Medicine and Health Sciences Commons^™

Culture-Independent Meta-Pangenomics Enabled By Long-Read Metagenomics Reveals Associations With Pediatric Undernutrition, Jeremiah J Minich, Nicholas Allsing, M Omar Din, Michael J Tisza, Kenneth Maleta, Daniel Mcdonald, Nolan Hartwick, Allen Mamerto, Caitriona Brennan, Lauren Hansen, Justin Shaffer, Emily R Murray, Tiffany Duong, Rob Knight, Kevin Stephenson, Mark J Manary, Todd P Michael

Faculty, Staff and Students Publications

The human gut microbiome is linked to child malnutrition, yet traditional microbiome approaches lack resolution. We hypothesized that complete metagenome-assembled genomes (cMAGs), recovered through long-read (LR) DNA sequencing, would enable pangenome and microbial genome-wide association study (GWAS) analyses to identify microbial genetic associations with child linear growth. LR methods produced 44-64× more cMAGs per gigabase pair (Gbp) than short-read methods, with PacBio (PB) yielding the most accurate and cost-effective assemblies. In a Malawian longitudinal pediatric cohort, we generated 986 cMAGs (839 circular) from 47 samples and applied this database to an expanded set of 210 samples. Machine learning identified species …

Implementing Pst In Older Adults Facing Major Surgery: A Randomised Controlled Pilot Study, Victoria Tang, Lejla Pepic, Erika Higuchi, Christina Keny, Elizabeth Macias Lopez, Ezenwa C Onyema, Harleen Sandhu, Veronica Yank, Patrick J Raue

Faculty, Staff and Student Publications

Introduction: Depressive symptoms are common in the growing geriatric surgical population and are associated with important patient-centred surgical outcomes, including postoperative delirium, discharge to postacute care facility and decline in functional status. Few interventions have been developed to address depressive symptoms in the perioperative setting.

Methods and analysis: We designed a feasibility and acceptability study of a nine-session problem-solving therapy (PST) telehealth perioperative intervention aimed at reducing postoperative functional decline and depressive symptoms among at-risk older adults undergoing major surgical procedures. Acceptability will be evaluated using a patient-centred five-question survey, assessing participant satisfaction and perceived usefulness of the perioperative intervention. …

Low Mutation Rate But High Male-Bias In The Germline Of A Short-Lived Opossum, Yadira Peña-García, Richard J Wang, Muthuswamy Raveendran, R Alan Harris, Paul B Samollow, Jeffrey Rogers, Matthew W Hahn

Faculty, Staff and Students Publications

Age and sex have been found to be important determinants of the mutation rate per generation in mammals, but the mechanisms underlying these factors are still unclear. One approach to distinguishing between alternative mechanisms is to study species that reproduce at very young ages, as competing hypotheses make different predictions about patterns of mutation in these organisms. Here, we study the germline mutation rate in the gray short-tailed opossum, Monodelphis domestica, a laboratory model species that becomes reproductively mature at less than 6 mo of age. Whole-genome sequencing of 22 trios reveals one of the lowest mutation rates per generation …

Slc35g3 Is A Udp-N-Acetylglucosamine Transporter For Sperm Glycoprotein Formation And Underpins Male Fertility In Mice, Daisuke Mashiko, Shingo Tonai, Haruhiko Miyata, Martin M Matzuk, Masahito Ikawa

Faculty, Staff and Students Publications

Despite the recognized importance of glycans in biological phenomena, their complex roles in spermatogenesis and sperm function remain unclear. SLC35G3, a 10-transmembrane protein specifically found in early round spermatids, belongs to the sugar-nucleotide transporter family, indicating its involvement in glycan formation. In this study, we found that Slc35g3 knockout male mice were sterile due to impaired sperm functions in uterotubal junction passage, zona pellucida binding, and oocyte fusion. Mouse SLC35G3 has UDP-GlcNAc transporter activity, and its ablation caused abnormal processing of the sperm plasma membrane and acrosome membrane proteins. Reported human SLC35G3 mutations (F267L and T179HfsTer27) diminished the UDP-GlcNAc transporter …

Host Cysteine Proteases Promote The Severity Of Catheter-Associated Urinary Tract Infection And Kidney Fibrosis, Wei Xu, Jian Chen, Lisa K Mclellan, Ana L Flores-Mireles, David A Hunstad, Michael G Caparon

2020-Current year OA Pubs

UNLABELLED: The bacterium

IMPORTANCE: Catheter-associated urinary tract infections (CAUTIs) are the most prevalent healthcare-associated infection globally, with

Anticipation Of A Therapeutic Odyssey Following Predictive Testing For Autism, Katherine E Macduffie, Aurora M Washington, Catherine A Burrows, Stephen R Dager, Jed T Elison, Annette M Estes, Rebecca Grzadzinski, Chimei M Lee, Joseph Piven, Mark D Shen, Benjamin S Wilfond, Jason Wolff, Lonnie Zwaigenbaum, John R Pruett Jr

2020-Current year OA Pubs

Brain-based tools are being developed to identify infants at ultra-high likelihood for developing autism and enable presymptomatic intervention, though such interventions are not yet clinically available. Given persistent challenges in accessing autism services, we sought to understand how families might use early predictive results to seek support. We analyzed 55 interviews with parents of infants aged 6-13 months; one group had experience parenting an older autistic child (n = 30), the other had no prior autism parenting experience (n = 25). All parents were asked what steps they would take if told their infant was likely to develop autism. Both …

Metabolic Dysfunction-Associated Steatotic Liver Disease And Colorectal Neoplasms Risk: A Global Propensity Score-Matched Retrospective Cohort Study, Mohammad Aldiabat, Ali Osman, Malek Ayoub, Mahmoud Y Madi, Kamran Qureshi, Wing-Kin Syn

2020-Current year OA Pubs

OBJECTIVES: To evaluate the association between metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic-associated steatohepatitis (MASH), and the risk of colorectal cancer (CRC) and benign colorectal neoplasms (BCN), and to explore whether liver fibrosis/cirrhosis modifies these associations.

DESIGN: Retrospective cohort study with 1:1 propensity score matching.

SETTING: Global, multicentre real-world analysis using deidentified electronic health records from over 130 healthcare organisations in the TriNetX Global Collaborative Network.

PARTICIPANTS: Hospitalised adults aged 45-75 years between October 2019 and October 2024. Patients with prior diagnoses of colorectal neoplasia or other chronic liver diseases were excluded. Final matched cohorts included 138 902 MASLD and …

Posterior Fossa Decompression In Syndromic Children With Chiari-Like Posterior Fossa Crowding: A Nationwide Us-Based Study, Victor Gabriel El-Hajj, Josué Aganze Mwambali, Ihab Ahmad Al-Rikabi, Erik Öhlen, Maria Gharios, Victor E. Staartjes, Joanna M. Roy, Basel Musmar, Pascal Jabbour, Erik Edström, Adrian Elmi-Terander

Department of Neurosurgery Faculty Papers

INTRODUCTION: Posterior fossa crowding, due to cerebellar tonsil herniation, often requires surgery with posterior fossa decompression (PFD). Although most cases are due to a Chiari-1 malformation (CM1), some are due to concomitant congenital conditions, mimicking a radiological CM1. The aim of this study was to compare PFD outcomes between CM1 and the syndromic Chiari-like crowding of the posterior fossa. A national pediatric surgical database was used to compare baseline characteristics and short-term postoperative outcomes.

METHODS: Pediatric patients undergoing PFD (2012-2021) were identified in the ACS NSQIP-P database. Baseline characteristics and 30-day outcomes were compared between syndromic and non-syndromic cases. Multivariate …

Reprogramming Tumor Microenvironment Via Systemic Delivery Of Tlr3 Agonist And Manganese Nanoparticle, Young Seok Cho, Xingwu Zhou, Xiaoqi Sun, Ziye Wan, Julia Crowther, Mariko Takahashi, Swetha Kodamasimham, Qi Wu, May Thazin Phoo, Youngseo Na, Kai Han, Zaiye Li, Anna Schwendeman, Steven P Schwendeman, Yu Leo Lei, James J Moon

Faculty, Staff and Student Publications

Toll-like receptor (TLR) agonists, as potent immunostimulatory adjuvants, play a critical role in linking the innate and adaptive immune responses. However, their antitumor effects as cancer immunotherapeutic agents have been limited. Here, we report our finding that manganese ion (Mn2+) potentiates various TLR agonists, leading to robust activation of the TLR pathway and the stimulator of interferon genes (STING) pathway among innate immune cells. In particular, we have observed robust antitumor efficacy after intratumoral administration of a TLR3 agonist and Mn2+. To achieve systemic codelivery of TLR3 agonist and Mn2+, we have developed a low-molecular-weight poly(inosinic:cytidylic acid)-Mn2+ coordination lipid nanoparticle …

Reducing Moral Distress Through Interdisciplinary Collaboration: The Impact Of A Weekly Palliative Care And Neonatology Conference, Kirthi Devireddy, Riddhi Shukla, Rachel Boren, James E Slaven, Rebecca A Baker, Jayme D Allen, Karen M Moody

Faculty, Staff and Student Publications

Background: Moral distress is the experience of knowing what ethically right action to take, but being unable to act accordingly, due to external factors. It is an experience common to providers working in the neonatal intensive care unit (NICU) where care for infants, often born at the edges of viability or with other life-limiting diagnoses, includes life and death medical decision-making in the context of uncertain prognoses. Palliative care, which aims to reduce suffering, can assist with staff moral distress by providing space for conversations regarding goals-of-care and end-of-life decision making.

Methods: The palliative care and NICU teams co-developed a …

Real-World Outcomes Of Infections Following Tisagenlecleucel In Patients With B-Cell All: A Cibmtr Analysis, Hemalatha G Rangarajan, Prakash Satwani, Megan M Herr, Min Chen, Michael J Martens, Kitsada Wudhikarn, Samuel John, Vanessa A Fabrizio, Emily M Hsieh, Amar H Kelkar, Erin Doherty, David I Marks, Olle Ringden, Brian Friend, Matthew S Kelly, Nosha Farhadfar, Tim Prestidge, Nasheed M Hossain, Hongtao Liu, Shahrukh Hashmi, Dipenkumar Modi, Lena E Winestone, Zeinab El Boghdadly, Hemant S Murthy, Miguel-Angel Perales, Roy F Chemaly, Christopher E Dandoy, Joshua A Hill, Anna Huppler, Marcie Riches, Jeffery J Auletta

Faculty, Staff and Students Publications

Tisagenlecleucel (tisa-cel) is a CD19-directed chimeric antigen receptor T-cell therapy for relapsed/refractory precursor B-cell acute lymphoblastic leukemia (R/R B-ALL). We report infectious complications for 100 days (D100) following tisa-cel therapy in 471 pediatric and young adults (median age 13.8 years) with R/R B-ALL reported from September 2017 to June 2022. By D100, 137 (29%) patients had an infectious event, with an infection density of 0.542 per 100 person-days at risk. D100 cumulative incidences of bacterial, viral, and fungal infections were 14.1%, 11.6%, and 1.3%, corresponding to infection density scores of 0.296, 0.213, and 0.033 per 100 person-days at risk, respectively. …

Infection After Cd19 Chimeric Antigen Receptor T-Cell Therapy For Large B-Cell Lymphoma: Real-World Analysis From Cibmtr, Kitsada Wudhikarn, Megan M Herr, Min Chen, Michael J Martens, John H Baird, Lohith Gowda, Hemalatha G Rangarajan, Muhammad Bilal Abid, Mohamed A Kharfan-Dabaja, Kirsten M Williams, Siddhartha Ganguly, Jo-Anne H Young, Akshay Sharma, Giancarlo Fatobene, Tania Jain, Christopher G Kanakry, Dipenkumar Modi, Natalie S Grover, Baheyeldin Salem, Marjorie Vieira Batista, Paschalis Vergidis, Dwight E Yin, Amer M Beitinjaneh, Amar H Kelkar, Taiga Nishihori, Jennifer Holter Chakrabarty, Usama Gergis, Melody Smith, Zeinab El Boghdadly, Christopher E Dandoy, Hemant S Murthy, Anna R Huppler, Miguel-Angel Perales, Roy F Chemaly, Joshua A Hill, Marcie Riches, Jeffery J Auletta

Faculty, Staff and Students Publications

Infection is increasingly recognized as a significant cause of morbidity and mortality in patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL) receiving CD19 chimeric antigen receptor (CAR) T-cell therapy. The current study analyzed the natural history, risk factors, and outcomes of infection in 3350 patients with R/R LBCL receiving commercial CD19 CAR T-cell therapy (n = 2804 axicabtagene ciloleucel [axi-cel], n = 546 tisagenlecleucel) from December 2017 to June 2022. Infection developed in 834 patients (24.9%) within 100 days after infusion, resulting in an infection density of 0.43 per 100 patient days and a 100-day cumulative incidence of 22%. Bacterial, …

Concordance Of Cancer-Associated Cytokines And Mitochondrial Dna Deletions In Individuals With Hepatocellular Carcinoma And People Living With Hiv In Ghana, James Odame Aboagye, Ruth Ayanful-Torgby, Lei Zhou, Prince Peter Wormenor, Vincent Ganu, Kenneth Tachi, Bernard Nii Akrashie Attoh, Miriam Mensah, Timothy Kuuguu, Sedzro Kojo Mensah, George Boateng Kyei, Elijah Paintsil

2020-Current year OA Pubs

BACKGROUND: Hepatocellular carcinoma (HCC) is becoming increasingly prevalent as a non-AIDS-defining cancer closely tied to chronic HIV infection. It is associated with increased secretion of inflammatory cytokines, immune system dysfunction, and alterations in mitochondrial function. The objective of this study was to investigate the levels of cytokine secretion and mitochondrial DNA (mtDNA) deletion in people living with HIV (PLWH) compared with individuals diagnosed with HCC without HIV.

METHODS: A cross-sectional study was conducted with PLWH and HCC patients recruited from the Korle-Bu Teaching Hospital, Accra, Ghana. Participants donated whole blood for the isolation of plasma and peripheral blood mononuclear cells …

‘In Texas, Everybody Wants Antibiotics’: Reducing Inappropriate Antibiotic Expectations And Use With A Provider-Patient Communication Tool In Primary Care, Ashley Collazo, Paige Wermuth, Johanan Luna Rodriguez, Kiara Olmeda, Azalia Mancera, Fabrizia Faustinella, Michael K Paasche-Orlow, Roger Zoorob, Barbara Wells Trautner, Larissa Grigoryan

Faculty, Staff and Students Publications

Background/objective: Patients often expect antibiotics for self-limiting diseases, pressuring providers to prescribe antibiotics unnecessarily. These expectations also contribute to the unsafe practice of taking antibiotics without a prescription (non-prescription use), such as pills retained from prior prescriptions or antibiotics from non-medical sources. Previous work shows that non-prescription use is due to strong, widely held misconceptions regarding the curative power of antibiotics. To reduce unnecessary use of antibiotics, we developed and pilot-tested a patient-focused, bilingual (English and Spanish) educational tool with patient and provider stakeholder input. The tool, a trifold brochure, included information on safe antibiotic use, potential antibiotic harms and …

Chronic Rhinosinusitis Is A Risk Factor For Interstitial Lung Disease In Sjogren’S Syndrome, Brian Schonewald, Christopher Xie, Andrew Engel, Ross Summer, Giorgos Loizidis

Division of Pulmonary, Allergy, and Critical Care Medicine Faculty Papers

BACKGROUND: Interstitial lung disease (ILD) is a leading cause of morbidity and mortality in Sjögren's syndrome (SS), but its risk factors remain unclear. Although SS affects both the upper and lower respiratory epithelium, it is unknown whether this occurs simultaneously or separately. In other autoimmune conditions-such as eosinophilic granulomatosis with polyangiitis and granulomatosis with polyangiitis-upper airway disease precedes lower lung involvement by months or even years. We hypothesized that chronic rhinosinusitis (CRS), as an upper airway disease, may be a risk factor for ILD in SS.

METHODS: We analyzed the TriNetX Research Network database to compare incident ILD in SS …

Peripheral Microvascular And Cerebral White Matter Dysfunction In Schizophrenia: Implications Of A Body-Brain Endothelial Pathophysiology, Eric L Goldwaser, Alexa Yuen, Wyatt Marshall, Bhim M Adhikari, Joshua Chiappelli, Andrew Van Der Vaart, Mark Kvarta, Yizhou Ma, Xiaoming Du, Si Gao, Heather Bruce, Patrick Donnelly, Braxton Mitchell, Charles Hong, Danny J J Wang, Peter Kochunov, L Elliot Hong

Faculty, Staff and Student Publications

Background and hypothesis: Schizophrenia spectrum disorder (SSD) is a chronic neuropsychiatric illness accompanied by significant brain structural and functional abnormalities and higher rate of cardio- and cerebrovascular comorbidities. We hypothesized that genetic and environmental risk factors that led to SSD act throughout the body and demonstrated the association between lower integrity of peripheral vascular endothelium and white matter (WM) microstructure.

Study design: Microvascular endothelial function was evaluated using brachial artery post-occlusive reactive hyperemia (PORH), in which endothelial responses are measured under reduced blood flow and after blood flow is restored. White matter microstructure was assessed by multi-shell diffusion tensor imaging …

Investigating Prognostic Features In High-Grade Serous Ovarian Cancer Through Gene Regulatory Network Inference With Single-Cell Transcriptomic Profiles, Toshiyuki Itai, Yulin Dai, Wendao Liu, Dung-Fang Lee, Zhongming Zhao

Faculty, Staff and Student Publications

This study aimed to identify prognostic features in high-grade serous ovarian cancer (HGSOC) through the application of gene regulatory network (GRN) inference with single-cell RNA-sequencing (scRNA-seq) profiles. To achieve this goal, we developed a workflow comprising scRNA-seq analysis, metacell construction, GRN inference, and a binary classification task for prognosis prediction. We curated 118,173 cells from HGSOC patients in three conditions (Before-chemotherapy, After-chemotherapy, and control samples) from previous studies, and then constructed 1,211 metacells. GRN inference analysis revealed 312 regulons, each consisting of one transcription factor and its targeted features. For prognosis evaluation, we used bulk RNA-seq data covering 342 HGSOC …

Beyond Distraction: Music Therapy For Chronic Pain Management In People With Advanced Cancer, Joke Bradt, Lynn Gumert, Carrie Cottone, Ming Yuan Low, Clarissa Lacson, Kate Myers-Coffman, Karolina Bryl, Preethi Selvan, Jacelyn Biondo, Allison Millstein, Anna Cephas, Stephenie Sofield, Brooke Worster, Amy Leader

Department of Medical Oncology Faculty Papers

OBJECTIVE: Effective, non-pharmacological approaches to pain management for people with advanced cancer that can enhance quality of life while minimizing adverse effects are urgently needed. While music therapy has been demonstrated to be effective in reducing pain and improving pain-related outcomes across various patient populations, it has not been specifically examined in addressing chronic pain among people with advanced cancer. This study aims to enhance understanding of how people with advanced cancer experience music therapy for pain management.

METHODS: As part of a mixed methods intervention trial, we conducted semi-structured interviews with a subsample of 25 outpatients with advanced cancer …

A High-Density Diffuse Optical Tomography Dataset Of Naturalistic Viewing, Arefeh Sherafati, Aahana Bajracharya, Michael S Jones, Emma Speh, Monalisa Munsi, Chen-Hao P Lin, Andrew K Fishell, Tamara Hershey, Adam T Eggebrecht, Joseph P Culver, Jonathan E Peelle

2020-Current year OA Pubs

Traditional laboratory tasks offer tight experimental control but lack the richness of our everyday human experience. As a result, many cognitive neuroscientists have been motivated to adopt experimental paradigms that are more natural, such as stories and movies. Here we describe data collected from 58 healthy adult participants (aged 18-76 years) who viewed 10 minutes of a movie (The Good, the Bad, and the Ugly, 1966). Most (36) participants viewed the clip more than once, resulting in 106 sessions of data. Cortical responses were mapped using high-density diffuse optical tomography (first- through fourth nearest neighbor separations of 1.3, 3.0, 3.9, …

Ezhip Boosts Neuronal-Like Synaptic Gene Programs And Depresses Polyamine Metabolism, Elham Hasheminasabgorji, Huey-Miin Chen, Taylor A Gatesman, Subhi Talal Younes, Gabrielle A Nobles, Farhang Jaryani, Heather Mao, Kwanha Yu, Benjamin Deneen, Wee Yong, Michael D Taylor, Sameer Agnihotri, Marco Gallo

Faculty, Staff and Students Publications

It is currently understood that the characteristic loss of the repressive histone mark H3K27me3 in PFA ependymoma and diffuse midline glioma (DMG) are caused by complementary mechanisms mediated by EZHIP and the oncohistone H3K27M, respectively. To support the complementarity of these mechanisms, rare H3K27M-negative DMGs express EZHIP. Interestingly, EZHIP is one of the few genes recurrently mutated in PFA. The significance of EZHIP mutations in PFA, and whether EZHIP has wider functions in addition to repression of H3K27me3 deposition, are not known. Here, we investigated the mutational landscape of EZHIP in pediatric brain tumors. We found that EZHIP mutations occur …

Genetic Architecture And Analysis Practices Of Circulating Metabolites In The Nhlbi Trans-Omics For Precision Medicine Program, Nannan Wang, Franklin P Ockerman, Laura Y Zhou, Megan L Grove, Taryn Alkis, John Barnard, Russell P Bowler, Clary B Clish, Shinhye Chung, Emily Drzymalla, Anne M Evans, Nora Franceschini, Robert E Gerszten, Madeline G Gillman, Scott R Hutton, Rachel S Kelly, Charles Kooperberg, Martin G Larson, Jessica Lasky-Su, Deborah A Meyers, Prescott G Woodruff, Alexander P Reiner, Stephen S Rich, Jerome I Rotter, Edwin K Silverman, Ramachandran S Vasan, Scott T Weiss, Kari E Wong, Alexis C Wood, Lang Wu, Nhlbi Trans-Omics For Precision Medicine (Topmed) Consortium, Ronit Yarden, Thomas W Blackwell, Albert V Smith, Han Chen, Laura M Raffield, Bing Yu

Faculty, Staff and Students Publications

Circulating metabolite levels partly reflect the state of human health and diseases and can be impacted by genetic determinants. Hundreds of loci associated with circulating metabolites have been identified; however, most findings focus on predominantly European ancestry or single-study analyses. Leveraging the rich metabolomics resources generated by the National Heart, Lung, and Blood Institute (NHLBI) Trans-Omics for Precision Medicine (TOPMed) Program, we harmonized and accessibly cataloged 1,729 circulating metabolites among 25,058 ancestrally diverse samples. From our comparison of multiple methods, we provided a set of reasonable strategies for outlier and imputation handling to process metabolite data and show that inverse …

Use Of An Expert Panel For Symptomatic Patients With Grade I Degenerative Lumbar Spondylolisthesis: A Randomized Clinical Trial, Zoher Ghogawala, Tasneem Rizvi, Zhibang Lin, Adam Kanter, Praveen Mummaneni, Erica Bisson, Todd Albert, Daniel Resnick, Michael Wang, Steven Glassman, David Polly, Mohamad Bydon, Subu Magge, Luis Tumialan, Michael Fehlings, Michael Steinmetz, Robert Whitmore, Vedantam Rajshekhar, James Harrop, Roger Härtl, Elnasri Ahmed, Dom Coric, Paul Mccormick, Richard Assaker, Abdul Msaddi, Langston Holly, Yoshiharu Kawaguchi, Asdrubal Falavigna, Fred Barker, Edward Benzel

Department of Neurosurgery Faculty Papers

BACKGROUND AND OBJECTIVES: The appropriate utilization of lumbar fusion when performing laminectomy for lumbar spondylolisthesis is uncertain. The objective was to determine whether the use of a surgical expert review panel recommending fusion might improve patient selection, possibly reducing surgical failures.

METHODS: Randomized clinical trial of patients with symptomatic degenerative lumbar stenosis with spondylolisthesis enrolled from 14 North American hospitals was conducted with patients randomized to receive an expert panel review of their case or not. Spinal expert review consisted of 10 to 15 surgeons' review of patient images and clinical data with voting on the appropriateness of fusion. Primary …

Distinct Tumor-Associated Macrophage Signatures Shape The Immune Microenvironment And Patient Prognosis In Renal Cell Carcinoma, Youngsoo Han, Aidan Shen, Cheng-Chi Chao, Lucas Yeung, Aliesha Garrett, Jianming Zeng, Satoru Kawakita, Jesse Wang, Zhaohui Wang, Alireza Hassani, Xiling Shen, Chongming Jiang

Faculty, Staff and Student Publications

Renal cell carcinoma (RCC) accounts for 90% of adult renal cancer cases and is characterized by significant heterogeneity within its tumor microenvironment. This study tests the hypothesis that tumor-associated macrophages (TAMs) influence RCC progression and patient response to treatment by investigating the prognostic implications of TAM signatures. Utilizing independent single-cell RNA sequencing data from RCC patients, we developed eight distinct TAM signatures reflective of TAM presence. A LASSO Cox regression model was constructed to predict survival outcomes, evaluated using the TCGA dataset, and validated across independent RCC cohorts. Model performance was assessed through Kaplan-Meier survival plots, receiver operating characteristic (ROC) …

Distinguishing Syndromic And Nonsyndromic Cleft Palate Through Analysis Of Protein-Altering De Novo Variants In 818 Trios, Kelsey R Robinson, Sarah W Curtis, Justin E Paschall, Wasiu Lanre Adeyemo, Terri H Beaty, Azeez Butali, Carmen J Buxó, David J Cutler, Michael P Epstein, Lord J J Gowans, Jacqueline T Hecht, Gary M Shaw, Lina Moreno Uribe, Jeffrey C Murray, Harrison Brand, Seth M Weinberg, Mary L Marazita, Kimberly F Doheny, Elizabeth J Leslie-Clarkson

Faculty, Staff and Student Publications

De novo variants (DNs) are sporadically occurring variants found in an offspring but absent in both parents. DNs most commonly arise in the germline and are not under selective pressure; therefore, they may be enriched for disease-causing alleles. In fact, DNs have been implicated in multiple rare genetic disorders. Cleft palate (CP) is a craniofacial congenital anomaly occurring in ∼1 in 1,700 live births. Genome-wide association studies have found fewer than a dozen CP-specific loci, while exome and targeted sequencing studies in family-based and case-control cohorts often lack statistical power to conclusively identify causal variants. We therefore hypothesized that CP …

Compadre: Combined Pedigree-Aware Distant Relatedness Estimation For Improved Pedigree Reconstruction, Grahame F Evans, James T Baker, Lauren E Petty, Alexander S Petty, Hannah G Polikowsky, Ryan J Bohlender, Hung-Hsin Chen, Che-Yu Chou, Kathryn Z Viljoen, Janet M Beilby, Shelly Jo Kraft, Wanying Zhu, Joshua M Landman, Autumn R Morrow, Dayi Bian, Alyssa C Scartozzi, Chad D Huff, Jennifer E Below

Faculty, Staff and Student Publications

Designing powerful and unbiased genomic studies requires accurate assessment of familial relatedness even when this information is not captured from participants. Characterization of pairwise degrees of relatedness from participants' genetic data enables reconstruction of pedigrees, and several pedigree reconstruction tools have emerged in the last decade. However, limitations of these tools include high computational burden in large datasets, reliance on external information, reduced accuracy in admixed populations, and most notably, an inability to accurately reconstruct pedigrees when only a subset of family members is represented in the genetic data. To improve pedigree reconstruction in large-scale data and in pedigrees with …

Influenza Vaccine Effectiveness Against Medically Attended Outpatients Illness, United States, 2023-2024 Season, Jessie R Chung, Stacey L House, Tara Curley, Et Al.

2020-Current year OA Pubs

BACKGROUND: The 2023-2024 US influenza season was characterized by a predominance of A(H1N1)pdm09 virus circulation with cocirculation of A(H3N2) and B/Victoria viruses. We estimated vaccine effectiveness (VE) in the United States against mild-to-moderate medically attended influenza illness in the 2023-2024 season.

METHODS: We enrolled outpatients aged ≥8 months with acute respiratory illness in 7 states. Respiratory specimens were tested for influenza type/subtype by reverse-transcriptase polymerase chain reaction. Influenza VE was estimated with a test-negative design comparing odds of testing positive for influenza among vaccinated versus unvaccinated participants. We estimated VE by virus subtype/lineage and A(H1N1)pdm09 genetic subclades.

RESULTS: Among 6629 …

Prospective Phase Ii Clinical Trial Of Molecular Glioblastoma (Historical Grade 2 And 3 Idh Wildtype Gliomas) Preliminary Novel Exploratory Analyses: Treatment Intensification, Margin Reduction And Epigenetic Stratified Outcomes With Radiation Therapy And Chemotherapy, Debra Nana Yeboa, Benjamin T Whitfield, Ruitao Lin, Chinenye Lynette Ejezie, Todd A Swanson, Thomas H Beckham, Chenyang Wang, Brian De, Subha Perni, Martin C Tom, Jing Li, Susan L Mcgovern, Rebecca Harrison, Nazanin K Majd, Vinay K Puduvalli, Ashley E Aaroe, Monica Loghin, Barbara J O'Brien, Anuj D Patel, Chirag B Patel, Jeffrey S Wefel, Ceylan Altintas Taslicay, Maria Gule-Monroe, Arnold C Paulino, Mary Frances Mcaleer, David R Grosshans, Amol J Ghia, Wen Jiang, Caroline Chung, Moshe Maor, Cheng-Han Yang, Maria A Gubbiotti, Carlos Kamiya-Matsuoka, Leomar Y Ballester, Shiao-Pei Weathers, Jason T Huse

Faculty, Staff and Student Publications

Purpose: Molecular glioblastoma (molGBM) is a variant lacking the full histopathological profile of glioblastoma. We report a trial aimed at addressing the optimal management of this newly recognized rarer form of glioma.

Methods: In this phase II study, molGBM patients were treated with radiation to a dose of 60Gy to the gross tumor volume (GTV) only, and a single smaller margin potentially as low as 1cm to the clinical tumor volume (CTV). As the trial is ongoing, we report on important exploratory biomarker findings correlating with median overall survival (mOS). Analysis included Kaplan-Meier and univariable/multivariable cox proportional hazard models. Available …

Cofilin Inhibition Ameliorates Piezo2 And Ampa Dysfunction In A Mouse Model Of Angelman Syndrome, Luis O Romero, Manisha Bade, Elisa Carrillo, Sonia Paz-López, Syed A M Hasan, William James Antonisamy, Vasanthi Jayaraman, Zahoor A Shah, Valeria Vásquez, Julio F Cordero-Morales

Faculty, Staff and Student Publications

Angelman syndrome (AS) is a neurogenetic disorder characterized by motor coordination and cognitive deficits. In AS, hippocampal neurons show reduced filamentous (F-)actin, a decrease we also reported in dorsal root ganglia (DRG) neurons, along with impaired mechanosensitive ion channel activity. Currently, there are no pharmacological targets to prevent the decrease of F-actin in AS. Here, we utilize a first-in-class selective cofilin inhibitor (SZ-3) to restore PIEZO2 function in DRG neurons and glutamate-evoked currents in hippocampal neurons from AS mice. Using atomic force microscopy, we demonstrate that inhibiting cofilin, an actin-severing protein, with SZ-3 increases cellular stiffness by stabilizing the actin …

Mutant P53 Variants Differentially Impact Replication Initiation And Activate Cgas-Sting To Affect Immune Checkpoint Inhibition, Kang Liu, Lidija A Wilhelms Garan, Fang-Tsyr Lin, Weei-Chin Lin

Faculty, Staff and Students Publications

Prior research shows that Akt-dependent phosphorylation of TopBP1 in S phase results in the switch of TopBP1/Treslin binding to TopBP1/E2F1 binding, which is important to prevent replication re-initiation in late S and G2 phases. Here, we demonstrate that contact, but not conformational, mutant p53 can override this switch by binding to both TopBP1 and Treslin, thereby facilitating persistent TopBP1/Treslin interaction in late S and G2 phases, which ultimately leads to over-firing of replication initiation. This increases micronuclei formation, which is further enhanced by genotoxic stressors such as doxorubicin, PARP inhibitors, or ATR inhibitors. Consequently, contact mutant p53 increases the sensitivity …

Family Planning Interventions Across The League Of Arab States: A Regional Scoping Review, Basil H. Aboul-Enein, Suha Ballout, Patricia J. Kelly

College of Nursing Faculty Papers & Presentations

Family planning is crucial in improving maternal and child health, reducing fertility rates and promoting gender equity. Despite global advancements in contraceptive access, disparities persist across the League of Arab States due to sociocultural, economic and policy barriers. Understanding the effectiveness of existing family planning interventions in this region is essential for addressing unmet needs and guiding policy improvements. This scoping review aims to identify and appraise family planning interventions conducted across the League of Arab States. A comprehensive search of 14 databases was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews guidelines, focusing …