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Human Phenotype Ontology (HPO)-based approaches have gained popularity in recent times as a tool for genomic diagnostics of rare diseases. However, these approaches do not make full use of the available information on disease and patient phenotypes. We present a new method called Phen2Disease, which utilizes the bidirectional maximum matching semantic similarity between two phenotype sets of patients and diseases to prioritize diseases and genes. Our comprehensive experiments have been conducted on six real data cohorts with 2051 cases (Cohort 1, n  = 384; Cohort 2, n  = 281; Cohort 3, n  = 185; Cohort 4, n  = 784; Cohort 5, n  = 208; and Cohort 6, n  = 209) and two simulated data cohorts with 1000 cases. The results of the experiments showed that Phen2Disease outperforms the three state-of-the-art methods when only phenotype information and HPO knowledge base are used, particularly in cohorts with fewer average numbers of HPO terms. We also observed that patients with higher information content scores have more specific information, leading to more accurate predictions. Moreover, Phen2Disease provides high interpretability with ranked diseases and patient HPO terms presented. Our method provides a novel approach to utilizing phenotype data for genomic diagnostics of rare diseases, with potential for clinical impact. Phen2Disease is freely available on GitHub at https://github.com/ZhuLab-Fudan/Phen2Disease. [ABSTRACT FROM AUTHOR]

Although high-throughput data allow researchers to interrogate thousands of variables simultaneously, it can also introduce a significant number of spurious results. Here we demonstrate that correlation analysis of large datasets can yield numerous false positives due to the presence of outliers that canonical methods fail to identify. We present Correlations Under The InfluencE (CUTIE), an open-source jackknifing-based method to detect such cases with both parametric and non-parametric correlation measures, and which can also uniquely rescue correlations not originally deemed significant or with incorrect sign. Our approach can additionally be used to identify variables or samples that induce these false correlations in high proportion. A meta-analysis of various omics datasets using CUTIE reveals that this issue is pervasive across different domains, although microbiome data are particularly susceptible to it. Although the significance of a correlation eventually depends on the thresholds used, our approach provides an efficient way to automatically identify those that warrant closer examination in very large datasets. [ABSTRACT FROM AUTHOR]

Objective The long non-coding RNA plays an important role in inflammation and autoimmune diseases. The aim of this study is to screen and identify abnormally expressed lncRNAs in peripheral blood neutrophils of SLE patients as novel biomarkers and to explore the relationship between lncRNAs levels and clinical features, disease activity and organ damage. Methods RNA-seq technology was used to screen differentially expressed lncRNAs in neutrophils from SLE patients and healthy donors. Based on the results of screening, candidate lncRNA levels in neutrophils of 88 SLE patients, 35 other connective disease controls, and 78 healthy controls were qualified by real-time quantitative polymerase chain reaction. Results LncRNA expression profiling revealed 360 up-regulated lncRNAs and 224 down-regulated lncRNAs in neutrophils of SLE patients when compared with healthy controls. qPCR assay validated that the expression of Lnc-FOSB-1:1 was significantly decreased in neutrophils of SLE patients when compared with other CTD patients or healthy controls. It correlated negatively with SLE Disease Activity Index 2000 (SLEDAI-2K) score (r = −0.541, P < 0.001) and IFN scores (r = −0.337, P = 0.001). More importantly, decreased Lnc-FOSB-1:1 expression was associated with lupus nephritis. Lower baseline Lnc-FOSB-1:1 level was associated with higher risk of future renal involvement (within an average of 2.6 years) in patients without renal disease at baseline (P = 0.019). Conclusion LncRNA expression profile in neutrophils of SLE patients revealed differentially expressed lncRNAs. Validation study on Lnc-FOSB-1:1 suggest that it is a potential biomarker for prediction of near future renal involvement. [ABSTRACT FROM AUTHOR]

Abstract: Systemic juvenile idiopathic arthritis (SJIA) is a severe childhood arthropathy with features of autoinflammation. Monocytes and macrophages in SJIA have a complex phenotype with both pro‐ and anti‐inflammatory properties that combine features of several well characterized in vitro conditions used to activate macrophages. An important anti‐inflammatory phenotype is expression of CD163, a scavenger receptor that sequesters toxic pro‐inflammatory complexes that is highly expressed in both active SJIA and macrophage activation syndrome (MAS). CD163 is most strongly up‐regulated by IL‐10 (M(IL‐10)), and not by other conditions that reflect features seen in SJIA monocytes such as M(LPS+IC). MicroRNA plays key roles in integrating cellular signals such as those in macrophage polarization, and as such we hypothesize microRNAs regulate macrophage functional responses in SJIA including CD163 expression. We find that 2 microRNAs previously found to be elevated in active SJIA, miR‐125a‐5p and miR‐181c, significantly reduced macrophage CD163 expression through 2 distinct mechanisms. Neither microRNA was elevated in M(IL‐10) with robust CD163 expression, but were instead induced in M(LPS+IC) where they restricted CD163 mRNA expression. Mir‐181 species directly targeted CD163 mRNA for degradation. In contrast, miR‐125a‐5p functions indirectly, as transcriptome analysis of miR‐125a‐5p overexpression identified “cytokine‐cytokine receptor interactions” as the most significantly repressed gene pathway, including decreased IL10RA, required for IL‐10‐mediated CD163 expression. Finally, overexpression of miR‐181c inhibited CD163 anti‐inflammatory responses to hemoglobin or high mobility group box 1 (HMGB1) complexes. Together, these data show that microRNA utilizes multiple mechanisms to integrate well‐characterized polarization phenotypes and regulate macrophage functional properties seen in SJIA. [ABSTRACT FROM AUTHOR]

Aim MicroRNAs (miRNAs) play key roles in inflammatory responses of macrophages. However, the function of miRNAs in macrophage-derived foam cell formation is unclear. Here, we investigated the role of miRNAs in macrophage-derived foam cell formation and atherosclerotic development. Methods and results Using quantitative reverse transcription-PCR (qRT–PCR), we found that the level of miR-155 expression was increased significantly in both plasma and macrophages from atherosclerosis (ApoE−/−) mice. We identified that oxidized low density lipoprotein (oxLDL) induced the expression and release of miR-155 in macrophages, and that miR-155 was required to mediate oxLDL-induced lipid uptake and reactive oxygen species (ROS) production of macrophages. Furthermore, ectopic overexpression and knockdown experiments identified that HMG box-transcription protein1 (HBP1) is a novel target of miR-155. Knockdown of HBP1 enhanced lipid uptake and ROS production in oxLDL-stimulated macrophages, and overexpression of HBP1 repressed these effects. Furthermore, bioinformatics analysis identified three YY1 binding sites in the promoter region of pri-miR-155 and verified YY1 binding directly to its promoter region. Detailed analysis showed that the YY1/HDAC2/4 complex negatively regulated the expression of miR-155 to suppress oxLDL-induced foam cell formation. Importantly, inhibition of miR-155 by a systemically delivered antagomiR-155 decreased clearly lipid-loading in macrophages and reduced atherosclerotic plaques in ApoE−/− mice. Moreover, we observed that the level of miR-155 expression was up-regulated in CD14+ monocytes from patients with coronary heart disease. Conclusion Our findings reveal a new regulatory pathway of YY1/HDACs/miR-155/HBP1 in macrophage-derived foam cell formation during early atherogenesis and suggest that miR-155 is a potential therapeutic target for atherosclerosis. [ABSTRACT FROM PUBLISHER]

Objectives. Recently, a non-synonymous (Gly307Ser) variant, rs763361, in the CD226 gene was shown to be associated with multiple autoimmune diseases (ADs) in European Caucasian populations. However, shared autoimmunity with CD226 has not been evaluated in non-European populations. The aim of the present study is to assess the association of this single nucleotide polymorphism (SNP) with ADs in non-European populations. [ABSTRACT FROM PUBLISHER]

The article presents a study which developed and validated a liquid chromatographic-electrospray ionization-tandem mass spectrometric (LC-ESI-MS-MS) method to monitor accurately the steady-state concentrations of aripiprazole in human plasma. It notes that aripiprazole is used to treat schizophrenia or schizoaffective disorders. The researchers considered haloperidol-d4 as the internal standard for the study. The methods used and the results obtained by the study are discussed. The study showed that aripiprazole is stable in plasma samples under certain conditions, and demonstrated the effectiveness of the method.

The article discusses the development and validation of a liquid chromatography-electrospray ionization-tandem mass spectrometry method to detect (R)- and (S)-methadone and (R)- and (S)-2ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) in human plasma with cross substantiation to urine and liver microsomes. It is suggested that the use of deuterated internal standards and liquid-liquid extraction matched with chiral separation allowed for baseline separation with a lower limit of quantitation (LLOQ) of 2.5ng/ml.

Discusses the development of a liquid chromatographic-electrospray-tandem mass spetrometric method combined with a simple liquid-liquid extraction for the measurement of quetiapine in human plasma and in human liver microsomes (HLM). Utilization of quetiapine during incubation with HLM; Efficacy of quetiapine, a dibenzothiazepine derivative, in treating acute schizophrenia; Effect of the pharmacokinetics of a single oral dose of the drug in healthy volunteers.