Evidence map›Paper›PMID 26884555›Full record

ArticleJournal of clinical oncology : official journal of the American Society of Clinical Oncology2016

Phase I Study of the Aurora A Kinase Inhibitor Alisertib in Combination With Irinotecan and Temozolomide for Patients With Relapsed or Refractory Neuroblastoma: A NANT (New Approaches to Neuroblastoma Therapy) Trial.

Steven G DuBois, Araz Marachelian, Elizabeth Fox, Rachel A Kudgus, Joel M Reid, Susan Groshen, Jemily Malvar, Rochelle Bagatell, Lars Wagner, John M Maris and 9 more

Abstract readClinical Trial, Phase IMulticenter Study
In one paragraph

Article in Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.

0numbers the graph read from it
0cells of the map it votes in
75citing papers in PubMed
13.2field-weighted citation impact, top 1% 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

75 citing papers in PubMed, 132 citations in OpenAlex.

  1. Trial
  2. Phase II Trial of Alisertib in Combination with Irinotecan and Temozolomide for Patients with Relapsed or Refractory Neuroblastoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2018
    Trial
  3. Trial
  4. Review
  5. Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Review
  11. Article
  12. Comparison ofHeliyon · 2024
    Article
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  14. Review
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  16. Article
  17. Review
  18. Article
  19. Combination Early-Phase Trials of Anticancer Agents in Children and Adolescents.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2023
    Review
  20. Article

15 more citing papers are in PubMed but not listed here.

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

19 authors at 1 institution in 1 country.

Steven G DuBoisSteven G. DuBois, Dana-Farber/Boston Children's Cancer and Blood Disorders Center and Harvard Medical School, Boston, MA; Araz Marachelian, Susan Groshen, Jemily Malvar, Hollie Lai, Fariba Goodarzian, Hiroyuki Shimada, Scarlett Czarnecki, and Denice Tsao-Wei, University of Southern California Keck School of Medicine and Children's Hospital Los Angeles, Los Angeles; Randall Hawkins, Jesse Courtier, and Katherine K. Matthay, University of California, San Francisco, School of Medicine and Benioff Children's Hospital, San Francisco, CA; Elizabeth Fox, Rochelle Bagatell, John M. Maris, and Yael P. Mosse, Children's Hospital of Philadelphia and University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; Rachel A. Kudgus and Joel M. Reid, Mayo Clinic, Rochester, MN; and Lars Wagner, University of Kentucky College of Medicine, Lexington, KY. steven_dubois@dfci.harvard.edu.
Araz MarachelianSteven G. DuBois, Dana-Farber/Boston Children's Cancer and Blood Disorders Center and Harvard Medical School, Boston, MA; Araz Marachelian, Susan Groshen, Jemily Malvar, Hollie Lai, Fariba Goodarzian, Hiroyuki Shimada, Scarlett Czarnecki, and Denice Tsao-Wei, University of Southern California Keck School of Medicine and Children's Hospital Los Angeles, Los Angeles; Randall Hawkins, Jesse Courtier, and Katherine K. Matthay, University of California, San Francisco, School of Medicine and Benioff Children's Hospital, San Francisco, CA; Elizabeth Fox, Rochelle Bagatell, John M. Maris, and Yael P. Mosse, Children's Hospital of Philadelphia and University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; Rachel A. Kudgus and Joel M. Reid, Mayo Clinic, Rochester, MN; and Lars Wagner, University of Kentucky College of Medicine, Lexington, KY.
Elizabeth FoxSteven G. DuBois, Dana-Farber/Boston Children's Cancer and Blood Disorders Center and Harvard Medical School, Boston, MA; Araz Marachelian, Susan Groshen, Jemily Malvar, Hollie Lai, Fariba Goodarzian, Hiroyuki Shimada, Scarlett Czarnecki, and Denice Tsao-Wei, University of Southern California Keck School of Medicine and Children's Hospital Los Angeles, Los Angeles; Randall Hawkins, Jesse Courtier, and Katherine K. Matthay, University of California, San Francisco, School of Medicine and Benioff Children's Hospital, San Francisco, CA; Elizabeth Fox, Rochelle Bagatell, John M. Maris, and Yael P. Mosse, Children's Hospital of Philadelphia and University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; Rachel A. Kudgus and Joel M. Reid, Mayo Clinic, Rochester, MN; and Lars Wagner, University of Kentucky College of Medicine, Lexington, KY.
Rachel A KudgusSteven G. DuBois, Dana-Farber/Boston Children's Cancer and Blood Disorders Center and Harvard Medical School, Boston, MA; Araz Marachelian, Susan Groshen, Jemily Malvar, Hollie Lai, Fariba Goodarzian, Hiroyuki Shimada, Scarlett Czarnecki, and Denice Tsao-Wei, University of Southern California Keck School of Medicine and Children's Hospital Los Angeles, Los Angeles; Randall Hawkins, Jesse Courtier, and Katherine K. Matthay, University of California, San Francisco, School of Medicine and Benioff Children's Hospital, San Francisco, CA; Elizabeth Fox, Rochelle Bagatell, John M. Maris, and Yael P. Mosse, Children's Hospital of Philadelphia and University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; Rachel A. Kudgus and Joel M. Reid, Mayo Clinic, Rochester, MN; and Lars Wagner, University of Kentucky College of Medicine, Lexington, KY.
Joel M ReidSteven G. DuBois, Dana-Farber/Boston Children's Cancer and Blood Disorders Center and Harvard Medical School, Boston, MA; Araz Marachelian, Susan Groshen, Jemily Malvar, Hollie Lai, Fariba Goodarzian, Hiroyuki Shimada, Scarlett Czarnecki, and Denice Tsao-Wei, University of Southern California Keck School of Medicine and Children's Hospital Los Angeles, Los Angeles; Randall Hawkins, Jesse Courtier, and Katherine K. Matthay, University of California, San Francisco, School of Medicine and Benioff Children's Hospital, San Francisco, CA; Elizabeth Fox, Rochelle Bagatell, John M. Maris, and Yael P. Mosse, Children's Hospital of Philadelphia and University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; Rachel A. Kudgus and Joel M. Reid, Mayo Clinic, Rochester, MN; and Lars Wagner, University of Kentucky College of Medicine, Lexington, KY.
Susan GroshenSteven G. DuBois, Dana-Farber/Boston Children's Cancer and Blood Disorders Center and Harvard Medical School, Boston, MA; Araz Marachelian, Susan Groshen, Jemily Malvar, Hollie Lai, Fariba Goodarzian, Hiroyuki Shimada, Scarlett Czarnecki, and Denice Tsao-Wei, University of Southern California Keck School of Medicine and Children's Hospital Los Angeles, Los Angeles; Randall Hawkins, Jesse Courtier, and Katherine K. Matthay, University of California, San Francisco, School of Medicine and Benioff Children's Hospital, San Francisco, CA; Elizabeth Fox, Rochelle Bagatell, John M. Maris, and Yael P. Mosse, Children's Hospital of Philadelphia and University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; Rachel A. Kudgus and Joel M. Reid, Mayo Clinic, Rochester, MN; and Lars Wagner, University of Kentucky College of Medicine, Lexington, KY.
Jemily MalvarSteven G. DuBois, Dana-Farber/Boston Children's Cancer and Blood Disorders Center and Harvard Medical School, Boston, MA; Araz Marachelian, Susan Groshen, Jemily Malvar, Hollie Lai, Fariba Goodarzian, Hiroyuki Shimada, Scarlett Czarnecki, and Denice Tsao-Wei, University of Southern California Keck School of Medicine and Children's Hospital Los Angeles, Los Angeles; Randall Hawkins, Jesse Courtier, and Katherine K. Matthay, University of California, San Francisco, School of Medicine and Benioff Children's Hospital, San Francisco, CA; Elizabeth Fox, Rochelle Bagatell, John M. Maris, and Yael P. Mosse, Children's Hospital of Philadelphia and University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; Rachel A. Kudgus and Joel M. Reid, Mayo Clinic, Rochester, MN; and Lars Wagner, University of Kentucky College of Medicine, Lexington, KY.
Rochelle BagatellSteven G. DuBois, Dana-Farber/Boston Children's Cancer and Blood Disorders Center and Harvard Medical School, Boston, MA; Araz Marachelian, Susan Groshen, Jemily Malvar, Hollie Lai, Fariba Goodarzian, Hiroyuki Shimada, Scarlett Czarnecki, and Denice Tsao-Wei, University of Southern California Keck School of Medicine and Children's Hospital Los Angeles, Los Angeles; Randall Hawkins, Jesse Courtier, and Katherine K. Matthay, University of California, San Francisco, School of Medicine and Benioff Children's Hospital, San Francisco, CA; Elizabeth Fox, Rochelle Bagatell, John M. Maris, and Yael P. Mosse, Children's Hospital of Philadelphia and University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; Rachel A. Kudgus and Joel M. Reid, Mayo Clinic, Rochester, MN; and Lars Wagner, University of Kentucky College of Medicine, Lexington, KY.
Lars WagnerSteven G. DuBois, Dana-Farber/Boston Children's Cancer and Blood Disorders Center and Harvard Medical School, Boston, MA; Araz Marachelian, Susan Groshen, Jemily Malvar, Hollie Lai, Fariba Goodarzian, Hiroyuki Shimada, Scarlett Czarnecki, and Denice Tsao-Wei, University of Southern California Keck School of Medicine and Children's Hospital Los Angeles, Los Angeles; Randall Hawkins, Jesse Courtier, and Katherine K. Matthay, University of California, San Francisco, School of Medicine and Benioff Children's Hospital, San Francisco, CA; Elizabeth Fox, Rochelle Bagatell, John M. Maris, and Yael P. Mosse, Children's Hospital of Philadelphia and University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; Rachel A. Kudgus and Joel M. Reid, Mayo Clinic, Rochester, MN; and Lars Wagner, University of Kentucky College of Medicine, Lexington, KY.
John M MarisSteven G. DuBois, Dana-Farber/Boston Children's Cancer and Blood Disorders Center and Harvard Medical School, Boston, MA; Araz Marachelian, Susan Groshen, Jemily Malvar, Hollie Lai, Fariba Goodarzian, Hiroyuki Shimada, Scarlett Czarnecki, and Denice Tsao-Wei, University of Southern California Keck School of Medicine and Children's Hospital Los Angeles, Los Angeles; Randall Hawkins, Jesse Courtier, and Katherine K. Matthay, University of California, San Francisco, School of Medicine and Benioff Children's Hospital, San Francisco, CA; Elizabeth Fox, Rochelle Bagatell, John M. Maris, and Yael P. Mosse, Children's Hospital of Philadelphia and University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; Rachel A. Kudgus and Joel M. Reid, Mayo Clinic, Rochester, MN; and Lars Wagner, University of Kentucky College of Medicine, Lexington, KY.
Randall HawkinsSteven G. DuBois, Dana-Farber/Boston Children's Cancer and Blood Disorders Center and Harvard Medical School, Boston, MA; Araz Marachelian, Susan Groshen, Jemily Malvar, Hollie Lai, Fariba Goodarzian, Hiroyuki Shimada, Scarlett Czarnecki, and Denice Tsao-Wei, University of Southern California Keck School of Medicine and Children's Hospital Los Angeles, Los Angeles; Randall Hawkins, Jesse Courtier, and Katherine K. Matthay, University of California, San Francisco, School of Medicine and Benioff Children's Hospital, San Francisco, CA; Elizabeth Fox, Rochelle Bagatell, John M. Maris, and Yael P. Mosse, Children's Hospital of Philadelphia and University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; Rachel A. Kudgus and Joel M. Reid, Mayo Clinic, Rochester, MN; and Lars Wagner, University of Kentucky College of Medicine, Lexington, KY.
Jesse CourtierSteven G. DuBois, Dana-Farber/Boston Children's Cancer and Blood Disorders Center and Harvard Medical School, Boston, MA; Araz Marachelian, Susan Groshen, Jemily Malvar, Hollie Lai, Fariba Goodarzian, Hiroyuki Shimada, Scarlett Czarnecki, and Denice Tsao-Wei, University of Southern California Keck School of Medicine and Children's Hospital Los Angeles, Los Angeles; Randall Hawkins, Jesse Courtier, and Katherine K. Matthay, University of California, San Francisco, School of Medicine and Benioff Children's Hospital, San Francisco, CA; Elizabeth Fox, Rochelle Bagatell, John M. Maris, and Yael P. Mosse, Children's Hospital of Philadelphia and University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; Rachel A. Kudgus and Joel M. Reid, Mayo Clinic, Rochester, MN; and Lars Wagner, University of Kentucky College of Medicine, Lexington, KY.
Hollie LaiSteven G. DuBois, Dana-Farber/Boston Children's Cancer and Blood Disorders Center and Harvard Medical School, Boston, MA; Araz Marachelian, Susan Groshen, Jemily Malvar, Hollie Lai, Fariba Goodarzian, Hiroyuki Shimada, Scarlett Czarnecki, and Denice Tsao-Wei, University of Southern California Keck School of Medicine and Children's Hospital Los Angeles, Los Angeles; Randall Hawkins, Jesse Courtier, and Katherine K. Matthay, University of California, San Francisco, School of Medicine and Benioff Children's Hospital, San Francisco, CA; Elizabeth Fox, Rochelle Bagatell, John M. Maris, and Yael P. Mosse, Children's Hospital of Philadelphia and University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; Rachel A. Kudgus and Joel M. Reid, Mayo Clinic, Rochester, MN; and Lars Wagner, University of Kentucky College of Medicine, Lexington, KY.
Fariba GoodarzianSteven G. DuBois, Dana-Farber/Boston Children's Cancer and Blood Disorders Center and Harvard Medical School, Boston, MA; Araz Marachelian, Susan Groshen, Jemily Malvar, Hollie Lai, Fariba Goodarzian, Hiroyuki Shimada, Scarlett Czarnecki, and Denice Tsao-Wei, University of Southern California Keck School of Medicine and Children's Hospital Los Angeles, Los Angeles; Randall Hawkins, Jesse Courtier, and Katherine K. Matthay, University of California, San Francisco, School of Medicine and Benioff Children's Hospital, San Francisco, CA; Elizabeth Fox, Rochelle Bagatell, John M. Maris, and Yael P. Mosse, Children's Hospital of Philadelphia and University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; Rachel A. Kudgus and Joel M. Reid, Mayo Clinic, Rochester, MN; and Lars Wagner, University of Kentucky College of Medicine, Lexington, KY.
Hiroyuki ShimadaSteven G. DuBois, Dana-Farber/Boston Children's Cancer and Blood Disorders Center and Harvard Medical School, Boston, MA; Araz Marachelian, Susan Groshen, Jemily Malvar, Hollie Lai, Fariba Goodarzian, Hiroyuki Shimada, Scarlett Czarnecki, and Denice Tsao-Wei, University of Southern California Keck School of Medicine and Children's Hospital Los Angeles, Los Angeles; Randall Hawkins, Jesse Courtier, and Katherine K. Matthay, University of California, San Francisco, School of Medicine and Benioff Children's Hospital, San Francisco, CA; Elizabeth Fox, Rochelle Bagatell, John M. Maris, and Yael P. Mosse, Children's Hospital of Philadelphia and University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; Rachel A. Kudgus and Joel M. Reid, Mayo Clinic, Rochester, MN; and Lars Wagner, University of Kentucky College of Medicine, Lexington, KY.
Scarlett CzarneckiSteven G. DuBois, Dana-Farber/Boston Children's Cancer and Blood Disorders Center and Harvard Medical School, Boston, MA; Araz Marachelian, Susan Groshen, Jemily Malvar, Hollie Lai, Fariba Goodarzian, Hiroyuki Shimada, Scarlett Czarnecki, and Denice Tsao-Wei, University of Southern California Keck School of Medicine and Children's Hospital Los Angeles, Los Angeles; Randall Hawkins, Jesse Courtier, and Katherine K. Matthay, University of California, San Francisco, School of Medicine and Benioff Children's Hospital, San Francisco, CA; Elizabeth Fox, Rochelle Bagatell, John M. Maris, and Yael P. Mosse, Children's Hospital of Philadelphia and University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; Rachel A. Kudgus and Joel M. Reid, Mayo Clinic, Rochester, MN; and Lars Wagner, University of Kentucky College of Medicine, Lexington, KY.
Denice Tsao-WeiSteven G. DuBois, Dana-Farber/Boston Children's Cancer and Blood Disorders Center and Harvard Medical School, Boston, MA; Araz Marachelian, Susan Groshen, Jemily Malvar, Hollie Lai, Fariba Goodarzian, Hiroyuki Shimada, Scarlett Czarnecki, and Denice Tsao-Wei, University of Southern California Keck School of Medicine and Children's Hospital Los Angeles, Los Angeles; Randall Hawkins, Jesse Courtier, and Katherine K. Matthay, University of California, San Francisco, School of Medicine and Benioff Children's Hospital, San Francisco, CA; Elizabeth Fox, Rochelle Bagatell, John M. Maris, and Yael P. Mosse, Children's Hospital of Philadelphia and University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; Rachel A. Kudgus and Joel M. Reid, Mayo Clinic, Rochester, MN; and Lars Wagner, University of Kentucky College of Medicine, Lexington, KY.
Katherine K MatthaySteven G. DuBois, Dana-Farber/Boston Children's Cancer and Blood Disorders Center and Harvard Medical School, Boston, MA; Araz Marachelian, Susan Groshen, Jemily Malvar, Hollie Lai, Fariba Goodarzian, Hiroyuki Shimada, Scarlett Czarnecki, and Denice Tsao-Wei, University of Southern California Keck School of Medicine and Children's Hospital Los Angeles, Los Angeles; Randall Hawkins, Jesse Courtier, and Katherine K. Matthay, University of California, San Francisco, School of Medicine and Benioff Children's Hospital, San Francisco, CA; Elizabeth Fox, Rochelle Bagatell, John M. Maris, and Yael P. Mosse, Children's Hospital of Philadelphia and University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; Rachel A. Kudgus and Joel M. Reid, Mayo Clinic, Rochester, MN; and Lars Wagner, University of Kentucky College of Medicine, Lexington, KY.
Yael P MosseSteven G. DuBois, Dana-Farber/Boston Children's Cancer and Blood Disorders Center and Harvard Medical School, Boston, MA; Araz Marachelian, Susan Groshen, Jemily Malvar, Hollie Lai, Fariba Goodarzian, Hiroyuki Shimada, Scarlett Czarnecki, and Denice Tsao-Wei, University of Southern California Keck School of Medicine and Children's Hospital Los Angeles, Los Angeles; Randall Hawkins, Jesse Courtier, and Katherine K. Matthay, University of California, San Francisco, School of Medicine and Benioff Children's Hospital, San Francisco, CA; Elizabeth Fox, Rochelle Bagatell, John M. Maris, and Yael P. Mosse, Children's Hospital of Philadelphia and University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; Rachel A. Kudgus and Joel M. Reid, Mayo Clinic, Rochester, MN; and Lars Wagner, University of Kentucky College of Medicine, Lexington, KY.
Dana-Farber/Boston Children's Cancer and Blood Disorders Center · US

Funding

UCSF CLINICAL AND TRANSLATIONAL SCIENCE INSTITUTEUL1RR024131 · NCRR · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI JOHNSTON, S. CLAIBORNE · 2006 to 2011
$111.2M
Vascular endothelial cell integrins in angiogenesisP01CA081403 · NCI · CHILDREN'S HOSPITAL OF LOS ANGELES · PI SEEGER, ROBERT CHARLES · 2000 to 2014
$28.5M
Tumor microenvironment-dependent therapy resistanceP01CA217959 · NCI · CHILDREN'S HOSP OF PHILADELPHIA · PI Kimberly Stegmaier · 2017 to 2026
$20.7M
NCI NIH HHS P01 CA217959NCI NIH HHS P01 CA81403NCRR NIH HHS UL1 RR024131
6 · The paper itself

Abstract

purposeAlisertib is an oral Aurora A kinase inhibitor with preclinical activity in neuroblastoma. Irinotecan and temozolomide have activity in patients with advanced neuroblastoma. The goal of this phase I study was to determine the maximum tolerated dose (MTD) of alisertib with irinotecan and temozolomide in this population. PATIENTS AND

methodsPatients age 1 to 30 years with relapsed or refractory neuroblastoma were eligible. Patients received alisertib tablets at dose levels of 45, 60, and 80 mg/m(2) per day on days 1 to 7 along with irinotecan 50 mg/m(2) intravenously and temozolomide 100 mg/m(2) orally on days 1 to 5. Dose escalation of alisertib followed the rolling six design. Samples for pharmacokinetic and pharmacogenomic testing were obtained.

resultsTwenty-three patients enrolled, and 22 were eligible and evaluable for dose escalation. A total of 244 courses were administered. The MTD for alisertib was 60 mg/m(2), with mandatory myeloid growth factor support and cephalosporin prophylaxis for diarrhea. Thrombocytopenia and neutropenia of any grade were seen in the majority of courses (84% and 69%, respectively). Diarrhea in 55% of courses and nausea in 54% of courses were the most common nonhematologic toxicities. The overall response rate was 31.8%, with a 50% response rate observed at the MTD. The median number of courses per patient was eight (range, two to 32). Progression-free survival rate at 2 years was 52.4%. Pharmacokinetic testing did not show evidence of drug-drug interaction between irinotecan and alisertib.

conclusionAlisertib 60 mg/m(2) per dose for 7 days is tolerable with a standard irinotecan and temozolomide backbone and has promising response and progression-free survival rates. A phase II trial of this regimen is ongoing.

Indexed as

Administration, OralAdolescentAdultAntineoplastic Combined Chemotherapy ProtocolsAurora Kinase AAzepinesCamptothecinChildChild, PreschoolDacarbazineDisease-Free SurvivalDisease ProgressionDrug Administration ScheduleDrug Resistance, NeoplasmFemaleGenotypeAURKA protein, humanAurora Kinase AAzepinesCamptothecinDacarbazineGlucuronosyltransferaseIrinotecanMLN 8237Protein Kinase InhibitorsPyrimidinesTabletsTemozolomideUGT1A1 Enzyme

Identifiers

PMID26884555
PMCPMC4872349
OpenAlexW2274409794

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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.