Digital Commons Network^™

Short Signature Rpob Gene Sequence To Differentiate Species In Mycobacterium Abscessus Group, Jian R Bao, Kileen L Shier, Ronald N Master, Robert S Jones, Richard B Clark

Faculty, Staff and Student Publications

Mycobacterium abscessus group (MAG) are rapidly growing acid-fast bacteria that consist of three closely related species: M. abscessus (Ma), M. bolletii (Mb), and M. massiliense (Mm). Differentiation of these species can be difficult but is increasingly requested owing to recent infectious outbreaks and their differential drug resistance. We developed a novel and rapid pyrosequencing method using short signature sequences (35 to 45 bp) at a hypervariable site in the rpoB gene to differentiate the three MAG species, along with M. chelonae (Mc), and M. immunogenum (Mi). This method was evaluated …

Optimal Urine Culture Diagnostic Stewardship Practice- Results From An Expert Modified-Delphi Procedure, Kimberly C Claeys, Stephen Y Liang, Et Al.

2020-Current year OA Pubs

BACKGROUND: Urine cultures are nonspecific and often lead to misdiagnosis of urinary tract infection and unnecessary antibiotics. Diagnostic stewardship is a set of procedures that modifies test ordering, processing, and reporting in order to optimize diagnosis and downstream treatment. In this study, we aimed to develop expert guidance on best practices for urine culture diagnostic stewardship.

METHODS: A RAND-modified Delphi approach with a multidisciplinary expert panel was used to ascertain diagnostic stewardship best practices. Clinical questions to guide recommendations were grouped into three thematic areas (ordering, processing, reporting) in practice settings of emergency department, inpatient, ambulatory, and long-term care. Fifteen …

Phage Resistance Accompanies Reduced Fitness Of Uropathogenic Escherichia Coli In The Urinary Environment, Jacob J Zulk, Justin R Clark, Samantha Ottinger, Mallory B Ballard, Marlyd E Mejia, Vicki Mercado-Evans, Emmaline R Heckmann, Belkys C Sanchez, Barbara W Trautner, Anthony W Maresso, Kathryn A Patras

Faculty, Staff and Students Publications

Urinary tract infection (UTI) is among the most common infections treated worldwide each year and is caused primarily by uropathogenic Escherichia coli (UPEC). Rising rates of antibiotic resistance among uropathogens have spurred a consideration of alternative treatment strategies, such as bacteriophage (phage) therapy; however, phage-bacterial interactions within the urinary environment are poorly defined. Here, we assess the activity of two phages, namely, HP3 and ES17, against clinical UPEC isolates using in vitro and in vivo models of UTI. In both bacteriologic medium and pooled human urine, we identified phage resistance arising within the first 6 to 8 h of coincubation. …

A Pilot Randomized Trial To Examine Effects Of A Hybrid Closed-Loop Insulin Delivery System On Neurodevelopmental And Cognitive Outcomes In Adolescents With Type 1 Diabetes, Allan L Reiss, Ana Maria Arbelaez, Et Al

2020-Current year OA Pubs

Type 1 diabetes (T1D) is associated with lower scores on tests of cognitive and neuropsychological function and alterations in brain structure and function in children. This proof-of-concept pilot study (ClinicalTrials.gov Identifier NCT03428932) examined whether MRI-derived indices of brain development and function and standardized IQ scores in adolescents with T1D could be improved with better diabetes control using a hybrid closed-loop insulin delivery system. Eligibility criteria for participation in the study included age between 14 and 17 years and a diagnosis of T1D before 8 years of age. Randomization to either a hybrid closed-loop or standard diabetes care group was performed …

Endophenotype Effect Sizes Support Variant Pathogenicity In Monogenic Disease Susceptibility Genes, Jennifer L Halford, Valerie N Morrill, Seung Hoan Choi, Sean J Jurgens, Giorgio Melloni, Nicholas A Marston, Lu-Chen Weng, Victor Nauffal, Amelia W Hall, Sophia Gunn, Christina A Austin-Tse, James P Pirruccello, Shaan Khurshid, Heidi L Rehm, Emelia J Benjamin, Eric Boerwinkle, Jennifer A Brody, Adolfo Correa, Brandon K Fornwalt, Namrata Gupta, Christopher M Haggerty, Stephanie Harris, Susan R Heckbert, Charles C Hong, Charles Kooperberg, Henry J Lin, Ruth J F Loos, Braxton D Mitchell, Alanna C Morrison, Wendy Post, Bruce M Psaty, Susan Redline, Kenneth M Rice, Stephen S Rich, Jerome I Rotter, Peter F Schnatz, Elsayed Z Soliman, Nona Sotoodehnia, Eugene K Wong, Nhlbi Trans-Omics For Precision Medicine (Topmed) Consortium, Marc S Sabatine, Christian T Ruff, Kathryn L Lunetta, Patrick T Ellinor, Steven A Lubitz

Faculty, Staff and Student Publications

Accurate and efficient classification of variant pathogenicity is critical for research and clinical care. Using data from three large studies, we demonstrate that population-based associations between rare variants and quantitative endophenotypes for three monogenic diseases (low-density-lipoprotein cholesterol for familial hypercholesterolemia, electrocardiographic QTc interval for long QT syndrome, and glycosylated hemoglobin for maturity-onset diabetes of the young) provide evidence for variant pathogenicity. Effect sizes are associated with pathogenic ClinVar assertions (P < 0.001 for each trait) and discriminate pathogenic from non-pathogenic variants (area under the curve 0.82-0.84 across endophenotypes). An effect size threshold of ≥ 0.5 times the endophenotype standard deviation nominates up to 35% of rare variants of uncertain significance or not in ClinVar in disease susceptibility genes with pathogenic potential. We propose that variant associations with quantitative endophenotypes for monogenic diseases can provide evidence supporting pathogenicity.

Spatiotemporal Correlation Analysis Of Hydraulic Fracturing And Stroke In The United States, Chuanbo Hu, Bin Liu, Shuo Wang, Zhenduo Zhu, Amelia Adcock, James Simpkins, Xin Li

2020-Current year OA Pubs

Hydraulic fracturing or fracking has led to a rapid growth of oil and gas production in the United States, but the impact of fracking on public health is an important but underresearched topic. We designed a methodology to study spatiotemporal correlations between the risk of fracking and stroke mortality. An annualized loss expectancy (ALE) model is applied to quantify the risk of fracking. The geographically and temporally weighted regression (GTWR) model is used to analyze spatiotemporal correlations of stroke mortality, fracking ALE, and nine other socioeconomic- and health-related factors. The analysis shows that fracking ALE is moderately correlated with stroke …

Integrated Relationship Of Nasopharyngeal Airway Host Response And Microbiome Associates With Bronchiolitis Severity, Michimasa Fujiogi, Yoshihiko Raita, Marcos Pérez-Losada, Robert J Freishtat, Juan C Celedón, Jonathan M Mansbach, Pedro A Piedra, Zhaozhong Zhu, Carlos A Camargo, Kohei Hasegawa

Faculty, Staff and Students Publications

Bronchiolitis is a leading cause of infant hospitalizations but its immunopathology remains poorly understood. Here we present data from 244 infants hospitalized with bronchiolitis in a multicenter prospective study, assessing the host response (transcriptome), microbial composition, and microbial function (metatranscriptome) in the nasopharyngeal airway, and associate them with disease severity. We investigate individual associations with disease severity identify host response, microbial taxonomical, and microbial functional modules by network analyses. We also determine the integrated relationship of these modules with severity. Several modules are significantly associated with risks of positive pressure ventilation use, including the host-type I interferon, neutrophil/interleukin-1, T cell …

Subcortical-Cortical Dynamical States Of The Human Brain And Their Breakdown In Stroke, Chiara Favaretto, Michele Allegra, Gustavo Deco, Nicholas V Metcalf, Joseph C Griffis, Gordon L Shulman, Andrea Brovelli, Maurizio Corbetta

2020-Current year OA Pubs

The mechanisms controlling dynamical patterns in spontaneous brain activity are poorly understood. Here, we provide evidence that cortical dynamics in the ultra-slow frequency range (<0.01-0.1 Hz) requires intact cortical-subcortical communication. Using functional magnetic resonance imaging (fMRI) at rest, we identify Dynamic Functional States (DFSs), transient but recurrent clusters of cortical and subcortical regions synchronizing at ultra-slow frequencies. We observe that shifts in cortical clusters are temporally coincident with shifts in subcortical clusters, with cortical regions flexibly synchronizing with either limbic regions (hippocampus/amygdala), or subcortical nuclei (thalamus/basal ganglia). Focal lesions induced by stroke, especially those damaging white matter connections between basal ganglia/thalamus and cortex, provoke anomalies in the fraction times, dwell times, and transitions between DFSs, causing a bias toward abnormal network integration. Dynamical anomalies observed 2 weeks after stroke recover in time and contribute to explaining neurological impairment and long-term outcome.

Phenotypic And Genetic Spectrum Of Atp6v1a Encephalopathy: A Disorder Of Lysosomal Homeostasis, Renzo Guerrini, Davide Mei, Katalin Kerti-Szigeti, Sara Pepe, Mary Kay Koenig, Gretchen Von Allmen, Megan T Cho, Kimberly Mcdonald, Janice Baker, Vikas Bhambhani, Zöe Powis, Lance Rodan, Rima Nabbout, Giulia Barcia, Jill A Rosenfeld, Carlos A Bacino, Cyril Mignot, Lillian H Power, Catharine J Harris, Dragan Marjanovic, Rikke S Møller, Trine B Hammer, Riikka Keski Filppula, Päivi Vieira, Clara Hildebrandt, Stephanie Sacharow, Luca Maragliano, Fabio Benfenati, Katherine Lachlan, Andreas Benneche, Florence Petit, Jean Madeleine De Sainte Agathe, Barbara Hallinan, Yue Si, Ingrid M Wentzensen, Fanggeng Zou, Vinodh Narayanan, Naomichi Matsumoto, Alessandra Boncristiano, Giancarlo La Marca, Mitsuhiro Kato, Kristin Anderson, Carmen Barba, Luisa Sturiale, Domenico Garozzo, Roberto Bei, Laura Masuelli, Valerio Conti, Gaia Novarino, Anna Fassio

Faculty, Staff and Student Publications

Vacuolar-type H+-ATPase (V-ATPase) is a multimeric complex present in a variety of cellular membranes that acts as an ATP-dependent proton pump and plays a key role in pH homeostasis and intracellular signalling pathways. In humans, 22 autosomal genes encode for a redundant set of subunits allowing the composition of diverse V-ATPase complexes with specific properties and expression. Sixteen subunits have been linked to human disease. Here we describe 26 patients harbouring 20 distinct pathogenic de novo missense ATP6V1A variants, mainly clustering within the ATP synthase α/β family-nucleotide-binding domain. At a mean age of 7 years (extremes: 6 weeks, youngest deceased …

Somatic Variants In Diverse Genes Leads To A Spectrum Of Focal Cortical Malformations, Dulcie Lai, Meethila Gade, Edward Yang, Hyun Yong Koh, Jinfeng Lu, Nicole M Walley, Anne F Buckley, Tristan T Sands, Cigdem I Akman, Mohamad A Mikati, Guy M Mckhann, James E Goldman, Peter Canoll, Allyson L Alexander, Kristen L Park, Gretchen K Von Allmen, Olga Rodziyevska, Meenakshi B Bhattacharjee, Hart G W Lidov, Hannes Vogel, Gerald A Grant, Brenda E Porter, Annapurna H Poduri, Peter B Crino, Erin L Heinzen

Faculty, Staff and Student Publications

Post-zygotically acquired genetic variants, or somatic variants, that arise during cortical development have emerged as important causes of focal epilepsies, particularly those due to malformations of cortical development. Pathogenic somatic variants have been identified in many genes within the PI3K-AKT-mTOR-signalling pathway in individuals with hemimegalencephaly and focal cortical dysplasia (type II), and more recently in SLC35A2 in individuals with focal cortical dysplasia (type I) or non-dysplastic epileptic cortex. Given the expanding role of somatic variants across different brain malformations, we sought to delineate the landscape of somatic variants in a large cohort of patients who underwent epilepsy surgery with hemimegalencephaly …

Chap-Child: An Open Source Method For Estimating Sit-To-Stand Transitions And Sedentary Bout Patterns From Hip Accelerometers Among Children., Jordan A. Carlson, Nicola D. Ridgers, Supun Nakandala, Rong Zablocki, Fatima Tuz-Zahra, John Bellettiere, Paul R Hibbing, Chelsea Steel, Marta M. Jankowska, Dori E. Rosenberg, Mikael Anne Greenwood-Hickman, Jingjing Zou, Andrea Z. Lacroix, Arun Kumar, Loki Natarajan

Manuscripts, Articles, Book Chapters and Other Papers

Background: Hip-worn accelerometer cut-points have poor validity for assessing children's sedentary time, which may partly explain the equivocal health associations shown in prior research. Improved processing/classification methods for these monitors would enrich the evidence base and inform the development of more effective public health guidelines. The present study aimed to develop and evaluate a novel computational method (CHAP-child) for classifying sedentary time from hip-worn accelerometer data.

Methods: Participants were 278, 8-11-year-olds recruited from nine primary schools in Melbourne, Australia with differing socioeconomic status. Participants concurrently wore a thigh-worn activPAL (ground truth) and hip-worn ActiGraph (test measure) during up to 4 …

Cancer-Driving Mutations Are Enriched In Genic Regions Intolerant To Germline Variation, Dimitrios Vitsios, Ryan S Dhindsa, Dorota Matelska, Jonathan Mitchell, Xuequing Zou, Joshua Armenia, Fengyuan Hu, Quanli Wang, Ben Sidders, Andrew R Harper, Slavé Petrovski

Duncan NRI Faculty and Staff Publications

Large reference datasets of protein-coding variation in human populations have allowed us to determine which genes and genic subregions are intolerant to germline genetic variation. There is also a growing number of genes implicated in severe Mendelian diseases that overlap with genes implicated in cancer. We hypothesized that cancer-driving mutations might be enriched in genic subregions that are depleted of germline variation relative to somatic variation. We introduce a new metric, OncMTR (oncology missense tolerance ratio), which uses 125,748 exomes in the Genome Aggregation Database (gnomAD) to identify these genic subregions. We demonstrate that OncMTR can significantly predict driver mutations …

Fundamentals Of Arterial Blood Gas Interpretation, Jerry Yee, Stan Frinak, Naushaba Mohiuddin, Junior Uduman

Nephrology Articles

Acid-base disturbances in patients with cardiopulmonary or other disorders are common and are often misinterpreted or interpreted incompletely. Treating acid-base disorders in greater detail facilitates pathophysiologic understanding and improved therapeutic planning. Understanding the ratiometric relationship between the lungs, which excrete volatile acid as carbon dioxide, and the kidneys, which contribute to maintenance of plasma bicarbonate, allows precise identification of the dominant acid-base disturbance when more than a simple disorder is present and aids in executing a measured treatment response. Concordantly, mapping paired values of the partial pressure of carbon dioxide (PCO2) and the bicarbonate concentration ([HCO3^–]) on a …

Perioperative Mental Health Intervention Bundle For Older Surgical Patients: Protocol For An Intervention Development And Feasibility Study, Joanna Abraham, Katherine J Holzer, Emily M Lenard, Kenneth E Freedland, Bethany R Tellor Pennington, Rachel C Wolfe, Theresa A Cordner, Ana A Baumann, Mary Politi, Michael Simon Avidan, Eric Lenze

2020-Current year OA Pubs

INTRODUCTION: The perioperative period is high risk for older adults. Depression and anxiety are common perioperative problems, frequently coexisting with cognitive impairment. Older patients with these conditions are more likely than younger patients to experience postoperative delirium, long hospital stays, poor quality of life and rehospitalisation. These experiences can, in turn, exacerbate anxiety and depressive symptoms. Despite these risks, little is known about how to treat perioperative anxiety and depression among older adults.

METHODS AND ANALYSIS: We designed a feasibility study of a perioperative mental health intervention bundle to improve perioperative mental health, specifically depression and anxiety. The overarching goals …

Non-Linear Machine Learning Models Incorporating Snps And Prs Improve Polygenic Prediction In Diverse Human Populations, Michael Elgart, Genevieve Lyons, Santiago Romero-Brufau, Nuzulul Kurniansyah, Jennifer A Brody, Xiuqing Guo, Henry J Lin, Laura Raffield, Yan Gao, Han Chen, Paul De Vries, Donald M Lloyd-Jones, Leslie A Lange, Gina M Peloso, Myriam Fornage, Jerome I Rotter, Stephen S Rich, Alanna C Morrison, Bruce M Psaty, Daniel Levy, Susan Redline, Nhlbi’S Trans-Omics In Precision Medicine (Topmed) Consortium, Tamar Sofer

Faculty, Staff and Student Publications

Polygenic risk scores (PRS) are commonly used to quantify the inherited susceptibility for a trait, yet they fail to account for non-linear and interaction effects between single nucleotide polymorphisms (SNPs). We address this via a machine learning approach, validated in nine complex phenotypes in a multi-ancestry population. We use an ensemble method of SNP selection followed by gradient boosted trees (XGBoost) to allow for non-linearities and interaction effects. We compare our results to the standard, linear PRS model developed using PRSice, LDpred2, and lassosum2. Combining a PRS as a feature in an XGBoost model results in a relative increase in …

Adiposity, Insulin Resistance, Cardiorespiratory Fitness, And Bone Health In Hispanic Children, Reem S Shawar, Maurice Puyau, Roman Shypailo, Salma Musaad, Nancy F Butte, Fida Bacha

Faculty, Staff and Students Publications

CONTEXT: Childhood obesity disproportionately affects Hispanic youth. The skeletal system appears to be a target organ of the adverse effects of obesity. Yet, the relationship between adiposity and bone health in youth and the modulating factors are not well understood.

OBJECTIVE: This work aims to examine the relationship between adiposity, insulin resistance (IR), cardiorespiratory fitness (CRF), and bone mass in Hispanic youth.

METHODS: A total of 951 Hispanic youth (50% male), aged 4 to 19 years, participated in this cross-sectional design study from the Viva La Familia Study at Children's Nutrition Research Center. Bone mineral content (BMC) and density (BMD), …

Non-Canonical Odor Coding In The Mosquito, Margaret Herre, Olivia V Goldman, Tzu-Chiao Lu, Gabriela Caballero-Vidal, Yanyan Qi, Zachary N Gilbert, Zhongyan Gong, Takeshi Morita, Saher Rahiel, Majid Ghaninia, Rickard Ignell, Benjamin J Matthews, Hongjie Li, Leslie B Vosshall, Meg A Younger

Center on Aging Staff Publications

Aedes aegypti mosquitoes are a persistent human foe, transmitting arboviruses including dengue when they feed on human blood. Mosquitoes are intensely attracted to body odor and carbon dioxide, which they detect using ionotropic chemosensory receptors encoded by three large multi-gene families. Genetic mutations that disrupt the olfactory system have modest effects on human attraction, suggesting redundancy in odor coding. The canonical view is that olfactory sensory neurons each express a single chemosensory receptor that defines its ligand selectivity. We discovered that Ae. aegypti uses a different organizational principle, with many neurons co-expressing multiple chemosensory receptor genes. In vivo electrophysiology demonstrates …

Heritable Vaginal Bacteria Influence Immune Tolerance And Relate To Early-Life Markers Of Allergic Sensitization In Infancy, Kathryn E. Mccauley, Elze Rackaityte, Brandon Lamere, Douglas W. Fadrosh, Kei E. Fujimura, Ariane R. Panzer, Din L. Lin, Kole V. Lynch, Joanna Halkias, Ventura F. Mendoza, Trevor D. Burt, Casper Bendixsen, Kathrine Barnes, Haejin Kim, Kyra Jones, Dennis R. Ownby, Christine C. Johnson, Christine M. Seroogy, James E. Gern, Homer A. Boushey, Susan V. Lynch

Allergy & Immunology Articles

Maternal asthma status, prenatal exposures, and infant gut microbiota perturbation are associated with heightened risk of atopy and asthma risk in childhood, observations hypothetically linked by intergenerational microbial transmission. Using maternal vaginal (n = 184) and paired infant stool (n = 172) samples, we identify four compositionally and functionally distinct Lactobacillus-dominated vaginal microbiota clusters (VCs) that relate to prenatal maternal health and exposures and infant serum immunoglobulin E (IgE) status at 1 year. Variance in bacteria shared between mother and infant pairs relate to VCs, maternal allergy/asthma status, and infant IgE levels. Heritable bacterial gene pathways associated with infant IgE …

The Prostate Cancer Androgen Receptor Cistrome In African American Men Associates With Upregulation Of Lipid Metabolism And Immune Response, Jacob E Berchuck, Elio Adib, Sarah Abou Alaiwi, Amit K Dash, Jin Na Shin, Dallin Lowder, Collin Mccoll, Patricia Castro, Ryan Carelli, Elisa Benedetti, Jenny Deng, Matthew Robertson, Sylvan C Baca, Connor Bell, Heather M Mcclure, Talal El Zarif, Matthew P Davidsohn, Gitanjali Lakshminarayanan, Kinza Rizwan, Darlene G Skapura, Sandra L Grimm, Christel M Davis, Erik A Ehli, Kaitlin M Kelleher, Ji-Heui Seo, Nicholas Mitsiades, Cristian Coarfa, Mark M Pomerantz, Massimo Loda, Michael Ittmann, Matthew L Freedman, Salma Kaochar

Faculty, Staff and Students Publications

African-American (AA) men are more likely to be diagnosed with and die from prostate cancer than European American (EA) men. Despite the central role of the androgen receptor (AR) transcription factor in prostate cancer, little is known about the contribution of epigenetics to observed racial disparities. We performed AR chromatin immunoprecipitation sequencing on primary prostate tumors from AA and EA men, finding that sites with greater AR binding intensity in AA relative to EA prostate cancer are enriched for lipid metabolism and immune response genes. Integration with transcriptomic and metabolomic data demonstrated coinciding upregulation of lipid metabolism gene expression and …

A Single-Cell Transcriptional Gradient In Human Cutaneous Memory T Cells Restricts Th17/Tc17 Identity, Christopher P Cook, Mark Taylor, Yale Liu, Ralf Schmidt, Andrew Sedgewick, Esther Kim, Ashley Hailer, Jeffrey P North, Paymann Harirchian, Hao Wang, Sakeen W Kashem, Yanhong Shou, Timothy C Mccalmont, Stephen C Benz, Jaehyuk Choi, Elizabeth Purdom, Alexander Marson, Silvia B V Ramos, Jeffrey B Cheng, Raymond J Cho

Staff and Researcher Publications

The homeostatic mechanisms that fail to restrain chronic tissue inflammation in diseases, such as psoriasis vulgaris, remain incompletely understood. We profiled transcriptomes and epitopes of single psoriatic and normal skin-resident T cells, revealing a gradated transcriptional program of coordinately regulated inflammation-suppressive genes. This program, which is sharply suppressed in lesional skin, strikingly restricts Th17/Tc17 cytokine and other inflammatory mediators on the single-cell level. CRISPR-based deactivation of two core components of this inflammation-suppressive program, ZFP36L2 and ZFP36, replicates the interleukin-17A (IL-17A), granulocyte macrophage-colony-stimulating factor (GM-CSF), and interferon gamma (IFNγ) elevation in psoriatic memory T cells deficient in these transcripts, functionally validating …

Serious Hazards Of Transfusion: Evaluating The Dangers Of A Wrong Patient Autologous Salvaged Blood In Cardiac Surgery., Masashi Uramatsu, Hideyuki Maeda, Shiro Mishima, Megumi Takahashi, Jun Wada, Kagehiro Amano, Paul Barach, Tamotsu Miki

College of Population Health Faculty Papers

BACKGROUND: The past half century has seen the near eradication of transfusion-associated hazards. Intraoperative cell salvage while widely used still poses significant risks and hazards due to human error. We report on a case in which blood collected from a patient with lung cancer was mistakenly administered to a patient undergoing cardiac surgery who should have received his own collected blood. The initial investigation found that the cause of the patient harm was violations of procedures by hospital personnel. A detailed investigation revealed that not only violations were the cause, but also that the underlying causes included haphazard organizational policies, …

Precision Dynamical Mapping Using Topological Data Analysis Reveals A Hub-Like Transition State At Rest, Manish Saggar, James M Shine, Raphaël Liégeois, Nico U F Dosenbach, Damien Fair

2020-Current year OA Pubs

In the absence of external stimuli, neural activity continuously evolves from one configuration to another. Whether these transitions or explorations follow some underlying arrangement or lack a predictable ordered plan remains to be determined. Here, using fMRI data from highly sampled individuals (~5 hours of resting-state data per individual), we aimed to reveal the rules that govern transitions in brain activity at rest. Our Topological Data Analysis based Mapper approach characterized a highly visited transition state of the brain that acts as a switch between different neural configurations to organize the spontaneous brain activity. Further, while the transition state was …

Malic Enzyme 1 Absence In Synovial Sarcoma Shifts Antioxidant System Dependence And Increases Sensitivity To Ferroptosis Induction With Acxt-3102, Caitlyn B Brashears, Bethany C Prudner, Richa Rathore, Katharine E Caldwell, Sara E S Lange, Jennifer K Sehn, Dirk Spitzer, Regis O'Keefe, Jason M Held, William Hawkins, Brian A Van Tine, Carina A. Dehner, Et Al

2020-Current year OA Pubs

PURPOSE: To investigate the metabolism of synovial sarcoma (SS) and elucidate the effect of malic enzyme 1 absence on SS redox homeostasis.

EXPERIMENTAL DESIGN: ME1 expression was measured in SS clinical samples, SS cell lines, and tumors from an SS mouse model. The effect of ME1 absence on glucose metabolism was evaluated utilizing Seahorse assays, metabolomics, and C13 tracings. The impact of ME1 absence on SS redox homeostasis was evaluated by metabolomics, cell death assays with inhibitors of antioxidant systems, and measurements of intracellular reactive oxygen species (ROS). The susceptibility of ME1-null SS to ferroptosis induction was interrogated in vitro …

Good Scientific Practice In Eeg And Meg Research: Progress And Perspectives, Guiomar Niso, Laurens R Krol, Etienne Combrisson, A Sophie Dubarry, Madison A Elliott, Clément François, Yseult Héjja-Brichard, Sophie K Herbst, Karim Jerbi, Vanja Kovic, Katia Lehongre, Steven J Luck, Manuel Mercier, John C Mosher, Yuri G Pavlov, Aina Puce, Antonio Schettino, Daniele Schön, Walter Sinnott-Armstrong, Bertille Somon, Anđela Šoškić, Suzy J Styles, Roni Tibon, Martina G Vilas, Marijn Van Vliet, Maximilien Chaumon

Faculty, Staff and Student Publications

Good scientific practice (GSP) refers to both explicit and implicit rules, recommendations, and guidelines that help scientists to produce work that is of the highest quality at any given time, and to efficiently share that work with the community for further scrutiny or utilization. For experimental research using magneto- and electroencephalography (MEEG), GSP includes specific standards and guidelines for technical competence, which are periodically updated and adapted to new findings. However, GSP also needs to be regularly revisited in a broader light. At the LiveMEEG 2020 conference, a reflection on GSP was fostered that included explicitly documented guidelines and technical …

Secure Human Action Recognition By Encrypted Neural Network Inference, Miran Kim, Xiaoqian Jiang, Kristin Lauter, Elkhan Ismayilzada, Shayan Shams

Faculty, Staff and Student Publications

Advanced computer vision technology can provide near real-time home monitoring to support "aging in place" by detecting falls and symptoms related to seizures and stroke. Affordable webcams, together with cloud computing services (to run machine learning algorithms), can potentially bring significant social benefits. However, it has not been deployed in practice because of privacy concerns. In this paper, we propose a strategy that uses homomorphic encryption to resolve this dilemma, which guarantees information confidentiality while retaining action detection. Our protocol for secure inference can distinguish falls from activities of daily living with 86.21% sensitivity and 99.14% specificity, with an average …

Genetic Variants In Cyp2b6 And Hsd17b12 Associated With Risk Of Squamous Cell Carcinoma Of The Head And Neck, Hongliang Liu, Guojun Li, Erich M Sturgis, Sanjay Shete, Kristina R Dahlstrom, Mulong Du, Christopher I Amos, David C Christiani, Philip Lazarus, Qingyi Wei

Faculty, Staff and Students Publications

Polycyclic aromatic hydrocarbons (PAH) and tobacco-specific nitrosamines (TSNA) metabolism-related genes play an important role in the development of cancers. We assessed the associations of genetic variants in genes involved in the metabolism of PAHs and TSNA with risk of squamous cell carcinoma of the head and neck (SCCHN) in European populations using two published genome-wide association study datasets. In the single-locus analysis, we identified two SNPs (rs145533669 and rs35246205) in CYP2B6 to be associated with risk of SCCHN (P = 1.57 × 10

Targeting Hyaluronic Acid Synthase-3 (Has3) For The Treatment Of Advanced Renal Cell Carcinoma, Xiaohan Xu, Kyle L Poulsen, Lijuan Wu, Shan Liu, Tatsunori Miyata, Qiaoling Song, Qingda Wei, Chenyang Zhao, Chunhua Lin, Jinbo Yang

Faculty, Staff and Student Publications

Non-alcohol-associated fatty liver/steatohepatitis (NAFL/NASH) has become the leading cause of liver disease worldwide. NASH, an advanced form of NAFL, can be progressive and more susceptible to developing cirrhosis and hepatocellular carcinoma. Currently, lifestyle interventions are the most essential and effective strategies for preventing and controlling NAFL without the development of fibrosis. While there are still limited appropriate drugs specifically to treat NAFL/NASH, growing progress is being seen in elucidating the pathogenesis and identifying therapeutic targets. In this review, we discussed recent developments in etiology and prospective therapeutic targets, as well as pharmacological candidates in pre/clinical trials and patents, with a …

Standardizing Evaluation Of Patient-Specific 3d Printed Models In Surgical Planning: Development Of A Cross-Disciplinary Survey Tool For Physician And Trainee Feedback, Lauren Schlegel, Michelle Ho, M. Fields, Erik Backlund, Robert S. Pugliese, Kristy M. Shine

Department of Emergency Medicine Faculty Papers

Background: 3D printed models are becoming increasingly popular in healthcare as visual and tactile tools to enhance understanding of anatomy and pathology in medical trainee education, provide procedural simulation training, and guide surgical procedures. Patient-specific 3D models are currently being used preoperatively for trainee medical education in planning surgical approaches and intraoperatively to guide decision-making in several specialties. Our study group utilized a modified Delphi process to create a standardized assessment for trainees using patient-specific 3D models as a tool in medical education during pre-surgical planning.

Methods: A literature review was conducted to identify survey questions administered to clinicians in …

Making The Rounds: Exploring The Role Of Circulating Tumor Dna (Ctdna) In Non-Small Cell Lung Cancer, Misty Dawn Shields, Kevin Chen, Giselle Dutcher, Ishika Patel, Bruna Pellini

2020-Current year OA Pubs

Advancements in the clinical practice of non-small cell lung cancer (NSCLC) are shifting treatment paradigms towards increasingly personalized approaches. Liquid biopsies using various circulating analytes provide minimally invasive methods of sampling the molecular content within tumor cells. Plasma-derived circulating tumor DNA (ctDNA), the tumor-derived component of cell-free DNA (cfDNA), is the most extensively studied analyte and has a growing list of applications in the clinical management of NSCLC. As an alternative to tumor genotyping, the assessment of oncogenic driver alterations by ctDNA has become an accepted companion diagnostic via both single-gene polymerase chain reactions (PCR) and next-generation sequencing (NGS) for …

Structural Covariance Of The Ventral Visual Stream Predicts Posttraumatic Intrusion And Nightmare Symptoms: A Multivariate Data Fusion Analysis, Nathaniel G. Harnett, Katherine E. Finegold, Lauren A. M Lebois, Sanne J. H Van Rooij, Timothy D. Ely, Vishnu P. Murty, Tanja Jovanovic, Steven E. Bruce, Stacey L. House, Francesca L. Beaudoin, Xinming An, Donglin Zeng, Thomas C. Neylan, Gari D. Clifford, Sarah D. Linnstaedt, Laura T. Germine, Kenneth A. Bollen, Scott L. Rauch, John P. Haran, Alan B. Storrow, Christopher A. Lewandowski, Paul I. Musey, Phyllis L. Hendry, Sophia Sheikh, Christopher W. Jones, Brittany E. Punches, Michael C. Kurz, Robert A. Swor, Lauren A. Hudak, Jose L. Pascual, Mark J. Seamon, Erica Harris, Anna M. Chang, Claire Pearson, David A. Peak, Robert M. Domeier, Niels K. Rathlev, Brian J. O'Neil, Paulina Sergot, Leon D. Sanchez, Mark W. Miller, Robert H. Pietrzak, Jutta Joormann, Deanna M. Barch, Diego A. Pizzagalli, John F. Sheridan, Steven E. Harte, James M. Elliott, Ronald C. Kessler, Karestan C. Koenen, Samuel A. Mclean, Lisa D. Nickerson, Kerry J. Ressler, Jennifer S. Stevens

Emergency Medicine Articles

Visual components of trauma memories are often vividly re-experienced by survivors with deleterious consequences for normal function. Neuroimaging research on trauma has primarily focused on threat-processing circuitry as core to trauma-related dysfunction. Conversely, limited attention has been given to visual circuitry which may be particularly relevant to posttraumatic stress disorder (PTSD). Prior work suggests that the ventral visual stream is directly related to the cognitive and affective disturbances observed in PTSD and may be predictive of later symptom expression. The present study used multimodal magnetic resonance imaging data (n = 278) collected two weeks after trauma exposure from the AURORA …