ORCID Profile
0000-0002-5400-4029
Current Organisations
Westmead Institute for Medical Research
,
Defence Science and Technology Group Melbourne
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Publisher: Elsevier BV
Date: 12-2017
Publisher: Springer Science and Business Media LLC
Date: 15-04-2019
Publisher: Springer Science and Business Media LLC
Date: 02-04-1299
Publisher: Cold Spring Harbor Laboratory
Date: 11-12-2020
DOI: 10.1101/2020.12.10.20244707
Abstract: Dysregulated immune response is a key driver of disease progression in sepsis and known to be associated with impaired cellular metabolism. This association has been studied mostly in the late stage sepsis patients. Here, we investigate whether such impairment in cellular metabolism is present in uncomplicated infection patients who do not develop sepsis. Forty sepsis (fulfilled Sepsis-3 criteria) and 27 uncomplicated infection patients were recruited from the emergency department along with 20 healthy volunteers. Whole blood was collected for measurement of gene expression, cytokine levels and cellular metabolic functions (including mitochondrial respiration, oxidative stress and apoptosis). Our analysis revealed the impairment of mitochondrial respiration in uncomplicated infection and sepsis patients (p value .05), with greater degree of impairment noted in the established sepsis. The impairment was significantly correlated with increased mitochondrial oxidative stress level the latter was increased in uncomplicated infection and more so in established sepsis patients. Further analysis revealed that the oxidative stress level correlated significantly with cytokine level (tumor necrosis factor-α) and gene expression levels (CYCS, TP53, SLC24A24 and TSPO). These findings suggest that impaired immune cell metabolism is present in infection patients without presenting sepsis, thereby opening potential window for early diagnosis and intervention (e.g. antioxidant therapy) in such patients.
Publisher: Springer Science and Business Media LLC
Date: 17-04-2018
Publisher: Springer Science and Business Media LLC
Date: 17-02-2020
DOI: 10.1186/S12920-020-0672-7
Abstract: Influenza infections produce a spectrum of disease severity, ranging from a mild respiratory illness to respiratory failure and death. The host-response pathways associated with the progression to severe influenza disease are not well understood. To gain insight into the disease mechanisms associated with progression to severe infection, we analyzed the leukocyte transcriptome in severe and moderate influenza patients and healthy control subjects. Pathway analysis on differentially expressed genes was performed using a topology-based pathway analysis tool that takes into account the interaction between multiple cellular pathways. The pathway profiles between moderate and severe influenza were then compared to delineate the biological mechanisms underpinning the progression from moderate to severe influenza. 107 patients (44 severe and 63 moderate influenza patients) and 52 healthy control subjects were included in the study. Severe influenza was associated with upregulation in several neutrophil-related pathways, including pathways involved in neutrophil differentiation, migration, degranulation and neutrophil extracellular trap (NET) formation. The degree of upregulation in neutrophil-related pathways were significantly higher in severely infected patients compared to moderately infected patients. Severe influenza was also associated with downregulation in immune response pathways, including pathways involved in antigen presentation such as CD4+ T-cell co-stimulation, CD8+ T cell and Natural Killer (NK) cells effector functions. Apoptosis pathways were also downregulated in severe influenza patients compare to moderate and healthy controls. These findings showed that there are changes in gene expression profile that may highlight distinct pathogenic mechanisms associated with progression from moderate to severe influenza infection.
Publisher: American Chemical Society (ACS)
Date: 28-02-2008
DOI: 10.1021/BI702390K
Abstract: Orotidine 5'-monophosphate (OMP) decarboxylase from Plasmodium falciparum (PfODCase, EC 4.1.1.23) has been overexpressed, purified, subjected to kinetic and biochemical analysis, and crystallized. The native enzyme is a homodimer with a subunit molecular mass of 38 kDa. The saturation curve for OMP as a substrate conformed to Michaelis-Menten kinetics with K m = 350 +/- 60 nM and V max = 2.70 +/- 0.10 micromol/min/mg protein. Inhibition patterns for nucleoside 5'-monophosphate analogues were linear competitive with respect to OMP with a decreasing potency of inhibition of PfODCase in the order: pyrazofurin 5'-monophosphate ( K i = 3.6 +/- 0.7 nM) > xanthosine 5'-monophosphate (XMP, K i = 4.4 +/- 0.7 nM) > 6-azauridine 5'-monophosphate (AzaUMP, K i = 12 +/- 3 nM) > allopurinol-3-riboside 5'-monophosphate ( K i = 240 +/- 20 nM). XMP is an approximately 150-fold more potent inhibitor of PfODCase compared with the human enzyme. The structure of PfODCase was solved in the absence of ligand and displays a classic TIM-barrel fold characteristic of the enzyme. Both the phosphate-binding loop and the betaalpha5-loop have conformational flexibility, which may be associated with substrate capture and product release along the reaction pathway.
Publisher: Springer Science and Business Media LLC
Date: 18-06-2008
DOI: 10.1007/S00216-008-2201-Y
Abstract: The aim of the present investigation was to develop a biosensor based on a quartz crystal nanobalance (QCN) for the detection of histidine (His). A thin layer of nickel was electrochemically deposited over the gold crystal electrode and exposed to H(2)O(2) to form nickel oxide. The composite electrode was then used to determine His. The frequency shifts were linear with respect to the concentration of His in solution. His can be measured in the range of 100-2000 mg L(-1). A lower limit of detection of 48 mg L(-1) and a sensitivity factor of 0.0307 Hz/mg L(-1) was obtained. Some possible interferences were checked for, and the performance of the sensor was found to be unaffected by any interference except for those from arginine, cysteine and NaH(2)PO(4). Principal component analysis (PCA) was used to process the frequency response data of the single piezoelectric crystal at various times, considering the different adsorption-desorption dynamics of His and the interfering compounds. Over 85% of the variance in the data was explained by two principal components. A score plot of the data for the first two PCs showed that the modified QCN yields favorable identification and quantification performances for His and the interfering compounds.
Publisher: Elsevier BV
Date: 09-2022
Publisher: Springer Science and Business Media LLC
Date: 31-07-2019
DOI: 10.1038/S41467-019-11249-Y
Abstract: Severe influenza infection has no effective treatment available. One of the key barriers to developing host-directed therapy is a lack of reliable prognostic factors needed to guide such therapy. Here, we use a network analysis approach to identify host factors associated with severe influenza and fatal outcome. In influenza patients with moderate-to-severe diseases, we uncover a complex landscape of immunological pathways, with the main changes occurring in pathways related to circulating neutrophils. Patients with severe disease display excessive neutrophil extracellular traps formation, neutrophil-inflammation and delayed apoptosis, all of which have been associated with fatal outcome in animal models. Excessive neutrophil activation correlates with worsening oxygenation impairment and predicted fatal outcome (AUROC 0.817–0.898). These findings provide new evidence that neutrophil-dominated host response is associated with poor outcomes. Measuring neutrophil-related changes may improve risk stratification and patient selection, a critical first step in developing host-directed immune therapy.
Publisher: Elsevier BV
Date: 2017
Publisher: Springer Science and Business Media LLC
Date: 03-2018
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 11-2013
Publisher: Frontiers Media SA
Date: 20-01-2023
DOI: 10.3389/FIMMU.2022.1043219
Abstract: Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Infected in iduals display a wide spectrum of disease severity, as defined by the World Health Organization (WHO). One of the main factors underlying this heterogeneity is the host immune response, with severe COVID-19 often associated with a hyperinflammatory state. Our current study aimed to pinpoint the specific genes and pathways underlying differences in the disease spectrum and outcomes observed, through in-depth analyses of whole blood transcriptomics in a large cohort of COVID-19 participants. All WHO severity levels were well represented and mild and severe disease displaying distinct gene expression profiles. WHO severity levels 1-4 were grouped as mild disease, and signatures from these participants were different from those with WHO severity levels 6-9 classified as severe disease. Severity level 5 (moderate cases) presented a unique transitional gene signature between severity levels 2-4 (mild/moderate) and 6-9 (severe) and hence might represent the turning point for better or worse disease outcome. Gene expression changes are very distinct when comparing mild/moderate or severe cases to healthy controls. In particular, we demonstrated the hallmark down-regulation of adaptive immune response pathways and activation of neutrophil pathways in severe compared to mild/moderate cases, as well as activation of blood coagulation pathways. Our data revealed discrete gene signatures associated with mild, moderate, and severe COVID-19 identifying valuable candidates for future biomarker discovery.
Publisher: Springer Science and Business Media LLC
Date: 15-09-2016
DOI: 10.1038/NCOMMS12757
Abstract: Cirrhosis likely shares common pathophysiological pathways despite arising from a variety of liver diseases. A recent GWAS identified rs641738, a polymorphism in the MBOAT7 locus, as being associated with the development of alcoholic cirrhosis. Here we explore the role of this variant on liver inflammation and fibrosis in two cohorts of patients with chronic hepatitis C. In 2,051 patients, rs641738 associated with severe hepatic inflammation and increased risk of fibrosis, as well as fast fibrosis progression. At functional level, rs641738 associated with MBOAT7 transcript and protein levels in liver and blood, and with serum inflammatory, oxidative stress and macrophage activation markers. MBOAT7 was expressed in immune cell subsets, implying a role in hepatic inflammation. We conclude that the MBOAT7 rs641738 polymorphism is a novel risk variant for liver inflammation in hepatitis C, and thereby for liver fibrosis.
Publisher: Frontiers Media SA
Date: 05-01-2023
DOI: 10.3389/FIMMU.2022.1060438
Abstract: Robust biomarkers that predict disease outcomes amongst COVID-19 patients are necessary for both patient triage and resource prioritisation. Numerous candidate biomarkers have been proposed for COVID-19. However, at present, there is no consensus on the best diagnostic approach to predict outcomes in infected patients. Moreover, it is not clear whether such tools would apply to other potentially pandemic pathogens and therefore of use as stockpile for future pandemic preparedness. We conducted a multi-cohort observational study to investigate the biology and the prognostic role of interferon alpha-inducible protein 27 ( IFI27 ) in COVID-19 patients. We show that IFI27 is expressed in the respiratory tract of COVID-19 patients and elevated IFI27 expression in the lower respiratory tract is associated with the presence of a high viral load. We further demonstrate that the systemic host response, as measured by blood IFI27 expression, is associated with COVID-19 infection. For clinical outcome prediction (e.g., respiratory failure), IFI27 expression displays a high sensitivity (0.95) and specificity (0.83), outperforming other known predictors of COVID-19 outcomes. Furthermore, IFI27 is upregulated in the blood of infected patients in response to other respiratory viruses. For ex le, in the pandemic H1N1/09 influenza virus infection, IFI27- like genes were highly upregulated in the blood s les of severely infected patients. These data suggest that prognostic biomarkers targeting the family of IFI27 genes could potentially supplement conventional diagnostic tools in future virus pandemics, independent of whether such pandemics are caused by a coronavirus, an influenza virus or another as yet-to-be discovered respiratory virus.
Publisher: Royal Society of Chemistry (RSC)
Date: 2014
DOI: 10.1039/C4RA00802B
Publisher: European Respiratory Society (ERS)
Date: 06-2017
DOI: 10.1183/13993003.02098-2016
Abstract: Host response biomarkers can accurately distinguish between influenza and bacterial infection. However, published biomarkers require the measurement of many genes, thereby making it difficult to implement them in clinical practice. This study aims to identify a single-gene biomarker with a high diagnostic accuracy equivalent to multi-gene biomarkers. In this study, we combined an integrated genomic analysis of 1071 in iduals with in vitro experiments using well-established infection models. We identified a single-gene biomarker, IFI27 , which had a high prediction accuracy (91%) equivalent to that obtained by multi-gene biomarkers. In vitro studies showed that IFI27 was upregulated by TLR7 in plasmacytoid dendritic cells, antigen-presenting cells that responded to influenza virus rather than bacteria. In vivo studies confirmed that IFI27 was expressed in influenza patients but not in bacterial infection, as demonstrated in multiple patient cohorts (n=521). In a large prospective study (n=439) of patients presented with undifferentiated respiratory illness (aetiologies included viral, bacterial and non-infectious conditions), IFI27 displayed 88% diagnostic accuracy (AUC) and 90% specificity in discriminating between influenza and bacterial infections. IFI27 represents a significant step forward in overcoming a translational barrier in applying genomic assay in clinical setting its implementation may improve the diagnosis and management of respiratory infection.
Publisher: Springer International Publishing
Date: 2016
Publisher: Elsevier BV
Date: 05-2021
Publisher: Elsevier
Date: 2016
Publisher: Springer Science and Business Media LLC
Date: 17-12-2008
DOI: 10.1007/S12010-008-8464-0
Abstract: Homovanillic acid (HVA) and vanillylmandelic acid (VMA) were selectively determined by quartz crystal nanobalance sensor in conjunction with net analyte signal (NAS)-based method called HLA/GO. An orthogonal design was applied for the formation of calibration and prediction sets including HVA, VMA, and some common and structurally similar urine compounds. The selection of the optimal time range involved the calculation of the NAS regression plot in any considered time window for each test s le. The searching of a region with maximum linearity of NAS regression plot (minimum error indicator) and minimum of predicted error sum of squares value was carried out by applying a moving window strategy. Based on the obtained results, the differences on the adsorption profiles in the time range between 1 and 300 s were used to determine mixtures of compounds by HLA/GO method. Several figures of merit like selectivity, sensitivity, analytical sensitivity, and limit of detection were calculated for both compounds. The results showed that the method was successfully applied for the determination of VMA and HVA.
Publisher: Informa UK Limited
Date: 26-12-2017
Publisher: Informa UK Limited
Date: 07-2010
DOI: 10.1080/10934529.2010.486345
Abstract: Quartz crystal nanobalance (QCN) sensors are considered as powerful mass sensitive sensors to determine materials in the sub-nanogram level. In the first part of this study, a single piezoelectric QCN modified with polypyrrole (PPy) has been tested for detection and determination of nickel ions in the solution at room temperature. The developed method was successfully applied for detection of total nickel in s les taken from several hot springs located at the Northwest of Iran. The frequency shifts were linear with respect to the concentration of nickel in solution. Using this method, nickel can be measured in the range of 3-20 mg L(-1). A lower limit of detection of 0.79 mg L(-1) and a sensitivity factor of 4.429 Hz/mg L(-1) were obtained. Some possible interference such as heavy metal ions (lead, mercury, and cadmium) was checked. No major interference was observed with the performance of the sensor except for mercury. To evaluate the ability of the PPy-modified QCN in discriminating between nickel ions and interfering mercury ions, a principal component analysis (PCA) was carried out. PCA was utilized to process the frequency response data of the single piezoelectric crystal at different times, considering different adsorption-desorption dynamics of nickel and interfering mercury ions on electrode. Using PCA, it was found that about 97.90% of the data variance could still be explained by two principal components (PC1 and PC2). The score plot of the data for the first two PCs showed that the PPy-modified QCN yields favorable identification and quantification performances for nickel ions. The accuracy of method for hot spring s les was evaluated and RSD of 4.10% was obtained.
Publisher: IOP Publishing
Date: 17-06-2004
Publisher: American Association for the Advancement of Science (AAAS)
Date: 11-11-2022
Abstract: Knowledge of the mechanisms underpinning the development of protective immunity conferred by mRNA vaccines is fragmentary. Here, we investigated responses to coronavirus disease 2019 (COVID-19) mRNA vaccination via high–temporal resolution blood transcriptome profiling. The first vaccine dose elicited modest interferon and adaptive immune responses, which peaked on days 2 and 5, respectively. The second vaccine dose, in contrast, elicited sharp day 1 interferon, inflammation, and erythroid cell responses, followed by a day 5 plasmablast response. Both post-first and post-second dose interferon signatures were associated with the subsequent development of antibody responses. Yet, we observed distinct interferon response patterns after each of the doses that may reflect quantitative or qualitative differences in interferon induction. Distinct interferon response phenotypes were also observed in patients with COVID-19 and were associated with severity and differences in duration of intensive care. Together, this study also highlights the benefits of adopting high-frequency s ling protocols in profiling vaccine-elicited immune responses.
Publisher: Springer Science and Business Media LLC
Date: 10-2008
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 08-2014
Publisher: Elsevier BV
Date: 09-2014
Publisher: Scientific Research Publishing, Inc.
Date: 2009
Publisher: American Chemical Society (ACS)
Date: 19-05-2006
DOI: 10.1021/BI0604025
Abstract: In the pyrimidine biosynthetic pathway, N-carbamyl-L-aspartate (CA-asp) is converted to L-dihydroorotate (DHO) by dihydroorotase (DHOase). The mechanism of this important reaction was probed using primary and secondary 15N and 13C isotope effects on the ring opening of DHO using isotope ratio mass spectrometry (IRMS). The reaction was performed at three different temperatures (25, 37, and 45 degrees C for hamster DHOase 37, 50, and 60 degrees C for Bacillus caldolyticus), and the product CA-asp was purified for analysis. The primary and secondary kinetic isotope effects for the ring opening of the DHO were determined from analysis of the N and C of the carbamyl group after hydrolysis. In addition, the beta-carboxyl of the residual aspartate was liberated enzymatically by transamination to oxaloacetate with aspartate aminotransferase and then decarboxylation with oxaloacetate decarboxylase. The 13C/12C ratio from the released CO2 was determined by IRMS, yielding a second primary isotope effect. The primary and secondary isotope effects for the reaction catalyzed by DHOase showed little variation between enzymes or temperatures, the primary 13C and 15N isotope effects being approximately 1% on average, while the secondary 13C isotope effect is negligible or very slightly normal (>1.0000). These data indicate that the chemistry is at least partially rate-limiting while the secondary isotope effects suggest that the transition state may have lost some bending and torsional modes leading to a slight lessening of bond stiffness at the carbonyl carbon of the amide of CA-asp. The equilibrium isotope effects for DHO --> CA-asp have also been measured (secondary 13K(eq) = 1.0028 +/- 0.0002, primary 13K(eq) = 1.0053 +/- 0.0003, primary 15K(eq) = 1.0027 +/- 0.0003). Using these equilibrium isotope effects, the kinetic isotope effects for the physiological reaction (CA-asp --> DHO) have been calculated. These values indicate that the carbon of the amide group is more stiffly bonded in DHO while the slightly lesser, but still normal, values of the primary kinetic isotope effect show that the chemistry remains at least partially rate-limiting for the physiological reaction. It appears that the ring opening and closing is the slow step of the reaction.
Publisher: Elsevier BV
Date: 12-2013
DOI: 10.1016/J.COLSURFB.2013.07.069
Abstract: Coronary artery disease (CAD) is still the leading cause of death throughout the world. Metal stents are used to widen narrowed arteries. In addition, drug-eluting stents (DES) are widely implanted to decrease the risk of in-stent restenosis. Commercially available polymer-based DES suffer from some limitations. To avoid these drawbacks, the use of self-assembled monolayers (SAMs) in DES has recently been investigated. In this study, methyl- and carboxyl-terminated mixed SAMs on gold (Au) surfaces were successfully prepared. The s les were characterized using scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), Fourier transform infrared spectroscopy (FTIR), and contact angle goniometry (CA). The mixed SAM-coated surfaces were evaluated for everolimus delivery. The drug release in PBS was studied using high performance liquid chromatography (HPLC) and quartz crystal nanobalance (QCN). The results were compared with those related to homogenous SAM-coated surfaces. Significant differences (p<0.05) were found in the amount of drug eluted between the mixed SAM and the homogenous one. The findings are promising for the application of mixed SAMs in DES.
Publisher: Informa UK Limited
Date: 31-12-2004
Publisher: Wiley
Date: 08-02-2023
DOI: 10.1111/ECI.13957
Abstract: Indiscriminate use of antimicrobials and antimicrobial resistance is a public health threat. IMX‐BVN‐1, a 29‐host mRNA classifier, provides two separate scores that predict likelihoods of bacterial and viral infections in patients with suspected acute infections. We validated the performance of IMX‐BVN‐1 in adults attending acute health care settings with suspected influenza. We lified 29‐host response genes in RNA extracted from blood by NanoString nCounter. IMX‐BVN‐1 calculated two scores to predict probabilities of bacterial and viral infections. Results were compared against the infection status (no infection highly probable ossible infection confirmed infection) determined by clinical adjudication. Amongst 602 adult patients (74.9% ED, 16.9% ICU, 8.1% outpatients), 7.6% showed in‐hospital mortality and 15.5% immunosuppression. Median IMX‐BVN‐1 bacterial and viral scores were higher in patients with confirmed bacterial (0.27) and viral (0.62) infections than in those without bacterial (0.08) or viral (0.21) infection, respectively. The AUROC distinguishing bacterial from nonbacterial illness was 0.81 and 0.87 when distinguishing viral from nonviral illness. The bacterial top quartile's positive likelihood ratio (LR) was 4.38 with a rule‐in specificity of 88% the bacterial bottom quartile's negative LR was 0.13 with a rule‐out sensitivity of 96%. Similarly, the viral top quartile showed an infinite LR with rule‐in specificity of 100% the viral bottom quartile had a LR of 0.22 and a rule‐out sensitivity of 85%. IMX‐BVN‐1 showed high accuracy for differentiating bacterial and viral infections from noninfectious illness in patients with suspected influenza. Clinical utility of IMX‐BVN will be validated following integration into a point of care system.
Publisher: BMJ
Date: 2021
DOI: 10.1136/BMJOPEN-2020-044497
Abstract: Accurate triage is an important first step to effectively manage the clinical treatment of severe cases in a pandemic outbreak. In the current COVID-19 global pandemic, there is a lack of reliable clinical tools to assist clinicians to perform accurate triage. Host response biomarkers have recently shown promise in risk stratification of disease progression however, the role of these biomarkers in predicting disease progression in patients with COVID-19 is unknown. Here, we present a protocol outlining a prospective validation study to evaluate the biomarkers’ performance in predicting clinical outcomes of patients with COVID-19. This prospective validation study assesses patients infected with COVID-19, in whom blood s les are prospectively collected. Recruited patients include a range of infection severity from asymptomatic to critically ill patients, recruited from the community, outpatient clinics, emergency departments and hospitals. Study s les consist of peripheral blood s les collected into RNA-preserving (PAXgene/Tempus) tubes on patient presentation or immediately on study enrolment. Real-time PCR (RT-PCR) will be performed on total RNA extracted from collected blood s les using primers specific to host response gene expression biomarkers that have been previously identified in studies of respiratory viral infections. The RT-PCR data will be analysed to assess the diagnostic performance of in idual biomarkers in predicting COVID-19-related outcomes, such as viral pneumonia, acute respiratory distress syndrome or bacterial pneumonia. Biomarker performance will be evaluated using sensitivity, specificity, positive and negative predictive values, likelihood ratios and area under the receiver operating characteristic curve. This research protocol aims to study the host response gene expression biomarkers in severe respiratory viral infections with a pandemic potential (COVID-19). It has been approved by the local ethics committee with approval number 2020/ETH00886. The results of this project will be disseminated in international peer-reviewed scientific journals.
Publisher: Elsevier BV
Date: 09-2017
Publisher: Royal Society of Chemistry (RSC)
Date: 2014
DOI: 10.1039/C3RA46157B
Publisher: Trans Tech Publications, Ltd.
Date: 03-2014
DOI: 10.4028/WWW.SCIENTIFIC.NET/AMR.891-892.594
Abstract: Marine composite structures subject to dynamic loading typically incorporate more than one material type, and consist of laminate sections up to hundreds of millimetres in thickness. These solid hybrid laminates exhibit different behaviour in static and fatigue loading from thin aerospace composite laminates and sandwich structures. There is therefore a need to better understand the likely damage and degradation mechanisms that will occur in these thick structures and to concurrently develop nondestructive evaluation (NDE) technology to meet the consequent inspection problems. In this paper we present details of an ongoing fatigue program on marine composite blades. The challenges for ultrasonic NDE of thick composites, and emerging inspection methods using state-of-the-art inspection systems and analysis tools will be discussed.
Publisher: Cold Spring Harbor Laboratory
Date: 08-12-2020
DOI: 10.1101/2020.12.07.20230235
Abstract: Determining the severity of COVID-19 remains an unmet medical need. Our objective was to develop a blood-based host-gene-expression classifier for the severity of viral infections and validate it in independent data, including COVID-19. We developed the classifier for the severity of viral infections and validated it in multiple viral infection settings including COVID-19. We used training data (N=705) from 21 retrospective transcriptomic clinical studies of influenza and other viral illnesses looking at a preselected panel of host immune response messenger RNAs. We selected 6 host RNAs and trained logistic regression classifier with a cross-validation area under curve of 0.90 for predicting 30-day mortality in viral illnesses. Next, in 1,417 s les across 21 independent retrospective cohorts the locked 6-RNA classifier had an area under curve of 0.91 for discriminating patients with severe vs. non-severe infection. Next, in independent cohorts of prospectively (N=97) and retrospectively (N=100) enrolled patients with confirmed COVID-19, the classifier had an area under curve of 0.89 and 0.87, respectively, for identifying patients with severe respiratory failure or 30-day mortality. Finally, we developed a loop-mediated isothermal gene expression assay for the 6-messenger-RNA panel to facilitate implementation as a rapid assay. With further study, the classifier could assist in the risk assessment of COVID-19 and other acute viral infections patients to determine severity and level of care, thereby improving patient management and reducing healthcare burden.
Publisher: MDPI AG
Date: 28-01-2023
DOI: 10.3390/IJMS24032524
Abstract: Patients with preexisting metabolic disorders such as diabetes are at a higher risk of developing severe coronavirus disease 2019 (COVID-19). Mitochondrion, the very organelle that controls cellular metabolism, holds the key to understanding disease progression at the cellular level. Our current study aimed to understand how cellular metabolism contributes to COVID-19 outcomes. Metacore pathway enrichment analyses on differentially expressed genes (encoded by both mitochondrial and nuclear deoxyribonucleic acid (DNA)) involved in cellular metabolism, regulation of mitochondrial respiration and organization, and apoptosis, was performed on RNA sequencing (RNASeq) data from blood s les collected from healthy controls and patients with mild/moderate or severe COVID-19. Genes from the enriched pathways were analyzed by network analysis to uncover interactions among them and up- or downstream genes within each pathway. Compared to the mild/moderate COVID-19, the upregulation of a myriad of growth factor and cell cycle signaling pathways, with concomitant downregulation of interferon signaling pathways, were observed in the severe group. Matrix metallopeptidase 9 (MMP9) was found in five of the top 10 upregulated pathways, indicating its potential as therapeutic target against COVID-19. In summary, our data demonstrates aberrant activation of endocrine signaling in severe COVID-19, and its implication in immune and metabolic dysfunction.
Publisher: Springer Science and Business Media LLC
Date: 27-02-2021
DOI: 10.1186/S13104-021-05488-W
Abstract: Hospitalized patients who presented within the last 24 h with a bacterial infection were recruited. Participants were assigned into sepsis and uncomplicated infection groups. In addition, healthy volunteers were recruited as controls. RNA was prepared from whole blood, depleted from beta-globin mRNA and sequenced. This dataset represents a highly valuable resource to better understand the biology of sepsis and to identify biomarkers for severe sepsis in humans. The data presented here consists of raw and processed transcriptome data obtained by next generation RNA sequencing from 105 peripheral blood s les from patients with uncomplicated infections, patients who developed sepsis, septic shock patients, and healthy controls. It is provided as raw sequenced reads and as normalized log 2 transformed relative expression levels. This data will allow performing detailed analyses of gene expression changes between uncomplicated infections and sepsis patients, such as identification of differentially expressed genes, co-regulated modules as well as pathway activation studies.
Publisher: Trans Tech Publications, Ltd.
Date: 06-2010
DOI: 10.4028/WWW.SCIENTIFIC.NET/MSF.654-656.2079
Abstract: This paper overviews some recent S& T innovations in smart materials and structures at the Australian Defence Science and Technology Organisation (DSTO) under a Corporate Enabling Research Program (CERP) on Signatures, Materials and Energy. The CERP program includes development and transitioning of technology across the maritime, air and land domains, with the major focus of the smart materials program component being to increase the safety, availability and maintainability of Defence assets. Three specific ex les are provided of the smart materials and structures program, ranging across the spectrum of technology readiness from new concept phase to technology transitioning, viz.: (i) Advances in smart sensing for prognostics-based platform management (ii) Fabrication of nanostructured and ultrafine grained materials through top-down severe plastic deformation processing of bulk materials (iii) Innovative application of carbon nanotubes/conducting polymers as artificial muscles for low-power propulsion and control of small autonomous underwater systems. In each case, the DSTO effort is underpinned by strong university or industry linkages to deliver challenging interdisciplinary S& T.
No related grants have been discovered for maryam shojaei.