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Early detection of infectious diseases is crucial for reducing transmission and facilitating early intervention. In this study, we built a real-time smartwatch-based alerting system that detects aberrant physiological and activity signals (heart rates and steps) associated with the onset of early infection and implemented this system in a prospective study. In a cohort of 3,318 participants, of whom 84 were infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), this system generated alerts for pre-symptomatic and asymptomatic SARS-CoV-2 infection in 67 (80%) of the infected individuals. Pre-symptomatic signals were observed at a median of 3 days before symptom onset. Examination of detailed survey responses provided by the participants revealed that other respiratory infections as well as events not associated with infection, such as stress, alcohol consumption and travel, could also trigger alerts, albeit at a much lower mean frequency (1.15 alert days per person compared to 3.42 alert days per person for coronavirus disease 2019 cases). Thus, analysis of smartwatch signals by an online detection algorithm provides advance warning of SARS-CoV-2 infection in a high percentage of cases. This study shows that a real-time alerting system can be used for early detection of infection and other stressors and employed on an open-source platform that is scalable to millions of users., (© 2021. The Author(s).)

The internalizing psychopathologies (IP) are a highly prevalent group of disorders for which little data exists to guide treatment selection. We examine whether graph theoretical metrics from white matter connectomes may serve as biomarkers of disease and predictors of treatment response. We focus on the uncinate fasciculus subnetwork, which has been previously implicated in these disorders. We compared baseline graph measures from a transdiagnostic IP cohort with controls. Patients were randomized to either SSRI or cognitive behavioral therapy and we determined if graph theory metrics change following treatment, and whether these changes correlated with treatment response. Lastly, we investigated whether baseline metrics correlated with treatment response. Several baseline nodal graph metrics differed at baseline. Of note, right amygdala betweenness centrality was increased in patients relative to controls. In addition, white matter integrity of the uncinate fasciculus was decreased at baseline in patients versus controls. The SSRI and CBT cohorts had increased left frontal superior orbital betweenness centrality and left frontal medial orbital clustering coefficient, respectively, suggesting the presence of treatment specific neural correlates of treatment response. This study provides insight on shared white matter network features of IPs and elucidates potential biomarkers of treatment response that may be modality-specific., Competing Interests: Declarations of competing interest Authors AL and OA are the co-founders of KeyWise, Inc. OA serves on the advisory board of Blueprint Health and Embodied Labs. AL serves on the advisory board of Buoy Health., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Somatic mutations in the estrogen receptor alpha (ERα) gene (ESR1), especially Y537S and D538G, have been linked to acquired resistance to endocrine therapies. Cell-based studies demonstrated that these mutants confer ERα constitutive activity and antiestrogen resistance and suggest that ligand-binding domain dysfunction leads to endocrine therapy resistance. Here, we integrate biophysical and structural biology data to reveal how these mutations lead to a constitutively active and antiestrogen-resistant ERα. We show that these mutant ERs recruit coactivator in the absence of hormone while their affinities for estrogen agonist (estradiol) and antagonist (4-hydroxytamoxifen) are reduced. Further, they confer antiestrogen resistance by altering the conformational dynamics of the loop connecting Helix 11 and Helix 12 in the ligand-binding domain of ERα, which leads to a stabilized agonist state and an altered antagonist state that resists inhibition.