Miscellaneous Research Thread

[Jonathan Edwards]

That seems very mysterious.
They used AI to prove that dead people were not conscious?

 

[Jonathan Edwards]

They seem to ave made the usual mistake of thinking that people are conscious, rather than cells.
But they might discover something important about how cells report their consciousness.

 

[Nightsong]

A quite interesting review in Nature Immunology today -

Sex differences in immune responses to viruses, bacteria and vaccines

Abstract:
Sex differences in immune function arise from sex chromosome complement, which drives differential expression and activity of X-linked genes in immune cells, and gonadal steroids that transcriptionally regulate innate and adaptive immune cells through their respective receptors. These fundamental differences shape divergent outcomes between male and female individuals in viral and bacterial infections, post-acute infection syndromes and vaccine responses throughout the lifespan. Understanding these sex-specific immune mechanisms represents a critical frontier for developing novel therapeutic targets and advancing personalized medicine.

Link

 

[Jonathan Edwards]

TLR7 innit.

Well worth reading.
And then reading again.

 

[Murph]

A paper that interests me because it illustrates the type of mechanism that could be behind a well-known phenomenon: "this treatment seemed to work for a while. Then it stopped."

The drug here is one being clinical trialled by Deakin university in Australia for mecfs but this study is on a different condition.

Metabolic Adaptation of CD8⁺ T Cells Limits the Efficacy of Fatty Acid Oxidation Inhibition in Type 1 Diabetes

Manuel Salzmann et al. Int J Biol Sci. 2026.

Abstract
Type 1 Diabetes Mellitus (T1D) is an organ-specific autoimmune disease characterized by persistent hyperglycemia due to immune-mediated destruction of pancreatic islet β-cells. Targeting immune cell metabolism has emerged as a promising therapeutic strategy.

We investigated whether the fatty acid oxidation (FAO) inhibitor trimetazidine (TMZ), one of only three approved drugs directly targeting cellular metabolism, can restrain autoreactive immunity and delay T1D in non-obese diabetic mice (NOD). TMZ enhanced mitochondrial membrane potential, suppressed FAO, and curtailed activation and proliferation of human CD8+ T cells. In dysglycemic NOD mice, a clinically approved dose of TMZ delayed progression to T1D, reduced mean glycemia, and decreased islet CD4⁺/CD8⁺ infiltration. Single-cell RNA sequencing revealed depletion of FAO-high, stress-responsive cells and mitochondrially active stromal cells, indicating improved pancreatic health. Prolonged exposure induced compensatory upregulation of carnitine-palmitoyl-transferase-1A (CPT1A) in CD8⁺ subsets, counterbalancing early benefits.

In summary, TMZ transiently restrains CD8⁺ T cell activity, reduces islet infiltration, and improves pancreatic health. The adaptive upregulation of CPT1A demonstrates a novel evasion mechanism to FAO inhibition and underscores the central role of FAO in sustaining pathogenic T cells. Our work highlights metabolic adaptation as a key determinant of autoimmune progression, validating FAO as a therapeutic target in T1D.

 

[Nightsong]

There's a review of the post-acute sequelae of Lassa fever in the Journal of Infection (open access) -

https://www.sciencedirect.com/science/article/pii/S016344532600068X

and a fascinating paper in Science Translational Medicine on the development of a novel genomic medicine based treatment (targeting SCN9A, which I think we have discussed before - it codes for a sodium channel that controls pain signalling) in an animal model of neuropathic pain -

https://www.science.org/doi/10.1126/scitranslmed.adu0217

 

[Nightsong]

A short comment by four authors associated with the Patient-Led Research group advocating that patients should routinely review all manuscripts on Long COVID. Mentions ME/CFS. A few quotes:

Spoiler: Quotes

The history of myalgic encephalomyelitis, another infection-associated chronic condition and common phenotype of long COVID,7 illustrates this dynamic. Institutional researchers frequently conflate two distinct facets of myalgic encephalomyelitis: the symptom of fatigue and the pathophysiological state of post-exertional malaise. Post-exertional malaise is the often-delayed substantial worsening of symptoms following exertion that was tolerated before the illness onset, and can last days, weeks, or permanently. This conflation, and the subsequent failure to understand key features of myalgic encephalomyelitis, is the result of systematic exclusion of patient expertise.

Structural incentives are therefore needed to ensure institutional researchers engage patient expertise meaningfully throughout the research process. We believe that routine patient review of all manuscripts on long COVID, including but not limited to clinical trial protocols and results, pathophysiological research, and opinion pieces, can play this incentivising role.

Anticipation of patient scrutiny at the review stage creates a clear incentive to design and conduct studies that patients would deem methodologically sound and relevant, and meaningfully collaborate with patients throughout the research process. The risk of introducing bias would be low, as the primary purpose of patient review is to ensure the real-world applicability of research and faithfulness to lived experience, although we caution that the technical expertise of some patients should not be underestimated

ScienceDirect Link

 

[Felis Catus]

A short comment by four authors associated with the Patient-Led Research group advocating that patients should routinely review all manuscripts on Long COVID. Mentions ME/CFS. A few quotes:


ScienceDirect Link

Like they reviewed evidence supporting the use of 40 or so treatments for LC?

 

[Nightsong]

There were three papers in Nature yesterday reporting on a seven year project that reviewed 3900 social science papers -

Investigating the replicability of the social and behavioural sciences
Investigating the reproducibility of the social and behavioural sciences
Investigating the analytical robustness of the social and behavioural sciences

There's a Nature News summary here:

Half of social-science studies fail replication test in years-long project

A massive seven-year project exploring 3,900 social-science papers has ended with a disturbing finding: researchers could replicate the results of only half of the studies that they tested

When some of SCORE’s team members attempted to reproduce the data analyses of 600 papers, they found that only 145 contained enough details to do so. And of these, only 53% could be reproduced so that results matched precisely

Finally, SCORE checked papers’ replicability — the most onerous of the three tasks. Researchers endeavoured to repeat entire experiments, gathering and analysing the data from scratch. Of the 164 studies that they focused on, they were able to replicate only 49% with statistical significance

 

[Sean]

While the analytics component is a critical part of overall methodology, and worthy of review on its own, did they also do a separate study on the non-analytical component, the part that constitutes the primary data generation/collection phase?

No good checking how robust the analysis of the data is, if it was not inherently robust data in the first place.

 

[EndME]

A short comment by four authors associated with the Patient-Led Research group advocating that patients should routinely review all manuscripts on Long COVID. Mentions ME/CFS. A few quotes:


ScienceDirect Link

This is just going to produce the same old issues of peer review and in some circumstances make things worse. They should have already noticed this problem with their own piece: Did they ask patients to review this piece and if so which ones? Only the ones who already share their opinion? It is a bit comedic that this was published behind a paywall, so not accessible to most patients.

 

[Nightsong]

I haven't created a new account to check but I noticed earlier today that the version of the LC paper on the Lancet site (but not the one on ScienceDirect) has been updated to say "Free with registration", so I think this might be more accessible now. (I've noticed before with Elsevier journals that sometimes it takes a few days for open-access papers to be made open-access.)

Link (Lancet Infectious Diseases)

 

[rvallee]

There were three papers in Nature yesterday reporting on a seven year project that reviewed 3900 social science papers -

Investigating the replicability of the social and behavioural sciences
Investigating the reproducibility of the social and behavioural sciences
Investigating the analytical robustness of the social and behavioural sciences

There's a Nature News summary here:

Half of social-science studies fail replication test in years-long project

Even far more disturbing is the huge number of studies and trials that duplicate the same mistakes. No one seems to think of that. I wrote the beginning of an article on that yesterday but I'm all out of juice dealing with some family health issues.

CBT has been 'promising' for decades, for everything, and the kitchen sink. And yet every trial published this year is the same as the first ones. This is so incredibly, and obviously, wasteful. Most pragmatic trials and pretty much everything biopsychosocial is just as bankrupt. Replicating the same mistakes appears to be the main solution to the crisis of replicability.

When some of SCORE’s team members attempted to reproduce the data analyses of 600 papers, they found that only 145 contained enough details to do so. And of these, only 53% could be reproduced so that results matched precisely

Oh, so this is even worse. This is how an industry ends up producing things so worthless that literature reviews find almost all of them to be so useless they can't even be used for anything, have to be rejected.

 

[forestglip]

An abstract about ME/CFS guidelines has been moved to a new thread: Physical activity for myalgic encephalomyelitis/chronic fatigue syndrome: A clinical practice guideline, 2026, Kirsh et al

 

[SNT Gatchaman]

Mapping pesticide mixtures to cancer risk at the country scale with spatial exposomics (2026)

Spoiler: Abstract

Despite decades of concern over the carcinogenic potential of agricultural pesticides, toxicological studies relying on single endpoints have yet to establish a definitive link between environmental pesticide exposure and cancer in real-world contexts.

Here we use an integrative spatial Bayesian framework that merges high-resolution environmental pesticide risk modelling with comprehensive cancer registry data to map pesticide-linked cancer clusters in Peru with unprecedented precision. Our process-based model, encompassing 31 key pesticide active ingredients, together with an innovative stratification of cancer cases by developmental lineage, reveals a robust spatial association between environmental pesticide exposure risk and cancer incidence.

In pesticide-associated cancer hotspots, exposomic profiling of liver tissue—a primary target of chemical carcinogens—uncovers a distinct transcriptomic signature of pesticide exposure, implicating a non-genotoxic mode of action that disrupts core regulatory circuitries sustaining cell identity. Collectively, these findings strongly support a mechanistic link between pesticide exposure and cancer, challenging assumptions of human non-carcinogenicity derived from reductionist experimental models.

This study redefines the exposome as a lineage-conditioned, mechanistically tractable framework and shows how complex pesticide mixtures can contribute to carcinogenic trajectories, with profound and far-reaching implications for global health policy and socio-ecological equity.

Web | PDF | Nature Health | Open Access

 

[Nightsong]

Not directly related to ME/CFS, but as some severely affected pwME with GI issues or feeding problems have been placed under the "disorders of gut-brain interaction" umbrella: there is a new classification system for "DGBIs", the Rome V criteria, which replace the earlier Rome IV criteria. There have been a couple of papers on this but this one is open access and gives an overview:

Disorders of Gut-Brain Interaction and the Rome V Process (Gastroenterology, April 2026, open access)

 

[Nightsong]

There are at least four LC & ME/CFS poster abstracts among those from the 2026 Biological Psychiatry meeting -

Link (Molecular Psychiatry, April 2026)

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214. 7T MRI Reveals Morphological Changes and Associations Between Neuropsychological Function and Brain Volumes in Long-COVID

Long-COVID patients demonstrated reduced subcortical volumes of left caudate and right thalamus (p<0.05), and increased cortical thickness across multiple PFC regions (left-rostral middle-frontal-cortex, left-caudal middle-frontal-cortex, and others; p <0.05) compared to controls. Left-rostral anterior-cingulate-cortex (lrACC) volume showed positive associations with HVLT-R-Immediate (R2=0.16, p<0.01) and Number Span Forward (R2=0.09, p <0.05)

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211. Reduced Functional Connectivity and Structural Volumes in the Striato-Thalamo-Cerebellar Circuit in Individuals With Self-Reported Long COVID

Compared with COVID Controls, Long COVID participants showed reduced functional connectivity in the striato-thalamo-cerebellar circuit, specifically among right thalamus, bilateral putamen, and cerebellar regions IV-VII (ps<.001). Long COVID participants also had smaller structural volumes in these regions (ps <.01).

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568. No Objective Evidence of Neuropsychological Deficits in People With Subjective Cognitive Deficits Following COVID-19 Infection

Subjective cognitive complaints following COVID-19 were not accompanied by measurable neuropsychological deficits but were linked to elevated affective symptoms and biological risk markers. Findings highlight a dissociation between perceived and objective cognition and suggest that inflammatory, genetic, and affective factors may shape self-perceived decline. Longitudinal studies are needed to determine whether these markers confer vulnerability to future cognitive decline.

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581. A Window Into Mitochondrial Dysfunction in Myalgic Encephalitis/Chronic Fatigue Syndrome (ME/CFS): Increased Lactate Production During Brain Stimulation With a Flashing Checkerboard Using 7T Functional MRS

20 CFS/ME patients and 20 HC were included; in-dependent samples t-test showed that while the groups did not differ in terms of baseline lactate levels (t=0.034,p=0.973), the ME/CFS patients had a significantly higher increase in lactate during stimulation compared to the baseline rest period, expressed as a % change of the rest value (t=2.847, p=0.007; mean (SD): ME/CFS 22.20 % (12.74), HC 10.55 % (13.14)). A change in comparator, NAA, did not differ between groups (t=0.85, p=0.932).