Dynamical Analysis of Biological Signals with the 0–1 Test: A Case Study of the PhotoPlethysmoGraphic (PPG) Signal

Round 1

Reviewer 1 Report

This paper clearly shows how to describe the dynamics of the PPG signal by applying the 0–1 test to the reference signals and evaluating a modified version of the test. The analysis was carried out at different timescales to extract the distinct and relevant dynamics present. It is valuable for researchers working on biosensors and autonomic nervous science. To improve this paper, the following comments are made:

 

1. In “3.2 Reference signals and PPG”, headers are complected. Is the section of “PPG signal” in the section of “Biological signals”? If so, it should be “Biological signal” because the PPG signal is the only example treated in this paper.
2. I recommend modifying the title. It’s composed of two phrases and the second one doesn't make a sense.
3. The author concluded that the quasi-periodic dynamics imposed by the cardiorespiratory system prevail on a small timescale and the other factors related to the cardiovascular system come into play on a large timescale. But the terms of “small timescale” and “large timescale” are vague words. Does the small timescale really correspond to the period of the cardiorespiratory system or several tens times per minute, and what is the exact number for the long timescale?

Author Response

Thanks for your helpful comments.

• In “3.2 Reference signals and PPG”, headers are completed. Is the section of “PPG signal” in the section of “Biological signals”? If so, it should be “Biological signal” because the PPG signal is the only example treated in this paper.

We have replaced Biological signals by 3.3. Biological signal and change the position of subsections in section 3 (see new version of the paper with the change).

• I recommend modifying the title. It’s composed of two phrases and the second one doesn't make a sense.

 The new title may be: “Dynamic analysis of biological signals with the 0-1 test: a case study of the PhotoPlethysmoGraphic (PPG) signal.”

• The author concluded that the quasi-periodic dynamics imposed by the cardiorespiratory system prevail on a small timescale and the other factors related to the cardiovascular system come into play on a large timescale. But the terms of “small timescale” and “large timescale” are vague words. Does the small timescale really correspond to the period of the cardiorespiratory system or several tens times per minute, and what is the exact number for the long timescale?

The division between small and large timescale depends on each particular case. In the case of the PPG signal the dominant frequency, which coincides with the heart rate modulated by the respiratory rhythm, characterizes the small timescale. With blocks from 5000 to 15000 points the statistic has higher consistency and lower bias. Below the dominant frequency, slow variations of amplitude, frequency and intensity of PPG cycles identify the large timescale. These variations are due to respiration, vasomotor activity, etc.

Reviewer 2 Report

Manuscript ID: applsci-1267290

Title: Dynamical analysis of biological signals with the 0–1 test. A PhotoPlethysmoGraphic signal a case study

Recommendation: Revise

 

Brief summary

The authors of this manuscript propose a modified version of 0-1 test to be applied to biological signals to distinguish between regular and chaotic dynamics. In particular, they consider photoplethysmographic (PPG) signal, finding that it can be considered mainly quasi-periodic in short-time domain.

 

Broad comments

The topic is relevant, since at present PPG signals are used in manifold applications (e.g. wearable devices) to extract different types of information (from Heart Rate to blood oxygen saturation, through blood pressure and other metrics).

However, the manuscript structure should be improved and sometimes the English is not so fluent. Thoroughly re-reading the paper is necessary to correct typos and grammatical errors, as well as checking the use of punctuation to improve the readability and the fluency of the manuscript.

The article is quite well contextualized in the literature background, even if this aspect could be improved by adding some references, also from Applied Sciences journal.

Some suggestions are provided in the next comments, which may help the authors in improving the quality of this paper.

 

Specific comments

Introduction: some further discussion on PPG signals should be added, considering, for example, the different application areas (with a particular focus on its employment in wearable devices), the factors influencing the measurement (e.g. motion artifacts), etc.

See for example:

• Goh, C. H., Tan, L. K., Lovell, N. H., Ng, S. C., Tan, M. P., & Lim, E. (2020). Robust PPG motion artifact detection using a 1-D convolution neural network. Computer methods and programs in biomedicine, 196, 105596.
• Islam TT, Ahmed MS, Hassanuzzaman M, Bin Amir SA, Rahman T. Blood Glucose Level Regression for Smartphone PPG Signals Using Machine Learning. Applied Sciences. 2021; 11(2):618. https://doi.org/10.3390/app11020618
• Cosoli, G. Iadarola, A. Poli, and S. Spinsante, “Learning classifiers for analysis of Blood Volume Pulse signals in IoT-enabled systems,” in IEEE MetroInd4.0&IoT, 2021.
• Liu S-H, Li R-X, Wang J-J, Chen W, Su C-H. Classification of Photoplethysmographic Signal Quality with Deep Convolution Neural Networks for Accurate Measurement of Cardiac Stroke Volume. Applied Sciences. 2020; 10(13):4612. https://doi.org/10.3390/app10134612

Line 3: please check this sentence.

Line 8: maybe it would be better to substitute “small timescales” with “short span of time”.

Line 10: please correct “base” with “based”.

Line 16: please check the verb “preserve”.

Lines 22-24: please check this sentence.

Lines 27-31: proper references should be added.

Line 37: please check this sentence.

Line 42: please substitute “several” with the number of tested subjects.

Line 65: please check this sentence.

Line 70: please check this sentence.

Line 86: this statement should be justified, also with a proper reference.

Line 89: I think it would be better to substitute “the absolute value of the calculated Kc values” with “the median of the absolute value of the calculated Kc values”.

Lines 111-112: please check this sentence.

Figure 1: the axes labels are not readable. Please modify this Figure, also improving the plots resolution. Moreover, please put references to this figure within the text when explaining the different reference signals (e.g. Figure 1 (a) in the paragraph titled “Periodic”, etc.), for a better readability.

Lines 145-154: proper references should be added.

Line 156: please note that the term “samples” in signals usually refers to single point. Maybe it would be better to speak of “signals” or “acquisitions”.

Lines 156-158: did the subjects sign an informed consent? How about the ethical approval? The authors should report information about these aspects.

Lines 158-161: other metrological characteristics (e.g. resolution, etc.) should be reported, if available.

Line 162: how can you say that this sample is representative of the whole population? Any followed criteria for the sample size determination should be reported.

Line 163: please check the subject-verb agreement.

Lines 171-175: proper references should be added.

Figure 2: please modify resolution and font size of labels, since it cannot be read in the present form.

Line 176: please check the format of the titles in Section 3.2, since it seems that they are not always appropriate, hindering the readiness of the manuscript.

Line 177-181: please check these sentences, paying particular attention to the verbs.

Table 2: please pay attention to font size within the table (text in the first line seems too big). The same for Table 3.

Line 215: the authors speak about “tiny” values for Km; however, a range should be reported, maybe in parentheses. The same for line 217, when writing “very little”.

Line 232: “filtrated” should be replaced with “filtered”.

Line 249-252: please check this sentence, since it seems not so clear.

Line 286: the authors should precise that only 5 subjects have been considered in the present manuscript.

Conclusions: the authors should add a discussion on the potential impact of the proposed method on the use of PPG signals in the different application areas, trying to underline the reasons why such an analysis is significant.

Figure A3: the authors should comment on the different variability found with different scale factors, trying to explain while standard deviation is initially very high, then very low and finally increases again.

Author Response

Thanks a lot for your helpful comments.

Specific comments

Point 1: Introduction: some further discussion on PPG signals should be added, considering, for example, the different application areas (with a particular focus on its employment in wearable devices), the factors influencing the measurement (e.g. motion artifacts), etc.

Response 1: We have added the following paragraph in the introduction (see changes in the new version of the paper) which incorporates references 4,5,6,7,8,9,10,11,12,13,14,15.

The PPG signal, while seemingly simple, contains sluggish dynamic variations that make it an extraordinarily complex signal. These dynamic subtleties blurry by artifacts like motion artifacts or baseline drift [4,5] share the same low-frequency range. The PPG signal contains relevant physiological information that is not limited to heart rate or blood oxygen saturation, indicators that are broadly representative of clinical settings [6]. The application of classical filtering techniques is restricted because they remove some of this relevant physiological information. These inconveniences remove with more sophisticated denoising techniques with some success [7–10], especially in wearable PPG devices [11,12], but are beyond the scope of this paper. Self-care today, a culture that improves the quality of life and promotes the sustainability of the healthcare system, encourages the widespread use of wearable pulse oximeters for home healthcare [13]. New generations of pulse oximeters, such as contactless pulse oximeters, aim at a better ergonomic fitting to the daily events of day-to-day life. The medical device industry is committed to getting out of the hospital and improving the population's quality of life through personal self-diagnosis at home [14,15]. Hat new pulse oximeters and new PPG-based biomedical applications will likely emerge in the near future with a more thorough screening of the patient's physiological condition. Accordingly, a better understanding of the PPG signal dynamics would reveal the intricate physiological mechanisms involved in the cardiovascular system, facilitating the implementation of biomedical applications for the early diagnosis of possible cardiorespiratory pathologies with more accuracy.

4. Goh, C.H.; Tan, L.K.; Lovell, N.H.; Ng, S.C.; Tan, M.P.; Lim, E. Robust PPG motion artifact detection using a 1-D convolution neural network. Computer Methods and Programs in Biomedicine 2020, 196, 105596.doi:10.1016/j.cmpb.2020.105596.
5. Liu, S.H.; Li, R.X.;Wang, J.J.; Chen,W.; Su, C.H. Classification of Photoplethysmographic Signal Quality with Deep Convolution Neural Networks for Accurate Measurement of Cardiac Stroke Volume. Applied Sciences 2020, 10, 4612. doi:10.3390/app10134612. Version July 5, 2021 submitted to Appl. Sci. 17 of 19
6. Cannesson, M.; Talke, P. Recent advances in pulse oximetry. F1000 Medicine Reports 2009, 1. doi:10.3410/m1-66.
7. Kim, B.; Yoo, S. Motion Artifact Reduction in Photoplethysmography Using Independent Component Analysis. IEEE Transactions on Biomedical Engineering 2006, 53, 566–568. doi:10.1109/tbme.2005.869784.
8. Hanyu, S.; Xiaohui, C. Motion artifact detection and reduction in PPG signals based on statistics analysis. 2017 29th Chinese Control And Decision Conference (CCDC). IEEE, 2017. doi:10.1109/ccdc.2017.7979043.
9. Majeed, I.A.; Jos, S.; Arora, R.; Choi, K.; Bae, S. Motion Artifact Removal of Photoplethysmogram (PPG) Signal. 2019 41st Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC). IEEE, 2019. doi:10.1109/embc.2019.8857131.
10. Pollreisz, D.; TaheriNejad, N. Detection and Removal of Motion Artifacts in PPG Signals. Mobile Networks and Applications 2019. doi:10.1007/s11036-019-01323-6.
11. Lee, J.; Kim, M.; Park, H.K.; Kim, I.Y. Motion Artifact Reduction in Wearable Photoplethysmography Based on Multi-Channel Sensors with Multiple Wavelengths. Sensors 2020, 20, 1493. doi:10.3390/s20051493.
12. Seok, D.; Lee, S.; Kim, M.; Cho, J.; Kim, C. Motion Artifact Removal Techniques for Wearable EEG and PPG Sensor Systems. Frontiers in Electronics 2021, 2. doi:10.3389/felec.2021.685513.
13. Tamura, T. Current progress of photoplethysmography and SPO2 for health monitoring. Biomedical Engineering Letters 2019, 9, 21–36. doi:10.1007/s13534-019-00097-w.
14. Islam, T.T.; Ahmed,M.S.; Hassanuzzaman,M.; Amir, S.A.B.; Rahman, T. Blood Glucose Level Regression for Smartphone PPG Signals Using Machine Learning. Applied Sciences 2021, 11, 618. doi:10.3390/app11020618.

Point 2: Line 3: please check this sentence.

Response 2: We have replaced the phrase with (see changes in the new version of the paper):

A modification of the 0–1 test allows determining a more comprehensive range of signal dynamic behaviors, particularly in the field of biological signals.

Point 3: Line 8: maybe it would be better to substitute “small timescales” with “short span of time”.

Response 3: We have replaced the phrase with (see changes in the new version of the paper):

We show that the PPG signal, on a healthy young individual, is predominantly quasi-periodic on small timescales (short span of time concerning the dominant frequency).

Point 4: Line 10: please correct “base” with “based”.

Response 4: We have corrected the typo (see changes in the new version of the paper).

Point 5: Line 16: please check the verb “preserve”.

Response 5: We have replaced the verb preserve by ensure (see changes in the new version of the paper).

Point 6: Lines 22-24: please check this sentence.

Response 6: We have replaced the phrase with (see changes in the new version of the paper):

The PPG signal takes its name from the optical technique, called photoplethysmogram, applied for volumetric analysis of an organ (plethysmogram); or from the device used to measure it, the photoplethysmograph, introduced by A. Hertzman in 1937 [2].

Point 7: Lines 27-31: proper references should be added.

Response 7: We have added references 16,17,18,19 (see changes in the new version of the paper).

16. Sprott, J.C. Chaos and Time-Series Analysis; Oxford University Press, 2003.
17. Kantz, H.; Schreiber, T. Nonlinear Time Series Analysis, 2 ed.; Cambridge nonlinear science series, Cambridge University Press, 2004.
18. Tsonis, A.A. Chaos: From Theory to Applications; Springer US, 2012.
19. Toker, D.; Sommer, F.T.; D’Esposito, M. A simple method for detecting chaos in nature. Communications Biology 2020, 3. doi:10.1038/s42003-019-0715-9.

Point 8: Line 37: please check this sentence.

Response 8: We have replaced the phrase with (see changes in the new version of the paper):

 This test makes it possible—calculating the grown rate Kc, with a value of 0 for regular (periodic) behavior, and a value of 1 for a chaotic one—to recognize the presence of chaos in a dynamical system without the requirement of phase space reconstruction from a real-world time series [24].

Point 9:. Line 42: please substitute “several” with the number of tested subjects.

Response 9: We have replaced several by 40 (see new version of the paper with the change).

Point 10: Line 65: please check this sentence.

Response 10: We have replaced the paragraph with (see changes in the new version of the paper):

 The K_c values determine the type of deterministic behavior of a dynamic system. If Kc \approx  0, the system dynamic behaves regularly; if K_c \approx 1, it evolves chaotically. In the case of a dynamic system’s regular evolution , the equations, defined by Eq. (1 ), describe bounded paths (bounded space-filling in (p_c ,q_c )-plane; in a chaotic dynamical system the evolution undergone by the paths proposed at Eq. (1) resembles a 2-dimensional Brownian motion, that is, its evolution is diffusive (unbounded space-filling in (p_c ,q_c )-plane.

Point 11: Line 70: please check this sentence.

Response 11: We have replaced the paragraph with (see changes in the new version of the paper):

 The mean square fluctuation Mc(n)  enables the identification of the growth rate of the paths, whether it be a bounded growth rate (regular case), with fluctuations tending to zero, or a linear growth rate (if chaotic), with random fluctuations typical of erratic motion. In any case, the parameter Kc  captures this growth rate.

Point 12: Line 86: this statement should be justified, also with a proper reference.

Response 12: We have added the reference 31(already in the paper) and the justification (see changes in the new version of the paper):

 …[31], so to ensure a higher degree of convergence of the statistic.

Point 13: Line 89: I think it would be better to substitute “the absolute value of the calculated Kc values” with “the median of the absolute value of the calculated Kc values”.

Response 13: We have introduced the change proposed (see the new version of the paper with the change).

Point 14: Lines 111-112: please check this sentence.

Response 14: We have replaced the phrase with (see changes in the new version of the paper):

 … range of intermediate dynamic options; as a dynamic variant approaches a most irregular regime, as in the case of a chaotic signal, it acquires greater degrees of freedom or versatility, without losing determinism in its dynamic behavior.

After this sentence, it is included a subsection:  3.2. Reference signals

Point 15: Figure 1: the axes labels are not readable. We have corrected the typo (see changes in the new version of the paper). Please modify this Figure, also improving the plots resolution. Moreover, please put references to this figure within the text when explaining the different reference signals (e.g. Figure 1 (a) in the paragraph titled “Periodic”, etc.), for a better readability.

Response 15: We have increased the font sizes (see changes in the new version of the paper).

Point 16: Lines 145-154: proper references should be added.

Response 16: We have added references 13 (previously saw in this review answer), 36,37 (see changes in the new version of the paper).

36. Chen,M.; Zhu, Q.;Wu,M.;Wang, Q. ModulationModel of the Photoplethysmography Signal for Vital Sign Extraction. IEEE Journal of Biomedical and Health Informatics 2021, 25, 969–977. doi:10.1109/jbhi.2020.3013811.
37. Jr., J.M.; Vieira,M.; Pires,M.; Jr., S.S. Sensor Fusion and Smart Sensor in Sports and Biomedical Applications. Sensors 2016, 16, 1569. doi:10.3390/s16101569.

Point 17: Line 156: please note that the term “samples” in signals usually refers to single point. Maybe it would be better to speak of “signals” or “acquisitions”.

Response 17: We have replaced samples by signals (see new version of the paper with the change).

Point 18: Lines 156-158: did the subjects sign an informed consent? How about the ethical approval? The authors should report information about these aspects.

Response 18: We have added a new entry at the end of the paper entitled Informed Consent Statement (see changes in the new version of the paper):

 The study includes 40 students from Universidad Politécnica de Madrid (UPM), between age 18 and 30. All signals captured from the middle finger of the left hand and sampled at a frequency of 250 Hz, say, sampling time $\Delta t=4$ ms. The UPM Ethics Committee approved the study protocol. Participants gave their written informed consent. They were instructed to avoid using any psychotropic substance, alcohol, or tobacco, avoid physical exercise 24 hours before each session, get up two hours before starting the sessions, and consume a light breakfast without coffee or tea.

Point 19:  Lines 158-161: other metrological characteristics (e.g. resolution, etc.) should be reported, if available.

Response 19: No information available. 

Point 20: Line 162: how can you say that this sample is representative of the whole population? Any followed criteria for the sample size determination should be reported.

Response 20: We have replaced the phrase with (see changes in the new version of the paper): 

The main body of this paper shows the data of five subjects, illustrating the overall dynamic behavior of the 40 subjects who participated in the experiment (see Appendix A Supplementary material).

Point 21: Line 163: please check the subject-verb agreement.

Response 21: We have replaced the phrase with (see changes in the new version of the paper):

 The chosen PPG signals are represented in Figure 2. Depending on the analyzed factor, up to 600,000 points (40 minutes) were used, those corresponding to the total data recorded in the indicated research project.

Point 22: Lines 171-175: proper references should be added.

Response 22: We have added references 36,40,41,42,43,44,45 (see changes in the new version of the paper).

Point 23: Figure 2: please modify resolution and font size of labels, since it cannot be read in the present form.

Response 23: We have increased the font sizes (see changes in the new version of the paper).

Point 24: Line 176: please check the format of the titles in Section 3.2, since it seems that they are not always appropriate, hindering the readiness of the manuscript.

Response 24: We have restructured the section (see changes in the new version of the paper).

Section 3. Method and materials

...

subsection 3.2. Reference signals

...

subsection 3.3. Biological signal

 This paper focuses only on a single biological signal, the PhotoPlethysmoGraphic (PPG) signal; forward publications will describe the results for more biological signals. We have chosen the PPG signal because it is easily accessible and the information provided allows to monitor physiological vital signs.

 PPG signal

 A pulse oximeter consists of…

Point 25: Lines 177-181: please check these sentences, paying particular attention to the verbs.

Response 25: These sentences have been removed. Instead of it: next sentences have been included at the beginning of section 3,  (see changes in the new version of the paper):

 First, we apply the modified 0–1 test with the new parameter Km and its trend, as explained in subsection 3.1, comparing results on reference signals and the biological signal under study.  Subsections 3.2 and 3.3 describe all signals used, reference and biological, respectively. Section 4 shows a multiscale 0—1 test study. As the text 0—1 does not differentiate between random and chaotic, it is necessary to evaluate the information provided by the biological signal with a more appropriate technique. Its dynamic characteristics are analyzed with appropriate nonlinear techniques, the fractal dimension, and the maximal Lyapunov exponent for the biological signals, whose justification is in section 4.

Point 26: Table 2: please pay attention to font size within the table (text in the first line seems too big). The same for Table 3.

Response 26: We have reduced the font sizes of the first line in both tables (see changes in the new version of the paper).

Point 27:  Line 215: the authors speak about “tiny” values for Km; however, a range should be reported, maybe in parentheses. The same for line 217, when writing “very little”.

Response 27: We have added  Km is tiny (K_m <0.07) and  Km grows very little (\approx 0.1 or higher) (see changes in the new version of the paper).

Point 28: Line 232: “filtrated” should be replaced with “filtered”.

Response 28: We have corrected the typo (see changes in the new version of the paper).

Point 29: Line 249-252: please check this sentence, since it seems not so clear.

Response 29: We have replaced the phrase with (see changes in the new version of the paper):

 The results summarized in Table 2 also indicate the K_m  trend, namely, the cumulative effect of Km as the size of the data block increases.  Starting with a 5000-point data block and in 5000-point incremental steps. So Km is calculated for an initial 5000-point data block, then 10,000, 15,000, and so on up to 60,000 points, taken from the mid-session of the signal acquisition phase.

Point 30: Line 286: the authors should precise that only 5 subjects have been considered in the present manuscript.

Response 30: We have replaced the phrase with (see changes in the new version of the paper):

 The analysis has been  carried out at different timescales to extract the distinct and relevant dynamics present. Only five users are shown in the main body of this paper, while the supplementary material (see appendix A) covers the main results of the 40 subjects that make up the dataset.

Point 31: Conclusions: the authors should add a discussion on the potential impact of the proposed method on the use of PPG signals in the different application areas, trying to underline the reasons why such an analysis is significant.

Response 31: We have added the following paragraph in Conclusions (see changes in the new version of the paper) which incorporates the reference 56.

The PPG signal dynamic behavior analysis moves away from the conventional morphological analysis of the PPG signal, whereby changes in different morphological indicators correlate with cardiovascular disorders and ageing. An accurate characterization of the PPG signal dynamic would allow functional modeling of hemodynamics and peripheral circulation, whatever the physiological peculiarities of each individual. We have indeed used a diffusive model of the PPG signal as a biometric marker, in which the hemodynamic specificity of each individual prevails with time and possible psychophysiological disturbances [56]. It is possible to build wearable devices that, in real-time, will not only authenticate an individual but also anticipate, through the dynamic parameterization of functional models, dynamic symptomatic perturbations of mild dysfunctions, such as stress, or even more severe ones, such as those related to cardiovascular diseases.

56.  de Pedro-Carracedo, J.; Fuentes-Jimenez, D.; Ugena, A.M.; Gonzalez-Marcos, A.P.  Transcending conventional biometry frontiers: Diffusive Dynamics PPG Biometry, 2020,  [arXiv:eess.SP/http://arxiv.org/abs/2007.15060v3].

Point 32: Figure A3: the authors should comment on the different variability found with different scale factors, trying to explain while standard deviation is initially very high, then very low and finally increases again.

Response 32: We have added comments in the caption of Figure A3 (see changes in the new version of the paper).

 In the absence of more in-depth analysis, we hypothesize that the high dynamic variability on small timescales subordinate to the psychosomatic deviations of the individuals who participated in the experiment. Some individuals were already more excited (stressed) than others because they knew they were participating in a study or because of personal circumstances beyond our knowledge. As the scale factor increases, the low-frequency dynamic coupling that regulates the cardiovascular system comes into play within normal operating ranges, with low variability. However, at very low frequency, the dynamic variability increases, yet it is not very pronounced. There is a statistical bias due to the unavailability of sufficient data or artifacts that could not be removed or going further to our lack of knowledge concerning subsystems coupled in the regulation process.

 

Round 2

Reviewer 2 Report

Manuscript ID: applsci-1267290

Title: Dynamical analysis of biological signals with the 0–1 test. A PhotoPlethysmoGraphic signal a case study

Recommendation: Revise

 

Brief summary

This is the revised version of a previously submitted manuscript.

 

Broad comments

The authors addressed most of the comments made on my previous review. In my opinion, after some minor revisions, the paper can be published in Applied Sciences journal. Some comments are provided below to help the authors improving the manuscript quality. Furthermore, re-reading the paper is necessary to improve the fluency and correct eventual typos/grammatical errors.

 

Specific comments

Lines 33-35: please check this sentence.

Lines 35-37: it could be interesting to add a brief comment on the use of wearables in the COVID-19 pandemic context. See for example:

• Cosoli, G., Scalise, L., Poli, A., & Spinsante, S. (2021). Wearable devices as a valid support for diagnostic excellence: lessons from a pandemic going forward. Health and Technology, 11(3), 673-675.
• Quer G, et al. Wearable sensor data and self-reported symptoms for COVID-19 detection. Nat Med. 2021;27(1):73–7.

Figures 1-2: the labels of the axes should be further increased to improve the readability.

Author Response

Thanks again for the comments. We have included, line 375, the phrase: Finally, the authors would like to thank the referees for their useful comments.

 Broad comments

 … Furthermore, re-reading the paper is necessary to improve the fluency and correct eventual typos/grammatical errors.

We have revised the paper and tried to fix some typos/grammatical errors.

 Specific comments

 Point 1: Lines 33-35: please check this sentence.

Response 1: We have replaced the phrase with (see changes in the new version of the paper):

To overcome this, especially critical in wearable PPG devices [7,8], new sophisticated denoising techniques have been successfully developed [9–12], but are beyond the scope of this paper. 


Point 2:  Lines 35-37: it could be interesting to add a brief comment on the use of wearables in the COVID-19 pandemic context.

Response 2: We have added the following text (highlighted in red) in the introduction (see changes in the new version of the paper) which incorporates the reference 16.

Self-care today, a culture that improves the quality of life and promotes the sustainability of the healthcare system, encourages the widespread use of wearable pulse oximeters for home healthcare [13], particularly in the last year, during COVID-19 emergency. New generations of pulse oximeters, such as contactless pulse oximeters, aim at a better ergonomic fitting to the daily events of day-to-day life. The medical device industry is committed to getting out of the hospital and improving the population’s quality of life through personal self-diagnosis at home [14,15]. Hat new pulse oximeters and new PPG-based biomedical applications will likely emerge in the near future with a more thorough screening of the patient’s physiological condition. In epidemic events, their capacity to identify patterns discriminating between healthy and infected people could be exploited, thus limiting the contagion risk. This would easily prevent the healthcare system collapse [16]. …

 

16. Cosoli, G.; Scalise, L.; Poli, A.; Spinsante, S. Wearable devices as a valid support for diagnostic excellence: lessons from a pandemic going forward. Health and Technology 2021, 11, 673–675. doi:10.1007/s12553-021-00540-y.

 

Point 3: Figures 1-2: the labels of the axes should be further increased to improve the readability.

Response 3: We cannot increase the font size anymore, as the font sizes are 26 in LaTeX format, and an increase would make the texts go out of the picture boxes. We are aware that five pictures per row complicate the task, but we consider that the reader can get an overview of the method at a glance.

We have therefore planned to include all the pictures in a separate file, as supplementary material for downloading (file AllFigures1-2.zip). Hence, we have added a new entry at line 356 (see changes in the new version of the paper):

Supplementary Materials: The following are available online at www.mdpi.com/xxx/s1, all pictures in Figures 1–2: AllFigures1-2.zip.

In Figure captions we have included the following at the beginning of the text: (These pictures are made available for downloading).