Volume 25 Issue 1, January 2019

Volume 25 Issue 1

Medicine in the digital age

As Nature Medicine celebrates its 25th anniversary, we bring our readers a special Focus on Digital Medicine that highlights the new technologies transforming medicine and healthcare, as well as the related regulatory challenges ahead.

See Focus

Image credit: Peter Crowther. Cover design: Erin Dewalt

Editorial

  • Editorial |

    As Nature Medicine celebrates its 25th anniversary, we bring you a special Focus on Digital Medicine that highlights the new technologies transforming medicine and healthcare, as well as the related regulatory challenges ahead.

News Feature

Turning Points

  • Turning Points |

    Rima Arnaout is an assistant professor of cardiology and a member of the University of California San Francisco Bakar Computational Health Sciences Institute. She has received a Chan Zuckerberg Biohub Intercampus Research Award, as well as funding support from the US National Institutes of Health and the American Heart Association’s Institute for Precision Cardiovascular Medicine.

    • Rima Arnaout
  • Turning Points |

    Kee Yuan Ngiam is the group chief technology officer at National University Health System, Singapore, and assistant professor at the School of Medicine of the National University of Singapore. His research focuses on the effects of using artificial intelligence in healthcare. He is the 2018 recipient of Singapore’s National Health IT Excellence Award, which recognizes individuals who advanced healthcare through innovation.

    • Kee Yuan Ngiam

Comment

  • Comment |

    Here we argue that now is the time to create smarter healthcare systems in which the best treatment decisions are computationally learned from electronic health record data by deep-learning methodologies.

    • Beau Norgeot
    • , Benjamin S. Glicksberg
    •  & Atul J. Butte
  • Comment |

    In this Comment, we provide guidelines for reinforcement learning for decisions about patient treatment that we hope will accelerate the rate at which observational cohorts can inform healthcare practice in a safe, risk-conscious manner.

    • Omer Gottesman
    • , Fredrik Johansson
    • , Matthieu Komorowski
    • , Aldo Faisal
    • , David Sontag
    • , Finale Doshi-Velez
    •  & Leo Anthony Celi

Research Highlights

News & Views

Perspectives

Review Articles

Brief Communications

  • Brief Communication |

    An algorithm trained on half a million electronic medical records predicts chronic kidney disease in diabetic patients using a small set of defined clinical features, outperforming predictions derived from clinical trial data.

    • Stefan Ravizza
    • , Tony Huschto
    • , Anja Adamov
    • , Lars Böhm
    • , Alexander Büsser
    • , Frederik F. Flöther
    • , Rolf Hinzmann
    • , Helena König
    • , Scott M. McAhren
    • , Daniel H. Robertson
    • , Titus Schleyer
    • , Bernd Schneidinger
    •  & Wolfgang Petrich

Letters

  • Letter |

    A deep-learning algorithm, trained on over 17,000 real-world patient facial images, achieves high accuracy in identifying rare genetic disorders.

    • Yaron Gurovich
    • , Yair Hanani
    • , Omri Bar
    • , Guy Nadav
    • , Nicole Fleischer
    • , Dekel Gelbman
    • , Lina Basel-Salmon
    • , Peter M. Krawitz
    • , Susanne B. Kamphausen
    • , Martin Zenker
    • , Lynne M. Bird
    •  & Karen W. Gripp
  • Letter |

    A deep learning algorithm applied to the electrocardiogram—a test of the heart’s electrical activity—can detect abnormally low contractile function of the heart, opening up the possibility for a simple screening tool for this condition.

    • Zachi I. Attia
    • , Suraj Kapa
    • , Francisco Lopez-Jimenez
    • , Paul M. McKie
    • , Dorothy J. Ladewig
    • , Gaurav Satam
    • , Patricia A. Pellikka
    • , Maurice Enriquez-Sarano
    • , Peter A. Noseworthy
    • , Thomas M. Munger
    • , Samuel J. Asirvatham
    • , Christopher G. Scott
    • , Rickey E. Carter
    •  & Paul A. Friedman
  • Letter |

    A new population of T helper cells employs unique signals to support autoreactive B cells in patients with systemic lupus erythematosus.

    • Simone Caielli
    • , Diogo Troggian Veiga
    • , Preetha Balasubramanian
    • , Shruti Athale
    • , Bojana Domic
    • , Elise Murat
    • , Romain Banchereau
    • , Zhaohui Xu
    • , Manjari Chandra
    • , Cheng-Han Chung
    • , Lynnette Walters
    • , Jeanine Baisch
    • , Tracey Wright
    • , Marilynn Punaro
    • , Lorien Nassi
    • , Katie Stewart
    • , Julie Fuller
    • , Duygu Ucar
    • , Hideki Ueno
    • , Joseph Zhou
    • , Jacques Banchereau
    •  & Virginia Pascual
  • Letter |

    Intratumoral T cells that are capable of recognizing adjacent tumor tissue antigens can be exceedingly rare.

    • Wouter Scheper
    • , Sander Kelderman
    • , Lorenzo F. Fanchi
    • , Carsten Linnemann
    • , Gavin Bendle
    • , Marije A. J. de Rooij
    • , Christian Hirt
    • , Riccardo Mezzadra
    • , Maarten Slagter
    • , Krijn Dijkstra
    • , Roelof J. C. Kluin
    • , Petur Snaebjornsson
    • , Katy Milne
    • , Brad H. Nelson
    • , Henry Zijlmans
    • , Gemma Kenter
    • , Emile E. Voest
    • , John B. A. G. Haanen
    •  & Ton N. Schumacher
  • Letter |

    RNA editing enzyme ADAR1 is a therapeutic vulnerability in tumors with constitutive cell-autonomous production of interferon-stimulated genes

    • Huayang Liu
    • , Javad Golji
    • , Lauren K. Brodeur
    • , Franklin S. Chung
    • , Julie T. Chen
    • , Rosalie S. deBeaumont
    • , Caroline P. Bullock
    • , Michael D. Jones
    • , Grainne Kerr
    • , Li Li
    • , Daniel P. Rakiec
    • , Michael R. Schlabach
    • , Sosathya Sovath
    • , Joseph D. Growney
    • , Raymond A. Pagliarini
    • , David A. Ruddy
    • , Kenzie D. MacIsaac
    • , Joshua M. Korn
    •  & E. Robert McDonald III
  • Letter |

    High-resolution sequencing of longitudinal patient samples reveals subclonal mutational diversity in the stem cell compartment driving parallel evolution patterns in acute myeloid leukemia progression.

    • Jiahao Chen
    • , Yun-Ruei Kao
    • , Daqian Sun
    • , Tihomira I. Todorova
    • , David Reynolds
    • , Swathi-Rao Narayanagari
    • , Cristina Montagna
    • , Britta Will
    • , Amit Verma
    •  & Ulrich Steidl
  • Letter |

    Nongenetic activation of Aurora kinase A in the majority of patients with non-small-cell lung cancer mediates adaptive resistance to EGFR inhibition and offers an opportunity for combination treatment.

    • Khyati N. Shah
    • , Roma Bhatt
    • , Julia Rotow
    • , Julia Rohrberg
    • , Victor Olivas
    • , Victoria E. Wang
    • , Golzar Hemmati
    • , Maria M. Martins
    • , Ashley Maynard
    • , Jonathan Kuhn
    • , Jacqueline Galeas
    • , Hayley J. Donnella
    • , Swati Kaushik
    • , Angel Ku
    • , Sophie Dumont
    • , Gregor Krings
    • , Henry J. Haringsma
    • , Liliane Robillard
    • , Andrew D. Simmons
    • , Thomas C. Harding
    • , Frank McCormick
    • , Andrei Goga
    • , Collin M. Blakely
    • , Trever G. Bivona
    •  & Sourav Bandyopadhyay

Articles

  • Article |

    Molecular alterations in ctDNA of patients with mantle cell lymphoma uncovers mutations in SWI–SNF associated with resistance to ibrutinib and venetoclax combination and provide a rationale for restoring sensitivity through Bcl-xL inhibition.

    • Rishu Agarwal
    • , Yih-Chih Chan
    • , Constantine S. Tam
    • , Tane Hunter
    • , Dane Vassiliadis
    • , Charis E. Teh
    • , Rachel Thijssen
    • , Paul Yeh
    • , Stephen Q. Wong
    • , Sarah Ftouni
    • , Enid Y. N. Lam
    • , Mary Ann Anderson
    • , Christiane Pott
    • , Omer Gilan
    • , Charles C. Bell
    • , Kathy Knezevic
    • , Piers Blombery
    • , Kathleen Rayeroux
    • , Adrian Zordan
    • , Jason Li
    • , David C. S. Huang
    • , Meaghan Wall
    • , John F. Seymour
    • , Daniel H. D. Gray
    • , Andrew W. Roberts
    • , Mark A. Dawson
    •  & Sarah-Jane Dawson
  • Article |

    WASP is a novel tumor-suppressor gene in ALK-driven anaplastic large cell lymphoma through modulation of CDC42 and MAPK signaling and provides a rationale for combination therapy.

    • Matteo Menotti
    • , Chiara Ambrogio
    • , Taek-Chin Cheong
    • , Chiara Pighi
    • , Ines Mota
    • , Seth H. Cassel
    • , Mara Compagno
    • , Qi Wang
    • , Riccardo Dall’Olio
    • , Valerio G. Minero
    • , Teresa Poggio
    • , Geeta Geeta Sharma
    • , Enrico Patrucco
    • , Cristina Mastini
    • , Ramesh Choudhari
    • , Achille Pich
    • , Alberto Zamo
    • , Roberto Piva
    • , Silvia Giliani
    • , Luca Mologni
    • , Clayton K. Collings
    • , Cigall Kadoch
    • , Carlo Gambacorti-Passerini
    • , Luigi D. Notarangelo
    • , Ines M. Anton
    • , Claudia Voena
    •  & Roberto Chiarle
  • Article |

    Obesity promotes tumor growth yet simultaneously increases susceptibility to PD-1-targeted cancer immunotherapy.

    • Ziming Wang
    • , Ethan G. Aguilar
    • , Jesus I. Luna
    • , Cordelia Dunai
    • , Lam T. Khuat
    • , Catherine T. Le
    • , Annie Mirsoian
    • , Christine M. Minnar
    • , Kevin M. Stoffel
    • , Ian R. Sturgill
    • , Steven K. Grossenbacher
    • , Sita S. Withers
    • , Robert B. Rebhun
    • , Dennis J. Hartigan-O’Connor
    • , Gema Méndez-Lagares
    • , Alice F. Tarantal
    • , R. Rivkah Isseroff
    • , Thomas S. Griffith
    • , Kurt A. Schalper
    • , Alexander Merleev
    • , Asim Saha
    • , Emanual Maverakis
    • , Karen Kelly
    • , Raid Aljumaily
    • , Sami Ibrahimi
    • , Sarbajit Mukherjee
    • , Michael Machiorlatti
    • , Sara K. Vesely
    • , Dan L. Longo
    • , Bruce R. Blazar
    • , Robert J. Canter
    • , William J. Murphy
    •  & Arta M. Monjazeb
  • Article |

    Evolutionarily conserved gene modules mediate neurodegenerative dementia in a variety of mouse models and in postmortem brain tissue from patients.

    • Vivek Swarup
    • , Flora I. Hinz
    • , Jessica E. Rexach
    • , Ken-ichi Noguchi
    • , Hiroyoshi Toyoshiba
    • , Akira Oda
    • , Keisuke Hirai
    • , Arjun Sarkar
    • , Nicholas T. Seyfried
    • , Chialin Cheng
    • , Stephen J. Haggarty
    • , Raffaele Ferrari
    • , Jonathan D. Rohrer
    • , Adaikalavan Ramasamy
    • , John Hardy
    • , Dena G. Hernandez
    • , Michael A. Nalls
    • , Andrew B. Singleton
    • , John B. J. Kwok
    • , Carol Dobson-Stone
    • , William S. Brooks
    • , Peter R. Schofield
    • , Glenda M. Halliday
    • , John R. Hodges
    • , Olivier Piguet
    • , Lauren Bartley
    • , Elizabeth Thompson
    • , Eric Haan
    • , Isabel Hernández
    • , Agustín Ruiz
    • , Mercè Boada
    • , Barbara Borroni
    • , Alessandro Padovani
    • , Nigel J. Cairns
    • , Carlos Cruchaga
    • , Giuliano Binetti
    • , Roberta Ghidoni
    • , Luisa Benussi
    • , Gianluigi Forloni
    • , Diego Albani
    • , Daniela Galimberti
    • , Chiara Fenoglio
    • , Maria Serpente
    • , Elio Scarpini
    • , Jordi Clarimón
    • , Alberto Lleó
    • , Rafael Blesa
    • , Maria Landqvist Waldö
    • , Karin Nilsson
    • , Christer Nilsson
    • , Ian R. A. Mackenzie
    • , Ging-Yuek R. Hsiung
    • , David M. A. Mann
    • , Jordan Grafman
    • , Christopher M. Morris
    • , Johannes Attems
    • , Timothy D. Griffiths
    • , Ian G. McKeith
    • , Alan J. Thomas
    • , Evelyn Jaros
    • , Pietro Pietrini
    • , Edward D. Huey
    • , Eric M. Wassermann
    • , Michael C. Tierney
    • , Atik Baborie
    • , Pau Pastor
    • , Sara Ortega-Cubero
    • , Cristina Razquin
    • , Elena Alonso
    • , Robert Perneczky
    • , Janine Diehl-Schmid
    • , Panagiotis Alexopoulos
    • , Alexander Kurz
    • , Innocenzo Rainero
    • , Elisa Rubino
    • , Lorenzo Pinessi
    • , Ekaterina Rogaeva
    • , Peter St. George-Hyslop
    • , Giacomina Rossi
    • , Fabrizio Tagliavini
    • , Giorgio Giaccone
    • , James B. Rowe
    • , Johannes C. M. Schlachetzki
    • , James Uphill
    • , John Collinge
    • , Simon Mead
    • , Adrian Danek
    • , Vivianna M. Van Deerlin
    • , Murray Grossman
    • , John Q. Trojanowski
    • , Stuart Pickering-Brown
    • , Parastoo Momeni
    • , Julie van der Zee
    • , Marc Cruts
    • , Christine Van Broeckhoven
    • , Stefano F. Cappa
    • , Isabelle Leber
    • , Alexis Brice
    • , Didier Hannequin
    • , Véronique Golfier
    • , Martine Vercelletto
    • , Benedetta Nacmias
    • , Sandro Sorbi
    • , Silvia Bagnoli
    • , Irene Piaceri
    • , Jørgen E. Nielsen
    • , Lena E. Hjermind
    • , Matthias Riemenschneider
    • , Manuel Mayhaus
    • , Gilles Gasparoni
    • , Sabrina Pichler
    • , Bernd Ibach
    • , Martin N. Rossor
    • , Nick C. Fox
    • , Jason D. Warren
    • , Maria Grazia Spillantini
    • , Huw R. Morris
    • , Patrizia Rizzu
    • , Peter Heutink
    • , Julie S. Snowden
    • , Sara Rollinson
    • , Alexander Gerhard
    • , Anna Richardson
    • , Amalia C. Bruni
    • , Raffaele Maletta
    • , Francesca Frangipane
    • , Chiara Cupidi
    • , Livia Bernardi
    • , Maria Anfossi
    • , Maura Gallo
    • , Maria Elena Conidi
    • , Nicoletta Smirne
    • , Rosa Rademakers
    • , Matt Baker
    • , Dennis W. Dickson
    • , Neill R. Graff-Radford
    • , Ronald C. Petersen
    • , David Knopman
    • , Keith A. Josephs
    • , Bradley F. Boeve
    • , Joseph E. Parisi
    • , Bruce L. Miller
    • , Anna M. Karydas
    • , Howard Rosen
    • , William W. Seeley
    • , John C. van Swieten
    • , Elise G. P. Dopper
    • , Harro Seelaar
    • , Yolande A. L. Pijnenburg
    • , Philip Scheltens
    • , Giancarlo Logroscino
    • , Rosa Capozzo
    • , Valeria Novelli
    • , Annibale A. Puca
    • , Massimo Franceschi
    • , Alfredo Postiglione
    • , Graziella Milan
    • , Paolo Sorrentino
    • , Mark Kristiansen
    • , Huei-Hsin Chiang
    • , Caroline Graff
    • , Florence Pasquier
    • , Adeline Rollin
    • , Vincent Deramecourt
    • , Thibaud Lebouvier
    • , Luigi Ferrucci
    • , Dimitrios Kapogiannis
    • , Murray Grossman
    • , Vivianna M. Van Deerlin
    • , John Q. Trojanowski
    • , James J. Lah
    • , Allan I. Levey
    • , Shinichi Kondou
    •  & Daniel H. Geschwind
  • Article |

    Expression of the exercise-induced myokine irisin (FNDC5) is lower in patients with AD. Whereas knockdown of FNDC5/irisin is sufficient to induce learning and memory deficits, restoration of its expression can ameliorate these phenotypes in rodent models.

    • Mychael V. Lourenco
    • , Rudimar L. Frozza
    • , Guilherme B. de Freitas
    • , Hong Zhang
    • , Grasielle C. Kincheski
    • , Felipe C. Ribeiro
    • , Rafaella A. Gonçalves
    • , Julia R. Clarke
    • , Danielle Beckman
    • , Agnieszka Staniszewski
    • , Hanna Berman
    • , Lorena A. Guerra
    • , Letícia Forny-Germano
    • , Shelby Meier
    • , Donna M. Wilcock
    • , Jorge M. de Souza
    • , Soniza Alves-Leon
    • , Vania F. Prado
    • , Marco A. M. Prado
    • , Jose F. Abisambra
    • , Fernanda Tovar-Moll
    • , Paulo Mattos
    • , Ottavio Arancio
    • , Sergio T. Ferreira
    •  & Fernanda G. De Felice

Resources

  • Resource |

    An integrated analysis of glioma samples from patients with neurofibromatosis 1 annotates their mutational, epigenetic, transcriptional, and immunological features and uncovers similitudes with a subset of sporadic gliomas.

    • Fulvio D’Angelo
    • , Michele Ceccarelli
    • , Tala
    • , Luciano Garofano
    • , Jing Zhang
    • , Véronique Frattini
    • , Francesca P. Caruso
    • , Genevieve Lewis
    • , Kristin D. Alfaro
    • , Luc Bauchet
    • , Giulia Berzero
    • , David Cachia
    • , Mario Cangiano
    • , Laurent Capelle
    • , John de Groot
    • , Francesco DiMeco
    • , François Ducray
    • , Walid Farah
    • , Gaetano Finocchiaro
    • , Stéphane Goutagny
    • , Carlos Kamiya-Matsuoka
    • , Cinzia Lavarino
    • , Hugues Loiseau
    • , Véronique Lorgis
    • , Carlo E. Marras
    • , Ian McCutcheon
    • , Do-Hyun Nam
    • , Susanna Ronchi
    • , Veronica Saletti
    • , Romuald Seizeur
    • , John Slopis
    • , Mariona Suñol
    • , Fanny Vandenbos
    • , Pascale Varlet
    • , Dominique Vidaud
    • , Colin Watts
    • , Viviane Tabar
    • , David E. Reuss
    • , Seung-Ki Kim
    • , David Meyronet
    • , Karima Mokhtari
    • , Hector Salvador
    • , Krishna P. Bhat
    • , Marica Eoli
    • , Marc Sanson
    • , Anna Lasorella
    •  & Antonio Iavarone

Amendments & Corrections