Ruben Fossion’s research while affiliated with National Autonomous University of Mexico and other places

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Publications (15)


Flowchart of the study design and the steps and main effects performed. SP = supine position; AS = active standing; RB = Rhythmic breathing. *To perform the regression models, the mean of sex hormones and the mean of HRV indices were used
Flowchart of the statistical analyses performed step by step
HRV = heart rate variability, T2DM = type 2 diabetes mellitus.
Comparison of sex hormone levels (Mean ± SD) between the different participant groups
For all sex hormones, the main effect of the menstrual cycle phase was significant (p < 0.001) while the main effect of T2DM was non-significant (p > 0.1) and the interaction term (menstrual cycle phase * T2DM) was non-significant (p >0.1). ANOVA with Bonferroni correction. * p < 0.05 vs postmenopause (in the same health status: healthy or T2DM). # p < 0.05 vs proliferative phase (in the same health status: healthy or T2DM). & p < 0.05 vs luteal phase (in the same health status: healthy or T2DM).
Comparison of time-domain HRV indices between healthy women and women with T2DM in postmenopause and each phase of the menstrual cycle
The main effect of the menstrual cycle phase, and T2DM, and the interaction term (menstrual cycle phase * T2DM) were non-significant for all HRV indices (p>0.1). The main effect of T2DM was significant for MeanNN and RMSSD (p<0.01), but non-significant for SDNN and pNN20. The main effect of the maneuver was significant for all indices (p<0.05), and the interaction terms (maneuver * T2DM; maneuver * menstrual cycle phase; maneuver * T2DM * menstrual cycle phase) were non-significant (p>0.5). ANOVA with Bonferroni correction. # p<0.05 vs. healthy (same menstrual phase and maneuver). & p<0.05 vs. supine position (same health status and menstrual phase). π p<0.05 vs. active standing (same health status and menstrual phase).
Comparison of frequency-domain HRV indices between healthy women and women with T2DM during postmenopause and each phase of menstrual cycle
The main effect of the menstrual cycle phase, and T2DM, and the interaction term (menstrual cycle phase * T2DM) were non-significant for all HRV indices (p > 0.1). The main effect of the maneuver was significant for all HRV indices (p<0.05), but the interaction terms (maneuver * T2DM; maneuver * menstrual cycle phase; maneuver * T2DM * menstrual cycle phase) were not significant for any of the HRV indices (p>0.5). ANOVA with Bonferroni correction. * p<0.05 vs. postmenopause for the same health status (healthy or T2DM) and maneuver (supine position, active standing or controlled breathing). # p<0.05 vs. healthy (same menstrual phase and maneuver). & p<0.05 vs. supine position (same health status and menstrual phase). π p<0.05 vs. active standing (same health status and menstrual phase).

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Sex hormones correlate with heart rate variability in healthy women and this correlation is conserved in women with well-controlled type 2 diabetes mellitus
  • Article
  • Full-text available

April 2025

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22 Reads

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Claudia Lerma

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Silvia Ruiz-Velasco Acosta

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Ruben Fossion

The autonomic nervous system and the endocrine system regulate cardiovascular physiology, and their alterations, as occurs in type 2 diabetes mellitus, are related to the development of cardiovascular complications. Sex hormones are major regulators of both cardiovascular and nervous tissue, and during postmenopause, the lack in hormone production can increase the risk for cardiovascular and autonomic diseases, even more in metabolic impairment such as in T2DM However, the evidence regarding whether sex hormones are related to autonomic activity is inconclusive. The goal of this paper was to evaluate the correlation between sex hormones and cardiac autonomic activity, as assessed by heart rate variability (HRV), women with well-controlled type 2 diabetes (T2DM) and healthy women as the control group. Subjects and methods In this study, four groups of women were designated according to their health status (control or T2DM) and fertility status (premenopausal or postmenopausal). Five serum sex hormones were measured (estradiol, progesterone, testosterone, LH and FSH), and time-domain and frequency-domain HRV indices were determined during three conditions: supine position, active standing, and rhythmic breathing. For the complete sample (n=118), bivariate Pearson correlations and linear multiple regressions were used to analyze the relationship between sex hormones, HRV indices, and other independent variables, such as glycemia and age. A p-value <0.05 was considered as significant. Results There were no differences in sex hormones or HRV indices when comparing the healthy and T2DM groups. All bivariate Pearson correlations were significant between sex hormones and HRV indices; estradiol, progesterone, and testosterone have positive correlations; meanwhile, LH and FSH were negative in the time-domain (SDNN, RMSSD, pNN20) and frequency domain (PLF and PHF) indices. Regression models adjusted for mean heartbeat intervals confirmed an association between all sex hormones and HRV indices. Estradiol maintained significance in the regression models for specific HRV indices during supine and active standing conditions even after adjusting for age and glucose levels. Conclusions All sex hormones correlate with HRV indices. Regression analysis confirms that this correlation is independent from the mean heartbeat interval. However, in regression models adjusted for age and glucose levels, only estradiol was found to be significant, and should be considered an important variable related to cardiovascular and autonomic balance in T2DM women and may provide crucial information to improve cardiovascular risk algorithms.

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Temporal dynamics in laboratory medicine: cosinor analysis and real-world data (RWD) approaches to population chronobiology

February 2025

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18 Reads

Objectives Chronobiology is the science that studies biological rhythms based on direct methods and empirical time series of individual subjects. In laboratory medicine, the factor of time is often underestimated, and no methods currently exist to study biological rhythms in population databases of point-like, real-world data (RWD). Methods Retrospective databases (24 months, 2022–2023) were extracted for four measurands (sodium, potassium, chloride and leukocytes) from the emergency laboratory. Two different strategies for data grouping were applied: data clouds (with or without outliers) and population-averaged profiles. Cosinor regression analysis was performed on the grouped data to derive circadian parameters. The parameters obtained here were compared to results from the literature, using direct methods and time series. Results A total of 409,719 data points were analyzed. All measurands exhibited symmetrical data distributions, except for leukocytes. The data clouds did not visually display rhythmicity, but cosinor analysis revealed a significant circadian rhythm. The removal of outliers had minimal impact on the results. In contrast, population-averaged profiles showed visible rhythmicity, which was confirmed by cosinor analysis with a better goodness-of-fit compared to the data clouds. Conclusions Population-averaged profiles have advantages over data clouds in characterizing circadian rhythms and deriving circadian parameters. Population chronobiology, based on RWD, is presented as an alternative to classical individual chronobiology, based on time series and overcomes the limitations of direct methods. Utilizing RWD provides new insights into the relationship between chronobiology and clinical laboratory practice.


Flowchart of the selection process of the participants based on the inclusion and exclusion
Box-whisker charts of MANOVA scores, for (a) the factor Susceptibility (p>0.05), (b) the factor Sex (p<0.001) and (c) the interaction Susceptibility × Sex (p = 0.033). Baseline values are shown for male and female participants who remained seronegative (M- and F-), or who were found to have been infected (M+ and F+), during a follow-up study six months later. Outliers are shown explicitly (black dots).
Box-whisker charts of values of the continuous variables that show significant pairwise differences between groups using the Mann-Whitney U test, (a) waist-to-hip ratio (WHR), (b) mean arterial pressure (MAP), (c) creatinine, (d) uric acid, (e) urea, and (f) breathing rate (BR). Baseline values are shown for male and female participants who remained seronegative (M- and F-), or who were found to have been infected (M+ and F+), during a follow-up study six months later. Normative ranges of reference values are indicated for male (blue-shaded background) and female participants (pink-shaded background). Outliers are shown explicitly (black dots).
Composition of the cohort in terms of male (M) and female participants (F), and post-hoc defined groups of participants that remain seronegative (IgG-) or become seropositive (IgG+) over the course of 6 months
Baseline values for anthropometric, biochemical, and physiological variables of the groups of male and female participants that remain seronegative (M- and F-, respectively) and become seropositive over the course of 6 months (M+ and F+, respectively)
All variables, except cholesterol, are non-normal for at least one of the groups, and therefore are reported in standard units as Q2(Q1, Q3) (upper half of the table), where Q2 is second quartile, i.e., the median, Q1 y Q3 are first and third quartiles respectively. Non-normal data is log transformed and represented as mean (SD) (bottom half of the table), where SD is standard deviation. For completeness, cholesterol is given in both formats without log transformation. Statistically significant factors and/or interaction using 2-way ANOVA and statistically significant pairwise group comparisons using the Mann-Whitney U test are also indicated for individual variables.
Risk factors contributing to infection with SARS-CoV-2 are modulated by sex

February 2024

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96 Reads

Throughout the early stages of the COVID-19 pandemic in Mexico (August—December 2020), we closely followed a cohort of n = 100 healthcare workers. These workers were initially seronegative for Immunoglobulin G (IgG) antibodies against SARS-CoV-2, the virus that causes COVID-19, and maintained close contact with patients afflicted by the disease. We explored the database of demographic, physiological and laboratory parameters of the cohort recorded at baseline to identify potential risk factors for infection with SARS-CoV-2 at a follow-up evaluation six months later. Given that susceptibility to infection may be a systemic rather than a local property, we hypothesized that a multivariate statistical analysis, such as MANOVA, may be an appropriate statistical approach. Our results indicate that susceptibility to infection with SARS-CoV-2 is modulated by sex. For men, different physiological states appear to exist that predispose to or protect against infection, whereas for women, we did not find evidence for divergent physiological states. Intriguingly, male participants who remained uninfected throughout the six-month observation period, had values for mean arterial pressure and waist-to-hip ratio that exceeded the normative reference range. We hypothesize that certain risk factors that worsen the outcome of COVID-19 disease, such as being overweight or having high blood pressure, may instead offer some protection against infection with SARS-CoV-2.


Table 1
Communicating Cutting Edge Research on Physiological Networks: A Three-Step Method

February 2024

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74 Reads

Medical knowledge and practice are usually structured and implemented by dividing the various organs and systems of the human body. This makes it easier to provide healthcare services and education, and to distribute tasks and responsibilities among different professionals. However, this approach has its limitations, as it overlooks the interactions between different systems that often transcend these divisions. Moreover, it neglects the systemic properties and behavior of the whole organism. Calmecac is a transdisciplinary research group at the National Autonomous University of Mexico (UNAM), founded in 2019, with the goal of enhancing human health by viewing the human body as a complex system. The group carries out innovative research on physiological networks, exploring how human physiological systems and organs are interconnected. To share its main findings with various audiences, Calmecac hired a science communicator who followed a three-step method: 1. A thorough immersion into Calmecac's research, including involvement in experimental activities. 2. The identification and concise explanation of the main concepts and results to be communicated. 3. The integration of three essential elements of discursive strategies (credibility, legitimacy, and attention capture) in the creation of science communication materials: a popular science article and a series of TikTok videos. The next stage of this research will consist of evaluating the effectiveness of these videos in transmitting scientific information using four memory tasks: recall, identify, remember, and contextualize (RIRC Method). The study will also aim to ascertain if the information best remembered by participants matches well with the features related to the three elements of discursive strategies.


Achalasia alters physiological networks depending on sex

January 2024

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110 Reads

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2 Citations

Achalasia is a rare esophageal motility disorder for which the etiology is not fully understood. Evidence suggests that autoimmune inflammatory infiltrates, possibly triggered by a viral infection, may lead to a degeneration of neurons within the myenteric plexus. While the infection is eventually resolved, genetically susceptible individuals may still be at risk of developing achalasia. This study aimed to determine whether immunological and physiological networks differ between male and female patients with achalasia. This cross-sectional study included 189 preoperative achalasia patients and 500 healthy blood donor volunteers. Demographic, clinical, laboratory, immunological, and tissue biomarkers were collected. Male and female participants were evaluated separately to determine the role of sex. Correlation matrices were constructed using bivariate relationships to generate complex inferential networks. These matrices were filtered based on their statistical significance to identify the most relevant relationships between variables. Network topology and node centrality were calculated using tools available in the R programming language. Previous occurrences of chickenpox, measles, and mumps infections have been proposed as potential risk factors for achalasia, with a stronger association observed in females. Principal component analysis (PCA) identified IL-22, Th2, and regulatory B lymphocytes as key variables contributing to the disease. The physiological network topology has the potential to inform whether a localized injury or illness is likely to produce systemic consequences and the resulting clinical presentation. Here we show that immunological involvement in achalasia appears localized in men because of their highly modular physiological network. In contrast, in women the disease becomes systemic because of their robust network with a larger number of inter-cluster linkages.




FIGURE 2. Circadian parameters for actigraphy. a) period T , b) mesor M , c) amplitude A and d) acrophase φ 0 . Week-average values are shown and, where possible, also error bars with the standard deviation of the day-to-day variability. Also the mean value for each parameter over all methods is indicated (horizontal lines).
FIGURE 4. Fourier power spectra of time series of actigraphy (green shaded curves), circadian cycles as extracted by different methods (black continuous curves), and compared to standard cosinor analysis (black dashed curve). All spectra are presented in semilogarithmic scale. Angular frequencies ω are shown in units of number of cycles for 7 consecutive days.
Circadian cycles: A time-series approach

September 2023

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171 Reads

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3 Citations

Revista Mexicana de Física

The extraction of circadian cycles from experimental data can be interpreted as a specific case of time-series or signal analysis, but chrono- biology and time-series analysis appear to have developed according to separate paths. Whereas some techniques such as continuous (CWT) and discrete wavelet analysis (DWT) are used frequently in rhythmobiology, other specialized methdos such as digital filters, nonlinear mode decomposition (NMD), singular spectrum analysis (SSA), empirical mode decomposition (EMD), ensemble empirical mode decomposition (EEMD) and complete ensemble empirical model decomposition with adaptive noise (CEEMDAN) have only occasionally been applied. No studies are available that compare the applicability between a wide variety of different methods or for different variables, and this is the purpose of the present contribution. These methods improve the goodness-of-fit of the circadian cycle with respect to the standard approach of cosinor analysis. They have the additional advantage of being able to quantify the day-to-day variability of the circadian parameters of mesor, amplitude, period and acrophase around their average values, with potential clinical applications to distinguish between healthy and unhealthy populations. Finally, the circadian parameters are interpreted within the context of homeostatic regulation with distinctive statistics for regulated and effector variables.


Figure 3. Gait parameters along the magnitude axis, (a) vector acceleration Δa, (b) anteroposterior acceleration ΔaAP, and vertical acceleration ΔaVT, and (c) mediolateral acceleration ΔaML. The evolution of gait parameters is shown for young adults (group C1), middle-aged adults (group C2), nonFigure 3. Gait parameters along the magnitude axis, (a) vector acceleration ∆a, (b) anteroposterior acceleration ∆a AP , and vertical acceleration ∆a VT , and (c) mediolateral acceleration ∆a ML . The evolution of gait parameters is shown for young adults (group C1), middle-aged adults (group C2), non-frail older adults (group nF), and frail older adults (group F). Indicated are mean ± standard error, and pairwise statistically significant differences with p < 0.05 (*), p < 0.005 (**), p < 0.001 (***).
Demographic and anthropometric measures (mean and standard error) are shown for each group. The sample size is represented with n. Results are given for young control adults (group C1), middle-aged control adults (group C2), non-frail older adults (group nF), and frail older adults (group F).
Frailty Syndrome as a Transition from Compensation to Decompensation: Application to the Biomechanical Regulation of Gait

May 2023

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133 Reads

Most gait parameters decrease with age and are even more importantly reduced with frailty. However, other gait parameters exhibit different or even opposite trends for aging and frailty, and the underlying reason is unclear. Literature focuses either on aging, or on frailty, and a comprehensive understanding of how biomechanical gait regulation evolves with aging and with frailty seems to be lacking. We monitored gait dynamics in young adults (19-29 years, n = 27, 59% women), middle-aged adults (30-59 years, n = 16, 62% women), and non-frail (>60 years, n = 15, 33% women) and frail older adults (>60 years, n = 31, 71% women) during a 160 m walking test using the triaxial accelerometer of the Zephyr Bioharness 3.0 device (Zephyr Technology, Annapolis, MD, USA). Frailty was evaluated using the Frail Scale (FS) and the Clinical Frailty Scale (CFS). We found that in non-frail older adults, certain gait parameters, such as cadence, were increased, whereas other parameters, such as step length, were decreased, and gait speed is maintained. Conversely, in frail older adults, all gait parameters, including gait speed, were decreased. Our interpretation is that non-frail older adults compensate for a decreased step length with an increased cadence to maintain a functional gait speed, whereas frail older adults decompensate and consequently walk with a characteristic decreased gait speed. We quantified compensation and decompensation on a continuous scale using ratios of the compensated parameter with respect to the corresponding compensating parameter. Compensation and decompensation are general medical concepts that can be applied and quantified for many, if not all, biomechanical and physiological regulatory mechanisms of the human body. This may allow for a new research strategy to quantify both aging and frailty in a systemic and dynamic way.



Citations (7)


... In this context, the role of sex, hormonal and immunosuppressive factors that could potentially influence the pathophysiology of achalasia have been considered in the literature, with controversial results [30,36,39,41,51]. No discernible variations in the clinical presentation of achalasia or its medical management have been observed between the sexes [97]. Furthermore, particular caution must be taken in the study design, paying attention to the biosamples to be analyzed (blood, serum, plasma). ...

Reference:

Focus on Achalasia in the Omics Era
Achalasia alters physiological networks depending on sex

... One of the main findings of this study is the possible existence of different physiological states that are associated with varying degrees of susceptibility to infection with SARS-CoV-2. We recently published a series of contributions on physiological networks, where the central idea is that the human body is a complex system and that demographic, anthropomorphic, clinical, and laboratory variables do not exist in isolation but correlate into systemic physiological states that define the overall health condition [36,[38][39][40][41][42]. These physiological networks are influenced by sex [39,42] and are disrupted by COVID-19 [39,42]. ...

Polymerised type I collagen modifies the physiological network of post-acute sequelae of COVID-19 depending on sex: a randomised clinical trial

... One of the main findings of this study is the possible existence of different physiological states that are associated with varying degrees of susceptibility to infection with SARS-CoV-2. We recently published a series of contributions on physiological networks, where the central idea is that the human body is a complex system and that demographic, anthropomorphic, clinical, and laboratory variables do not exist in isolation but correlate into systemic physiological states that define the overall health condition [36,[38][39][40][41][42]. These physiological networks are influenced by sex [39,42] and are disrupted by COVID-19 [39,42]. ...

Poincaré maps on population-based data of subjects with a confirmatory diagnosis of COVID-19

AIP Conference Proceedings

... [8][9][10] One promising and easy-to-interpret approach is to assess the intraindividual variability of a set of fundamental descriptive properties of the circadian rhythmfor example, amplitude-measured across multiple consecutive days. This approach has also been referred to as "day-to-day variability" 11,12 or "circadian variability." 4 Intraindividual variability is designed to detect persistent irregularities in circadian rhythms over longterm physiological recordings. ...

Circadian cycles: A time-series approach

Revista Mexicana de Física

... Their interplay and cross-influence give rise to the regulation of complex high-level processes. Being a hallmark of central organizing principle of physiology 4 , homeostasis increasingly attracts researchers aiming at the development of artificial systems for the purposes of bio-inspired electronics 2,9 , neuromorphic engineering [10][11][12] , soft robotics 13 , and control systems engineering [14][15][16] . It is expected that mimicking basal functional operation of living organisms, like homeostasis, and transferring their principles to artificial systems will lead to new flexible and robust control design architectures 16 and efficient neuromorphic computing applications 12 . ...

Parallels between homeostatic regulation and control theory

AIP Conference Proceedings

... Multimedia Appendices 8 and 9 provide details on AI model characteristics in each cited study. [27][28][29][31][32][33][34][35][37][38][39][41][42][43][44][45][46][47][50][51][52][53]56,57,59,62,70] 27 (59) Specificity [27,[39][40][41][42]44,45,48,49,54,58,61,63,65,67,69] 16 (35) F 1 -score [27,28,33,35,38,40,41,43,[46][47][48][49]51,54,59,62,63,67,69] 19 (41) Positive predictive value (precision) [29,30,33,46,47,49,51,52,59,61,62] 11 (24) Cohen κ [28,35,40,42,46,47,51,58,59,62,67] 11 (24) Area under the curve [28,33,35,38,43,46,47,51,62] 9 (20) Negative predictive value [35,40,46,47 ...

Differentiating acute from chronic insomnia with machine learning from actigraphy time series data

Frontiers in Network Physiology

... The middle-aged adults who participated in the study were family members and/or caretakers of frail and non-frail older adult participants; they were completely independent and functional, and therefore nonfrail. The inclusion and exclusion criteria have been explained in a previous publication [38] and are summarized here. To obtain a more realistic sample of frailty within the older adult population, we included individuals of both genders and with diverse medical histories. ...

Chronotropic Response and Heart Rate Variability before and after a 160 m Walking Test in Young, Middle-Aged, Frail, and Non-Frail Older Adults