Digital Commons Network^™

Socioeconomic, Behavioral, And Health Profiles Of Women With Eclampsia: Findings From The 2020–2022 National Pregnancy Risk Assessment Monitoring System Data, Jessi Bates, Gurgen Grigoryants, Hongyun Fu

Cardiovascular Research Symposium

Background: Eclampsia is a severe obstetric complication with significant maternal health implications, disproportionately affects women with certain sociodemographic and health risk factors. This study investigates the characteristics and outcomes of women who experienced eclampsia using data from the national Pregnancy Risk Assessment Monitoring System (PRAMS).

Methods: This analysis included a sample of 729 women with eclampsia from the 2020–2022 PRAMS (N = 238,575). Descriptive statistics, chi-square tests, and multivariate logistic regression were conducted to examine patterns and factors associated with preterm-birth, low birth weight (LBW), and cesarean delivery.

Results: Over half of the women were aged ≥35 years (50.6%), unmarried …

Timely Resection Of Juvenile Nasopharyngeal Angiofibroma Following Embolization For Uncontrolled Acute Epistaxis Case Report., Koffi L. Lakpa, Timothy Mcculloch, Michael D. Puricelli

Manuscripts, Articles, Book Chapters and Other Papers

Uncontrolled epistaxis in patients with juvenile nasopharyngeal angiofibroma requires prompt intervention. When embolization is required, neovascularization can occur, making expedited surgical resection essential. We conducted a single-institution, retrospective review of one patient. This case study details the patient's clinical presentation and his preoperative, intraoperative, and postoperative course. We present the management of a 14-year-old male with a juvenile nasopharyngeal angiofibroma, who 3 days after initial evaluation at our institution, developed uncontrolled epistaxis requiring embolization at an outside hospital before transfer back to our institution for further management. He initially presented to an outside emergency department with acute epistaxis refractory to …

Hiv-1 Controllers Possess A Unique Cd8+ T Cell Activation Phenotype And Loss Of Control Is Associated With Increased Expression Of Exhaustion Markers, Amber D. Jones, Zachary Capriotti, Erin Santos, Angel Lin, Rachel Van Duyne, Stephen Smith, Zachary Klase

Kimmel Cancer Center Papers, Presentations, and Grand Rounds

BACKGROUND: HIV-1 controllers are a rare population of individuals that exhibit spontaneous control of HIV-1 infection without antiretroviral therapy. Understanding the mechanisms by which HIV-1 controllers maintain and eventually lose this ability would be highly valuable in HIV-1 cure or vaccine research. Previous work revealed the ability of CD8+ T cells isolated from HIV-1 controllers to suppress HIV-1 replication in matched CD4+ T cells and PBMCs ex vivo and suggested the loss of control may be tied to CD8+ T cell exhaustion.

RESULTS: We explored whether CD8+ T cell exhaustion plays a role in the maintenance and loss of control …

C-C Motif Chemokine Receptor-Like 2 Promotes The Interferon-Γ Signaling Response In Myeloid Neoplasms With Erythroid Differentiation And Mutated Tp53, Nour Sabiha Naji, Sergiu Pasca, Theodora Chatzilygeroudi, Pablo Toledano-Sanz, Joseph Rimando, Yuju An, Yashvi Hemani, Brandy Perkins, Xinghan Zeng, Conover Talbot, Bogdan Paun, Abdulmuez Abdulmalik, Chen Lossos, Tatianna R Boronina, Ilias Sinanidis, Panagiotis Tsakiroglou, Priyanka Fernandes, Christopher Esteb, Alexander J Ambinder, Robert N Cole, Rena Xian, Ivana Gojo, Suman Paul, Mark J Levis, Amy E Dezern, Leo Luznik, Styliani Karanika, Linda S Resar, Richard J Jones, Frederick Bunz, Lukasz Gondek, Marios Arvanitis, Theodoros Karantanos

Faculty, Staff and Students Publications

Patients with myeloid neoplasms with loss-of-function TP53 mutations and erythroid differentiation have poor outcomes, and a better understanding of disease biology is required. Upregulation of interferon-γ (IFN-γ) signaling has been associated with acute myeloid leukemia (AML) progression, selection of TP53 mutated clones and chemotherapy resistance, but its drivers remain unclear. In this study, we found that the surface receptor C-C motif chemokine receptor-like 2 (CCRL2) is overexpressed in AML with erythroid differentiation and TP53 mutations compared to other AML subtypes and healthy hematopoietic cells. CCRL2 knockout (KO) suppressed erythroleukemia growth in vitro and in vivo. Further proteomics and transcriptomics analysis …

Conventional Versus Advanced Imaging Selection For Endovascular Treatment Of Basilar Artery Occlusion Strokes, Huanwen Chen, Marco Colasurdo, Hidetoshi Matsukawa, Conor Cunningham, Ilko Maier, Sami Al Kasab, Pascal Jabbour, Joon-Tae Kim, Stacey Quintero Wolfe, Ansaar Rai, Robert M Starke, Marios-Nikos Psychogios, Edgar A Samaniego, Nitin Goyal, Shinichi Yoshimura, Hugo Cuellar, Jonathan A Grossberg, Ali Alawieh, Ali Alaraj, Mohamad Ezzeldin, Daniele G Romano, Omar Tanweer, Justin Mascitelli, Isabel Fragata, Adam Polifka, Fazeel Siddiqui, Joshua Osbun, Roberto Crosa, Charles Matouk, Min S Park, Michael R Levitt, Waleed Brinjikji, Mark Moss, Travis Dumont, Ergun Daglioglu, Richard Williamson, Pedro Navia, Reade De Leacy, Shakeel Chowdhry, David J Altschul, Alejandro M Spiotta, Peter Kan

Faculty, Staff and Students Publications

Introduction: Endovascular thrombectomy (EVT) is an effective treatment for basilar artery occlusion (BAO) stroke in select patients. While there is a growing body of literature suggesting that advanced imaging modalities such as computed tomography perfusion (CTP) and magnetic resonance (MR) may not be necessary for selecting anterior circulation large vessel occlusion stroke patients for EVT, whether advanced imaging may be superior to conventional imaging (non-contrast CT and CT angiography) in identifying good treatment candidates among BAO patients is less clear.

Patients and methods: This was a multicenter retrospective cohort study of BAO EVT patients treated from 2013 to 2022 in …

The Immunophenotypic And Genetic Characterization Of Pediatric T -L Ymphoblastic Leukemia With A Mature Immunophenotype, Mahsa Khanlari, Wei Wang, Parastou Tizro, Mohammad K Eldomery

Faculty, Staff and Student Publications

Not available.

Adams Contribute To Triple Negative Breast Cancer Via Mtorc1 Pathway: Targeting Adam-Mtor Axis Improves Efficacy, Shuying Liu, Huiqin Chen, Mihai Gagea, Lorenzo Federico, Fan Zhang, Javier Gomez, Kim-Anh Do, William F Symmans, Gabriel N Hortobagyi, Gordon B Mills, Ana M Gonzalez-Angulo, Debasish Tripathy

Faculty, Staff and Student Publications

Breast cancer is the most frequently diagnosed cancer globally and the second leading cause of cancer-related deaths in American women. Triple-negative breast cancer (TNBC) lacks estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. Thus, fewer targeting therapies are available for this most aggressive subtype. The A Disintegrin and Metalloproteinase (ADAM) family plays a vital role in cancer pathophysiology. Previous studies focused on single ADAM members. However, none of these have entered into the clinical arena as diagnostics or therapeutics for breast cancer. In this study, we demonstrate the upregulation of a panel of ADAM members in TNBC, …

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 …

Concussions 101, Bob Underwood, Greg Canty

Pediatrics in Practice: A CME Podcast

In this episode, we’re joined by Dr. Greg Canty, Medical Director of the Sports Medicine Center at Children’s Mercy in Kansas City, to explore the latest in pediatric concussion care. From updated return-to-play protocols to the evolving science of rest and recovery, Dr. Canty shares practical insights every pediatrician can use. We’ll also discuss risk factors for prolonged recovery, the role of schools in concussion management, and how pediatricians can stay current in this rapidly changing field.

Click here to stream the podcast episode.

Lip Tie Management And Treatment, Bob Underwood, Jairrah Godsil

Pediatrics in Practice: A CME Podcast

In this episode, we’re joined by Jairrah Godsil, Occupational Therapist at Children’s Mercy, to explore the often misunderstood topic of lip ties in infants. Jairrah shares how lip ties can impact feeding, oral motor development, and long-term function—and what pediatricians should look for during early assessments. We’ll also discuss the importance of a multidisciplinary approach, the role of occupational therapy in treatment, and how to navigate the balance between anatomical structure and functional impact. Whether you’re seeing infants in your clinic or collaborating with feeding specialists, this conversation offers practical insights you won’t want to miss.

Click here to stream …

Letter To The Editor Regarding "Trends In Lumbar Epidural Injection Selection: A Survey Of Practitioner Preferences And Practice Patterns"., Ryan Triglia, Andrew Walrond, Jesse Wagner, Paul M. Kitei, Jeffrey Boyd, Jeremy I Simon

Jefferson Hospital Staff Papers and Presentations

No abstract provided.

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 …

The 9th Annual Lafora Science Symposium: A Rare Epilepsy Community Makes Progress Towards Clinical Readiness, Meredith I. Williams, Katherine J. Donahue, Pascual Sanz, Souad Messahel, Jose M. Serratosa, Jordi Duran, Roberto Michelucci, Lorenzo Muccioli, Antonio Delgado-Escueta, Viet-Hong Nguyen, Berge A. Minassian, Matthew S. Gentry

Pharmacy Faculty Articles and Research

Lafora disease (LD) is a fatal childhood progressive myoclonus epilepsy and glycogen storage disease that is caused by recessive mutations in either EPM2A or EPM2B. The hallmarks of LD are cytoplasmic, aberrant glycogen-like aggregates, called Lafora bodies (LBs), that drive disease progression. The 9th Annual Lafora Science Symposium was held in San Diego, California and brought together over 70 researchers, clinicians, academic trainees, and friends and family members of patients with LD and 80 attendees joined virtually. This symposium focused primarily on international collaborations for therapeutic development and biomarker identification and strategies for preparing the Lafora community for upcoming …

Modulating Treatment Outcomes Of Patients With Solid Tumors In Immunotherapy Trials: A Drug Interaction Analysis From A Phase 1 Unit, Camila Braganca Xavier, Clark R Andersen, Joann Lim, Julian H Slade, Stacie A Bean, Lei Kang, Hung Le, Apostolia M Tsimberidou, Aung Naing, David S Hong, Ecaterina E Dumbrava, Jordi Rodon Ahnert, Paula R Pohlmann, Sarina A Piha-Paul, Stephane Champiat, Timothy A Yap, Tin-Yun Tang, Funda Meric-Bernstam, Siqing Fu

Faculty, Staff and Student Publications

Concurrent use of medications can modulate the effectiveness of immunotherapy. Although this interaction is well documented for immune checkpoint inhibitors, whether this occurs with new experimental compounds has not been evaluated. A computerized data extraction tool was used to collect clinical data and identify the prescription of a predefined set of medications within 30 days of immunotherapy infusion in the Department of Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center. The primary endpoints were median overall survival (OS) and progression-free survival. Tumor responses were addressed using RECIST. We identified 897 patients. The most prevalent tumor types …

Role Of Artificial Intelligence-Based Ocular Biomarkers In Hepatobiliary Diseases: A Scoping Review, Uday Pratap Singh Parmar, Arvind Kumar Morya, Parul C Gupta, Atul Arora, Nipun Verma

Faculty, Staff and Students Publications

Artificial intelligence (AI) has become an indispensable tool in modern health care, offering transformative potential across clinical workflows and diagnostic innovations. This review explores the sation of AI technologies in synthesizing and analyzing multimodal data to enhance efficiency and accuracy in health care delivery. Specifically, deep learning models have demonstrated remarkable capabilities in identifying seven categories of hepatobiliary disorders using ocular imaging datasets, including slit-lamp, retinal fundus, and optical coherence tomography images. Leveraging ResNet-101 neural networks, researchers have developed screening models and independent diagnostic tools, showcasing how AI can redefine diagnostic practices and improve accessibility, particularly in resource-limited settings. By …

Heterozygous Variants In Plcg1 Affect Hearing, Vision, Cardiac, And Immune Function, Mengqi Ma, Yiming Zheng, Mingxi Deng, Shenzhao Lu, Xueyang Pan, Xi Luo, Michelle Etoundi, David Li-Kroeger, Kim C Worley, Lindsay C Burrage, Lauren S Blieden, Aimee Allworth, Wei-Liang Chen, Giuseppe Merla, Barbara Mandriani, Catherine E Otten, Pierre Blanc, Jill A Rosenfeld, Debdeep Dutta, Shinya Yamamoto, Michael F Wangler, Ian A Glass, Jingheng Chen, Elizabeth Blue, Paolo Prontera, Jeremie Rosain, Sandrine Marlin, Seema R Lalani, Hugo J Bellen, Undiagnosed Diseases Network

Duncan NRI Faculty and Staff Publications

Phospholipase C isozymes (PLCs) hydrolyze phosphatidylinositol 4,5-bisphosphate (PIP₂) into inositol 1,4,5-trisphosphate (IP₃) and diacylglycerol (DAG), important signaling molecules involved in many cellular processes including Ca²⁺ release from the endoplasmic reticulum (ER). PLCG1 encodes the PLCγ1 isozyme that is broadly expressed. Hyperactive somatic mutations of PLCG1 are observed in multiple cancers, but only one germline variant has been reported. Here, we describe seven individuals with heterozygous missense variants in PLCG1 [p.(Asp1019Gly), p.(His380Arg), p.(Asp1165Gly), and p.(Leu597Phe)] who present with hearing impairment (5/7), ocular pathology (4/7), cardiac septal defects (3/6), and various immunological issues (5/7). To model these …

A Protective Role Of Src-1 Against Aging Associated Cognitive Decline, Hesong Liu, Yongjie Yang, Jonathan C Bean, Yang He, Hailan Liu, Rambabu Majji, Chen Liang, Nan Zhang, Meng Yu, Longlong Tu, Qingzhuo Liu, Yue Deng, Kristine M Conde, Na Yin, Mengjie Wang, Yongxiang Li, Junying Han, Sanika Vattakuzhiyil Jossy, Megan Elyse Burt, Hari Krishna Yalamanchili, Chunmei Wang

Duncan NRI Faculty and Staff Publications

Introduction: Research indicates a strong correlation between obesity and the risk of dementia, both are linked to steroid receptor coactivator-1 (SRC-1), a transcriptional coactivator.

Methods: We used RNA sequencing analysis (RNA-Seq) to investigate the transcriptome of SRC-1-KO mice, and identified S100 calcium-binding protein A6 (S100A6), an AD associated gene, as one target of SRC-1. We tested cognitive behaviors in SRC-1-KO mice and mice with a humanized SRC-1 mutation (SRC-1L1376P), and performed promoter luciferase assays on S100A6.

Results: Loss of SRC-1 caused alterations in gene signatures that are commonly associated with neurodegenerative diseases, including AD, and diminished the neural plasticity of …

Transcatheter Pulmonary Valve Replacement (Tpvr): A Saudi Consensus Statement, Khalid Alnajashi, Ahmed Al Zahrani, Atif Al Qabani, Mohamed Al Humaid, Mishael Binobaidan, Ahmed Krimley, Ahmed Al Omrani, Dhafer Al Shahrani, Ahmed Al Samman, Abdullah Al Quei, Khalid Al Twirqi, Wail Alkashkari, Adel Tash

Journal of the Saudi Heart Association

Objectives: To provide an expert consensus on the appropriate use of transcatheter pulmonary valve replacement (TPVR) in managing chronic pulmonary regurgitation (PR), particularly in patients with congenital heart defects such as Tetralogy of Fallot (TOF). The consensus aims to address current practices, patient selection criteria, procedural planning, and device-specific considerations to guide clinicians in optimizing outcomes. Methods: A multidisciplinary panel reviewed existing literature, clinical guidelines, and real-world practices. Key domains covered include epidemiology, anatomical and hemodynamic evaluation, pre- and post-procedural imaging, device characteristics, and patient selection. Imaging modalities such as echocardiography, cardiac magnetic resonance (CMR), and computed tomography (CT) were …

Aorto-Septal Angle As A Predictor Of Left Ventricular Outflow Tract Obstruction In Pediatric Patients With Subaortic Stenosis And Subaortic Membrane Development: A Study At Prince Sultan Cardiac Center, Buraydah, Saudi Arabia 2023, Rehab N. Alharbi, Ali A. Alakhfash, Abdullah M. Alqwaiee, Abdulrahman A. Almesned, Abdulrahman O. Alharbi

Journal of the Saudi Heart Association

Background: The angle between the interventricular septum and the anterior aortic wall is shallow and measured at 120 degrees in normal individuals. In patients with LVOT narrowing, aortic valve anomalies, and a subaortic membrane, this angle is more acute. This will change the flow hemodynamics and might lead to the formation or progression of the subaortic membrane. Objectives: This study aims to assess the IVS/Anterior Aortic wall angle in patients with abnormal aortic valves and/or LVOT obstruction and its association with SAM development. Methodology: A one-year prospective observational study (September 2022 to June 2023) at PSCC-Qassim's pediatric cardiology department included …

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 …

The Role Of Recruited Adipose Stromal Cells And Their Fibroblastic Differentiation In Cancer, Lingyi Cai, Mikhail G Kolonin, Dimitris Anastassiou

Faculty, Staff and Student Publications

Adipose stromal cells (ASCs) are perivascular mesenchymal progenitors of adipose tissue. In cancer patients, ASCs can mobilize and migrate to the tumor, where they subsequently play an important role in cancer progression. This biological process involves the conversion of recruited ASCs into cancer-associated fibroblasts (CAFs). ASC-derived CAFs influence the tumor microenvironment through extracellular matrix remodeling, vascularization, and immunomodulation. These and other processes mediated by secreted paracrine factors also affect gene expression in carcinoma cells to promote the epithelial-mesenchymal transition (EMT), metabolic adaptation, survival, and invasiveness of cancer cells. ASC-derived CAFs can enhance tumor aggressiveness, accounting in part for the link …

Suppression Of Cardiac Allograft Vasculopathy By A Macrophage Efferocytosis Receptor, Sahil Shah, Aparnaa Ananthakrishnan, Matthew Deberge, Kristofor Glinton, Rebecca T L Jones, Mallory Filipp, Ivana Shen, Joey Lockhart, Connor W Lantz, Edward B Thorp

Faculty, Staff and Student Publications

Cardiac allograft vasculopathy remains a major cause of late morbidity following heart transplantation. While accumulating evidence implicates innate macrophages in the inflammatory progression of CAV, the underlying mechanisms remain incompletely understood. In murine models of CAV, we identified proteolytic cleavage of MERTK, a key anti-inflammatory receptor on macrophages, as a contributing factor to CAV progression. In a model of CAV, MERTK deficiency accelerated allograft rejection and increased intimal leukocyte infiltration. In contrast, mice expressing a genetically cleavage-resistant form of MERTK (MertkCR/CR) exhibited prolonged graft survival, reduced intimal thickening, diminished immune cell infiltration, and decreased circulating effector T cells. …

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 …

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 …

Reproducibility Of Statistically Significant Phase Iii Oncology Trials: An In Silico Meta-Epidemiological Analysis, Alexander D Sherry, Pavlos Msaouel, Avital M Miller, Timothy A Lin, Joseph Abi Jaoude, Ramez Kouzy, Adina H Passy, Tomer Meirson, Nikolaos Ignatiadis, Zachary R Mccaw, Erik Van Zwet, Ethan B Ludmir

Faculty, Staff and Student Publications

Purpose: The conventional assumption that P values ≤ 0.05 imply reproducible effects has come under recent criticism. This concern is particularly relevant in oncology, as phase III oncology trials, which directly inform practice, are usually not repeated. Using advanced modeling techniques, we investigated the relationship between P values and reproducibility in oncology.

Methods: We obtained the signal-to-noise ratio distribution in phase III oncology using outcomes from 632 two-arm superiority trials enrolling 496,219 patients. With this distribution, we estimated successful replication probability as the probability that a replicate trial, having the same design, effect size, and standard error, would have a …

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 …

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 …

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 …

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 …

Mrna Vaccines Encoding Variant Forms Of Sm-Tsp-2 Confer Protective Immunity Against Schistosoma Mansoni, Athos Silva Oliveira, Sevan Alwan, Philip T Loverde, Ramiz Shaheed, Pranav Mandyam, Rakesh Adhikari, Peter Hotez, Maria Elena Bottazzi, Jeroen Pollet

Faculty, Staff and Students Publications

Despite the global burden of helminth infections, no human vaccines have yet been licensed against these parasites. This study explored the development and evaluation of mRNA vaccine candidates targeting Schistosoma mansoni tetraspanin-2 (Sm-TSP-2), an antigen currently under evaluation as a protein vaccine. We designed constructs encoding either full-length Sm-TSP-2, or its large extracellular loop (EC2) domain in secretory, membrane-anchored, or cytosolic forms. In a murine challenge model, the secreted and membrane-anchored versions of Sm-TSP-2-EC2 induced the highest of antigen-specific antibody titers. These two construct designs, along with full-length Sm-TSP-2 mRNA, also significantly reduced adult worm …