GBMdeconvoluteR accurately infers proportions of neoplastic and immune cell populations from bulk glioblastoma transcriptomics data

alexandrossfakianakis shared this article with you from Inoreader GBMdeconvoluteR accurately infers proportions of neoplastic and immune cell populations from bulk glioblastoma transcriptomics data via Neuro-Oncology Advance Access Abstract Background Characterising and quantifying cell types within glioblastoma (GBM) tumours at scale will facilitate a better understanding of the association between the cellular landscape and tumour phenotypes or clinical correlates. We aimed to develop a tool that deconvolutes immune and neoplastic cells within the GBM tumour microenvironment from bulk RNA sequencing data. Methods We developed an IDH wild-type (IDHwt) GBM-specific single immune cell reference consisting of B cells, T cells, NK cells, microglia, tumour associated macrophages, monocytes, mast and DC cells. We used this alongside an existing neoplastic single cell-type reference for astrocyte-like, oligodendrocyte- and neuronal-progenitor like and mesenchymal GBM cancer cells to create both marker and gene signature matrix-based deconvolution tools. We applied single-cell resolution imaging mass cytometry (IMC) to ten IDHwt GBM samples, five paired primary and recur rent tumours, to determine which deconvolution approach performed best. Results Marker based deconvolution using GBM tissue specific markers was most accurate for both immune cells and cancer cells, so we packaged this approach as GBMdeconvoluteR. We applied GBMdeconvoluteR to bulk GBM RNAseq data from The Cancer Genome Atlas and recapitulated recent findings from multi-omics single cell studies with regards associations between mesenchymal GBM cancer cells and both lymphoid and myeloid cells. Furthermore, we expanded upon this to show that these associations are stronger in patients with worse prognosis. Conclusions GBMdeconvoluteR accurately quantifies immune and neoplastic cell proportions in IDHwt GBM bulk RNA sequencing data and is accessible here: https : // gbmdeconvoluter.leeds.ac.uk View on Web

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Vitamin D levels in the assessment of Crohn's disease activity and their relation to nutritional status and inflammation

alexandrossfakianakis shared this article with you from Inoreader Vitamin D levels in the assessment of Crohn's disease activity and their relation to nutritional status and inflammation via Journal of Human Nutrition and Dietetics Abstract Background Crohn's disease (CD) is frequently associated with malnutrition, inflammation, and a deficiency of vitamin D (VD) with the relationships between these symptoms being poorly defined. Vitamin D is a modulator of the immune system and is associated with the onset of CD and disease activity. The level of serum VD may have potential in the assessment of CD activity. This study aimed to evaluate the relationships between VD, nutritional status, and inflammation, and to identify more accurate VD thresholds. Methods The study included 76 outpatients with CD diagnosed between October 2018 and October 2020 and 76 healthy volunteers. Levels of serum 25(OH)D and nutritional indicators, as well as biochemical and disease activity assessments were conducted. Results Patients with CD and healthy participants were found to differ significantly in their 25(OH)D levels as well in levels of nutritional and inflammatory indicators. The optimal VD cut-off value was found to be 46.81 nmol/L for CD development and 35.32 nmol/L for disease activity. Levels of 25(OH)D were correlated with both nutritional status and inflammation. Conclusions The VD level is likely to be a useful additional tool in the evaluation of CD patients and predicting the disease activity and clinical response. The VD level may relate both to the nutritional status and levels of inflammation in CD patients, as well as disease progression. This article is protected by copyright. All rights reserved. View on Web

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Impact of air pollutants on influenza−like illness outpatient visits under COVID−19 pandemic in the sub−center of Beijing, China

alexandrossfakianakis shared this article with you from Inoreader Impact of air pollutants on influenza−like illness outpatient visits under COVID−19 pandemic in the sub−center of Beijing, China via Journal of Medical Virology Abstract Objective This study aimed to explore the association between air pollutants and outpatient visits for influenza−like illnesses (ILI) under the coronavirus disease 2019 (COVID−19) stage in the sub−center of Beijing. Methods The data on ILI in the sub−center of Beijing from 1 January 2018 to 31 December 2020 were obtained from the Beijing Influenza Surveillance Network. A generalized additive Poisson model was applied to examine the associations between the concentrations of air pollutants and daily outpatient visits for ILI when controlling meteorological factors and temporal trend. Results A total of 171,943 ILI patients were included. In the pre−COVID−19 stage, an increased risk of ILI outpatient visits was associated to a high air quality index (AQI) and the high concentrations of particulate matter less than 2.5 (PM2.5), particulate matter 10 (PM10), sulphur dioxide (SO2), nitrogen dioxide (NO2), and carbon monoxide (CO), and a low concentration of ozone (O3) on lag0 day and lag1 day, while a higher increased risk of ILI outpatient visits was observed by the air pollutants in the COVID−19 stage on lag0 day. Except for PM10，the concentrations of other air pollutants on lag1 day were not significantly associated with an increased risk of ILI outpatient visits during the COVID−19 stage. Conclusion The findings that air pollutants had enhanced immediate effects and diminished lag-effects on the risk of ILI outpatient visits during the COVID−19 pandemic, which is important for the development of public health and environmental governance strategies. This article is protected by copyright. All rights reserved. View on Web

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Torque teno virus (TTV): a gentle spy virus of immune status, predictive marker of seroconversion to COVID‐19 vaccine in kidney and lung transplant recipients

alexandrossfakianakis shared this article with you from Inoreader Torque teno virus (TTV): a gentle spy virus of immune status, predictive marker of seroconversion to COVID‐19 vaccine in kidney and lung transplant recipients via Journal of Medical Virology Abstract To date, no comprehensive marker to monitor the immune status of patients is available. Given that Torque teno virus (TTV), a known human virome component, has previously been identified as a marker of immunocompetence, it was retrospectively investigated whether TTV viral load may also represent a marker of ability to develop antibody in response to COVID-19-BNT162B2 vaccine in solid organ transplant recipients (SOT). Specifically, 273 samples from 146 kidney and 26 lung transplant recipients after successive doses of vaccine were analyzed. An inverse correlation was observed within the TTV copy number and anti-Spike IgG antibody titer with a progressive decrease in viremia the further away from the transplant date. Analyzing the data obtained after the second dose, a significant difference in TTV copy number between responsive and non-responsive patients was observed, considering a 5 log10 TTV copies/ml threshold to discriminate between the two groups. Moreover , for 86 patients followed in their response to the second and third vaccination doses a 6 log10 TTV copies/ml threshold was used to predict responsivity to the booster dose. Although further investigation is necessary, possibly extending the analysis to other patient categories, this study suggests that TTV can be used as a good marker of vaccine response in transplant patients. This article is protected by copyright. All rights reserved. View on Web

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Regulatory B cells (Bregs) in Helicobacter pylori chronic infection

alexandrossfakianakis shared this article with you from Inoreader Regulatory B cells (Bregs) in Helicobacter pylori chronic infection via Helicobacter Abstract Background Helicobacter pylori (H. pylori) infection is linked with a wide variety of diseases and was reported in more than half of the world's population. Chronic H. pylori infection and its final clinical outcome depend mainly on the bacterial virulence factors and its ability to manipulate and adapt to human immune responses. Bregs blood levels have been correlated with increased bacterial load and infection chronicity, especially Gram-negative bacterial infection. This study aimed to identify prevalence and virulence factors of chronic H. pylori infection among symptomatic Egyptian patients and to examine its possible correlation to levels of regulatory B cells (Bregs) in blood. Materials and Methods Gastric biopsies and blood samples from each of 113 adult patients, who underwent upper endoscopy, were examined for the detection of H. pylori by culture and PCR methods. Conventional PCR was used to determine various virulent genes prevalence and association to clinical outcome. Flow cytometry was used to evaluate Bregs levels. Results Helicobacter pylori prevalence was 49.1% (55/112). Regarding virulence genes incidence, flaA gene was detected in 73% (40/55), vir B11 in 56.4% (31/55), hopZ1 in 34.5% (19/55), hopZ2 in 89% (49/55), babA2 in 52.7% (29/55), dupA jhp917 in 61.8% (34/55), vacA m1/m2 in 70.9% (39/55), and vacA s1/s2 in 69% (38/55) strains. Bregs levels were significantly lower in H. pylori-infected patients (p = 0.013), while total leukocyte count (TLC) showed no significant differences. Conclusion Helicobacter pylori infection prevalence was almost 49%, and the infection was found to be related to inflammatory conditions as gastritis and ulcers rather than malignant transformations. Also, we found that CD24+CD38+ B cells were downregulated in H. pylori-infected patients. View on Web

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Developmental Outcomes in Children Born to Women with Possible Subclinical Rubella Exposures During Pregnancy

alexandrossfakianakis shared this article with you from Inoreader Developmental Outcomes in Children Born to Women with Possible Subclinical Rubella Exposures During Pregnancy via Journal of Medical Virology Abstract This study investigated outcomes of children born to women who seroconverted to rubella immune during pregnancy. In a prior 2012-2013 study of 296 women who were rubella non-immune, 26 (8.8%) seroconverted to rubella immune during pregnancy. These same women and their now 8-9 years-old children were queried as to the children's developmental health. After removing exclusions and those lost to follow-up, the total response rate was 115/204 (56.4%). Three sets of twins in the non-immune group increased the total to 118. The seroconversion group had more autism (12.5% versus 3.9%, P=.19), ADHD (37.5% versus 18.6%, P=.10), and any developmental disability (43.8% versus 31.4%, P=.39) but none showed a statistical difference between the two groups. Compared to Autism and Developmental Disabilities Monitoring data, the seroconversion group had a greater prevalence of autism (OR 6.07, P=0.051, nonsignificant); and to data derived from the National Health Interview Survey, a nonsignificant higher odds of autism (OR 5.57, P=0.060), higher odds of ADHD (OR 5.65, P=0.0027) and of an y developmental disability (OR 3.59, P=0.014).The non-immune group also demonstrated a statistically significant increase for both ADHD and any developmental disability, but not for autism. This article is protected by copyright. All rights reserved. View on Web

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IFNL3/4 polymorphisms as a two‐edged sword: an association with COVID‐19 outcome

alexandrossfakianakis shared this article with you from Inoreader IFNL3/4 polymorphisms as a two‐edged sword: an association with COVID‐19 outcome via Journal of Medical Virology ABSTRACT Background COVID-19 has been ranked among the most fatal infectious diseases worldwide, with host's immune response significantly affecting the prognosis. Aim of the study With an aim to timely predict the most likely outcome of SARS-CoV-2 infection, we investigated the association of IFNL3 and IFNL4 polymorphisms, as well as other potentially relevant factors, with the COVID-19 mortality. Methods This prospective observational case-control study involved 178 COVID-19 patients, hospitalized at Corona Center or Clinic for Infectious Diseases of University Clinical Centre Kragujevac, Serbia, followed up until hospital discharge or in-hospital death. Demographic and clinical data on all participants were retrieved from the electronic medical records, and TaqMan assays were employed in genotyping for IFNL3 and IFNL4 SNPs, namely rs12980275, rs8099917, rs12979860 and rs368234815. Results 21.9% and 65.0% of ho spitalized and critically ill COVID-19 patients, respectively, died in-hospital. Multivariable logistic regression analysis revealed increased CCI, N/L, and LDH level to be associated with an increased likelihood of a lethal outcome. Similarly, females and the carriers of at least one variant allele of IFNL3 rs8099917 were almost 36-fold more likely not to survive SARS-CoV-2 infection. On the other hand, the presence of at least one ancestral allele of IFNL4 rs368234815 decreased more than 15-fold the likelihood of mortality from COVID-19. Conclusion Our results suggest that, in addition to LDH level, N/L ratio, and CCI, IFNL4 rs368234815 and IFNL3 rs8099917 polymorphisms, but also patients' gender, significantly affect the outcome of COVID-19. This article is protected by copyright. All rights reserved. View on Web

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