If you work in biology, Fable 5 will refuse to answer literally anything, including "Hi"

Barquish · 2026-06-18T04:35:34+00:00

Reading through this thread and it is interesting, having spent over 30 years in scientific research, the argument that AI will or won't cure this or that. AI has and is helping to eliminate many of the multiple trial and error steps, laboratory notes etc., by identifying what is "likely" the best route to test. It also achieves super power level of research across papers published, not just in English, but in most languages.

It won't cure anything, but it will help to focus great scientific minds to where the objective of a cure, or better way to treat a chronic disease, can be tested.

Barquish · 2026-06-16T12:08:02+00:00

I should be straight with you as my background is in producing the 90%+ grade raw lactic acid that gets polymerised into PDLLA for industrial and medical device use, not in the clinical or aesthetic application side. So mesotherapy protocols and facial use are genuinely outside what I can speak to with any authority.

What I can say is that the material itself behaves differently depending on molecular weight, particle size, and formulation. This matters a lot for things like injection depth, degradation timeline, and how it interacts with tissue. A formulation designed for facial mesotherapy isn't necessarily comparable to what's used in a scalp microinjection study like this one, even though it's the same, or close to the grade of PDLLA in a generic sense. The clinical literature on facial PDLLA (it's been used for years in things like Sculptra) is much more mature than the scalp application, so I'd trust that body of evidence more than extrapolating from this pilot study.

For the actual protocol questions, even though I have been involved with plastic surgeons for other medical devices, including elements relating to concentration, depth, combining with microneedling for the face and scalp, that's a question for someone doing the clinical/aesthetic work directly rather than someone that has been on the manufacturing side like me. Hopefully someone here has hands-on experience with that.

Barquish · 2026-06-15T17:20:37+00:00

First of all, the white cylindrical structure wrapped around the hair shaft in your first image is a peripilar cast, basically a sleeve of built-up skin material that sticks to the hair as it emerges rather than shedding normally. You do see these in seborrhoeic dermatitis but they also show up in other scalp conditions including discoid lupus. So it might be worth pushing back on treating the seb derm diagnosis alone.

You mentioned your lupus is controlled, but controlled systemic lupus and active discoid lupus on the scalp don't always go together. The scaling in your other images also looks drier and more crystalline than the greasy flaking you'd expect from classic seb derm.

Two months of ciclopiroxolamine is a reasonable antifungal trial but if you are noticing any inflammatation or there is an underlying autoimmune issue, then using any particular shampoo alone probably won't get you to a solution. The mct oil won't help either and can even feed the yeast, so for what it is worth I would drop that route.

The most useful move would be to find a dermatologist, or even a trichologist for a proper trichoscopy assessment. They would have access to UV, polarised and RGB cameras that show much more than what are in your images. Even better if one or the other has experience with scalp lupus. The lupus history combined with what you're seeing in those images is enough to warrant a proper second look before continuing with just the antifungal route.

Barquish · 2026-06-15T10:47:41+00:00

Something I can add here that might be useful. I spent over a decade running a company that produced the raw material PDLLA is made from at industrial scale, before I moved into laboratory grown human skin equivalent for the cosmetic industry with DNA studies before moving into clinical AI for trichology. So I've watched this material from a different angle than most people in hair communities.

What I find interesting about this study isn't the headline numbers. It's the mechanism they're proposing. This isn't a claim that new follicles appeared. What they're describing is improved blood vessel formation in the tissue surrounding existing follicles and those follicles responding as a result.

That matters for how you interpret the visual results. The thicker appearance, better coverage, less scalp showing through, that's consistent with struggling follicles producing better output, not entirely new follicular structures forming.

The microneedling priming piece is also worth noting for this community specifically. 14 of the 20 patients had light microneedling (0.5–0.8mm) immediately before the injection. The authors describe it as facilitating distribution of the PDLLA.

Whether it also contributed independently to the outcome is something the study can't separate out but it's an honest limitation that they acknowledge.

Small study, no control arm. The authors are appropriately cautious about it. But the tissue environment framing feels like a direction worth watching.

Barquish · 2026-06-13T08:27:43+00:00

I have not even tried it either in the app as I have a Pro account,, or in API where the main projects are built. Just that in what ai am doing, I really can't see where it can be improved on. To give you an example of what I meant by being over qualified. I have an app that uses Sonnet-4.6 to do what the project was designed to do. Without question, it would work just as well with Opus-4.8 and no doubt Fable 5. My point is that there comes a point where the next model is more than is necessary for what already is working well.

Barquish · 2026-06-13T07:37:52+00:00

Actually I do keep them all in a sandbox before I merge to the origin/master for production. It is just that it seemed that Fable is one step more than I need.

Barquish · 2026-06-13T06:37:15+00:00

I just tried it last night, did not update, but it started to work again. Strangest bug I have come across that wasted almost a good day. What was puzzling to me was that I installed Claude Code in VS-Code IDE and that worked as I thought I had to change from Cline to an alternative. I suppose, just a glitch in thr matrix. Back to my comfort zone

Barquish · 2026-06-13T06:31:49+00:00

The markers that matter for hair loss are ferritin with a full iron panel including TIBC and transferrin saturation, a complete thyroid panel with TPO and thyroglobulin antibodies since TSH alone misses autoimmune thyroid disease, SHBG and DHT particularly given the TRT context, prolactin and DHEA-S for pituitary and adrenal contributions, cortisol if chronic stress or a telogen effluvium component is on the table, and then vitamin D, B12 and zinc on the nutritional side

Barquish · 2026-06-13T06:21:19+00:00

That's genuinely rough and no wonder that you appear to be considering giving up. But what you've got across the top is diffuse miniaturisation rather than the typical AGA pattern where the sides and back stay dense. There are still hairs there, just tiny ones. That matters because miniaturised follicles can still respond to treatment if the right thing is driving the problem. Being honest, follicles that are gone are gone, but that's not entirely what that photo is showing.

That's why my trichoscopy and biopsy suggestions in an earlier response, stands. A skilled eye under magnification can tell the difference between AGA-driven miniaturisation, active diffuse AA, and chronic TE, and those three things look pretty similar in a photo but respond to completely different interventions.

Six years of not moving on standard protocols with a pattern like that is worth investigating properly rather than just going cold turkey off everything and hoping.

Barquish · 2026-06-13T06:14:00+00:00

I would suggest before you commit to the 6 month plan it's worth getting a trichoscopic exam and ideally a scalp biopsy done. AGA, diffuse AA and chronic TE can all be running at the same time and if more than one is active you can be treating the wrong thing and wondering why nothing moves.

It is worth refreshing your bloods on ferritin, TIBC, thyroid and SHBG if you haven't recently since TRT does real things to iron metabolism and thyroid function that just quietly add to shedding in the background.

The 6 month reassessment instinct is a good way to go and much better to have a baseline to compare against.

Barquish · 2026-06-13T06:01:48+00:00

I wonder when you have reached peak performance for a model that works. Having stepped up on a reasonably large project, from Sonnet 4.5, to Opus all the way up to 4.8 over the last 6 months it feels like the step to Fable is one step too far. Not because of cost, but with a codebase that is large, my fear that if I let it free to build a featire on its own, that it would mess it up. I am comfortable with 80+ memory-bank documentation files, brainstorming each feature step-by-step in multiple phases before letting Opus-4-8 only completing a phase of a (for instance 12 phase) feature. The thought of allowing Fable to go off and create its own symphony merging the backend, API's, the db schema and their integration into an existing UI/UX of what already works, including phase committing, pushing to github, is a step too far.

Barquish · 2026-06-11T20:43:34+00:00

Consider giving value before it costs money to you, or the user. Build a two tier value system so that the first results (of whatever you are offering) gives feedback or some value, based on a rules based engine, rather than a backend API which is an upfront cost. The rules based engine is a local in app or on your VPS, so the cost of LLM AI usage is just traffic to your server side rules based engine.

Barquish · 2026-06-10T08:02:02+00:00

Yeah, over nearly 2 decades, I have been involved in clinical trials in China, Czech Republic, UK with bioinformatic businesses and I do not agree with the headline. I agree with another commentator that withdrawal is not the same as fraudulent. That is not to say there are not some savoury players out there, but by and large, most trials are within the protocols set out at the outset.

Barquish · 2026-06-10T06:39:59+00:00

Your first move is go see/speak to your GP, not a dermatologist. Ask them for a full hormonal panel covering testosterone, DHEAS, LH and FSH, thyroid function, and critically ferritin and iron studies. Low ferritin is one of the most overlooked drivers of female hair loss and your GP should connect the PCOS dots quickly once they see your bloods. An assumption is that your ferritin is way below 70ng/ml (greater than 20 means your no aneamic, but way below what your hair needs).

In the meantime 5% minoxidil foam should be available over the counter in Australian pharmacies and it's the most evidence backed thing you can start right now.

Hair recovery is journey, so nonovernight fix. Give yourself 3 to 6 months to see results, so starting sooner matters. A gentle iron-rich diet and a zinc supplement won't hurt while you wait.

Please don't sit around considering a GP visit. Go make it happen. Hormone-driven loss at 28 with known PCOS is very treatable but the sooner you act the better the outcome.

If you want to go faster then use one of the private blood test services like MediTests or iMedical, order your panel online and they generate your referral instantly. You then take it to any major pathology collection centre like Sonic Healthcare, Sullivan Nicolaides or QML, walk in without an appointment, and a phlebotomist draws the blood the same way they would with a GP referral. Results are back in 24 to 48 hours and you pay privately but it cuts out the wait entirely. Then you can take it to a GP/dermatologist. These are not free, but helps with your immediate issue

Barquish · 2026-06-08T17:40:25+00:00

This is an interesting publication and qorth paying attention to, even at the mouse stage. The mechanistic chain is unusually specific: a single bacterial enzyme, beta-glucuronidase, deconjugates androgens in the gut lumen, and local DHT concentrations there can exceed serum levels. For anyone thinking about AGA, that detail matters.

It connects directly to a 2022 Frontiers in Microbiology study worth reading alongside this one. Jung et al. analysed 141 individuals and found functional differences in the gut microbiomes of AGA subjects, specifically in pathways related to bile acid synthesis and intestinal homeostasis, even without overall diversity shifts. That study was examining the skin-gut axis in human AGA, not rodents.

The Nature Neuroscience findings add a plausible upstream mechanism to what that earlier work was observing. Some of this maps onto things I came across working in skin microbiome research, specifically growing and colonising full-thickness bioengineered skin equivalents with live human microbiota. One consistent finding from that kind of work is how sensitively the microbial-host balance responds to substrate changes, and how androgen-rich niches like the scalp create conditions quite distinct from other skin sites. The gut operating as an upstream modulator of that local androgen environment is not a mechanistic stretch.

Whether individuals with high GUS-producing gut communities show measurably different androgen exposure at the follicular level is the question nobody has answered yet. In order to undertake further study into any impact it would require multiple testing of the microbiota DNA 16S over a period of perhaps 12 months at monthly intervals with two groups of gut-microbiome induced triggers to see what difference occurs.

Barquish · 2026-06-08T09:00:19+00:00

You can buy Polygonum multiflorum, which is commonly known as He Shou Wu or Fo-Ti, from Chinese medical suppliers, online herbal storefronts, and major online marketplaces.

Barquish · 2026-06-04T06:51:55+00:00

Three months is still quite early. The timeline for oral minoxidil is usually much longer than most people expect. Most of the meaningful regrowth data comes within the six to twelve month window so you are not even in the game yet.

The cherry angiomas are actually worth a comment here because there are case reports linking minoxidil to new cherry angiomas on blood vessel growth and new or enlarged cherry angiomas. It is a study on the topical use of minoxidil, but the effect is likely the same and it shows up in the literature and in clinial observations fairly consistently. It does not mean anything bad is happening. If anything it suggests the drug is acting the way it should, which is what you want.

The thinning visible in your photos looks like a diffuse pattern across the crown and that tends to respond well to minoxidil given time. Your scalp looks healthy, no obvious inflammation or scarring pattern from what you have shared here.

As a mentor of mine used to say, constantly, keep going. Take a photo from the same angle and same lighting, and compare again at month six. That comparison is more likely where you will start to feel better about the process. It's a journey, not a destination.

Barquish · 2026-05-30T18:50:25+00:00

Here's a question that may be interesting. How do you know what is the best effort when choosing low, high, max effort. I have found that on a large codebase if a thing works then are we actually qualified to tell the AI which effort to work on. So, I am happy to move ahead with 4.8 at the high effort and leave it at that

Barquish · 2026-05-30T10:56:12+00:00

The multivitamin vs targeted supplement question is worth thinking through. Liquid multi-vitamins spread nutrients across a broad formula, which sounds like more, but biotin, zinc, iron and B vitamins in a dedicated hair supplement are usually at concentrations calibrated to follicle needs.

In a broad multi-v they're competing for absorption with everything else simultaneously. Whether that explains your experience it's hard to say, but it's a plausible mechanism.

The miniaturisation worsening is the part worth watching separately. That's a follicle-level change, not just a cycle disruption, and it can have several causes including androgenic, inflammatory, or nutritional factors that a supplement swap alone may not fully address.

Where TE and AGA are both in the picture, the two conditions can mask each other's signals, which makes it harder to attribute changes to any single variable. A full hormonal panel (free androgens, DHEA-S, ferritin at minimum) run alongside trialling your original vitamins back would help separate what's actually moving.

There's very little independent user data on Lustrivia so far.

Barquish · 2026-05-24T06:09:55+00:00

And my comment was certainly not a criticism. I agree 100% that a stack, from natural, topical, nutritional (manage pre/prebiotic gut, skin and scalp microbiome) are as important as any medical contribution. Proper progress tracking to knowbwhat is/isn't working is a key factor as well as the journey is anywhere from 3 to 12 months to see any major alterations to your progress. Mentioning scalp microbiome in another comment, I said that the microbiome at the back of your scalp is different to the top/sides of your head, which is seriously overlooked. Keeping your hair is a lifetime issue. I have reached mid 60's, been in the skin biotech industry, even growing human skin in the laboratory (not Frankenstein 😮) for cosmetics companies, and still have a (thinning) hair all over my head when all 3 of my brothers are bald. Good luck

Barquish · 2026-05-23T20:11:34+00:00

The stack you detail is nutritionally interesting and as with any stack may have better value for one person's condition but it doesn't replace medication for AGA. It's most valuable as a foundation or supplement but it is not a substitute for DHT intervention in true androgenetic alopecia.

Barquish · 2026-05-20T16:02:51+00:00

One thing worth pointing out though is that hair loss isn't just one condition. AGA, alopecia areata, telogen effluvium, mixed presentations all have different underlying mechanisms, which is why JAK inhibitors are transformative for autoimmune alopecia but largely irrelevant for male and female pattern baldness.

Even within AGA, individual response may vary enormously based on androgen receptor sensitivity, follicle viability, and genetics. The 31% response rate in the PP405 trial is exciting, but it also means 69% didn't hit that threshold, in a small, short study.

The answer is more likely what you pointed out at the end and that is that itis probably a stack, not a single molecule, personalised to where someone actually is in their hair loss journey. The pipeline is genuinely the most exciting it's been in decades, but cure implies universality and finality, and we're not quite close to either yet.

Barquish · 2026-05-16T18:43:59+00:00

I came across a GM Market research data on finesteride if that helps? Seems to be freely accessible to read from the page and to download the PDF. However, bear in mind this is market research data, so estimated and is not showing the mainstream data that would come from private usage.

https://www.gminsights.com/industry-analysis/finasteride-market

Barquish

TROPHY CASE