{"hypotheses":[{"hub_id":"ext_3e0a5a227299","title":"The hnRNPA1 RGG-box accelerates UP1-mediated telomeric G4 unfolding via a diffusible trans-complementation interface that is functionally separable from its G4-","domain":"oncology","one_liner":"The hnRNPA1 RGG-box accelerates UP1-mediated telomeric G4 unfolding via a diffusible trans-complementation interface that is functionally separable from its G4-recognition surface, predicting a recognition-competent/UP1-non-interacting RGG variant that binds G4 but does not accelerate UP1 unfolding.","clinical_question":"Is the hnRNPA1 RGG-box acceleration of UP1-mediated telomeric G4 unfolding mediated by a diffusible trans-complementation interface functionally separable from its G4-recognition surface, such that a recognition-competent/UP1-non-interactin","feasibility":"AMBER","novelty_score":0.72,"evidence_count":2,"ethics_verdict":"amber","contribution_count":1,"view_count":0,"published_at":"2026-10-15T21:47:25.166000"},{"hub_id":"ext_1225e9bfa77b","title":"PA48625 is not represented in any indexed reporter-gene, target, or bioactivity record, so the proposed MOTIFS reporter prediction is untested prior art-free te","domain":"general","one_liner":"PA48625 is not represented in any indexed reporter-gene, target, or bioactivity record, so the proposed MOTIFS reporter prediction is untested prior art-free territory whose first falsifiable step is a luminescence dose-response in a MOTIFS-reporter line.","clinical_question":"Does the compound PA48625 activate the MOTIFS pathway in a reporter cell line with a dose-dependent EC50 < 10 µM, and has any prior paper already tested this exact compound-target-reporter combination?","feasibility":"AMBER","novelty_score":0.72,"evidence_count":3,"ethics_verdict":"amber","contribution_count":7,"view_count":1,"published_at":"2026-10-15T18:34:06.696000"},{"hub_id":"ext_0ef157d6bfd9","title":"RelB/p100 heterodimers act as a kinetic coincidence detector whose enhancer residence time is set by the RelB:p100 binding equilibrium that competes with NIK/IK","domain":"oncology","one_liner":"RelB/p100 heterodimers act as a kinetic coincidence detector whose enhancer residence time is set by the RelB:p100 binding equilibrium that competes with NIK/IKK1, so partial IKKbeta inhibition extends residence time and lowers the pulse threshold for irreversible AP-1-gated memory.","clinical_question":"Does RelB/p100 heterodimer residence time at NF-kappa-B enhancers set a kinetic integration window converting sub-threshold IL-6/TNF pulses into irreversible AP-1-gated inflammatory memory only when IKKbeta-dependent p100 processing is part","feasibility":"AMBER","novelty_score":0.72,"evidence_count":5,"ethics_verdict":"amber","contribution_count":11,"view_count":2,"published_at":"2026-10-15T17:12:30.578000"},{"hub_id":"ext_4571210ba573","title":"The hnRNPA1 RGG-box acts as a diffusible, trans-acting accelerator of UP1-mediated telomeric G-quadruplex unfolding, a non-prior-art mechanism distinct from the","domain":"oncology","one_liner":"The hnRNPA1 RGG-box acts as a diffusible, trans-acting accelerator of UP1-mediated telomeric G-quadruplex unfolding, a non-prior-art mechanism distinct from the cis-domain cooperation reported for the intact protein.","clinical_question":"Does the isolated, diffusible RGG-box of hnRNPA1 trans-complement UP1 to accelerate telomeric G-quadruplex unfolding, and is this acceleration abolished when RGG-box is added in trans to a G4 that UP1 alone cannot unfold?","feasibility":"AMBER","novelty_score":0.72,"evidence_count":5,"ethics_verdict":"amber","contribution_count":1,"view_count":0,"published_at":"2026-10-15T14:49:46.400000"},{"hub_id":"ext_4250666ebb3a","title":"SIRT1 deacetylates TDP-43 at K136, and this deacetylation directly inhibits TDP-43 phase separation and aggregation, suggesting that SIRT1 activation is a viabl","domain":"general","one_liner":"SIRT1 deacetylates TDP-43 at K136, and this deacetylation directly inhibits TDP-43 phase separation and aggregation, suggesting that SIRT1 activation is a viable therapeutic strategy for TDP-43 proteinopathies.","clinical_question":"Does SIRT1-mediated deacetylation of TDP-43 at lysine-136 reduce its pathological phase separation and aggregation, and can this be harnessed therapeutically?","feasibility":"AMBER","novelty_score":0.85,"evidence_count":5,"ethics_verdict":"amber","contribution_count":6,"view_count":1,"published_at":"2026-10-15T12:28:25.298000"},{"hub_id":"ext_e0f944cc473d","title":"Does the paper that already tested PA48625 plus 5Hz/2µm substrate vibration on cortical neuron ROS exist, and if not, does NOX2 (uniprot:P04839) rather than mit","domain":"general","one_liner":"No prior study has combined PA48625 with 5Hz/2µm substrate vibration in cortical neurons; the predicted ROS surge is mechanistically attributable to NOX2 (P04839) activation, not mitochondrial or GPX1 (P07203) failure, making the feed's prediction testable and falsifiable with a NOX2-selective inhib","clinical_question":"Does the paper that already tested PA48625 plus 5Hz/2µm substrate vibration on cortical neuron ROS exist, and if not, does NOX2 (uniprot:P04839) rather than mitochondrial ROS mediate the predicted ≥50% CellROX Green increase?","feasibility":"AMBER","novelty_score":0.72,"evidence_count":4,"ethics_verdict":"amber","contribution_count":6,"view_count":1,"published_at":"2026-10-15T10:11:41.419000"},{"hub_id":"ext_6aff3d3aa029","title":"The RGG-box of hnRNPA1 is predicted to act as a diffusible G4-remodeling cofactor that accelerates UP1-mediated telomeric G4 unfolding by an avidity-scaled rate","domain":"oncology","one_liner":"The RGG-box of hnRNPA1 is predicted to act as a diffusible G4-remodeling cofactor that accelerates UP1-mediated telomeric G4 unfolding by an avidity-scaled rate enhancement, not by direct UP1 binding.","clinical_question":"Does the diffusible RGG-box of hnRNPA1 trans-complement UP1 G4-unfolding, and can that acceleration be predicted from the RGG-box's own G4-recognition affinity (pmid:30247678, pmid:40209951, pmid:32128583)?","feasibility":"AMBER","novelty_score":0.72,"evidence_count":7,"ethics_verdict":"amber","contribution_count":6,"view_count":1,"published_at":"2026-10-15T07:57:51.305000"},{"hub_id":"ext_89564ba4cb92","title":"Matrix stiffness activates latent TGF-β primarily through stiffness-induced MMP-14/MT1-MMP proteolysis of LTBP2's hinge, converting LTBP2 from a latency clamp i","domain":"pulmonology","one_liner":"Matrix stiffness activates latent TGF-β primarily through stiffness-induced MMP-14/MT1-MMP proteolysis of LTBP2's hinge, converting LTBP2 from a latency clamp into a release substrate rather than a force-unfolded mechanosensor.","clinical_question":"Does matrix stiffness activate latent TGF-β not by force-unfolding LTBP2, but by stiffness-driven MMP-14 (MT1-MMP) ectodomain shedding of LTBP2 that releases the latent complex, making stiffness a proteolytic rather than purely mechanical s","feasibility":"AMBER","novelty_score":0.72,"evidence_count":2,"ethics_verdict":"amber","contribution_count":6,"view_count":1,"published_at":"2026-10-14T22:50:10.331000"},{"hub_id":"ext_6c61c7ee0492","title":"RABV cell-to-cell spread is not motor-limited but release-limited: the p75NTR/dynein motor can move virus at 50-100 mm/day, yet measured trans-synaptic spread r","domain":"infectious diseases","one_liner":"RABV cell-to-cell spread is not motor-limited but release-limited: the p75NTR/dynein motor can move virus at 50-100 mm/day, yet measured trans-synaptic spread rates (~0.5-2 mm/day) are 50-200x slower, implying synaptic vesicle release frequency, not dynein velocity, is the rate-limiting step and pre","clinical_question":"Does RABV spread kinetics decelerate rather than accelerate once encephalitis begins, because p75NTR/dynein retrograde transport (~50-100 mm/day) is rate-limited by synaptic vesicle release frequency rather than by motor speed?","feasibility":"AMBER","novelty_score":0.72,"evidence_count":5,"ethics_verdict":"amber","contribution_count":6,"view_count":1,"published_at":"2026-10-14T20:37:11.971000"},{"hub_id":"ext_10afcda96dce","title":"Does prior art already establish that AKR1C1 and AKR1C3 form a substrate-channeling relay in tumor-associated macrophages where AKR1C1-derived 20α-hydroxyproges","domain":"oncology","one_liner":"No retrieved prior art demonstrates an AKR1C1→20α-hydroxyprogesterone→AKR1C3→PGF2α channeling relay in tumor-associated macrophages; existing AKR1C1/AKR1C3 literature instead documents parallel, independent roles in chemoresistance and steroid hormone metabolism, leaving the proposed relay and its 7","clinical_question":"Does prior art already establish that AKR1C1 and AKR1C3 form a substrate-channeling relay in tumor-associated macrophages where AKR1C1-derived 20α-hydroxyprogesterone is the rate-limiting precursor for AKR1C3-mediated PGF2α synthesis, such","feasibility":"AMBER","novelty_score":0.72,"evidence_count":3,"ethics_verdict":"amber","contribution_count":1,"view_count":0,"published_at":"2026-10-14T18:19:58.307000"},{"hub_id":"ext_c7532a621f5e","title":"N4BP1 degrades JunB mRNA through a transferable CDS-embedded element, making JunB the first identified physiological N4BP1 substrate and providing the molecular","domain":"oncology","one_liner":"N4BP1 degrades JunB mRNA through a transferable CDS-embedded element, making JunB the first identified physiological N4BP1 substrate and providing the molecular basis for the IKKbeta-JunB-IL10/IRF1 bistable switch.","clinical_question":"Does N4BP1's coding-sequence (CDS) mRNA degradation of JunB require a specific sequence element in the JunB CDS, and is that element sufficient to confer N4BP1 sensitivity on a heterologous transcript?","feasibility":"AMBER","novelty_score":0.72,"evidence_count":4,"ethics_verdict":"amber","contribution_count":6,"view_count":1,"published_at":"2026-10-14T16:04:44.841000"},{"hub_id":"ext_1f2382fb3159","title":"The binding-versus-functional potency offset is a cell-state property, so in diffuse glioma it becomes a measurable per-cell 'functional infiltration index' tha","domain":"oncology","one_liner":"The binding-versus-functional potency offset is a cell-state property, so in diffuse glioma it becomes a measurable per-cell 'functional infiltration index' that separates cells whose transporter/efflux function is decoupled from ligand binding — a decoupling that predicts surgical resectability bet","clinical_question":"Can the assay-cell-dependent binding-versus-functional potency offset, a non-biological measurement artifact defined in monoamine transporter pharmacology, be repurposed as a quantitative 'resection-margin index' that predicts which diffuse","feasibility":"AMBER","novelty_score":0.72,"evidence_count":3,"ethics_verdict":"amber","contribution_count":0,"view_count":0,"published_at":"2026-10-14T12:53:37.060000"},{"hub_id":"ext_580e256d2c4a","title":"Amyloid-beta accumulation causally drives Alzheimer's progression via a threshold-dependent cascade where regional amyloid burden predicts downstream tau spread","domain":"neurology","one_liner":"Amyloid-beta accumulation causally drives Alzheimer's progression via a threshold-dependent cascade where regional amyloid burden predicts downstream tau spreading and neurodegeneration, identifiable through counterfactual inference models applied to longitudinal imaging.","clinical_question":"Does amyloid-beta accumulation drive Alzheimer's progression through a specific causal pathway that can be identified by counterfactual inference on longitudinal imaging data?","feasibility":"AMBER","novelty_score":0.75,"evidence_count":3,"ethics_verdict":"amber","contribution_count":0,"view_count":0,"published_at":"2026-10-13T22:35:21.908000"},{"hub_id":"ext_89f04fe0cf3a","title":"Apoptotic immune cells release MMP-cleaved collagen fragments that engage LAIR1 on newly cultured T cells, converting the 'mortality-conditioned' collagen matri","domain":"general","one_liner":"Apoptotic immune cells release MMP-cleaved collagen fragments that engage LAIR1 on newly cultured T cells, converting the 'mortality-conditioned' collagen matrix from a proliferative scaffold into an exhaustion-inducing niche, inverting the feed's predicted >30% proliferation and >25% IFN-gamma gain","clinical_question":"Does apoptotic immune-cell pre-conditioning of a 3D collagen matrix deposit LAIR1-ligand collagen fragments that reprogram new T cells toward exhaustion rather than the predicted >30% proliferation boost?","feasibility":"AMBER","novelty_score":0.72,"evidence_count":2,"ethics_verdict":"amber","contribution_count":7,"view_count":1,"published_at":"2026-10-13T11:29:20.403000"},{"hub_id":"ext_cb71cc653ba0","title":"Apoptotic immune cells pre-conditioning a 3D collagen matrix deposit collagen fragments and phosphatidylserine-bearing debris that engage LAIR1 on incoming CD8 ","domain":"general","one_liner":"Apoptotic immune cells pre-conditioning a 3D collagen matrix deposit collagen fragments and phosphatidylserine-bearing debris that engage LAIR1 on incoming CD8 T cells, converting the same collagen-LAIR1 axis that drives anti-PD-1 resistance in tumors into a proliferation-licensing signal when the m","clinical_question":"Does apoptotic immune-cell pre-conditioning of a 3D collagen matrix generate a LAIR1-ligand-rich niche that licenses CD8 T-cell proliferation, and can this be predicted from collagen-LAIR1 signaling topology rather than tested empirically?","feasibility":"AMBER","novelty_score":0.72,"evidence_count":4,"ethics_verdict":"amber","contribution_count":8,"view_count":1,"published_at":"2026-10-13T09:09:15.472000"},{"hub_id":"ext_0f1409ab5f00","title":"The STAT5A:STAT5B heterodimer dominance switchpoint is not set by the STAT5A:STAT5B protein ratio but by the PTP1B-gated kinetic proofreading window, so the swi","domain":"oncology","one_liner":"The STAT5A:STAT5B heterodimer dominance switchpoint is not set by the STAT5A:STAT5B protein ratio but by the PTP1B-gated kinetic proofreading window, so the switchpoint is tunable by PTP1B activity independently of STAT5A abundance.","clinical_question":"Does the V617F:wild-type JAK2 activity ratio set the STAT5A→STAT5B dominance switchpoint at the STAT5A:STAT5B protein ratio, or is the switchpoint instead fixed by a PTP1B-gated kinetic proofreading window on STAT5B SH2-pY off-rate?","feasibility":"AMBER","novelty_score":0.72,"evidence_count":3,"ethics_verdict":"amber","contribution_count":6,"view_count":1,"published_at":"2026-10-13T06:48:39.431000"},{"hub_id":"ext_e72be6b97acb","title":"The MUC1-C/NF-κB chemoresistance lock in signet-ring/mucin-vacuole carcinoma is predicted to be sustained by an EGLN2-HIF-1α feed-forward loop, so vATPase block","domain":"oncology","one_liner":"The MUC1-C/NF-κB chemoresistance lock in signet-ring/mucin-vacuole carcinoma is predicted to be sustained by an EGLN2-HIF-1α feed-forward loop, so vATPase blockade plus MUC1-C inhibition must be tripled with EGLN2/HIF-1α axis interruption to collapse the acidified sequestration compartment.","clinical_question":"Does MUC1-C/NF-κB-driven chemoresistance in signet-ring/mucin-vacuole carcinoma require a hypoxia-HIF-1α-EGLN2 feed-forward loop that locks vacuolar-ATPase-dependent drug sequestration, making combined vATPase blockade plus MUC1-C inhibitio","feasibility":"AMBER","novelty_score":0.72,"evidence_count":3,"ethics_verdict":"amber","contribution_count":6,"view_count":1,"published_at":"2026-10-13T04:42:08.416000"},{"hub_id":"ext_b4fc2352a362","title":"STAT5B's bistable dominance is set by a PTP1B-gated kinetic proofreading window in which the slower SH2-pY off-rate, not on-rate, defines the nucleation-site oc","domain":"oncology","one_liner":"STAT5B's bistable dominance is set by a PTP1B-gated kinetic proofreading window in which the slower SH2-pY off-rate, not on-rate, defines the nucleation-site occupancy threshold for stable dimer survival.","clinical_question":"Does STAT5B's bistable dominance arise from a PTP1B-gated kinetic proofreading window in which the intrinsically slower SH2-pY off-rate, not a faster on-rate, sets the threshold nucleation-site occupancy required for stable dimer survival?","feasibility":"AMBER","novelty_score":0.72,"evidence_count":3,"ethics_verdict":"amber","contribution_count":18,"view_count":3,"published_at":"2026-10-13T02:37:32.354000"},{"hub_id":"ext_72a204acbb71","title":"STAT5B bistability is a PTP1B-mediated kinetic proofreading filter in which the SH2-pY off-rate sets the dephosphorylation window, so the nucleation-site occupa","domain":"oncology","one_liner":"STAT5B bistability is a PTP1B-mediated kinetic proofreading filter in which the SH2-pY off-rate sets the dephosphorylation window, so the nucleation-site occupancy threshold is governed by off-rate, not on-rate.","clinical_question":"Does STAT5B's bistable dominance arise because PTP1B acts as a kinetic-proofreading gate whose dephosphorylation rate is set by SH2-pY off-rate, making the threshold nucleation-site occupancy a function of off-rate rather than on-rate?","feasibility":"AMBER","novelty_score":0.72,"evidence_count":4,"ethics_verdict":"amber","contribution_count":13,"view_count":2,"published_at":"2026-10-13T00:18:58.115000"},{"hub_id":"ext_d8355366417e","title":"RABV spread kinetics can be modeled as a two-regime system where p75NTR/dynein retrograde transport (~50-100 mm/day) dominates pre-symptomatically but is rate-l","domain":"infectious diseases","one_liner":"RABV spread kinetics can be modeled as a two-regime system where p75NTR/dynein retrograde transport (~50-100 mm/day) dominates pre-symptomatically but is rate-limited by synaptic vesicle release frequency once encephalitis begins, predicting a measurable deceleration rather than acceleration of spre","clinical_question":"Does RABV trans-synaptic spread rate during clinical encephalitis exceed the p75NTR/dynein retrograde transport rate, and can the switch be quantified as a diffusible-vs-motor-bound transition?","feasibility":"AMBER","novelty_score":0.72,"evidence_count":3,"ethics_verdict":"amber","contribution_count":18,"view_count":3,"published_at":"2026-10-12T22:10:54.041000"}],"total":290,"page":1,"page_size":20,"has_more":true,"domain_stats":{"general":10,"endocrinology":2,"pulmonology":1,"general medicine":2,"neurology":36,"diabetes":29,"infectious diseases":36,"oncology":174}}