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2021

ICTS (Institute of Clinical and Translational Sciences)

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Full-Text Articles in Medicine and Health Sciences

Women And Ethnoracial Minorities With Poor Cardiovascular Health Measures Associated With A Higher Risk Of Developing Mood Disorder, Aixia Guo, Kari A Stephens, Yosef M Khan, James R Langabeer, Randi E Foraker Dec 2021

Women And Ethnoracial Minorities With Poor Cardiovascular Health Measures Associated With A Higher Risk Of Developing Mood Disorder, Aixia Guo, Kari A Stephens, Yosef M Khan, James R Langabeer, Randi E Foraker

2020-Current year OA Pubs

BACKGROUND: Mood disorders (MDS) are a type of mental health illness that effects millions of people in the United States. Early prediction of MDS can give providers greater opportunity to treat these disorders. We hypothesized that longitudinal cardiovascular health (CVH) measurements would be informative for MDS prediction.

METHODS: To test this hypothesis, the American Heart Association's Guideline Advantage (TGA) dataset was used, which contained longitudinal EHR from 70 outpatient clinics. The statistical analysis and machine learning models were employed to identify the associations of the MDS and the longitudinal CVH metrics and other confounding factors.

RESULTS: Patients diagnosed with MDS …


Transcriptional Reprogramming Differentiates Active From Inactive Esr1 Fusions In Endocrine Therapy-Refractory Metastatic Breast Cancer, Xuxu Gou, Shunqiang Li, Et Al. Dec 2021

Transcriptional Reprogramming Differentiates Active From Inactive Esr1 Fusions In Endocrine Therapy-Refractory Metastatic Breast Cancer, Xuxu Gou, Shunqiang Li, Et Al.

2020-Current year OA Pubs

Genomic analysis has recently identified multiple


Stat3 Inhibitor Mitigates Cerebral Amyloid Angiopathy And Parenchymal Amyloid Plaques While Improving Cognitive Functions And Brain Networks, Jogender Mehla, Itender Singh, Deepti Diwan, James W Nelson, Molly Lawrence, Eunjae Lee, Adam Q Bauer, David M Holtzman, Gregory J Zipfel Dec 2021

Stat3 Inhibitor Mitigates Cerebral Amyloid Angiopathy And Parenchymal Amyloid Plaques While Improving Cognitive Functions And Brain Networks, Jogender Mehla, Itender Singh, Deepti Diwan, James W Nelson, Molly Lawrence, Eunjae Lee, Adam Q Bauer, David M Holtzman, Gregory J Zipfel

2020-Current year OA Pubs

Previous reports indicate a potential role for signal transducer and activator of transcription 3 (STAT3) in amyloid-β (Aβ) processing and neuritic plaque pathogenesis. In the present study, the impact of STAT3 inhibition on cognition, cerebrovascular function, amyloid pathology, oxidative stress, and neuroinflammation was studied using in vitro and in vivo models of Alzheimer's disease (AD)-related pathology. For in vitro experiments, human brain vascular smooth muscle cells (HBVSMC) and human brain microvascular endothelial cells (HBMEC) were used, and these cultured cells were exposed to Aβ peptides followed by measurement of activated forms of STAT3 expression and reactive oxygen species (ROS) generation. …


Overexpression Screen Of Interferon-Stimulated Genes Identifies Rarres3 As A Restrictor Of Toxoplasma Gondii Infection, Nicholas Rinkenberger, Michael E Abrams, Sumit K Matta, John W Schoggins, Neal M Alto, L David Sibley Dec 2021

Overexpression Screen Of Interferon-Stimulated Genes Identifies Rarres3 As A Restrictor Of Toxoplasma Gondii Infection, Nicholas Rinkenberger, Michael E Abrams, Sumit K Matta, John W Schoggins, Neal M Alto, L David Sibley

2020-Current year OA Pubs

No abstract provided.


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 Dec 2021

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 …


A Pilot Study Of Urine Proteomics In Covid-19-Associated Acute Kidney Injury, Yinyin Ye, Madhurima Kaushal, Diane Salamon, Amanda Knoten, Laura Marks, Joseph P Gaut, Anitha Vijayan, Philip A Mudd, Jane A O'Halloran, Sanjay Jain, Et Al. Dec 2021

A Pilot Study Of Urine Proteomics In Covid-19-Associated Acute Kidney Injury, Yinyin Ye, Madhurima Kaushal, Diane Salamon, Amanda Knoten, Laura Marks, Joseph P Gaut, Anitha Vijayan, Philip A Mudd, Jane A O'Halloran, Sanjay Jain, Et Al.

2020-Current year OA Pubs

No abstract provided.


Development Of A Qualified Clinical Data Registry For Emergency Medicine, Stephen K Epstein, Richard T Griffey, Michelle P Lin, James J Augustine, Pawan Goyal, Arjun K Venkatesh Dec 2021

Development Of A Qualified Clinical Data Registry For Emergency Medicine, Stephen K Epstein, Richard T Griffey, Michelle P Lin, James J Augustine, Pawan Goyal, Arjun K Venkatesh

2020-Current year OA Pubs

The passage of the Medicare Access and CHIP Reauthorization Act (MACRA) in 2015 marked a fundamental transition in physician payment by the Centers for Medicare and Medicaid Services (CMS) from traditional fee-for service to value-based models. MACRA led to the creation of the CMS Quality Payment Program (QPP), which bases the value of physician care in large part on physician quality reporting. The QPP enabled a shift away from legacy CMS-stewarded quality measures that had limited applicability to individual specialties toward specialty-specific quality measures developed and stewarded by physician specialty societies using Qualified Clinical Data Registries (QCDRs). This article describes …


Single-Cell Rna-Sequencing Analysis Of The Ciliary Epithelium And Contiguous Tissues In The Mouse Eye, J C Youkilis, S Bassnett Dec 2021

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 …


Ogden Type I To Iii Tibial Tubercle Fractures In Skeletally Immature Patients: Is Routine Anterior Compartment Fasciotomy Of The Leg Indicated?, Corey Brown, Brian A. Kelly, Kirsten Brouillet, Scott J. Luhmann Dec 2021

Ogden Type I To Iii Tibial Tubercle Fractures In Skeletally Immature Patients: Is Routine Anterior Compartment Fasciotomy Of The Leg Indicated?, Corey Brown, Brian A. Kelly, Kirsten Brouillet, Scott J. Luhmann

2020-Current year OA Pubs

PURPOSE: Determine the frequency of compartment syndrome of the leg after displaced, operatively treated modified Ogden I to III tibial tubercle fractures (TTFxs), evaluate the preoperative assessment and use of advanced imaging, and need for prophylactic fasciotomies.

METHODS: Retrospective analysis of operatively treated, displaced modified Ogden I to III TTFxs, at our level 1 paediatric trauma centre between 2007 and 2019. Modified Ogden Type IV and V fracture patterns were excluded. Fracture patterns were determined by plain radiographs.

RESULTS: There were 49 modified Ogden I to III TTFxs in 48 patients. None had signs nor symptoms of vascular compromise, compartment …


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 Dec 2021

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 …


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 Dec 2021

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 …


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. Dec 2021

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, …


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 Dec 2021

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 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 Nov 2021

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 Nov 2021

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 …


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 Nov 2021

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 …


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 Nov 2021

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. …


The Ga4gh Variation Representation Specification: A Computational Framework For Variation Representation And Federated Identification, Alex H Wagner, Malachi Griffith, Obi L Griffith, Et Al. Nov 2021

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 …


Physical Activity And Fat-Free Mass During Growth And In Later Life, Klaas R Westerterp, Susan B Racette, Et Al. Nov 2021

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 …


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 Nov 2021

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, …


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 Nov 2021

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 …


Riociguat For The Treatment Of Phe508del Homozygous Adults With Cystic Fibrosis, Nico Derichs, Daniel Rosenbluth, Et Al. Nov 2021

Riociguat For The Treatment Of Phe508del Homozygous Adults With Cystic Fibrosis, Nico Derichs, Daniel Rosenbluth, Et Al.

2020-Current year OA Pubs

BACKGROUND: Riociguat is a first-in-class soluble guanylate cyclase stimulator for which preclinical data suggested improvements in cystic fibrosis transmembrane conductance regulator (CFTR) function.

METHODS: This international, multicenter, two-part, Phase II study of riociguat enrolled adults with cystic fibrosis (CF) homozygous for Phe508del CFTR. Part 1 was a 28-day, randomized, double-blind, placebo-controlled study in participants not receiving CFTR modulator therapy. Twenty-one participants were randomized 1:2 to placebo or oral riociguat (0.5 mg three times daily [tid] for 14 days, increased to 1.0 mg tid for the subsequent 14 days). The primary and secondary efficacy endpoints were change in sweat chloride concentration …


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 Nov 2021

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 …


A Prospective Examination Of Sex Differences In Posttraumatic Autonomic Functioning, Antonia V. Seligowski, Stacey L. House, Deanna M. Barch, Et Al. Nov 2021

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 …


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 Nov 2021

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 …


Use Of A Risk Analytic Algorithm To Inform Weaning From Vasoactive Medication In Patients Following Pediatric Cardiac Surgery, Michael P. Goldsmith, Vinay M. Nadkarni, Craig Futterman, Avihu Z. Gazit, Dimitar Baronov, Adam Tomczak, Peter C. Laussen, Joshua W. Salvin Nov 2021

Use Of A Risk Analytic Algorithm To Inform Weaning From Vasoactive Medication In Patients Following Pediatric Cardiac Surgery, Michael P. Goldsmith, Vinay M. Nadkarni, Craig Futterman, Avihu Z. Gazit, Dimitar Baronov, Adam Tomczak, Peter C. Laussen, Joshua W. Salvin

2020-Current year OA Pubs

OBJECTIVES: Advanced clinical decision support tools, such as real-time risk analytic algorithms, show promise in assisting clinicians in making more efficient and precise decisions. These algorithms, which calculate the likelihood of a given underlying physiology or future event, have predominantly been used to identify the risk of impending clinical decompensation. There may be broader clinical applications of these models. Using the inadequate delivery of oxygen index, a U.S. Food and Drug Administration-approved risk analytic algorithm predicting the likelihood of low cardiac output state, the primary objective was to evaluate the association of inadequate delivery of oxygen index with success or …


Oncogenic Kras-Induced Feedback Inflammatory Signaling In Pancreatic Cancer: An Overview And New Therapeutic Opportunities, Sapana Bansod, Paarth B Dodhiawala, Kian-Huat Lim Oct 2021

Oncogenic Kras-Induced Feedback Inflammatory Signaling In Pancreatic Cancer: An Overview And New Therapeutic Opportunities, Sapana Bansod, Paarth B Dodhiawala, Kian-Huat Lim

2020-Current year OA Pubs

Pancreatic ductal adenocarcinoma (PDAC) remains highly refractory to treatment. While the


Coffee, Tea, And Mammographic Breast Density In Premenopausal Women, Adashi Margaret Odama, Valerie Otti, Shuai Xu, Olamide Adebayo, Adetunji T Toriola Oct 2021

Coffee, Tea, And Mammographic Breast Density In Premenopausal Women, Adashi Margaret Odama, Valerie Otti, Shuai Xu, Olamide Adebayo, Adetunji T Toriola

2020-Current year OA Pubs

Studies have investigated the associations of coffee and tea with mammographic breast density (MBD) in premenopausal women with inconsistent results. We analyzed data from 375 premenopausal women who attended a screening mammogram at Washington University School of Medicine, St. Louis, MO in 2016, and stratified the analyses by race (non-Hispanic White (NHW) vs. Black/African American). Participants self-reported the number of servings of coffee, caffeinated tea, and decaffeinated tea they consumed. Volpara software was used to determine volumetric percent density (VPD), dense volume (DV), and non-dense volume (NDV). We used generalized linear regression models to quantify the associations of coffee and …


Factors Associated With Viremia In People Living With Hiv On Antiretroviral Therapy In Guatemala, Dean W Ortíz, Olivia Roberts-Sano, Hugo E Marroquin, Lindsey Larson, Katherine B Franco, Andrej Spec, Johanna R Melendez, Rodolfo Pinzón, Ana J Samayoa, Carlos Mejia-Chew, Jane A O Halloran Oct 2021

Factors Associated With Viremia In People Living With Hiv On Antiretroviral Therapy In Guatemala, Dean W Ortíz, Olivia Roberts-Sano, Hugo E Marroquin, Lindsey Larson, Katherine B Franco, Andrej Spec, Johanna R Melendez, Rodolfo Pinzón, Ana J Samayoa, Carlos Mejia-Chew, Jane A O Halloran

2020-Current year OA Pubs

INTRODUCTION: Viral suppression prevents HIV transmission and disease progression, but socio-economic and clinical factors can hinder the goal of suppression. We evaluated factors associated with viral non suppression (VNS) and persistent viremia (PV) in people living with HIV (PLHIV) receiving antiretroviral therapy (ART) in Guatemala.

METHODS: We conducted a cross sectional analysis using data from an ongoing cohort of PLHIV attending the largest HIV clinic in Guatemala. Univariable and multivariable analyses were conducted between PLHIV with viral suppression and detectable viremia. VNS was defined as most recent HIV RNA ≥ 200 copies/ml and PV as two consecutive HIV RNA ≥ …


Non-Invasive Monitoring Of Arthritis Treatment Response Via Targeting Of Tyrosine-Phosphorylated Annexin A2 In Chondrocytes, Shaw-Wei D Tsen, Luke E Springer, Krishna Sharmah Gautam, Rui Tang, Kexian Liang, Gail Sudlow, Amir Kucharski, Christine T N Pham, Samuel Achilefu Oct 2021

Non-Invasive Monitoring Of Arthritis Treatment Response Via Targeting Of Tyrosine-Phosphorylated Annexin A2 In Chondrocytes, Shaw-Wei D Tsen, Luke E Springer, Krishna Sharmah Gautam, Rui Tang, Kexian Liang, Gail Sudlow, Amir Kucharski, Christine T N Pham, Samuel Achilefu

2020-Current year OA Pubs

BACKGROUND: The development and optimization of therapies for rheumatoid arthritis (RA) is currently hindered by a lack of methods for early non-invasive monitoring of treatment response. Annexin A2, an inflammation-associated protein whose presence and phosphorylation levels are upregulated in RA, represents a potential molecular target for tracking RA treatment response.

METHODS: LS301, a near-infrared dye-peptide conjugate that selectively targets tyrosine 23-phosphorylated annexin A2 (pANXA2), was evaluated for its utility in monitoring disease progression, remission, and early response to drug treatment in mouse models of RA by fluorescence imaging. The intraarticular distribution and localization of LS301 relative to pANXA2 was determined …