Digital Commons Network^™

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 …

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 …

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, …

Preclinical Efficacy Of Tasquinimod-Based Combinations In Advanced Myeloproliferative Neoplasms In Blastic Phase, Warren Fiskus, Lucia Masarova, Christopher P Mill, Christine E Birdwell, Kaberi Das, Hanxi Hou, John A Davis, Antrix Jain, Anna Malovannaya, Taghi Manshouri, Andrew Dunbar, Surbhi Sharma, Tapan M Kadia, Courtney D Dinardo, Prithviraj Bose, Naveen Pemmaraju, Sanam Loghavi, Xiaoping Su, Raajit K Rampal, Marie Törngren, Kapil N Bhalla

Faculty, Staff and Students Publications

The alarmins, S100A8 (A8) and S100A9 (A9), are low molecular weight proteins belonging to the S100 protein family. A8 and A9 are secreted into the extracellular space and plasma, in which they interact with Toll-like receptor 4, receptor for advanced glycation end products, and CD33. In these studies, we determined the preclinical efficacy of tasquinimod (TQ) against advanced myeloproliferative neoplasm (MPN) cell lines and patient-derived (PD) CD34+ blastic phase (BP; >5% blasts in the peripheral blood) MPN cells. TQ induced loss of viability in cell lines and PD MPN-BP cells, but not in normal CD34+ progenitor cells. In TQ-treated PD …

‘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 …

Cgas-Agonistic Spherical Nucleic Acids Reprogram The Glioblastoma Immune Microenvironment And Promote Antitumor Immunity, Akanksha S Mahajan, Corey Dussold, Seunghyun Kim, Rachel Jarvis, Lisa A Hurley, Serena Tommasini-Ghelfi, Jungsoo Park, Connor M Forsyth, Bin Zhang, Jason Miska, Amy B Heimberger, Chad A Mirkin, Alexander H Stegh

2020-Current year OA Pubs

The cyclic GMP-AMP synthase-Stimulator of Interferon Genes (cGAS-STING) pathway is an important DNA-sensing mechanism that increases T cell trafficking and activation in tumors and reverses the immunosuppressive phenotype of myeloid cells. Therefore, direct STING targeting using synthetic cyclic dinucleotides (CDNs) is an attractive strategy for treating lymphocyte-depleted and myeloid cell-enriched tumors, such as glioblastoma (GBM). However, inadequate bioavailability and poor cellular accumulation limit the clinical development of CDNs, particularly for noninvasive administration strategies. Spherical nucleic acids (SNAs) have emerged as promising modular constructs for creating therapeutic lead compounds for many diseases, including different forms of cancer. Here, we report the …

Protocol For A Multicenter, Cluster-Randomized, Stepped-Wedge, Implementation Trial Of A Prehospital Sepsis Protocol, Shamie Das, Stacey House, Melissa Kroll, Et Al.

2020-Current year OA Pubs

BACKGROUND: Sepsis is a common, life-threatening medical emergency in which early recognition and treatment are cornerstones of management. Best practice guidelines recommend standardized sepsis screening in hospitals to facilitate early recognition. In contrast, very little is known about the efficacy and safety of standardized sepsis screening in the prehospital Emergency Medical Services (EMS) environment. To help address this knowledge gap, this study protocol will evaluate the impact of implementing an evidence-based sepsis protocol in ambulances.

METHODS: We plan to conduct a multicenter, stepped-wedge, cluster-randomized trial at 3 sites and enroll 984 participants over 24 months. EMS personnel will be trained …

A Prodrug Strategy For Sustained Release Of Lactic Acid From Silicone Elastomer Vaginal Rings., Yahya H. Dallal Bashi, Xinyu Zhao, Clare F. Mccoy, Narender Kumar, Natalia Teleshova, Dolores J. Lamb, José A. Fernández Romero, Abigail Meyer, Patrick Barnable, Meropi Aravantinou, Osaretin E. Asowata, Melissa A. White, Alexander J. Travis, Lisa B. Haddad, Xin Shen, Vicky-Leigh Young, Peter Boyd, R Karl Malcolm

Manuscripts, Articles, Book Chapters and Other Papers

Lactic acid is the most abundant organic weak acid in the healthy human vagina and plays a pivotal role in maintaining an acidic vaginal environment protective against exogenous bacteria and viruses. However, in dysbiotic or non-optimal vaginal environments, significantly decreased concentrations of lactobacilli result in reduced lactic acid production, increased vaginal pH, and enhanced risk of sexually transmitted infections (including human immunodeficiency virus), and bacterial vaginosis. Various gel-based products are marketed to administer lactic acid vaginally for the treatment of bacterial vaginosis and non-hormonal contraception, and there is interest in developing vaginal ring products for sustained/controlled release of lactic acid. …

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 …

Genome-Wide Crispr Screens Identify Critical Targets To Enhance Car-Nk Cell Antitumor Potency, Alexander Biederstädt, Rafet Basar, Jeong-Min Park, Nadima Uprety, Rejeena Shrestha, Francia Reyes Silva, Merve Dede, John Watts, Sunil Acharya, Donghai Xiong, Bin Liu, May Daher, Hind Rafei, Pinaki Banerjee, Ping Li, Sanjida Islam, Huihui Fan, Mayra Shanley, Jingling Jin, Bijender Kumar, Vernikka Woods, Paul Lin, Silvia Tiberti, Ana Karen Nunez Cortes, Xin Ru Jiang, Inci Biederstädt, Patrick Zhang, Ye Li, Seema Rawal, Enli Liu, Luis Muniz-Feliciano, Gary M Deyter, Elizabeth J Shpall, Natalie Wall Fowlkes, Ken Chen, Katayoun Rezvani

Faculty, Staff and Student Publications

Adoptive cell therapy using engineered natural killer (NK) cells is a promising approach for cancer treatment, with targeted gene editing offering the potential to further enhance their therapeutic efficacy. However, the spectrum of actionable genetic targets to overcome tumor and microenvironment-mediated immunosuppression remains largely unexplored. We performed multiple genome-wide CRISPR screens in primary human NK cells and identified critical checkpoints regulating resistance to immunosuppressive pressures. Ablation of MED12, ARIH2, and CCNC significantly improved NK cell antitumor activity against multiple treatment-refractory human cancers in vitro and in vivo. CRISPR editing augmented both innate and CAR-mediated NK cell function, associated with enhanced …

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 …

Development Of A Targeted Bioprotac Degrader Selective For Misfolded Sod1, Christen G Chisholm, Rachael Bartlett, Mikayla L Brown, Emma-Jayne Proctor, Natalie E Farrawell, Jody Gorman, Fabien Delerue, Lars M Ittner, Kara L Vine-Perrow, Heath Ecroyd, Neil R Cashman, Darren N Saunders, Luke Mcalary, Jeremy S Lum, Justin J Yerbury

Faculty, Staff and Student Publications

The accumulation of misfolded proteins underlies a broad range of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Due to their dynamic nature, these misfolded proteins have proven challenging to target therapeutically. Here, we specifically target misfolded disease variants of the ALS-associated protein superoxide dismutase 1 (SOD1), using a biological proteolysis targeting chimera (BioPROTAC) composed of a SOD1-specific intrabody and an E3 ubiquitin ligase. Screening of intrabodies and E3 ligases for optimal BioPROTAC construction reveals a candidate capable of degrading multiple disease variants of SOD1, preventing their aggregation in cells. Using CRISPR/Cas9 technology to develop a BioPROTAC transgenic mouse line, we …

Dissemination Of A Facilitation Strategy To De-Implement Unnecessary Post-Operative Antibiotics At Children's Hospitals: The Optimizing Perioperative Antibiotic In Children (Operatic) Trial 2.0, Emmanuel K Tetteh, Harry Obeng, Andrew Atkinson, Sara Malone, Matt Sattler, Tyler Walsh, Lauren Walsh, Jacqueline M Saito, Shawn J Rangel, Jason G Newland, Virginia R Mckay

2020-Current year OA Pubs

BACKGROUND: Excessive postoperative antibiotic use in pediatric surgical patients contributes to antibiotic resistance and increases the risk of Clostridioides difficile infection. Despite established guidelines recommending limited postoperative antibiotic duration, many hospitals struggle with de-implementation. This study aims to disseminate and evaluate the impact of a combined strategy to reduce unnecessary postoperative antibiotic use which combines enhanced antimicrobial stewardship program facilitation, defined as a set of actions to enable implementation, combined with order set review and modification. This multi-center study builds on an initial stepped wedge cluster randomized trial involving nine children's hospitals, where facilitation training improved implementation of surgical prophylaxis …

Use And Reporting Of Intervention Mapping For Adaptation: A Systematic Review Protocol, Eunyoung Kang, Hugo R Sánchez-Blas, Elizabeth O Obekpa, Maria E Fernandez

Faculty, Staff and Student Publications

Introduction: Intervention adaptation is likely to occur to some extent when implementing interventions in new implementation contexts. Using systematic frameworks can guide intentional and effective adaptation processes. Intervention Mapping for Adaptation (IM-ADAPT) is a framework that offers step-by-step guidance for systematic, theory-based intervention adaptation. Despite the increasing use of IM-ADAPT, there is limited understanding of the contexts in which it has been applied and how effectively it is used and reported. Addressing this knowledge gap can improve current adaptation practices and inform future enhancements of the IM-ADAPT framework and the broader science of intervention adaptation. This review aims to (1) …

Glucagon-Like Peptide 1 Receptor Agonists And The Clinical Outcomes Of Inflammatory Bowel Disease: A Systematic Review And Meta-Analysis, Ahmed B Bayoumy, Lindsay M Clarke, Parakkal Deepak, Aakash Desai, Priya Sehgal, Uri Gorelik, Haggai Bar-Yoseph, Marie Villumsen, Chris J J Mulder, Dirk J Stenvers, Maarten E Tushuizen, Nanne K H De Boer

2020-Current year OA Pubs

BACKGROUND: Prior studies showed worse outcomes in obese inflammatory bowel disease (IBD) patients, especially those related to hospitalizations, surgery, and steroid-free remission. Glucagon-like peptide-1 receptor agonists (GLP1-RAs) have demonstrated significant metabolic benefits for patients with type 2 diabetes mellitus (T2DM) and obesity. Hence, GLP1-RAs may improve clinical outcomes in patients with IBD, especially those with obesity. The objective was to systematically evaluate the impact of GLP1-RAs on clinical outcomes in patients with IBD.

METHODS: A comprehensive literature search was performed using the databases PubMed, Embase, Web of Science, and Cochrane Library from inception to March 15, 2025. Studies reporting outcomes …

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 …

Comparative Risk Of End-Stage Renal Disease, Myocardial Infarction And Stroke In Young And Older Onset Diabetes In Uk Biobank, Debasish Kar, Mariam Molokhia, Anthony Wierzbicki, Ania Koziell, Richard Byng, Stuart Spicer, Nicolas Farina, Jonathan Pinkney, Soon Song, Bedowra Zabeen, Shubharthi Kar, Jitendra Jonnagaddala, Siaw-Teng Liaw, Aya El-Wazir, Mintu Nath, Moien Khan, Aziz Sheikh, Simon De Lusignan

Peninsula Medical School

In recent years, coinciding with the increasing incidence of type 2 diabetes mellitus (T2DM) in children and adolescents, the global prevalence of diabetic kidney disease (DKD) and end-stage renal disease (ESRD) are rising year on year. In contrast, the mortality and morbidity due to cardiovascular disease (CVD) and stroke in people with diabetes have been declining. The precise cause of the disparate vascular outcomes in diabetes remains unexplored. To elucidate the relationship, we conducted a retrospective cohort study on the UK Biobank data. In our study, the exposure variables were the age of diabetes and hypertension diagnosis, while the outcome …

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 …

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, …

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 …

Rising Metastatic Prostate Cancer Rates But Narrowing Racial Gap, Hanna Zurl, Zhiyu Qian, Klara K Pohl, Andrea Piccolini, Stephan M Korn, Muhieddine Labban, Stuart R Lipsitz, Mansoo Cho, Sean A Fletcher, Marianne Leitsmann, Sascha Ahyai, Quoc-Dien Trinh, Alexander P Cole

Faculty, Staff and Student Publications

Background: In recent years, there has been considerable interest in addressing racial disparities in prostate cancer (PCa) care including risk-adapted screening. This study examined trends in metastatic PCa incidence by race and placed them in context of changes in PSA screening recommendations.

Methods: We analyzed metastatic PCa incidence trends by race (using Surveillance Epidemiology and End Results data, 2005-2021) and PSA screening trends (using Behavioral Risk Factors Surveillance Survey data, 2012-2020). We fitted a generalized linear model with an interaction term for race and year of diagnosis and calculated annual incidence rate ratios (metastatic disease) and odds ratios (screening) for …

Advancing Delirium Detection Through The Open Health Natural Language Processing Consortium And The Evolve To Next-Gen Accrual To Clinical Trials Network, Sunyang Fu, Min Ji Kwak, Jaerong Ahn, Zhiyi Yue, Shreyas Ranganath, Joseph R Applegate, Andrew Wen, Liwei Wang, Chenyu Li, Michele Morris, Kelly M Toth, Timothy D Girard, John D Osborne, Richard E Kennedy, Nelly-Estefanie Garduno-Rapp, Phillip Reeder, Justin F Rousseau, Chao Yan, You Chen, Mayur B Patel, Tyler J Murphy, Bradley A Malin, Chan Mi Park, Heling Jia, Sandeep Pagali, Allyson K Palmer, Jennifer St Sauver, Sunghwan Sohn, Elmer V Bernstam, Shyam Visweswaran, Yanshan Wang, Hongfang Liu

Faculty, Staff and Student Publications

Background: Delirium is often underdiagnosed in clinical practice and is not routinely coded for billing. While manual chart review can identify delirium, it is labor-intensive and impractical for large-scale studies. Natural language processing (NLP) can analyze unstructured text in electronic health records (EHRs) to extract meaningful clinical information.

Methods: To support national integration of NLP for EHR-based delirium identification across different institutions, we launched the Delirium Interest Group within the national Evolve to Next-Gen Accrual to Clinical Trials (ENACT) NLP Working Group. This paper outlines our initial efforts to standardize, evaluate, and translate an NLP-based delirium detection model into the …

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 …

Updated Systematic Review Of Current Randomised Controlled Trials In Chronic Subdural Haematoma, On Be Half Of The International Collaborative Research Initiative On Chronic Subdural Haematoma (Icoric) Study Group, R Fakhry, C Yesildal, J Bartek, J Duerinck, T S R Jensen, J Soleman, C Iorio-Morin, C M F Dirven, R Dammers, E Edlmann, D C Holl

Peninsula Medical School

BACKGROUND: Chronic subdural haematoma (CSDH) is a common neurosurgical condition with an increasing incidence due to an aging population. Given the expanding research landscape, assessing the state of recent trials is essential. This systematic review updates a previous review, which included randomised controlled trials (RCTs) up to 2019, by summarizing recently published and ongoing RCTs in CSDH, highlighting key areas of investigation and identifying directions for future research. METHODS: Clinical trial registries - including the Cochrane Controlled Register of Trials, WHO ICTRP, clinicaltrials.gov, and Clinical Trials Information System - were systematically searched for RCTs on CSDH from June 1, 2019, …