Differences in brain metabolic activation to the task (percent change) when given with MP when compared with placebo (PL) between subjects in whom MP attenuated brain activation versus those in whom it enhanced activation along with their baseline metabolic measures.

<p>Two subjects showed no differences between MP and placebo (data not included). Comparisons correspond to chi square for the subject numbers (Ss) and to student t-tests (unpaired, two test) for the other comparisons.</p

Regional glucose metabolism (µg/100 g/min) when subjects were tested during the neutral non-task with placebo (control condition), cognitive task with MP and cognitive task with placebo.

<p>Data corresponds to mean and standard deviation. Subscripts correspond to paired t-test comparisons with respect to the control condition:</p>a<p>p<0.05, ^b p<0.01, ^c p<0.005, ^d p<0.001. The last column corresponds to the significance level for comparison between the cognitive task when given with MP or when given with placebo (PL).</p

Schematic diagram of experimental procedure.

<p>Placebo (PL) or methylphenidate (MP) was given 60 minutes prior to initiation of Cognitive or Neutral tasks, which lasted 45 minutes. [¹⁸F]FDG was injected 15 minutes after task initiation (75 minutes after MP or PL) and scans were started 35 minutes after injection.</p

Brain activation with the task after placebo (PL) and after methylphenidate (MP).

<p>A. SPM results showing the areas that had increases in metabolism for the cognitive task with placebo versus the control conditions; B. SPM results showing the areas that had increases in metabolism for the cognitive task with MP versus the control conditions. Comparisons correspond to paired t tests (p<0.001 uncorrected >100 pixels). None of the brain regions had higher metabolism for the control condition (neutral non-task with placebo) than for the cognitive task conditions.</p

Differences in task activation between placebo (PL) and methylphenidate (MP).

<p>SPM results showing the areas that had greater increases in metabolism when the cognitive task was given with placebo versus when it was given with methylphenidate (MP). Comparisons correspond to paired t-tests (p<0.005 uncorrected >100 pixels). None of the brain regions had higher metabolism for the cognitive task when given with MP than with placebo.</p

The genomics of colorectal cancer in populations with African and European ancestry

Black people have a higher incidence of colorectal cancer and worse survival rates when compared with white people. Comprehensive genomic profiling was performed in 46,140 colorectal adenocarcinoma cases. Ancestry-informative markers identified 5,301 patients of African descent (AFR) and 33,770 patients of European descent (EUR). AFR were younger, had fewer microsatellite instability-high (MSI-H) tumors, and had significantly more frequent alterations in KRAS, APC, and PIK3CA. AFR had increased frequency of KRAS mutations, specifically KRASG12D and KRASG13. There were no differences in rates of actionable kinase driver alterations (HER2, MET, NTRK, ALK, ROS1, and RET). In patients with young-onset colorectal cancer ( Significance: KRAS (particularly KRASG12D/G13), APC, and PIK3CA were more frequently altered in AFR who had a lower frequency of MSI-H tumors. There were no differences in actionable kinase driver alterations. In young-onset colorectal cancer, both ancestries had a similar frequency of MSI-H/TMB-H tumors, but strikingly different trends in APC. See related commentary by Eng and Holowatyj, p. 1187. This article is highlighted in the In This Issue feature, p. 1171.</p