Publications by authors named "Noursadeghi M"

Blood transcriptional biomarkers of acute viral infections typically reflect type 1 interferon (IFN) signalling, but it is not known whether there are biological differences in their regulation that can be leveraged for distinct translational applications. We use high frequency sampling in the SARS-CoV-2 human challenge model to show induction of IFN-stimulated gene (ISG) expression with different temporal and cellular profiles. MX1 gene expression correlates with a rapid and transient wave of ISG expression across all cell types, which may precede PCR detection of replicative infection.

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Multisystem inflammatory syndrome in children (MIS-C) is a rare condition following SARS-CoV-2 infection associated with intestinal manifestations. Genetic predisposition, including inborn errors of the OAS-RNAseL pathway, has been reported. We sequenced 154 MIS-C patients and utilized a novel statistical framework of gene burden analysis, "burdenMC," which identified an enrichment for rare predicted-deleterious variants in BTNL8 (OR = 4.

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  • Dilated cardiomyopathy (DCM) is a major cause of heart failure, and this study analyzes genetic factors by examining 14,256 DCM cases and 36,203 participants from the UK Biobank for related traits.
  • Researchers discovered 80 genomic risk loci and pinpointed 62 potential effector genes tied to DCM, including some linked to rare variants.
  • The study uses advanced transcriptomics to explore how cellular functions contribute to DCM, showing that polygenic scores can help predict the disease in the general population and emphasize the importance of genetic testing and development of precise treatments.
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Background: Concerted efforts aim to reduce the burden of 6 months of anti-tuberculous treatment for tuberculosis (TB). Treatment cessation at 8 weeks is effective for most but incurs increased risk of disease relapse. We tested the hypothesis that blood RNA signatures or C-reactive protein (CRP) measurements discriminate 8-week sputum culture status, as a prerequisite for a biomarker to stratify risk of relapse following treatment cessation at this time-point.

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Background: Limited data are available on the diagnostic accuracy of blood RNA biomarker signatures for extrapulmonary TB (EPTB). We addressed this question among people investigated for TB lymphadenitis and TB pericarditis, in Cape Town, South Africa.

Methods: We enrolled 440 consecutive adults referred to a hospital for invasive sampling for presumptive TB lymphadenitis (n=300) or presumptive TB pericarditis (n=140).

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  • The study investigates early cellular responses to SARS-CoV-2 infection using single-cell profiling in individuals with no prior immunity to the virus.
  • Significant changes in cell types and immune responses were observed over time, indicating different patterns of infection severity, especially in nasopharyngeal regions.
  • Key findings suggest that early interferon responses and specific immune cell behaviors, like high expression of HLA-DQA2, could be crucial in preventing sustained infections, while a novel computational tool, Cell2TCR, enhanced the analysis of T cell responses.
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  • Tuberculosis is a leading global health threat, necessitating new treatment strategies due to rising antibiotic resistance.
  • The pseudokinase Tribbles1 (Trib1) plays a critical role in regulating macrophage functions and inflammation, making it a promising target for new therapies against infections like tuberculosis.
  • Research using a zebrafish model revealed that overexpressing Trib1 provides significant protection against mycobacterial infection, suggesting that increasing Trib1 levels in macrophages could enhance immune responses and improve treatment outcomes for tuberculosis.
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Background: Persistent radiological lung abnormalities are evident in many survivors of acute coronavirus disease 2019 (COVID-19). Consolidation and ground glass opacities are interpreted to indicate subacute inflammation whereas reticulation is thought to reflect fibrosis. We sought to identify differences at molecular and cellular level, in the local immunopathology of post-COVID inflammation and fibrosis.

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Background: Undiagnosed tuberculosis remains a major threat for people living with HIV. Multiple blood transcriptomic biomarkers have shown promise for tuberculosis diagnosis. We sought to evaluate their diagnostic accuracy and clinical utility for systematic pre-antiretroviral therapy (ART) tuberculosis screening.

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Background: Tuberculosis, a major cause of death in people living with HIV, remains challenging to diagnose. Diagnostic accuracy data are scarce for promising triage and confirmatory tests such as C-reactive protein (CRP), sputum and urine Xpert MTB/RIF Ultra (Xpert Ultra), and urine Determine TB LAM Ag (a lateral flow lipoarabinomannan [LF-LAM] test), without symptom selection. We evaluated novel triage and confirmatory tests in ambulatory people with HIV initiating antiretroviral therapy (ART).

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  • The study investigates whether abnormal immune responses during acute SARS-CoV-2 infection contribute to Long Covid symptoms.
  • Researchers analyzed immune responses in 86 healthcare workers with mild or asymptomatic infections, focusing on antibody and T cell responses over time.
  • Findings indicate no significant differences in immune responses between individuals with persistent symptoms and those without, suggesting that immune response variations are unlikely to cause Long Covid.
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Background: Undiagnosed tuberculosis (TB) remains a major threat for people living with HIV (PLHIV). Multiple blood transcriptomic biomarkers have shown promise for TB diagnosis. We sought to evaluate their diagnostic accuracy and clinical utility for systematic pre-antiretroviral therapy (ART) TB screening.

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Background: Tuberculosis (TB), a major cause of death in people living with HIV (PLHIV), remains challenging to diagnose. Diagnostic accuracy data are lacking for promising triage tests, such as C-reactive protein (CRP), and confirmatory tests, such as sputum and urine Xpert MTB/RIF Ultra (Ultra), and urine LAM, without prior symptom selection.

Methods: 897 PLHIV initiating antiretroviral therapy were consecutively recruited in settings with high TB incidence, irrespective of symptoms.

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Background: The World Health Organization (WHO) recommends that outpatient people living with HIV (PLHIV) undergo tuberculosis screening with the WHO four-symptom screen (W4SS) or C-reactive protein (CRP) (5 mg·L cut-off) followed by confirmatory testing if screen positive. We conducted an individual participant data meta-analysis to determine the performance of WHO-recommended screening tools and two newly developed clinical prediction models (CPMs).

Methods: Following a systematic review, we identified studies that recruited adult outpatient PLHIV irrespective of tuberculosis signs and symptoms or with a positive W4SS, evaluated CRP and collected sputum for culture.

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T cell responses precede antibody and may provide early control of infection. We analyzed the clonal basis of this rapid response following SARS-COV-2 infection. We applied T cell receptor (TCR) sequencing to define the trajectories of individual T cell clones immediately.

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  • Over 1,000 unexplained pediatric hepatitis cases have been identified globally, with a study focusing on 38 cases and various control groups to understand potential viral causes.
  • High levels of adeno-associated virus 2 (AAV2) DNA were found in most cases, while low levels of adenovirus and human herpesvirus 6B were also detected; however, AAV2 appeared infrequently in healthy controls even when they were immunocompromised.
  • The study suggests that abnormal replication of AAV2, potentially influenced by other viruses like HAdV and HHV-6B, may be responsible for immune-related liver disease in susceptible children.
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  • The liver is constantly exposed to bacterial products from the gut but usually maintains a tolerant state; understanding how this tolerance can shift to immunity or pathology is crucial for improving liver disease treatments.
  • A specific type of T cell, called CD14CD8 T cells, is found in high numbers in the liver, particularly in liver transplants and conditions like cirrhosis, and they show unique activation and immunomodulatory capabilities.
  • These CD14CD8 T cells can be influenced by bacterial components and local tissue signals, enhancing their ability to interact with the environment and potentially improve anti-tumor and antiviral responses.
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(SPN) is a globally significant cause of meningitis, the pathophysiology of which involves damage to the brain by both bacterial virulence factors and the host inflammatory response. In most cases of SPN meningitis bacteria translocate from the blood into the central nervous system (CNS). The principal site of SPN translocation into the CNS is not known, with possible portals of entry proposed to be the cerebral or meningeal blood vessels or the choroid plexus.

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Host-response profiles can discriminate different infections. A new 8-gene blood RNA signature to discriminate bacterial and viral infections extends our focus hitherto on the case mix from the US and Europe to include that of low- and middle-income countries. Challenges remain.

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Background: Identification of an accurate, low-cost triage test for pulmonary TB among people presenting to healthcare facilities is an urgent global research priority. We assessed the diagnostic accuracy and clinical utility of C-reactive protein (CRP) for TB triage among symptomatic adult outpatients, irrespective of HIV status.

Methods: We prospectively enrolled adults reporting at least one (for people with HIV) or two (for people without HIV) symptoms of cough, fever, night sweats, or weight loss at two TB clinics in Cape Town, South Africa.

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  • A study analyzed the plasma proteome of 156 healthcare workers in the UK who had SARS-CoV-2 infections during the first wave, focusing on the relationship between the plasma proteins and the severity/duration of symptoms.
  • The researchers tracked 91 specific proteins before and after infection, finding that changes in the plasma proteome lasted up to 6 weeks post-infection and were linked to symptom severity and antibody responses.
  • Results indicated that specific protein changes were associated with persistent symptoms even 12 months later, suggesting these plasma proteome alterations could help understand the long-term effects of COVID-19.
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