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Record W4394687825 · doi:10.1002/sam.11679

Data‐driven stochastic model for quantifying the interplay between amyloid‐beta and calcium levels in Alzheimer's disease

2024· article· en· W4394687825 on OpenAlex

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.
fundA Canadian funder is recorded on the work.

Bibliographic record

VenueStatistical Analysis and Data Mining The ASA Data Science Journal · 2024
Typearticle
Languageen
FieldMedicine
TopicAlzheimer's disease research and treatments
Canadian institutionsUniversity of Prince Edward IslandWilfrid Laurier UniversityUniversity of Manitoba
FundersJanssen Alzheimer Immunotherapy Research And DevelopmentJohnson and Johnson Pharmaceutical Research and DevelopmentNational Institute on AgingAgencia Estatal de InvestigaciónNational Institute of Biomedical Imaging and BioengineeringCanadian Institutes of Health ResearchGenentechNational Institutes of HealthEisai CanadaH. Lundbeck A/SServierEisaiShared Hierarchical Academic Research Computing NetworkMinisterio de Ciencia, Innovación y UniversidadesNorthern California Institute for Research and EducationIXICOTakeda Pharmaceutical CompanyAlzheimer's AssociationFujirebio USDoD Alzheimer's Disease Neuroimaging InitiativeNatural Sciences and Engineering Research Council of CanadaPfizerBiogenBioClinicaF. Hoffmann-La RocheRocheAbbVie CanadaUniversity of Southern CaliforniaNovartis Pharmaceuticals CorporationChesapeake Research ConsortiumU.S. Department of DefenseEli Lilly and CompanyAlliance de recherche numérique du CanadaBristol-Myers SquibbAlzheimer's Drug Discovery FoundationMerckGE HealthcareBasque Center for Applied MathematicsAlzheimer's Disease Neuroimaging InitiativeMeso Scale Diagnostics
KeywordsDiseaseBETA (programming language)Amyloid (mycology)Amyloid betaAlzheimer's diseaseNeuroscienceComputer scienceBiologyMedicinePathology

Abstract

fetched live from OpenAlex

Abstract The abnormal aggregation of extracellular amyloid‐ β in senile plaques resulting in calcium dyshomeostasis is one of the primary symptoms of Alzheimer's disease (AD). Significant research efforts have been devoted in the past to better understand the underlying molecular mechanisms driving deposition and dysregulation. Importantly, synaptic impairments, neuronal loss, and cognitive failure in AD patients are all related to the buildup of intraneuronal accumulation. Moreover, increasing evidence show a feed‐forward loop between and levels, that is, disrupts neuronal levels, which in turn affects the formation of . To better understand this interaction, we report a novel stochastic model where we analyze the positive feedback loop between and using ADNI data. A good therapeutic treatment plan for AD requires precise predictions. Stochastic models offer an appropriate framework for modeling AD since AD studies are observational in nature and involve regular patient visits. The etiology of AD may be described as a multi‐state disease process using the approximate Bayesian computation method. So, utilizing ADNI data from ‐year visits for AD patients, we employ this method to investigate the interplay between and levels at various disease development phases. Incorporating the ADNI data in our physics‐based Bayesian model, we discovered that a sufficiently large disruption in either metabolism or intracellular homeostasis causes the relative growth rate in both and , which corresponds to the development of AD. The imbalance of ions causes disorders by directly or indirectly affecting a variety of cellular and subcellular processes, and the altered homeostasis may worsen the abnormalities of ion transportation and deposition. This suggests that altering the balance or the balance between and by chelating them may be able to reduce disorders associated with AD and open up new research possibilities for AD therapy.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.004
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesScholarly communication
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Simulation or modeling · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: none
Teacher disagreement score0.918
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0040.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0010.001
Scholarly communication0.0010.002
Open science0.0020.003
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.303
GPT teacher head0.488
Teacher spread0.185 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it