Medicine and Health Sciences Commons^™

Changing Global Epidemiology Of Liver Cancer From 2010 To 2019: Nash Is The Fastest Growing Cause Of Liver Cancer, Daniel Q Huang, Amit G Singal, Yuko Kono, Darren J H Tan, Hashem B El-Serag, Rohit Loomba

Faculty, Staff and Students Publications

Liver cancer epidemiology is changing due to increasing alcohol consumption, rising prevalence of obesity, and advances in hepatitis B virus (HBV) and hepatitis C virus (HCV) treatment. However, the impact of these changes on global liver cancer burden remains unclear. We estimated global and regional temporal trends in the burden of liver cancer and the contributions of various liver disease etiologies using the methodology framework of the Global Burden of Disease study. Between 2010 and 2019, there was a 25% increase in liver cancer deaths. Age-standardized death rates (ASDRs) increased only in the Americas and remained stable or fell in …

Structure-Activity Relationship And Antitumor Activity Of 1,4-Pyrazine-Containing Inhibitors Of Histone Acetyltransferases P300/Cbp, Shenyou Nie, Fangrui Wu, Jingyu Wu, Xin Li, Chao Zhou, Yuan Yao, Yongcheng Song

Faculty, Staff and Students Publications

Acetylation of histone lysine residues by histone acetyltransferase (HAT) p300 and its paralog CBP play important roles in gene regulation in health and diseases. The HAT domain of p300/CBP has been found to be a potential drug target for cancer. Compound screening followed by structure-activity relationship studies yielded a novel series of 1,4-pyrazine-containing inhibitors of p300/CBP HAT with their IC50s as low as 1.4 μM. Enzyme kinetics and other studies support the most potent compound 29 is a competitive inhibitor of p300 HAT against the substrate histone. It exhibited a high selectivity for p300 and CBP, with negligible activity on …

Pilot Study For Correlation Of Heart Rate Variability And Dopamine Transporter Brain Imaging In Patients With Parkinsonian Syndrome, Devdutta S Warhadpande, Jiayan Huo, William A Libling, Carol Stuehm, Bijan Najafi, Scott Sherman, Hong Lei, Janet Meiling Roveda, Phillip H Kuo

Center on Aging Staff Publications

Background: Parkinsonian syndrome (PS) is a broad category of neurodegenerative movement disorders that includes Parkinson disease, multiple system atrophy (MSA), progressive supranuclear palsy, and corticobasal degeneration. Parkinson disease (PD) is the second most common neurodegenerative disorder with loss of dopaminergic neurons of the substantia nigra and, thus, dysfunction of the nigrostriatal pathway. In addition to the motor symptoms of bradykinesia, rigidity, tremors, and postural instability, nonmotor symptoms such as autonomic dysregulation (AutD) can also occur. Heart rate variability (HRV) has been used as a measure of AutD and has shown to be prognostic in diseases such as diabetes mellitus and …

Modeling The Prognostic Impact Of Circulating Tumor Cells Enumeration In Metastatic Breast Cancer For Clinical Trial Design Simulation, Lorenzo Gerratana, Andrew A Davis, Et Al.

2020-Current year OA Pubs

Despite the strong prognostic stratification of circulating tumor cells (CTCs) enumeration in metastatic breast cancer (MBC), current clinical trials usually do not include a baseline CTCs in their design. This study aimed to generate a classifier for CTCs prognostic simulation in existing datasets for hypothesis generation in patients with MBC. A K-nearest neighbor machine learning algorithm was trained on a pooled dataset comprising 2436 individual MBC patients from the European Pooled Analysis Consortium and the MD Anderson Cancer Center to identify patients likely to have CTCs ≥ 5/7 mL blood (StageIVaggressive vs StageIVindolent). The model had a 65.1% accuracy and …

South African University Staff And Students’ Perspectives, Preferences, And Drivers Of Hesitancy Regarding Covid-19 Vaccines: A Multi-Methods Study, Gavin George, Michael Strauss, Emma Lansdell, Nisha Nadesan-Reddy, Numfundo Moroe, Tarylee Reddy, Ingrid Eshun-Wilsonova, Mosa Moshabela

2020-Current year OA Pubs

No abstract provided.

Gene-Based Polygenic Risk Scores Analysis Of Alcohol Use Disorder In African Americans, Dongbing Lai, Arpana Agrawal, Et Al

2020-Current year OA Pubs

Genome-wide association studies (GWAS) in admixed populations such as African Americans (AA) have limited sample sizes, resulting in poor performance of polygenic risk scores (PRS). Based on the observations that many disease-causing genes are shared between AA and European ancestry (EA) populations, and some disease-causing variants are located within the boundaries of these genes, we proposed a novel gene-based PRS framework (PRS

Mapping The Single-Cell Transcriptomic Response Of Murine Diabetic Kidney Disease To Therapies, Haojia Wu, Romer Gonzalez Villalobos, Xiang Yao, Dermot Reilly, Tao Chen, Matthew Rankin, Eugene Myshkin, Matthew D. Breyer, Benjamin D. Humphreys

2020-Current year OA Pubs

Diabetic kidney disease (DKD) occurs in ∼40% of patients with diabetes and causes kidney failure, cardiovascular disease, and premature death. We analyzed the response of a murine DKD model to five treatment regimens using single-cell RNA sequencing (scRNA-seq). Our atlas of ∼1 million cells revealed a heterogeneous response of all kidney cell types both to DKD and its treatment. Both monotherapy and combination therapies targeted differing cell types and induced distinct and non-overlapping transcriptional changes. The early effects of sodium-glucose cotransporter-2 inhibitors (SGLT2i) on the S1 segment of the proximal tubule suggest that this drug class induces fasting mimicry and …

Reduction And Resolution Of A Hiatal Hernia Using Osteopathic Manipulative Treatment: A Case Report, Mikhail Volokitin, Anthony Song, Meredith T. Peck, Susan Milani

Touro College of Osteopathic Medicine (New York) Publications and Research

No abstract provided.

Effect Of Behavioural Practice Targeted At The Motor Action Selection Network After Stroke, Jill C. Stewart, Jessica F. Baird, Stacy L. Fritz, Julius Fridriksson Ph.D.

Faculty Publications

Motor action selection engages a network of frontal and parietal brain regions. After stroke, individuals activate a similar network, however, activation is higher, especially in the contralesional hemisphere. The current study examined the effect of practice on action selection performance and brain activation after stroke. Sixteen individuals with chronic stroke (Upper Extremity Fugl–Meyer motor score range: 18–61) moved a joystick with the more-impaired hand in two conditions: Select (externally cued choice; move right or left based on an abstract rule) and Execute (simple response; move same direction every trial). On Day 1, reaction time (RT) was longer in Select compared …

The Use Of Second-Generation Antipsychotics And The Changes In Physical Growth In Children And Adolescents With Perinatally Acquired Hiv, Nan Xin, Jenni Durieux, Chunxia Yang, Suzanne Wolff, Hyun-Eui Kim, Andrew Dillin

Faculty, Staff and Student Publications

The mitochondrial unfolded protein response (UPRmt) is dedicated to promoting mitochondrial proteostasis and is linked to extreme longevity. The key regulator of this process is the transcription factor ATFS-1, which, upon UPRmt activation, is excluded from the mitochondria and enters the nucleus to regulate UPRmt genes. However, the repair proteins synthesized as a direct result of UPRmt activation must be transported into damaged mitochondria that had previously excluded ATFS-1 owing to reduced import efficiency. To address this conundrum, we analyzed the role of the import machinery when the UPRmt was induced. Using in vitro and in vivo analysis of mitochondrial …

Transcription Factor Runx3 Mediates Plasticity Of Thgm Cells Toward Th1 Phenotype, Javad Rasouli, Giacomo Casella, Weifeng Zhang, Dan Xiao, Gaurav Kumar, Paolo Fortina, Guang-Xian Zhang, Bogoljub Ciric, Abdolmohamad Rostami

Department of Neurology Faculty Papers

GM-CSF-producing T helper (Th) cells play a crucial role in the pathogenesis of autoimmune diseases such as multiple sclerosis (MS). Recent studies have identified a distinct population of GM-CSF-producing Th cells, named ThGM cells, that also express cytokines TNF, IL-2, and IL-3, but lack expression of master transcription factors (TF) and signature cytokines of commonly recognized Th cell lineages. ThGM cells are highly encephalitogenic in a mouse model of MS, experimental autoimmune encephalomyelitis (EAE). Similar to Th17 cells, in response to IL-12, ThGM cells upregulate expression of T-bet and IFN-γ and switch their phenotype to Th1. Here we show that …

Exogenous Short Chain Fatty Acid Effects In App/Ps1 Mice, Diana J. Zajac, Benjamin C. Shaw, David J. Braun, Stefan J. Green, Joshua M. Morganti, Steven Estus

Sanders-Brown Center on Aging Faculty Publications

Elucidating the impact of the gut microbiome on Alzheimer’s Disease (AD) is an area of intense interest. Short chain fatty acids (SCFAs) are major microbiota metabolites that have been implicated as a mediator of gut microbiome effects in the brain. Here, we tested the effects of SCFA-treated water vs. saline-treated water on APPswe/PSEN1dE9 mice maintained under standard laboratory conditions. Mice were treated with SCFAs from five months of age until ten months of age, when they were evaluated for microbiome profile, impaired spatial memory as evaluated with the radial arm water maze, astrocyte activation as measured by Gfap expression and …

Natural Products Inhibitors Of Monoamine Oxidases—Potential New Drug Leads For Neuroprotection, Neurological Disorders, And Neuroblastoma, Narayan D. Chaurasiya, Francisco León Ph.D., Ilias Muhammad, Babu L. Tekwani

Faculty Publications

Monoamine oxidase inhibitors (MAOIs) are an important class of drugs prescribed for treatment of depression and other neurological disorders. Evidence has suggested that patients with atypical depression preferentially respond to natural product MAOIs. This review presents a comprehensive survey of the natural products, predominantly from plant sources, as potential new MAOI drug leads. The psychoactive properties of several traditionally used plants and herbal formulations were attributed to their MAOI constituents. MAO inhibitory constituents may also be responsible for neuroprotective effects of natural products. Different classes of MAOIs were identified from the natural product sources with non-selective as well as selective …

Regulating Phase Transition In Neurodegenerative Diseases By Nuclear Import Receptors, Amandeep Girdhar, Lin Guo

Department of Biochemistry and Molecular Biology Faculty Papers

RNA-binding proteins (RBPs) with a low-complexity prion-like domain (PLD) can undergo aberrant phase transitions and have been implicated in neurodegenerative diseases such as ALS and FTD. Several nuclear RBPs mislocalize to cytoplasmic inclusions in disease conditions. Impairment in nucleocytoplasmic transport is another major event observed in ageing and in neurodegenerative disorders. Nuclear import receptors (NIRs) regulate the nucleocytoplasmic transport of different RBPs bearing a nuclear localization signal by restoring their nuclear localization. NIRs can also specifically dissolve or prevent the aggregation and liquid–liquid phase separation of wild-type or disease-linked mutant RBPs, due to their chaperoning activity. This review focuses on …

Predicting Suicide In Counties: Creating A Quantitative Measure Of Suicide Risk, Kate Mobley, Gita Taasoobshirazi

Faculty Articles

Rising rates of suicide over the past two decades have increased the need for wide-ranging suicide prevention efforts. One approach is to target high-risk groups, which requires the identification of the characteristics of these population sub-groups. This suicidology study was conducted using large-scale, secondary data to answer the question: using the research on suicide, are there variables studied at the community level that are linked to suicide and are measurable using quantitative, demographic data that are already collected and updated? Data on deaths from suicide in U.S. counties for the years 2000, 2005, 2010 and 2015 were analyzed using multiple …

Pd-1/Pd-L1 Pathway: A Therapeutic Target In Cd30+ Large Cell Lymphomas, Wei Xie, L Jeffrey Medeiros, Shaoying Li, Guilin Tang, Guang Fan, Jie Xu

Faculty, Staff and Student Publications

The programmed death-ligands, PD-L1 and PD-L2, reside on tumor cells and can bind with programmed death-1 protein (PD-1) on T-cells, resulting in tumor immune escape. PD-1 ligands are highly expressed in some CD30+ large cell lymphomas, including classic Hodgkin lymphoma (CHL), primary mediastinal large B-cell lymphoma (PMBL), Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (EBV+ DLBCL), and anaplastic large cell lymphoma (ALCL). The genetic alteration of the chromosome 9p24.1 locus, the location of

Activation Of Autophagic Flux Maintains Mitochondrial Homeostasis During Cardiac Ischemia/Reperfusion Injury, Lihao He, Sumanth D Prabhu, Et Al

2020-Current year OA Pubs

Reperfusion injury after extended ischemia accounts for approximately 50% of myocardial infarct size, and there is no standard therapy. HDAC inhibition reduces infarct size and enhances cardiomyocyte autophagy and PGC1α-mediated mitochondrial biogenesis when administered at the time of reperfusion. Furthermore, a specific autophagy-inducing peptide, Tat-Beclin 1 (TB), reduces infarct size when administered at the time of reperfusion. However, since SAHA affects multiple pathways in addition to inducing autophagy, whether autophagic flux induced by TB maintains mitochondrial homeostasis during ischemia/reperfusion (I/R) injury is unknown. We tested whether the augmentation of autophagic flux by TB has cardioprotection by preserving mitochondrial homeostasis both …

Engaging Public Health Critical Race Praxis In Local Social Determinants Of Health Research: The Youth Health Equity And Action Research Training Program In Portland, Or—Yheartpdx, Ryan J. Petteway, Lourdes Gonzalez

OHSU-PSU School of Public Health Faculty Publications and Presentations

The social determinants of health (SDH) have long been considered a core mechanism through which racial health inequities are (re)produced and incubated in the U.S. Moreover, scholars have expressly—and appropriately—named structural racism as a precursor to inequities associated with SDH. However, while research on racial health inequities—SDH-related or otherwise—continues to grow, communities of color remain grossly underrepresented as public health researchers and practitioners. Additionally, although SDH are experienced in a very local sense, much research and practice fails to more deeply and thoroughly engage and center local community knowledges. Thus, much work around SDH and racial health inequities presents, ironically, …

Assessing Smoking Status And Risk Of Sars-Cov-2 Infection: A Machine Learning Approach Among Veterans, Alice B S Nono Djotsa, Drew A Helmer, Catherine Park, Kristine E Lynch, Amir Sharafkhaneh, Aanand D Naik, Javad Razjouyan, Christopher I Amos

Center for Medical Ethics and Health Policy Staff Publications

The role of smoking in the risk of SARS-CoV-2 infection is unclear. We used a retrospective cohort design to study data from veterans' Electronic Medical Record to assess the impact of smoking on the risk of SARS-CoV-2 infection. Veterans tested for the SARS-CoV-2 virus from 02/01/2020 to 02/28/2021 were classified as: Never Smokers (NS), Former Smokers (FS), and Current Smokers (CS). We report the adjusted odds ratios (aOR) for potential confounders obtained from a cascade machine learning algorithm. We found a 19.6% positivity rate among 1,176,306 veterans tested for SARS-CoV-2 infection. The positivity proportion among NS (22.0%) was higher compared …

Etiology Of Persistent Microalbuminuria In Nigeria (P_Micro Study): Protocol And Study Design, C William Wester, Philip J Budge, Et Al.

2020-Current year OA Pubs

BACKGROUND: Microalbuminuria is an independent risk factor for cardiovascular and kidney disease and a predictor of end organ damage, both in the general population and in persons with HIV (PWH). Microalbuminuria is also an important risk factor for mortality in PWH treated with antiretroviral therapy (ART). In the ongoing Renal Risk Reduction (R3) study in Nigeria, we identified a high prevalence of microalbuminuria confirmed by two measurements 4-8 weeks apart in ART-experienced, virologically suppressed PWH. Although Stage 1 or 2 hypertension and exposure to potentially nephrotoxic antiretroviral medications were common in R3 participants, other traditional risk factors for albuminuria and …

Dcs At The Center Of Help: Origins And Evolution Of The Three-Cell-Type Hypothesis, Renee Wu, Kenneth M Murphy

2020-Current year OA Pubs

Last year was the 10th anniversary of Ralph Steinman's Nobel Prize awarded for his discovery of dendritic cells (DCs), while next year brings the 50th anniversary of that discovery. Current models of anti-viral and anti-tumor immunity rest solidly on Steinman's discovery of DCs, but also rely on two seemingly unrelated phenomena, also reported in the mid-1970s: the discoveries of "help" for cytolytic T cell responses by Cantor and Boyse in 1974 and "cross-priming" by Bevan in 1976. Decades of subsequent work, controversy, and conceptual changes have gradually merged these three discoveries into current models of cell-mediated immunity against viruses and …

High-Resolution Label-Free Mapping Of Murine Kidney Vasculature By Raster-Scanning Optoacoustic Mesoscopy: An Ex Vivo Study, Colin A Goebel, Emma Brown, Fabian B Fahlbusch, Alexandra L Wagner, Adrian Buehler, Thomas Raupach, Martin Hohmann, Moritz Späth, Neal Burton, Joachim Woelfle, Michael Schmidt, Andrea Hartner, Adrian P Regensburger, Ferdinand Knieling

2020-Current year OA Pubs

BACKGROUND: Chronic kidney disease (CKD) is a global burden affecting both children and adults. Novel imaging modalities hold great promise to visualize and quantify structural, functional, and molecular organ damage. The aim of the study was to visualize and quantify murine renal vasculature using label-free raster scanning optoacoustic mesoscopy (RSOM) in explanted organs from mice with renal injury.

MATERIAL AND METHODS: For the experiments, freshly bisected kidneys of alpha 8 integrin knock-out (KO) and wildtype mice (WT) were used. A total of n=7 female (n=4 KO, n=3 WT) and n=6 male animals (n=2 KO, n=4 WT) aged 6 weeks were …

Effects Of Chronic Cannabidiol In A Mouse Model Of Naturally Occurring Neuroinflammation, Neurodegeneration, And Spontaneous Seizures, Joshua T Dearborn, Hemanth R Nelvagal, Nicholas R Rensing, Keigo Takahashi, Stephanie M Hughes, Thomas M Wishart, Jonathan D Cooper, Michael Wong, Mark S Sands

2020-Current year OA Pubs

Cannabidiol (CBD) has gained attention as a therapeutic agent and is purported to have immunomodulatory, neuroprotective, and anti-seizure effects. Here, we determined the effects of chronic CBD administration in a mouse model of CLN1 disease (Cln1

Arab Health Promoters’ Perspectives On Religious/Cultural Challenges To Adopt Healthy Lifestyle Behaviours Among Arab Immigrants In Canada, Hussein Baharoon, Judy King

The Qualitative Report

Despite the importance of faith and cultural background in Arab immigrants’ lives, little is known about their role in preventing cardiovascular diseases. To understand the challenges among Arab immigrants related to acculturation and religiosity in adopting healthy lifestyle behaviours and managing stress, we conducted three face-to-face focus groups with 17 Arab health promoters who were members of the Canadian Arab Health Coalition. Averaging 80 minutes in length, the focus groups were conducted in Ottawa, Canada, in February and March 2018. Data were analyzed with an inductive thematic analysis approach; we identified four themes: “Culture first!”: dominant influence of home country …

Covid-19 Vaccination Drive In A Low-Volume Primary Care Clinic: Challenges & Lessons Learned In Using Homegrown Self-Scheduling Web-Based Mobile Platforms, Reita N. Agarwal, Rajesh Aggarwal, Pridhviraj Nandarapu, Hersheth Aggarwal, Ashmit Verma, Absarul Haque, Manish Tripathi

School of Medicine Publications

Background: The whole of humanity has suffered dire consequences related to the novel coronavirus disease 2019 (COVID-19). Vaccination of the world base population is considered the most promising and challenging approach to achieving herd immunity. As healthcare organizations took on the extensive task of vaccinating the entire U.S. population, digital health companies expanded their automated health platforms in order to help ease the administrative burdens of mass inoculation. Although some software companies offer free applications to large organizations, there are prohibitive costs for small clinics such as the Good Health Associates Clinic (GHAC) for integrating and implementing new self-scheduling software …

Single Cell Rna-Sequence Analyses Reveal Uniquely Expressed Genes And Heterogeneous Immune Cell Involvement In The Rat Model Of Intervertebral Disc Degeneration, Milad Rohanifar, Sade W. Clayton, Garret W.D. Easson, Deepanjali S. Patil, Frank Lee, Luifang Jing, Marcos N. Barcellona, Julie E. Speer, Jordan J. Stivers, Simon Y. Tang, Lori A. Setton

2020-Current year OA Pubs

No abstract provided.

2022-07-02_Michiganoverview_Covidsymptoms, Michigan Department Of Health & Human Services

Michigan COVID-19 Syndromic Surveillance System Data

The Syndromic Surveillance System Data report was obtained from Michigan's COVID-19 dashboard, from under the link "​Coronavirus Symptoms": https://www.michigan.gov/coronavirus/stats/coronavirus-symptoms. Data was compiled by the Michigan Department of Health and Human Services (MDHHS). The information was updated twice a week on Mondays and Thursdays.

Syndromic Surveillance System data is obtained from approximately 216 facilities participating in syndromic surveillance (139 Emergency Departments (ED), 77 Urgent Cares) across the State of Michigan. The reporting is based on individuals who present at EDs and may not be representative of the overall population. The coronavirus-like symptoms query searches visit free-text (chief complaint, triage notes, …

Multi-Scale Phase Separation By Explosive Percolation With Single-Chromatin Loop Resolution., Kaustav Sengupta, Michał Denkiewicz, Mateusz Chiliński, Teresa Szczepińska, Ayatullah Faruk Mollah, Sevastianos Korsak, Raissa D'Souza, Yijun Ruan, Dariusz Plewczynski

Faculty Research 2022

The 2 m-long human DNA is tightly intertwined into the cell nucleus of the size of 10 μm. The DNA packing is explained by folding of chromatin fiber. This folding leads to the formation of such hierarchical structures as: chromosomal territories, compartments; densely-packed genomic regions known as Topologically Associating Domains (TADs), or Chromatin Contact Domains (CCDs), and loops. We propose models of dynamical human genome folding into hierarchical components in human lymphoblastoid, stem cell, and fibroblast cell lines. Our models are based on explosive percolation theory. The chromosomes are modeled as graphs where CTCF chromatin loops are represented as edges. …

A Comparative Study On Deep Learning Models For Text Classification Of Unstructured Medical Notes With Various Levels Of Class Imbalance, Hongxia Lu, Louis Ehwerhemuepha, Cyril Rakovski

Mathematics, Physics, and Computer Science Faculty Articles and Research

Background

Discharge medical notes written by physicians contain important information about the health condition of patients. Many deep learning algorithms have been successfully applied to extract important information from unstructured medical notes data that can entail subsequent actionable results in the medical domain. This study aims to explore the model performance of various deep learning algorithms in text classification tasks on medical notes with respect to different disease class imbalance scenarios.

Methods

In this study, we employed seven artificial intelligence models, a CNN (Convolutional Neural Network), a Transformer encoder, a pretrained BERT (Bidirectional Encoder Representations from Transformers), and four typical …

Developing Standards For Cultural Competency Training For Health Care Providers To Care For Lesbian, Gay, Bisexual, Transgender, Queer, Intersex, And Asexual Persons: Consensus Recommendations From A National Panel, Mandi L. Pratt-Chapman, Kristen Eckstrand, Amorie Robinson, Lauren B. Beach, Charles Kamen, Alex S. Keuroghlian, Scott Cook, Asa Radix, Markus P. Bidell, Daniel Bruner, Liz Margolies

Publications and Research

Purpose: Lesbian, gay, bisexual, transgender, queer, intersex, and/or asexual and other sexual and gender diverse persons (LGBTQIA + or SGD persons) experience barriers to equitable health care. The purpose of this article is to describe a collaborative process that resulted in core cultural competency recommendations addressing training for those who provide health care and/or social services to LGBTQIA + patients.

Methods: In 2018 and 2019, Whitman-Walker Health, a Federally Qualified Community Health Center in Washing- ton, DC, and the National LGBT Cancer Network purposively selected leaders of community clinics and community-based organizations, cultural competency trainers, and clinicians and researchers with …