Dr. Omene MD, PhD

This is what a brain looks like with no priors. Your brain is a prediction machine. Every sensory input gets compared against an expected input built from prior experience. When reality matches your model, you feel nothing. When reality breaks your model, you feel wonder. She's around two. Her model of the world is microscopic. A train is 200 tons of metal moving 50 mph through her field of view, and her brain has no template that fits. The prediction error is so large her face becomes the prediction error. This is Karl Friston's free energy principle in real time. The brain minimizes surprise by updating its model. Children update constantly because almost everything is new. Adults update almost never because almost everything matches a prior. That's why adults can stand next to the same train and feel nothing. Their model already contains it. The signal gets predicted away before it reaches conscious awareness. The wonder window narrows as priors fill in. After that, you have to manufacture novelty. She still gets it for free. You used to react to everything this way. Then your brain finished its training run.

@MichaelRedd_ 🎯🎯🎯

There's likely a reason within the analytics and model, but if you ask me, LJ's best run was that second stint in Cleveland (15-18). So, for that to be his least HOF-worthy stretch is weird. Lot of ways to explain it, but still, weird.

@EricTopol @NatureCancer This is promising. However, up to 60% of cells in the GBM TME are immunosuppressive myeloid cells, mostly macrophages. Amplifying T-cell response against this brick wall isn't going to cut it. That's why the median survival data is barely better than standard of care.

Personalized neoantigen vaccines vs cancer: we've seen benefits for pancreatic, renal and melanoma. Today initial, encouraging results vs glioblastoma in 9 patients with this deadly brain cancer @NatureCancer nature.com/articles/s4301…

@tomhaberstroh @YahooSports How could Cleveland 2 have only 50.5% probability. Something is broken in the model sir.

NEW @YahooSports: If last night was truly LeBron James’ final game as a Laker, he’ll walk away knowing he had a Hall of Fame career *based solely on his 8 Lakers years.* LeBron has now stacked 4 HOF careers, and I shared all the data to prove it: sports.yahoo.com/nba/article/ki…

La biología en PDF acaba de morir. Un tío hizo una app donde exploras estructuras 3D como un videojuego. UI: GPT Images 2. Código: Gemini 3.1 Pro. Los libros de texto ya no sirven.

🚨: Neuroscience considers metacognition the highest form of intelligence..... "the ability to think about your own thinking."

@YannickBuccella Wait you are reporting on this but not on the vitamin C study? Or did I miss it?

This pill has just more than doubled the median survival time of patients with stage 4 pancreatic cancer, where one chemotherapy has already failed. > 90% of patients are eligible, since the necessary gene mutation is abundant in pancreatic cancer. Amazing breakthrough!

@bobvarkey CAR-T likely unwise in GBM: x.com/DoctorOmene/st…

The new treatments for glioblastoma are going to be very expensive. Are they going to be cost effective? GBM CAR-T: The idea is enthralling: — engineered immune cells targeting GBM cells. The data from trials in autoimmune diseases is startling But after years of trials, the reality is still complicated in GBM Response rates are < 10% in most studies. Median progression-free survival? About two months in recurrent GBM. The tumor microenvironment is a quagmire , it’s hypoxic, immunosuppressive, and actively hostile to T cells. T cells arrive exhausted and die fast. There are durable responses in select patients, proof that intracranial delivery is feasible, and rapid advances in T-cell engineering. However this is offset by abysmal response rates, significant neurotoxicity (cerebral edema, ICANS), and the stubborn fact that T cell exhaustion in solid tumors remains largely unsolved. Phase II dual-target CAR-T come out late this year. The threshold for clinical meaning is PFS exceeding six months in recurrent GBM : ie triple the historical baseline. If that happens, then CAR-T becomes a legitimate standard-of-care option. If not, it evolves further. At an expected cost of 5 Cr or more , it will not make financial sense for most Indians, unless it delivers realistic outcomes. 🤞🤞

@AlexanderMWolf7 @Outdoctrination It's a logical consequence of the mechanism. The link between AGE and aging is in the literature. On what grounds do you think they don't contribute to aging? You are basically claiming "absence of evidence" but no affirmative mechanism. Also, evidence isn't absent.

@DoctorOmene @Outdoctrination Yes, but there's essentially no evidence that AGEs play any significant role in aging.

Calorie restriction can increase lifespan by ~40% - but a stunning study showed that it's NOT because of fat loss or insulin sensitivity. In fact, the animals who were the fattest actually lived the longest! (🧵1/8):

@AlexanderMWolf7 @Outdoctrination Yes we see the water makes the steel rust but we have no idea whether or not it causes wear and tear 😂😂

@DoctorOmene @Outdoctrination The mechanisms of how they are produced is fairly well known, and yes, "there's literature around it". But there's still essentially no evidence that they play any significant role in aging.

@5_utr @RWJE_BA LOL

What we really need is more biomarker-driven personalized therapy incorporating gut microbiota, immune micro environment, to allow for a robust translational pipeline to intercept evolution utilizing next generation causal AI with do-operators and graphical displays 😅 @RWJE_BA

Yes but not both at once and not multi-agent across transporters and receptors. Glutamine blockade by itself will fail. Glucose blockade by itself will fail. I am aware of all the DON pro-drugs and some glycolytic drugs. The DON pro-drugs limit toxicity though I'd argue the GI toxicity from DON isn't terrible compared to chemo. Also there seems to be little attention paid to ketosis mitigating toxicity.

@DoctorOmene @YannickBuccella My view at the moment is that both glucose and glutamine targeting are well known in the literature/field

PET scans follow the fuel, they don’t prove sugar is the driver of cancer. 3 reasons why this theory is wrong: 1) In a PET scan it’s not only cancer tissue, which lights up. It’s also your brain, your heart, your kidneys, inflammation and even lymph nodes after vaccines showing activity. 2) All cells need glucose, not just cancer cells. Glucose is basic fuel for every cell, and if carbohydrate intake is very low, the body can make glucose from fat and protein because cells need it to survive. 3) You cannot selectively starve cancer cells of glucose by avoiding dessert. Blood glucose is regulated by the body, tumors are supplied by blood, and the body will maintain glucose for essential organs. It doesn’t matter at all, if you eat sugar or you don’t. The body will always try to keep the blood sugar levels within a healthy range. The caveat here is that high sugar intake can contribute to excess calories, obesity, insulin resistance and diabetes, which are all known risk factors for several cancers, but for different reasons. For example we know that there is chronic inflammation in fat tissue, which is the risk driver for cancer, not glucose. It’s a different story, if you already are a cancer patient as described above. You gain absolutely nothing by avoiding sugar, tumor cells always get the energy they need.

@teamoncology I don't see any coherent story here other than different sets of mutations for different clones. What was your takeaway?

A new Nature paper shows how lung cancer metastases evolve and spread through the body. The study used sophisticated genomic analysis to reconstruct how one metastasis can seed another, and how the pattern of spread is shaped by anatomy, tumor evolution, and cancer biology. The same probably can be said with breast cancer. nature.com/articles/s4158…

@AlexanderMWolf7 @Outdoctrination If you look at how AGEs work its a problem of radicals ultimately.

@DoctorOmene @Outdoctrination Why? Which byproducts of proliferative metabolism? Net excess electrons? Sorry, but seems like incoherent rambling ...

@AlexanderMWolf7 @Outdoctrination Cell proliferation in and of itself would not drive aging. Byproducts of proliferative metabolism would. There's no free lunch. Consider that glucose is a primary proliferative substrate then consider AGEs. I still suspect that net excess electrons are going to be the driver.

@Outdoctrination Exactly. That's because proliferation driven by signaling through conserved aging pathways like mTOR determines the rate of aging, not fat mass or degree of adiposity. dx.doi.org/10.2139/ssrn.6…

Precisely. In a general sense, halting the proliferation of a tumor isn't the same as getting rid of the tumor. However, if you stop growth clinically you have "stable disease". This is a worthy goal and should be achievable by blocking proliferative biosynthesis. That means blocking glucose and glutamine. The next step is getting rid of the tumor entirely. Surgery does a great job. Radiation is not bad. Cytotoxic chemo is ok. I would prefer to use cytotoxic T cells. It just so happens that blocking glucose an glutamine metabolism might allow T-cells to breakthrough in the tumor microenvironment.

@DoctorOmene @YannickBuccella I agree about one-carbon & glucose metabolism and T cells (also good is PMID: 37961420) OxPhos is less clear - if you stimulate CD4+ cells to proliferate, total OxPhos capacity drops (PMID: 34132194) I think there's more to it than just proliferation, i.e. cell death vs growth

May the 4th

@MattZirwas Keep doing what you are doing.

So, I opened my email today and found out from the American Academy of Dermatology member email that USA Today ran AAD's Practice Safe Sun survey. The same day I posted about how dermatology is killing people and had it go viral, closing in on a million views. Talk about a lucky coincidence. Honestly. It's not like the AAD keeps me informed about their PR schedule. The headline finding: 16 million Americans have reduced sunscreen use because of online "misinformation." Based on timing, they obviously weren't talking about my post specifically, but given the "there is no such thing as a safe tan" quote in the article, I'll bet they'd call it misinformation, even though I'm not anti-sunscreen. Man I hope @aadskin or @aadmember engages. It'd make them engage with the peer-reviewed evidence base that sun avoidance increases mortality: -MISS cohort, 29,500 Swedish women, 25 years. Lowest sun exposure had mortality comparable to smokers. -UK Biobank, ~400,000 participants. Highest UV exposure had 19% lower cardiovascular mortality, 15% lower all-cause mortality. -Korean NBUVB study, 12,000 vitiligo patients. 100+ clinic phototherapy sessions associated with 36% fewer cardiovascular events. The AAD is worried "misinformation" is causing people to wear less sunscreen. I'm worried the AAD is killing people.

@5_utr x.com/DoctorOmene/st… Precision oncology started with imatinib. It was a bit of a red herring. Why not target brc-abl's ultimate target? Proliferative biosynthesis

Another Precision Failure