MétaCan
Menu
Back to cohort
Record W2800275773 · doi:10.1186/s13287-018-0881-6

Generation of three-dimensional human neuronal cultures: application to modeling CNS viral infections

2018· article· en· W2800275773 on OpenAlex
Leonardo D’Aiuto, Jennifer N. Naciri, Nicholas M. Radio, Sesha Tekur, Dennis R. Clayton, Gerard Apodaca, Roberto Di Maio, Yun Zhi, Peter Dimitrion, Paolo Piazza, Matthew Demers, Joel Wood, Charleen T. Chu, Jason Callio, Lora McClain, Robert H. Yolken, James McNulty, Paul R. Kinchington, David C. Bloom, Vishwajit L. Nimgaonkar

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.

Bibliographic record

VenueStem Cell Research & Therapy · 2018
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicVirus-based gene therapy research
Canadian institutionsMcMaster University
FundersNational Institute on AgingAvid RadiopharmaceuticalsSanofi GenzymeAllerganNational Institutes of HealthH. Lundbeck A/SStanley Medical Research InstituteNational Institute of Neurological Disorders and StrokePittsburgh Center for Kidney Research, University of PittsburghTeva Pharmaceutical IndustriesSanofiBiogenGlaxoSmithKlineServierGenentechUniversity of PittsburghNational Institute of Mental HealthPfizerEli Lilly and CompanyBristol-Myers SquibbNational Institute of Diabetes and Digestive and Kidney DiseasesMichael J. Fox Foundation for Parkinson's Research
KeywordsInduced pluripotent stem cellBiologyHerpes simplex virusDrug discoveryIn vivoFlow cytometryCentral nervous systemNeuroscienceStem cellVirologyImmunologyVirusCell biologyEmbryonic stem cellBioinformaticsGenetics

Abstract

fetched live from OpenAlex

BACKGROUND: A variety of neurological disorders including neurodegenerative diseases and infection by neurotropic viruses can cause structural and functional changes in the central nervous system (CNS), resulting in long-term neurological sequelae. An improved understanding of the pathogenesis of these disorders is important for developing efficacious interventions. Human induced pluripotent stem cells (hiPSCs) offer an extraordinary window for modeling pathogen-CNS interactions, and other cellular interactions, in three-dimensional (3D) neuronal cultures that can recapitulate several aspects of in vivo brain tissue. METHODS: Herein, we describe a prototype of scaffold-free hiPSC-based adherent 3D (A-3D) human neuronal cultures in 96-well plates. To test their suitability for drug screening, A-3D neuronal cultures were infected with herpes simplex virus type 1 (HSV-1) with or without acyclovir. RESULTS: The half maximal inhibitory concentration (IC50) of acyclovir was 3.14 μM and 3.12 μM determined using flow cytometry and the CX7 High Content Screening platform, respectively. CONCLUSIONS: Our A-3D neuronal cultures provide an unprecedented opportunity for high-content drug screening programs to treat human CNS infections.

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)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.015
Threshold uncertainty score0.608

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0010.000
Scholarly communication0.0000.000
Open science0.0000.000
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 head0.096
GPT teacher head0.391
Teacher spread0.295 · 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