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I'm keen to see if we can trawl existing data to find patterns. There are enough small and medium-sized studies out there - could real findings emerge from combining them? Tis thread is for that purpose and I'd like it to include: A list of data that's available: metabolomics, proteomics...

I have no idea who is right but I like that Prof Scheibenbogen et al are not playing collegiate and politely ignoring a study they disagree with. I would like to see more public fights like this.

I'm not sure they've identified people doing intermittent fasting very well, as opposed to people skipping meals. They have a 2-day eating recall then an 8 year follow up. You want a big sample size for that. They have 20,000 people but even still I'm not sure that's enough given the...

Yep, Rob Wust found necrosis in muscle cells after exercise (pictured below, panel B). A possible explanation is acute endoplasmic reticulum stress that led to an unfolded protein response which didn't resolve the problem and caused necrosis instead.

There's also this "anticipatory" UPR pathway, which is not very well described in the literature yet but affected by estrogen, which is relevant to our purposes here. It seems to depend on cells leaking ATP, which leads me to wonder if Naviaux's long-lingering suramin idea could be useful if...

When I want to feel hopeful I re-read this paper. The irony is that while Wallitt was wasting $8million on his silly preconceived notion, on the other side of the NIH Hwang was doing this work with cancer funding. And I'm increasingly hopeful he has cracked it wide open. To me this puzzle piece...

A detail in Hwang's 2023 WASF3 paper is that the UPR he found isn't working right. While PERK is switched on, there's no phosphorylation of eiF2a. if eiF2a doesn't pick up its phosphate, it doesn't do its job and the PERK signalling presumably gets stuck on. I believe UPR activation that...

I'm extremely excited by the WASF3 work by Hwang et al; so I can't help wondering about a possible link from their finding of endoplasmic reticulum stress to this finding of bigger lipid droplets. Pharmacological ER stress promotes hepatic lipogenesis and lipid droplet formation Jin-Sook Lee...

I really loved this article. I did a bunch of reading on how they developed the cure. It's worth understanding what pathways to success look like. 1. Success came when they stopped looking for a solution to the most upstream factor: the genetic defect. And started focussing on helping the...

I recently joined this forum and am posting links to some of the analysis I've done in recent years. One big piece of work relates to this Hanson study. I collected the data and put it online in a format that allows users to examine any metabolite...

Thanks for the kind feedback and intelligent questions. just the few mecfs studies I've looked at. I started this project expecting to find a great deal of agreement. One reason I fizzled out is that all I couldn't find much agreement. What's more despite the studies often measuring thousands...

A long time ago I compared the findings of this study to those of Germain, Hanson et al 2018. You can see the results below. Agreement between the two studies is moderate and that's a consistent feature of metabolomic studies. I hope to do more like this.

I agree with this take. The metabolome is very dynamic and highly individualised. Which means I think that a lot of metabolomic snapshots are less than useful. If there's no consistency in something then measuring it once is of dubious value. The that chart above is not the first time I've...

Related to peroxisomal function and a key product of the peroxisome, the plasmalogen: Having considered this paper on plasmalogen replacement therapy I've bought shark liver oil and started taking a couple of tablets a day. The product I got is this one...

Big picture: This was a challenging paper to write - difficult topic and difficult circumstances. It needed an exceptional scientist to guide it. Nath was not that scientist. He let down the mission of science by permitting this to be published in its current form. As the sample size receded...

This was a challenging paper to write - difficult topic and difficult circumstances. It needed an exceptional scientist to guide it. Nath was not that scientist. He let down the mission of science by permitting this to be published in its current form. As the sample size receded they needed to...

I think this is likely. Another possibility for some patients - and another reason the test might not be valid - is some might be aware of the history and when they see this easy/hard game come along, choose hard as much as they can with one eye on how the data might be intepreted !!

This does matter a lot. I consider it part of my #1 reason this test fails but you've made me realise it could be expressed more powerfully and directly.

I did a quick dig to see if their measurement of metabolites in cerebrospinal fluid lined up with a previous study on the same topic. I bring bad news. The folllowing plot is just a rough draft of the final analysis but it shows big disagreement. Many things Baraniuk 2021 found high, NIH found...

His strategy dominates everyone else's. Losing easy tasks is the simplest way to not dilute whatever hard tasks you've won (or those you hope to win later) ; in terms of prizes "in the basket". Winning easy tasks is an almost* pure bad strategy. Even if you're not sure if you can win a hard...