Physical Sciences and Mathematics Commons^™

Keap1 Cancer Mutants: A Large-Scale Molecular Dynamics Study Of Protein Stability., Carter J Wilson, Megan Chang, Mikko Karttunen, Wing-Yiu Choy

Chemistry Publications

We have performed 280 μs of unbiased molecular dynamics (MD) simulations to investigate the effects of 12 different cancer mutations on Kelch-like ECH-associated protein 1 (KEAP1) (G333C, G350S, G364C, G379D, R413L, R415G, A427V, G430C, R470C, R470H, R470S and G476R), one of the frequently mutated proteins in lung cancer. The aim was to provide structural insight into the effects of these mutants, including a new class of ANCHOR (additionally NRF2-complexed hypomorph) mutant variants. Our work provides additional insight into the structural dynamics of mutants that could not be analyzed experimentally, painting a more complete picture of their mutagenic effects. Notably, blade-wise …

Quality Of Diabetes Care In Blended Fee-For-Service And Blended Capitation Payment Systems., Mary Aderayo Bamimore, Rose Anne Devlin, Gregory S Zaric, Amit X Garg, Sisira Sarma

Epidemiology and Biostatistics Publications

OBJECTIVES: In the middle to late 2000s, many family physicians switched from a Family Health Group (FHG; a blended fee-for-service model) to a Family Health Organization (FHO; a blended capitation model) in Ontario, Canada. The evidence on the link between physician remuneration schemes and quality of diabetes care is mixed in the literature. We examined whether physicians who switched from the FHG to FHO model provided better care for individuals living with diabetes relative to those who remained in the FHG model.

METHODS: Using longitudinal health administrative data from 2006 to 2016, we investigated the impact of physicians switching from …

Generalized And Transferable Patient Language Representation For Phenotyping With Limited Data, Yuqi Si, Elmer V Bernstam, Kirk Roberts

Faculty, Staff and Student Publications

The paradigm of representation learning through transfer learning has the potential to greatly enhance clinical natural language processing. In this work, we propose a multi-task pre-training and fine-tuning approach for learning generalized and transferable patient representations from medical language. The model is first pre-trained with different but related high-prevalence phenotypes and further fine-tuned on downstream target tasks. Our main contribution focuses on the impact this technique can have on low-prevalence phenotypes, a challenging task due to the dearth of data. We validate the representation from pre-training, and fine-tune the multi-task pre-trained models on low-prevalence phenotypes including 38 circulatory diseases, 23 …

Addressing Artificial Intelligence Bias In Retinal Diagnostics, Philippe Burlina, Neil Joshi, William Paul, Katia D Pacheco, Neil M Bressler

Faculty, Staff and Students Publications

PURPOSE: This study evaluated generative methods to potentially mitigate artificial intelligence (AI) bias when diagnosing diabetic retinopathy (DR) resulting from training data imbalance or domain generalization, which occurs when deep learning systems (DLSs) face concepts at test/inference time they were not initially trained on.

METHODS: The public domain Kaggle EyePACS dataset (88,692 fundi and 44,346 individuals, originally diverse for ethnicity) was modified by adding clinician-annotated labels and constructing an artificial scenario of data imbalance and domain generalization by disallowing training (but not testing) exemplars for images of retinas with DR warranting referral (DR-referable) from darker-skin individuals, who presumably have greater …

Emergency Department Use Following Incentives To Provide After-Hours Primary Care: A Retrospective Cohort Study., Michael Hong, Amardeep Thind, Gregory S Zaric, Sisira Sarma

Epidemiology and Biostatistics Publications

BACKGROUND: Access to primary care outside of regular working hours is limited in many countries. This study investigates the relation between the after-hours premium, an incentive for primary care physicians to provide services after hours, and less-urgent visits to the emergency department in Ontario, Canada.

METHODS: We analyzed a retrospective cohort of a random sample of Ontario residents from April 2002 to March 2006, and a subcohort of patients followed from April 2005 to March 2016. We linked patient and primary care physician data with emergency department visit data. We used fixed-effects regression models to analyze the association between the …

Physician Remuneration Schemes, Psychiatric Hospitalizations And Follow-Up Care: Evidence From Blended Fee-For-Service And Capitation Models., Thyna Vu, Kelly K Anderson, Rose Anne Devlin, Nibene H Somé, Sisira Sarma

Epidemiology and Biostatistics Publications

Psychiatric hospitalizations could be reduced if mental illnesses were detected and treated earlier in the primary care setting, leading to the World Health Organization recommendation that mental health services be integrated into primary care. The mental health services provided in primary care settings may vary based on how physicians are incentivized. Little is known about the link between physician remuneration and psychiatric hospitalizations. We contribute to this literature by studying the relationship between physician remuneration and psychiatric hospitalizations in Canada's most populous province, Ontario. Specifically, we study family physicians (FPs) who switched from blended fee-for-service (FFS) to blended capitation remuneration …

Law Library Blog (January 2021): Legal Beagle's Blog Archive, Roger Williams University School Of Law

Law Library Newsletters/Blog

No abstract provided.

A Comparison Of Exhaustive And Non-Lattice-Based Methods For Auditing Hierarchical Relations In Gene Ontology, Rashmie Abeysinghe, Fengbo Zheng, Licong Cui

Faculty, Staff and Student Publications

Uncovering and fixing errors in biomedical terminologies is essential so that they provide accurate knowledge to downstream applications that rely on them. Non-lattice-based methods have been applied to identify various kinds of inconsistencies in different biomedical terminologies. In previous work, we have introduced two inference-based approaches that were applied in an exhaustive manner to audit hierarchical relations in the Gene Ontology: (1) Lexical-based inference framework, and (2) Subsumption-based sub-term inference framework. However, it is unclear how effective these exhaustive approaches perform compared with their corresponding non-lattice-based approaches. Therefore, in this paper, we implement the non-lattice versions of these two exhaustive …

Identifying Sleep-Related Factors Associated With Cognitive Function In A Hispanics/Latinos Cohort: A Dual Random Forest Approach, Li Xiaojin, Cui Licong, Wang Fei, Paul E Schulz, Guo-Qiang Zhang

Faculty, Staff and Student Publications

Disordered sleep is associated with poor cognitive function and cognitive decline. However, little is known regarding the association of sleep-related factors with cognitive function in underrepresented cohorts such as the Hispanic/Latino population. Leveraging the National Sleep Research Resource, one of the most comprehensive collections of sleep studies, we identified a Hispanic/Latino cohort of 1,031 lower cognitive function cases and 2,062 normal controls. We developed a novel dual random forest (DRF) approach to discriminate cases against controls for estimating the potential impact of sleep-related variables related to the decline of cognitive function. Several important sleep-related factors were identified which may be …

Analysis Of Subtelomeric Rextal Assemblies Using Quast, Tunazzina Islam, Desh Ranjan, Mohammad Zubair, Eleanor Young, Ming Xiao, Harold Riethman

Computer Science Faculty Publications

Genomic regions of high segmental duplication content and/or structural variation have led to gaps and misassemblies in the human reference sequence, and are refractory to assembly from whole-genome short-read datasets. Human subtelomere regions are highly enriched in both segmental duplication content and structural variations, and as a consequence are both impossible to assemble accurately and highly variable from individual to individual. Recently, we developed a pipeline for improved region-specific assembly called Regional Extension of Assemblies Using Linked-Reads (REXTAL). In this study, we evaluate REXTAL and genome-wide assembly (Supernova) approaches on 10X Genomics linked-reads data sets partitioned and barcoded using the …

The Impact Of The Diabetes Management Incentive On Diabetes-Related Services: Evidence From Ontario, Canada., Thaksha Thavam, Rose Anne Devlin, Amardeep Thind, Gregory S Zaric, Sisira Sarma

Epidemiology and Biostatistics Publications

Financial incentives have been introduced in several countries to improve diabetes management. In Ontario, the most populous province in Canada, a Diabetes Management Incentive (DMI) was introduced to family physicians practicing in patient enrollment models in 2006. This paper examines the impact of the DMI on diabetes-related services provided to individuals with diabetes in Ontario. Longitudinal health administrative data were obtained for adults diagnosed with diabetes and their family physicians. The study population consisted of two groups: DMI group (patients enrolled with a family physician exposed to DMI for 3 years), and comparison group (patients affiliated with a family physician …

Participatory Video As A Novel Recovery-Oriented Intervention In Early Psychosis: A Pilot Study., Arlene G Macdougall, Sahana Kukan, Elizabeth Price, Sarah Glen, Richelle Bird, Laura Powe, Joshua C. Wiener, Paul H Lysaker, Kelly K Anderson, Ross Mg Norman

Epidemiology and Biostatistics Publications

BACKGROUND: Personal narrative plays an important role in the process of recovery from psychotic illnesses. Participatory video is a novel, active intervention that can be used as a tool for fostering narrative development among people with psychosis.

AIM: To assess the feasibility, acceptability and potential clinical utility of participatory video as an innovative tool for promoting recovery in early psychosis.

METHODS: Ten outpatients of an early psychosis intervention programme were recruited to participate in 13 biweekly workshops to plan, film and produce documentary-style videos of their experiences. Feasibility was measured through recruitment and retention. Acceptability was measured through workshop attendance …

Stirring The Pot: Switching From Blended Fee-For-Service To Blended Capitation Models Of Physician Remuneration., Nibene H Somé, Rose Anne Devlin, Nirav Mehta, Gregory S Zaric, Sisira Sarma

Epidemiology and Biostatistics Publications

In Canada's most populous province, Ontario, family physicians may choose between the blended fee-for-service (Family Health Group [FHG]) and blended capitation (Family Health Organization [FHO] payment models). Both models incentivize physicians to provide after-hours (AH) and comprehensive care, but FHO physicians receive a capitation payment per enrolled patient adjusted for age and sex, plus a reduced fee-for-service while FHG physicians are paid by fee-for-service. We develop a theoretical model of physician labor supply with multitasking to predict their behavior under FHG and FHO, and estimable equations are derived to test the predictions empirically. Using health administrative data from 2006 to …

Law Library Blog (November 2020): Legal Beagle's Blog Archive, Roger Williams University School Of Law

Law Library Newsletters/Blog

No abstract provided.

Delineating Heme-Mediated Versus Direct Protein Oxidation In Peroxidase-Activated Cytochrome, Victor Yin, Derek Holzscherer, Lars Konermann

Chemistry Publications

Oxidation of key residues in cytochrome c (cyt c) by chloramine T (CT) converts the protein from an electron transporter to a peroxidase. This peroxidase-activated state represents an important model system for exploring the early steps of apoptosis. CT-induced transformations include oxidation of the distal heme ligand Met80 (MetO, +16 Da) and carbonylation (LysCHO, -1 Da) in the range of Lys53/55/72/73. Remarkably, the 15 remaining Lys residues in cyt c are not susceptible to carbonylation. The cause of this unusual selectivity is unknown. Here we applied top-down mass spectrometry (MS) to examine whether CT-induced oxidation is catalyzed by heme. …

Representation Of Ehr Data For Predictive Modeling: A Comparison Between Umls And Other Terminologies, Laila Rasmy, Firat Tiryaki, Yujia Zhou, Yang Xiang, Cui Tao, Hua Xu, Degui Zhi

Faculty, Staff and Student Publications

OBJECTIVE: Predictive disease modeling using electronic health record data is a growing field. Although clinical data in their raw form can be used directly for predictive modeling, it is a common practice to map data to standard terminologies to facilitate data aggregation and reuse. There is, however, a lack of systematic investigation of how different representations could affect the performance of predictive models, especially in the context of machine learning and deep learning.

MATERIALS AND METHODS: We projected the input diagnoses data in the Cerner HealthFacts database to Unified Medical Language System (UMLS) and 5 other terminologies, including CCS, CCSR, …

Near Simultaneous Laser Scanning Confocal And Atomic Force Microscopy (Conpokal) On Live Cells, Joree N. Sandin, Surya P. Aryal, Thomas E. Wilkop, Christopher I. Richards, Martha E. Grady

Physiology Faculty Publications

Techniques available for micro- and nano-scale mechanical characterization have exploded in the last few decades. From further development of the scanning and transmission electron microscope, to the invention of atomic force microscopy, and advances in fluorescent imaging, there have been substantial gains in technologies that enable the study of small materials. Conpokal is a portmanteau that combines confocal microscopy with atomic force microscopy (AFM), where a probe "pokes" the surface. Although each technique is extremely effective for the qualitative and/or quantitative image collection on their own, Conpokal provides the capability to test with blended fluorescence imaging and mechanical characterization. Designed …

Risk Of New Bloodstream Infections And Mortality Among People Who Inject Drugs With Infective Endocarditis., Charlie Tan, Esfandiar Shojaei, Joshua C. Wiener, Meera Shah, Sharon Koivu, Michael Silverman

Epidemiology and Biostatistics Publications

IMPORTANCE: People who inject drugs (PWID) who are being treated for infective endocarditis remain at risk of new bloodstream infections (BSIs) due to ongoing intravenous drug use (IVDU).

OBJECTIVES: To characterize new BSIs in PWID receiving treatment for infective endocarditis, to determine the clinical factors associated with their development, and to determine whether new BSIs and treatment setting are associated with mortality.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study was performed at 3 tertiary care hospitals in London, Ontario, Canada, from April 1, 2007, to March 31, 2018. Participants included a consecutive sample of all PWID 18 years or …

The Impact Of Improved Access To After-Hours Primary Care On Emergency Department And Primary Care Utilization: A Systematic Review., Michael Hong, Amardeep Thind, Gregory S Zaric, Sisira Sarma

Epidemiology and Biostatistics Publications

Access to after-hours primary care is problematic in many developed countries, leading patients to instead visit the emergency department for non-urgent conditions. However, emergency department utilization for conditions treatable in primary care settings may contribute to emergency department overcrowding and increased health system costs. This systematic review examines the impact of various initiatives by developed countries to improve access to after-hours primary care on emergency department and primary care utilization. We performed a systematic review on the impact of improved access to after-hours primary and searched CINAHL, EMBASE, MEDLINE, and Scopus. We identified 20 studies that examined the impact of …

Covid-19 Testnorm: A Tool To Normalize Covid-19 Testing Names To Loinc Codes, Xiao Dong, Jianfu Li, Ekin Soysal, Jiang Bian, Scott L Duvall, Elizabeth Hanchrow, Hongfang Liu, Kristine E Lynch, Michael Matheny, Karthik Natarajan, Lucila Ohno-Machado, Serguei Pakhomov, Ruth Madeleine Reeves, Amy M Sitapati, Swapna Abhyankar, Theresa Cullen, Jami Deckard, Xiaoqian Jiang, Robert Murphy, Hua Xu

Faculty, Staff and Student Publications

Large observational data networks that leverage routine clinical practice data in electronic health records (EHRs) are critical resources for research on coronavirus disease 2019 (COVID-19). Data normalization is a key challenge for the secondary use of EHRs for COVID-19 research across institutions. In this study, we addressed the challenge of automating the normalization of COVID-19 diagnostic tests, which are critical data elements, but for which controlled terminology terms were published after clinical implementation. We developed a simple but effective rule-based tool called COVID-19 TestNorm to automatically normalize local COVID-19 testing names to standard LOINC (Logical Observation Identifiers Names and Codes) …

Age At Migration And The Risk Of Psychotic Disorders: A Systematic Review And Meta-Analysis., Kelly K. Anderson, Jordan Edwards

Epidemiology and Biostatistics Publications

OBJECTIVE: To conduct a systematic review and meta-analysis of the existing evidence on the association between age at migration and the risk of psychotic disorders.

METHODS: Observational studies were eligible for inclusion if they presented data on the association between age at migration and the risk of psychotic disorders among first-generation migrant groups. We used two random effects meta-analyses to pool effect estimates for each stratum of age at migration relative to (i) a native-born reference category and (ii) the youngest age stratum (0 to 2 years).

RESULTS: Ten studies met inclusion criteria, and five were included in the meta-analysis. …

Deep Learning In Clinical Natural Language Processing: A Methodical Review, Stephen Wu, Kirk Roberts, Surabhi Datta, Jingcheng Du, Zongcheng Ji, Yuqi Si, Sarvesh Soni, Qiong Wang, Qiang Wei, Yang Xiang, Bo Zhao, Hua Xu

Faculty, Staff and Student Publications

OBJECTIVE: This article methodically reviews the literature on deep learning (DL) for natural language processing (NLP) in the clinical domain, providing quantitative analysis to answer 3 research questions concerning methods, scope, and context of current research.

MATERIALS AND METHODS: We searched MEDLINE, EMBASE, Scopus, the Association for Computing Machinery Digital Library, and the Association for Computational Linguistics Anthology for articles using DL-based approaches to NLP problems in electronic health records. After screening 1,737 articles, we collected data on 25 variables across 212 papers.

RESULTS: DL in clinical NLP publications more than doubled each year, through 2018. Recurrent neural networks (60.8%) …

Plasmodium Falciparum Resistance To A Lead Benzoxaborole Due To Blocked Compound Activation And Altered Ubiquitination Or Sumoylation., Kirthana M. V. Sindhe, Wesley Wu, Jenny Legac, Yong-Kang Zhang, Eric E. Easom, Roland A. Cooper, Jacob J. Plattner, Yvonne R. Freund, Joseph L. Derisi, Philip J. Rosenthal

Natural Sciences and Mathematics | Faculty Scholarship

New antimalarial drugs are needed. The benzoxaborole AN13762 showed excellent activity against cultured Plasmodium falciparum, against fresh Ugandan P. falciparum isolates, and in murine malaria models. To gain mechanistic insights, we selected in vitro for P. falciparum isolates resistant to AN13762. In all of 11 independent selections with 100 to 200 nM AN13762, the 50% inhibitory concentration (IC50) increased from 18–118 nM to 180–890 nM, and whole-genome sequencing of resistant parasites demonstrated mutations in prodrug activation and resistance esterase (PfPARE). The introduction of PfPARE mutations led to a similar level of resistance, and recombinant PfPARE hydrolyzed AN13762 to the benzoxaborole …

Evaluating The Effectiveness Of Aquatic Therapy On Mobility, Balance, And Level Of Functional Independence In Stroke Rehabilitation: A Systematic Review And Meta-Analysis., Alice Mary Iliescu, Amanda Mcintyre, Joshua C. Wiener, Jerome Iruthayarajah, Andrea Lee, Sarah Caughlin, Robert Teasell

Epidemiology and Biostatistics Publications

OBJECTIVE: To meta-analyze and systematically review the effectiveness of aquatic therapy in improving mobility, balance, and functional independence after stroke.

DATA SOURCES: Articles published in Medline, Embase, CINAHL, PsycINFO, and Scopus up to 20 August 2019.

STUDY SELECTION: Studies met the following inclusion criteria: (1) English, (2) adult stroke population, (3) randomized or non-randomized prospectively controlled trial (RCT or PCT, respectively) study design, (4) the experimental group received >1 session of aquatic therapy, and (5) included a clinical outcome measure of mobility, balance, or functional independence.

DATA EXTRACTION: Participant characteristics, treatment protocols, between-group outcomes, point measures, and measures of variability …

Digilego For Peripartum Depression: A Novel Patient-Facing Digital Health Instantiation, J Rodin, C Timko, S Harris

Faculty, Staff and Student Publications

Digital health technologies offer unique opportunities to improve health outcomes for mental health conditions such as peripartum depression (PPD), a disorder that affects approximately 10-15% of women in the U.S. every year. In this paper, we present the adaption of a digital technology development framework, Digilego, in the context of PPD. Methods include mapping of the Behavior Intervention Technology (BIT) model and the Patient Engagement Framework (PEF) to translate patient needs captured through focus groups. This informs formative development and implementation of digital health features for optimal patient engagement in PPD screening and management. Results show an array ofPPD-specific Digilego …

Causal Discovery In Radiographic Markers Of Knee Osteoarthritis And Prediction For Knee Osteoarthritis Severity With Attention-Long Short-Term Memory, Yanfei Wang, Lei You, Jacqueline Chyr, Lan Lan, Weiling Zhao, Yujia Zhou, Hua Xu, Philip Noble, Xiaobo Zhou

Faculty, Staff and Student Publications

The goal of this study is to build a prognostic model to predict the severity of radiographic knee osteoarthritis (KOA) and to identify long-term disease progression risk factors for early intervention and treatment. We designed a long short-term memory (LSTM) model with an attention mechanism to predict Kellgren/Lawrence (KL) grade for knee osteoarthritis patients. The attention scores reveal a time-associated impact of different variables on KL grades. We also employed a fast causal inference (FCI) algorithm to estimate the causal relation of key variables, which will aid in clinical interpretability. Based on the clinical information of current visits, we accurately …

Protein And Polysaccharide-Based Magnetic Composite Materials For Medical Applications., Elizabeth J Bealer, Kyril Kavetsky, Sierra Dutko, Samuel Lofland, Xiao Hu

College of Science & Mathematics Departmental Research

The combination of protein and polysaccharides with magnetic materials has been implemented in biomedical applications for decades. Proteins such as silk, collagen, and elastin and polysaccharides such as chitosan, cellulose, and alginate have been heavily used in composite biomaterials. The wide diversity in the structure of the materials including their primary monomer/amino acid sequences allow for tunable properties. Various types of these composites are highly regarded due to their biocompatible, thermal, and mechanical properties while retaining their biological characteristics. This review provides information on protein and polysaccharide materials combined with magnetic elements in the biomedical space showcasing the materials used, …

Impact Of Motor Therapy With Dynamic Body-Weight Support On Functional Independence Measures In Traumatic Brain Injury: An Exploratory Study, Emily F. Anggelis, Elizabeth Salmon Powell, Philip M. Westgate, Amanda C. Glueck, Lumy Sawaki

Physical Medicine and Rehabilitation Faculty Publications

BACKGROUND: Contemporary goals of rehabilitation after traumatic brain injury (TBI) aim to improve cognitive and motor function by applying concepts of neuroplasticity. This can be challenging to carry out in TBI patients with motor, balance, and cognitive impairments.

OBJECTIVE: To determine whether use of dynamic body-weight support (DBWS) would allow safe administration of intensive motor therapy during inpatient rehabilitation and whether its use would yield greater improvement in functional recovery than standard-of-care (SOC) therapy in adults with TBI.

METHODS: Data in this retrospective cohort study was collected from patients with TBI who receive inpatient rehabilitation incorporating DBWS (n = …

Chronic Muscle Weakness And Mitochondrial Dysfunction In The Absence Of Sustained Atrophy In A Preclinical Sepsis Model, Allison M. Owen, Samir P. Patel, Jeffrey D. Smith, Beverly K. Balasuriya, Stephanie F. Mori, Gregory S. Hawk, Arnold J. Stromberg, Naohide Kuriyama, Masao Kaneki, Alexander G. Rabchevsky, Timothy A. Butterfield, Karyn A. Esser, Charlotte A. Peterson, Marlene E. Starr, Hiroshi Saito

Physiology Faculty Publications

Chronic critical illness is a global clinical issue affecting millions of sepsis survivors annually. Survivors report chronic skeletal muscle weakness and development of new functional limitations that persist for years. To delineate mechanisms of sepsis-induced chronic weakness, we first surpassed a critical barrier by establishing a murine model of sepsis with ICU-like interventions that allows for the study of survivors. We show that sepsis survivors have profound weakness for at least 1 month, even after recovery of muscle mass. Abnormal mitochondrial ultrastructure, impaired respiration and electron transport chain activities, and persistent protein oxidative damage were evident in the muscle of …

Production Of Physician Services Under Fee-For-Service And Blended Fee-For-Service: Evidence From Ontario, Canada., Nibene H Somé, Rose Anne Devlin, Nirav Mehta, Greg Zaric, Lihua Li, Salimah Shariff, Bachir Belhadji, Amardeep Thind, Amit Garg, Sisira Sarma

Epidemiology and Biostatistics Publications

We examine family physicians' responses to financial incentives for medical services in Ontario, Canada. We use administrative data covering 2003-2008, a period during which family physicians could choose between the traditional fee for service (FFS) and blended FFS known as the Family Health Group (FHG) model. Under FHG, FFS physicians are incentivized to provide comprehensive care and after-hours services. A two-stage estimation strategy teases out the impact of switching from FFS to FHG on service production. We account for the selection into FHG using a propensity score matching model, and then we use panel-data regression models to account for observed …