Digital Commons Network^™

Understanding The Why: Patient, Parent, And Oncologist Perspectives On Prognostic Communication Preferences In Advanced Childhood Cancer, Erin Batchelor, Rachel A Kentor, Calliope Reeves, Harmony Farner, Shoshana Mehler, Caroline Christianson, Erica C Kaye

Faculty, Staff and Students Publications

Background/objectives: High-quality prognostic communication in pediatric oncology is essential to support informed decision making, foster trust, and honor goals of care. While families differ in their preferences for how prognosis is discussed, clinicians often rely on assumptions rather than directly eliciting these preferences, risking misalignment and distress. To address this gap, we aimed to characterize patient, parent, and oncologist perspectives on key variables, experiences, and circumstances that influence their preferences for prognostic communication.

Methods: Semi-structured interviews were conducted with 85 participants (25 patients aged 12-25, 40 parents, and 20 oncologists) to elicit their preferences for prognostic communication and the reasons …

Nf1-Depleted Er+ Breast Cancers Are Differentially Sensitive To Cdk4/6 Inhibitors, Ze-Yi Zheng, Anran Chen, Eric J Jaehnig, Meenakshi Anurag, Jonathan T Lei, Long Feng, Chenwei Wang, Diana Fandino, Purba Singh, Hilda Kennedy, Ghazal Yadav, Craig T Vollert, Jill Tsai, Xi Chen, Yi Li, Bora Lim, Alastair Thompson, Shunqiang Li, Charles E Foulds, Bing Zhang, Matthew J Ellis, Eric C Chang

Faculty, Staff and Students Publications

Neurofibromin/NF1 is a RAS (rat sarcoma virus) GTPase activating protein and estrogen receptor (ER) transcriptional corepressor. NF1low status, identified by copy number loss or low mRNA/protein expression is associated with endocrine therapy resistance in approximately 20% of ER+/HER2− (human epidermal growth factor receptor 2) early-stage breast cancers. The identification of targeted treatments for NF1low ER+/HER2− breast cancer is therefore a priority. In this study proteogenomic analysis of ER+/HER2− breast cancer demonstrated that NF1low tumors exhibited elevated cyclin-dependent kinase 4/6 (CDK4/6) activity. In cell lines, NF1-deletion had a dual effect on CDK4 activity. First, by promoting ER recruitment to CCND1 …

Pfkfb3 Activates Cad To Enhance De Novo Pyrimidine Synthesis For Cell Growth, Qingen Da, Yongfeng Cai, Qian Ma, Qiuhua Yang, Yapeng Cao, Yaqi Zhou, Dingwei Zhao, Zhiping Liu, Jiean Xu, Junming Quan, Liang Zhang, Rui Wang, Xuejun Jiang, Xiao Liu, Kunfu Ouyang, Zhen Han, Jikui Liu, Tao Wang, Chunxiang Zhang, Neal L Weintraub, David J R Fulton, Jun Zhao, Mei Hong, Zigang Li, Yuqing Huo

Faculty, Staff and Students Publications

Aerobic glycolysis, termed the Warburg effect, is one of the aberrant metabolic pathways in highly proliferating cells. Glycolysis provides glycolytic metabolites to support the generation of biomass, such as nucleotides, amino acids, and lipids. Research on the direct interactions between glycolysis and other metabolic pathways is an emerging field that has garnered significant interest. Phosphofructokinase-2/fructose-2,6-bisphosphatase 3 (PFKFB3) activates glycolysis by synthesizing fructose-2,6-bisphosphate (F2,6BP), which allosterically activates the rate-limiting enzyme 6-phosphofructo-1-kinase (PFK-1). In this study, we found that PFKFB3 directly interacts with and regulates the phosphorylation of carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase (CAD), the enzyme catalyzing the first three …

Multiplex Imaging Mass Cytometry Reveals Prognostic Immunosuppressive Subpopulations And Macrophage-Driven Metastasis In Osteosarcoma, Benjamin B Gyau, Junyan Wang, Weiguo Wu, Brooks Scull, Angela M Major, Weidong Jin, Justin M M Cates, John Hicks, Tsz-Kwong Man

Faculty, Staff and Students Publications

Osteosarcoma is a type of bone cancer that mostly affects kids and teens. The biggest danger is when the cancer spreads to the lungs, and current treatments do not work well for those cases. Immunotherapy, which helps the body’s immune system fight cancer, has worked for other cancers but is limited for osteosarcoma because we do not fully understand the environment around the tumor. Our research looked at various cells around the tumor to study why patients have worse outcomes. We found that certain cells, called M2 macrophages (M2) and myeloid-derived suppressor cells (MDSC), which weaken the immune system, are …

High-Speed Voltage Imaging Of Action Potentials In Molecular Layer Interneurons Reveals Sensory-Driven Synchrony That Augments Movement, Spencer T Brown, Meghana R Holla, Michelle A Land, Shuyuan Yang, Alex J Mcdonald, François St-Pierre, Indira M Raman

Faculty, Staff and Students Publications

Testing whether the synchrony of action potential firing is a cerebellar coding mechanism requires simultaneous recording, with high temporal fidelity, from populations of identified neurons. Here, we used targeted one-photon voltage imaging at 2–4 kHz to record action potentials from groups of ~10–300 molecular layer interneurons (MLIs) expressing a positively tuned, genetically encoded voltage indicator, FORCE1f or pAce. In awake resting mice, crus I MLIs fired brief (~1-ms) spikes at 20–60 spikes/s. Sensory stimuli of air puffs to the whiskers evoked short-latency (< 10 ms) increases in spiking probability. In most trials, >50% of MLIs fired synchronously with 4-ms temporal precision. The magnitude of puff-evoked whisks correlated tightly with …

Cathartocytosis: Jettisoning Of Cellular Material During Reprogramming Of Differentiated Cells, Jeffrey W Brown, Xiaobo Lin, Gabriel Anthony Nicolazzi, Xuemei Liu, Thanh Nguyen, Megan D Radyk, Joseph Burclaff, Jason C Mills

Faculty, Staff and Students Publications

Injury causes differentiated cells to undergo massive reprogramming to become proliferative and repair tissue via paligenosis. Gastric chief cells use paligenosis to reprogram into progenitor-like spasmolytic-polypeptide-expressing metaplasia (SPEM) cells. Stage 1 of paligenosis is the downscaling of mature cell architecture via a process involving lysosomes. Here, we notice that sulfated glycoproteins are not only digested during paligenosis but also excreted into the gland. Various genetic and pharmacological approaches show that endoplasmic reticulum membranes and secretory granule cargo are also excreted and that the process proceeds in parallel with but is mechanistically independent of autophagy. Three-dimensional light and electron microscopy demonstrated …

Computer-Aided Reading Of Chest Radiographs For Paediatric Tuberculosis: Current Status And Future Directions, Mackenzie Dupont, Robert Castro, Sandra V Kik, Megan Palmer, James A Seddon, Devan Jaganath

Faculty, Staff and Students Publications

Computer-aided detection (CAD) systems for automated reading of chest x-rays (CXRs) have been developed and approved for tuberculosis triage in adults but not in children. However, CXR is frequently the only adjunctive tool for clinical assessment in the evaluation of paediatric tuberculosis in primary care settings, and children would benefit from CAD models that can detect their unique clinical and radiographic features. To advance CAD for childhood tuberculosis, large, diverse paediatric CXR datasets linked to standardised tuberculosis classifications are required. These datasets would be used to train and validate paediatric-specific models for tuberculosis screening, diagnosis, and severity stratification. Previous studies …

Influenza-Associated Acute Necrotizing Encephalopathy In Us Children, Andrew Silverman, Rachel Walsh, Jonathan D Santoro, Katherine Thomas, Elizabeth Ballinger, Kristen S Fisher, Ajay X Thomas, Brian Appavu, Michael C Kruer, Derek Neilson, Jasmine Knoll, April N Sharp, Hannah E Edelman, Scott Otallah, Alexandra Morgan, Aniela Grzezulkowska, John Nguyen, Lekha M Rao, Shaina M Hecht, Laura Catalano, Hunter Daigle, Catherine Kronfol, Jessica Wharton, David Adams, Adam Z Kalawi, Michael Kung, Janetta L Arellano, Lauren Smith, Devorah Segal, Kristina Feja, Eileen Broomall, Anuj Jayakar, Sandra R Arnold, Hanna Retallack, Craig A Press, Grace Gombolay, Madeleine H Mclaughlin, Varun Kannan, Kavita Thakkar, Tasmia Rezwan, Erin Hulfish, Dalia Eid, Jennifer Meylor, Diane Peng, Ryan Hurtado, Taylor Nickerson, Iris Mandell, Abigail U Carbonell, Mallory Kerner-Rossi, Divya Jayaraman, Mallory Davis, Rosemary Olivero, Neel Shah, Christina M Osborne, Bo Zhang, Christopher Cortina, Adrienne G Randolph, Suchitra Rao, Thomas Larocca, Keith P Van Haren, Molly Wilson-Murphy

Faculty, Staff and Students Publications

Importance: Acute necrotizing encephalopathy (ANE) is a rare, but severe, neurologic condition for which epidemiologic and management data remain limited. During the 2024-2025 US influenza season, clinicians at large pediatric centers anecdotally reported an increased number of children with influenza-associated ANE, prompting this national investigation.

Objective: To understand the clinical presentation, interventions, and outcomes among US children diagnosed with influenza-associated ANE.

Design, setting, and participants: This study was a multicenter case series of children diagnosed with ANE with longitudinal follow-up. A call for cases was issued via academic societies, public health agencies, and by directly contacting pediatric specialists at 76 …

Outcomes Of Brexucabtagene Autoleucel In Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia With Cns Involvement, Ibrahim N Muhsen, Gregory W Roloff, Rawan Faramand, Tamer Othman, Yannis Valtis, Noam E Kopmar, Simone E Dekker, Matthew Connor, Santiago Mercadal, Timothy E O'Connor, Kaitlyn C Dykes, Mohamed Ahmed, Nikeshan Jeyakumar, Amy Zhang, Katharine Miller, Katherine C Sutherland, Caitlin Guzowski, Vishal K Gupta, Navneet Majhail, Minoo Battiwalla, Melhem M Solh, Shahbaz A Malik, John Mathews, Caspian H Oliai, Paul Shaughnessy, Luke Mountjoy, Catherine J Lee, Aaron C Logan, Stephanie B Tsai, Jessica T Leonard, Marc Schwartz, Joshua P Sasine, Muthu Kumaran, Noelle Frey, Jae H Park, Divya Koura, Ryan D Cassaday, Bijal D Shah, Ibrahim Aldoss, Lori S Muffly, Laquisa C Hill

Faculty, Staff and Students Publications

Patients with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) with central nervous system (CNS) involvement (CNS B-ALL) have poor outcomes and were frequently excluded from CD19-targeting chimeric antigen receptor (CAR) T-cell clinical trials. The efficacy and safety of brexucabtagene autoleucel (brexu-cel) in adults with R/R B-ALL was established by the ZUMA-3 trial, which excluded patients with advanced or symptomatic CNS involvement. In this retrospective multicenter analysis, we investigated the safety and efficacy of brexu-cel in patients with CNS B-ALL using data from the ROCCA (Real-World Outcomes Collaborative for CAR T in ALL) consortium. Of 189 patients who received infusion, 31 …

Progressive Respiratory Failure In A Term Neonate With Abca3 Surfactant Deficiency: Beyond The Common Causes Of Respiratory Distress, Andrew M Beverstock, Hillary C Lee, David S Moreno Mcneill, Morcos Hanna

Faculty, Staff and Students Publications

Background

Case

Bridging Diagnostic Safety And Mental Health: A Systematic Review Highlighting Inequities In Autism Spectrum Disorder Diagnosis, Abirami Srivarathan, Andrea Bradford, Sara Shearkhani, Layla Heimlich, Sheryl Jefferson, Kristen E Miller, Kelly Smith, Helen Haskell, Traber D Giardina

Faculty, Staff and Students Publications

Introduction: There is increased recognition that diagnostic errors disproportionately affect marginalised and underserved patient populations in the USA. However, evidence on diagnostic inequities in mental disorders is sparse and not well integrated into the overall diagnostic safety literature.

Objective: We systematically reviewed and narratively synthesised evidence on inequities in diagnosis of mental disorders, guided by the Diagnostic Process Framework developed by The National Academies of Sciences, Engineering, and Medicine.

Methods: We conducted a systematic review and a narrative synthesis. Medline, Embase, PsycInfo and CINAHL were searched for studies published between 2015 and 2024. Studies were eligible if they reported on …

Mri-Guided Focused Ultrasound Thalamotomy For Neuropathic Pain In An Adolescent With Cranial Metastases: Illustrative Case, Sarah G Van Winkle, Danika L Paulo, Ashwin Viswanathan, Daniel Curry, Nisha Gadgil

Faculty, Staff and Students Publications

Background: Neuropathic cancer pain (NCP) is a debilitating condition that is often refractory to conventional medical management. MRI-guided focused ultrasound (MRgFUS) central lateral thalamotomy (CLT) is an incisionless neurosurgical option for neuropathic pain palliation, but its use in pediatric patients and those with cranial metastases, a relative contraindication to MRgFUS, remains largely unexamined.

Observations: A 16-year-old male with metastatic rhabdomyosarcoma (RMS) with numerous cranial metastases experienced severe, diffuse, refractory NCP. The patient underwent bilateral CLT with MRgFUS. After the procedure, the patient experienced complete and durable resolution of his neuropathic pain. He only reported occasional somatic pain at sites of …

Placental Polycyclic Aromatic Hydrocarbon (Pah) Levels Are Associated With Spontaneous Preterm Birth, Gwendolynn Hummel, Sohini Banerjee, Vasanta Putluri, Inaara Malick, Grace Johnson, Abu Hena Mostafa Kamal, Chandra Shekar R Ambati, Nagireddy Putluri, Lori Showalter, Cynthia D Shope, Joseph Hagan, Kjersti M Aagaard, Bhagavatula Moorthy, Melissa A Suter

Faculty, Staff and Students Publications

While the cause of preterm birth (PTB) (i.e., delivery before 37 weeks of gestation) is likely multifactorial, ambient exposure to environmental chemicals has been postulated to play a role in its etiology. Our prior studies of exposure to polycyclic aromatic hydrocarbons (PAHs) in pregnancy have shown an increased level of placental PAH-induced bulky DNA adducts with increasing levels of PAH exposures. In this investigation, we hypothesized that higher levels of placental PAHs would be associated with an increased risk of PTB. Using gas chromatography and mass spectrometry (GC-MS/MS), we measured levels of benzo(a)pyrene (BaP), benzo(b)fluoranthene (BbF) and dibenz(a,h)anthracene (DBA) from …

Targeting Sting To Disrupt Macrophage-Mediated Adhesion In Encapsulating Peritoneal Sclerosis, Juan Sun, Yuxiang Sun, Dandan Guo, Huolin Ye, Qiang Huang, Hu Zhou, Canming Li, Mei Liao, Yujia You, Hongli Shang, Pan Zhou, Dongxuan Wu, Janusz Witowski, Zhaoyong Hu, Hui Peng

Faculty, Staff and Students Publications

Encapsulating peritoneal sclerosis (EPS) is a life-threatening fibrotic condition characterized by severe abdominal adhesions, chronic inflammation, and significant morbidity. The lack of effective treatments for EPS stems from a limited understanding of its underlying mechanisms. In this study, we developed a modified mouse model of PD-induced EPS and investigated the role of the STING signaling pathway in disease progression. Our findings reveal that STING activation in peritoneal mesothelial cells significantly increases the secretion of the macrophage chemokine CCL2, leading to enhanced macrophage infiltration and the formation of pathological adhesions. Notably, pharmacological inhibition of STING using the inhibitor H151 effectively reduced …

Review Of Human Papillomavirus Vaccination Programs In United States Schools, Cassandra Duran, Aditi Gupta, Lynda Aririguzo, Norma Castillo, Sanghamitra M Misra

Faculty, Staff and Students Publications

Background: School vaccination programs (school-based and school-located) that include the human papillomavirus (HPV) vaccine have been implemented throughout the United States since 2009.

Methods: We conducted a review of school HPV vaccination programs in PUBMED, Google Scholar, Web of Science, Ovid, Medline, and Embase and included peer-reviewed studies originating in the United States that focused on any aspect of HPV school vaccination programs.

Results: Our review yielded 47 articles that fell into several categories: (1) parent and child perceptions, (2) school nurse perceptions, (3) development, (4) implementation, (5) outcomes, and (6) barriers and facilitators of HPV vaccination programs in schools. …

Prolonging Lung Cancer Response To Egfr Inhibition By Targeting The Selective Advantage Of Resistant Cells, Lisa Brunet, David Alexandre, Jiyoung Lee, Maria Del Mar Blanquer-Rosselló, David Bracquemond, Alexis Guernet, Houssein Chhouri, Mathilde Goupil, Zoulika Kherrouche, Arnaud Arabo, Maicol Mancini, Dorthe Cartier, Shen Yao, David Godefroy, Julie Dehedin, Jian-Rong Li, Céline Duparc, Philippe Jamme, Audrey Vinchent, Caroline Bérard, David Tulasne, Sabrina Arena, Alberto Bardelli, Chao Cheng, Byoung Chul Cho, Olivier Wurtz, Cédric Coulouarn, Antonio Maraver, Stuart A Aaronson, Alexis B Cortot, Youssef Anouar, Luca Grumolato

Faculty, Staff and Students Publications

Non-small cell lung cancers (NSCLCs) treated with tyrosine kinase inhibitors (TKIs) of the epidermal growth factor receptor (EGFR) almost invariably relapse in the long term, due to the emergence of subpopulations of resistant cells. Through a DNA barcoding approach, we show that the clinically approved drug sorafenib specifically abolishes the selective advantage of EGFR-TKI-resistant cells, while preserving the response of EGFR-TKI-sensitive cells. Sorafenib is active against multiple mechanisms of resistance/tolerance to EGFR-TKIs and its effects depend on early inhibition of MAPK-interacting kinase (MKNK) activity and signal transducer and activator of transcription 3 (STAT3) phosphorylation, and later down-regulation of MCL1 and …

Organizational Climate And Decision Aid Sustainability In Lupus Care: Mixed Methods Study, Aizhan Karabukayeva, Larry R Hearld, Nathan W Carroll, Reena Kelly, Jasvinder A Singh

Faculty, Staff and Students Publications

Background: Digital decision aids (DAs) are increasingly used in health care to support shared decision-making and promote patient engagement. In the context of systemic lupus erythematosus (SLE), a complex autoimmune disease characterized by diverse symptoms and uncertain prognoses, DAs offer guidance to patients in navigating treatment risks and benefits. Although numerous studies have examined the initial implementation of evidence-based tools, there is limited evidence on the organizational factors that influence their long-term sustainability in clinical practice. This gap is particularly salient for digital interventions, where integration into routine workflows and ongoing use require alignment with clinic readiness and culture. This …

Β-Catenin Functions As A Molecular Adapter For Disordered Cbaf Interactions, Yuen San Chan, Qinyu Gao, Sarah A Robinson, Wenzhi Wang, Ruzena Filandrova, Lisa-Maria Weinhold, Mario Loeza Cabrera, Miao Zhang, Chandra Shekar R Ambati, Antonio M Lerario, Nagireddy Putluri, Katja Kiseljak-Vassiliades, Margaret E Wierman, Mouhammed Amir Habra, Gary D Hammer, Vaclav Veverka, Katerina Cermakova, H Courtney Hodges

Faculty, Staff and Students Publications

BAF (SWI/SNF) chromatin remodelers engage binding partners to generate site-specific DNA accessibility. However, the basis for interaction between BAF and divergent binding partners has remained unclear. Here, we tested the hypothesis that scaffold proteins augment BAF's binding repertoire by examining β-catenin (CTNNB1) and steroidogenic factor 1 (SF-1, NR5A1), a transcription factor central to steroid production in human cells. BAF inhibition rapidly opposed SF-1/β-catenin enhancer occupancy, impairing SF-1 target activation and SF-1/β-catenin autoregulation. These effects arise due to β-catenin's role as a molecular adapter between SF-1 and an intrinsically disordered region (IDR) of the canonical BAF (cBAF) subunit ARID1A. In contrast …

Germline Structural Variations Involving The Pediatric Brain Tumor Transcriptome Include Disease-Relevant And Ancestry-Related Genes, Fengju Chen, Yiqun Zhang, Luis F Paulin, Fritz J Sedlazeck, Chad J Creighton

Faculty, Staff and Students Publications

Background: Germline Structural Variants (SVs) represent an important source of genetic diversity, in large part due to their influence on gene transcription. It is necessary to systematically catalog germline SVs and their associated impacted genes across different cohorts and tissue and cellular contexts, including pediatric brain or Central Nervous System (CNS) tumors.

Methods: We combined RNA with whole genome sequencing across 1430 pediatric brain or CNS tumor patients from the Children's Brain Tumor Network. We set out to systematically identify genes for which the proximity of germline SVs was recurrently and significantly associated with differential expression in the tumor sample …

Changes In Self-Reported Excessive Daytime Sleepiness Are Associated With 5-Year All-Cause Mortality Risk Among Veterans, Katherine G Bay, Arash Maghsoudi, Amin Ramezani, Drew A Helmer, Amir Sharafkhaneh, Javad Razjouyan

Faculty, Staff and Students Publications

Excessive daytime sleepiness (EDS) is linked to adverse clinical outcomes. This study evaluated changes in a validated tool to assess EDS, the Epworth Sleepiness Scale (ESS) and mortality risk. This retrospective cohort study included Veterans receiving sleep-related services in the Department of Veterans Affairs (VA) from October 4, 1999 to August 18, 2018, with two qualifying ESS measures. ESS values were extracted from patient notes using a validated natural language processing (NLP) pipeline (96% accuracy). ESS scores were categorised as Normal (0-10) or Abnormal (11-24). Patients were grouped based on ESS changes: Normal-Normal, Normal-Abnormal, Abnormal-Abnormal and Abnormal-Normal. Cox proportional hazards …

Dna Methylation Signatures Of Cardiovascular Health Provide Insights Into Diseases, Madeleine Carbonneau, Yi Li, Yishu Qu, Yinan Zheng, Alexis C Wood, Mengyao Wang, Chunyu Liu, Tianxiao Huan, Roby Joehanes, Xiuqing Guo, Jie Yao, Kent D Taylor, Russell P Tracy, Peter Durda, Yongmei Liu, W Craig Johnson, Wendy S Post, Tom Blackwell, Jerome I Rotter, Stephen S Rich, Susan Redline, Myriam Fornage, Jun Wang, Hongyan Ning, Lifang Hou, Donald Lloyd-Jones, Kendra Ferrier, Yuan-I Min, April P Carson, Laura M Raffield, Alexander Teumer, Hans J Grabe, Henry Völzke, Matthias Nauck, Marcus Dörr, Arce Domingo-Relloso, Amanda Fretts, Maria Tellez-Plaza, Shelley A Cole, Ana Navas-Acien, Meng Wang, Joanne M Murabito, Nancy L Heard-Costa, Brenton Prescott, Vanessa Xanthakis, Dariush Mozaffarian, Daniel Levy, Jiantao Ma

Faculty, Staff and Students Publications

Background: The association of overall cardiovascular health (CVH) with changes in DNA methylation (DNAm) has not been well characterized.

Methods: We calculated the American Heart Association's Life's Essential 8 score to reflect CVH in 5 cohorts with diverse backgrounds (mean age 54 years, 55% women, and enrollment year ranging from 1989 to 2012). Epigenome-wide association studies (EWAS) for Life's Essential 8 score were conducted, followed by bioinformatic analyses. DNAm loci significantly associated with Life's Essential 8 score were used to calculate a CVH DNAm score. We examined the association of the CVH DNAm score with incident cardiovascular disease (CVD), cardiovascular …

Extraction-Free Rt-Rpa Assay For Detection Of Hpv16, Hpv18, And Hpv45 Mrna Expression, Emilie Newsham Novak, Ariel Ma, Kathryn A Kundrod, Megan M Chang, Cannon J Hansen, Jane Richards Montealegre, Michael E Scheurer, Philip E Castle, Ming Guo, Mila P Salcedo, Kathleen Schmeler, Rebecca Richards-Kortum

Faculty, Staff and Students Publications

Messenger RNA (mRNA) from high-risk genotypes of human papillomavirus (hrHPV) is a more specific biomarker for cervical cancer risk than hrHPV DNA due to its ability to differentiate clinically significant infections from transient ones. Detecting mRNA from exfoliated cervical cells, however, is a complex, expensive, and equipment-intensive process, making it infeasible in resource-limited settings. Here we describe a sensitive, specific, and minimally instrumented method to detect HPV16, HPV18, and HPV45 mRNA in exfoliated cervical cells. First, reverse transcription recombinase polymerase amplification (RT-RPA) exo assays were designed to amplify and detect HPV16, HPV18, and HPV45 E7 mRNA ≥100 copies per reaction …

Proteogenomic Characterization Unveils Biomarkers Associated With Chemoresistance In Muscle-Invasive Bladder Cancer, Matthew V Holt, Yongchao Dou, Meggie N Young, Alexander B Saltzman, Meenakshi Anurag, Jonathan T Lei, Antrix Jain, Mei Leng, Beom-Jun Kim, Lacey E Dobrolecki, Stefanie F Faucher, Sara Savage, Chenwei Wang, Zhiao Shi, Hugo Villanueva, Karoline Kremers, Kyle D Drinnon, Patricia D Castro, Michael M Ittmann, Mehak Mehboob Khatani, Sung Han Kim, Matthew J Ellis, Bing Zhang, Anna Malovannaya, Seth P Lerner

Faculty, Staff and Students Publications

To explore potential chemoresistance mechanisms and identify therapeutic opportunities in muscle-invasive bladder cancer (MIBC), we conduct comprehensive proteogenomic characterization of 46 pre- and 14 post-treatment MIBC tumors incorporating genomics, transcriptomics, proteomics, and phosphoproteomics. Multi-omics clustering not only recapitulated established molecular subtypes but also revealed subtypes associated with chemotherapy sensitivity. Protein isoform level analysis identifies protein abundance of a short isoform of ATAD1 and RAF family proteins as biomarkers of chemosensitivity. Integration of proteomic and phosphoproteomic data reveals Wnt signaling via GSK3B-S9 phosphorylation and the JAK/STAT pathway as potential targets to overcome chemoresistance. Correlations between PD-L1 and TROP-2/NECTIN-4 indicate an additive …

Ethical Considerations Of Deep Brain Stimulation For Treatment Refractory Schizophrenia: Surveying Stakeholders, Judith M Gault, Nicola Cascella, Nidal Moukaddam, Stephanie Lehto, Patrick Hosokawa, Paul S Appelbaum, Akira Sawa, Jocelyn Lippman-Bell, William S Anderson, Wayne Goodman, Sameer A Sheth, Daniel Kramer, John A Thompson, Elyn R Saks, Rachel A Davis

Faculty, Staff and Students Publications

Introduction: Ethical concerns have been raised by both current and historically controversial neurosurgical interventions for treatment-refractory schizophrenia and schizoaffective disorder (TR-SZ). Considering advances in next-generation deep brain stimulation (DBS), initial success in treating a few cases of TR-SZ, and how challenging trial enrollment is, transparency and disseminating knowledge about DBS is important, as is input from involved groups. Here information was presented about DBS as an experimental treatment option for TR-SZ to stakeholders to gauge enthusiasm after consideration of potential risks and benefits.

Methods: Stakeholders were presented with information about DBS (total n = 629). Opinions about whether DBS should …

Heart Failure And Death In Older Adults With Elevated Cardiac Biomarkers But Without Risk Factors: The Atherosclerosis Risk In Communities Study, Xiaoming Jia, Mahmoud Al Rifai, Chiadi Ndumele, Amil Shah, Elizabeth Selvin, Salim S Virani, Ron C Hoogeveen, Biykem Bozkurt, Christie M Ballantyne, Vijay Nambi

Faculty, Staff and Students Publications

No abstract provided.

Extended Survival With Pancreatic Carcinosarcoma: A Case Report And Literature Review, Tian Xiao, Claire Browne, Morgan Black, Celia Marginean, Elena Tsvetkova

Faculty, Staff and Students Publications

Pancreatic carcinosarcoma is a rare and aggressive malignancy that can mimic pancreatic adenocarcinomas in presentation but often has different disease biology and different responses to conventional treatment for pancreatic adenocarcinoma. Case reports have documented a 5-year overall survival of approximately 13% only if the disease is caught at an earlier stage and is amenable to multi-modality treatment, including surgery, chemotherapy, and radiation. In the advanced stage, treatments do not often provide benefit, and patients may decline rapidly. There are currently no studies demonstrating survival benefits with chemotherapy in patients with metastatic carcinosarcoma, owing to both the rarity and the often …

High-Grade Glioma With Pleomorphic And Pseudopapillary Features: A Single-Institution Series Of Three Cases, Eric A Goethe, Rasha Alfattal, Subhiksha Srinivasan, Pushan Dasgupta, Vinay Puduvalli, Shiao-Pei Weathers, Leomar Y Ballester, Jeffrey S Weinberg, Sujit Prabhu, Sherise D Ferguson, Maria A Gubbiotti

Faculty, Staff and Students Publications

Introduction: Modern molecular diagnostic techniques such as DNA methylation profiling are leading to the reclassification of several central nervous system malignancies and discovery of novel diagnostic entities, such as high-grade glioma with pleomorphic and pseudopapillary features (HPAP).

Methods: We performed a retrospective chart review of all patients with HPAP confirmed with methylation profiling at a single institution between 2023 and 2025. Demographic, radiographic, surgical, and outcome data were collected.

Results: Three patients were identified: two females and one male with a mean age of 49.7 years (range 25-62). No patients had a prior cancer history. One patient had an incidentally …

Improving Automated Deep Phenotyping Through Large Language Models Using Retrieval-Augmented Generation, Brandon T Garcia, Lauren Westerfield, Priya Yelemali, Nikhita Gogate, E Andres Rivera-Munoz, Haowei Du, Moez Dawood, Angad Jolly, James R Lupski, Jennifer E Posey

Faculty, Staff and Students Publications

Background: Diagnosing rare genetic disorders relies on precise phenotypic and genotypic analysis, with the Human Phenotype Ontology (HPO) providing a standardized language for capturing clinical phenotypes. Rule-based HPO extraction tools use concept recognition to automatically identify phenotypes, but they often struggle with incomplete phenotype assignment, requiring significant manual review. While large language models (LLMs) hold promise for more context-driven phenotype extraction, they are prone to errors and "hallucinations," making them less reliable without further refinement. We present RAG-HPO, a Python-based tool that leverages retrieval-augmented generation (RAG) to elevate accuracy of HPO term assignment by LLM. This approach bypasses the limitations …

Mechano-Signal Transduction Pathways Of The Diaphragmatic Muscle And Role Of Cytoskeleton, Junaith S Mohamed, Patricia S Pardo, Aladin M Boriek

Faculty, Staff and Students Publications

Mechanotransduction, also referred to as mechano-signal transduction, is a biophysical process wherein cells perceive and respond to mechanical stimuli by converting them into biochemical signals that initiate specific cellular responses. This mechanism is fundamental to the development and growth, and proper functioning of mechanically active tissues, such as the diaphragm-a respiratory muscle vital for breathing in mammals. In vivo, the diaphragm is subjected to transdiaphragmatic pressure, and therefore, its muscle fibers are subjected to mechanical forces not only in the direction of the muscle fibers but also in the direction transverse to the fibers. Previous research conducted in our laboratory …

Bioinspired Ruthenium-Manganese-Oxygen Complex For Biocatalytic And Radiosensitization Therapies To Eradicate Primary And Metastatic Tumors, Ruidan Li, Ting Wang, Shengdong Mu, Zhenyu Xing, Zhiying Ding, Qinlong Wen, Zhigong Wei, Xiaolin Wang, Mohsen Adeli, Shuang Li, Chong Cheng, Xingchen Peng

Faculty, Staff and Students Publications

Designing efficient, biocompatible radiation-sensitive materials to activate systemic immune responses can maximize tumoricidal effects against malignant tumors. Here, inspired by natural Mn-peroxidase, we propose the de novo design of the RuMn-oxygen complex (MnBTC-Ru) for biocatalytic and radiosensitization therapies to eradicate primary and metastatic tumors. Our results reveal that Mn-organic ligands can enhance the electron density of Ru clusters, thereby optimizing their binding to oxygen species and resulting in high reactive oxygen species and oxygen generation. Accordingly, MnBTC-Ru with radiation can enhance cell membrane and DNA damage, triggering apoptosis though oxidative damage, heightening radiosensitization, and activating CD8