Digital Commons Network^™

Antibody-Drug Conjugates Targeting The Egfr Ligand Epiregulin Elicit Robust Antitumor Activity In Colorectal Cancer, Joan Jacob, Yasuaki Anami, Peyton C High, Zhengdong Liang, Shraddha Subramanian, Sukhen C Ghosh, Solmaz Aghaamiri, Cara Guernsey-Biddle, Ha Tran, Julie Rowe, Ali Azhdarinia, Kyoji Tsuchikama, Kendra S Carmon

Faculty, Staff and Student Publications

As colorectal cancer remains a leading cause of cancer-related death, identifying therapeutic targets and approaches is essential to improve patient outcomes. The EGFR ligand epiregulin (EREG) is highly expressed in RAS wild-type (WT) and mutant colorectal cancer, with minimal expression in normal tissues, making it an attractive target for antibody-drug conjugate (ADC) development. In this study, we produced and purified an EREG mAb, H231, which had high specificity and affinity for human and mouse EREG. H231 also internalized to lysosomes, which is important for ADC payload release. ImmunoPET and ex vivo biodistribution studies showed significant tumor uptake of zirconium-89-labeled H231, …

Researcher Perceptions Of Inclusion Of Study Participants Who Use Languages Other Than English., Henry Hoffman, Tran T. Doan, Olivia Migliori, Alisa Khan, Jaime Sidani, Sabrina Liu, Abby Jo Perez, Lani Mears, Benoit Kihumbu, Khara Timsina, Diego Chaves-Gnecco, John Cowden, Maya I. Ragavan

Manuscripts, Articles, Book Chapters and Other Papers

IMPORTANCE: Despite constituting 8% of the US population, people who speak languages other than English (LOE) are consistently underrepresented in health-focused research. To make research more inclusive and generalizable, it is crucial to better understand researcher perspectives on barriers to inclusion of participants using LOE and solutions to promote language justice.

OBJECTIVE: To assess researcher perspectives on barriers to and best practices for inclusion of participants using LOE and to generate strategies to make research more inclusive.

DESIGN, SETTING, AND PARTICIPANTS: This exploratory cross-sectional survey study used an anonymous digital Qualtrics survey distributed between March 1 and June 30, 2023. …

First-In-Human Clinical Trial Of A Small-Molecule Ebna1 Inhibitor, Vk-2019, In Patients With Epstein-Barr-Positive Nasopharyngeal Cancer, With Pharmacokinetic And Pharmacodynamic Studies, A Dimitrios Colevas, Zahra Talebi, Elizabeth Winters, Caroline Even, Victor Ho-Fun Lee, Maura L Gillison, Saad A Khan, Rong Lu, Benjamin A Pinsky, Samantha S Soldan, Olga Vladmirova, Paul M Lieberman, Troy E Messick

Faculty, Staff and Student Publications

Purpose: A first-in-human phase I study was conducted in patients with nasopharyngeal carcinoma to assess the safety and tolerability of VK-2019, a small-molecule selective inhibitor of Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1).

Patients and methods: Pharmacokinetic and pharmacodynamic studies were performed, including the measurement of EBV DNA plasma levels. Twenty-three patients received VK-2019 orally once daily at doses ranging from 60 to 1,800 mg using an accelerated titration design, with cohort expansion at 1,800 mg. EBV genome copy number and spatial transcriptomic analyses were conducted on biopsies collected from three patients at baseline and after treatment.

Results: VK-2019 was …

Ancestral Differences In Anticancer Treatment Efficacy And Their Underlying Genomic And Molecular Alterations, Mei Luo, Jingwen Yang, Alejandro A Schäffer, Chengxuan Chen, Yuan Liu, Yamei Chen, Chunru Lin, Lixia Diao, Yong Zang, Yanyan Lou, Huda Salman, Gordon B Mills, Eytan Ruppin, Leng Han

Faculty, Staff and Student Publications

Systematic multi-omics analysis revealed ancestry-dependent molecular alterations, but their impact on the efficacy of anti-cancer treatment is yet largely unknown. Here, we analyzed clinical trials from ClinicalTrials.gov and found that only 8,779/102,721 (8.5%) oncology clinical trials posted information on enrollment by race/ethnicity. The underrepresentation of non-White populations suggests that it remains challenging to determine differences in the efficacy of anti-tumor treatments among different racial groups. Through a comprehensive analysis of clinically actionable genes, imputed drug responses, and immune features, we identified potential differences in treatment response to targeted, chemo and immunotherapies between different ancestral populations. Further analysis of multiple independent …

Pleural Effusion: Shedding Light On Pleural Disease Beyond Infection And Malignancy, William C Harding, Abdul R Halawa, Mazen M Aiche, Bilal Zafar, Hyeon-Ju R Ali, Lara Bashoura, Saadia A Faiz

Faculty, Staff and Student Publications

Background and Objectives: Non-malignant pleural effusions (NMPEs) are the most frequently encountered pleural disease. They arise from various non-malignant, non-infectious clinical conditions, including cardiac, renal, and hepatic organ dysfunction. Despite their wide prevalence, there is a lack of literature for NMPE. This publication aims to provide an updated overview of the causes, diagnostic strategies, and management options for NMPE.

Materials and Methods: This review synthesizes findings from studies published on NMPE, focusing on the presentation, diagnosis (such as imaging and pleural fluid analysis), and management strategies. Studies were selected based on relevance and were analyzed to provide a comprehensive summary …

Targeted Normoxemia And Supplemental Oxygen-Free Days In Critically Injured Adults: A Stepped-Wedge Cluster Randomized Clinical Trial, David J Douin, John D Rice, Erin L Anderson, Conner L Jackson, Alex C Cheng, Mengli Xiao, Jessica Cwik, Laurel E Beaty, Jessica L Wild, Mohamud R Daya, Pratik B Doshi, Shannon C Eastham, Michael D Goodman, Scott R Gunn, Jason S Haukoos, Jessica A Hudson, Jan O Jansen, Jason T Mcmullan, Julie A Rizzo, Martin A Schreiber, Wesley H Self, Matthew W Semler, Aimee Steinwand, Nicole Werner, Vikhyat S Bebarta, Steven G Schauer, Adit A Ginde

Faculty, Staff and Student Publications

Importance: Supplemental oxygen is fundamental to caring for critically injured adults but can expose them to excess inspired oxygen.

Objective: To determine the safety and effectiveness of targeting normoxemia in critically ill trauma patients.

Design, setting, and participants: This multicenter, stepped-wedge, cluster randomized clinical trial compared targeted normoxemia (defined as a peripheral oxygen saturation [Spo2] of 90% to 96%) with usual care among adult trauma patients admitted to an intensive care unit (ICU) at 8 level I trauma centers across the US. These trauma centers were randomized at 3-month intervals when they crossed over from usual care to targeting normoxemia. …

Accumulation Of Cd38 In Hybrid Epithelial/Mesenchymal Cells Promotes Immune Remodeling And Metastasis In Breast Cancer, Tanvi H Visal, Recep Bayraktar, Petra Den Hollander, Michael A Attathikhun, Tieling Zhou, Jing Wang, Li Shen, Corina-Elena Minciuna, Meng Chen, Elizve Barrientos-Toro, Harsh Batra, Maria Gabriela Raso, Fei Yang, Edwin R Parra, Aysegul A Sahin, George A Calin, Sendurai A Mani

Faculty, Staff and Student Publications

Triple-negative breast cancer (TNBC) is a highly metastatic subtype of breast cancer. The epithelial-to-mesenchymal transition is a nonbinary process in the metastatic cascade that generates tumor cells with both epithelial and mesenchymal traits known as hybrid EM cells. Recent studies have elucidated the enhanced metastatic potential of cancers featuring the hybrid EM phenotype, highlighting the need to uncover molecular drivers and targetable vulnerabilities of the hybrid EM state. Here, we discovered that hybrid EM breast tumors are enriched in CD38, an immunosuppressive molecule associated with worse clinical outcomes in liquid malignancies. Altering CD38 expression in tumor cell impacted migratory, invasive, …

A Novel Sensitivity Maximization At A Given Specificity Method For Binary Classifications, Seyyed Mahmood Ghasemi, Chunhui Gu, Johannes F Fahrmann, Samir Hanash, Kim-Anh Do, James P Long, Ehsan Irajizad

Faculty, Staff and Student Publications

In the cancer early detection field, logistic regression (LR) is a frequently used approach to establish a combination rule that differentiates cancer from noncancer. However, the application of LR relies on a maximum likelihood approach, which may not yield optimal combination rules for maximizing sensitivity at a clinically desirable specificity and vice versa. In this article, we have developed an improved regression framework, sensitivity maximization at a given specificity (SMAGS), for binary classification that finds the linear decision rule, yielding the maximum sensitivity for a given specificity or the maximum specificity for a given sensitivity. We additionally expand the framework …

Connectome-Based Predictive Modeling Of Ptsd Development Among Recent Trauma Survivors, Ziv Ben-Zion, Alexander J Simon, Matthew Rosenblatt, Nachshon Korem, Or Duek, Israel Liberzon, Arieh Y Shalev, Talma Hendler, Ifat Levy, Ilan Harpaz-Rotem, Dustin Scheinost

Staff and Researcher Publications

Importance: The weak link between subjective symptom-based diagnostics for posttraumatic psychopathology and objective neurobiological indices hinders the development of effective personalized treatments.

Objective: To identify early neural networks associated with posttraumatic stress disorder (PTSD) development among recent trauma survivors.

Design, setting, and participants: This prognostic study used data from the Neurobehavioral Moderators of Posttraumatic Disease Trajectories (NMPTDT) large-scale longitudinal neuroimaging dataset of recent trauma survivors. The NMPTDT study was conducted from January 20, 2015, to March 11, 2020, and included adult civilians who were admitted to a general hospital emergency department in Israel and screened for early PTSD symptoms indicative …

Geographic Access To Cancer Care And Treatment And Outcomes Of Early-Stage Non-Small Cell Lung Cancer, Pratibha Shrestha, Ying Liu, James Struthers, Benjamin Kozower, Min Lian

2020-Current year OA Pubs

IMPORTANCE: Data on the impact of geographic access to cancer care on early-stage non-small cell lung cancer (NSCLC) treatment and outcomes are limited.

OBJECTIVE: To examine the associations of geographic access to cancer care with guideline-recommended treatment and outcomes in patients with early-stage NSCLC.

DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study included patients with early-stage NSCLC newly diagnosed between January 1, 2007, and December 31, 2015, followed up through December 31, 2016, and identified from the Surveillance, Epidemiology, and End Results dataset. Data analysis was performed from March to November 2024.

EXPOSURES: Geographic access to thoracic surgeons and radiation …

Assessment Of The Sensitivity Of A Smartphone App To Assist Patients In The Identification Of Stroke And Myocardial Infarction: Cross-Sectional Study, Amar Dhand, Rama Mangipudi, Anubodh S Varshney, Jonathan R Crowe, Andria L Ford, Nancy K Sweitzer, Min Shin, Samuel Tate, Haissam Haddad, Michael E Kelly, James Muller, Jay S Shavadia

2020-Current year OA Pubs

BACKGROUND: Most people do not recognize symptoms of neurological and cardiac emergencies in a timely manner. This leads to delays in hospital arrival and reduced access to therapies that can open arteries. We created a smartphone app to help patients and families evaluate if symptoms may be high risk for stroke or heart attack (myocardial infarction, MI). The ECHAS (Emergency Call for Heart Attack and Stroke) app guides users to assess their risk through evidence-based questions and a test of weakness in one arm by evaluating finger-tapping on the smartphone.

OBJECTIVE: This study is an initial step in the accuracy …

Sex Differences In Apolipoprotein E And Alzheimer Disease Pathology Across Ancestries, Xiaoyi Xu, Jiseon Kwon, Ruiqi Yan, Catherine Apio, Soomin Song, Gyujin Heo, Qijun Yang, Jigyasha Timsina, Menghan Liu, John Budde, John C Morris, Carlos Cruchaga, Yun Ju Sung, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Age, sex, and apolipoprotein E (APOE) are the strongest risk factors for late-onset Alzheimer disease (AD). The role of APOE in AD varies with sex and ancestry. While the association of APOE with AD biomarkers also varies across sex and ancestry, no study has systematically investigated both sex-specific and ancestry differences of APOE on cerebrospinal fluid (CSF) biomarkers together, resulting in limited insights and generalizability.

OBJECTIVE: To systematically investigate the association of sex and APOE-ε4 with 3 core CSF biomarkers across ancestries.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study examined 3 CSF biomarkers (amyloid β1-42 [Aβ42], phosphorylated tau 181 …

Racial Equity In Urine Drug Screening Policies In Labor And Delivery, Vahid Azimi, Cassandra Trammel, Lauren Nacke, Alexandra Rubin, Lori Stevenson, Brittaney Vaughn, Stephen M Roper, Mark A Zaydman, Ronald Jackups, Noor Riaz, Kim P Schamel, Jeannie C Kelly

2020-Current year OA Pubs

IMPORTANCE: Black pregnant patients are significantly more likely than their White counterparts to undergo peripartum urine drug screening (UDS) and subsequent reporting to child protective services (CPS).

OBJECTIVE: To evaluate the association of removing isolated cannabis use and limited prenatal care as order indications, combined with clinician-facing clinical decision support, with racial parity in peripartum UDS and CPS reporting.

DESIGN, SETTING, AND PARTICIPANTS: This quality improvement study assessed 9396 pregnant patients at a single tertiary care center in a Midwestern US urban metropolitan region who delivered before (June 1, 2021, to September 31, 2022) and after (October 1, 2022, to …

Clinical Performance Of An N-Terminal Pro-B-Type Natriuretic Peptide Assay In Acute Heart Failure Diagnosis, Lori B Daniels, Patience Ajongwen, Robert H Christenson, Carol L Clark, Deborah B Diercks, Gregory J Fermann, Sharon E Mace, Simon A Mahler, Peter S Pang, Zubaid Rafique, Michael S Runyon, James Tauras, Christopher R Defilippi

Faculty, Staff and Students Publications

Background: We evaluated the Vitros® Immunodiagnostic Products N-terminal pro B-type natriuretic peptide (NT-proBNP) II assay for aiding in diagnosis of heart failure (HF) in patients with acute dyspnea.

Methods: Serum concentrations of NT-proBNP were measured in patient samples from 20 emergency departments across the United States. Study endpoints included sensitivity, specificity, likelihood ratios, and predictive values for diagnosis of acute HF according to age-stratified cutoffs (450, 900, and 1800 pg/mL), and a rule-out age-independent cutoff (300 pg/mL). Additional measures were area under the curve (AUC) for receiver operating characteristic (ROC) curves. Results were also interpreted in patient subgroups with relevant …

Recovery Potential In Patients After Cardiac Arrest Who Die After Limitations Or Withdrawal Of Life Support, Jonathan Elmer, Patrick J Coppler, Cecelia Ratay, Alexis Steinberg, Sara Difiore-Sprouse, Nicholas Case, Baruch Fischhoff, Maria De-Arteaga, Alain Cariou, Alejandro A Rabinstein, Andrea O Rossetti, Ankur A Doshi, Bradley J Molyneaux, Cameron Dezfulian, Carolina B Maciel, Christoph Leithner, Cindy H Hsu, Claudio Sandroni, David M Greer, David B Seder, Francis X Guyette, Fabio Silvio Taccone, Hiromichi Naito, Jasmeet Soar, Jean-Baptiste Lascarrou, Jerry P Nolan, Karen G Hirsch, Katherine M Berg, Marion Moseby-Knappe, Markus B Skrifvars, Michael C Kurz, Min Jung Kathy Chae, Mypinder S Sekhon, Nicholas J Johnson, Pedro Kurtz, Romergryko G Geocadin, Sachin Agarwal, Teresa L May, Theresa M Olasveengen, Clifton W Callaway, Optimizing Recovery Prediction After Cardiac Arrest (Orca) Study Group

Faculty, Staff and Students Publications

Importance: Understanding the relationship between patients' clinical characteristics and outcomes is fundamental to medicine. When critically ill patients die after withdrawal of life-sustaining therapy (WLST), the inability to observe the potential for recovery with continued aggressive care could bias future clinical decisions and research.

Objective: To quantify the frequency with which experts consider patients who died after WLST following resuscitated cardiac arrest to have had recovery potential if life-sustaining therapy had been continued.

Design, setting, and participants: This prospective cohort study included comatose adult patients (aged ≥18 years) treated following resuscitation from cardiac arrest at a single academic medical center …

Predicting The Impact Of Rare Variants On Rna Splicing In Cagi6., Jenny Lord, Carolina Jaramillo Oquendo, Htoo A Wai, Andrew G L Douglas, David J Bunyan, Yaqiong Wang, Zhiqiang Hu, Zishuo Zeng, Daniel Danis, Panagiotis Katsonis, Amanda Williams, Olivier Lichtarge, Yuchen Chang, Richard D Bagnall, Stephen M Mount, Brynja Matthiasardottir, Chiaofeng Lin, Thomas Van Overeem Hansen, Raphael Leman, Alexandra Martins, Claude Houdayer, Sophie Krieger, Constantina Bakolitsa, Yisu Peng, Akash Kamandula, Predrag Radivojac, Diana Baralle

Faculty Research 2025

Variants which disrupt splicing are a frequent cause of rare disease that have been under-ascertained clinically. Accurate and efficient methods to predict a variant's impact on splicing are needed to interpret the growing number of variants of unknown significance (VUS) identified by exome and genome sequencing. Here, we present the results of the CAGI6 Splicing VUS challenge, which invited predictions of the splicing impact of 56 variants ascertained clinically and functionally validated to determine splicing impact. The performance of 12 prediction methods, along with SpliceAI and CADD, was compared on the 56 functionally validated variants. The maximum accuracy achieved was …

Cascades, A Novel Sox2 Super-Enhancer-Associated Long Noncoding Rna, Regulates Cancer Stem Cell Specification And Differentiation In Glioblastoma., Uswa Shahzad, Marina Nikolopoulos, Christopher Li, Michael Johnston, Jenny J Wang, Nesrin Sabha, Frederick S Varn, Alexandra Riemenschneider, Stacey Krumholtz, Pranathi Meda Krishnamurthy, Christian A Smith, Jason Karamchandani, Jonathan K Watts, Roel G W Verhaak, Marco Gallo, James T Rutka, Sunit Das

Faculty Research 2025

Glioblastoma is the most common primary malignant brain tumor in adults, with a median survival of just over 1 year. The failure of available treatments to achieve remission in patients with glioblastoma (GBM) has been attributed to the presence of cancer stem cells (CSCs), which are thought to play a central role in tumor development and progression and serve as a treatment-resistant cell repository capable of driving tumor recurrence. In fact, the property of "stemness" itself may be responsible for treatment resistance. In this study, we identify a novel long noncoding RNA (lncRNA), cancer stem cell-associated distal enhancer of SOX2 …

A Systematic Approach To Prioritise Diagnostically Useful Findings For Inclusion In Electronic Health Records As Discrete Data To Improve Clinical Artificial Intelligence Tools And Genomic Research., P Guillod, A Savvas, Peter N Robinson, D Nai, K N Naresh, G Ott, A Schuh, W A Sewell, M Anderson, N Matentzoglu, D Durgavarjhula, M L Xu, M J Druzdzel, J M Astle

Faculty Research 2025

AIMS: The recent widespread use of electronic health records (EHRs) has opened the possibility for innumerable artificial intelligence (AI) tools to aid in genomics, phenomics, and other research, as well as disease prevention, diagnosis, and therapy. Unfortunately, much of the data contained in EHRs are not optimally structured for even the most sophisticated AI approaches. There are very few published efforts investigating methods for recording discrete data in EHRs that would not slow current clinical workflows or ways to prioritise patient characteristics worth recording. Here, we propose an approach to identify and prioritise findings (phenotypes) useful for differentiating diseases, with …

Just As Expected? Older Adults’ Aging Expectations Are Associated With Subjective Cognition, Nikki Hill, Sakshi Bhargava, Justin Do, Emily Bratlee-Whitaker, Monique Brown, Renata Komalasari, Rachel Wu, Jacqueline Mogle

SKMC Student Presentations and Publications

OBJECTIVES: This study investigated the relationship between older adults' expectations regarding aging and subjective cognition. Specifically, we examined whether the three domains of aging expectations (physical health, mental health, and cognitive function) were associated with two aspects of subjective cognition: current subjective cognition and subjective cognitive decline (SCD).

METHOD: An online survey was conducted among U.S. adults aged 65-90 (N = 581; M_age=71.4, SD ± 4.81; 51% female). Measures included the 12-item Expectations Regarding Aging scale, the 8-item PROMIS Cognitive Abilities scale (current subjective cognition), and the 12-item Everyday Cognition scale (SCD). We used generalized linear models …

The Efficacy Of The Minimally Invasive Lumbar Decompression (Mild®) Procedure: A Prisma-Compliant Systemic Review And Meta-Analysis, Xin-Yu Zhang, Jian-Li Zhao, Ya-Jing Wang, Jie Luan, Hong-Qi Lin, Dajie Wang

Department of Anesthesiology Faculty Papers

BACKGROUND: Lumbar spinal stenosis is the most common cause for spinal surgery of older adults. It is associated with pain in the legs and back as well as impaired ambulation. Minimally Invasive Lumbar Decompression (MILD®, Vertos Medical) is a percutaneous, image-guided lumbar decompression technique for central canal stenosis secondary to a hypertrophied ligamentum flavum. However, whether MILD can achieve adequate beneficial results in patients with lumbar spinal stenosis remains undetermined.

OBJECTIVE: To assess the efficacy and complications of MILD for lumbar spinal stenosis.

STUDY DESIGN: A systematic review and meta-analysis.

METHODS: Electronic databases were searched to identify all clinical trials …

Leveraging Artificial Intelligence And Machine Learning To Accelerate Discovery Of Disease-Modifying Therapies In Type 1 Diabetes., Melanie R. Shapiro, Erin M. Tallon, Matthew E. Brown, Amanda L. Posgai, Mark A. Clements, Todd M. Brusko

Manuscripts, Articles, Book Chapters and Other Papers

Progress in developing therapies for the maintenance of endogenous insulin secretion in, or the prevention of, type 1 diabetes has been hindered by limited animal models, the length and cost of clinical trials, difficulties in identifying individuals who will progress faster to a clinical diagnosis of type 1 diabetes, and heterogeneous clinical responses in intervention trials. Classic placebo-controlled intervention trials often include monotherapies, broad participant populations and extended follow-up periods focused on clinical endpoints. While this approach remains the 'gold standard' of clinical research, efforts are underway to implement new approaches harnessing the power of artificial intelligence and machine learning …

Cervical Necrotizing Fasciitis And Shock In The Post-Operative Pediatric Patient., Paul Bryan Hankey, Jason R. Brown

Manuscripts, Articles, Book Chapters and Other Papers

Cervical necrotizing fasciitis (CNF) is a rare infection that can quickly lead to devastating patient outcomes. Considering the vital importance of surrounding neck structures, rapid control of the infection is essential. Infection is most frequently polymicrobial and occurs in the adult patient in the context of certain medical comorbidities. Complications are typically limited to tissue destruction in the form of necrosis. There are no current reports describing CNF complicated by acute shock in the post-operative pediatric patient. Here, we present a pediatric case of CNF complicated by acute shock following Sistrunk procedure for removal of a supposed thyroglossal duct cyst. …

"Inpatient Pharmacological Thromboprophylaxis In The Antepartum Period: An Argument For Universal Thromboprophylaxis", Julia Burd, Amanda Zofkie

2020-Current year OA Pubs

Venous thromboembolism (VTE), a largely preventable condition, accounts for almost 15% of maternal mortalities. The physiologic changes of pregnancy, including quantitative changes in coagulation factors and compression of vasculature by the gravid uterus, cause an increase in risk of VTE, including deep vein thromboembolism (DVT), pulmonary embolism, and stroke (CVA). Long term antepartum admission for preeclampsia, preterm prelabor rupture of membranes (PPROM) or other high-risk pregnancy needs present additional risk factors for VTE due to the patient's medical condition and their inpatient status. Given the near-universal support for anticoagulation in patients with a history of venous thromboembolism or high-risk thrombophilia, …

Use Of Robust Norming To Create A Sensitive Cognitive Summary Score In De Novo Parkinson's Disease: An Illustrative Example, Daniel Weintraub, Michael C Brumm, Ryan Kurth, Michele K York

Faculty, Staff and Students Publications

Background: Cognitive impairment is common at all stages of Parkinson's disease (PD), but there is no consensus on which neuropsychological tests to use or how to interpret cognitive battery results. A cognitive summary score (CSS) combines the richness of a neuropsychological battery with the simplicity of a single score.

Objective: The objective of this study was to determine whether a CSS created using robust norming can detect early cognitive deficits in de novo, untreated PD.

Methods: Baseline cognitive data from PD participants and healthy control participants (HCs) in the Parkinson's Progression Markers Initiative were used to (1) create a robust …

Care Utilization For Acute Respiratory Infections In Children Requiring Invasive Long-Term Mechanical Ventilation, Carolyn C Foster, Todd A Florin, Derek J Williams, Katherine L Freundlich, Rebecca L Steuart, Julia A Heneghan, Cara Cecil, Nathan M Pajor, Robert J Graham, Sriram Ramgopal

Faculty, Staff and Student Publications

Introduction: Children who use invasive long-term mechanical ventilation (LTMV) are a rare, clinically heterogenous population with relatively high hospitalization rates, most commonly for acute respiratory infection (ARI). We sought to describe patterns of ARI-related utilization and mortality in pediatric patients with LTMV, evaluating the association of a pre-existing neurologic diagnoses with outcomes.

Methods: We studied a longitudinal retrospective cohort across 40 U.S. children's hospital emergency department (ED) and hospital encounters for patients (< 21 years) with LTMV and an ARI diagnosis code (10/1/2016-6/30/2023). We examined mortality and ED/hospital utilization outcomes, defining short-stay hospitalizations as ≤ 2 calendar days. We stratified analyses by high intensity neurologic impairment (HINI) using a validated coding algorithm.

Results: We included 4866 patients (median age 4.5 years; 58.6% male) with LTMV and ≥ 1 ARI encounter. Most (95.1%) were hospitalized on their index encounter, and …

Causes Of Mortality In The Congenital Disorders Of Glycosylation, Hana Alharbi, Seishu Horikoshi, Sabrina Malone Jenkins, Fernando Scaglia, Christina Lam, Eva Morava, Austin Larson, Andrew C Edmondson

Faculty, Staff and Students Publications

Congenital Disorders of Glycosylation (CDG) are a group of some 200 genetic disorders with PMM2-CDG being the most common disease. These disorders individually remain rare with poorly understood natural history (NH) and causes of mortality. We established a NH study for CDG and collected both prospective and retrospective data on CDG outcomes. In the current data set analysis on deceased patients, we describe the clinical phenotype and causes of death for thirty-seven individuals with various genetic causes of CDG. About a third of this cohort were affected with PMM2-CDG. All of the patients presented with multisystem features with involvement of …

Assessing The Predicted Impact Of Single Amino Acid Substitutions In Calmodulin For Cagi6 Challenges, Paola Turina, Giuditta Dal Cortivo, Carlos A Enriquez Sandoval, Emil Alexov, David B Ascher, Giulia Babbi, Constantina Bakolitsa, Rita Casadio, Piero Fariselli, Lukas Folkman, Akash Kamandula, Panagiotis Katsonis, Dong Li, Olivier Lichtarge, Pier Luigi Martelli, Shailesh Kumar Panday, Douglas E V Pires, Stephanie Portelli, Fabrizio Pucci, Carlos H M Rodrigues, Marianne Rooman, Castrense Savojardo, Martin Schwersensky, Yang Shen, Alexey V Strokach, Yuanfei Sun, Junwoo Woo, Predrag Radivojac, Steven E Brenner, Daniele Dell'orco, Emidio Capriotti

Faculty, Staff and Students Publications

Recent thermodynamic and functional studies have been conducted to evaluate the impact of amino acid substitutions on Calmodulin (CaM). The Critical Assessment of Genome Interpretation (CAGI) data provider at University of Verona (Italy) measured the melting temperature (Tm) and the percentage of unfolding (%unfold) of a set of CaM variants (CaM challenge dataset). Thermodynamic measurements for the equilibrium unfolding of CaM were obtained by monitoring far-UV Circular Dichroism as a function of temperature. These measurements were used to determine the Tm and the percentage of protein remaining unfolded at the highest temperature.

The CaM challenge dataset, comprising a total of …

Analysis And Benchmarking Of Small And Large Genomic Variants Across Tandem Repeats, Adam C English, Egor Dolzhenko, Helyaneh Ziaei Jam, Sean K Mckenzie, Nathan D Olson, Wouter De Coster, Jonghun Park, Bida Gu, Justin Wagner, Michael A Eberle, Melissa Gymrek, Mark J P Chaisson, Justin M Zook, Fritz J Sedlazeck

Faculty, Staff and Students Publications

Tandem repeats (TRs) are highly polymorphic in the human genome, have thousands of associated molecular traits and are linked to over 60 disease phenotypes. However, they are often excluded from at-scale studies because of challenges with variant calling and representation, as well as a lack of a genome-wide standard. Here, to promote the development of TR methods, we created a catalog of TR regions and explored TR properties across 86 haplotype-resolved long-read human assemblies. We curated variants from the Genome in a Bottle (GIAB) HG002 individual to create a TR dataset to benchmark existing and future TR analysis methods. We …

Irisin-Mediated Muscle-Renal Crosstalk As A Protective Mechanism Against Contrast-Induced Acute Kidney Injury Via Cgas-Sting Signalling Inhibition, Long Peng, Suhua Li, Qiang Huang, Yuxiang Sun, Juan Sun, Ting Luo, Yanlin Wang, Zhaoyong Hu, Weiyan Lai, Hui Peng

Faculty, Staff and Students Publications

Background: Contrast-induced acute kidney injury (CI-AKI) continues to pose a pressing clinical challenge during invasive cardiovascular procedures due to the limited availability of preventative strategies. We aimed to demonstrate that irisin, a myokine induced by exercise, protects against CI-AKI by inhibiting the cGAS-STING inflammatory pathway.

Methods and results: We explored the relationship between serum irisin levels and CI-AKI incidence in patients administered the contrast media iohexol. Notably, lower serum irisin levels were strongly associated with an increased incidence of CI-AKI following contrast media administration. To establish a causal link between serum irisin levels and CI-AKI, we utilised a mouse model …

Self-Collection For Primary Hpv Testing: Acceptability In A Large Urban Emergency Department, Itunu O Sokale, Dick C Kuo, Claire M Hoppenot, Lorraine R Reitzel, Luis H Juarez, Katherine J Hernandez, Susan L Parker, Chris Amos, Maria Daheri, Kelly R Keene, Jane R Montealegre, Aaron P Thrift

Faculty, Staff and Students Publications

Study objective: Overdue cervical cancer screening increases the risk of invasive cervical cancer. It is important to identify settings where self-collection for primary human papillomavirus (HPV) testing can be implemented to have high effect on cervical cancer screening among hard-to-reach women with overdue screening. Herein, we examined the acceptability of HPV self-collection, including completion rates, attitudes, and experiences among women seeking noncritical care at a high-volume urban safety-net hospital emergency department (ED) in Houston, Texas, United States.

Methods: In this single-arm intervention pilot study, we recruited women overdue for cervical cancer screening in the waiting areas of a safety-net hospital …