Miscellaneous Research Thread

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.
 
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
 
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.
 
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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
 
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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:

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.
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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.
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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
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ScienceDirect Link
 
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
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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
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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
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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.
 
Nightsong said:
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
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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.
 
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)
 
Nightsong said:
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
Click to expand...
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
Click to expand...
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.
 
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