Featured
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Article
| Open Access
GDF15 linked to maternal risk of nausea and vomiting during pregnancy
Elevated circulating levels of GDF15 in pregnant women are associated with severe nausea and vomiting, and sensitivity to such symptoms during pregnancy is partly determined by prepregnancy levels of this hormone.
- M. Fejzo
- , N. Rocha
- & S. O’Rahilly
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Article |
Genetic risk converges on regulatory networks mediating early type 2 diabetes
Integration of multiomics data with functional analysis of pancreatic tissues from individuals with early-stage type 2 diabetes indicates that the genetic risk converges on RFX6, which regulates chromatin architecture at multiple risk loci.
- John T. Walker
- , Diane C. Saunders
- & Marcela Brissova
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Article
| Open Access
Cingulate dynamics track depression recovery with deep brain stimulation
This study demonstrates how activity in the cingulate cortex tracks depression recovery, providing symptom relief using deep brain stimulation.
- Sankaraleengam Alagapan
- , Ki Sueng Choi
- & Christopher J. Rozell
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Article
| Open Access
A foundation model for generalizable disease detection from retinal images
RETFound, a foundation model for retinal images that learns generalizable representations from unlabelled images, is trained on 1.6 million unlabelled images by self-supervised learning and then adapted to disease detection tasks with explicit labels.
- Yukun Zhou
- , Mark A. Chia
- & Pearse A. Keane
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Article
| Open Access
Netrin-1 blockade inhibits tumour growth and EMT features in endometrial cancer
We describe netrin-1 upregulation in a majority of human endometrial carcinomas and demonstrate that netrin-1 blockade, using the anti-netrin-1 antibody NP137, is effective both in a mouse model and in patients with endometrial carcinomas.
- Philippe A. Cassier
- , Raul Navaridas
- & Patrick Mehlen
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Article
| Open Access
cGAS–STING drives ageing-related inflammation and neurodegeneration
The cGAS–STING signalling pathway is a critical driver of chronic inflammation and functional decline during ageing, and could be targeted to halt neurodegenerative processes during old age.
- Muhammet F. Gulen
- , Natasha Samson
- & Andrea Ablasser
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Perspective |
CAR T therapy beyond cancer: the evolution of a living drug
The rationale behind chimaeric antigen receptor T cell therapy is reviewed, and current challenges in oncology, preliminary reports in noncancerous diseases and relevant emerging technologies are discussed.
- Daniel J. Baker
- , Zoltan Arany
- & Carl H. June
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Article
| Open Access
An atlas of healthy and injured cell states and niches in the human kidney
A high-resolution kidney cellular atlas of 51 main cell types, including rare and previously undescribed cell populations, represents a comprehensive benchmark of cellular states, neighbourhoods, outcome-associated signatures and publicly available interactive visualizations.
- Blue B. Lake
- , Rajasree Menon
- & Sanjay Jain
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Article
| Open Access
A framework for individualized splice-switching oligonucleotide therapy
Whole-genome sequencing analyses in a cohort of individuals with ataxia-telangiectasia are used to identify genetic variants that might be amenable to treatment with splice-switching antisense oligonucleotides (ASOs), and develop ASOs with therapeutic potential.
- Jinkuk Kim
- , Sijae Woo
- & Timothy W. Yu
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Article
| Open Access
Health system-scale language models are all-purpose prediction engines
A clinical language model trained on unstructured clinical notes from the electronic health record enhances prediction of clinical and operational events.
- Lavender Yao Jiang
- , Xujin Chris Liu
- & Eric Karl Oermann
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Article
| Open Access
The evolution of lung cancer and impact of subclonal selection in TRACERx
Analyses of multiregional tumour samples from 421 patients with non-small cell lung cancer prospectively enrolled to the TRACERx study reveal determinants of tumour evolution and relationships between intratumour heterogeneity and clinical outcome.
- Alexander M. Frankell
- , Michelle Dietzen
- & Charles Swanton
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Co-opting signalling molecules enables logic-gated control of CAR T cells
Logic gating is used to develop a CAR T cell platform that is highly specific and allows the activity of T cells to be restricted to the encounter of two antigens, thus reducing on-target, off-tumour toxicity.
- Aidan M. Tousley
- , Maria Caterina Rotiroti
- & Robbie G. Majzner
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Article
| Open Access
FXR inhibition may protect from SARS-CoV-2 infection by reducing ACE2
FXR regulates the levels of ACE2 in tissues of the respiratory and gastrointestinal systems that are affected by COVID-19, and inhibiting FXR with ursodeoxycholic acid downregulates ACE2 and reduces susceptibility to SARS-CoV-2 infection.
- Teresa Brevini
- , Mailis Maes
- & Fotios Sampaziotis
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Article
| Open Access
Personalizing exoskeleton assistance while walking in the real world
A portable ankle exoskeleton uses a data-driven method and wearable sensors to adapt to the user as they walk in a natural setting.
- Patrick Slade
- , Mykel J. Kochenderfer
- & Steven H. Collins
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Article
| Open Access
Brain–phenotype models fail for individuals who defy sample stereotypes
Predictive models that relate brain activity to phenotype reliably fail when applied to subgroups of participants who do not fit stereotypical profiles, showing that the utility of a one-size-fits-all modelling approach is limited.
- Abigail S. Greene
- , Xilin Shen
- & R. Todd Constable
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Article
| Open Access
Brown-fat-mediated tumour suppression by cold-altered global metabolism
Mild cold exposure activates a substantial amount of brown adipose tissue (BAT) in a patient with cancer, reducing tumour-associated glucose uptake, and activation of BAT in mice inhibits the growth of tumours by decreasing blood glucose and impeding glycolysis-based metabolism in cancer cells.
- Takahiro Seki
- , Yunlong Yang
- & Yihai Cao
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Androgen receptor blockade promotes response to BRAF/MEK-targeted therapy
Treatment with neoadjuvant BRAF/MEK-targeted therapy results in higher rates of major pathological response in female compared with male patients with melanoma, and pharmacological inhibition of androgen receptor signalling improved the responses of male and female mice to BRAF/MEK-targeted therapy.
- Christopher P. Vellano
- , Michael G. White
- & Jennifer A. Wargo
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Immune regulation by fungal strain diversity in inflammatory bowel disease
Genetically diverse Candida albicans strains in patients with inflammatory bowel disease secrete a toxin and aggravate IL-1β-dependent intestinal inflammation.
- Xin V. Li
- , Irina Leonardi
- & Iliyan D. Iliev
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Article |
FSH blockade improves cognition in mice with Alzheimer’s disease
Follicle-stimulating hormone acts directly on hippocampal and cortical neurons to accelerate amyloid-β and Tau deposition and impair cognition in mice displaying features of Alzheimer’s disease.
- Jing Xiong
- , Seong Su Kang
- & Keqiang Ye
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Perspective |
An open science study of ageing in companion dogs
The Dog Aging Project is an open-data, community science study to identify genetic, environmental and lifestyle factors associated with canine healthy lifespan, generating knowledge that could readily translate to human ageing.
- Kate E. Creevy
- , Joshua M. Akey
- & Benjamin S. Wilfond
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Article
| Open Access
Multi-omic machine learning predictor of breast cancer therapy response
Integration of pre-treatment tumour features in predictive models using machine learning could inform on response to therapy.
- Stephen-John Sammut
- , Mireia Crispin-Ortuzar
- & Carlos Caldas
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Article |
The CLIP1–LTK fusion is an oncogenic driver in non‐small‐cell lung cancer
Whole-transcriptome sequencing of a subset of 75 non-small-cell lung cancer specimens in a multi-institutional genome screening study identified a fusion of the CLIP1 and LTK genes with transformational potential due to constitutive LTK kinase activity.
- Hiroki Izumi
- , Shingo Matsumoto
- & Koichi Goto
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Article |
Antibody epitopes in vaccine-induced immune thrombotic thrombocytopaenia
Alanine-scanning mutagenesis is used to identify the PF4 epitope that is recognized by anti-PF4 antibodies in patients with vaccine-induced immune thrombotic thrombocytopaenia, revealing that the epitope corresponds to the heparin-binding site on PF4.
- Angela Huynh
- , John G. Kelton
- & Ishac Nazy
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Article |
PIK3CA and CCM mutations fuel cavernomas through a cancer-like mechanism
Aggressive cerebral cavernous malformations (CCMs) are found to grow through a three-hit cancer-like mechanism, involving gain of function of a gene that promotes vascular growth, and loss of function of genes that suppress it.
- Aileen A. Ren
- , Daniel A. Snellings
- & Mark L. Kahn
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The AIM2 inflammasome exacerbates atherosclerosis in clonal haematopoiesis
Accelerated atherosclerosis in a mouse model of clonal haematopoiesis is prevented by genetic interruption of AIM2 inflammasome activation or by inhibition of interleukin-1β.
- Trevor P. Fidler
- , Chenyi Xue
- & Alan R. Tall
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Local immune response to food antigens drives meal-induced abdominal pain
In mice, oral tolerance to food antigens can break down after enteric infection, and this leads to food-induced pain resembling irritable bowel syndrome in humans.
- Javier Aguilera-Lizarraga
- , Morgane V. Florens
- & Guy E. Boeckxstaens
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Article |
Decoding myofibroblast origins in human kidney fibrosis
A range of techniques are used to investigate the molecular landscape of chronic kidney disease, and the results suggest that distinct populations of pericytes and fibroblasts are the main source of myofibroblasts in kidney fibrosis.
- Christoph Kuppe
- , Mahmoud M. Ibrahim
- & Rafael Kramann
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snRNA-seq reveals a subpopulation of adipocytes that regulates thermogenesis
Single-nucleus RNA sequencing in mouse and human adipose tissue identifies a subpopulation of adipocytes that regulates thermogenesis in neighbouring adipocytes in a paracrine manner by modulating acetate signalling.
- Wenfei Sun
- , Hua Dong
- & Christian Wolfrum
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Matters Arising |
Transparency and reproducibility in artificial intelligence
- Benjamin Haibe-Kains
- , George Alexandru Adam
- & Hugo J. W. L. Aerts
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Article |
IGF1R is an entry receptor for respiratory syncytial virus
Respiratory syncytial virus enters cells by binding to cell-surface IGFR1, which activates PKCζ and induces trafficking of the NCL coreceptor to the RSV particles at the cell surface.
- Cameron D. Griffiths
- , Leanne M. Bilawchuk
- & David J. Marchant
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Proteomics of SARS-CoV-2-infected host cells reveals therapy targets
SARS-CoV-2 modulates central cellular pathways, such as translation, splicing, carbon metabolism, proteostasis and nucleic acid metabolism, in human cells; these pathways can be inhibited by small-molecule inhibitors to prevent viral replication in the cells.
- Denisa Bojkova
- , Kevin Klann
- & Christian Münch
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Article |
Epigenetic therapy inhibits metastases by disrupting premetastatic niches
In mouse models of pulmonary metastasis, adjuvant epigenetic therapy targeting myeloid-derived suppressor cells disrupts the premetastatic microenvironment after resection of primary tumours and inhibits the dissemination of residual tumour cells.
- Zhihao Lu
- , Jianling Zou
- & Malcolm V. Brock
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Article |
Bacteriophage targeting of gut bacterium attenuates alcoholic liver disease
In patients with alcoholic hepatitis, cytolysin-positive Enterococcus faecalis strains are correlated with liver disease severity and increased mortality, and in mouse models these strains can be specifically targeted by bacteriophages.
- Yi Duan
- , Cristina Llorente
- & Bernd Schnabl
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Matters Arising |
Reversion after replacement of mitochondrial DNA
- Gavin Hudson
- , Yuko Takeda
- & Mary Herbert
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Matters Arising |
Reply to: Reversion after replacement of mitochondrial DNA
- Eunju Kang
- , Amy Koski
- & Shoukhrat Mitalipov
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Letter |
The fungal mycobiome promotes pancreatic oncogenesis via activation of MBL
In humans and mouse models, the mycobiome of pancreatic ductal adenocarcinoma tumours is markedly enriched in Malassezia species compared to that of normal pancreas, which implicates these pathogenic fungi in oncogenesis.
- Berk Aykut
- , Smruti Pushalkar
- & George Miller
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Letter |
CD24 signalling through macrophage Siglec-10 is a target for cancer immunotherapy
CD24 interacts with the tumour-associated-macrophage receptor Siglec-10 to inhibit the macrophage-mediated clearance of cancer cells, revealing a new ‘don’t eat me’ signal as a potential target for cancer immunotherapy.
- Amira A. Barkal
- , Rachel E. Brewer
- & Irving L. Weissman
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Letter |
A clinically applicable approach to continuous prediction of future acute kidney injury
A deep learning approach that predicts the risk of acute kidney injury may help to identify patients at risk of health deterioration within a time window that enables early treatment.
- Nenad Tomašev
- , Xavier Glorot
- & Shakir Mohamed
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Article |
Incompatible and sterile insect techniques combined eliminate mosquitoes
A field trial succeeded in eliminating populations of the mosquito Aedes albopictus through inundative mass release of incompatible Wolbachia-infected males, which were also irradiated to sterilize any accidentally-released females, and so prevent population replacement.
- Xiaoying Zheng
- , Dongjing Zhang
- & Zhiyong Xi
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Letter |
Immune evasion before tumour invasion in early lung squamous carcinogenesis
The immune response is modulated at a early stage of carcinogenesis, such that both immune activation and evasion precede tumour invasion.
- Céline Mascaux
- , Mihaela Angelova
- & Jérôme Galon
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Letter |
Genomic characterization of metastatic breast cancers
Patient data from six clinical trials are used to compare the genomic landscapes of breast cancer metastases with those of primary tumours, revealing an increase in mutational burden and clonal diversity.
- François Bertucci
- , Charlotte K. Y. Ng
- & Fabrice André
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Article |
Progenitors from the central nervous system drive neurogenesis in cancer
In a mouse model of prostate cancer, neural progenitors from the central nervous system that express doublecortin infiltrate tumours and metastases, and can generate new adrenergic neurons in tumours.
- Philippe Mauffrey
- , Nicolas Tchitchek
- & Claire Magnon
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Letter |
The CH25H–CYP7B1–RORα axis of cholesterol metabolism regulates osteoarthritis
In experimentally induced osteoarthritis, chondrocytes show increased uptake and metabolism of cholesterol, implicating the CH25H–CYP7B1–RORα axis in the pathogenesis of osteoarthritis.
- Wan-Su Choi
- , Gyuseok Lee
- & Jang-Soo Chun
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Letter |
Consistent success in life-supporting porcine cardiac xenotransplantation
α1,3-galactosyltransferase-knockout pig hearts that express human CD46 and human thrombomodulin require non-ischaemic preservation with continuous perfusion and post-transplantation growth control to ensure long-term orthotopic function of the xenograft in baboons.
- Matthias Längin
- , Tanja Mayr
- & Jan-Michael Abicht
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Targeted therapy in patients with PIK3CA-related overgrowth syndrome
A PI3KCA inhibitor reverses symptoms in a mouse model of PROS/CLOVES syndrome, which results from gain-of-function mutations in PI3KCA, and produces improvements in patients with PROS/CLOVES syndrome.
- Quitterie Venot
- , Thomas Blanc
- & Guillaume Canaud
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A randomized trial of normothermic preservation in liver transplantation
Normothermic machine perfusion of the liver improved early graft function, demonstrated by reduced peak serum aspartate transaminase levels and early allograft dysfunction rates, and improved organ utilization and preservation times, although no differences were seen in graft or patient survival.
- David Nasralla
- , Constantin C. Coussios
- & Peter J. Friend
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Letter |
Moving magnetoencephalography towards real-world applications with a wearable system
A new magnetoencephalography system allows high-spatiotemporal-resolution imaging of human brain function in moving subjects.
- Elena Boto
- , Niall Holmes
- & Matthew J. Brookes
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Article
| Open Access
The landscape of genomic alterations across childhood cancers
Analyses of genomes from 914 children, adolescents, and young adults provide a comprehensive resource of genomic alterations across a spectrum of common childhood cancers.
- Susanne N. Gröbner
- , Barbara C. Worst
- & Stefan M. Pfister
Monolithic silicon for high spatiotemporal translational photostimulation
Restoring vision