Medicine and Health Sciences Commons^™

Hybrid Repair Strategies For Acute Type B Aortic Dissection Complicating Prior Standard And Complex Endovascular Aortic Repair, Jesse Chait, Bernardo C Mendes, Lily E Johnston, Fahad Shuja, Gustavo S Oderich, Manju Kalra

Faculty, Staff and Student Publications

Type B aortic dissection (TBAD) in the presence of an existing aortic endograft is a rare, but potentially catastrophic, event. False lumen pressurization and propagation leads to several failure modes. Endograft collapse can lead to spinal cord, visceral, or lower extremity ischemia, and rupture of a previously sealed aneurysm sac is often fatal. A successful treatment strategy must incorporate the patient's symptoms, urgency of intervention, extent of dissection, and the location and status of the existing graft. In this series, we present three cases of TBAD complicating prior endovascular aortic repairs-infrarenal, iliac branched, and thoracoabdominal branched endografts-successfully treated with tailored, …

Hemorrhagic Herpes Zoster Duplex Unilateralis In A Patient Taking Clopidogrel, Austinn C Miller, Anthony Thompson, Alexzandra Mattia, Laurie A Temiz, Susuana Adjei, Stephen K Tyring

Faculty, Staff and Student Publications

No abstract provided.

Artificial Intelligence Cad Tools In Trauma Imaging: A Scoping Review From The American Society Of Emergency Radiology (Aser) Ai/Ml Expert Panel, David Dreizin, Pedro V Staziaki, Garvit D Khatri, Nicholas M Beckmann, Zhaoyong Feng, Yuanyuan Liang, Zachary S Delproposto, Maximiliano Klug, J Stephen Spann, Nathan Sarkar, Yunting Fu

Faculty, Staff and Student Publications

BACKGROUND: AI/ML CAD tools can potentially improve outcomes in the high-stakes, high-volume model of trauma radiology. No prior scoping review has been undertaken to comprehensively assess tools in this subspecialty.

PURPOSE: To map the evolution and current state of trauma radiology CAD tools along key dimensions of technology readiness.

METHODS: Following a search of databases, abstract screening, and full-text document review, CAD tool maturity was charted using elements of data curation, performance validation, outcomes research, explainability, user acceptance, and funding patterns. Descriptive statistics were used to illustrate key trends.

RESULTS: A total of 4052 records were screened, and 233 full-text …

A Phase Ii Study Of Neoadjuvant Atezolizumab And Nab-Paclitaxel In Patients With Anthracycline-Resistant Early-Stage Triple-Negative Breast Cancer, Clinton Yam, Elizabeth A Mittendorf, Haven R Garber, Ryan Sun, Senthil Damodaran, Rashmi K Murthy, David Ramirez, Meghan Karuturi, Rachel M Layman, Nuhad Ibrahim, Gaiane M Rauch, Beatriz E Adrada, Rosalind P Candelaria, Jason B White, Elizabeth Ravenberg, Alyson Clayborn, Qing Qing Ding, W Fraser Symmans, Sabitha Prabhakaran, Alastair M Thompson, Vicente Valero, Debu Tripathy, Lei Huo, Stacy L Moulder, Jennifer K Litton

Faculty, Staff and Student Publications

Purpose: Neoadjuvant anti-PD-(L)1 therapy improves the pathological complete response (pCR) rate in unselected triple-negative breast cancer (TNBC). Given the potential for long-term morbidity from immune-related adverse events (irAEs), optimizing the risk-benefit ratio for these agents in the curative neoadjuvant setting is important. Suboptimal clinical response to initial neoadjuvant therapy (NAT) is associated with low rates of pCR (2-5%) and may define a patient selection strategy for neoadjuvant immune checkpoint blockade. We conducted a single-arm phase II study of atezolizumab and nab-paclitaxel as the second phase of NAT in patients with doxorubicin and cyclophosphamide (AC)-resistant TNBC (NCT02530489).

Methods: Patients …

The Lure Of Cardiac Metabolism In The Diagnosis, Prevention, And Treatment Of Heart Failure, Daniele Rodolico, Gabriele G Schiattarella, Heinrich Taegtmeyer

Faculty, Staff and Student Publications

Energy substrate metabolism and contractile function are tightly coupled in the heart. Within this framework, heart failure may be viewed as a state of impaired energy transfer. The metabolic changes in the failing heart are linked to functional and structural changes. A worthwhile goal is to measure metabolic flux and its regulation quantitatively, and to do this in a manner that leads to targeted interventions. For several good reasons, this goal has been elusive until now. The development of new analytical and imaging techniques offers the potential of exploring the landscape of metabolic changes across the different stages of heart …

Sex And Gender Differences In Acute Stroke Care: Metrics, Access To Treatment And Outcome A Territorial Analysis Of The Stroke Code System Of Catalonia, Yolanda Silva, Laura Sánchez-Cirera, Mikel Terceño, Laura Dorado, Adrián Valls, Marina Martínez, Sònia Abilleira, Marta Rubiera, Helena Quesada, Laura Llull, Ana Rodríguez-Campello, Joan Martí-Fàbregas, Laia Seró, Francisco Purroy, Iago Payo, Sònia García, David Cánovas, Jurek Krupinski, Natalia Mas, Ernest Palomeras, Dolores Cocho, Maria Àngels Font, Esther Catena, Elsa Puiggròs, Claudia Pedroza, Gemma Marín, Dolors Carrión, Xavier Costa, Mari Cruz Almendros, Ivan Torres, Carla Colom, John Alejandro Velasquez, Gloria Diaz, Xavier Jiménez, Teresa Subirats, Anna Deulofeu, Verónica Hidalgo, Mercè Salvat-Plana, Natalia Pérez De La Ossa, Catalan Stroke Code And Reperfusion Consortium (Cat-Scr)

Faculty, Staff and Student Publications

INTRODUCTION: Previous studies have reported differences in the management and outcome of women stroke patients in comparison with men. We aim to analyze sex and gender differences in the medical assistance, access to treatment and outcome of acute stroke patients in Catalonia.

PATIENTS AND METHODS: Data were obtained from a prospective population-based registry of stroke code activations in Catalonia (CICAT) from January/2016 to December/2019. The registry includes demographic data, stroke severity, stroke subtype, reperfusion therapy, and time workflow. Centralized clinical outcome at 90 days was assessed in patients receiving reperfusion therapy.

RESULTS: A total of 23,371 stroke code activations were …

Evaluation Of Alisertib Alone Or Combined With Fulvestrant In Patients With Endocrine-Resistant Advanced Breast Cancer: The Phase 2 Tbcrc041 Randomized Clinical Trial, Tufia C Haddad, Vera J Suman, Antonino B D'Assoro, Jodi M Carter, Karthik V Giridhar, Brendan P Mcmenomy, Katelyn Santo, Erica L Mayer, Meghan S Karuturi, Aki Morikawa, P Kelly Marcom, Claudine J Isaacs, Sun Young Oh, Amy S Clark, Ingrid A Mayer, Khandan Keyomarsi, Timothy J Hobday, Prema P Peethambaram, Ciara C O'Sullivan, Roberto A Leon-Ferre, Minetta C Liu, James N Ingle, Matthew P Goetz

Faculty, Staff and Student Publications

IMPORTANCE: Aurora A kinase (AURKA) activation, related in part to AURKA amplification and variants, is associated with downregulation of estrogen receptor (ER) α expression, endocrine resistance, and implicated in cyclin-dependent kinase 4/6 inhibitor (CDK 4/6i) resistance. Alisertib, a selective AURKA inhibitor, upregulates ERα and restores endocrine sensitivity in preclinical metastatic breast cancer (MBC) models. The safety and preliminary efficacy of alisertib was demonstrated in early-phase trials; however, its activity in CDK 4/6i-resistant MBC is unknown.

OBJECTIVE: To assess the effect of adding fulvestrant to alisertib on objective tumor response rates (ORRs) in endocrine-resistant MBC.

DESIGN, SETTING, AND PARTICIPANTS: This phase …

Ehealth Technology In Cardiac Exercise Therapeutics For Pediatric Patients With Congenital And Acquired Heart Conditions: A Summary Of Evidence And Future Directions., David A. White, Aimee M. Layton, Tracy Curran, Naomi Gauthier, William B. Orr, Kendra Ward, Meg Vernon, Matthew N. Martinez, Malloree C. Rice, Katherine Hansen, Megan Prusi, Jesse E. Hansen

Manuscripts, Articles, Book Chapters and Other Papers

Many children and adolescents with congenital and acquired heart disease (CHD) are physically inactive and participate in an insufficient amount of moderate-to-vigorous intensity exercise. Although physical activity (PA) and exercise interventions are effective at improving short- and long-term physiological and psychosocial outcomes in youth with CHD, several barriers including resource limitations, financial costs, and knowledge inhibit widespread implementation and dissemination of these beneficial programs. New and developing eHealth, mHealth, and remote monitoring technologies offer a potentially transformative and cost-effective solution to increase access to PA and exercise programs for youth with CHD, yet little has been written on this topic. …

Climate Change Imperils Pediatric Health: Child Advocacy Through Fossil Fuel Divestment., Sandra H. Jee, Elizabeth Friedman, Ruth A. Etzel, Vi T. Nguyen, Todd L. Sack, Kathi J. Kemper

Manuscripts, Articles, Book Chapters and Other Papers

Climate change poses an existential threat to children's health. Divestment of ownership stakes in fossil fuel companies is one tool available to pediatricians to address climate change. Pediatricians are trusted messengers regarding children's health and therefore bear a unique responsibility to advocate for climate and health policies that affect children. Among the impacts of climate change on pediatric patients are allergic rhinitis and asthma; heat-related illnesses; premature birth; injuries from severe storms and fires; vector-borne diseases; and mental illnesses. Children are disproportionately affected as well by climate-related displacement of populations, drought, water shortages, and famine. The human-generated burning of fossil …

Real-World Safety Of Neurohormonal Antagonist Initiation Among Older Adults Following A Heart Failure Hospitalization, Parag Goyal, Andrew R Zullo, Barbara Gladders, Chukwuma Onyebeke, Min Ji Kwak, Larry A Allen, Emily B Levitan, Monika M Safford, Lauren Gilstrap

Faculty, Staff and Student Publications

AIMS: To optimize guideline-directed medical therapy for heart failure, patients may require the initiation of multiple neurohormonal antagonists (NHAs) during and following hospitalization. The safety of this approach for older adults is not well established.

METHODS AND RESULTS: We conducted an observational cohort study of 207 223 Medicare beneficiaries discharged home following a hospitalization for heart failure with reduced ejection fraction (HFrEF) (2008-2015). We performed Cox proportional hazards regression to examine the association between the count of NHAs initiated within 90 days of hospital discharge (as a time-varying exposure) and all-cause mortality, all-cause rehospitalization, and fall-related adverse events over the …

Efficacy And Adverse Effects Of Ketamine Versus Electroconvulsive Therapy For Major Depressive Disorder: A Systematic Review And Meta-Analysis, Debora De A Simoes Moreira, Luís Eduardo Gauer, Guilherme Teixeira, Amanda Carolina Fonseca Da Silva, Stefanie Cavalcanti, João Quevedo

Faculty, Staff and Student Publications

Background: ECT is considered the fastest and most effective treatment for TRD. Ketamine seems to be an attractive alternative due to its rapid-onset antidepressant effects and impact on suicidal thoughts. This study aimed to compare efficacy and tolerability of ECT and ketamine for different depression outcomes (PROSPERO/CRD42022349220).

Methods: We searched MEDLINE, Web of Science, Embase, PsycINFO, Google Scholar, Cochrane Library and trial registries, which were the ClinicalTrials.gov and the World Health Organization's International Clinical Trials Registry Platform, without restrictions on publication date.

Selection criteria: randomized controlled trials or cohorts comparing ketamine versus ECT in patients with TRD.

Results: Eight studies …

Antibody Toolkit To Investigate Eef1a Methylation Dynamics In Mrna Translation Elongation, Robert Mealey-Farr, Jinho Jeong, Juhyung Park, Shuo Liu, Simone Hausmann, Joel W Francis, Maria Angulo Ibanez, Joonseok Cho, Katrin Chua, Pawel K Mazur, Or Gozani

Faculty, Staff and Student Publications

Protein synthesis is a fundamental step in gene expression, with modulation of mRNA translation at the elongation step emerging as an important regulatory node in shaping cellular proteomes. In this context, five distinct lysine methylation events on eukaryotic elongation factor 1A (eEF1A), a fundamental nonribosomal elongation factor, are proposed to influence mRNA translation elongation dynamics. However, a lack of affinity tools has hindered progress in fully understanding how eEF1A lysine methylation impacts protein synthesis. Here we develop and characterize a suite of selective antibodies to investigate eEF1A methylation and provide evidence that methylation levels decline in aged tissue. Determination of …

Comparison Of Vmat Beam Complexity With Different Mlc Collimator Rotation And Their Impact On Psqa Pass Rates, David T. To, Michael G. Snyder, Jian Liang

Conference Presentation Abstracts

Purpose: I t has been previously shown that utilizing a collimator angle of ±45° has demonstrated a reduction in MU and VMAT beam complexity. Studies have demonstrated this for VMAT prostate plans with small sample size. In this study we evaluate multiple collimator angles with a larger sample size and different treatment sites. Methods: A total of 17273 VMAT beams were evaluated with beam collimator rotations of 0°, ±5°, ±10°, ±15°, ±30°, ±45°, and ±90°. QA Gamma pass rates for our institution use a 3%/2mm criteria 10% threshold with 95% limit pass rate utilizing Sun Nuclear ArcCheck (helical diode array). …

Targeting Unc51-Like Autophagy Activating Kinase 1 (Ulk1) Overcomes Adaptive Drug Resistance In Acute Myelogenous Leukemia, Seemana Bhattacharya, Sujan Piya, Huaxian Ma, Priyanka Sharma, Qi Zhang, Natalia Baran, Vivian R Ruvolo, Teresa Mcqueen, R Eric Davis, Rasoul Pourebrahim, Marina Konopleva, Hagop Kantarjian, Nicholas D P Cosford, Michael Andreeff, Gautam Borthakur

Faculty, Staff and Student Publications

UNLABELLED: Despite effective new therapies, adaptive resistance remains the main obstacle in acute myelogenous leukemia (AML) therapy. Autophagy induction is a key mechanism for adaptive resistance. Leukemic blasts at diagnosis express higher levels of the apical autophagy kinase ULK1 compared with normal hematopoietic cells. Exposure to chemotherapy and targeted agents upregulate ULK1, hence we hypothesize that developing ULK1 inhibitors may present the unique opportunity for clinical translation of autophagy inhibition. Accordingly, we demonstrate that ULK1 inhibition, by genetic and pharmacologic means, suppresses treatment-induced autophagy, overcomes adaptive drug-resistance, and synergizes with chemotherapy and emerging antileukemia agents like venetoclax (ABT-199). The study …

A Bayesian Feature Allocation Model For Identifying Cell Subpopulations Using Cytof Data, Arthur Lui, Juhee Lee, Peter F Thall, May Daher, Katy Rezvani, Rafet Basar

Faculty, Staff and Student Publications

A Bayesian feature allocation model (FAM) is presented for identifying cell subpopulations based on multiple samples of cell surface or intracellular marker expression level data obtained by cytometry by time of flight (CyTOF). Cell subpopulations are characterized by differences in marker expression patterns, and cells are clustered into subpopulations based on their observed expression levels. A model-based method is used to construct cell clusters within each sample by modeling subpopulations as latent features, using a finite Indian buffet process. Non-ignorable missing data due to technical artifacts in mass cytometry instruments are accounted for by defining a static missingship mechanism. In …

Selective Immune Suppression Using Interleukin-6 Receptor Inhibitors For Management Of Immune-Related Adverse Events, Faisal Fa'ak, Maryam Buni, Adewunmi Falohun, Huifang Lu, Juhee Song, Daniel H Johnson, Chrystia M Zobniw, Van A Trinh, Muhammad Osama Awiwi, Nourel Hoda Tahon, Khaled M Elsayes, Kaysia Ludford, Emma J Montazari, Julia Chernis, Maya Dimitrova, Sabina Sandigursky, Jeffrey A Sparks, Osama Abu-Shawer, Osama Rahma, Uma Thanarajasingam, Ashley M Zeman, Rafee Talukder, Namrata Singh, Sarah H Chung, Petros Grivas, May Daher, Ala Abudayyeh, Iman Osman, Jeffrey Weber, Jean H Tayar, Maria E Suarez-Almazor, Noha Abdel-Wahab, Adi Diab

Faculty, Staff and Student Publications

BACKGROUND: Management of immune-related adverse events (irAEs) is important as they cause treatment interruption or discontinuation, more often seen with combination immune checkpoint inhibitor (ICI) therapy. Here, we retrospectively evaluated the safety and effectiveness of anti-interleukin-6 receptor (anti-IL-6R) as therapy for irAEs.

METHODS: We performed a retrospective multicenter study evaluating patients diagnosed with de novo irAEs or flare of pre-existing autoimmune disease following ICI and were treated with anti-IL-6R. Our objectives were to assess the improvement of irAEs as well as the overall tumor response rate (ORR) before and after anti-IL-6R treatment.

RESULTS: We identified a total of 92 patients …

Newer Surveillance Data Extends Our Understanding Of The Niche Of Rickettsia Montanensis (Rickettsiales: Rickettsiaceae) Infection Of The American Dog Tick (Acari: Ixodidae) In The United States, Catherine A. Lippi, Holly D. Gaff, Robyn M. Nadolny, Sadie J. Ryan

Biological Sciences Faculty Publications

Background: Understanding the geographic distribution of Rickettsia montanensis infections in Dermacentor variabilis is important for tick-borne disease management in the United States, as both a tick-borne agent of interest and a potential confounder in surveillance of other rickettsial diseases. Two previous studies modeled niche suitability for D. variabilis with and without R. montanensis, from 2002-2012, indicating that the D. variabilis niche overestimates the infected niche. This study updates these, adding data since 2012.

Methods: Newer surveillance and testing data were used to update Species Distribution Models (SDMs) of D. variabilis, and R. montanensis infected D. variabilis, in …

Characteristics Of Long-Term Survival In Breast Cancer Brain Metastasis After Stereotactic Radiation, Joseph D Tang, Matthew Mills Md, Chetna Thawani, Daniel E. Oliver, Aixa Soyano, Arnold Etame, Hsiang-Hsuan Michael Yu, Nam Tran, Michael A. Vogelbaum, Peter A. Forsyth, Brian J. Czerniecki, Hatem H. Soliman, Hyo S. Han, Kamran Ahmed

USF-LVHN SELECT

No abstract provided.

Analyzing The Medical History Of Homeless Adolescents: An Opportunity To Reduce Ed Visits, Michele Karn, Brittany Gaudet Bs, Msph, Nina Liu Md, Taylor Jarvill Md, Cecilia E. Zemanek Md, Hoonani M. Cuadrado, Amy B. Smith Phd, Marna R. Greenberg Do, Mph, Facep

USF-LVHN SELECT

No abstract provided.

Mitigating Risks To Improve Hypertension Medication Adherence In A Medically Vulnerable Population, Donna Hales-Teat

Doctor of Nursing Practice Projects

This project assessed the effect of an evidence-based medication adherence intervention on adherence rates at a Northern Indiana clinic led by a sole nurse practitioner, receptionist, and continuous rotation of graduate nursing students from several nursing programs in the Northern Indiana area. Patient education and comprehension were poor in terms of understanding disease process, treatment options, and disease management that led to poor communication with the medical provider. The process and steps in which patients matriculate through was described by Johnson’s (2002) Medication Adherence Model (MAM) with concepts of purposeful action, pattern behavior, and feedback; these helped to construct, steer, …

Interpretable Machine Learning Models To Predict Hospital Patient Readmission, Xiaoquan Gao, Sabriya Alam, Pengyi Shi, Franklin Dexter, Nan Kong

Research Collection Lee Kong Chian School Of Business

Background: Advanced machine learning models have received wide attention in assisting medical decision making due to the greater accuracy they can achieve. However, their limited interpretability imposes barriers for practitioners to adopt them. Recent advancements in interpretable machine learning tools allow us to look inside the black box of advanced prediction methods to extract interpretable models while maintaining similar prediction accuracy, but few studies have investigated the specific hospital readmission prediction problem with this spirit. Methods: Our goal is to develop a machine-learning (ML) algorithm that can predict 30- and 90- day hospital readmissions as accurately as black box algorithms …

Impact Of Cross-Ancestry Genetic Architecture On Gwass In Admixed Populations, Rachel Mester, Kangcheng Hou, Yi Ding, Gillian Meeks, Kathryn S Burch, Arjun Bhattacharya, Brenna M Henn, Bogdan Pasaniuc

Faculty, Staff and Student Publications

Genome-wide association studies (GWASs) have identified thousands of variants for disease risk. These studies have predominantly been conducted in individuals of European ancestries, which raises questions about their transferability to individuals of other ancestries. Of particular interest are admixed populations, usually defined as populations with recent ancestry from two or more continental sources. Admixed genomes contain segments of distinct ancestries that vary in composition across individuals in the population, allowing for the same allele to induce risk for disease on different ancestral backgrounds. This mosaicism raises unique challenges for GWASs in admixed populations, such as the need to correctly adjust …

An Integrated Cell Atlas Of The Lung In Health And Disease, Lisa Sikkema, Ciro Ramírez-Suástegui, Daniel C Strobl, Tessa E Gillett, Luke Zappia, Elo Madissoon, Nikolay S Markov, Laure-Emmanuelle Zaragosi, Yuge Ji, Meshal Ansari, Marie-Jeanne Arguel, Leonie Apperloo, Martin Banchero, Christophe Bécavin, Marijn Berg, Evgeny Chichelnitskiy, Mei-I Chung, Antoine Collin, Aurore C A Gay, Janine Gote-Schniering, Baharak Hooshiar Kashani, Kemal Inecik, Manu Jain, Theodore S Kapellos, Tessa M Kole, Sylvie Leroy, Christoph H Mayr, Amanda J Oliver, Michael Von Papen, Lance Peter, Chase J Taylor, Thomas Walzthoeni, Chuan Xu, Linh T Bui, Carlo De Donno, Leander Dony, Alen Faiz, Minzhe Guo, Austin J Gutierrez, Lukas Heumos, Ni Huang, Ignacio L Ibarra, Nathan D Jackson, Preetish Kadur Lakshminarasimha Murthy, Mohammad Lotfollahi, Tracy Tabib, Carlos Talavera-López, Kyle J Travaglini, Anna Wilbrey-Clark, Kaylee B Worlock, Masahiro Yoshida, Maarten Van Den Berge, Yohan Bossé, Tushar J Desai, Oliver Eickelberg, Naftali Kaminski, Mark A Krasnow, Robert Lafyatis, Marko Z Nikolic, Joseph E Powell, Jayaraj Rajagopal, Mauricio Rojas, Orit Rozenblatt-Rosen, Max A Seibold, Dean Sheppard, Douglas P Shepherd, Don D Sin, Wim Timens, Alexander M Tsankov, Jeffrey Whitsett, Yan Xu, Nicholas E Banovich, Pascal Barbry, Thu Elizabeth Duong, Christine S Falk, Kerstin B Meyer, Jonathan A Kropski, Dana Pe'er, Herbert B Schiller, Purushothama Rao Tata, Joachim L Schultze, Sara A Teichmann, Alexander V Misharin, Martijn C Nawijn, Malte D Luecken, Fabian J Theis

Faculty, Staff and Student Publications

Single-cell technologies have transformed our understanding of human tissues. Yet, studies typically capture only a limited number of donors and disagree on cell type definitions. Integrating many single-cell datasets can address these limitations of individual studies and capture the variability present in the population. Here we present the integrated Human Lung Cell Atlas (HLCA), combining 49 datasets of the human respiratory system into a single atlas spanning over 2.4 million cells from 486 individuals. The HLCA presents a consensus cell type re-annotation with matching marker genes, including annotations of rare and previously undescribed cell types. Leveraging the number and diversity …

Addition Of Metastasis-Directed Therapy To Intermittent Hormone Therapy For Oligometastatic Prostate Cancer: The Extend Phase 2 Randomized Clinical Trial, Chad Tang, Alexander D Sherry, Cara Haymaker, Tharakeswara Bathala, Suyu Liu, Bryan Fellman, Lorenzo Cohen, Ana Aparicio, Amado J Zurita, Alexandre Reuben, Enrica Marmonti, Stephen G Chun, Jay P Reddy, Amol Ghia, Sean Mcguire, Eleni Efstathiou, Jennifer Wang, Jianbo Wang, Patrick Pilie, Craig Kovitz, Weiliang Du, Samantha J Simiele, Rachit Kumar, Yerko Borghero, Zheng Shi, Brian Chapin, Daniel Gomez, Ignacio Wistuba, Paul G Corn

Faculty, Staff and Student Publications

IMPORTANCE: Despite evidence demonstrating an overall survival benefit with up-front hormone therapy in addition to established synergy between hormone therapy and radiation, the addition of metastasis-directed therapy (MDT) to hormone therapy for oligometastatic prostate cancer, to date, has not been evaluated in a randomized clinical trial.

OBJECTIVE: To determine in men with oligometastatic prostate cancer whether the addition of MDT to intermittent hormone therapy improves oncologic outcomes and preserves time with eugonadal testosterone compared with intermittent hormone therapy alone.

DESIGN, SETTING, PARTICIPANTS: The External Beam Radiation to Eliminate Nominal Metastatic Disease (EXTEND) trial is a phase 2, basket randomized clinical …

Phase I/Ii Sequencing Study Of Azacitidine, Epacadostat, And Pembrolizumab In Advanced Solid Tumors, Jason J Luke, Marwan Fakih, Charles Schneider, E Gabriela Chiorean, Johanna Bendell, Rebecca Kristeleit, Razelle Kurzrock, Sarah P Blagden, Irene Brana, Laura W Goff, Kevin O'Hayer, Ryan Geschwindt, Michael Smith, Feng Zhou, Aung Naing

Faculty, Staff and Student Publications

Background: Indoleamine 2,3-dioxygenase 1 (IDO1), an interferon-inducible enzyme, contributes to tumor immune intolerance. Immune checkpoint inhibition may increase interferon levels; combining IDO1 inhibition with immune checkpoint blockade represents an attractive strategy. Epigenetic agents trigger interferon responses and may serve as an immunotherapy priming method. We evaluated whether epigenetic therapy plus IDO1 inhibition and immune checkpoint blockade confers clinical benefit to patients with advanced solid tumors.

Methods: ECHO-206 was a Phase I/II study where treatment-experienced patients with advanced solid tumors (N = 70) received azacitidine plus an immunotherapy doublet (epacadostat [IDO1 inhibitor] and pembrolizumab). Sequencing of treatment was also assessed. Primary …

Factors Predictive Of Being Bullies Or Victims Of Bullies In Us Elementary Schools, Paul L Morgan, George Farkas, Adrienne D Woods, Yangyang Wang, Marianne M Hillemeier, Yoonkyung Oh

Faculty, Staff and Student Publications

We analyzed a population-representative cohort (N=13,611; Mage at kindergarten, first, and second grade = 67.5, 79.5, and 91.5 months, respectively) to identify kindergarten to second grade factors predictive of being bullies or victims during third to fifth grade. We did so by estimating a block recursive structural equation model (SEM) with three sets of predictors. These were: (a) individual and school socio-demographics; (b) family distress and harsh parenting; and (c) individual behavior and achievement. Relations between each of the included variables and the bullying outcomes were simultaneously estimated within the SEM. Thus, each variable served as a control …

Vagus Nerve Stimulation Paired With Rehabilitation For Upper Limb Motor Impairment And Function After Chronic Ischemic Stroke: Subgroup Analysis Of The Randomized, Blinded, Pivotal, Vns-Rehab Device Trial, Jesse Dawson, Navzer D Engineer, Steven C Cramer, Steven L Wolf, Rushna Ali, Michael W O'Dell, David Pierce, Cecília N Prudente, Jessica Redgrave, Wuwei Feng, Charles Y Liu, Gerard E Francisco, Benjamin L Brown, Anand Dixit, Jen Alexander, Louis Demark, Vibor Krishna, Steven A Kautz, Arshad Majid, Brent Tarver, Duncan L Turner, Teresa J Kimberley

Faculty, Staff and Student Publications

BACKGROUND: Vagus Nerve Stimulation (VNS) paired with rehabilitation improved upper extremity impairment and function in a recent pivotal, randomized, triple-blind, sham-controlled trial in people with chronic arm weakness after stroke.

OBJECTIVE: We aimed to determine whether treatment effects varied across candidate subgroups, such as younger age or less injury.

METHODS: Participants were randomized to receive rehabilitation paired with active VNS or rehabilitation paired with sham stimulation (Control). The primary outcome was the change in impairment measured by the Fugl-Meyer Assessment Upper Extremity (FMA-UE) score on the first day after completion of 6-weeks in-clinic therapy. We explored the effect of VNS …

Hes1 Marks Peri-Condensation Mesenchymal Cells That Generate Both Chondrocytes And Perichondrial Cells In Early Bone Development, Yuki Matsushita, Hiroaki Manabe, Takahiro Ohyama, Shogo Nakamura, Mizuki Nagata, Wanida Ono, Noriaki Ono

Faculty, Staff and Student Publications

Bone development starts with condensations of undifferentiated mesenchymal cells that set a framework for future bones within the primordium. In the endochondral pathway, mesenchymal cells inside the condensation differentiate into chondrocytes and perichondrial cells in a SOX9-dependent mechanism. However, the identity of mesenchymal cells outside the condensation and how they participate in developing bones remain undefined. Here we show that mesenchymal cells surrounding the condensation contribute to both cartilage and perichondrium, robustly generating chondrocytes, osteoblasts, and marrow stromal cells in developing bones. Single-cell RNA-seq analysis of Prrx1-cre-marked limb bud mesenchymal cells at E11.5 reveals that Notch effector Hes1 is …

A Role For Protein Arginine Methyltransferase 7 In Repetitive And Mild Traumatic Brain Injury, Christina H Acosta, Garrett A Clemons, Cristiane T Citadin, William C Carr, Mariana Sayuri Berto Udo, Vesna Tesic, Henry W Sanicola, Anne H Freelin, Jamie B Toms, J Dedrick Jordan, Bharat Guthikonda, Celeste Yin-Chieh Wu, Reggie Hui-Chao Lee, Hung Wen Lin

Faculty, Staff and Student Publications

Mild traumatic brain injury affects the largest proportion of individuals in the United States and world-wide. Pre-clinical studies of repetitive and mild traumatic brain injury (rmTBI) have been limited in their ability to recapitulate human pathology (i.e. diffuse rotational injury). We used the closed-head impact model of engineered rotation acceleration (CHIMERA) to simulate rotational injury observed in patients and to study the pathological outcomes post-rmTBI using C57BL/6J mice. Enhanced cytokine production was observed in both the cortex and hippocampus to suggest neuroinflammation. Furthermore, microglia were assessed via enhanced iba1 protein levels and morphological changes using immunofluorescence. In addition, LC/MS analyses …

Towards Neuromarkers For Tailored Smoking Cessation Treatments, Francesco Versace, Jason D Robinson, Paul M Cinciripini

Faculty, Staff and Student Publications

Vulnerability to compulsive drug use stems from dysregulated activity within the neural networks that underlie reward and executive functions. Empirical evidence suggests that a) attributing high motivational salience to drug-related stimuli leads to compulsive drug seeking and b) cognitive control deficits lead to compulsive drug taking. Noninvasive neuroimaging techniques enable brain activity monitoring during affective and cognitive processing and are paving the way to precision medicine for substance use disorders. Identifying robust neuromarkers of affective and cognitive dysregulation would allow clinicians to personalize treatments by targeting individual psychophysiological vulnerabilities. However, methodological choices have biased the field toward experimental paradigms that …