Small study of 24 total individuals only 6 of which are pre pandemic controls - and whose images are obtained separate from the work in this paper. They say their dye [18F]F-AraG works by becoming phosphorylated by cytoplasmic deoxycytidine kinase (dCK) and deoxyguanosine kinase (dGK) - markers...
Seahorse Respirometry - Assaying mitochondrial aerobic respiration
Lastly they do Seahorse respirometry to assay aerobic respiration on n=9 PASC and n=14 mild-recovered controls and see a significantly reduced aerobic capacity both under normal conditions and also when the oxidative...
Metabolomics of respiratory and other processes
The authors go on to do metabolomics of respiratory and other processes related metabolites (3). Unfortunately they don't multiple test correct but at least they are transparent about that and state it's for exploratory purposes. Kynurenine pops...
Immunohistochemistry
In their histology experiments (2) they show some stains where it looks like there is greater IDO-2 expression in PBMCs generally in at least one PASC patient compared to a healthy control. (CD14 is a marker for monocytes):
They don't quantify or test for differences...
Overall there are some possibly interesting bits in the paper but they don't all hang together as a cogent story in my opinion. There is no single experiment that directly backs up results seen in another experiment and all look at slightly different things - small n~15 sample sizes throughout...
Great news! I'm guessing maybe that means 14-15k DNA samples actually being received with an ~80% sample return rate. Fingers crossed we'll get there and thanks for all you do.
this is getting a bit off topic but I'm curious if you think there is a sensible tissue to look at/biopsy in general for ME. Or with our current level of knowledge would it be too much of a blind guess?
My partner thinks it might not be unreasonable to not see things like this if the phenotype is not that strong, as the coverage can be quite low in scRNA-seq as they're looking at many PBMC cell types besides CD8s, and also depending on how many patients they're putting on a chip/ doing on a...
You might already know this - One of the proteins in this talk PD-1 was associated with a recent nobel prize along with CTLA-4. These genes are supposedly abused by certain advanced cancers to escape the immune system, and targeted inhibition with drugs can improve outcomes in some cases. I...
Good point! Just looking back at their scRNA-seq preprint and they do report they see some differences (measured by gene ontology enrichment scores not levels of individual genes) in CD4+ T cells but don't mention CD8+s at all, except to say there is a marginal decrease in counts.
I suppose...
The logic kind of seems fair enough, although I wonder if comparing the whole curve might in someway dilute the signal from whichever source of diversity is actually most relevant - but I suppose in the absence of knowing exactly what kind of diversity you are looking for this makes sense. They...
They are using Renyi entropy which is sort of a generalised measure of diversity which includes many different measures of diversity within it. You get a curve like one of these (taken from this website):
Where the y axis Ha(X) is the entropy a.k.a a measure of diversity, and the x axis is a...
Things like this also make it sound like the technique has potential:
Would be cool to see it done on GWAS data from other diseases where much more is known about the biology, to see if it provides insights beyond what the GWAS is capable of alone but also correlate with what is known from...
They outline the methods in a bit more detail in the ME paper and I think I have a slightly better handle on how they're doing the statistics. It seems like they test each disease signature with a fisher's exact test against the overall population (I guess the biobank) - this test basically asks...
Just catching up on the threads on the ME paper precision life and @Simon M's blog post - really interesting. They find 14 possible genes in the ME/CFS study and see 9 of those pop up here in long covid? Seems like a pretty big overlap on the surface but I feel a bit nervous about interpreting...
It's fundamentally a bad faith argument though isn't it. He's using an argument about the condition having a bad name to somehow justify the leap to saying a guideline which could help a real clinically defined group of people shouldn't exist.
It's a very small experiment with 4 controls and 4 'chronic fatigue' patients with no mention of diagnosis criteria or age and sex matching etc. Plots aren't great and the panels aren't labelled which makes it a bit hard to read. As well as the barplots @Hutan posted they show the data as a...
I seem to remember it being because Ron's student R Esfandyarpour - the first author on the nanoneedle paper - was starting his own lab and needed the NIH grants to get set upright. As you say Ron mentioned they applied for multiple NIH grants and were repeatedly rejected. Would also make sense...
I dîd the lightning process about a decade ago and you have to read a book about it first and do an interview. I was just in a relapse so health definitely wasn't improving in that moment and I told them so - I was about 2 years into ME and was mostly moderate at the time. I don't think there...
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