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Targeting the progeria mutation Nat. Med. (IF 36.13) Pub Date : 2021-01-25 Hannah Stower
Base editors correct a mutation that causes progeria in a mouse model the disease.
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Ethical considerations of COVID-19-related adjustments to clinical research Nat. Med. (IF 36.13) Pub Date : 2021-01-25 Nina S. Hsu; Saskia Hendriks; Khara M. Ramos; Christine Grady
Unexpected direct and indirect risks of participating in clinical trials have emerged during COVID-19 that investigators and institutional review boards may not be sure how to investigate. How should existing guidance and ethical frameworks for clinical trials be applied in a pandemic setting?
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Opposing immune and genetic mechanisms shape oncogenic programs in synovial sarcoma Nat. Med. (IF 36.13) Pub Date : 2021-01-25 Livnat Jerby-Arnon; Cyril Neftel; Marni E. Shore; Hannah R. Weisman; Nathan D. Mathewson; Matthew J. McBride; Brian Haas; Benjamin Izar; Angela Volorio; Gaylor Boulay; Luisa Cironi; Alyssa R. Richman; Liliane C. Broye; Joseph M. Gurski; Christina C. Luo; Ravindra Mylvaganam; Lan Nguyen; Shaolin Mei; Johannes C. Melms; Christophe Georgescu; Ofir Cohen; Jorge E. Buendia-Buendia; Asa Segerstolpe; Malika
Synovial sarcoma (SyS) is an aggressive neoplasm driven by the SS18–SSX fusion, and is characterized by low T cell infiltration. Here, we studied the cancer–immune interplay in SyS using an integrative approach that combines single-cell RNA sequencing (scRNA-seq), spatial profiling and genetic and pharmacological perturbations. scRNA-seq of 16,872 cells from 12 human SyS tumors uncovered a malignant
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Life expectancy and mortality in 363 cities of Latin America Nat. Med. (IF 36.13) Pub Date : 2021-01-25 Usama Bilal; Philipp Hessel; Carolina Perez-Ferrer; Yvonne L. Michael; Tania Alfaro; Janeth Tenorio-Mucha; Amelia A. L. Friche; Maria Fatima Pina; Alejandra Vives; Harrison Quick; Marcio Alazraqui; Daniel A. Rodriguez; J. Jaime Miranda; Ana V. Diez-Roux
The concept of a so-called urban advantage in health ignores the possibility of heterogeneity in health outcomes across cities. Using a harmonized dataset from the SALURBAL project, we describe variability and predictors of life expectancy and proportionate mortality in 363 cities across nine Latin American countries. Life expectancy differed substantially across cities within the same country. Cause-specific
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Author Correction: The effect of LRRK2 loss-of-function variants in humans Nat. Med. (IF 36.13) Pub Date : 2021-01-22 Nicola Whiffin; Irina M. Armean; Aaron Kleinman; Jamie L. Marshall; Eric V. Minikel; Julia K. Goodrich; Nicholas M. Quaife; Joanne B. Cole; Qingbo Wang; Konrad J. Karczewski; Beryl B. Cummings; Laurent Francioli; Kristen Laricchia; Anna Guan; Babak Alipanahi; Peter Morrison; Marco A. S. Baptista; Kalpana M. Merchant; James S. Ware; Aki S. Havulinna; Bozenna Iliadou; Jung-Jin Lee; Girish N. Nadkarni;
A Correction to this paper has been published: https://doi.org/10.1038/s41591-020-01185-6.
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The effects of tobacco control policies on global smoking prevalence Nat. Med. (IF 36.13) Pub Date : 2021-01-21 Luisa S. Flor; Marissa B. Reitsma; Vinay Gupta; Marie Ng; Emmanuela Gakidou
Substantial global effort has been devoted to curtailing the tobacco epidemic over the past two decades, especially after the adoption of the Framework Convention on Tobacco Control1 by the World Health Organization in 2003. In 2015, in recognition of the burden resulting from tobacco use, strengthened tobacco control was included as a global development target in the 2030 Agenda for Sustainable Development2
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Personal neoantigen vaccines induce persistent memory T cell responses and epitope spreading in patients with melanoma Nat. Med. (IF 36.13) Pub Date : 2021-01-21 Zhuting Hu; Donna E. Leet; Rosa L. Allesøe; Giacomo Oliveira; Shuqiang Li; Adrienne M. Luoma; Jinyan Liu; Juliet Forman; Teddy Huang; J. Bryan Iorgulescu; Rebecca Holden; Siranush Sarkizova; Satyen H. Gohil; Robert A. Redd; Jing Sun; Liudmila Elagina; Anita Giobbie-Hurder; Wandi Zhang; Lauren Peter; Zoe Ciantra; Scott Rodig; Oriol Olive; Keerthi Shetty; Jason Pyrdol; Mohamed Uduman; Patrick C. Lee;
Personal neoantigen vaccines have been envisioned as an effective approach to induce, amplify and diversify antitumor T cell responses. To define the long-term effects of such a vaccine, we evaluated the clinical outcome and circulating immune responses of eight patients with surgically resected stage IIIB/C or IVM1a/b melanoma, at a median of almost 4 years after treatment with NeoVax, a long-peptide
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Effect of a plant-based, low-fat diet versus an animal-based, ketogenic diet on ad libitum energy intake Nat. Med. (IF 36.13) Pub Date : 2021-01-21 Kevin D. Hall; Juen Guo; Amber B. Courville; James Boring; Robert Brychta; Kong Y. Chen; Valerie Darcey; Ciaran G. Forde; Ahmed M. Gharib; Isabelle Gallagher; Rebecca Howard; Paule V. Joseph; Lauren Milley; Ronald Ouwerkerk; Klaudia Raisinger; Irene Rozga; Alex Schick; Michael Stagliano; Stephan Torres; Mary Walter; Peter Walter; Shanna Yang; Stephanie T. Chung
The carbohydrate–insulin model of obesity posits that high-carbohydrate diets lead to excess insulin secretion, thereby promoting fat accumulation and increasing energy intake. Thus, low-carbohydrate diets are predicted to reduce ad libitum energy intake as compared to low-fat, high-carbohydrate diets. To test this hypothesis, 20 adults aged 29.9 ± 1.4 (mean ± s.e.m.) years with body mass index of
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Looking beyond COVID-19 vaccine phase 3 trials Nat. Med. (IF 36.13) Pub Date : 2021-01-19 Jerome H. Kim; Florian Marks; John D. Clemens
After the recent announcement of COVID-19 vaccine efficacy in clinical trials by several manufacturers for protection against severe disease, a comprehensive post-efficacy strategy for the next steps to ensure vaccination of the global population is now required. These considerations should include how to manufacture billions of doses of high-quality vaccines, support for vaccine purchase, coordination
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State-dependent responses to intracranial brain stimulation in a patient with depression Nat. Med. (IF 36.13) Pub Date : 2021-01-18 Katherine W. Scangos; Ghassan S. Makhoul; Leo P. Sugrue; Edward F. Chang; Andrew D. Krystal
Deep brain stimulation is a promising treatment for severe depression, but lack of efficacy in randomized trials raises questions regarding anatomical targeting. We implanted multi-site intracranial electrodes in a severely depressed patient and systematically assessed the acute response to focal electrical neuromodulation. We found an elaborate repertoire of distinctive emotional responses that were
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The androgen receptor is a tumor suppressor in estrogen receptor–positive breast cancer Nat. Med. (IF 36.13) Pub Date : 2021-01-18 Theresa E. Hickey; Luke A. Selth; Kee Ming Chia; Geraldine Laven-Law; Heloisa H. Milioli; Daniel Roden; Shalini Jindal; Mun Hui; Jessica Finlay-Schultz; Esmaeil Ebrahimie; Stephen N. Birrell; Suzan Stelloo; Richard Iggo; Sarah Alexandrou; C. Elizabeth Caldon; Tarek M. Abdel-Fatah; Ian O. Ellis; Wilbert Zwart; Carlo Palmieri; Carol A. Sartorius; Alex Swarbrick; Elgene Lim; Jason S. Carroll; Wayne D
The role of the androgen receptor (AR) in estrogen receptor (ER)-α-positive breast cancer is controversial, constraining implementation of AR-directed therapies. Using a diverse, clinically relevant panel of cell-line and patient-derived models, we demonstrate that AR activation, not suppression, exerts potent antitumor activity in multiple disease contexts, including resistance to standard-of-care
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High-frequency neuromodulation improves obsessive–compulsive behavior Nat. Med. (IF 36.13) Pub Date : 2021-01-18 Shrey Grover; John A. Nguyen; Vighnesh Viswanathan; Robert M. G. Reinhart
Nearly one billion people worldwide suffer from obsessive–compulsive behaviors1,2, yet our mechanistic understanding of these behaviors is incomplete, and effective therapeutics are unavailable. An emerging perspective characterizes obsessive–compulsive behaviors as maladaptive habit learning3,4, which may be associated with abnormal beta–gamma neurophysiology of the orbitofrontal–striatal circuitry
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Impaired meningeal lymphatic drainage in patients with idiopathic Parkinson’s disease Nat. Med. (IF 36.13) Pub Date : 2021-01-18 Xue-Bing Ding; Xin-Xin Wang; Dan-Hao Xia; Han Liu; Hai-Yan Tian; Yu Fu; Yong-Kang Chen; Chi Qin; Jiu-Qi Wang; Zhi Xiang; Zhong-Xian Zhang; Qin-Chen Cao; Wei Wang; Jia-Yi Li; Erxi Wu; Bei-Sha Tang; Ming-Ming Ma; Jun-Fang Teng; Xue-Jing Wang
Animal studies implicate meningeal lymphatic dysfunction in the pathogenesis of neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease (PD). However, there is no direct evidence in humans to support this role1,2,3,4,5. In this study, we used dynamic contrast-enhanced magnetic resonance imaging to assess meningeal lymphatic flow in cognitively normal controls and patients with
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Durvalumab compared to maintenance chemotherapy in metastatic breast cancer: the randomized phase II SAFIR02-BREAST IMMUNO trial Nat. Med. (IF 36.13) Pub Date : 2021-01-18 Thomas Bachelot; Thomas Filleron; Ivan Bieche; Monica Arnedos; Mario Campone; Florence Dalenc; Florence Coussy; Marie-Paule Sablin; Marc Debled; Claudia Lefeuvre-Plesse; Anthony Goncalves; Marie-Ange Mouret Reynier; William Jacot; Benoit You; Philippe Barthelemy; Benjamin Verret; Nicolas Isambert; Xavier Tchiknavorian; Christelle Levy; Jean-Christophe Thery; Tifenn L’Haridon; Jean-Marc Ferrero; Alice
The impact of single-agent antibodies against programmed death-ligand 1 (PD-L1) as maintenance therapy is unknown in patients with metastatic breast cancer. The SAFIR02-BREAST IMMUNO substudy included patients with human epidermal growth factor receptor type 2 (Her2)-negative metastatic breast cancer whose disease did not progress after six to eight cycles of chemotherapy. Patients (n = 199) were randomized
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Artificial intelligence for disparities in knee pain assessment Nat. Med. (IF 36.13) Pub Date : 2021-01-13 Said A. Ibrahim
An algorithm developed through machine learning on existing radiological data from diverse people has the potential to improve the diagnosis and management of knee pain from osteoarthritis and reduce racial disparities in the assessment of knee pain.
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Identifying subgroups of people at risk for type 2 diabetes Nat. Med. (IF 36.13) Pub Date : 2021-01-13 Miriam S. Udler
Analysis of glycemic and non-glycemic characteristics in individuals at risk for type 2 diabetes identifies six putative subgroups that differ in terms of risk of diabetes progression and complications.
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Women and children last? Shaking up exclusion criteria for vaccine trials Nat. Med. (IF 36.13) Pub Date : 2021-01-13 Beate Kampmann
Is it time to shift to a model of ‘inclusion unless otherwise justified’ in trials of vaccines for pandemics?
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Patients could share virtual medical appointments for better access to telemedicine Nat. Med. (IF 36.13) Pub Date : 2021-01-13 Kamalini Ramdas; Soumya Swaminathan
Shared medical appointments, whereby patients with similar medical conditions consult their medical practitioner together, alleviate pressure on the health system and provide an instant support network for the patient. Why not make them virtual?
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2021: a new year for the WHO Nat. Med. (IF 36.13) Pub Date : 2021-01-13
The United Nations Assembly has named 2021 the International Year of Peace and Trust. In that spirit, the world can look forward with hope to the international collaborations spearheaded by the World Health Organization and consider the challenges the agency has yet to face.
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Eight ways machine learning is assisting medicine Nat. Med. (IF 36.13) Pub Date : 2021-01-13 Mike May
There has been a lot of hype around the applications of machine learning in medicine. But how is machine learning actually helping bench-to-bedside scientists and clinicians do their jobs?
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Liver metastases inhibit immunotherapy efficacy Nat. Med. (IF 36.13) Pub Date : 2021-01-13 Katherine E. Lindblad; Amaia Lujambio
Liver metastases lead to resistance to immunotherapy through the ‘siphoning’ of tumor antigen–specific CD8+ T cells into the liver, which results in a systemic ‘immune desert’ incapable of controlling tumor burden.
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On the origins of SARS-CoV-2 Nat. Med. (IF 36.13) Pub Date : 2021-01-13 Angela L. Rasmussen
Stakeholders in public health must lobby policy makers to make decisions based on evidence, not political expediency, particularly when the studies that hang in the balance are critical to understanding the origins of epidemics.
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What do journalists say about covering science during the COVID-19 pandemic? Nat. Med. (IF 36.13) Pub Date : 2021-01-13 Anita Makri
The pandemic has thrust many mainstream journalists into unfamiliar grounds, including coverage of expert opinion that is not backed up by peer-reviewed content, reporting on preprints, and assessing high-complexity instant-response science. How did they manage? We asked five journalists from mainstream media about their experience.
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Immune determinants of COVID-19 disease presentation and severity Nat. Med. (IF 36.13) Pub Date : 2021-01-13 Petter Brodin
COVID-19, caused by SARS-CoV-2 infection, is mild to moderate in the majority of previously healthy individuals, but can cause life-threatening disease or persistent debilitating symptoms in some cases. The most important determinant of disease severity is age, with individuals over 65 years having the greatest risk of requiring intensive care, and men are more susceptible than women. In contrast to
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An algorithmic approach to reducing unexplained pain disparities in underserved populations Nat. Med. (IF 36.13) Pub Date : 2021-01-13 Emma Pierson; David M. Cutler; Jure Leskovec; Sendhil Mullainathan; Ziad Obermeyer
Underserved populations experience higher levels of pain. These disparities persist even after controlling for the objective severity of diseases like osteoarthritis, as graded by human physicians using medical images, raising the possibility that underserved patients’ pain stems from factors external to the knee, such as stress. Here we use a deep learning approach to measure the severity of osteoarthritis
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Targeting metastatic cancer Nat. Med. (IF 36.13) Pub Date : 2021-01-13 Karuna Ganesh; Joan Massagué
Despite recent therapeutic advances in cancer treatment, metastasis remains the principal cause of cancer death. Recent work has uncovered the unique biology of metastasis-initiating cells that results in tumor growth in distant organs, evasion of immune surveillance and co-option of metastatic microenvironments. Here we review recent progress that is enabling therapeutic advances in treating both
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Cabozantinib for neurofibromatosis type 1–related plexiform neurofibromas: a phase 2 trial Nat. Med. (IF 36.13) Pub Date : 2021-01-13 Michael J. Fisher; Chie-Schin Shih; Steven D. Rhodes; Amy E. Armstrong; Pamela L. Wolters; Eva Dombi; Chi Zhang; Steven P. Angus; Gary L. Johnson; Roger J. Packer; Jeffrey C. Allen; Nicole J. Ullrich; Stewart Goldman; David H. Gutmann; Scott R. Plotkin; Tena Rosser; Kent A. Robertson; Brigitte C. Widemann; Abbi E. Smith; Waylan K. Bessler; Yongzheng He; Su-Jung Park; Julie A. Mund; Li Jiang; Khadijeh
Neurofibromatosis type 1 (NF1) plexiform neurofibromas (PNs) are progressive, multicellular neoplasms that cause morbidity and may transform to sarcoma. Treatment of Nf1fl/fl;Postn-Cre mice with cabozantinib, an inhibitor of multiple tyrosine kinases, caused a reduction in PN size and number and differential modulation of kinases in cell lineages that drive PN growth. Based on these findings, the Neurofibromatosis
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Author Correction: A global survey of potential acceptance of a COVID-19 vaccine Nat. Med. (IF 36.13) Pub Date : 2021-01-11 Jeffrey V. Lazarus; Scott C. Ratzan; Adam Palayew; Lawrence O. Gostin; Heidi J. Larson; Kenneth Rabin; Spencer Kimball; Ayman El-Mohandes
A Correction to this paper has been published: https://doi.org/10.1038/s41591-020-01226-0
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The distribution of cellular turnover in the human body Nat. Med. (IF 36.13) Pub Date : 2021-01-11 Ron Sender; Ron Milo
We integrated ubiquity, mass and lifespan of all major cell types to achieve a comprehensive quantitative description of cellular turnover. We found a total cellular mass turnover of 80 ± 20 grams per day, dominated by blood cells and gut epithelial cells. In terms of cell numbers, close to 90% of the (0.33 ± 0.02) × 1012 cells per day turnover was blood cells.
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Modeling human adaptive immune responses with tonsil organoids Nat. Med. (IF 36.13) Pub Date : 2021-01-11 Lisa E. Wagar; Ameen Salahudeen; Christian M. Constantz; Ben S. Wendel; Michael M. Lyons; Vamsee Mallajosyula; Lauren P. Jatt; Julia Z. Adamska; Lisa K. Blum; Neha Gupta; Katherine J. L. Jackson; Fan Yang; Katharina Röltgen; Krishna M. Roskin; Kelly M. Blaine; Kara D. Meister; Iram N. Ahmad; Mario Cortese; Emery G. Dora; Sean N. Tucker; Anne I. Sperling; Aarti Jain; D. Huw Davies; Philip L. Felgner;
Most of what we know about adaptive immunity has come from inbred mouse studies, using methods that are often difficult or impossible to confirm in humans. In addition, vaccine responses in mice are often poorly predictive of responses to those same vaccines in humans. Here we use human tonsils, readily available lymphoid organs, to develop a functional organotypic system that recapitulates key germinal
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Microbiome connections with host metabolism and habitual diet from 1,098 deeply phenotyped individuals Nat. Med. (IF 36.13) Pub Date : 2021-01-11 Francesco Asnicar; Sarah E. Berry; Ana M. Valdes; Long H. Nguyen; Gianmarco Piccinno; David A. Drew; Emily Leeming; Rachel Gibson; Caroline Le Roy; Haya Al Khatib; Lucy Francis; Mohsen Mazidi; Olatz Mompeo; Mireia Valles-Colomer; Adrian Tett; Francesco Beghini; Léonard Dubois; Davide Bazzani; Andrew Maltez Thomas; Chloe Mirzayi; Asya Khleborodova; Sehyun Oh; Rachel Hine; Christopher Bonnett; Joan Capdevila;
The gut microbiome is shaped by diet and influences host metabolism; however, these links are complex and can be unique to each individual. We performed deep metagenomic sequencing of 1,203 gut microbiomes from 1,098 individuals enrolled in the Personalised Responses to Dietary Composition Trial (PREDICT 1) study, whose detailed long-term diet information, as well as hundreds of fasting and same-meal
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Robust breast cancer detection in mammography and digital breast tomosynthesis using an annotation-efficient deep learning approach Nat. Med. (IF 36.13) Pub Date : 2021-01-11 William Lotter; Abdul Rahman Diab; Bryan Haslam; Jiye G. Kim; Giorgia Grisot; Eric Wu; Kevin Wu; Jorge Onieva Onieva; Yun Boyer; Jerrold L. Boxerman; Meiyun Wang; Mack Bandler; Gopal R. Vijayaraghavan; A. Gregory Sorensen
Breast cancer remains a global challenge, causing over 600,000 deaths in 2018 (ref. 1). To achieve earlier cancer detection, health organizations worldwide recommend screening mammography, which is estimated to decrease breast cancer mortality by 20–40% (refs. 2,3). Despite the clear value of screening mammography, significant false positive and false negative rates along with non-uniformities in expert
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Exome-wide evaluation of rare coding variants using electronic health records identifies new gene–phenotype associations Nat. Med. (IF 36.13) Pub Date : 2021-01-11 Joseph Park; Anastasia M. Lucas; Xinyuan Zhang; Kumardeep Chaudhary; Judy H. Cho; Girish Nadkarni; Amanda Dobbyn; Geetha Chittoor; Navya S. Josyula; Nathan Katz; Joseph H. Breeyear; Shadi Ahmadmehrabi; Theodore G. Drivas; Venkata R. M. Chavali; Maria Fasolino; Hisashi Sawada; Alan Daugherty; Yanming Li; Chen Zhang; Yuki Bradford; JoEllen Weaver; Anurag Verma; Renae L. Judy; Rachel L. Kember; John D
The clinical impact of rare loss-of-function variants has yet to be determined for most genes. Integration of DNA sequencing data with electronic health records (EHRs) could enhance our understanding of the contribution of rare genetic variation to human disease1. By leveraging 10,900 whole-exome sequences linked to EHR data in the Penn Medicine Biobank, we addressed the association of the cumulative
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Liver metastasis restrains immunotherapy efficacy via macrophage-mediated T cell elimination Nat. Med. (IF 36.13) Pub Date : 2021-01-04 Jiali Yu; Michael D. Green; Shasha Li; Yilun Sun; Sara N. Journey; Jae Eun Choi; Syed Monem Rizvi; Angel Qin; Jessica J. Waninger; Xueting Lang; Zoey Chopra; Issam El Naqa; Jiajia Zhou; Yingjie Bian; Long Jiang; Alangoya Tezel; Jeremy Skvarce; Rohan K. Achar; Merna Sitto; Benjamin S. Rosen; Fengyun Su; Sathiya P. Narayanan; Xuhong Cao; Shuang Wei; Wojciech Szeliga; Linda Vatan; Charles Mayo; Meredith
Metastasis is the primary cause of cancer mortality, and cancer frequently metastasizes to the liver. It is not clear whether liver immune tolerance mechanisms contribute to cancer outcomes. We report that liver metastases diminish immunotherapy efficacy systemically in patients and preclinical models. Patients with liver metastases derive limited benefit from immunotherapy independent of other established
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Pathophysiology-based subphenotyping of individuals at elevated risk for type 2 diabetes Nat. Med. (IF 36.13) Pub Date : 2021-01-04 Robert Wagner; Martin Heni; Adam G. Tabák; Jürgen Machann; Fritz Schick; Elko Randrianarisoa; Martin Hrabě de Angelis; Andreas L. Birkenfeld; Norbert Stefan; Andreas Peter; Hans-Ulrich Häring; Andreas Fritsche
The state of intermediate hyperglycemia is indicative of elevated risk of developing type 2 diabetes1. However, the current definition of prediabetes neither reflects subphenotypes of pathophysiology of type 2 diabetes nor is predictive of future metabolic trajectories. We used partitioning on variables derived from oral glucose tolerance tests, MRI-measured body fat distribution, liver fat content
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A neuroimaging biomarker for sustained experimental and clinical pain Nat. Med. (IF 36.13) Pub Date : 2021-01-04 Jae-Joong Lee; Hong Ji Kim; Marta Čeko; Bo-yong Park; Soo Ahn Lee; Hyunjin Park; Mathieu Roy; Seong-Gi Kim; Tor D. Wager; Choong-Wan Woo
Sustained pain is a major characteristic of clinical pain disorders, but it is difficult to assess in isolation from co-occurring cognitive and emotional features in patients. In this study, we developed a functional magnetic resonance imaging signature based on whole-brain functional connectivity that tracks experimentally induced tonic pain intensity and tested its sensitivity, specificity and generalizability
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Brown adipose tissue is associated with cardiometabolic health Nat. Med. (IF 36.13) Pub Date : 2021-01-04 Tobias Becher; Srikanth Palanisamy; Daniel J. Kramer; Mahmoud Eljalby; Sarah J. Marx; Andreas G. Wibmer; Scott D. Butler; Caroline S. Jiang; Roger Vaughan; Heiko Schöder; Allyn Mark; Paul Cohen
White fat stores excess energy, whereas brown and beige fat are thermogenic and dissipate energy as heat. Thermogenic adipose tissues markedly improve glucose and lipid homeostasis in mouse models, although the extent to which brown adipose tissue (BAT) influences metabolic and cardiovascular disease in humans is unclear1,2. Here we retrospectively categorized 134,529 18F-fluorodeoxyglucose positron
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Single-cell dissection of intratumoral heterogeneity and lineage diversity in metastatic gastric adenocarcinoma Nat. Med. (IF 36.13) Pub Date : 2021-01-04 Ruiping Wang; Minghao Dang; Kazuto Harada; Guangchun Han; Fang Wang; Melissa Pool Pizzi; Meina Zhao; Ghia Tatlonghari; Shaojun Zhang; Dapeng Hao; Yang Lu; Shuangtao Zhao; Brian D. Badgwell; Mariela Blum Murphy; Namita Shanbhag; Jeannelyn S. Estrella; Sinchita Roy-Chowdhuri; Ahmed Adel Fouad Abdelhakeem; Yuanxin Wang; Guang Peng; Samir Hanash; George A. Calin; Xingzhi Song; Yanshuo Chu; Jianhua Zhang;
Intratumoral heterogeneity (ITH) is a fundamental property of cancer; however, the origins of ITH remain poorly understood. We performed single-cell transcriptome profiling of peritoneal carcinomatosis (PC) from 15 patients with gastric adenocarcinoma (GAC), constructed a map of 45,048 PC cells, profiled the transcriptome states of tumor cell populations, incisively explored ITH of malignant PC cells
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Difficult trade-offs in response to COVID-19: the case for open and inclusive decision making Nat. Med. (IF 36.13) Pub Date : 2020-12-18 Ole F. Norheim; Joelle M. Abi-Rached; Liam Kofi Bright; Kristine Bærøe; Octávio L. M. Ferraz; Siri Gloppen; Alex Voorhoeve
We argue that deliberative decision making that is inclusive, transparent and accountable can contribute to more trustworthy and legitimate decisions on difficult ethical questions and political trade-offs during the pandemic and beyond.
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T cell and antibody responses induced by a single dose of ChAdOx1 nCoV-19 (AZD1222) vaccine in a phase 1/2 clinical trial Nat. Med. (IF 36.13) Pub Date : 2020-12-17 Katie J. Ewer; Jordan R. Barrett; Sandra Belij-Rammerstorfer; Hannah Sharpe; Rebecca Makinson; Richard Morter; Amy Flaxman; Daniel Wright; Duncan Bellamy; Mustapha Bittaye; Christina Dold; Nicholas M. Provine; Jeremy Aboagye; Jamie Fowler; Sarah E. Silk; Jennifer Alderson; Parvinder K. Aley; Brian Angus; Eleanor Berrie; Sagida Bibi; Paola Cicconi; Elizabeth A. Clutterbuck; Irina Chelysheva; Pedro M
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus Disease 2019 (COVID-19), has caused a global pandemic, and safe, effective vaccines are urgently needed1. Strong, Th1-skewed T cell responses can drive protective humoral and cell-mediated immune responses2 and might reduce the potential for disease enhancement3. Cytotoxic T cells clear virus-infected host
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Phase 1/2 trial of SARS-CoV-2 vaccine ChAdOx1 nCoV-19 with a booster dose induces multifunctional antibody responses Nat. Med. (IF 36.13) Pub Date : 2020-12-17 Jordan R. Barrett; Sandra Belij-Rammerstorfer; Christina Dold; Katie J. Ewer; Pedro M. Folegatti; Ciaran Gilbride; Rachel Halkerston; Jennifer Hill; Daniel Jenkin; Lisa Stockdale; Marije K. Verheul; Parvinder K. Aley; Brian Angus; Duncan Bellamy; Eleanor Berrie; Sagida Bibi; Mustapha Bittaye; Miles W. Carroll; Breeze Cavell; Elizabeth A. Clutterbuck; Nick Edwards; Amy Flaxman; Michelle Fuskova; Andrew
More than 190 vaccines are currently in development to prevent infection by the novel severe acute respiratory syndrome coronavirus 2. Animal studies suggest that while neutralizing antibodies against the viral spike protein may correlate with protection, additional antibody functions may also be important in preventing infection. Previously, we reported early immunogenicity and safety outcomes of
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Individual and community-level risk for COVID-19 mortality in the United States Nat. Med. (IF 36.13) Pub Date : 2020-12-11 Jin Jin; Neha Agarwala; Prosenjit Kundu; Benjamin Harvey; Yuqi Zhang; Eliza Wallace; Nilanjan Chatterjee
Reducing COVID-19 burden for populations will require equitable and effective risk-based allocations of scarce preventive resources, including vaccinations1. To aid in this effort, we developed a general population risk calculator for COVID-19 mortality based on various sociodemographic factors and pre-existing conditions for the US population, combining information from the UK-based OpenSAFELY study
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COVID-19: what health experts could and could not predict Nat. Med. (IF 36.13) Pub Date : 2020-12-07 Devi Sridhar
Nearly a year after the first cases of COVID-19 were reported, it is time to look back and assess what could have been predicted by health experts.
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2021: research and medical trends in a post-pandemic world Nat. Med. (IF 36.13) Pub Date : 2020-12-07 Mike May
Goodbye 2020, a year of arguably too many challenges for the world. As tempting as it is to leave this year behind, the biomedical community is forever changed by the pandemic, while business as usual needs to carry on. Looking forward to a new year, experts share six trends for the biomedical community in 2021.
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Meeting the challenge of long COVID Nat. Med. (IF 36.13) Pub Date : 2020-12-07
In formulating the response of the healthcare system to the COVID-19 pandemic, the true toll of the chronic consequences of SARS-CoV-2 infection must be uncovered and strategies must be devised for providing integrated care to those with long-term illness.
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A chimeric hemagglutinin-based universal influenza virus vaccine approach induces broad and long-lasting immunity in a randomized, placebo-controlled phase I trial Nat. Med. (IF 36.13) Pub Date : 2020-12-07 Raffael Nachbagauer; Jodi Feser; Abdollah Naficy; David I. Bernstein; Jeffrey Guptill; Emmanuel B. Walter; Franceso Berlanda-Scorza; Daniel Stadlbauer; Patrick C. Wilson; Teresa Aydillo; Mohammad Amin Behzadi; Disha Bhavsar; Carly Bliss; Christina Capuano; Juan Manuel Carreño; Veronika Chromikova; Carine Claeys; Lynda Coughlan; Alec W. Freyn; Christopher Gast; Andres Javier; Kaijun Jiang; Chiara Mariottini;
Seasonal influenza viruses constantly change through antigenic drift and the emergence of pandemic influenza viruses through antigenic shift is unpredictable. Conventional influenza virus vaccines induce strain-specific neutralizing antibodies against the variable immunodominant globular head domain of the viral hemagglutinin protein. This necessitates frequent re-formulation of vaccines and handicaps
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Effective control of SARS-CoV-2 transmission in Wanzhou, China Nat. Med. (IF 36.13) Pub Date : 2020-11-30 Qiuling Shi; Yaoyue Hu; Bin Peng; Xiao-Jun Tang; Wei Wang; Kun Su; Chao Luo; Bo Wu; Fan Zhang; Yong Zhang; Benjamin Anderson; Xiao-Ni Zhong; Jing-Fu Qiu; Cheng Yong Yang; Ai-Long Huang
The effectiveness of control measures to contain coronavirus disease 2019 (COVID-19) in Wanzhou, China was assessed. Epidemiological data were analyzed for 183 confirmed COVID-19 cases and their close contacts from five generations of transmission of severe acute respiratory syndrome coronavirus 2 throughout the entire COVID-19 outbreak in Wanzhou. Approximately 67.2% and 32.8% of cases were symptomatic
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Author Correction: Uncovering hidden antimicrobial resistance patterns within the hospital microbiome Nat. Med. (IF 36.13) Pub Date : 2020-11-27 Bastiaan W. Haak; W. Joost Wiersinga
A Correction to this paper has been published: https://doi.org/10.1038/s41591-020-0919-z.
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Publisher Correction: Responding to the hidden pandemic for healthcare workers: stress Nat. Med. (IF 36.13) Pub Date : 2020-11-27 John H. Krystal
A Correction to this paper has been published: https://doi.org/10.1038/s41591-020-01176-7
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Author Correction: Modeling COVID-19 scenarios for the United States Nat. Med. (IF 36.13) Pub Date : 2020-11-27
A Correction to this paper has been published: https://doi.org/10.1038/s41591-020-01181-w
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Author Correction: A dynamic COVID-19 immune signature includes associations with poor prognosis Nat. Med. (IF 36.13) Pub Date : 2020-11-27 Adam G. Laing; Anna Lorenc; Irene del Molino del Barrio; Abhishek Das; Matthew Fish; Leticia Monin; Miguel Muñoz-Ruiz; Duncan R. McKenzie; Thomas S. Hayday; Isaac Francos-Quijorna; Shraddha Kamdar; Magdalene Joseph; Daniel Davies; Richard Davis; Aislinn Jennings; Iva Zlatareva; Pierre Vantourout; Yin Wu; Vasiliki Sofra; Florencia Cano; Maria Greco; Efstathios Theodoridis; Joshua D. Freedman; Sarah
A Correction to this paper has been published: https://doi.org/10.1038/s41591-020-01186-5
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Using single-cell analysis to predict CAR T cell outcomes Nat. Med. (IF 36.13) Pub Date : 2020-11-23 Sneha Ramakrishna; Nirali N. Shah
Single-cell analysis provides novel insights into elements of CAR T cell toxicities and response.
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Liquid biopsy versus tumor biopsy for clinical-trial recruitment Nat. Med. (IF 36.13) Pub Date : 2020-11-23 Ryan B. Corcoran
Studies demonstrate the efficacy of screening by liquid biopsy for enrollment in clinical trials of precision cancer therapy.
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Malaria parasites hide in plain sight in the dry season Nat. Med. (IF 36.13) Pub Date : 2020-11-23 Philip Bejon
Plasmodium falciparum parasites survive the dry season by accepting increased clearance rates through the host spleen, which leads to a persistent lower-level infection.
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Dysregulated ribonucleoprotein granules promote cardiomyopathy in RBM20 gene-edited pigs Nat. Med. (IF 36.13) Pub Date : 2020-11-13 Jay W. Schneider; Saji Oommen; Muhammad Y. Qureshi; Sean C. Goetsch; David R. Pease; Rhianna S. Sundsbak; Wei Guo; Mingming Sun; Han Sun; Hidehito Kuroyanagi; Dennis A. Webster; Alexander W. Coutts; Kimberly A. Holst; Brooks S. Edwards; Nikolas Newville; Matthew A. Hathcock; Tamene Melkamu; Francesca Briganti; Wu Wei; Maria G. Romanelli; Scott C. Fahrenkrug; Doug E. Frantz; Timothy M. Olson; Lars M
Ribonucleoprotein (RNP) granules are biomolecular condensates—liquid–liquid phase-separated droplets that organize and manage messenger RNA metabolism, cell signaling, biopolymer assembly, biochemical reactions and stress granule responses to cellular adversity. Dysregulated RNP granules drive neuromuscular degenerative disease but have not previously been linked to heart failure. By exploring the
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Characterization of pre-existing and induced SARS-CoV-2-specific CD8 + T cells Nat. Med. (IF 36.13) Pub Date : 2020-11-12 Isabel Schulien; Janine Kemming; Valerie Oberhardt; Katharina Wild; Lea M. Seidel; Saskia Killmer; Sagar; Franziska Daul; Marilyn Salvat Lago; Annegrit Decker; Hendrik Luxenburger; Benedikt Binder; Dominik Bettinger; Oezlem Sogukpinar; Siegbert Rieg; Marcus Panning; Daniela Huzly; Martin Schwemmle; Georg Kochs; Cornelius F. Waller; Alexandra Nieters; Daniel Duerschmied; Florian Emmerich; Henrik E.
Emerging data indicate that SARS-CoV-2-specific CD8+ T cells targeting different viral proteins are detectable in up to 70% of convalescent individuals1,2,3,4,5. However, very little information is currently available about the abundance, phenotype, functional capacity and fate of pre-existing and induced SARS-CoV-2-specific CD8+ T cell responses during the natural course of SARS-CoV-2 infection. Here
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Using common genetic variation to examine phenotypic expression and risk prediction in 22q11.2 deletion syndrome Nat. Med. (IF 36.13) Pub Date : 2020-11-09 Robert W. Davies; Ania M. Fiksinski; Elemi J. Breetvelt; Nigel M. Williams; Stephen R. Hooper; Thomas Monfeuga; Anne S. Bassett; Michael J. Owen; Raquel E. Gur; Bernice E. Morrow; Donna M. McDonald-McGinn; Ann Swillen; Eva W. C. Chow; Marianne van den Bree; Beverly S. Emanuel; Joris R. Vermeesch; Therese van Amelsvoort; Celso Arango; Marco Armando; Linda E. Campbell; Joseph F. Cubells; Stephan Eliez;
The 22q11.2 deletion syndrome (22q11DS) is associated with a 20–25% risk of schizophrenia. In a cohort of 962 individuals with 22q11DS, we examined the shared genetic basis between schizophrenia and schizophrenia-related early trajectory phenotypes: sub-threshold symptoms of psychosis, low baseline intellectual functioning and cognitive decline. We studied the association of these phenotypes with two
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Rapid pathogen detection by metagenomic next-generation sequencing of infected body fluids Nat. Med. (IF 36.13) Pub Date : 2020-11-09 Wei Gu; Xianding Deng; Marco Lee; Yasemin D. Sucu; Shaun Arevalo; Doug Stryke; Scot Federman; Allan Gopez; Kevin Reyes; Kelsey Zorn; Hannah Sample; Guixia Yu; Gurpreet Ishpuniani; Benjamin Briggs; Eric D. Chow; Amy Berger; Michael R. Wilson; Candace Wang; Elaine Hsu; Steve Miller; Joseph L. DeRisi; Charles Y. Chiu
We developed a metagenomic next-generation sequencing (mNGS) test using cell-free DNA from body fluids to identify pathogens. The performance of mNGS testing of 182 body fluids from 160 patients with acute illness was evaluated using two sequencing platforms in comparison to microbiological testing using culture, 16S bacterial PCR and/or 28S–internal transcribed ribosomal gene spacer (28S–ITS) fungal
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Make the climate crisis your own research priority Nat. Med. (IF 36.13) Pub Date : 2020-11-05
Scientists and health professionals must commit to preparing for the health effects of climate change through increased research, education and self-assessment.
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Post-hoc analysis could give new life to the Alzheimer’s drug aducanumab Nat. Med. (IF 36.13) Pub Date : 2020-11-02 Carrie Arnold
The aducanumab saga continues as an FDA panel determines whether a post-hoc analysis could be enough to approve the drug
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