parkinson, Parkinson's research notebook

Six readers

reader	found	score
genetics Open Targets	no genetic evidence; overall 0.12 from other evidence	0.00
cell type Human Protein Atlas	cell type enhanced, including microglia; strongest in monocytes	0.75
chemistry Open Targets	hard to drug	0.00
trials ClinicalTrials.gov	7 Parkinson's trials, 2 stopped	0.77
literature PubMed	666 Parkinson's papers of 28,738: well-trodden	0.14
pathways Reactome	7 pathways; mostly immune signalling	0.90

No case: the score is under the bar. Receipt 2330

receipt 2337: NLRP3 in dopamine neurons, braak

power: full sample -0.50 (p 0.033, n 18), 95% CI -0.79 to -0.05. the interval excludes zero: something may be there, smaller than a half can see.
confounder: adjusted for sex: -0.50 (p 0.033, n 18). holds up.
composition: dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.62 (p 0.0060, n 18). not the mix.
skeptic: leave-one-out range -0.59 to -0.44, sign flips 0; without severely affected donors -0.50 (p 0.033, n 18). robust.
cell type: no other cell group does better.
axis: no measure beats "tracks Braak Lewy-body stage" for NLRP3 in dopamine neurons.

case closed: nothing better to follow up.

receipt 2336: NLRP3 in microglia, braak

power: full sample +0.07 (p 0.781, n 18), 95% CI -0.41 to +0.52. the interval is wide: not enough donors to tell.
confounder: adjusted for sex: +0.08 (p 0.761, n 18). does not hold up.
composition: microglia share of nuclei vs axis -0.11 (p 0.652); controlling for it: +0.01 (p 0.969, n 18). could be the mix.
skeptic: leave-one-out range -0.06 to +0.23, sign flips 3; without severely affected donors +0.07 (p 0.781, n 18). fragile.
cell type: no other cell group does better.
axis: no measure beats "tracks Braak Lewy-body stage" for NLRP3 in microglia.

case closed: nothing better to follow up.

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