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| Open AccessGenome-wide association study identifies susceptibility loci for acute myeloid leukemia
Genome wide association studies in cancer are used to understand the heritable genetic contribution to disease risk. Here, the authors perform a genome wide association study in European patients with acute myeloid leukemia and identify loci associated with risk of developing the disease.
- Wei-Yu Lin
- , Sarah E. Fordham
- & James M. Allan
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Article
| Open AccessTET2 mutations are associated with hypermethylation at key regulatory enhancers in normal and malignant hematopoiesis
TET2 mutations are frequent in myeloid malignancies and in elderly individuals with or without cytopenia. Here, the authors analyse the association between TET2 mutations and methylation changes in healthy elderly twins and patients with cytopenia and compare them to those from leukemia.
- Morten Tulstrup
- , Mette Soerensen
- & Kirsten Grønbæk
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| Open AccessDirect on-swab metabolic profiling of vaginal microbiome host interactions during pregnancy and preterm birth
Here, the authors apply DESI-MS, a sample preparation-free, direct on-swab mass spectrometry analytical tool, to profile the cervicovaginal metabolome of two independent cohorts of pregnant women and, combined with matched metataxonomic and immuno-profiling data, show that DESI-MS predicts vaginal microbiota composition and local inflammatory status associated with preterm birth and clinical interventions used during pregnancy.
- Pamela Pruski
- , Gonçalo D. S. Correia
- & David A. MacIntyre
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| Open AccessA cross-sectional analysis of meteorological factors and SARS-CoV-2 transmission in 409 cities across 26 countries
Possible effects of weather conditions on COVID-19 transmission are debated. Here, the authors analyse data from early in the pandemic and show that although temperature and humidity had small effects on transmission, they were far out-weighed by the effects of non-pharmaceutical interventions.
- Francesco Sera
- , Ben Armstrong
- & Rachel Lowe
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| Open AccessA scalable workflow to characterize the human exposome
Humans are exposed to millions of chemicals but mass spectrometry (MS)-based targeted biomonitoring assays are usually limited to a few hundred known hazards. Here, the authors develop a workflow for MS-based untargeted exposome profiling of known and unidentified environmental chemicals.
- Xin Hu
- , Douglas I. Walker
- & Dean P. Jones
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| Open AccessDeep neural network-estimated electrocardiographic age as a mortality predictor
The electrocardiogram (ECG) is the most commonly used exam for the screening and evaluation of cardiovascular diseases. Here, the authors propose that the age predicted by artificial intelligence from the raw ECG tracing can be a measure of cardiovascular health and provide prognostic information.
- Emilly M. Lima
- , Antônio H. Ribeiro
- & Antonio Luiz P. Ribeiro
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| Open AccessPlacental DNA methylation signatures of maternal smoking during pregnancy and potential impacts on fetal growth
Maternal smoking during pregnancy contributes to poor birth outcomes. Here the authors perform a meta-analysis of the associations between maternal smoking during pregnancy and placental DNA methylation and identify links between these and poor birth outcomes, which may better inform the mechanisms through which smoking impacts placental function and fetal growth.
- Todd M. Everson
- , Marta Vives-Usano
- & Mariona Bustamante
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| Open AccessCOVID-19 spread, detection, and dynamics in Bogota, Colombia
Detailed information on SARS-CoV-2 infection rates in Latin America by occupation, socioeconomic group and geographic area are rarely available. Here, the authors provide these estimates for in Bogota, Colombia using data from a sentinel surveillance scheme, and find that over half the population had been infected by March 2021.
- Rachid Laajaj
- , Camilo De Los Rios
- & Duncan Webb
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Article
| Open AccessAn umbrella review of the evidence associating diet and cancer risk at 11 anatomical sites
Diet and food intake have been associated with a risk of developing different types of cancer but individual nutritional epidemiology studies are prone to inherent bias. Here, the authors perform an umbrella review of meta-analyses of observational studies and show the level of evidence for associating food and nutrients to cancer risk.
- Nikos Papadimitriou
- , Georgios Markozannes
- & Konstantinos K. Tsilidis
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Article
| Open AccessLack of consideration of sex and gender in COVID-19 clinical studies
Sex and gender have been associated with differences in SARS-CoV-2 incidence and clinical outcomes and therefore warrant consideration in study designs. Here, the authors assess registered and published clinical COVID-19 studies and find that sex-disaggregated analyses are infrequently presented or planned.
- Emer Brady
- , Mathias Wullum Nielsen
- & Sabine Oertelt-Prigione
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Article
| Open AccessCommunity factors and excess mortality in first wave of the COVID-19 pandemic in England
COVID-19-related mortality in England shows geographical variation but the reasons for this are not well understood. This study estimated excess mortality in the first wave of the pandemic and found associations with higher density of care homes, overcrowding, and economic deprivation, but not with population density or air pollution.
- Bethan Davies
- , Brandon L. Parkes
- & Paul Elliott
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Article
| Open AccessNeighborhood-level disparities and subway utilization during the COVID-19 pandemic in New York City
Neighborhood disadvantage and capacity to socially distance have been discussed as factors involved in COVID-19 disparities. Here, the authors develop an inequity index on zip code-level infections, and examine differences in neighborhood utilization of subways in New York City.
- Daniel Carrión
- , Elena Colicino
- & Allan C. Just
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Article
| Open AccessEffect of COVID-19 response policies on walking behavior in US cities
Mobility restrictions implemented to reduce the spread of COVID-19 have significantly impacted walking behavior. In this study, the authors integrated mobility data from mobile devices and area-level data to study the walking patterns of 1.62 million anonymous users in 10 US metropolitan areas.
- Ruth F. Hunter
- , Leandro Garcia
- & Esteban Moro
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Article
| Open AccessSeasonality of agricultural exposure as an important predictor of seasonal yellow fever spillover in Brazil
Yellow fever virus (YFV) is an arbovirus affecting humans and non-human primates (NHPs) with seasonal transmission. Here Hamlet et al. model the monthly occurrence of YF in humans and NHPs across Brazil and show that seasonality of agriculture is an important predictor of seasonal YF transmission.
- Arran Hamlet
- , Daniel Garkauskas Ramos
- & Neil M. Ferguson
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| Open AccessRole of meteorological factors in the transmission of SARS-CoV-2 in the United States
The role of meteorological factors in SARS-COV-2 transmission is not well understood. Here, the authors use county-level data from the United States to the end of 2020 and find evidence of a moderate association between increased transmissibility and cold, dry weather and low ultraviolet radiation.
- Yiqun Ma
- , Sen Pei
- & Kai Chen
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Article
| Open AccessMaternal iron deficiency perturbs embryonic cardiovascular development in mice
From mouse experiments, the authors link iron deficiency in mothers with cardiovascular defects and increased retinoic acid signalling in their offspring, and giving iron early in pregnancy can prevent most defects.
- Jacinta I. Kalisch-Smith
- , Nikita Ved
- & Duncan B. Sparrow
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Article
| Open AccessGenetic variation associated with thyroid autoimmunity shapes the systemic immune response to PD-1 checkpoint blockade
Endocrinopathies, such as thyroid autoimmunity, are common among patients treated with immune checkpoint inhibitors. Here, by using a polygenic risk score (PRS) derived from a hypothyroidism GWAS, the authors show that cancer patients with high PRS are at increased risk of atezolizumab (anti-PD-L1)-induced thyroid dysfunction, a condition associated with systemic response to PD-1 checkpoint blockade and longer overall survival.
- Zia Khan
- , Christian Hammer
- & G. Scott Chandler
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Article
| Open AccessCommon variants in Alzheimer’s disease and risk stratification by polygenic risk scores
Known genetic loci account for only a fraction of the genetic contribution to Alzheimer’s disease. Here, the authors have performed a large genome-wide meta-analysis comprising 409,435 individuals to discover 6 new loci and demonstrate the efficacy of an Alzheimer’s disease polygenic risk score.
- Itziar de Rojas
- , Sonia Moreno-Grau
- & Agustín Ruiz
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| Open AccessDeep learning predicts cardiovascular disease risks from lung cancer screening low dose computed tomography
Low dose computed tomography (LDCT) for lung cancer screening offers an opportunity for simultaneous CVD risk estimation in at-risk patients. Here, the authors develop a deep learning model to perform this task, showing human-level performance.
- Hanqing Chao
- , Hongming Shan
- & Pingkun Yan
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Article
| Open AccessPerfluoroalkyl substance pollutants activate the innate immune system through the AIM2 inflammasome
The double-stranded DNA receptor AIM2 is able to sense the environmental pollutant perfluorooctane sulfonate, a prototypical perfluoro-alkyl substrate. Activation of the AIM2 pathway leads to inflammation and tissue damage via IL-1β secretion and pyroptosis of affected innate immune cells.
- Li-Qiu Wang
- , Tao Liu
- & Jun Cui
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Article
| Open AccessBlood n-3 fatty acid levels and total and cause-specific mortality from 17 prospective studies
Associations between of omega-3 fatty acids and mortality are not clear. Here the authors report that, based on a pooled analysis of 17 prospective cohort studies, higher blood omega-3 fatty acid levels correlate with lower risk of all-cause mortality.
- William S. Harris
- , Nathan L. Tintle
- & Dariush Mozaffarian
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Article
| Open AccessAssociation of sleep duration in middle and old age with incidence of dementia
Sleep dysregulation has been linked to dementia, but it is unknown whether sleep duration earlier in life is associated with dementia risk. Here, the authors show higher dementia risk associated with short sleep duration (six hours or less) in a longitudinal study of middle and older age adults.
- Séverine Sabia
- , Aurore Fayosse
- & Archana Singh-Manoux
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Article
| Open AccessDigital proximity tracing on empirical contact networks for pandemic control
Digital contact tracing is increasingly considered as one of the tools to control infectious disease outbreaks, in particular the COVID-19 epidemic. Here, the authors present a modeling framework informed by empirical high-resolution contact data to analyze the impact of digital contact tracing apps.
- G. Cencetti
- , G. Santin
- & B. Lepri
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| Open AccessTropical cyclone exposure is associated with increased hospitalization rates in older adults
Tropical cyclones can cause severe damage and can thus have devastating impacts on societies. Here, the authors use Medicare data to show that tropical cyclone exposure in the United States is associated with increased hospitalization rates for older adults from many different acute causes.
- Robbie M. Parks
- , G. Brooke Anderson
- & Marianthi-Anna Kioumourtzoglou
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Article
| Open AccessThe prevalence of antibodies to SARS-CoV-2 among blood donors in China
Here, the authors determine seroprevalence of antibodies to SARS-CoV-2 in healthy blood donors in the cities of Wuhan, Shenzhen, and Shijiazhuang in China between January and April 2020. The age- and sex-standardized SARS-CoV-2 seroprevalence among 18–60 year-old adults is, with 2.66%, the highest in Wuhan.
- Le Chang
- , Wangheng Hou
- & Lunan Wang
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| Open AccessInterleukin-3 is a predictive marker for severity and outcome during SARS-CoV-2 infections
Here, the authors identify interleukin-3 as a predictive marker for severity and outcome of SARS-CoV-2 infection in a multi-center, prospective study and find that patients with severe COVID-19 have reduced circulating plasmacytoid dendritic cell levels compared to non-severe COVID-19 patients.
- Alan Bénard
- , Anne Jacobsen
- & Georg F. Weber
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Article
| Open AccessA case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers
Breast cancer risk for BRCA1/BRCA2 mutation carriers varies depending on other genetic factors. Here, the authors perform a case-only genome-wide association study and highlight novel loci associated with breast cancer risk for BRCA1/BRCA2 mutation carriers.
- Juliette Coignard
- , Michael Lush
- & Antonis C. Antoniou
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Article
| Open AccessReal-time prediction of COVID-19 related mortality using electronic health records
Identifying COVID-19 patients with the highest mortality risk early is critical to enable effective intervention and optimal prioritisation of care. Here, the authors present a clinical risk scoring system trained on a large data set of patients from 69 healthcare institutions in multiple countries.
- Patrick Schwab
- , Arash Mehrjou
- & Stefan Bauer
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Article
| Open AccessProjecting heat-related excess mortality under climate change scenarios in China
Global warming is expected to increase mortality due to heat stress in many regions. Here, the authors asses how mortality due to high temperatures changes in China changes for different demographic groups and show that heat-related excess mortality is increasing under climate change, a process that is strongly amplified by population ageing.
- Jun Yang
- , Maigeng Zhou
- & Qiyong Liu
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Article
| Open AccessSARS-CoV-2 antibody prevalence in England following the first peak of the pandemic
REACT-2 is a large-scale community study of SARS-CoV-2 seroprevalence in England. Here, the authors estimate that 6% of adults in England had been infected by mid-July 2020, with health and long-term care workers and those of Black or South Asian ethnicity disproportionately affected.
- Helen Ward
- , Christina Atchison
- & Paul Elliott
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| Open AccessWhole genome sequencing of skull-base chordoma reveals genomic alterations associated with recurrence and chordoma-specific survival
Skull base chordomas are treated with surgery and chemotherapy but often recur due to incomplete resection, understanding the molecular underpinnings of the tumours may provide additional therapeutic strategies. Here, the authors carry out whole genome sequencing of 80 skull base chordoma tumours and identify the SWI/SNF component—PBRM1—as a frequently mutated gene.
- Jiwei Bai
- , Jianxin Shi
- & Xiaohong R. Yang
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| Open AccessThe natural history of symptomatic COVID-19 during the first wave in Catalonia
Establishing the natural history of COVID-19 requires longitudinal data from population-based cohorts. Here, the authors use linked primary care, testing, and hospital data to describe the disease in ~100,000 individuals with a COVID-19 diagnosis among a population of ~5.5 million in Catalonia, Spain.
- Edward Burn
- , Cristian Tebé
- & Talita Duarte-Salles
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Article
| Open AccessDeep convolutional neural networks to predict cardiovascular risk from computed tomography
Coronary artery calcium is an accurate predictor of cardiovascular events but this information is not routinely quantified. Here the authors show a robust and time-efficient deep learning system to automatically quantify coronary calcium on CT scans and predict cardiovascular events in a large, multicentre study.
- Roman Zeleznik
- , Borek Foldyna
- & Hugo J. W. L. Aerts
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| Open AccessIntegrating deep learning CT-scan model, biological and clinical variables to predict severity of COVID-19 patients
The SARS-COV-2 pandemic has put pressure on intensive care units, so that predicting severe deterioration early is a priority. Here, the authors develop a multimodal severity score including clinical and imaging features that has significantly improved prognostic performance in two validation datasets compared to previous scores.
- Nathalie Lassau
- , Samy Ammari
- & Michael G. B. Blum
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| Open AccessGenome-wide analyses of behavioural traits are subject to bias by misreports and longitudinal changes
Conflicting reports have found disease to sometimes be positively and sometimes negatively correlated with alcohol consumption. Here, the authors show that misreporting and reduction of alcohol consumption is associated with disease, leading to misleading associations between alcohol and disease.
- Angli Xue
- , Longda Jiang
- & Jian Yang
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Article
| Open AccessLysosomal SLC46A3 modulates hepatic cytosolic copper homeostasis
The environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes hepatic toxicity associated with prominent lipid accumulation in humans. Here, the authors report that the lysosomal copper transporter SLC46A3 is induced by TCDD and underlies the hepatic lipid accumulation in mice, potentially via effects on mitochondrial function.
- Jung-Hwan Kim
- , Tsutomu Matsubara
- & Frank J. Gonzalez
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Article
| Open AccessMale sex identified by global COVID-19 meta-analysis as a risk factor for death and ITU admission
Anecdotal reports suggest potential severity and outcome differences between sexes following infection by SARS-CoV-2. Here, the authors perform meta-analyses of more than 3 million cases collected from global public data to demonstrate that male patients with COVID-19 are 3 times more likely to require intensive care, and have ~40% higher death rate.
- Hannah Peckham
- , Nina M. de Gruijter
- & Claire T. Deakin
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| Open AccessA cross-sectional study of cardiovascular disease risk clustering at different socio-geographic levels in India
Despite its importance for the targeting of interventions, little is known about the degree to which cardiovascular risk factors cluster within different socio-geographic levels in South Asia. Here the authors report on a cross-sectional study identifying wide variations in the clustering between risk factors and socio-geographic levels in India.
- Anne C. Bischops
- , Jan-Walter De Neve
- & Pascal Geldsetzer
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Article
| Open AccessAssociations between blood type and COVID-19 infection, intubation, and death
Recent evidence has suggested that blood type may be associated with severe COVID-19. Here, the authors use data from ~14,000 individuals tested for SARS-CoV-2 at a New York City hospital, and find that certain ABO and Rh blood types are associated with infection, intubation, and death.
- Michael Zietz
- , Jason Zucker
- & Nicholas P. Tatonetti
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Article
| Open AccessCollider bias undermines our understanding of COVID-19 disease risk and severity
Many published studies of the current SARS-CoV-2 pandemic have analysed data from non-representative samples from populations. Here, using UK BioBank samples, Gibran Hemani and colleagues discuss the potential for such studies to suffer from collider bias, and provide suggestions for optimising study design to account for this.
- Gareth J. Griffith
- , Tim T. Morris
- & Gibran Hemani
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Article
| Open AccessApplication of an analytical framework for multivariate mediation analysis of environmental data
Diverse toxicological mechanisms may mediate the impact of environmental toxicants on pregnancy outcomes. In this study the authors introduce an analytical framework for multivariate mediation analysis to identify mediation pathways in the relationship between environmental toxicants and gestational age at delivery.
- Max T. Aung
- , Yanyi Song
- & Bhramar Mukherjee
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Article
| Open AccessHormonal contraception alters vaginal microbiota and cytokines in South African adolescents in a randomized trial
Hormonal contraception may alter women’s susceptibility to HIV. Here, the authors report the results of a randomized clinical trial substudy assessing the effects of injectable Net-En, oral contraceptives (COC) and Nuvaring on vaginal microbiota and cytokines, associating COC with lower microbial diversity and Nuvaring with increased inflammation.
- Christina Balle
- , Iyaloo N. Konstantinus
- & Heather B. Jaspan
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Article
| Open AccessMendelian randomization study of maternal influences on birthweight and future cardiometabolic risk in the HUNT cohort
Observationally, lower birthweight is a risk factor for cardiometabolic disease. Using Mendelian Randomization, the authors investigate whether maternal genetic factors that lower offspring birthweight also increase offspring cardiometabolic risk and show that the observational correlation is unlikely to be due to the intrauterine environment.
- Gunn-Helen Moen
- , Ben Brumpton
- & David M. Evans
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Article
| Open AccessGenome-wide association study of smoking trajectory and meta-analysis of smoking status in 842,000 individuals
Genome-wide association studies (GWASs) for cigarette smoking have identified several hundred loci that account for a small proportion of the overall genetic risk. Here, the authors report a large GWAS for smoking trajectories and meta-analysis for smoking status, finding multiple plausible loci.
- Ke Xu
- , Boyang Li
- & Amy C. Justice
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Article
| Open AccessA population-based cohort study of socio-demographic risk factors for COVID-19 deaths in Sweden
Better understanding of who is at highest risk of death from COVID-19 is important for public health planning. Here, the authors demonstrate an unequal mortality burden associated with socially disadvantaged groups in Sweden.
- Sven Drefahl
- , Matthew Wallace
- & Gunnar Andersson
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Article
| Open AccessMachine learning based early warning system enables accurate mortality risk prediction for COVID-19
Methods to stratify patients according to mortality risk are essential to allocate limited heath resources during the COVID-19 crisis. Here, using machine learning methods, the authors present a mortality risk prediction model for COVID-19 that uses patients’ clinical data on admission to stratify patients by mortality risk.
- Yue Gao
- , Guang-Yao Cai
- & Qing-Lei Gao
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Article
| Open AccessDeep phenotyping of 34,128 adult patients hospitalised with COVID-19 in an international network study
Detailed knowledge of the characteristics of COVID-19 patients helps with public health planning. Here, the authors use routinely-collected data from seven databases in three countries to describe the characteristics of >30,000 patients admitted with COVID-19 and compare them with those admitted for influenza in previous years.
- Edward Burn
- , Seng Chan You
- & Patrick Ryan
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Article
| Open AccessEarly prediction of disease progression in COVID-19 pneumonia patients with chest CT and clinical characteristics
Early identification of COVID-19 patients at risk of progression may facilitate more individually aligned treatment plans. Here the authors develop an online nomogram incorporating CT severity score and clinical characteristics for early predicting the disease progression risk among COVID-19 pneumonia patients.
- Zhichao Feng
- , Qizhi Yu
- & Wei Wang
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Article
| Open AccessA cell-type deconvolution meta-analysis of whole blood EWAS reveals lineage-specific smoking-associated DNA methylation changes
Smoking-associated DNA methylation changes in whole blood have been reported by many EWAS. Here, the authors use a cell-type deconvolution algorithm to identify cell-type specific DNA methylation signals in seven EWAS, identifying lineage-specific smoking-associated DNA methylation changes.
- Chenglong You
- , Sijie Wu
- & Andrew E. Teschendorff