sam537

I have completely lost track of what I have read and my thoughts. I really should journal. That being said as somebody else mentioned this is very pleasing to the eye. The UI with no ads and no buy buttons is so refreshing. I see that some of the covers are from specific editions. Any way to change those? Where are they coming from? I will give it a try and add a few books and see. Good job!

I came to say this. Free episode to listen to. If you are interested in this it is Nx more cost-effective to listen to Liemandt than to read the adjective laden article.

Popular and incompletely understood. That analogy is unhelpful to understand processes. It's attempting to explain a incompletely understood phenomenon with another. As someone else said below, the problem of the genome being the 'compressed representation' is reductive since genomes do not exist in isolation in an organism. Genomes were environmentally selected for millenia and many unicellular organisms share genomic material with other organisms or the environment. I think the framework is useful but it does not scale.

You should check out a currently approved drug that is very similar called amivantamab (Rybrevant). Also targets EGFR and MET (MET can sometimes be a resistance mechanism to EGFR blockade).

The problem here is the potential toxicity of this combination. In lung cancer for example, the combination of anti-EGFR therapy + pembrolizumab led to deadly pneumonitis (lung inflammation). We want to cure more patients, but we don't want to kill them before their cancer.

Maybe I can help. Progression is usually defined by radiological endpoints (RECIST 1.1 criteria) meaning that at timepoint x the tumor stayed the same size, got smaller, or grew less than 20%. Radiological measurement is very subjective so most of these trials centralize measurement of 'target lesions' (some patients have many tumors but not all are measured in clinical trials). It is worth nothing that inside PFS not only progression is an event but also death. So if you progressed and/or died, you count as an event.

The overall response rate is a combination of complete response (tumor not measurable radiologically) and partial response (>20% reduction in size). That is a common trial endpoint.

As someone else said the Breakthrough designation is common and does not necessarily lead to efficacious drug approvals.

I am close to some of these institutions and it pains me to hear the trouble you had just getting an answer a yes or no answer or getting your paperwork checked for eligibility. In large institutions there is not only an institutional culture but a Department-specific culture (as crazy as that sounds!). I am lucky to be part of a Department that has a immediate attention and transfer attitude from leadership and it permeates down to the faculty and next-day appointment slots are kept open and things accommodated.

I wish you the best, and it makes me want to work even harder to hear about the challenges we still face.

Some comments about dietary science are true. It is extremely impossible to isolate the effect of a single substance (ethically).

This person greatly benefited from stopping caffeine intake which is great. It is part of the journey to understand ourselves and what makes us work/improve/feel better.

If you have a anxiety-o-meter that looks like this: [-----------------------------------]

and your baseline is here: [-------------------------X---------] - you just need a little push to go into anxiety/can't sleep mode which can come from caffeine.

But if your baseline is around here: [--x--------------------------------] -maybe some coffee in the morning, right after lunch will greatly increase your clarity/make you able to fulfill your duties. People who drink caffeine for pleasure (I love the taste of coffee and sometimes I get beans so good that I just want to drink several cups) will notice the negative effect in their sleep/anxiety levels. We must go back to Paracelsus 'dosis sola facit venenum'. The dose makes the poison.

The text was ok, I do not know anything about spermatogenesis but a fair bit about the JAK/STAT pathway. The abstract was pure LLM, however. It has been retracted.

Not only that. The JAK "pathway" is complete gibberish. The third figure is a pool of random spheres in "differentiation" steps. The whole Frontiers publishing group is widely seen in academia as worthless, however, since most promotion committees just count the number of publications no matter where they may be, they continue to publish anything and make bank.

As an animal with similar fastidiousness, I agree. I am happy to have found this. Reminded me of After Dark by Murakami.

You should also try immunotherapy (pembrolizumab) with chemo if your CPS is >1% before experimental early phase trials.

Mildly interesting.

The lowest of the low? Based on consonant pronunciation? How can you extract a value judgment from how someone speaks?

This is the bottleneck for one company. We have many companies this size doing the same thing.

The issue is large companies (novartis/BMS) sometimes sit on compounds and refuse to develop because they think it may not be worth it, may think a certain disease (read market) is saturated, or they may be waiting for the 'right time'. It can be frustrating.

Smaller companies have 2-3 compounds which they actively work to develop but most of them end up getting acquired by the big fish.

There are a few vaccines that try to 'make' your immune system recognize an abnormal (read cancerous) protein as foreign (Sipleucel T for prostate, GMCSF vaccine for melanoma). Minimal activity.

Look at GRAIL therapeutics. Cancer sheds DNA that can be detected and amplified. We use this sometimes to try to tell if someone will have a recurrence before scans actually show it. Sequencing is hard, and there are contaminants and difficulties calling a mutation/sequence cancerous, but I have had patients self-refer after a positive GRAIL test, no symptoms, and bam, biopsy from area of interest shows early cancer.

Oncologist here. You can think of drug development as an extremely wide funnel with a minuscule exit hole. At any given time a medium sized pharmaceutical company has 300-500 drug candidates. From this group 50 make it to phase 1 trials. 40 get slashed due to toxicity, company abandons them, gets bought by third party and sits in sleepy storage. 10 advance to phase 2 trials where 5-8 may not end up having enough efficacy/too toxic, does not improve survival. The remaining 3-5 advance to phase 3 where they can suffer the above as well.

Tl:dr: Things usually work in the lab where all ideas start. Until a compound goes through thorough human experimentation believe little.

The internet can still be a beautiful place.

I wonder how many of us got sidetracked into playing at work today.

There are two types PD1 and PDL1 inhibitors.

Cancer cells (and our own cells) express PDL1. Our immune cells touch PDL1 with their PD1 and if this connection works then the immune cell does not kill.

If the connection does not work (PDL1 or PD1 absent) the immune cell will kill the target cell.

These antibodies either block PDL1 or PD1.

This is misleading. Yes, the response rate is extremely high but all of this patients shared a mutation or a group of mutations in mismatch repair proteins (they were all MMR deficient, or mismatch instability high).

This effect is shared across many tumors with this feature not only rectal and the FDA approved a drug with the same exact mechanism in 2017 (https://www.fda.gov/drugs/resources-information-approved-dru...)

If I had to guess this is a huge marketing plot to bring yet another extremely expensive drug to the market. What is happening is that different drugs (ie different companies) take the space of a specific tumor (Keytruda for lung, Opdivo for melanoma, Tecentriq for liveer cancer) and Dostarlimab is going to claim the rectal cancer space.

Thank you.

It's great to talk in terms of indices and devaluations and of "breaking the bank of England". The lives affected are not even spared an afterthought.

This just made my day.

Simplify it like this:

T-cell: very effective at killing; not as good at recognizing specific things.

Antibodies: not that effective at killing; excellent at specifically recognizing things.

CAR-T: Let's stick an antibody against X (eg CD19, CD22) to a T-cell surface so it can recognize with the antibody and kill with its innate capacity to kill.

Ta da!

It's fascinating, it is changing hematologic oncology. The bad news is, as always, the price and the manufacturing time (2-8 weeks). This last part seems to be getting better.

Thank you for sharing this.

Insta-bookmark. Thank you.

How does notebook/Jupyter help? What does it add?

I'll check that out. Thanks!