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| Open AccessTherapeutic homology-independent targeted integration in retina and liver
Limits of AAV-mediated gene therapy include targeting dominant mutations and inducing long-term transgene expression. Here, the authors show that AAV-HITI results in efficient allele-independent integration of a donor DNA in both retina and liver providing therapeutic benefit in mouse models of either a genetic form of blindness or a lysosomal storage disease, respectively.
- Patrizia Tornabene
- , Rita Ferla
- & Alberto Auricchio
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| Open AccessUsing high-resolution contact networks to evaluate SARS-CoV-2 transmission and control in large-scale multi-day events
Here, the authors simulate COVID-19 outbreaks on an empirical contact network derived from digital contact data collected on cruise ships. They model impacts of different control measures and find that combinations of measures, particularly vaccination and rapid antigen testing, are important for mitigating outbreaks.
- Rachael Pung
- , Josh A. Firth
- & Adam J. Kucharski
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| Open AccessCarbonized paramagnetic complexes of Mn (II) as contrast agents for precise magnetic resonance imaging of sub-millimeter-sized orthotopic tumors
Improving the imaging of cancer may enhance the treatment of patients, Here, the authors develop a Mn(II) based nanoparticle contrast agent for MRI imaging and show that the nanoparticles can cross the brain barrier and image glioma cells.
- Ruixue Qin
- , Shi Li
- & Hongmin Chen
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Article
| Open AccessAccurate auto-labeling of chest X-ray images based on quantitative similarity to an explainable AI model
Here the authors develop a method for accurate auto-labelling of CXR images from large public datasets based on quantitative probability-of similarity to an explainable AI model. The labels can be used to fine-tune the original model through iterative re-training.
- Doyun Kim
- , Joowon Chung
- & Synho Do
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| Open AccessHigh failure rate of ChAdOx1-nCoV19 immunization against asymptomatic infection in healthcare workers during a Delta variant surge
The authors study a cohort of healthcare workers in India who received two doses of the ChAdOx-1-nCoV19 vaccine during the Delta wave. Using serological data, they infer that 25% of the cohort were infected within 60 days of vaccination, although there were no severe infections leading to hospitalisations.
- Rajat Ujjainiya
- , Akansha Tyagi
- & Shantanu Sengupta
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| Open AccessDigital plasmonic nanobubble detection for rapid and ultrasensitive virus diagnostics
Digital immunoassays are powerful platforms but are complex and require multiple steps to perform. Here the authors show that digital plasmonic nanobubble detection allows rapid and ultrasensitive diagnostics via a one-step homogeneous immunoassay.
- Yaning Liu
- , Haihang Ye
- & Zhenpeng Qin
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Article
| Open AccessAutomated multilabel diagnosis on electrocardiographic images and signals
The application of artificial intelligence for automated diagnosis of electrocardiograms can improve care in remote settings but is limited by the reliance on infrequently available signal-based data. Here, the authors report the development of a multi-label automated diagnosis model for electrocardiographic images.
- Veer Sangha
- , Bobak J. Mortazavi
- & Rohan Khera
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| Open AccessComparative effectiveness and safety of homologous two-dose ChAdOx1 versus heterologous vaccination with ChAdOx1 and BNT162b2
Different homologous and heterologous vaccination regimens have been used for COVID-19. Here the authors show in a cohort analysis from Catalonia that heterologous vaccination with ChAdOx1 followed by BNT162b2 has better vaccine effectiveness than two doses of ChAdOx1.
- Eduardo Hermosilla
- , Ermengol Coma
- & Daniel Prieto-Alhambra
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| Open AccessReconstructing antibody dynamics to estimate the risk of influenza virus infection
Serological classification of influenza infection has classically been based on a four-fold or higher increase in antibody levels, but this approach may not be optimal. Here, the authors develop a Bayesian model to improve identification of infections in serological samples by accounting for individual antibody dynamics.
- Tim K. Tsang
- , Ranawaka A. P. M. Perera
- & Simon Cauchemez
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Article
| Open AccessSpelling interface using intracortical signals in a completely locked-in patient enabled via auditory neurofeedback training
The authors record neural firing rates in a patient with ALS in completely locked-in state and show that the patient can modulate neural firing rates based on auditory feedback to select letters to form words and phrases to communicate his needs and experiences.
- Ujwal Chaudhary
- , Ioannis Vlachos
- & Niels Birbaumer
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| Open AccessIdentifying regions for enhanced control of gambiense sleeping sickness in the Democratic Republic of Congo
Gambiense human African trypanosomiasis (sleeping sickness or gHAT) has been targeted for elimination of transmission by 2030. Here, the authors project impacts of gHAT interventions in the Democratic Republic of the Congo and derive a priority list of health zones requiring enhanced control to achieve this target.
- Ching-I Huang
- , Ronald E. Crump
- & Kat S. Rock
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Article
| Open AccessAgent-based modelling of reactive vaccination of workplaces and schools against COVID-19
The authors use an agent-based model to investigate the potential of reactive vaccination strategies for COVID-19 outbreak mitigation. They find that distributing vaccines in schools and workplaces where cases are detected is more impactful than non-reactive strategies in a wide range of epidemic scenarios.
- Benjamin Faucher
- , Rania Assab
- & Chiara Poletto
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| Open AccessIn vivo three-dimensional multispectral photoacoustic imaging of dual enzyme-driven cyclic cascade reaction for tumor catalytic therapy
Photoacoustic imaging can be used to monitor chemical reaction in cells and tissues. Here, the authors develop a Pd based nanozyme conjugated with glucose oxidase that can induce the change of photoacoustic signals during the catalytic cascade process, the system can also be used to treat tumor-bearing mice.
- Shan Lei
- , Jing Zhang
- & Peng Huang
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| Open AccessActive label cleaning for improved dataset quality under resource constraints
High quality labels are important for model performance, evaluation and selection in medical imaging. As manual labelling is time-consuming and costly, the authors explore and benchmark various resource-effective methods for improving dataset quality.
- Mélanie Bernhardt
- , Daniel C. Castro
- & Ozan Oktay
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| Open AccessPopulation-scale dietary interests during the COVID-19 pandemic
The SARS-CoV-2 virus has altered people’s lives around the world, not only through the disease it causes, but also through unprecedented restrictions. Here the authors document population-wide shifts in dietary interests in 18 countries in 2020, as revealed through time series of Google search volumes.
- Kristina Gligorić
- , Arnaud Chiolero
- & Robert West
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| Open AccessCost-effectiveness of sleeping sickness elimination campaigns in five settings of the Democratic Republic of Congo
Gambiense human African trypanosomiasis has been targeted for elimination of transmission by 2030. Here, the authors assess the cost-effectiveness of elimination strategies in the Democratic Republic of the Congo and find that those which lead to elimination of transmission might also be considered cost-effective by conventional thresholds.
- Marina Antillon
- , Ching-I Huang
- & Fabrizio Tediosi
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Article
| Open AccessGenomic assessment of quarantine measures to prevent SARS-CoV-2 importation and transmission
Post-international travel quarantine has been widely implemented to mitigate SARS-CoV-2 transmission, but the impacts of such policies are unclear. Here, the authors used linked genomic and contact tracing data to assess the impacts of a 14-day quarantine on return to England in summer 2020.
- Dinesh Aggarwal
- , Andrew J. Page
- & Ewan M. Harrison
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| Open AccessFine-scale heterogeneity in population density predicts wave dynamics in dengue epidemics
Population density can influence the dynamics of emerging infections, but the specific effects at a local (within-city) level are not well understood. Here, the authors investigate the influence of population density on dynamics of dengue outbreaks in Rio de Janeiro and propose that this variable holds the key to how space should be aggregated.
- Victoria Romeo-Aznar
- , Laís Picinini Freitas
- & Mercedes Pascual
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| Open AccessRandomized controlled trial for time-restricted eating in healthy volunteers without obesity
Time-restricted eating, both early (eTRF) and mid-day (mTRF), have been shown to have metabolic benefits. Here the authors report a randomized controlled trial to compare the effects of eTRF and mTRF in healthy volunteers without obesity, and find that eTRF is more effective in improving the primary outcome insulin sensitivity.
- Zhibo Xie
- , Yuning Sun
- & Yilei Mao
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Article
| Open AccessPopulation antibody responses following COVID-19 vaccination in 212,102 individuals
The authors present results from the REACT-2 study, a series of cross-sectional community surveys during the SARS-CoV-2 pandemic in England. They measure antibodies by self-administered lateral flow tests and describe antibody positivity by time since vaccination, age, sex, co-morbidities, infection history, and vaccine type.
- Helen Ward
- , Matthew Whitaker
- & Graham S. Cooke
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| Open AccessEffects of early-life antibiotics on the developing infant gut microbiome and resistome: a randomized trial
Here, in a randomized trial of 147 infants receiving distinct antibiotic regimens for early-onset neonatal sepsis, Reyman et al. characterize the gut microbiome and resistance profiles, finding differential effects of antibiotic combinations on microbial community composition and antimicrobial resistance genes.
- Marta Reyman
- , Marlies A. van Houten
- & Debby Bogaert
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| Open AccessGut metagenome associations with extensive digital health data in a volunteer-based Estonian microbiome cohort
Here, the authors present results of the Estonian Microbiome Project, which combines metagenomics and electronic health data from 2500 individuals, expanding microbiome-host interactions in particular with regards to effects of long-term antibiotic usage on the microbiome across diseases.
- Oliver Aasmets
- , Kertu Liis Krigul
- & Elin Org
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Article
| Open AccessMark-release-recapture experiment in Burkina Faso demonstrates reduced fitness and dispersal of genetically-modified sterile malaria mosquitoes
Release of genetically-modified sterile mosquitoes is a potential method of malaria control but has yet to be tested in the field. Here, the authors perform a mark-release-recapture experiment and show that genetically-modified mosquitoes have reduced survival and dispersal compared to wild-types.
- Franck Adama Yao
- , Abdoul-Azize Millogo
- & Abdoulaye Diabaté
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| Open AccessGenomic epidemiology of SARS-CoV-2 under an elimination strategy in Hong Kong
Hong Kong has used an elimination strategy to control SARS-CoV-2 with stringent measures including traveller quarantine. Here, the authors show that the majority of community-acquired cases until January 2021 resulted from three importations, and that increased transmission followed prolonged periods of restrictions, likely due to adherence fatigue.
- Haogao Gu
- , Ruopeng Xie
- & Leo L. M. Poon
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| Open AccessGenomic epidemiology of SARS-CoV-2 in a UK university identifies dynamics of transmission
In this study, Aggarwal and colleagues perform prospective sequencing of SARS-CoV-2 isolates derived from asymptomatic student screening and symptomatic testing of students and staff at the University of Cambridge. They identify important factors that contributed to within university transmission and onward spread into the wider community.
- Dinesh Aggarwal
- , Ben Warne
- & Ian G. Goodfellow
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| Open AccessMultiple expansions of globally uncommon SARS-CoV-2 lineages in Nigeria
SARS-CoV-2 genomic surveillance has been important for informing pandemic responses but many regions remain under-sampled, limiting knowledge of circulating strains. Here, the authors sequence 378 isolates from Nigeria and identify two strains that appear to be important locally though globally uncommon.
- Egon A. Ozer
- , Lacy M. Simons
- & Ramon Lorenzo-Redondo
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Article
| Open AccessEfficient, biosafe and tissue adhesive hemostatic cotton gauze with controlled balance of hydrophilicity and hydrophobicity
Cotton gauze is widely used as haemostatic material for bleeding control, but its high blood absorption capacity can to cause extra blood loss. Here, the authors develop a cotton gauze whose surface is modified with a catechol compound featuring a flexible long hydrophobic alkyl chain which demonstrates excellent haemostatic performance.
- Huaying He
- , Weikang Zhou
- & Haiqing Liu
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Article
| Open AccessOptimising genomic approaches for identifying vancomycin-resistant Enterococcus faecium transmission in healthcare settings
Vancomycin-resistant Enterococcus faecium is an important healthcare-associated pathogen and genomic analyses could inform targeted interventions. Here, the authors optimise an analysis pipeline for identification of putative transmission events using core genome multilocus sequence type clustering and split kmer analysis.
- Charlie Higgs
- , Norelle L. Sherry
- & Benjamin P. Howden
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| Open AccessMultimorbidity and adverse events of special interest associated with Covid-19 vaccines in Hong Kong
Adverse events resulting from COVID-19 vaccination are a public health concern and it is not known whether pre-existing conditions may impose an increased risk. Here, using electronic health records from Hong Kong, the authors show that adverse events are rare for all groups, and there is no evidence of risk modification due to multimorbidity.
- Francisco Tsz Tsun Lai
- , Lei Huang
- & Ian Chi Kei Wong
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| Open AccessImmune-related adverse events and the balancing act of immunotherapy
The benefit from immune checkpoint inhibitors is tempered by immunologic toxicities, which involve diverse organs, have varying biology, onset time, and severity. Herein, we identify important areas of controversy and open research questions in the field of immune-related toxicity.
- Michael Conroy
- & Jarushka Naidoo
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| Open AccessCombination of pre-adapted bacteriophage therapy and antibiotics for treatment of fracture-related infection due to pandrug-resistant Klebsiella pneumoniae
In this case study of a patient with fracture-related pandrug-resistant Klebsiella pneumoniae infection after long-term antibiotic therapy, the authors use a combination therapy of pre-adapted bacteriophage and antibiotics resulting in clinical, microbiological and radiological improvement.
- Anaïs Eskenazi
- , Cédric Lood
- & Jean-Paul Pirnay
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| Open AccessNon-invasive MR imaging of human brain lymphatic networks with connections to cervical lymph nodes
Studies in animal models have visualized drainage of interstitial or cerebrospinal fluid via lymphatic vessels, but there is limited data on in humans. Here, the authors non-invasively visualize lymphatic structures in the human brain, including evidence of lymphatic flow from cranial nerves to cervical lymph nodes, and differences by age and sex, without use of contrast agents.
- Mehmet Sait Albayram
- , Garrett Smith
- & Onder Albayram
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| Open AccessRapid antigen testing as a reactive response to surges in nosocomial SARS-CoV-2 outbreak risk
Healthcare facilities are vulnerable to SARS-CoV-2 introductions and subsequent nosocomial outbreaks. Here, the authors simulate transmission in a long-term care facility with varying containment measures in place and evaluate reactive response with antigen rapid diagnostic testing.
- David R. M. Smith
- , Audrey Duval
- & Laura Temime
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| Open AccessSystematic analysis of drug-associated myocarditis reported in the World Health Organization pharmacovigilance database
Multiple drugs have been in the past associated with myocarditis. Here the authors perform a pharmacovigilance study and analyze 5108 reports of drug-induced myocarditis reporting temporal trends and overall mortality and identifying emerging drug classes among the treatments associated with myocarditis.
- Lee S. Nguyen
- , Leslie T. Cooper
- & Joe-Elie Salem
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| Open AccessA machine and human reader study on AI diagnosis model safety under attacks of adversarial images
While active efforts are advancing medical AI model development and clinical translation, safety issues of medical AI models have emerged. Here, the authors investigate the effects on an AI model and on human experts of potential fake/adversarial images for breast cancer diagnosis.
- Qianwei Zhou
- , Margarita Zuley
- & Shandong Wu
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Article
| Open AccessA low-cost and shielding-free ultra-low-field brain MRI scanner
A low cost MRI scanner may have the potential to meet clinical needs at point of care or in low and middle income countries. Here the authors describe a low cost 0.055 Tesla MRI scanner that operates using a standard AC power outlet, and demonstrate its preliminary feasibility in diagnosing brain tumor and stroke.
- Yilong Liu
- , Alex T. L. Leong
- & Ed X. Wu
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| Open AccessThe effect of COVID-19 vaccination in Italy and perspectives for living with the virus
Vaccination campaigns against COVID-19 are allowing the progressive release of physical distancing restrictions in many countries. Here, the authors assess the impact of the vaccination program in Italy and evaluate possible prospects for reopening the society while at the same time keeping COVID-19 under control.
- Valentina Marziano
- , Giorgio Guzzetta
- & Stefano Merler
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| Open AccessIncreased transmissibility of SARS-CoV-2 lineage B.1.1.7 by age and viral load
Establishing the relative transmissibility of emerging variants of SARS-CoV-2 is key for pandemic management. Here, the authors use full-population administrative data from Denmark linked to PCR test results and estimate that the Alpha variant was ~60% higher than other strains circulating in early 2021.
- Frederik Plesner Lyngse
- , Kåre Mølbak
- & Carsten Thure Kirkeby
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Article
| Open AccessSerological responses and vaccine effectiveness for extended COVID-19 vaccine schedules in England
The UK extended the interval until the second COVID-19 vaccine dose up to 12 weeks. Here, the authors show in a cohort of 750 participants aged 50–89 years that the extended schedule results in higher antibody titers and estimate a higher vaccine effectiveness for the extended schedule.
- Gayatri Amirthalingam
- , Jamie Lopez Bernal
- & Mary E. Ramsay
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Article
| Open AccessA deep learning framework identifies dimensional representations of Alzheimer’s Disease from brain structure
Alzheimer’s disease is heterogeneous in its neuroimaging and clinical phenotypes. Here the authors present a semi-supervised deep learning method, Smile-GAN, to show four neurodegenerative patterns and two progression pathways providing prognostic and clinical information.
- Zhijian Yang
- , Ilya M. Nasrallah
- & Balebail Ashok Raj
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| Open AccessPaper microfluidic implementation of loop mediated isothermal amplification for early diagnosis of hepatitis C virus
Current HCV nucleic acid-based diagnosis is largely performed in centralised laboratories. Here, the authors present a pan-genotypic RNA assay, based on reverse transcriptase loop mediated isothermal amplification and develop a low-cost prototype paper-based lateral flow device for point-of-care use, providing a visually read result within 40 min.
- Weronika Witkowska McConnell
- , Chris Davis
- & Jonathan M. Cooper
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Article
| Open AccessChanges in notifiable infectious disease incidence in China during the COVID-19 pandemic
Non-pharmaceutical interventions implemented to mitigate COVID-19 transmission are likely to have impacted spread of other infectious diseases. Here, the authors investigate changes in the incidence of 31 notifiable infectious diseases using surveillance data from China.
- Meng-Jie Geng
- , Hai-Yang Zhang
- & Wei Liu
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Article
| Open AccessRisk-stratification of febrile African children at risk of sepsis using sTREM-1 as basis for a rapid triage test
Identification of febrile children at risk of death in low-resource settings can improve survival, but tools for their prompt recognition are lacking. Here, the authors show that sTREM-1 measured at clinical presentation predicts in-hospital mortality in febrile children in Uganda.
- Aleksandra Leligdowicz
- , Andrea L. Conroy
- & Kevin C. Kain
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Article
| Open AccessImprinted lncRNA Dio3os preprograms intergenerational brown fat development and obesity resistance
Maternal obesity predisposes offspring to obesity and metabolic disorders through incompletely understood mechanisms. Here the authors report that Dio3os is an imprinted long-coding RNA that modulates brown adipose tissue development and obesity resistance in the offspring.
- Yan-Ting Chen
- , Qi-Yuan Yang
- & Min Du
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Article
| Open AccessAdaptation, spread and transmission of SARS-CoV-2 in farmed minks and associated humans in the Netherlands
SARS-CoV-2 was detected in mink farms in the Netherlands in the first wave of the pandemic with evidence of human-to-mink and mink-to-human transmission. Here, the authors investigate this outbreak using phylodynamic analysis and show that personnel links and spatial proximity are predictors of transmission between farms.
- Lu Lu
- , Reina S. Sikkema
- & Marion P. G. Koopmans
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Article
| Open AccessBST1 regulates nicotinamide riboside metabolism via its glycohydrolase and base-exchange activities
Nicotinamide riboside (NR) is a NAD + precursor exhibiting beneficial effects against aging. Here the authors demonstrate that orally administered NR increases NAD + levels in a diphasic manner and that bone marrow stromal cell antigen 1 plays a crucial role for NAD + synthesis from NR.
- Keisuke Yaku
- , Sailesh Palikhe
- & Takashi Nakagawa
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Article
| Open AccessAge-seroprevalence curves for the multi-strain structure of influenza A virus
Multi-strain pathogens, such as influenza, present challenges for interpretation of seroprevalence data as estimates may vary by strain. Here, the authors develop a method for estimating age-specific seroprevalence based on principal components analysis and apply it to influenza data from Vietnam.
- Dao Nguyen Vinh
- , Nguyen Thi Duy Nhat
- & Maciej F. Boni
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Article
| Open AccessThe reduction of race and gender bias in clinical treatment recommendations using clinician peer networks in an experimental setting
Race and gender bias in healthcare contribute to health disparities. Here the authors show in an experimental setting that structured information sharing networks among clinicians can reduce race and gender bias in medical decisions.
- Damon Centola
- , Douglas Guilbeault
- & Jingwen Zhang
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Article
| Open AccessBurdens of post-acute sequelae of COVID-19 by severity of acute infection, demographics and health status
Post-acute sequelae of COVID-19 (PASC, or ‘Long COVID’) has caused concern but the burden and risk factors are not well understood. Here, the authors use US electronic health record data and estimate an overall burden of PASC of ~7% at six months, with variation by severity of acute infection, baseline health status and demographics.
- Yan Xie
- , Benjamin Bowe
- & Ziyad Al-Aly