Digital Commons Network^™

A Whole-Brain Voxel-Based Analysis Of Structural Abnormalities In Ptsd: An Enigma-Pgc Study, Cheryl R Z See, Shuqing Si, C Lexi Baird, Courtney C Haswell, Ahmed Hussain, Miranda Olff, Dick J Veltman, Jessie L Frijling, Mirjam Van Zuiden, Saskia B J Koch, Laura Nawijn, Li Wang, Ye Zhu, Gen Li, Yuval Neria, Xi Zhu, Benjamin Suarez-Jimenez, Sigal Zilcha-Mano, Amit Lazarov, Jennifer S Stevens, Kerry Ressler, Negar Fani, Tanja Jovanovic, Sanne J H Van Rooij, Milissa L Kaufman, Lauren A M Lebois, Isabelle M Rosso, Elizabeth A Olson, Justin T Baker, Scott R Sponheim, Seth G Disner, Nicholas D Davenport, Amit Etkin, Adi Maron-Katz, Murray B Stein, Martha E Shenton, Dan J Stein, Jonathan Ipser, Sheri-Michelle Koopowitz, Soraya Seedat, Stefan Du Plessis, Leigh L Van Den Heuvel, Shmuel Lissek, Hannah Berg, Thomas Straube, David Hofman, Lee A Baugh, Gina L Forster, Raluca M Simons, Jeffrey S Simons, Vincent A Magnotta, Kelene A Fercho, Xin Wang, Andrew S Cotton, Erin N O'Leary, Hong Xie, Daniel W Grupe, Jack B Nitschke, Richard J Davidson, Christine L Larson, Terri A Deroon-Cassini, Carissa W Tomas, Jacklynn M Fitzgerald, Jennifer Urbano Blackford, Bunmi O Olatunji, Evan M Gordon, Geoffrey May, Steven M Nelson, Ruth Lanius, Jean Théberge, Maria Densmore, Richard W J Neufeld, Chadi G Abdallah, Christopher L Averill, Ilan Harpaz-Rotem, Ifat Levy, John H Krystal, Elbert Geuze, Remko Van Lutterveld, Emily L Dennis, David F Tate, David X Cifu, William C Walker, Elisabeth A Wilde, Nic J A Van Der Wee, Robert R J M Vermeiren, Steven J A Van Der Werff, Katie Mclaughlin, Kelly Sambrook, Matthew Peverill, Joaquim Radua, Lauren E Salminen, Neda Jahanshad, Sophia I Thomopoulos, Anthony James, Lucia Valmaggia, Paul M Thompson, Rajendra A Morey, Matthew J Kempton

Faculty, Staff and Students Publications

Background: Patients with posttraumatic stress disorder (PTSD) exhibit smaller regional brain volumes in commonly reported regions including the amygdala and hippocampus, regions associated with fear and memory processing. In the current study, we have conducted a voxel-based morphometry (VBM) meta-analysis using whole-brain statistical maps with neuroimaging data from the ENIGMA-PGC PTSD working group.

Methods: T1-weighted structural neuroimaging scans from 36 cohorts (PTSD n = 1309; controls n = 2198) were processed using a standardized VBM pipeline (ENIGMA-VBM tool). We meta-analyzed the resulting statistical maps for voxel-wise differences in gray matter (GM) and white matter (WM) volumes between PTSD patients and …

An Alternative Neural Basis Underlying Leptin Resistance, Hongli Li, Cunjin Su, Yuanzhong Xu, Mette Q Ludwig, Jon Davis, Qingchun Tong

Faculty, Staff and Student Publications

Overconsumption of a palatable Western diet, a condition linked to central leptin resistance, contributes extensively to the current obesity epidemic. In this context, intensive efforts have focused on detailing the molecular mechanisms underlying leptin resistance. Here, we demonstrate that chronic inhibition of hypothalamic arcuate GABAergic neurons (ArcGABA) effectively reduced diet-induced obesity (DIO). Interestingly, palatable food exposure increased the activity level of ArcGABA neurons, which do not express the leptin receptor (non-LepR neurons; nonresponsive to leptin). Chronic activation of ArcGABA non-LepR neurons led to massive obesity, which was associated with normal leptin-induced pSTAT3 signaling but phenotypic leptin resistance; i.e., high leptin …

Left Atrial Remodeling Parameters And Brain Natriuretic Peptide Levels In Nonvalvular Atrial Fibrillation, Osama Amin, Ahmed Alaarag, Haidy Khattab, Mahmoud Abou-Omar

Journal of the Saudi Heart Association

Objectives: Left atrial (LA) remodeling, categorized by functional and structural variations, is predominant in heart failure with preserved ejection fraction (HFpEF) and atrial fibrillation (AF). Brain natriuretic peptide (BNP) levels, implying atrial strain, may lead management by indicating LA remodeling severity. This study was instructed to correlate BNP levels with LA volume index (LAVI) in HFpEF patients with nonvalvular AF against sinus rhythm (SR), to evaluate diagnostic implications.

Methods: This two-center, observational, cross-sectional study (April 2023–October 2024) registered 340 patients with de novo HFpEF (140 AF, 200 SR). Patients with left ventricular ejection fraction (LVEF) less than 50%, valvular disease, …

The Use Of Physical Therapy In Gymnastics: A Systematic Review, Anna Bergman

Scholarly Horizons: University of Minnesota, Morris Undergraduate Journal

Gymnastics is a popular sport with hundreds of thousands of participants. Gymnastics also has a high injury rate among participants. Unfortunately, gymnastics requires specific rehabilitation and not much information exists on how to properly rehab gymnasts. The goal of this paper was to find existing literature about treating gymnasts’ injuries and analyze the results. Finally, recommendations were made in terms of future research.

Investigating The Necessity Of Adaptive Radiotherapy In Tomotherapy Of Head And Neck Cancer Patients, Ali Chaparian, Mahsa Kianinia, Mahnaz Roayaei, Nadia Najafizade, Abolfazl Kanani, Leili Mahani, Hamidreza Nourzadeh

Department of Radiation Oncology Faculty Papers

BACKGROUND: Anatomical variations that occur during radiation therapy in head and neck cancer (HNC) patients can lead to significant dosimetric changes. The purpose of this study is to evaluate dosimetric and volume changes in key anatomical structures for different treatment sites in HNC patients, and to determine the percentage of patients who need adaptive radiotherapy (ART) per treatment site.

METHODS: A total of 1,740 megavoltage computed tomography (MVCT) images from 58 HNC patients treated with helical tomotherapy (HT) were exported to the PreciseART™ (Accuray) software. Volume changes in the planning target volume (PTV) and the organs at risk (OARs) in …

Hospitalization Trends For Thromboembolic Events In Atrial Fibrillation: A 12-Year National Analysis, Moises Vasquez, Crystal Yan, Natacha Vargas, Samuel Vasquez, Litsa Lambrakos, Alex Velasquez, Jeffrey Goldberger, Raul Mitrani

Division of Cardiology Faculty Papers

BACKGROUND: Direct oral anticoagulants and percutaneous left atrial appendage occlusion (LAAO) devices were approved for use in 2010 and 2015, respectively. It is unknown to what extent, if any, these new stroke preventive therapies have impacted hospitalizations for thromboembolic (TE) events.

OBJECTIVES: To evaluate temporal trends in AF-related hospitalizations for acute ischemic stroke (AIS), transient ischemic attack (TIA), and systemic embolism (SEE) in the U.S. from 2010 to 2021.

METHODS: Using the National Inpatient Sample, we identified hospitalizations for TE events with comorbid AF. Data were grouped into two periods (2010-2015 and 2016-2021). Linear regression assessed trends in TE frequency. …

The Effect Of Tranexamic Acid On Blood Coagulation In Primary Total Hip Arthroplasty Using Rotational Thromboelastometry: A Randomized Controlled Trial, Uzung Yoon, David Beausang, Elia Elia, Marc Torjman, Jeffrey Mojica, James J. Purtill, David Nazarian, P. Maxwell Courtney, Yoogoo Kang

Department of Anesthesiology Faculty Papers

BACKGROUND: Tranexamic acid (TXA), is commonly administered prophylactically to reduce blood loss in patients undergoing total hip arthroplasty (THA). However, its effect has never been studied. We hypothesized that no difference exists in the degree of fibrinolysis and blood loss between patients receiving prophylactic TXA and placebo.

METHODS: This double-blinded randomized-controlled trial included 50 patients undergoing primary THA in 2021-2023. Clinicaltrials.gov (NCT03897621). Rotational-thromboelastometry (ROTEM) were performed to test blood coagulability using non citrated whole blood (NATEM) and blood treated with TXA (T-APTEM). The intervention group received TXA intravenously. The placebo group received 0.9% sodium chloride solution. The primary outcome measure …

Smartboot: Real-Time Monitoring Of Patient Activity Via Remote Edge Computing Technologies, Gozde Cay, Myeounggon Lee, David G Armstrong, Bijan Najafi

Center on Aging Staff Publications

Diabetic foot ulcers (DFUs) are a serious complication of diabetes, associated with high recurrence and amputation rates. Adherence to offloading devices is critical for wound healing but remains inadequately monitored in real-world settings. This study evaluates the SmartBoot edge-computing system-a wearable, real-time remote monitoring solution integrating an inertial measurement unit (Sensoria Core) and smartwatch-for its validity in quantifying cadence and step count as digital biomarkers of frailty, and for detecting adherence. Twelve healthy adults wore two types of removable offloading boots (Össur and Foot Defender) during walking tasks at varied speeds; system outputs were validated against a gold-standard wearable and …

Secondary Malignancies In Patients With Meningioma: A Surveillance, Epidemiology, And End Results Data Analysis, Maxwell W. Pickles, Thomas Z. Rohan, Shreya Vinjamuri, Nikolaos Mouchtouris, Roger Murayi, David P. Bray, James J. Evans

Department of Neurosurgery Faculty Papers

BACKGROUND: The risk of secondary primary malignancies (SPMs) in meningioma patients is not well understood. In this unidirectional analysis, we evaluated the risk of SPMs occurring following a primary diagnosis of meningioma.

METHODS: The Surveillance, Epidemiology, and End Results (SEER-17) database (2000-2020) was used to identify 124,769 meningioma patients from a total of 9,208,295 cancer cases. Standardized incidence ratios (SIRs) were calculated using SEER's statistical analysis package to evaluate SPM risk. Basic demographic and treatment information was collected as well.

RESULTS: Of the 124,769 patients, 11,411 (9.2%) received diagnoses of an SPM, which correlates to a higher risk than the …

Truncated Ntrk2 Is Induced In Cap1 Endothelial Cells During Mouse Lung Injury-Repair, Celine Shuet Lin Kong, Mitheera V, Jezreel Pantaleón-García, Scott E Evans, Jichao Chen

Faculty, Staff and Student Publications

Pulmonary capillary endothelial cells (ECs) consist of two populations, CAP1 and CAP2; how each population reacts to diverse tissue injury is incompletely understood. Using single-cell multiome and mouse genetics, we characterize the induction and function of a truncated isoform of Ntrk2, Ntrk2-T1, in multiple lung injury models. Upon Sendai parainfluenza infection, Ntrk2-T1 is broadly induced in CAP1s after the initial interferon response, associated with increased intronic chromatin accessibility, and persists for weeks. Ntrk2-T1 ECs arise from CAP1s but not CAP2s-traced by

Utility Of The Us Preventive Services Task Force For Preeclampsia Risk Assessment And Aspirin Prophylaxis, Thomas Mcelrath, Arun Jeyabalan, Arkady Khodursky, Alison Moe, Manfred Lee, Maneesh Jain, Laura Goetzl, Elizabeth Sutton, Pamela Simmons, George Saade, Antonio Saad, Luis Pacheco, Esther Park-Hwang, Antonina Frolova, Ebony Carter, Ai-Ris Collier, Daniel Kiefer, Vincenzo Berghella, Rupsa Boelig, Michal Elovitz, Cynthia Gyamfi-Bannerman, Joseph Biggio, Kara Rood, William Grobman, Carrie Haverty, Morten Rasmussen

Department of Obstetrics and Gynecology Faculty Papers

IMPORTANCE: The US Preventive Services Task Force (USPSTF) guidelines on preeclampsia risk assessment and aspirin prophylaxis (AP) have not been evaluated for clinical utility.

OBJECTIVE: To evaluate which characteristics in the USPSTF guidelines identify risk status and the association of preeclampsia risk with AP recommendations.

DESIGN, SETTING, AND PARTICIPANTS: This observational cohort study enrolled from July 2020 to March 2023 with data analysis performed from October to December 2024. Enrollment occurred at 11 centers throughout the US or via direct-to-participant recruitment. Pregnant participants aged 18 years or older with a singleton pregnancy less than 22 weeks' gestation were selected via …

Publisher Correction: Comprehensive Evaluation Of Phosphoproteomic-Based Kinase Activity Inference, Sophia Müller-Dott, Eric J Jaehnig, Khoi Pham Munchic, Wen Jiang, Tomer M Yaron-Barir, Sara R Savage, Martin Garrido-Rodriguez, Jared L Johnson, Alessandro Lussana, Evangelia Petsalaki, Jonathan T Lei, Aurelien Dugourd, Karsten Krug, Lewis C Cantley, D R Mani, Bing Zhang, Julio Saez-Rodriguez

Faculty, Staff and Students Publications

No abstract provided.

Ldt Fda Ruling: A Conundrum For Laboratories Across The Usa, Charma Henry

MSMLS Capstone Projects

Abstract

In the article “The Future of Laboratory Medicine Understanding the New Pressures," author Mauro Panteghini expresses that the clinical laboratory has always undergone significant changes due to technological advances and external economic pressures. “Laboratories are indeed an easy target for economic restrictions and limitations due to their technological characteristics.” (Panteghini, 2004, pg. 205) Though these words were written over 20 years ago, no more valid words have been spoken in light of the newest pressure all laboratories face with the new LDT regulation set by the FDA.

This regulation places drastic economic pressure on laboratories to pay the FDA …

Vibration-Based Detection For The Monitoring Of Neonatal Bcpap Respiratory Support To Minimize Duration Of Disconnections, Kaitlyn G. Calabresi, Meera R. Bhat, Lavinia L. Kong, Eli J. Foster, Jonathan Wang, Sangeeta Koilada, Angela Mak, Aastha Kapadia, Niam Mohseni, W. Keith Leung, Suneetha Desiraju, Constanza Miranda

School of Medicine Faculty Publications

Bubble continuous positive airway pressure (bCPAP) is a minimally invasive respiratory support for neonates experiencing respiratory distress syndrome (RDS). It exerts continuous, oscillatory air pressure to encourage lung function and development. Neonates’ movement may cause disconnections at the nasal interface. These disconnections are characterized by the cessation of bubbling at the bCPAP respiratory circuit output and frequently go unnoticed until hypoxia develops. Common Neonatal Intensive Care Unit (NICU) bCPAP systems lack a built-in alarm or accessory device to monitor for disconnections. As a result, nursing personnel must exercise extreme caution utilizing current bCPAP procedure. If a neonate is disconnected, it …

Specialty Grand Challenge: Existing Issues And Emerging Frontiers In Renal Endocrinology, A. T. M. Emdadul Haque, Mohammed S. Razzaque

School of Medicine Publications

We are currently in an exciting time to advance the field of renal endocrinology. There has never been a more favorable time to study the molecular and cellular mechanisms underlying renal hormone functions in physiology, pharmacology, and pathophysiology. The availability of advanced research tools provides unique opportunities to dissect the complex regulatory roles of renal hormones. The kidneys are vital organs in the human body; each one is composed of approximately one million functional nephrons. Understanding the precise roles and regulation of kidney-derived hormones and hormones that exert endocrine effects on the kidneys will help in preventing or delaying various …

Race-Neutral Pft: Implementing Patient Activation Measure Following Race- Neutral Pulmonary Function Testing, Ann M. Way

Dissertations

Abstract

Background

The introduction of a race-neutral equation to predict normal values on pulmonary function testing (PFT) has led to changes in the diagnosis of pulmonary diseases previously diagnosed using a race specific equation. Minority patients appear to be most likely impacted by this change, potentially impacting how they self-manage their pulmonary health. Patient self-management can be measured and assessed by using the Patient Activation Measure (PAM) tool.

Purpose

The purpose of this project is to assess patient activation levels amongst minority patients with a new or changed pulmonary diagnosis to identify a possible need for interventions to improve patient …

Best Practice Toolkit For Burnout Prevention In Emergency Department Nurses, Moises A. De Oleo

Student Scholarly Projects

Practice Problem: Burnout Syndrome (BS) is a serious problem in emergency department (ED) nurses and is associated with higher nurse turnover rates. A burnout prevention toolkit is needed.

PICOT: The project was guided by the following PICO question: "For emergency department nurses (P), how does the development of the best practice burnout prevention toolkit (I), compared to the absence of a structured intervention (C), support the establishment of nurse burnout best practices when evaluated using the CDC Program Evaluation Framework? (O)".

Evidence: The analysis of the literature supported the implementation of active interventions in the form of workshops.

Intervention: A …

Predictors Of Final Visual Outcome In Patients With Leber Hereditary Optic Neuropathy Treated With Lenadogene Nolparvovec Gene Therapy, Robert C Sergott, Valerio Carelli, Nancy Newman, Valérie Biousse, Patrick Yu-Wai-Man, Catherine Vignal-Clermont, Constant Josse, Magali Taiel, José-Alain Sahel, Piero Barboni

Wills Eye Hospital Papers

PURPOSE: This exploratory analysis aimed to identify predictive factors of final best-corrected visual acuity (BCVA) in patients with Leber hereditary optic neuropathy (LHON) harboring the m.11778G>A mutation who received lenadogene nolparvovec gene therapy.

METHODS: The following covariates were individually evaluated as possible factors associated with improved final BCVA: age, gender, timing of treatment, baseline BCVA value, and baseline optical coherence tomography (OCT) parameters. Univariate analyses were performed from three phase 3 studies (RESCUE, REVERSE, and REFLECT), using BCVA at 1.5 years post-treatment as the dependent variable.

RESULTS: In 113 eyes treated at least 6 months after disease onset, the …

Patient Information Needs During Ambulatory Medication Changes: A Qualitative Study, Elaine Giletta, Vanessa B. Hurley, Yushi Yang, Jessica L. Schwartz, Rabia Jalalzai, Nicole L. Mollenkopf, Raquel Mayne, Samantha I. Pitts

Journal of Patient-Centered Research and Reviews

Purpose: We performed interviews with patients and caregivers to explore whole-person, whole-regimen information needs at times of routine outpatient medication changes. We categorized information needs in this relatively unstudied context and identified which needs were commonly recognized as insufficiently met.

Methods: We explored the content of the semi-structured interviews, which involved nine patients and two caregivers of pediatric patients, all of whom experienced a recent medication change in the outpatient setting of a large urban academic healthcare system. We used inductive thematic analysis to organize information needs into categories to identify key information gaps.

Results: We identified five categories of …

Non-Invasive Telemonitoring In Heart Failure: A Systematic Review, Patrick A. Kwaah, Emmanuel Olumuyide, Kassem Farhat, Barbara Malaga-Espinoza, Ahmed Abdullah, Michael H. Beasley, Novi Y. Sari, Lily K. Stern, Julio A. Lamprea-Montealegre, Adrian Dasilva-Deabreu, Jiun-Ruey Hu

School of Medicine Publications

Background and Objectives: Heart failure (HF) represents a major public health challenge worldwide, with rising prevalence, high morbidity and mortality rates, and substantial healthcare costs. Non-invasive telemonitoring has emerged as a promising adjunct in HF management, yet its clinical effectiveness remains unclear. Materials and Methods: In this systematic review, we summarize randomized controlled trials (RCTs) between 2004 and 2024 examining the efficacy of non-invasive telemonitoring on mortality, readmission, and quality of life (QoL) in HF. In addition, we characterize the heterogeneity of features of different telemonitoring interventions. Results: In total, 32 RCTs were included, comprising 13,294 participants. While some individual …

Serum Metabolomic Profiling Of Incident Type 2 Diabetes Mellitus In The Multi-Ethnic Study Of Atherosclerosis And Rotterdam Study, Xuanwei Jiang, Fang Zhu, Gonçalo Graça, Xihao Du, Jinjun Ran, Fariba Ahmadizar, Alexis C Wood, Yanqiu Zhou, Denise M Scholtens, Ali Farzaneh, M Arfan Ikram, Alan Kuang, Carel W Le Roux, Meghana D Gadgil, Marilyn C Cornelis, Kent D Taylor, Xiuqing Guo, Mohsen Ghanbari, Laura J Rasmussen-Torvik, Russell P Tracy, Alain G Bertoni, Jerome I Rotter, David M Herrington, Philip Greenland, Maryam Kavousi, Victor W Zhong

Children’s Nutrition Research Center Staff Publications

Objective: This study aimed to investigate serum metabolomic biomarkers associated with incident type 2 diabetes mellitus (T2DM) and evaluate their performance in improving T2DM risk prediction.

Methods: Untargeted proton nuclear magnetic resonance (1H NMR) spectroscopy-based metabolomics analyses were conducted in the Multi-Ethnic Study of Atherosclerosis (MESA; n = 3460; discovery cohort) and The Rotterdam Study (RS; n = 1556; replication cohort). Multivariable cause-specific hazards models were used to analyze the associations between 23 571 serum metabolomic spectral variables and incident T2DM. Replicated metabolites required an false discovery rate-adjusted P < .01 in MESA, P < .05 in RS, and consistent direction of association. Pathway and network analyses were conducted to elucidate biological mechanisms underlying T2DM development. The utility of the replicated metabolites in improving T2DM risk prediction was assessed based on the Framingham Diabetes Risk Score. A 2-sample Mendelian randomization was conducted to assess causal associations.

Results: Nineteen metabolites were significantly associated with incident T2DM. Pathway analyses …

Role Of Lipoprotein(A) In Atherosclerotic Cardiovascular Disease In South Asian Individuals, Darshan Patel, Marlys L Koschinsky, Anandita Agarwala, Pradeep Natarajan, Harpreet S Bhatia, Anurag Mehta, Jaideep Patel, Matthew Peters, Shreya Pandya, Usman Sagheer, Raman Puri, Salim S Virani, Dinesh K Kalra

Faculty, Staff and Students Publications

South Asian individuals (SA), representing approximately one quarter of the global population, experience a disproportionately high burden of cardiovascular disease. Some of this increased susceptibility is accounted for by traditional risk factors such as diabetes, hypertension, carbohydrate-rich diets, and rising rates of obesity and metabolic syndrome. However, other previously underappreciated risk factors may also play a crucial role. These include environmental pollution, genetic factors, and Lp(a) (lipoprotein(a)). Various epidemiological and genetic studies support the role of Lp(a) as a causal and independent risk factor for atherosclerotic cardiovascular disease. SA have a higher prevalence of elevated Lp(a) levels (25% have levels …

Antitumor Efficacy Of Intermittent Low-Dose Erlotinib Plus Sulindac Via Mhc Upregulation And Remodeling Of The Immune Cell Niche, Chakrapani Tripathi, Jorge E Tovar Perez, Sabeeta Kapoor, Ahmed Muhsin, Wan Mohaiza Dashwood, Yunus Demirhan, Melek Demirhan, Alessandro Shapiro, Altaf Mohammed, Shizuko Sei, Jacklyn Thompson, Mahira Zaheer, Krishna M Sinha, Powel H Brown, Michelle I Savage, Eduardo Vilar, Praveen Rajendran, Roderick H Dashwood

Faculty, Staff and Student Publications

A previously reported clinical trial in familial adenomatous polyposis (FAP) patients treated with erlotinib plus sulindac (ERL + SUL) highlighted immune response/interferon-γ signaling as a key pathway. In this study, we combine intermittent low-dose ERL ± SUL treatment in the polyposis in rat colon (Pirc) model with mechanistic studies on tumor-associated immune modulation. At clinically relevant doses, short-term (16 weeks) and long-term (46 weeks) ERL ± SUL administration results in near-complete tumor suppression in Pirc colon and duodenum (p < 0.0001). We identify a low-dose threshold for significant antitumor activity in Pirc rats given SUL at 125 ppm in the diet plus ERL at 5 mg/kg body weight via twice-weekly oral gavage (SUL125 + ERL5 × 2). Longitudinal analyses show diminished expression of MHC class I and II genes in polyps larger than Grade 5, a novel finding in the Pirc model. Treatment with ERL ± SUL upregulates the corresponding MHC and immune-associated factors in a subset of Pirc colon polyps, Pirc tumor cell lines, murine colon carcinoma cells, and FAP patient-derived organoids, with Nlrc5 playing a critical role in this effect. Imaging mass cytometry reveals that SUL125 + ERL5 × 2 increases tumor-associated Cd4+ T cells by ~2.6-fold (p < 0.05), with no apparent effect on Cd8+ T cells. The treatment also increases tumor-associated Cd68+ cells (p < 0.05) and decreases Foxp3+ (p < 0.01) and Arg1+ (p < 0.05) cells. Thus, intermittent low-dose ERL + SUL treatment enhances tumor-associated MHC expression and remodels the immune cell niche toward a more permissive "helper" immune microenvironment. We conclude that early immune-interception strategies targeting interferon-γ signaling may benefit FAP patients at drug doses below the clinical standard of care.

Targeting The Cd40 Costimulatory Receptor To Improve Virotherapy Efficacy In Diffuse Midline Gliomas, Sara Labiano, Javier Marco-Sanz, Iker Ausejo-Mauleon, Virginia Laspidea, Reyes Hernández-Osuna, Marc Garcia-Moure, Daniel De La Nava, Sara Nuin, Marisol Gonzalez-Huarriz, Timothy N Phoenix, Ibon Tamayo, Marta Zalacain, Andrea Lacalle, Lucía Marrodan, Montserrat Puigdelloses, Irati Hervás-Corpión, Maria C Ochoa, Noelia Casares, Oren J Becher, Candelaria Gomez-Manzano, Juan Fueyo, Jaime Gallego Perez-Larraya, Ana Patiño-Garcia, Marta M Alonso

Faculty, Staff and Student Publications

Diffuse midline glioma (DMG) is a devastating pediatric brain tumor. The oncolytic adenovirus Delta-24-RGD has shown promising efficacy and safety in DMG patients but is not yet curative. Thus, we hypothesized that activating dendritic cells (DCs) through the CD40 costimulatory receptor could increase antigen presentation and enhance the anti-tumor effect of the virus, resulting in long-term responses. This study shows that the intratumoral co-administration of Delta-24-RGD and a CD40 agonistic antibody is well tolerated and induces long-term anti-tumor immunity, including complete responses (up to 40%) in DMG preclinical models. Mechanistic studies revealed that this therapy increased tumor-proliferating T lymphocytes and …

The Integrated Stress Response Pathway Coordinates Translational Control Of Multiple Immune Checkpoints In Lung Cancer, Shayna Thomas-Jardin, Shruthy Suresh, Ariana Arce, Nicole Novaresi, Qing Deng, Emily Stein, Lisa Thomas, Cheryl Lewis, Chul Ahn, Bret M Evers, Esra A Akbay, Maria E Salvatierra, Wei Lu, Khaja Khan, Luisa M Solis Soto, Ignacio I Wistuba, John D Minna, Kathryn A O'Donnell

Faculty, Staff and Student Publications

The integrated stress response (ISR) is an adaptive pathway hijacked by cancer cells to survive cellular stresses in the tumor microenvironment. ISR activation potently induces PD-L1, leading to suppression of antitumor immunity. In this study, we sought to uncover additional immune checkpoint proteins regulated by the ISR to elucidate mechanisms of tumor immune escape. The ISR coordinately induced cluster of differentiation 155 (CD155) and PD-L1, enhancing translation of both immune checkpoint proteins through bypass of inhibitory upstream open reading frames in their 5' untranslated regions. Analysis of primary human lung tumors identified a significant correlation between expression of PD-L1 and …

The Feasibility Of Passively Tracking Children’S Tv Viewing And Mobile Device Use In Naturalistic Settings, Teresia M O'Connor, Tatyana Garza, Uzair Alam, Anil Kumar Vadathya, Jennette P Moreno, Alicia Beltran, Samah Haidar, Nimah Haidar, Sheryl O Hughes, Debbe Thompson, Salma M A Musaad, Tom Baranowski, Jason A Mendoza, Joseph Young, Akane Sano, Ashok Veeraraghavan

Faculty, Staff and Students Publications

Research on children's technology and digital media (TDM) is hampered by a lack of robust approaches for assessing TDM use. This study assessed the feasibility of passively measuring children's TV screens and mobile devices (TDM) in a naturalistic setting. In the three-day feasibility study, FLASH-TV was set up on one to two TVs the child (5-12 year olds) typically used in the home (n=20). Children's mobile device use was assessed with either the Chronicle App or ScreenTime screenshots. Parents completed three TDM diaries. An exit interview with the parent explored their perceptions of the assessments and the child's TDM use …

Digitally Fabricated Interocclusal Wafer Versus Wafer-Less Distal Segment Repositioning For Bilateral Sagittal Split Osteotomy (Bsso) In Skeletal Mandibular Deformities (Randomized Controlled Trial), Hesham Osama Morsi Ass.Lect., Mohammed Abdelsalam Omara Ass.Prof., Mostafa Ibrahim Shindy Prof, Galal Gamal El Behairy Prof.

Dentistry

Objective: This study aimed to compare the accuracy of condylar positioning between 2 computer-guided orthognathic surgical protocols: a waferless screw hole plate locating (WSL CPD) technique versus an occlusal splint with distal extending arms (OWDA-CPD) approach. Materials and Methods: Twenty-four patients requiring mandibular orthognathic surgery (class II or III deformities) were randomly allocated into 2 groups (n=12 each). Group I underwent a waferless protocol utilizing 3D-printed osteotomy and screw hole locating guides, while group II received an occlusal splint with distal extensions for condylar positioning. Preoperative and postoperative cone-beam computed tomography (CBCT) scans were used to assess condylar displacement in …

The Current And Future Burden Of Long Covid In The United States, Sarah M Bartsch, Kevin L Chin, Ulrich Strych, Danielle C John, Tej D Shah, Maria Elena Bottazzi, Kelly J O'Shea, Mckaylee Robertson, Colleen Weatherwax, Jessie Heneghan, Marie F Martinez, Allan Ciciriello, Sarah Kulkarni, Kavya Velmurugan, Alexis Dibbs, Sheryl A Scannell, Yanhan Shen, Denis Nash, Peter J Hotez, Bruce Y Lee

Faculty, Staff and Students Publications

Background: Long coronavirus disease (COVID), which affects an estimated 44.69-48.04 million people in the United States, is an ongoing public health concern that will persist as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread.

Methods: We developed a computational simulation model representing the clinical course, health effects, and associated costs of a person with long COVID.

Results: Simulations show that the average total cost of a long COVID case can range from $5084-$11 646 (assuming symptoms only last 1 year) with 92.5%-95.2% of these costs being productivity losses. Therefore, the current number of long COVID cases could cost …

Oral Dosing Of The Nucleoside Analog Obeldesivir Is Efficacious Against Rsv Infection In African Green Monkeys, Jared Pitts, J Lizbeth Reyes Zamora, Savrina Manhas, Thomas Aeschbacher, Josolyn Chan, Vincent Cutillas, Varsha Nair, Nicholas C Riola, Arya Vijjapurapu, Meghan S Vermillion, Stacey Eng, Christopher Richards, Dong Han, Jason K Perry, Subhra Chaudhuri, Szu-Wen Liu, Clarissa Martinez, Nadine Peinovich, Kai-Hui Sun, Arthur Cai, Ross Martin, Jasmine Moshiri, Charlotte Hedskog, Darius Babusis, Dustin S Siegel, Rao Kalla, Vasanthi Avadhanula, Pedro A Piedra, Kim Stobbelaar, Peter L Delputte, Caleb Marceau, Roberto Mateo, Evguenia Maiorova, Hongmei Mo, Raju Subramanian, Richard L Mackman, Tomas Cihlar, Simon P Fletcher, John P Bilello

Faculty, Staff and Students Publications

Respiratory syncytial virus (RSV) is a significant cause of morbidity and mortality in high-risk populations. Although prophylactic options are available, there are no effective oral therapeutics for RSV infection. Obeldesivir (ODV) is an orally bioavailable prodrug of the nucleoside analog GS-441524, which is converted intracellularly to its active nucleoside triphosphate and inhibits the RSV RNA polymerase. Here we report the potent antiviral activity of ODV against geographically and temporally diverse RSV A and B clinical isolates (EC50: 0.20–0.66 μM). Resistance selection studies with ODV and GS-441524 against RSV identify a single amino acid substitution, I777L, in the L polymerase with …

Hepatitis Patients Undergoing Cardiac Surgery: A Single-Center Retrospective Study, Jin-Long Ju, Yun-Tai Yao, Jun Li, Zhi Cheng, Ling-Ling Fan, Yu-Long Zhong

Faculty, Staff and Student Publications

This study aimed to investigate whether there is difference among various clinical variables, especially blood loss and total drainage volume, among patients with different types of hepatitis undergoing cardiac surgery. A retrospective study was performed on 150 hepatitis patients (127 hepatitis B and 23 hepatitis C) who underwent cardiac surgery at a single cardiovascular center in 2020. Data on their preoperative, intraoperative, and postoperative variables were collected and statistically analyzed to assess the inter-group differences in the following variables: intraoperative blood loss, postoperative drainage volume, proportion of patients treated with blood transfusion, proportion of patients treated with vasoactive drugs, and …