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Nature Medicine

Sunad Rangarajan, Nathaniel B Bone, Anna A Zmijewska, Shaoning Jiang, Dae Won Park, Karen Bernard, Morgan L Locy, Saranya Ravi, Jessy Deshane, Roslyn B Mannon, Edward Abraham, Victor Darley-Usmar, Victor J Thannickal, Jaroslaw W Zmijewski
In the version of this article originally published, a grant was omitted from the Acknowledgements section. The following sentence should have been included: "R.B.M. was supported by a Department of Veterans Affairs Merit Award (5I01BX003272)." The error has been corrected in the HTML and PDF versions of this article.
August 13, 2018: Nature Medicine
Yonathan Lissanu Deribe, Yuting Sun, Christopher Terranova, Fatima Khan, Juan Martinez-Ledesma, Jason Gay, Guang Gao, Robert A Mullinax, Tin Khor, Ningping Feng, Yu-Hsi Lin, Chia-Chin Wu, Claudia Reyes, Qian Peng, Frederick Robinson, Akira Inoue, Veena Kochat, Chang-Gong Liu, John M Asara, Cesar Moran, Florian Muller, Jing Wang, Bingliang Fang, Vali Papadimitrakopoulou, Ignacio I Wistuba, Kunal Rai, Joseph Marszalek, P Andrew Futreal
In the version of this article originally published, information regarding several funding sources was omitted from the Acknowledgements section. The following sentences should have been included: "This work was supported by the generous philanthropic contributions to The University of Texas MD Anderson Lung Cancer Moon Shots Program, the UT Lung SPORE 5 P50 CA07090, and the MD Anderson Cancer Center Support Grant P30CA01667. V.P is supported by R01CA155196-01A1 from the National Cancer Institute." Also, reference 18 was incorrect...
August 13, 2018: Nature Medicine
Jeffrey De Fauw, Joseph R Ledsam, Bernardino Romera-Paredes, Stanislav Nikolov, Nenad Tomasev, Sam Blackwell, Harry Askham, Xavier Glorot, Brendan O'Donoghue, Daniel Visentin, George van den Driessche, Balaji Lakshminarayanan, Clemens Meyer, Faith Mackinder, Simon Bouton, Kareem Ayoub, Reena Chopra, Dominic King, Alan Karthikesalingam, Cían O Hughes, Rosalind Raine, Julian Hughes, Dawn A Sim, Catherine Egan, Adnan Tufail, Hugh Montgomery, Demis Hassabis, Geraint Rees, Trevor Back, Peng T Khaw, Mustafa Suleyman, Julien Cornebise, Pearse A Keane, Olaf Ronneberger
The volume and complexity of diagnostic imaging is increasing at a pace faster than the availability of human expertise to interpret it. Artificial intelligence has shown great promise in classifying two-dimensional photographs of some common diseases and typically relies on databases of millions of annotated images. Until now, the challenge of reaching the performance of expert clinicians in a real-world clinical pathway with three-dimensional diagnostic scans has remained unsolved. Here, we apply a novel deep learning architecture to a clinically heterogeneous set of three-dimensional optical coherence tomography scans from patients referred to a major eye hospital...
August 13, 2018: Nature Medicine
Joseph J Titano, Marcus Badgeley, Javin Schefflein, Margaret Pain, Andres Su, Michael Cai, Nathaniel Swinburne, John Zech, Jun Kim, Joshua Bederson, J Mocco, Burton Drayer, Joseph Lehar, Samuel Cho, Anthony Costa, Eric K Oermann
Rapid diagnosis and treatment of acute neurological illnesses such as stroke, hemorrhage, and hydrocephalus are critical to achieving positive outcomes and preserving neurologic function-'time is brain'1-5 . Although these disorders are often recognizable by their symptoms, the critical means of their diagnosis is rapid imaging6-10 . Computer-aided surveillance of acute neurologic events in cranial imaging has the potential to triage radiology workflow, thus decreasing time to treatment and improving outcomes...
August 13, 2018: Nature Medicine
Pakawat Chongsathidkiet, Christina Jackson, Shohei Koyama, Franziska Loebel, Xiuyu Cui, S Harrison Farber, Karolina Woroniecka, Aladine A Elsamadicy, Cosette A Dechant, Hanna R Kemeny, Luis Sanchez-Perez, Tooba A Cheema, Nicholas C Souders, James E Herndon, Jean-Valery Coumans, Jeffrey I Everitt, Brian V Nahed, John H Sampson, Michael D Gunn, Robert L Martuza, Glenn Dranoff, William T Curry, Peter E Fecci
T cell dysfunction contributes to tumor immune escape in patients with cancer and is particularly severe amidst glioblastoma (GBM). Among other defects, T cell lymphopenia is characteristic, yet often attributed to treatment. We reveal that even treatment-naïve subjects and mice with GBM can harbor AIDS-level CD4 counts, as well as contracted, T cell-deficient lymphoid organs. Missing naïve T cells are instead found sequestered in large numbers in the bone marrow. This phenomenon characterizes not only GBM but a variety of other cancers, although only when tumors are introduced into the intracranial compartment...
August 13, 2018: Nature Medicine
Lesley Hoyles, José-Manuel Fernández-Real, Massimo Federici, Matteo Serino, James Abbott, Julie Charpentier, Christophe Heymes, Jèssica Latorre Luque, Elodie Anthony, Richard H Barton, Julien Chilloux, Antonis Myridakis, Laura Martinez-Gili, José Maria Moreno-Navarrete, Fadila Benhamed, Vincent Azalbert, Vincent Blasco-Baque, Josep Puig, Gemma Xifra, Wifredo Ricart, Christopher Tomlinson, Mark Woodbridge, Marina Cardellini, Francesca Davato, Iris Cardolini, Ottavia Porzio, Paolo Gentileschi, Frédéric Lopez, Fabienne Foufelle, Sarah A Butcher, Elaine Holmes, Jeremy K Nicholson, Catherine Postic, Rémy Burcelin, Marc-Emmanuel Dumas
In the version of this article originally published, the received date was missing. It should have been listed as 2 January 2018. The error has been corrected in the HTML and PDF versions of this article.
August 9, 2018: Nature Medicine
Gabrielle S Wong, Jin Zhou, Jie Bin Liu, Zhong Wu, Xinsen Xu, Tianxia Li, David Xu, Steven E Schumacher, Jens Puschhof, James McFarland, Charles Zou, Austin Dulak, Les Henderson, Peng Xu, Emily O'Day, Rachel Rendak, Wei-Li Liao, Fabiola Cecchi, Todd Hembrough, Sarit Schwartz, Christopher Szeto, Anil K Rustgi, Kwok-Kin Wong, J Alan Diehl, Karin Jensen, Francesco Graziano, Annamaria Ruzzo, Shaunt Fereshetian, Philipp Mertins, Steven A Carr, Rameen Beroukhim, Kenichi Nakamura, Eiji Oki, Masayuki Watanabe, Hideo Baba, Yu Imamura, Daniel Catenacci, Adam J Bass
In the Supplementary Information originally published with this article, a lane was missing in the β-actin blot in Supplementary Fig. 2. The lane has been added. The error has been corrected in the Supplementary Information associated with this article.
August 9, 2018: Nature Medicine
Xinyi Guo, Yuanyuan Zhang, Liangtao Zheng, Chunhong Zheng, Jintao Song, Qiming Zhang, Boxi Kang, Zhouzerui Liu, Liang Jin, Rui Xing, Ranran Gao, Lei Zhang, Minghui Dong, Xueda Hu, Xianwen Ren, Dennis Kirchhoff, Helge Gottfried Roider, Tiansheng Yan, Zemin Zhang
In the version of this article originally published, the P statistic described in Fig. 3d was incorrect. It was described as "P < 22 × 10-16 ". It should have been "P < 2.2 × 10-16 ". Also, the "CD8+ Treg" label in Fig. 4f was incorrect. It should have been "CD4+ Treg". The errors have been corrected in the HTML and PDF versions of this article.
August 9, 2018: Nature Medicine
Wenfei Sun, Hua Dong, Anton S Becker, Dianne H Dapito, Salvatore Modica, Gerald Grandl, Lennart Opitz, Vissarion Efthymiou, Leon G Straub, Gitalee Sarker, Miroslav Balaz, Lucia Balazova, Aliki Perdikari, Elke Kiehlmann, Sara Bacanovic, Caroline Zellweger, Daria Peleg-Raibstein, Pawel Pelczar, Wolf Reik, Irene A Burger, Ferdinand von Meyenn, Christian Wolfrum
In the version of this article originally published, the bars in the mean temperature graph in Fig. 1a were incorrectly aligned. The left-most bar should have been aligned with the Apr label on the projected month of conception axis. The error has been corrected in the print, PDF and HTML versions of this article.
August 7, 2018: Nature Medicine
Wenfei Sun, Hua Dong, Anton S Becker, Dianne H Dapito, Salvatore Modica, Gerald Grandl, Lennart Opitz, Vissarion Efthymiou, Leon G Straub, Gitalee Sarker, Miroslav Balaz, Lucia Balazova, Aliki Perdikari, Elke Kiehlmann, Sara Bacanovic, Caroline Zellweger, Daria Peleg-Raibstein, Pawel Pelczar, Wolf Reik, Irene A Burger, Ferdinand von Meyenn, Christian Wolfrum
In the version of this article originally published, the months on the axis labeled projected month of conception in Fig. 1a were out of order. April and March should have been the first and last months listed, respectively. The error has been corrected in the print, PDF and HTML versions of this article.
August 7, 2018: Nature Medicine
David R Gandara, Sarah M Paul, Marcin Kowanetz, Erica Schleifman, Wei Zou, Yan Li, Achim Rittmeyer, Louis Fehrenbacher, Geoff Otto, Christine Malboeuf, Daniel S Lieber, Doron Lipson, Jacob Silterra, Lukas Amler, Todd Riehl, Craig A Cummings, Priti S Hegde, Alan Sandler, Marcus Ballinger, David Fabrizio, Tony Mok, David S Shames
Although programmed death-ligand 1-programmed death 1 (PD-L1-PD-1) inhibitors are broadly efficacious, improved outcomes have been observed in patients with high PD-L1 expression or high tumor mutational burden (TMB). PD-L1 testing is required for checkpoint inhibitor monotherapy in front-line non-small-cell lung cancer (NSCLC). However, obtaining adequate tumor tissue for molecular testing in patients with advanced disease can be challenging. Thus, an unmet medical need exists for diagnostic approaches that do not require tissue to identify patients who may benefit from immunotherapy...
August 6, 2018: Nature Medicine
Adam B Roberts, Xiaodong Gu, Jennifer A Buffa, Alex G Hurd, Zeneng Wang, Weifei Zhu, Nilaksh Gupta, Sarah M Skye, David B Cody, Bruce S Levison, William T Barrington, Matthew W Russell, Jodie M Reed, Ashraf Duzan, Jennifer M Lang, Xiaoming Fu, Lin Li, Alex J Myers, Suguna Rachakonda, Joseph A DiDonato, J Mark Brown, Valentin Gogonea, Aldons J Lusis, Jose Carlos Garcia-Garcia, Stanley L Hazen
Trimethylamine N-oxide (TMAO) is a gut microbiota-derived metabolite that enhances both platelet responsiveness and in vivo thrombosis potential in animal models, and TMAO plasma levels predict incident atherothrombotic event risks in human clinical studies. TMAO is formed by gut microbe-dependent metabolism of trimethylamine (TMA) moiety-containing nutrients, which are abundant in a Western diet. Here, using a mechanism-based inhibitor approach targeting a major microbial TMA-generating enzyme pair, CutC and CutD (CutC/D), we developed inhibitors that are potent, time-dependent, and irreversible and that do not affect commensal viability...
August 6, 2018: Nature Medicine
Afam A Okoye, Scott G Hansen, Mukta Vaidya, Yoshinori Fukazawa, Haesun Park, Derick M Duell, Richard Lum, Colette M Hughes, Abigail B Ventura, Emily Ainslie, Julia C Ford, David Morrow, Roxanne M Gilbride, Alfred W Legasse, Joseph Hesselgesser, Romas Geleziunas, Yuan Li, Kelli Oswald, Rebecca Shoemaker, Randy Fast, William J Bosche, Bhavesh R Borate, Paul T Edlefsen, Michael K Axthelm, Louis J Picker, Jeffrey D Lifson
Prophylactic vaccination of rhesus macaques with rhesus cytomegalovirus (RhCMV) vectors expressing simian immunodeficiency virus (SIV) antigens (RhCMV/SIV) elicits immune responses that stringently control highly pathogenic SIV infection, with subsequent apparent clearance of the infection, in ~50% of vaccinees. In contrast, here, we show that therapeutic RhCMV/SIV vaccination of rhesus macaques previously infected with SIV and given continuous combination antiretroviral therapy (cART) beginning 4-9 d post-SIV infection does not mediate measurable SIV reservoir clearance during over 600 d of follow-up on cART relative to RhCMV/control vaccination...
August 6, 2018: Nature Medicine
Shraddha Chakradhar
No abstract text is available yet for this article.
August 1, 2018: Nature Medicine
Claire Vinel, Laura Lukjanenko, Aurelie Batut, Simon Deleruyelle, Jean-Philippe Pradère, Sophie Le Gonidec, Alizée Dortignac, Nancy Geoffre, Ophelie Pereira, Sonia Karaz, Umji Lee, Mylène Camus, Karima Chaoui, Etienne Mouisel, Anne Bigot, Vincent Mouly, Mathieu Vigneau, Allan F Pagano, Angèle Chopard, Fabien Pillard, Sophie Guyonnet, Matteo Cesari, Odile Burlet-Schiltz, Marco Pahor, Jerome N Feige, Bruno Vellas, Philippe Valet, Cedric Dray
Sarcopenia, the degenerative loss of skeletal muscle mass, quality and strength, lacks early diagnostic tools and new therapeutic strategies to prevent the frailty-to-disability transition often responsible for the medical institutionalization of elderly individuals. Herein we report that production of the endogenous peptide apelin, induced by muscle contraction, is reduced in an age-dependent manner in humans and rodents and is positively associated with the beneficial effects of exercise in older persons...
July 30, 2018: Nature Medicine
Katharine Gammon
No abstract text is available yet for this article.
July 30, 2018: Nature Medicine
Alexandra M Ortiz, Jacob K Flynn, Sarah R DiNapoli, Ivan Vujkovic-Cvijin, Carly E Starke, Stephen H Lai, MacKenzie E Long, Ornella Sortino, Carol L Vinton, Joseph C Mudd, Leslie Johnston, Kathleen Busman-Sahay, Yasmine Belkaid, Jacob D Estes, Jason M Brenchley
Intestinal microbial dysbiosis has been described in individuals with an HIV-1 infection and may underlie persistent inflammation in chronic infection, thereby contributing to disease progression. Herein, we induced an HIV-1-like intestinal dysbiosis in rhesus macaques (Macaca mulatta) with vancomycin treatment and assessed the contribution of dysbiosis to SIV disease progression. Dysbiotic and control animals had similar disease progression, indicating that intestinal microbial dysbiosis similar to that observed in individuals with HIV is not sufficient to accelerate untreated lentiviral disease progression...
July 30, 2018: Nature Medicine
Anila K Madiraju, Yang Qiu, Rachel J Perry, Yasmeen Rahimi, Xian-Man Zhang, Dongyan Zhang, João-Paulo G Camporez, Gary W Cline, Gina M Butrico, Bruce E Kemp, Gregori Casals, Gregory R Steinberg, Daniel F Vatner, Kitt F Petersen, Gerald I Shulman
Metformin, the universal first-line treatment for type 2 diabetes, exerts its therapeutic glucose-lowering effects by inhibiting hepatic gluconeogenesis. However, the primary molecular mechanism of this biguanide remains unclear, though it has been suggested to act, at least partially, by mitochondrial complex I inhibition. Here we show that clinically relevant concentrations of plasma metformin achieved by acute intravenous, acute intraportal or chronic oral administration in awake normal and diabetic rats inhibit gluconeogenesis from lactate and glycerol but not from pyruvate and alanine, implicating an increased cytosolic redox state in mediating metformin's antihyperglycemic effect...
July 23, 2018: Nature Medicine
Delphine Gomez, Richard A Baylis, Brittany G Durgin, Alexandra A C Newman, Gabriel F Alencar, Sidney Mahan, Cynthia St Hilaire, Werner Müller, Ari Waisman, Sheila E Francis, Emmanuel Pinteaux, Gwendalyn J Randolph, Hermann Gram, Gary K Owens
Despite decades of research, our understanding of the processes controlling late-stage atherosclerotic plaque stability remains poor. A prevailing hypothesis is that reducing inflammation may improve advanced plaque stability, as recently tested in the Canakinumab Anti-inflammatory Thrombosis Outcome Study (CANTOS) trial, in which post-myocardial infarction subjects were treated with an IL-1β antibody. Here, we performed intervention studies in which smooth muscle cell (SMC) lineage-tracing Apoe-/- mice with advanced atherosclerosis were treated with anti-IL-1β or IgG control antibodies...
July 23, 2018: Nature Medicine
Caroline Junqueira, Camila R R Barbosa, Pedro A C Costa, Andréa Teixeira-Carvalho, Guilherme Castro, Sumit Sen Santara, Rafael P Barbosa, Farokh Dotiwala, Dhelio B Pereira, Lis R Antonelli, Judy Lieberman, Ricardo T Gazzinelli
Plasmodium vivax causes approximately 100 million clinical malaria cases yearly1,2 . The basis of protective immunity is poorly understood and thought to be mediated by antibodies3,4 . Cytotoxic CD8+ T cells protect against other intracellular parasites by detecting parasite peptides presented by human leukocyte antigen class I on host cells. Cytotoxic CD8+ T cells kill parasite-infected mammalian cells and intracellular parasites by releasing their cytotoxic granules5,6 . Perforin delivers the antimicrobial peptide granulysin and death-inducing granzymes into the host cell, and granulysin then delivers granzymes into the parasite...
July 23, 2018: Nature Medicine
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