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Article ; Online: Serology versus nucleic acid amplification to diagnose acute hepatitis E, United Kingdom, 2014-18.

Skittrall, Jordan P / Jalal, Hamid

2022 Volume 85, Issue 3, Page(s) 327–333

Abstract: Objectives: Diagnosing hepatitis E infection usually involves specific IgM testing, but sensitivity/specificity concerns mean many guidelines and practices include confirmatory tests. We studied whether additional information confirmatory tests provide ... ...

Abstract	Objectives: Diagnosing hepatitis E infection usually involves specific IgM testing, but sensitivity/specificity concerns mean many guidelines and practices include confirmatory tests. We studied whether additional information confirmatory tests provide justifies their use. Methods: We examined 9131 records of anti-hepatitis E IgM assays, 7615 of IgG assays, and 1726 of RT-PCR assays from our regional laboratory, spanning October 2014-October 2018. We paired 495 IgM assay results with a RT-PCR result. We examined whether IgM results predicted PCR results, reviewed discrepant pairs, and investigated the correlation between IgG and PCR results in patients with strongly reactive IgM assays. Results: Anti-hepatitis E IgM titres are bimodal. A high cut-off value optimises prediction of RNA detectability. 7/404 low-IgM samples had detectable RNA, 6 from immunosuppressed patients. 26/91 high-IgM samples did not have detectable RNA. In high-IgM samples, RNA detectability was not associated with IgG titre (one-tailed Mann-Whitney U test, p = 0.14). Conclusions: In immunocompetent patients, tests beyond IgM seldom add clinically useful information. In patients with immunocompromise, IgM and RNA could contribute information. Additional tests' extra costs/intervention delays cannot be justified. IgM assay cut-offs should reflect titres' bimodal distribution, with values standardised using international units.
MeSH term(s)	Hepatitis Antibodies ; Hepatitis E/diagnosis ; Hepatitis E virus/genetics ; Humans ; Immunoglobulin G ; Immunoglobulin M ; Nucleic Acids ; RNA ; RNA, Viral
Chemical Substances	Hepatitis Antibodies ; Immunoglobulin G ; Immunoglobulin M ; Nucleic Acids ; RNA, Viral ; RNA (63231-63-0)
Language	English
Publishing date	2022-06-23
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	424417-5
ISSN	1532-2742 ; 0163-4453
ISSN (online)	1532-2742
ISSN	0163-4453
DOI	10.1016/j.jinf.2022.06.017
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Article: Evolution of transient RNA structure-RNA polymerase interactions in respiratory RNA virus genomes.

Rigby, Charlotte / Sabsay, Kimberly / Bisht, Karishma / Eggink, Dirk / Jalal, Hamid / Te Velthuis, Aartjan J W

bioRxiv : the preprint server for biology

2023

Abstract: RNA viruses are important human pathogens that cause seasonal epidemics and occasional pandemics. Examples are influenza A viruses (IAV) and coronaviruses (CoV). When emerging IAV and CoV spill over to humans, they adapt to evade immune responses and ... ...

Abstract	RNA viruses are important human pathogens that cause seasonal epidemics and occasional pandemics. Examples are influenza A viruses (IAV) and coronaviruses (CoV). When emerging IAV and CoV spill over to humans, they adapt to evade immune responses and optimize their replication and spread in human cells. In IAV, adaptation occurs in all viral proteins, including the viral ribonucleoprotein (RNP) complex. RNPs consists of a copy of the viral RNA polymerase, a double-helical coil of nucleoprotein, and one of the eight segments of the IAV RNA genome. The RNA segments and their transcripts are partially structured to coordinate the packaging of the viral genome and modulate viral mRNA translation. In addition, RNA structures can affect the efficiency of viral RNA synthesis and the activation of host innate immune response. Here, we investigated if RNA structures that modulate IAV replication processivity, so called template loops (t-loops), vary during the adaptation of pandemic and emerging IAV to humans. Using cell culture-based replication assays and
Language	English
Publishing date	2023-08-02
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.05.25.542331
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Article: Evolution of transient RNA structure-RNA polymerase interactions in respiratory RNA virus genomes.

Rigby, Charlotte V / Sabsay, Kimberly R / Bisht, Karishma / Eggink, Dirk / Jalal, Hamid / Te Velthuis, Aartjan J W

Virus evolution

2023 Volume 9, Issue 2, Page(s) vead056

Abstract	RNA viruses are important human pathogens that cause seasonal epidemics and occasional pandemics. Examples are influenza A viruses (IAV) and coronaviruses (CoV). When emerging IAV and CoV spill over to humans, they adapt to evade immune responses and optimize their replication and spread in human cells. In IAV, adaptation occurs in all viral proteins, including the viral ribonucleoprotein (RNP) complex. RNPs consist of a copy of the viral RNA polymerase, a double-helical coil of nucleoprotein, and one of the eight segments of the IAV RNA genome. The RNA segments and their transcripts are partially structured to coordinate the packaging of the viral genome and modulate viral mRNA translation. In addition, RNA structures can affect the efficiency of viral RNA synthesis and the activation of host innate immune response. Here, we investigated if RNA structures that modulate IAV replication processivity, so-called template loops (t-loops), vary during the adaptation of pandemic and emerging IAV to humans. Using cell culture-based replication assays and
Language	English
Publishing date	2023-08-26
Publishing country	England
Document type	Journal Article
ZDB-ID	2818949-8
ISSN	2057-1577
ISSN	2057-1577
DOI	10.1093/ve/vead056
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Article: Quantification of influenza virus mini viral RNA dynamics using Cas13.

Lamb, Caitlin / Pitre, Emmanuelle / Elshina, Elizaveta / Rigby, Charlotte / Bisht, Karishma / Oade, Michael S / Jalal, Hamid / Myhrvold, Cameron / Te Velthuis, Aartjan J W

bioRxiv : the preprint server for biology

2024

Abstract: Influenza A virus RNA synthesis produces full-length and aberrant RNA molecules, which include defective viral genomes (DVG) and mini viral RNAs (mvRNA). Sequencing approaches have shown that aberrant RNA species may be present during infection, and that ...

Abstract	Influenza A virus RNA synthesis produces full-length and aberrant RNA molecules, which include defective viral genomes (DVG) and mini viral RNAs (mvRNA). Sequencing approaches have shown that aberrant RNA species may be present during infection, and that they can vary in size, segment origin, and sequence. Moreover, a subset of aberrant RNA molecules can bind and activate host pathogen receptor retinoic acid-inducible gene I (RIG-I), leading to innate immune signaling and the expression of type I and III interferons. Understanding the kinetics and distribution of these immunostimulatory aberrant RNA sequences is important for understanding their function in IAV infection. Here, we use an amplification-free LbuCas13a-based detection method to quantify mvRNA amplification dynamics and subcellular distributions. We show that our assay can quantify the copy numbers of specific mvRNA sequences in infected tissue culture cells, ferret upper and lower respiratory tract tissue infected with two different pandemic H1N1 IAV strains, or clinical nasopharyngeal swab extracts of hospitalized patients infected with seasonal H1N1 or H3N2 strains. In addition, we find dynamic differences between immunostimulatory and non-immunostimulatory mvRNAs, as well as among mvRNAs derived from different segments, during IAV infection. Overall, our results reveal a hitherto hidden diversity in the behavior of IAV mvRNAs and suggest that individual aberrant RNAs are not produced stochastically.
Language	English
Publishing date	2024-05-02
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.11.03.565460
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Article ; Online: Waste tire rubber and pozzolans in concrete: A trade-off between cleaner production and mechanical properties in a greener concrete

Jalal, Mostafa / Nassir, Navid / Jalal, Hamid

Journal of cleaner production 2019 Nov. 20, v. 238, p. 117882

2019 , Page(s) 117882

Abstract: This study presents a cleaner production of a concrete by incorporating waste rubber chips and pozzolans to make a greener concrete through partial replacement of aggregates and cement. For this purpose, aggregate was replace by 10 and 15% by graded ... ...

Abstract	This study presents a cleaner production of a concrete by incorporating waste rubber chips and pozzolans to make a greener concrete through partial replacement of aggregates and cement. For this purpose, aggregate was replace by 10 and 15% by graded waste rubber (RB) and cement was partially replaced by pozzolans, namely silica fume (SF) and zeolite (ZE) by 10%. Fresh and hardened properties of the concrete was investigated through slump, compressive strength and elasticity modulus. The effect of RB, SF and ZE addition on fresh properties was assessed which indicated 5% and 14.6% slump reduction for 10% and 15% rubber replacement, 4% increase due to SF addition, and 4% decrease as a result of ZE addition. The microstructure of the pozzolans was also investigated using SEM micrographs. Compressive strengths of the samples were measured at different ages of 3, 7, 28, and 42 days and compared with ACI 318 equation in order to modify the coefficients for the greener concrete. Elasticity moduli of the concrete mixes were determined according to ASTM C469. The results indicated that 10% and 15% rubber replacement led to 30% and 50% strength drop, respectively. The corresponding reduction in elastic modulus was observed as 14% and 32%. The elastic modulus was also estimated using relationships presented in different standards based on compressive strength. It was found that ACI 318 relationship underestimates the elastic modulus for which the correction factors were determined. Three different regression models namely Linear, Logarithmic, and Power were also developed in order to predict the compressive strength of greener concrete. Power regression with R2 = 0.92 proved to be more powerful among other assessed regression models.
Keywords	Greener concrete ; Cleaner product ; Waste tire rubber ; Pozzolans ; Mechanical properties ; Strength prediction
Language	English
Dates of publication	2019-1120
Size	p. 117882
Publishing place	Elsevier Ltd
Document type	Article ; Online
Note	Resource is Open Access ; Consyn License Information
ISSN	0959-6526
DOI	10.1016/j.jclepro.2019.117882
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: In vitro sensitivity of human parainfluenza 3 clinical isolates to ribavirin, favipiravir and zanamivir.

Smielewska, Anna / Emmott, Edward / Goodfellow, Ian / Jalal, Hamid

Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology

2018 Volume 102, Page(s) 19–26

Abstract: Background: Human parainfluenza type 3 (HPIV3) is an important respiratory pathogen. Although a number of potential therapeutic candidates exist, there is currently no licensed therapy or vaccine. Ribavirin (RBV), favipiravir (FVP) and zanamivir (ZNV) ... ...

Abstract	Background: Human parainfluenza type 3 (HPIV3) is an important respiratory pathogen. Although a number of potential therapeutic candidates exist, there is currently no licensed therapy or vaccine. Ribavirin (RBV), favipiravir (FVP) and zanamivir (ZNV) are inhibitors with proven activity against influenza and with potential inhibitory activity against HPIV3 laboratory adapted strains in vitro. Objectives: To evaluate RBV, FVP and ZNV as inhibitors of minimally passaged UK clinical strains of HPIV3 as well as a laboratory adapted strain MK9 in vitro. Study design: The inhibitory action of RBV, FVP and ZNV was evaluated against nine minimally passaged clinical strains and a laboratory adapted strain MK9 using plaque reduction and growth curve inhibition in a cell culture model. Results: Clinical isolates were found to be at least as susceptible as the laboratory adapted strains to RBV and FVP and significantly more susceptible to ZNV. However the inhibitory concentrations achieved by ZNV against clinical strains remain prohibitively high in vivo. Conclusions: RBV, FVP and ZNV were found to be effective inhibitors of HPIV3 in vitro. The lack of efficacy of RBV in vivo may be due to inability to reach required therapeutic levels. FVP, on the other hand, is a good potential therapeutic agent against HPIV3. Further studies using wild type clinical strains, as well as better formulation and delivery mechanisms may improve the utility of these three inhibitors.
MeSH term(s)	Amides/pharmacology ; Antiviral Agents/pharmacology ; Cell Line, Tumor ; Cytopathogenic Effect, Viral/drug effects ; Humans ; Parainfluenza Virus 3, Human/drug effects ; Parainfluenza Virus 3, Human/physiology ; Pyrazines/pharmacology ; Respirovirus Infections/virology ; Ribavirin/pharmacology ; Virus Attachment/drug effects ; Virus Replication/drug effects ; Zanamivir/pharmacology
Chemical Substances	Amides ; Antiviral Agents ; Pyrazines ; Ribavirin (49717AWG6K) ; favipiravir (EW5GL2X7E0) ; Zanamivir (L6O3XI777I)
Language	English
Publishing date	2018-02-15
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1446080-4
ISSN	1873-5967 ; 1386-6532
ISSN (online)	1873-5967
ISSN	1386-6532
DOI	10.1016/j.jcv.2018.02.009
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Zs.A 3790: Show issues

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Article: Behavior assessment, regression analysis and support vector machine (SVM) modeling of waste tire rubberized concrete

Jalal, Mostafa / Arabali, Poura / Grasley, Zachary / Bullard, Jeffrey W / Jalal, Hamid

Journal of cleaner production. 2020 Nov. 10, v. 273

2020

Abstract: An experimental study was undertaken to assess the properties of rubberized concrete made by recycled tire rubber. Mechanical tests were carried out and the ultrasonic technique was also used to measure the acoustic properties of the rubberized concrete, ...

Abstract	An experimental study was undertaken to assess the properties of rubberized concrete made by recycled tire rubber. Mechanical tests were carried out and the ultrasonic technique was also used to measure the acoustic properties of the rubberized concrete, such as wave velocity, and the relationships between the mechanical properties and pulse velocity for different mixtures were investigated. Then, based on the experimental data, a thorough strength modeling was performed using regression analysis and support-vector machine (SVM) technique. To develop the predictive models for strength behavior of the recycled rubber concrete, a comprehensive regression analyses including ANOVA, t-test and F-test were conducted, and the significance of the influencing variables was determined. Then, several regression models by incorporating different combinations of the variables were developed and compared. Finally, the SVM method as a machine-learning technique was utilized to develop several models by using different kernel functions, optimization algorithms, and hyperparameters optimization to predict the compressive strength of the recycled rubber concrete. The results obtained were compared with those of regression models and it was found that SVM outperforms all the regression models assessed in this study.
Keywords	acoustic properties ; compression strength ; concrete ; construction technology ; mechanical properties ; mechanical testing ; models ; regression analysis ; rubber ; support vector machines ; t-test ; tires ; ultrasonics ; wastes
Language	English
Dates of publication	2020-1110
Publishing place	Elsevier Ltd
Document type	Article
ISSN	0959-6526
DOI	10.1016/j.jclepro.2020.122960
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Evolution of transient RNA structure-RNA polymerase interactions in respiratory RNA virus genomes

Rigby, Charlotte V / Sabsay, Kimberly R / Bisht, Karishma / Eggink, Dirk / Jalal, Hamid / te Velthuis, Aartjan J.W.

bioRxiv

Abstract	RNA viruses are important human pathogens that cause seasonal epidemics and occasional pandemics. Examples are influenza A viruses (IAV) and coronaviruses (CoV). When emerging IAV and CoV spill over to humans, they adapt to evade immune responses and optimize their replication and spread in human cells. In IAV, adaptation occurs in all viral proteins, including the viral ribonucleoprotein (RNP) complex. RNPs consists of a copy of the viral RNA polymerase, a double-helical coil of nucleoprotein, and one of the eight segments of the IAV RNA genome. The RNA segments and their transcripts are partially structured to coordinate the packaging of the viral genome and modulate viral mRNA translation. In addition, RNA structures can affect the efficiency of viral RNA synthesis and the activation of host innate immune response. Here, we investigated if RNA structures that modulate IAV replication processivity, so called template loops (t-loops), vary during the adaptation of pandemic and emerging IAV to humans. Using cell culture-based replication assays and in silico sequence analyses, we find that the sensitivity of the IAV H3N2 RNA polymerase to t-loops increased between isolates from 1968 and 2017, whereas the total free energy of t-loops in the IAV H3N2 genome was reduced. This reduction is particularly prominent in the PB1 gene. In H1N1 IAV, we find two separate reductions in t-loop free energy, one following the 1918 pandemic and one following the 2009 pandemic. No destabilization of t-loops is observed in the IBV genome, whereas analysis of SARS-CoV-2 isolates reveals destabilization of viral RNA structures. Overall, we propose that a loss of free energy in the RNA genome of emerging respiratory RNA viruses may contribute to the adaption of these viruses to the human population.
Keywords	covid19
Language	English
Publishing date	2023-05-26
Publisher	Cold Spring Harbor Laboratory
Document type	Article ; Online
DOI	10.1101/2023.05.25.542331
Database	COVID19

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Article ; Online: Adenovirus pseudo-outbreak in a large UK neonatal intensive care unit.

Jones, Nick K / Ranellou, Kyriaki / Zhang, Hongyi / Jalal, Hamid

American journal of infection control

2018 Volume 46, Issue 12, Page(s) 1411–1413

Abstract: An unusually high number of positive adenovirus stool antigen tests were observed in neonatal samples from a large tertiary referral unit over a 10-week period, prompting the declaration of an outbreak and escalation of infection control precautions. ... ...

Abstract	An unusually high number of positive adenovirus stool antigen tests were observed in neonatal samples from a large tertiary referral unit over a 10-week period, prompting the declaration of an outbreak and escalation of infection control precautions. Subsequent testing of original samples by alternative methods revealed a series of false-positive results. This is the first adenovirus pseudo-outbreak to be reported in the United Kingdom and the first to involve the Proflow Rotavirus-Adenovirus Combi test.
MeSH term(s)	Adenoviruses, Human/isolation & purification ; Diarrhea/diagnosis ; Diarrhea/virology ; False Positive Reactions ; Feces/virology ; Female ; Humans ; Infant ; Infant, Newborn ; Infection Control ; Intensive Care Units, Neonatal ; Male ; Polymerase Chain Reaction/methods ; United Kingdom
Language	English
Publishing date	2018-05-21
Publishing country	United States
Document type	Journal Article
ZDB-ID	392362-9
ISSN	1527-3296 ; 0196-6553
ISSN (online)	1527-3296
ISSN	0196-6553
DOI	10.1016/j.ajic.2018.04.220
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Zs.A 1773: Show issues

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Article ; Online: Streamlining SARS-CoV-2 confirmatory testing to reduce false positive results.

Wilson, Michael J / Sparkes, Dominic / Myers, Chloe / Smielewska, Anna A / Husain, Mir Mubariz / Smith, Christopher / Rolfe, Kathryn J / Zhang, Hongyi / Jalal, Hamid

Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology

2021 Volume 136, Page(s) 104762

Abstract: Background: Confirmatory testing of SARS-CoV-2 results is essential to reduce false positives, but comes at a cost of significant extra workload for laboratories and increased turnaround time. A balance must be sought. We analysed our confirmatory ... ...

Abstract	Background: Confirmatory testing of SARS-CoV-2 results is essential to reduce false positives, but comes at a cost of significant extra workload for laboratories and increased turnaround time. A balance must be sought. We analysed our confirmatory testing pathway to produce a more refined approach in preparation for rising case numbers. Methods: Over a 10-week low prevalence period we performed confirmatory testing on all newly positive results. Turnaround time was measured and results were analysed to identify a threshold that could be applied as a cut-off for future confirmatory testing and reduce overall workload for the laboratory. Results: Between 22/06/20 and 31/08/20 confirmatory testing was performed on 108 newly positive samples, identifying 32 false positive results (30 %). Turnaround time doubled, increasing by an extra 17 h. There was a highly statistically significant difference between initial Relative Light Unit (RLU) of results that confirmed compared to those that did not, 1176 vs 721 (P < 0.00001). RLU = 1000 was identified as a suitable threshold for confirmatory testing in our laboratory: with RLU ≥ 1000, 55/56 (98 %) confirmed as positive, whereas with RLU < 1000 only 12/38 (32 %) confirmed. Conclusions: False positive SARS-CoV-2 tests can be identified by confirmatory testing, yet this may significantly delay results. Establishing a threshold for confirmatory testing streamlines this process to focus only on samples where it is most required. We advise all laboratories to follow a similar process to identify thresholds that trigger confirmatory testing for their own assays, increasing accuracy while maintaining efficiency for when case numbers are high.
MeSH term(s)	COVID-19/diagnosis ; COVID-19 Testing/methods ; False Negative Reactions ; False Positive Reactions ; Humans ; Real-Time Polymerase Chain Reaction/methods ; SARS-CoV-2/isolation & purification ; Sensitivity and Specificity
Language	English
Publishing date	2021-02-11
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1446080-4
ISSN	1873-5967 ; 1386-6532
ISSN (online)	1873-5967
ISSN	1386-6532
DOI	10.1016/j.jcv.2021.104762
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