All papers ingested into the project, organized by confidence tier. Each carries a one-line hook and a link to the full normalized note (claims-as-triples, methods, limitations, triangulation notes). Tier badges encode whether a paper is foundational, recently ingested, or drawn from non-FM literature as a bridge.
Foundational FM-RNFL anchor. 116 FM vs 144 controls, dual-OCT-device (Cirrus + Spectralis) replication of RNFL / GCL / IPL thinning in FM. Anchor for the retinal-biomarker-diagnostic-priority track.
FM-IgG sensitization runs through MRGPRX2/Mrgprb2 on mast cells; MC ablation OR Mrgprb2 deletion abolishes passive-transfer pain phenotype. H1×H2 unified mechanism anchor.
Long-COVID IgG passive transfer to mice → DRG-localized mechanical allodynia + thermal hypersensitivity; NO cognitive/anxiety effects. First mechanistic dissociation of LC pain from LC brain fog.
Passive transfer of FM patient IgG reproduces pain & SFN in mice.
Consolidation review: FM as autoimmune; passive transfer replicated in 3 cohorts.
IgG binding to DRG in 68/184 FM sera vs. 0/controls; 9 binding clusters.
FM serum activates SGCs across DRG + trigeminal + vagal + sympathetic ganglia.
Microbial bile acids correlate with anti-SGC IgG and disease severity.
Microglial activation in nociplastic pain via TSPO-PET; FM as prototype.
Large-scale brain network FC dysfunction; thalamocortical decoupling in FM.
Predictive-coding "central overload" framework for ME/CFS, extended to FM.
Serum GRIN1 / P2RX1 / P2RY2 as FM diagnostic biomarkers (AUCs 0.78–0.84).
emBODY task: FM patients show reduced differentiation of body-state maps; elevated alexithymia.
Gut microbiome scoping review: dysbiosis, intestinal-permeability compromise, immune activation in FM.
FMT in nociplastic pain: systematic review (13 studies, n=409); pain reduction in FM and IBS subgroups.
Long COVID neuropathy: mast-cell activation as central mechanism, mirrors SFN/ME-CFS.
Neuro-cognitive trigger model: FM flares as cognitive-load + emotional-stress + recovery-failure dynamics.
Altered lipid concentrations correlate with anti-SGC IgG and FM symptom severity.
Increased gut permeability + bacterial translocation in FM and ME/CFS (zonulin, LPS, sCD14, anti-β-LGB elevated).
Anti-SGC IgG titer correlates with FM symptom severity (load-bearing for BASIS-FM design).
Daratumumab pilot in ME/CFS: 6/10 marked responders; plasma-cell depletion strategy.
First robust FM GWAS (n=2.5M; 26 loci; heritability exclusively brain-tissue enriched). Anchors H3 dominance at population level.
Disentangling interoception in FM: heartbeat-detection IAc tracks cognitive performance; second modality replicating Herman 2026.
Hereditary alpha-tryptasemia (HαT): TPSAB1 copy-number variation; ~5% population frequency; heritable substrate for H2-MC subtype.
HERV expression profiles classify FM, ME/CFS, co-diagnosed, healthy. HERV-W ENV in 33% FM, 48% long COVID, 9% controls.
HERV dysregulation case (ME+MS); rituximab worked; HERV-W ENV negative but other HERVs altered.
Plasmapheresis + IVIG pilot (n=7) in autoantibody-positive ME/CFS; titer-QoL inverse correlation.
Multi-marker blood panel; 100% sens / 71.9% spec for post-COVID vs FM/ME-CFS/HC.
High-dose continuous-regimen cromolyn in ME/CFS+MCAS (n=5 case series, all responders). H2 hypothesis salvage path.
Mast cells + estrogen-induced pain sensitization (endometriosis review). Candidate mechanism for FM female predominance.
Persistent amplification of three HERV loci in PASC monocytes (n=12); JAKMIP2-intronic locus most amplified. Q40 input expansion.
Peripheral mast cells in FM mouse model; MC stabilization rescues pain. Reconciles with Ang 2014 negative human RCT.
Pan IgG Fc receptor blockade (PRIM) reverses chronic pain in IgG-mediated mouse IVD-injury model. Fourth converging line of antibody-removal evidence.
HERV-K10 reactivated in HBV/HCV; MAG1 domain immunostimulatory; chronic HBV patients show MAG1-specific responses + IL-6/IL-1β elevation. Q40 input expansion.
Viral hypothesis of schizophrenia (review). Cross-condition support for multi-hit viral-pathogenesis framework.
EBV seroconversion → 32-fold MS risk in 10M military cohort. Cross-condition empirical anchor for viral-genome-modification framework.
P2X7 → mtDNA → cGAS-STING in chronic-stress mouse depression model. Parallel upstream entry to HERV-mito loop; STING inhibition rescues.
SARS-CoV-2 RNA → LINE-1 retrotransposon integration into host genome. Contested; third candidate viral-genome-modification mechanism (bridging).
Comprehensive review of B-cell dysregulation and autoantibody production in long COVID. Closes citation gap for viral-genome-modification framework §6.4.
Resveratrol blocks STING ER-Golgi translocation + TBK1 phosphorylation; rescues microglial senescence + cognition in mouse aging model. OTC candidate STING-pathway interrupter for HERV-mito loop.
Metformin clinical-trial landscape in CNS disorders: 23 trials, 5 in MS via AMPK / remyelination / neuroprotection. Drug-repurposing candidate for HERV+/EBV+ FM.
FM-direct review of metformin's anti-inflammatory + neurotransmitter-modulating + neuroprotective mechanisms. Closes v0.3 §12.9 FM-direct citation gap.
Metformin in reserpine-induced FM mouse model: reverses pain + mood phenotype both sexes; sex-specific neurotransmitter modulation (males only).
Dahl SS rat as predictive FM animal model via FAM index; metformin and green-light exposure both significantly reduce FAM scores.
UK CPRD 624K cohort: metformin within 90 days of COVID reduces PCC by 63% (HR 0.36). Largest real-world signal on a v0.3 cure-path arm.
Metformin alters mitochondria-related metabolism in human OPCs; MS brain donor concordance. Mitochondrial-quality-control mechanism anchor.
Metformin + pioglitazone suppress A1-astrocyte activation in EAE via AKT/mTOR/STAT3. Adds pioglitazone as candidate companion arm.
Metformin in MS: AMPK + GDF15 mechanism review.
Repurposed agents in diabetic neuropathy: metformin + pioglitazone + GLP-1 agonists + SGLT2 inhibitors as broader cross-condition class.
Insulin resistance in MDD; metabolic-MDD subtype; more consistent pioglitazone evidence vs. mixed metformin — relevant to FM-depression overlap.
Human crossover trial of green light in knee OA (n=19): WOMAC 44.1→32.5 with green light, no effect with white. Abstract notes FM as established green-light-responsive condition.
Green light analgesia mechanism in OA rats: N-acyl-glycine endolipid upregulation → endocannabinoid system engagement (CB-1 antagonist AM281 attenuates).
Green-light analgesia mini-review: lateral geniculate → dorsal raphe + RVM descending-inhibition mechanism; FM-direct effect noted.
V2M glutamatergic → thalamic LP nucleus circuit modulates neuropathic pain; candidate circuit mechanism for green-light analgesia bridging Hypothesis 2's thalamocortical-decoupling framework.
Creatine RCT in post-COVID-19 condition fatigue; adds creatine to Hypothesis 1 mitochondrial-protective intervention class.
4-arm placebo-controlled RCT of HBOT in long COVID (n=101); first methodologically rigorous HBOT trial in project.
HBOT efficacy across rheumatic/immune diseases; 87.5-100% FM pain-relief rate.
Genomic SEM identifies shared latent genetic factor across FM + insomnia + depression + anxiety; extends Kerrebijn 2025.
First FM-direct epigenetic mechanism finding: OPRM1 promoter hypermethylation in ME/CFS/FM patients (n=28 vs 26).
17-study systematic review + meta-analysis of dysautonomia prevalence in chronic musculoskeletal pain including FM; anchors Q29.
62% ANA-positivity in n=289 JHS/hEDS cohort; 80% unidentified autoantigen target. Anchors new B26 bridge.
n=97 pSjD patients with FM-co-occurrence framework via FSQ + ESSPRI + ENG/EMG + CNS imaging.
Ketamine NMDA-antagonism review; closes GRIN1-NMDA cure-path-arm gap via new B27 bridge.
Cochrane-style network meta-analysis of FM sleep interventions across 168 RCTs / 35 treatment categories / 8,247 participants.
Three-cohort validation of exosomal pHERV-W ENV as RRMS relapse-prediction biomarker. Methodology refinement for the project's biomarker-mapping cohort dimension #5.
HERVs as cross-condition therapeutic targets in neurodegenerative disorders; anchors v0.3.3 §14 cross-condition framing.
Cellular therapies in autoimmune rheumatic disease (SLE, IIM, SSc); characterizes Mackensen-protocol landscape relevant to FM advanced-therapy WATCH-LIST.
Plasma-derived exosomal HERV-K biomarker validation in ALS (n=21 + n=16); pairs with exosomal pHERV-W ENV MS paper.
First named clinical-track reversible covalent STING antagonist beyond H-151 / resveratrol; preclinical.
Commentary on MS-immunosuppression vs. EBV-driven disease; refines H1 cure-path framing (daratumumab vs. anti-EBV mechanism distinction).
Anifrolumab cross-indication expansion to systemic sclerosis; type-I-IFN-blocker therapy class validation.
Microbial-driven plasmablast-storm framework bridging viral / dysbiotic / herpesvirus triggers to autoimmune flares.
Long COVID + hypermobility shared pathophysiology; 30-57% hypermobility prevalence in ME/CFS / FM / POTS / LC cluster. Anchors B26 bridge.
FM RNFL/GCL/IPL thinning dual-device replication (PLoS One). Foundational established-tier FM-retinal anchor.
Choroidal mast cells drive choroidal thinning in lens-induced-myopia mouse model; cromolyn + pemirolast block both degranulation and choroidal/refractive phenotype. Extends H2-MC axis to retinal tissue; supplies non-invasive choroidal-thickness readout candidate for the H1×H2 cure-path program.
Gut-retina axis in AMD review. Dysbiosis → SCFA / bile-acid depletion → retinal microglial priming → inflammasome → IL-6/IL-1β/TNF-α/VEGF → retinal inflammation. Extends B2 bridge framework to retinal microglia.
Serum NfL elevated in FM at levels comparable to small fiber neuropathy. n=60 FM + 61 endometriosis + 24 SFN + 30 HC, Simoa SR-X digital immunoassay. Blood-side companion to OCT RNFL thinning for the retinal-biomarker panel.
Anti-GFAP IgG elevated in 19% of FM patients; serum GFAP numerically elevated. Antigen-specific candidate within the broader anti-SGC reactivity; mechanistic linkage to retinal Müller cells (GFAP-rich retinal radial glia).
Strategic review of objective FM biomarkers and digital phenotyping. Independent confirmation of the field's direction toward objective FM diagnostics; context anchor for the retinal-biomarker-diagnostic-priority document.
Post-COVID SFN systematic review identifying corneal in vivo microscopy + optic nerve tomography as diagnostic modalities. Cross-condition methodology anchor for the retinal-biomarker priority panel; reinforces B1 bridge with diagnostic-modality continuity.
Corneal CFM in T2D SFN methodology validation; retinopathy-positive patients show significantly reduced CNFD/CNFL — first paper in project anchoring corneal-nerve ↔ retinal-substrate coupling. Bridging-tier (T2D not FM).
HLA-modulated viral persistence in ME/CFS. ME/CFS susceptibility alleles (C07:04, DQB103:03) bind herpesvirus antigens weakly vs protective alleles (P<0.001); extends to SARS-CoV-2 and Borrelia. Cross-condition mechanism anchor partially closing B-Gen-1.
Calcium-barrier-inflammation vicious cycle in asthma: SOCE + Piezo1 + calcium-protease → OCLN degradation → Th2 release. Cross-condition mechanism anchor for B-Gen-3. Adds Piezo1 as candidate H5b extension gene.
First patient-cohort SOCE-pathway dysregulation in autoimmune CNS disease (n=45+45). Stage-progressive serum SARAF (3× control); reduced STIM1/ORAI1 expression; elevated intracellular calcium. B-Gen-3 cross-condition patient evidence. Adds SARAF as biomarker entity.
Non-coeliac wheat sensitivity narrative review — innate immunity + barrier failure + dysbiosis without classical HLA-DQ2/DQ8 + anti-tTG signature. Extends B-Gen-2 to non-celiac arm. Promotes previously-deferred candidate.
Mechanism-loading review for B-Gen-2: zonulin → tight-junction failure + larazotide acetate (Phase 3) + IMU-856 (investigational) as barrier-restoring cure-path-arm.
Evolutionary framing for H5: ancestral HLA-II haplotypes (DR2-DQ6, DR4-DQ8, DR3-DQ2) selected for pathogen response → modern hyperreactivity → tolerance breakdown. Conceptual framing layer the H5 framework was missing.
Soluble CTLA-4 explains 55-58% variance in Fibro-Fatigue + HAMD + HAMA scores in preeclampsia (n=90+60). sCTLA-4/sCD80 ratio inversely correlates with FF score. First patient-cohort biomarker linking immune-checkpoint activation to chronic-fatigue phenotype. Candidate Q-Gen-6 (abatacept) stratifier.
Lifelines familial-coaggregation n=166,774: FM coaggregates with autoimmune disease (λR 1.06-1.24) AND cardiometabolic disease (λR 1.00-1.23). Population-scale empirical anchor for both H5 and H4 framings. Direct data for Q-IBC-8 (H4/H5/H5b cohort overlap question).
Q-Gen-7 boundary-defining negative: low-dose IL-2 fails to expand Tregs in alemtuzumab-treated RRMS due to IL-2-receptor-density shift on Teffs (30%→73% post-treatment). Narrows H5/H5b Treg-restoration cure-path arm to non-reconstitution-context patients OR alternative IL-2 formulations.
NEGATIVE: choroidal vascularity index does NOT differ between FM and controls in unselected cohort. Within-FM test of B-Re-2 (choroidal MC mechanism extension); boundary-defines bridge to autoimmune-subtype-stratification or dynamic-imaging endpoints. Sharpens retinal-substrate priority toward inner-retinal layers.
Multimodal biomarker panel template: sNfL + GFAP + RNFL + thalamic volumetry in T1DM + RR-MS + HC (n=76 + 12 long-duration T1DM). Templates the FM biomarker-mapping cohort design. New bridge B-Re-9 (T1DM ↔ FM via shared multimodal pattern).
NEGATIVE: sNfL fails to differentiate hereditary OPA1-DOA from controls or correlate with RNFL. Boundary-defines B-Re-4: sNfL × RNFL coupling probably operates in sporadic immune-mediated injury but NOT in hereditary chronic axon attrition. Sharpens mechanism-restricted framing.
Glial activation Cx43 SGC review: external consensus anchor for CA-I2. Names connexin-43-mediated satellite-glial coupling as established mechanism for DRG hyperexcitability — promotes CA-I2 intersection from project-internal hypothesis to consensus-tier. Adds Cx43 hemichannel blockers (carbenoxolone, mefloquine, peptide5, INI-0602) as new cure-path-arm class.
Explicit calcium-overload mechanism in ME/CFS via E/I imbalance. Reduced GABAergic + elevated glutamatergic + elevated noradrenergic → skeletal-muscle calcium overload → mitochondrial dysfunction → exertional intolerance. Reinforces Wirth-Scheibenbogen 2026 framework; extends CA-I3 + CA-I4 intersections via B4 bridge.
FM-direct mechanism: acetate-producing diet reduces FM-like pain in reserpine model. Spinal microglial quiescence → IL-10 elevation in DRG → reduced dorsal-horn hyperexcitability → restored glycinergic inhibition via PGE2 reduction. Within-FM closing anchor for B2.
sNfL as treatment-monitoring biomarker for peripheral nerve injury. Rat oxaliplatin neuropathy model; A. muciniphila + sodium butyrate reduces sNfL + IENFD loss + behavioral pain. Methodology cross-condition validation for B-Re-4.
FM-POTS-MCAS-IBS overlap quantified. Meta-analysis n=8,268; 21.6% FM, 36.3% MCAS, 26.8% IBS in POTS patients. Epidemiological grounding for cross-chain autonomic-dysregulation cohort framing.
NEW H4 chain candidate: immuno-metabolic chain. Leptin → JAK2/STAT3 + MAPK/ERK + PI3K/Akt → reactive microglia in FM. Selective leptin resistance framework. Distinct from H1/H2/H3 chains. New bridge B-IM-1 (adipose ↔ FM CNS via dual MC + leptin pathways).
NEW Mincle/CLEC4E innate-immune-receptor arm: intrathecal Mincle ligand TDB produces persistent neuropathic pain independent of nerve injury, faster glial activation than SNL. New ontology entity; new bridge B-Mincle. Watchlist for clinical-stage Mincle inhibitors.
Developmental-window H2-chain extension. MC-substance-P-microglia axis structurally identical to adult-FM H2 chain. Childhood MC priming → primed H2-substrate → adult FM under triggering event. HαT (TPSAB1) provides genetic-vulnerability layer from birth. New bridge B-DevMC.
FM-IgG → MRGPRX2/Mrgprb2 on mast cells; Mrgprb2 deletion OR MC ablation abolishes IgG-induced hypersensitivity; LAD2 cells produce MRGPRX2-dependent IL-6. Single most important mechanism advance since Goebel 2021; unifies H1 and H2 axes.
LC-IgG passive transfer mirror of Goebel paradigm in PASC; sensory-only phenotype, no cognitive transfer. Closes major fraction of Q7 (post-COVID FM clusters in autoimmune subtype) and bridge B1.
HαT/TPSAB1-duplication extends to mucosal MC physiology via MRGPRX2 expression amplification. Heritable amplifier of the Sanchez 2025 mechanism.
MC-substance-P bidirectional loop via MRGPRX2/NK1R. Supplies long-missing mechanism behind FM's established CSF SP elevation; SP and IgG converge on the same receptor.
Lipedema gfWAT-IIT2 framework: MC-estrogen-receptor activation at gluteofemoral adipose tissue; 35-40% FM comorbidity gets mechanism. New bridge B8 (lipedema ↔ FM via MC-estrogen).
Bidirectional FMT in APP/PS1 AD mice: dysbiosis → butyrate↓ + LPS↑ → microglial M1 polarization → TREM2 downregulation + SYK phosphorylation + NF-κB activation → synaptic loss + cognitive decline. Healthy FMT reverses; AD-FMT into WT induces. SYK inhibition or TREM2 activation independently attenuate in vitro. Microglial-receptor-signaling resolution layer for B2 bridge; fostamatinib as candidate SYK-inhibitor repurposing-tier arm.
Comprehensive update of the 2020 vasoconstrictive-ME/CFS-subtype framework: reduced GABA + elevated glutamate + elevated noradrenergic → skeletal-muscle calcium overload → mitochondrial dysfunction → PEM. Candidate 5th upstream entry to H1's mtDNA-cGAS-STING amplifier; directly addresses Q59 (Azcue β2-AR overlap).
PRISMA systematic review of 18 gene-therapy studies across FM, CRPS, neuropathy, arthritis. RNAi + viral vector + CRISPR/Cas9 + gene replacement + endogenous opioid gene delivery. Closes the systematic-review-anchor gap for §12.10 advanced-therapy tier.
Tissue-based Western blotting on 114 Long COVID + 36 controls. Standard ANA HEp-2 = NO discriminatory value; tissue-Western caught 83% LC vs 53% controls (vascular AAbs 34% vs 8%). Methodology refinement anchor for biomarker-mapping cohort dimension #7.
Head-to-head autoantibody panel across 96 PCC + 59 ME/CFS + 36 HCs. β2-adrenergic AAbs elevated in ME/CFS; M3-muscarinic AAbs elevated in PCC. Differentiates the two phenotypes at the molecular biomarker level. Cohort dimension #7 anchor.
Cross-sectional autonomic-receptor-AAb panel in CRPS vs other chronic pain vs HCs (n=70). Negative result: AAbs not CRPS-specific. Discipline check on B3 framing.
Tempol (nitroxide ROS scavenger) interrupts oxidative-stress → mtDNA → cGAS-STING-NF-κB in EAU rat model; sh-cGAS + H-151 confirm pathway. Candidate fourth OTC-tier loop-interrupter for §12.6 alongside resveratrol.
FM-specific bioinformatics PPI: hub genes AGT (RAS), SNCA (synaptic), EZH2 (epigenetic); estrogen-pathway alterations ESR2↓/ABHD2↓/SULT1E1↑. Extends Kerrebijn 2025 GWAS at transcriptome layer.
HERV ribosome profiling in healthy tissues; identifies translated HERV ORFs. Q40 Step 1 translation filter.
HERV-K Env cryo-EM prefusion/postfusion structures. Q40 Step 6 ground truth for Env structural biology.
HERV-W ENV → cGAS axis → neuronal apoptosis in schizophrenia model. Q40 Step 6 mandatory positive control; HERV-mito loop empirical anchor.
HERV therapeutic targets in neurodegenerative disorders. Cure-path framing for HERV-W ENV-directed and STING-inhibitor classes.
Ketotifen RCT in unstratified FM (n=51): NEGATIVE. Tempers H2 (Mast-Cell) hypothesis in current form.
Metformin pilot RCT in established RRMS (n=30): NEGATIVE on sNFL/NF-κB/EDSS/MRI. Tempers v0.3 §12.9 metformin enthusiasm; counterweight to Chaichana 2026 PCC-prevention positive signal.