Machine Learning-assisted Research on CFS

Valentijn

Senior Member
Messages
15,786
Likes
45,616
I believe that you should not dismiss theories so easily ....
Then prove to me why the entire scientific community is wrong, and you're right about every SNP being relevant.

I'm not getting drawn into your liver theories, when you can't bother to get the extreme basics right regarding genetics.
 

mariovitali

Senior Member
Messages
1,104
Likes
1,216
Then prove to me why the entire scientific community is wrong, and you're right about every SNP being relevant.

I'm not getting drawn into your liver theories, when you can't bother to get the extreme basics right regarding genetics.
Sorry, i believe that it is a far greater mistake not to take into account things already known (=Normal Liver Enzymes cannot rule out Liver Disease). I also noticed that you repeatedly avoid admitting that your statement in this case is wrong. This is not my Liver theories, these are facts.

Actually, -in my opinion- your are putting Emotions over facts. Not scientific at all i am afraid @Valentijn

You also repeatedly fail to understand that the Theory looks at combinations of Genes and not individual mutations.

What is your opinion regarding SLC19A2 and the observed frequencies on a sample of 62 people? Do you think that it requires further investigation or not?
 

Valentijn

Senior Member
Messages
15,786
Likes
45,616
Sorry, i believe that it is a far greater mistake not to take into account things already known (=Normal Liver Enzymes cannot rule out Liver Disease). I also noticed that you repeatedly avoid admitting that your statement in this case is wrong.
Right. I don't want to talk about livers, ergo it doesn't matter if you're spouting nonsense about SNPs?
This is Emotions over facts. Not scientific at all i am afraid
Agreed. Please start being scientific about genetics. I've repeatedly listed free introductory courses which you can take.

You also repeatedly fail to understand that the Theory looks at combinations of Genes and not individual mutations.
That doesn't make your claims about SNPs any more sensible.

What is your opinion regarding SLC19A2 and the observed frequencies on a sample of 62 people? Do you think that it requires further investigation or not?
My opinion is that it's reckless to base treatments off of something off a system which isn't supported by any scientific evidence. It's irresponsible to treat first and investigate later.
 

mariovitali

Senior Member
Messages
1,104
Likes
1,216
Just found out that a 100K Prize is given for solving PSSD, PFS and several other Syndromes.

The idea for a RxISK Prize began with our involvement with sufferers from Post-SSRI Sexual Dysfunction (PSSD) some years ago, and soon after people with comparable problems following Accutane and Finasteride. The motivation and endurance of those affected has been inspiring.

A complete and permanent wipe-out of your ability to make love is among the most debilitating side effects of a drug imaginable. In the case of all these drugs when it happens it affects men and women, young and old, can appear after a few days on the drug or only after treatment stops. It can last for decades, perhaps longer. It leads to suicides, the break-up of relationships and job losses. There is no upside to it.

PSSD shares many common features and looks like it is closely related to Post-Finasteride Syndrome (PFS), and Post-Retinoid Sexual Dysfunction (PRSD) triggered primarily by isotretinoin (Accutane). Isotretinoin is both a serotonin reuptake inhibitor and a 5-alpha reductase inhibitor (5ARI), so it could give rise to PSSD or PFS, or all three conditions may have something else in common.

We have recently submitted a paper for review describing 300 cases of PSSD, PFS and PRSD, and we are aware of many more cases and comparable phenomena happening on some other drugs. There may be tens of thousands affected as some evidence suggests that less than half of those who have been on SSRIs for months will regain full and normal function.
At last, a possible connection is considered that these Syndromes may have a common Biological basis.


https://rxisk.org/launching-the-rxisk-prize/


Apparently, Sexual Dysfunction may also be a problem with CFS patients :


I first got sick in 2010. I was 22, looking to graduate from college, working as a group fitness instructor, and pursuing my passion for bodybuilding. One day, when I was doing sub-maximal squats with 315 pounds, I became violently ill. I spent the rest of the day in a fetal position curled around the toilet before finally going to urgent care. It turned out I had mononucleosis, at least initially, but my condition only got worse over time. Then after months of misery, I was diagnosed with myalgic encephalomyelitis, a mysterious neurological disease sometimes patronizingly referred to as “Chronic Fatigue Syndrome.
Although it is rare, myalgic encephalomyelitis can be fatal. So when I became bedridden in January 2015, I appeared to be on a slow crawl toward death. I couldn't speak, chew food, tolerate light or, it turns out, have sex.
http://www.mensjournal.com/health-f...get-to-tell-you-about-chronic-illness-w449761
 
Last edited:

NotThisGuy

Senior Member
Messages
303
Likes
353
@mariovitali
any News?
I'm really impressed by your work and hopes are high you can find a cure for my cfs.
I looked over you work again and again. It is incredible how many Matches you have with Symptoms.
From you Website:

1)Sulfation --- check, got a Probleme there
2)Bile Acid Homeostasis--- check, no bile flow and increased Bilirubin
3)Vitamin K --- check, wisdom teeth not growing, only when I take Vitamin K. Teeth Demineralisation etc.
4)carboxylation --- no idea
5)Urea cycle--- check, low uric acid
6) adrenal fatigue --- check. low adrenal Hormones (except of aldosterone) and low testosterone (not adrenal but mentioned it anyway)

The best Treatment I had til now was extra Thiamin. i also have low ALA, so I guess pyruvate Dehydrogenase is inhibited.
One Thing I can't explain to myself: I have a real heavy reaction to tiny doses of selenium. It always almost kills me and this new low in my disease goes on for several months after trying selenium. Whats going on there?
 

mariovitali

Senior Member
Messages
1,104
Likes
1,216
@NotThisGuy

Regarding Selenium : I do not know why you had this reaction but it could greatly help if you have 23andme data that you could share with me.

I am trying to get in contact with any Researchers wishing to validate this Hypothesis further. I continue to believe that a significant subgroup of ME/CFS patients has Liver issues, some sort of compensated Liver Disease. I am really happy that more ME/CFS patients start seeing this as a possibility too. Apparently one of them who i happened to meet recently in person also tried to contact several Researchers asking them to consider Liver Disease and received no replies about this possibility. Same thing happened to me. I think we must exert more pressure towards this direction.

As a side note : I wanted some extra days to confirm this but as it seems, two symptoms which i had for many-many years subsided as well : Photosensitiviity and infrequent "Bathroom Visits"

I do not have to wear sunglasses all the time any more when it's sunny outside. Of course direct sun i do not tolerate but i do tolerate sun glare. This is yet one more evidence -at least for me- that something major is happening here.

Regarding the Frequency of "bathroom visits" these are now twice a day. This is something that hasn't happened so consistently for almost a decade, maybe more.
 
Last edited:

NotThisGuy

Senior Member
Messages
303
Likes
353
Are you taking Zinc?
yeah, when I tried selenium in the past I was taking zinc.
When I had my first selenium Crash (I tried it twice) zinc was the only Thing that kept me alive, since this was the only Supplement I Kind of tolerated.

Unfortunately it made me really anemic so I always had to take Iron to solve this after zinc Supplementation... and Iron made me feel worse in some other way... it was a nightmare back then.

Last month it occured to me that B12 might be the missing Piece:

I switched from liquid to sublingual B12 and my health started to decline... didn't know what to do and thought I might give a Little selenium a try... bam hard Crash-> intolerance to all supplements.

I only fully recovered from the first Crash with liquid B12 and B1 months later.
hen I switched B12 Brands again (liquid to sublingual) and my health started to decline again.

Again I thought it could be selenium deficiency and tried a Little bit...Bam Crash again-> intolerance to all Supplements.

I will try liquid B12 the next days... I avoided it because I'm oversensitive to potassium but still get severe potassium deficiency like muscle paralysis, heart arrhythmia, breathing troubles etc.
So the B12 induced potassium deficiency might not end well.

However after my first Crash my potassium intolerance (and General intolerance to electrolytes) got better after B12 but I wasn't in such a bad shape as I'm now.
Maybe B12 fixed the potassium-pump in cells.

But there seems no way arround this... I will let you all know how this Ends.
I just hope that potassium won't tank that much after a Little B12 so my muscles can still function.
If u dont see me arround here again you can guess it didn't end well :/

@mariovitali

I ordered the 23andme test kit. I guess it will take 2 months until I get results.
I think the liver is a big part of CFS.
I dont know if it is the cause of CFS or just another consequence.

what is your current Supplement Regime?

I just have to say again that I love your algorithm. Thats the future of medical Systems.
Sadly Technology always gets slowed down by politics and humanity so we still have to deal with doctors who are useless and unnecessary...
 

mariovitali

Senior Member
Messages
1,104
Likes
1,216
@NotThisGuy

As previously discussed, i believe that a personalised regimen should be used. For example i took at one point Selenium without any issues whereas you had problems. For me taking N-Acetyl-Cysteine (NAC) was very problematic.

The regimen is as follows :
-Epsom Salts
-Zinc (100 % RDA, not more)
-Metafolin (400 mcg)
-P5P (50 mg)
-Benfotiamine (3 * 150 mg)
-Biotin (3 * 1000 mcg)
-Jiaogulan (250 mg *3)
-K2 (100 mcg * 6)
-FMN (1/4 tablet - Source Naturals brand)
 
Last edited:

Gondwanaland

Senior Member
Messages
5,002
Likes
4,138
Do you apply it transdermally? baths, foot baths? orally? how much daily? does it lower blood sugar? (I have had a severe reaction to it in the past with hypothermia and possibly hypoglycemia followed by acidosis but at the ER they haven't measured any of that).

What type of zinc do you prefer?

Don't you need potassium?
 

mariovitali

Senior Member
Messages
1,104
Likes
1,216
@Violeta i will add glyoxylate so that the software scores its potential relevance.

@Gondwanaland I actually drink it, around 600 mg per day but i wouldn't recommend it to everyone. I now tolerate many things but apparently people that have this condition for many years may feel symptoms just by taking a simple vitamin complex.

I never had any issues with Epsom Salts apart from the first time i tried it where i felt increased thirst for a day.

Potassium i tried at some point, didn't make a difference. The zinc i take is gluconate zinc.

But again, what i believe is needed is a personalised regimen. Whatever works for me may not work for you.
 

mariovitali

Senior Member
Messages
1,104
Likes
1,216
@Jesse2233

I had a quick look for it at my notes. Haven't found anything but the way this works is that all PubMed entries for Zonulin are collected and then after about 48 hours the system can score its relevance to ME/CFS.

I did find a connection of Zonulin with Glycosylation at my notes however.

Please recall that one area of particular importance is -in my opinion- N-Linked Glycosylation.

N-Acetyl-Glucosamine (NAG) is a product of Glycosylation and it is related to the Gut Lining (being a Glucosaminoglycan)

http://forums.phoenixrising.me/inde...sted-research-on-cfs.51283/page-6#post-900640

N-Linked glycosylation also helps in proper protein folding in the ER :

http://dmm.biologists.org/content/7/3/331


Inflammatory Cytokines yes. Appear as being very important.

I will add Zonulin and get back to you as soon as the scoring finishes.
 
Last edited:

mariovitali

Senior Member
Messages
1,104
Likes
1,216
Here is the latest update :

I am currently looking at Tocotrienol. Network Analysis suggests a very central role. I started taking it and will report back.

More about Tocotrienol can be found here :

https://en.wikipedia.org/wiki/Tocotrienol#Health_effects


EDIT : This appears to be quite interesting :


Tocotrienols Balancing the Mitochondrial Crosstalk Between Apoptosis and Autophagy
http://www.tandfonline.com/doi/pdf/10.4161/auto.5088



I also post here the latest Network Analysis diagram (the one that i have on my Blog was generated in April 2017 and i will not be updating it at my Blog) although the central nodes are not shown at present below.

Nevertheless i wanted to stress out the potential importance of Tocotrienol (not shown), Glycoproteins, JNK Pathway, G Actin, Hypothalamic Inflammation and Rapamycin. Rapamycin does not appear to have central role here but is selected as being very important by Machine Learning Algorithms.

Basically we use several analytical techniques, combine their results and generate hypotheses using results which appear to be common across the majority of these techniques.

network-latest.png

@Jesse2233 I will let you know as soon as i have more results with the topics you discussed.
 
Last edited:

Hip

Senior Member
Messages
12,970
Likes
23,943
Unfortunately i fail to understand what you mean by "trendy molecules" and "sifting technique" so i would really appreciate if you can elaborate.
Let me try to explain what Prof Edwards means by trendy research (= fashionable scientific ideas in circulation, that hold scientists' attention during certain decades or eras, but which often turn out to be wrong).

Let's take a disease like peptic ulcers (eg stomach ulcers). In 1874, Arther Boettcher published a study detailing a small curved bacterium that he repeatedly found in stomach ulcers (we now know this bacterium was Helicobacter pylori). Over the next 50 years from 1874 onwards, other scientists confirmed Boettcher's findings. By the late 1940s, peptic ulcers were successfully being treated with antibiotics in New York City hospitals, and stomach ulcers were at that time considered to be an infectious disease, at least in New York.

Then in the 1950s, discussions of infectious causation of peptic ulcers disappeared from the medical literature and disappeared from the treatment regimen. From the 1950s to the early 1990s, the medical texts forgot about the infectious theory of peptic ulcers, and instead attributed peptic ulcers to excess stomach acid, stress, smoking, alcohol — but not to bacterial infection.

So for some unknown reason, from the 1950s onwards, medical and scientific fashions changed, and suddenly bacterial causes of peptic ulcers were out of fashion, and stomach acidity etc became the fashionable hypothesis to explain peptic ulcers. So antibiotics were no longer used to treat ulcers, and antacids were given instead (which did not help this disease).

Then famously in 1984, in a courageous self-experiment, Dr Barry Marshall drank an infectious broth of Helicobacter pylori, as he theorized that this bacterium was the cause of peptic ulcers (interestingly he had not heard of Boettcher's work). Drinking this infectious broth rapidly led to gastritis of Marshall's stomach, and this self-experiment then paved the way to the modern understanding that Helicobacter pylori is a major cause of peptic ulcers. As a result, from the early 1990s onwards, medical thinking returned to Arther Boettcher's original explanation of a bacterial cause of peptic ulcers.

These days we understand that stomach acid is not a cause of peptic ulcers, and that the major causal factors are Helicobacter pylori and NSAIDS, with tobacco smoking and stress due to serious illness being minor causes (this is according to Wikipedia).

(Source for the above info: Plague Time: The New Germ Theory of Disease by Paul W. Ewald. Page 99)



So, if you were to run your algorithm on peptic ulcers studies, but restricting the algorithm to papers published before Dr Barry Marshall's famous experiment in 1984 (in other words, run your algorithm as if we were back in 1984), I would guess that your algorithm would provide a strong link to stomach acid as a suspected cause of peptic ulcers (which we now know to be wrong), because for four decades, from the 1950s to the early 1990s, the excess stomach acid hypothesis was the main fashion in medical thinking about ulcers.
 
Last edited: