Digital Commons Network^™

An Annotated Biobank Of Triple-Negative Breast Cancer Patient-Derived Xenografts Features Treatment-Naïve And Longitudinal Samples During Neoadjuvant Chemotherapy, Amanda L Rinkenbaugh, Yuan Qi, Shirong Cai, Jiansu Shao, Faiza Baameur Hancock, Sabrina L Jeter-Jones, Xiaomei Zhang, Emily Powell, Lei Huo, Rosanna Lau, Chunxiao Fu, Rebekah Gould, Petra Den Hollander, Elizabeth E Ravenberg, Jason B White, Gaiane M Rauch, Banu Arun, Clinton Yam, Alastair M Thompson, Gloria V Echeverria, Stacy L Moulder, W Fraser Symmans, Jeffrey T Chang, Helen Piwnica-Worms

Faculty, Staff and Student Publications

Triple-negative breast cancer (TNBC) that fails to respond to neoadjuvant chemotherapy (NACT) can be lethal. Developing effective strategies to eradicate chemoresistant disease requires experimental models that recapitulate the heterogeneity characteristic of TNBC. To that end, we established a biobank of 92 orthotopic patient-derived xenograft (PDX) models of TNBC from the tumors of 75 patients enrolled in the ARTEMIS clinical trial (NCT02276443), including 12 longitudinal sets generated from serial patient biopsies collected throughout NACT treatment and from metastatic disease. Models were established from both chemosensitive and chemoresistant tumors, and nearly 30% of the PDX models were capable of metastasizing …

A Clinical Practice Guideline For The Management Of Pregnancy Alloimmunized To Red Blood Cell Antigens, Kenneth J Moise, Jay Malone, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Red blood cell alloimmunization is typically associated with the transplacental transfer of incompatible fetal red blood cells into maternal circulation. Subsequent pregnancies can be affected by fetal anemia, hydrops fetalis, and perinatal death. Most cases of Rhesus D (RhD) alloimmunization due to pregnancy can be prevented by the proper administration of Rhesus immune globulin. However, an emerging practice of using low-titer, O, RhD-positive whole blood (LTOWB) in cases of life-threatening hemorrhage has the potential to increase the exposure of the female population to a new source of incompatible red blood cells.

OBJECTIVE: To establish recommendations for the management of …

Availability Of Multidisciplinary Treatment Modalities And Outcomes Among Patients With Resected Early-Stage Non-Small Cell Lung Cancer, Brendan T Heiden, Su-Hsin Chang, Yan Yan, Ana A Baumann, Theodore S Thomas, Steven Tohmasi, Nikki Rossetti, Daniel Kreisel, Ruben G Nava, Bryan F Meyers, Benjamin D Kozower, Varun Puri, Et Al.

2020-Current year OA Pubs

BACKGROUND: Comprehensive, multidisciplinary care is crucial for managing early-stage non-small cell lung cancer (NSCLC), typically treated via lung resection or stereotactic body radiation therapy (SBRT). We evaluated how variable access to on-site SBRT may be associated with clinical outcomes for patients with stage I NSCLC receiving surgical resection within an integrated health-care system.

METHODS: We performed a retrospective cohort study of patients with stage I NSCLC treated with lung resection at Veterans Health Administration (VHA) facilities between 2006 and 2016. The VHA provides thoracic surgery at approximately 100 facilities, whereas lung SBRT is currently available at approximately 20 facilities. We …

Therapeutic Radiation Drives Leptomeningeal Dissemination Of Medulloblastoma Through An Innate Immune Process, Carolina Nör, Kaitlin Kharas, Alex Rasnitsyn, Maria C Vladoiu, Nam Woo Cho, Jacob S Young, Felipe Nör, Ncedile Mankahla, Joonas Haapasalo, Kristiina Nordfors, Sara Rapic, Patryk Skowron, Raúl A Suárez, Alexander T Bahcheli, Oliver Ocsenas, Xin Chen, Shahrzad Bahrampour, Ali Momin, Lakshmikirupa Sundaresan, Winnie Ong, Liam D Hendrikse, Namal Abeysundara, Kyle Juraschka, Michelle Ly, Jonelle G Pallota, Tajana Douglas, Ning Huang, Hao Wang, Esta Mak, Lei Qin, Jessica Liu, Lily Shen, Betty Luu, Alex Manno, Sachin A Kumar, Laura K Donovan, Vernon Fong, Cory Richman, Craig Daniels, Livia Garzia, Jeremy N Rich, Cynthia Hawkins, Xiaochong Wu, Ralph Dacosta, Jüri Reimand, Xi Huang, Vijay Ramaswamy, David R Raleigh, Michael D Taylor

Faculty, Staff and Students Publications

Leptomeningeal metastases are the most important source of morbidity and mortality for medulloblastoma patients. Radiation of the entire brain is highly effective in the treatment and/or prevention of medulloblastoma leptomeningeal metastases. Infants treated on clinical trials with focal tumor radiation recur metastatically, whereas infants treated with only chemotherapy relapse locally. In murine medulloblastoma model systems, provision of a single dose of radiation to the tumor drives leptomeningeal dissemination. An inflammatory response after radiation-induced tumor cell death recruits a variety of immune cells. Inflammation opens the local blood-brain barrier, allowing intravasation of medulloblastoma cells. Experimental induction of inflammation with lipopolysaccharide drives …

Orphan Nuclear Receptor 4a1 (Nr4a1) And Nr4a2 Are Endogenous Regulators Of Cd71 And Their Ligands Induce Ferroptosis In Breast Cancer, Arafat Rahman Oany, Srijana Upadhyay, Wai Ning Tiffany Tsui, Amanuel Hailemariam, Sarah Latka, John D Landua, Sandra D Scherer, Alana L Welm, Hugo Villanueva, Michael T Lewis, Stephen Safe

Faculty, Staff and Students Publications

Ferroptosis is an iron-dependent cell death pathway that involves multiple genes, including the transferrin receptor (TFRC/CD71), glutathione peroxidase 4 (GPX4) and cystine-glutamate antiporter (SLC7A11). This study is based on the hypothesis that orphan nuclear receptor 4A1 (NR4A1) and NR4A2 maintain low levels of ferroptosis in triple negative breast cancer (TNBC) cells and bis-indole derived (CDIM) compounds act as NR4A1/2 ligands that induce ferroptosis by enhancing CD71 expression. 1,1-Bis(3'-indolyl)-1-(3,5-disubstitutedphenyl)methane (DIM-3,5) analogs were investigated for their cytotoxicity and effects on NR4A1 and NR4A2 regulated genes and induction of ferroptosis. Several assays also determined enhanced lipoperoxidation, reactive oxygen species and malondialdehyde formation in …

A Multiomics Recovery Factor Predicts Long Covid In The Impacc Study, Gisela Gabernet, Jessica Maciuch, Jeremy P Gygi, John F Moore, Annmarie Hoch, Caitlin Syphurs, Tianyi Chu, Naresh Doni Jayavelu, David B Corry, Farrah Kheradmand, Lindsey R Baden, Rafick-Pierre Sekaly, Grace A Mccomsey, Elias K Haddad, Charles B Cairns, Nadine Rouphael, Ana Fernandez-Sesma, Viviana Simon, Jordan P Metcalf, Nelson I Agudelo Higuita, Catherine L Hough, William B Messer, Mark M Davis, Kari C Nadeau, Bali Pulendran, Monica Kraft, Chris Bime, Elaine F Reed, Joanna Schaenman, David J Erle, Carolyn S Calfee, Mark A Atkinson, Scott C Brakenridge, Esther Melamed, Albert C Shaw, David A Hafler, Alison D Augustine, Patrice M Becker, Al Ozonoff, Steven E Bosinger, Walter Eckalbar, Holden T Maecker, Seunghee Kim-Schulze, Hanno Steen, Florian Krammer, Kerstin Westendorf, Bjoern Peters, Slim Fourati, Matthew C Altman, Ofer Levy, Kinga K Smolen, Ruth R Montgomery, Joann Diray-Arce, Steven H Kleinstein, Leying Guan, Lauren Ir Ehrlich

Faculty, Staff and Students Publications

Background: Following SARS-CoV-2 infection, approximately 10%–35% of patients with COVID-19 experience long COVID (LC), in which debilitating symptoms persist for at least 3 months. Elucidating the biologic underpinnings of LC could identify therapeutic opportunities.

Methods: We utilized machine learning methods on biologic analytes provided over 12 months after hospital discharge from more than 500 patients with COVID-19 in the IMPACC cohort to identify a multiomics “recovery factor,” trained on patient-reported physical function survey scores. Immune profiling data included PBMC transcriptomics, serum O-link and plasma proteomics, plasma metabolomics, and blood mass cytometry by time of flight (CyTOF) protein levels. Recovery factor …

Integrative Proteogenomics And Forward Genetics Reveal A Novel Mitotic Vulnerability In Triple-Negative Breast Cancer, Nicholas J Neill, Shankha Satpathy, Karsten Krug, Jitendra K Meena, Nivetha Ramesh Babu, Cheyenne Calderon, Desmon Reed, Marcus J Weber, Lacey E Dobrolecki, Alaina Lewis, Christina Sallas, Meenakshi Anurag, Kimberly R Holloway, Chen Huang, Suhas Vasaikar, Maria F Cardenas, Beom-Jun Kim, Doug W Chan, Shayan C Avanessian, Siddhartha Tyagi, Mayra Orellana, Sufeng Mao, Heyuan Li, Fade Gong, Sarah J Kurley, Kristen L Meerbrey, Calla M Olson, Amritha Nair, Tingting Sun, Hsiang-Ching Chung, Elizabeth A Bowling, Jarey H Wang, Pengju Zhang, Peng Xiao, Duxiao Yang, Fabio Stossi, Mei-Yin C Polley, Alexander B Saltzman, Filip Mundt, D R Mani, Michael A Gillette, Susan G Hilsenbeck, George Miles, Carolina Gutierrez, C Kent Osborne, Charles Y Lin, Nathanael S Gray, Jinpeng Sun, David A Wheeler, Charles M Perou, Anna Malovannaya, Michael T Lewis, Bing Zhang, Matthew J Ellis, Steven A Carr, Thomas F Westbrook

Faculty, Staff and Students Publications

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with few effective targeted therapies. Taxanes and other microtubule-targeting agents (MTAs) are frontline chemotherapies for TNBC; however, the molecular pathways that cause TNBC taxane sensitivity are largely unknown, preventing selection of taxane-responsive patients and development of more selective therapeutic strategies. In this study, we identified tumor-selective vulnerabilities in TNBC harboring inactivation of the tumor suppressor PTPN12 by integrating proteogenomic characterization and synthetic lethality screening. We discovered that PTPN12 inactivation drives mitotic defects through aberrant hyperactivation of the ubiquitin ligase complex APCFZR1, a critical regulator of the cell cycle. Consistent …

Availability, Healthiness And Sodium Content Of Packaged And Unpackaged Foods And Beverages In Nigeria: A Cross-Sectional Study, Adedayo E Ojo, Erica L Jamro, Iyer Guhan, Mark D Huffman, Et Al.

2020-Current year OA Pubs

BACKGROUND: Nigeria is experiencing a growing burden of diet-related non-communicable diseases, particularly hypertension and cardiovascular disease, largely driven by high sodium intake and poor diet quality. Unhealthy dietary patterns characterized by excessive sodium, sugars, and unhealthy fats, and low intake of essential nutrients contribute to approximately 31% of global deaths annually. However, there is limited data on the sodium content and nutritional quality of foods in Nigerian markets. This study assessed and compared the availability, healthiness, and sodium content of packaged and unpackaged foods in Nigerian markets.

METHODS: From August 2022 to December 2022, we collected and compared nutrition data …

National Alliance Of Sickle Cell Centers Consensus Recommendations On Sickle Cell Disease Health Maintenance: A Consensus Statement, Seethal A Jacob, Sana Saif-Ur-Rehman, Et Al.

2020-Current year OA Pubs

IMPORTANCE: The most common inherited blood disorder in the world, sickle cell disease (SCD) is a known global health concern. While survival of children into adulthood has improved significantly over the last few decades in high-resource countries, substantial gaps in care standards and limited practice harmonization persist.

OBJECTIVE: To provide up-to-date recommendations for preventive care and treatment of all people living with SCD and its related comorbidities.

EVIDENCE REVIEW: As part of the National Alliance of Sickle Cell Centers (NASCC), 41 pediatric and adult sickle cell disease experts developed consensus standards and recommendations based on available evidence and expert consensus …

Diffusely Metastatic Glioblastoma With Fgfr3::Tacc3 Fusion: Cell-Free Dna Fragmentation Analyses And Molecular Characterization Of Matched Primary And Metastatic Tumor Sites, Miguel A Hernandez-Rovira, Alicia Vagnozzi, Tyler Bales, Keerthana N Prabhu, Noushin Niknafs, Milan Chheda, Jiayi Huang, Albert H Kim, Michelle Miller-Thomas, Omar Butt, Katie D Vo, Bhargavi S Sovani, Ashwin Singh Parihar, Suzanne Crumley, Sonika Dahiya, Dimitrios Mathios

2020-Current year OA Pubs

Extracranial metastasis of IDH-wildtype glioblastoma is very rare and poorly understood at the molecular level. We report a case of FGFR3::TACC3 fusion IDH-wildtype glioblastoma in a 61-year-old male, whose preoperative blood sample showed highly aberrant cfDNA fragmentation patterns, which could be suggestive of early systemic dissemination, undetected by standard-of-care imaging of his body. Eleven months post-resection and adjuvant therapy, he developed widespread extracranial metastases. Comprehensive molecular profiling of matched primary and metastatic tumors revealed broadly conserved genomic, transcriptomic, and copy number landscapes, with the metastasis harboring an additional ERCC6 deletion and enriched expression of receptor tyrosine kinase signaling genes. These …

Overexpression Of The Signaling Coordinator Gab2 Can Play An Important Role In Acute Myeloid Leukemia Progression, Michael H. Kramer, Stephanie N. Richardson, Yang Li, Tiankai Yin, Nichole M. Helton, Daniel R. George, Michelle Cai, Sai Mukund Ramakrishnan, Casey Ds Katerndahl, Christopher A. Miller, Timothy J. Ley

2020-Current year OA Pubs

Mutations that initiate acute myeloid leukemia (AML) can cause clonal expansion without transformation (clonal hematopoiesis). Cooperating mutations, usually in signaling genes, are needed to cause overt disease, but these may require a specific fitness state to be tolerated. Here, we show that nearly all AMLs arising in a mouse model expressing 2 common AML-initiating mutations (Dnmt3aR878H and Npm1cA) acquired a single copy amplification of chromosome 7 (chr7), followed by activating mutations in signaling genes. We show that overexpression of a single gene on chr7 (Gab2, which coordinates signaling pathways) was tolerated in the presence of the Npm1cA mutation, could accelerate …

Proteomic Perspectives On Kras-Driven Cancers And Emerging Therapeutic Approaches, Ramesh Karki, Ru Chen, Sheng Pan

Faculty, Staff and Student Publications

KRAS mutations are implicated in approximately 23% of all human malignancies, with particularly high prevalence in pancreatic ductal adenocarcinoma (PDAC) (~92%), colorectal cancer (CRC) (~49%), and non-small cell lung cancer (NSCLC) (~35%). The recent approval of the KRASG12C-specific inhibitors for NSCLC represents a pivotal advancement in KRAS-targeted therapy. Nevertheless, the emergence of intrinsic and acquired resistance to KRAS-targeted therapies poses a significant clinical obstacle to targeting KRAS, which necessitates a deeper understanding of the resistance mechanisms. Recent progress in proteomic studies has enabled comprehensive profiling of the proteomic alterations driven by KRAS mutations, offering valuable insights into the disrupted KRAS …

Prenatal Metabolomics Analysis And Fetal Congenital Anomalies And Genetic Conditions: A Review Of Current Literature, Sarah Araji, Onur Turkoglu, Mohamad Ali Maktabi, Tracy Ashby, Ignatia B Van Den Veyver

Library Staff Publications

Fetal congenital anomalies and genetic disorders complicate 3%-5% of pregnancies and can have a significant impact on pregnancy outcomes. Precise and individualized prenatal diagnosis is crucial for effective counseling and management. The identification of new biomarkers holds promise for enhancing prenatal screening, diagnosis, and prognostic counseling in affected pregnancies. Recently, metabolomics has emerged as a potential adjunct in the interpretation of genetic variants identified through genome-wide sequencing for rare genetic conditions. To assess the potential of metabolomic profiling as a functional assay capable of providing deeper insights into the pathological processes and genetic findings associated with prenatal congenital anomalies, we …

Insights Into Early Adoption And Physician Learning Curve Of Pulsed Field Ablation In The United States., Amin Al-Ahmad, Daniela Hincapie-Tabares, Paul C Zei, Andrea Natale, David Kessler, Joe Gallinghouse, Weeranun Bode, Jose Osorio, Jonathan W Dukes, Robert Eckart, Anish Amin, Yoel Vivas, Luis Mora, Amit Thosani, Joshua Silverstein, Anil Rajendra, Gustavo Morales, Michael Manogue, Joseph Donnelly, Frank Cuoco, Darren Sidney, Robert Brewer, Jason Meyers, Mark D Metzl, Guru Mohanty, Michael Rehorn, Paari Dominic, John D Day, Nischala Nannapaneni, John Costello

OhioHealth Research Institute Articles

BACKGROUND: Pulsed field ablation (PFA) has been available in Europe since 2021. In the United States, PFA became commercially available in 2024, and practice patterns are expected to differ from those in Europe. The objective of this study was to describe acute procedural efficiency and safety outcomes, clinical workflow patterns, and the physician learning curve associated with PFA for paroxysmal and nonparoxysmal atrial fibrillation in the first US real-world registry.

METHODS: DISRUPT-AF (A Registry Based Collaborative to Measure Efficiency, Effectiveness, and Safety of Farapulse PFA Technology for AF) is a prospective, multicenter registry capturing patient-level data on first-time PFA procedures …

From Human To Mouse And Back Again: Genetic And Genomic Ta(I)Les Of Islet Dysfunction In Type 2 Diabetes., Romy Kursawe, Khushdeep Bandesh, Sai Nivedita Krishnan, Kevin S Liu, Redwan M Bhuiyan, Michael L. Stitzel

Faculty Research 2025

Type 2 diabetes (T2D) is a complex genetic disease with substantial environmental inputs leading to glucose homeostasis defects. Insulin production is central to proper glucose control, and islet cell dysfunction and death lie at the nexus of T2D genetics and pathophysiology. Comprehensive identification of genes and pathways contributing to these processes is essential for mechanistic understanding and therapeutic targeting. Here, we summarize the latest human and mouse T2D genetic and genomic studies and assess how these parallel variant-to-function efforts and associated data contribute convergent or complementary insights and new opportunities to dissect T2D islet (dys)function. We distill mechanistic and phenotypic …

Neurometabolic And Vascular Dysfunction As An Early Diagnostic For Alzheimer's Disease And Related Dementias., Juan Antonio K Chong Chie, Scott A Persohn, Ravi S Pandey, Gregory W. Carter, Olivia R Simcox, Paul Salama, Paul R Territo, The Alzheimer’S Disease Neuroimaging Initiative

Faculty Research 2025

INTRODUCTION: Recent studies suggest that the brain undergoes anatomical and functional restructuring, resulting in neurometabolic and vascular dysregulation (MVD) prior to amyloid beta accumulation, which begins at an early age and leads to the onset of Alzheimer's disease (AD).

METHODS: Using a retrospective clinical population (n = 403) from the Alzheimer's Disease Neuroimaging Initiative, cerebral perfusion and metabolism changes across 59 brain regions were evaluated from clinical studies. Results were verified by transcriptomic signatures and clinical cognitive assessments.

RESULTS: Our findings suggest that disease progression follows a stage-dependent MVD pattern that can identify at-risk regions. Although each region progresses at …

Retention Of Lysosomal Acid Sphingomyelinase Protects From Niemann-Pick Disease., Cameron A Beard, Kyra N Hermanson, Justin M Snider, Aki Hara, Brandon K Dahl, Janet J Allopenna, Marilyn T Marron, Benjamin Newcomb, Benjamin E. Low, Michael V. Wiles, Russell W Jenkins, Lina M Obeid, Yusuf A Hannun, Ashley J Snider

Faculty Research 2025

Niemann-Pick Disease (NPD) types A and B are lysosomal storage disorders resulting from dysfunction or loss of acid sphingomyelinase (aSMase), which hydrolyzes sphingomyelin (SM) to ceramide and phosphocholine. Patients with NPD-A develop severe neurologic and visceral pathology and rarely live beyond the age of 3 years, while patients with NPD-B typically live to adolescence/early adulthood without neurologic involvement. There are currently no therapies for NPD-A. SMPD1, the gene that encodes aSMase, gives rise to two distinct enzymes - lysosomal sphingomyelinase (L-SMase) and secretory sphingomyelinase (S-SMase), with the latter being associated with inflammation and chemokine amplification. This study sought to define …

The Ecological Genome Project And The Promises Of Ecogenomics For Society: Realising A Shared Vision As One Health., Benjamin Capps, Ruth Chadwick, Yann Joly, Claire Lajaunie, Iva Hauptmannova, Susannah Mackenzie, John J Mulvihill, Elizabeth Mumford, Sonja A Rasmussen, Kunal Sanghavi, Donrich W Thaldar, James Yeates, Maud C Quinzin, Zohar Lederman

Faculty Research 2025

This paper develops a vision for The Ecological Genome Project: an aspirational, global endeavour to connect human genomic sciences with the ethos of ecological sciences. The Project's goal is to strengthen interdisciplinary networks that relate to diverse initiatives using genomic technologies, with respect to shared ethical frameworks and governance structures. To this end, this paper proposes a practical definition of ecogenomics to align various methodologies and values in a single environmental field using principles used to safeguard all forms of life in their habitats. We achieve this by using a One Health approach as a pretext for disparate disciplines to …

Consistent Performance Of Large Language Models In Rare Disease Diagnosis Across Ten Languages And 4917 Cases., Leonardo Chimirri, J Harry Caufield, Yasemin Bridges, Nicolas Matentzoglu, Michael Gargano, Mario Cazalla, Shihan Chen, Daniel Danis, Alexander J M Dingemans, Klara Gehle, Petra Gehle, Adam S L Graefe, Weihong Gu, Markus S Ladewig, Pablo Lapunzina, Julián Nevado, Enock Niyonkuru, Soichi Ogishima, Dominik Seelow, Jair A Tenorio Castaño, Marek Turnovec, Bert B A De Vries, Kai Wang, Kyran Wissink, Zafer Yüksel, Gabriele Zucca, Melissa A Haendel, Christopher J Mungall, Justin Reese, Peter N Robinson

Faculty Research 2025

BACKGROUND: Large language models (LLMs) are increasingly used medicine for diverse applications including differential diagnostic support. The training data used to create LLMs such as the Generative Pretrained Transformer (GPT) predominantly consist of English-language texts, but LLMs could be used across the globe to support diagnostics if language barriers could be overcome. Initial pilot studies on the utility of LLMs for differential diagnosis in languages other than English have shown promise, but a large-scale assessment on the relative performance of these models in a variety of European and non-European languages on a comprehensive corpus of challenging rare-disease cases is lacking. …

Single-Cell Transcriptomics Of The Myeloid Milieu Reveals An Angiogenic Niche In Triple-Negative Breast Cancer., Yechan Choi, Minkyu Shim, Suhn Hyung Kim, Duk Ki Kim, Juhee Jeong, Jinyoung Byeon, Giyong Jang, Ji-Yeon Kim, Paul Robson, Charles Lee, Han-Byoel Lee, Keehoon Jung

Faculty Research 2025

Intratumoral myeloid cells are highly heterogeneous in terms of development and function and are pivotal for forming and regulating the tumor microenvironment. However, the myeloid milieu in triple-negative breast cancer (TNBC) remains poorly understood. Here, to elucidate this myeloid milieu, we integrated in-house and public single-cell RNA sequencing data. We detected diverse neutrophil and mononuclear-phagocyte subtypes and delineated their developmental trajectories and functions. Of particular interest were the VEGFA

The Ecological Genome Project And The Promises Of Ecogenomics For Society: Realising A Shared Vision As One Health., Benjamin Capps, Ruth Chadwick, Yann Joly, Claire Lajaunie, Iva Hauptmannova, Susannah Mackenzie, John J Mulvihill, Elizabeth Mumford, Sonja A Rasmussen, Kunal Sanghavi, Donrich W Thaldar, James Yeates, Maud C Quinzin, Zohar Lederman

Faculty Research 2025

This paper develops a vision for The Ecological Genome Project: an aspirational, global endeavour to connect human genomic sciences with the ethos of ecological sciences. The Project's goal is to strengthen interdisciplinary networks that relate to diverse initiatives using genomic technologies, with respect to shared ethical frameworks and governance structures. To this end, this paper proposes a practical definition of ecogenomics to align various methodologies and values in a single environmental field using principles used to safeguard all forms of life in their habitats. We achieve this by using a One Health approach as a pretext for disparate disciplines to …

Use Of Osteopathic Manipulation Techniques For Management Of Acute Otitis Media In Pediatric Patients: A Scoping Review., Cory Hyun-Su Kim, Lauren R Mccray, Shaun A Nguyen, Carl Shermetaro, Wayne K Robbins

Ambulatory and Primary Care Articles

OBJECTIVE: To map and summarize the existing literature on the use of osteopathic manipulative techniques (OMT) in the management of acute otitis media (AOM) in pediatric patients, with an emphasis on reported outcomes and identifying gaps in the current evidence.

DATA SOURCES: CINAHL, PubMed, and SCOPUS.

REVIEW METHODS: A comprehensive literature search was conducted across multiple databases following the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines. Studies were charted and summarized based on key characteristics, including study design, population, types of OMT applied, and reported outcomes on management of AOM and recurrent AOM …

J. Robert Gladden Orthopaedic Society Research Grants: What Is The Return On Invesments, Lancelot Benn, Susan Stephens, Mark Ehioghae, Rishi Balkissoon, Brendan A. Williams, Shaina Lipa, David N. Bernstein, Gbolabo Sokunbi, Barrett I. Woods, Wakenda Tyler, Jaysson Brooks, Randall C. Morgan, Kwadwo Owusu-Akyaw, Wayne Johnson, Eric Carson, George V. Russell, Addisu Mesfin

Rothman Institute Papers

INTRODUCTION: The J. Robert Gladden Orthopaedic Society (JRGOS) aims to increase diversity in orthopaedic surgery and promote high-quality musculoskeletal care for all. Through targeted research funding, JRGOS supports projects aligned with its mission. Despite awarding over $300,000 in research grants since 2011, the return on investment (ROI) of this program has not been analyzed. This study evaluates the ROI of JRGOS research grants from 2011 to 2023.

METHODS: We conducted a retrospective review of all JRGOS research grants awarded between 2011 and 2023. Data included recipient demographics, grant titles, award year, institution, and amount. PubMed and Google Scholar were used …

Bilateral Hypoglossal Nerve Stimulation For Obstructive Sleep Apnea: A Nonrandomized Clinical Trial, B. Tucker Woodson, David T. Kent, Colin Huntley, Melyssa K Hancock, Douglas J. Van Daele, Maurits S. Boon, Tod C. Huntley, Sam Mickelson, M. Boyd Gillespie, Maria V. Suurna, Ashutosh Kacker, Asim Roy, Stuart Mackay, Kirk P. Withrow, Raj C. Dedhia, Phillip Huyett, Clemens Heiser, Sylvie Di Nicola, Fatima Makori, Olivier M. Vanderveken, Tapan A. Padyha, Ulysses J. Magalang, Eugene Chio, Eric J. Kezirian, Richard Lewis

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

Study Objectives: To evaluate the safety and efficacy of a novel bilateral hypoglossal nerve stimulation (HNS_BL) device for the treatment of obstructive sleep apnea.

Methods: Adult patients with moderate-to-severe obstructive sleep apnea who refused, failed, or did not tolerate positive airway pressure therapy underwent implantation and nightly use of HNS_BL. The coprimary endpoints at 12 months were (1) a minimum of 50% reduction in the 4% apnea-hypopnea index (AHI) from baseline with a final AHI of less than 20 events/h, and (2) a minimum of 25% reduction in the 4% oxygen desaturation index. Objective secondary endpoints …

Adolescent Coronal Shear Fractures Of The Distal Humerus: Surgical Approach And Outcomes, David Wright, Zachary Meyer, Charles A Goldfarb, Lindley B Wall

2020-Current year OA Pubs

PURPOSE: Isolated coronal shear fractures of the distal humerus in adolescents are rare injuries with unique surgical challenges. Respect for the posterior blood supply, open physes, and need for direct visualization to achieve anatomic reduction are critical considerations in surgical fixation. This study presents a case series and a surgical approach used in treating these patients.

METHODS: A retrospective review of patients aged 10-19 presenting to a single quaternary-care academic center from 2016 to 2023 with isolated capitellar and trochlear shear fractures was performed. Demographic data, injury mechanism, fracture classification, and surgical approach were recorded. Outcomes included elbow range of …

Identifying Performance Differences Between Two Pulse Oximetry Systems In Simulated Critical Neonatal Conditions, Brian King, Jake Dove, Scott J Mcgonigle, Warwick A Ames, Zachary A Vesoulis

2020-Current year OA Pubs

OBJECTIVE: Pulse oximetry is used to guide critical clinical decisions in neonatology. We used a vital signs simulator to compare performance of two pulse oximetry systems in conditions not tested in standardized clinical verification studies.

STUDY DESIGN: We devised a set of simulated tissue translucency, perfusion, peripheral oxygen saturation (SpO

RESULTS: The mean SpO

CONCLUSION: Significant performance differences can be observed when comparing pulse oximeters at low translucency and perfusion conditions. Patient simulators cannot replace clinical testing but provide a safe and cost-effective method for additional performance profiling.

Episodic Memory Involves Transient And Sparse Connectivity Aligned To Both Internal And External Events, Adam J. O. Dede, Peter Brunner, Jarod L. Roland, Et Al.

2020-Current year OA Pubs

Episodic memory depends on the coordination of local processing, indexed by high-frequency broadband (HFB) activity, with global organization, indexed by theta oscillations. However, theta and HFB exhibit asynchronous timing, raising the question of how results of local processing are communicated. Using intracranial EEG in patients performing a recognition memory task, we examined this coordination across medial temporal (MTL) and prefrontal (PFC) regions. HFB peaks occurred earlier in the MTL than in the PFC. Contrasting analyses were anchored either to these internally driven HFB peaks or to the external event of stimulus presentation. We discovered three key results. First, the role …

Hand Swelling And Other Non-Raynaud Phenomenon Symptoms As The Initial Presentation Of Systemic Sclerosis: Prevalence And Clinical Associations In Two Us Cohorts, Iqtidar Hanif, Shervin Assassi, Maureen D Mayes, Zsuzsanna H Mcmahan, Meng Zhang, Julio Charles, John M Vanburen, Jessica S Alvey, Kimia Ghaffari, Elana J Bernstein, Flavia V Castelino, Lorinda Chung, Luke Evnin, Tracy M Frech, Jessica K Gordon, Faye N Hant, Laura K Hummers, Dinesh Khanna, Kimberly S Lakin, Dorota Lebiedz-Odrobina, Yiming Luo, Ashima Makol, Jerry A Molitor, Duncan F Moore, Carrie Richardson, Nora Sandorfi, Ami A Shah, Ankoor Shah, Victoria K Shanmugam, Virginia D Steen, Elizabeth R Volkmann, Carleigh Zahn, Brian Skaug

Faculty, Staff and Student Publications

Objective: Raynaud phenomenon (RP) is often the initial clinical manifestation of systemic sclerosis (SSc), but some patients develop other manifestations first. To help elucidate the diversity of SSc presentation in its early stages, we describe the initial clinical manifestations and antinuclear antibody (ANA) profiles of patients in two early SSc cohorts.

Methods: All patient data in the Genetics vs Environment in Scleroderma Outcomes Study (GENISOS) and Collaborative National Quality and Efficacy Registry (CONQUER) cohorts were reviewed. Both studies enrolled patients within five years of the first non-RP symptom.

Results: In GENISOS and CONQUER, respectively, 194 (44.2%) of 439 and 292 …

Real-World Impact Of Amiodarone On Apixaban Population Pharmacokinetics In Hospitalized Patients, Samantha Kolowrat, Chazmyn Riley, Kevin Lam, Lynda Thomson, Douglas F. Stickle, Walter K. Kraft

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Despite common coadministration in nonvalvular atrial fibrillation (NVAF), there is minimal evidence regarding the impact of concomitant amiodarone use on apixaban pharmacokinetics (PK). We described the population PK of apixaban (2.5 and 5mg twice daily) in 106 hospitalized patients with and without concomitant amiodarone administration at steady state. Apixaban PK was reasonably described by a one-compartment model with first-order absorption and linear elimination. Aside from the receipt of amiodarone, age was retained as a statistically significant covariate on apparent clearance. Model-based simulations depicted concomitant amiodarone use increasing AUCT for both 2.5mg (1.58, 90% CI [1.28, 1.87]) and 5mg (1.12, 90% …

Comparison Of Model-Predicted And Observed Evinacumab Pharmacokinetics And Efficacy In Children Aged < 5 Years With Homozygous Familial Hypercholesterolemia., Sébastien Bihorel, Robert Dingman, Jeanne Mendell, Katy C. Norman, Richard T. George, Xue-Qiao Zhao, Robert Pordy, Daniel Garcia, Wendy S. Putnam, Geetha Raghuveer, Brian W. Mccrindle, Elena Fornari, Ivo Baric, Shubha Srinivasan, Melissa Diamond, Eliot A. Brinton, John D. Davis, A Thomas Dicioccio, Lutz Harnisch

Manuscripts, Articles, Book Chapters and Other Papers

Evinacumab, an angiopoietin-like 3 inhibitor, significantly reduces low-density lipoprotein cholesterol (LDL-C) in patients with homozygous familial hypercholesterolemia (HoFH). Herein, we report pharmacokinetic and efficacy analyses of evinacumab in <  5-year-old patients with HoFH. Population pharmacometric models characterizing evinacumab exposure and LDL-C response accounting for lipoprotein apheresis effect in ≥ 5-year-old patients were adapted for growth and maturation to predict and compare evinacumab and LDL-C concentrations across age/weight groups in virtual ≥ 6-month-old patients receiving 15 mg/kg evinacumab intravenous (iv) infusions every 4 weeks (q4w). As expected from allometric theory, weight-based dosing resulted in decreasing evinacumab exposures with declining body weight. Consistent with trends observed in > 5-year-old patients, the predicted percent change from LDL-C baseline (%∆LDL-C) was generally comparable or even higher in <  5-year-old patients (63.0%-68.5%) than in 5- to <  18-year-old patients (61.3%-67.8%) or adults (51.7%), with the predicted percentages of patients achieving %∆LDL-C > 50% also higher in <  5-year-old patients (82.0%-86.9%) versus 5- to <  18-year-old patients (72.0%-84.5%) and adults (54.8%). Through a managed access program, six 1- to <  5-year-old patients received between 5 and 23 iv infusions of 15 mg/kg evinacumab q4w. Rapid and clinically meaningful LDL-C reductions were observed, with %∆LDL-C at the last reported dose ranging from 41.3% to 77.3%. Based on the actual patient dosing and plasmapheresis history, model-predicted evinacumab and LDL-C concentrations were comparable to the observed data collected in the managed access program. Overall, this analysis provides evidence for the use of evinacumab 15 mg/kg iv q4w dosing regimen in 6-month-old to 5-year-old patients.