Tornado diagram representing the net health benefit (QALYs, with WTP = $11,034) in univariate sensitivity analysis for infliximab + rituximabvs tDMARD strategy in changing baseline parameters.

<p>The width of the bars represents the range of the results when the variables were changed. The vertical dotted line represents the base-case results.HAQ  = Health Assessment Questionnaire; ACR  = American College of Rheumatology criteria.</p

Cost-effectiveness acceptability curves of 7 competing strategies corresponding to probabilistic sensitivity analysisusing an ACR20 threshold.

<p>The bold vertical two-dash and solid lines represent the thresholds of 3×the per capita GDP of China and Shanghai per QALY gained, respectively.</p

Probabilistic scatterplot of the incremental cost-effectiveness ratio (ICER) between tDMARD and (A) Etanercept, (B) Etanercept+Rituxiumab, (C) Infliximab, (D) Infliximab+Rituxiumab, (E) Adalimumab and (F) Adalimumab+Rituxiumab for a cohort of 1,000 moderate to severe RA patients withan ACR20, ACR50, and ACR70 endpoint, respectively.

<p>The x-axis and y-axisrepresent lifetime incremental QALYsand costs, respectively. Each dot represents the ICER for 1 simulation. Ellipse surrounds 95% of estimates. The solid and dashed lines represent the cost-effectiveness threshold of 3×the per capita GDP of China and Shanghai per QALY gained, respectively. Dots that located below the ICER threshold representcost-effective simulations for the active strategy compared with the tDMARD strategy.</p

Model architecture: (A) model treatment sequences, and (B) decision analysis for the treatment.

<p>Model architecture: (A) model treatment sequences, and (B) decision analysis for the treatment.</p

ACR response and withdrawal probability of treatments.

<p>NA: Not applicable.</p>#<p>It was calculated by weighted average methods: (Response₁ × n₁ + Response₂ × n₂)/(n₁+n₂). Response₁ and Response₂ were indicated as the response in control arm of trial 1 and 2, and n₁ and n₂ were the patient number, respectively. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0047373#pone.0047373-Weinblatt2" target="_blank">[14]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0047373#pone.0047373-Keystone1" target="_blank">[15]</a>.</p>*<p>Adjusted response  = RP + (1-RP) × ([TT-TP]/[1-TP]), RP, TT and TP was indicated for the response of reference placebo, trial treatment, and trial placebo, respectively. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0047373#pone.0047373-Bansback1" target="_blank">[10]</a>.</p>&<p>Withdraw probability (t)  = 1 – exp(λ× (t–1) ^γ–λ×t^γ). In this formula, t was indicated as the current cycle number, and λ and γ were scale and shape parameters, respectively.</p

Estimated costs and resource use.

*<p>The range was assumed for one-way sensitivity analysis.</p>#<p>The range was estimated from local hospitals.</p>$<p>The range was derived from Chinese National Bureau of Statistics.</p

Path analysis model used to estimate the effect of smoking duration on SS and the role of potential confounding factors.

<p>The standardized path coefficients, significant odds ratios (OR) and p-values (in bold) are shown next to each path. A. Effect of smoking duration on SS, conditional on socioeconomic status; B. Model used to estimate the effect of smoking duration on SS, conditional on body mass index.</p

Logistic Regression models exploring the effect of covariates of smoking on the risk of classification as Sjögren’s Syndrome.

<p>The only significant predictor was smoking duration.</p

Differentially expressed transcripts between 115 anti-Ro/SSA positive SS cases and 56 controls identified through transcriptome profiling.

<p>(A) We identified 73 genes (represented by 83 probes on the heatmap) differentially expressed between anti-Ro/SSA positive SS cases and healthy controls (absolute FC >2 and <i>q</i><0.05). Among the differentially expressed genes, 57 were type I IFN-regulated genes (black bar on right) and formed an IFN signature where most genes were overexpressed in SS patients (yellow indicates overexpressed genes compared to controls). (B) The 57 differentially expressed type I IFN-regulated genes were re-clustered in anti-Ro/SSA positive SS cases using <i>k</i>-means (<i>k</i> = 3) algorithm and heterogeneity of the IFN signature levels in anti-Ro/SSA positive SS cases was observed.</p

Functional characterizations of <i>OAS1</i> isoforms.

<p>(A) Protein expression of OAS1 isoforms was evaluated in EBV-transformed B cells from SS patients (four independent samples from each genotype group) using anti-OAS1 antibody targeting the shared epitope of all the isoforms. The stimulated cells were treated with universal type I IFN (1500U/ml) for 24hrs. The p44 isoform was not detectable using western-blot due to its low expression. The right panel shows quantified band intensity normalized to the GAPDH in each sample. (B) The transcript levels of each <i>OAS1</i> isoform from the same sets of cells described above were determined using real-time PCR. Consistent with the RNA-seq results, the SS-associated risk allele A of rs10774671 was correlated with decreased levels of p46 and increased expression of the p42, p48, and p44 isoforms (significance levels are shown at the bottom). The transcript levels of all the isoforms significantly increased after IFN stimulation (two-tailed <i>t</i> test); however, only p46 had increased protein production after IFN stimulation. (Significance level: ** <i>P</i><0.01; *** <i>P</i><0.001) (C) Individual isoforms of <i>OAS1</i> tagged with Xpress epitope were cloned and transfected into HEK 293T cells for 48hrs. The p48 and p44 isoforms had impaired protein expression compared to p46 and p42, although their transcript levels were equivalent as determined by real-time PCR (n = 4; normalized to <i>HMBS</i>). (D) The full-length and truncated <i>OAS1</i> p48 and p44 isoforms were cloned into HEK 293T cells. Western-blot indicated the lack of expression of the full-length p48 and p44 isoforms, whereas the truncation of both isoform transcripts (T2 and T4) was able to restore protein expression. (E) The 3' alternatively spliced terminus of different <i>OAS1</i> isoforms were linked to the 3'-end of GFP to observe their influence on GFP protein expression in HEK 293T cells. The 3'-terminus from the p48 and p44 isoforms resulted in decreased expression of GFP.</p