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Combo Metformin And Syrosingopine!!!! Looks Awesome!

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GgE
 GgE
(@gge)
Joined: 3 years ago
Posts: 240
 

@hanen

Hanen, would you mind sharing with us your experience with syrosingopine? We would love to know things like if it had any effects in your case and where you got it from. Thanks!


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John Pizzuto
(@jpizzuto)
Joined: 2 years ago
Posts: 214
 

My wife's last two PET scans show progression.  I ordered syrosingopine about two months ago.  Apparently, their production has not caught up with demand.  My order just shipped and will be here next week.


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Daniel
(@daniel)
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@jpizzuto

Thanks for posting John. What is the cancer type and with what are you going to combine Syrosingopine?


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John Pizzuto
(@jpizzuto)
Joined: 2 years ago
Posts: 214
 

She has MBC.  She had a lumpectomy in 2013.  The surgeon said "I got it all", so she opted for no post op chem or radiation.  Five years later, debilitating pain.  An MRI showed bone mets all over her back, spine broken, and mets on her hips.  She's been bedridden for 18 months.

I put us both on keto, plus we did 50 sessions of hyperbaric treatments with no apparent affect.  Letrozole is all she's been taking.  She tried Ibrance a year ago but she had to stop after 9 days.  They just started her on Faslodex, saying the Letrozole is not strong enough.

I made a presentation to her oncologist about syrosingopine  in  combination with metformin.  I expected her to say "don't try this at home", but instead, she cautioned and said "be very careful".

I posted links last night on freerepublic to the research article, the patent, and the team inspire forum where one member is having success with it here:

https://www.freerepublic.com/focus/religion/3790562/posts?page=21#21


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Daniel
(@daniel)
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@jpizzuto

Thank you John. Please keep me up to date and if you have questions please let me know. From your post I understand you have challenges with getting Metformin. Here is a link of an online pharmacy from which I was ordering drugs many years ago and was always happy with their service https://www.buy-pharma.md From your post I understand people order Syrosingopine from Alibaba. Some suppliers can be trusted and have good quality products others not. Those ordering drugs should test the ordered product to make sure it is what they ordered. 


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John Pizzuto
(@jpizzuto)
Joined: 2 years ago
Posts: 214
 

Daniel:  Thanks very much for the pharma link.  The supplier has posted graphs of the purity and composition.  FWIW.  🙂

https://dideu.en.alibaba.com/?spm=a2700.8443308.0.0.3a2c3e5fnEelYd


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Jcancom
(@jcancom)
Joined: 4 years ago
Posts: 547
Topic starter  

JohnnyP, is that you?

I am so glad that you have arrived on this forum. D has generated a great many ideas and there is a real feeling here that progress is being made. Once we clued into the idea of metronomic dosing, consistent responses began to occur. These results are in line with the remarkable results from the Turkish metabolic clinic. Some of those on forum are using highly innovative approaches that might be shown to be quite effective.

Best Wishes, Jcancom 


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John Pizzuto
(@jpizzuto)
Joined: 2 years ago
Posts: 214
 

J:  Yes, it is I.  Allow myself to introduce myself.  🙂  

Shirley's PET/CT scan in early October shows further progression and bone fractures.  She continues to lose about a pound a week, was down to 127 last week at her oncology follow up.

I had high hopes for the hyperbaric treatments.  Oh well, now we have hope again with the syro/metformin.  I have the scale set up on the dining room table.  The dose is just 2 or 3 mg's, so I need to start practicing with baking soda.

Daniel:  Do you know of anyone here using syro/metformin?  SteveK on the team inspire forum is the only other one I know of using it, though he says there are a few others using it after seeing his success.


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Daniel
(@daniel)
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@jpizzuto

Dear JohnnyP,

Nice to hear that you are J's friend from CancerCompass. I saw some of your posts there. I met J there nearly 5 years ago 🙂

I am not in contact with people using this combo - for many is difficult to get Syrosingopine. However, if I would try this (which I think its a good idea), I will not rely on the two only but this about the following and do more accordingly:

1. Do I want to focus on inhibiting energy production of cells with this combo?

If yes, I would add 3 inhibitors of glyco and 3 of mitochondria from the glyco inhibitors such as discussed here https://www.cancertreatmentsresearch.com/drugs-and-supplements-that-block-fermentation-and-help-fight-cancer/ with mitho inhibitors such as discussed here https://www.cancertreatmentsresearch.com/a-list-of-mitochondria-inhibitors/  

2. Do I want to acidify the cell?

This is also a very good idea and the strategy has been discussed here https://www.cancertreatmentsresearch.com/ph-cancer-a-top-treatment-strategy/

Actually, the combo of Syrosingopine with Metformin is more of a cell acidifying strategy instead of energy depletion strategy. I know this strategy https://www.cancertreatmentsresearch.com/ph-cancer-a-top-treatment-strategy/ has led to positive results in cancer patients with breast cancer. 

In order to make it stronger, I would consider adding at least one more mithocondria inhibitor from the list discussed here https://www.cancertreatmentsresearch.com/a-list-of-mitochondria-inhibitors/ and more proton pump inhibitors. One such example of a combo to enhance syrosingopine+metformin would be the following:

1. Inhibiting mitochondria:

  • Metformin - inhibiting complex I
  • Atovaquone inhibiting comples III or Doxycicline inhibiting mitochondrial protein translation

2. Inhibiting proton transport

  • Syrosingopine - inhibiting MCT4
  • Amiloride (this is diuretic and blood potassium should be tested every other week to make sure it stais normal) inhibiting Na/H exchange
  • Acetazolamide - inhibiting CA IX

All are powerful so I would expect results. But also because they are powerful I would make sure they are implemented in a safe manner, not all at once and with the help of a medical trained person.

Have a look at Sulfasalazine as it may help with bone pain https://www.cancertreatmentsresearch.com/cancer-addiction-to-cystinecysteine-another-piece-in-the-puzzel/

There is more that could be done but this would be a minimum I would do to make the strategy stronger.

Kind regards,
Daniel


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Jcancom
(@jcancom)
Joined: 4 years ago
Posts: 547
Topic starter  

JohnnyP, I am so glad that you migrated here. These posters often use intense around the clock treatments for cancer control. At the least an increased level of intensity is needed to address cancer. Just by being on forum you will feel this intensity and it will change your perspective. D's advice above is an example of the thinking that is required for a better chance of success. What is especially remarkable is that we have seen some here that are clearly doing better than what one would expect.

There have been a number of successes. Consider the example of Jess (see the visitor tab above). Jess's dad was coping with metastatic pancreatic cancer which is recognized as a particularly difficult form of cancer. When they tried a metronomic metabolic approach with 2-DG there was an abrupt collapse in the cancer marker; apparently this even impressed their oncologist. This result mirrors those reported from Turkey using a similar metabolic protocol. As a result of successes on forum and elsewhere, D has become active in advancing this therapy through his foundation. 

The idea of duration dosing is intuitive, though we had not clued into it until about a year ago. This was possibly motivated by comments on the vitamin C thread in which the original vitamin C clinical trials from the 1970s were re-considered as being demonstrations of metronomic dosing. What is especially remarkable about this research was that in the first series of 50 patients 8% (4 patients) actually had fatal TLS responses to the all day dosing regimen used; others had substantial responses. I still do not understand how these results have largely been lost for the last 50 years.

TLS is fairly rare, even now patients with solid cancer who experience TLS will be written up in journal articles as examples of a medical curiosity. How could people have ever been lead to believe that this vitamin C trial had not demonstrated efficacy? The arguments about the legitimacy of the placebo arm and the trials that used oral dosing etc. never addressed the very large responses that a fair number of the patients demonstrated. One might guess that with all of our modern technology that it should be possible to determine prospectively who would respond to such treatment.  

It has been a struggle, though through time we do seem to have made forward progress. Metronomic dosing is one highlight, as is our focus on the metabolic approach (glycolysis and OXPHOS  inhibition especially), along with additional downstream metabolic effects. Another idea that has gained at least some traction is chaotic dosing. The idea here is that merely treating in nice straight lines with uniform treatment schedules gives cancer a large advantage as simply repeating the same stressor repeatedly will ultimately result in selecting cancer lines that are immune to the stressor. This typically happens even with the latest and greatest cancer breakthroughs. Yet, with the very wide range of treatments that are constantly posted to this forum, more complex treatment schedules have been devised that add in a higher level of complexity and seemingly a greater stress on cancer.

This forum is more directed to those who are self-starters with many having a substantial amount of technical knowledge related to treatments, though it still offers those with a range of competencies numerous helpful suggestions. Large placebo controlled phase 3 trials for the various treatments suggested here are not available and likely never will be, so there is a clear sense that we are out on the frontier and answers must be imagined instead of being empirically demonstrated. We all want there to be clear answers and effective treatments, yet the clinical trial process in cancer research has almost become completely obstructed.

Even monotherapy trials with highly promising treatments (e.g., 3-BP) can be blocked for decades, though as we are very aware monotherapy is often not an effective strategy. It is extremely disappointing that clinical trials are not conducted according to integrative medicine rules in which patients in the treatment arm could be rapidly cycled through a large number of treatments in order to find something that could help them.

D and I have talked off forum about how exciting it would be to have 10 shots on goal with different powerful cancer therapies with success being defined as scoring at least once (i.e., a large cancer response). With the therapies mentioned on this forum, 10 shots on goal would seem more than sufficient.

I greatly hope that you will find something here that will be helpful.          

Best Wishes, J

   


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John Pizzuto
(@jpizzuto)
Joined: 2 years ago
Posts: 214
 

@jcancom

Our syrosingopine shipment should arrive later today, so we will get started on the syro/metformin combo.  I spent the evening translating the manual for the scales I ordered from China, to measure the syro.  The translation produced words in English.  FWIW.  🙂

Can you or Daniel recommend the top two or things to add to her treatment? 

I clicked on the links in Daniel's reply and was overwhelmed.  Trying to sort through them, Canaglifozin looks like the first one to try if we can get a prescription.  Phlorizin/phloretin looks good but it's IV only.  Not practical to do at home.

How hard is 2dg to get?  Anyone here using it?

 


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Jcancom
(@jcancom)
Joined: 4 years ago
Posts: 547
Topic starter  

JohnnyP, D has quite a bit of experience with clinical management. It is very impressive how several of the posters to this forum have learned the skills needed to do IVs and some other procedures. Perhaps you might want help with this from a home care nurse or other. IVs open a great number of options. One of these is metronomic 2-DG, in fact this is what D and his foundation is advancing.Several of those on forum have have 2-DG treatment experience.

Notice with Jess's story that when they had a quintiple combo of 3-BP, sali, fasting, PDT, and 2-DG along with chemo the tumor markers rapidly collapsed. The lesson here was that  if you had a chemo response then metabolic pressure could add overwhelming stress to the cancer. Probably for many patients when they add in metabolic treatments, the stress on the cancer is not sufficient; however, with metronomic 2-DG etc. the cancer quickly ATP depleted and is no longer viable. The Turkish clinic talked of how they believe that they could achieve such results without the chemo; it is not entirely clear to us yet how this might be done reproducibly. 

https://www.cancertreatmentsresearch.com/a-new-approach-to-improve-effectiveness-of-cancer-therapies-is-getting-ready-to-begin-human-trials/

I realize that this seems all quite too much, though gradually building up and developing confidence in your skills will get you up to speed. However, I would tend towards caution and begin with your intended plan of using syro/metformin by themselves until you develop confidence and then add in others.

 

 

 

 

 

 

 


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John Pizzuto
(@jpizzuto)
Joined: 2 years ago
Posts: 214
 

Thank you.  Yes, home IV is a little scary.  I wanted to learn how to do it for IVC while we were doing hyperbaric therapy.  But, we stopped HBOT as there was nothing positive in her latest scan.

I thought about paying to have a pic line or port inserted, but that requires a prescription and hospital visit, about $1k from what I can see.  Doable if we could get the prescription.

Is anyone mixing their own IVC?  I watched a Cathcart video where he says he uses Bronson's sodium ascorbate, 50/50 by volume.


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Shanti
(@shanti)
Joined: 4 years ago
Posts: 60
 

@jpizzuto

Hi JP-

We mix our own vitamin C. We typically do 75g sodium ascorbate. This is mixed with sterile water so that the total final volume of IV solution is 750ml. We prepare it according to the instructions found in this document: https://riordanclinic.org/research-study/vitamin-c-research-ivc-protocol

Please ask Daniel for my email if you would like to correspond on the details.

 


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GgE
 GgE
(@gge)
Joined: 3 years ago
Posts: 240
 

I spent the evening translating the manual for the scales I ordered from China, to measure the syro.  The translation produced words in English.

Johnny, would you mind sharing your English translation of the scale instructions manual? I ordered the same scale model and have no idea of Chinese. Daniel can give you my email address.

I would check not only the interactions and incompatibilities when you combine several drugs. I would also check how they are eliminated. Most times they are processed by the liver and/or kidneys. If these organs get too overloaded by a heavy load of the drugs at one time they can get seriously damaged. If she gets kidney or liver necrosis she’d have a serious problem. She would probably not be able to take most of the drugs any more…

Thanks.


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John Pizzuto
(@jpizzuto)
Joined: 2 years ago
Posts: 214
 

@gge

Where would you like me to send the files?

The google translator produced English, but it's not very usable. 

I have a friend who is trying to get a better translation from someone that reads Chinese.


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John Pizzuto
(@jpizzuto)
Joined: 2 years ago
Posts: 214
 

Zip file ok or do I have to load individual files?


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John Pizzuto
(@jpizzuto)
Joined: 2 years ago
Posts: 214
 

Zip file ok or do I have to load individual files?


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John Pizzuto
(@jpizzuto)
Joined: 2 years ago
Posts: 214
 

I tried to upload a zip file but it didn't work.  Oh well, send me your email address.


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John Pizzuto
(@jpizzuto)
Joined: 2 years ago
Posts: 214
 

MY friend had the manual translated for us.  Text only, in Word.


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GgE
 GgE
(@gge)
Joined: 3 years ago
Posts: 240
 

@jpizzuto

Thanks to you and your friend! Good job!


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GgE
 GgE
(@gge)
Joined: 3 years ago
Posts: 240
 

@jpizzuto

One more note of caution. The syrosingopine/metformin combo worked preclinically in several subtypes of breast cancer. Hopefully it will work in her subtype. If so, it will kill off the cancer cells gradually. This will give her body time to remove the dead cells and grow normal cells in their place (bone cells and soft tissues) to repair the damage.

However, it is possible to overshoot it with the treatment agents and bring in excessive killing power. If this happens, then you might kill all the tumors in her body at once within a short time. If she has a high cancer burden, this might cause her a Tumor Lysis Syndrome (TLS) which could kill her faster than her tumors…It is necessary to find a fine balance.


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John Pizzuto
(@jpizzuto)
Joined: 2 years ago
Posts: 214
 

Approach death, but do not touch it.  Got it.  🙂

Not satisfied with the translation of the manual, I emailed the seller and asked if he could supply one.  Voila.  🙂


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GgE
 GgE
(@gge)
Joined: 3 years ago
Posts: 240
 

@jpizzuto

Great! I thought they did not have. I wonder why wouldn't they send it in the first place...


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GgE
 GgE
(@gge)
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There is a possibility that cancer cells may survive the combined assault of syrosingopine and metformin by exporting protons (by their proton pumps such as CAIX and many other enzymes) even if syro blocks their MCTs and they can’t export lactate. This way they could maintain a higher, livable pH than otherwise.

I guess this is why Daniel wrote in his “A List of Mitochondria Inhibitors, Disrupting Cancer Cell Function” file that “combining mito inhibitors with glycolisis inhibitors makes sense... using only mito inhibitors is expected to lead to an increase of the glycolisis and systemic acidity. Therefore, if mito inhibitors are used for longer time, it may be not only good but desirable to combine them with glycolisis inhibitors (such as 2DG, high dose Vitamin C, etc.) and proton pump inhibitors (such as discussed here.)” The latter reference is to his file “pH in Cancer & Tumor Acidification: A Top Treatment Strategy.” This paper mentions several PPIs and mentions some of their pros and cons. I wonder if anyone knows of a complete, systematic review of the PPIs used in cancer studies stating their dosage, effects and side effects.

There is this list of PPIs at https://www.drugs.com/drug-class/proton-pump-inhibitors.html but they are only rated as anti-acids.


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Daniel
(@daniel)
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@gge

Hi, indeed this is why I reply to John with this https://www.cancertreatmentsresearch.com/community/metabolic-inhibitors/combo-metformin-and-syrosingopine-looks-awesome/paged/3/#post-1368

Some of the best known PPIs I already mentioned in here https://www.cancertreatmentsresearch.com/ph-cancer-a-top-treatment-strategy/

But if you like to search the literature you can use PubMed and search for the author Salvador Harguindey. He wrote many reviews on PPIs including dose and maybe possible side effects.

Kind regards,
Daniel


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Jcancom
(@jcancom)
Joined: 4 years ago
Posts: 547
Topic starter  

JohnnyP,  yes, scary was the word that I had in mind as well. The posters on this forum exhibit a great deal of initiative in their treatment efforts. It is a personal decision, though it needs to be remembered that metastatic cancer is even more scary.

I am glad that TLS was noted by GgE. Some of these metabolic approaches do open up that potential ( I would still love to see a continuous monitor that could keep an idea on biomarkers for TLS; it remains unclear to me why this does not appear to be part of the tool kit of clinics). 

J


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John Pizzuto
(@jpizzuto)
Joined: 2 years ago
Posts: 214
 

@jcancom

J:

Our oncologist has been providing a low dose of metformin for a few months, 250mg (1/2 a pill) twice a day.

I started Shirley on the syro/met combo Friday.  I doubled the dose of metformin to 500mg,  and added 3mg syro, twice a day.  But, that gave her diarrhea.  Don't know yet if it was the higher dose of metformin, the syro, or the combo, so, we are back to the low dose metformin for a while.  She took half a pill this morning with a little food, then 2mg syro, and all is well.  I will gradually raise the syro dose to see if diarrhea returns.

The scales I bought work really well, but you can get by without them.  I also ordered a set of mg spoons from amazon.  I found that a level scoop in the smallest spoon (the blue one) measured 2.9mg.  To measure, I place a 1" square of aluminum foil on the measuring tray, zero the scale, then dump the scoop of syro onto the foil.  If I am satisfied with the quantity, I carefully retrieve the foil, then surround the syro with a couple drops of olive oil to stabilize it for transport.

As far as I can tell, the pills we have are quick release, which give a higher serum concentration, so I think we should stick with those if we can.

I've been studying the research paper, trying to determine the minimum dose of metformin required to achieve "x" umol/L concentration in the blood.  Also would like to know the minimum syro dose.

The research paper also talks about adding the MCT1 inhibitor ARC155858.  Refer to figure 5 here:  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6302548/#mmc1

The graphs show a dramatic reduction in the required quantities of syro and metformin to work.


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Yudaitheska
(@yudaitheska)
Joined: 3 years ago
Posts: 32
 

@jpizzuto

Hello Jhon! I believe the diarrhea was caused by metformin. It is a common side effect, many patients complain of that, lowering the dose was the right choice if you decide to give a higher dose try little by little to check her tolerance. Saludos! 


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Jcancom
(@jcancom)
Joined: 4 years ago
Posts: 547
Topic starter  

JohnnyP, D suggested a starting dose of syro of 1 mg/day. Did I read your post correctly? You started on 3 mg twice daily? Titrating up would always seem the best approach.

 

I was reviewing the patent and literature on Met/Syro. The patent described an in vitro method that could be used to determine efficacy pretreatment.

When I reread the 2016 article on Met/Syro, my attention was drawn to the description of the combo as a glyco/OXPHOs inhibition strategy. This is THE goto strategy of the forum. Simultaneously shutting down  glycolysis and OXPHOS (selectively) is an extremely powerful anti-cancer approach.{In my original post I focused in on the idea that the combo shut down NAD recycling.} Starting off cautiously would be especially in order for such a strong combo.

The article goes on to note that almost all the OXPHOS inhibitors aside from metformin were also effective. The one notable inhibitor not mentioned was methyglyoxal. MG is an OXPHOS subunit 1 inhibitor, as is metformin, that D has written about elsewhere. Of particular interest is that MG selectively inhibits OXPHOS I in cancer cells. Having NanoMG might be a very powerful way to amplify syrosingopine.  

Thank you for your citation of the recent MCT syrosingopine article. The escape routes for cancer cells are being identified and closed off.

Yes, I believe I recall also going through the metformin calculations.The patent does not seem overly helpful in this regard as it gave an order of magnitude range to choose from. It is so often frustrating that there are effective anti-cancer drugs such as metformin though they can be dose limited. This dose limitation problem is what inspired the search for a synergistic combo and syro was found.

 

The mito-Met research is startling!

Recent article:

https://www.ncbi.nlm.nih.gov/pubmed/31191823

Earlier research:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4930686/

"In particular, the analogue Mito-Met10, synthesized by attaching TPP(+) to Met via a 10-carbon aliphatic side chain, was nearly 1,000 times more efficacious than Met at inhibiting cell proliferation in pancreatic ductal adenocarcinoma (PDAC). Notably, in PDAC cells, Mito-Met10 potently inhibited mitochondrial complex I, stimulating superoxide and AMPK activation, but had no effect in nontransformed control cells."

These mitocans are extremely powerful anti-cancer drugs. Synthesizing them might be of great help. 

 


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