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Mayfield et al. describe the implementation and feasibility of an exclusively remote randomized clinical trial of hydroxychloroquine and azithromycin for the treatment of COVID-19. The trial included monitoring of cardiovascular safety which was successfully done using digital technologies.
Liu et al. develop a deep learning-based tool to detect and segment diffusion abnormalities seen on magnetic resonance imaging (MRI) in acute ischemic stroke. The tool is tested in two clinical MRI datasets and outperforms existing algorithms in the detection of small lesions, potentially allowing clinicians and clinical researchers to more quickly and accurately diagnose and assess ischemic strokes.
Phan et al. assess the presence of human endogenous retrovirus K (HERV-K) in the serum and brain samples of individuals with behavioral variant frontotemporal dementia (bvFTD) with TDP-43 pathology, as seen in amyotrophic lateral sclerosis. The authors show HERV-K is associated with manifestations of bvFTD with TDP-43 pathology.
Sun et al. perform a two-sample Mendelian randomization study of a large number of traits with the aim of identifying risk factors of severe COVID-19. They show that body mass index-related traits, specific white blood cells, and some circulating proteins are risk factors for the development of severe COVID-19.
Lee et al. use an antibody-drug conjugate to treat pathologic ocular neovascularization in mouse models. The antibody-drug conjugate targets PDGFRβ-expressing pericytes, with similar therapeutic effects to an anti-VEGF agent and with limited unwanted toxicity.
Di Domenico and Sabbatini et al. model the impact of lockdowns of varying duration and intensity on the control of COVID-19, using data from the third wave of the epidemic in the Paris region of France. The authors introduce a measure of policy-induced fatigue, the ‘distress index’, that helps to explain why shorter, more stringent restrictions might be more effective.
Papillon-Cavanagh et al. evaluate the impact of biopsy site on measurements of tumor mutational burden (TMB) in a large cohort of tumor samples. The authors observe cancer- and tissue-specific patterns in TMB scores, as well as differences in TMB scores between primary and metastatic samples from the same cancer type.
Kalka and Gavrieli et al. assessed the heritability of variation in the glycaemic response to metformin by leveraging electronic health records data gathered from a large cohort of patients with diabetes and combining it with pedigree information. The authors show that although the variability in this response has a heritable component, most of it is likely non-genetic.
Marks and Calix et al. perform a case-control genomic epidemiology study comparing Staphylococcus aureus isolates from intravenous drug use-associated bloodstream infections with those from other bloodstream infections. The authors show there is clonal expansion of lineages in intravenous drug use-associated bloodstream infections suggesting person-to-person transmission of S. aureus.
Nahkuri et al. evaluate potential prognostic factors for COVID-19 mortality in a large US database of electronic health records. They find that fluid, pH and electrolyte imbalances – diagnosed at least one month prior to COVID-19 diagnosis – are associated with mortality.
Coutinho et al. use genomic and epidemiological data from Manaus, Brazil, to estimate the transmissibility and potential for reinfection with the SARS-CoV-2 variant-of-concern P.1 (gamma). Using mathematical modelling, the authors estimate that P.1 is 2.6 times more transmissible than previous SARS-CoV-2 variants circulating in Manaus and underlies a large proportion of reinfections in Manaus.
Wurzel et al. describe the kinetics of the immune response in relation to clinical and virological features in a 5-month old infant with congenital heart disease and severe COVID-19. The immune response was characterised by an elevated inflammatory response in the acute phase of infection, followed by Th2 skewing and prolonged T cell activation.
Kongsuphol et al. develop a paper-based, vertical flow assay to detect SARS-CoV-2 neutralizing antibodies. The point-of-care assay has comparable performance to lab-based tests and provides results in 10 min.
Campos et al. study the genetic aetiology of antidepressant side effects. Using data from the Australian Genetics of Depression study, the authors show that polygenic risk scores for traits such as BMI, insomnia and headaches have a shared genetic basis with side effects to commonly used antidepressant drugs.
Jeong et al. report a series of COVID-19 patients with hearing- and balance-related symptoms. The authors show that human and mouse inner ear tissues, as well as human inner ear cells and organoids derived from induced pluripotent stem cells, express SARS-CoV-2 entry factors, and that these in vitro models of the human inner ear are susceptible to SARS-CoV-2 infection
Zhang et al. develop a natural language processing approach, based on the BERT model, to extract linguistic information from chest X-ray radiography reports. The authors establish a 25-label classification system for abnormal findings described in the reports and validate their model using data from multiple sites.
Konigsberg et al. profile DNA methylation in blood samples from SARS-CoV-2 cases and controls. The authors use machine learning to classify infected vs. non-infected individuals and predict clinical outcomes related to disease severity.
Sachak-Patwa et al. estimate the risk of SARS-CoV-2 outbreaks in low prevalence settings following the removal of travel restrictions and other non-pharmaceutical interventions, with the Isle of Man and Israel as case studies. Using a branching process mathematical model, the authors show that even after a large proportion of the population is vaccinated, there remains a risk of local outbreaks from imported cases.
Dalle Carbonare et al. perform a serology study in participants with a prior infection of SARS-CoV-2 and those who are SARS-CoV-2-naïve, who received two doses of the Pfizer-BioNTech BNT162b2 vaccine. After a single dose they observe a quicker recall of pseudovirus neutralization titres in previously-infected participants and a potent IgA response in both groups that was not associated with serum neutralization titres.
Plontke et al. report data on the preservation of vestibular function in a series of patients undergoing surgical removal of intracochlear tumors. Using objective clinical tests, the authors show that in most patients the vestibular system can function normally despite major surgical trauma to the cochlea.