Medicine and Health Sciences Commons^™

Genomic Variant Benchmark: If You Cannot Measure It, You Cannot Improve It, Sina Majidian, Daniel Paiva Agustinho, Chen-Shan Chin, Fritz J Sedlazeck, Medhat Mahmoud

Faculty, Staff and Students Publications

Genomic benchmark datasets are essential to driving the field of genomics and bioinformatics. They provide a snapshot of the performances of sequencing technologies and analytical methods and highlight future challenges. However, they depend on sequencing technology, reference genome, and available benchmarking methods. Thus, creating a genomic benchmark dataset is laborious and highly challenging, often involving multiple sequencing technologies, different variant calling tools, and laborious manual curation. In this review, we discuss the available benchmark datasets and their utility. Additionally, we focus on the most recent benchmark of genes with medical relevance and challenging genomic complexity.

Literature-Based Predictions Of Mendelian Disease Therapies, Cole A Deisseroth, Won-Seok Lee, Jiyoen Kim, Hyun-Hwan Jeong, Ryan S Dhindsa, Julia Wang, Huda Y Zoghbi, Zhandong Liu

Faculty, Staff and Students Publications

In the effort to treat Mendelian disorders, correcting the underlying molecular imbalance may be more effective than symptomatic treatment. Identifying treatments that might accomplish this goal requires extensive and up-to-date knowledge of molecular pathways-including drug-gene and gene-gene relationships. To address this challenge, we present "parsing modifiers via article annotations" (PARMESAN), a computational tool that searches PubMed and PubMed Central for information to assemble these relationships into a central knowledge base. PARMESAN then predicts putatively novel drug-gene relationships, assigning an evidence-based score to each prediction. We compare PARMESAN's drug-gene predictions to all of the drug-gene relationships displayed by the Drug-Gene Interaction …

Yeast Rad52 Is A Homodecamer And Possesses Brca2-Like Bipartite Rad51 Binding Modes, Jaigeeth Deveryshetty, Rahul Chadda, Jenna R Mattice, Simrithaa Karunakaran, Michael J Rau, Katherine Basore, Nilisha Pokhrel, Noah Englander, James A J Fitzpatrick, Brian Bothner, Edwin Antony

2020-Current year OA Pubs

Homologous recombination (HR) is an essential double-stranded DNA break repair pathway. In HR, Rad52 facilitates the formation of Rad51 nucleoprotein filaments on RPA-coated ssDNA. Here, we decipher how Rad52 functions using single-particle cryo-electron microscopy and biophysical approaches. We report that Rad52 is a homodecameric ring and each subunit possesses an ordered N-terminal and disordered C-terminal half. An intrinsic structural asymmetry is observed where a few of the C-terminal halves interact with the ordered ring. We describe two conserved charged patches in the C-terminal half that harbor Rad51 and RPA interacting motifs. Interactions between these patches regulate ssDNA binding. Surprisingly, Rad51 …

Sars-Cov-2: Tale Of A Microscopic Murderer, Josiah P. Garner

Quest

Independent Study

Research in progress for BIOL1406: Biology for Science Majors I

Faculty Mentor: Amina Tassa, Ph.D.

I am delighted to introduce Josiah Garner’s “SARS-CoV-2: Tale of a Microscopic Murderer.” This independent study assignment explores the impact of a novel, deadly, and worldwide virus. The assignment also examines the fast development of vaccines to control the spread and reduce the symptoms of the virus.

Josiah’s paper focuses on the early history of the emergence of COVID-19, the world response, and vaccine development. He demonstrates critical thinking skills and effectively utilizes various research methods to obtain and communicate his information. Josiah …

Cognitive Decrements In 1991 Gulf War Veterans: Associations With Gulf War Illness And Neurotoxicant Exposures In The Boston Biorepository, Recruitment, And Integrative Network (Bbrain) Cohorts., D Keating, M Krengel, J Dugas, R Toomey, L Chao, L Steele, Lloyd P Janulewicz, T Heeren, E Quinn, N Klimas, K Sullivan

HPD Articles

BACKGROUND: During deployment, veterans of the 1991 Gulf War (GW) were exposed to multiple war-related toxicants. Roughly a third of these veterans continue to exhibit neurotoxicant induced symptoms of Gulf War Illness (GWI), a multi-faceted condition that includes fatigue, pain and cognitive decrements. When studied empirically, both deployed veterans with exposures and those who meet the criteria for GWI are more likely to show deficits in the area of neuropsychological functioning. Although studies have shown cognitive impairments in small sample sizes, it is necessary to revisit these findings with larger samples and newer cohorts to see if other areas of …

Validation Of Automated Data Abstraction For Sccm Discovery Virus Covid-19 Registry: Practical Ehr Export Pathways (Virus-Peep), Diana J. Valencia Morales, Vikas Bansal, Smith F. Heavner, Janna C. Castro, Mayank Sharma, Aysun Tekin, Marija Bogojevic, Simon Zec, Nikhil Sharma, Rodrigo Cartin-Ceba, Rahul S. Nanchal, Devang K. Sanghavi, Abigail T. La Nou, Syed A. Khan, Katherine A. Belden, Jen-Ting Chen, Roman R. Melamed, Imran A. Sayed, Ronald A. Reilkoff, Vitaly Herasevich, Juan Pablo Domecq Garces, Allan J. Walkey, Karen Boman, Vishakha K. Kumar, Rahul Kashyap

Division of Infectious Diseases and Environmental Medicine Faculty Papers

BACKGROUND: The gold standard for gathering data from electronic health records (EHR) has been manual data extraction; however, this requires vast resources and personnel. Automation of this process reduces resource burdens and expands research opportunities.

OBJECTIVE: This study aimed to determine the feasibility and reliability of automated data extraction in a large registry of adult COVID-19 patients.

MATERIALS AND METHODS: This observational study included data from sites participating in the SCCM Discovery VIRUS COVID-19 registry. Important demographic, comorbidity, and outcome variables were chosen for manual and automated extraction for the feasibility dataset. We quantified the degree of agreement with Cohen's …

Feasibility And Outcomes Of Supplemental Gait Training By Robotic And Conventional Means In Acute Stroke Rehabilitation, Mukul Talaty, Alberto Esquenazi

Moss-Magee Rehabilitation Papers

INTRODUCTION: Practicality of implementation and dosing of supplemental gait training in an acute stroke inpatient rehabilitation setting are not well studied but can have positive impact on outcomes.

OBJECTIVES: To determine the feasibility of early, intense supplemental gait training in inpatient stroke rehabilitation, compare functional outcomes and the specific mode of delivery.

DESIGN AND SETTING: Assessor blinded, randomized controlled trial in a tertiary Inpatient Rehabilitation Facility.

PARTICIPANTS: Thirty acute post-stroke patients with unilateral hemiparesis (≥ 18 years of age with a lower limb MAS ≤ 3).

INTERVENTION: Lokomat® or conventional gait training (CGT) in addition to standard mandated therapy time. …

Multivariate Gwas Of Alzheimer's Disease Csf Biomarker Profiles Implies Grin2d In Synaptic Functioning, Alexander Neumann, Jigyasha Timsina, Thomas W Marsh, Priyanka Gorijala, Carlos Cruchaga, Et Al.

2020-Current year OA Pubs

BACKGROUND: Genome-wide association studies (GWAS) of Alzheimer's disease (AD) have identified several risk loci, but many remain unknown. Cerebrospinal fluid (CSF) biomarkers may aid in gene discovery and we previously demonstrated that six CSF biomarkers (β-amyloid, total/phosphorylated tau, NfL, YKL-40, and neurogranin) cluster into five principal components (PC), each representing statistically independent biological processes. Here, we aimed to (1) identify common genetic variants associated with these CSF profiles, (2) assess the role of associated variants in AD pathophysiology, and (3) explore potential sex differences.

METHODS: We performed GWAS for each of the five biomarker PCs in two multi-center studies (EMIF-AD …

Chemerin Triggers Migration Of A Cd8 T Cell Subset With Natural Killer Cell Functions, Romain Ballet, Melissa Lajevic, Noelle Huskey-Mullin, Rachel Roach, Kevin Brulois, Ying Huang, Muhammad A Saeed, Ha X Dang, Russell K Pachynski, Elizabeth Wilson, Eugene C Butcher, Brian A Zabel

2020-Current year OA Pubs

The recruitment of cells with effector functions into the tumor microenvironment holds potential for delaying cancer progression. We show that subsets of human CD28-effector CD8 T cells, CCR7

Analysis And Prediction Of Liver Volume Change Maps Derived From Computational Tomography Scans Acquired Pre- And Post-Radiation Therapy, Guillaume Cazoulat, Aashish C Gupta, Mais M Al Taie, Eugene J Koay, Kristy K Brock

Faculty, Staff and Student Publications

External beam radiation therapy (EBRT) of liver cancers can cause local liver atrophy as a result of tissue damage or hypertrophy as a result of liver regeneration. Predicting those volumetric changes would enable new strategies for liver function preservation during treatment planning. However, understanding of the spatial dose/volume relationship is still limited. This study leverages the use of deep learning-based segmentation and biomechanical deformable image registration (DIR) to analyze and predict this relationship. Pre- and Post-EBRT imaging data were collected for 100 patients treated for hepatocellular carcinomas, cholangiocarcinoma or CRC with intensity-modulated radiotherapy (IMRT) with prescription doses ranging from 50 …

Detection Of Early Myocardial Dysfunction By Imaging Biomarkers In Cancer Patients Undergoing Photon Beam Vs Proton Beam Radiotherapy: A Prospective Study, Muhannad Aboud Abbasi, Giulia Bruno, Cristina Di Stefano, Laura Garcia Bello, Nadia N Laack, Kimberly S Corbin, Thomas J Whitaker, Patricia A Pellikka, Robert W Mutter, Hector R Villarraga

Faculty, Staff and Student Publications

1. Background: We sought to determine acute and subacute changes in cardiac function after proton beam (PBT) and photon beam (PhT) radiotherapy (RT) using conventional and two-dimensional speckle tracking echocardiography (2D-STE) in patients with malignant breast and thoracic tumors. 2. Methods: Between March 2016 and March 2017, 70 patients with breast or thoracic cancer were prospectively enrolled and underwent transthoracic echocardiography with comprehensive strain analysis at pretreatment, mid-treatment, end of treatment, and 3 months after RT. 3. Results: PBT was used to treat 44 patients; PhT 26 patients. Mean ± SD age was 55 ± 12 years; most patients (93%) …

The Use Of Electronic Health Record Data To Identify Variation In Referral, Consent, And Engagement In A Pediatric Intervention For Overweight And Obesity: A Cross-Sectional Study, Joshua S Yudkin, Marlyn A Allicock, Folefac D Atem, Carol A Galeener, Sarah E Messiah, Sarah E Barlow

Faculty, Staff and Student Publications

Clinical weight management programs face low participation. The authors assessed whether using electronic health record (EHR) data can identify variation in referral, consent, and engagement in a pediatric overweight and obesity (OW/OB) intervention. Using Epic EHR data collected between August 2020 and April 2021, sociodemographic and clinical diagnostic data (ie, International Classification of Disease [ICD] codes from visit and problem list [PL]) were analyzed to determine their association with referral, consent, and engagement in an OW/OB intervention. Bivariate analyses and multivariable logistic regression modeling were performed, with Bayesian inclusion criterion score used for model selection. Compared with the 581 eligible …

Disrupted Stiffness Ratio Alters Nuclear Mechanosensing, Brandon K Walther, Adam P Sears, Anahita Mojiri, Reza Avazmohammadi, Jianhua Gu, Olga V Chumakova, Navaneeth Krishna Rajeeva Pandian, Abishai Dominic, Jean-Louis Martiel, Saami K Yazdani, John P Cooke, Jacques Ohayon, Roderic I Pettigrew

Faculty, Staff and Student Publications

The ability of endothelial cells to sense and respond to dynamic changes in blood flow is critical for vascular homeostasis and cardiovascular health. The mechanical and geometric properties of the nuclear and cytoplasmic compartments affect mechanotransduction. We hypothesized that alterations to these parameters have resulting mechanosensory consequences. Using atomic force microscopy and mathematical modeling, we assessed how the nuclear and cytoplasmic compartment stiffnesses modulate shear stress transfer to the nucleus within aging endothelial cells. Our computational studies revealed that the critical parameter controlling shear transfer is not the individual mechanics of these compartments, but the stiffness ratio between them. Replicatively …

Index Of Consciousness Monitoring During General Anesthesia May Effectively Enhance Rehabilitation In Elderly Patients Undergoing Laparoscopic Urological Surgery: A Randomized Controlled Clinical Trial, Fengling Qi, Long Fan, Chunxiu Wang, Yang Liu, Shuyi Yang, Zhen Fan, Fangfang Miao, Minhui Kan, Kunpeng Feng, Tianlong Wang

Faculty, Staff and Student Publications

Background: Based on electroencephalogram (EEG) analysis, index of consciousness (IoC) monitoring is a new technique for monitoring anesthesia depth. IoC is divided into IoC1 (depth of sedation) and IoC2 (depth of analgesia). The potential for concurrent monitoring of IoC1 and IoC2 to expedite postoperative convalescence remains to be elucidated. We investigated whether combined monitoring of IoC1 and IoC2 can effectively enhances postoperative recovery compared with bispectral index (BIS) in elderly patients undergoing laparoscopic urological surgery under general anesthesia.

Methods: In this prospective, controlled, double-blinded trail, 120 patients aged 65 years or older were arbitrarily assigned to either the IoC group …

Influence Of Sex On Meat And Fat Quality From Heavy Alentejano Pigs Finished Outdoors On Commercial And High Fiber Diets, José Manuel Martins, Rui Charneca, Nicolás Garrido, André Albuquerque, Eliana Jerónimo, Olinda Guerreiro, Patrícia Lage, Carla Marmelo, Filipa Costa, Amélia Ramos, Luísa Martin

Faculty, Staff and Student Publications

This work aimed to examine the effects of sex on meat and fat quality traits from thirty Portuguese Alentejano (AL) pigs reared in outdoor conditions. These pigs were divided into three groups and fed ad libitum. From ~40 to 130 kg LW, castrated (C group) and intact animals (I and IExp) consumed commercial diets. Until slaughter (~160 kg), C and I pigs remained on commercial diets, and IExp changed to a more sustainable experimental diet with locally produced pulses and byproducts. Samples were collected from the Longissimus lumborum (LL), Psoas major (PM), and dorsal subcutaneous fat (DSF). At ~160 …

Gut Microbiota Aggravates Neutrophil Extracellular Traps-Induced Pancreatic Injury In Hypertriglyceridemic Pancreatitis, Guanqun Li, Liwei Liu, Tianqi Lu, Yuhang Sui, Can Zhang, Yongwei Wang, Tao Zhang, Yu Xie, Peng Xiao, Zhongjie Zhao, Chundong Cheng, Jisheng Hu, Hongze Chen, Dongbo Xue, Hua Chen, Gang Wang, Rui Kong, Hongtao Tan, Xuewei Bai, Zhibo Li, Florencia Mcallister, Le Li, Bei Sun

Faculty, Staff and Student Publications

Hypertriglyceridemic pancreatitis (HTGP) is featured by higher incidence of complications and poor clinical outcomes. Gut microbiota dysbiosis is associated with pancreatic injury in HTGP and the mechanism remains unclear. Here, we observe lower diversity of gut microbiota and absence of beneficial bacteria in HTGP patients. In a fecal microbiota transplantation mouse model, the colonization of gut microbiota from HTGP patients recruits neutrophils and increases neutrophil extracellular traps (NETs) formation that exacerbates pancreatic injury and systemic inflammation. We find that decreased abundance of Bacteroides uniformis in gut microbiota impairs taurine production and increases IL-17 release in colon that triggers NETs formation. …

One-Step Simultaneous Liquid Phase Exfoliation-Induced Chirality In Graphene And Their Chirality-Mediated Microrna Delivery, Pranav, Eswara N. H. K. Ghali, Neeraj Chauhan, Rahul Tiwari, Subhash Chauhan, Murali M. Yallapu

School of Medicine Publications

Graphene (G) has established itself as an exciting prospect for a broad range of applications owing to its remarkable properties. Recent innovations in chiral nanosystems have led to sensors, drug delivery, catalysis, etc. owing to the stereospecific interactions between various nanosystems and enantiomers. As the molecular structure of G itself is achiral introducing chirality in G by simple attachment of a functional group (a chiral ligand) on the G nanosheet may result in more diverse applications. Herein, we demonstrate direct liquid phase exfoliation and chiral induction in G nanosheets abbreviated as L-graphene and D-graphene in the presence of chiral L-tyrosine …

Global Impact Of Proteoglycan Science On Human Diseases, Christopher Xie, Liliana Schaefer, Renato V. Iozzo

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

In this comprehensive review, we will dissect the impact of research on proteoglycans focusing on recent developments involved in their synthesis, degradation, and interactions, while critically assessing their usefulness in various biological processes. The emerging roles of proteoglycans in global infections, specifically the SARS-CoV-2 pandemic, and their rising functions in regenerative medicine and biomaterial science have significantly affected our current view of proteoglycans and related compounds. The roles of proteoglycans in cancer biology and their potential use as a next-generation protein-based adjuvant therapy to combat cancer is also emerging as a constructive and potentially beneficial therapeutic strategy. We will discuss …

Bacillus Calmette-Guérin Vaccination As Defense Against Sars-Cov-2 (Badas): A Randomized Controlled Trial To Protect Healthcare Workers In The Usa By Enhanced Trained Immune Responses, Andrew R Dinardo, Moshe Arditi, Ashish M Kamat, Kent J Koster, Santiago Carrero, Tomoki Nishiguchi, Maxim Lebedev, Aaron B Benjamin, Pablo Avalos, Marisa Lozano, Madeleine G Moule, Brittany Mccune, Baysia Herron, Malik Ladki, Daanish Sheikh, Matthew Spears, Ivan A Herrejon, Courtney Dodge, Sathish Kumar, Robert W Hutchison, Theresa U Ofili, Lynne A Opperman, Jessica A Bernard, Seth P Lerner, George Udeani, Gabriel Neal, Mihai G Netea, Jeffrey D Cirillo

Faculty, Staff and Students Publications

BACKGROUND: A large epidemic, such as that observed with SARS-CoV-2, seriously challenges available hospital capacity, and this would be augmented by infection of healthcare workers (HCW). Bacillus Calmette-Guérin (BCG) is a vaccine against tuberculosis, with protective non-specific effects against other respiratory tract infections in vitro and in vivo. Preliminary analyses suggest that regions of the world with existing BCG vaccination programs have lower incidence and mortality from COVID-19. We hypothesize that BCG vaccination can reduce SARS-CoV-2 infection and disease severity.

METHODS: This will be a placebo-controlled adaptive multi-center randomized controlled trial. A total of 1800 individuals considered to be at …

Excitatory Neuron-Specific Suppression Of The Integrated Stress Response Contributes To Autism-Related Phenotypes In Fragile X Syndrome, Mehdi Hooshmandi, Vijendra Sharma, Carolina Thörn Perez, Rapita Sood, Konstanze Krimbacher, Calvin Wong, Kevin C Lister, Alba Ureña Guzmán, Trevor D Bartley, Cecilia Rocha, Gilles Maussion, Emma Nadler, Patricia Margarita Roque, Ilse Gantois, Jelena Popic, Maxime Lévesque, Randal J Kaufman, Massimo Avoli, Elisenda Sanz, Karim Nader, Randi Jenssen Hagerman, Thomas M Durcan, Mauro Costa-Mattioli, Masha Prager-Khoutorsky, Jean-Claude Lacaille, Veronica Martinez-Cerdeno, Jay R Gibson, Kimberly M Huber, Nahum Sonenberg, Christos G Gkogkas, Arkady Khoutorsky

Faculty, Staff and Students Publications

Dysregulation of protein synthesis is one of the key mechanisms underlying autism spectrum disorder (ASD). However, the role of a major pathway controlling protein synthesis, the integrated stress response (ISR), in ASD remains poorly understood. Here, we demonstrate that the main arm of the ISR, eIF2α phosphorylation (p-eIF2α), is suppressed in excitatory but not inhibitory neurons in a mouse model of fragile X syndrome (FXS; Fmr1−/y). We further show that the decrease in p-eIF2α is mediated via activation of the mTORC1. Genetic reduction of p-eIF2α only in excitatory neurons is sufficient to increase general protein synthesis and cause autism-like …

Hemizygous Variants In Protein Phosphatase 1 Regulatory Subunit 3f (Ppp1r3f) Are Associated With A Neurodevelopmental Disorder Characterized By Developmental Delay, Intellectual Disability And Autistic Features, Zhigang Liu, Baozhong Xin, Iris N Smith, Valerie Sency, Julia Szekely, Anna Alkelai, Alan Shuldiner, Stephanie Efthymiou, Farrah Rajabi, Stephanie Coury, Catherine A Brownstein, Sabine Rudnik-Schöneborn, Ange-Line Bruel, Julien Thevenon, Shimriet Zeidler, Parul Jayakar, Axel Schmidt, Kirsten Cremer, Hartmut Engels, Sophia O Peters, Maha S Zaki, Ruizhi Duan, Changlian Zhu, Yiran Xu, Chao Gao, Tania Sepulveda-Morales, Reza Maroofian, Issam A Alkhawaja, Mariam Khawaja, Hunaida Alhalasah, Henry Houlden, Jill A Madden, Valentina Turchetti, Dana Marafi, Pankaj B Agrawal, Ulrich Schatz, Ari Rotenberg, Joshua Rotenberg, Grazia M S Mancini, Somayeh Bakhtiari, Michael Kruer, Isabelle Thiffault, Steffen Hirsch, Maja Hempel, Lara G Stühn, Tobias B Haack, Jennifer E Posey, James R Lupski, Hyunpil Lee, Nicholas B Sarn, Charis Eng, Claudia Gonzaga-Jauregui, Bin Zhang, Heng Wang

Faculty, Staff and Students Publications

Protein phosphatase 1 regulatory subunit 3F (PPP1R3F) is a member of the glycogen targeting subunits (GTSs), which belong to the large group of regulatory subunits of protein phosphatase 1 (PP1), a major eukaryotic serine/threonine protein phosphatase that regulates diverse cellular processes. Here, we describe the identification of hemizygous variants in PPP1R3F associated with a novel X-linked recessive neurodevelopmental disorder in 13 unrelated individuals. This disorder is characterized by developmental delay, mild intellectual disability, neurobehavioral issues such as autism spectrum disorder, seizures and other neurological findings including tone, gait and cerebellar abnormalities. PPP1R3F variants segregated with disease in affected hemizygous males …

Effect Of Preoperative Programmed Death-1 Or Programmed Death Ligand-1 Immune Check Point Inhibition On Complications After Surgery For Primary Head And Neck Cancer, Ramez Philips, Angela Alnemri, Dev Amin, Jena Patel, Michael C. Topf, Jennifer M. Johnson, Voichita Bar-Ad, Rita Axelrod, Athanassios Argiris, Christopher Fundakowski, Adam J. Luginbuhl, David M. Cognetti, Joseph M. Curry

Jefferson Hospital Staff Papers and Presentations

BACKGROUND: There is sparse literature on the effect of preoperative immunotherapy on complications after surgery for primary head and neck squamous cell carcinoma (HNSCC). The objectives are to compare complication rates in patients receiving surgery with and without neoadjuvant immune checkpoint inhibitors (nICI) for primary HNSCC and to evaluate factors associated with increased odds of surgical complications.

METHODS: A retrospective review of patients who underwent ablation and free flap reconstruction or transoral robotic surgery (TORS) for primary HNSCC between 2017-2021 was conducted. Complications were compared between patients who underwent surgery with or without nICI before and after propensity score matching. …

The Impact Of Helminth-Induced Immunity On Infection With Bacteria Or Viruses, Hong Chen, Zengguo Cao, Mingyuan Liu, Michael S Diamond, Xuemin Jin

2020-Current year OA Pubs

Different human and animal pathogens trigger distinct immune responses in their hosts. The infection of bacteria or viruses can trigger type I pro-inflammatory immune responses (e.g., IFN-γ, TNF-α, T

Relationship Between Epa Level Of Supervision With Their Associated Subcompetency Milestone Levels In Pediatric Fellow Assessment., Richard B. Mink, Carol L. Carraccio, Bruce E. Herman, Pnina Weiss, David A. Turner, Diane E J Stafford, Kathleen A. Mcgann, Jennifer Kesselheim, Deborah C. Hsu, Pamela C. High, Jill J. Fussell, Megan L. Curran, Patricia R. Chess, Cary Sauer, Sarah Pitts, Angela Myers, John D. Mahan, Christiane E L Dammann, Tandy Aye, Alan Schwartz, Subspecialty Pediatrics Investigator Network

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Entrustable Professional Activities (EPA) and competencies represent components of a competency-based education framework. EPAs are assessed based on the level of supervision (LOS) necessary to perform the activity safely and effectively. The broad competencies, broken down into narrower subcompetencies, are assessed using milestones, observable behaviors of one's abilities along a developmental spectrum. Integration of the two methods, accomplished by mapping the most relevant subcompetencies to each EPA, may provide a cross check between the two forms of assessment and uncover those subcompetencies that have the greatest influence on the EPA assessment.

OBJECTIVES: We hypothesized that 1) there would be …

Was Covid-19 Associated With Worsening Inequities In Stroke Treatment And Outcomes?, Laurent G Glance, Curtis G Benesch, Karen E Joynt Maddox, Matthew T Bender, Jingjing Shang, Patricia W Stone, Stewart J Lustik, Jacob W Nadler, Christopher Galton, Andrew W Dick

2020-Current year OA Pubs

Background COVID-19 stressed hospitals and may have disproportionately affected the stroke outcomes and treatment of Black and Hispanic individuals. Methods and Results This retrospective study used 100% Medicare Provider Analysis and Review file data from between 2016 and 2020. We used interrupted time series analyses to examine whether the COVID-19 pandemic exacerbated disparities in stroke outcomes and reperfusion therapy. Among 1 142 560 hospitalizations for acute ischemic strokes, 90 912 (8.0%) were Hispanic individuals; 162 752 (14.2%) were non-Hispanic Black individuals; and 888 896 (77.8%) were non-Hispanic White individuals. The adjusted odds of mortality increased by 51% (adjusted odds ratio …

Association Between Socioeconomic Factors, Race, And Use Of A Specialty Memory Clinic, Abigail Lewis, Aditi Gupta, Inez Oh, Suzanne E. Schindler, Nupur Ghoshal, Zachary Abrams, Randi Foraker, Barbara Joy Snider, John C. Morris, Joyce Balls-Berry, Mahendra Gupta, Philip R. O. Payne, Albert M. Lai

2020-Current year OA Pubs

BACKGROUND AND OBJECTIVES: The capacity of specialty memory clinics in the United States is very limited. If lower socioeconomic status or minoritized racial group is associated with reduced use of memory clinics, this could exacerbate health care disparities, especially if more effective treatments of Alzheimer disease become available. We aimed to understand how use of a memory clinic is associated with neighborhood-level measures of socioeconomic factors and the intersectionality of race.

METHODS: We conducted an observational cross-sectional study using electronic health record data to compare the neighborhood advantage of patients seen at the Washington University Memory Diagnostic Center with the …

Changes In Cardiovascular Spending, Care Utilization, And Clinical Outcomes Associated With Participation In Bundled Payments For Care Improvement - Advanced, Sukruth A. Shashikumar, Jie Zheng, E. John Orav, Arnold M. Epstein, Karen E. Joynt Maddox

2020-Current year OA Pubs

BACKGROUND: Bundled Payments for Care Improvement - Advanced (BPCI-A) is a Medicare initiative that aims to incentivize reductions in spending for episodes of care that start with a hospitalization and end 90 days after discharge. Cardiovascular disease, an important driver of Medicare spending, is one of the areas of focus BPCI-A. It is unknown whether BPCI-A is associated with spending reductions or quality improvements for the 3 cardiovascular medical events or 5 cardiovascular procedures in the model.

METHODS: In this retrospective cohort study, we conducted difference-in-differences analyses using Medicare claims for patients discharged between January 1, 2017, and September 30, …

High-Level Ceftazidime/Avibactam Resistance In Escherichia Coli Conferred By The Novel Plasmid-Mediated Β-Lactamase Cmy-185 Variant, William C Shropshire, Bradley T Endres, Jovan Borjan, Samuel L Aitken, William C Bachman, Christi L Mcelheny, Chin-Ting Wu, Stephanie L Egge, Ayesha Khan, William R Miller, Micah M Bhatti, Pranoti Saharasbhojane, Akito Kawai, Ryan K Shields, Samuel A Shelburne, Yohei Doi

Faculty, Staff and Student Publications

OBJECTIVES: To characterize a blaCMY variant associated with ceftazidime/avibactam resistance from a serially collected Escherichia coli isolate.

METHODS: A patient with an intra-abdominal infection due to recurrent E. coli was treated with ceftazidime/avibactam. On Day 48 of ceftazidime/avibactam therapy, E. coli with a ceftazidime/avibactam MIC of >256 mg/L was identified from abdominal drainage. Illumina and Oxford Nanopore Technologies WGS was performed on serial isolates to identify potential resistance mechanisms. Site-directed mutants of CMY β-lactamase were constructed to identify amino acid residues responsible for ceftazidime/avibactam resistance.

RESULTS: WGS revealed that all three isolates were E. coli ST410. The ceftazidime/avibactam-resistant strain uniquely …

Lung Resident Memory B Cells Maintain Allergic Ige Responses In The Respiratory Tract, Alexander James Nelson

Dissertations

Immunoglobulin E (IgE) is the primary cause of allergic asthma. Allergen-specific IgE can be detected in the airway of allergic asthma patients even in the absence of circulating IgE, suggesting that IgE can be synthesized locally in the respiratory tract. However, the source of IgE-producing B cells, as well as how IgE responses arise and persist at mucosal sites are not fully understood. To address these questions, we modeled allergic asthma in mice by repeated intranasal administration of ragweed pollen and ovalbumin (OVA). We found that allergen exposure induced the production of local IgE in the airway and formation of …

Bricks And Mortar Of Well-Being: Exploring The Housing-Health Connection, Roshanak Mehdipanah, Lara Weinstein

Department of Family & Community Medicine Faculty Papers

Housing is a determinant of health. Increasing housing costs and worsening housing conditions have impacted populations worldwide. This Editorial aims to examine the dynamic connection between housing and health and the role of public health in addressing this relationship for a Collection launched at BMC Public Health on Housing as a determinant of health and well-being.