Decision spine
Frames the controlling thesis, evidence status, buyer implications, and research-use limits.
Neurology
Zemi Dossier
Research-use only
Bioelectronic Neuro-Immune Closed Loop
A decision package on whether closed-loop neuromodulation can become a generalizable neuro-immune intervention rather than a bespoke sensing-and-stimulation demo.
Decision this dossier helps answer
Which indications have enough biomarker, sensing, decoding, and reimbursement logic to justify a closed-loop bioelectronic program?
Problem this dossier solves
The moat is the generalizable biomarker, not the electrode.
The dossier argues that closed-loop value appears only when a sensed signal travels across patients, settings, and decisions. It helps buyers distinguish a technically impressive loop from one that can substitute for, sequence with, or de-risk a therapeutic intervention.
What is moving: current field evidence and platform activity
What is unresolved: decision-grade proof, endpoint logic, and failure modes
What Zemi solves: evidence-gated next-study strategy
Full decision package
114-page research report plus 36-sheet Evidence & Decision Workbook
Buy now
$3,500$5,500Launch price
Controlling thesis
The moat is the generalizable biomarker, not the electrode.
The dossier argues that closed-loop value appears only when a sensed signal travels across patients, settings, and decisions. It helps buyers distinguish a technically impressive loop from one that can substitute for, sequence with, or de-risk a therapeutic intervention.
A Zemi Dossier turns uncertain emerging research into a decision package: what is known, what is inferred, what is hypothetical, what would falsify the thesis, and what should be built, funded, avoided, monitored, or validated next.
Research report preview
First 30 pages of the actual Bioelectronic Neuro-Immune Closed Loop research report.
The public page shows the real document style, density, evidence posture, and decision framing before a buyer requests access to the full Zemi Dossier package.
Research report
The research report is the argument. It is not the whole product.
The PDF research report is the structured argument: field status, evidence maturity, buyer implications, falsifiable hypotheses, power-calculated next studies, strategic recommendations, limitations, and traceability posture.
Inspectable infrastructure
Pairs the report with claim ledgers, evidence tables, power rows, audit surfaces, and decision tools.
Executable next studies
Links hypotheses to endpoint logic, assumptions, sample-size logic, budget, and timeline planning.
Research report table of contents
Public TOC generated from the source report.
The full research report is delivered as a licensed PDF. This table shows the decision structure without publishing the full product.
| Section | What it covers | Buyer value |
|---|---|---|
| Decision Brief Read This First | Turns the report into immediate buyer triage: what matters now, what is still uncertain, and what to do next. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| Contents | Shows the report structure and where to inspect the argument, evidence, workbook logic, and limits. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| Executive Summary | Condenses the dossier thesis, evidence posture, buyer implications, and next-study priorities. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| Scope and Evidence Integrity | Defines the evidence window, source boundaries, research-use limits, and labeling discipline. | Lets the buyer audit support strength before relying on the package. |
| Decision Snapshot Overview | Maps findings to buyer actions: build, fund, avoid, monitor, or validate next. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| Buy Build Wait Avoid | Maps findings to buyer actions: build, fund, avoid, monitor, or validate next. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| Buyer Decision Matrix | Maps findings to buyer actions: build, fund, avoid, monitor, or validate next. | Gives the buyer a reusable way to compare programs, risks, and evidence states. |
| Source Quality Dashboard | Shows how strong the source base is and where conclusions depend on indirect or thinner support. | Lets the buyer audit support strength before relying on the package. |
| The Closed Loop Value Stack Model | Defines the governing argument and the evidence gates that would support or falsify it. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| The Clrc Classifier | Operationalizes the thesis as a reusable decision surface for comparing programs or evidence states. | Gives the buyer a reusable way to compare programs, risks, and evidence states. |
| Current Signal Refresh 2025 2026 | Frames the field's June 2026 state, active programs, research fronts, and timing signals. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| Cross Domain Synthesis Map | Shows how separate research signals converge, diverge, or interact across domains, mechanisms, or study layers. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| Evidence Maturity and Context Matrix | Links claims to source support so users can separate what is known, inferred, and hypothetical. | Gives the buyer a reusable way to compare programs, risks, and evidence states. |
| Comparative Platform Matrix | Operationalizes the thesis as a reusable decision surface for comparing programs or evidence states. | Gives the buyer a reusable way to compare programs, risks, and evidence states. |
| The Three Hard Questions | Operationalizes the thesis as a reusable decision surface for comparing programs or evidence states. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| Key Findings | Summarizes the most decision-relevant findings and their implications for the dossier thesis. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| The neuro-immune full PMA (open-loop) | Summarizes a report component that ties field evidence to the dossier's decision logic. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| Device-vs-biologic substitution (modeled) | Defines the governing argument and the evidence gates that would support or falsify it. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| Reimbursement gate cleared | Operationalizes the thesis as a reusable decision surface for comparing programs or evidence states. | Gives the buyer a reusable way to compare programs, risks, and evidence states. |
| Long-term durability (small cohort) | Summarizes a report component that ties field evidence to the dossier's decision logic. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| Adaptive DBS - the biomarker moat, shown negatively | Explains which biological signals matter for interpreting the field and discriminating between programs. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| Beta is necessary, validated, insufficient | Summarizes a report component that ties field evidence to the dossier's decision logic. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| The generalizable decoder (the disruptor) | Summarizes a report component that ties field evidence to the dossier's decision logic. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| Psychiatry's N-of-1 biomarker barrier | Explains which biological signals matter for interpreting the field and discriminating between programs. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| Autonomic restoration - the universal-biomarker loop | Explains which biological signals matter for interpreting the field and discriminating between programs. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| Autonomic dysreflexia - mechanism reversed | Explains which biological signals matter for interpreting the field and discriminating between programs. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| State-dependence (why open-loop is lossy) | Summarizes a report component that ties field evidence to the dossier's decision logic. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| The cholinergic pathway as a cross-disease substrate | Explains which biological signals matter for interpreting the field and discriminating between programs. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| The selective-write frontier (splenic) | Defines the governing argument and the evidence gates that would support or falsify it. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| Non-invasive write modalities (frontier) | Defines the governing argument and the evidence gates that would support or falsify it. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| The regulatory channel encodes maturity | Identifies translational, regulatory, safety, or delivery constraints that shape whether the thesis can be tested. | Shows where the thesis could fail or require more validation before action. |
| The competitive split (hardware vs loop) | Connects research maturity to competitive position, program strategy, and diligence watchpoints. | Connects research claims to practical diligence and monitoring decisions. |
| The substitution reverses (refractory segment) | Summarizes a report component that ties field evidence to the dossier's decision logic. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| Non-invasive autonomic stimulation (adjacent) | Summarizes a report component that ties field evidence to the dossier's decision logic. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| The Generalizability Inversion (the core synthesis) | Defines the governing argument and the evidence gates that would support or falsify it. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
| The inflammatory reflex is a cross-organ substrate | Shows how separate research signals converge, diverge, or interact across domains, mechanisms, or study layers. | Helps the buyer inspect the argument, evidence posture, and decision logic before relying on the package. |
Evidence & Decision Workbook
The workbook is the decision engine.
A locked public preview of selected workbook-derived sheets: sheet structure, decision modules, power rows, traceability, and audit posture. Licensed buyers receive the full workbook files.
Read-only workbook preview with clipped values and no formulas. Licensed buyers receive the full Evidence & Decision Workbook with editable assumptions and working files.
Workbook inventory
Delivered workbook sheets.
Full inventories belong on dossier pages, not the homepage. Sheet names below are extracted from the actual workbook file.
| # | Workbook sheet | What it does |
|---|---|---|
| 1 | 1. Workbook Guide | Navigation layer for using the workbook, understanding sheet roles, and following the decision package. Public preview exposes Source-audit reconciliation, 78 audited = 50 kept + 28. fields and clipped entries such as Verification, 74 identifiers. |
| 2 | 2. Claim Ledger | Claim-by-claim ledger showing verdicts, source support, inference status, and decision relevance. Public preview exposes claim_id, claim_text, report_section, report_page fields and clipped entries such as kf-reset-ra-pivotal, The RA neuro-immune device. |
| 3 | 3. Evidence Table | Evidence-verification surface for checking sources, support quality, and the audit trail. Public preview exposes identifier, type, title, journal / sponsor fields and clipped entries such as 10.1186/s42234-024-00163-4, DOI, Next generation bioelectronic.. |
| 4 | 4. Source-Support Verdicts | Independent check on whether key claims are actually supported by cited sources. Public preview exposes source_support_verdict, count_customer_facing_key_findings, definition, release_action fields and clipped entries such as SUPPORTS_EXACTLY, Primary source. |
| 5 | 5. Source-Quality Summary | Summary of source strength, gaps, and areas where conclusions depend on weaker evidence. Public preview exposes Metric, (a) 62 verified claim-units, (b) 23 customer-facing key., Superseded (source strict screen) fields and clipped entries such as Definition,. |
| 6 | 6. Evidence-Maturity Matrix | Evidence-verification surface for checking sources, support quality, and the audit trail. Public preview exposes Program (indication x circuit), Highest loop rung, Biomarker generalizability, Best clinical evidence fields and clipped entries such as RA. |
| 7 | 7. CLRC Input & Class Output | Executable decision surface for classifying programs, risks, gates, or evidence states. Public preview exposes Input feature, Meaning, Score 0-3, Worked example: RA neuro-immune fields and clipped entries such as Biomarker-Validity (BV), Physiological signal. |
| 8 | 7a. CLRC Feature Score | Executable decision surface for classifying programs, risks, gates, or evidence states. Public preview exposes feature, score_0, score_1, score_2 fields and clipped entries such as BV, no measurable state signal, weak/proxy signal. |
| 9 | 7b. CLRC Minimum Assay | Executable decision surface for classifying programs, risks, gates, or evidence states. Public preview exposes assay_or_data_panel, minimum_required, maps_to_feature, source_or_rationale fields and clipped entries such as physiological disease-state signal,. |
| 10 | 7c. CLRC Traceability Map | Traceability surface linking claims, figures, calculations, and workbook outputs back to sources. Public preview exposes classifier_feature_or_output, claim_ids, source_ids, workbook_origin fields and clipped entries such as BV/BG,. |
| 11 | 7d. CLRC Validation Targets | Executable decision surface for classifying programs, risks, gates, or evidence states. Public preview exposes target_element, specification, linked_hypothesis_or_study, performance_target fields and clipped entries such as training target, predict dominant. |
| 12 | 8. CLRC Decision Rules | Executable decision surface for classifying programs, risks, gates, or evidence states. Public preview exposes binding_gate, strategy_it_dictates, required_next_experiment, primary_functional_endpoint fields and clipped entries such as BIOMARKER-ABSENT,. |
| 13 | 9. CLRC Archetype Cards | Executable decision surface for classifying programs, risks, gates, or evidence states. Public preview exposes All-zero neutral stress test, 0, 0, 0, 0 fields from this sheet. |
| 14 | 10. CLRC Validation & Version | Release-discipline surface for revisions, unresolved issues, audit findings, and readiness tracking. Public preview exposes Scoring rule, No naive argmax. Class-deficit. fields and clipped entries such as Weights, Expert-initialized; to be., Output fields. |
| 15 | 11. Platform - Modality Scoreca | Executable decision surface for classifying programs, risks, gates, or evidence states. Public preview exposes Platform / modality, Loop status, Biomarker, Effector selectivity fields and clipped entries such as Open-loop neuro-immune VNS (RA), Open (fixed. |
| 16 | 12. Biomarker - Sensing Tracker | Tracks biomarkers or readouts that determine whether the thesis is moving toward testable evidence. Public preview exposes Indication, Candidate biomarker, Generalizability, Sensing maturity fields and clipped entries such as Parkinson's motor, Subthalamic. |
| 17 | 13. Loop-Maturity Tracker | Tracks programs, trials, sponsors, or competitive context for diligence and monitoring. Public preview exposes Indication x circuit, Rung today, What would advance it, Disconfirming test fields and clipped entries such as RA neuro-immune,. |
| 18 | 14. Substitution Economics Trac | Workbook surface supporting a specific evidence, decision, study-planning, or release-control workflow. Public preview exposes Metric, Value (modeled), Horizon, Note fields and clipped entries such as Incremental cost-saving vs biologic, -$25,397, 2-year. |
| 19 | 15. Regulatory - Reimbursement | Tracks regulatory, endpoint, reimbursement, or qualification requirements that shape testing strategy. Public preview exposes Program, Channel (NAMED, verified), Date, Status / note fields and clipped entries such as SetPoint System (RA), Full PMA P240039. |
| 20 | 16. Trial - Catalyst Tracker | Tracks programs, trials, sponsors, or competitive context for diligence and monitoring. Public preview exposes NCT, Title, Status, Phase fields and clipped entries such as NCT04547712, Adaptive DBS Algorithm for., COMPLETED. |
| 21 | 17. Company - Sponsor Tracker | Tracks programs, trials, sponsors, or competitive context for diligence and monitoring. Public preview exposes Company, Asset (circuit), Indication, Stage / channel fields and clipped entries such as SetPoint Medical, SetPoint System (cervical vagus), RA. |
| 22 | 18. Safety - Failure-Mode Track | Captures failure modes and constraints that could invalidate or narrow a program. Public preview exposes Failure mode, Layer, Mechanism, Mitigation maturity fields and clipped entries such as Off-target vagal effects., Write-side, Mixed cervical-vagus. |
| 23 | 19. Hypotheses Ledger | Maps hypotheses to evidence state, falsification logic, endpoints, and next-study design. Public preview exposes hypothesis_id, tier, title, evidence_layer fields and clipped entries such as H1, Flagship, The Generalizable Inflammatory.. |
| 24 | 20. Most Valuable Next Studies | Prioritizes next studies that could change the decision, including endpoints and evidence gates. Public preview exposes study_id, study_title, research_question, hypothesis_tested fields and clipped entries such as S1, Inflammatory-state decoder cohort, Can. |
| 25 | 21. Validation - Falsification | Connects proposed validation work to falsification criteria, readouts, and decision gates. Public preview exposes gate_id, gate_name, linked_hypothesis_ids, linked_study_ids fields and clipped entries such as G1, Generalizable biomarker gate, H1,H10. |
| 26 | 22. Figure Source Map | Traceability surface linking claims, figures, calculations, and workbook outputs back to sources. Public preview exposes figure_id, figure_title, figure_family, section_anchor fields and clipped entries such as fig01_grade_recalibration, Fig01 Grade. |
| 27 | 23. Figure Attempt Ledger | Figure and numeric reproduction log for validating calculations, chart inputs, or displayed values. Public preview exposes #, figure_id, family, status fields and clipped entries such as fig01_grade_recalibration, evidence_grade_distribut, PASS. |
| 28 | 24. Verification - Search Log | Release-discipline surface for revisions, unresolved issues, audit findings, and readiness tracking. Public preview exposes api, query / params, status fields and clipped entries such as idconv, format=json, efetch. |
| 29 | 25. Excluded Claims | Disposition log for rejected, bounded, or quarantined claims so they do not leak into the decision thesis. Public preview exposes #, disposition, claim (truncated), reason fields and clipped entries such as Excluded — structural (ungroundable., SetPoint. |
| 30 | 26. Salvage Ledger | Disposition log for rejected, bounded, or quarantined claims so they do not leak into the decision thesis. Public preview exposes 12 current-signal 2025-2026., currency additions, Independently verified, Throughout; deepening sections fields and clipped. |
| 31 | 27. Competitive Landscape | Tracks programs, trials, sponsors, or competitive context for diligence and monitoring. Public preview exposes company, asset_platform, modality, target_indication fields and clipped entries such as SetPoint Medical, SetPoint System, implantable cervical. |
| 32 | 28. Score Basis | Explains how scores or ratings were assigned so the decision instrument can be inspected. Public preview exposes fig16 Evidence-maturity matrix, 0-3 per dimension, 3=pivotal/approved/validated;. fields and clipped entries such as fig17 Comparative platform,. |
| 33 | 29. Power Calculations | Power-calculation layer for assumptions, endpoint logic, computed sample sizes, and sensitivity checks. Public preview exposes hypothesis_id, study_id, endpoint, test_type fields and clipped entries such as H2, S2, ACR50 at 24wk, closed-loop vs.. |
| 34 | 30. Traceability Certificate | Traceability surface linking claims, figures, calculations, and workbook outputs back to sources. Public preview exposes report_section/page, report_anchor, claim_id, claim_text fields and clipped entries such as Key Findings / body anchor,. |
| 35 | 31. Version Registry | Release-discipline surface for revisions, unresolved issues, audit findings, and readiness tracking. Public preview exposes Version, Component, Status fields and clipped entries such as v1.0, Evidence base, 78 audited re-graded; 12 currency.. |
| 36 | 32. Audit Issues Log | Release-discipline surface for revisions, unresolved issues, audit findings, and readiness tracking. Public preview exposes #, Issue (review), Severity, Disposition fields and clipped entries such as Two scatter figures clipped., Medium, Numbered markers +. |
Power-calculated next studies
Power calculations are the execution bridge.
Power calculations are planning-grade research calculations for endpoint logic, assumptions, sample size, budget, and timeline. They do not prove hypotheses or constitute clinical protocol.
| Hypothesis | Primary endpoint | Test | Effect | α | Power | Computed n | Design n |
|---|---|---|---|---|---|---|---|
| H2 | ACR50 at 24wk, closed-loop vs fixed-schedule open-loop | two-proportion superiority | 0.56 | 0.05 | 0.80 | 152 | 152 |
| H4 | ACR20 at 24wk, device vs next-line biologic | two-proportion non-inferiority | 0.4 | 0.03 | 0.80 | 168 | 168 |
| H5 | ADFSCI/seated-BP responder at 3 months, active vs sham | two-proportion superiority | 0.6 | 0.05 | 0.80 | 42 | 60 |
| H7 | Cytokine suppression without vagal AE, splenic vs cervical vagus | two-proportion superiority | 0.7 | 0.05 | 0.80 | 61 | 70 |
| H8 | Pro-remyelination MRI responder, RRMS active vs sham | two-proportion superiority | 0.55 | 0.05 | 0.80 | 96 | 96 |
Release audit discipline
Audit posture is part of the product.
Public pages do not publish exact audit scores. They should state the release discipline, revision posture, and limitations without implying peer review or validated clinical guidance.
Research-use decision package
Not medical advice, clinical guidance, investment advice, or a clinical protocol.
Known / inferred / hypothetical
The package separates cited evidence from inference and frontier hypothesis generation.
Audit-gated and revision-controlled
Adversarial audit checks source support, formulas, figures, limitations, and release readiness.
Buy this dossier
Full decision package — 114-page report + 36-sheet workbook
Buy now
- Decision research report (114 pages, PDF)
- Evidence & Decision Workbook (36 sheets, .xlsx) — claims, source-support verdicts, power calculations, traceability, and audit log
- Live, editable power-calculated next studies
$3,500$5,500Launch price