HN rank: 1

HN score: 339

comments: 235

original url: https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/dad2.70432

评论信号：tdlr: This is a Novo Nordisk-funded study focusing on predictive biomarkers rather than real-world dementia cases. Novo Nordisk's actual dedicated clinical trials for Alzheimer's completely failed to show that semaglutide stops cognitive decline."A predictive biomarker is like a "check engine" light on your dashboard. It warns you that there is a risk of a future problem. In this study, the researchers only checked if the drug turned off the "check engine" light (by measuring blood proteins), rather than testing if the car was actually driving properly (by testing the patients' actual memory and brain function)."Always do FIRST analysis on studies. Or have AI do it for you. I used Gemini to dig into this:"Novo Nordisk funded this study, and several of the researchers are employees or minor shareholders. While corporate funding doesn't automatically mean the data is fabricated, it does mean the company is highly motivated to find and publish data that makes their blockbuster drug (semaglutide, marketed as Wegovy, Ozempic, and Rybelsus) look like a preventative treatment for a wider range of conditions, expanding its market and driving up profits.""Funding:... reply:...

评论信号：So has anyone managed to separate the effects of semaglutide from the effects of weight loss?If this is caused by the weight loss, it is a little disappointing that public health didn't act quicker - lots of people have been overweight for a century now, so literally 10's of millions of people could have been saved from dementia had action been taken 100 years ago. reply: I have some individual anecdotal evidence. I spent a long time, basically a year, relatively heavy but on a very small dose of GLP drugs due to tolerability issues, and my labs improved dramatically, to a degree we redid them out of disbelief, even without weight loss. I believe one of the suspected underlying causes is reduction in fatty liver despite constant body weight and composition, and also inflammation reduction directly through GLP influence in other areas of the body.I'm not great evidence because N=1 and all the confounders, but I found that it absolutely made me much healthier without weight loss. I then went on to increase the dose slowly and have lost a bunch of weight and my labs improved even more, which I attribute mostly to the body mass reduction.

评论信号：If you're overweight or especially if you're T2D I highly encourage you to discuss GLP-1 with your doctor. If you're T2D then get research retatrutide which looks to be an actual cure for T2D by clearing liver fat. It should be released early next year but research-use is available and what everybody is taking. Companies like finnrick do public testing of research peptides and a good place to gather names. reply: I’m on tirzepatide right now from Eli lily, and I’ve been very interested in Reta, but I can’t say that I jump at the chance to inject something into myself that hasn’t been tested directly on the actual thing I’m about to put into my body. I know there are testing companies that will test certain sources but it’s not like they’ve tested the vial you get. If there’s some kind of pathogen or bacteria or whatever in the vial you get, well, there’s no recourse: it was “for research use only”. That seems like an unacceptable risk, but I see so many people on the internet claiming miraculous results. Maybe if I knew someone in real life, but I know those biohacking subreddits and such are astroturfed to no end by companies looking to sell sketchy peptides.

HN rank: 2

HN score: 69

comments: 17

original url: https://www.henrikkarlsson.xyz/p/good-ideas

评论信号：Just read the beginning but I feel like there are obvious counter examples. Basically lots of academic environments. I personally (and somewhat sadly) did my best work in grad school, thanks entirely to the environment. All of us in the lab I studied in benefitted from being around each other every day. From what I’ve seen, this is very common throughout history in academia.Maybe it’s pressure that kills ideas, or competition, or premature desire to commercialize, or just the kind of people that become founders; it’s definitely not co-working in and of itself.Should add I agree that solitary reflection is important, just not that being surrounded by like minded people is detrimental. reply: I thought Grothendieck's "example" was a good one. It's not that the academic environment stymied him, it's that he built up a practice of solitary creativity that helped him take inputs from his surroundings and fold them into his own framework. Both the solitary practice and the communication with fellow leading mathematicians was essential for his growth and output.I think the point the post was trying to make was that;...

评论信号：Probably not enough data on this yet since it's a new unlock, but I think it's perfectly possible to do great work today without interfacing with other humans directly. Some weird off-spectrum people (the kind this article is talking about) might even prefer to or work better this way. reply: It seems social dynamics exist all the same in technology, the internet, and AI. The evidence is obvious - all of these things were created by humans with social goals and conditioning. I'd say truly distancing is not a new unlock but something very old. It's so hard to get away.

评论信号：Owl in owl's way I in mine Can't get to sleepWind from the sea Butterflies in embankment weeds Never resting (1915) Taneda Santoka

HN rank: 3

HN score: 82

comments: 42

original url: https://www.science.org/content/blog-post/so-how-ai-drug-discovery-doing-really

评论信号：I'm a structural biologist at a mid-sized biotech. I use AI tools daily. They make accomplishing the same things I was able to accomplish before quite a lot faster and easier. They don't help me magically accomplish new things that I couldn't previously.For example, it helps me install academic software, debug things. It helps me take a large dataset and write scripts to ask questions. It helps me go through experiment drafts to see if I'm missing things. It helps me remember obscure formulas I use every 6 months. It has not, at least in my experience, come up with anything truly novel.A concrete example: AlphaFold is great...to come up with a starting model for a chimeric fusion or something. What would have taken me 1-2 hours fumbling around in PDB or CIF files is now a quick prompt. reply: do you feel this is the same trade off of UI builders like android studio (or msvb6). you do in minutes what you previously did in 2, 3 hours.is it all the work? no, but it's a part that's early on and have high perceived impact.then, as you progress, that tool actually gets in the way and a new feature that would take 2 hours, now is around 2 days.

评论信号：Derek Lowe discusion of the paper https://www.science.org/content/blog-post/so-how-ai-drug-dis...I think that was originally linked but got changed to the £30 to Elsevier version for some reason. reply: OP here: the title of the thread still links to Derek Lowe's blog post, but the article discussed in the blog post was added to the body of the original post (not by me).

评论信号：We're all about to come face to face with this reality. This dance can only last so long. reply: >We're all about to come face to face with this reality. This dance can only last so long.Only for values of 'all' that exclude well-connected members of the billionaire class and their select associates.

HN rank: 4

HN score: 207

comments: 71

original url: https://www.smithsonianmag.com/innovation/the-first-at-home-test-for-infected-ticks-could-improve-lyme-disease-diagnosis-180989235/

评论信号：Unfortunately, there are major issues with this approach.The vendor claims "lab-level accuracy" (conveniently omitting the actual accuracy numbers), but the test is a lateral flow test, which means its Limit of Detection is going to be orders of magnitude worse than molecular tests. Tick tests do not require FDA clearance, so their claims are most likely unreviewed.Existing lab tests for ticks are almost universally based on PCR.Ticks are small (especially nymphs) and extracting enough material can be tricky even for molecular testing, so I can't imagine an LFT test working terribly well, especially for nymphs, which are responsible for a lot of Lyme infections due to being easy to miss.The other, bigger problem is that the test result is mostly useless.The risk of Lyme transmission from an infected tick ranges rougly from <1% for a fresh bite (<24h) to ~10-25% once the tick is engorged (72h+).... reply: "so I can't imagine an LFT test working terribly well, especially for nymphs, which are responsible for a lot of Lyme infections due to being easy to miss."Even smaller and less noticeable are the larvae....

评论信号：Wow, this seems a pretty big deal.Here in the UK, Lyme traditionally been a marginal problem (tick bites aren't) but we now have such rapid climate change, along with rapidly increasing wild deer and boar populations, that some areas in the UK are becoming risk zones on more or less the same level of risk as some US regions.Alas the difference here is that education has not caught up to the USA: very few people have any grasp of the risk of Lyme because the high risk zones are, by and large, not well known, and they don't always correlate that well with the basic risk of acquiring a tick.I think most specialists in the UK think this is likely to lead to a pretty big increase to infections before people learn, so maybe this sort of tool will help offset that.I walk a lot in an area with some wild deer and boar, and I would love to have one of these in my cupboard as a precaution. Would be great to see them in supermarkets in high risk areas, too. reply: I have a friend who got a tick bite on holiday in America many years ago. Turns out they got Lyme disease but no doctors in the UK were experienced with it so they dealt with years of misdiagnosis....

评论信号：Buried way way down:LymeAlert, which will sell for about $50, is designed to detect the presence of Borrelia burgdorferi, the pathogen known to cause Lyme disease, in a tick.The test kit, which remains effective for up to 12 months, is simple to use. After carefully removing the tick with either tweezers or a tick-removal tool, you place it into the kit’s “Tick Crusher.” The grinder pulverizes the tick’s chitinous exterior, exposing the internal contents where the Borrelia burgdorferi is located. A patent-pending buffer solution readies the sample for testing. The user then inserts a test strip into a slot in the grinder. The strip’s chemically treated nitrocellulose paper functions as an immunochromatographic assay that can detect the presence of Borrelia burgdorferi.

HN rank: 5

HN score: 132

comments: 95

original url: https://www.acc.org/about-acc/press-releases/2026/08/11/14/59/abdominal-fat-predicts-heart-disease-risk-better-than-bmi

评论信号：Relatedly, there is evidence that certain types of "resistant starch" can help reduce visceral fat. This starch comes from green bananas, potatoes, legumes, etc. It has to be either raw (there are supplements for this) or cooked and cooled."Resistant starch intake facilitates weight loss in humans by reshaping the gut microbiota"https://pmc.ncbi.nlm.nih.gov/articles/PMC10963277/Edit: Ah, HN submission 2 years ago: https://news.ycombinator.com/item?id=39592367 reply: I feel like I've heard this story 1 million times before.

评论信号：For non-invasive heart disease risk prediction nothing beat ECG, period.Somehow American Heart Association and its European counterpart are in denial, and still pushing dinasour screening mechanism with very low accuracy for heart disease risk prediction.The standard risk model for CVD based on PREVENT (US) and SCORE-2 (Europe) like parameters are very poor as reported in the recently published paper on the their accuracy performance by the Swedish team [1]. As all CVD risk stratification with cardiologist review (expert-in-the-loop), the most important accuracy metric is sensivity/recall (avoiding false negative that will escape review) of PREVENT and SCORE-2, 26% and 48%, respectively.The paper alternative proposal increased the sensitivity to 58% by performing clustering instead of conventional regression models as practiced in the PREVENT and SCORE-2.These type of models including the latest proposal performed very poorly as indicated by their otherwise excellent and intuitive display of graphical abstract results [1].[1] Risk stratification for cardiovascular disease:... reply: Get as many scans you can under insurance....

评论信号：I thought this was pretty well known already. Being “overfat” is the problem, not being overweight (though they’re often correlated). BMI is really easy to measure, and is mostly accurate, that’s why it’s so pervasive. However it remains a pretty rudimentary metric (and really should use the third power or your height instead of the second). reply: > BMI is really easy to measure, and is mostly accurate, that’s why it’s so pervasive.BMI is easily misunderstood by people who know just enough to see that it’s imperfect, but not enough to understand why it’s still a valuable screening tool.I’ve been in the “overweight” BMI range with low body fat before. It’s not too hard to get there if you’re lifting weights and paying attention to your diet consistently for years, but it takes a lot of work to get there....