Digital Commons Network^™

Asynchronous Transitions From High-Risk Hepatoblastoma To Carcinoma, Xinjian Yu, Stephen Sarabia, Martin Urbicain, Sonal Somvanshi, Roma Patel, Priyanka Rao, Tuan M Tran, Yen-Ping Yeh, Keng-Shih Chang, Yi-Tzu Lo, Jessica Epps, Kathleen A Scorsone, Hua-Sheng Chiu, Emporia Faith Hollingsworth, Cintia R Perez, Mohammad Javad Najaf Panah, Barry Zorman, Jordan Muscal, Milton J Finegold, John A Goss, Rita Alaggio, Angshumoy Roy, Kevin E Fisher, Andras Heczey, Sarah Woodfield, Sanjeev Vasudevan, Kalyani Patel, Ting-Wen Chen, Dolores Lopez-Terrada, Pavel Sumazin

Faculty, Staff and Students Publications

Background & aims: Most pediatric hepatocellular tumors are classified as hepatoblastoma (HB) or hepatocellular carcinoma (HCC), yet a subset exhibits mixed histological and molecular features. These hepatoblastomas with carcinoma features (HBCs) include cases provisionally designated as hepatocellular neoplasm-not otherwise specified (HCN-NOS). Their biology remains poorly understood, with unresolved questions about their cellular composition and outcomes. It is unclear whether HBCs comprise hybrid cells with combined HB and HCC characteristics (HBC cells) or admixtures of distinct HB and HCC cells. We characterized the biology, etiology, cellular composition, and evolutionary dynamics of HBCs.

Methods: We performed multi-omics profiling - including single-nucleus RNA …

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.

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 …

Factors Associated With Pre-Donation Health-Related Quality-Of-Life Among Pediatric Sibling Hematopoietic Cell Donors: A Donorkids Ql Study., Galen E. Switzer, Jessica G. Bruce, Bronwen E. Shaw, Vidya Kuniyil, James W. Varni, Brandan J. Butler, Connor Erickson, Alisha Mussetter, Allison Neutzling, Hisham Abdel-Azim, Paibel Aguayo-Hiraldo, Eric J. Anderson, Victor M. Aquino, Karlie Boone, Farid Boulad, Joseph H. Chewning, Jessica Cooper, Ann Dahlberg, Christopher C. Dvorak, Jorge Galvez-Silva, Ann E. Haight, Jennifer A. Hoag, Michelle Hudspeth, David Jacobsohn, Kimberly A. Kasow, Carrie L. Kitko, Lakshmanan Krishnamurti, Lisa Madden, Holly K. Miller, Erin Morales, Timothy S. Olson, Anna B. Pawlowska, Vinod K. Prasad, Troy C. Quigg, Andromachi Scaradavou, Niketa C. Shah, Shalini Shenoy, Nancy Terwilliger, Lori Wiener, Gregory A. Yanik, Lolie C. Yu, Michael A. Pulsipher

Manuscripts, Articles, Book Chapters and Other Papers

Due to limited published data assessing pediatric hematopoietic cell donor experiences, we previously conducted one of the largest quantitative investigations of pediatric donor experiences and health-related quality-of-life (HRQoL) at the time (RDSafe). Findings from RDSafe demonstrated that a subset of pediatric HC donors experienced very poor HRQoL; unfortunately, that dataset addressed only a limited number of factors, and key associations explaining this poor HRQoL were not found. In this study, our goal was to address that deficit by describing pre-donation donor HRQoL in detail and identifying factors across five key domains that were associated with donor HRQoL. We conducted a …

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 …

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. …

Functional Assessment Of A Convergent Gene Network Underlying Allergic Diseases And Ige., Pradeep Eranti, Raphaël Vernet, Christophe Linhard, Bing Ge, Laura Beaumier, Anne-Marie Madore, Sébastien Chanoine, Bénédicte L. Tremblay, Xiaojian Shao, Isabelle Pin, Mark Lathrop, Elin Grundberg, Valérie Siroux, Tomi Pastinen, Catherine Laprise, Emmanuelle Bouzigon, Florence Demenais

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: The relationships between allergic diseases (AD) and IgE levels are complex.

OBJECTIVE: We sought to identify genes associated with AD and IgE having close proximity in the interactome and to elucidate the associated biological mechanisms.

METHODS: We integrated a comprehensive interactome with data from genome-wide (GWAS) and epigenome-wide (EWAS) association studies of AD and IgE levels, respectively. We used the SigMod algorithm to identify gene modules enriched in AD- and IgE-associated signals. We performed a connectivity analysis of these two modules to characterize direct cross-trait connections. Finally, we conducted an in-depth functional analysis of the directly-connected AD and IgE …

State And Regional Variation In Access To Pediatric Extracorporeal Membrane Oxygenation., Allan M. Joseph, Andrew J. Lautz, Carlie N. Myers, Ranjit S. Chima, Juan P. Gurria, Shafee Salloum, Wendy Hasson, Matthew P. Malone, Jenna Miller, Reanna Smith, Maya L. Dewan

Manuscripts, Articles, Book Chapters and Other Papers

Extracorporeal membrane oxygenation (ECMO) is only available in specialized medical centers. We conducted a geospatial analysis and found state- and region-level variation in the supply of ECMO centers, and the number of children who had access to ECMO. These findings may help target areas for the development of new ECMO programs.

The Critical Pediatric Obesity Window: Pre-Pubertal Metabolic Disease And The Fallacy Of Delayed Intervention., Matthew Lindquist, Brooke Sweeney

Manuscripts, Articles, Book Chapters and Other Papers

Despite increasing recognition of pediatric obesity as a chronic disease, many clinicians continue to rely on "watchful waiting," assuming pubertal growth will mitigate excess weight and metabolic risk. Current evidence contradicts this approach. Children under 12 years of age with obesity frequently demonstrate clinically significant metabolic disease, including insulin resistance, dyslipidemia, dysglycemia, and metabolic dysfunction-associated steatotic liver disease (MASLD), often before symptoms emerge. Puberty does not reverse these processes; rather, physiologic pubertal insulin resistance amplifies preexisting metabolic dysfunction and accelerates disease progression. Delayed intervention allows potentially irreversible injury during a critical period of metabolic plasticity. This article reviews contemporary biologic …

Cytokine-Based Strategies To Improve Prognostic Enrichment Of Pediatric Ards., E Scott Halstead, Todd M. Umstead, Zissis C. Chroneos, Cainan Riccio-Baum, S Rameeza Allie, Daniel J. Mckeone, Debbie Spear, Ryan A. Nofziger, Ronald C. Sanders, Danielle Ahn, Jasmine C. Dowell, Asdis Finnsdottir Wagner, Neal J. Thomas, Prithvi Sendi, W Joshua Frazier, Courtney M. Rowan, Parag N. Jain, Dalia A. Bashir, Stuart H. Friess, Brian M. Varisco, Jocelyn Grunwell, Aline B. Maddux, Stephen T. Famularo, Nadir Yehya

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Hyper-inflammation is common to multiple critical care syndromes, including acute respiratory distress syndrome (ARDS) and sepsis, and is associated with worse outcomes. A signature of hyper-inflammatory ARDS has been described in adults using IL-6, TNFR1, and bicarbonate, and has prognostic utility. We investigated the application of this traditional parsimonious signature to pediatric ARDS patients and tested whether we could improve prognostic enrichment using other cytokines.

METHODS: We leveraged a prospective multicenter cohort study of 500 children with ARDS (Linking Endotypes and Outcomes in Pediatric Acute Respiratory Distress Syndrome [LEOPARDS]; NCT04113434) study. Plasma samples were obtained within 24 h of …

Insurance Type And Menopausal Hormone Therapy Use Among Us Women, Arina Chesnokova, Sunni Mumford, Allison Schachter, Rebecca Hamm, Scott Lorch, Matthew Klebanoff, Sarah Lindley, Erika Harness, Makeba Williams, Marilyn Schapira

Student Papers, Posters & Projects

IMPORTANCE: Access to menopausal hormone therapy (MHT) in the US remains low. Understanding whether insurance type is associated with MHT underuse and racial disparities in menopausal care is critical for designing interventions that increase evidence-based and equitable menopause care.

OBJECTIVE: To examine whether Medicaid compared with private insurance is associated with lower MHT use among US women. A secondary objective explored the degree that payer type is associated with observed racial differences in MHT use.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used the 2013-2014, 2015-2016, and 2017-2020 cycles of the National Health and Nutrition Examination Survey (NHANES) to identify …

Donor-Derived Cell-Free Dna As A Prognostic Biomarker After Heart Transplantation: The Define-Ht Study, Palak Shah, Paul J. Kim, Kelly H. Schlendorf, David A. Baran, Monica M. Colvin, Adam D. Devore, Howard Eisen, Kambiz Ghafourian, Michael M. Givertz, Eileen Hsich, Jaime L. W. Kennedy, Evan P. Kransdorf, Jose N. Nativi-Nicolau, Jignesh Patel, Eleni Tseliou, Omar Wever-Pinzon, Andrew Doud, Michelle S. Bloom, Sandra A. Carey, Navchetan Kaur, D Giovanni Biagini, Kyle E. Marshall, Michael Olympios, Mandeep R. Mehra, Josef Stehlik

Department of Medicine Faculty Papers

BACKGROUND: Measurement of donor-derived cell-free DNA fraction (dd-cfDNA%) and donor quantity score (DQS) is a noninvasive biomarker of acute rejection in heart transplantation (HT). Its prognostic value beyond histopathology remains uncertain.

OBJECTIVES: This study sought to evaluate associations between donor-derived cell-free DNA (dd-cfDNA) and clinically meaningful outcomes using a composite endpoint of treated rejection, graft dysfunction, retransplantation, or death within 1 year post-HT.

METHODS: The DEFINE-HT (Development of Noninvasive Cell-free DNA to Supplant Invasive Biopsy in Heart Transplantation) was a prospective, observational study following adult HT recipients at 10 U.S. centers for 1-year post-HT; blood was collected for dd-cfDNA testing …

Fluoroquinolone Use And Risk Of Pneumothorax In Adults Hospitalized With Community Acquired Pneumonia: A Retrospective Cohort Study, Steven Yi B. S., Saurav Sumughan B.S., Jessica Cobb M. D., Erika J. Yoo

Department of Medicine Faculty Papers

Objectives: The objective of this study is to examine the relationship between fluoroquinolone exposure and pneumothorax risk in patients hospitalized with pneumonia.

Methods: This retrospective cohort study used the TriNetX US Collaborative Network. We defined two mutually exclusive cohorts of hospitalized adults based on exposure to antibiotic classes commonly used to treat community acquired pneumonia: fluoroquinolone (ciprofloxacin, moxifloxacin, levofloxacin, and ofloxacin) versus nonfluoroquinolone (amoxicillin, azithromycin, ceftriaxone, and doxycycline). Patients with connective tissue disorders were excluded. The primary outcome was the occurrence of pneumothorax within 60 days. We used Cox proportional hazards regression to estimate hazard ratios (HRs) adjusted for demographics, …

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 …

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 …

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 …

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 …

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, …

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 …

Folr1-Targeted Actinium-225-Based Alpha-Particle Therapy Eliminates Ovarian Cancer, Neetu Singh, Esther Need, Ayden Berndt, Matthew Goff, Lydia J. Wilson, Firas Mourtada, Feng Guo, Tara Mastren, Taslim Al-Hilal, Anil K. Sood, Amit Maity, Scott C. Miller, Satoshi Minoshima, Shreya Goel, Sixiang Shi

Department of Radiation Oncology Faculty Papers

Despite the advancement in therapies, ovarian cancer treatment is challenging because of poor prognosis and high relapse associated with acquired resistance. Emerging targeted alpha particles, particularly actinium-225 (225Ac), for treating refractory cancers have opened avenues for improved therapeutic options. Here, we describe a successful example of folate receptor 1 (FOLR1)–targeted 225Ac alpha-particle therapy for treatment of ovarian cancer. Longitudinal positron emission tomography imaging demonstrated high tumor-specific uptake of αFOLR1 (anti-FOLR1 antibody) in SKOV3 xenografts. FOLR1-targeted 225Ac demonstrated high therapeutic efficacy, achieving marked tumor regression, 80% survival, and 40% complete tumor elimination. The therapy resulted in tumor-specific double-stranded DNA damage, and …

Plasma Gdf15 Affects Long-Term Dementia Risk And Alters Neuroimmune Signaling, Cassandra O Blew, Michael R Duggan, Dimitrios Tsitsipatis, Gabriela T Gomez, Zulema Rodriguez-Hernandez, Luke C Pilling, Jingsha Chen, Eva Jacobsen, Heather E Dark, Yifei Lu, Shannon M Drouin, Cassandra M Joynes, Minhao Yao, Murat Bilgel, Abhay Moghekar, Qu Tian, Julián Candia, Mary Kaileh, Aditi Gupta, Krystyna Mazan-Mamczarz, Myriam Gorospe, Alexey Lyashkov, Yevgeniya Lukyanenko, Mika Kivimaki, Philipp Frank, Lori L Jennings, Valborg Gudmundsdottir, Vilmundur Gudnason, Lenore J Launer, Naoto Kaneko, Shintaro Kato, Makio Furuichi, Masaki Shibayama, Masahisa Katsuno, Keita Hiraga, Yukiko Nishita, Rei Otsuka, James R Pike, Mary R Rooney, Pascal Schlosser, Yuhan Cui, Guray Erus, Christos Davatzikos, Rebecca F Gottesman, Iwao Waga, Priya Palta, Christie Ballantyne, Michael Griswold, Zhonghua Liu, Luigi Ferrucci, Allison B Herman, Keenan A Walker

Faculty, Staff and Students Publications

Growth/differentiation factor-15 (GDF15) is a secreted cytokine strongly associated with dementia risk. However, the extent to which GDF15 represents a biomarker and driver of dementia risk remains unclear. Across multiple cohorts, we demonstrated that plasma GDF15 is associated with greater dementia risk over 15- to 25-year follow-up periods when measured in midlife, with stronger associations observed for vascular, compared to Alzheimer's disease (AD), dementia. Two-sample Mendelian randomization supported plasma GDF15's mechanistic role in AD and related dementias, while cohort studies linked it to cerebral small vessel disease, neurodegeneration, phosphorylated tau, and a cerebrospinal fluid proteomic signature indicative of neuroimmune activation. …

Adaptation Of The Transition Readiness Assessment Questionnaire For Pediatric-Onset Multiple Sclerosis: Protocol For A User-Centered Design Approach, Claudia Gambrah-Lyles, Aaron W Abrams, Sara Loud, Hollie Schmidt, Emily Blosberg, Melissa Wright, Kelsey E Poisson, Kristen S Fisher, Kimberly A O'Neill, Akash Virupakshaiah, John W Rose

Faculty, Staff and Students Publications

Background: Pediatric-onset multiple sclerosis (POMS) is a chronic, progressive neurologic condition requiring lifelong management and coordinated transition from pediatric to adult care. Evidence-based guidelines identify transition readiness assessment as a core component of successful transition; however, most POMS clinics do not formally assess readiness, and existing tools do not address POMS-specific challenges, such as fluctuating disability, complex treatment regimens, and cognitive impairment. This gap underscores the need for a transition readiness measure tailored to POMS.

Objective: This paper aims to describe a stakeholder-engaged, implementation science-guided protocol for adapting the Transition Readiness Assessment Questionnaire (TRAQ) version 6.0 to reflect the unique …

Meeting Report From The 2025 Cure Ocular Melanoma (Cure Om) Global Science Meeting, Amsterdam, The Netherlands, October 2025, Andrew E. Aplin, Katherina Alsina, Allison S. Betof, Joseph Birkett, Marcus O. Butler, George Cole, Rizwan Haq, Florian A. Karreth, Vinit B. Mahajan, Rahul Marpadga, Prithvi Mruthyunjaya, Paul Nathan, Jonas A. Nilsson, Gary Palmer, Joseph J. Sacco, Takami Sato, Sarah Stanhope, Pang-Ning Teng, Kyleigh Lipira

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

The 2025 Cure Ocular Melanoma (CURE OM) Global Science Meeting took place in Amsterdam, The Netherlands on October 25th, 2025. Several promising drug candidates are in development; however, there is still an urgent need for better prevention, detection, and treatment of uveal melanoma. The purpose of this meeting was to promote international collaboration and idea exchange between scientists, industry, and patient advocates.

Intersection Of Pediatric Hypertension And Cardiovascular-Kidney-Metabolic Disease, Jessica O'Keeffe, Christina Kingshill, Jack Tompson, Andrew M. South, Carissa M. Baker-Smith

Department of Medicine Faculty Papers

PURPOSE OF REVIEW: The purpose of this review is to describe the intersection between pediatric hypertension and advancing stages of cardiovascular, kidney metabolic syndrome in children and adolescents.

RECENT FINDINGS: Cardiovascular-kidney-metabolic syndrome is highly prevalent in the pediatric population. The onset of CKM in childhood is influenced by the presence of antenatal risk factors such as maternal hypertensive disorders of pregnancy. Advancing stages of CKM in children and adolescents are strongly influenced by food insecurity and social determinants of health that impact the risk for childhood obesity. Activation of the renin-angiotensin-aldosterone system is a key mediator in the relationship between …