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Our metabolic screening was sufficiently detailed to demonstrate that plasma BCAA are the only metabolites that differ between the HD patients and controls.
In fact, we have likely underestimated the proportion of metabolites that differ between the sexes, as we excluded all metabolites that were absent in more than 5% of samples from either sex.
All the preceding work was focused on the question: Are there any metabolites that differ in concentration levels between samples from the test population indicative of a specific pathophysiology?
We have previously completed proof of principle studies showing that we can identify serum metabolites that differ between AL-fed rats and rats undergoing CR[ 37], confirmed these findings in an independent cohort[ 18], and generated expert systems/trained algorithms that can objectively identify these groups [ 19, 21].
Partial Least Squares Discriminant analysis (PLS-DA) [21] was used to identify metabolites that differ in their change between day 0 and day 9 in fasted conditions between treatment groups (Figure 1, analysis a).
Similar(55)
The Mann–Whitney Wilcoxon test was used to analyse metabolites that differed in abundance between groups corrected for the FDR.
The nonparametric univariate method (Mann–Whitney Wilcoxon test) was used to analyse metabolites that differed in abundance between the NCy group and the Cy group corrected for the FDR to ensure that the peak of each metabolite was reproducibly detected in the samples.
To identify metabolites that differed in changes over time between the treatment groups, it was necessary to discriminate between the time and the metabolite information.
We identified 33, 32, and 28 metabolites that differed significantly (p<0.05) between OB and OB/D subjects at T0, T3, and T6, respectively (TABLE 2).
While many metabolites may contribute to this separation, we considered only those metabolites that differed between OB and OB/D subjects with p<0.05 at each time point according to the mixed-effects ANOVA, allowing group:time-interactions when statistically adequate.
The 15 remaining metabolites that differed between OB and OB/D subjects at all time points were asparagine, cysteine, lysophosphatidylcholine (C18 2), phosphatidylcholine (C16:0, C18 2), nervonic acid (C24 cis[15]1), cholic acid, pantothenic acid, lycopene, lactate, testosterone-17-sulfate, p-Cresol sulfate, fructose-6-phosphate, glucose-1-phosphate, glucose, and mannose.
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