Development of a single-domain antibody to target a G-quadruplex located on the hepatitis B virus covalently closed circular DNA genome.

To achieve a virological cure for hepatitis B virus (HBV), innovative strategies are required to target the covalently closed circular DNA (cccDNA) genome. Guanine-quadruplexes (G4s) are a secondary structure that can be adopted by DNA and play a significant role in regulating viral replication, transcription, and translation. Antibody-based probes and small molecules have been developed to study the role of G4s in the context of the human genome, but none have been specifically made to target G4s in viral infection. Herein, we describe the development of a humanized single-domain antibody (S10) that can target a G4 located in the PreCore (PreC) promoter of the HBV cccDNA genome. MicroScale Thermophoresis demonstrated that S10 has a strong nanomolar affinity to the PreC G4 in its quadruplex form and a structural electron density envelope of the complex was determined using Small-Angle X-ray Scattering. Lentiviral transduction of S10 into HepG2-NTCP cells shows nuclear localization, and chromatin immunoprecipitation coupled with next-generation sequencing demonstrated that S10 can bind to the HBV PreC G4 present on the cccDNA. This research validates the existence of a G4 in HBV cccDNA and demonstrates that this DNA secondary structure can be targeted with high structural and sequence specificity using S10.

The 3' terminal region of Zika virus RNA contains a conserved G-quadruplex and is unfolded by human DDX17.

Zika virus (ZIKV) infection remains a worldwide concern, and currently no effective treatments or vaccines are available. Novel therapeutics are an avenue of interest that could probe viral RNA-human protein communication to stop viral replication. One specific RNA structure, G-quadruplexes (G4s), possess various roles in viruses and all domains of life, including transcription and translation regulation and genome stability, and serves as nucleation points for RNA liquid-liquid phase separation. Previous G4 studies on ZIKV using a quadruplex forming G-rich sequences Mapper located a potential G-quadruplex sequence in the 3' terminal region (TR) and was validated structurally using a 25-mer oligo. It is currently unknown if this structure is conserved and maintained in a large ZIKV RNA transcript and its specific roles in viral replication. Using bioinformatic analysis and biochemical assays, we demonstrate that the ZIKV 3' TR G4 is conserved across all ZIKV isolates and maintains its structure in a 3' TR full-length transcript. We further established the G4 formation using pyridostatin and the BG4 G4-recognizing antibody binding assays. Our study also demonstrates that the human DEAD-box helicases, DDX3X132-607 and DDX17135-555, bind to the 3' TR and that DDX17135-555 unfolds the G4 present in the 3' TR. These findings provide a path forward in potential therapeutic targeting of DDX3X or DDX17's binding to the 3' TR G4 region for novel treatments against ZIKV.

Acoustic Voice and Speech Biomarkers of Treatment Status during Hospitalization for Acute Decompensated Heart Failure.

This study investigates acoustic voice and speech features as biomarkers for acute decompensated heart failure (ADHF), a serious escalation of heart failure symptoms including breathlessness and fatigue. ADHF-related systemic fluid accumulation in the lungs and laryngeal tissues is hypothesized to affect phonation and respiration for speech. A set of daily spoken recordings from 52 patients undergoing inpatient ADHF treatment was analyzed to identify voice and speech biomarkers for ADHF and to examine the trajectory of biomarkers during treatment. Results indicated that speakers produce more stable phonation, a more creaky voice, faster speech rates, and longer phrases after ADHF treatment compared to their pre-treatment voices. This project builds on work to develop a method of monitoring ADHF using speech biomarkers and presents a more detailed understanding of relevant voice and speech features.

A comprehensive review of methods to study lncRNA-protein interactions in solution.

The long non-coding RNAs (lncRNAs) other than rRNA and tRNA were earlier assumed to be 'junk genomic material'. However, recent advancements in genomics methods have highlighted their roles not only in housekeeping but also in the progression of diseases like cancer as well as viral infections. lncRNAs owing to their length, have both short-range and long-range interactions resulting in complex folded structures that recruit various biomolecules enabling lncRNAs to undertake their various biological functions. Using cell lysate pull-down assays increasing number of lnRNAs-interacting proteins are being identified. These interactions can be further exploited to develop targeted novel therapeutic strategies to inhibit lncRNA-protein interactions. This review attempts to succinctly techniques that can identify and characterize the lnRNAs-protein interactions (i.e. affinity, stoichiometry, and thermodynamics). Furthermore, using other sophisticated biophysical techniques, one can also perform size estimations, and determine low-resolution structures. Since these methods study the biomolecules in solution, large-scale structural observations can be performed in real-time. This review attempts to briefly introduce the readers to biochemical and biophysical techniques, such that they can utilize these methods to obtain a holistic characterization of the biomolecules of interest. Additionally, it should be noted that the use of these methods is not limited to the characterization of the interacting molecules but can also be used to determine the efficacy of the therapeutic molecules to disrupt these interactions.

Smartphone camera based assessment of adiposity: a validation study.

Body composition is a key component of health in both individuals and populations, and excess adiposity is associated with an increased risk of developing chronic diseases. Body mass index (BMI) and other clinical or commercially available tools for quantifying body fat (BF) such as DXA, MRI, CT, and photonic scanners (3DPS) are often inaccurate, cost prohibitive, or cumbersome to use. The aim of the current study was to evaluate the performance of a novel automated computer vision method, visual body composition (VBC), that uses two-dimensional photographs captured via a conventional smartphone camera to estimate percentage total body fat (%BF). The VBC algorithm is based on a state-of-the-art convolutional neural network (CNN). The hypothesis is that VBC yields better accuracy than other consumer-grade fat measurements devices. 134 healthy adults ranging in age (21-76 years), sex (61.2% women), race (60.4% White; 23.9% Black), and body mass index (BMI, 18.5-51.6 kg/m2) were evaluated at two clinical sites (N = 64 at MGH, N = 70 at PBRC). Each participant had %BF measured with VBC, three consumer and two professional bioimpedance analysis (BIA) systems. The PBRC participants also had air displacement plethysmography (ADP) measured. %BF measured by dual-energy x-ray absorptiometry (DXA) was set as the reference against which all other %BF measurements were compared. To test our scientific hypothesis we run multiple, pair-wise Wilcoxon signed rank tests where we compare each competing measurement tool (VBC, BIA, …) with respect to the same ground-truth (DXA). Relative to DXA, VBC had the lowest mean absolute error and standard deviation (2.16 ± 1.54%) compared to all of the other evaluated methods (p < 0.05 for all comparisons). %BF measured by VBC also had good concordance with DXA (Lin's concordance correlation coefficient, CCC: all 0.96; women 0.93; men 0.94), whereas BMI had very poor concordance (CCC: all 0.45; women 0.40; men 0.74). Bland-Altman analysis of VBC revealed the tightest limits of agreement (LOA) and absence of significant bias relative to DXA (bias -0.42%, R2 = 0.03; p = 0.062; LOA -5.5% to +4.7%), whereas all other evaluated methods had significant (p < 0.01) bias and wider limits of agreement. Bias in Bland-Altman analyses is defined as the discordance between the y = 0 axis and the regressed line computed from the data in the plot. In this first validation study of a novel, accessible, and easy-to-use system, VBC body fat estimates were accurate and without significant bias compared to DXA as the reference; VBC performance exceeded those of all other BIA and ADP methods evaluated. The wide availability of smartphones suggests that the VBC method for evaluating %BF could play an important role in quantifying adiposity levels in a wide range of settings.Trial registration: ClinicalTrials.gov Identifier: NCT04854421.

Biophysical characterisation of human LincRNA-p21 sense and antisense Alu inverted repeats.

Human Long Intergenic Noncoding RNA-p21 (LincRNA-p21) is a regulatory noncoding RNA that plays an important role in promoting apoptosis. LincRNA-p21 is also critical in down-regulating many p53 target genes through its interaction with a p53 repressive complex. The interaction between LincRNA-p21 and the repressive complex is likely dependent on the RNA tertiary structure. Previous studies have determined the two-dimensional secondary structures of the sense and antisense human LincRNA-p21 AluSx1 IRs using SHAPE. However, there were no insights into its three-dimensional structure. Therefore, we in vitro transcribed the sense and antisense regions of LincRNA-p21 AluSx1 Inverted Repeats (IRs) and performed analytical ultracentrifugation, size exclusion chromatography, light scattering, and small angle X-ray scattering (SAXS) studies. Based on these studies, we determined low-resolution, three-dimensional structures of sense and antisense LincRNA-p21. By adapting previously known two-dimensional information, we calculated their sense and antisense high-resolution models and determined that they agree with the low-resolution structures determined using SAXS. Thus, our integrated approach provides insights into the structure of LincRNA-p21 Alu IRs. Our study also offers a viable pipeline for combining the secondary structure information with biophysical and computational studies to obtain high-resolution atomistic models for long noncoding RNAs.

Targeting Xist with compounds that disrupt RNA structure and X inactivation.

Although more than 98% of the human genome is non-coding1, nearly all of the drugs on the market target one of about 700 disease-related proteins. The historical reluctance to invest in non-coding RNA stems partly from requirements for drug targets to adopt a single stable conformation2. Most RNAs can adopt several conformations of similar stabilities. RNA structures also remain challenging to determine3. Nonetheless, an increasing number of diseases are now being attributed to non-coding RNA4 and the ability to target them would vastly expand the chemical space for drug development. Here we devise a screening strategy and identify small molecules that bind the non-coding RNA prototype Xist5. The X1 compound has drug-like properties and binds specifically the RepA motif6 of Xist in vitro and in vivo. Small-angle X-ray scattering analysis reveals that RepA can adopt multiple conformations but favours one structure in solution. X1 binding reduces the conformational space of RepA, displaces cognate interacting protein factors (PRC2 and SPEN), suppresses histone H3K27 trimethylation, and blocks initiation of X-chromosome inactivation. X1 inhibits cell differentiation and growth in a female-specific manner. Thus, RNA can be systematically targeted by drug-like compounds that disrupt RNA structure and epigenetic function.

Bioinformatic Analysis of Structure and Function of LIM Domains of Human Zyxin Family Proteins.

Members of the human Zyxin family are LIM domain-containing proteins that perform critical cellular functions and are indispensable for cellular integrity. Despite their importance, not much is known about their structure, functions, interactions and dynamics. To provide insights into these, we used a set of in-silico tools and databases and analyzed their amino acid sequence, phylogeny, post-translational modifications, structure-dynamics, molecular interactions, and functions. Our analysis revealed that zyxin members are ohnologs. Presence of a conserved nuclear export signal composed of LxxLxL/LxxxLxL consensus sequence, as well as a possible nuclear localization signal, suggesting that Zyxin family members may have nuclear and cytoplasmic roles. The molecular modeling and structural analysis indicated that Zyxin family LIM domains share similarities with transcriptional regulators and have positively charged electrostatic patches, which may indicate that they have previously unanticipated nucleic acid binding properties. Intrinsic dynamics analysis of Lim domains suggest that only Lim1 has similar internal dynamics properties, unlike Lim2/3. Furthermore, we analyzed protein expression and mutational frequency in various malignancies, as well as mapped protein-protein interaction networks they are involved in. Overall, our comprehensive bioinformatic analysis suggests that these proteins may play important roles in mediating protein-protein and protein-nucleic acid interactions.

Identification and characterization of a G-quadruplex structure in the pre-core promoter region of hepatitis B virus covalently closed circular DNA.

Approximately 250 million people worldwide are chronically infected with the hepatitis B virus (HBV) and are at increased risk of developing cirrhosis and hepatocellular carcinoma. The HBV genome persists as covalently closed circular DNA (cccDNA), which serves as the template for all HBV mRNA transcripts. Current nucleos(t)ide analogs used to treat HBV do not directly target the HBV cccDNA genome and thus cannot eradicate HBV infection. Here, we report the discovery of a unique G-quadruplex structure in the pre-core promoter region of the HBV genome that is conserved among nearly all genotypes. This region is central to critical steps in the viral life cycle, including the generation of pregenomic RNA, synthesis of core and polymerase proteins, and genome encapsidation; thus, an increased understanding of the HBV pre-core region may lead to the identification of novel anti-HBV cccDNA targets. We utilized biophysical methods (circular dichroism and small-angle X-ray scattering) to characterize the HBV G-quadruplex and the effect of three distinct G to A mutants. We also used microscale thermophoresis to quantify the binding affinity of G-quadruplex and its mutants with a known quadruplex-binding protein (DHX36). To investigate the physiological relevance of HBV G-quadruplex, we employed assays using DHX36 to pull-down cccDNA and compared HBV infection in HepG2 cells transfected with wild-type and mutant HBV plasmids by monitoring the levels of genomic DNA, pregenomic RNA, and antigens. Further evaluation of this critical host-protein interaction site in the HBV cccDNA genome may facilitate the development of novel anti-HBV therapeutics against the resilient cccDNA template.

Maternal plasma soluble neuropilin-1 is downregulated in fetal growth restriction complicated by abnormal umbilical artery Doppler: a pilot study.

OBJECTIVES: Placental expression of neuropilin-1 (NRP1), a proangiogenic member of the vascular endothelial growth factor receptor family involved in sprouting angiogenesis, was recently discovered to be downregulated in pregnancies with fetal growth restriction (FGR) and abnormal umbilical artery (UA) Doppler. Soluble NRP1 (sNRP1) is an antagonist to NRP1; however, little is known about its role in normal and FGR pregnancies. This study tested the hypotheses that, first, sNRP1 would be detectable in maternal circulation and, second, its concentration would be upregulated in FGR pregnancies compared to those with normal fetal growth and this would correlate with the severity of the disease as assessed by UA Doppler. METHODS: This was a prospective case-control pilot study of 40 singleton pregnancies (20 FGR cases and 20 uncomplicated controls) between 24 + 0 and 40 + 0 weeks' gestation followed in an academic perinatal center from January 2015 to May 2017. FGR was defined as an ultrasound-estimated fetal weight < 10th percentile for gestational age. The control group was matched to the FGR group for maternal age and gestational age at assessment. Fetal ultrasound biometry and UA Doppler were performed using standard protocols. Maternal plasma sNRP1 measurements were performed using a commercially available ELISA. RESULTS: Contrary to the study hypothesis, maternal plasma sNRP1 levels were significantly decreased in FGR pregnancies as compared to those with normal fetal growth (137.4 ± 44.8 pg/mL vs 166.7 ± 36.9 pg/mL; P = 0.03). However, there was no significant difference in sNRP1 concentration between the control group and FGR pregnancies that had normal UA Doppler. Plasma sNRP1 was downregulated in FGR pregnancies with elevated UA systolic/diastolic ratio (P = 0.023) and those with UA absent or reversed end-diastolic flow (P = 0.005) in comparison to FGR pregnancies with normal UA Doppler. This suggests that biometrically small fetuses without hemodynamic compromise are small-for-gestational age rather than FGR. CONCLUSIONS: This study demonstrated a significant decrease in maternal plasma sNRP1 concentration in growth-restricted pregnancies with fetoplacental circulatory compromise. These findings suggest a possible role of sNRP1 in modulating fetal growth and its potential as a biomarker for FGR. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Observational study on wearable biosensors and machine learning-based remote monitoring of COVID-19 patients.

Patients infected with SARS-CoV-2 may deteriorate rapidly and therefore continuous monitoring is necessary. We conducted an observational study involving patients with mild COVID-19 to explore the potentials of wearable biosensors and machine learning-based analysis of physiology parameters to detect clinical deterioration. Thirty-four patients (median age: 32 years; male: 52.9%) with mild COVID-19 from Queen Mary Hospital were recruited. The mean National Early Warning Score 2 (NEWS2) were 0.59 ± 0.7. 1231 manual measurement of physiology parameters were performed during hospital stay (median 15 days). Physiology parameters obtained from wearable biosensors correlated well with manual measurement including pulse rate (r = 0.96, p < 0.0001) and oxygen saturation (r = 0.87, p < 0.0001). A machine learning-derived index reflecting overall health status, Biovitals Index (BI), was generated by autonomous analysis of physiology parameters, symptoms, and other medical data. Daily BI was linearly associated with respiratory tract viral load (p < 0.0001) and NEWS2 (r = 0.75, p < 0.001). BI was superior to NEWS2 in predicting clinical worsening events (sensitivity 94.1% and specificity 88.9%) and prolonged hospitalization (sensitivity 66.7% and specificity 72.7%). Wearable biosensors coupled with machine learning-derived health index allowed automated detection of clinical deterioration.

Shape-function insights into bifunctional O-GlcNActransferase of Listeria monocytogenes EGD-e.

O-GlcNAcylation is an important post-translational modification of proteins. O-GlcNAcylated proteins have crucial roles in several cellular contexts both in eukaryotes and bacteria. O-GlcNActransferase (OGT) is the enzyme instrumental in O-GlcNAcylation of proteins. OGT is conserved across eukaryotes. The first bacterial OGT discovered is GmaR in Listeria monocytogenes. GmaR is a GT-2 family bifunctional protein that catalyzes glycosylation of the flagellin protein FlaA and controls transcription of flagellar motility genes in a temperature-dependent manner. Here, we provide methods for heterologous expression and purification of recombinant GmaR and FlaA, in vivo/in vitro glycosylation assays, analysis of the molecular form of recombinant GmaR and detailed enzyme kinetics. We study the structure and functional dynamics of GmaR. Using solution small-angle X-ray scattering and molecular modeling, we show that GmaR adopts an extended shape with two distinctly spaced structural units in the presence of cofactor Mg2+ and with donor UDP-GlcNAc and cofactor combined. Comparisons of restored structures revealed that in-solution binding of Mg2+ ions brings about shape rearrangements and induces structural-rigidity in hyper-variable regions at the N-terminus of GmaR protein. Taking function and shape data together, we describe that Mg2+ binding enables GmaR to adopt a shape that can bind the substrate. The manuscript provides the first 3D solution structure of a bacterial OGT of GT-2 family and detailed biochemical characterization of GmaR to facilitate its future applications.

Heat induces end to end repetitive association in P. furiosus L-asparaginase which enables its thermophilic property.

It remains undeciphered how thermophilic enzymes display enhanced stability at elevated temperatures. Taking L-asparaginase from P. furiosus (PfA) as an example, we combined scattering shapes deduced from small-angle X-ray scattering (SAXS) data at increased temperatures with symmetry mates from crystallographic structures to find that heating caused end-to-end association. The small contact point of self-binding appeared to be enabled by a terminal short ß-strand in N-terminal domain, Leu179-Val-Val-Asn182 (LVVN). Interestingly, deletion of this strand led to a defunct enzyme, whereas suplementation of the peptide LVVN to the defunct enzyme restored structural frameworkwith mesophile-type functionality. Crystal structure of the peptide-bound defunct enzyme showed that one peptide ispresent in the same coordinates as in original enzyme, explaining gain-of lost function. A second peptide was seen bound to the protein at a different location suggesting its possible role in substrate-free molecular-association. Overall, we show that the heating induced self-assembly of native shapes of PfA led to an apparent super-stable assembly.

Analytical ultracentrifuge: an ideal tool for characterization of non-coding RNAs.

Analytical ultracentrifugation (AUC) has emerged as a robust and reliable technique for biomolecular characterization with extraordinary sensitivity. AUC is widely used to study purity, conformational changes, biomolecular interactions, and stoichiometry. Furthermore, AUC is used to determine the molecular weight of biomolecules such as proteins, carbohydrates, and DNA and RNA. Due to the multifaceted role(s) of non-coding RNAs from viruses, prokaryotes, and eukaryotes, research aimed at understanding the structure-function relationships of non-coding RNAs is rapidly increasing. However, due to their large size, flexibility, complicated secondary structures, and conformations, structural studies of non-coding RNAs are challenging. In this review, we are summarizing the application of AUC to evaluate the homogeneity, interactions, and conformational changes of non-coding RNAs from adenovirus as well as from Murray Valley, Powassan, and West Nile viruses. We also discuss the application of AUC to characterize eukaryotic long non-coding RNAs, Xist, and HOTAIR. These examples highlight the significant role AUC can play in facilitating the structural determination of non-coding RNAs and their complexes.

Antioxidant and Wound Healing Property of Gelsolin in 3T3-L1 Cells.

Delineation of factors which affect wound healing would be of immense value to enable on-time or early healing and reduce comorbidities associated with infections or biochemical stress like diabetes. Plasma gelsolin has been identified earlier to significantly enable injury recovery compared to placebo. This study evaluates the role of rhuGSN for its antioxidant and wound healing properties in murine fibroblasts (3T3-L1 cell line). Total antioxidant capacity of rhuGSN increased in a concentration-dependent manner (0.75-200 µg/mL). Cells pretreated with 0.375 and 0.75 µg/mL rhuGSN for 24 h exhibited a significant increase in viability in a MTT assay. Preincubation of cells with rhuGSN for 24 h followed by oxidative stress induced by exposure to H2O2 for 3 h showed cytoprotective effect. rhuGSN at 12.5 and 25 µg/mL concentration showed an enhanced cell migration after 20 h of injury in a scratch wound healing assay. The proinflammatory cytokine IL-6 levels were elevated in the culture supernatant. These results establish an effective role of rhuGSN against oxidative stress induced by H2O2 and in wound healing of 3T3-L1 fibroblast cells.

Host Transcription Factors in Hepatitis B Virus RNA Synthesis.

The hepatitis B virus (HBV) chronically infects over 250 million people worldwide and is one of the leading causes of liver cancer and hepatocellular carcinoma. HBV persistence is due in part to the highly stable HBV minichromosome or HBV covalently closed circular DNA (cccDNA) that resides in the nucleus. As HBV replication requires the help of host transcription factors to replicate, focusing on host protein-HBV genome interactions may reveal insights into new drug targets against cccDNA. The structural details on such complexes, however, remain poorly defined. In this review, the current literature regarding host transcription factors' interactions with HBV cccDNA is discussed.

Protective effects of gelsolin in acute pulmonary thromboembolism and thrombosis in the carotid artery of mice.

The present study provides first evidence on the role of plasma gelsolin in protecting pulmonary thromboembolism and thrombosis in a mouse model. Gelsolin is the most abundant actin depolymerizing protein in plasma and its significantly depleted values have been reported in metabolic disorders including cardiovascular diseases and myocardial infarction. Though gelsolin replacement therapy (GRT) has been shown to be effective in some animal models, no such study has been reported for thrombotic diseases that are acutely in need of bio-therapeutics for immediate and lasting relief. Here, using mice model and recombinant human gelsolin (rhuGSN), we demonstrate the antithrombotic effect of gelsolin in ferric chloride induced thrombosis in carotid artery and thrombin induced acute pulmonary thromboembolism. In thrombosis model, arterial occlusion time was significantly enhanced upon subcutaneous (SC) treatment with 8 mg of gelsolin per mice viz. 15.83 minutes vs. 8 minutes in the placebo group. Pertinently, histopathological examination showed channel formation within the thrombi in the carotid artery following injection of gelsolin. Fluorescence molecular tomography imaging further confirmed that administration of gelsolin reduced thrombus formation following carotid artery injury. In thrombin-induced acute pulmonary thromboembolism, mice pretreated with aspirin or gelsolin showed 100 and 83.33% recovery, respectively. In contrast, complete mortality of mice was observed in vehicle treated group within 5 minutes of thrombin injection. Overall, our studies provide conclusive evidence on the thrombo-protective role of plasma gelsolin in mice model of pulmonary thromboembolism and thrombosis.

Utilizing mobile technologies to improve physical activity and medication adherence in patients with heart failure and diabetes mellitus: Rationale and design of the TARGET-HF-DM Trial.

Heart failure (HF) and diabetes mellitus (DM) are major public health issues that place significant burden on patients and health care systems. Patients with both HF and DM are at higher risk of adverse cardiovascular and HF outcomes than those with either disease in isolation. Different antihyperglycemic medications (even within the same medication class) have conflicting results of benefit or harm in patients with established and incident HF. Recent data highlight the importance of a renewed focus on optimal pharmacotherapy for this population with DM and HF (or at risk for HF). Both HF and DM require major lifestyle modification for optimal management, in terms of both optimizing health behaviors (eg, physical activity, diet) and adherence to complex medical and self-care regimens. Mobile health (mHealth) technologies (eg, apps, wearables) are widely available in the community and may play a role in optimizing the health status of patients; however, there is limited and conflicting information on whether such technologies are actually beneficial in at-risk populations. In this article, we summarize current strategies, including mobile health interventions, to improve physical activity levels, drug adherence, and outcomes in patients with DM, HF, or both and describe the design and rationale for the Technologies to improve drug Adherence and Reinforce Guideline based Exercise Targets in patients with heart Failure and Diabetes Mellitus trial, which is designed to test the efficacy of using mHealth technology to improve health behaviors and outcomes in this high-risk population.

Design Rationale and Performance Evaluation of the Wavelet Health Wristband: Benchtop Validation of a Wrist-Worn Physiological Signal Recorder.

BACKGROUND: Wearable and connected health devices along with the recent advances in mobile and cloud computing provide a continuous, convenient-to-patient, and scalable way to collect personal health data remotely. The Wavelet Health platform and the Wavelet wristband have been developed to capture multiple physiological signals and to derive biometrics from these signals, including resting heart rate (HR), heart rate variability (HRV), and respiration rate (RR). OBJECTIVE: This study aimed to evaluate the accuracy of the biometric estimates and signal quality of the wristband. METHODS: Measurements collected from 35 subjects using the Wavelet wristband were compared with simultaneously recorded electrocardiogram and spirometry measurements. RESULTS: The HR, HRV SD of normal-to-normal intervals, HRV root mean square of successive differences, and RR estimates matched within 0.7 beats per minute (SD 0.9), 7 milliseconds (SD 10), 11 milliseconds (SD 12), and 1 breaths per minute (SD 1) mean absolute deviation of the reference measurements, respectively. The quality of the raw plethysmography signal collected by the wristband, as determined by the harmonic-to-noise ratio, was comparable with that obtained from measurements from a finger-clip plethysmography device. CONCLUSIONS: The accuracy of the biometric estimates and high signal quality indicate that the wristband photoplethysmography device is suitable for performing pulse wave analysis and measuring vital signs.