Medicine and Health Sciences Commons^™

Novel Csf Biomarkers For Facilitating Diagnosis Of Cns-Hlh From Other Neuroinflammatory Disorders, Sharat Chandra, Kenneth D Greis, Somchai Chutipongtanate, Nathan Luebbering, Aaron Webster, Kelsey E Poisson, Kristen S Fisher, Kristi Smiley, Rebecca A Marsh, Michael B Jordan, Stella M Davies

Faculty, Staff and Students Publications

Central nervous system (CNS)-hemophagocytic lymphohistiocytosis (HLH) can mimic other neuroinflammatory disorders (ONID), often leading to misdiagnosis. Current diagnostic studies do not reliably distinguish CNS-HLH from ONID. We hypothesized that novel cerebrospinal fluid (CSF) biomarkers identified using unbiased proteomic analysis can facilitate diagnosis of CNS-HLH from ONID. Banked CSF samples were categorized into 3 groups, CNS-HLH, ONID, and controls without CNS inflammation. Proteomic analysis was performed on 25 samples per group (total N = 75). Proteins demonstrating significant changes (>1.5-fold higher and P< .05) in the CNS-HLH compared with ONID and associated with HLH pathophysiology were selected as candidate biomarkers. Cross-platform validation of candidate biomarkers, along with known biomarkers CXCL9 and osteopontin, was performed using enzyme-linked immunosorbent assay (ELISA). One hundred twenty-two proteins were identified on CSF proteomic analysis at 99% confidence. Of these, 10 proteins demonstrated a >1.5-fold change with a P< .05 in CNS-HLH compared with ONID. SerpinG1, lysozyme, and CD14 were selected as candidate biomarkers. ELISA confirmed significant elevation of all 5 biomarkers in CNS-HLH relative to ONID. Median SerpinG1 levels were1242.9 ng/mL in CNS-HLH vs 292.2 ng/mL in ONID (P ≤ .001), lysozyme 222.2 ng/mL vs 65.6 ng/mL (P = .001), and CD14 180.3 ng/mL vs 64.5 ng/mL (P ≤ .001). Median CXCL9 levels were 223.7 ng/mL in CNS-HLH vs 15.5 ng/mL in ONID (P ≤ .001), and osteopontin levels were 356.5 ng/mL vs 92.9 ng/mL (P = .001). These findings demonstrate that novel CSF biomarkers SerpinG1, lysozyme, CD14, and CXCL9 can facilitate diagnosis of CNS-HLH from ONID.

"The Only Place I Feel Understood": A Mixed Methods Survey Of Adolescent And Caregiver Perspectives On Social Media And Parental Controls, Melanie Watt Ramos, Constance M Wiemann, Lauren A Bretz

Faculty, Staff and Students Publications

Purpose

Methods

Results

Celf1 Is A Non-Canonical Eif4e Binding Protein That Promotes Translation Of Epithelial-Mesenchymal Transition Effector Mrnas, Arindam Chaudhury, Natee Kongchan, Shebna A Massey, Rajesh Sharma, Rituraj Pal, Na Zhao, Phoebe Tsoi, Yingmin Zhu, Emuejevoke Olokpa, Sufeng Mao, Sonia Del Rincon, Lucas C Reineke, Richard E Lloyd, Marco Sardiello, Jeffrey M Rosen, Choel Kim, Josephine C Ferreon, Joel R Neilson

Faculty, Staff and Students Publications

Mounting evidence is revealing an increasing complexity of gene regulation at the level of messenger RNA (mRNA) translation. Within mammalian cells, canonical cap-dependent mRNA translation depends on the eIF4F complex, consisting of the m7G mRNA cap-binding protein eukaryotic initiation factor 4E (eIF4E), the helicase eIF4A (eIF4A), and the eIF4G (eIF4G1) scaffolding protein. eIF4G1 additionally binds poly(A) binding protein (PABPC1) to facilitate mRNA circularization and nucleates pre-translation initiation complex assembly to initiate ribosomal scanning. In breast epithelial cells, the CELF1 RNA-binding protein specifically promotes the translation of select epithelial-to-mesenchymal transition (EMT) effector mRNAs by binding GU-rich elements (GREs) within their 3' …

Author Correction: Machine Learning Models Predict Long Covid Outcomes Based On Baseline Clinical And Immunologic Factors, Naresh Doni Jayavelu, Hady Samaha, Sonia Tandon Wimalasena, Annmarie Hoch, Jeremy P Gygi, Gisela Gabernet, Al Ozonoff, Shanshan Liu, Carly E Milliren, Ofer Levy, Lindsey R Baden, Esther Melamed, Lauren I R Ehrlich, Grace A Mccomsey, Rafick P Sekaly, Charles B Cairns, Elias K Haddad, Joanna Schaenman, Albert C Shaw, David A Hafler, Ruth R Montgomery, David B Corry, Farrah Kheradmand, Mark A Atkinson, Scott C Brakenridge, Nelson I Agudelo Higuit, Jordan P Metcalf, Catherine L Hough, William B Messer, Bali Pulendran, Kari C Nadeau, Mark M Davis, Linda N Geng, Ana Fernandez Sesma, Viviana Simon, Florian Krammer, Monica Kraft, Chris Bime, Carolyn S Calfee, David J Erle, Charles R Langelier, Impacc Network, Leying Guan, Holden T Maecker, Bjoern Peters, Steven H Kleinstein, Elaine F Reed, Alison D Augustine, Joann Diray-Arce, Patrice M Becker, Nadine Rouphael, Matthew C Altman

Faculty, Staff and Students Publications

This corrects the article "Machine learning models predict long COVID outcomes based on baseline clinical and immunologic factors", 1.

Steroid Receptor Coactivators - From Basic Research To Translational Opportunities, Yosef Gilad, Sang Jun Han, David M Lonard

Faculty, Staff and Students Publications

The concept of nuclear receptor (NR) coregulation was proposed nearly two decades before it was experimentally validated. According to this model, NRs - executors of a vast array of transcriptional programs - do not act independently but are governed by a network of regulatory proteins that either activate or repress their biological function. NRs identify the genes to be regulated. However, coregulators ultimately serve as the true controllers of transcriptional outcomes. They recruit cofactors and coordinate the activity of transcriptional complexes, thereby shaping NR-mediated gene expression beyond NRs' intrinsic functionality. The Steroid Receptor Coactivator (SRC) family is the most extensively …

Unbalanced Chromatin Binding Of Polycomb Complexes Drives Neurodevelopmental Disorders, Rodrigo L Borges, Gretter González-Blanco, Harikumar Arigela, Yingyu Huang, Lucas D Caeiro, Nikolai Fattakhov, Stefano Lepore, Liliana Garcia-Martinez, Matea Maurice, Pushti D Mehta, Emily J Park, Kailynn Macgillivray, Jevithen Nehru, Matthew Chau, Maria C Robayo, Clemer Abad, Alicia Bilbao-Martinez, Fabiola Monteiro, Xi Luo, Song Tan, Daniel Bilbao, Simone Sidoli, Bruno Di Stefano, Katherina Walz, Arneet L Saltzman, Ramiro E Verdun, Ramin Shiekhattar, Lluis Morey

Faculty, Staff and Students Publications

The prevalence of neurodevelopmental disorders (NDDs) in children is increasing, yet their underlying causes remain largely unknown. We identified heterozygous mutations in the Polycomb repressive complex 1 (PRC1) E3 ligases RING1 and RNF2 in individuals with NDDs and revealed distinct mechanisms by which they compromise PRC1 activity. We developed cellular and mouse models carrying the Ring1b

Online Decision Support For Implementing Evidence-Based Hpv Vaccination Strategies In Texas Safety-Net Pediatric Clinics: Impact On Hpv, Mcv, And Tdap Initiation, Ross Shegog, Hanxiao Sun, Erica L Frost, Laura C Thormaehlen, Travis A Teague, Catherine Mary Healy, Hina Azam, Aadeel Khawaja, Laura Aubree Shay, Dale S Mantey, Sally W Vernon, Lara S Savas

Faculty, Staff and Students Publications

Introduction: HPV vaccination rates for adolescents in the United States are below recommended levels. The Adolescent Vaccination Program (AVP) guides pediatric clinics on how to implement evidence-based strategies to increase HPV vaccination rates. These strategies comprise the adoption of (1) immunization champions, (2) provider assessment and feedback, (3) continuing education, and (4) prompts, (5) parent reminders, and (6) parent education. The AVP systems-based intervention has demonstrated increased HPV vaccination rates in large urban pediatric clinic networks. The purpose of this study was to assess the feasibility of using an online decision support tool, the AVP Implementation Tool (AVP-IT), to …

Spatiotemporal Histogenesis Of The Developing Human Cerebellum Reveals Dynamic Layering Of Bergmann Glia, Guanyi He, Simon Du, Henry Tan, Sri Yellampally, Anders W Erickson, Virginia Fernandez, Ferechte Encha-Razavi, Kimberley A Phillips, Christine Haberler, Nicole Amberg, Victor Borrell, Paul A Northcott, Michael D Taylor, Kathleen J Millen, Parthiv Haldipur

Faculty, Staff and Students Publications

Bergmann glia (BG) are a specialized glial population essential for cerebellar development, yet their developmental timeline and molecular identity in the human cerebellum remain poorly understood. Here, we combined detailed histopathological analysis with spatial transcriptomics and single-nucleus RNA sequencing to generate a developmental atlas of human cerebellar BG. Histology revealed that BG emerge around 11 post-conception weeks (PCW), initially serving as a scaffold for Purkinje cells (PCs) migrating into the PC layer of the cerebellar cortex. Following the establishment of a multilayered PC arrangement, BG form a distinct parallel layer separated from the PCs by the lamina dissecans (LD), with …

Lipidomic Profiles Associated With Treatment Related Hepatotoxicity In Children With Acute Lymphoblastic Leukemia., Emily J Mason, Jeremy M Schraw, John P Woodhouse, M Monica Gramatges, Kevin J Williams, Baojiang Chen, Melissa B Harrell, Olga A Taylor, Michael E Scheurer, Philip J Lupo, Karen R Rabin, Joanna S Yi, Van Huynh, Steven D Mittelman, Etan Orgel, Austin Brown

Faculty, Staff and Students Publications

Introduction: Treatment for childhood acute lymphoblastic leukemia (ALL) can result in hepatotoxicity. Despite being a common complication of ALL therapy, mechanisms and biomarkers of treatment-associated hepatotoxicity (TAH) are not well described.

Methods: We conducted lipidomic profiling to identify plasma lipids associated with TAH in children receiving ALL therapy utilizing a nested case-control framework. TAH was defined as (1) transaminitis: ALT/AST ≥ CTCAE grade 3, and/or (2) conjugated hyperbilirubinemia: > 3.0 mg/dL during induction therapy or > 2.0 mg/dL post induction. A total of 90 patients (45 matched pairs) treated at Texas Children's Hospital between 2012 and 2021 were selected for lipidomic profiling, …

Strspy2.0: Unlocking The Potential Of Long Reads For Forensic Dna Profiling, Courtney L Hall, Rupesh K Kesharwani, Katherine E Mcbroom Henson, Bupe Kapema, Nicole R Phillips, Fritz J Sedlazeck, Roxanne R Zascavage

Faculty, Staff and Students Publications

Forensic human identification relies on length-based differences in short tandem repeats (STRs) across autosomal and Y chromosomes, which require separate reactions and provide limited resolution. While next-generation sequencing offers greater discriminatory power, most platforms are expensive and restricted to traditional lab settings. Nanopore sequencing has the potential to change this with the real-time, portable MinION sequencer. However, forensic-specific tools that generate STR profiles compatible with established length-based databases are lacking. To address this, we developed STRspy2.0, which simultaneously profiles autosomal and Y-STRs using nanopore reads. STRspy2.0 produced accurate profiles for 54 multiplexed control libraries and 41 mock casework samples (blood, …

Author Correction: Intracranial Directed Connectivity Links Subregions Of The Prefrontal Cortex To Major Depression, John Myers, Jiayang Xiao, Raissa K Mathura, Ben Shofty, Victoria Gates, Joshua Adkinson, Anusha B Allawala, Adrish Anand, Ron Gadot, Ricardo Najera, Hernan G Rey, Sanjay J Mathew, Kelly Bijanki, Garrett Banks, Andrew Watrous, Eleonora Bartoli, Sarah R Heilbronner, Nicole Provenza, Wayne K Goodman, Nader Pouratian, Benjamin Y Hayden, Sameer A Sheth

Faculty, Staff and Students Publications

No abstract provided.

Epigenetic Age Acceleration In Young Adults With Congenital Heart Disease, Parag N Jain, Beryl C Zhuang, Joanne Whitehead, Julia L Macisaac, Kristy Dever, Mallory Gahm, Peter Ermis, Thomas W Mcdade, Michael S Kobor, Paul A Checchia

Faculty, Staff and Students Publications

Background: Adults with congenital heart disease (ACHD) having undergone palliative surgery experience chronic stress due to altered physiology and repeated surgical interventions since infancy.

Objectives: To investigate whether ACHD, who had experienced chronic physiological stress from their underlying condition and early-life cardiac surgeries, was associated with epigenetic age acceleration (EAA) and other DNA methylation (DNAm)-based biomarkers, and to assess the potential contribution of derived inflammatory markers to EAA.

Methods: A case-control study comparing ACHD patients and healthy adults. Whole blood DNAm profile was used to estimate DNAm-based blood cell type proportions, multiple epigenetic age measures, and interleukin-6 (IL-6) and C-reactive …

First Detection Of Xylazine In Texas Wastewater And Its Association With Fentanyl Use, Katherine M Joseph, Xuan Qin, Dhvani Parikh, Feng Li, John Balliew, Kristina D Mena, Fuqing Wu

Faculty, Staff and Students Publications

Xylazine is a veterinary sedative increasingly found in the U.S. illicit drug supply and is a growing public health concern due to its association with overdose events. To investigate its spatial distribution and relationship with fentanyl use, we analyzed 124 wastewater samples from four treatment plants serving the City of El Paso, Texas, over 13 months (June 2023 to July 2024) using liquid chromatography tandem mass spectrometry. Xylazine detections varied across sewersheds, with detection rates of 29.0%, 12.9%, 9.7%, and 0% and peak loads of 110±40 μg/day/1000 people. Norfentanyl (a primary fentanyl metabolite) was detected in all samples (100%), reaching …

Small Patients, Big Gaps: Why Adult Crrt Timing Evidence Does Not Translate To Children, Katja M Gist, Dana Y Fuhrman, Ayse Akcan-Arikan

Faculty, Staff and Students Publications

No abstract provided.

Three-Dimensional Versus Two-Dimensional Echocardiographic Assessment Of Left Atrial Volume And Deformation In Children, Alexander J Kiener, James Croft, Krista N Harris, Ankona Banerjee, Aura A Sanchez, Xander H T Wehrens, Anitha Parthiban, Xiaotian Gao, Tam T Doan, Minh B Nguyen

Faculty, Staff and Students Publications

Background: Left atrial (LA) volume and function are important for assessing pediatric diastolic dysfunction (DD). Three-dimensional echocardiographic (3DE) LA assessment may overcome limitations and assumptions inherent in two-dimensional echocardiographic (2DE).

Methods: We conducted a cross-sectional study of children under 18 years of age with structurally normal hearts, using transthoracic 3DE apical volume datasets. LA volumetric function and phasic deformation analyses were performed using 3DE (GE, EchoPAC 4DLAQ v206, near fully-automated) and 2DE (TomTec, TTA2.51, CPA, manual) was performed by three operators and processing time was collected. Agreement and reproducibility was assessment for each modality.

Results: Fifty patients (median age 12.8 …

Leveraging Clinical Sleep Data Across Multiple Pediatric Cohorts For Insights Into Neurodevelopment: The Retrospective Analysis Of Sleep In Pediatric (Rasp) Cohorts Study, Naihua N Gong, Aditya Mahat, Samya Ahmad, Daniel Glaze, Mirjana Maletic-Savatic, Matthew Mcginley, Anne Marie Morse, Alcibiades J Rodriguez, Audrey Thurm, Susan Redline, Kiran Maski, Peter Davis, Shaun Purcell, Ashura Buckley

Faculty, Staff and Students Publications

Sleep disturbances are prominent across neurodevelopmental disorders (NDDs) and may reflect specific abnormalities in brain development and function. Overnight polysomnography (PSG) allows for detailed investigation of sleep architecture, offering a unique window into neurocircuit function. Analysis of existing pediatric PSGs from clinical studies could enhance the availability of sleep studies in pediatric patients with NDDs towards a better understanding of mechanisms underlying abnormal development in NDDs. Here, we introduce and characterize a retrospective collection of 1527 clinical pediatric overnight PSGs across five different sites. We first developed an automated stager trained on independent pediatric sleep data, which yielded better performance …

Myokine Sirpα Exacerbates Kidney Disease In Diabetes, Jiao Wu, Elisa Russo, Daniela Verzola, Qingtian Li, Helena Zhang, Bhuvaneswari Krishnan, David Sheikh-Hamad, Zhaoyong Hu, William E Mitch, Sandhya S Thomas

Faculty, Staff and Students Publications

Mechanisms responsible for skeletal muscle kidney crosstalk have not been defined. We have determined that a circulating mediator, signal regulatory protein α (SIRPα), impairs intracellular insulin-mediated functions. To elucidate the effect of myokine SIRPα on diabetic kidney disease (DKD), flox mice and muscle-specific (m-specific) SIRPα-KO mice were subjected to an obesity-induced model of diabetes, high-fat diet (HFD; 60%) or insulin-deficient hyperglycemia model, streptozotocin (STZ), and were subsequently exposed to anti-SIRPα monoclonal antibodies. In the obesity-induced diabetic mice, serum SIRPα increased. Genetic deletion of muscle SIRPα protected against obesity and improved intracellular insulin signaling in muscle and adipose tissue, with reduced …

“U’R-In(E)!- Urine-Albumin-Creatinine Ratio–The Old Kid On A New Block!, Yakubu Bene-Alhasan, Vijay Nambi, Christie Ballantyne

Faculty, Staff and Students Publications

No abstract provided.

Consensus Paper: Models Of Cerebellar Functions, Shinji Kakei, Andreea C Bostan, Timothy J Ebner, Mohammad Amin Fakharian, Hiroaki Gomi, Xavier Guell, Marie Hemelt, Huu Hoang, Court Hull, Masato Inoue, Takahiro Ishikawa, Masashi Kameda, Mitsuo Kawato, Shigeru Kitazawa, Mario Manto, Javier F Medina, Hiroshi Mitoma, Keiko Ohmae, Shogo Ohmae, Ken-Ichi Okada, Laurentiu S Popa, Jeremy D Schmahmann, Reza Shadmehr, Peter L Strick, Hirokazu Tanaka, Masaki Tanaka, Tadashi Yamazaki

Faculty, Staff and Students Publications

For a long time, from the nineteenth century to most of the twentieth century, the cerebellum was thought to be an organ that regulates movement. Towards the end of the twentieth century, the brain functions associated with the cerebellum began to extend beyond motor control. Now, there is a consensus that the cerebellum is involved not only in motor functions but also in the most basic autonomic functions and the most complex cognitive and emotional functions, with a focus on predictions and internal models. A new functional model of the cerebellum is needed to explain all layers of brain functions …

Fractionated Radiotherapy Adjuvant To Surgery Of Who-2 Meningioma With And Without Gross Total Resection: A Multicenter, Retrospective Cohort Study Of 1,452 Patients, Christian Mirian, Lasse Rehné Jensen, Adam Gorm Hoffmann, Tareq A Juratli, Andrea Daniela Maier, Pernilla Lindner, Anders Broechner, Sverre H Torp, Helen A Shih, Ramin A Morshed, Jacob S Young, Stephen T Magill, Walter Stummer, Dorothee Cäcilia Spille, Benjamin Brokinkel, Martin Proescholdt, Yasuhiro Kuroi, Konstantinos Gousias, Matthias Simon, Ricardo Prat-Acin, Stéphane Goutagny, Johannes Wach, Erdem Güresir, Junkoh Yamamoto, Young Zoon Kim, Joo Ho Lee, Daniel W Kim, Matthew Koshy, Donald M Cannon, Dennis C Shrieve, Chang-Ok Suh, Jong Hee Chang, Maria Kamenova, Sven Straumann, Jehuda Soleman, Ilker Y Eyüpoglu, Tony Catalan, Austin Lui, Philip V Theodosopoulos, Michael W Mcdermott, Pedro Góes, Fang Wang, Luis Souhami, Marie-Christine Guiot, Tamás Csonka, Toshiki Endo, Tejpal Gupta, Akash J Patel, Tiemo J Klisch, Jun Won Kim, Francesco Maiuri, Valeria Barresi, María Dolores Tabernero, Simon Skyrman, Mechthild Krause, Ian Law, Bjarne Winther Kristensen, Tina Nørgaard Munch, Torstein Meling, Kåre Fugleholm, Paul Blanche, Tiit Mathiesen

Faculty, Staff and Students Publications

Purpose

The role of adjuvant fractionated radiotherapy (aFRT) after gross total resection (GTR) of WHO-2 meningiomas remains unclear. We aimed to estimate the effect of aFRT on recurrence risk and survival following GTR and subtotal resection (STR).

Methods

We analyzed 1452 patients with WHO-2 from our international, multicenter database (followed between 1989 and 2019). Outcomes were recurrence (10-year follow-up) and death (5-year follow-up). Risk estimates were obtained using competing risks and survival analysis. Average treatment effects were estimated by G-computation, adjusted for potential confounding by age, sex, Simpson grade, Ki-67 proliferation index, location, country group (universal healthcare or not), …

Discovery And Characterization Of A Novel Pseudomonas Phage Of A New Genus, Paul Nicholls, Justin R Clark, Anthony Maresso

Faculty, Staff and Students Publications

Background: Bacteriophages exhibit great diversity and are classically divided into lytic and temperate lifestyles. Commonly, bioinformatics is used to predict the temperate lifestyle. As the nosocomial pathogen Pseudomonas aeruginosa is common in freshwater, this biome represents an ideal location for the discovery of Pseudomonas phages.

Materials and methods: We characterized a genetically distinct species of Pseudomonas phage using next-generation sequencing and conventional microbiological methods. We characterized its lifestyle by purifying infected colonies and identifying persistent phage production.

Results: Genetics revealed a phage of a novel genus. Characterization showed a narrow host range and bioinformatics suggested a lytic lifestyle. Experimental data …

Overcoming Host Restrictions To Enable Continuous Passaging Of Gii.3 Human Norovirus In Human Intestinal Enteroids, Gurpreet Kaur, Sue E Crawford, Sara Javornik Cregeen, Anil Surathu, B Vijayalakshmi Ayyar, Carmen V Apostol, Hoa Nguyen Phuc, Khalil Ettayebi, Aaya Boussattach, Xi-Lei Zeng, Sarah E Blutt, Harsha Doddapaneni, Donna M Muzny, Cristian Coarfa, Ramakrishnan Anish, B V Venkataram Prasad, Robert L Atmar, Sasirekha Ramani, Mary K Estes

Faculty, Staff and Students Publications

The establishment of human intestinal enteroids (HIEs) as a model for human norovirus (HuNoV) replication has been transformative for studying this leading cause of gastroenteritis. However, indefinite passaging of HuNoVs in HIEs remained a challenge, necessitating the use of patient stool samples as viral inocula. Using RNA-seq, we identified CXCL10, CXCL11, and CCL5 as up-regulated chemokines, suggesting their potential as host restriction factors. TAK-779, a CXCR3/CCR5/CCR2 antagonist, enhanced GII.3 HuNoV replication and viral spread in a dose- and time-dependent manner, enabling successful passaging of GII.3 HuNoV in two different HIE lines and generation of viral stocks. Sequencing passaged virus revealed …

Defining Clinically Relevant Responses In Erectile Function: An Smsna Position Statement, Landon Trost, Faysal Yafi, Alan Shindel, Mohit Khera, Raymond C Rosen, Petar Bajic, Helen Bernie, Martin Gross, Johanna Hannan, Sevann Helo, Lawrence Jenkins Ii, Carol Podlasek, Daniel Watter, Matthew Ziegelmann, Tobias Köhler

Faculty, Staff and Students Publications

Background: To date, no scoring system has adequately defined clinical efficacy of erectile dysfunction (ED) therapies when evaluating differences between cohorts or in meta-analytic studies.

Aim: To outline the minimal criteria required for any therapy to be considered clinically effective in the treatment of ED.

Methods: An analytic review was performed of standardized ED questionnaires, with a particular emphasis placed on the International Index of Erectile Function, Erectile Function Domain (IIEF-EFD), and the minimally clinically important difference (MCID) concept. The data were used to create a societal position statement and recommendations on best practices within clinical trials to determine treatment …

Improving Prediction Accuracy Of Radiation-Induced Temporal Lobe Injury In Nasopharyngeal Carcinoma Using Adc-Based Deep Learning And Dosiomics, Li Wang, Yang Li, Ting Qiu, Junyi Liu, Jiawei Zhou, Han Gao, Hongliang Yu, Yinsu Zhu, Baozhou Sun, Guanyu Yang, Shengfu Huang, Lirong Wu, Li Sun, Xia He

Faculty, Staff and Students Publications

Background: To investigate the potential of apparent diffusion coefficient (ADC) map-based deep learning and dose distribution-based dosiomics in predicting radiation-induced temporal lobe injury (RTLI) in nasopharyngeal carcinoma (NPC).

Methods: This retrospective study included 3578 NPC patients from Jiangsu Cancer Hospital receiving intensity-modulated radiation therapy (IMRT). Ninety-four RTLI patients were recruited based on inclusion criteria and matched 1:1 with 97 control subjects using propensity scores. Patients were randomly assigned to the training cohort (n = 135) and the validation cohort (n = 59). Deep transfer learning (DTL) features and dosiomics features were extracted from ADC map and three-dimensional dose distribution, respectively. …

Extracellular Matrix Mediates Circulating Tumor Cell Clustering In Triple-Negative Breast Cancer Metastasis, Georg Om Bobkov, Khushali J Patel, Bree M Lege, Rong Zheng, Gad Shaulsky, Matthew J Ellis, Chonghui Cheng

Faculty, Staff and Students Publications

Metastatic tumor cell dissemination is the leading cause of cancer-related deaths. Clustered circulating tumor cells (CTCs) possess higher metastatic potential than single CTCs. Epithelial adherens junction (AJ) proteins typically mediate stable cell-cell interactions; however, these proteins are frequently lost in highly aggressive triple-negative breast cancers (TNBCs), raising the question of how CTCs from such tumors cluster. Here we show that the extracellular matrix (ECM) component hyaluronan (HA) mediates AJ-independent CTC clustering in TNBCs. HA is necessary and sufficient to drive clustering of tumor cells expressing its receptor CD44. Mechanistically, HA initiates contact between neighboring cells through actin-based membrane protrusions. As …

Bi-Allelic Variants In Neuronal Adhesion Molecule Astrotactin 1 Gene Astn1 Cause Diverse Neurodevelopmental Disorders, Jesse M Levine, Daniel G Calame, Riccardo Sangermano, Haowei Du, Ahmed Saad, Jasmin Lisfeld, Tatjana Bierhals, Jonas Denecke, Eyyup Uctepe, Merve Yoldas Celik, Ahmet Yesilyurt, Hilal Yildiz Er, Elif Yilmaz Gulec, Aziza Mushiba, Naif Almontashiri, Pawel Gawlinski, Wojciech Wiszniewski, Ender Karaca, Lama Alabdi, Davut Pehlivan, Dana Marafi, Maha S Zaki, Fowzan S Alkuraya, Joseph G Gleeson, Shalini N Jhangiani, Richard A Gibbs, Jennifer E Posey, Kinga M Bujakowska, James R Lupski

Faculty, Staff and Students Publications

ASTN1 encodes astrotactin 1, a neuronal-glial ligand in the developing brain that promotes neuronal migration along radial glia in brain structures with laminar organization, such as the cerebral cortex, hippocampus, and cerebellum. In mouse models, disruption of Astn1 results in neuronal migration deficits, a mild reduction in cerebellar volume, and balance and coordination deficits. In humans, bi-allelic ASTN1 variants have been identified in nine individuals with neurodevelopmental disorders (NDDs) with or without brain malformations. ASTN1 additionally interacts with astrotactin 2 (ASTN2) to implement neuronal migration; ASTN2 deletions associate with NDDs with reduced penetrance. Here, we describe eighteen individuals with NDDs …

Infectious Causes Of Acute Febrile Illness In Belize, 2020-2022, Adrianna Maliga, Shannon E Ronca, Russell Manzanero, Roberto Melendez, Sarah M Gunter, Allison Lino, Joy Mackey, Andres Espinosa-Bode, Beatriz Lopez, Rafael Chacon-Fuentes, Freedom M Green, Oluwadara Okeremi, Sarah Strobel, Daniel P Rehm, Flor M Muñoz, Loren Cadena, Melissa Diaz-Musa, Francis Morey, Emily Zielinski-Gutierrez, Gerhaldine Morazan, Kristy O Murray

Faculty, Staff and Students Publications

Acute febrile illness (AFI) surveillance networks can play a key role in identifying emerging pathogens and promoting global health security, especially for vulnerable populations in low- and middle-income countries. In January 2020, the Belize AFI Surveillance network was formed, and 5,643 participants were enrolled over the first 3-year period across 11 participating public hospitals. Using real-time polymerase chain reaction testing for vector-borne pathogen detection and BioFire® diagnostic testing for respiratory and gastrointestinal pathogens, the causes of illness were examined in relation to 54 pathogens in these participants. In response to the coronavirus disease 2019 pandemic, surveillance was expanded to detect …

Patient-Specific Computational Flow Simulation Reveals Adverse Hemodynamic Factors Associated With Occlusion Of Directional Branches After Fenestrated-Branched Endovascular Aneurysm Repair, Kenneth Tran, Jesse Chait, Emmanuel Tenorio, Weiguang Yang, Alison Marsden, Bernardo Mendes, Jason T Lee, Gustavo S Oderich

Faculty, Staff and Students Publications

Background: Fenestrated and branched endovascular aneurysm repair can be complicated by branch vessel occlusion in the absence of structural stenosis. We hypothesized that computational flow simulation could identify adverse hemodynamic features associated with postfenestrated and branched endovascular aneurysm repair branch occlusion.

Methods: Patients undergoing 4-vessel fenestrated and branched endovascular aneurysm repair for Extent II to IV thoracoabdominal aortic aneurysms were retrospectively reviewed. Branches that occluded without identifiable kinking or stenosis on computed tomography were included, along with an equal cohort of anatomy-matched patent controls. Patient-specific pulsatile rigid-wall simulations were performed using SimVascular with individualized geometries and boundary conditions. Abnormal time-averaged …

Mapping The Causal Chain From Genetic Risk Variants To Lipid Dysmetabolism In Parkinson’S Disease, Ruth B De-Paula, Jonggeol Kim, Herve Rhinn, Hiba Saade, Fatima Chavez, Téah Segura, Maria Valeria Lozano, Michelle Etoundi, Karla Silos, Naomi Kass, Viktoriya Korchina, Harshavardhan Doddapaneni, Eric Venner, Joseph C Masdeu, Valory Pavlik, Melissa M Yu, Chi-Ying R Lin, Joseph Jankovic, Aron S Buchman, Donna Muzny, Richard A Gibbs, Sarah H Elsea, Asa Abeliovich, Peter Lansbury, Nora Vanegas-Arroyave, Chad A Shaw, Joshua M Shulman

Faculty, Staff and Students Publications

The molecular pathways linking genetic variants to Parkinson's disease (PD) onset and progression remain incompletely defined; however, risk alleles in multiple genes, including GBA1, strongly implicate lipid metabolism. To systematically identify causal biomarker signatures, we analyzed comprehensive metabolome profiles from blood plasma in 149 PD patients and 150 controls, along with complementary genetic, RNA-sequencing, and metabolic data from other available clinical and pathologic cohorts. Using colocalization and summary-data-based Mendelian randomization, we tested whether expression and metabolic quantitative trait loci mediate the association between implicated genetic variants and PD risk. We further integrated differential metabolomics and proteomics from blood and brain …

Clinical Features Of Infantile Epileptic Spasms Syndrome: A Systematic Review, Xiao Meng, Danielle S Takacs, Yashaswini Kelagere, Zihan Zhang, Sanjanaa Seshadri, Jiyeon Cha, Ming Li, Lei-Shih Chen

Faculty, Staff and Students Publications

Introduction

Infantile Epileptic Spasms Syndrome (IESS) is a severe epilepsy in children between one month and two years of age. Urgent referral of possible IESS cases from pediatricians and family physicians who care for children to neurologists for diagnosis and treatment has been shown to significantly improve patient health outcomes. Yet, a comprehensive list of IESS clinical features is lacking. We conducted a systematic review of studies to report IESS clinical features.

Methods

Articles from the MEDLINE Complete and Embase databases were searched from the earliest years of databases availability (1979) to July 31, 2024. We followed the Preferred Reporting …