Digital Commons Network^™

Implementation And Evaluation Of The Owll Intervention To Improve The Quality And Safety Of Pediatric Dental Sedation: A Mixed-Methods Approach, Kawtar Zouaidi, Jan Yeager, Sayali Tungare, Suhasini Bangar, Janelle Urata, Alfa-Ibrahim Yansane, Jungsoo Kim, Emily Sedlock, Krishna K Kookal, Yan Xiao, Oluwabunmi Tokede, Heiko Spallek, Amy Franklin, Gregory Olson, Joel White, Elsbeth Kalenderian, Muhammad F Walji

Faculty, Staff and Student Publications

Background: The OWLL (Open-Wide Learning Lab) intervention was developed using Human-Centered Design to improve the quality and safety of pediatric dental sedation. The intervention includes a patient-facing informational sedation brochure and video, and an enhanced set of clinical sedation records. Here, we report on the process evaluation 6 months after implementation in daily clinical practice.

Methods: This study was conducted at the outpatient pediatric dental clinics of 2 large US academic dental institutions. We used a mixed-methods design to assess the fidelity, acceptability, appropriateness, and feasibility of the OWLL intervention. Quantitative data were gathered through chart reviews, while qualitative data …

Mosaic Loss Of Y Chromosome Associates With Lung Function, Emphysema, And Epigenetic Aging, Woei-Yuh Saw, Kangjin Kim, Yichen Huang, Jeong H Yun, Xiaolong Ma, Jason Bacon, Yash Pershad, Daniel Levy, George T O'Connor, Eric Boerwinkle, R Graham Barr, Stephen S Rich, Jerome I Rotter, April P Carson, Laura M Raffield, Sina A Gharib, Traci M Bartz, Bruce M Psaty, Tamar Sofer, Kari E North, Robert C Kaplan, Elizabeth C Oelsner, Ani Manichaikul, Alexander G Bick, Paul Scheet, Alexander P Reiner, Nhlbi Trans-Omics For Precision Medicine Consortium, Yasminka A Jakubek, Paul L Auer, Michael H Cho, Dawn L Demeo

Faculty, Staff and Student Publications

Rationale: As the global population ages, identifying risk factors for age-related diseases, such as COPD, is crucial for public health. Mosaic loss of Y chromosome (mLOY) in blood cells is an age-related somatic mosaicism event, but its relationship with pulmonary health remains undercharacterized.

Objectives: To examine the association between mLOY and pulmonary outcomes in men.

Methods: Leveraging mLOY assessment (cell fraction ≥ 5%) in over 12 000 men, including 5097 from the COPDGene Study and 7235 from six additional cohorts in the Trans-Omics for Precision Medicine program, we investigated mLOY associations with respiratory outcomes and epigenetic aging using multivariable cross-sectional, …

Current Adoption Of The Prosthodontic Diagnostic Index For Clinical Care-A Cross-Sectional Survey Study, Esther O Kuyinu, Joseph B Breitman, Arthur Nimmo, Jay S Patel

Faculty, Staff and Student Publications

Purpose: To assess current utilization of the Prosthodontic Diagnostic Index (PDI), identify perceived benefits and limitations, and evaluate support for future updates.

Materials and methods: A survey regarding the use of the PDI was made available through email invitations to 68 US dental school prosthodontic/restorative department chairs (PD), 48 graduate prosthodontic program directors (GP), and 1834 private practice prosthodontists (PP) from the American College of Prosthodontists (ACP) member database. The results of this initial survey were inconclusive due to low response rates. The survey was also administered during the 2024 ACP Annual Session with an improved response rate for educators. …

Kras G12c And Kras G12d Respond To Lipid Metabolism In An Allele-Specific Manner, Neha Arora, Hong Liang, Walaa Kattan, Wantong Yao, Haoqiang Ying, Junchen Liu, Yong Zhou

Faculty, Staff and Student Publications

KRAS mutated at hotspots G12, G13, and Q61 possess profound allele-specific oncogenesis. Signaling of KRAS mutants is mostly compartmentalized to the proteolipid nanoclusters on the plasma membrane (PM), illustrating critical roles of spatiotemporal organization in KRAS cancer signaling. The activated GTP-bound KRAS molecules, including the wild type and mutants, have been traditionally thought to favor similar lipids. We recently reported distinct lipid sensing capabilities of different KRAS mutants, especially with KRASG12D favoring unsaturated lipids and KRASG12C gaining additional enrichment of saturated lipids. As such, KRAS mutants may respond to lipid acyl chain remodeling in an allele-specific manner. Lysophosphatidylcholine acyltransferase 1 …

Erk-Mediated Phosphorylation Of Yap Defines A Noncanonical Fgf Signaling Mechanism In Stem Cells, Xiaolei Zhao, Shannon Erhardt, Li Tang, Xiaotong Chen, Stephen M Farmer, Zixiu Cheng, Wen Chen, Ella Ziyuan Lu, Kihan Sung, Chang-Ru Tsai, Mingjie Zheng, Sheng Zhang, Yang Liu, Jianxin Wang, Min Li, James F Martin, Jun Wang

Faculty, Staff and Student Publications

While Fgf and Hippo-Yap signaling are fundamental for proper development, homeostasis, and disease, their crosstalk remains largely unknown. Here, we identified that Yap and Taz, canonical Hippo effectors, function as noncanonical effectors of Fgf signaling to maintain the proper function of neural crest (NC) lineages. NC cells are a multipotent stem cell population during vertebrate embryogenesis that contribute to numerous structures and diverse cell lineages, including craniofacial and cardiac tissues, neurons, and suture mesenchymal cells (SMCs), a specified cell population required for cranial bone growth and repair. We observed that activation of Fgf signaling in NC cells and NC-derived SMCs …

Cefepime Pharmacokinetics In Critically Ill Children With Multiple Organ Dysfunction Syndrome Using Volumetric Absorptive Microsampling, Victor Amajor, Amanda Bwint, Steven Shein, Janet Hume, Courtney Rowan, Leeanne Flygt, Matthew Malone, Erin Stenson, Scott Weiss, Matt Zinter, Sujatha Kannan, Mary Dahmer, Ryan Nofziger, Manjunath Pai, Athena Zuppa, Nathaniel Rhodes, Mark Hall, Marc Scheetz, Kevin Downes

Department of Pediatrics Faculty Papers

Up to half of critically ill children experience multiple organ dysfunction syndrome (MODS), which worsens outcomes and increases mortality risk. Cefepime is a broad-spectrum antibiotic commonly used in pediatric sepsis, but its pharmacokinetics during MODS has not been evaluated. We performed a prospective, observational study of critically ill children with MODS who were administered cefepime and collected up to 15 whole blood samples over 3 days using volumetric absorptive microsampling (VAMS). We performed nonlinear mixed-effects modeling to develop a population PK model for cefepime in children with MODS. We then reran our final population PK model using estimated plasma concentrations …

Development And Implementation Of Educational Modules On Management Of Neonates With Critical Congenital Heart Disease In The Delivery Room (Learn-Chd)., Noorjahan Ali, Brenda Law, Alyssa R. Thomas, Philip T. Levy, Ruby Gupta, Summer Elshenawy, Danielle Reed, Leeann R. Pavlek, Jennifer Shepherd, Sharada H. Gowda, Molly K. Ball, Beth Ann Johnson, Chloe Joynt

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Neonates with congenital heart disease may require delivery room interventions beyond standard care. Because existing guidelines and educational programs rarely address these needs, we developed and evaluated targeted educational modules.

METHODS: Teams were randomized to online eLearning modules or directed readings. Individual pre-/post-knowledge scores were compared. Team performance was tested in simulated delivery scenarios including abruption, hypoplastic left heart syndrome, d-transposition of great arteries and congenital complete heart block.

RESULTS: 32 teams from 9 centers participated. The module group had improved knowledge scores (mean change 6% vs -0.3% e-Learning group, p = 0.01). Simulation performance was similar between groups …

Clinical Ethics Training Needs Among Pediatricians And Pediatric Residents In Ethiopia: Conference-Based Cross-Sectional Survey., Betelehem Kassa, Addishiwot Melesse, Eyob Kebede Etissa, Bitseat W. Haile, Atnafu Mekonnen Tekleab, Stephanie Kukora

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Pediatricians encounter ethically challenging cases in clinical practice throughout the world. In Ethiopia, ethically distressing pediatric cases are heightened by limited resources, lack of ethical frameworks to guide clinical care and withdrawal of supportive therapies, absence of child protection laws, and dearth of trained ethics consultants or institutional ethics committees providing clinical ethics consultation. Ethics training remains limited in undergraduate medical programs and absent in the resident curriculum at most institutions.

METHODS: A survey of Pediatric Residents and Pediatricians attending the Ethiopian Pediatric Society's 24th Annual Conference on March 2023 was conducted using a self-administered, clinical ethics needs assessment. …

Current Practices And Variations Among Pediatric Severe Asthma Programs In The United States-The North American Severe Pediatric Asthma Consortium., Kristina Gaietto, Nadia Krupp, Avani V. Shah, Erhan Ararat, Samantha H. Averill, Sachin Baxi, Matejka Cernelc-Kohan, Jeffrey M. Chambliss, Heather De Keyser, Monica Federico, Bob Geng, Akilah A. Jefferson, Parisa Kaviany, Lila C. Kertz, Kirsten Kloepfer, Allyson Larkin, Sydney Leibel, Tanya Martinez-Fernandez, Samira Naime, Robert D. Pesek, Dinesh K. Pillai, Deepa Rastogi, Katherine Rivera-Spoljaric, Kristie R. Ross, Franziska J. Rosser, Tregony C. Simoneau, Jade Tam-Williams, Kelan G. Tantisira, William Anderson, Jonathan M. Gaffin, Theresa W. Guilbert, Erick Forno

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Severe and difficult to treat asthma in children is a complex condition causing significant morbidity and associated healthcare costs. While treatment guidelines exist for severe asthma, optimal treatment approaches for the pediatric population are less well established. Furthermore, best practices regarding real world management and implementation of guidelines for the severe pediatric asthma population are lacking. In order to provide care for this population, institutions around the United States have developed multidisciplinary severe pediatric asthma programs (SPAPs). In recent years, the North American Severe Pediatric Asthma Consortium (NASPAC) was established as a mechanism for SPAPs to collaborate and share …

Relationship Between Sociodemographic Characteristics At Presentation And Outcomes Of Provoked Venous Thromboembolism In United States Children: A Secondary Analysis Of The Multinational Kids-Duration Of Therapy For Thrombosis Trial., Hope P. Wilson, Maua M. Alleyne, Sanjay Ahuja, Ernest Amankwah, Aisha Bruce, Shannon L. Carpenter, Fernando F. Corrales-Medina, Craig A. Mullen, Arun Panigrahi, Lakshmi Srivaths, Courtney D. Thornburg, Anupam Verma, Gary Woods, Neil A. Goldenberg, Madhvi Rajpurkar

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Venous thromboembolism (VTE) is associated with adverse long-term sequelae, including recurrence and development of chronic venous insufficiency following limb deep vein thrombosis (postthrombotic syndrome [PTS]). Adult VTE studies have demonstrated that lower socioeconomic status, Black race, and Latinx ethnicity are associated with an increased risk of recurrence. Clinical trial-derived pediatric VTE data are limited.

OBJECTIVES: The objective of this study was to assess whether clinical features of provoked VTE and outcomes vary across sociodemographic characteristics and proxies for social determinants of health among children enrolled in the Kids-duration of therapy for thrombosis trial.

METHODS: We conducted a secondary analysis …

A Phase-Ii Randomized Controlled Pilot Study Of Nicotinamide Riboside Supplementation In Older Adults With Amnestic Mild Cognitive Impairment, Christopher Martens, Kevin Decker, Theodore Deconne, Faria Sanjana, Fiona Horvat, Nicholas Rizzi, Catherine Awad, Elizabeth Habash, Joshua Hobson, Mary Kramer, Michael Armstrong, Nichole Reisdorph, Ryan Pohlig, Alyssa Lanzi, Curtis Johnson, Matthew Cohen, James Ellison

Department of Psychiatry and Human Behavior Faculty Papers

INTRODUCTION: Declining nicotinamide adenine dinucleotide (NAD+) may elevate risk of Alzheimer's disease.

METHODS: We conducted a 12-week double-blind, randomized, placebo-controlled pilot study to evaluate the safety, tolerability, and preliminary efficacy of the NAD+ precursor, nicotinamide riboside (NR), for enhancing cognitive function and cerebral blood flow (CBF) in adults with amnestic mild cognitive impairment (aMCI).

RESULTS: 42 participants completed the study (NR = 22, placebo = 20). Adherence was similar between groups with no serious adverse effects. Blood NAD+ increased twofold in the NR group. There were no improvements in cognitive function (primary outcome), total CBF, or blood pressure (secondary outcomes). …

Risk Factors And Implications Of The Unplanned Shunt In Carotid Endarterectomy, Luisa Trujillo-Guerrero, Camilo Ramírez-Giraldo, Gordon H Martin, Naveed U Saqib, Akiko Tanaka, Margaret L Jackson, Shah-Jahan Dodwad, S Keisin Wang

Faculty, Staff and Student Publications

Background: The implications of intraoperative shunting during carotid endarterectomy (CEA) have been studied often with variable recommendations. While some surgeons favor routine shunting to minimize cerebral hypoperfusion, others reserve shunting based on intraoperative monitoring or high-risk clinical features. Predictors of shunt need not remain poorly defined. This study aimed to identify risk factors associated with overall shunt use and unplanned shunting in patients undergoing CEA.

Methods: We performed a retrospective review of a prospectively maintained large academic United States-based health system carotid surgery database between December 2004 and June 2024. Patients were stratified into two groups: procedures performed in absence …

Evaluation Of The Impact Of A Pathology Trainee-Driven Manual Review Process For Reference Testing At A Large Academic Center, Carly Maucione, Christopher W Farnsworth, Mark A Zaydman

2020-Current year OA Pubs

BACKGROUND: Increasing reliance on and complexity of laboratory testing necessitates laboratory stewardship initiatives to ensure appropriate test ordering, especially as reference testing costs continue to rise. Prospective manual review processes, although demanding of resources, have been shown to be cost-effective, but literature addressing the value of such a process is lacking.

METHODS: The pathology trainee-driven manual review process of 444 chemistry and microbiology tests on approval at a large academic center was reviewed. Data were extracted from an internal-use call-log and analyzed for test volumes, cancellation rates, and cost savings. A hypergeometric distribution was used to model random variation in …

Longitudinal And Cross-Sectional Evidence That Daily Resting And Activity Energy Expenditures Are Independent In Humans, Andrew K Yegian, Elizabeth Pachus, Leanne M Redman, Steven B Heymsfield, K Falkenhain, Alexandra R Harris, Shaji K Chacko, William W Wong, Daniel E Lieberman

Faculty, Staff and Students Publications

Total energy expenditure (TEE) is commonly modelled as the sum of resting energy expenditure (REE), activity energy expenditure (AEE), and diet-induced thermogenesis (DIT). This additive model has recently been challenged by the constrained energy balance model, which proposes that reductions in mass-adjusted REE compensate to some extent for increases in AEE, rendering mass-adjusted TEE effectively invariant. We tested these competing models using two complementary approaches. First, we conducted a short-term longitudinal, repeated-measures experiment in 12 adults who completed 10-day periods of high and low physical activity separated by a washout period. TEE was measured with doubly labelled water, AEE with …

Multi-Center Comparison Of Corticotropin Releasing Hormone Vs. Desmopressin Stimulation Responses In Inferior Petrosal Sinus Sampling For Cushing's Disease, Samuel A Tenhoeve, Julie M Silverstein, Albert H Kim, Et Al.

2020-Current year OA Pubs

OBJECTIVES: Inferior petrosal sinus sampling (IPSS) is important for confirming Cushing's Disease (CD). Due to lack of corticotropin releasing hormone (CRH) availability, desmopressin/DDAVP is being used as the alternative stimulating agent but has limited data regarding testing cutoffs.

DESIGN: We compared the stimulation profiles of desmopressin and CRH in patients with CD.

METHODS: Data from the multi-center Registry of Adenomas of the PItuitary and Related Disorders (RAPID) was evaluated. 93 patients with CD confirmed by pathology or biochemical remission that underwent IPSS testing prior to surgical resection (desmopressin [n = 57], CRH [n = 36] or both [n = 1]). …

Diagnostic Stewardship Of Respiratory Cultures Using Clinical Decision Support In The Picu, Anna C Sick-Samuels, John C Lin, Rebecca G Same, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Endotracheal aspirate culture (EAC) practices for evaluation of ventilator-associated infections (VAI) vary widely across pediatric hospitals, and overuse can contribute to overdiagnosis and overtreatment for VAI. Diagnostic stewardship strategies to optimize EAC testing practices may reduce overtesting and unnecessary antibiotic treatment.

OBJECTIVE: To evaluate the association of diagnostic stewardship of EACs using clinical decision support with culture rates, antibiotic use, and patient outcomes across a multicenter collaborative of pediatric intensive care units (PICUs).

DESIGN, SETTING, AND PARTICIPANTS: This was a multicenter cohort study with a pre-post study design among the BrighT STAR (Testing Stewardship for Antibiotic Reduction) Quality Improvement …

Patient-Centered Approach To Surgical Prevention Of Ovarian Cancer: A Nonrandomized Clinical Trial, Karen H Lu, Andrea R Hagemann, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Risk-reducing salpingo-oophorectomy (RRSO) is an effective option to prevent ovarian cancer in high-risk individuals, but adverse effects from premature menopause are a barrier to uptake. Interval salpingectomy with delayed oophorectomy (ISDO) may be an effective alternative.

OBJECTIVE: To evaluate the association of ISDO vs RRSO and sexual function and menopausal symptoms.

DESIGN, SETTING, AND PARTICIPANTS: This prospective, multicenter, nonrandomized (patient preference) clinical trial was performed among Women Choosing Surgical Prevention participants with a pathogenic or likely pathogenic germline variant conferring an increased risk for ovarian cancer. Patients from 9 US centers were enrolled from June 2, 2016, to October …

Prescribed Short-Acting Hormonal Contraceptive Use Among Premenopausal Females, Israel Bacha, Suleepon Uttamapinan, Hannah Harsanyi, Abigail Liberty, Lin Yang, Adetunji T Toriola

2020-Current year OA Pubs

IMPORTANCE: Hormonal contraceptive use has important implications for both reproductive and general health. However, the patterns and trends of short-acting hormonal contraceptive use among US premenopausal females remain insufficiently characterized.

OBJECTIVE: To evaluate trends in and factors associated with prescribed short-acting hormonal contraceptive use among US premenopausal females.

DESIGN, SETTING, AND PARTICIPANTS: Serial, cross-sectional analyses were conducted using US nationally representative data from the National Health and Nutrition Examination Survey (NHANES), including 10 survey cycles between 1999 to 2000 and 2017 to 2020 (before the COVID-19 pandemic). Participants included noninstitutionalized premenopausal females aged 15 years to younger than 60 years …

Maternal Health And Sociodemographic Characteristics Influence Infant Growth To 24 Months In The Tunza Mwana Cohort: A Prospective Cohort Study, David Taylor Hendrixson, Mark J Manary, Et Al.

2020-Current year OA Pubs

Upstream pathways influencing child growth are complex. Weight-for-age z-score (WAZ) reflects both ponderal and linear growth and can identify children at high mortality risk. Using data from a prospective cohort of 326 mother-child pairs in Kenya, we evaluated whether associations between maternal exposures and child growth outcomes in early and later childhood. Growth trajectories were examined using locally weighted scatterplot smoothing and piecewise linear mixed-effect models with a knot at age 3 months. Poisson regression models examined associations between maternal characteristics and child underweight (WAZ <  -2) and stunting (LAZ <  -2) before and after 3 months. Mean WAZ increased to a peak at 3 months before declining steadily through 24 months. Lower maternal education (adjusted β [aβ] -0.18; 95% CI: -0.24, -0.13), household crowding (aβ -0.2; 95% CI: -0.28, -0.11), lower wealth quintile (aβ -0.04; 95% CI: -0.06, -0.02) and multiparity (aβ -0.16; 95% CI: -0.23, -0.1) were associated with lower monthly rate of change in WAZ prior to age 3 months. Younger maternal age was associated with an increased monthly rate of change in WAZ (aβ = 0.13; 95% CI: 0.08, 0.18) before 3 months and decreased monthly WAZ (aβ -0.02; 95% CI: -0.03, -0.01) after 3 months. Preterm birth was associated with increased risk of underweight in both periods (aRR 2.77; 95% CI: 1.39-5.50). Maternal mental health, intimate partner violence and adverse childhood experiences were not significantly associated with child growth. Maternal nutritional, socio-economic and household-level factors shape early growth, emphasising the need for cross-sectoral programs to support growth.

Arrhythmia Burden And Clinical Responses Under Continuous Monitoring In Heart Failure: Observations From The Alleviate-Hf Trial., Rami Kahwash, Javed Butler, Muhammad Shahzeb Khan, David Zhang, Jonathan Dukes, Madhu Reddy, Rachel M Kaplan, Anish Amin, Rahul Kanwar, Shantanu Sarkar, Verla Laager, Jennifer Wehking, Brian Van Dorn, Bart Gerritse, Nirav Patel, Aimee Laechelt, Michael R Zile, Alleviate-Hf Investigators

OhioHealth Research Institute Articles

BACKGROUND: Arrhythmia burden in ambulatory patients with symptomatic heart failure (HF) without cardiac implantable electronic devices (CIEDs) is not well defined, and it remains uncertain whether device-guided remote congestion management modifies arrhythmia occurrence.

OBJECTIVES: The goal was to assess whether arrhythmia burden differed between randomized congestion-management strategies and characterize the occurrences and associations of insertable cardiac monitor (ICM)-detected arrhythmias with therapeutic actions and clinical events.

METHODS: In ALLEVIATE-HF, patients with NYHA functional class II-III HF with any ejection fraction (EF) and a recent HF event, without prior CIEDs, underwent ICM implantation and were randomized to ICM-guided, physician-directed, nurse-facilitated congestion management …

Risk-Based Nurse-Managed Personalized Heart Failure Interventions: The Alleviate-Hf Trial., Javed Butler, Rami Kahwash, Muhammad Shahzeb Khan, David Zhang, Jonathan W Dukes, Madhu Reddy, Anupam Basuray, Elie Gharib, Bart Gerritse, Aimee Laechelt, Jennifer Wehking, Shantanu Sarkar, Brian Van Dorn, Nirav Patel, Verla Laager, Michael R Zile, Alleviate-Hf Investigators

Heart and Vascular Articles

BACKGROUND: Early identification of worsening heart failure (HF) may improve outcomes.

OBJECTIVES: This study aims to assess if insertable cardiac monitor (ICM)-based high-risk detection combined with centrally managed, nurse-facilitated, individually protocolized diuretic interventions is safe and improves HF outcomes.

METHODS: A Reveal LINQ (Medtronic) ICM with an investigational HF risk-status software was implanted in participants with HF who were randomized 1:1 to an intervention arm (high-risk HF alert triggering protocolized diuretic regimen) or an observation arm (standard care). The primary safety endpoint was intervention-related serious adverse events and the primary efficacy endpoint was a 5-component hierarchical composite including cardiovascular death …

Fractionated Stereotactic Radiotherapy (Fsrt) For Symptomatic Who Grade 1 Cavernous Sinus Meningiomas: Long-Term Local Control, Clinical Response, And Toxicity Outcomes, Ryan Shah, Shray Jain, Nilanjan Haldar, Lauren A. Holt, Robert Walker, Christopher J Farrell, Md, Debanjan Haldar, James J. Evans, Gregory S. Alexander, Wenyin Shi

Department of Radiation Oncology Faculty Papers

PURPOSE: Cavernous sinus meningiomas represent a significant clinical challenge, given the high prevalence of neurological deficits and limited surgical options. Radiation therapy is often the preferred treatment. This study evaluates the effectiveness of fractionated stereotactic radiation therapy (fSRT) in achieving local control and symptomatic relief in patients with cavernous sinus meningiomas.

METHODS: This is a single-institution retrospective analysis of patients with symptomatic presumed WHO grade 1 cavernous sinus meningiomas treated with fSRT (1.8-2 Gy per fraction). Clinical data were collected by chart review. Kaplan-Meier curves were generated to assess local control. Clinical responses were evaluated for symptom improvement, stability, or …

Crispr/Cas9-Based Genome Editing: Understanding Differences In Dna Repair Pathways, Profiles, And Outcomes, Samuel Effah, Shirley Barrera, Nahia Urturi Ortiz, Will Dampier, Michael Nonnemacher, Brian Wigdahl

Kimmel Cancer Center Faculty Papers

Over a decade of advances in Clustered Regularly Interspersed Short Palindromic Repeats (CRISPR) and CRISPR-associated protein 9 (Cas9)-based technologies have culminated in the first-ever FDA-approved CRISPR/Cas-based therapy. Aside from this approved therapy for sickle cell anemia, several CRISPR/Cas-based therapies are currently under development or testing for a range of chronic diseases, including viral diseases like human immunodeficiency virus type 1 (HIV-1) infection, genetic diseases like familial hypercholesterolemia, and cancer. The success of these therapies hinges on the effective delivery of CRISPR/Cas9 components to target regions, efficient Cas endonuclease editing, repair profiles generated, and their resulting outcomes. Here, we discuss the …

Fgfr3::Tacc3 Fusion And Notch1 Loss-Of-Function In A Case Of Hpv-Associated Sinonasal Squamous Cell Carcinoma: Diagnostic Challenge And Implications For Targeted Therapy, Xu Cao, Hong Yu, Reham Hamdy Abdulazim Soliman, Pei Ying, Songlin Zhang, Li Liang

Faculty, Staff and Students Publications

Sinonasal squamous cell carcinoma (SNSCC) comprises a heterogeneous group of tumors with emerging molecular subtypes. Human papillomavirus (HPV)-associated SNSCC is a distinct entity, although actionable genomic alterations beyond HPV-driven pathways remain underexplored. Distinguishing HPV-associated SNSCC from carcinoma ex inverted papilloma can be particularly challenging in limited biopsy specimens, as these lesions may appear morphologically similar. We report a case of HPV-associated SNSCC with concurrent FGFR3::TACC3 fusion and NOTCH1 p.C1416 stop-gain mutation.

Oncocytic Intraductal Carcinoma Of The Parotid Gland With Strn::Alk Fusion, Reham H Soliman, Chris Shi, Kevin E Fisher, Hong Yu, Fouad El-Dana, Xu Cao, Li Liang, Pei Ying, Songlin Zhang

Faculty, Staff and Students Publications

Intraductal carcinoma (IDC) of the salivary gland is an uncommon epithelial neoplasm characterized by a predominantly intraductal or intracystic proliferation rimmed by a myoepithelial cell layer. Advances in molecular profiling have revealed recurrent gene fusions in IDC, most frequently involving RET, although fusions implicating other kinase genes have also been described. Among these, ALK rearrangements are rare and remain poorly characterized. Herein, we report a case of oncocytic IDC of the parotid gland harboring a STRN::ALK fusion, further expanding the molecular landscape of this tumor. Although this fusion has been previously reported in intercalated duct IDC, to our knowledge, this …

Comprehensive Prediction Analysis Of Novel Noncoding Regulatory Variants Identified In The Microrna Binding Regions In Complement System Genes, Anthony Shadid, Haydn E Rich, Kathryn D Hok, Marie-Francoise Doursout, Marcos I Restrepo, Nirmal K Banda, Lavanya Gunamalai, Pooja Shivshankar

The Brown Foundation: Institute of Molecular Medicine

The complement system is a central component of innate immunity that coordinates host defense, immune surveillance, and inflammatory responses through tightly regulated proteolytic cascades. Genetic variation within complement genes contributes substantially to interindividual differences in complement activity and disease susceptibility. While coding variants directly alter complement protein structure and function, the microRNA (miRNA)-mediated control and post-transcriptional regulation is not fully understood in shaping complement gene expression across immune and inflammatory mechanisms. Complement pathway genes exhibit extensive and heterogeneous 3'-untranslated regions (3'UTRs), which serve as primary platforms for miRNA binding and RNA-binding protein interactions. Both common and rare single-nucleotide polymorphisms within …

Chemotherapeutic Induction Of Cytosolic Single-Stranded Dna Accumulation Sensitizes Triple-Negative Breast Cancer To Immunotherapy, Yong Du, Li Yang, Hui Dai, Jianli Zhou, Zhicheng Zhou, Ruoxi Yuan, Rui Ye, Anh Thai Quynh Nguyen, Kishor Bhatia, Shiaw-Yih Lin

Faculty, Staff and Students Publications

Background: Despite the widespread adoption of chemoimmunotherapy in triple-negative breast cancer (TNBC), the mechanisms by which cytotoxic chemotherapy engages antitumor immunity remain poorly defined. Identifying tumor-intrinsic immunogenic programs that predict and enhance responsiveness to immune checkpoint blockade (ICB) is therefore of critical clinical importance.

Methods: Transcriptomic signatures of TREX1 deficiency were generated from CRISPR-engineered TNBC models and applied to multiple independent TNBC cohorts treated with chemoimmunotherapy. Cytosolic single-stranded DNA (ssDNA) accumulation was quantified using a flow cytometry-based assay to functionally screen chemotherapeutic agents. Immune activation and therapeutic efficacy were evaluated using in vitro assays, syngeneic mouse tumor models, flow cytometry, …

Obesity And Keratoconus: A Mediation Study Based On The Chinese Keratoconus Cohort, Kaili Yang, Anqi Chang, Runqi Tu, Liyan Xu, Yuwei Gu, Qi Fan, Shanshan Yin, Yi Yuan, Yifan Wang, Chenchen Yin, Yonghao Zang, Changxiu Li, Chenjiu Pang, Daniela Oehring, Yibin Hao, Shengwei Ren

School of Health Professions

Purpose: Growing evidence indicates a strong association between obesity and keratoconus (KC), although the potential mediating factors remain largely unknown. This study aimed to explore the potential pathways through which corneal biomechanical and topographic parameters might link obesity and KC using structural equation modeling (SEM). Methods: This case-control study included 759 participants (363 patients with KC and 396 controls) from the Chinese Keratoconus (CKC) Cohort Study. Associations among body mass index (BMI), corneal biomechanical parameters, topographic parameters, and KC were analyzed using generalized linear regression models. SEM was used to construct latent variables for corneal biomechanical and topographic parameters. Three …

Association Of Cerebrovascular Center Volume With Patient Outcomes, Stacey Quintero Wolfe, Justin R. Mascitelli, Kyle Fargen, Peter Kan, Ketan Bulsara, Christopher P. Kellner, Brian M. Howard, Michael R. Levitt, Rocco Armonda, Joshua Osbun, Clemens Schirmer, Mark Bain, William J. Mack, Stavropoula Tjoumakaris, Adam Arthur

Department of Neurosurgery Faculty Papers

Current guidelines acknowledge the importance of both microsurgical and neuroendovascular expertise in the treatment of cerebrovascular disease. To achieve optimal care for these patients, it is becoming increasingly evident that procedural volumes impact patient outcomes. This is demonstrated across various cerebrovascular diseases.In this literature review, we demonstrate the association of volume with patient outcomes across multiple cerebrovascular disease states and interventions. Microsurgical aneurysm clipping remains essential even with the rise of endovascular therapy and mortality and patient-safety indicator events are clearly lower at high-volume centers for both ruptured and unruptured aneurysms. Likewise, patients undergoing surgery for cerebrovascular malformations and carotid …

Unveiling Unwritten Curricula: Enhancing Junior Faculty Development In Academic Emergency Medicine, Abagayle Bierowski, Casey Morrone, Erin Hoag, Ridhima Ghei, Michael Pasirstein, Julie Blaszczak, Dimitrios Papanagnou

Department of Emergency Medicine Faculty Papers

INTRODUCTION: The transition from resident to junior faculty in academic emergency medicine (EM) may be shaped not only by formal training and institutional policies but also by the "unwritten curriculum," a set of norms and expectations embedded in institutional culture. However, the unwritten curriculum and its potential to impact junior faculty development remains largely unexplored. Little is known about how junior faculty perceive, experience, and navigate these informal expectations, or the formal and informal structures that influence this process. In this study we aimed to explore junior faculty members' experiences with the unwritten curriculum in academic EM, with a focus …