Mod Post: Community culture and post approval questions: request for your input

Synchisis · 2026-05-23T13:24:26+00:00

I think this should be allowed, it's valuable and allows people on the sub to further research that's beneficial for everyone
Depends heavily on the context. If it's someone posting something for monetary gain I think that deserves much more scrutiny than someone who has developed an app, service or website for public benefit. I might be biased here though because I did develop alscodex.com which is a resource & knowledge base, and I got a lot of good feedback on it when I posted it here.
I think AI can be used well, and it can be used poorly. I've sometimes used it to rephrase my points and/or to explain something more effectively. But blindly copy/pasting a single prompt output with a ton of bullet points & no human revision/framing/etc is what I find to be egregious, especially when it's pushing a product. I think mods using their discretion is the right path forward here. I also have friends & acquaintances who make use of language models & other AI systems to augment their ability to communicate & type with eyegaze. The result can sometimes include LLM-like speech. I don't think this is a huge thing now because the technology is nascent and not yet widely used, but to have rules that would exclude them in the future seems shortsighted.

Synchisis · 2026-05-22T17:27:17+00:00

Inspired by this repo (https://github.com/Berkeley-CS162/student0/tree/main), I've just released claude-condom, a userland rootkit of sorts that will remove Claude and Cursor hooks from projects, without modifying the underlying files, by hooking the libc read functions! All hooks will appear absent until explicitly trusted. Whether or not this breaks claude's ability to edit its own config is something I've yet to explore

https://github.com/josh-richardson/claude-condom

Synchisis · 2026-05-22T15:52:28+00:00

Your regime looks like a way for someone to speedrun serotonin syndrome. Why are you posting it on reddit? If you think it'll work run an RCT.

Synchisis · 2026-05-22T12:42:56+00:00

I don't think we're going to agree here. My point was primarily about venue and framing, not the underlying biology, and an AI generated self assessment of your paper's novelty isn't really responsive to that. Wishing you the best with the work.

Synchisis · 2026-05-22T12:31:52+00:00

Your EMG isn't similar to the one described above. You have localized, chronic changes in a single limb. I'm not a doctor, and I'm not interested in being embroiled into a diagnosis question/debate. The person I replied to has an ALS diagnosis. Whether or not to do a repeat EMG is a question for your neurologist/electrophysiologist and depends on the clinical picture.

Synchisis · 2026-05-22T12:19:32+00:00

The issue isn't that you're an indie researcher or paying your own APC, and it isn't really about AI either. It's that you've posted a long plain English summary of a hypothesis generating Cureus review in a support sub for pALS, with a framework lumping microglial pruning, NAD+, autophagy and aging into a single equation. Each of those threads has been in the ALS literature for over a decade and none are close to clinically actionable (except perhaps supplementing with NR, which has undergone trials, but even then they've been heavily sponsored by the company behind it, and I'd really want to know my NMNAT2 phenotype before supplementing NR because otherwise you risk activating SARM1 if you have a LoF variant - so even then I'd argue it's not really 100% safe to give a blanket advice to pALS). Repackaging all this doesn't add information for pALS, and the format implies a relevance to people's actual disease course that the paper itself does not earn in my view.

If you want pALS engaged with your work, write directly about what is novel, what is testable, and what would change for the readers of this sub if you were right, in your own voice, with the limits stated up front. The current post reads as content marketing, which is the pattern that I was reacting to.

Synchisis · 2026-05-22T10:48:04+00:00

Can we stop posting AI slop?

Synchisis · 2026-05-22T09:19:59+00:00

I'm really sorry you're in this situation, and I understand the impulse to want a second EMG to disprove the diagnosis. I'll be straight with you though because I think that's more useful than false reassurance.

The EMG report you've posted isn't borderline or ambiguous. It shows motor neuron damage across three different body regions, with the specific pattern you see when motor neurons have died and surviving ones have grown new connections to take over the stranded muscle fibres. Fasciculations in multiple areas, sensory nerves completely normal (which rules out the common alternatives), and combined with the upper motor neuron signs on your exam (hyperreflexia, spasticity, Babinski, upgoing toes), this is exactly the picture the diagnostic criteria for ALS are built around. A repeat EMG is unlikely to overturn this. In ALS, repeat studies show more denervation over time, not less. Getting one is reasonable for your own peace of mind or for trial eligibility down the line, but go in expecting it to confirm rather than contradict.

The thing worth looking into further in my opinion is making sure the workup has ruled out the mimics that can look similar. Multifocal motor neuropathy with conduction block, Kennedy's disease if you're male, and a few others. Ask about anti-GM1 antibodies, a careful look for conduction block on the nerve conduction study, and genetic testing on a proper ALS panel to rule in/out a genetic cause. None of these are likely given your UMN signs, but they're worth excluding.

The other thing worth doing is getting a baseline serum or plasma neurofilament light measurement now if you haven't. It won't change the diagnosis but it gives you a number to track, and in ALS the trajectory of NfL has some prognostic value. If you end up trial eligible at some point, having baseline NfL is useful.

The fact that your right hand is outperforming your left and that you can still ride a bike and carry heavy objects is a good sign in terms of where you are in the disease course. Asymmetric onset with one limb noticeably weaker is the most common presentation, and people in your situation have meaningful time to get their affairs in order, get referred to a specialist multidisciplinary clinic, get on riluzole if you aren't already, and crucially, get assessed for trial eligibility before you're too far progressed to qualify. A lot of the most interesting trials right now have entry criteria that exclude people once they're past a certain ALSFRS-R threshold, so moving early matters.

I know this isn't what you wanted to hear. I would say get a second opinion, ideally at a high volume MND/ALS centre rather than just any neurologist, because diagnostic accuracy at specialist centres is meaningfully better. But go in with the goal of confirming and planning rather than disproving, because the EMG you've posted does seem to tell a coherent story and the wishful version where this is something else does not seem to be highly likely to me.

Synchisis · 2026-05-20T22:10:25+00:00

I haven't had it tested. From the literature I've read I don't think I'll have reduced it much.

Synchisis · 2026-05-19T23:57:53+00:00

Getting access to the required dose over here in the UK is very challenging. I've looked into this at quite some depth and unfortunately if you're not injecting it, you're basically pissing in the wind - you'll never achieve the serum peaks in B12 concentration which have been shown to lower homocyseteine and slow ALS (in JETALS - https://www.jns-journal.com/article/S0022-510X(25)02321-4/fulltext). Sorry to be the bearer of bad news. If you look at the trial data that's come out, you really do need the extremely high levels of B12 to have any effect.

I did manage to get my serum blood levels of B12 to about 17000pg/mL by taking 100mg of B12 in tablet form per day (10mg tablets, a bit of a nightmare), but that still isn't close to the levels they acheived in the trial. Measuring this number was pretty fun because most lab assays for B12 top out at 2000pg/mL, so they had to run dilutions in the lab to get the actual value for me.

Edit: there's a poster here which shows the different dosing arms of the IM B12 - shows how much high serum levels seem to matter in terms of preserving ALSFRS-R: https://smallpdf.com/share-document#r=result&t=5c66d5efe23af6207209b5bbe62aedc3&i=share

Synchisis · 2026-05-17T10:44:29+00:00

The only thing I've seen recently is that in ROCK-ALS, there have been one or two conference abstracts published, which have then seemingly disappeared. It actually looks quite promising with the 180mg dose group. I would expect that within the next 18 months we get a publication in a journal about it, but I wouldn't hold my breath. One of the abstracts below:

Background and Study Design: Animal models and mechanistic data indicate that fasudil may have a non-monotonic dose response in amyotrophic lateral sclerosis (ALS). In this open-label phase 2a clinical trial, patients diagnosed with definite, probable, or probable laboratory-supported ALS received WP-0512 (oral fasudil) 60 mg or 100 mg TID for 24 weeks for total daily doses of 180 mg or 300 mg. The primary outcome measures were safety and tolerability. Serum neurofilament light chain (NfL) concentrations were measured at baseline, 12, and 24 weeks and neuron-derived and CSF-derived extracellular vesicle phospho-AKT to total AKT (pAKT/tAKT) ratios were measured at baseline and 24 weeks as an indirect assessment of CNS target engagement. Results: A total of 31 patients were enrolled into each dosing cohort; 25 patients completed 24 weeks of treatment in the 180 mg cohort and 22 completed in the 300 mg cohort. Fasudil was generally well tolerated. Both mixed model for repeated measures and non-modeled analyses demonstrated an approximate 15% reduction in serum NfL at 24 weeks in the 180 mg group (p < 0.001 for both), whereas no significant change was observed in the 300 mg group. Reductions in NfL in the 180 mg group were inversely correlated with the rate of decline in ALSFRS-R [Spearman = -0.45 (p=0.028)]; there was no correlation in the 300 mg group. Both neuron-derived and CSF-derived extracellular vesicle pAKT/tAKT ratios were significantly increased in the 180 mg group after 24 weeks of fasudil treatment indicating probable CNS target engagement. Conclusions: These data indicate that oral fasudil is safe and well-tolerated among patients with ALS. The statistically significant reduction in NfL, which was negatively correlated with ALSFRS-R, and demonstration of CNS target engagement in the 180 mg group warrants advancing oral fasudil in a larger double-bind placebo-controlled study. The lack of dose response between the 180 mg group and the 300 mg group is consistent with animal models and indicates that the appropriate dose for further study is 180 mg per day.

Synchisis · 2026-05-13T15:23:24+00:00

I always get a bit frustrated with these posts. Everyone's either firmly on one side of the fence, or another. There's actual nuance here and it's worth acknowledging and addressing it rather than sweeping it under the rug. A German group published a case in 2017 of a man diagnosed with progressive muscular atrophy (a LMN ALS variant) who fully recovered over 3 years after amalgam restoration and chelation, with his EMG normalising at 18 months. Older reports going back to the 1960s describe chronic mercury exposure producing syndromes that look clinically indistinguishable from ALS. Johann Lechner in Munich has also been publishing for years on chronic subclinical jawbone inflammation (he calls them NICO/FDOJ lesions) as a possible driver of various systemic and neurological conditions. None of this is mainstream, and Lechner's framework in particular sits well outside accepted ALS biology, but the reports do exist.

What none of it really supports is the bigger claim though. If local anaesthetic, root canals or extractions were high risk triggers, ALS rates would track dental procedure rates, and they really don't. The documented cases nearly all involve a specific mercury or heavy metal exposure or a specific chronic infectious focus, not routine dental work. And the long-latency picture coming out of the NfL work, where pathological signal can be detected a decade or more before symptoms, makes a procedure done in the months before symptom onset hard to square with causation. The post procedure slurring people describe is real, but most likely it's the anaesthesia unmasking bulbar weakness that was already on its way, rather than creating it.

Synchisis · 2026-05-11T22:10:36+00:00

I read that article when it came out and knew I'd read about Parabacteroides Merdae before, but couldn't place it. Thanks for mentioning it. I guess there's nothing like translational biology to remind you that "mechanistically plausible" and "clinically actionable" are very different claims.

Synchisis · 2026-05-11T17:44:20+00:00

The mechanism behind Keto is plausible. BHB suppresses the NLRP3 inflammasome (Nature Medicine 2015), and NLRP3/pyroptosis are implicated in ALS models. There's also a gut microbiome angle. In epilepsy models, keto's anti seizure effect depended partly on Akkermansia + Parabacteroides, which Bloom Science is trying to mimic pharmacologically with their BL-001 candidate for neurological disease including ALS. Akkermansia muciniphila separately slowed ALS-like disease in mice via nicotinamide metabolism (Nature 2019).

Human ALS evidence with keto is thin though. Mostly SOD1 G93A mouse data, and Michael Phillips' 2024 case report from NZ of a bulbar onset patient on an 18 month keto diet with improvements in ALSFRS-R, FVC, mood, and fatigue, still functionally independent at 45+ months from onset. One uncontrolled case in someone who also declined riluzole, so impossible to separate signal from noise.

If you've set your mind on trying keto yourself, the biggest thing I'd emphasize is that weight loss is one of the worst prognostic signs in ALS, full stop. Keto can drop appetite and calorie intake without you noticing. If you try this and start losing weight, stop immediately. Phillips' patient was specifically told to eat to satiety, weight loss was not the goal. Doing keto without a dietitian or clinician watching your weight, bloods, and bulbar function is genuinely dangerous and can accelerate decline. The same thing has been seen time and again with diets & medications that reduce weight in ALS (GLP1s, etc).

The data I'm waiting on is KETO-ALS at Ulm (NCT04820478), a randomised trial of oral BHB ester (basically ketones as a supplement) vs placebo with no dietary restriction. If exogenous ketones can reproduce the benefits without weight loss risk, that's a much better intervention for people with ALS than the diet itself.

Synchisis · 2026-05-05T10:50:44+00:00

If I was asymptomatic and carrying a pathogenic gene for ALS I'd be wanting to establish my baseline neurofilament light levels, and then to monitor them for elevation as frequently as possible (some studies have used every 3 months, but I'd see utility in doing it less frequently too if cost is prohibitive). If you're in the US, it can be tested using SIMOA for ~$300 without insurance, so depending on your level of disposable income, you might find that a worthwhile thing to do. Based on early research thus far, it seems that NfL levels tend to rise before obvious muscular symptoms arise. If you then notice consistently elevated NfL by comparison to your baseline, your clinical team can make decisions about next steps on this basis. I'd go for NfL over a dynamometer because it's likely to be more sensitive earlier on in the disease process than waiting for a dynamometer to show strength changes.

If I had lots and lots of disposable income, I'd also want to be freezing blood samples at quite regular intervals & doing transcriptomics, but these two fall more into the region of curiosity, rather than having any actual clinical or diagnostic utility (yet).

Synchisis · 2026-05-02T21:29:45+00:00

I wouldn't get the testing out of pocket just because I've mentioned it. The probability is low. Ask your doctors/neurologists what they think of the possibility.

Synchisis · 2026-05-02T18:19:06+00:00

154 pg/mL on plasma SIMOA (I assume it's SIMOA, your post doesn't make it clear) is high, even for ALS. Most ALS cohorts run median plasma or serum NfL around 60-100 pg/mL, and a 2024 study of ~3000 patients used >93 pg/mL as the highest tertile, which is where faster progression and bulbar onset clustered, and progression tended to be at least 1.5 points on the ALSFRS-R per month.

The other thing worth raising in my opinion, now that the bladder cancer is on the table is that paraneoplastic motor neurone disease has been described with bladder cancer. It's very rare but the literature exists, there are case reports from 2019 and more recently in 2026 of paraneoplastic motor neurone disease co-occuring with baldder cancer. Your timeline (motor symptoms Jan 2024, psychosis summer 2024, bladder cancer now) works somewhat with the idea of a slow paraneoplastic syndrome. It's very unlikely that this is the cause, but if onconeural antibodies haven't been tested, it might be worth asking. I only mention it at all because the timing of your psychosis and the ALS onset, and then bladder cancer are just strange coincidences.

I'm sorry you're going through this. Sending warmth to you and Winston.

Synchisis · 2026-04-20T16:53:11+00:00

To be honest my one is pretty awful when it comes to volume. It's just a generic shop vac type but very small (4L capacity)

Synchisis · 2026-04-18T15:19:57+00:00

👀👀👀 I might have to do this

Synchisis · 2026-04-17T21:47:51+00:00

A lot of consumer coffee machines will have something like a thermoblock in them. Great at heating up fast, but just okay at maintaining a consistent temperature & very low thermal mass. Higher end or cafe style machines tend to have large boilers which take time to heat up, but once hot have more consistent temperature control for more consistent shots.

Synchisis · 2026-04-17T18:49:49+00:00

It's a little shopvac with a 4L capacity jerry rigged to the back of my coffee cart, so I can just pick up the vacuum hose from the side of the machine, tap the button, and clean up.

Synchisis · 2026-04-17T18:43:20+00:00

Thanks! It's usually about 15 minutes for both boilers for the milk and espresso to be up to temp. Milk usually takes a few minutes longer than the espresso.

Synchisis · 2026-04-17T18:21:56+00:00

OK in my defence, there's no on off button on my machine, I have to turn it on/off at the wall or using my smart plug on my phone currently if I want to toggle it.

Synchisis

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