.

Methods: In 12 558 individuals enrolled in 14 population studies (48.8% women; mean age, 59.3 years), AASI was derived by regressing 24-hour diastolic on systolic blood pressure (mm Hg/mm Hg). Using Cox regression, the risk-carrying AASI threshold was established by examining stepwise increasing AASI levels and by determining the AASI level, yielding a 10-year risk similar to an office systolic pressure …

Optimal Timing Of Cranioplasty Post-Decompressive Craniectomy In Traumatic Brain Injury: A Systematic Review, Meta-Analysis, And Overview Of Ongoing Trials, Ashviniy Thamilmaran, Shaan Patel, Shiva A. Nischal, Honey Panchal, Kush Kale, Pious D. Patel, Jack Jallo, James S. Harrop

Department of Neurosurgery Faculty Papers

BACKGROUND: The optimal timing of cranioplasty (CP) following decompressive craniectomy (DC) for the management of traumatic brain injury (TBI) remains debated. Prior studies comparing early CP (EC) and late CP (LC) report conflicting outcomes, compounded by inconsistent timing thresholds and limited attention to effect modifiers such as implant material.

OBJECTIVE: To perform a systematic review and meta-analysis comparing outcomes of EC (≤ 90 days) versus LC (> 90 days) after DC for TBI, with particular evaluation of ultra-EC (<  35 days) and implant material.

METHODS: MEDLINE, Embase, and CENTRAL were electronically searched from inception to April 2025, supplemented by manual screening of references and grey …

Multi-Institutional Normal Tissue Complication Probability (Ntcp) Prediction Model For Mandibular Osteoradionecrosis: Results From The Predmorn Study, Laia Humbert-Vidan, Christian R Hansen, Steven Petit, Carles Muñoz-Montplet, Katrina Hueniken, Abdallah S R Mohamed, Deborah P Saunders, Vinod Patel, Gerda M Verduijn, Wilma D Heemsbergen, Arjen Van Der Schaaf, Max Witjes, Suzanne P M De Vette, Mohammad Moharrami, Abdul A Khan, Jordi Marruecos Querol, Irene Oliveras Cancio, Mike Oliver, Peter Reich, Stacey A Santi, Andrew G Pearce, Stephen Y Lai, Andrew P King, Ali Hosni, Andrew J Hope, Erin E Watson, Johannes A Langendijk, Jørgen Johansen, Amy C Moreno, Clifton D Fuller, Lisanne V Van Dijk, Teresa Guerrero Urbano

Faculty, Staff and Student Publications

Purpose: Mandibular osteoradionecrosis (ORN) is a severe late complication affecting patients with head and neck cancer (HNC) treated with radiation therapy (RT) that significantly impacts patients' quality of life and can require costly interventions. Although radiation dose is a key factor, other clinical and demographic risk factors also influence ORN development. Previous predictive models have primarily been single-institutional, limiting their generalizability. In this first analysis from the PREDMORN Consortium, we have aimed to reproduce existing statistical association and modeling analyses on the largest and most diverse mandibular ORN cohort worldwide to allow comparison with previous studies.

Methods and materials: This …

Disparities In Cardiovascular Disease Burden Among Black And Hispanic Survivors Of Adolescent And Young Adult (Aya) Cancer, Tori Tonn, Maanvi Thawani, Margaret Mazer, Greg Aune, Debra Eshelman-Kent, Karen Albritton, Efstratios Koutroumpakis, Michael E Roth, Michelle A T Hildebrandt

Faculty, Staff and Student Publications

Background: Despite significant improvements in long-term survival outcomes for adolescents and young adults (AYAs) with cancer, common treatment regimens often pose substantial risks to the cardiovascular health of this survivor population. Differences in cardiovascular events by race/ethnicity and genetic ancestry within this at risk population remain unclear.

Methods: In this study, we investigated adverse cardiovascular outcomes in a diverse population of AYA cancer survivors (n = 346) treated at MD Anderson Cancer Center for Hodgkin lymphoma and sarcoma. Analysis was conducted by self-identified race/ethnicity and by genetic ancestry.

Results: Black and Hispanic survivors demonstrated the greatest burden of poor …

Acute Stemi In A Young Adult On Therapeutic Anticoagulation Following Diclofenac Use, Naeem Hasanfatta, Naveed Ahmed, Debabrata Dash

Journal of the Saudi Heart Association

Background: Acute coronary syndrome (ACS) in young adults is uncommon. The case of a 34-year-old male, post mechanical mitral valve replacement (MVR), who developed anterior ST-elevation myocardial infarction (STEMI) despite therapeutic anticoagulation (INR 3.17), shortly after the initiation of diclofenac, highlights an important clinical scenario.

Case Presentation: The patient presented with atypical upper back pain and was diagnosed with anterior STEMI. Coronary angiography revealed a 100% thrombotic occlusion in the mid left anterior descending (LAD) artery. Percutaneous transluminal coronary angioplasty (PTCA) was successfully performed. Importantly, the patient had no history of hypercoagulable states or atherosclerosis and had been compliant with …

Embedding Interprofessional Education In Pediatric Clerkships: Lessons From Nebraska’S Tracking Infant Progress Statewide (Tips) Program, Grace E. Berentson, Liliana Bronner, Paige Hardy, Neil Kalsi, Brianna Brei, Kerry Miller

Posters and Presentations: Munroe-Meyer Institute

Background: NICU graduates experience disproportionate developmental and health challenges. Their families face barriers to equitable care including access to coordinated follow-up services. Traditional medical education rarely exposes students to authentic interprofessional models of care that address these inequities. The Tracking Infant Progress Statewide (TIPS) program provides developmental, social, and medical follow-up for NICU graduates across Nebraska, bringing together physicians, nurse practitioners, child developmental specialists, and nurses in a single family-centered visit. Embedding third-year medical students into this setting models collaborative practice, builds understanding of interprofessional competencies, and fosters awareness of systemic inequities affecting NICU families. This innovative curricular approach differs …

Systematic Review And Meta-Analysis Of Placebo Cure In Onychomycosis Clinical Trials, Julianne M. Falotico, Zachary J.K. Neubauer, Anjile An, Shari R. Lipner

Student Papers, Posters & Projects

No abstract provided.

The Vascular Density/Angiogenesis Marker Cd31/Pecam1 Does Not Correlate With Overall Survival In Neuroendocrine Tumors, Nicholas J. Skill, Kenneth Avanzino, Yvette Bren-Mattison, J. Philip Boudreaux, Ramcharan Thiagarajan, Mary Maluccio

School of Medicine Faculty Publications

Abstract: Neuroendocrine neoplasms (NENs) are rare cancers. CD31/PECAM1 is an adhesion molecule that modulates endothelial cell-to-cell contact. Increased CD31 expression is a marker for tumor growth, and cancer aggressiveness. The purpose of this study was to better understand the prognostic value of CD31 expression in primary and metastatic NEN tumors in terms of correlations with overall survival and pathological metrics, tumor grade, and tumor primary/metastatic location. As NENs are highly vascular tumors, the hypothesis is that CD31 staining is an important prognostic biomarker and target. This is based on prior correlations between CD31 staining and 3-year recurrence-free survival in pancreas …

The Role Of Micrornas As Potential Biomarkers In Diffuse Large B-Cell Lymphoma, Eirini Panteli, Epameinondas Koumpis, Vasileios Georgoulis, Georgios Petros Barakos, Evangelos Kolettas, Panagiotis Kanavaros, Alexandra Papoudou-Bai, Eleftheria Hatzimichael

Computational Medicine Center Faculty Papers

Diffuse large B-cell lymphoma (DLBCL) is the most common and clinically aggressive subtype of non-Hodgkin lymphoma (NHL). While novel therapies such as rituximab and polatuzumab vedotin have led to improved outcomes, approximately 35% of patients eventually develop relapsed or refractory disease. MicroRNAs (miRNAs), a class of endogenous single-stranded RNAs approximately 22 nucleotides in length, play a pivotal role in the regulation of gene expression at the post-transcriptional level through interactions with complementary target RNAs and contribute significantly to the development, progression, and treatment response of DLBCL. Oncogenic miRNAs, such as miR-155, miR-21, and the miR-17-92 cluster, promote proliferation, survival, immune …

Thermodynamic Stability Modulates Chaperone-Mediated Disaggregation Of Α-Synuclein Fibrils, Celia Fricke, Antonin Kunka, Rasmus K Norrild, Shuangyan Wang, Thi Lieu Dang, Jonas Folke, Mohammad Shahnawaz, Claudio Soto, Susana Aznar, Anne S Wentink, Bernd Bukau, Alexander K Buell

Faculty, Staff and Student Publications

Aggregation of the intrinsically disordered protein alpha-synuclein into amyloid fibrils and their subsequent intracellular accumulation are hallmark features of several neurodegenerative disorders, including Parkinson's disease, for which no curative treatments currently exist. In this study, we investigate the relationship between fibril morphology, thermodynamic stability, and susceptibility to disaggregation by the human chaperone system comprising HSP70, DNAJB1, and Apg2. By varying assembly conditions and incubation times, we generated alpha-synuclein fibrils with diverse morphological and biochemical properties, including a broad range of thermodynamic stabilities, which we quantified using a chemical depolymerization assay. The chaperone system effectively disaggregated three of the four fibril …

Characterization Of Inflammatory Pseudotumors In A Large Animal Model Of Liver Cancer, Erik N K Cressman, Samantha Hicks, Natalie W Fowlkes, Danielle L Stolley, Maria Sophia Stenkamp

Faculty, Staff and Student Publications

Background: The development of relevant and robust large animal models of hepatocellular carcinoma is needed to test new therapeutic strategies for this disease. Transgenic approaches hold promise in addressing this complex problem. One such model, the Oncopig, has been reported to develop tumors of up to 4 cm in diameter within 7-14 days at sites of in situ vector inoculation. However, the resulting lesions reportedly contained an extensive inflammatory component that has not been evaluated in detail.

Methods: Herein, we describe our results from multiparametric characterization of the lesions generated using liver biopsy cores incubated in vector solution and replaced …

Loss Of Kdm6a-Mediated Genomic Instability And Metabolic Reprogramming Regulates Response To Therapeutic Perturbations In Bladder Cancer, Pratishtha Singh, Ranit D'Rozario, Bidisha Chakraborty, Swadhin Meher, Deblina Raychaudhuri, Aminah J Tannir, Yang Li, Anurag Majumdar, Jessalyn Hawkins, Yun Xiong, Philip Lorenzi, Padmanee Sharma, Kadir Akdemir, Patrick Pilie, Abhinav K Jain, Byron Hing Lung Lee, Sangeeta Goswami

Faculty, Staff and Student Publications

Mutations in epigenetic regulators are common in bladder cancer, yet their impact on therapeutic responses remains unclear. Here, we identify that loss-of-function mutations in KDM6A, a histone demethylase altered in about 26% of advanced bladder cancers, are associated with poor survival after cisplatin chemotherapy, whereas they correlate with improved outcomes with anti-PD-1 therapy. Using CRISPR-Cas9-engineered murine and human bladder cancer models, we show that KDM6A deficiency increases formation of extrachromosomal circular DNA carrying chemoresistance loci, promoting cisplatin resistance. In parallel, KDM6A loss impairs DNA repair and rewires tumor metabolism, reducing glycolysis and lactate output. This metabolic shift diminishes histone lactylation …

3d Reconstruction Of Spatial Transcriptomics With Spatial Pattern Enhanced Graph Convolutional Neural Network, Chen Tang, Yuansheng Zhou, Xue Xiao, Lei Dong, Lei Yu, Qiwei Li, Guanghua Xiao, Lin Xu

Faculty, Staff and Student Publications

Spatially resolved transcriptomics (SRT) is a promising new technology that enables simultaneous analysis of gene expression and spatial information for biomedical research. However, the existing statistical and deep learning algorithms used for analyzing SRT data rely solely on two-dimensional (2D) spatial coordinates, which limits their ability to accurately identify spatial domains, spatially variable genes (SVGs), cell-to-cell communications, and developmental trajectories in a three-dimensional (3D) spatial manner. To address these limitations, we introduced Spa3D, which utilized the anti-leakage Fourier transform and graph convolutional neural network model to reconstruct 3D-based spatial structures from multiple 2D SRT slices. We demonstrate that Spa3D is …

Machine Learning-Based Multimodal Biomarkers Enable Accurate Diagnosis And Early Detection Of Pancreatic Ductal Adenocarcinoma, Tsung-Hung Yao, Warapen Treekitkarnmongkol, Nagireddy Putluri, Deivendran Sankaran, Tristian Nguyen, Seetharaman Balasenthil, Mark W Hurd, Meng Chen, Randall E Brand, Paul D Lampe, Abu Hena M Kamal, Vasanta Putluri, Tony Y Hu, Anirban Maitra, Eugene J Koay, Ann M Killary, Subrata Sen, Suprateek Kundu

Faculty, Staff and Students Publications

While there has been some progress on discovering clinically validated biomarkers for early detection in pancreatic ductal adenocarcinoma (PDAC), several challenges remain. Most approaches rely on single-modality biomarkers with limited sensitivity and/or specificity. Using data from a multicenter study with an age-matched cohort (n = 203 with healthy controls n = 46, pancreatitis controls n = 36, and diagnosed cases n = 121), we developed a machine learning approach integrating 2,096 microRNAs, 125 metabolites, and CA19-9. Our method performs unsupervised selection of an optimal subset of biomarkers with maximal discriminatory power for diagnosis and early detection. In training data, the …

Spatially Resolved Integrative Analysis Of Transcriptomic And Metabolomic Changes In Tissue Injury Studies, Eleanor C Williams, Lovisa Franzén, Martina Olsson Lindvall, Gregory Hamm, Steven Oag, Muntasir Mamun Majumder, James Denholm, Azam Hamidinekoo, Javier Escudero Morlanes, Marco Vicari, Joakim Lundeberg, Laura Setyo, Trevor M Godfrey, Livia S Eberlin, Aleksandr Zakirov, Jorrit J Hornberg, Marianna Stamou, Patrik L Ståhl, Anna Ollerstam, Jennifer Y Tan, Irina Mohorianu

Faculty, Staff and Students Publications

Recent developments in spatially resolved -omics have enabled the joint study of gene expression, metabolite levels and tissue morphology, offering greater insights into biological pathways. Integrating these modalities from matched tissue sections to probe spatially-coordinated processes, however, remains challenging. Here we introduce MAGPIE, a framework for co-registering spatially resolved transcriptomics, metabolomics, and tissue morphology from the same or consecutive sections. We show MAGPIE's generalisability and scalability on spatial multi-omics data from multiple tissues, combining Visium with MALDI and DESI mass spectrometry imaging. MAGPIE was also applied to new multi-modal datasets generated with a specialised sampling strategy to characterise the metabolic …

Defective Dna Damage Response Is A Targetable Therapeutic Vulnerability In Esr1 Mutant Breast Cancer, Sarah K Herzog, Jessica H Stevens, Guowei Gu, Sandra L Grimm, Kloma Cardoza, Autumn G M Hawkins, Hangqing Lin, Daniela Ramos, Amanda R Beyer, David G Edwards, Derek Dustin, Harry J Yang, Nicole Liang, Ashfia F Khan, Tasneem Bawa-Khalfe, Daniel J Mcgrail, Shiaw-Yih Lin, Cristian Coarfa, Suzanne A W Fuqua

Faculty, Staff and Student Publications

ESR1 mutations are the leading cause of endocrine therapy resistance and progression in ER-positive metastatic breast cancer. ESR1 mutations are detected in ~50% of metastatic breast cancer patients, and identification of effective targeted therapeutics are critically needed. Here, we identified enrichment of dysregulated replication stress and DNA damage responses in multiple ESR1 mutant models. Targeting the replication stress response utilizing checkpoint inhibition in combination with PARP inhibition synergistically suppressed growth, induced cell cycle arrest, and attenuated DNA replication. PARP inhibition blocked metastatic dissemination in vivo and reduced both PARP1 and ER-regulated protein expression. PARP trapping by olaparib treatment with or …