Shin
@shinjieyong.bsky.social
MSc (Research) | World's top 1% most-cited scientists (Stanford ranking) | Independent researcher and writer | National athlete | Malaysian | https://theinfectedneuron.substack.com/
Study link: www.science.org/doi/10.1126/...
December 14, 2025 at 4:24 AM
Study link: www.science.org/doi/10.1126/...
Even though the infection clears, the APOBEC-driven mutations persist in bladder cells, accumulating over years or decades until a tumour becomes detectable.
December 14, 2025 at 4:24 AM
Even though the infection clears, the APOBEC-driven mutations persist in bladder cells, accumulating over years or decades until a tumour becomes detectable.
A new study, titled “Virus-induced APOBEC3 transmutagenesis in bladder cancer initiation,” shows that BK polyomavirus infection can activate APOBEC3, an antiviral enzyme that mutates DNA to fight viruses.
December 14, 2025 at 4:24 AM
A new study, titled “Virus-induced APOBEC3 transmutagenesis in bladder cancer initiation,” shows that BK polyomavirus infection can activate APOBEC3, an antiviral enzyme that mutates DNA to fight viruses.
While this suggests possible directionality (brain tract changes preceding symptoms) within the model, it doesn’t rule out reverse causation or deconditioning.
So in hindsight, a more appropriate phrasing would be “suggestive of causality” rather than causal in a strict sense.
So in hindsight, a more appropriate phrasing would be “suggestive of causality” rather than causal in a strict sense.
December 14, 2025 at 4:16 AM
While this suggests possible directionality (brain tract changes preceding symptoms) within the model, it doesn’t rule out reverse causation or deconditioning.
So in hindsight, a more appropriate phrasing would be “suggestive of causality” rather than causal in a strict sense.
So in hindsight, a more appropriate phrasing would be “suggestive of causality” rather than causal in a strict sense.
What the authors did beyond simple correlation is causal-inference modeling, which prioritizes certain frontal–limbic and attention/pain-related tracts as statistically upstream of fatigue and cognitive scores under specific assumptions.
December 14, 2025 at 4:16 AM
What the authors did beyond simple correlation is causal-inference modeling, which prioritizes certain frontal–limbic and attention/pain-related tracts as statistically upstream of fatigue and cognitive scores under specific assumptions.
Yeah, that’s a fair point. The study is largely cross-sectional, so it can’t distinguish white-matter changes that (i) cause symptoms from those that (ii) arise because of living with ME/CFS (e.g., reduced activity, chronic stress).
December 14, 2025 at 4:16 AM
Yeah, that’s a fair point. The study is largely cross-sectional, so it can’t distinguish white-matter changes that (i) cause symptoms from those that (ii) arise because of living with ME/CFS (e.g., reduced activity, chronic stress).
Study link: www.sciencedirect.com/science/arti...
Microstructural white matter impairments in chronic fatigue syndrome: Evidence of segmental injury in the cingulum bundle
Chronic fatigue syndrome (CFS) is a neurological disorder characterized by persistent fatigue. Previous studies have shown structural and functional b…
www.sciencedirect.com
December 13, 2025 at 12:35 PM
Study link: www.sciencedirect.com/science/arti...
3. Results were robust across analytic pipelines, arguing against preprocessing or model artefacts.
The authors then conclude that ME/CFS reflects network-level brain disconnection, not just fatigue without brain pathology.
The authors then conclude that ME/CFS reflects network-level brain disconnection, not just fatigue without brain pathology.
December 13, 2025 at 12:35 PM
3. Results were robust across analytic pipelines, arguing against preprocessing or model artefacts.
The authors then conclude that ME/CFS reflects network-level brain disconnection, not just fatigue without brain pathology.
The authors then conclude that ME/CFS reflects network-level brain disconnection, not just fatigue without brain pathology.
2. Causal analysis linked abnormalities in the frontal–limbic and attention/pain-related tracts to core symptoms like cognitive dysfunction and fatigue.
December 13, 2025 at 12:35 PM
2. Causal analysis linked abnormalities in the frontal–limbic and attention/pain-related tracts to core symptoms like cognitive dysfunction and fatigue.
1. Advanced diffusion MRI + machine learning models identified widespread white-matter microstructural damage that reliably distinguished ME/CFS patients from controls.
December 13, 2025 at 12:35 PM
1. Advanced diffusion MRI + machine learning models identified widespread white-matter microstructural damage that reliably distinguished ME/CFS patients from controls.
• Telomere attrition: some pathogens integrate near telomeres or accelerate their shortening.
• Cognitive decline: viral proteins can seed amyloid or tau and activate neuroinflammation.
• Cognitive decline: viral proteins can seed amyloid or tau and activate neuroinflammation.
December 7, 2025 at 7:32 PM
• Telomere attrition: some pathogens integrate near telomeres or accelerate their shortening.
• Cognitive decline: viral proteins can seed amyloid or tau and activate neuroinflammation.
• Cognitive decline: viral proteins can seed amyloid or tau and activate neuroinflammation.
• Inflammaging: persistent cytokine and chemokine activation drives chronic low-grade inflammation.
• Cellular senescence: infections trigger senescence pathways that amplify inflammatory signaling.
• Cellular senescence: infections trigger senescence pathways that amplify inflammatory signaling.
December 7, 2025 at 7:32 PM
• Inflammaging: persistent cytokine and chemokine activation drives chronic low-grade inflammation.
• Cellular senescence: infections trigger senescence pathways that amplify inflammatory signaling.
• Cellular senescence: infections trigger senescence pathways that amplify inflammatory signaling.
• Immunosenescence and exhaustion: long-term immune stimulation pushes the system toward dysfunction.
• Epigenetic alterations: pathogens induce shifts in methylation and gene expression.
• Epigenetic alterations: pathogens induce shifts in methylation and gene expression.
December 7, 2025 at 7:32 PM
• Immunosenescence and exhaustion: long-term immune stimulation pushes the system toward dysfunction.
• Epigenetic alterations: pathogens induce shifts in methylation and gene expression.
• Epigenetic alterations: pathogens induce shifts in methylation and gene expression.
• Mitochondrial dysfunction: pathogens hijack mitochondrial signaling, use ROS, or exploit lipid droplets for replication.
• Microbiome dysbiosis: chronic infection destabilizes microbial communities and disrupts immune–metabolic crosstalk.
• Microbiome dysbiosis: chronic infection destabilizes microbial communities and disrupts immune–metabolic crosstalk.
December 7, 2025 at 7:32 PM
• Mitochondrial dysfunction: pathogens hijack mitochondrial signaling, use ROS, or exploit lipid droplets for replication.
• Microbiome dysbiosis: chronic infection destabilizes microbial communities and disrupts immune–metabolic crosstalk.
• Microbiome dysbiosis: chronic infection destabilizes microbial communities and disrupts immune–metabolic crosstalk.
But as far as I know, we don’t yet have a study showing mast cell-mediated disruption of the brainstem or its connective tissues in long COVID specifically (or its related conditions like fibromyalgia or ME/CFS). So while it's a plausible idea, I think future studies still need to demonstrate it.
November 29, 2025 at 5:20 PM
But as far as I know, we don’t yet have a study showing mast cell-mediated disruption of the brainstem or its connective tissues in long COVID specifically (or its related conditions like fibromyalgia or ME/CFS). So while it's a plausible idea, I think future studies still need to demonstrate it.
Thanks for sharing that preprint and your idea. The experimental evidence for autoimmune-driven mast-cell activation is indeed relevant. Mast cells can influence connective-tissue structures around the brain, so the hypothesis makes biological sense.
November 29, 2025 at 5:20 PM
Thanks for sharing that preprint and your idea. The experimental evidence for autoimmune-driven mast-cell activation is indeed relevant. Mast cells can influence connective-tissue structures around the brain, so the hypothesis makes biological sense.
2. IgG didn’t enter the brain and did not reproduce cognitive deficit, anxiety, or depression in mice, suggesting that cognitive/mental long COVID may involve mechanisms other than IgG autoantibodies.
November 28, 2025 at 3:21 PM
2. IgG didn’t enter the brain and did not reproduce cognitive deficit, anxiety, or depression in mice, suggesting that cognitive/mental long COVID may involve mechanisms other than IgG autoantibodies.
1. No single antigen was identified. The autoimmunity appears heterogeneous rather than driven by one dominant antibody.
November 28, 2025 at 3:21 PM
1. No single antigen was identified. The autoimmunity appears heterogeneous rather than driven by one dominant antibody.
But there are two main mechanistic caveats:
November 28, 2025 at 3:21 PM
But there are two main mechanistic caveats:
This is one of the strongest demonstrations to date that long COVID pain can be antibody-mediated “autoimmune pain.”
November 28, 2025 at 3:21 PM
This is one of the strongest demonstrations to date that long COVID pain can be antibody-mediated “autoimmune pain.”