Forecasting COVID-19 Severity by Intelligent Optical Fingerprinting of Blood Samples.

Forecasting COVID-19 disease severity is key to supporting clinical decision making and assisting resource allocation, particularly in intensive care units (ICUs). Here, we investigated the utility of time- and frequency-related features of the backscattered signal of serum patient samples to predict COVID-19 disease severity immediately after diagnosis. ICU admission was the primary outcome used to define disease severity. We developed a stacking ensemble machine learning model including the backscattered signal features (optical fingerprint), patient comorbidities, and age (AUROC = 0.80), which significantly outperformed the predictive value of clinical and laboratory variables available at hospital admission (AUROC = 0.71). The information derived from patient optical fingerprints was not strongly correlated with any clinical/laboratory variable, suggesting that optical fingerprinting brings unique information for COVID-19 severity risk assessment. Optical fingerprinting is a label-free, real-time, and low-cost technology that can be easily integrated as a front-line tool to facilitate the triage and clinical management of COVID-19 patients.

Author Correction: iLoF: An intelligent Lab on Fiber Approach for Human Cancer Single-Cell Type Identification.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

iLoF: An intelligent Lab on Fiber Approach for Human Cancer Single-Cell Type Identification.

With the advent of personalized medicine, there is a movement to develop "smaller" and "smarter" microdevices that are able to distinguish similar cancer subtypes. Tumor cells display major differences when compared to their natural counterparts, due to alterations in fundamental cellular processes such as glycosylation. Glycans are involved in tumor cell biology and they have been considered to be suitable cancer biomarkers. Thus, more selective cancer screening assays can be developed through the detection of specific altered glycans on the surface of circulating cancer cells. Currently, this is only possible through time-consuming assays. In this work, we propose the "intelligent" Lab on Fiber (iLoF) device, that has a high-resolution, and which is a fast and portable method for tumor single-cell type identification and isolation. We apply an Artificial Intelligence approach to the back-scattered signal arising from a trapped cell by a micro-lensed optical fiber. As a proof of concept, we show that iLoF is able to discriminate two human cancer cell models sharing the same genetic background but displaying a different surface glycosylation profile with an accuracy above 90% and a speed rate of 2.3 seconds. We envision the incorporation of the iLoF in an easy-to-operate microchip for cancer identification, which would allow further biological characterization of the captured circulating live cells.

Optical fiber-based sensing method for nanoparticle detection through supervised back-scattering analysis: a potential contributor for biomedicine.

BACKGROUND: In view of the growing importance of nanotechnologies, the detection/identification of nanoparticles type has been considered of utmost importance. Although the characterization of synthetic/organic nanoparticles is currently considered a priority (eg, drug delivery devices, nanotextiles, theranostic nanoparticles), there are many examples of "naturally" generated nanostructures - for example, extracellular vesicles (EVs), lipoproteins, and virus - that provide useful information about human physiology or clinical conditions. For example, the detection of tumor-related exosomes, a specific type of EVs, in circulating fluids has been contributing to the diagnosis of cancer in an early stage. However, scientists have struggled to find a simple, fast, and low-cost method to accurately detect/identify these nanoparticles, since the majority of them have diameters between 100 and 150 nm, thus being far below the diffraction limit. METHODS: This study investigated if, by projecting the information provided from short-term portions of the back-scattered laser light signal collected by a polymeric lensed optical fiber tip dipped into a solution of synthetic nanoparticles into a lower features dimensional space, a discriminant function is able to correctly detect the presence of 100 nm synthetic nanoparticles in distilled water, in different concentration values. RESULTS AND DISCUSSION: This technique ensured an optimal performance (100% accuracy) in detecting nanoparticles for a concentration above or equal to 3.89 µg/mL (8.74E+10 particles/mL), and a performance of 90% for concentrations below this value and higher than 1.22E-03 µg/mL (2.74E+07 particles/mL), values that are compatible with human plasmatic levels of tumor-derived and other types of EVs, as well as lipoproteins currently used as potential biomarkers of cardiovascular diseases. CONCLUSION: The proposed technique is able to detect synthetic nanoparticles whose dimensions are similar to EVs and other "clinically" relevant nanostructures, and in concentrations equivalent to the majority of cell-derived, platelet-derived EVs and lipoproteins physiological levels. This study can, therefore, provide valuable insights towards the future development of a device for EVs and other biological nanoparticles detection with innovative characteristics.

Stress among on-duty firefighters: an ambulatory assessment study.

BACKGROUND: Stress at work has been broadly acknowledged as a worldwide problem and has been the focus of concern for many researchers. Firefighting, in particular, is frequently reported as a highly stressful occupation. In order to investigate firefighters' occupational health in terms of stress events, perceptions, symptoms, and physiological reactions under real-world conditions, an ambulatory assessment protocol was developed. METHODS: Seventeen firefighters' cardiac signal was continuously monitored during an average of three shifts within a working week with medical clinically certified equipment (VitalJacket®), which allows for continuous electrocardiogram (ECG) and actigraphy measurement. Psychological data were collected with a software application running on smartphones, collecting potential stressful events, stress symptoms, and stress appraisal. RESULTS: A total of 450.56 h of medical-quality ECG were collected, and heart rate variability (HRV) analysis was performed. Findings suggest that although 'fire' situations are more common, 'accidents' are more stressful. Additionally, firefighters showed high levels of physiological stress (based on AVNN and LF/HF HRV metrics) when compared to normative healthy population values that may not be diagnosed using merely self-reports. DISCUSSION: The proposed ambulatory study seems to be useful for the monitoring of stress levels and its potential impact on health of first responders. Additionally, it could also be an important tool for the design and implementation of efficient interventions and informed management resolutions in real time. Potential applications of this research include the development of quantified occupational health (qOHealth) devices for real life monitoring of emergency personnel stress reactions.

Psychophysiological Stress Assessment Among On-Duty Firefighters.

Firefighting is a hazardous profession commonly exposed to high stress that can interfere with firefighter's health and performance. Nevertheless, on-duty stress levels quantitative evaluations are very rare in the literature. In order to investigate firefighters' occupational health in terms of stress perceptions, symptoms, and quantified physiological reactions under real-world conditions, an ambulatory assessment protocol was developed. Therefore, cardiac signal from firefighters ($N =6$) was continuously monitored during two shifts within a working week with a medical clinically certified equipment (VitalJacket®), allowing continuous electrocardiogram (ECG) and actigraphy measurement. Psychological data were collected with an android application, collecting potential stressful events, stress symptoms, and stress appraisal. A total of 130 hours of medical-quality ECG were collected, from which heart rate variability (HRV) metrics were extracted and analyzed. Statistical significant differences were found in some HRV metrics - AVNN, RMSSD, pNN50 and LF/HF - between events and non-events, showing higher levels of physiological stress during events (p<0.05). Stress symptoms increase from the beginning to the end of the shift (from 1.54 ± 0.52 to 2.01 ± 0.73), however the mean stress self-perception of events was very low (3.22 ± 2.38 in a scale ranging from 0 to 10). Negative and strong correlations were also found between stress symptoms and some time-domain ECG measures (AVNN, SDNN and pNN50). It can be concluded that stress may not always be detected when using merely self-reports. These results enhance the importance of combining both self-report and ambulatory high-quality physiological stress measures in occupational health settings. Future studies should investigate not only what causes stress but also its impact on health and well-being of these professionals, in order to contribute to the design of efficient stress-management interventions.

Fabrication of Multimode-Single Mode Polymer Fiber Tweezers for Single Cell Trapping and Identification with Improved Performance.

Optical fiber tweezers have been gaining prominence in several applications in Biology and Medicine. Due to their outstanding focusing abilities, they are able to trap and manipulate microparticles, including cells, needing any physical contact and with a low degree of invasiveness to the trapped cell. Recently, we proposed a fiber tweezer configuration based on a polymeric micro-lens on the top of a single mode fiber, obtained by a self-guided photopolymerization process. This configuration is able to both trap and identify the target through the analysis of short-term portions of the back-scattered signal. In this paper, we propose a variant of this fabrication method, capable of producing more robust fiber tips, which produce stronger trapping effects on targets by as much as two to ten fold. These novel lenses maintain the capability of distinguish the different classes of trapped particles based on the back-scattered signal. This novel fabrication method consists in the introduction of a multi mode fiber section on the tip of a single mode (SM) fiber. A detailed description of how relevant fabrication parameters such as the length of the multi mode section and the photopolymerization laser power can be tuned for different purposes (e.g., microparticles trapping only, simultaneous trapping and sensing) is also provided, based on both experimental and theoretical evidences.

Cognitive Impact and Psychophysiological Effects of Stress Using a Biomonitoring Platform.

Stress can impact multiple psychological and physiological human domains. In order to better understand the effect of stress on cognitive performance, and whether this effect is related to an autonomic response to stress, the Trier Social Stress Test (TSST) was used as a testing platform along with a 2-Choice Reaction Time Task. When considering the nature and importance of Air Traffic Controllers (ATCs) work and the fact that they are subjected to high levels of stress, this study was conducted with a sample of ATCs (n = 11). Linear Heart Rate Variability (HRV) features were extracted from ATCs electrocardiogram (ECG) acquired using a medical-grade wearable ECG device (Vital Jacket® (1-Lead, Biodevices S.A, Matosinhos, Portugal)). Visual Analogue Scales (VAS) were also used to measure perceived stress. TSST produced statistically significant changes in some HRV parameters (Average of normal-to-normal intervals (AVNN), Standard Deviation of all NN (SDNN), root mean square of differences between successive rhythm-to-rhythm (RR) intervals (RMSSD), pNN20, and LF/HF) and subjective measures of stress, which recovered after the stress task. Although these short-term changes in HRV showed a tendency to normalize, an impairment on cognitive performance was evident. Despite that participant's reaction times were lower, the accuracy significantly decreased, presenting more errors after performing the acute stress event. Results can also point to the importance of the development of quantified occupational health (qOHealth) devices to allow for the monitoring of stress responses.

Single Particle Differentiation through 2D Optical Fiber Trapping and Back-Scattered Signal Statistical Analysis: An Exploratory Approach.

Recent trends on microbiology point out the urge to develop optical micro-tools with multifunctionalities such as simultaneous manipulation and sensing. Considering that miniaturization has been recognized as one of the most important paradigms of emerging sensing biotechnologies, optical fiber tools, including Optical Fiber Tweezers (OFTs), are suitable candidates for developing multifunctional small sensors for Medicine and Biology. OFTs are flexible and versatile optotools based on fibers with one extremity patterned to form a micro-lens. These are able to focus laser beams and exert forces onto microparticles strong enough (piconewtons) to trap and manipulate them. In this paper, through an exploratory analysis of a 45 features set, including time and frequency-domain parameters of the back-scattered signal of particles trapped by a polymeric lens, we created a novel single feature able to differentiate synthetic particles (PMMA and Polystyrene) from living yeasts cells. This single statistical feature can be useful for the development of label-free hybrid optical fiber sensors with applications in infectious diseases detection or cells sorting. It can also contribute, by revealing the most significant information that can be extracted from the scattered signal, to the development of a simpler method for particles characterization (in terms of composition, heterogeneity degree) than existent technologies.

Optical fiber tips for biological applications: From light confinement, biosensing to bioparticles manipulation.

BACKGROUND: The tip of an optical fiber has been considered an attractive platform in Biology. The simple cleaved end of an optical fiber can be machined, patterned and/or functionalized, acquiring unique properties enabling the exploitation of novel optical phenomena. Prompted by the constant need to measure and manipulate nanoparticles, the invention of the Scanning Near-field Optical Microscopy (SNOM) triggered the optimization and development of novel fiber tip microfabrication methods. In fact, the fiber tip was soon considered a key element in SNOM by confining light to sufficiently small extensions, challenging the diffraction limit. As result and in consequence of the newly proposed "Lab On Tip" concept, several geometries of fiber tips were applied in three main fields: imaging (in Microscopy/Spectroscopy), biosensors and micromanipulation (Optical Fiber Tweezers, OFTs). These are able to exert forces on microparticles, trap and manipulate them for relevant applications, as biomolecules mechanical study or protein aggregates unfolding. SCOPE OF REVIEW: This review presents an overview of the main achievements, most impactful studies and limitations of fiber tip-based configurations within the above three fields, along the past 10 years. MAJOR CONCLUSIONS: OFTs could be in future a valuable tool for studying several cellular phenomena such as neurodegeneration caused by abnormal protein fibrils or manipulating organelles within cells. This could contribute to understand the mechanisms of some diseases or biophenomena, as the axonal growth in neurons. GENERAL SIGNIFICANCE: To the best of our knowledge, no other review article has so far provided such a broad view. Despite of the limitations, fiber tips have key roles in Biology/Medicine.

Wearable Biomonitoring Platform for the Assessment of Stress and its Impact on Cognitive Performance of Firefighters: An Experimental Study.

BACKGROUND: Stress is a complex process with an impact on health and performance. The use of wearable sensor-based monitoring systems offers interesting opportunities for advanced health care solutions for stress analysis. Considering the stressful nature of firefighting and its importance for the community's safety, this study was conducted for firefighters. OBJECTIVES: A biomonitoring platform was designed, integrating different biomedical systems to enable the acquisition of real time Electrocardiogram (ECG), computation of linear Heart Rate Variability (HRV) features and collection of perceived stress levels. This platform was tested using an experimental protocol, designed to understand the effect of stress on firefighter's cognitive performance, and whether this effect is related to the autonomic response to stress. METHOD: The Trier Social Stress Test (TSST) was used as a testing platform along with a 2-Choice Reaction Time Task. Linear HRV features from the participants were acquired using an wearable ECG. Self-reports were used to assess perceived stress levels. RESULTS: The TSST produced significant changes in some HRV parameters (AVNN, SDNN and LF/HF) and subjective measures of stress, which recovered after the stress task. Although these short-term changes in HRV showed a tendency to normalize, an impairment on cognitive performance was found after performing the stress event. CONCLUSION: Current findings suggested that stress compromised cognitive performance and caused a measurable change in autonomic balance. Our wearable biomonitoring platform proved to be a useful tool for stress assessment and quantification. Future studies will implement this biomonitoring platform for the analysis of stress in ecological settings.

Supervised learning methods for pathological arterial pulse wave differentiation: A SVM and neural networks approach.

OBJECTIVE: The main goal of this study was to develop an automatic method based on supervised learning methods, able to distinguish healthy from pathologic arterial pulse wave (APW), and those two from noisy waveforms (non-relevant segments of the signal), from the data acquired during a clinical examination with a novel optical system. MATERIALS AND METHODS: The APW dataset analysed was composed by signals acquired in a clinical environment from a total of 213 subjects, including healthy volunteers and non-healthy patients. The signals were parameterised by means of 39pulse features: morphologic, time domain statistics, cross-correlation features, wavelet features. Multiclass Support Vector Machine Recursive Feature Elimination (SVM RFE) method was used to select the most relevant features. A comparative study was performed in order to evaluate the performance of the two classifiers: Support Vector Machine (SVM) and Artificial Neural Network (ANN). RESULTS AND DISCUSSION: SVM achieved a statistically significant better performance for this problem with an average accuracy of 0.9917±0.0024 and a F-Measure of 0.9925±0.0019, in comparison with ANN, which reached the values of 0.9847±0.0032 and 0.9852±0.0031 for Accuracy and F-Measure, respectively. A significant difference was observed between the performances obtained with SVM classifier using a different number of features from the original set available. CONCLUSION: The comparison between SVM and NN allowed reassert the higher performance of SVM. The results obtained in this study showed the potential of the proposed method to differentiate those three important signal outcomes (healthy, pathologic and noise) and to reduce bias associated with clinical diagnosis of cardiovascular disease using APW.

Beat-ID: Towards a computationally low-cost single heartbeat biometric identity check system based on electrocardiogram wave morphology.

In recent years, safer and more reliable biometric methods have been developed. Apart from the need for enhanced security, the media and entertainment sectors have also been applying biometrics in the emerging market of user-adaptable objects/systems to make these systems more user-friendly. However, the complexity of some state-of-the-art biometric systems (e.g., iris recognition) or their high false rejection rate (e.g., fingerprint recognition) is neither compatible with the simple hardware architecture required by reduced-size devices nor the new trend of implementing smart objects within the dynamic market of the Internet of Things (IoT). It was recently shown that an individual can be recognized by extracting features from their electrocardiogram (ECG). However, most current ECG-based biometric algorithms are computationally demanding and/or rely on relatively large (several seconds) ECG samples, which are incompatible with the aforementioned application fields. Here, we present a computationally low-cost method (patent pending), including simple mathematical operations, for identifying a person using only three ECG morphology-based characteristics from a single heartbeat. The algorithm was trained/tested using ECG signals of different duration from the Physionet database on more than 60 different training/test datasets. The proposed method achieved maximal averaged accuracy of 97.450% in distinguishing each subject from a ten-subject set and false acceptance and rejection rates (FAR and FRR) of 5.710±1.900% and 3.440±1.980%, respectively, placing Beat-ID in a very competitive position in terms of the FRR/FAR among state-of-the-art methods. Furthermore, the proposed method can identify a person using an average of 1.020 heartbeats. It therefore has FRR/FAR behavior similar to obtaining a fingerprint, yet it is simpler and requires less expensive hardware. This method targets low-computational/energy-cost scenarios, such as tiny wearable devices (e.g., a smart object that automatically adapts its configuration to the user). A hardware proof-of-concept implementation is presented as an annex to this paper.

Spontaneous Fluctuations in Sensory Processing Predict Within-Subject Reaction Time Variability.

When engaged in a repetitive task our performance fluctuates from trial-to-trial. In particular, inter-trial reaction time variability has been the subject of considerable research. It has been claimed to be a strong biomarker of attention deficits, increases with frontal dysfunction, and predicts age-related cognitive decline. Thus, rather than being just a consequence of noise in the system, it appears to be under the control of a mechanism that breaks down under certain pathological conditions. Although the underlying mechanism is still an open question, consensual hypotheses are emerging regarding the neural correlates of reaction time inter-trial intra-individual variability. Sensory processing, in particular, has been shown to covary with reaction time, yet the spatio-temporal profile of the moment-to-moment variability in sensory processing is still poorly characterized. The goal of this study was to characterize the intra-individual variability in the time course of single-trial visual evoked potentials and its relationship with inter-trial reaction time variability. For this, we chose to take advantage of the high temporal resolution of the electroencephalogram (EEG) acquired while participants were engaged in a 2-choice reaction time task. We studied the link between single trial event-related potentials (ERPs) and reaction time using two different analyses: (1) time point by time point correlation analyses thereby identifying time windows of interest; and (2) correlation analyses between single trial measures of peak latency and amplitude and reaction time. To improve extraction of single trial ERP measures related with activation of the visual cortex, we used an independent component analysis (ICA) procedure. Our ERP analysis revealed a relationship between the N1 visual evoked potential and reaction time. The earliest time point presenting a significant correlation of its respective amplitude with reaction time occurred 175 ms after stimulus onset, just after the onset of the N1 peak. Interestingly, single trial N1 latency correlated significantly with reaction time, while N1 amplitude did not. In conclusion, our findings suggest that inter-trial variability in the timing of extrastriate visual processing contributes to reaction time variability.

An automatic method for arterial pulse waveform recognition using KNN and SVM classifiers.

The measurement and analysis of the arterial pulse waveform (APW) are the means for cardiovascular risk assessment. Optical sensors represent an attractive instrumental solution to APW assessment due to their truly non-contact nature that makes the measurement of the skin surface displacement possible, especially at the carotid artery site. In this work, an automatic method to extract and classify the acquired data of APW signals and noise segments was proposed. Two classifiers were implemented: k-nearest neighbours and support vector machine (SVM), and a comparative study was made, considering widely used performance metrics. This work represents a wide study in feature creation for APW. A pool of 37 features was extracted and split in different subsets: amplitude features, time domain statistics, wavelet features, cross-correlation features and frequency domain statistics. The support vector machine recursive feature elimination was implemented for feature selection in order to identify the most relevant feature. The best result (0.952 accuracy) in discrimination between signals and noise was obtained for the SVM classifier with an optimal feature subset .

Changes in ST, QT and RR ECG intervals during acute stress in firefighters: a pilot study.

Firefighting is a stressful occupation. The monitoring of psychophysiological measures in those professionals can be a way to prevent and early detect cardiac diseases and other stress-related problems. The current study aimed to assess morphological changes in the ECG signal induced by acute stress. A laboratory protocol was conducted among 6 firefighters, including a laboratory stress-inducer task - the Trier Social Stress Task (TSST) - and a 2-choice reaction time task (CRTT) that was performed before (CRTT1) and after (CRTT2) the stress condition. ECG signals were continuously acquired using the VitalJacket®, a wearable t-shirt that acts as a medical certified ECG monitor. Results showed that ECG morphological features such as QT and ST intervals are able to differentiate stressful from non stressful events in first responders. Group mean Visual Analogue Scale (VAS) for stress assessment significantly increased after the stress task (TSST), relatively to the end of CRTT2 (after TSST: 4.67±1.63; after CRTT2: 3.17±0.75), a change that was accompanied by a significant increase in group mean QT and ST segments corrected for heart rate during TSST. These encouraging results will be followed by larger studies in order to explore those measures and its physiological impact under realistic environments in a higher scalability.