Digital Commons Network^™

Deletion Of Type Viii Collagen Reduces Blood Pressure, Increases Carotid Artery Functional Distensibility And Promotes Elastin Deposition, Amanda L Mohabeer, Jeffrey T Kroetsch, Meghan Mcfadden, Negin Khosraviani, Thomas J Broekelmann, Guangpei Hou, Hangjun Zhang, Yu-Qing Zhou, Minyao Wang, Anthony O Gramolini, Robert P Mecham, Scott P Heximer, Steffen-Sebastian Bolz, Michelle P Bendeck

2020-Current year OA Pubs

Arterial stiffening is a significant predictor of cardiovascular disease development and mortality. In elastic arteries, stiffening refers to the loss and fragmentation of elastic fibers, with a progressive increase in collagen fibers. Type VIII collagen (Col-8) is highly expressed developmentally, and then once again dramatically upregulated in aged and diseased vessels characterized by arterial stiffening. Yet its biophysical impact on the vessel wall remains unknown. The purpose of this study was to test the hypothesis that Col-8 functions as a matrix scaffold to maintain vessel integrity during extracellular matrix (ECM) development. These changes are predicted to persist into the adult …

A Brief History Of Nearly Ev-Erything - The Rise And Rise Of Extracellular Vesicles, Yvonne Couch, Edit I Buzàs, Dolores Di Vizio, Yong Song Gho, Paul Harrison, Andrew F Hill, Jan Lötvall, Graça Raposo, Philip D Stahl, Clotilde Théry, Kenneth W Witwer, David R F Carter

2020-Current year OA Pubs

Extracellular vesicles (EVs) are small cargo-bearing vesicles released by cells into the extracellular space. The field of EVs has grown exponentially over the past two decades; this growth follows the realisation that EVs are not simply a waste disposal system as had originally been suggested by some, but also a complex cell-to-cell communication mechanism. Indeed, EVs have been shown to transfer functional cargo between cells and can influence several biological processes. These small biological particles are also deregulated in disease. As we approach the 75th anniversary of the first experiments in which EVs were unknowingly isolated, it seems right to …

Emergency Clinicians' Perceptions Of Communication Tools To Establish The Mental Baseline Of Older Adults: A Qualitative Study, Anita Chary, Christopher Joshi, Noelle Castilla-Ojo, Ilianna Santangelo, Kei Ouchi, Aanand D. Naik, Christopher R. Carpenter, Shan W Liu, Maura Kennedy

2020-Current year OA Pubs

Background Evaluating older adults with altered mental status in emergency settings can be challenging due to the inability to obtain a history from patients directly and limited collateral information about the change from a patient's mental status baseline. Documents and videos establishing a patient's mental baseline could represent useful communication tools to aid emergency clinicians. Methods Qualitative interviews conducted with 22 emergency clinicians (12 physicians and 10 advanced practice providers) identified methods they use to determine baseline mental status of older adults in the ED and the perceived utility of document- and video-based information about an older adult's baseline mental …

Detecting Risk Level In Individuals Misusing Fentanyl Utilizing Posts From An Online Community On Reddit, Sanjana Garg, Jordan Taylor, Mai El Sherief, Erin Kasson, Talayeh Aledavood, Raven Riordan, Nina Kaiser, Patricia Cavazos-Rehg, Munmun De Choudhury

2020-Current year OA Pubs

INTRODUCTION: Opioid misuse is a public health crisis in the US, and misuse of synthetic opioids such as fentanyl have driven the most recent waves of opioid-related deaths. Because those who misuse fentanyl are often a hidden and high-risk group, innovative methods for identifying individuals at risk for fentanyl misuse are needed. Machine learning has been used in the past to investigate discussions surrounding substance use on Reddit, and this study leverages similar techniques to identify risky content from discussions of fentanyl on this platform.

METHODS: A codebook was developed by clinical domain experts with 12 categories indicative of fentanyl …

The Human Connectome Project: A Retrospective, Jennifer Stine Elam, Matthew F. Glasser, Michael P. Harms, Gregory C. Burgess, Sandra W. Curtiss, Michael R. Hodge, Eileen A. Cler, Daniel M. Marcus, Deanna M. Barch, David C. Van Essen, Et Al.

2020-Current year OA Pubs

The Human Connectome Project (HCP) was launched in 2010 as an ambitious effort to accelerate advances in human neuroimaging, particularly for measures of brain connectivity; apply these advances to study a large number of healthy young adults; and freely share the data and tools with the scientific community. NIH awarded grants to two consortia; this retrospective focuses on the "WU-Minn-Ox" HCP consortium centered at Washington University, the University of Minnesota, and University of Oxford. In just over 6 years, the WU-Minn-Ox consortium succeeded in its core objectives by: 1) improving MR scanner hardware, pulse sequence design, and image reconstruction methods, …

Unmasc: Tumor-Only Variant Calling With Unmatched Normal Controls, Paul Little, Heejoon Jo, Alan Hoyle, Angela Mazul, Xiaobei Zhao, Ashley H Salazar, Douglas Farquhar, Siddharth Sheth, Maheer Masood, Michele C Hayward, Joel S Parker, Katherine A Hoadley, Jose Zevallos, D Neil Hayes

2020-Current year OA Pubs

Despite years of progress, mutation detection in cancer samples continues to require significant manual review as a final step. Expert review is particularly challenging in cases where tumors are sequenced without matched normal control DNA. Attempts have been made to call somatic point mutations without a matched normal sample by removing well-known germline variants, utilizing unmatched normal controls, and constructing decision rules to classify sequencing errors and private germline variants. With budgetary constraints related to computational and sequencing costs, finding the appropriate number of controls is a crucial step to identifying somatic variants. Our approach utilizes public databases for canonical …

Corneal Perforation In Ocular Graft-Versus-Host Disease, Cathy Y Zhang, Asim V Farooq, George J Harocopos, Eric L Sollenberger, Joshua H Hou, Charles S Bouchard, Christine Shieh, Uyen L Tran, Anthony J Lubniewski, Andrew J W Huang, Grace L Paley

2020-Current year OA Pubs

PURPOSE: Corneal perforation is a rare, vision-threatening complication of ocular graft-versus-host disease (GVHD) and is not well understood. Our objective was to examine the clinical disease course and histopathologic correlation in patients who progressed to this outcome.

METHODS: This study is a retrospective case series from four academic centers in the United States. All patients received a hematopoietic stem cell transplant (HSCT) prior to developing ocular GVHD. Variables of interest included patient demographics, time interval between HSCT and ocular events, visual acuity throughout clinical course, corticosteroid and infection prophylaxis regimens at time of corneal perforation, medical/surgical interventions, and histopathology.

RESULTS: …

Genetic Liability To Cannabis Use Disorder And Covid-19 Hospitalization, Alexander S Hatoum, Claire L Morrison, Sarah M C Colbert, Evan A Winiger, Emma C Johnson, Arpana Agrawal, Ryan Bogdan

2020-Current year OA Pubs

BACKGROUND: Vulnerability to COVID-19 hospitalization has been linked to behavioral risk factors, including combustible psychoactive substance use (e.g., tobacco smoking). Paralleling the COVID-19 pandemic crisis have been increasingly permissive laws for recreational cannabis use. Cannabis use disorder (CUD) is a psychiatric disorder that is heritable and genetically correlated with respiratory disease, independent of tobacco smoking. We examined the genetic relationship between CUD and COVID-19 hospitalization.

METHODS: We estimated the genetic correlation between CUD (case:

RESULTS: Genetic vulnerability to COVID-19 was correlated with genetic liability to CUD (

CONCLUSIONS: Problematic cannabis use and vulnerability to serious COVID-19 complications share genetic underpinnings …

Metastatic Castrate-Resistant Prostate Cancer: A Rare Cause Of Bowel Obstruction, Syed Ehsanullah, Syeda Zarmeena Rashid, Saiyed Abdullah A. Ehsanullah

2020-Current year OA Pubs

Prostate cancer most commonly metastasizes to bone, lymph nodes, lungs, or liver, but rarely spreads to the large intestine. This case highlights a rare case of castrate-resistant prostate cancer (CRPC) that spread locally to the large intestine and rectum, significant enough to cause bowel obstruction. Metastatic prostate carcinomas are considered an infrequent cause of bowel obstruction.

Single-Cell Rna-Sequencing Analysis Of The Ciliary Epithelium And Contiguous Tissues In The Mouse Eye, J C Youkilis, S Bassnett

2020-Current year OA Pubs

The ciliary epithelium plays a central role in ocular homeostasis but cells of the pigmented and non-pigmented layers are difficult to isolate physically and study. Here we used single-cell RNA-sequencing (scRNA-seq) to analyze the transcriptional signatures of cells harvested from the ciliary body and contiguous tissues. Microdissected tissue was dissociated by collagenase digestion and the transcriptomes of individual cells were obtained using a droplet-based scRNA-seq approach. In situ hybridization was used to verify the expression patterns of selected differentially-expressed genes. High quality transcriptomes were obtained from 10,024 cells and unsupervised clustering distinguished 22 cell types. Although efforts were made to …

Clustering Of Aromatic Residues In Prion-Like Domains Can Tune The Formation, State, And Organization Of Biomolecular Condensates, Alex S Holehouse, Garrett M Ginell, Daniel Griffith, Elvan Böke

2020-Current year OA Pubs

In immature oocytes, Balbiani bodies are conserved membraneless condensates implicated in oocyte polarization, the organization of mitochondria, and long-term organelle and RNA storage. In

Sex Modifies Apoe Ε4 Dose Effect On Brain Tau Deposition In Cognitively Impaired Individuals, Shaozhen Yan, Chaojie Zheng, Manish D Paranjpe, Yanxiao Li, Weihua Li, Xiuying Wang, Tammie L S Benzinger, Jie Lu, Yun Zhou

2020-Current year OA Pubs

Recent studies in cognitively unimpaired elderly individuals suggest that the APOE ε4 allele exerts a dosage-dependent effect on brain tau deposition. The aim of this study was to investigate sex differences in APOE ε4 gene dosage effects on brain tau deposition in cognitively impaired individuals using quantitative 18F-flortaucipir PET. Preprocessed 18F-flortaucipir tau PET images, T1-weighted structural MRI, demographic information, global cortical amyloid-β burden measured by 18F-florbetapir PET, CSF total tau and phosphorylated tau measurements were obtained from the Alzheimer's Disease Neuroimaging Initiative database. Two hundred and sixty-eight cognitively impaired individuals with 146 APOE ε4 non-carriers and 122 carriers (85 heterozygotes …

A Scoping Review Of De-Implementation Frameworks And Models, Callie Walsh-Bailey, Edward Tsai, Rachel G Tabak, Alexandra B Morshed, Wynne E Norton, Virginia R Mckay, Ross C Brownson, Sheyna Gifford

2020-Current year OA Pubs

BACKGROUND: Reduction or elimination of inappropriate, ineffective, or potentially harmful healthcare services and public health programs can help to ensure limited resources are used effectively. Frameworks and models (FM) are valuable tools in conceptualizing and guiding the study of de-implementation. This scoping review sought to identify and characterize FM that can be used to study de-implementation as a phenomenon and identify gaps in the literature to inform future model development and application for research.

METHODS: We searched nine databases and eleven journals from a broad array of disciplines (e.g., healthcare, public health, public policy) for de-implementation studies published between 1990 …

Low-Dose Dobutamine Cardiovascular Magnetic Resonance Segmental Strain Study Of Early Phase Of Intramyocardial Hemorrhage Rats, Rui Xia, Bo He, Tong Zhu, Yu Zhang, Yushu Chen, Lei Wang, Yang Zhou, Jichun Liao, Jie Zheng, Yongmei Li, Fajin Lv, Fabao Gao

2020-Current year OA Pubs

BACKGROUND: This study investigates the segmental myocardial strain of the early phase of intramyocardial hemorrhage (IMH) caused by reperfused myocardial infarction (MI) in rats by low-dose dobutamine (LDD) cardiovascular magnetic resonance (CMR) feature-tracking.

METHODS: Nine sham rats and nine rats with 60-min myocardial ischemia followed by 48-h reperfusion were investigated using CMR, including T2*-mapping sequence and fast imaging with steady-state precession (FISP)-cine sequence. Another FISP-cine sequence was acquired after 2 min of dobutamine injection; the MI, IMH, and Non-MI (NMI) areas were identified. The values of peak radial strains (PRS) and peak circumferential strains (PCS) of the MI, IMH and …

Gasdermin D Deficiency Attenuates Arthritis Induced By Traumatic Injury But Not Autoantibody-Assembled Immune Complexes, Tong Yang, Kai Sun, Chun Wang, Gaurav Swarnkar, Songtao Quan, Dustin Kress, Jianqiu Xiao, Yael Alippe, Hongjun Zheng, Robert H Brophy, Dingjun Hao, Audrey Mcalinden, Yousef Abu-Amer, Jie Shen, Gabriel Mbalaviele

2020-Current year OA Pubs

BACKGROUND: Gasdermin D (GSDMD) is cleaved by several proteases including by caspase-1, a component of intracellular protein complexes called inflammasomes. Caspase-1 also converts pro-interleukin-1β (pro-IL-1β) and pro-IL-18 into bioactive IL-1β and IL-18, respectively. GSDMD amino-terminal fragments form plasma membrane pores, which mediate the secretion of IL-1β and IL-18 and cause the inflammatory form of cell death pyroptosis. Here, we tested the hypothesis that GSDMD contributes to joint degeneration in the K/BxN serum transfer-induced arthritis (STIA) model in which autoantibodies against glucose-6-phosphate isomerase promote the formation of pathogenic immune complexes on the surface of myeloid cells, which highly express the inflammasomes. …

Developing And Demonstrating The Viability And Availability Of The Multilevel Implementation Strategy For Syncope Optimal Care Through Engagement (Mission) Syncope App: Evidence-Based Clinical Decision Support Tool, Shiraz Amin, Vedant Gupta, Gaixin Du, Colleen Mcmullen, Matthew Sirrine, Mark V Williams, Susan S Smyth, Romil Chadha, Seth Stearley, Jing Li

2020-Current year OA Pubs

BACKGROUND: Syncope evaluation and management is associated with testing overuse and unnecessary hospitalizations. The 2017 American College of Cardiology/American Heart Association (ACC/AHA) Syncope Guideline aims to standardize clinical practice and reduce unnecessary services. The use of clinical decision support (CDS) tools offers the potential to successfully implement evidence-based clinical guidelines. However, CDS tools that provide an evidence-based differential diagnosis (DDx) of syncope at the point of care are currently lacking.

OBJECTIVE: With input from diverse health systems, we developed and demonstrated the viability of a mobile app, the Multilevel Implementation Strategy for Syncope optImal care thrOugh eNgagement (MISSION) Syncope, as …

Enhancing Dopamine Tone Modulates Global And Local Cortical Perfusion As A Function Of Comt Val158met Genotype, Daniella J Furman, Ioannis Pappas, Robert L White 3rd, Andrew S Kayser, Mark D'Esposito

2020-Current year OA Pubs

The cognitive effects of pharmacologically enhancing cortical dopamine (DA) tone are variable across healthy human adults. It has been postulated that individual differences in drug responses are linked to baseline cortical DA activity according to an inverted-U-shaped function. To better understand the effect of divergent starting points along this curve on DA drug responses, researchers have leveraged a common polymorphism (rs4680) in the gene encoding the enzyme catechol-O-methyltransferase (COMT) that gives rise to greater (Met allele) or lesser (Val allele) extracellular levels of cortical DA. Here we examined the extent to which changes in resting cortical perfusion following the administration …

Development And Immunogenicity Of A Prototype Multivalent Group B Streptococcus Bioconjugate Vaccine, Jeremy A Duke, Amy V Paschall, Lloyd S Robinson, Cory J Knoot, Evgeny Vinogradov, Nichollas E Scott, Mario F Feldman, Fikri Y Avci, Christian M Harding

2020-Current year OA Pubs

Group B

The Ga4gh Variation Representation Specification: A Computational Framework For Variation Representation And Federated Identification, Alex H Wagner, Malachi Griffith, Obi L Griffith, Et Al.

2020-Current year OA Pubs

Maximizing the personal, public, research, and clinical value of genomic information will require the reliable exchange of genetic variation data. We report here the Variation Representation Specification (VRS, pronounced "verse"), an extensible framework for the computable representation of variation that complements contemporary human-readable and flat file standards for genomic variation representation. VRS provides semantically precise representations of variation and leverages this design to enable federated identification of biomolecular variation with globally consistent and unique computed identifiers. The VRS framework includes a terminology and information model, machine-readable schema, data sharing conventions, and a reference implementation, each of which is intended to …

Storytelling To Improve Disease Outcomes In Gout (Stride-Go): A Multicenter, Randomized Controlled Trial In African American Veterans With Gout, Jasvinder A Singh, Amy Joseph, Joshua Baker, Joshua S Richman, Terrence Shaneyfelt, Kenneth G Saag, Seth Eisen

2020-Current year OA Pubs

BACKGROUND: Urate-lowering therapy (ULT) adherence is low in gout, and few, if any, effective, low-cost, interventions are available. Our objective was to assess if a culturally appropriate gout-storytelling intervention is superior to an attention control for improving gout outcomes in African-Americans (AAs).

METHODS: In a 1-year, multicenter, randomized controlled trial, AA veterans with gout were randomized to gout-storytelling intervention vs. a stress reduction video (attention control group; 1:1 ratio). The primary outcome was ULT adherence measured with MEMSCap™, an electronic monitoring system that objectively measured ULT medication adherence.

RESULTS: The 306 male AA veterans with gout who met the eligibility …

Physical Activity And Fat-Free Mass During Growth And In Later Life, Klaas R Westerterp, Susan B Racette, Et Al.

2020-Current year OA Pubs

BACKGROUND: Physical activity may be a way to increase and maintain fat-free mass (FFM) in later life, similar to the prevention of fractures by increasing peak bone mass.

OBJECTIVES: A study is presented of the association between FFM and physical activity in relation to age.

METHODS: In a cross-sectional study, FFM was analyzed in relation to physical activity in a large participant group as compiled in the International Atomic Energy Agency Doubly Labeled Water database. The database included 2000 participants, age 3-96 y, with measurements of total energy expenditure (TEE) and resting energy expenditure (REE) to allow calculation of physical …

A Whole Genome Duplication Drives The Genome Evolution Of Phytophthora Betacei, A Closely Related Species To Phytophthora Infestans, David A Ayala-Usma, Martha Cárdenas, Romain Guyot, Maryam Chaib De Mares, Adriana Bernal, Alejandro Reyes Muñoz, Silvia Restrepo

2020-Current year OA Pubs

BACKGROUND: Pathogens of the genus Phytophthora are the etiological agents of many devastating diseases in several high-value crops and forestry species such as potato, tomato, cocoa, and oak, among many others. Phytophthora betacei is a recently described species that causes late blight almost exclusively in tree tomatoes, and it is closely related to Phytophthora infestans that causes the disease in potato crops and other Solanaceae. This study reports the assembly and annotation of the genomes of P. betacei P8084, the first of its species, and P. infestans RC1-10, a Colombian strain from the EC-1 lineage, using long-read SMRT sequencing technology. …

Competitive Binding Of E3 Ligases Trim26 And Wwp2 Controls Sox2 In Glioblastoma, Tatenda Mahlokozera, Bhuvic Patel, Hao Chen, Patrick Desouza, Xuan Qu, Diane D Mao, Daniel Hafez, Wei Yang, Rukayat Taiwo, Mounica Paturu, Afshin Salehi, Amit D Gujar, Gavin P Dunn, Nima Mosammaparast, Allegra A Petti, Hiroko Yano, Albert H Kim

2020-Current year OA Pubs

The pluripotency transcription factor SOX2 is essential for the maintenance of glioblastoma stem cells (GSC), which are thought to underlie tumor growth, treatment resistance, and recurrence. To understand how SOX2 is regulated in GSCs, we utilized a proteomic approach and identified the E3 ubiquitin ligase TRIM26 as a direct SOX2-interacting protein. Unexpectedly, we found TRIM26 depletion decreased SOX2 protein levels and increased SOX2 polyubiquitination in patient-derived GSCs, suggesting TRIM26 promotes SOX2 protein stability. Accordingly, TRIM26 knockdown disrupted the SOX2 gene network and inhibited both self-renewal capacity as well as in vivo tumorigenicity in multiple GSC lines. Mechanistically, we found TRIM26, …

Influential Periods In Longitudinal Clinical Cardiovascular Health Scores, Amy E Krefman, Vito M R Muggeo, Et Al.

2020-Current year OA Pubs

The prevalence of ideal cardiovascular health (CVH) among adults in the United States is low and decreases with age. Our objective was to identify specific age windows when the loss of CVH accelerates, to ascertain preventive opportunities for intervention. Data were pooled from 5 longitudinal cohorts (Project Heartbeat!, Cardiovascular Risk in Young Finns Study, The Bogalusa Heart Study, Coronary Artery Risk Development in Young Adults, Special Turku Coronary Risk Factor Intervention Project) from the United States and Finland from 1973 to 2012. Individuals with clinical CVH factors (i.e., body mass index, blood pressure, cholesterol, blood glucose) measured from ages 8 …

Reward Deficiency Syndrome (Rds): A Cytoarchitectural Common Neurobiological Trait Of All Addictions, Kenneth Blum, Abdalla Bowirrat, Eric R Braverman, David Baron, Jean Lud Cadet, Shan Kazmi, Igor Elman, Panyotis K Thanos, Rajendra D Badgaiyan, William B Downs, Debasis Bagchi, Luis Llanos-Gomez, Mark S Gold

2020-Current year OA Pubs

Alcohol and other substance use disorders share comorbidity with other RDS disorders, i.e., a reduction in dopamine signaling within the reward pathway. RDS is a term that connects addictive, obsessive, compulsive, and impulsive behavioral disorders. An estimated 2 million individuals in the United States have opioid use disorder related to prescription opioids. It is estimated that the overall cost of the illegal and legally prescribed opioid crisis exceeds one trillion dollars. Opioid Replacement Therapy is the most common treatment for addictions and other RDS disorders. Even after repeated relapses, patients are repeatedly prescribed the same opioid replacement treatments. A recent …

A Prospective Examination Of Sex Differences In Posttraumatic Autonomic Functioning, Antonia V. Seligowski, Stacey L. House, Deanna M. Barch, Et Al.

2020-Current year OA Pubs

BACKGROUND: Cross-sectional studies have found that individuals with posttraumatic stress disorder (PTSD) exhibit deficits in autonomic functioning. While PTSD rates are twice as high in women compared to men, sex differences in autonomic functioning are relatively unknown among trauma-exposed populations. The current study used a prospective design to examine sex differences in posttraumatic autonomic functioning.

METHODS: 192 participants were recruited from emergency departments following trauma exposure (

RESULTS: 2-week systolic BP was significantly higher in men, while 2-week HR was significantly higher in women, and a sex by PTSD interaction suggested that women who developed PTSD demonstrated the highest HR …

Anca Vasculitis Induction Management During The Covid-19 Pandemic, Antonio Salas, Tingting Li, Et Al.

2020-Current year OA Pubs

No abstract provided.

Trends In Rotator Cuff Repair Rates And Comorbidity Burden Among Commercially Insured Patients Younger Than The Age Of 65 Years, United States 2007-2016, Elizabeth L Yanik, Aaron M Chamberlain, Jay D Keener

2020-Current year OA Pubs

BACKGROUND: Prior US studies have shown increasing rotator cuff repair rates through 2009. We hypothesize that rotator cuff repair rates are continuing to increase and the comorbidity profiles of patients are becoming more complex over time.

METHODS: We identified rotator cuff repairs in a large US cohort of people 18-64 years of age with ≥1 year of commercial insurance coverage. Repair rate trends across time were standardized by age, sex, and geographic region. Procedures were categorized as inpatient vs. outpatient and as arthroscopic vs. open. Prevalent comorbidities were defined as 1 inpatient diagnosis claim or 2 outpatient diagnosis claims during …

Implementing Stereotactic Accelerated Partial Breast Irradiation Using Magnetic Resonance Guided Radiation Therapy, Alex T Price, William R Kennedy, Lauren E Henke, Sean R Brown, Olga L Green, Maria A Thomas, John Ginn, Imran Zoberi

2020-Current year OA Pubs

INTRODUCTION: Accelerated partial breast irradiation (APBI) seeks to reduce irradiated volumes and radiation exposure for patients while maintaining acceptable clinical outcomes. Magnetic resonance image-guided radiotherapy (MRgRT) provides excellent soft-tissue contrast for treatment localization, which can reduce setup uncertainty, thus reducing margins in the external beam setting. Additionally, stereotactic body radiotherapy (SBRT)-style regimens with high gradients can also be executed. This MR-guided stereotactic APBI (MRgS-APBI) approach can be utilized for a lower number of fractions and spare a greater volume of healthy tissues compared to conventional 3D external beam APBI.

METHODS: Our MRgS-APBI program was developed for two prospective non-randomized phase …

Phase 1b Study Of Avb-500 In Combination With Paclitaxel Or Pegylated Liposomal Doxorubicin Platinum-Resistant Recurrent Ovarian Cancer, Katherine C Fuh, Michael A Bookman, Joyce F Liu, Robert L Coleman, Thomas J Herzog, Premal H Thaker, Bradley J Monk, Randy Anderson, Gail Mcintyre, Reshma Rangwala, Kathleen N Moore

2020-Current year OA Pubs

OBJECTIVE: GAS6 and AXL are expressed in high-grade serous ovarian cancer but not in normal ovarian tissue. AVB-500, a novel high affinity Fc-sAXL fusion protein, binds GAS6 preventing AXL signaling. This Phase 1b study (NCT03639246) evaluated safety, efficacy, and exploratory predictive markers of AVB-500 combined with paclitaxel (PAC) or pegylated liposomal doxorubicin (PLD) in patients with platinum-resistant ovarian cancer (PROC), and used a model informed drug development (MIDD) approach for identification of the recommended phase 2 dose (RP2D).

METHODS: Eligible patients received AVB-500 at 10, 15, or 20 mg/kg IV q2wk combined with PAC (n = 23) or PLD (n …