Evidence map›Paper›PMID 27501182›Full record

ArticleEndocrinology2016

Type 2 Deiodinase Disruption in Astrocytes Results in Anxiety-Depressive-Like Behavior in Male Mice.

Barbara M L C Bocco, João Pedro Werneck-de-Castro, Kelen C Oliveira, Gustavo W Fernandes, Tatiana L Fonseca, Bruna P P Nascimento, Elizabeth A McAninch, Esther Ricci, Zsuzsanna Kvárta-Papp, Csaba Fekete and 4 more

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In one paragraph

Article in Endocrinology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
4.7field-weighted citation impact, top 5% 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

41 citing papers in PubMed, 64 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Variable transduction of thyroid hormone signaling in structures of the mouse brain.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  5. Article
  6. Article
  7. Review
  8. Review
  9. Review
  10. Article
  11. The Physiological Functions and Polymorphisms of Type II Deiodinase.Endocrinology and metabolism (Seoul, Korea) · 2023
    Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Primary hypothyroidism and quality of life.Nature reviews. Endocrinology · 2022
    Review
  17. Article
  18. Brain Fog in Hypothyroidism: Understanding the Patient's Perspective.Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists · 2022
    Article
  19. Article
  20. Review
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 3 countries.

Barbara M L C BoccoDivision of Endocrinology and Metabolism (B.M.L.C.B., J.P.W.-d.C., G.W.F., T.L.F., E.A.M., A.C.B.), Rush University Medical Center, Chicago, Illinois 60612; Department of Translational Medicine (B.M.L.C.B., G.W.F., B.P.P.N.), Federal University of Sao Paulo, Sao Paulo SP, 04039-002, Brazil; Biophysics Institute and School of Physical Education and Sports (J.P.W.-d.C.), Federal University of Rio de Janeiro, RJ 21941-599, Brazil; Department of Clinic Endocrinology (K.C.O.), Federal University of Sao Paulo, Sao Paulo SP 04039-032, Brazil; Developmental Disorders Program (B.P.P.N., E.R., M.O.R.), Center of Biological Science and Health, Mackenzie Presbyterian University, Sao Paulo SP 01302-900 Brazil; Department of Endocrine Neurobiology (Z.K.-P., C.F., B.G.), Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest H-1083, Hungary; Department of Medicine (C.F.), Division of Endocrinology, Diabetes, and Metabolism, Tupper Research Institute, Tufts Medical Center, Boston, Massachusetts 02111; and Graduate Program of Environmental and Experimental Pathology (M.M.B.), Graduate Program of Dentistry, Universidade Paulista, Sao Paulo SP 04026-002, Brazil.
João Pedro Werneck-de-CastroDivision of Endocrinology and Metabolism (B.M.L.C.B., J.P.W.-d.C., G.W.F., T.L.F., E.A.M., A.C.B.), Rush University Medical Center, Chicago, Illinois 60612; Department of Translational Medicine (B.M.L.C.B., G.W.F., B.P.P.N.), Federal University of Sao Paulo, Sao Paulo SP, 04039-002, Brazil; Biophysics Institute and School of Physical Education and Sports (J.P.W.-d.C.), Federal University of Rio de Janeiro, RJ 21941-599, Brazil; Department of Clinic Endocrinology (K.C.O.), Federal University of Sao Paulo, Sao Paulo SP 04039-032, Brazil; Developmental Disorders Program (B.P.P.N., E.R., M.O.R.), Center of Biological Science and Health, Mackenzie Presbyterian University, Sao Paulo SP 01302-900 Brazil; Department of Endocrine Neurobiology (Z.K.-P., C.F., B.G.), Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest H-1083, Hungary; Department of Medicine (C.F.), Division of Endocrinology, Diabetes, and Metabolism, Tupper Research Institute, Tufts Medical Center, Boston, Massachusetts 02111; and Graduate Program of Environmental and Experimental Pathology (M.M.B.), Graduate Program of Dentistry, Universidade Paulista, Sao Paulo SP 04026-002, Brazil.
Kelen C OliveiraDivision of Endocrinology and Metabolism (B.M.L.C.B., J.P.W.-d.C., G.W.F., T.L.F., E.A.M., A.C.B.), Rush University Medical Center, Chicago, Illinois 60612; Department of Translational Medicine (B.M.L.C.B., G.W.F., B.P.P.N.), Federal University of Sao Paulo, Sao Paulo SP, 04039-002, Brazil; Biophysics Institute and School of Physical Education and Sports (J.P.W.-d.C.), Federal University of Rio de Janeiro, RJ 21941-599, Brazil; Department of Clinic Endocrinology (K.C.O.), Federal University of Sao Paulo, Sao Paulo SP 04039-032, Brazil; Developmental Disorders Program (B.P.P.N., E.R., M.O.R.), Center of Biological Science and Health, Mackenzie Presbyterian University, Sao Paulo SP 01302-900 Brazil; Department of Endocrine Neurobiology (Z.K.-P., C.F., B.G.), Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest H-1083, Hungary; Department of Medicine (C.F.), Division of Endocrinology, Diabetes, and Metabolism, Tupper Research Institute, Tufts Medical Center, Boston, Massachusetts 02111; and Graduate Program of Environmental and Experimental Pathology (M.M.B.), Graduate Program of Dentistry, Universidade Paulista, Sao Paulo SP 04026-002, Brazil.
Gustavo W FernandesDivision of Endocrinology and Metabolism (B.M.L.C.B., J.P.W.-d.C., G.W.F., T.L.F., E.A.M., A.C.B.), Rush University Medical Center, Chicago, Illinois 60612; Department of Translational Medicine (B.M.L.C.B., G.W.F., B.P.P.N.), Federal University of Sao Paulo, Sao Paulo SP, 04039-002, Brazil; Biophysics Institute and School of Physical Education and Sports (J.P.W.-d.C.), Federal University of Rio de Janeiro, RJ 21941-599, Brazil; Department of Clinic Endocrinology (K.C.O.), Federal University of Sao Paulo, Sao Paulo SP 04039-032, Brazil; Developmental Disorders Program (B.P.P.N., E.R., M.O.R.), Center of Biological Science and Health, Mackenzie Presbyterian University, Sao Paulo SP 01302-900 Brazil; Department of Endocrine Neurobiology (Z.K.-P., C.F., B.G.), Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest H-1083, Hungary; Department of Medicine (C.F.), Division of Endocrinology, Diabetes, and Metabolism, Tupper Research Institute, Tufts Medical Center, Boston, Massachusetts 02111; and Graduate Program of Environmental and Experimental Pathology (M.M.B.), Graduate Program of Dentistry, Universidade Paulista, Sao Paulo SP 04026-002, Brazil.
Tatiana L FonsecaDivision of Endocrinology and Metabolism (B.M.L.C.B., J.P.W.-d.C., G.W.F., T.L.F., E.A.M., A.C.B.), Rush University Medical Center, Chicago, Illinois 60612; Department of Translational Medicine (B.M.L.C.B., G.W.F., B.P.P.N.), Federal University of Sao Paulo, Sao Paulo SP, 04039-002, Brazil; Biophysics Institute and School of Physical Education and Sports (J.P.W.-d.C.), Federal University of Rio de Janeiro, RJ 21941-599, Brazil; Department of Clinic Endocrinology (K.C.O.), Federal University of Sao Paulo, Sao Paulo SP 04039-032, Brazil; Developmental Disorders Program (B.P.P.N., E.R., M.O.R.), Center of Biological Science and Health, Mackenzie Presbyterian University, Sao Paulo SP 01302-900 Brazil; Department of Endocrine Neurobiology (Z.K.-P., C.F., B.G.), Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest H-1083, Hungary; Department of Medicine (C.F.), Division of Endocrinology, Diabetes, and Metabolism, Tupper Research Institute, Tufts Medical Center, Boston, Massachusetts 02111; and Graduate Program of Environmental and Experimental Pathology (M.M.B.), Graduate Program of Dentistry, Universidade Paulista, Sao Paulo SP 04026-002, Brazil.
Bruna P P NascimentoDivision of Endocrinology and Metabolism (B.M.L.C.B., J.P.W.-d.C., G.W.F., T.L.F., E.A.M., A.C.B.), Rush University Medical Center, Chicago, Illinois 60612; Department of Translational Medicine (B.M.L.C.B., G.W.F., B.P.P.N.), Federal University of Sao Paulo, Sao Paulo SP, 04039-002, Brazil; Biophysics Institute and School of Physical Education and Sports (J.P.W.-d.C.), Federal University of Rio de Janeiro, RJ 21941-599, Brazil; Department of Clinic Endocrinology (K.C.O.), Federal University of Sao Paulo, Sao Paulo SP 04039-032, Brazil; Developmental Disorders Program (B.P.P.N., E.R., M.O.R.), Center of Biological Science and Health, Mackenzie Presbyterian University, Sao Paulo SP 01302-900 Brazil; Department of Endocrine Neurobiology (Z.K.-P., C.F., B.G.), Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest H-1083, Hungary; Department of Medicine (C.F.), Division of Endocrinology, Diabetes, and Metabolism, Tupper Research Institute, Tufts Medical Center, Boston, Massachusetts 02111; and Graduate Program of Environmental and Experimental Pathology (M.M.B.), Graduate Program of Dentistry, Universidade Paulista, Sao Paulo SP 04026-002, Brazil.
Elizabeth A McAninchDivision of Endocrinology and Metabolism (B.M.L.C.B., J.P.W.-d.C., G.W.F., T.L.F., E.A.M., A.C.B.), Rush University Medical Center, Chicago, Illinois 60612; Department of Translational Medicine (B.M.L.C.B., G.W.F., B.P.P.N.), Federal University of Sao Paulo, Sao Paulo SP, 04039-002, Brazil; Biophysics Institute and School of Physical Education and Sports (J.P.W.-d.C.), Federal University of Rio de Janeiro, RJ 21941-599, Brazil; Department of Clinic Endocrinology (K.C.O.), Federal University of Sao Paulo, Sao Paulo SP 04039-032, Brazil; Developmental Disorders Program (B.P.P.N., E.R., M.O.R.), Center of Biological Science and Health, Mackenzie Presbyterian University, Sao Paulo SP 01302-900 Brazil; Department of Endocrine Neurobiology (Z.K.-P., C.F., B.G.), Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest H-1083, Hungary; Department of Medicine (C.F.), Division of Endocrinology, Diabetes, and Metabolism, Tupper Research Institute, Tufts Medical Center, Boston, Massachusetts 02111; and Graduate Program of Environmental and Experimental Pathology (M.M.B.), Graduate Program of Dentistry, Universidade Paulista, Sao Paulo SP 04026-002, Brazil.
Esther RicciDivision of Endocrinology and Metabolism (B.M.L.C.B., J.P.W.-d.C., G.W.F., T.L.F., E.A.M., A.C.B.), Rush University Medical Center, Chicago, Illinois 60612; Department of Translational Medicine (B.M.L.C.B., G.W.F., B.P.P.N.), Federal University of Sao Paulo, Sao Paulo SP, 04039-002, Brazil; Biophysics Institute and School of Physical Education and Sports (J.P.W.-d.C.), Federal University of Rio de Janeiro, RJ 21941-599, Brazil; Department of Clinic Endocrinology (K.C.O.), Federal University of Sao Paulo, Sao Paulo SP 04039-032, Brazil; Developmental Disorders Program (B.P.P.N., E.R., M.O.R.), Center of Biological Science and Health, Mackenzie Presbyterian University, Sao Paulo SP 01302-900 Brazil; Department of Endocrine Neurobiology (Z.K.-P., C.F., B.G.), Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest H-1083, Hungary; Department of Medicine (C.F.), Division of Endocrinology, Diabetes, and Metabolism, Tupper Research Institute, Tufts Medical Center, Boston, Massachusetts 02111; and Graduate Program of Environmental and Experimental Pathology (M.M.B.), Graduate Program of Dentistry, Universidade Paulista, Sao Paulo SP 04026-002, Brazil.
Zsuzsanna Kvárta-PappDivision of Endocrinology and Metabolism (B.M.L.C.B., J.P.W.-d.C., G.W.F., T.L.F., E.A.M., A.C.B.), Rush University Medical Center, Chicago, Illinois 60612; Department of Translational Medicine (B.M.L.C.B., G.W.F., B.P.P.N.), Federal University of Sao Paulo, Sao Paulo SP, 04039-002, Brazil; Biophysics Institute and School of Physical Education and Sports (J.P.W.-d.C.), Federal University of Rio de Janeiro, RJ 21941-599, Brazil; Department of Clinic Endocrinology (K.C.O.), Federal University of Sao Paulo, Sao Paulo SP 04039-032, Brazil; Developmental Disorders Program (B.P.P.N., E.R., M.O.R.), Center of Biological Science and Health, Mackenzie Presbyterian University, Sao Paulo SP 01302-900 Brazil; Department of Endocrine Neurobiology (Z.K.-P., C.F., B.G.), Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest H-1083, Hungary; Department of Medicine (C.F.), Division of Endocrinology, Diabetes, and Metabolism, Tupper Research Institute, Tufts Medical Center, Boston, Massachusetts 02111; and Graduate Program of Environmental and Experimental Pathology (M.M.B.), Graduate Program of Dentistry, Universidade Paulista, Sao Paulo SP 04026-002, Brazil.
Csaba FeketeDivision of Endocrinology and Metabolism (B.M.L.C.B., J.P.W.-d.C., G.W.F., T.L.F., E.A.M., A.C.B.), Rush University Medical Center, Chicago, Illinois 60612; Department of Translational Medicine (B.M.L.C.B., G.W.F., B.P.P.N.), Federal University of Sao Paulo, Sao Paulo SP, 04039-002, Brazil; Biophysics Institute and School of Physical Education and Sports (J.P.W.-d.C.), Federal University of Rio de Janeiro, RJ 21941-599, Brazil; Department of Clinic Endocrinology (K.C.O.), Federal University of Sao Paulo, Sao Paulo SP 04039-032, Brazil; Developmental Disorders Program (B.P.P.N., E.R., M.O.R.), Center of Biological Science and Health, Mackenzie Presbyterian University, Sao Paulo SP 01302-900 Brazil; Department of Endocrine Neurobiology (Z.K.-P., C.F., B.G.), Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest H-1083, Hungary; Department of Medicine (C.F.), Division of Endocrinology, Diabetes, and Metabolism, Tupper Research Institute, Tufts Medical Center, Boston, Massachusetts 02111; and Graduate Program of Environmental and Experimental Pathology (M.M.B.), Graduate Program of Dentistry, Universidade Paulista, Sao Paulo SP 04026-002, Brazil.
Maria Martha BernardiDivision of Endocrinology and Metabolism (B.M.L.C.B., J.P.W.-d.C., G.W.F., T.L.F., E.A.M., A.C.B.), Rush University Medical Center, Chicago, Illinois 60612; Department of Translational Medicine (B.M.L.C.B., G.W.F., B.P.P.N.), Federal University of Sao Paulo, Sao Paulo SP, 04039-002, Brazil; Biophysics Institute and School of Physical Education and Sports (J.P.W.-d.C.), Federal University of Rio de Janeiro, RJ 21941-599, Brazil; Department of Clinic Endocrinology (K.C.O.), Federal University of Sao Paulo, Sao Paulo SP 04039-032, Brazil; Developmental Disorders Program (B.P.P.N., E.R., M.O.R.), Center of Biological Science and Health, Mackenzie Presbyterian University, Sao Paulo SP 01302-900 Brazil; Department of Endocrine Neurobiology (Z.K.-P., C.F., B.G.), Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest H-1083, Hungary; Department of Medicine (C.F.), Division of Endocrinology, Diabetes, and Metabolism, Tupper Research Institute, Tufts Medical Center, Boston, Massachusetts 02111; and Graduate Program of Environmental and Experimental Pathology (M.M.B.), Graduate Program of Dentistry, Universidade Paulista, Sao Paulo SP 04026-002, Brazil.
Balázs GerebenDivision of Endocrinology and Metabolism (B.M.L.C.B., J.P.W.-d.C., G.W.F., T.L.F., E.A.M., A.C.B.), Rush University Medical Center, Chicago, Illinois 60612; Department of Translational Medicine (B.M.L.C.B., G.W.F., B.P.P.N.), Federal University of Sao Paulo, Sao Paulo SP, 04039-002, Brazil; Biophysics Institute and School of Physical Education and Sports (J.P.W.-d.C.), Federal University of Rio de Janeiro, RJ 21941-599, Brazil; Department of Clinic Endocrinology (K.C.O.), Federal University of Sao Paulo, Sao Paulo SP 04039-032, Brazil; Developmental Disorders Program (B.P.P.N., E.R., M.O.R.), Center of Biological Science and Health, Mackenzie Presbyterian University, Sao Paulo SP 01302-900 Brazil; Department of Endocrine Neurobiology (Z.K.-P., C.F., B.G.), Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest H-1083, Hungary; Department of Medicine (C.F.), Division of Endocrinology, Diabetes, and Metabolism, Tupper Research Institute, Tufts Medical Center, Boston, Massachusetts 02111; and Graduate Program of Environmental and Experimental Pathology (M.M.B.), Graduate Program of Dentistry, Universidade Paulista, Sao Paulo SP 04026-002, Brazil.
Antonio C BiancoDivision of Endocrinology and Metabolism (B.M.L.C.B., J.P.W.-d.C., G.W.F., T.L.F., E.A.M., A.C.B.), Rush University Medical Center, Chicago, Illinois 60612; Department of Translational Medicine (B.M.L.C.B., G.W.F., B.P.P.N.), Federal University of Sao Paulo, Sao Paulo SP, 04039-002, Brazil; Biophysics Institute and School of Physical Education and Sports (J.P.W.-d.C.), Federal University of Rio de Janeiro, RJ 21941-599, Brazil; Department of Clinic Endocrinology (K.C.O.), Federal University of Sao Paulo, Sao Paulo SP 04039-032, Brazil; Developmental Disorders Program (B.P.P.N., E.R., M.O.R.), Center of Biological Science and Health, Mackenzie Presbyterian University, Sao Paulo SP 01302-900 Brazil; Department of Endocrine Neurobiology (Z.K.-P., C.F., B.G.), Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest H-1083, Hungary; Department of Medicine (C.F.), Division of Endocrinology, Diabetes, and Metabolism, Tupper Research Institute, Tufts Medical Center, Boston, Massachusetts 02111; and Graduate Program of Environmental and Experimental Pathology (M.M.B.), Graduate Program of Dentistry, Universidade Paulista, Sao Paulo SP 04026-002, Brazil.
Miriam O RibeiroDivision of Endocrinology and Metabolism (B.M.L.C.B., J.P.W.-d.C., G.W.F., T.L.F., E.A.M., A.C.B.), Rush University Medical Center, Chicago, Illinois 60612; Department of Translational Medicine (B.M.L.C.B., G.W.F., B.P.P.N.), Federal University of Sao Paulo, Sao Paulo SP, 04039-002, Brazil; Biophysics Institute and School of Physical Education and Sports (J.P.W.-d.C.), Federal University of Rio de Janeiro, RJ 21941-599, Brazil; Department of Clinic Endocrinology (K.C.O.), Federal University of Sao Paulo, Sao Paulo SP 04039-032, Brazil; Developmental Disorders Program (B.P.P.N., E.R., M.O.R.), Center of Biological Science and Health, Mackenzie Presbyterian University, Sao Paulo SP 01302-900 Brazil; Department of Endocrine Neurobiology (Z.K.-P., C.F., B.G.), Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest H-1083, Hungary; Department of Medicine (C.F.), Division of Endocrinology, Diabetes, and Metabolism, Tupper Research Institute, Tufts Medical Center, Boston, Massachusetts 02111; and Graduate Program of Environmental and Experimental Pathology (M.M.B.), Graduate Program of Dentistry, Universidade Paulista, Sao Paulo SP 04026-002, Brazil.
Rush University Medical Center · USHungarian Academy of Sciences · HUUniversidade Federal de São Paulo · BRUniversidade Presbiteriana Mackenzie · BRUniversidade Federal do Rio de Janeiro · BRUniversidade Paulista · BR

Funding

Metabolic and Xenobiotic Control of Thyroid Hormone MetabolismR01DK077148 · NIDDK · UNIVERSITY OF TEXAS MED BR GALVESTON · PI ANTONIO C BIANCO · 2007 to 2026
$4.5M
NIDDK NIH HHS R01 DK077148
6 · The paper itself

Abstract

Millions of levothyroxine-treated hypothyroid patients complain of impaired cognition despite normal TSH serum levels. This could reflect abnormalities in the type 2 deiodinase (D2)-mediated T4-to-T3 conversion, given their much greater dependence on the D2 pathway for T3 production. T3 normally reaches the brain directly from the circulation or is produced locally by D2 in astrocytes. Here we report that mice with astrocyte-specific Dio2 inactivation (Astro-D2KO) have normal serum T3 but exhibit anxiety-depression-like behavior as found in open field and elevated plus maze studies and when tested for depression using the tail-suspension and the forced-swimming tests. Remarkably, 4 weeks of daily treadmill exercise sessions eliminated this phenotype. Microarray gene expression profiling of the Astro-D2KO hippocampi identified an enrichment of three gene sets related to inflammation and impoverishment of three gene sets related to mitochondrial function and response to oxidative stress. Despite normal neurogenesis, the Astro-D2KO hippocampi exhibited decreased expression of four of six known to be positively regulated genes by T3, ie, Mbp (∼43%), Mag (∼34%), Hr (∼49%), and Aldh1a1 (∼61%) and increased expression of 3 of 12 genes negatively regulated by T3, ie, Dgkg (∼17%), Syce2 (∼26%), and Col6a1 (∼3-fold) by quantitative real-time PCR. Notably, in Astro-D2KO animals, there was also a reduction in mRNA levels of genes known to be affected in classical animal models of depression, ie, Bdnf (∼18%), Ntf3 (∼43%), Nmdar (∼26%), and GR (∼20%), which were also normalized by daily exercise sessions. These findings suggest that defects in Dio2 expression in the brain could result in mood and behavioral disorders.

Indexed as

AnimalsAnxietyAstrocytesDepressionGene ExpressionHindlimb SuspensionHippocampusIodide PeroxidaseIodothyronine Deiodinase Type IIMaleMice, KnockoutPhysical Conditioning, AnimalTranscriptomeTriiodothyronineIodide PeroxidaseIodothyronine Deiodinase Type IITriiodothyronine

Identifiers

PMID27501182
PMCPMC5007895
OpenAlexW2510265237

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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.