Substrate observability

Operator dashboard. Counters and recent activity surfaced from substrate /v1/admin/stats — the JSON companion to the Prometheus /metrics endpoint. Auto-refreshes every 30s.

Substrate as_of 2026-07-24T15:32:35.676490+00:00

138,611 artifacts (latest)

0 KG entities

738,718 KG edges

902 debate sessions

416 senate proposals

0 contributions

8 working groups

5.00k net SCIDEX supply

Artifacts by type

Type	Count
`paper`	40,338
`wiki_page`	36,993
`open_question`	9,348
`figure`	8,120
`claim`	7,975
`kg_edge`	7,650
`hypothesis`	7,055
`knowledge_gap`	5,735
`paper_figure`	4,302
`notebook`	1,519
`experiment`	1,443
`analysis`	1,428
`agent_work_packet`	998
`visual_artifact`	955
`market_proposal`	909
`analysis_proposal`	446
`prediction`	441
`dataset`	419
`senate_proposal`	357
`dashboard`	343
`benchmark`	299
`research_plan`	247
`collider`	182
`pantheon_debate`	134
`evidence`	100
`protein_design`	99
`evidence_link`	89
`challenge`	75
`landscape`	67
`code_health_report`	61
`upstream_target`	56
`scientific_claim`	53
`decision_arena`	46
`arena`	36
`rigor_score_card`	36
`open_debate`	31
`squad`	30
`experiment_proposal`	23
`proposal`	23
`signal`	20
`clinical_trial`	16
`analysis_bundle`	10
`code_proposal`	10
`model`	9
`code_split_proposal`	8
`merge_recommendation`	8
`capsule`	6
`ai_image`	5
`funding_proposal`	5
`landscape_analysis`	5
`memo`	5
`quadratic_funding_round`	5
`mission`	4
`tabular_dataset`	4
`authored_paper`	3
`gov_proposal`	3
`sc_trajectory`	3
`skill`	3
`bounty_challenge`	2
`dashboard_snapshot`	2
`debate`	2
`experiment_result`	2
`test_version`	2
`bounty_challenge_submission`	1
`causal_cascade_analysis`	1
`code`	1
`debate_analysis`	1
`external_proposal`	1
`portfolio_artifact`	1
`squad_finding`	1
`squad_journal_entry`	1

Debate sessions by status

Status	Count
`completed`	885
`pending`	6
`scheduled`	6
`enrolling`	5

Proposals by status

Status	Count
`open`	416

Working groups by status

Status	Count
`active`	8

Token ledger

1 SCIDEX = 10,000 minor units. Net supply = mint − burn.

Event type	Events	Amount (SCIDEX)
`unknown`	43,184	0.0000
`debit`	4,106	410.60
`credit`	12	12.00k
`mint`	5	5.00k

Knowledge graph

Entities by kind

No KG entities.

Edges by relation

Relation	Count
`activates`	141,614
`associated_with`	104,714
`regulates`	76,158
`inhibits`	58,840
`interacts_with`	51,410
`expressed_in`	44,697
`therapeutic_target`	43,270
`causes`	35,761
`co_discussed`	24,690
`biomarker_for`	14,446
`protects_against`	12,040
`data_in`	10,791
`modulates`	10,344
`treats`	9,421
`participates_in`	8,684
`contributes_to`	8,128
`implicated_in`	7,413
`targets`	6,692
`involved_in`	4,526
`prevents`	4,118
`mediates`	3,811
`phosphorylates`	3,349
`degrades`	3,259
`causal_modulates`	3,133
`transports`	2,716
`promotes`	2,517
`causal_causes`	2,331
`belongs_to_pathway_cluster`	1,974
`upregulates`	1,896
`encodes`	1,839
`co_expressed_with`	1,730
`disrupts`	1,399
`debate_co_mention`	1,381
`enhances`	1,361
`stabilizes`	1,131
`expresses`	1,089
`risk_factor_for`	1,050
`causal_prevents`	1,025
`provides_data_for`	954
`downregulates`	941
`causal_extracted`	815
`references`	755
`cell_type_involved_in`	702
`targeted_by`	687
`binds`	685
`co_associated_with`	655
`suppresses`	631
`involves`	560
`co_mentioned`	552
`markers`	545
`resolved_by`	517
`mentions`	515
`decreases_risk`	514
`affects`	508
`active_in`	506
`correlates_with`	403
`drives`	357
`accumulates_in`	316
`produces`	304
`describes`	290
`binds_to`	283
`therapeutic_target_for`	245
`exacerbates`	241
`component_of`	228
`increases_risk`	214
`reduces`	205
`protective_against`	198
`upstream_of`	193
`targets_gene`	185
`self_reference`	171
`predicts`	158
`impairs`	154
`investigates`	151
`modifies`	140
`participates_in_pathway`	137
`increases`	135
`member_of_pathway`	132
`crosstalk_with`	127
`expression`	122
`induces`	109
`catalyzes`	104
`part_of`	101
`cleaves`	92
`cited_by`	88
`cites`	88
`demonstrates`	78
`depleted_in`	74
`supports`	74
`analogous_to`	71
`member_of`	70
`linked_to`	64
`improves`	59
`metabolizes`	59
`maintains`	55
`methylates`	55
`triggers`	54
`depletes`	52
`associated with`	51
`co_cited_with`	49
`secreted_by`	49
`transported_by`	49
`neuroprotective`	47
`loss_affects`	46
`product_of`	46
`identifies`	45
`is associated with`	45
`neurotoxic`	44
`enables`	43
`implicates_in`	41
`precedes`	41
`attenuates`	40
`decreases`	40
`processes`	40
`releases`	40
`destabilizes`	39
`synergizes_with`	39
`restores`	37
`facilitates`	36
`recruits`	34
`ubiquitinates`	34
`contributes to`	33
`translocates_to`	32
`alters`	30
`co_mentioned_with`	30
`documents`	30
`has_variant`	30
`downstream_of`	29
`investigated_in`	29
`leads to`	29
`described_by`	28
`has_wiki`	28
`involves_gene`	28
`cross_disease_mechanism_in`	27
`accelerates`	26
`alleviates`	26
`controls`	26
`is involved in`	26
`found_in`	25
`preserves`	25
`substrate_of`	25
`ameliorates`	24
`converts`	24
`is`	24
`released_by`	24
`enriched_in`	22
`implicates`	22
`amplifies`	21
`implicated in`	21
`addresses_gap`	20
`contradicts_prediction`	20
`correlates with`	20
`is required for`	20
`differentiates_to`	19
`NULL`	19
`type_of`	18
`has_risk_variant`	17
`indicates`	17
`represses`	17
`cause`	16
`coexpressed_with`	16
`influences`	16
`protects`	16
`sensitizes_to`	16
`associates_with`	15
`generated`	15
`generates`	15
`increased`	15
`interacts with`	15
`mitigates`	15
`produced`	15
`regulate`	15
`requires`	15
`secretes`	15
`stimulates`	14
`undergoes`	14
`vulnerable_to`	14
`related_to`	13
`required_for`	13
`risk_factor`	13
`aggravates`	12
`associated_with_microglial_priming`	12
`clears`	12
`involved in`	12
`reduced`	12
`regulated_by`	12
`relates_to`	12
`contribute to`	11
`deacetylates`	11
`dysregulates`	11
`is a risk factor for`	11
`limits`	11
`localizes_to`	11
`promote`	11
`binds to`	10
`crosses`	10
`determines`	10
`essential_for`	10
`propagates`	10
`proposes_shared_mechanism`	10
`damages`	9
`has`	9
`impacts`	9
`increases risk of`	9
`induce`	9
`linked to`	9
`reduce`	9
`results in`	9
`sequesters`	9
`aggregation`	8
`are involved in`	8
`attenuated`	8
`dysregulated_in`	8
`improved`	8
`increase`	8
`initiates`	8
`mediated_by`	8
`plays a critical role in`	8
`plays a role in`	8
`rescues`	8
`reverses`	8
`senses`	8
`suppressed`	8
`upregulated_in`	8
`worsens`	8
`acetylates`	7
`activate`	7
`antagonizes`	7
`blocks`	7
`critical_for`	7
`decreased`	7
`eliminates`	7
`induced`	7
`is characterized by`	7
`is expressed in`	7
`is identified as`	7
`is implicated in`	7
`is linked to`	7
`links`	7
`marker_of`	7
`mediate`	7
`models`	7
`modulate`	7
`protects against`	7
`relevant_to`	7
`used_for`	7
`ameliorated`	6
`associates with`	6
`co_localizes_with`	6
`competes with`	6
`compromises`	6
`correlated with`	6
`enhance`	6
`enhanced`	6
`have`	6
`lead to`	6
`may contribute to`	6
`mechanistic_target`	6
`projects_to`	6
`required for`	6
`acts as`	5
`aggregates_with`	5
`bridges`	5
`co_localizes`	5
`contains`	5
`cooperates_with`	5
`cross-seeds`	5
`defines`	5
`deubiquitinates`	5
`elevated in`	5
`elevates`	5
`enriched in`	5
`expressed in`	5
`forms`	5
`increased in`	5
`influence`	5
`inhibited`	5
`is a key regulator of`	5
`is upregulated in`	5
`measures`	5
`normalizes`	5
`orchestrates`	5
`present in`	5
`recognizes`	5
`relates_to_disease`	5
`remodels`	5
`rescued`	5
`scavenges`	5
`sustains`	5
`undergo`	5
`activated`	4
`are`	4
`are associated with`	4
`are expressed in`	4
`biomarker_of`	4
`can lead to`	4
`caused`	4
`causes_injury_to`	4
`contributing to`	4
`correlate with`	4
`counteracts`	4
`creates`	4
`cross-links`	4
`delivers`	4
`depends_on`	4
`detects`	4
`distinguishes`	4
`dysfunction_causes`	4
`enables_genetic_modification_of`	4
`engages`	4
`exerts`	4
`expressed_on`	4
`functions as`	4
`has been linked to`	4
`impair`	4
`includes`	4
`increases_risk_of`	4
`independent_of`	4
`induces_transcription`	4
`inhibit`	4
`is activated by`	4
`is a hallmark of`	4
`is a potential target for`	4
`is decreased in`	4
`is highly expressed in`	4
`is the primary risk factor for`	4
`localized_to`	4
`localizes to`	4
`lowers`	4
`may be a potential therapeutic target for`	4
`necessary_for`	4
`negatively regulates`	4
`nucleates`	4
`observed in`	4
`overlaps`	4
`performs`	4
`plays an important role in`	4
`potentiates`	4
`prevent`	4
`prevented`	4
`regulates_production_of`	4
`removes`	4
`repairs`	4
`represents`	4
`restored`	4
`restricts`	4
`role in`	4
`serves as`	4
`showed`	4
`signals through`	4
`slows`	4
`templates`	4
`used_for_treatment`	4
`was`	4
`abolishes`	3
`accumulates`	3
`activated_in`	3
`are enriched in`	3
`augments`	3
`belongs to`	3
`binds directly to`	3
`biomarker_target`	3
`boosts`	3
`breaks down with`	3
`can reduce`	3
`causes_aggregation_of`	3
`causes_degeneration_of`	3
`causes_loss_of`	3
`causes_toxicity`	3
`characterized by`	3
`co-expressed_with`	3
`co-localizes`	3
`contributes`	3
`coordinates`	3
`decrease`	3
`decreased in`	3
`delays`	3
`demethylates`	3
`differentiates`	3
`directly regulates`	3
`disrupt`	3
`disrupted_in`	3
`downregulated_in`	3
`elevated`	3
`exacerbate`	3
`exhibit`	3
`exhibits`	3
`express`	3
`forms a heterodimer with`	3
`forms_complex_with`	3
`found in`	3
`fuels`	3
`has essential role in`	3
`have been implicated in`	3
`impaired_in`	3
`inactivates`	3
`increased under`	3
`increased with`	3
`increase risk of`	3
`increases expression of`	3
`increases susceptibility to`	3
`infiltrates`	3
`is a major contributor to`	3
`is a major risk factor for`	3
`is a marker for`	3
`is a promising target for`	3
`is a risk locus for`	3
`is caused by`	3
`is essential for`	3
`is expressed by`	3
`is expressed on`	3
`is reduced in`	3
`is the driver of`	3
`is the most significant risk factor for`	3
`is the strongest genetic risk factor for`	3
`leads to reduced`	3
`lipidates`	3
`may cause`	3
`may correlate with`	3
`mediated`	3
`mediates_clearance`	3
`modify`	3
`not different in`	3
`occurs_in`	3
`part of shared mechanisms linking`	3
`plays a key role in`	3
`positively correlate with`	3
`potentiated in`	3
`prolongs`	3
`promotes_aggregation_of`	3
`protected`	3
`protein_interaction`	3
`proteolytically_cleaves`	3
`provides`	3
`reduces_expression`	3
`reduces expression of`	3
`regulated`	3
`regulates expression of`	3
`resists`	3
`resolves`	3
`responds_to`	3
`scaffolds`	3
`selectively_targets`	3
`serve as`	3
`shares_mechanism`	3
`show`	3
`shows`	3
`shows a major correlative association with`	3
`signals downstream of`	3
`silences`	3
`studied_in`	3
`supersedes`	3
`target`	3
`transcription_factor_regulates`	3
`transfers`	3
`traps`	3
`underlies`	3
`underlying`	3
`upregulated in`	3
`aberrantly deposited in`	2
`abrogates`	2
`accelerate`	2
`accompanied by`	2
`accompanies`	2
`accumulated indels slower than`	2
`accumulated sSNVs faster than`	2
`accumulate indels slower than`	2
`accumulates_at`	2
`accumulate sSNVs faster than`	2
`activates_parallel`	2
`acts as independent biomarker of`	2
`acts via`	2
`acutely increased`	2
`addresses`	2
`affect`	2
`affected`	2
`affects_clearance_of`	2
`age_related_decline_source`	2
`aggregates and deposits in`	2
`aggregates_in`	2
`agonized_by`	2
`alleviated`	2
`altered`	2
`are categorized as`	2
`are characterized by`	2
`are commonly disrupted in`	2
`are critically dependent on`	2
`are harmful to`	2
`are implicated in`	2
`are important for`	2
`are increased in`	2
`are not mediated by`	2
`are powered by`	2
`are present in`	2
`are risk factors for`	2
`are selectively vulnerable in`	2
`are tagged with`	2
`are the nodes of`	2
`benefits`	2
`binds and stabilizes`	2
`binds at the nucleotide pocket of`	2
`binds_receptor`	2
`blocks reuptake of`	2
`bypasses`	2
`can be genetically modified to express CAR specific for`	2
`can cause`	2
`can contribute significantly to`	2
`can further stimulate`	2
`can have major effects on`	2
`causes acceleration of`	2
`causes (CRISPRa coupled with base editors simultaneously u)`	2
`causes decrease in`	2
`causes lysosomal degradation of`	2
`causes reduction in`	2
`changes with`	2
`change their activity with`	2
`characterized_by`	2
`colocalizes with`	2
`communicates_with`	2
`compensates`	2
`competes_with`	2
`complements`	2
`composes`	2
`comprises`	2
`connected with`	2
`consists primarily of`	2
`contributes to fibrillization of`	2
`controls_cell_fate_via_crosstalk`	2
`converges_with`	2
`converts_to`	2
`co_occurs`	2
`co_occurs_with`	2
`could affect`	2
`could be precipitating a cascade of events leading to`	2
`could contribute to`	2
`could provide effective treatment for`	2
`counteract`	2
`counteracts the effects of`	2
`crossed`	2
`decreases disease severity in a dose-dependent manner`	2
`decreases_with`	2
`demonstrated sustained target engagement in`	2
`depends on`	2
`destabilizes_closed_state`	2
`detected in`	2
`determine risk of developing`	2
`did not reduce`	2
`diminishes`	2
`directly activates`	2
`directly interacts with and phosphorylates`	2
`directs transcription of genes defining`	2
`disaggregates`	2
`distinct_from`	2
`does not associate with`	2
`does_not_cause`	2
`does not predispose to`	2
`driven by`	2
`driver of`	2
`driving the release of`	2
`elevate`	2
`encodes_subunit_of`	2
`encompasses`	2
`engineered to identify and eliminate`	2
`enhances microglia phagocytosis of`	2
`enriches`	2
`enters_cells_via`	2
`epigenetic_regulation`	2
`excludes`	2
`exerts cell non-autonomous effect on`	2
`exhibit decrease in`	2
`exhibit distinct 3D genome organization compared to`	2
`exhibited`	2
`exhibits pathological synergy with`	2
`expressed by`	2
`extends`	2
`facilitated`	2
`formed puncta in`	2
`forms receptor signaling complex with`	2
`functionally_coupled_to`	2
`functions_together_with`	2
`generate`	2
`genetic modifier of`	2
`had marginal effect on`	2
`has an important link with`	2
`has been implicated in`	2
`has been proven to be a major contributor to`	2
`has been shown to interact with`	2
`has crucial role in`	2
`has emerged as`	2
`has isolated effects on`	2
`has neuroprotective roles in`	2
`has potential as`	2
`has potential for treating`	2
`has potential in preventing and treating`	2
`has role in`	2
`has significant genetic correlation with`	2
`have a bidirectional relationship with`	2
`have a role in`	2
`have distinct responses to`	2
`have diverse functions at`	2
`have effect sizes ~10 times larger than`	2
`have limited efficacy against due to`	2
`hyperphosphorylates`	2
`identified patients for`	2
`identifies_regulators_of`	2
`impairs formation and function of`	2
`impede`	2
`improve`	2
`increases risk for`	2
`increases risk for developing`	2
`increase the risk for developing`	2
`induced by`	2
`induced in`	2
`induces downregulation of`	2
`induces_formation_of`	2
`induces_transcriptional_reprogramming_via`	2
`inhibits_overactivation`	2
`inhibits_removal_of`	2
`interact with`	2
`interact with and cause`	2
`interferes with`	2
`is a`	2
`is a convergent hallmark of`	2
`is a direct checkpoint inhibitor of`	2
`is age-associated and occurs before`	2
`is a genetic modifier of`	2
`is age-regulated in`	2
`is a humanized monoclonal immunoglobulin G4 antibody targeting`	2
`is altered in`	2
`is a modification of`	2
`is an early step in`	2
`is an endogenous substrate of`	2
`is an important target for`	2
`is an independent risk factor for`	2
`is an inhibitor of`	2
`is a novel druggable target for`	2
`is a positive regulator of`	2
`is a potential target in`	2
`is a predictive marker for`	2
`is a substrate of`	2
`is a target for`	2
`is connected with`	2
`is considered the disease-causative mechanism of`	2
`is converted to`	2
`is critical for`	2
`is degraded in`	2
`is down-regulated in`	2
`is downregulated in`	2
`is expressed outside`	2
`is genetically linked to`	2
`is genetic risk factor for`	2
`is important for`	2
`is important in`	2
`is increased in`	2
`is independent biomarker of`	2
`is instrumental in mediating`	2
`is involved in maintaining`	2
`is key early pathological process in`	2
`is leading cause of`	2
`is lipidated via`	2
`is lower in`	2
`is mainly expressed in`	2
`is mediated by`	2
`is not required for`	2
`is potential target for`	2
`is potential treatment for`	2
`is present in`	2
`is preserved in`	2
`is recruited to`	2
`is required for basal transcription of`	2
`is required for optimal release of`	2
`is responsible for`	2
`is restricted to`	2
`is the catalytic site of`	2
`is the most important modifiable risk factor for`	2
`is the primary lipid carrier within`	2
`is the principal correlate of`	2
`is the strongest genetic risk factor associated with`	2
`is the strongest predictor for`	2
`is ultimately converted to`	2
`is vital for maintaining`	2
`leads_to`	2
`leads to increase in`	2
`limits diffusion of CAR T cells across`	2
`limits efficacy of CAR T cells against`	2
`linked with`	2
`localizes to inclusions in`	2
`located_in`	2
`loses capacity to bind`	2
`loss-of-function results in`	2
`marks`	2
`may be`	2
`may be important as a therapeutic target in`	2
`may be involved in`	2
`may block the reuptake of`	2
`may impact`	2
`may increase`	2
`may induce`	2
`may mechanistically explain`	2
`may mediate`	2
`may modify risk for`	2
`may play a role in`	2
`may serve as`	2
`mediated by`	2
`mediates downregulation of`	2
`mediates protein stabilization of`	2
`mediates uptake of`	2
`mimics`	2
`misfunctions to precipitate`	2
`mislocalizes to`	2
`modification of`	2
`modulating the aggregation and clearance of`	2
`more readily recruited to the Golgi and activated by`	2
`negatively correlated with`	2
`negatively_regulates`	2
`normally associates with and stabilizes`	2
`occurs in brain regions with high`	2
`offers mitochondria-targeting strategy for treatment of`	2
`palmitoylates`	2
`partially_agonizes`	2
`participate in`	2
`participates in`	2
`pathological_aggregation`	2
`penetrates`	2
`permits`	2
`perturbs`	2
`phagocytoses`	2
`phagocytosis`	2
`phosphorylates_at_T217`	2
`play role in`	2
`plays a crucial role in modulating`	2
`plays a crucial role in the regulation of`	2
`plays an essential role in developing`	2
`plays a prominent role in`	2
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`causes (27-hydroxycholesterol promotes oligodendrocyte mat)`	1
`causes (30-50% reduction in somatic CAG expansion leads to)`	1
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`causes activation of`	1
`causes (adult-onset CNS myelin sulfatide deficiency is suf)`	1
`causes (aged brain exosomes specifically activate neuronal)`	1
`causes (age-related activation of cGAS-STING drives microg)`	1
`causes (age-related CD300f dysfunction allows excessive ne)`	1
`causes (age-related cytokine secretion specifically suppre)`	1
`causes (age-related decline in microglial profilin-1 disru)`	1
`causes (age-related downregulation of AP1S1 disrupts clath)`	1
`causes (aging activation of microglia leads to increased C)`	1
`causes (aging causes early transcriptomic changes in oligo)`	1
`causes (aging mitochondrial dysfunction triggers STING pat)`	1
`causes_alterations_in`	1
`causes (altered glia-neuron communication in Alzheimer's D)`	1
`causes (APOE4 C130R mutation is disease-associated while A)`	1
`causes (APOE4 disrupts lipid metabolism and synaptic suppo)`	1
`causes (APOE4 mediates myelin breakdown by targeting oligo)`	1
`causes_apoptosis_of`	1
`causes (APP overexpression causes selective vulnerability )`	1
`causes (astrocyte-derived inflammatory signals aberrantly )`	1
`causes (astrocyte-specific APOE4 knockout may worsen outco)`	1
`causes (astrocytic APOE4 drives synaptic phagocytosis by m)`	1
`causes (CaMKII-dependent process that promotes spine gener)`	1
`causes (CaMKII enhancement promotes dendrite ramification )`	1
`causes (causes cell death through lysosomal membrane perme)`	1
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`causes (chronic hypoperfusion leads to pericyte-derived BM)`	1
`causes (complete APOE4 removal may disrupt normal lipid ho)`	1
`causes (complex I defects are found in substantia nigra ne)`	1
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`causes (converting disease-associated APOE4 to protective )`	1
`causes (coordinated dysfunction across astrocyte-microglia)`	1
`causes (creates a feed-forward loop of neuroinflammation l)`	1
`causes (CRISPRa with chromatin modifiers can reactivate si)`	1
`causes (CXCL10 acts as chemokine to recruit cytotoxic CD8+)`	1
`causes (CXCL10 antagonists would preserve white matter int)`	1
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`causes_damage_to`	1
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`causes (disease-associated microglia show dysregulated TRE)`	1
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`causes (disrupted cytoskeletal checkpoints lead to prematu)`	1
`causes (disrupted endosomal-lysosomal trafficking creates )`	1
`causes (disrupted WNT signaling affects inhibitory interne)`	1
`causes (DNA damage in oligodendrocytes precedes amyloid pa)`	1
`causes (dysfunction precedes and triggers compensatory TFE)`	1
`causes (dysregulated ISR in vulnerable neurons leads to pr)`	1
`causes (dysregulated microglial transitions fail to suppor)`	1
`causes (early enhancement prevents pathology by promoting )`	1
`causes (early proteasome downregulation and dysfunction dr)`	1
`causes emergence of`	1
`causes (energy metabolism disorders cause Parkinson's dise)`	1
`causes (enhanced ACE expression in microglia increases Aβ )`	1
`causes (enhances proton pumping to restore acidic pH in ly)`	1
`causes (enhances TFEB activity to promote selective cleara)`	1
`causes (enhancing TREM2 expression activates microglia and)`	1
`causes (environmental stressors induce energy metabolism d)`	1
`causes (epigenetic silencing of neuroprotective genes occu)`	1
`causes escape from`	1
`causes escape from osimertinib and initiates`	1
`causes (excessive complement activation leads to neurotoxi)`	1
`causes failure of`	1
`causes/impaired expression leads to`	1
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`causes increased`	1
`causes (increased autophagy leads to lysosomal overload an)`	1
`causes increases in`	1
`causes (induces autophagy through multiple pathways includ)`	1
`causes (iron-dependent ferroptosis contributes to α-synucl)`	1
`causes (ischemic conditions induce autophagy pathway activ)`	1
`causes (loss of natural sensory input leads to degeneratio)`	1
`causes (loss of sulfatides removes suppression of microgli)`	1
`causes (microglia activate CXCL10-mediated recruitment of )`	1
`causes (microglial ACE enhancement activates spleen tyrosi)`	1
`causes (microglial activation orchestrates CXCL10-mediated)`	1
`causes (mitochondrial dysfunction is central to ALS pathog)`	1
`causes (MSH3 drives somatic expansion of HTT CAG repeats t)`	1
`causes (myelin sulfatide deficiency causes cognitive impai)`	1
`causes (NAD+ supplementation improves mitophagy and mitoch)`	1
`causes (NMDA receptors mediate synaptic depression in amyl)`	1
`causes (NOMO1 function improves endoplasmic reticulum home)`	1
`causes (oligodendrocyte dysfunction leads to loss of myeli)`	1
`causes (optogenetic activation selectively restores gamma )`	1
`causes (optogenetic activation selectively restores theta )`	1
`causes (PARP1 activation enhances base excision repair pat)`	1
`causes (pericyte-derived BMP4 causes white matter damage a)`	1
`causes (PMS1 drives somatic expansion of HTT CAG repeats t)`	1
`causes (prevents energy needed for enhanced autophagy desp)`	1
`causes (prevents enzyme function despite increased biogene)`	1
`causes (promotes contact sites that enable energy-dependen)`	1
`causes (protein aggregation drives cell-to-cell spreading )`	1
`causes (proteostasis failure leads to protein aggregation )`	1
`causes (recruited CD8+ T cells promote aging-related white)`	1
`causes (recruited CD8+ T cells promote white matter degene)`	1
`causes reduced`	1
`causes reductions in`	1
`causes (selective CXCR3 blockade could preserve white matt)`	1
`causes (selective downregulation of MSH3 creates temporal )`	1
`causes (selective modulation of GluN2B-containing NMDA rec)`	1
`causes (selective noradrenaline depletion exacerbates syna)`	1
`causes (selective removal of astrocytic APOE4 strongly pro)`	1
`causes (selective silencing may trigger compensatory mecha)`	1
`causes (senescence creates a self-perpetuating cycle by pr)`	1
`causes_sensitivity_to`	1
`causes (specifically disrupt parvalbumin-positive interneu)`	1
`causes (specifically disrupt somatostatin-positive interne)`	1
`causes (STING activation leads to cellular senescence and )`	1
`causes stress-induced pathogenic increase in`	1
`causes (suppressed mitochondrial function creates vulnerab)`	1
`causes (tau aggregation triggers cellular senescence respo)`	1
`causes (tau pathology spreads from locus coeruleus to hipp)`	1
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`causes (VIP interneuron-mediated disinhibition allows pyra)`	1
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`dephosphorylates and triggers nuclear translocation of`	1
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`depletion_impairs_ubiquitylation`	1
`Deploy selective small molecule inhibitors targeting the tau-binding domain of LRP1 to prevent cellu`	1
`deposits`	1
`desensitization_mechanism`	1
`Design allosteric modulators that specifically enhance HSP90's tau disaggregation activity without a`	1
`designed to clear`	1
`Design selective allosteric activators of VCP/p97 ATPase activity specifically for tau-containing au`	1
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`NLGN1 modulates tau_propagation`	1
`no change`	1
`no evidence of longer-lasting influence on`	1
`no_GWAS_AD_association`	1
`nominated proteins implicated in`	1
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`promoted: Aryl Hydrocarbon Receptor (AhR) Activation by Microbiome Metabolites Promotes A2 Polarization`	1
`promoted: Aryl Hydrocarbon Receptor (AHR) Activation in B Cells Determines AQP4 Tolerance Fate`	1
`promoted: Beta-Hydroxybutyrate Receptor (HCAR2) Signaling Links Ketone Deficiency to Neuroinflammation`	1
`promoted: C3aR Blockade Disrupts the Microglial-Astrocyte Feedforward Neurotoxic Loop`	1
`promoted: Complement-SASP Amplification Cascade as Mechanistic Link`	1
`promoted: Context-Dependent Cx43 Modulation Based on Disease Stage`	1
`promoted: CSF1R Inhibition-Mediated Microglial Replacement as a State Transition Reset`	1
`promoted: CSF Biomarker-Guided ABCA7 Therapeutic Dosing`	1
`promoted: CSF sTREM2 as Pharmacodynamic Biomarker for Therapeutic Window Identification`	1
`promoted: DAPK1 Inhibition as Dual-Mechanism Neuroprotection Against Tau-Induced Destabilization`	1
`promoted: DLK MAPK Pathway Inhibition to Block Tau-Induced Neurotoxicity Without Directly Targeting Tau`	1
`promoted: ER Stress Reduction as Adjunctive Therapy to Support Autophagy`	1
`promoted formation of`	1
`promoted: GPC4/HSPGs Collaborate with ApoE Isoforms to Dictate Tau Conformational Strain Uptake Efficiency`	1
`promoted: H2: Indole-3-Propionate (IPA) as the Actual Neuroprotective Effector`	1
`promoted: H7: Enteric Nervous System Alpha-Synuclein Propagation Blocker via Gut Barrier Restoration`	1
`promoted: HDAC6 Selective Inhibition to Restore Acetylation Balance and Microtubule Stability`	1
`promoted: IL-10-Producing B10 Cells Establish AQP4-Specific Peripheral Tolerance Through Macrophage Reprogramm`	1
`promoted: IL-6 Trans-Signaling Blockade at the Oligodendrocyte-Microglia Interface`	1
`promoted: Interneuron SYNGAP1 Deficiency Disrupts Cortical Circuit Assembly During Development`	1
`promoted: Ketone-Based Metabolic Switching to Restore PV Interneuron Function`	1
`promoted: M1 Muscarinic Receptor Agonism as Pharmacological Exercise Substitute`	1
`promoted M1 polarization and inhibited M2 polarization by binding to`	1
`promoted: MEF2C-Dependent Synaptic Gene Regulation`	1
`promoted: MFSD2A-Targeted Lysophosphatidylcholine-SPM Conjugates as CNS-Penetrant Pro-Resolving Prodrugs`	1
`promoted: NAMPT-SIRT1 Axis as Master Regulator of SASP-Dependent Complement Amplification`	1
`promoted: Optimized Temporal Window for Metabolic Boosting Therapy Determines Success of Microglial State Tran`	1
`promoted: p38α Inhibitor and PRMT1 Activator Combination to Restore Physiological TDP-43 Phosphorylation-Methy`	1
`promoted: Parvalbumin Interneuron Vulnerability Links Lactate Transport to Gamma Oscillation Dysfunction`	1
`promoted: PDE4 Inhibition as Inflammatory Reset for PD Oligodendrocytes`	1
`promoted: PIKFYVE Inhibition Activates Aggregate Exocytosis via PI(3,5)P2→TRPML1→Calcineurin→TFEB Cascade in A`	1
`promoted: REDD1-mTOR Axis as the Master Regulator — Preservation Over Chelation`	1
`promoted: SARM1-Mediated NAD+ Depletion as Terminal Executor of MCT1-Dependent Axon Degeneration`	1
`promoted: Selective C1q-CRP vs. C1q-IgG Axis Inhibition`	1
`promoted: Sequential TRPML1 Activation Following Autophagy Priming`	1
`promoted: SIRT1/PGC-1α Axis Activation to Preserve Mitochondrial Resiliency Against Microbiome-Induced Neuroin`	1
`promoted: Stathmin-2 Splice Switching to Prevent Axonal Degeneration Across the ALS-FTD-AD Spectrum`	1
`promoted: STING Antagonism Prevents Acute-to-Chronic Neuroinflammation Transition via Interruption of IFN-I Fe`	1
`promoted: SUMO1-Mediated Synaptotagmin-1 SUMOylation at Lys124 Impairs Calcium Sensing and Links Synaptic Dysf`	1
`promoted: SYK-Independent TREM2 Pathways Remain Functional in TYROBP Deficiency`	1
`promoted: Targeting SASP-Complement Amplification Through HIF-1α Downstream Effectors`	1
`promoted: TDP-43 Cryptic Exon–Targeted ASOs to Restore Hippocampal Gamma Oscillations`	1
`promoted: TFEB Nuclear Translocation to Reset Lysosomal-Hypoxia Axis`	1
`promoted: Timed Senolytic Therapy Eliminates p16^Ink4a/p21^Cip1-Senescent Microglia to Prevent SASP-Driven Com`	1
`promoted: TLR4/MyD88/NF-κB Axis Blockade to Interrupt LPS-Mediated Gut-Brain Neuroinflammation in PD`	1
`promoted: TREM2 Agonism to Restore Microglial Phagocytosis Across Both Pathologies`	1
`promoted: TREM2 R47H Metabolic Lock-in at Cholesterol Ester Accumulation`	1
`promoted: TRPML1-PINK1/Parkin Axis Coordinates Mitophagy with Lysosomal Biogenesis`	1
`promotes_apoptosis`	1
`promotes_autophagic_degradation`	1
`promotes_autophagic_degradation_of`	1
`promotes autophagy-lysosome degradation of`	1
`promotes clearance of`	1
`promotes death of`	1
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`promotes efficient elimination of`	1
`promotes_escape`	1
`promotes_ferroptosis`	1
`promotes fibrillation of`	1
`promotes greater expression of`	1
`promotes healthy ageing through regulation of`	1
`promotes M1 polarization of microglia following SCI by upregulating`	1
`promotes maintenance of`	1
`promotes mitophagy via`	1
`promotes_nuclear_import_of`	1
`promotes_nuclear_translocation`	1
`promotes nuclear translocation of`	1
`promotes_recruitment`	1
`promotes release of`	1
`promotes_SUMOylation_of`	1
`promotes the formation of`	1
`propagate from`	1
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`propagates from neuron to neuron in`	1
`propagates_through`	1
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`propagating from`	1
`propagation_route_for`	1
`proposed as possible early biomarkers of`	1
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`recruits FOXG1 to`	1
`recruits_Hsc70_clients_to`	1
`recruits JIP4 to lysosomes in a kinase-dependent manner via phosphorylation of`	1
`recruits JIP4 to lysosomes via phosphorylation of`	1
`recruits_to_mitochondria`	1
`recruits_to_TGN`	1
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`regulates_alternative_splicing`	1
`regulates Ca2+ influx into photoreceptor cells by activating`	1
`regulates ceramide levels by mediating stability of`	1
`regulates cholesterol and lipid metabolism in`	1
`regulates GPX4/HO-1 by alleviating lipid peroxidation induced by suppression of`	1
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`regulates_stability_by_targeting_FBXL7`	1
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`show vulnerability and myelin alterations`	1
`shuttle`	1
`signaling_dysregulated_in`	1
`signaling molecule mediating`	1
`signaling_requires`	1
`signals_via`	1
`significantly altered`	1
`significantly delayed`	1
`significantly elevated in`	1
`significantly slowed`	1
`sits at the interface between`	1
`slow`	1
`SNAP25 modulates tau_propagation`	1
`spans a spectrum of`	1
`specifically phosphorylates`	1
`specifically reduced`	1
`specifically regulates`	1
`specifically targets`	1
`specifying`	1
`spreads_along`	1
`spreads and worsens with time, taking over more regions`	1
`spreads in`	1
`spreads_to`	1
`spreads_via`	1
`start to increase at very early stages of`	1
`stimulate directly`	1
`stimulates_differentiation`	1
`stimulates mitochondrial respiration via`	1
`stimulates stability of`	1
`stimulates SYK activation more potently than`	1
`strengthened with`	1
`strongly binds to`	1
`strongly increases the risk of developing`	1
`substrate_for`	1
`successful in controlling`	1
`successfully mitigates`	1
`suggested to be`	1
`suggested to be associated with`	1
`suggests`	1
`SUMOylates`	1
`SUMOylation`	1
`support`	1
`support biological coherence of`	1
`supports utility as potential`	1
`suppressed and induced`	1
`suppressed_by_high_dose_melatonin`	1
`suppressed while sparing`	1
`suppresses and induces`	1
`suppresses_transcription`	1
`suppression_associated_with`	1
`susceptible_to`	1
`sustained_activation_in_AD`	1
`synapse_loss_linked_to`	1
`synaptic output onto`	1
`synchronizes`	1
`synergistically_mediates`	1
`synergistic_with`	1
`synergize to drive`	1
`synthetic_lethal_with`	1
`tag and are consequently removed by`	1
`taken_up_by`	1
`take up`	1
`targeted`	1
`targeted and negatively regulated`	1
`Target ESCRT-III complex components (CHMP4B, VPS4) to selectively reduce tau-containing extracellula`	1
`target_for_age_adjusted_replacement`	1
`targets and negatively regulates`	1
`Target SNAP25 interactions to prevent tau uptake at presynaptic terminals during vesicle recycling.`	1
`target_validation_failed`	1
`T_cell_recruitment`	1
`terminate directly in`	1
`therapeutic_for`	1
`therapeutic_reduction_of_extends_lifespan_and_reduces_pathology`	1
`therapeutic_target_of`	1
`toxic_to`	1
`traffics`	1
`traffics_across`	1
`transactivation_is_crucial_for`	1
`transcribe`	1
`transcriptional_activation`	1
`transcriptional_activator_of`	1
`transcriptional_complex`	1
`transcriptional_regulation`	1
`transduce`	1
`transduce and communicate via`	1
`transfer mitochondria to`	1
`transfers_via_TNT`	1
`transiently_rescues`	1
`transitions into`	1
`translocated to`	1
`translocates to and promotes removal of`	1
`transmits`	1
`transmits extracellular signals from`	1
`transmits information about`	1
`transmits information about protein folding status to`	1
`transmits signals for`	1
`transmits signals involved in`	1
`transported from`	1
`transport_via_transcytosis`	1
`travel to and aggravate`	1
`TREM2 modulates tau_propagation`	1
`trended toward an inverse relationship with`	1
`triggered`	1
`triggered by`	1
`trigger multicellular response that ultimately leads to`	1
`triggers_dysfunction`	1
`triggers SASP via activation of`	1
`triggers_ubiquitination_dependent_degradation_by_TRIM25`	1
`triggers_via_CD18`	1
`typically show a negative correlation with`	1
`ubiquitinated_by`	1
`ubiquitin-mediated degradation`	1
`undergo a developmental switch from`	1
`undergoes glutathionylation of`	1
`undergoes incorporation into`	1
`underlie`	1
`underlie_sensitivity_to`	1
`underlies_sensitivity_to`	1
`underlying pathophysiological mechanisms`	1
`underscores important role for`	1
`universally presents with`	1
`upregulate`	1
`upregulated HMGB1 expression by sponging`	1
`up-regulated or down-regulated in`	1
`upregulates expression of through`	1
`upregulates_in_DAM`	1
`upstream_driver`	1
`used for treatment of`	1
`used_to_treat`	1
`uses_neurotransmitter`	1
`uses signaling pathways to ameliorate`	1
`uses to convert`	1
`valid as`	1
`varies by`	1
`vary in their ability to clear`	1
`VCP modulates tau_propagation`	1
`vulnerability_for`	1
`vulnerability_locus_for`	1
`vulnerable_in`	1
`was activated in`	1
`was associated with`	1
`was associated with reduced`	1
`was attenuated by`	1
`was common in`	1
`was delayed until`	1
`was dependent on`	1
`was elevated`	1
`was elevated in`	1
`was found`	1
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`was highly expressed in`	1
`was highly increased in`	1
`was identified as`	1
`was increased by`	1
`was increased in microglia near`	1
`was inversely associated with`	1
`was investigated as`	1
`was largely devoid of`	1
`was largely restricted to`	1
`was located in`	1
`was negatively correlated with`	1
`was not associated with increased risk of`	1
`was not associated with significant`	1
`was not associated with significant change in`	1
`was not correlated with`	1
`was not detected`	1
`was not responsive to`	1
`was only`	1
`was positively correlated with`	1
`was proven to be safe and well tolerated in`	1
`was reduced in`	1
`was reduced in early stages and highly increased in`	1
`was safe and well-tolerated in`	1
`was significantly associated with higher levels of`	1
`was significantly correlated to`	1
`was strongly activated in`	1
`was the best predictor of`	1
`was the highest among`	1
`was unlikely to meet`	1
`was upregulated and localized to`	1
`was up-regulated in`	1
`weakened binding to`	1
`weakened in`	1
`weakly_related_to`	1
`were almost undetectable in`	1
`were available to mice for`	1
`were categorized and listed as`	1
`were correlated with`	1
`were detected in`	1
`were higher along the septo-temporal axis in the septal direction`	1
`were identified as potential targets of`	1
`were increased in`	1
`were largely`	1
`were neuroprotective against`	1
`were overactivated, releasing abundant`	1
`were present at significantly higher frequency in`	1
`were reduced in relation to`	1
`were significantly higher in`	1
`were strong predictors of`	1
`were task-related (changed firing rate)`	1
`widespread in`	1
`will be measured in individuals with FRDA using`	1
`would facilitate transformation to`	1

Recent debate sessions

ID	Question	Status	Quality
`wrap_SDA-2026-04-17-gap-debate-20260417-033037-c43d12c2_1776594195`	The fundamental premise remains unvalidated despite extensive mechanistic speculation. Independent validation using purified proteins and orthogonal binding assays is essential before pursuing mechanistic studies. This determines whether any C1q-related effects are direct or indirect. Source: Debate session sess_SDA-2026-04-16-gap-pubmed-20260410-095709-4e97c09e (Analysis: SDA-2026-04-16-gap-pubmed-20260410-095709-4e97c09e)	`completed`	1.00
`test-session-4`	Test debate topic for persona ladder testing	`completed`	0.50
`test-session-3`	Test debate topic for persona ladder testing	`completed`	0.50
`test-session-2`	Test debate topic for persona ladder testing	`completed`	0.50
`test-session-1`	Test debate topic for persona ladder testing	`completed`	0.50

Recent proposals

ID	Type	Title	Status
`ba98e59b`	`policy_change`	Experiment Proposal: TLR9-agonist + anti-PD-1 adjuvant trial to reverse CD8+ T cell exhaustion and restore vaccine response in adults ≥65 years	`open`
`6a890336`	`policy_change`	Analysis Proposal: CD8+ T cell exhaustion as causal predictor of age-associated vaccine response decline (Allen/Sound Life GSE271896)	`open`
`828d03d4`	`policy_change`	Experiment Proposal: TLR9-agonist + anti-PD-1 adjuvant trial to reverse CD8+ T cell exhaustion and restore vaccine response in adults ≥65 years	`open`
`2d9c472a`	`policy_change`	Experiment Proposal: TLR9-agonist + anti-PD-1 adjuvant trial to reverse CD8+ T cell exhaustion and restore vaccine response in adults ≥65 years	`open`
`86bb1252`	`policy_change`	Analysis Proposal: CD8+ T cell exhaustion as causal predictor of age-associated vaccine response decline (Allen/Sound Life GSE271896)	`open`