Digital Commons Network^™

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

Faculty, Staff and Students Publications

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

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

Department of Neurosurgery Faculty Papers

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

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

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

Faculty, Staff and Student Publications

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

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

Faculty, Staff and Student Publications

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

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

Faculty, Staff and Student Publications

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

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

2020-Current year OA Pubs

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

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

RESULTS: Among 6629 …

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

Faculty, Staff and Student Publications

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

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

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

Faculty, Staff and Student Publications

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

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

Faculty, Staff and Students Publications

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

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

College of Nursing Faculty Papers & Presentations

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

Use And Outcomes Of The Medical Hybrid Procedure For Stage 1 Palliation In Infants With Hypoplastic Left Heart Syndrome And Variants., Daniel N. Beauchamp, Christopher J. Statile, Huaiyu Zang, David A. Parra, Justin Godown, Natalie Jayaram, Matthew L. Moehlmann, Garick D. Hill

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Staged palliation of hypoplastic left heart syndrome and variants begins with the Norwood or hybrid procedure. Hybrid palliation is used in a minority of cases and often reserved for high-risk patients. Stented hybrid (SH) comprises bilateral pulmonary artery bands and ductal stenting, and medical hybrid (MH) comprises bilateral pulmonary artery bands and prostaglandins. MH use and outcomes have not been well described. We sought to compare MH, SH, and surgical stage 1 (SS1) using a national database.

METHODS: Patients from the National Pediatric Cardiology Quality Improvement Collaborative database born between 2016 and 2021 were categorized by initial intervention: MH, …

Large-Scale Profiling Of Antibody Reactivity To Glycolipids In Patients With Guillain-Barré Syndrome, Robin C M Thomma, Susan K Halstead, Laura C De Koning, Eveline J A Wiegers, Dawn S Gourlay, Anne P Tio-Gillen, Wouter Van Rijs, Henning Andersen, Giovanni Antonini, Samuel Arends, Shahram Attarian, Fabio A Barroso, Kathleen J Bateman, Luana Benedetti, Peter Van Den Bergh, Jan Bürmann, Mark Busby, Carlos Casasnovas, Efthimios Dardiotis, Amy Davidson, Thomas E Feasby, Janev Fehmi, Giuliana Galassi, Tania Garcia-Sobrino, Volkan Granit, Gerardo Gutiérrez-Gutiérrez, Robert D M Hadden, Thomas Harbo, Hans-Peter Hartung, Imran Hasan, James K L Holt, Zhahirul Islam, Summer Karafiath, Hans D Katzberg, Noah Kolb, Susumu Kusunoki, Satoshi Kuwabara, Motoi Kuwahara, Helmar C Lehmann, Sonja E Leonhard, Lorena Martín-Aguilar, Soledad Monges, Eduardo Nobile-Orazio, Julio Pardo, Yann Pereon, Luis Querol, Ricardo C Reisin, Simon Rinaldi, Paolo Ripellino, Rhys C Roberts, Olivier Scheidegger, Nortina Shahrizaila, Kazim A Sheikh, Nicholas J Silvestri, Soren H Sindrup, Beth Stein, Cheng Y Tan, Hatice Tankisi, Leo H Visser, Waqar Waheed, Ruth Huizinga, Bart C Jacobs, Hugh J Willison

Faculty, Staff and Student Publications

Guillain-Barré syndrome is an acute polyradiculoneuropathy in which preceding infections often elicit the production of antibodies that target peripheral nerve antigens, principally gangliosides. Anti-ganglioside antibodies are thought to play a key role in the clinical diversity of the disease and can be helpful in clinical practice. Extensive research into clinical associations of individual anti-ganglioside antibody specificities has been performed. Recent research has highlighted glycolipid complexes, glycolipid combinations that may alter antibody binding, as targets. In this study, we investigated antibody reactivity patterns to glycolipids and glycolipid complexes using combinatorial array, in relation to clinical features in Guillain-Barré syndrome. In total, …

Pregnancy Outcomes In Women With Heritable Thoracic Aortic Disease: Data From The Eorp Esc Registry Of Pregnancy And Cardiac Disease (Ropac) Iii, Puck N J Peters, Johanna A Van Der Zande, Julie De Backer, Guillaume Jondeau, Osama Ahmad, Marjorie Richardson, Francesca M Comoglio, Heleen Van Der Zwaan, Siddharth K Prakash, Christina Christersson, Karishma P Ramlakhan, Roger Hall, Mark R Johnson, Jolien W Roos-Hesselink, Ropac Investigators

Faculty, Staff and Student Publications

Aims: The risk of pregnancy in women with heritable thoracic aortic disease (HTAD) is estimated to be high, but supporting data are scarce. The aim of this study is to prospectively investigate pregnancy outcomes to improve patient management and care.

Methods and results: The Registry of Pregnancy and Cardiac disease (ROPAC) III is a prospective global registry including pregnant women with known aortic pathology between 2018 and 2023. Cardiac, obstetric and fetal outcomes, beta-blocker use, and the impact of breastfeeding were investigated. Additionally, changes in aortic diameters were assessed. In total, 176 pregnancies in 170 women (mean age 32 years, …

Global Trends And Forecast Of Cardiovascular Diseases, Cancer, And Shared Risk Factors: Insights From The Gbd 2021, Chieh Y Koo, Bryan Chong, Jayanth Jayabaskaran, Srinithy Nagarajan, Silingga M Jauhari, Yiming Chen, Li L Tan, Anurag Mehta, Muhammad S Khan, Mark Muthiah, Derek Hausenloy, A M Richards, Dennis T Ko, Christian D Mallen, Eric A Secemsky, Mark Y Chan, Paaladinesh Thavendiranathan, Nicholas W S Chew, Mamas A Mamas

Faculty, Staff and Students Publications

Background: Cardiovascular disease (CVD) and cancer share multiple risk factors and are the leading causes of morbidity and death worldwide. This study aims to examine historical and projected trends of the combined CVD-cancer global estimates and their shared risk factors.

Methods: Death and disability-adjusted life years (DALYs) associated with CVDs, cancers, and their risk factors were obtained from the GBD (Global Burden of Disease) 2021 study. Historical estimates from 1990 to 2021 and forecast data from 2025 to 2050 were examined across age groups, regions, sociodemographic index, and sex.

Results: In 2021, CVD-cancer resulted in age-standardized DALY rates of 8009 …

A Recurrent Acaa2 Variant Causes A Dominant Syndrome Of Lipodystrophy, Lipomatosis, Infantile Steatohepatitis And Hypoglycemia, Vinaya Simha, Mary Kate Lopiccolo, Anna Platt, Rebecca J Brown, Xandria Johnson, Deanna Alexis Carere, Colleen Donnelly, Matthew T Snyder, Chao Xing, Thomas P Mathews, Purva Gopal, Stephen C Ward, Diana R Tomchick, Anil K Agarwal, Ralph J Deberardinis, Abhimanyu Garg

Faculty, Staff and Student Publications

No abstract provided.

A Multiomics Approach To Defining Target-Organ Injury In Youths With Primary Hypertension: The Ship Ahoy Cohort, Kalyani Ananthamohan, Tammy M Brady, Mohammed Arif, Stephen R Daniels, Bonita Falkner, Michael Ferguson, Joseph T Flynn, Coral Hanevold, Stephen R Hooper, Julie R Ingelfinger, Marc Lande, Lisa J Martin, Kevin E Meyers, Mark Mitsnefes, Bernard Rosner, Joshua A Samuels, Gina Kuffel, Michael J Zilliox, Qin M Chen, Richard C Becker, Elaine M Urbina, Sakthivel Sadayappan

Faculty, Staff and Student Publications

Background: Primary hypertension in childhood tracks into adulthood and is associated with increased cardiovascular risk. Studies conducted in individuals aged < 18 years, an age group without many of the confounding comorbid cardiovascular disease risk factors in adults, provide an opportunity to explore early cardiovascular target-organ injury.

Methods: Youths (n=132, mean age, 15.8 years) were stratified by blood pressure (BP) as low-BP, mid-BP, and high-BP and by left ventricular mass index as low-and high left ventricular mass index. Systemic circulating RNA, microRNA, and methylation profiles in peripheral blood mononuclear cells and deep proteome profiles in serum were determined using high-throughput sequencing techniques. In vitro cell culture experiments assessed angiotensin II- and microRNA-mediated Vash1 (vasohibin-1 protein) regulation and Vash1-mediated hypertrophic response.

Results: In high-BP youths, transcriptomics analysis identified …

Effects Of Combining Traditional East Asian And Conventional Western Medicine On Acute Stroke Outcomes, Dong-Seok Gwak, Jong-Sik Lee, Dawid Schellingerhout, Jinyong Chung, Hyerin Oh, Sang-Wuk Jeong, Ji Sung Lee, Hee-Joon Bae, Mikyung Kim, Dong-Jun Choi, Dong-Eog Kim

Faculty, Staff and Student Publications

Background: Traditional East Asian medicine (TM) is widely used in Korea and other East Asian countries. However, the effects of TM treatment on acute ischemic stroke (AIS) outcomes remain unclear, as previous studies lacked a sufficient sample size, a consecutive series design, or a prospective outcome capture approach. We aimed to investigate whether combining TM with conventional Western medicine (CM) treatments (C+TM) leads to better outcomes after AIS, relative to CM treatment alone.

Methods: We retrospectively analyzed 2157 consecutive patients with AIS from a prospectively collected registry (2011-2021) at our center and compared the CM and C+TM groups in terms …

Association Of Acute Kidney Injury Risk And Same-Day Discharge Practices After Percutaneous Coronary Intervention., Anezi Uzendu, Rayan El Zein, Jennifer A Rymer, Dan D Nguyen, R Angel Garcia, Nobuhiro Ikemura, Neel Butala, Howard M Julien, Saket Girotra, Dharam J Kumbhani, Oladipupo Olafiranye, Rebecca Young, Leo Brothers, John A Spertus

Heart and Vascular Articles

BACKGROUND: Same-day discharge (SDD) after percutaneous coronary intervention (PCI) may be altered when complications occur. We sought to determine whether risk of the most common complication, acute kidney injury (AKI), is associated with SDD in practice.

METHODS: Using the NCDR (National Cardiovascular Data Registry) CathPCI registry, we calculated the AKI risk for elective PCIs from 2018 to 2022 using the NCDR prediction model. Hierarchical logistic regression models were constructed to predict SDD with AKI risk and procedural variables as fixed effects, and site as a random effect. Trends in SDD rate across AKI risk categories were described and variability across …

Timing And Mode Of Death Following Treatment Of Neonatal Symptomatic Tetralogy Of Fallot, Sara M Trucco, Yun Zhang, Andrew C Glatz, Michael L O'Byrne, Christopher J Petit, Athar M Qureshi, Jeffrey D Zampi, Shabana Shahanavaz, George T Nicholson, Allen Ligon, Jennifer C Romano, Shiraz A Maskatia, Jeffery J Meadows, Christopher Mascio, Jay Patel, Kathryn Stack, Asaad G Beshish, Mark Law, Sarosh P Batlivala, Jeannette Wong-Siegel, Kristal Hock, Sarah Speed, Hala Khan, Disha Goel, Courtney Mccracken, Bryan H Goldstein

Faculty, Staff and Students Publications

Background: Neonates with tetralogy of Fallot and symptomatic cyanosis (sTOF) require early intervention, using a staged or primary repair strategy. Postprocedural mortality risk within this group is considerable. The mode of death and associated factors have been inadequately defined in early childhood mortality following treatment of sTOF. This study aims to describe the timing, cause, and associated risk factors of postprocedural death in infants with sTOF.

Methods: Neonates with sTOF who had an initial intervention from 2005 to 2017 at 9 centers of the Congenital Cardiac Research Collaborative were reviewed. Among nonsurvivors, details regarding timing, cause of death, and last …

Optimising Drowning Prevention Counselling Through A Physician Maintenance Of Certification (Moc) Quality Improvement (Qi) Initiative, Tracy E Mccallin, Anthony R Arredondo, Elizabeth A Camp, Shabana Yusuf

Faculty, Staff and Students Publications

Drowning is the leading cause of death in children 1–4 years old in the USA. Paediatricians play an important role in giving anticipatory guidance on drowning prevention. This quality improvement initiative aimed to increase the rate of drowning prevention counselling with provision of educational materials to caregivers of children aged 0–10 years during clinical encounters in an outpatient setting.

We refined a previously published Texas state educational programme that included evidence-based counselling strategies across three Plan Do Study Act (PDSA) cycles, with the addition of preintervention baseline counselling phase during expansion of the programme nationally to 17 and 21 states …

Serum Response Factor Is Essential For Endometrial Function And Prevention Of Inflammatory Fibrosis, Ryan M Marquardt, Sara A Grimm, San-Pin Wu, Peter F Lais, Shu-Yun Li, Xin Xu, Erin Smithberger, David Cunefare, Charan Ganta, David Olson, Eunhee M Jeong, Jae-Wook Jeong, Bruce A Lessey, John P Lydon, Francesco J Demayo

Faculty, Staff and Students Publications

Pregnancy requires a supportive uterine environment facilitated by steroid hormone–regulated differentiation of endometrial stromal fibroblasts into decidual cells and tight control of inflammation. Serum response factor (SRF) is a widely expressed transcription factor essential for mesenchymal cell growth and differentiation with noted roles in hormonal regulation of muscle tissues but little characterization in reproductive organs. Here, we reveal that endometrial SRF is dysregulated in human endometriosis and is critical for female reproductive success in mice through regulation of endometrial stromal and epithelial cells. Immunohistochemical analysis identified decreased endometrial SRF expression in infertile endometriosis patient tissues. RNAi-based SRF knockdown in human …

Timing And Mode Of Death Following Treatment Of Neonatal Symptomatic Tetralogy Of Fallot, Sara M Trucco, Andrew C Glatz, Et Al.

2020-Current year OA Pubs

BACKGROUND: Neonates with tetralogy of Fallot and symptomatic cyanosis (sTOF) require early intervention, using a staged or primary repair strategy. Postprocedural mortality risk within this group is considerable. The mode of death and associated factors have been inadequately defined in early childhood mortality following treatment of sTOF. This study aims to describe the timing, cause, and associated risk factors of postprocedural death in infants with sTOF.

METHODS: Neonates with sTOF who had an initial intervention from 2005 to 2017 at 9 centers of the Congenital Cardiac Research Collaborative were reviewed. Among nonsurvivors, details regarding timing, cause of death, and last …

Semaglutide And Diabetic Retinopathy: An Ohdsi Network Study, Cindy Xinji Cai, Linying Zhang, Ruochong Fan, Adam Wilcox, Albert Lai, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA) used to treat type 2 diabetes mellitus (T2D), has potential associations with higher rates of diabetic retinopathy (DR) complications including proliferative DR (PDR) and diabetic macular edema (DME). The purpose of this study was to determine whether an association exists between semaglutide and PDR and treatment-requiring DR/DME.

RESEARCH DESIGN AND METHODS: This was a retrospective cohort study of 14 databases (six administrative claims and eight electronic health records) in the Observational Health Data Sciences and Informatics Evidence Network. Adults with T2D on semaglutide, other GLP-1RA (dulaglutide, exenatide), or non-GLP-1RA medications (empagliflozin, sitagliptin, …

Telehealth Education Leveraging Electronic Transitions Of Care For Copd Patients (Tele-Toc): A Study Protocol For A Type Ii Hybrid Effectiveness-Implementation Randomised, Pragmatic Clinical Trial Of A Pharmacist-Led Intervention, Deepa Ramadurai, Cathryn T Lee, Leah Traeger, Geoff Pucci, Andrea Jackson-Sagredo, Sachin Shah, Joanna Abraham, Vineet M Arora, Valerie G Press

2020-Current year OA Pubs

INTRODUCTION: Transitions of care (TOC) between hospital, ambulatory and home settings for high-risk adults with chronic diseases are complex, costly and often result in poor health outcomes. Suboptimal care transitions lead to medication errors, non-adherence, decreased self-management skills and inadequate follow-up, all of which contribute to readmissions or emergency department visits. The Transitional Care Model aims to address these challenges through patient-centred, in-home interventions. We propose to implement and evaluate TELE-TOC: Telehealth Education Leveraging Electronic Transitions Of Care for Chronic Obstructive Pulmonary Disease (COPD) patients. This study will evaluate the added value of a virtual, pharmacy-based intervention integrated into an …

Evaluation Of Integrative Oncology Modalities For Symptom Management: A Mascc/Sio Global Survey, Alexandre Chan, Reem Nasr, Daniela Arcos, Dalia Kagramanov, Chioma Asuzu, Ting Bao, Yin Ting Cheung, Jung Hye Kwon, Judith Lacey, Richard T. Lee, Maryam Lustberg, Beatrice M. Ohaeri, Santosh Rao, Enrique Soto-Perez-De-Celis, Claudia M. Witt, Ana M. Lopez

Kimmel Cancer Center Faculty Papers

BACKGROUND: With growing evidence pointing towards the potential of integrative oncology modalities (IOM) in addressing cancer and cancer-treatment related symptoms, research on IOM utilization and implementation is warranted. This study examines global stakeholder perspectives on integrative oncology (IO) utilization for supportive cancer care.

METHODS: Members of the Multinational Association of Supportive Care in Cancer (MASCC) and the Society for Integrative Oncology (SIO) completed a survey on the utilization of IOM for supportive cancer care. Descriptive statistics were used to assess demographic data, IOM usage patterns, IOM education, and financial considerations for utilizing IOM.

RESULTS: Among 344 participants representing eight geographical …

Risk Of Late-Onset Depression In Long-Term Survivors Of Breast, Prostate, And Colorectal Cancer, Melissa Taylor, Sarah Westvold, Jessica Long, Terry Hyslop, Andrea Silber, Rebecca Forman, Faiza Yasin, Tendai Kwaramba, Shi-Yi Wang, Michael Leapman, Michael Cecchini, Ira Leeds, Lisa Spees, Stephanie Wheeler, Cary Gross, Kevin Oeffinger, Michaela Dinan

Kimmel Cancer Center Faculty Papers

IMPORTANCE: The prevalence of depression is higher in cancer survivors than in the general population. As the long-term cancer survivor population increases, it is increasingly important to understand risk factors for late-onset depression.

OBJECTIVE: To identify risk factors associated with late-onset depression in long-term (5-year) survivors of breast, prostate, or colorectal cancer.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used 2022 linkage of Surveillance, Epidemiology, and End Results (SEER) and Medicare data to identify 5-year survivors of breast, prostate, or colorectal cancer 66 years or older who were enrolled in fee-for-service Medicare and had no previous depression diagnosis. Long-term …

Validation Of A Risk Score For Cancer-Associated Thrombosis Using Nationwide Ehr Data, Ang Li, Omid Jafari, Barbara D Lam, Jun Y Jiang, Rock Bum Kim, Shengling Ma, Emily Zhou, Joyce W Tiong, Elizabeth C Chiang, Justine Ryu, Christopher I Amos, Jennifer La, Nathanael R Fillmore

Faculty, Staff and Student Publications

Importance: Venous thromboembolism (VTE) is associated with increased mortality and morbidity in patients with cancer. Existing risk prediction models are typically validated within individual sites, a fragmented approach that limits clinical adoption.

Objective: To validate the electronic health record cancer-associated thrombosis (EHR-CAT) score compared with the benchmark Khorana score in a contemporary cohort of patients with cancer across the nation, before and after treatment, excluding those at high risk of bleeding.

Design, setting, and participants: This prognostic study included patients in a nationwide longitudinal EHR database from January 2018 to December 2023 with follow-up continuing to April 2025. Patients with …

Genomic Profiling Of Intraocular Leiomyomas Reveals Recurrent Copy Number Alterations, Vivian Tang, Yubai Chou, Cuyan Demirkesen, Michele M. Bloomer, Joseph B. Crawford, Ahmet M. Sarici, Carol L. Shields, Ralph C. Eagle Jr., Codrin E. Iacob, Walter P. Devine, Tatyana Milman, Melike Pekmezci

Wills Eye Hospital Papers

PURPOSE: Leiomyomas are benign smooth muscle tumors that commonly present in the uterus, soft tissue, skin, and gastrointestinal tract but in rare cases can also arise within the eye. Notably, intraocular leiomyomas often show slightly different histopathologic and immunohistochemical features, referred to as mesectodermal morphology, given their presumed neural crest origin. Genetic and cytogenetic alterations of intraocular leiomyomas, as well as their association with various clinical and histopathologic features, have not been previously studied.

METHODS: We identified eight patients diagnosed with intraocular leiomyoma and performed targeted next-generation sequencing, whole transcriptome RNA sequencing, and chromosomal copy number analysis on those with …

A Temperature-Sensitive Crispr-Cas12a System For Sterile Insect Technique, Christina Nguyen, Ahmed Idowu Omotayo, Sara Sanz Juste, Xuechun Feng, Víctor López Del Amo

Faculty, Staff and Student Publications

The sterile insect technique (SIT) reduces population numbers by releasing sterile males that produce non-viable progeny. Specifically, CRISPR/Cas9-based precision-guided SIT (pgSIT) generates sterile males through genetic crosses of two transgenic lines: a Cas9 strain and a guide RNA (gRNA) strain targeting male sterility and female viability or infertility. However, pgSIT requires separate maintenance of the two lines and sorting to obtain sterile males, creating possible challenges for scaling. To overcome this, we propose using Cas12a nuclease, which is inoperative at lower temperatures but active at higher temperatures. Here, we develop a Cas12a-based pgSIT system involving a single strain containing both …

Early Ctdna Dynamics Inform First-Line Therapy In Patients With Extensive-Stage Small Cell Lung Cancer, Carmela Ciardullo, Luis Tobalina, T Hedley Carr, Philip Szekeres, Silvija Kraljevic, Lauren Averett Byers, Giulia Fabbri

Faculty, Staff and Student Publications

Purpose: Small cell lung cancer (SCLC) is an aggressive malignancy with a poor prognosis despite initial treatment responses. This study evaluates ctDNA for monitoring disease and assessing the efficacy of first-line therapy in patients with extensive-stage SCLC (1L ES-SCLC).

Experimental design: In the TAZMAN trial, 31 patients with 1L ES-SCLC received standard treatment with durvalumab and etoposide plus carboplatin or cisplatin. We analyzed 228 plasma samples from 27 of 31 patients using a liquid biopsy approach to detect somatic mutations and copy-number aberrations, while also accounting for clonal hematopoiesis mutations.

Results: Baseline ctDNA analysis detected somatic alterations in 96.3% of …