Evidence map›Paper›PMID 33564058›Full record

ArticleScientific reports2021

Machine intelligence identifies soluble TNFa as a therapeutic target for spinal cord injury.

J R Huie, A R Ferguson, N Kyritsis, J Z Pan, K-A Irvine, J L Nielson, P G Schupp, M C Oldham, J C Gensel, A Lin and 4 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 1 pooled it
1.7field-weighted citation impact, top 17% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 1 synthesis or guideline pooled it, 12 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 6 institutions in 1 country.

J R Huie *Department of Neurological Surgery, Brain and Spinal Injury Center (BASIC), University of California, San Francisco, CA, USA.
A R Ferguson *Department of Neurological Surgery, Brain and Spinal Injury Center (BASIC), University of California, San Francisco, CA, USA. adam.ferguson@ucsf.edu.
N KyritsisDepartment of Neurological Surgery, Brain and Spinal Injury Center (BASIC), University of California, San Francisco, CA, USA.
J Z PanDepartment of Anesthesiology, University of California San Francisco, San Francisco, USA.
K-A IrvineDepartment of Anesthesiology, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA.
J L NielsonDepartment of Psychiatry and Behavioral Sciences, University of Minnesota, Minneapolis, USA.
P G SchuppBrain Tumor Research Center, University of California, San Francisco, USA.
M C OldhamBrain Tumor Research Center, University of California, San Francisco, USA.
J C GenselSCoBIRC, University of Kentucky, Lexington, USA.
A LinDepartment of Neurological Surgery, Brain and Spinal Injury Center (BASIC), University of California, San Francisco, CA, USA.
M R SegalDepartment of Epidemiology and Biostatistics, Center for Bioinformatics and Molecular Biostatistics, University of California San Francisco, San Francisco, USA.
R R RatanDepartment of Neurology and Neuroscience, Burke-Cornell Medical Research Institute, Weill Medical College of Cornell University, New York, USA.
J C BresnahanDepartment of Neurological Surgery, Brain and Spinal Injury Center (BASIC), University of California, San Francisco, CA, USA.
M S BeattieDepartment of Neurological Surgery, Brain and Spinal Injury Center (BASIC), University of California, San Francisco, CA, USA. michael.beattie@ucsf.edu.
University of California, San Francisco · USNeurological Surgery · USBurke Medical Research Institute · USStanford Medicine · USUniversity of Kentucky · USUniversity of Minnesota · US

Funding

University of Minnesota Clinical and Translational Science Institute (UMN CTSI)UL1TR002494 · NCATS · UNIVERSITY OF MINNESOTA · PI BLAZAR, BRUCE R, WEISDORF, DANIEL J · 2018 to 2022
$34.9M
Training Program in Translational Brain Tumor ResearchT32CA151022 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Joseph F Costello · 2010 to 2026
$6.6M
Mechanisms of secondary injury after SCIR01NS038079 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BEATTIE, MICHAEL S, BRESNAHAN, JACQUELINE C · 1999 to 2015
$5.8M
Comprehensive Anesthesia Research TrainingT32GM008440 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Judith Hellman · 1996 to 2026
$5.5M
Maladaptive Plasticity in Spinal Cord Injury: Cellular MechanismsR01NS088475 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FERGUSON, ADAM R · 2015 to 2019
$1.7M
Bioinformatics For Translational Spinal Cord Injury ResearchR01NS067092 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FERGUSON, ADAM R · 2010 to 2014
$1.6M
Translational Outcomes Project: Visualizing Syndromic Information and Outcomes for Neurotrauma (TOP-VISION)UH3NS106899 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BEATTIE, MICHAEL S, BRESNAHAN, JACQUELINE C · 2020 to 2022
$1.2M
Translational Outcomes Project: Visualizing Syndromic Information and Outcomes for Neurotrauma (TOP-VISION)UG3NS106899 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BEATTIE, MICHAEL S, BRESNAHAN, JACQUELINE C · 2018 to 2019
$480k
Cervical spinal injury and demyelination in aged ratsR21AG032518 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BEATTIE, MICHAEL S · 2009 to 2010
$346k
SCI Consortium Study: Harnessing big-data for plasticity and rehabilitation in translational SCII01RX002245 · VA · VETERANS AFFAIRS MED CTR SAN FRANCISCO · PI ADAM R FERGUSON · 2017 to 2026
–
NIA NIH HHS R21 AG032518NIGMS NIH HHS T32 GM008440NINDS NIH HHS R01 NS038079NINDS NIH HHS R01 NS067092NINDS NIH HHS R01 NS088475RRD VA I01 RX002245RRD VA I01 RX002787
6 · The paper itself

Abstract

Traumatic spinal cord injury (SCI) produces a complex syndrome that is expressed across multiple endpoints ranging from molecular and cellular changes to functional behavioral deficits. Effective therapeutic strategies for CNS injury are therefore likely to manifest multi-factorial effects across a broad range of biological and functional outcome measures. Thus, multivariate analytic approaches are needed to capture the linkage between biological and neurobehavioral outcomes. Injury-induced neuroinflammation (NI) presents a particularly challenging therapeutic target, since NI is involved in both degeneration and repair. Here, we used big-data integration and large-scale analytics to examine a large dataset of preclinical efficacy tests combining five different blinded, fully counter-balanced treatment trials for different acute anti-inflammatory treatments for cervical spinal cord injury in rats. Multi-dimensional discovery, using topological data analysis (TDA) and principal components analysis (PCA) revealed that only one showed consistent multidimensional syndromic benefit: intrathecal application of recombinant soluble TNFα receptor 1 (sTNFR1), which showed an inverse-U dose response efficacy. Using the optimal acute dose, we showed that clinically-relevant 90 min delayed treatment profoundly affected multiple biological indices of NI in the first 48 h after injury, including reduction in pro-inflammatory cytokines and gene expression of a coherent complex of acute inflammatory mediators and receptors. Further, a 90 min delayed bolus dose of sTNFR1 reduced the expression of NI markers in the chronic perilesional spinal cord, and consistently improved neurological function over 6 weeks post SCI. These results provide validation of a novel strategy for precision preclinical drug discovery that is likely to improve translation in the difficult landscape of CNS trauma, and confirm the importance of TNFα signaling as a therapeutic target.

Indexed as

Artificial IntelligenceModels, NeurologicalAnimalsDisease Models, AnimalFemaleInjections, SpinalRatsRats, Long-EvansReceptors, Tumor Necrosis Factor, Type IRecombinant ProteinsSpinal Cord InjuriesTumor Necrosis Factor-alphaReceptors, Tumor Necrosis Factor, Type IRecombinant ProteinsTnfrsf1a protein, ratTumor Necrosis Factor-alpha

Identifiers

PMID33564058
PMCPMC7873211
OpenAlexW3127099942

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.