Medicine and Health Sciences Commons^™

Co-Clinical Fdg-Pet Radiomic Signature In Predicting Response To Neoadjuvant Chemotherapy In Triple-Negative Breast Cancer, Sudipta Roy, Timothy D Whitehead, Shunqiang Li, Foluso O Ademuyiwa, Richard L Wahl, Farrokh Dehdashti, Kooresh I Shoghi

2020-Current year OA Pubs

PURPOSE: We sought to exploit the heterogeneity afforded by patient-derived tumor xenografts (PDX) to first, optimize and identify robust radiomic features to predict response to therapy in subtype-matched triple negative breast cancer (TNBC) PDX, and second, to implement PDX-optimized image features in a TNBC co-clinical study to predict response to therapy using machine learning (ML) algorithms.

METHODS: TNBC patients and subtype-matched PDX were recruited into a co-clinical FDG-PET imaging trial to predict response to therapy. One hundred thirty-one imaging features were extracted from PDX and human-segmented tumors. Robust image features were identified based on reproducibility, cross-correlation, and volume independence. A …

Characterization Of The Genomic And Immunologic Diversity Of Malignant Brain Tumors Through Multisector Analysis, Maximilian O Schaettler, Megan M Richters, Anthony Z Wang, Zachary L Skidmore, Bryan Fisk, Albert H Kim, Michael R Chicoine, Joshua W Osbun, Eric C Leuthardt, Joshua L Dowling, Gregory J Zipfel, Ralph G Dacey, Hsiang-Chih Lu, Tanner M Johanns, Obi L Griffith, Malachi Griffith, Gavin P Dunn, Et Al.

2020-Current year OA Pubs

Despite some success in secondary brain metastases, targeted or immune-based therapies have shown limited efficacy against primary brain malignancies such as glioblastoma (GBM). Although the intratumoral heterogeneity of GBM is implicated in treatment resistance, it remains unclear whether this diversity is observed within brain metastases and to what extent cancer cell-intrinsic heterogeneity sculpts the local immune microenvironment. Here, we profiled the immunogenomic state of 93 spatially distinct regions from 30 malignant brain tumors through whole-exome, RNA, and T-cell receptor sequencing. Our analyses identified differences between primary and secondary malignancies, with gliomas displaying more spatial heterogeneity at the genomic and neoantigen …

Semaphorin-Plexin Signaling: From Axonal Guidance To A New X-Linked Intellectual Disability Syndrome, Jacqueline L Steele, Marwan S Shinawi, Et Al.

2020-Current year OA Pubs

BACKGROUND: Semaphorins and plexins are ligands and cell surface receptors that regulate multiple neurodevelopmental processes such as axonal growth and guidance. PLXNA3 is a plexin gene located on the X chromosome that encodes the most widely expressed plexin receptor in fetal brain, plexin-A3. Plexin-A3 knockout mice demonstrate its role in semaphorin signaling in vivo. The clinical manifestations of semaphorin/plexin neurodevelopmental disorders have been less widely explored. This study describes the neurological and neurodevelopmental phenotypes of boys with maternally inherited hemizygous PLXNA3 variants.

METHODS: Data-sharing through GeneDx and GeneMatcher allowed identification of individuals with autism or intellectual disabilities (autism/ID) and hemizygous …

Automated Detection Of Vaping-Related Tweets On Twitter During The 2019 Evali Outbreak Using Machine Learning Classification, Yang Ren, Dezhi Wu, Avineet Singh, Erin Kasson, Ming Huang, Patricia Cavazos-Rehg

2020-Current year OA Pubs

There are increasingly strict regulations surrounding the purchase and use of combustible tobacco products (i.e., cigarettes); simultaneously, the use of other tobacco products, including e-cigarettes (i.e., vaping products), has dramatically increased. However, public attitudes toward vaping vary widely, and the health effects of vaping are still largely unknown. As a popular social media, Twitter contains rich information shared by users about their behaviors and experiences, including opinions on vaping. It is very challenging to identify vaping-related tweets to source useful information manually. In the current study, we proposed to develop a detection model to accurately identify vaping-related tweets using machine …

Modulation Of Mirisc-Mediated Gene Silencing In Eukaryotes, Courtney F Jungers, Sergej Djuranovic

2020-Current year OA Pubs

Gene expression is regulated at multiple levels in eukaryotic cells. Regulation at the post-transcriptional level is modulated by various

Isotopically Nonstationary 13c Metabolic Flux Analysis In Resting And Activated Human Platelets, Cara L Sake, Alexander J Metcalf, Michelle Meagher, Jorge Di Paola, Keith B Neeves, Nanette R Boyle

2020-Current year OA Pubs

Platelet metabolism is linked to platelet hyper- and hypoactivity in numerous human diseases. Developing a detailed understanding of the link between metabolic shifts and platelet activation state is integral to improving human health. Here, we show the first application of isotopically nonstationary

Outcomes Following In-Hospital Cardiopulmonary Resuscitation In People Receiving Maintenance Dialysis, Fahad Saeed, Haris F Murad, Richard E Wing, Jianbo Li, Jesse D Schold, Kevin A Fiscella

2020-Current year OA Pubs

RATIONALE & OBJECTIVE: Previous studies showing poor cardiopulmonary resuscitation (CPR) outcomes in the dialysis population have largely been derived from claims data and are somewhat limited by a lack of detailed characterization of CPR events. We aimed to analyze CPR-related outcomes in individuals receiving maintenance dialysis.

STUDY DESIGN: Retrospective chart review.

SETTING & PARTICIPANTS: Using electronic medical records from a single academic health care system, we identified all hospitalized adult patients receiving maintenance dialysis who had undergone in-hospital CPR between 2006 and 2014.

EXPOSURE: Initial in-hospital CPR.

OUTCOMES: Overall survival, predictors of unsuccessful CPR, predictors of death during the same …

Calorie Restriction Improves Lipid-Related Emerging Cardiometabolic Risk Factors In Healthy Adults Without Obesity: Distinct Influences Of Bmi And Sex From Calerie™ A Multicentre, Phase 2, Randomised Controlled Trial, Kim M Huffman, Susan B Racette, Et Al.

2020-Current year OA Pubs

BACKGROUND: For many cardiovascular risk factors there is no lower limit to which further reduction will result in decreased disease risk; this includes values within ranges considered normal for healthy adults. This seems to be true for new emerging metabolic risk factors identified by innovative technological advances. Further, there seems to be ever evolving evidence of differential responses to lifestyle interventions by sex and body compositions in the normal range. In this secondary analysis, we had the opportunity to test these principles for newly identified molecular biomarkers of cardiometabolic risk in a young (21-50 years), normal weight healthy population undergoing …

Psychiatric Diagnoses And Medications In Wolfram Syndrome, Angela M Reiersen, Jacob S Noel, Tasha Doty, Richa A Sinkre, Anagha Narayanan, Tamara Hershey

2020-Current year OA Pubs

BACKGROUND: Wolfram Syndrome is a rare genetic disorder usually resulting from pathogenic variation in the

OBJECTIVE: To examine lifetime psychiatric diagnoses and medication history in Wolfram Syndrome.

METHOD: Child, adolescent, and young adult Wolfram Syndrome participants (n=39) were assessed by a child & adolescent psychiatrist to determine best estimate DSM-5 lifetime psychiatric diagnoses as well as psychoactive medication history. In addition, the Child & Adolescent Symptom Inventory-5 (CASI-5) Parent Checklist was used to determine likely psychiatric diagnoses based on symptom counts in Wolfram Syndrome patients (n=33), type 1 diabetes (n=15), and healthy comparison (n=18) groups.

RESULTS: Study participants with Wolfram …

Job-Exposure Matrix: A Useful Tool For Incorporating Workplace Exposure Data Into Population Health Research And Practice, Alexis Descatha, Marc Fadel, Grace Sembajwe, Susan Peters, Bradley A Evanoff

2020-Current year OA Pubs

Workplace exposures to physical, chemical, and psychosocial factors account for a large burden of chronic diseases. Obtaining useful estimates of current and past workplace exposures is challenging, particularly in large general population studies. Job-exposure matrices (JEMs) are a useful tool for exposure assessment, particularly when no individual level exposure data are available. A JEM provides a cross-tabulation of job titles (sometimes combined with industry) and estimated exposures to workers carrying out these jobs during different time periods. The major limitation of JEMs is that they do not account for individual variation in exposures within the same job. This limitation is …

Preclinical Antibody-Pet Imaging Of Pd-L1, Emma L Brown, Rachel A Deweerd, Abbey Zidel, Patricia M R Pereira

2020-Current year OA Pubs

Programmed cell death protein-1/ligand-1 (PD-1/PD-L1) blockade, including antibody therapeutics, has transformed cancer treatment. However, a major challenge in the field relates to selecting patients who are likely to respond to immune checkpoint inhibitors. Indeed, biopsy-based diagnostic tests to determine immune checkpoint protein levels do not accurately capture the inherent spatial and temporal heterogeneity of PD-L1 tumor expression. As a result, not all PD-L1-positive tumors respond to immunotherapies, and some patients with PD-L1-negative tumors have shown clinical benefits. In 2018, a first-in-human study of the clinically-approved anti-PD-L1 antibody Atezolizumab labeled with the positron emitter zirconium-89 validated the ability of positron emission …

Sustainability Of Breastfeeding Interventions To Reduce Child Mortality Rates In Low, Middle-Income Countries: A Systematic Review Of Randomized Controlled Trials, Alexis Engelhart, Stacey Mason, Ucheoma Nwaozuru, Chisom Obiezu-Umeh, Victoria Carter, Thembekile Shato, Titilola Gbaja-Biamila, David Oladele, Juliet Iwelunmor

2020-Current year OA Pubs

Child mortality is the lowest it has ever been, but the burden of death in low- and middle-income countries (LMICs) is still prevalent, and the numbers average above the global mean. Breastfeeding contributes to the reduction of child mortality by improving chance of survival beyond childhood. Therefore, it is essential to examine how evidence-based breastfeeding interventions are being maintained in resource-constrained settings. Guided by Scheirer and Dearing's sustainability framework, the aim of this systematic review was to explore how evidence-based breastfeeding interventions implemented to address child mortality in LMICs are sustained. The literature search included randomized controlled trials (RCTs) of …

Sustainability In Pediatric Hospitals: An Exploration At The Intersection Of Quality Improvement And Implementation Science, Sara Malone, Jason Newland, Sapna R Kudchadkar, Kim Prewitt, Virginia Mckay, Beth Prusaczyk, Enola Proctor, Ross C Brownson, Douglas A Luke

2020-Current year OA Pubs

BACKGROUND: Although new evidence-based practices are frequently implemented in clinical settings, many are not sustained, limiting the intended impact. Within implementation science, there is a gap in understanding sustainability. Pediatric healthcare settings have a robust history of quality improvement (QI), which includes a focus on continuation of change efforts. QI capability and sustainability capacity, therefore, serve as a useful concept for connecting the broader fields of QI and implementation science to provide insights on improving care. This study addresses these gaps in understanding of sustainability in pediatric settings and its relationship to QI.

METHODS: This is a cross-sectional observational study …

Il-1 Reprogramming Of Adult Neural Stem Cells Limits Neurocognitive Recovery After Viral Encephalitis By Maintaining A Proinflammatory State, Allison L Soung, Veronica A Davé, Charise Garber, Eric D Tycksen, Lauren L Vollmer, Robyn S Klein

2020-Current year OA Pubs

Innate immune responses to emerging RNA viruses are increasingly recognized as having significant contributions to neurologic sequelae, especially memory disorders. Using a recovery model of West Nile virus (WNV) encephalitis, we show that, while macrophages deliver the antiviral and anti-neurogenic cytokine IL-1β during acute infection; viral recovery is associated with continued astrocyte inflammasome-mediated production of inflammatory levels of IL-1β, which is maintained by hippocampal astrogenesis via IL-1R1 signaling in neural stem cells (NSC). Accordingly, aberrant astrogenesis is prevented in the absence of IL-1 signaling in NSC, indicating that only newly generated astrocytes exert neurotoxic effects, preventing synapse repair and promoting …

Genome-Wide Analysis Of Mitochondrial Dna Copy Number Reveals Loci Implicated In Nucleotide Metabolism, Platelet Activation, And Megakaryocyte Proliferation, R J Longchamps, Mary Feitosa, Mary Wojczynski, Aldi Kraja, Michael Province, Et Al.

2020-Current year OA Pubs

Mitochondrial DNA copy number (mtDNA-CN) measured from blood specimens is a minimally invasive marker of mitochondrial function that exhibits both inter-individual and intercellular variation. To identify genes involved in regulating mitochondrial function, we performed a genome-wide association study (GWAS) in 465,809 White individuals from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the UK Biobank (UKB). We identified 133 SNPs with statistically significant, independent effects associated with mtDNA-CN across 100 loci. A combination of fine-mapping, variant annotation, and co-localization analyses was used to prioritize genes within each of the 133 independent sites. Putative causal genes …

A Phase 1b Study Of Telisotuzumab Vedotin In Combination With Nivolumab In Patients With Nsclc, D Ross Camidge, Daniel Morgensztern, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Telisotuzumab vedotin (Teliso-V) is an anti-c-Met-directed antibody-drug conjugate that has exhibited antitumor activity as monotherapy in NSCLC. Its potential activity combined with programmed cell death protein-1 inhibitors has not been previously evaluated.

METHODS: In a phase 1b study (NCT02099058), adult patients (≥18 y) with advanced NSCLC received combination therapy with Teliso-V (1.6, 1.9, or 2.2 mg/kg, every 2 wk) plus nivolumab (3 mg/kg, 240 mg, or per locally approved label). The primary objective was to assess safety and tolerability; secondary objectives included the evaluation of antitumor activity.

RESULTS: As of January 2020, a total of 37 patients received treatment …

Functional Tic-Like Presentations Differ Strikingly From Provisional Tic Disorder, Amanda L Arbuckle, Emily C Bihun, Bradley L Schlaggar, Kevin J. Black

2020-Current year OA Pubs

No abstract provided.

Protocol For A Proof-Of-Concept Study Evaluating Systematic Quality Improvement With Realtime Event Support (Squires), Arianna Montes De Oca, Thaddeus P. Budelier, Rachel C. Wolfe, Teresa M. Murray-Torres, Melissa Milbrandt, Ryan Guffey, Alex Kronzer, Mara L. Bollini, Brian A. Torres, Bernadette Henrichs, Arbi Ben Abdallah, Sherry L. Mckinnon, Ivan Kangrga, Andrea Reidy, Paul W. Kerby, Michael S. Avidan, Troy S. Wildes

2020-Current year OA Pubs

No abstract provided.

Protocol For The Perioperative Outcome Risk Assessment With Computer Learning Enhancement (Periop Oracle) Randomized Study, Bradley Fritz, Christopher King, Yixin Chen, Alex Kronzer, Joanna Abraham, Arbi Ben Abdallah, Thomas Kannampallil, Thaddeus Budelier, Arianna Montes De Oca, Sherry Mckinnon, Bethany Tellor Pennington, Troy Wildes, Michael Avidan

2020-Current year OA Pubs

No abstract provided.

Decision-Making Factors For An Autologous Stem Cell Transplant For Older Adults With Newly Diagnosed Multiple Myeloma: A Qualitative Analysis, Owais Mian, Martine Puts, Arleigh Mccurdy, Tanya M Wildes, Mark A Fiala, Matthew Kang, Mary Salib, Shabbir Alibhai, Hira Mian

2020-Current year OA Pubs

PURPOSE: A utologous stem cell transplant (ASCT) remains a standard of care among older adults (aged ≥65) with multiple myeloma (MM). However, heterogeneity in the eligibility and utilization of ASCT remains. We identified decision-making factors that influence ASCT eligibility and utilization among older adults with MM.

METHODS: A qualitative study across two academic and two community centres in Ontario was conducted between July 2019-July 2020. Older adults with MM (newly diagnosed MM aged 65-75 in whom a decision had been made about ASCT in <12 months) and treating oncologists completed a baseline survey and a subsequent interview, which was analyzed using thematic analysis.

RESULTS: Eighteen patients completed the survey and 9 follow-up interviews were conducted. Patients were happy with …

A Perspective On Implementation Outcomes And Strategies To Promote The Uptake Of Covid-19 Vaccines, Meagan Pilar, A Rani Elwy, Larissa Lushniak, Grace Huang, Gabriella M Mcloughlin, Cole Hooley, Nisha Nadesan-Reddy, Brittney Sandler, Mosa Moshabela, Olakunle Alonge, Elvin Geng, Enola Proctor

2020-Current year OA Pubs

Recent articles have highlighted the importance of incorporating implementation science concepts into pandemic-related research. However, limited research has been documented to date regarding implementation outcomes that may be unique to COVID-19 vaccinations and how to utilize implementation strategies to address vaccine program-related implementation challenges. To address these gaps, we formed a global COVID-19 implementation workgroup of implementation scientists who met weekly for over a year to review the available literature and learn about ongoing research during the pandemic. We developed a hierarchy to prioritize the applicability of "lessons learned" from the vaccination-related implementation literature. We identified applications of existing implementation …

"Provider Discretionary Power Practices To Support Implementation Of Patient-Centered Hiv Care In Lusaka, Zambia", Chanda Mwamba, Njekwa Mukamba, Anjali Sharma, Kasapo Lumbo, Marksman Foloko, Herbert Nyirenda, Sandra Simbeza, Kombatende Sikombe, Charles B Holmes, Izukanji Sikazwe, Carolyn Bolton Moore, Aaloke Mody, Elvin Geng, Laura K Beres

2020-Current year OA Pubs

INTRODUCTION: Traditional patient-provider relationships privilege the providers, as they possess the formal authority and clinical knowledge applied to address illness, but providers also have discretion over how they exercise their power to influence patients' services, benefits, and sanctions. In this study, we assessed providers' exercise of discretionary power in implementing patient-centered care (PCC) practices in Lusaka, Zambia.

METHODS: HIV clinical encounters between patients on antiretroviral therapy (ART) and providers across 24 public health facilities in Lusaka Province were audio recorded and transcribed verbatim. Using qualitative content analysis, we identified practices of discretionary power (DP) employed in the implementation of PCC …

Resting State Network Mapping In Individuals Using Deep Learning, Patrick H Luckett, John J Lee, Ki Yun Park, Ryan V Raut, Karin L Meeker, Evan M Gordon, Abraham Z Snyder, Beau M Ances, Eric C Leuthardt, Joshua S Shimony

2020-Current year OA Pubs

INTRODUCTION: Resting state functional MRI (RS-fMRI) is currently used in numerous clinical and research settings. The localization of resting state networks (RSNs) has been utilized in applications ranging from group analysis of neurodegenerative diseases to individual network mapping for pre-surgical planning of tumor resections. Reproducibility of these results has been shown to require a substantial amount of high-quality data, which is not often available in clinical or research settings.

METHODS: In this work, we report voxelwise mapping of a standard set of RSNs using a novel deep 3D convolutional neural network (3DCNN). The 3DCNN was trained on publicly available functional …

Expert Guidance On Prophylaxis And Treatment Of Dermatologic Adverse Events With Tumor Treating Fields (Ttfields) Therapy In The Thoracic Region, Milan J Anadkat, Mario Lacouture, Adam Friedman, Zachary D Horne, Jae Jung, Benjamin Kaffenberger, Sujith Kalmadi, Liza Ovington, Rupesh Kotecha, Huda Ismail Abdullah, Federica Grosso

2020-Current year OA Pubs

Tumor Treating Fields (TTFields) are electric fields, delivered via wearable arrays placed on or near the tumor site, that exert physical forces to disrupt cellular processes critical for cancer cell viability and tumor progression. As a first-in-class treatment, TTFields therapy is approved for use in newly diagnosed glioblastoma, recurrent glioblastoma, and pleural mesothelioma. Additionally, TTFields therapy is being investigated in non-small cell lung cancer (NSCLC), brain metastases from NSCLC, pancreatic cancer, ovarian cancer, hepatocellular carcinoma, and gastric adenocarcinoma. Because TTFields therapy is well tolerated and delivery is locoregional, there is low risk of additive systemic adverse events (AEs) when used …

Postnatal Osterix But Not Dmp1 Lineage Cells Significantly Contribute To Intramembranous Ossification In Three Preclinical Models Of Bone Injury, Evan G Buettmann, Susumu Yoneda, Pei Hu, Jennifer A Mckenzie, Matthew J Silva

2020-Current year OA Pubs

Murine models of long-bone fracture, stress fracture, and cortical defect are used to discern the cellular and molecular mediators of intramembranous and endochondral bone healing. Previous work has shown that Osterix (Osx

3d Bi-Directional Transformer U-Net For Medical Image Segmentation, Xiyao Fu, Zhexian Sun, Haoteng Tang, Eric M Zou, Heng Huang, Yong Wang, Liang Zhan

2020-Current year OA Pubs

As one of the popular deep learning methods, deep convolutional neural networks (DCNNs) have been widely adopted in segmentation tasks and have received positive feedback. However, in segmentation tasks, DCNN-based frameworks are known for their incompetence in dealing with global relations within imaging features. Although several techniques have been proposed to enhance the global reasoning of DCNN, these models are either not able to gain satisfying performances compared with traditional fully-convolutional structures or not capable of utilizing the basic advantages of CNN-based networks (namely the ability of local reasoning). In this study, compared with current attempts to combine FCNs and …

Mortality In Pediatric Oncology And Stem Cell Transplant Patients With Bloodstream Infections, Daniel N Willis, Mary Claire Mcglynn, Patrick J Reich, Robert J Hayashi

2020-Current year OA Pubs

BACKGROUND: Bloodstream infections (BSI) continue to represent a significant source of morbidity for pediatric oncology patients, however less is known regarding this population's risk of death. We sought to evaluate the risk of BSI and death at a large pediatric cancer center.

METHODS: We retrospectively collected inpatient data from pediatric oncology and hematopoietic stem cell transplant (HSCT) patients over a 9-year period. We performed univariate and multivariable modeling to assess risk of BSI and mortality examining the following variables: demographics, underlying malignancy, history of HSCT, central line type, and febrile neutropenia (FN).

RESULTS: During the study period, 6763 admissions from …

Sentience And Sentient Minds, John Anthony Webster

Animal Sentience

My commentary builds on Rowan et al.’s (2022) comprehensive review to address the question ‘what do we mean by sentience?’ It suggests how we might recognise degrees of sentience within the animal kingdom, ranging from primitive sensations such as hunger and pain to more complex emotions that determine quality of life.

Defining Patient-Level Molecular Heterogeneity In Psoriasis Vulgaris Based On Single-Cell Transcriptomics, Yale Liu, Hao Wang, Christopher Cook, Mark A Taylor, Jeffrey P North, Ashley Hailer, Yanhong Shou, Arsil Sadik, Esther Kim, Elizabeth Purdom, Jeffrey B Cheng, Raymond J Cho

Staff and Researcher Publications

Identifying genetic variation underlying human diseases establishes targets for therapeutic development and helps tailor treatments to individual patients. Large-scale transcriptomic profiling has extended the study of such molecular heterogeneity between patients to somatic tissues. However, the lower resolution of bulk RNA profiling, especially in a complex, composite tissue such as the skin, has limited its success. Here we demonstrate approaches to interrogate patient-level molecular variance in a chronic skin inflammatory disease, psoriasis vulgaris, leveraging single-cell RNA-sequencing of CD45+ cells isolated from active lesions. Highly psoriasis-specific transcriptional abnormalities display greater than average inter-individual variance, nominating them as potential sources of clinical …

A Novel Approach To Link Genetics And Human Mri Identifies Akap7-Dependent Subicular/Prefrontal Functional Connectivity As Altered In Suicidality, Guillermo Poblete, Tien Nguyen, Savannah Gosnell, Olutayo Sofela, Michelle Patriquin, Sanjay J Mathew, Alan Swann, David A Nielsen, Thomas R Kosten, Ramiro Salas

Staff and Researcher Publications

Background: Brain imaging and genetics are fields acquiring data at increasing speed, but more information does not always result in a better understanding of the underlying biology. We developed the ProcessGeneLists (PGL) approach to use genetics and mRNA gene expression data to generate regions of interest for imaging studies.

Methods: We applied PGL to past suicide attempt (ATT): We averaged the mRNA expression levels of genes (n = 130) possibly associated with ATT (p ≤ 10-3 in a published genome-wide association study, GWAS) in each brain region studied in the Human Allen Brain Atlas (6 ex-vivo brains, 158 to 946 …