Immunological Evidence for the Role of Mycobacteria in Sarcoidosis: A Meta-Analysis

<div><p>Background</p><p>Sarcoidosis is a granulomatous disease, the etiology of which is currently unknown. The role of mycobacteria in the etiology of sarcoidosis has been extensively investigated. In this meta-analysis, we assessed the immunological evidence of the possible role of mycobacteria in the pathogenesis and development of sarcoidosis.</p><p>Methods</p><p>We performed a systematic search of relevant articles from PubMed, Embase and Cochrane Library databases published between January 1990 and October 2015. Data extracted from the articles were analyzed with Review Manager 5.3 (Cochrane Collaboration, Oxford, UK).</p><p>Results</p><p>In this meta-analysis, 13 case-control studies (733 participants) were considered eligible according to our criteria. Methodological quality was assessed using the Newcastle-Ottawa Scale (NOS). The positivity incidence of the immune response (either the cell-mediated response or humoral response) in sarcoidosis patients was significantly higher than that in controls, as determined using fixed-effects model. The odds ratio (OR) of the positivity incidence of T-cell response in the patients with sarcoidosis versus the controls with PPD- or unknown PPD status was 5.54 (95% CI 3.56–8.61); the ORs were 16.70 (95% CI 8.19–34.08) and 1.48 (95% CI 0.74–2.96) for the two subgroups with PPD- controls and unknown PPD status respectively. However, the OR of the positivity incidence in patients with sarcoidosis versus PPD+ controls (latent tuberculosis infection; LTBI) was 0.26 (95% 0.10–0.66). Regarding the humoral response, pooled analysis of the positivity incidence revealed an OR (95%CI) of 20.43 (5.53–75.53) for the patients with sarcoidosis versus controls; the ORs were 11.93 (95% CI 2.15–66.27) and 41.97 (95% CI 5.24–336.15) in two subgroups of controls with PPD- and unknown PPD statuses respectively. Data on heterogeneity and evidence of publication bias were examined.</p><p>Conclusions</p><p>This meta-analysis confirmed the existence of an association between mycobacteria (especially <i>M</i>.<i>tuberculosis</i>) and sarcoidosis. The current available evidence indicates that some insoluble mycobacterial antigens that preferentially within the body are involved in the pathogenesis of sarcoidosis rather than the whole mycobacteria and that they elicit a type IV immune response.</p></div

Funnel plot assessing publication bias.

<p><b>a. Funnel plot for the studies on the T-cell response to <i>M</i>. <i>tuberculosis</i> antigens with controls of PPD- or unknown PPD status; b. Funnel plot for the studies on the T-cell response to <i>M</i>. <i>tuberculosis</i> antigens with PPD+ controls; c. Funnel plot for studies on the humoral response to <i>M</i>. <i>tuberculosis</i> antigens</b>. SA = sarcoidosis.</p

Flow diagram of assessment of studies identified in meta-analysis.

<p>Flow diagram of assessment of studies identified in meta-analysis.</p

Forest plot of trials analyzing the positivity incidence of T-cell response to <i>M</i>. <i>tuberculosis</i> antigens in sarcoidosis patients versus PPD+ controls (LTBI).

<p>LTBI = latent tuberculosis infection.</p

The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomized studies.

<p>The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomized studies.</p

Forest plot of trials analyzing the positivity incidence of the humoral response to <i>M</i>. <i>tuberculosis</i> antigens in sarcoidosis patients versus controls.

<p>Forest plot of trials analyzing the positivity incidence of the humoral response to <i>M</i>. <i>tuberculosis</i> antigens in sarcoidosis patients versus controls.</p

High-Energy Density Redox Flow Lithium Battery with Unprecedented Voltage Efficiency

A redox flow lithium battery (RFLB) has decoupled energy storage and power generation units like a conventional redox flow battery, while it stores energy in solid materials by virtue of the unique redox targeting concept. Hence, it presents superior energy density and represents a promising approach for large-scale energy storage. In a RFLB, the potential difference between the redox shuttle molecules used in the same electrolyte normally brings about an intrinsic voltage hysteresis, resulting in a compromised voltage efficiency of the battery. Here we report a novel redox shuttle molecule pair to minimize the voltage hysteresis: anatase TiO₂ is reduced by bis­(pentamethylcyclopentadienyl)­chromium (CrCp*₂), while Li_<i>x</i>TiO₂ is oxidized by cobaltocene (CoCp₂). The potential difference between CoCp₂ and CrCp*₂ is only 0.15 V. A redox flow lithium battery is successfully demonstrated with an unprecedented voltage efficiency of 84%. The RFLB shows good cycling stability, and >90% Coulombic efficiency was demonstrated in the first 50 cycles

Graphical Principal Component Analysis of Multivariate Functional Time Series

In this paper, we consider multivariate functional time series with a two-way dependence structure: a serial dependence across time points and a graphical interaction among the multiple functions within each time point. We develop the notion of dynamic weak separability, a more general condition than those assumed in literature, and use it to characterize the two-way structure in multivariate functional time series. Based on the proposed weak separability, we develop a unified framework for functional graphical models and dynamic principal component analysis, and further extend it to optimally reconstruct signals from contaminated functional data using graphical-level information. We investigate asymptotic properties of the resulting estimators and illustrate the effectiveness of our proposed approach through extensive simulations. We apply our method to hourly air pollution data that were collected from a monitoring network in China.</p

Dual Role of Alkynyl Bromides in One-Step Synthesis of Bromo-Substituted Alkynyl Sulfides

<div><p></p><p>An atom-economical and environmentally friendly method for synthesis of bromo-substituted alkynyl sulfides has been developed. In the absence of any additive, alkynyl bromides could react with tetrahydrothiophene to give bromo-substituted alkynyl sulfides in moderate to perfect yields.</p> </div

Regio- and Stereoselective Synthesis of 2‑Amino-dienes via Decarboxylative Amination of 4‑(Ethoxycarbonyl)-2,3-allenols by TsNCO

A metal-free decarboxylative amination of 4-(ethoxy­carbonyl)-2,3-allenols by TsNCO via base-induced aza-Michael addition/elimination has been developed. A variety of substituted <i>N</i>-tosyl 1,3-dien-2-yl amines were obtained in good yields and excellent regio- and stereoselectivity. Moreover, this transformation could be applied in preparation of 2-amino-trienes