Journal: bioRxiv

Article Title: SOX9-regulated matrix proteins predict poor outcomes in patients with COVID-19 and pulmonary fibrosis

doi: 10.1101/2024.01.21.576509

Figure Lengend Snippet: ( A ) Cohort 1 (acute hospitalised COVID-19) outcome groups. Serum concentration of biomarkers, at admission, of ( B ) Tenascin C (TNC) and ( C ) TIMP1 (ng/ml) stratified by eventual illness severity. Statistical significance (p<0.05) was tested by one way ANOVA. ( D ) TNC expression and ( E ) TIMP1 serum concentration (ng/ml) at admission, stratified by mortality (7/32). Statistical significance (p<0.05) was tested by two-way unpaired t-test. ( F ) Cohort 2 (convalescent COVID-19, excluding fibrosis) outcome groups. ( G-J ) Serum TNC and Osteopontin (OPN) concentration (ng/ml), at outpatient review, stratified by respiratory symptoms. Statistical significance (p<0.05) tested by two way t-test. ( K ) Table showing lung function performed on non-fibrotic convalescent patients hospitalised with COVID-19, stratified by radiological outcome. Statistical significance (p<0.05) tested by one way ANOVA. Units of measurement: FEV 1 , litres/min; FVC, litres; millilitres CO/minute/mm Hg. % predicted is a comparison to the GLI (2017) reference values. Values in () represent standard deviation of the mean. ( L-M ) Serum Osteopontin (OPN) and Tenascin C (TNC) concentration (ng/ml) in convalescence, stratified by radiological resolution. Statistical significance (p<0.05) tested by two way t-test. ( N-P ) Images represent data from quantitative CT analysis by Imbio (USA) lung texture analysis (LTA™) artificial intelligence based software. Images show representative LTA™ analysis results, stratified by COVID-19 convalescent disease status (Healthy control n=6; Symptomatic n=13; COVID-19 n=17). See methods for explanation of radiological terms. See for LTA™ statistical analysis and values between groups.

Article Snippet: To explore this further we applied automated artificial intelligence quantitative lung texture analysis™ (IMBIO, USA) to healthy control and symptomatic patient computerised tomography (CT) scans to quantify lung abnormalities across recovering groups ( and - ).

Techniques: Concentration Assay, Expressing, Comparison, Standard Deviation, Software

Journal: bioRxiv

Article Title: SOX9-regulated matrix proteins predict poor outcomes in patients with COVID-19 and pulmonary fibrosis

doi: 10.1101/2024.01.21.576509

Figure Lengend Snippet: ( A ) Cohort 3 characteristics and outcome grouping. ( B ) TNC serum concentration (ng/ml) at diagnosis stratified by fibrosis progression. ( C ) Protein expression for TNC in healthy lung (left image). SOX9 (middle; DAB, brown) and TNC (right; DAB, brown) expression in sequential sections of human idiopathic pulmonary fibrosis lung. ( D ) IGFBP2 serum concentration (ng/ml) at diagnosis stratified by fibrosis progression. ( E ) Protein expression for IGFBP2 in healthy lung (left image). SOX9 (middle; DAB, brown) and IGFBP2 (right; DAB, brown) in the same areas (shown by black arrows). Abbreviations: AC, alveolar capillary; BV, blood vessel. Scale bars, 50μm. Counterstaining with toluidine blue. ( B , D ) statistical significance (p<0.05) tested by one way ANOVA. ( F ) TNC and ( G ) IGFBP2 serum concentration (ng/ml) linear regression with change in forced vital capacity (ΔFVC; ml/year), p=0.02, p=0.003. ( H ) IGFBP2 serum concentration (ng/ml) linear regression with change in predicted DLCO (ΔDLCO), p=0.01. ( i ) Change (Δ) in lung function values, per year, in stable and progressive fibrosis patients (INBUILD criteria). Units of measurement: FEV 1 , litres/min; FVC, litres; millilitres CO/minute/mm Hg. % predicted is a comparison to the GLI (2017) reference values. Values in () represent standard deviation of the mean. ( J - N ) Radiological change in CT scans 6 months apart in COVID-19 fILD patients, analysed using Imbio (USA) lung texture analysis (LTA™) artificial intelligence based software. ( J ) Rendered image representing quantitative LTA™ analysis of repeat scans in a COVID-19 fILD patient. ( K ) TNC and ( L ) IGFBP2 linear regression with Δtotal lung volume (L/year), p=0.009, p=0.03. ( M ) TNC (ng/ml) linear regression with Δreticulations (%), p=0.12. ( N ) IGFBP2 (ng/ml) linear regression with Δreticulations (%), p=0.07. ( O ) TNC (p=0.07) and ( P ) Lumican (LUM; p=0.01) serum concentration (ng/ml) at diagnosis, stratified by 3 year survival status. Statistical significance (p<0.05) determined by two way t-test.

Article Snippet: To explore this further we applied automated artificial intelligence quantitative lung texture analysis™ (IMBIO, USA) to healthy control and symptomatic patient computerised tomography (CT) scans to quantify lung abnormalities across recovering groups ( and - ).

Techniques: Concentration Assay, Expressing, Comparison, Standard Deviation, Software

Journal: bioRxiv

Article Title: SOX9-regulated matrix proteins predict poor outcomes in patients with COVID-19 and pulmonary fibrosis

doi: 10.1101/2024.01.21.576509

Figure Lengend Snippet: Radiological change in CT scans 6 months apart in COVID-19 FILD patients, analysed using Imbio (USA) lung texture analysis (LTA™) artificial intelligence based software (n=10). ( A ) Rendered image representing quantitative LTA™ analysis of repeat scans in a COVID-19 FILD patient. and quantitative output (% affected regions). ( B ) Table showing change (Δ) in LTA™ quantitative CT analysis values. ( C-K ) scatter plots showing diagnosis serum biomarker expression (ng/ml) regression (line) with ΔLTA™ quantitative CT analysis values. ( c ) TNC predicts Δtotal lung volume (L/year), p=0.009. ( D ) IGFBP2 predicts Δtotal lung volume (L/year), p=0.03. ( E ) OPN does not predict Δtotal lung volume (L/year), p=0.35. ( F ) TNC predicts Δground glass (%), p=0.04. ( G ) IGFBP2 predicts Δground glass (%), p=0.009. ( H ) OPN predicts Δground glass (%), p=0.03. ( I ) TNC does not predict Δreticulations (%), p=0.12. ( J ) IGFBP2 does not predict Δreticulations (%), p=0.07. ( k ) OPN predicts Δreticulations (%), p=0.05. Abbreviations: LU, left upper lung; LM, left middle lung; LL, left lower lung; RU, right upper lung; RM, right middle lung; RL, right lower lung; TNC, tenascin C; IGFBP2, insulin growth factor binding protein 2; OPN, osteopontin. Values in () represent standard deviation of the mean. Dotted lines represent 95% confidence intervals.

Article Snippet: To explore this further we applied automated artificial intelligence quantitative lung texture analysis™ (IMBIO, USA) to healthy control and symptomatic patient computerised tomography (CT) scans to quantify lung abnormalities across recovering groups ( and - ).

Techniques: Software, Biomarker Assay, Expressing, Binding Assay, Standard Deviation