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Another interesting slide from the same talk, 1h24 mark. Seems to show that a rise in succinate during exercise correlates with mild mecfs. germain Hanson et al 2022 found that patient succinate levels rose less than controls, on average. However they were equivalent before exercise...

INteresting slide from video 2. Via an American researcher called Singh who works in concert with David Systrom. They made two subgroups out of their long covid patients: those who delivered oxygen well and those who didn't. They were able to find the ones who did well had some compensatory...

There are some great points here about the limits of knowledge. I want to describe how I see it. We know most studies cover only a fraction of the metabolites in the body. Even when thousands are measured it's possible there's a smoking gun that we haven't measured or that science can't yet...

Here's another one while I'm on a roll. Naviaux vs Fluge 2021. This is the Fluge paper where they run some unsupervised machine learning to create subsets. This chart has all the subsets bundled together but the next step might be to see how it looks if you plot each separately. code for...

This next chart compares Hanson 2020 to Naviaux 2017. There's not loads of metabolites in common but the ones I found in common do not show strong agreement. Note this chart has lipids and other molecules all mixed in. here's the code for this one...

1. This is so wonderful to see, thanks heaps for your hard work! my dream with this project was the many impressive people in this community would pitch in and it is starting already! 2. Is your topline takeaway from this that hanson 2020 and 2022 have no standout areas of agreement? Is that a...

Great work @chillier ! :heart: i want to come back and respond to that but first I will post the data and code for the analysis I did above. So here's a link for the Hanson 2020 data (clicking this will download a zip file to your computer) https://www.mdpi.com/2218-1989/10/1/34/s1 and here's...

Getting organised to submit an FOI request is very much not my skillset but trawling through 1000 pages of correspondence looking for a smoking gun is my happy place. (Executive function vs hyperfocus; I never had adhd symptoms pre mecfs but i have them now!)

Excellent diligence, Lone wolf! I respect your grind a lot.

This is an excellent question. We can cut it by significance and we should. I'll try to do it myself at some point soon but if someone else wants to have a go before I get to that, that would be delightful! My intial sense is that for some pairs of studies cutting down to metabolites that are...

One possible thing we may be able to point out is that untargeted metabolomics delivers no consistency in findings and isn't worth pursuing. In fact noticing that lit a fire under my curiosity. I'm pretty shocked at how little correspondence I find between different metabolomic studies. For...

I'd like to shout out to a couple of inspirational projects for this kind of meta-analysis. Brydges, Che Lipkin &Fiehn 2023 and Kaczmarek 2023. The former does a Bayesian analysis on 3 metabolomics papers and finds peroxisomes and prostaglandins stand out as important. The latter does a...

So this is some code for analysing the Hanson 2022 data. https://github.com/jasemurphy/mecfs/blob/main/Hanson%202022.R and this is the data (via google drive, you'd need to download it to excel and then load it into R to use the code above.)

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...