Association of Smartwatch-Based Heart Rate and Physical Activity With Cardiorespiratory Fitness Measures in the Community: Cohort Study.

BACKGROUND: Resting heart rate (HR) and routine physical activity are associated with cardiorespiratory fitness levels. Commercial smartwatches permit remote HR monitoring and step count recording in real-world settings over long periods of time, but the relationship between smartwatch-measured HR and daily steps to cardiorespiratory fitness remains incompletely characterized in the community. OBJECTIVE: This study aimed to examine the association of nonactive HR and daily steps measured by a smartwatch with a multidimensional fitness assessment via cardiopulmonary exercise testing (CPET) among participants in the electronic Framingham Heart Study. METHODS: Electronic Framingham Heart Study participants were enrolled in a research examination (2016-2019) and provided with a study smartwatch that collected longitudinal HR and physical activity data for up to 3 years. At the same examination, the participants underwent CPET on a cycle ergometer. Multivariable linear models were used to test the association of CPET indices with nonactive HR and daily steps from the smartwatch. RESULTS: We included 662 participants (mean age 53, SD 9 years; n=391, 59% women, n=599, 91% White; mean nonactive HR 73, SD 6 beats per minute) with a median of 1836 (IQR 889-3559) HR records and a median of 128 (IQR 65-227) watch-wearing days for each individual. In multivariable-adjusted models, lower nonactive HR and higher daily steps were associated with higher peak oxygen uptake (VO2), % predicted peak VO2, and VO2 at the ventilatory anaerobic threshold, with false discovery rate (FDR)-adjusted P values <.001 for all. Reductions of 2.4 beats per minute in nonactive HR, or increases of nearly 1000 daily steps, corresponded to a 1.3 mL/kg/min higher peak VO2. In addition, ventilatory efficiency (VE/VCO2; FDR-adjusted P=.009), % predicted maximum HR (FDR-adjusted P<.001), and systolic blood pressure-to-workload slope (FDR-adjusted P=.01) were associated with nonactive HR but not associated with daily steps. CONCLUSIONS: Our findings suggest that smartwatch-based assessments are associated with a broad array of cardiorespiratory fitness responses in the community, including measures of global fitness (peak VO2), ventilatory efficiency, and blood pressure response to exercise. Metrics captured by wearable devices offer a valuable opportunity to use extensive data on health factors and behaviors to provide a window into individual cardiovascular fitness levels.

Immune regulation and prognosis indicating ability of a newly constructed multi-genes containing signature in clear cell renal cell carcinoma.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the most common renal malignancy, although newly developing targeted therapy and immunotherapy have been showing promising effects in clinical treatment, the effective biomarkers for immune response prediction are still lacking. The study is to construct a gene signature according to ccRCC immune cells infiltration landscape, thus aiding clinical prediction of patients response to immunotherapy. METHODS: Firstly, ccRCC transcriptome expression profiles from Gene Expression Omnibus (GEO) database as well as immune related genes information from IMMPORT database were combine applied to identify the differently expressed meanwhile immune related candidate genes in ccRCC comparing to normal control samples. Then, based on protein-protein interaction network (PPI) and following module analysis of the candidate genes, a hub gene cluster was further identified for survival analysis. Further, LASSO analysis was applied to construct a signature which was in succession assessed with Kaplan-Meier survival, Cox regression and ROC curve analysis. Moreover, ccRCC patients were divided as high and low-risk groups based on the gene signature followed by the difference estimation of immune treatment response and exploration of related immune cells infiltration by TIDE and Cibersort analysis respectively among the two groups of patients. RESULTS: Based on GEO and IMMPORT databases, a total of 269 differently expressed meanwhile immune related genes in ccRCC were identified, further PPI network and module analysis of the 269 genes highlighted a 46 genes cluster. Next step, Kaplan-Meier and Cox regression analysis of the 46 genes identified 4 genes that were supported to be independent prognosis indicators, and a gene signature was constructed based on the 4 genes. Furthermore, after assessing its prognosis indicating ability by both Kaplan-Meier and Cox regression analysis, immune relation of the signature was evaluated including its association with environment immune score, Immune checkpoint inhibitors expression as well as immune cells infiltration. Together, immune predicting ability of the signature was preliminary explored. CONCLUSIONS: Based on ccRCC genes expression profiles and multiple bioinformatic analysis, a 4 genes containing signature was constructed and the immune regulation of the signature was preliminary explored. Although more detailed experiments and clinical trials are needed before potential clinical use of the signature, the results shall provide meaningful insight into further ccRCC immune researches.

Step Count, Self-reported Physical Activity, and Predicted 5-Year Risk of Atrial Fibrillation: Cross-sectional Analysis.

BACKGROUND: Physical inactivity is a known risk factor for atrial fibrillation (AF). Wearable devices, such as smartwatches, present an opportunity to investigate the relation between daily step count and AF risk. OBJECTIVE: The objective of this study was to investigate the association between daily step count and the predicted 5-year risk of AF. METHODS: Participants from the electronic Framingham Heart Study used an Apple smartwatch. Individuals with diagnosed AF were excluded. Daily step count, watch wear time (hours and days), and self-reported physical activity data were collected. Individuals' 5-year risk of AF was estimated, using the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE)-AF score. The relation between daily step count and predicted 5-year AF risk was examined via linear regression, adjusting for age, sex, and wear time. Secondary analyses examined effect modification by sex and obesity (BMI≥30 kg/m2), as well as the relation between self-reported physical activity and predicted 5-year AF risk. RESULTS: We examined 923 electronic Framingham Heart Study participants (age: mean 53, SD 9 years; female: n=563, 61%) who had a median daily step count of 7227 (IQR 5699-8970). Most participants (n=823, 89.2%) had a <2.5% CHARGE-AF risk. Every 1000 steps were associated with a 0.08% lower CHARGE-AF risk (P<.001). A stronger association was observed in men and individuals with obesity. In contrast, self-reported physical activity was not associated with CHARGE-AF risk. CONCLUSIONS: Higher daily step counts were associated with a lower predicted 5-year risk of AF, and this relation was stronger in men and participants with obesity. The utility of a wearable daily step counter for AF risk reduction merits further investigation.

[Unconstrained detection of ballistocardiogram and heart rate based on vibration acceleration].

The requirement for unconstrained monitoring of heartbeat during sleep is increasing, but the current detection devices can not meet the requirements of convenience and accuracy. This study designed an unconstrained ballistocardiogram (BCG) detection system using acceleration sensor and developed a heart rate extraction algorithm. BCG is a directional signal which is stronger and less affected by respiratory movements along spine direction than in other directions. In order to measure the BCG signal along spine direction during sleep, a 3-axis acceleration sensor was fixed on the bed to collect the vibration signals caused by heartbeat. An approximate frequency range was firstly assumed by frequency analysis to the BCG signals and segmental filtering was conducted to the original vibration signals within the frequency range. Secondly, to identify the true BCG waveform, the accurate frequency band was obtained by comparison with the theoretical waveform. The J waves were detected by BCG energy waveform and an adaptive threshold method was proposed to extract heart rates by using the information of both amplitude and period. The accuracy and robustness of the BCG detection system proposed and the algorithm developed in this study were confirmed by comparison with electrocardiogram (ECG). The test results of 30 subjects showed a high average accuracy of 99.21% to demonstrate the feasibility of the unconstrained BCG detection method based on vibration acceleration.

Depressive symptoms are not associated with clinically important levels of digital home blood pressure in the electronic Framingham Heart Study.

Background: Depressive symptoms are common and share many biopsychosocial mechanisms with hypertension. Association studies between depressive symptoms and blood pressure (BP) have been inconsistent. Home BP monitoring may provide insight. Objective: To investigate the association between depressive symptoms and digital home BP. Methods: Electronic Framingham Heart Study (eFHS) participants were invited to obtain a smartphone app and digital BP cuff at research exam 3 (2016-2019). Participants with ≥3 weeks of home BP measurements within 1 year were included. Depressive symptoms were measured using the Center for Epidemiological Studies Depression Scale (CES-D). Multivariable linear mixed models were used to test the associations of continuous CES-D score and dichotomous depressive symptoms (CES-D ≥16) (independent) with home BP (dependent), adjusting for age, sex, cohort, number of weeks since baseline, lifestyle factors, diabetes, and cardiovascular disease. Results: Among 883 participants (mean age 54 years, 59% women, 91% White), the median CES-D score was 4. Depressive symptom prevalence was 7.6%. Mean systolic and diastolic BP at exam 3 were 119 and 76 mm Hg; hypertension prevalence was 48%. A 1 SD higher CES-D score was associated with 0.9 (95% CI: 0.18-1.56, P = .01) and 0.6 (95% CI: 0.06-1.07, P = .03) mm Hg higher home systolic BP and diastolic BP, respectively. Dichotomous depressive symptoms were not significantly associated with home BP (P > .2). Conclusion: Depressive symptoms were not associated with clinically substantive levels of home BP. The association between depression and cardiovascular disease risk factors warrants more data, which may be supported by mobile health measures.

Association of Arterial Stiffness With Mid- to Long-Term Home Blood Pressure Variability in the Electronic Framingham Heart Study: Cohort Study.

BACKGROUND: Short-term blood pressure variability (BPV) is associated with arterial stiffness in patients with hypertension. Few studies have examined associations between arterial stiffness and digital home BPV over a mid- to long-term time span, irrespective of underlying hypertension. OBJECTIVE: This study aims to investigate if arterial stiffness traits were associated with subsequent mid- to long-term home BPV in the electronic Framingham Heart Study (eFHS). We hypothesized that higher arterial stiffness was associated with higher home BPV over up to 1-year follow-up. METHODS: At a Framingham Heart Study research examination (2016-2019), participants underwent arterial tonometry to acquire measures of arterial stiffness (carotid-femoral pulse wave velocity [CFPWV]; forward pressure wave amplitude [FWA]) and wave reflection (reflection coefficient [RC]). Participants who agreed to enroll in eFHS were provided with a digital blood pressure (BP) cuff to measure home BP weekly over up to 1-year follow-up. Participants with less than 3 weeks of BP readings were excluded. Linear regression models were used to examine associations of arterial measures with average real variability (ARV) of week-to-week home systolic (SBP) and diastolic (DBP) BP adjusting for important covariates. We obtained ARV as an average of the absolute differences of consecutive home BP measurements. ARV considers not only the dispersion of the BP readings around the mean but also the order of BP readings. In addition, ARV is more sensitive to measurement-to-measurement BPV compared with traditional BPV measures. RESULTS: Among 857 eFHS participants (mean age 54, SD 9 years; 508/857, 59% women; mean SBP/DBP 119/76 mm Hg; 405/857, 47% hypertension), 1 SD increment in FWA was associated with 0.16 (95% CI 0.09-0.23) SD increments in ARV of home SBP and 0.08 (95% CI 0.01-0.15) SD increments in ARV of home DBP; 1 SD increment in RC was associated with 0.14 (95% CI 0.07-0.22) SD increments in ARV of home SBP and 0.11 (95% CI 0.04-0.19) SD increments in ARV of home DBP. After adjusting for important covariates, there was no significant association between CFPWV and ARV of home SBP, and similarly, no significant association existed between CFPWV and ARV of home DBP (P>.05). CONCLUSIONS: In eFHS, higher FWA and RC were associated with higher mid- to long-term ARV of week-to-week home SBP and DBP over 1-year follow-up in individuals across the BP spectrum. Our findings suggest that higher aortic stiffness and wave reflection are associated with higher week-to-week variation of BP in a home-based setting over a mid- to long-term time span.

A meta-analysis of the three-dimensional reconstruction visualization technology for hepatectomy.

This meta-analysis was conducted to systematically evaluate the short-term efficacy and safety of the three-dimensional (3D) reconstruction visualization technology (3D-RVT) technique for hepatectomy. A systematic literature search was used to gather information on the 3D reconstruction visualization technology technique for hepatectomy from retrospective cohort studies and comparative studies. The retrieval period was up to March 2022. Publications and conference papers in English were manually searched and references in bibliographies traced. After evaluating the quality of selected studies, a meta-analysis was conducted using Review Manager 5.1 software. We included 12 studies comprising 2053 patients with liver disease. Our meta-results showed that 3D-RVT significantly shortened operation times [weighted mean differences (WMD) = -29.36; 95% confidence interval (CI): -55.20 to -3.51; P = 0.03], reduced intraoperative bleeding [WMD = -93.53; 95% CI: -152.32 to -34.73; P = 0.002], reduced blood transfusion volume [WMD = -66.06; 95% CI: -109.13 to -22.99; P = 0.003], and shortened hospital stays [WMD = -1.90; 95% CI: -3.05 to -0.74; P = 0.001]. Additionally, the technique reduced the use of hepatic inflow occlusion and avoided overall postoperative complications [odds ratio (OR) = 0.60; 95% CI: 0.46 to 0.79; P < 0.001]. 3D-RVT is safe and effective for liver surgery and provides safety assessments before anatomical hepatectomy.

Association of Depressive Symptom Trajectory With Physical Activity Collected by mHealth Devices in the Electronic Framingham Heart Study: Cohort Study.

BACKGROUND: Few studies have examined the association between depressive symptom trajectories and physical activity collected by mobile health (mHealth) devices. OBJECTIVE: We aimed to investigate if antecedent depressive symptom trajectories predict subsequent physical activity among participants in the electronic Framingham Heart Study (eFHS). METHODS: We performed group-based multi-trajectory modeling to construct depressive symptom trajectory groups using both depressive symptoms (Center for Epidemiological Studies-Depression [CES-D] scores) and antidepressant medication use in eFHS participants who attended 3 Framingham Heart Study research exams over 14 years. At the third exam, eFHS participants were instructed to use a smartphone app for submitting physical activity index (PAI) surveys. In addition, they were provided with a study smartwatch to track their daily step counts. We performed linear mixed models to examine the association between depressive symptom trajectories and physical activity including app-based PAI and smartwatch-collected step counts over a 1-year follow-up adjusting for age, sex, wear hour, BMI, smoking status, and other health variables. RESULTS: We identified 3 depressive symptom trajectory groups from 722 eFHS participants (mean age 53, SD 8.5 years; n=432, 60% women). The low symptom group (n=570; mean follow-up 287, SD 109 days) consisted of participants with consistently low CES-D scores, and a small proportion reported antidepressant use. The moderate symptom group (n=71; mean follow-up 280, SD 118 days) included participants with intermediate CES-D scores, who showed the highest and increasing likelihood of reporting antidepressant use across 3 exams. The high symptom group (n=81; mean follow-up 252, SD 116 days) comprised participants with the highest CES-D scores, and the proportion of antidepressant use fell between the other 2 groups. Compared to the low symptom group, the high symptom group had decreased PAI (mean difference -1.09, 95% CI -2.16 to -0.01) and the moderate symptom group walked fewer daily steps (823 fewer, 95% CI -1421 to -226) during the 1-year follow-up. CONCLUSIONS: Antecedent depressive symptoms or antidepressant medication use was associated with lower subsequent physical activity collected by mHealth devices in eFHS. Future investigation of interventions to improve mood including via mHealth technologies to help promote people's daily physical activity is needed.

Ultrasensitive quantitation of circulating miR-195-5p with triple strand displacement amplification cascade.

Circulating miR-195-5p has been proposed as a promising peripheral biomarker for the diagnosis, prognosis and severity assessment of various diseases. However, the demand for its sensitive and convenient quantification has not been met yet. Herein, we proposed a one-pot isothermal approach, in which the target signal acquisition, amplification and conversion (fluorescence read-out) system was integrated by a triple strand displacement amplification (SDA) cascade. Using this triple SDA strategy, miR-195-5p can be at least detected at 1 aM, and the linear dynamic range (from 100 aM to 1 pM) is wide enough to meet the detection needs of clinical miRNA level. A proof-of-principle study, using this novel methodology to directly analyze the spiking serum samples with different levels of miR-195-5p, demonstrated the potential of circulating miR-195-5p detection for clinical point-of-care assay. This one-pot isothermal triple SDA approach, we believe, will be a simple and feasible tool for ultrasensitive quantification of circulating miR-195-5p, and may promote the wide application of this potential biomarker in non-invasive clinical diagnosis.

Factors associated with long-term use of digital devices in the electronic Framingham Heart Study.

Long-term use of digital devices is critical for successful clinical or research use, but digital health studies are challenged by a rapid drop-off in participation. A nested e-cohort (eFHS) is embedded in the Framingham Heart Study and uses three system components: a new smartphone app, a digital blood pressure (BP) cuff, and a smartwatch. This study aims to identify factors associated with the use of individual eFHS system components over 1-year. Among 1948 eFHS enrollees, we examine participants who returned surveys within 90 days (n = 1918), and those who chose to use the smartwatch (n = 1243) and BP cuff (n = 1115). For each component, we investigate the same set of candidate predictors for usage and use generalized linear mixed models to select predictors (P < 0.1, P value from Z test statistic), adjusting for age, sex, and time (app use: 3-month period, device use: weekly). A multivariable model with the predictors selected from initial testing is used to identify factors associated with use of components (P < 0.05, P value from Z test statistic) adjusting for age, sex, and time. In multivariable models, older age is associated with higher use of all system components. Female sex and higher education levels are associated with higher completion of app-based surveys whereas higher scores for depressive symptoms, and lower than excellent self-rated health are associated with lower use of the smartwatch over the 12-month follow-up. Our findings show that sociodemographic and health related factors are significantly associated with long-term use of digital devices. Future research is needed to test interventional strategies focusing on these factors to evaluate improvement in long-term engagement.

Early Inflammatory Signatures Predict Subsequent Cognition in Long-Term Virally Suppressed Women With HIV.

Immunologic function is an important determinant of cognition. Here we examined the contribution of early immune signatures to cognitive performance among HIV-infected, virally suppressed women (HIV+VS) and in HIV-uninfected (HIV-) women. Specifically, we measured serum inflammatory markers, developed combinatory immune signatures, and evaluated their associations with cognition. Forty-nine HIV+VS women in the Women's Interagency HIV Study (WIHS) who achieved viral suppression shortly after effective antiretroviral therapy (ART) initiation, and 56 matched HIV- women were selected. Forty-two serum inflammatory markers were measured within 2 years of effective ART initiation for HIV+VS women, and at an initial timepoint for HIV- women. The same inflammatory markers were also measured approximately 1, 7, and 12 years later for all women. Of the 105 women with complete immune data, 83 (34 HIV+VS, 49 HIV-) also had cognitive data available 12 years later at ≥1 time points (median = 3.1). We searched for combinatory immune signatures by adapting a dynamic matrix factorization analytic method that builds upon Tucker decomposition followed by Ingenuity® Pathway Analysis to facilitate data interpretation. Seven combinatory immune signatures emerged based on the Frobenius residual. Three signatures were common between HIV+VS and HIV- women, while four signatures were unique. These inflammatory signatures predicted subsequent cognitive performance in both groups using mixed-effects modeling, but more domain-specific associations were significant in HIV+VS than HIV- women. Leukocyte influx into brain was a major contributor to cognitive function in HIV+VS women, while T cell exhaustion, inflammatory response indicative of depressive/psychiatric disorders, microglial activity, and cytokine signaling predicted both global and domain-specific performance for HIV- women. Our findings suggest that immune signatures may be useful diagnostic, prognostic, and immunotherapeutic targets predictive of subsequent cognitive performance. Importantly, they also provide insight into common and distinct inflammatory mechanisms underlying cognition in HIV- and HIV+VS women.

Brief Report: Higher Peripheral Monocyte Activation Markers Are Associated With Smaller Frontal and Temporal Cortical Volumes in Women With HIV.

BACKGROUND: Persistent inflammation is a life-long complication of HIV infection, even in virally suppressed individuals. Elevated plasma concentrations of soluble(s) CD14 and CD163 have been established as biomarkers of chronic inflammation, conferring higher risk for cognitive, neurovascular, and structural abnormalities. METHODS: Structural magnetic resonance imaging (frontal and temporal regions) as well as plasma inflammatory biomarkers of monocyte activation (sCD14 and sCD163), general inflammation (plasma C-reactive protein, interleukin[IL]-6), and gut microbial translocation (plasma intestinal fatty acid-binding protein) were available on 38 women (25 with HIV) from the Chicago Women's Interagency HIV Study site. Partial least-squares models adjusting for relevant covariates (eg, age, education, and race) were conducted to evaluate the relationship between inflammatory biomarkers and brain volume in the overall sample and among women with HIV (WWH). RESULTS: In the total sample, higher plasma sCD14 was associated with smaller volumes in multiple frontal and temporal lobe regions. In the WWH-only sample, sCD163 was associated with smaller volumes only in one region of the left frontal lobe. C-reactive protein, IL-6, and intestinal fatty acid-binding protein were not associated with brain volumes for either group of women. CONCLUSIONS: Of the inflammatory monocyte markers evaluated, sCD14 was associated with smaller frontal and temporal cortical volume in the overall and WWH-only samples, while plasma sCD163 was only associated with smaller left caudal middle frontal gyrus in the WWH-only group. Validating these monocyte proteins as neurological biomarkers of structural brain deficits in a larger sample is critical for understanding HIV-associated neurobiological complications.