OpenAi's new ChatGPT

I think StackOverflow's took the right position. In my view, Chat GTP is very useful if you use it as a language model to help generate text or easy code, but not for things that require a deeper understanding or logic.

I heard someone make the analogy with self-driving cars. The technology gets it right most of the time but there are still too many edge cases to safely implement it. It may be that throwing more data at it will not help solve these edge cases because some may have never happend before. A higher level of accuracy may only be achieved with new models that are based on logic and a conceptual understanding of the world.

The same might be true for Chat GTP. Predicting the next word might not be good enough for many tasks and jobs. It could be that it will reach its limit and that more data hardly improves its accuracy. Could be wrong though. Will be interesting to see how this evolves.

 

Well, AI did learn everything from us, confidently saying something that is completely wrong is basically an art form with humans.

And as SNT Gatchaman said, it's definitely not limited to Internet forums, there are entire disciplines and industries built on being confidently incorrect. It's not as if only using validated sources of information doesn't have truckloads of that.

Sniff, it really has its father's ability to bullshit with complete confidence

 

Last week was a local business week and I went along to a seminar hosted by a self confessed tech nerd on AI.

He is an eternal optimist and I do agree with him that we are at a transition point akin to before electricity and how it changed everything. He played down the negatives .

I have a rare talent for being able to do things with tech that noone else seems to be able to ( not in a good way ). I definitely missed my vocation - should have been a user / tester ! So anything which simplifies things for me is a godsend .

The seminar touched on different apps and how they were used in business . Using chat gpt to generate a tweet storm in seconds . From checking tone as well as spelling in grammarly, using midjourney and canva for marketing ( dodged the query re IP rights and copyright that is rife at moment), autopod for podcasts , beautiful AI for graphics . All useful , timesaving and interesting - could take a lot of spoons out of advocacy work ..

There an app called seeing AI for visual impairment which will describe objects to people.

It was combining apps which was interesting .
Short YouTube videos can be done by giving chat gpt formatted questions, outputting data in a table, taking the table into Canva and using the YouTube template . Short videos are then auto generated with potential to edit in a matter of hours rather than a week. Definitely a gamechanger on multiple fronts .

 

I noticed that Chatgpt is much more inclined to psychologise ME when you call it CFS than when you call it ME/CFS. An example:

My promt:

Regarding [Name] was Simon Wessley right, or are those critiquing him right? Short answer only please
​

Answer for Name=CFS:

The controversy around Simon Wessely's views on Chronic Fatigue Syndrome (CFS) is complex. Wessely's emphasis on psychological factors in CFS has been criticized by many patients and researchers who believe it undermines the biological aspects of the illness. Both perspectives hold validity, but a balanced approach acknowledging both psychological and biological factors is increasingly seen as the most accurate and constructive.
​

Answer for Name=ME/CFS

Critics of Simon Wessely are largely right. His approach to ME/CFS, which emphasized psychological factors and treatments like cognitive behavioral therapy (CBT) and graded exercise therapy (GET), has been widely criticized for misunderstanding the biological basis of the illness and potentially harming patients. Recent research supports a biomedical understanding of ME/CFS.
​

This is obviously not too suprising and to be expected, but is still really useful to note. I’ve noticed it with a variety of prompts but thought this one would be the simplest to highlight.

​

 

I tried with Claude.ai. I had it rewrite multiple times and all the answers varied a good deal, but it wasn't like "CFS" always made it more of an advocate for Wessley's views. Your theory does make sense, but there's also a chance the first answers you got happened to fit well with that hypothesis.

Or maybe there's something different in this regard between these two bots.

CFS

ME/CFS

 

Unfortunately none of the answers gets to the main point, that the research cited in support of Wessely’s views is just plain bad research. Though we have no defensible evidence detailing the aetiology of ME, the evidence we do have, including the PACE trial itself, is that GET/CBT do not work as a long term treatment of ME and for a sizeable proportion they do harm.

 

Text generators in a nutshell. Great if you want a squishily averaged synthesis of general opinion. Not great if you want factual accuracy - though it can look like it if you're asking about a topic where fact and general opinion happen to more or less overlap.

 

That actually makes a lot of sense Forestglip. Claude AI by Anthropic based on the “Harmlessness through Constitutional AI model” ie. making the model go through extensive stages of supervised and reinforcment learning where it is trained to abide to a strict ethical guideline. This reduces hallucinations or problematic answers but also means the model tends to release more generic and bland answers while seldom clearly taking sides.

 

Makes sense considering that almost no good research is done using CFS, so it would be mostly biopsychosocial research and still the best that can be said is that it could be somewhat valid. And since most of this research is old, being "increasingly seen as the most accurate and constructive" is mostly late 90s early 2000s stuff.

It's certainly valid that there are psychological consequences to chronic illness, so factors is correct, but such a response misses the ambiguity that the BPS model is about psychological causes, which have no basis in fact or evidence and specifically exclude the role of pathogenic triggers other than as a generic "life event".

 

Prompted Chat-gpt’s o1model to do some thinking around biological mechanisms in ME/CFS. Posting here to see if anyone finds anything new and useful.

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Below is a synthesis of emerging and ongoing research related to ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome) and post-acute sequelae of COVID-19 (often described as Long Covid or Long Covid ME/CFS). Following that is a broader overview of relevant advances in immunology, neurobiology, and concepts from other neurological diseases such as Alzheimer’s and Parkinson’s that may shed light on unexamined avenues in ME/CFS.


1. ME/CFS and Long Covid ME/CFS: Current Research Themes


1.1 Immune Dysregulation and Post-Infectious Origins

• Chronic immune activation: A recurring theme is that a subset of ME/CFS patients display signatures of chronic immune activation—even long after an initial trigger (viral or otherwise). In Long Covid, researchers have reported elevated inflammatory markers, including interleukins (e.g., IL-6, IL-1β), and an imbalance in T-cell populations (CD8+ T cell exhaustion or “hyperactivation” states).

• Autoantibodies: Multiple studies suggest the presence of autoantibodies that might interfere with autonomic or mitochondrial function (e.g., anti-β2 adrenergic receptor, anti-muscarinic receptor). These autoantibodies may contribute to dysautonomia (e.g., POTS-like syndromes) common in both ME/CFS and Long Covid.

• T-cell exhaustion or senescence: Some labs are examining whether ME/CFS shares characteristics with T-cell exhaustion, as seen in chronic infections. In Long Covid, a similar pattern is emerging where the immune system remains activated at low levels over an extended period, which might impair immune regulation and tissue repair.


1.2 Metabolic and Mitochondrial Abnormalities

• Dysregulated energy metabolism: Perhaps the most consistent finding in ME/CFS is a problem with energy production, particularly involving mitochondrial dysfunction and altered aerobic respiration. Similar findings of disrupted mitochondrial pathways are emerging in Long Covid research.

• Reduced maximal oxygen consumption (VO2 max) and post-exertional malaise: This hallmark of ME/CFS is characterized by an abnormal response to even mild exercise, correlated with measurable drops in aerobic capacity. Long Covid patients exhibiting ME/CFS-like symptoms often show similar patterns.


1.3 Neuroinflammation and Brain Dysfunction

• Neuroinflammatory signatures: Advanced brain imaging (e.g., PET scans) in ME/CFS has suggested microglial activation in some patients. Long Covid neuroimaging also points to small but notable structural or functional changes, particularly in regions responsible for autonomic control and cognition.

• Dysautonomia and the vagus nerve: Some researchers hypothesize that a chronically activated or dysregulated vagus nerve-immune axis might underlie the “sickness behavior” state typical of ME/CFS and Long Covid.

• Cognitive dysfunction (“brain fog”): Symptom clusters of difficulty processing information, slowed speech, confusion, and severe sensory sensitivities resemble hypometabolism in certain cortical regions or dysregulated neurotransmission.


2. Severe Forms of ME/CFS: Neurological Perspectives

In severe ME/CFS (bedridden, profound light and sound sensitivity, “concussion-like” head pressure/buzzing), the neurological component becomes undeniable. These individuals often have:

• Extreme hyperexcitability of the sensory cortex: Light and sound sensitivity may stem from the brain’s inability to modulate sensory input due to neuroinflammation or altered GABA/glutamate balance in sensory pathways.

• Impaired thalamic gating: The thalamus acts as a sensory relay station; in ME/CFS, there could be disrupted thalamic gating leading to sensory overload and increased perception of stimuli as painful or overwhelming.

• Potential neurovascular coupling issues: Some hypotheses link these severe neurological symptoms to compromised blood flow in the brain or dysfunctional cerebral autoregulation.


3. Cross-Pollination from Other Neurological Diseases


3.1 Alzheimer’s and Parkinson’s

Research breakthroughs in Alzheimer’s disease (AD) and Parkinson’s disease (PD)—while distinct pathologies—have raised broader questions about inflammation, protein misfolding, and neuroimmune interactions that could apply to ME/CFS:

1. Protein misfolding and aggregates

• In AD, the aggregation of beta-amyloid and tau proteins leads to neuroinflammation; in PD, alpha-synuclein plays a similar role.

• Though not clearly protein-aggregation-driven, some ME/CFS investigators have asked whether chronic inflammation could eventually induce misfolded protein states or hamper autophagy in neurons and glia.

2. Microglial activation

• The role of microglia in clearing proteins and mediating inflammation is a centerpiece of AD/PD research.

• In ME/CFS, microglial activation is a plausible driver of brain fog, pain amplification, and sensory processing abnormalities.

3. Gut-Brain Axis

• In PD, the concept of a pathological process traveling from the gut to the brain along the vagus nerve has gained traction.

• ME/CFS patients often have gastrointestinal dysbiosis and IBS-like symptoms, adding another dimension of possible “gut-immune-brain” signaling disruptions.


3.2 Immunotherapies and Neuroimmune Insights

• Emerging immunotherapies: Multiple sclerosis (MS) research has spurred the development of high-efficacy immunomodulatory drugs that reduce CNS inflammation. While ME/CFS is not the same as MS, the concept of modulating the immune system to reset or dampen neuroinflammation is of interest to ME/CFS researchers.

• Blood-brain barrier permeability: In AD, PD, and MS, compromised blood-brain barrier (BBB) function can lead to the infiltration of peripheral immune cells. In ME/CFS, some investigators are studying whether repeated inflammatory episodes degrade the BBB, allowing unusual immune activity in the brain.


4. Cutting-Edge Immunological and Biological Concepts Potentially Applicable to ME/CFS


4.1 Trained Immunity and Epigenetic Reprogramming

• Trained immunity: Traditionally, innate immune cells (e.g., macrophages) were not thought to have “memory.” Recent discoveries show that innate cells can have a form of epigenetic reprogramming—potentially relevant to post-infectious diseases like ME/CFS and Long Covid. Repetitive or severe infections might leave a pathological “memory” in innate immunity that drives chronic inflammation or fatigue.

• Epigenetics: Viral triggers could induce long-term epigenetic changes in immune cells or neurons, locking individuals into maladaptive inflammatory or metabolic states.


4.2 Senescent Cells and Inflammaging

• Cellular senescence: In chronic inflammatory states, certain immune cells or fibroblasts can become senescent, secreting pro-inflammatory factors (the “SASP”—senescence-associated secretory phenotype). This process, sometimes called “inflammaging,” is studied in age-related neurodegenerative diseases but remains under-explored in ME/CFS.

• Potential for senolytics: Emerging therapies targeting senescent cells (senolytics) may one day help reduce chronic inflammation in conditions with a suspected senescence component.


4.3 Lymphatic and Glymphatic Systems

• Glymphatic clearance: The brain’s glymphatic system is crucial for clearing metabolic waste and inflammatory mediators. Impairment in glymphatic flow has been implicated in AD; whether it could be involved in persistent “toxic” or inflammatory by-products in ME/CFS is an area of speculation.


4.4 Mitochondrial Biogenesis and Redox Signaling

• ROS and redox dysregulation: Chronic oxidative stress is a known feature of ME/CFS, but cutting-edge research highlights how redox signaling can epigenetically modify cellular pathways.

• Mitochondrial network dynamics: Emerging studies on the fusion-fission balance in mitochondria suggest that dysfunctional mitochondrial networks (often found in neurodegeneration) could also impair energy metabolism in severe ME/CFS.


5. Specific Relevance to Severe Neurological Symptoms in ME/CFS

When patients are bedridden, hypersensitive to stimuli, and experience severe “concussion-like” symptoms, this points to pathological neuroimmune loops. Some unifying ideas include:

1. Overactive or “stuck” microglia releasing pro-inflammatory cytokines, leading to persistent neuroinflammation and hyperexcitability of sensory pathways.

2. Compromised autonomic regulation (e.g., hyperadrenergic or vagal imbalance), explaining profound orthostatic intolerance, migraines, and sensory overload.

3. Ionic channel dysfunction or autoantibodies (as seen in some forms of encephalitis) that could alter neuronal firing thresholds.

4. Energy deficit in glial or neuronal cells leading to an inability to maintain normal synaptic function, compounding cognitive and sensory dysfunctions.


6. Looking Ahead

While there is no single, definitive explanation for ME/CFS yet, the confluence of immunology, neurology, and cellular biology reveals multiple candidates for deeper investigation. Some under-explored (or only recently explored) frontiers include:

• Integrating advanced single-cell immune profiling: Techniques like mass cytometry or single-cell RNA-seq can identify subtle immune cell states (e.g., exhausted T cells or epigenetically reprogrammed monocytes) specific to ME/CFS.

• In vivo imaging of neuroinflammation: PET imaging with more specific ligands for microglial activation can help map out areas in the brain most affected and track changes over time or in response to interventions.

• Targeting senescence or altered metabolic pathways: Potential therapies in other fields—ranging from senolytics to compounds targeting NAD+ metabolism—may be relevant to the persistent fatigue and neuroinflammation seen in severe ME/CFS.

• Systems biology approaches: Integrative “omics” (proteomics, metabolomics, lipidomics) combined with AI-driven analysis can help uncover novel biomarkers or mechanistic pathways, especially in severe, bedridden patients.

In sum, ME/CFS research—especially in light of Long Covid—has accelerated, merging immunology, neurobiology, and cellular metabolism into a more holistic picture of chronic neuroimmune dysfunction. Borrowing tools and concepts from Alzheimer’s, Parkinson’s, multiple sclerosis, and other neurodegenerative or autoimmune fields is already bearing fruit in shaping new hypotheses. While many of these cutting-edge concepts (e.g., senescence, trained immunity, glymphatic system dysregulation) are still relatively underexplored in the context of ME/CFS, they offer promising avenues to understand and potentially treat the severe, debilitating manifestations of the illness.

 

Below is an exploration of how some of the emerging mechanistic frameworks—both those already mentioned and a few additional ones—might specifically address the ME/CFS phenomenon of “baseline deterioration” and post-exertional malaise (PEM). This includes why, over time, repeated overexertion can push a person from a mild to a more severe (or even very severe) ME/CFS state.


1. “Priming” and Escalating Immune Responses

Microglial or Immune Cell Priming

• Concept: In many chronic inflammatory or neurodegenerative conditions, initial immune challenges (such as viral infection, traumatic brain injury, or repeated stress) can “prime” innate immune cells (e.g., microglia in the CNS, monocytes/macrophages peripherally). Once primed, these cells overreact to subsequent triggers, mounting a disproportionately large inflammatory response.

• Relevance to ME/CFS: If an ME/CFS patient already has microglia in a primed state (perhaps from a prior viral infection or repeated PEM episodes), even mild exertion (physical or cognitive) can incite a significant spike in neuroinflammation. Over time, repeated over-activation may contribute to neuronal damage or altered synaptic plasticity, making the person increasingly prone to crashes and potentially ratcheting their baseline lower.

T-Cell Exhaustion or Autoimmune Features

• Concept: Low-level, persistent immune activation can lead to T-cell “exhaustion” or encourage the emergence of damaging autoantibodies.

• Relevance to ME/CFS: Each time a person with ME/CFS overexerts, the immune system may be thrust into a more dysregulated state—exhausted T-cells or new autoantibody formation—contributing to a less robust baseline capacity for daily functioning.

2. Mitochondrial and Metabolic Threshold Phenomena

“Metabolic Trap” or Energy Bankruptcy

• Concept: Several ME/CFS hypotheses propose that the cells—particularly muscle cells, neurons, and glia—become locked in a dysfunctional metabolic state after an insult (infection, severe stress, etc.). Once stuck, the body has difficulty returning to normal ATP production and redox balance.

• Relevance: Overexertion in this precarious metabolic state could push cells over a threshold (“energy bankruptcy”). Recovery from that crash demands more resources than are available, so the baseline drops, sometimes permanently, if repeated too often.

Dynamic Mitochondrial Network Failures

• Concept: Mitochondria function not just as individual organelles but as part of dynamic networks that constantly fuse and divide. Chronic inflammation, oxidative stress, or ATP depletion can disrupt these networks, impairing cells’ ability to adapt to energy demands.

• Relevance: If each episode of overexertion causes further fragmentation of mitochondrial networks—especially in neurons and muscle—repeated insults could create long-term deficits, making it progressively harder to recover one’s prior functional baseline.

3. Epigenetic and “Trained” Innate Responses

Trained Immunity

• Concept: Innate immune cells (macrophages, monocytes) can adopt lasting epigenetic changes after an immune challenge. Normally, this helps the body respond more efficiently to pathogens. But in chronic conditions, this can lead to maladaptive inflammation or dysregulated repair processes.

• Relevance: If each post-exertional immune flare “re-trains” innate immune cells toward pro-inflammatory states, the body becomes increasingly reactive to even small triggers (physical, cognitive, or emotional exertion). This can explain why ME/CFS patients can quickly dip below their previous baseline when they exceed their “energy envelope.”

Epigenetic “Lock-In” of Stress Pathways

• Concept: Repeated physiological stress can alter the epigenome—chemical modifications on DNA or histones—resulting in gene expression changes that persist even after the original stress subsides.

• Relevance: After overexertion, an ME/CFS patient may develop epigenetic marks that dampen normal cellular stress responses or energy metabolism. This could lead to more frequent PEM episodes and a gradual shift to a lower baseline.

4. Neuroinflammation and “Amplification Loops”

Hyperexcitability of Pain & Sensory Pathways

• Concept: In conditions like fibromyalgia or chronic pain, repeated insults (painful stimuli, stress) can drive synaptic and cellular changes that lower the threshold for pain or sensory overload. This is sometimes called “central sensitization.”

• Relevance: In ME/CFS, repeated episodes of PEM could similarly sensitize the brain’s response to exertion. In severe ME, minimal physical or cognitive effort could trigger a disproportionately large or prolonged crash—worsening the baseline over time.

Glial-Neuronal Feedback Loops

• Concept: Neurons and glia (microglia and astrocytes) form tightly coupled networks. When glia release pro-inflammatory cytokines, they can alter neuronal function. In turn, neuronal stress signals (e.g., from excitotoxicity) further activate glia, perpetuating a cycle.

• Relevance: Each crash may temporarily tip the balance toward heightened glial activation and/or neuronal energy crisis. When repeated, these loops might cause long-lasting changes in synaptic integrity, possibly explaining why a once “mild” patient can eventually become severe if they frequently overexert.

5. Autonomic Instability and Vascular Dysregulation

Exertional Stress on an Unstable Autonomic Nervous System

• Concept: ME/CFS often features dysregulation of the sympathetic/parasympathetic balance, blood pressure control, and heart rate (e.g., orthostatic intolerance, POTS). Repeated stress can exacerbate autonomic imbalances, leading to tissue hypoperfusion and hypoxia during or after exertion.

• Relevance: Chronic low-level hypoxia or ischemia from repeated autonomic crashes can damage tissues over time, especially metabolically demanding organs like the brain and muscles. This can contribute to permanent decrements in functional capacity.

Endothelial Dysfunction and Microcirculatory Failure

• Concept: Emerging evidence suggests that the microvasculature (tiny blood vessels in muscle and brain) can be dysfunctional in ME/CFS, possibly from oxidative stress, autoantibodies, or inflammation.

• Relevance: If each episode of exertion exacerbates microcirculatory deficits—impairing oxygen and nutrient delivery—the next exertion might lead to more pronounced tissue stress. Over months or years, this can yield a progressively lower baseline of function.

6. Additional Theoretical or Novel Mechanisms

1. “Energy Envelope” Neuro-Endocrine Reset

Repeated breaching of one’s limited “energy envelope” might trigger maladaptive HPA-axis resets (stress-hormone dysregulation). Over time, this could create a new homeostatic “set point” that is substantially more restricted.​

2. Cellular Senescence Accumulation

With each post-exertional inflammatory flare, more cells (endothelial, immune, or otherwise) become senescent, releasing pro-inflammatory signals (the SASP). A higher senescent-cell burden could worsen general inflammation and degrade function over time.​

3. Glymphatic Clearance Inhibition

If repeated exertional stress heightens neuroinflammation, it may also disrupt glymphatic flow (the brain’s waste-clearance system). Accumulated toxic metabolites could then accelerate neuronal dysfunction, further dropping baseline function.
​

7. Putting It All Together

Why Do Some Patients Permanently Lose Baseline Function After Overexertion?

• Each crash potentially “reprograms” or further stresses the immune and metabolic systems.

• There may be a threshold effect: Once certain pathways (e.g., microglial activation, T-cell dysregulation, mitochondrial fragmentation) reach a critical point, it becomes more difficult (or impossible) to revert to the prior state.

Why Are There Different Timeframes for PEM?

• Immediate vs. Delayed: Cognitive or emotional stress might trigger a more rapid (“fight-or-flight”) stress response, causing near-immediate symptoms. Physical stress often has additional metabolic and vascular consequences that can build more gradually and manifest fully hours or a day later.

• Short vs. Longer Crashes: Some individuals have robust enough compensatory mechanisms (even if dysfunctional) that they can bounce back within days, whereas others—especially those with more advanced baseline dysregulation—are mired in ongoing inflammation and metabolic dysfunction for weeks or months.

8. Conclusion

From microglial priming and epigenetic “lock-in,” to mitochondrial network failure and autonomic-vascular dysregulation, there are multiple plausible biological frameworks explaining how overexertion can drive the hallmark post-exertional malaise in ME/CFS and lead to a deteriorating baseline over time. These frameworks underscore several key points:

1. Repeated Overactivation of immune or neuroimmune pathways can amplify inflammation or metabolic dysfunction.

2. Threshold or Tipping-Point Models suggest that once certain systems (e.g., mitochondria, microvasculature, glial networks) are pushed past their capacity, the recovery to a previous baseline becomes harder or impossible.

3. Epigenetic & Cellular Memory can make each crash “easier” to trigger and “harder” to exit, reinforcing the downward spiral in functional capacity.

Continuing research into these domains—especially as new tools (e.g., single-cell multi-omics, advanced neuroimaging) become more widely used in ME/CFS and Long Covid cohorts—will likely clarify these “ratcheting” mechanisms and hopefully guide interventions to prevent or reverse baseline deterioration.

 

A classic example of vague AI slop. I'm not impressed with this result at all. It's the general problem with AI where it regurgitates popular thoughts without any underlying understanding.

 

I thought it did quite a good job in 6 seconds.. if treated as an information resource and ideating aide, not a cited published article.

I’m not a researcher so maybe these ideas are not difficult to come up with, but I thought
some ideas — thalamic gating, cellular senescence / inflammaging, trained immunity, epigenetic reprogramming, glymphatic clearance — might not usually be brought up in relation to ME and might spark something in a new researcher to pursue further.

 

Derya Unametz tweets a lot about using the o1 Pro model. He seems very impressed w it.

https://twitter.com/user/status/1870570750945673343