Sleep is regulated by homeostatic processes, yet the biological basis of sleep pressure that accumulates during wakefulness, triggers sleep, and dissipates during sleep remains elusive. We explored a causal relationship between cellular synaptic strength and electroencephalography delta power indicating macro-level sleep pressure by developing a theoretical framework and a molecular tool to manipulate synaptic strength. The mathematical model predicted that increased synaptic strength promotes the neuronal “down state” and raises the delta power. Our molecular tool (synapse-targeted chemically induced translocation of Kalirin-7, SYNCit-K), which induces dendritic spine enlargement and synaptic potentiation through chemically induced translocation of protein Kalirin-7, demonstrated that synaptic potentiation of excitatory neurons in the prefrontal cortex (PFC) increases nonrapid eye movement sleep amounts and delta power. Thus, synaptic strength of PFC excitatory neurons dictates sleep pressure in mammals.

Human sleep phenotypes can be defined and diversified by both genetic and environmental factors. However, some sleep phenotypes are difficult to evaluate without long-term, precise sleep monitoring, for which simple yet accurate sleep measurement is required. To solve this problem, we recently developed a state-of-the-art sleep/wake classification algorithm based on wristband-type accelerometers, termed ACCEL (acceleration-based classification and estimation of long-term sleep-wake cycles). In this study, we optimized and applied ACCEL to large-scale analysis of human sleep phenotypes. The clustering of an about 100,000-arm acceleration dataset in the UK Biobank using uniform manifold approximation and projection (UMAP) dimension reduction and density-based spatial clustering of applications with noise (DBSCAN) clustering methods identified 16 sleep phenotypes, including those related to social jet lag, chronotypes (“morning/night person”), and seven different insomnia-like phenotypes. Considering the complex relationship between sleep disorders and other psychiatric disorders, these unbiased and comprehensive analyses of sleep phenotypes in humans will not only contribute to the advancement of biomedical research on genetic and environmental factors underlying human sleep patterns but also, allow for the development of better digital biomarkers for psychiatric disorders.

We evaluated the impact of the new coronavirus disease (COVID-19) on healthcare access in Japan in terms of the number of outpatients and hospitalized patients as well as the length of hospital stays, during the first wave of the pandemic, up to June 2020. This observational study evaluated the monthly average number of outpatients per day at hospitals, the average number of hospitalized patients per day, and the average length of hospital stays per patient, from December 2010 to June 2020, using the hospital reports data, which are open aggregated data on the utilization of hospitals from the Ministry of Health, Labour and Welfare. These numbers were compared with those from the same period of previous years, using a quasi-Poisson regression model. We found a nationwide decrease in the number of outpatients in general hospitals and hospitalized patients, particularly in long-term care beds in Japan, as well as the excess length of hospital stays among psychiatric care patients during the first wave of the COVID-19. This limited access to healthcare demonstrated the importance of the long-term health monitoring of vulnerable populations and the need for urgent management support to healthcare facilities in preparation for possible prolonged pandemics in the future.

Arm acceleration data have been used to measure sleep–wake rhythmicity. Although several methods have been developed for the accurate classification of sleep–wake episodes, a method with both high sensitivity and specificity has not been fully established. In this study, we developed an algorithm, named ACceleration-based Classification and Estimation of Long-term sleep–wake cycles (ACCEL) that classifies sleep and wake episodes using only raw accelerometer data, without relying on device-specific functions. The algorithm uses a derivative of triaxial acceleration (jerk), which can reduce individual differences in the variability of acceleration data. Applying a machine learning algorithm to the jerk data achieved sleep–wake classification with a high sensitivity (>90%) and specificity (>80%). A jerk-based analysis also succeeded in recording periodic activities consistent with pulse waves. Therefore, the ACCEL algorithm will be a useful method for large-scale sleep measurement using simple accelerometers in real-world settings.

Background: Comprehensive and evidence-based countermeasures against emerging infectious diseases have become increasingly important in recent years. COVID-19 and many other infectious diseases are spread by human movement and contact, but complex transportation networks in the 21st century make it difficult to predict disease spread in rapidly changing situations. It is especially challenging to estimate the network of infection transmission in countries where traffic and human movement data infrastructure is not yet developed. Methods: In this study, we devised a method utilizing an ordinary and partial differential equations-based mathematical model and a modified mathematical optimization method to estimate the network of transmission of COVID-19 from the time series data of its infection and applied it to determine its spread across areas in Japan. Furthermore, utilizing the estimated human mobility network, we predicted the spread of infection using the Tokyo Olympics as a model. Findings: We incorporated the effects of soft lockdowns, such as the declaration of a state of emergency, and changes in the infection network due to government-sponsored travel promotion, and revealed that the estimated effective distance captured human mobility changing dynamically in the different stages of the pandemic. The model predicted that the Tokyo Olympic and Paralympic Games would increase the number of infected cases in the host prefectures by up to 80%. Interpretation: The models used in this study are available online, and our data-driven infection network models are scalable, whether it be at the level of a city, town, country, or continent, and applicable anywhere in the world, as long as the time-series data of infections per region is available. These estimations of effective distance and the depiction of infectious disease networks based on actual infection data are expected to be useful in devising data-driven countermeasures against emerging infectious diseases worldwide.