The multiple regression analysis of the independent risk factors for the factor XIII activity level depression.

<p>The results of the multiple regression analysis of the factor XIII activity levels, sex and use of tocilizumab. **<i>P</i><0.05, ***<i>P</i><0.01.</p

Pelvic computed tomography of the RA patient with factor XIII deficiency.

<p>The white arrow indicates the intra-pelvic hemorrhage. (a) Transverse plane and (b) coronal plane.</p

Plasma factor XIII quantitative concentrations in the RA patients treated with biologics.

<p>(a) The relationship between the factor XIII activity levels and plasma concentrations was assessed according to Pearson's correlation coefficient. (r = 0.449, <i>P</i> = 0.019). (b) Comparison of the plasma factor XIII concentrations between the RA patients treated with TNFi and those treated with tocilizumab. * Student's <i>t</i>-test (<i>P</i><0.05). TNFi, tumor necrosis factor inhibitors; TCZ, tocilizumab.</p

Comparison of the baseline RA patient characteristics.

<p>Median (interquartile range (IQR)).</p>a<p>The Kruskal-Wallis test.</p>b<p>The chi-square test.</p>c<p>The Mann-Whitney U test.</p>*<p>Statistical significance (<i>P</i><0.05) was determined using the Kruskal-Wallis test for differences among the three groups. There was a significant difference between the patients treated without biologics and those treated with tocilizumab (<i>P</i><0.05), according to the Steel-Dwass method.</p>**<p>Statistical significance (<i>P</i><0.05) was calculated using the Mann-Whitney U test.</p>***<p>Statistical significance (<i>P</i><0.01) was calculated using Kruskal-Wallis test for differences among the three groups. There were significant differences between the patients treated without biologics and those treated with tocilizumab (<i>P</i><0.01) and between the patients treated with TNF inhibitors and those treated with tocilizumab (<i>P</i><0.01), according to the Steel-Dwass method.</p><p>MTX, methotrexate; TNF, tumor necrosis factor; RA, rheumatoid arthritis.</p

Single regression analyses between the factor XIII activity levels and the independent variables.

<p>Spearman's rank correlation coefficients between the factor XIII activity levels and the other variables.</p><p>d We inserted “0” as a parameters for the patients treated without methotrexate.</p>*<p>P<0.10, ***P<0.01.</p

Comparison of the plasma factor XIII activity levels in the healthy controls and RA patients.

<p>** the Steel-Dwass method (<i>P</i><0.01). MTX, methotrexate; TNFi, tumor necrosis factor inhibitors; TCZ, tocilizumab.</p

Coagulation tests in the RA patient with factor XIII deficiency.

*<p>The data were below than the lower limit of the standard value.</p><p>APTT, activated partial thromboplastin time; PT, prothrombin time; FDP, fibrin/brinogen degradation products.</p

Characterization of transplanted human VPC-derived vascular cells.

<p>a) Flow cytometric analysis of cell surface markers on expanded human VPC-derived VEGF-R2⁺VE-cadherin⁺ cells ( = EC). b) Immunofluorescence image of CD31 (green) and αSMA (red) with nuclear staining (blue) in expanded EC. Scale bar: 100 µm. c) Immunostaining of mural cell markers (brown) with hematoxyline counter-staining of expanded VPC-derived VEGF-R2⁺VE⁻cadherin- cells ( = MC). Scale bar: 100 µm. d, e) RT-PCR analysis of mural cell (d) and skeletal/cardiac specific (e) markers in human VPC-derived vascular cells.</p

Fluorescence-conjugated monoclonal antibodies used for FACS analysis

<p>Fluorescence-conjugated monoclonal antibodies used for FACS analysis</p

Primers for reverse transcription-polymerase chain reaction

1<p>Ref. 21.</p>2<p>We used a single pair of PCR primers that cover the sequence specific to SM2, because these two isoforms are produced from a single gene by alternative splicing.</p>3<p>Ref. 22.</p>4<p>Ref. 23.</p