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The metabolites that contribute to each PC score were assessed using the corresponding PC loadings.

First, for all the variables, the relevance of differences between classes is assessed using the corresponding statistical test (ANOVA, Kruskall-Wallis test or chi-2 independence test).

Headache and dizziness, were assessed using individual items from the PHQ (recall period =2 weeks; response categories = "not at all," "bothered a little," and "bothered a lot"); fatigue and difficulty concentrating were assessed using two items from the PHQ depression scale; insomnia and irritability were assessed using the corresponding items from the PCL-C.

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Statistical heterogeneity between trials was assessed using the chi2 test, its corresponding P-value and the I2 test[ 18].

The significance of geographic region and interaction term was assessed using the chi-squared test for the corresponding HR term in the full model (region and interaction term assessed simultaneously with all listed variables).

The affinity between two local landscapes is assessed using the Wave-Hedges similarity function applied to the two corresponding histograms.

In the CBGT group, the corresponding number of participants was 34 (55%) as assessed using the CGI-I (95% CI, 42.5%–67.2%).

Calibration was also assessed using the quartiles of the predicted survival at 3 and 5 years and calculation of the corresponding observed Kaplan Meier estimates.

After immunohistochemistry, cases were assessed using the H-score (histochemical score) to measure staining intensity and the percentage of stained tumour cells corresponding to each intensity [ 28].

Dementia severity was assessed using the CDR.

Protein concentrations were assessed using the Pierce ™ BCA Protein Assay Kit

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