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Machine Learning-assisted Research on CFS

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OK, This may be interesting perhaps.
First, a discussion about Lupus, Rituximab and CFS :
https://www.healthrising.org/forums/threads/rituximab-lupus-and-chronic-fatigue-syndrome.3889/
You may also find a lot of hits on PR about Lupus.
Then we have the following (Note that GAS6, TYRO3, AXL, MERTK are mentioned):
Link : https://arthritis-research.biomedcentral.com/articles/10.1186/ar4199
I also see several posts on PR mentioning SLE, so any comments much appreciated!
PS : @JaimeS what do you think?
Unfortunately the paper Cort quotes on lupus is just very bad science. Remember that it was I who introduced rituximab for the treatment of lupus in 2000. The author of this paper works in my old department and seems to understand nothing about autoimmunity. The stuff is very trendy, but as I said, trendy stuff tends to be garbage.

It seems as if your sifting technique with machine learning is going to be garbage in garbage out.

I do not know anything about the second paper but that looks like a list of trendy molecules again. Understanding the mechanisms of disease cannot be done at this superficial level.
 

mariovitali

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Unfortunately the paper Cort quotes on lupus is just very bad science. Remember that it was I who introduced rituximab for the treatment of lupus in 2000. The author of this paper works in my old department and seems to understand nothing about autoimmunity. The stuff is very trendy, but as I said, trendy stuff tends to be garbage.

It seems as if your sifting technique with machine learning is going to be garbage in garbage out.

I do not know anything about the second paper but that looks like a list of trendy molecules again. Understanding the mechanisms of disease cannot be done at this superficial level.
Thank you for your prompt reply.

Unfortunately i fail to understand what you mean by "trendy molecules" and "sifting technique" so i would really appreciate if you can elaborate.

I have stated several times that i am not a Medical professional so please forgive my ignorance in advance.
 

Tunguska

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@Tunguska

This is your interpretation i am afraid. Since 2015, i am discussing about a common basis that these syndromes may potentially have (hypothesis) and not for all or some of these syndromes being the same.

It also appears to me that you are confident on what really is behind CFS and PFS : If you know then please make a statement about it.

Again, i do not suggest that these syndromes are the same, i suggest that they have a common basis. I really cannot say anything more if you repeatedly fail to understand the difference.

Nevertheless, could you comment -especially since you also took Accutane!- on the same topics i pointed to @Valentijn in this post ? http://forums.phoenixrising.me/inde...sted-research-on-cfs.51283/page-2#post-852531
Sorry I don't have the time I'd like to do this during the week anymore. 2015 is obsolete, my description of CFS/ME is simply Dr. Davis's findings together with Naviaux, Fluge Mella and analysis from 2016-17 and sticking to the most observable parameters only. The latest PFS findings are from April 2017: http://www.pfsfoundation.org/news/p...fs-patients-severe-ed-new-study-demonstrates/ Some of the most important links and observations are not on propeciahelp but buried in this long thread: https://raypeatforum.com/community/...r-and-post-finasteride-syndrome.16194/page-24 and other parts of that forum where PFS sufferers have flocked.

Don't you find it curious how there are almost no PFS sufferers reporting on this CFS/ME forum? The only guy I remember who recently posted and attributed his severe symptoms in part to PFS clearly stated he doesn't think he has CFS/ME. Even self-reported they instinctively diverge.

I counted maybe 5 people posting here who took accutane including myself, but I can tell you, I never at any point had any sexual side effects nor most the one attributed to PFS. Accutane produces a heterogenic sufferer population, such that I have nothing in common with half the sufferers posting on the acne forums. They read PhoenixRising frequently but unfortunately they get nowhere and get sidetracked by the methylation stuff. Retinoic acid is simply one of the most powerful and complicated natural substances in the body and without real research understanding it and most of all giving a good interpretation of its roles, they're basically screwed. To make matters worse, the persistence syndrome may have nothing to do with retinoic acid, and 13-cis has some unique effects from retinoic acid.

I know your ideas were about ER stress and liver. But there's no one and no research placing that much relevance to ER stress in these diseases as a cause of persistence. It blends together with excess ROS in acute drug reactions - absolutely - but there isn't very much linking it to maintaining persistence syndromes. Improving liver is very important to disease management in a lot of these cases, but it's not identifying so far.

Anyhow, I'm going nowhere with this and out of time. What I really want to say, is building a model on the premise these disease share a common basis is simply an error, especially now. If you're doing disease management like I am, then common effects are exactly what to look at to find solutions, but as far as I can tell, you're trying to build a tool to help discover causes and cures. This makes no sense to me, sorry.
 

mariovitali

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@Tunguska

First of all, i do appreciate the fact that you found some time to answer this.

Don't you find it curious how there are almost no PFS sufferers reporting on this CFS/ME forum?
Actually i don't care. I would care if my hypothesis stated that PFS and CFS are the same syndromes. They are not. I hypothesise that these syndromes have a common basis (this is the fourth time i had to tell you this).

I counted maybe 5 people posting here who took accutane including myself, but I can tell you, I never at any point had any sexual side effects nor most the one attributed to PFS
*Please* do a simple search before you post something. Because you did not have ED it doesn't necessarily mean that others don't have this problem :

http://www.acne.org/messageboard/topic/295030-repairing-the-long-term-damage-from-accutane/

and

https://rxisk.org/accutane-30-years-of-trading-our-sex-lives-for-clear-skin/

and

http://www.webmd.com/drugs/2/drug-6661-39/accutane-capsule/details/list-sideeffects
 
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Tunguska

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*Please* do a simple search before you post something. Because you did not have ED it doesn't necessarily mean that others don't have this problem :

http://www.acne.org/messageboard/topic/295030-repairing-the-long-term-damage-from-accutane/
Look, if you can't be bothered to read the next sentence in the same paragraph:
Accutane produces a heterogenic sufferer population
I'm not going to bother replying anymore. I've read every single post in that thread since it started - that's 500 pages of my time.

Good luck with your project.
 

mariovitali

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Look, if you can't be bothered to read the next sentence in the same paragraph:

I'm not going to bother replying anymore. I've read every single post in that thread since it started - that's 500 pages of my time.

Good luck with your project.
Sorry to hear this. I really am.

Sincerely, Good Luck to you too.
 

adreno

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Unfortunately i fail to understand what you mean by "trendy molecules" and "sifting technique" so i would really appreciate if you can elaborate.
You don't need to be a medical professional to understand what Edwards is saying here. He simply means molecules that are trendy (popular) to study at the moment. Unfortunately, just because a topic is trendy to study ATM, and is often given grant money, doesn't necessarily mean it has muchsubstance or will pan out to anything useful in the end.

And as he says - garbage in equals garbage out. If most of the studies out there are garbage, then your algorithms aren't digging gold.
 

mariovitali

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You don't need to be a medical professional to understand what Edwards is saying here. He simply means molecules that are trendy (popular) to study at the moment. Unfortunately, just because a topic is trendy to study ATM, and is often given grant money, doesn't necessarily mean it has muchsubstance or will pan out to anything useful in the end.

And as he says - garbage in equals garbage out. If most of the studies out there are garbage, then your algorithms aren't digging gold.
@adreno Thank you for your reply


Right, let's assume that MERTK, AXL, GAS6 are "trendy" topics for a moment. Does this also imply that the following paragraphs on the paper (as an example) :

Among them, the Tyro3, Axl and MerTK (TAM) tyrosine kinases play an especially important role in the clearance of apoptotic cells by macrophages and dendritic cells [5]. Mice lacking the three TAM receptors rapidly develop lupus-like symptoms, being the MerTK receptor the most potent mediator in this instance [6, 7, 8].
and

In SLE, however, the clearance of apoptotic cells by macrophages is impaired, which may allow apoptotic cells to serve as immunogens for the induction of autoreactive T and B cells and drive the production of auto-antibodies

...Are incorrect / garbage? Is this what is implied here !?


If this is so, i would really like a scientific explanation to be honest.
 
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adreno

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...Are incorrect / garbage? Is this what is implied here !?


If this is so, i would really like a scientific explanation to be honest.
I don't know if the paper is garbage. But if a professor of immunology thinks that it is, I tend to take his word for it. After all, his understanding of the subject is infinitely greater than mine.
 

mariovitali

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I don't know if the paper is garbage. But if a professor of immunology thinks that it is, I tend to take his word for it. After all, his understanding of the subject is infinitely greater than mine.
Yes i should have probably make this more clear to you and everyone else reading this. Perhaps the paper is Garbage, but I was referring to the following paragraph contained in this paper that has references to 4 scientific papers (shown as 5,6,7,8):

Among them, the Tyro3, Axl and MerTK (TAM) tyrosine kinases play an especially important role in the clearance of apoptotic cells by macrophages and dendritic cells [5]. Mice lacking the three TAM receptors rapidly develop lupus-like symptoms, being the MerTK receptor the most potent mediator in this instance [6, 7, 8].
and this same paper has a reference to one more scientific paper (shown as [4] ) :

In SLE, however, the clearance of apoptotic cells by macrophages is impaired, which may allow apoptotic cells to serve as immunogens for the induction of autoreactive T and B cells and drive the production of auto-antibodies[4]
Professor @Jonathan Edwards please forgive me once again but i see paragraphs that point to references of scientific papers and these paragraphs are contained in the second link i provided. Do you agree with these two paragraphs i quoted (and the associated references)?

@Valentijn would you like to comment this time?



References to 4,5,6,7,8 (shown as 1,2,3,4,5) :



  1. Munoz LE, van Bavel C, Franz S, Berden J, Herrmann M, van der Vlag J: Apoptosis in the pathogenesis of systemic lupus erythematosus. Lupus. 2008, 17: 371-375. 10.1177/0961203308089990.View ArticlePubMedGoogle Scholar
  2. Seitz HM, Camenisch TD, Lemke G, Earp HS, Matsushima GK: Macrophages and dendritic cells use different Axl/Mertk/Tyro3 receptors in clearance of apoptotic cells. J Immunol. 2007, 178: 5635-5642.View ArticlePubMedGoogle Scholar
  3. Cohen PL, Caricchio R, Abraham V, Camenisch TD, Jennette JC, Roubey RA, Earp HS, Matsushima G, Reap EA: Delayed apoptotic cell clearance and lupus-like autoimmunity in mice lacking the c-mer membrane tyrosine kinase. J Exp Med. 2002, 196: 135-140. 10.1084/jem.20012094.PubMed CentralView ArticlePubMedGoogle Scholar
  4. Scott RS, McMahon EJ, Pop SM, Reap EA, Caricchio R, Cohen PL, Earp HS, Matsushima GK: Phagocytosis and clearance of apoptotic cells is mediated by MER. Nature. 2001, 411: 207-211. 10.1038/35075603.View ArticlePubMedGoogle Scholar
  5. Lu Q, Lemke G: Homeostatic regulation of the immune system by receptor tyrosine kinases of the Tyro 3 family. Science. 2001, 293: 306-311. 10.1126/science.1061663.View ArticlePubMedGoogle Scholar
 
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Valentijn

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Mouse models of disease are notoriously unreliable. In some cases they might not be too far off, but in something as complicated as Lupus there's unlikely to be anymore resemblance than there is between ME and making mice swim until they're exhausted.

At best they offer the crudest of starting points for future relevant research. I would not consider them relevant for reaching any conclusions about any disease.
 

mariovitali

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Mouse models of disease are notoriously unreliable. In some cases they might not be too far off, but in something as complicated as Lupus there's unlikely to be anymore resemblance than there is between ME and making mice swim until they're exhausted.

At best they offer the crudest of starting points for future relevant research. I would not consider them relevant for reaching any conclusions about any disease.
It appears that these two papers talk about patients. :


Increased plasma levels of the soluble Mer tyrosine kinase receptor in systemic lupus erythematosus relate to disease activity and nephritis.


Increased levels of, in particular, sMer and, to some extent, sTyro3, were found in patients with SLE or RA, but not in patients with CLI. Patients with SLE demonstrated the highest sMer levels and there was a strong correlation to higher SLE disease activity score (SLEDAI). In contrast, in patients with RA, the sMer levels did not correlate with the disease activity score (DAS). In SLE, sMer levels were particularly high in those with lupus nephritis, patients who also had decreased C1q levels and increased titers of anti-DNA antibodies. After therapy, the plasma concentrations of sMer decreased in parallel to the decrease in SLEDAI score.


and some more :


The association of Tyro3/Axl/Mer signaling with inflammatory response, disease activity in patients with primary Sjögren's syndrome.


RESULTS:
The mRNA expression levels of Tyro-3, Axl were decreased in pSS patients. When considering the plasma level, increased levels of soluble Mer was observed with statistically significant difference. Soluble Mer levels were positively correlated with IgG levels (r=0.53, P<0.01), Erythrocyte Sedimentation Rate levels (r=0.44, P<0.01) and Sjögren's Syndrome Disease Activity Index (r=0.48, P<0.01). And the levels of soluble Mer in patients with the presence of SSA/SSB were higher than those without SSA/SSB.

CONCLUSIONS:
The plasma levels of sMer were increased in pSS patients, which was associated with inflammatory response and disease activity.

Sjogren Syndrome is considered an autoimmune disease FYI :

https://en.wikipedia.org/wiki/Sjögren's_syndrome
 

mariovitali

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@Valentijn


And one more reference for humans :

Review The Role of TAM Family Receptors in Immune Cell Function: Implications for Cancer Therapy

<SNIP>

5. TAM Signaling in Autoimmunity

In humans, there is vast evidence showing an association between autoimmunity and abnormalities in TAM signaling components. Polymorphisms in the Mer gene are associated with systemic lupus erythematosus and multiple sclerosis [95,96].
Additional relations exist between single nucleotide polymorphisms (SNPs) in the Pros1 and Gas6 genes and patients with Behcet’s uveitis or type 2 diabetes [97,98]. Aberrant expression of TAM members also has been reported in autoimmune disorders. For instance, reduced expression of TAM receptors in circulating immune cells as well as low plasma concentrations of TAM ligands are evident in lupus, Behcet’s disease, rheumatoid arthritis, inflammatory bowel disease, and psoriasis patients [58,99–103].





FYI : Tyro-3, Axl, and Mer constitute the TAM family of receptor tyrosine kinases (RTKs)


Looking forward to your comments
 

Valentijn

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@mariovitali - I still don't see the relevance to your theories about CFS. Nor any explanation of how you believe SNPs are involved and could be used to make decisions about treatment.
 

mariovitali

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@mariovitali - I still don't see the relevance to your theories about CFS. Nor any explanation of how you believe SNPs are involved and could be used to make decisions about treatment.
Once again you choose not to comment on the specific research for *humans* i posted about TAM Signaling, B Cells and Autoimmunity

Do you have anything to comment regarding the Topics i mentioned ?
 
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Valentijn

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Once again you choose not to comment on the specific research for *humans* i posted about TAM Signaling, B Cells and Autoimmunity

Do you have anything to comment regarding the Topics i mentioned ?
No, and until you can answer the questions I have repeatedly asked, I really can't be arsed. Good luck.
 

mariovitali

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@Valentijn Thank you, i sincerely wish you the same too.


@JaimeS


This is a screenshot from string-db, a tool that i have used extensively. It produces a network of predicted associations between genes much like the software i use.

I entered MERTK, wishing to see its associations, here is what we get :


screen1.png

You may also see GAS6 which was also selected by the software i use. String-db however offers yet one more function. See below :

screen2.png
Notice the lines having as entries :

a) Biotin
b) acetyl-coa Metabolic Process
c) Fatty acid biosynthesis
d) Fatty acid Metabolism
e) Pyruvate Metabolism (...!!!)



FYI my lawyer is preparing a Non-Disclosure Agreement so i may give the undisclosed version of my Research. I will contact the OMF very shortly.

EDIT : I sincerely hope that the work done by the Swiss Institute of Bioinformatics (they created String-db) is not considered "Garbage".


https://www.sib.swiss/



Link here : https://string-db.org/cgi/network.pl?taskId=hzMCYd3p67W0
 
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I'm still new here. Is mariovitali an academic and what is his field? Is there a thread with a list of medical professionals as I would like to follow them.
 

mariovitali

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@Maya24

I am not an academic. I am a Data Scientist with over 17 years of experience on analysing Data. FWIW, I have been trying since 2015 to contact Researchers and have them evaluate my findings.

I will keep contacting them and documenting all of my efforts (both of my research and for having someone to at last evaluate it) on my Blog at algogenomics.blogspot.com

I believe that there is also great information within this Thread too, so i will be using it as well.

@adreno @Valentijn

I am trying to find the latest information on how Rituximab trials are going, are there any pointers to this information? Do we have any news regarding

a) LONG TERM results
b) Side Effects


I am asking this since i saw this thread :


https://sciencebasedmedicine.org/chronic-fatigue-syndrome-rituximab-revisited/



Thank you
 
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mariovitali

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@Ben Howell
@JaimeS

Not sure if you have this info but here goes: Do you know whether any Liver Biopsy (for checking Liver Fibrosis) has ever been performed to CFS patients since Research on CFS has started?

If it has been performed do you know how many areas of Liver were checked?
 
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