Very short sleep duration reveals a proteomic fingerprint that is selectively associated with incident diabetes mellitus but not with incident coronary heart disease: a cohort study.

BACKGROUND: The molecular pathways linking short and long sleep duration with incident diabetes mellitus (iDM) and incident coronary heart disease (iCHD) are not known. We aimed to identify circulating protein patterns associated with sleep duration and test their impact on incident cardiometabolic disease. METHODS: We assessed sleep duration and measured 78 plasma proteins among 3336 participants aged 46-68 years, free from DM and CHD at baseline, and identified cases of iDM and iCHD using national registers. Incident events occurring in the first 3 years of follow-up were excluded from analyses. Tenfold cross-fit partialing-out lasso logistic regression adjusted for age and sex was used to identify proteins that significantly predicted sleep duration quintiles when compared with the referent quintile 3 (Q3). Predictive proteins were weighted and combined into proteomic scores (PS) for sleep duration Q1, Q2, Q4, and Q5. Combinations of PS were included in a linear regression model to identify the best predictors of habitual sleep duration. Cox proportional hazards regression models with sleep duration quintiles and sleep-predictive PS as the main exposures were related to iDM and iCHD after adjustment for known covariates. RESULTS: Sixteen unique proteomic markers, predominantly reflecting inflammation and apoptosis, predicted sleep duration quintiles. The combination of PSQ1 and PSQ5 best predicted sleep duration. Mean follow-up times for iDM (n = 522) and iCHD (n = 411) were 21.8 and 22.4 years, respectively. Compared with sleep duration Q3, all sleep duration quintiles were positively and significantly associated with iDM. Only sleep duration Q1 was positively and significantly associated with iCHD. Inclusion of PSQ1 and PSQ5 abrogated the association between sleep duration Q1 and iDM. Moreover, PSQ1 was significantly associated with iDM (HR = 1.27, 95% CI: 1.06-1.53). PSQ1 and PSQ5 were not associated with iCHD and did not markedly attenuate the association between sleep duration Q1 with iCHD. CONCLUSIONS: We here identify plasma proteomic fingerprints of sleep duration and suggest that PSQ1 could explain the association between very short sleep duration and incident DM.

Genome-scale metabolic network reconstruction of model animals as a platform for translational research.

Genome-scale metabolic models (GEMs) are used extensively for analysis of mechanisms underlying human diseases and metabolic malfunctions. However, the lack of comprehensive and high-quality GEMs for model organisms restricts translational utilization of omics data accumulating from the use of various disease models. Here we present a unified platform of GEMs that covers five major model animals, including Mouse1 (Mus musculus), Rat1 (Rattus norvegicus), Zebrafish1 (Danio rerio), Fruitfly1 (Drosophila melanogaster), and Worm1 (Caenorhabditis elegans). These GEMs represent the most comprehensive coverage of the metabolic network by considering both orthology-based pathways and species-specific reactions. All GEMs can be interactively queried via the accompanying web portal Metabolic Atlas. Specifically, through integrative analysis of Mouse1 with RNA-sequencing data from brain tissues of transgenic mice we identified a coordinated up-regulation of lysosomal GM2 ganglioside and peptide degradation pathways which appears to be a signature metabolic alteration in Alzheimer's disease (AD) mouse models with a phenotype of amyloid precursor protein overexpression. This metabolic shift was further validated with proteomics data from transgenic mice and cerebrospinal fluid samples from human patients. The elevated lysosomal enzymes thus hold potential to be used as a biomarker for early diagnosis of AD. Taken together, we foresee that this evolving open-source platform will serve as an important resource to facilitate the development of systems medicines and translational biomedical applications.

Midlife Intakes of the Isoflavone Genistein and Soy and the Risk of Late-life Cognitive Impairment: The JPHC Saku Mental Health Study.

BACKGROUND: The number of people with cognitive impairment, including dementia, in the world is steadily increasing. Although the consumption of isoflavones and soy is associated with a reduced risk of cardiovascular disease, it might also be associated with cognitive impairment. The low number of studies investigating the association between soy/isoflavone intake and cognitive function warrant additional research. METHODS: The Japan Public Health Center-based prospective (JPHC) Study is a large population-based cohort. Midlife dietary intake of soy and the isoflavone genistein was assessed on two occasions: in the years 1995 and 2000. In 2014-2015, 1,299 participants from Nagano prefecture completed a mental health screening. Of these, a total of 1,036 participants were included in analyses. Logistic regression was used to determine Odds Ratios (OR) and 95% Confidence Intervals (CI) for the association between midlife energy-adjusted genistein and soy food intake and cognitive impairment. RESULTS: There were 392 cases of cognitive impairment (346 cases of MCI and 46 cases of dementia). Compared to the lowest dietary quartile of energy-adjusted genistein intake, the highest quartile was significantly associated with cognitive impairment (OR = 1.51; 95% CI, 1.02-2.24; P for trend = 0.03) in the final multivariable analysis. CONCLUSION: High midlife intake of the isoflavone genistein is associated with late-life cognitive impairment.

Sleep duration and risk of cancer incidence and mortality: A pooled analysis of six population-based cohorts in Japan.

Sleep duration is emerging as an important modifiable risk factor for morbidity and mortality. We assessed the association between sleep duration and cancer incidence and mortality among Japanese adults using data from six population-based cohorts with 271 694 participants. During a total follow-up period of about 5.9 million person-years, we identified 40 751 incident cancer cases and 18 323 cancer deaths. We computed study-specific hazard ratios (HRs) and 95% confidence intervals (CIs) using Cox proportional hazards regression models and pooled the estimates using random-effects meta-analysis. Sleep duration of ≥10 hours (vs 7 hours) was associated with increased risk of cancer incidence among women (HR 1.19, 95% CI 1.02-1.38), but not men, and increased risk of cancer mortality among men (HR 1.18, 95% CI 1.00-1.39) and women (HR 1.44, 95% CI 1.20-1.73). Sleep duration of ≤5 hours (vs 7 hours) was not associated with cancer incidence and mortality. However, among postmenopausal women, sleep durations of both ≤5 and ≥10 hours (vs 7 hours) were associated with an increased risk of cancer mortality. Among Japanese adults, sleep duration of ≥10 hours is associated with increased risk of cancer incidence and mortality among women and cancer mortality among men.

Correction: Ionotropic Chemosensory Receptors Mediate the Taste and Smell of Polyamines.

[This corrects the article DOI: 10.1371/journal.pbio.1002454.].

The Association Between Habitual Sleep Duration and Mortality According to Sex and Age: The Japan Public Health Center-based Prospective Study.

BACKGROUND: Short and long sleep durations are associated with mortality outcomes. The association between sleep duration and mortality outcomes may differ according to sex and age. METHODS: Participants of the Japan Public Health Center-based prospective study (JPHC Study) were aged 40-69 years and had completed a detailed questionnaire on lifestyle factors. Sex- and age-stratified analyses on the association between habitual sleep duration and mortality from all-causes, cardiovascular diseases (CVD), cancer and other causes included 46,152 men and 53,708 women without a history of CVD or cancer. Cox proportional hazards regression models, adjusted for potential confounders, were used to determine hazard ratios and 95% confidence intervals. RESULTS: Mean follow-up time was 19.9 years for men and 21.0 years for women. In the multivariable sex-stratified models, some categories of sleep durations ≥8 hours were positively associated with mortality from all-causes, CVD, and other causes in men and women compared with 7 hours. The sex- and age-stratified analyses did not reveal any major differences in the association between sleep duration and mortality outcomes in groups younger and older than 50 years of age. The only exception was the significant interaction between sleep duration and age in women for mortality from other causes. CONCLUSIONS: Sleep durations ≥8 hours are associated with mortality outcomes in men and women. Age may be an effect modifier for the association between sleep duration and mortality from other causes in women.

Heart Rate Modeling and Prediction Using Autoregressive Models and Deep Learning.

Physiological time series are affected by many factors, making them highly nonlinear and nonstationary. As a consequence, heart rate time series are often considered difficult to predict and handle. However, heart rate behavior can indicate underlying cardiovascular and respiratory diseases as well as mood disorders. Given the importance of accurate modeling and reliable predictions of heart rate fluctuations for the prevention and control of certain diseases, it is paramount to identify models with the best performance in such tasks. The objectives of this study were to compare the results of three different forecasting models (Autoregressive Model, Long Short-Term Memory Network, and Convolutional Long Short-Term Memory Network) trained and tested on heart rate beats per minute data obtained from twelve heterogeneous participants and to identify the architecture with the best performance in terms of modeling and forecasting heart rate behavior. Heart rate beats per minute data were collected using a wearable device over a period of 10 days from twelve different participants who were heterogeneous in age, sex, medical history, and lifestyle behaviors. The goodness of the results produced by the models was measured using both the mean absolute error and the root mean square error as error metrics. Despite the three models showing similar performance, the Autoregressive Model gave the best results in all settings examined. For example, considering one of the participants, the Autoregressive Model gave a mean absolute error of 2.069 (compared to 2.173 of the Long Short-Term Memory Network and 2.138 of the Convolutional Long Short-Term Memory Network), achieving an improvement of 5.027% and 3.335%, respectively. Similar results can be observed for the other participants. The findings of the study suggest that regardless of an individual's age, sex, and lifestyle behaviors, their heart rate largely depends on the pattern observed in the previous few minutes, suggesting that heart rate can be reasonably regarded as an autoregressive process. The findings also suggest that minute-by-minute heart rate prediction can be accurately performed using a linear model, at least in individuals without pathologies that cause heartbeat irregularities. The findings also suggest many possible applications for the Autoregressive Model, in principle in any context where minute-by-minute heart rate prediction is required (arrhythmia detection and analysis of the response to training, among others).

Family history of cancer and subsequent risk of cancer: A large-scale population-based prospective study in Japan.

Family history (FH) of cancer is an important factor of increased risk of several cancers. Although the association between FH of cancer and concordant cancer risk has been reported in many previous epidemiological studies, no comprehensive prospective study with adjustment for lifestyle habits has evaluated the association of FH of cancer and concordant cancer risk. We investigated the association between FH of cancer and concordant cancer risk in a Japanese population-based prospective study, initiated in 1990 for cohort I and in 1993 for cohort II. We analyzed data on 103,707 eligible subjects without a history of cancer who responded to a self-administered questionnaire including FH of cancer at baseline. Study subjects were followed through 2012 and analyzed using multivariable-adjusted Cox proportional hazards regression models. During 1,802,581 person-years of follow-up, a total of 16,336 newly diagnosed cancers were identified. Any site (Hazard ratios = 1.11 (95% confidence interval = 1.07-1.15]), esophagus (2.11 [1.00-4.45]), stomach (1.36 [1.19-1.55]), liver (1.69 [1.10-2.61]), pancreas (2.63 [1.45-4.79]), lung (1.51 [1.14-2.00]), uterus (1.93 [1.06-3.51]) and bladder cancers (6.06 [2.49-14.74]) with FH of the concordant cancer were associated with an increased risk compared to those without FH. Our findings suggest that having FH of cancer is associated with an increased risk of several concordant cancer incidences in an Asian population. Enquiring about FH of several types of cancer may be important in identifying groups at high-risk of those cancers.

Ionotropic Chemosensory Receptors Mediate the Taste and Smell of Polyamines.

The ability to find and consume nutrient-rich diets for successful reproduction and survival is fundamental to animal life. Among the nutrients important for all animals are polyamines, a class of pungent smelling compounds required in numerous cellular and organismic processes. Polyamine deficiency or excess has detrimental effects on health, cognitive function, reproduction, and lifespan. Here, we show that a diet high in polyamine is beneficial and increases reproductive success of flies, and we unravel the sensory mechanisms that attract Drosophila to polyamine-rich food and egg-laying substrates. Using a combination of behavioral genetics and in vivo calcium imaging, we demonstrate that Drosophila uses multisensory detection to find and evaluate polyamines present in overripe and fermenting fruit, their favored feeding and egg-laying substrate. In the olfactory system, two coexpressed ionotropic receptors (IRs), IR76b and IR41a, mediate the long-range attraction to the odor. In the gustatory system, multimodal taste sensation by IR76b receptor and GR66a bitter receptor neurons is used to evaluate quality and valence of the polyamine providing a mechanism for the fly's high attraction to polyamine-rich and sweet decaying fruit. Given their universal and highly conserved biological roles, we propose that the ability to evaluate food for polyamine content may impact health and reproductive success also of other animals including humans.

The Norway spruce genome sequence and conifer genome evolution.

Conifers have dominated forests for more than 200 million years and are of huge ecological and economic importance. Here we present the draft assembly of the 20-gigabase genome of Norway spruce (Picea abies), the first available for any gymnosperm. The number of well-supported genes (28,354) is similar to the >100 times smaller genome of Arabidopsis thaliana, and there is no evidence of a recent whole-genome duplication in the gymnosperm lineage. Instead, the large genome size seems to result from the slow and steady accumulation of a diverse set of long-terminal repeat transposable elements, possibly owing to the lack of an efficient elimination mechanism. Comparative sequencing of Pinus sylvestris, Abies sibirica, Juniperus communis, Taxus baccata and Gnetum gnemon reveals that the transposable element diversity is shared among extant conifers. Expression of 24-nucleotide small RNAs, previously implicated in transposable element silencing, is tissue-specific and much lower than in other plants. We further identify numerous long (>10,000 base pairs) introns, gene-like fragments, uncharacterized long non-coding RNAs and short RNAs. This opens up new genomic avenues for conifer forestry and breeding.

Incident diabetes mellitus may explain the association between sleep duration and incident coronary heart disease.

AIMS/HYPOTHESIS: Sleep duration is a risk factor for incident diabetes mellitus and CHD. The primary aim of the present study was to investigate, in sex-specific analyses, the role of incident diabetes as the possible biological mechanism for the reported association between short/long sleep duration and incident CHD. Considering that diabetes is a major risk factor for CHD, we hypothesised that any association with sleep duration would not hold for cases of incident CHD occurring before incident diabetes ('non-diabetes CHD') but would hold true for cases of incident CHD following incident diabetes ('diabetes-CHD'). METHODS: A total of 6966 men and 9378 women aged 45-73 years from the Malmö Diet Cancer Study, a population-based, prospective cohort, who had answered questions on habitual sleep duration and did not have a history of prevalent diabetes or CHD were included in the analyses. Incident cases of diabetes and CHD were identified using national registers. Sex-specific Cox proportional hazards regression models were stratified by BMI and adjusted for known covariates of diabetes and CHD. RESULTS: Mean follow-up times for incident diabetes (n = 1137/1016 [men/women]), incident CHD (n = 1170/578), non-diabetes CHD (n = 1016/501) and diabetes-CHD (n = 154/77) were 14.2-15.2 years for men, and 15.8-16.5 years for women. In men, short sleep duration (< 6 h) was associated with incident diabetes (HR 1.35, 95% CI 1.01, 1.80), CHD (HR 1.41, 95% CI 1.06, 1.89) and diabetes-CHD (HR 2.34, 95% CI 1.20, 4.55). Short sleep duration was not associated with incident non-diabetes CHD (HR 1.35, 95% CI 0.98, 1.87). Long sleep duration (≥ 9 h) was associated with incident diabetes (HR 1.37, 95% CI 1.03, 1.83), CHD (HR 1.33, 95% CI 1.01, 1.75) and diabetes-CHD (HR 2.10, 95% CI 1.11, 4.00). Long sleep duration was not associated with incident non-diabetes CHD (HR 1.33, 95% CI 0.98, 1.80). In women, short sleep duration was associated with incident diabetes (HR 1.53, 95% CI 1.16, 2.01), CHD (HR 1.46, 95% CI 1.03, 2.07) and diabetes-CHD (HR 2.88, 95% CI 1.37, 6.08). Short sleep duration was not associated with incident non-diabetes CHD (HR 1.29, 95% CI 0.86, 1.93). CONCLUSIONS/INTERPRETATION: The associations between sleep duration and incident CHD directly reflect the associations between sleep duration and incident diabetes. Incident diabetes may thus be the explanatory mechanism for the association between short and long sleep duration and incident CHD.

Dominant mutations in GRHL3 cause Van der Woude Syndrome and disrupt oral periderm development.

Mutations in interferon regulatory factor 6 (IRF6) account for ∼70% of cases of Van der Woude syndrome (VWS), the most common syndromic form of cleft lip and palate. In 8 of 45 VWS-affected families lacking a mutation in IRF6, we found coding mutations in grainyhead-like 3 (GRHL3). According to a zebrafish-based assay, the disease-associated GRHL3 mutations abrogated periderm development and were consistent with a dominant-negative effect, in contrast to haploinsufficiency seen in most VWS cases caused by IRF6 mutations. In mouse, all embryos lacking Grhl3 exhibited abnormal oral periderm and 17% developed a cleft palate. Analysis of the oral phenotype of double heterozygote (Irf6(+/-);Grhl3(+/-)) murine embryos failed to detect epistasis between the two genes, suggesting that they function in separate but convergent pathways during palatogenesis. Taken together, our data demonstrated that mutations in two genes, IRF6 and GRHL3, can lead to nearly identical phenotypes of orofacial cleft. They supported the hypotheses that both genes are essential for the presence of a functional oral periderm and that failure of this process contributes to VWS.

Coping strategies and risk of cardiovascular disease incidence and mortality: the Japan Public Health Center-based prospective Study.

AIMS: Coping strategies may be significantly associated with health outcomes. This is the first study to investigate the association between baseline coping strategies and cardiovascular disease (CVD) incidence and mortality in a general population cohort. METHODS AND RESULTS: The Japan Public Health Center-based prospective Study asked questions on coping in its third follow-up survey (2000-04). Analyses on CVD incidence and mortality included 57 017 subjects aged 50-79 without a history of CVD and who provided complete answers on approach- and avoidance-oriented coping behaviours and strategies. Cox regression models, adjusted for confounders, were used to determine hazard ratios (HRs) according to coping style. Mean follow-up time was 7.9 years for incidence and 8.0 years for mortality.The premorbid use of an approach-oriented coping strategy was inversely associated with incidence of stroke (HR = 0.85; 95% CI, 0.73-1.00) and CVD mortality (HR = 0.74; 95% CI, 0.55-0.99). Stroke subtype analyses revealed an inverse association between the approach-oriented coping strategy and incidence of ischaemic stroke (HR = 0.79; 95% CI, 0.64-0.98) and a positive association between the combined coping strategy and incidence of intra-parenchymal haemorrhage (HR = 2.03; 95% CI, 1.01-4.10). Utilizing an avoidance coping strategy was associated with increased mortality from ischaemic heart disease (IHD) only in hypertensive individuals (HR = 3.46; 95% CI, 1.07-11.18). The coping behaviours fantasizing and positive reappraisal were associated with increased risk of CVD incidence (HR = 1.24; 95% CI, 1.03-1.50) and reduced risk of IHD mortality (HR = 0.63; 95% CI, 0.40-0.99), respectively. CONCLUSION: An approach-oriented coping strategy, i.e. proactively dealing with sources of stress, may be associated with significantly reduced stroke incidence and CVD mortality in a Japanese population-based cohort.

The association between complete and partial non-response to psychosocial questions and suicide: the JPHC Study.

BACKGROUND: Non-participants to psychosocial studies have been shown to have higher mortality, and mortality differs between partial and complete responders to psychosocial questionnaires. Yet, there is very little information available directly linking survey response status with completing suicide. METHODS: The study population consisted of the participants of the Japanese Public Health Center-based prospective study. Ninety-nine thousand four hundred thirty-nine subjects who returned the 10-year follow-up questionnaire and 31 754 individuals who did not return the questionnaire were included in our analyses. The risk of dying by suicide according to response status was estimated by Cox regression models. RESULTS: There were 358 suicides during 1 128 831 person-years of follow-up (mean follow-up time: 8.6 years). Of those who returned the questionnaire, 53.9% were full responders, 42.8% were partial non-responders, and 3.3% were complete non-responders. The risk of suicide was increased for both complete non-responders [hazard ratio (HR) = 1.84, 95% confidence interval (CI), 0.51, 6.64] and partial non-responders (HR = 1.36, 95% CI, 0.999, 1.84) to the questionnaire as a whole. The adjusting variables explained around 40% of the risk for complete non-responders whereas they did not explain the increased risk of suicide for partial non-responders. The risk of dying by suicide was significantly increased for partial non-responders to the subscale on coping (HR = 1.36, 95% CI, 1.01, 1.85) and for complete non-responders to questions on sleep (HR = 2.07, 95% CI, 1.03, 4.16). CONCLUSIONS: Partial and complete non-responders have increased suicide risk compared with full responders. More than one non-responder category should therefore be considered when interpreting data pertaining to psychosocial questionnaires in longitudinal studies.

The Chironomus tentans genome sequence and the organization of the Balbiani ring genes.

BACKGROUND: The polytene nuclei of the dipteran Chironomus tentans (Ch. tentans) with their Balbiani ring (BR) genes constitute an exceptional model system for studies of the expression of endogenous eukaryotic genes. Here, we report the first draft genome of Ch. tentans and characterize its gene expression machineries and genomic architecture of the BR genes. RESULTS: The genome of Ch. tentans is approximately 200 Mb in size, and has a low GC content (31%) and a low repeat fraction (15%) compared to other Dipteran species. Phylogenetic inference revealed that Ch. tentans is a sister clade to mosquitoes, with a split 150-250 million years ago. To characterize the Ch. tentans gene expression machineries, we identified potential orthologus sequences to more than 600 Drosophila melanogaster (D. melanogaster) proteins involved in the expression of protein-coding genes. We report novel data on the organization of the BR gene loci, including a novel putative BR gene, and we present a model for the organization of chromatin bundles in the BR2 puff based on genic and intergenic in situ hybridizations. CONCLUSIONS: We show that the molecular machineries operating in gene expression are largely conserved between Ch. tentans and D. melanogaster, and we provide enhanced insight into the organization and expression of the BR genes. Our data strengthen the generality of the BR genes as a unique model system and provide essential background for in-depth studies of the biogenesis of messenger ribonucleoprotein complexes.

Validity and reliability of the Oura Ring Generation 3 (Gen3) with Oura sleep staging algorithm 2.0 (OSSA 2.0) when compared to multi-night ambulatory polysomnography: A validation study of 96 participants and 421,045 epochs.

PURPOSE: To evaluate the validity and the reliability of the Oura Ring Generation 3 (Gen3) with Oura Sleep Staging Algorithm 2.0 (OSSA 2.0) through multi-night polysomnography (PSG). PARTICIPANTS AND METHODS: Participants were 96 generally healthy Japanese men and women aged between 20 and 70 years contributing with 421,045 30-s epochs. Sleep scoring was performed according to American Academy of Sleep Medicine criteria. Each participant could contribute with a maximum of three polysomnography (PSG) nights. Within-participant means were created for each sleep measure and paired t-tests were used to compare equivalent measures obtained from the PSG and Oura Rings (non-dominant and dominant hand). Agreement between sleep measures were assessed using Bland-Altman plots. Interrater reliability for epoch accuracy was determined by prevalence-adjusted and bias-adjusted kappa (PABAK). RESULTS: The Oura Ring did not significantly differ from PSG for the measures time in bed, total sleep time, sleep onset latency, sleep period time, wake after sleep onset, time spent in light sleep, and time spent in deep sleep. Oura Rings worn on the non-dominant- and dominant-hand underestimated sleep efficiency by 1.1 %-1.5 % and time spent in REM sleep by 4.1-5.6 min. The Oura Ring had a sensitivity of 94.4 %-94.5 %, specificity of 73.0 %-74.6 %, a predictive value for sleep of 95.9 %-96.1 %, a predictive value for wake of 66.6 %-67.0 %, and accuracy of 91.7 %-91.8 %. PABAK was 0.83-0.84 and reliability was 94.8 %. Sleep staging accuracy ranged between 75.5 % (light sleep) and 90.6 % (REM sleep). CONCLUSIONS: The Oura Ring Gen3 with OSSA 2.0 shows good agreement with PSG for global sleep measures and time spent in light and deep sleep.

Associations of Subjective Sleep Quality with Wearable Device-Derived Resting Heart Rate During REM Sleep and Non-REM Sleep in a Cohort of Japanese Office Workers.

Background: Associations between subjective sleep quality and stage-specific heart rate (HR) may have important clinical relevance when aiming to optimize sleep and overall health. The majority of previously studies have been performed during short periods under laboratory-based conditions. The aim of this study was to investigate the associations of subjective sleep quality with heart rate during REM sleep (HR REMS) and non-REM sleep (HR NREMS) using a wearable device (Fitbit Versa). Methods: This is a secondary analysis of data from the intervention group of a randomized controlled trial (RCT) performed between December 3, 2018, and March 2, 2019, in Tokyo, Japan. The intervention group consisted of 179 Japanese office workers with metabolic syndrome (MetS), Pre-MetS or a high risk of developing MetS. HR was collected with a wearable device and sleep quality was assessed with a mobile application where participants answered The St. Mary's Hospital Sleep Questionnaire. Both HR and sleep quality was collected daily for a period of 90 days. Associations of between-individual and within-individual sleep quality with HR REMS and HR NREMS were analyzed with multi-level model regression in 3 multivariate models. Results: The cohort consisted of 92.6% men (n=151) with a mean age (± standard deviation) of 44.1 (±7.5) years. A non-significant inverse between-individual association was observed for sleep quality with HR REMS (HR REMS -0.18; 95% CI -0.61, 0.24) and HR NREMS (HR NREMS -0.23; 95% CI -0.66, 0.21), in the final multivariable adjusted models; a statistically significant inverse within-individual association was observed for sleep quality with HR REMS (HR REMS -0.21 95% CI -0.27, -0.15) and HR NREMS (HR NREMS -0.21 95% CI -0.27, -0.14) after final adjustments for covariates. Conclusion: The present study shows a statistically significant within-individual association of subjective sleep quality with HR REMS and HR NREMS. These findings emphasize the importance of considering sleep quality on the individual level. The results may contribute to early detection and prevention of diseases associated with sleep quality which may have important implications on public health given the high prevalence of sleep disturbances in the population.

A Disentangled VAE-BiLSTM Model for Heart Rate Anomaly Detection.

Cardiovascular diseases (CVDs) remain a leading cause of death globally. According to the American Heart Association, approximately 19.1 million deaths were attributed to CVDs in 2020, in particular, ischemic heart disease and stroke. Several known risk factors for CVDs include smoking, alcohol consumption, lack of regular physical activity, and diabetes. The last decade has been characterized by widespread diffusion in the use of wristband-style wearable devices which can monitor and collect heart rate data, among other information. Wearable devices allow the analysis and interpretation of physiological and activity data obtained from the wearer and can therefore be used to monitor and prevent potential CVDs. However, these data are often provided in a manner that does not allow the general user to immediately comprehend possible health risks, and often require further analytics to draw meaningful conclusions. In this paper, we propose a disentangled variational autoencoder (ß-VAE) with a bidirectional long short-term memory network (BiLSTM) backend to detect in an unsupervised manner anomalies in heart rate data collected during sleep time with a wearable device from eight heterogeneous participants. Testing was performed on the mean heart rate sampled both at 30 s and 1 min intervals. We compared the performance of our model with other well-known anomaly detection algorithms, and we found that our model outperformed them in almost all considered scenarios and for all considered participants. We also suggest that wearable devices may benefit from the integration of anomaly detection algorithms, in an effort to provide users more processed and straightforward information.

Association between Metabolic Syndrome Status and Daily Physical Activity Measured by a Wearable Device in Japanese Office Workers.

(1) Background: This study examined the cross-sectional association between metabolic syndrome (MetS) status classified into three groups and daily physical activity (PA; step count and active minutes) using a wearable device in Japanese office workers. (2) Methods: This secondary analysis used data from 179 participants in the intervention group of a randomized controlled trial for 3 months. Individuals who had received an annual health check-up and had MetS or were at a high risk of MetS based on Japanese guidelines were asked to use a wearable device and answer questionnaires regarding their daily life for the entire study period. Multilevel mixed-effects logistic regression models adjusted for covariates associated with MetS and PA were used to estimate associations. A sensitivity analysis investigated the associations between MetS status and PA level according to the day of the week. (3) Results: Compared to those with no MetS, those with MetS were not significantly associated with PA, while those with pre-MetS were inversely associated with PA [step count Model 3: OR = 0.60; 95% CI: 0.36, 0.99; active minutes Model 3: OR = 0.62; 95% CI: 0.40, 0.96]. In the sensitivity analysis, day of the week was an effect modifier for both PA (p < 0.001). (4) Conclusions: Compared to those with no MetS, those with pre-MetS, but not MetS, showed significantly lower odds of reaching their daily recommended PA level. Our findings suggest that the day of the week could be a modifier for the association between MetS and PA. Further research with longer study periods and larger sample sizes are needed to confirm our results.