Major Depressive Disorder and Chronic Fatigue Syndrome Show Characteristic Heart Rate Variability Profiles Reflecting Autonomic Dysregulations: Differentiation by Linear Discriminant Analysis.

Major depressive disorder (MDD) and chronic fatigue syndrome (CFS) have overlapping symptoms, and differentiation is important to administer the proper treatment. The present study aimed to assess the usefulness of heart rate variability (HRV) indices. Frequency-domain HRV indices, including high-frequency (HF) and low-frequency (LF) components, their sum (LF+HF), and their ratio (LF/HF), were measured in a three-behavioral-state paradigm composed of initial rest (Rest), task load (Task), and post-task rest (After) periods to examine autonomic regulation. It was found that HF was low at Rest in both disorders, but was lower in MDD than in CFS. LF and LF+HF at Rest were low only in MDD. Attenuated responses of LF, HF, LF+HF, and LF/HF to task load and an excessive increase in HF at After were found in both disorders. The results indicate that an overall HRV reduction at Rest may support a diagnosis of MDD. HF reduction was found in CFS, but with a lesser severity. Response disturbances of HRV to Task were observed in both disorders, and would suggest the presence of CFS when the baseline HRV has not been reduced. Linear discriminant analysis using HRV indices was able to differentiate MDD from CFS, with a sensitivity and specificity of 91.8% and 100%, respectively. HRV indices in MDD and CFS show both common and different profiles, and can be useful for the differential diagnosis.

High Accuracy Heartbeat Detection from CW-Doppler Radar Using Singular Value Decomposition and Matched Filter.

Heart rate measurement using a continuous wave Doppler radar sensor (CW-DRS) has been applied to cases where non-contact detection is required, such as the monitoring of vital signs in home healthcare. However, as a CW-DRS measures the speed of movement of the chest surface, which comprises cardiac and respiratory signals by body motion, extracting cardiac information from the superimposed signal is difficult. Therefore, it is challenging to extract cardiac information from superimposed signals. Herein, we propose a novel method based on a matched filter to solve this problem. The method comprises two processes: adaptive generation of a template via singular value decomposition of a trajectory matrix formed from the measurement signals, and reconstruction by convolution of the generated template and measurement signals. The method is validated using a dataset obtained in two different experiments, i.e., experiments involving supine and seated subject postures. Absolute errors in heart rate and standard deviation of heartbeat interval with references were calculated as 1.93±1.76bpm and 57.0±28.1s for the lying posture, and 9.72±7.86bpm and 81.3±24.3s for the sitting posture.

Evaluation of Remote Photoplethysmography Measurement Conditions toward Telemedicine Applications.

Camera-based remote photoplethysmography (rPPG) is a low-cost and casual non-contact heart rate measurement method suitable for telemedicine. Several factors affect the accuracy of measuring the heart rate and heart rate variability (HRV) using rPPG despite HRV being an important indicator for healthcare monitoring. This study aimed to investigate the appropriate setup for precise HRV measurements using rPPG while considering the effects of possible factors including illumination, direction of the light, frame rate of the camera, and body motion. In the lighting conditions experiment, the smallest mean absolute R-R interval (RRI) error was obtained when light greater than 500 lux was cast from the front (among the following conditions-illuminance: 100, 300, 500, and 700 lux; directions: front, top, and front and top). In addition, the RRI and HRV were measured with sufficient accuracy at frame rates above 30 fps. The accuracy of the HRV measurement was greatly reduced when the body motion was not constrained; thus, it is necessary to limit the body motion, especially the head motion, in an actual telemedicine situation. The results of this study can act as guidelines for setting up the shooting environment and camera settings for rPPG use in telemedicine.

Return-to-Work Screening by Linear Discriminant Analysis of Heart Rate Variability Indices in Depressed Subjects.

Using a linear discriminant analysis of heart rate variability (HRV) indices, the present study sought to verify the usefulness of autonomic measurement in major depressive disorder (MDD) patients by assessing the feasibility of their return to work after sick leave. When reinstatement was scheduled, patients' HRV was measured using a wearable electrocardiogram device. The outcome of the reinstatement was evaluated at one month after returning to work. HRV indices including high- and low-frequency components were calculated in three conditions within a session: initial rest, mental task, and rest after task. A linear discriminant function was made using the HRV indices of 30 MDD patients from our previous study to effectively discriminate the successful reinstatement from the unsuccessful reinstatement; this was then tested on 52 patients who participated in the present study. The discriminant function showed that the sensitivity and specificity in discriminating successful from unsuccessful returns were 95.8% and 35.7%, respectively. Sensitivity is high, indicating that normal HRV is required for a successful return, and that the discriminant analysis of HRV indices is useful for return-to-work screening in MDD patients. On the other hand, specificity is low, suggesting that other factors may also affect the outcome of reinstatement.

Endogenous thrombopoietin promotes non-small-cell lung carcinoma cell proliferation and migration by regulating EGFR signalling.

Thrombopoietin (TPO) is a haematopoietic cytokine mainly produced by the liver and kidneys, which stimulates the production and maturation of megakaryocytes. In the past decade, numerous studies have investigated the effects of TPO outside the haematopoietic system; however, the role of TPO in the progression of solid cancer, particularly lung cancer, has not been well studied. Exogenous TPO does not affect non-small-cell lung cancer (NSCLC) cells as these cells show no or extremely low TPO receptor expression; therefore, in this study, we focused on endogenous TPO produced by NSCLC cells. Immunohistochemical analysis of 150 paired NSCLC and adjacent normal tissues indicated that TPO was highly expressed in NSCLC tissues and correlated with clinicopathological parameters including differentiation, P-TNM stage, lymph node metastasis and tumour size. Suppressing endogenous TPO by small interfering RNA inhibited the proliferation and migration of NSCLC cells. Moreover, TPO interacted with the EGFR protein and delayed ligand-induced EGFR degradation, thus enhancing EGFR signalling. Notably, overexpressing TPO in EGF-stimulated NSCLC cells facilitated cell proliferation and migration, whereas no obvious changes were observed without EGF stimulation. Our results suggest that endogenous TPO promotes tumorigenicity of NSCLC via regulating EGFR signalling and thus could be a therapeutic target for treating NSCLC.

Tumor-suppressive activity of sTRAIL on circulating CD44+ cells in patients with non-small cell lung cancer.

Circulating CD44+ cells have been identified as a prognostic marker for patients with non-small cell lung cancer (NSCLC). Serum tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL) is involved in the pathophysiology of many cancers. However, no previous studies have shown the roles of sTRAIL in circulating CD44+ cells in the blood of NSCLC patients. We detected circulating CD44+ cells and sTRAIL levels in blood samples from NSCLC patients using flow cytometry and an enzyme-linked immunosorbent assay (ELISA). Anti-tumor roles of TRAIL in CD44+ cells were confirmed using a CCK-8 assay and mouse models. A higher number of circulating CD44+ cells were identified in NSCLC patients compared with healthy control individuals. In addition, we confirmed the anti-tumor roles and mechanisms of TRAIL in CD44+ cells both in vitro and in vivo. Our results indicate that (1) there is a negative correlation between sTRAIL and circulating CD44+ cells in NSCLC patients and (2) CD44+ cells have cancer stem cell properties and are more sensitive than CD44- cells to TRAIL.

Contactless Vital Signs Measurement System Using RGB-Thermal Image Sensors and Its Clinical Screening Test on Patients with Seasonal Influenza.

Background: In the last two decades, infrared thermography (IRT) has been applied in quarantine stations for the screening of patients with suspected infectious disease. However, the fever-based screening procedure employing IRT suffers from low sensitivity, because monitoring body temperature alone is insufficient for detecting infected patients. To overcome the drawbacks of fever-based screening, this study aims to develop and evaluate a multiple vital sign (i.e., body temperature, heart rate and respiration rate) measurement system using RGB-thermal image sensors. Methods: The RGB camera measures blood volume pulse (BVP) through variations in the light absorption from human facial areas. IRT is used to estimate the respiration rate by measuring the change in temperature near the nostrils or mouth accompanying respiration. To enable a stable and reliable system, the following image and signal processing methods were proposed and implemented: (1) an RGB-thermal image fusion approach to achieve highly reliable facial region-of-interest tracking, (2) a heart rate estimation method including a tapered window for reducing noise caused by the face tracker, reconstruction of a BVP signal with three RGB channels to optimize a linear function, thereby improving the signal-to-noise ratio and multiple signal classification (MUSIC) algorithm for estimating the pseudo-spectrum from limited time-domain BVP signals within 15 s and (3) a respiration rate estimation method implementing nasal or oral breathing signal selection based on signal quality index for stable measurement and MUSIC algorithm for rapid measurement. We tested the system on 22 healthy subjects and 28 patients with seasonal influenza, using the support vector machine (SVM) classification method. Results: The body temperature, heart rate and respiration rate measured in a non-contact manner were highly similarity to those measured via contact-type reference devices (i.e., thermometer, ECG and respiration belt), with Pearson correlation coefficients of 0.71, 0.87 and 0.87, respectively. Moreover, the optimized SVM model with three vital signs yielded sensitivity and specificity values of 85.7% and 90.1%, respectively. Conclusion: For contactless vital sign measurement, the system achieved a performance similar to that of the reference devices. The multiple vital sign-based screening achieved higher sensitivity than fever-based screening. Thus, this system represents a promising alternative for further quarantine procedures to prevent the spread of infectious diseases.

Inhibition of miR-361-5p suppressed pulmonary artery smooth muscle cell survival and migration by targeting ABCA1 and inhibiting the JAK2/STAT3 pathway.

MicroRNAs play a crucial role in the progression of pulmonary arterial hypertension (PAH). The aim of this study was to investigate the effect of miR-361-5p on the proliferation, migration and apoptosis of pulmonary artery smooth muscle cells (PASMCs) that under the treatment of hypoxia and explore the underlying mechanisms. The results proved that hypoxia noticeably up-regulated the expression of miR-361-5p in PASMCs in comparison to the normoxia-treated cells, while TNF-α and IL-6 stimulation had no obvious effects on miR-361-5p level. Hypoxia induced miR-361-5p elevation in a HIF-1α-dependent manner. Inhibition of miR-361-5p dramatically inhibited hypoxia-induced cell proliferation and migration. miR-361-5p inhibition also rescued hypoxia exposure caused suppression of PASMCs apoptosis. In addition, the results showed that ABCA1 was a direct target of miR-361-5p and was down-regulated in hypoxia-induced PASMCs. Hypoxia and TNF-α or IL-6 stimulation significantly inhibited ABCA1 expression. In addition, overexpression of ABCA1 enhanced the effect of miR-361-5p on hPASMCs. Furthermore, the inhibition of miR-361-5p significantly down-regulated the expression level of p-JAK2 and p-STAT3. In conclusion, it may suggest that the suppression of miR-361-5p suppressed PASMC survival and migration by targeting ABCA1 and inhibiting the JAK2/STAT3 pathway.

Study on the Autonomous Non-contact Measurement of Biometric Signals.

In this study, we developed a robot that can recognize and track a person, and autonomously measure two biological signals, respiration rate and heart rate, in a non-contact manner. Through experiments, we confirmed that both signals can be measured with high accuracy and that the robot can perform the measurement under conditions similar to those in actual workplaces. We also investigated factors that can affect the accuracy of the non-contact measurement and studied a method to evaluate the reliability of the measured signals.

Temporal pain processing in the primary somatosensory cortex and anterior cingulate cortex.

Pain is known to have sensory and affective components. The sensory pain component is encoded by neurons in the primary somatosensory cortex (S1), whereas the emotional or affective pain experience is in large part processed by neural activities in the anterior cingulate cortex (ACC). The timing of how a mechanical or thermal noxious stimulus triggers activation of peripheral pain fibers is well-known. However, the temporal processing of nociceptive inputs in the cortex remains little studied. Here, we took two approaches to examine how nociceptive inputs are processed by the S1 and ACC. We simultaneously recorded local field potentials in both regions, during the application of a brain-computer interface (BCI). First, we compared event related potentials in the S1 and ACC. Next, we used an algorithmic pain decoder enabled by machine-learning to detect the onset of pain which was used during the implementation of the BCI to automatically treat pain. We found that whereas mechanical pain triggered neural activity changes first in the S1, the S1 and ACC processed thermal pain with a reasonably similar time course. These results indicate that the temporal processing of nociceptive information in different regions of the cortex is likely important for the overall pain experience.

Pulse rate variability estimation method based on imaging-photoplethysmography and application to telepsychiatry.

The worldwide adoption of telehealth services may benefit people who otherwise would not be able to access mental health support. In this paper, we present a novel algorithm to obtain reliable pulse and respiration signals from non-contact facial image sequence analysis. The proposed algorithm involved a skin pixel extraction method in the image processing part and signal reconstruction using the spectral information of RGB signal in the signal processing part. The algorithm was tested on 15 healthy subjects in a laboratory setting. The results show that the proposed algorithm can accurately monitor respiration rate (RR), pulse rate (PR), and pulse rate variability (PRV) in rest conditions.Clinical Relevance- The main achievement of this study is enabling non-contact PR and RR signal extraction from facial image sequences, which has potential for future use and support for psychiatrists in telepsychiatry.

A prototype closed-loop brain-machine interface for the study and treatment of pain.

Chronic pain is characterized by discrete pain episodes of unpredictable frequency and duration. This hinders the study of pain mechanisms and contributes to the use of pharmacological treatments associated with side effects, addiction and drug tolerance. Here, we show that a closed-loop brain-machine interface (BMI) can modulate sensory-affective experiences in real time in freely behaving rats by coupling neural codes for nociception directly with therapeutic cortical stimulation. The BMI decodes the onset of nociception via a state-space model on the basis of the analysis of online-sorted spikes recorded from the anterior cingulate cortex (which is critical for pain processing) and couples real-time pain detection with optogenetic activation of the prelimbic prefrontal cortex (which exerts top-down nociceptive regulation). In rats, the BMI effectively inhibited sensory and affective behaviours caused by acute mechanical or thermal pain, and by chronic inflammatory or neuropathic pain. The approach provides a blueprint for demand-based neuromodulation to treat sensory-affective disorders, and could be further leveraged for nociceptive control and to study pain mechanisms.

Changes in alpha, theta, and gamma oscillations in distinct cortical areas are associated with altered acute pain responses in chronic low back pain patients.

Introduction: Chronic pain negatively impacts a range of sensory and affective behaviors. Previous studies have shown that the presence of chronic pain not only causes hypersensitivity at the site of injury but may also be associated with pain-aversive experiences at anatomically unrelated sites. While animal studies have indicated that the cingulate and prefrontal cortices are involved in this generalized hyperalgesia, the mechanisms distinguishing increased sensitivity at the site of injury from a generalized site-nonspecific enhancement in the aversive response to nociceptive inputs are not well known. Methods: We compared measured pain responses to peripheral mechanical stimuli applied to a site of chronic pain and at a pain-free site in participants suffering from chronic lower back pain (n = 15) versus pain-free control participants (n = 15) by analyzing behavioral and electroencephalographic (EEG) data. Results: As expected, participants with chronic pain endorsed enhanced pain with mechanical stimuli in both back and hand. We further analyzed electroencephalographic (EEG) recordings during these evoked pain episodes. Brain oscillations in theta and alpha bands in the medial orbitofrontal cortex (mOFC) were associated with localized hypersensitivity, while increased gamma oscillations in the anterior cingulate cortex (ACC) and increased theta oscillations in the dorsolateral prefrontal cortex (dlPFC) were associated with generalized hyperalgesia. Discussion: These findings indicate that chronic pain may disrupt multiple cortical circuits to impact nociceptive processing.

Medical Radar Signal Dataset for Non-Contact Respiration and Heart Rate Measurement.

Medical radars remotely measure the periodic movements of the chest wall induced by breathing and heartbeat and have been widely recognized in healthcare. To the best of our knowledge, no well-characterized medical radar datasets are shared publicly. Therefore, in this article, we provide non-contact respiratory and cardiac signal datasets measured using a medical radar and simultaneously measured reference signals using electrocardiogram (ECG) and respiratory belt transducer. The datasets were collected from nine healthy subjects using 24.25 GHz and 10.525 GHz Doppler radars at a physiological laboratory in Japan. Furthermore, we generated MATLAB code to pre-process the signals and calculate the respiratory and heart rates. The datasets generated could be reused by biomedical researchers to investigate the signal-processing algorithm for non-contact vital sign measurement.

TFAP4 Activates IGF2BP1 and Promotes Progression of Non-Small Cell Lung Cancer by Stabilizing TK1 Expression through m6A Modification.

Non-small cell lung cancer (NSCLC) is a well-known global health concern. TFAP4 has been reported to function as an oncogene. This study sought to investigate the molecular mechanism of TFAP4 in NSCLC development. Significantly highly-expressed gene IGF2BP1 was screened on online databases and its downstream gene TK1 was predicted. IGF2BP1 promoter sequence was identified. The binding site of TFAP4 and IGF2BP1 was predicted. The expression correlations among TFAP4, IGF2BP1, and TK1 were confirmed. The correlations between TFAP4, IGF2BP1, TK1, and NSCLC prognosis were predicted. NSCLC and paracancerous tissues were collected. The expressions of TFAP4, IGF2BP1, and TK1 were detected. NSCLC cell proliferation, migration, invasion, and apoptosis were detected. The binding of TFAP4 to the IGF2BP1 promoter was verified. m6A modification of TK1 mRNA was detected. The correlation between IGF2BP1 and TK1 was confirmed. A subcutaneous tumor xenograft model was established to validate the effect of TFAP4 in vivo. IGF2BP1 was highly expressed in NSCLC tissues and cells. IGF2BP1 knockdown repressed NSCLC cell proliferation, migration, and invasion and facilitated apoptosis. Mechanically, TFAP4 transcriptionally activated IGF2BP1. IGF2BP1 stabilized TK1 expression via m6A modification and promoted NSCLC cell proliferation, migration, and invasion. In vivo experiments confirmed that TFAP4 knockdown suppressed tumor growth by downregulating IGF2BP1/TK1. IMPLICATIONS: Our findings revealed that TFAP4 activated IGF2BP1 and facilitated NSCLC progression by stabilizing TK1 expression via m6A modification, which offered new insights into the diagnosis and treatment of NSCLC.

An mHealth App for the Non-contact Measurement of Pulmonary Function Using the Smartphone's Built-in Depth Sensor.

The use of smartphones in clinical practice is referred to as mobile health (mHealth). This has attracted great interest in both academia and industry because of its potential to augment healthcare. In this study, we developed an mHealth app for the non-contact measurement of chest-wall movements using the iPhone ' s built-in depth sensor, thereby enabling a pulmonary self-monitoring function for personal use. The depth sensor provides depth values for each pixel and 2D mapping of the chest-wall movements. To extract respiratory signals from the right and left thoracic regions and abdomen, a 2D-depth image-segmentation method was implemented. The method was based on the anatomy and physiology of chest-wall movements, assuming differences in the anterior displacement in the thoracic and abdominal regions. It was observed that the differences were significant in the segmented regions of interest (ROIs) of the right and left thoracic region and abdomen. Respiratory signals extracted from each ROI were compared with the contact bio-impedance signals, which were highly correlated (r=0.94).

Development of a Novel Vital-Signs-Based Infection Screening Composite-Type Camera With Truncus Motion Removal Algorithm to Detect COVID-19 Within 10 Seconds and Its Clinical Validation.

Background: To conduct a rapid preliminary COVID-19 screening prior to polymerase chain reaction (PCR) test under clinical settings, including patient's body moving conditions in a non-contact manner, we developed a mobile and vital-signs-based infection screening composite-type camera (VISC-Camera) with truncus motion removal algorithm (TMRA) to screen for possibly infected patients. Methods: The VISC-Camera incorporates a stereo depth camera for respiratory rate (RR) determination, a red-green-blue (RGB) camera for heart rate (HR) estimation, and a thermal camera for body temperature (BT) measurement. In addition to the body motion removal algorithm based on the region of interest (ROI) tracking for RR, HR, and BT determination, we adopted TMRA for RR estimation. TMRA is a reduction algorithm of RR count error induced by truncus non-respiratory front-back motion measured using depth-camera-determined neck movement. The VISC-Camera is designed for mobile use and is compact (22 cm × 14 cm × 4 cm), light (800 g), and can be used in continuous operation for over 100 patients with a single battery charge. The VISC-Camera discriminates infected patients from healthy people using a logistic regression algorithm using RR, HR, and BT as explanatory variables. Results are available within 10 s, including imaging and processing time. Clinical testing was conducted on 154 PCR positive COVID-19 inpatients (aged 18-81 years; M/F = 87/67) within the initial 48 h of hospitalization at the First Central Hospital of Mongolia and 147 healthy volunteers (aged 18-85 years, M/F = 70/77). All patients were on treatment with antivirals and had body temperatures <37.5°C. RR measured by visual counting, pulsimeter-determined HR, and BT determined by thermometer were used for references. Result: 10-fold cross-validation revealed 91% sensitivity and 90% specificity with an area under receiver operating characteristic curve of 0.97. The VISC-Camera-determined HR, RR, and BT correlated significantly with those measured using references (RR: r = 0.93, p < 0.001; HR: r = 0.97, p < 0.001; BT: r = 0.72, p < 0.001). Conclusion: Under clinical settings with body motion, the VISC-Camera with TMRA appears promising for the preliminary screening of potential COVID-19 infection for afebrile patients with the possibility of misdiagnosis as asymptomatic.

KBTBD7 promotes non-small cell lung carcinoma progression by enhancing ubiquitin-dependent degradation of PTEN.

The Kelch repeat and BTB domain containing 7 (KBTBD7) was first cloned in 2010. Its function as a transcriptional activator and a substrate adaptor during the ubiquitination process was soon found. KBTBD7 was shown to be involved in excessive inflammation after myocardial infarction, brain development, and neurofibromin stability. However, studies on the role of KBTBD7 in solid tumors, especially lung cancer, are still lacking. Therefore, in this study, we investigate the role of KBTBD7 in non-small cell lung cancer (NSCLC). Immunohistochemical staining of 104 paired NSCLC and peritumoral normal specimens indicated that KBTBD7 was highly expressed in NSCLC tissues and positively correlated with the histological type, P-TNM stage, lymph node metastasis, and tumor size. KBTBD7 was also well-expressed in NSCLC cell lines, and downregulation of KBTBD7 resulted in inhibition of NSCLC cell proliferation and invasion. Further investigation showed that KBTBD7 enhanced ubiquitin-dependent degradation of PTEN, thus activating EGFR/PI3K/AKT signaling and promoting NSCLC cell proliferation and invasion by regulating CCNE1, CDK4, P27, ZEB-1, Claudin-1, ROCK1, MMP-9, and E-cadherin protein levels. Our results indicate that KBTBD7 may be a potential therapeutic target for the treatment of NSCLC.