Project description:BackgroundGenetic variation around interleukin-28B (IL28B), encoding IFN-λ3, predict non-responders to pegylated interferon-α/ribavirin (Peg-IFN/RBV) therapy in chronic hepatitis C (CHC). However, it remains unclear the expression and the role of IL28B itself. The aim of this study is to develop easy and useful methods for the prediction of treatment outcomes.MethodsThe mRNA and protein levels of IFN-λ3 induced by ex vivo stimulation of peripheral blood mononuclear cells (PBMC) or magnetically selected dendritic cells (DCs) with toll-like receptor agonists (TLR3; poly I:C, TLR7; R-837) were measured by the quantitative real-time polymerase chain reaction and our newly developed chemiluminescence enzyme immunoassays, respectively, and compared with the clinical data.ResultsWe found that BDCA-4(+) plasmacytoid and BDCA-3(+) myeloid DCs were the main producers of IFN-λs when stimulated with R-837 and poly I:C, respectively. Detectable levels of IFN-λs were inducible even in a small amount of PBMC, and IFN-λ3 was more robustly up-regulated by R-837 in PBMC of CHC patients with favorable genotype for the response to Peg-IFN/RBV (TT in rs8099917) than those with TG/GG. Importantly, the protein levels of IFN-λ3 induced by R-837 clearly differentiated the response to Peg-IFN/RBV treatment (p = 1.0 × 10(-10)), including cases that IL28B genotyping failed to predict the treatment response. The measurement of IFN-λ3 protein more accurately predicted treatment efficacies (95.7 %) than that of IL28B genotyping (65.2 %).ConclusionsGenetic variations around IL28B basically affect IFN-λ3 production, but different amounts of IFN-λ3 protein determines the outcomes of Peg-IFN/RBV treatment. This study, for the first time, presents compelling evidence that IL28B confer a functional phenotype.

| S-EPMC3895210 | biostudies-literature

RETRACTED ARTICLE: Adoption of E-Learning during Lockdown in India

Project description: Not available

| S-EPMC7903031 | biostudies-literature

RETRACTED ARTICLE: Direct healthcare costs of spinal disorders in Brazil.

Project description: Not available

| S-EPMC6614539 | biostudies-literature

Deoxyguanosine is a TLR7 agonist.

Project description:Toll-like receptor 7 (TLR7) is an innate immune sensor for single-strand RNA (ssRNA). Recent structural analysis revealed that TLR7 has an additional binding site for nucleosides such as guanosine, and is activated when both guanosine and ssRNA bind. The nucleoside binding site also accommodates imidazoquinoline derivatives such as R848, which activate TLR7 in the absence of ssRNA. Here, we report that deoxyguanosine (dG) triggered cytokine production in murine bone marrow derived macrophages and plasmacytoid dendritic cells, as well as in human peripheral blood mononuclear cells, including type I interferons and pro-inflammatory factors such as TNF and IL-6. This signalling activity of dG was dependent on TLR7 and its adaptor MyD88 and did not require amplification via the type I interferon receptor. dG-triggered cytokine production required endosomal maturation but did not depend on the concurrent provision of RNA. We conclude that dG induces an inflammatory response through TLR7 and propose that dG is an RNA-independent TLR7 agonist.

| S-EPMC6972671 | biostudies-literature

RETRACTED ARTICLE: Deep learning system to screen coronavirus disease 2019 pneumonia

Project description: Not available

| S-EPMC7175452 | biostudies-literature

RETRACTED ARTICLE: Predatory publishing in Scopus: evidence on cross-country differences.

Project description:Predatory publishing represents a major challenge to scholarly communication. This paper maps the infiltration of journals suspected of predatory practices into the citation database Scopus and examines cross-country differences in the propensity of scholars to publish in such journals. Using the names of "potential, possible, or probable" predatory journals and publishers on Beall's lists, we derived the ISSNs of 3,293 journals from Ulrichsweb and searched Scopus with them. 324 of journals that appear both in Beall's lists and Scopus with 164 thousand articles published over 2015-2017 were identified. Analysis of data for 172 countries in 4 fields of research indicates that there is a remarkable heterogeneity. In the most affected countries, including Kazakhstan and Indonesia, around 17% of articles fall into the predatory category, while some other countries have no predatory articles whatsoever. Countries with large research sectors at the medium level of economic development, especially in Asia and North Africa, tend to be most susceptible to predatory publishing. Arab, oil-rich and/or eastern countries also appear to be particularly vulnerable. Policymakers and stakeholders in these and other developing countries need to pay more attention to the quality of research evaluation.Supplementary informationThe online version contains supplementary material available at (10.1007/s11192-020-03852-4).

| S-EPMC7867864 | biostudies-literature

RETRACTED ARTICLE: Coronary arteries and aortic valve calcifications in COVID-19.

Project description: Not available

| S-EPMC8783786 | biostudies-literature