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Article ; Online: Digging Deeper Into Hepatitis C Virus Outbreaks.

Olmstead, Andrea D

2016 Volume 213, Issue 6, Page(s) 880–882

MeSH term(s)	Disease Outbreaks ; Genetic Linkage ; Hepacivirus/genetics ; Hepacivirus/isolation & purification ; Hepatitis C/transmission ; Hepatitis C/virology ; Humans
Language	English
Publishing date	2016-03-15
Publishing country	United States
Document type	Comment ; Editorial
ZDB-ID	3019-3
ISSN	1537-6613 ; 0022-1899
ISSN (online)	1537-6613
ISSN	0022-1899
DOI	10.1093/infdis/jiv543
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Article: Photodynamic and Contact Killing Polymeric Fabric Coating for Bacteria and SARS-CoV-2

Wright, Taylor / Vlok, Marli / Shapira, Tirosh / Olmstead, Andrea D. / Jean, François / Wolf, Michael O.

ACS applied materials & interfaces. 2022 Jan. 03, v. 14, no. 1

2022

Abstract: The development of low-cost, non-toxic, scalable antimicrobial textiles is needed to address the spread of deadly pathogens. Here, we report a polysiloxane textile coating that possesses two modes of antimicrobial inactivation, passive contact ... ...

Abstract	The development of low-cost, non-toxic, scalable antimicrobial textiles is needed to address the spread of deadly pathogens. Here, we report a polysiloxane textile coating that possesses two modes of antimicrobial inactivation, passive contact inactivation through amine/imine functionalities and active photodynamic inactivation through the generation of reactive oxygen species (ROS). This material can be coated and cross-linked onto natural and synthetic textiles through a simple soak procedure, followed by UV cure to afford materials exhibiting no aqueous leaching and only minimal leaching in organic solvents. This coating minimally impacts the mechanical properties of the fabric while also imparting hydrophobicity. Passive inactivation of Escherichia coli (E. coli) and methicillin-resistant Staphylococcus aureus (MRSA) is achieved with >98% inactivation after 24 h, with a 23× and 3× inactivation rate increase against E. coli and MRSA, respectively, when green light is used to generate ROS. Up to 90% decrease in the infectivity of SARS-CoV-2 after 2 h of irradiated incubation with the material is demonstrated. These results show that modifying textiles with dual-functional polymers results in robust and highly antimicrobial materials that are expected to find widespread use in combating the spread of deadly pathogens.
Keywords	Escherichia coli ; Severe acute respiratory syndrome coronavirus 2 ; crosslinking ; fabrics ; green light ; hydrophobicity ; imines ; irradiation ; methicillin-resistant Staphylococcus aureus ; pathogenicity ; reactive oxygen species ; siloxanes
Language	English
Dates of publication	2022-0103
Size	p. 49-56.
Publishing place	American Chemical Society
Document type	Article
ISSN	1944-8252
DOI	10.1021/acsami.1c14178
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Photodynamic and Contact Killing Polymeric Fabric Coating for Bacteria and SARS-CoV-2.

Wright, Taylor / Vlok, Marli / Shapira, Tirosh / Olmstead, Andrea D / Jean, François / Wolf, Michael O

ACS applied materials & interfaces

2022 Volume 14, Issue 1, Page(s) 49–56

Abstract	The development of low-cost, non-toxic, scalable antimicrobial textiles is needed to address the spread of deadly pathogens. Here, we report a polysiloxane textile coating that possesses two modes of antimicrobial inactivation, passive contact inactivation through amine/imine functionalities and active photodynamic inactivation through the generation of reactive oxygen species (ROS). This material can be coated and cross-linked onto natural and synthetic textiles through a simple soak procedure, followed by UV cure to afford materials exhibiting no aqueous leaching and only minimal leaching in organic solvents. This coating minimally impacts the mechanical properties of the fabric while also imparting hydrophobicity. Passive inactivation of
MeSH term(s)	Anti-Infective Agents/chemistry ; Anti-Infective Agents/pharmacology ; Bacteria/drug effects ; COVID-19/prevention & control ; COVID-19/virology ; Coated Materials, Biocompatible/chemistry ; Coated Materials, Biocompatible/pharmacology ; Escherichia coli/drug effects ; Humans ; Methicillin-Resistant Staphylococcus aureus/drug effects ; Photochemotherapy/methods ; Polymers/chemistry ; Reactive Oxygen Species/metabolism ; SARS-CoV-2/drug effects ; SARS-CoV-2/isolation & purification ; Textiles/analysis ; Textiles/toxicity ; Ultraviolet Rays
Chemical Substances	Anti-Infective Agents ; Coated Materials, Biocompatible ; Polymers ; Reactive Oxygen Species
Language	English
Publishing date	2022-01-03
Publishing country	United States
Document type	Journal Article
ISSN	1944-8252
ISSN (online)	1944-8252
DOI	10.1021/acsami.1c14178
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: DEEMD: Drug Efficacy Estimation Against SARS-CoV-2 Based on Cell Morphology With Deep Multiple Instance Learning.

Saberian, M Sadegh / Moriarty, Kathleen P / Olmstead, Andrea D / Hallgrimson, Christian / Jean, Francois / Nabi, Ivan R / Libbrecht, Maxwell W / Hamarneh, Ghassan

IEEE transactions on medical imaging

2022 Volume 41, Issue 11, Page(s) 3128–3145

Abstract: Drug repurposing can accelerate the identification of effective compounds for clinical use against SARS-CoV-2, with the advantage of pre-existing clinical safety data and an established supply chain. RNA viruses such as SARS-CoV-2 manipulate cellular ... ...

Abstract	Drug repurposing can accelerate the identification of effective compounds for clinical use against SARS-CoV-2, with the advantage of pre-existing clinical safety data and an established supply chain. RNA viruses such as SARS-CoV-2 manipulate cellular pathways and induce reorganization of subcellular structures to support their life cycle. These morphological changes can be quantified using bioimaging techniques. In this work, we developed DEEMD: a computational pipeline using deep neural network models within a multiple instance learning framework, to identify putative treatments effective against SARS-CoV-2 based on morphological analysis of the publicly available RxRx19a dataset. This dataset consists of fluorescence microscopy images of SARS-CoV-2 non-infected cells and infected cells, with and without drug treatment. DEEMD first extracts discriminative morphological features to generate cell morphological profiles from the non-infected and infected cells. These morphological profiles are then used in a statistical model to estimate the applied treatment efficacy on infected cells based on similarities to non-infected cells. DEEMD is capable of localizing infected cells via weak supervision without any expensive pixel-level annotations. DEEMD identifies known SARS-CoV-2 inhibitors, such as Remdesivir and Aloxistatin, supporting the validity of our approach. DEEMD can be explored for use on other emerging viruses and datasets to rapidly identify candidate antiviral treatments in the future. Our implementation is available online at https://www.github.com/Sadegh-Saberian/DEEMD.
MeSH term(s)	Humans ; SARS-CoV-2 ; COVID-19 ; Antiviral Agents/pharmacology ; Antiviral Agents/chemistry ; Antiviral Agents/metabolism
Chemical Substances	Antiviral Agents
Language	English
Publishing date	2022-10-27
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	622531-7
ISSN	1558-254X ; 0278-0062
ISSN (online)	1558-254X
ISSN	0278-0062
DOI	10.1109/TMI.2022.3178523
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Article ; Online: Hijacking of Lipid Droplets by Hepatitis C, Dengue and Zika Viruses-From Viral Protein Moonlighting to Extracellular Release.

Cloherty, Alexandra P M / Olmstead, Andrea D / Ribeiro, Carla M S / Jean, François

International journal of molecular sciences

2020 Volume 21, Issue 21

Abstract: Hijacking and manipulation of host cell biosynthetic pathways by human enveloped viruses are essential for the viral lifecycle. ...

Abstract	Hijacking and manipulation of host cell biosynthetic pathways by human enveloped viruses are essential for the viral lifecycle.
MeSH term(s)	Animals ; Autophagy ; Cell Nucleus/metabolism ; Dengue Virus/metabolism ; Dengue Virus/pathogenicity ; Extracellular Space/metabolism ; Flaviviridae/metabolism ; Flaviviridae/pathogenicity ; Hepacivirus/metabolism ; Hepacivirus/pathogenicity ; Humans ; Lipid Droplets/metabolism ; Lipid Droplets/virology ; Viral Proteins/metabolism ; Zika Virus/metabolism ; Zika Virus/pathogenicity
Chemical Substances	Viral Proteins
Keywords	covid19
Language	English
Publishing date	2020-10-24
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms21217901
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Article ; Online: Characterizing Longitudinal Antibody Responses in Recovered Individuals Following COVID-19 Infection and Single-Dose Vaccination: A Prospective Cohort Study.

Olmstead, Andrea D / Nikiforuk, Aidan M / Schwartz, Sydney / Márquez, Ana Citlali / Valadbeigy, Tahereh / Flores, Eri / Saran, Monika / Goldfarb, David M / Hayden, Althea / Masud, Shazia / Russell, Shannon L / Prystajecky, Natalie / Jassem, Agatha N / Morshed, Muhammad / Sekirov, Inna

Viruses

2022 Volume 14, Issue 11

Abstract: Background: Investigating antibody titers in individuals who have been both naturally infected with SARS-CoV-2 and vaccinated can provide insight into antibody dynamics and correlates of protection over time.: Methods: Human coronavirus (HCoV) IgG ... ...

Abstract	Background: Investigating antibody titers in individuals who have been both naturally infected with SARS-CoV-2 and vaccinated can provide insight into antibody dynamics and correlates of protection over time. Methods: Human coronavirus (HCoV) IgG antibodies were measured longitudinally in a prospective cohort of qPCR-confirmed, COVID-19 recovered individuals (k = 57) in British Columbia pre- and post-vaccination. SARS-CoV-2 and endemic HCoV antibodies were measured in serum collected between Nov. 2020 and Sept. 2021 (n = 341). Primary analysis used a linear mixed-effects model to understand the effect of single dose vaccination on antibody concentrations adjusting for biological sex, age, time from infection and vaccination. Secondary analysis investigated the cumulative incidence of high SARS-CoV-2 anti-spike IgG seroreactivity equal to or greater than 5.5 log10 AU/mL up to 105 days post-vaccination. No re-infections were detected in vaccinated participants, post-vaccination by qPCR performed on self-collected nasopharyngeal specimens. Results: Bivariate analysis (complete data for 42 participants, 270 samples over 472 days) found SARS-CoV-2 spike and RBD antibodies increased 14-56 days post-vaccination ( Conclusions: Our study confirms that vaccination post-SARS-CoV-2 infection provides multiple benefits, such as increasing anti-spike IgG titers and preventing decay up to 85 days post-vaccination.
MeSH term(s)	Humans ; COVID-19/prevention & control ; Antibody Formation ; SARS-CoV-2 ; Prospective Studies ; COVID-19 Vaccines ; Antibodies, Viral ; Vaccination ; Immunoglobulin G
Chemical Substances	COVID-19 Vaccines ; Antibodies, Viral ; Immunoglobulin G
Language	English
Publishing date	2022-10-31
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v14112416
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Article ; Online: Intra-host evolutionary dynamics of the hepatitis C virus among people who inject drugs.

Montoya, Vincent / Howe, Anita Y M / Dong, Weiyan Y / Dong, Winnie / Brumme, Chanson J / Olmstead, Andrea D / Hayashi, Kanna / Richard Harrigan, P / Joy, Jeffrey B

Scientific reports

2021 Volume 11, Issue 1, Page(s) 9986

Abstract: Most individuals chronically infected with hepatitis C virus (HCV) are asymptomatic during the initial stages of infection and therefore the precise timing of infection is often unknown. Retrospective estimation of infection duration would improve ... ...

Abstract	Most individuals chronically infected with hepatitis C virus (HCV) are asymptomatic during the initial stages of infection and therefore the precise timing of infection is often unknown. Retrospective estimation of infection duration would improve existing surveillance data and help guide treatment. While intra-host viral diversity quantifications such as Shannon entropy have previously been utilized for estimating duration of infection, these studies characterize the viral population from only a relatively short segment of the HCV genome. In this study intra-host diversities were examined across the HCV genome in order to identify the region most reflective of time and the degree to which these estimates are influenced by high-risk activities including those associated with HCV acquisition. Shannon diversities were calculated for all regions of HCV from 78 longitudinally sampled individuals with known seroconversion timeframes. While the region of the HCV genome most accurately reflecting time resided within the NS3 gene, the gene region with the highest capacity to differentiate acute from chronic infections was identified within the NS5b region. Multivariate models predicting duration of infection from viral diversity significantly improved upon incorporation of variables associated with recent public, unsupervised drug use. These results could assist the development of strategic population treatment guidelines for high-risk individuals infected with HCV and offer insights into variables associated with a likelihood of transmission.
MeSH term(s)	Drug Users ; Genetic Variation ; Genome, Viral ; Hepacivirus/genetics ; Hepatitis C/virology ; Humans ; Linear Models ; Prospective Studies
Language	English
Publishing date	2021-05-11
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-021-88132-8
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Article ; Online: Treatment-Induced Viral Cure of Hepatitis C Virus-Infected Patients Involves a Dynamic Interplay among three Important Molecular Players in Lipid Homeostasis: Circulating microRNA (miR)-24, miR-223, and Proprotein Convertase Subtilisin/Kexin Type 9.

Hyrina, Anastasia / Olmstead, Andrea D / Steven, Paul / Krajden, Mel / Tam, Edward / Jean, François

EBioMedicine

2017 Volume 23, Page(s) 68–78

Abstract: In patients with chronic hepatitis C virus (HCV) infection, viral hijacking of the host-cell biosynthetic pathways is associated with altered lipid metabolism, which contributes to disease progression and may influence antiviral response. We investigated ...

Abstract	In patients with chronic hepatitis C virus (HCV) infection, viral hijacking of the host-cell biosynthetic pathways is associated with altered lipid metabolism, which contributes to disease progression and may influence antiviral response. We investigated the molecular interplay among four key regulators of lipid homeostasis [microRNA (miR)-122, miR-24, miR-223, and proprotein convertase subtilisin/kexin type 9 (PCSK9)] in HCV-infected patients (n=72) who achieved a treatment-based viral cure after interferon-based therapy with first-generation direct-acting antivirals. Real-time PCR was used to quantify microRNA plasma levels, and ELISA assays were used to determine plasma concentrations of PCSK9. We report that levels of miR-24 and miR-223 significantly increased in patients achieving sustained virologic response (SVR), whereas the levels of miR-122, a liver-specific cofactor for HCV infection, decreased in these patients. PCSK9 concentrations were significantly increased in SVRs, suggesting that PCSK9 may help impede viral infection. The modulatory effect of PCSK9 on HCV infection was also demonstrated in the context of HCV-infected Huh-7.5.1 cells employing recombinant human PCSK9 mutants. Together, these results provide insights into a novel coordinated interplay among three important molecular players in lipid homeostasis - circulating miR-24, miR-223 and PCSK9 - whose regulation is affected by HCV infection and treatment-based viral cure.
Language	English
Publishing date	2017-09
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2851331-9
ISSN	2352-3964
ISSN (online)	2352-3964
DOI	10.1016/j.ebiom.2017.08.020
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Book ; Online: DEEMD

Saberian, M. Sadegh / Moriarty, Kathleen P. / Olmstead, Andrea D. / Hallgrimson, Christian / Jean, François / Nabi, Ivan R. / Libbrecht, Maxwell W. / Hamarneh, Ghassan

Drug Efficacy Estimation against SARS-CoV-2 based on cell Morphology with Deep multiple instance learning

2021

Abstract	Drug repurposing can accelerate the identification of effective compounds for clinical use against SARS-CoV-2, with the advantage of pre-existing clinical safety data and an established supply chain. RNA viruses such as SARS-CoV-2 manipulate cellular pathways and induce reorganization of subcellular structures to support their life cycle. These morphological changes can be quantified using bioimaging techniques. In this work, we developed DEEMD: a computational pipeline using deep neural network models within a multiple instance learning framework, to identify putative treatments effective against SARS-CoV-2 based on morphological analysis of the publicly available RxRx19a dataset. This dataset consists of fluorescence microscopy images of SARS-CoV-2 non-infected cells and infected cells, with and without drug treatment. DEEMD first extracts discriminative morphological features to generate cell morphological profiles from the non-infected and infected cells. These morphological profiles are then used in a statistical model to estimate the applied treatment efficacy on infected cells based on similarities to non-infected cells. DEEMD is capable of localizing infected cells via weak supervision without any expensive pixel-level annotations. DEEMD identifies known SARS-CoV-2 inhibitors, such as Remdesivir and Aloxistatin, supporting the validity of our approach. DEEMD can be explored for use on other emerging viruses and datasets to rapidly identify candidate antiviral treatments in the future}. Our implementation is available online at https://www.github.com/Sadegh-Saberian/DEEMD
Keywords	Computer Science - Machine Learning ; Computer Science - Computer Vision and Pattern Recognition ; Quantitative Biology - Quantitative Methods
Subject code	004
Publishing date	2021-05-10
Publishing country	us
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Development and validation of a real-time, reverse transcription PCR assay for rapid and low-cost genotyping of hepatitis C virus genotypes 1a, 1b, 2, and 3a

Olmstead, Andrea D / Tracy D. Lee / Ron Chow / Kingsley Gunadasa / Brian Auk / Mel Krajden / Agatha N. Jassem

Journal of virological methods. 2017 June, v. 244

2017

Abstract: Hepatitis C virus (HCV) infection affects millions of people and leads to liver fibrosis, cirrhosis, and hepatocellular carcinoma. Treatment regimen selection requires HCV genotype (Gt) and Gt 1 subtype determination. Use of a laboratory developed, ... ...

Abstract	Hepatitis C virus (HCV) infection affects millions of people and leads to liver fibrosis, cirrhosis, and hepatocellular carcinoma. Treatment regimen selection requires HCV genotype (Gt) and Gt 1 subtype determination. Use of a laboratory developed, reverse transcription (RT)-PCR assay was explored as a low-cost, high-throughput screening approach for the major HCV genotypes and subtypes in North America. A commercial line probe assay (LiPA) was used for comparison. Sequencing and/or an alternative PCR assay were used for discordant analyses. Testing of 155 clinical samples revealed that a paired, duplex real-time RT-PCR assay that targets Gts 1a and 3a in one reaction and Gts 1b and 2 in another had 95% overall sensitivity and individual Gt sensitivity and specificity of 98â100% and 85â98%, respectively. The RT-PCR assay detected mixed HCV Gts in clinical and spiked samples and no false-positive reactions occurred with rare Gts 3b, 4, 5, or 6. Implementation of the RT-PCR assay, with some reflex LiPA testing, would cost only a small portion of the cost of using LiPA alone, and can also save 1.5h of hands-on time. The use of a laboratory developed RT-PCR assay for HCV genotyping has the potential to reduce cost and labour burdens in high-volume testing settings.
Keywords	Hepatitis C virus ; cost effectiveness ; false positive results ; genotype ; genotyping ; hepatoma ; labor ; liver cirrhosis ; people ; quantitative polymerase chain reaction ; reverse transcriptase polymerase chain reaction ; reverse transcription ; screening ; North America
Language	English
Dates of publication	2017-06
Size	p. 17-22.
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	8013-5
ISSN	1879-0984 ; 0166-0934
ISSN (online)	1879-0984
ISSN	0166-0934
DOI	10.1016/j.jviromet.2017.02.009
Database	NAL-Catalogue (AGRICOLA)

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