Accurate Localization of First and Second Heart Sounds via Template Matching in Forcecardiography Signals.

Cardiac auscultation is an essential part of physical examination and plays a key role in the early diagnosis of many cardiovascular diseases. The analysis of phonocardiography (PCG) recordings is generally based on the recognition of the main heart sounds, i.e., S1 and S2, which is not a trivial task. This study proposes a method for an accurate recognition and localization of heart sounds in Forcecardiography (FCG) recordings. FCG is a novel technique able to measure subsonic vibrations and sounds via small force sensors placed onto a subject's thorax, allowing continuous cardio-respiratory monitoring. In this study, a template-matching technique based on normalized cross-correlation was used to automatically recognize heart sounds in FCG signals recorded from six healthy subjects at rest. Distinct templates were manually selected from each FCG recording and used to separately localize S1 and S2 sounds, as well as S1-S2 pairs. A simultaneously recorded electrocardiography (ECG) trace was used for performance evaluation. The results show that the template matching approach proved capable of separately classifying S1 and S2 sounds in more than 96% of all heartbeats. Linear regression, correlation, and Bland-Altman analyses showed that inter-beat intervals were estimated with high accuracy. Indeed, the estimation error was confined within 10 ms, with negligible impact on heart rate estimation. Heart rate variability (HRV) indices were also computed and turned out to be almost comparable with those obtained from ECG. The preliminary yet encouraging results of this study suggest that the template matching approach based on normalized cross-correlation allows very accurate heart sounds localization and inter-beat intervals estimation.

A Narrowband IoT Personal Sensor for Long-Term Heart Rate Monitoring and Atrial Fibrillation Detection.

Long-term patient monitoring is required for detection of episodes of atrial fibrillation, one of the most widespread cardiac pathologies. Today, the most used non-invasive technique is Holter electrocardiographic (ECG) monitoring, which can often prove ineffective because of the short duration of recordings (e.g., one day). Other techniques such as photo-plethysmography are adopted by smartwatches for much longer duration monitoring, but this has the disadvantage of offering only intermittent measurements. This study proposes an Internet of Things (IoT) sensor that can provide a very long period of continuous monitoring. The sensor consists of an ECG-integrated Analog Front End (MAX30003), a microcontroller (STM32F401RE), and an IoT narrowband module (STEVAL-STMODLTE). The instantaneous heart rate is extracted from the ECG recording in real time. At intervals of two minutes, the sequence of inter-beat intervals is transmitted to an IoT cloud platform (ThingSpeak). Settled atrial fibrillation event recognition software runs on the cloud and generates alerts when it recognizes such arrhythmia. Performances of the proposed sensor were evaluated by generating analog ECG signals from a public dataset of ECG signals with atrial fibrillation episodes, the MIT-BIH Atrial Fibrillation Database, each recording lasting approximately 10 h. Software implementing the Lorentz algorithm, one of the best detectors of atrial fibrillation, was implemented on the cloud platform. The accuracy, sensitivity, and specificity in recognizing atrial fibrillation episodes of the proposed system was calculated by comparison with a cardiologist's reference data. Across all patients, the proposed method achieved an accuracy of 0.88, a sensitivity 0.71, and a specificity 0.99. The results obtained suggest that the developed system can continuously record and transmit heart rhythms effectively and efficiently and, in addition, offers considerable performance in recognizing atrial fibrillation episodes in real time.

Heartbeat Detection in Gyrocardiography Signals without Concurrent ECG Tracings.

A heartbeat generates tiny mechanical vibrations, mainly due to the opening and closing of heart valves. These vibrations can be recorded by accelerometers and gyroscopes applied on a subject's chest. In particular, the local 3D linear accelerations and 3D angular velocities of the chest wall are referred to as seismocardiograms (SCG) and gyrocardiograms (GCG), respectively. These signals usually exhibit a low signal-to-noise ratio, as well as non-negligible amplitude and morphological changes due to changes in posture and the sensors' location, respiratory activity, as well as other sources of intra-subject and inter-subject variability. These factors make heartbeat detection a complex task; therefore, a reference electrocardiogram (ECG) lead is usually acquired in SCG and GCG studies to ensure correct localization of heartbeats. Recently, a template matching technique based on cross correlation has proven to be particularly effective in recognizing individual heartbeats in SCG signals. This study aims to verify the performance of this technique when applied on GCG signals. Tests were conducted on a public database consisting of SCG, GCG, and ECG signals recorded synchronously on 100 patients with valvular heart diseases. The results show that the template matching technique identified heartbeats in GCG signals with a sensitivity and positive predictive value (PPV) of 87% and 92%, respectively. Regression, correlation, and Bland-Altman analyses carried out on inter-beat intervals obtained from GCG and ECG (assumed as reference) reported a slope of 0.995, an intercept of 4.06 ms (R2 > 0.99), a Pearson's correlation coefficient of 0.9993, and limits of agreement of about ±13 ms with a negligible bias. A comparison with the results of a previous study obtained on SCG signals from the same database revealed that GCG enabled effective cardiac monitoring in significantly more patients than SCG (95 vs. 77). This result suggests that GCG could ensure more robust and reliable cardiac monitoring in patients with heart diseases with respect to SCG.

ECG-Free Heartbeat Detection in Seismocardiography and Gyrocardiography Signals Provides Acceptable Heart Rate Variability Indices in Healthy and Pathological Subjects.

Cardio-mechanical monitoring techniques, such as Seismocardiography (SCG) and Gyrocardiography (GCG), have received an ever-growing interest in recent years as potential alternatives to Electrocardiography (ECG) for heart rate monitoring. Wearable SCG and GCG devices based on lightweight accelerometers and gyroscopes are particularly appealing for continuous, long-term monitoring of heart rate and its variability (HRV). Heartbeat detection in cardio-mechanical signals is usually performed with the support of a concurrent ECG lead, which, however, limits their applicability in standalone cardio-mechanical monitoring applications. The complex and variable morphology of SCG and GCG signals makes the ECG-free heartbeat detection task quite challenging; therefore, only a few methods have been proposed. Very recently, a template matching method based on normalized cross-correlation (NCC) has been demonstrated to provide very accurate detection of heartbeats and estimation of inter-beat intervals in SCG and GCG signals of pathological subjects. In this study, the accuracy of HRV indices obtained with this template matching method is evaluated by comparison with ECG. Tests were performed on two public datasets of SCG and GCG signals from healthy and pathological subjects. Linear regression, correlation, and Bland-Altman analyses were carried out to evaluate the agreement of 24 HRV indices obtained from SCG and GCG signals with those obtained from ECG signals, simultaneously acquired from the same subjects. The results of this study show that the NCC-based template matching method allowed estimating HRV indices from SCG and GCG signals of healthy subjects with acceptable accuracy. On healthy subjects, the relative errors on time-domain indices ranged from 0.25% to 15%, on frequency-domain indices ranged from 10% to 20%, and on non-linear indices were within 8%. The estimates obtained on signals from pathological subjects were affected by larger errors. Overall, GCG provided slightly better performances as compared to SCG, both on healthy and pathological subjects. These findings provide, for the first time, clear evidence that monitoring HRV via SCG and GCG sensors without concurrent ECG is feasible with the NCC-based template matching method for heartbeat detection.

ECG-Free Heartbeat Detection in Seismocardiography Signals via Template Matching.

Cardiac monitoring can be performed by means of an accelerometer attached to a subject's chest, which produces the Seismocardiography (SCG) signal. Detection of SCG heartbeats is commonly carried out by taking advantage of a simultaneous electrocardiogram (ECG). SCG-based long-term monitoring would certainly be less obtrusive and easier to implement without an ECG. Few studies have addressed this issue using a variety of complex approaches. This study proposes a novel approach to ECG-free heartbeat detection in SCG signals via template matching, based on normalized cross-correlation as heartbeats similarity measure. The algorithm was tested on the SCG signals acquired from 77 patients with valvular heart diseases, available from a public database. The performance of the proposed approach was assessed in terms of sensitivity and positive predictive value (PPV) of the heartbeat detection and accuracy of inter-beat intervals measurement. Sensitivity and PPV of 96% and 97%, respectively, were obtained by considering templates that included both systolic and diastolic complexes. Regression, correlation, and Bland-Altman analyses carried out on inter-beat intervals reported slope and intercept of 0.997 and 2.8 ms (R2 > 0.999), as well as non-significant bias and limits of agreement of ±7.8 ms. The results are comparable or superior to those achieved by far more complex algorithms, also based on artificial intelligence. The low computational burden of the proposed approach makes it suitable for direct implementation in wearable devices.

Contactless Electrocatheter Tracing within Human Body via Magnetic Sensing: A Feasibility Study.

During surgical procedures, real-time estimation of the current position of a metal lead within the patient's body is obtained by radiographic imaging. The inherent opacity of metal objects allows their visualization using X-ray fluoroscopic devices. Although fluoroscopy uses reduced radiation intensities, the overall X-ray dose delivered during prolonged exposure times poses risks to the safety of patients and physicians. This study proposes a potential alternative to real-time visualization of a lead inside the human body. In principle, by making a weak current flow through the lead and measuring the related magnetic field generated outside the body, it is possible to trace the position of the lead. This hypothesis was verified experimentally via two tests: one carried out on a curved copper wire in air and one carried out on a real pacemaker lead in a saline solution. In the second test, a pacemaker lead and a large return electrode were placed in a tank filled with a saline solution that reproduced the mean resistivity of the human torso. In both tests, a current flowed through the lead, which consisted of square pulses with short duration, to avoid any neuro-muscular stimulation effects in a real scenario. A small coil with a ferrite core was moved along a grid of points over a plastic sheet and placed just above the lead to sample the spatial amplitude distribution of the magnetic induction field produced by the lead. For each measurement point, the main coil axis was oriented along the x and y axes of the plane to estimate the related components of the magnetic induction field. The two matrices of measurements along the x and y axes were further processed to obtain an estimate of lead positioning. The preliminary results of this study support the scientific hypothesis since the positions of the leads were accurately estimated. This encourages to deepen the investigation and overcome some limitations of this feasibility study.

Changes in Forcecardiography Heartbeat Morphology Induced by Cardio-Respiratory Interactions.

The cardiac function is influenced by respiration. In particular, various parameters such as cardiac time intervals and the stroke volume are modulated by respiratory activity. It has long been recognized that cardio-respiratory interactions modify the morphology of cardio-mechanical signals, e.g., phonocardiogram, seismocardiogram (SCG), and ballistocardiogram. Forcecardiography (FCG) records the weak forces induced on the chest wall by the mechanical activity of the heart and lungs and relies on specific force sensors that are capable of monitoring respiration, infrasonic cardiac vibrations, and heart sounds, all simultaneously from a single site on the chest. This study addressed the changes in FCG heartbeat morphology caused by respiration. Two respiratory-modulated parameters were considered, namely the left ventricular ejection time (LVET) and a morphological similarity index (MSi) between heartbeats. The time trends of these parameters were extracted from FCG signals and further analyzed to evaluate their consistency within the respiratory cycle in order to assess their relationship with the breathing activity. The respiratory acts were localized in the time trends of the LVET and MSi and compared with a reference respiratory signal by computing the sensitivity and positive predictive value (PPV). In addition, the agreement between the inter-breath intervals estimated from the LVET and MSi and those estimated from the reference respiratory signal was assessed via linear regression and Bland-Altman analyses. The results of this study clearly showed a tight relationship between the respiratory activity and the considered respiratory-modulated parameters. Both the LVET and MSi exhibited cyclic time trends that remarkably matched the reference respiratory signal. In addition, they achieved a very high sensitivity and PPV (LVET: 94.7% and 95.7%, respectively; MSi: 99.3% and 95.3%, respectively). The linear regression analysis reported almost unit slopes for both the LVET (R2 = 0.86) and MSi (R2 = 0.97); the Bland-Altman analysis reported a non-significant bias for both the LVET and MSi as well as limits of agreement of ±1.68 s and ±0.771 s, respectively. In summary, the results obtained were substantially in line with previous findings on SCG signals, adding to the evidence that FCG and SCG signals share a similar information content.

Toward a priori noise characterization for real-time edge-aware denoising in fluoroscopic devices.

BACKGROUND: Low-dose X-ray images have become increasingly popular in the last decades, due to the need to guarantee the lowest reasonable patient's exposure. Dose reduction causes a substantial increase of quantum noise, which needs to be suitably suppressed. In particular, real-time denoising is required to support common interventional fluoroscopy procedures. The knowledge of noise statistics provides precious information that helps to improve denoising performances, thus making noise estimation a crucial task for effective denoising strategies. Noise statistics depend on different factors, but are mainly influenced by the X-ray tube settings, which may vary even within the same procedure. This complicates real-time denoising, because noise estimation should be repeated after any changes in tube settings, which would be hardly feasible in practice. This work investigates the feasibility of an a priori characterization of noise for a single fluoroscopic device, which would obviate the need for inferring noise statics prior to each new images acquisition. The noise estimation algorithm used in this study was tested in silico to assess its accuracy and reliability. Then, real sequences were acquired by imaging two different X-ray phantoms via a commercial fluoroscopic device at various X-ray tube settings. Finally, noise estimation was performed to assess the matching of noise statistics inferred from two different sequences, acquired independently in the same operating conditions. RESULTS: The noise estimation algorithm proved capable of retrieving noise statistics, regardless of the particular imaged scene, also achieving good results even by using only 10 frames (mean percentage error lower than 2%). The tests performed on the real fluoroscopic sequences confirmed that the estimated noise statistics are independent of the particular informational content of the scene from which they have been inferred, as they turned out to be consistent in sequences of the two different phantoms acquired independently with the same X-ray tube settings. CONCLUSIONS: The encouraging results suggest that an a priori characterization of noise for a single fluoroscopic device is feasible and could improve the actual implementation of real-time denoising strategies that take advantage of noise statistics to improve the trade-off between noise reduction and details preservation.

Respiration Monitoring via Forcecardiography Sensors.

In the last few decades, a number of wearable systems for respiration monitoring that help to significantly reduce patients' discomfort and improve the reliability of measurements have been presented. A recent research trend in biosignal acquisition is focusing on the development of monolithic sensors for monitoring multiple vital signs, which could improve the simultaneous recording of different physiological data. This study presents a performance analysis of respiration monitoring performed via forcecardiography (FCG) sensors, as compared to ECG-derived respiration (EDR) and electroresistive respiration band (ERB), which was assumed as the reference. FCG is a novel technique that records the cardiac-induced vibrations of the chest wall via specific force sensors, which provide seismocardiogram-like information, along with a novel component that seems to be related to the ventricular volume variations. Simultaneous acquisitions were obtained from seven healthy subjects at rest, during both quiet breathing and forced respiration at higher and lower rates. The raw FCG sensor signals featured a large, low-frequency, respiratory component (R-FCG), in addition to the common FCG signal. Statistical analyses of R-FCG, EDR and ERB signals showed that FCG sensors ensure a more sensitive and precise detection of respiratory acts than EDR (sensitivity: 100% vs. 95.8%, positive predictive value: 98.9% vs. 92.5%), as well as a superior accuracy and precision in interbreath interval measurement (linear regression slopes and intercepts: 0.99, 0.026 s (R2 = 0.98) vs. 0.98, 0.11 s (R2 = 0.88), Bland-Altman limits of agreement: ±0.61 s vs. ±1.5 s). This study represents a first proof of concept for the simultaneous recording of respiration signals and forcecardiograms with a single, local, small, unobtrusive, cheap sensor. This would extend the scope of FCG to monitoring multiple vital signs, as well as to the analysis of cardiorespiratory interactions, also paving the way for the continuous, long-term monitoring of patients with heart and pulmonary diseases.

Biosignal-Based Human-Machine Interfaces for Assistance and Rehabilitation: A Survey.

As a definition, Human-Machine Interface (HMI) enables a person to interact with a device. Starting from elementary equipment, the recent development of novel techniques and unobtrusive devices for biosignals monitoring paved the way for a new class of HMIs, which take such biosignals as inputs to control various applications. The current survey aims to review the large literature of the last two decades regarding biosignal-based HMIs for assistance and rehabilitation to outline state-of-the-art and identify emerging technologies and potential future research trends. PubMed and other databases were surveyed by using specific keywords. The found studies were further screened in three levels (title, abstract, full-text), and eventually, 144 journal papers and 37 conference papers were included. Four macrocategories were considered to classify the different biosignals used for HMI control: biopotential, muscle mechanical motion, body motion, and their combinations (hybrid systems). The HMIs were also classified according to their target application by considering six categories: prosthetic control, robotic control, virtual reality control, gesture recognition, communication, and smart environment control. An ever-growing number of publications has been observed over the last years. Most of the studies (about 67%) pertain to the assistive field, while 20% relate to rehabilitation and 13% to assistance and rehabilitation. A moderate increase can be observed in studies focusing on robotic control, prosthetic control, and gesture recognition in the last decade. In contrast, studies on the other targets experienced only a small increase. Biopotentials are no longer the leading control signals, and the use of muscle mechanical motion signals has experienced a considerable rise, especially in prosthetic control. Hybrid technologies are promising, as they could lead to higher performances. However, they also increase HMIs' complexity, so their usefulness should be carefully evaluated for the specific application.

Wearable Bluetooth Triage Healthcare Monitoring System.

Triage is the first interaction between a patient and a nurse/paramedic. This assessment, usually performed at Emergency departments, is a highly dynamic process and there are international grading systems that according to the patient condition initiate the patient journey. Triage requires an initial rapid assessment followed by routine checks of the patients' vitals, including respiratory rate, temperature, and pulse rate. Ideally, these checks should be performed continuously and remotely to reduce the workload on triage nurses; optimizing tools and monitoring systems can be introduced and include a wearable patient monitoring system that is not at the expense of the patient's comfort and can be remotely monitored through wireless connectivity. In this study, we assessed the suitability of a small ceramic piezoelectric disk submerged in a skin-safe silicone dome that enhances contact with skin, to detect wirelessly both respiration and cardiac events at several positions on the human body. For the purposes of this evaluation, we fitted the sensor with a respiratory belt as well as a single lead ECG, all acquired simultaneously. To complete Triage parameter collection, we also included a medical-grade contact thermometer. Performances of cardiac and respiratory events detection were assessed. The instantaneous heart and respiratory rates provided by the proposed sensor, the ECG and the respiratory belt were compared via statistical analyses. In all considered sensor positions, very high performances were achieved for the detection of both cardiac and respiratory events, except for the wrist, which provided lower performances for respiratory rates. These promising yet preliminary results suggest the proposed wireless sensor could be used as a wearable, hands-free monitoring device for triage assessment within emergency departments. Further tests are foreseen to assess sensor performances in real operating environments.

Forcecardiography: A Novel Technique to Measure Heart Mechanical Vibrations onto the Chest Wall.

This paper presents forcecardiography (FCG), a novel technique to measure local, cardiac-induced vibrations onto the chest wall. Since the 19th century, several techniques have been proposed to detect the mechanical vibrations caused by cardiovascular activity, the great part of which was abandoned due to the cumbersome instrumentation involved. The recent availability of unobtrusive sensors rejuvenated the research field with the most currently established technique being seismocardiography (SCG). SCG is performed by placing accelerometers onto the subject's chest and provides information on major events of the cardiac cycle. The proposed FCG measures the cardiac-induced vibrations via force sensors placed onto the subject's chest and provides signals with a richer informational content as compared to SCG. The two techniques were compared by analysing simultaneous recordings acquired by means of a force sensor, an accelerometer and an electrocardiograph (ECG). The force sensor and the accelerometer were rigidly fixed to each other and fastened onto the xiphoid process with a belt. The high-frequency (HF) components of FCG and SCG were highly comparable (r > 0.95) although lagged. The lag was estimated by cross-correlation and resulted in about tens of milliseconds. An additional, large, low-frequency (LF) component, associated with ventricular volume variations, was observed in FCG, while not being visible in SCG. The encouraging results of this feasibility study suggest that FCG is not only able to acquire similar information as SCG, but it also provides additional information on ventricular contraction. Further analyses are foreseen to confirm the advantages of FCG as a technique to improve the scope and significance of pervasive cardiac monitoring.

Real-Time EMG Based Pattern Recognition Control for Hand Prostheses: A Review on Existing Methods, Challenges and Future Implementation.

Upper limb amputation is a condition that significantly restricts the amputees from performing their daily activities. The myoelectric prosthesis, using signals from residual stump muscles, is aimed at restoring the function of such lost limbs seamlessly. Unfortunately, the acquisition and use of such myosignals are cumbersome and complicated. Furthermore, once acquired, it usually requires heavy computational power to turn it into a user control signal. Its transition to a practical prosthesis solution is still being challenged by various factors particularly those related to the fact that each amputee has different mobility, muscle contraction forces, limb positional variations and electrode placements. Thus, a solution that can adapt or otherwise tailor itself to each individual is required for maximum utility across amputees. Modified machine learning schemes for pattern recognition have the potential to significantly reduce the factors (movement of users and contraction of the muscle) affecting the traditional electromyography (EMG)-pattern recognition methods. Although recent developments of intelligent pattern recognition techniques could discriminate multiple degrees of freedom with high-level accuracy, their efficiency level was less accessible and revealed in real-world (amputee) applications. This review paper examined the suitability of upper limb prosthesis (ULP) inventions in the healthcare sector from their technical control perspective. More focus was given to the review of real-world applications and the use of pattern recognition control on amputees. We first reviewed the overall structure of pattern recognition schemes for myo-control prosthetic systems and then discussed their real-time use on amputee upper limbs. Finally, we concluded the paper with a discussion of the existing challenges and future research recommendations.

A Contactless Sensor for Pacemaker Pulse Detection: Design Hints and Performance Assessment.

Continuous monitoring of pacemaker activity can provide valuable information to improve patients' follow-up. Concise information is stored in some types of pacemakers, whereas ECG can provide more detailed information, but requires electrodes and cannot be used for continuous monitoring. This study highlights the possibility of a continuous monitoring of pacemaker pulses by sensing magnetic field variations due to the current pulses. This can be achieved by means of a sensor coil positioned near the patient's thorax without any need for physical contact. A simplified model of coil response to pacemaker pulses is presented in this paper, along with circuits suitable for pulse detection. In vitro tests were carried out using real pacemakers immersed in saline solution; experimental data were used to assess the accuracy of the model and to evaluate the sensor performance. It was found that the coil signal amplitude decreases with increasing distance from the pacemaker lead wire. The sensor was able to easily perform pacemaker spike detection up to a distance of 12 cm from the pacemaker leads. The stimulation rate can be measured in real time with high accuracy. Since any electromagnetic pulse triggers the same coil response, EMI may corrupt sensor measurements and thus should be discriminated.

A Piezoresistive Sensor to Measure Muscle Contraction and Mechanomyography.

Measurement of muscle contraction is mainly achieved through electromyography (EMG) and is an area of interest for many biomedical applications, including prosthesis control and human machine interface. However, EMG has some drawbacks, and there are also alternative methods for measuring muscle activity, such as by monitoring the mechanical variations that occur during contraction. In this study, a new, simple, non-invasive sensor based on a force-sensitive resistor (FSR) which is able to measure muscle contraction is presented. The sensor, applied on the skin through a rigid dome, senses the mechanical force exerted by the underlying contracting muscles. Although FSR creep causes output drift, it was found that appropriate FSR conditioning reduces the drift by fixing the voltage across the FSR and provides voltage output proportional to force. In addition to the larger contraction signal, the sensor was able to detect the mechanomyogram (MMG), i.e., the little vibrations which occur during muscle contraction. The frequency response of the FSR sensor was found to be large enough to correctly measure the MMG. Simultaneous recordings from flexor carpi ulnaris showed a high correlation (Pearson's r > 0.9) between the FSR output and the EMG linear envelope. Preliminary validation tests on healthy subjects showed the ability of the FSR sensor, used instead of the EMG, to proportionally control a hand prosthesis, achieving comparable performances.

Isatin Bis-Imidathiazole Hybrids Identified as FtsZ Inhibitors with On-Target Activity Against Staphylococcus aureus.

In the present study, a series of isatin bis-imidathiazole hybrids was designed and synthesized to develop a new class of heterocyclic compounds with improved antimicrobial activity against pathogens responsible for hospital- and community-acquired infections. A remarkable inhibitory activity against Staphylococcus aureus was demonstrated for a subset of compounds (range: 13.8-90.1 µM) in the absence of toxicity towards epithelial cells and human red blood cells. The best performing derivative was further investigated to measure its anti-biofilm potential and its effectiveness against methicillin-resistant Staphylococcus aureus strains. A structure-activity relationship study of the synthesized molecules led to the recognition of some important structural requirements for the observed antibacterial activity. Molecular docking followed by molecular dynamics (MD) simulations identified the binding site of the active compound FtsZ, a key protein in bacterial cell division, and the mechanism of action, i.e., the inhibition of its polymerization. The overall results may pave the way for a further rational development of isatin hybrids as FtsZ inhibitors, with a broader spectrum of activity against human pathogens and higher potency.

Identification of a new bisindolinone arresting IGROV1 cells proliferation.

In an initial screening, a series of novel Knoevenagel adducts were submitted to the National Cancer Institute for evaluation of antitumor activity in human cell lines. In particular, compound 5f showed remarkable selectivity against IGROV1, an ovarian cancer cell line, without affecting healthy human fibroblast cells. Analyses of cytotoxicity, cell proliferation, cell migration, epigenetic changes, gene expression, and DNA damage were performed to obtain detailed information about its antitumor properties. Our results show that 5f causes proliferation arrest, decrease in motility, histone hyperacetylation, downregulation of cyclin D1 and α5 subunit of integrin ß1 gene transcription. In addition, 5f treatment reduces transcript and protein levels of cyclin D1, which increases sensitivity to ionizing radiation and results in DNA damage comparable to cyclin D1 gene silencing.

A smart approach to EMG envelope extraction and powerful denoising for human-machine interfaces.

Electromyography (EMG) is widely used in human-machine interfaces (HMIs) to measure muscle contraction by computing the EMG envelope. However, EMG is largely affected by powerline interference and motion artifacts. Boards that directly provide EMG envelope, without denoising the raw signal, are often unreliable and hinder HMIs performance. Sophisticated filtering provides high performance but is not viable when power and computational resources must be optimized. This study investigates the application of feed-forward comb (FFC) filters to remove both powerline interferences and motion artifacts from raw EMG. FFC filter and EMG envelope extractor can be implemented without computing any multiplication. This approach is particularly suitable for very low-cost, low-power platforms. The performance of the FFC filter was first demonstrated offline by corrupting clean EMG signals with powerline noise and motion artifacts. The correlation coefficients of the filtered signals envelopes and the true envelopes were greater than 0.98 and 0.94 for EMG corrupted by powerline noise and motion artifacts, respectively. Further tests on real, highly noisy EMG signals confirmed these achievements. Finally, the real-time operation of the proposed approach was successfully tested by implementation on a simple Arduino Uno board.

Respiratory-Induced Amplitude Modulation of Forcecardiography Signals.

Forcecardiography (FCG) is a novel technique that records the weak forces induced on the chest wall by cardio-respiratory activity, by using specific force sensors. FCG sensors feature a wide frequency band, which allows us to capture respiration, heart wall motion, heart valves opening and closing (similar to the Seismocardiogram, SCG) and heart sounds, all simultaneously from a single contact point on the chest. As a result, the raw FCG sensors signals exhibit a large component related to the respiratory activity, referred to as a Forcerespirogram (FRG), with a much smaller, superimposed component related to the cardiac activity (the actual FCG) that contains both infrasonic vibrations, referred to as LF-FCG and HF-FCG, and heart sounds. Although respiration can be readily monitored by extracting the very low-frequency component of the raw FCG signal (FRG), it has been observed that the respiratory activity also influences other FCG components, particularly causing amplitude modulations (AM). This preliminary study aimed to assess the consistency of the amplitude modulations of the LF-FCG and HF-FCG signals within the respiratory cycle. A retrospective analysis was performed on the FCG signals acquired in a previous study on six healthy subjects at rest, during quiet breathing. To this aim, the AM of LF-FCG and HF-FCG were first extracted via a linear envelope (LE) operation, consisting of rectification followed by low-pass filtering; then, the inspiratory peaks were located both in the LE of LF-FCG and HF-FCG, and in the reference respiratory signal (FRG). Finally, the inter-breath intervals were extracted from the obtained inspiratory peaks, and further analyzed via statistical analyses. The AM of HF-FCG exhibited higher consistency within the respiratory cycle, as compared to the LF-FCG. Indeed, the inspiratory peaks were recognized with a sensitivity and positive predictive value (PPV) in excess of 99% in the LE of HF-FCG, and with a sensitivity and PPV of 96.7% and 92.6%, respectively, in the LE of LF-FCG. In addition, the inter-breath intervals estimated from the HF-FCG scored a higher R2 value (0.95 vs. 0.86) and lower limits of agreement (± 0.710 s vs. ±1.34 s) as compared to LF-FCG, by considering those extracted from the FRG as the reference. The obtained results are consistent with those observed in previous studies on SCG. A possible explanation of these results was discussed. However, the preliminary results obtained in this study must be confirmed on a larger cohort of subjects and in different experimental conditions.

A Comparison of Heart Pulsations Provided by Forcecardiography and Double Integration of Seismocardiogram.

Seismocardiography (SCG) is largely regarded as the state-of-the-art technique for continuous, long-term monitoring of cardiac mechanical activity in wearable applications. SCG signals are acquired via small, lightweight accelerometers fixed on the chest. They provide timings of important cardiac events, such as heart valves openings and closures, thus allowing the estimation of cardiac time intervals of clinical relevance. Forcecardiography (FCG) is a novel technique that records the cardiac-induced vibrations of the chest wall by means of specific force sensors, which proved capable of monitoring respiration, heart sounds and infrasonic cardiac vibrations, simultaneously from a single contact point on the chest. A specific infrasonic component captures the heart walls displacements and looks very similar to the Apexcardiogram. This low-frequency component is not visible in SCG recordings, nor it can be extracted by simple filtering. In this study, a feasible way to extract this information from SCG signals is presented. The proposed approach is based on double integration of SCG. Numerical double integration is usually very prone to large errors, therefore a specific numerical procedure was devised. This procedure yields a new displacement signal (DSCG) that features a low-frequency component (LF-DSCG) very similar to that of the FCG (LF-FCG). Experimental tests were carried out using an FCG sensor and an off-the-shelf accelerometer firmly attached to each other and placed onto the precordial region. Simultaneous recordings were acquired from both sensors, together with an electrocardiogram lead (used as a reference). Quantitative morphological comparison confirmed the high similarity between LF-FCG and LF-DSCG (normalized cross-correlation index >0.9). Statistical analyses suggested that LF-DSCG, although achieving a fair sensitivity in heartbeat detection (about 90%), has not a very high consistency within the cardiac cycle, leading to inaccuracies in inter-beat intervals estimation. Future experiments with high-performance accelerometers and improved processing methods are envisioned to investigate the potential enhancement of the accuracy and reliability of the proposed method.