The prominent veins sign (PVS) on susceptibility-weighted imaging (SWI) has been suggested to be related to the prognosis of patients with acute ischemic stroke (AIS). This meta-analysis aims to clarify the association between PVS and the prognosis of patients with AIS.Q-test and I2 value. Subgroup and sensitivity analyses were also performed to explore the potential sources of heterogeneity. Publication bias was assessed with funnel plots and using Begger's and Egger's tests.This meta-analysis was registered in PROSPERO (no. CRD42022343795). We performed systematic research in PubMed, Web of Science, EMBASE, and Cochrane Library databases for studies investigating the prognostic value of PVS. Based on the enrolled studies, patients were divided into two groups as follows: those with PVS cohort and those without PVS cohort. Outcomes were unfavorable functional outcome, early neurological deterioration (END), and hemorrhagic transformation (HT). The random-effects models were used for the meta-analytical pooled. Heterogeneity was estimated using Cochran's A total of 19 studies with 1,867 patients were included. PVS was correlated with an unfavorable functional outcome in patients with AIS , especially in those receiving recanalization therapy , but not in those treated conservatively . Moreover, PVS was related to END , while without an increased risk of HT .PVS was associated with an unfavorable prognosis of patients with AIS and increased the risk of END, while not correlated with an increased risk of HT. PVS might be useful for predicting functional outcomes of patients with AIS as a novel imaging maker.https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022343795. Acute ischemic stroke (AIS) has been demonstrated to be the leading cause of morbidity and mortality worldwide, accounting for 87% of all strokes . It is aSusceptibility-weighted imaging (SWI) is a blood oxygen level-dependent magnetic resonance technique developed as a useful tool for evaluating cerebral veins , 5. It i* or prominent or hypointense or cortical or medullary or deep cerebral” and “vessel* or vein*” and “susceptibility-weighted or susceptibility weighted or SWI” and “stroke or cerebral infarction or cerebrovascular disease or brain infarction” . Our search strategy was based on a combination of the following keywords: “asymmetricarction” . PubMed,The following eligibility criteria were used to reduce clinical heterogeneity: (1) patients aged ≥18 years and with an established diagnosis of AIS; (2) a baseline SWI was performed within 7 days after admission; (3) prognostic outcomes of patients with PVS and without PVS reported in eligible studies; and (4) the study design was a prospective or retrospective cohort study. We excluded (1) studies where outcomes were not separate for participants with and without PVS; (2) studies aim to investigate the relationship between PVS and other imaging features such as collateral circulation and perfusion status; and (3) all case series, case reports, letters, editorials, reviews, conference abstracts, guidelines, technical notes, and unrelated studies.Two authors (MZ and HW) independently reviewed the titles, abstracts, and full text of all the retrieved studies to determine their eligibility for inclusion. Disagreement was resolved by consensus with the corresponding author (ZL). If studies had overlapping samples, only the study with a larger sample size was included. Data extraction for each included study was done independently using a standardized electronic form. The discrepancies were resolved by consulting the third senior coauthor. The data extraction included (1) first author, publication year, study design, sample size, inclusion criteria, and clinical and imaging characteristics of enrolled patients at baseline , organic heart disease, history of stroke, time from stroke onset to SWI); (2) administration of research therapy ; (3) PVS definition or assessment method: (i) visual assessment method, which classified patients with PVS if hypointense vessels were observed in the ipsilateral hemisphere compared with the contralateral side; (ii) patients scored quantitatively according to the Alberta Stroke Program Early CT Score and categorized into the PVS-positive group; (iii) slice assessment method ; and (iv) pixel comparison method ; and (5) primary and other outcomes in patients with and without PVS on baseline SWI. In the case of incomplete or unclear data, the authors were contacted using the details given in articles or identified by Internet search.The modified Rankin Scale (mRS) score will be used to assess the prognosis of patients with AIS. The primary outcome was an unfavorable functional outcome, defined as a score of 2–6 or 3–6 with no limit to the duration of follow-up. Other outcomes were 90-day unfavorable functional outcome, early neurological deterioration (END), and hemorrhagic transformation (HT). END was defined as neurological deterioration with an increase in the National Institutes of Health Stroke Scale (NIHSS) score ≥ 2 points in the first 72 h after admission. HT was determined by CT or MRI within 7 days after admission.via consensus.The Newcastle–Ottawa scale (NOS) was used to assess the quality of the included cohort studies, which included three factors, namely, selection, comparability, and exposure to assess the quality of each enrolled study. The NOS scores of 1–3, 4–6, and 7–9 indicate low, moderate, and high quality of studies, respectively. Two investigators (YM and HZ) independently conducted the quality assessment, and the differences were settled p-value of <0.05 indicating statistical significance. We assessed statistical heterogeneity between studies using Cochran's Q-test (p < 0.1 indicating heterogeneity) and I2 statistic . The subgroup analysis of the primary outcome was based on the patients' treatment modalities, the types of PVS defined by location, and the stenosis rate of the intracranial artery. In addition, a random-effects meta-analysis was performed to show the association of clinical and imaging factors with the presence of PVS on baseline SWI. The publication bias was assessed using Begger's and Egger's tests of funnel plot symmetry in addition to visual inspection of the funnel plots.All meta-analyses were performed using Stata software (v.16.0). A random-effects model was applied to calculate the pooled proportion meta-analysis. Pooled risk ratios (RRs) with 95% CI were estimated using the DerSimonian and Laird random-effects model. The data are presented as forest plots, with a two-sided n = 23), data could not be extracted from the study (n = 4), or studies were conference abstracts (n = 11). In the case of overlap in patient cohorts of the two studies, only the largest study was included in this systematic review  (n = 951) reported END (n = 352) reported the risk of HT (The included studies and relevant characteristics are provided in n = 324) , 19, 20 n = 324) , 19, 20 n = 324)  of whichrted END , 15, 22,sk of HT . Data frsk of HT . The NOSp = 0.034) and AF  had an independent relationship with the presence of PVS. Furthermore, severe intracranial large-artery stenosis/occlusion (SILASO) was significantly associated with the presence of PVS .The factors related to the presence of PVS are shown in p < 0.001), especially in patients who underwent recanalization treatment , but not in patients treated conservatively  (I2 = 66.2%). Comparable results were obtained in a pooled analysis of the 90-day functional outcome . There were similar associations in subgroup analyses by stenosis rate of the intracranial artery and functional outcome: being associated with an unfavorable outcome for patients with SILASO  and without SILASO  (I2 = 69.4/I2 = 67.1).In general, PVS was associated with an unfavorable functional outcome  . There w outcome . The sub =0.005) . Heterogp<0.001, I2 = 0%) (n = 352) explored the relationship between PVS and HT. Among them, one study was excluded from the meta-analysis due to the definition time of HT was unclear. There was no significant association with HT   . Six stuI2 = 0%) .The funnel plot was symmetrical, indicating no publication bias in this meta-analysis. The Begg's and Egger's tests were insignificant, indicating no publication bias .In this systematic review and meta-analysis, we have identified the key factors determining the presence of PVS that were previous stroke/TIA, AF, and SILASO. While overall PVS was associated with an unfavorable outcome especially when recanalization treatment was performed, but not in patients treated conservatively. PVS was also associated with END but without an increased risk of HT. Those results may be helpful for clinicians to identify the high-risk populations with poor prognosis after AIS, thus providing timely and appropriate interventions.The incidence of PVS has been reported to be ranging from 6.8 to 64% , 23, 29.Our research demonstrated that PVS was significantly associated with poor prognosis in those who received recanalization therapy. Early recanalization has been proven to be the first line of therapy to improve the outcome of patients with AIS . HoweverInterestingly, the pooled results for PVS and poor prognosis in the conservative treatment group were not significant. On the one hand, it was believed that if the hypoperfusion state was not improved in time in patients with PVS, the structural integrity of brain cells was irreversibly damaged with the prolongation of the disease. Eventually, the cells lost their oxygen uptake capacity and died. At the same time, vasodilatory regulation gradually weakened, and the venous structures collapsed . Both thThe subgroup analysis based on location revealed that both cortical and medullary veins were related to an unfavorable outcome. Medullary veins are better than cortical veins as predictors of poor prognosis. A possible pathophysiological factor may be that compared with cortical PVS, the presence of medullary PVS reflects the increase in the deoxyhemoglobin level in the draining deep medullary veins above a limit of detection, suggesting the decompensation of oxygen capacity, which is more likely to be reached in severe strokes , 46. SubThis study had several limitations. First, the included studies were observational studies, leading to a selection bias. Second, due to the low number of studies and sample size related to END and HT, further meta-analyses with larger samples are needed.Our study suggests that PVS was closely related to the poor prognosis of patients with AIS treated with recanalization. Among the PVS-positive population, the efficacy of aggressive reperfusion therapy was not significant. However, we believe that reperfusion therapy should not be postponed because of the presence of PVS. PVS is valuable as a noninvasive imaging marker for predicting prognosis and warrants further investigation.The original contributions presented in the study are included in the article/ZL and WX conceived the idea and designed the research. MZ and HW searched databases and performed initial screening. YM and HZha performed data extraction and interpretation. ZS and YL performed the statistical analysis. WX wrote the first draft of the manuscript. ZL, WL, and HZhe revised the manuscript. All the authors read and approved the final version of the manuscript for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


This study aims to establish cut-off points for the number of minutes of physical activity intensity and the number of daily steps that identify overweight/obesity in adolescents, adults, and older adults. This study examined data from 2737 participants. Physical activity intensity and the number of daily steps were assessed using GT3X+ ActiGraph model accelerometers. Body mass index, waist-to-height ratio, and waist-to-hip ratio were used as indicators of overweight/obesity. The cut-off points for moderate-to-vigorous physical activity for the prevention of overweight/obesity according to body mass index in women ranged from 15.1 to 30.2 min/day; in men, the values were from 15.4 to 33.8 min/day. The lowest cut-off point for daily steps was established in the adolescent group for women and men (7304 and 5162). The highest value in women was 11,412 (51–65 years) and 13,234 in men (18–30 years). Results from measurements different from BMI, show average cut-off points for moderate-to-vigorous physical activity and daily steps of 29.1/8348 and 43.5/10,456 according to waist-to-height ratio; and results of 29.3/11,900 and 44.3/11,056 according to the waist-to-hip ratio; in women and men respectively. A more specific recommendation of physical activity and daily steps adjusted by sex and age range is suggested to prevent overweight/obesity. In Latin America, the prevalence of people with overweight/obesity is higher than in the rest of the world2, where two-thirds of women and half of men are overweight/obese in some countries, such as Chile and Mexico3. Overweight/obesity have been associated with metabolic diseases, increasing the risk of morbidity and mortality in the population with this condition5.Obesity is a multifactorial disease that has grown in recent decades, with almost a third of the global population been classified as overweight/obese7 and although this conventional measurement of obesity has some benefits, there is concern that not all individuals at risk of obesity-associated medical conditions are being identified. Also, the whole-body fat percentage and specifically visceral adipose tissue mass are correlated and potentially implicated in disease development, but are not fully accounted for through BMI evaluation8. For this reason, in addition to BMI, other measurements of visceral adiposity, such as waist-to-height ratio (WHtR) and waist-hip ratio (WHR), have been validated as predictors of cardiovascular risk and mortality9. Therefore, health professionals should consider these measurements10. Evidence suggests that the WHtR is a stronger diagnostic indicator of overweight/obesity than the BMI or the WHR11; however, the WHR has also shown a significant association with the prevalence of hypertension and type 2 diabetes12.Most epidemiological studies on obesity are based on the body mass index (BMI), which is generally accepted as a strong predictor of mortality13. In addition to the minutes/intensity approach, the number of steps per day has also been used as indicator and target to achieve the benefits of physical activity (PA), being widely recommended at least 10,000 steps per day to maintain good health in adults14. However, less clear evidence is available to support the step-based recommendation. In adolescents, a threshold of 11,111 daily steps have been suggested as a step-based recommendation related to both PA and sedentary behavior thresholds, demonstrating a healthier cardiorespiratory fitness profile compared to their sedentary peers15. In this context, although a greater number of daily steps  has been associated with lower mortality from all causes, a recent meta-analysis of 15 international cohorts studies suggested a plateau in the mortality risk reduction from 6000–8000 steps per day for older adults (≥ 60 years) and from 8000 to 10,000 steps per day for younger adults16. However, these recommendations are not specific for weigh management and do not consider samples from different sexes and age-groups out of the developed countries, which can influence the results analysis considering differences by age in functional capacity needs and PA recommendations. Thus, the aim of this study is to establish cut-off points for the number of minutes of MPA, VPA, MVPA, and the number of steps that identify overweight/obesity in adolescents, adults, and older adults from eight Latin American countries.Among the determinants of overweight/obesity, moderate-to-vigorous physical activity (MVPA) has been inversely associated with weight gainhttps://www.elansstudy.com and in other previously published studies17.This multinational cross-sectional study was obtained from the Latin American Study of Nutrition and Health (ELANS), which evaluated aspects of nutrition, PA, and sociodemographic characteristics in eight Latin American countries . The survey was conducted from 2014 to 2015 using a complex, multistage, multisampling design, stratified by clusters. A random selection was made according to the probability proportional to size method. The survey included only participants from urban areas. Full details of ELANS can be found at 18.In total, 92 cities participated in the ELANS study (from seven to 23 cities in each country). Respondents were selected from primary sampling unit areas . For the selection of households, a systematic 4-step randomization was implemented by establishing an interval selection: (1) the total urban population was used to proportionally describe the main regions and select cities that represent each region, (2) the samplers points (survey tranches) from each city were randomly designated, (3) groups of households were selected from each sampling unit, and (4) the designated respondent within each household was selected using the birthday method. A stratified recruitment participants was carried out in each country according to gender, age, and socioeconomic status (SES). The ELANS design and sample size have been described elsewhere18. A total of 2737 people  was considered in the current study, corresponding to all participants who had complete information from accelerometers regarding PA and daily steps and also had all the data on obesity indicators19. Participants with incomplete PA or anthropometric measurements data were excluded from the database.A total of 10,134 people (15.0–65.0 years of age) were invited to participate in the ELANS study. However, 9218 (4809 women) were included in the participants. In this study, participants who used accelerometers were considered according to gender, age, and SES ranges, thus ensuring a representative subsampleAll participants had to provide written informed consent before participating in the study, who voluntarily agreed to participate in the study and gave their permission for the future use of the recorded data. The ELANS protocol complies with the guidelines enunciated in the Declaration of Helsinki (2014) and has the approval of the ethics committee of the Western Institutional Review Board (#20140605), and registered with Clinical Trials (#NCT02226627). Also, a regional ethics committee approved the study in each country.20. Each measurement was evaluated twice for greater precision, and an average of both was used for the analysis. Body weight and height were measured with participants wearing light clothing and without shoes, using an electronic scale and a portable stadiometer, respectively. Circumferences were measured with an inelastic tape to the nearest 0.1 cm. The midpoint between the last rib and the iliac crest was considered to measure the waist circumference. HC was measured at the largest protuberance level at the buttocks level, without pressing the soft tissues.The indicators of overweight/obesity used in the present study were body weight (kg), height (cm), waist circumference (cm), and hip circumference , which were evaluated according to standardized protocols2)), WHtR (waist circumference (cm)/height (cm)), and WHR (waist circumference (cm)/HC (cm)) indices were calculated in relation to the absolute values. The categorical BMI of adolescent participants was derived from the World Health Organization reference curves for age and sex21. Adults with a BMI ≥ 25.0 were classified as overweight/obese22. For WHtR and WHR, the cut-off points were ≥ 0.55 for adolescents and adults of both sexes; ≥ 1.0 for men and ≥ 0.85 for women24. Participants were classified as eutrophic and overweight/obese.The BMI (weight (kg)/height  were used to assess PA intensity  and daily steps. Previous studies have widely documented its reliability and validity27.The accelerometers were given to the participants on a first visit, including a daily report for the following seven days, in which participants were instructed to complete a daily log to report the time they put the accelerometer belt on and the time when it was removed. The information they took in their daily logs, contributed to identify potential problems that could emerge from accelerometers use. They were removed on a second home visit. Participants were asked to wear the device on an elastic belt at hip level in the midaxillary line when they were awake and remove it when sleeping, showering, or swimming only, with specific instructions of removing the device only when going to sleep and wearing it immediately after waking up, without specifying the exact time. Excluding overnight sleep time, wake time without use was defined as any sequence of at least 60 consecutive minutes with zero activity. Data were collected at a sampling rate of 30 Hz and downloaded in 60-s time periods, then analyzed using ActiLife software 28. Cut-off points considered for this study were taken from adult population for standardization purposes, considering that there was not pediatric population who participated from the study. Cut-off points were stablished at: 1952–5724 activity counts/min as MPA, 5725–9498 activity counts/min as VPA, and ≥ 1952 activity counts/min as MVPA . In addition, we evaluated the number of daily steps. The mean absolute percent error of the GT3X+ accelerometer to measure daily steps is 14%29.The data included and analyzed in the study corresponded to those with at least 10 h of recording for five days, including at least one weekend day30, comparing the equivalized per-person income of each country/household with established thresholds for Latin Americans, drawn from national indexes used in each country.The selection of respondents within a household was made at each country's level, considering the variables of interest. The participants of this study were stratified by sex, country, age group and SES. Age was categorized into the following groups: 15–17, 18–30, 31–50 and 51–65 years according to data collected from the ELANS study and group similarities regarding characteristics and PA recommendations. Regarding SES, this was evaluated by questionnaire using a country-dependent format and based on the legislative requirements or established local standard layouts. Three classification levels  were considered for all countries31. All calculations were performed using SPSS version 26 software . The Kolmogorov–Smirnov test was performed to evaluate the distribution of the data. For continuous variables, mean and standard deviation (SD) were presented; and categorical variables were expressed in frequency and percentage. The t-Student test for independent samples and Chi-square were used to compare the variables between the sexes. For non-parametric data , the median and the 25th and 75th percentiles were also presented.The sample's weighting was applied at each country's level considering gender, age, and SES32. We then calculated sensitivity and specificity and cut-off points for MPA, VPA, MVPA, and the number of daily steps for prevention of overweight/obesity. Participants with low weight according to BMI were excluded from the ROC curve. Due to the significant difference in PA between the sexes, the results were presented for men and women separately. The significance of p < 0.05 was considered.The predictive power and cut-off points of MPA, VPA, MVPA (min/day), and daily steps to prevent overweight/obesity were identified using Receiver Operating Characteristic (ROC) curves. We identified the total area under the ROC curve between the number of MPA, VPA, MVPA (min/day), daily steps and the prevention of overweight/obesity for BMI, WHtR and WHR. The greater the area under the ROC curve, the greater the discriminatory power, and a 95% confidence interval (95% CI) was also used. The 95% CI calculation determines whether the predictive capacity is not due to chance, and its limit must be greater than 0.50Ethical approval was approved by the Western Institutional Review Board (#20140605), and by regional ethical review boards of the participating institutions belonging to each country. The ELANS protocol is registered at Clinical Trials #NCT02226627.Written informed consent/assent was obtained from all individuals before commencing the study.p < 0.05) were found between the sexes for age, anthropometric measurements , PA, and daily steps. On the other hand, no differences were found between the sexes only for SES and BMI categories  with a mean age of 36.4 years SD: 14.1) participated. Significant differences (4.1 partip < 0.05) than women in the 18–30 and 31–50 groups . Furthermore, significant differences were found between the sexes for WHtR, WHR, MPA, and MVPA in all age categories. On average, men took more steps per day (ps Table .Table 2CTables The cut-off points established for MVPA (min/day) according to BMI presented lower values than the WHtR and WHR in men and women. In the analysis by gender, men demonstrated higher cut-off points for daily steps than women in all age categories according to BMI, WHtR, and WHR. In the case of MVPA, the cut-off points for the male group were only higher than for women by WHtR and WHR, but not by BMI. Regarding age groups, the lowest cut-off point for MVPA was observed in the age group of 31–50 years (15.1 min/day) in women and in the adolescent group in men 15.4 min/day). In the case of daily steps, the adolescent group (15–17 years) showed the lowest cut-off point according to BMI, WHtR, and WHR in both sexes, both in men (5162) and in women (6143)  than women in all age groups. Likewise, other studies have concluded that a lower average daily PA characterizes women compared to men, especially at older ages35, proving to be less physically active, with lower average levels of light, moderate, and vigorous PA, and total PA19. The above may be attributable to a cultural issue that stablish a strong Latin American role of women in household and family-related activities, leading to less leisure time, lower engagement in PA and higher sedentary behavior in women compared to men, which can lead to a higher development of obesity-related diseases at early ages. The foregoing coincides with the analysis of this study, where the lowest average daily MVPA was observed in older women (51–65 years) according to BMI, who are characterized by carrying out light, mainly domestic activities, over more intense PA. In contrast, men tend to engage in vigorous work-related or recreational activities that may protect effect against abdominal obesity36.This study aimed to establish cut-off points for PA that identify overweight/obesity by sex and age groups in people from eight Latin American countries. The main results showed significantly higher BMI values in women than in men in all age groups, just as previous studies have shown a higher prevalence of obesity, high waist circumference, and the development of chronic diseases in non-Hispanic women37. The present study showed that women obtained lower cut-off points for daily steps than men, obtained according to BMI, WHtR, and WHR, as well as for MVPA, according to WHtR and WHR, suggesting that men will need to comply with a greater amount of minutes of MVPA and daily steps to achieve a protective effect against overweight/obesity. Likewise, although participation in 150 min or more of MPA has been associated with a reduction in the odds of abdominal obesity, only in women it is associated with lower odds of being overweight/obese36.The cut-off points for MPA, VPA, MVPA and daily steps were established based on BMI, WHtR, and WHR. Evidence shows different responses to the type of exercise found between the sexes in obese adults38. Although seems that more steps per day is associated with lower mortality risk, specific cut off points around 8000 steps per day were identified to screen overweight39. Thus, our findings expand previous evidence for different sexes and age groups, suggesting a cut-off point according to BMI between 9544 and 11,412 daily steps for women and 10,295–12,509 daily steps for men in adults (31–50 years) and older adults (51–65 years) respectively, which are within the recommendations for the prevention of overweight/obesity and other related health problems. On the other hand, this study showed the lowest cut-off point for daily steps according to BMI, WHtR, and WHR in the adolescent group (15–17 years), both in men (5162) and women (6143), unlike the number of 14,414 and 11,355 suggested by a Brazilian study based on waist circumference measurements40. This group could have a protective factor associated with age based on the fact that overweight/obesity could be related to cellular processes similar to aging, which is associated with an increase in the percentage of body fat of approximately 1% per decade41.Previous studies have established the relationship between the number of daily steps and a lower risk of all-cause mortalitySome limitations need to be considered, such as the study's cross-sectional design. Because the study was performed only among urban people, the results cannot be generalized to rural inhabitants. Also, accelerometers do not adequately capture some cycling and static exercise activities. These rule out certain types of movement that are not perceived and mainly measure accelerations translated into an activity count but do not discriminate in the type and/or intensity of PA performed. However, the study's strengths include that it was carried out considering the extensive database with participants from eight different countries in Latin America. In addition, in this study, the analysis was carried out by sex and age range, which allows for a more limited perspective of the needs of each age group in relation to PA and prevention of overweight/obesity. Moreover, these results presented by sex and age categories, represent a novelty for the prescription of specific PA for each group, contributing to reduce the high rates of obesity in Latin America and thus avoid the prevalence of chronic diseases associated with overweight from early ages and throughout the life cycle, improving people's functional capacity and quality of life. Lastly, better prevention of obesity will contribute to improvements in health programs implementation and the use of health resources of each nation for more preventive than curative purposes.The present study showed significant differences in all age categories between the sexes for WHtR, WHR, MPA, and MVPA. Women presented lower cut-off points for MVPA and daily steps than men to prevent overweight/obesity. In addition, the lowest cut-off point for daily steps was established in the adolescent group for both sexes and the highest in the older age groups in women, and adults in men. This research suggests that a universal recommendation for PA and daily steps is not enough and should be adjusted by sex, age range, and geographic region. Further research is required to establish the association between compliance with PA recommendations and the prevalence of other diseases associated with overweight/obesity.


The COVID-19 pandemic has greatly influenced the lifestyle and entertainment activities of the society that has significantly increased the growth rate of the gaming industry. While the studies on the game industry, one of the leading content industries, related to the pandemic has been done from various perspectives, little attention has been taken in regards to how the pandemic have impacted on the national digital game production and its industrial sustainability as a whole. Thus, this study was conducted to analyze the changes in the domestic game industry before and after the COVID-19 outbreak using the big data analysis of semantic network. This study aims to understand the growing trend in the gaming industry that can be helpful for the marketing and production of future games, as well as to guide the establishment of the public game policies in the game industry. The results showed that the COVID-19 pandemic positively decreased the public’s worries and the government’s restrictions towards gaming due to game addiction as a mental disease. However, its sudden change in the gamer’s attitudes and the current gaming policies implied that for the sustainable development of the domestic game production, laws and regulations related to the game industry need to be reliable and planned on a long term basis since the industry is immensely large and is also related to several industries such as computing, programming, arts, and story contents. Accordingly, it is necessary to build an industrial ecology through which cluster complexes specializing in developing startups and small and medium-sized business can grow along with political support. Face-to-face activities that form the basis of social life has converted into contact-free and outdoor leisure activities are also minimized [ (11.5%) , which i (11.5%) .The studies with the focus on the online-gaming related to the COVID-19 pandemic have been done from various perspectives. Yoon et al. designed a serious game aiming to prevent the virus disease and studied how it could directly change the target user’s behaviors  . Kim andThus, this study was conducted to identify and makes a comparison of the social issues associated with the Korean game industry between 2019 before COVID-19 pandemic and 2020 after its outbreak by using a big data analysis technique. This study has three main contributions as follows.The study can be helpful in understanding the trend of the Korean game industry.The results of the study can be helpful in establishing public game policies for the better improvement of the entire game industry in South Korea.The results of the study can also be helpful in predicting the upcoming trends in gaming contents production, distribution, and consumption which will be significantly useful for the marketing and game content industries.The remainder of this paper is organized as follows. Section 2 provides a discussion on the relevant studies. The background of the study is discussed in Section 3. Section 4 outlines the research methods used in this study. The results and the discussion on their interpretations are provided in Section 5 and Section 6 concludes the study.Battle Ground and identified the users’ behavioral patterns in order to suggest the way in which users can be protected from playing abnormally [Due to the rapid progress of information and communication technologies, every information in our daily life is digitalized and massively produced. People as both consumer and producer obtain and process digitalized information and knowledge from online communities, read online newspapers through portal sites, and access video games via the Internet. The accumulated big data is so large, fast, and complex that it is difficult or impossible to process by using traditional analysis methods. Thus, big data are processed more efficiently using a Big Data Technology that is designed to analyze, process, and extract information from extremely complex and large data sets . As an enormally . D. H. Ynormally .There is another field of study about how the COVID-19 pandemic has made changes in people’s daily life in South Korea by using big data analysis. E. M. Kang studied certain changes in consumers’ fashion recognition before and after the pandemic . J. M. LThe following related studies deals with the utilizing classification and prediction methods to understand the trends in the COVID-19 pandemic. In the study of Zhan et al. , a data-Big data analytics can also be utilized to understand current events to support the preparation for the future events. In the study of Bag et al. , the FuzAli et al.  proposedMost of the existing studies have been conducted in varying perspectives but limited studies were focused on how the COVID-19 pandemic has influenced the gaming perspectives of the society. In this regard, in order to understand the current trend of the gaming industry, this study was conducted aiming to help building the sustainability of the gaming industry in South Korea.Text mining refers to an AI technology that transforms unstructured text data sets into normalized and structured data suitable for analysis . Text miSemantic Network Analysis (SNA) is one of the social network analysis tools that refers to a text-based big data analysis . SNA visSNA extracts keywords that appear on the overall network and finds the relationships among these keywords (nodes) to analyze the detailed characteristics of the target information data .The ‘equivalence’ network shows whether the keywords or nodes within the network have similar levels of relationships with one another. When the keywords or nodes are in the same position, it is called a structural equivalence. The keywords or nodes within the structural equivalence can be substituted for each other.As shown in Before conducting the CONCOR procedure, the co-occurrence matrix among the keywords needs to be extracted. A co-occurrence matrix is a matrix that shows how many times keyword A in a row and keyword B in a column appear at the same time in the text. The co-occurrence matrix that was extracted in this study is illustrated in Textom is a data processing program that collects text data through various acquisition channels such as news, blogs, and web documents and it also provides highly practical data that can be applied to various big data programs. It then refines the keywords, calculates the frequency, and extracts its co-occurrence matrix –38. TextThis study utilized Textom in order to collect data and extract keywords. Then, SNA and its visualization were conducted through the UCINET6 program. The research methodology procedures are depicted in Data were collected from Google, Naver, and Daum which are the three leading search engines in South Korea. The search keyword was ‘game industry’. Data was collected separately, first, in the year 2019 before the spread of COVID-19 and then in the year 2020 as shown in Among the collected news data, unnecessary keywords for analysis such as name, company name, and area were removed. The top 40 words in frequency were selected and the TF-IDF value was calculated. TF-IDF refers to the importance of those keywords and their degree of centrality between keywords. TF-IDF is a statistical figure that shows the relative importance of a specific keyword of a document in a collection of documents . The TF-TF: Frequency of relevant keywordIN: Natural logarithmD: Total number of documentsDF: Number of documents which relevant words are includedThe degree of centrality is the number of link incidents that shows how much a specific keyword is directly related to other keywords . The degThe top 40 keywords in frequency were selected and visualized in The top 40 important keywords are as follows: Game (1195), Game industry (1032), Content industry (641), Korea (525), Disease code (258), Korea Association of Game Industry (255), Ministry of Culture, Sports and Tourism (254), China (209), Game addiction (184), Development (183), etc.The TF-IDF is as follows: Game (1070), Content industry (792.942), Korea (780.262), Game industry (741.966), Disease code (556.666), Korea Association of Game Industry (543.429), Ministry of Culture, Sports and Tourism (532.156), China (516.379), Assemblyman (481.785), and Game addiction (479.181).The degree of centrality is as follows; Game (0.147), Game industry (0.102), Content industry (0.091), Korea (0.069), Disease code (0.032), Korea Association of Game Industry (0.027), Ministry of Culture, Sports and Tourism (0.027), Game addiction (0.024), China (0.022), Regulation (0.021), etc.In summary, it was found that the most important keywords were Game, Game industry, Content industry, and Disease code. The overall results are depicted in By using the CONCOR and UCINET 6 programs, 40 keywords were selected for analysis as shown in The CONCOR analysis showed that Group 1 (red circle) includes Game, Game industry, Content industry, Korea, policy, and global, thus, it was named ‘Game industry’. Group 2 (pink circle) includes Investment and future, thus, it was named ‘Game industrial expansion’. Group 3 (sky blue circle) includes Education and Game institute, thus, it was named ‘Development of human resources’. Group 4 (yellow circle) includes World Health Organization (WHO) and Game addiction, thus, it was named ‘Game addiction’. Group 5 (green circle) includes Introduction and Concern, thus, it was named ‘Impediment to game industrial development’. Group 6 includes Host and Game awards while Group 7 includes Hold, G star, and Copyright which were excluded from the analysis because it was difficult to find out their meaning and significance. The details are depicted in The keywords can be classified into five groups that include Game industry, Game industrial expansion, Development of human resources, Game addiction, and Impediment to game industrial development. Thus, it can be suggested that the Korean game industry trend in 2019 was directed in two opposite ways, first, to a game industrial expansion associated with Game R&D and educating the game human resources, and second, to impediments to game industrial growth associated with game addiction or game disorder.The top 40 important keywords were selected by collecting and analyzing news articles regarding the game industry in 2020 after the COVID-19 outbreak in South Korea. Its word cloud analysis is illustrated in The results are Game (1232), Game industry (858), Content industry (639), Korea (509), Korea Association of Game Industry (344), Assemblyman (341), COVID-19 (332), Content (241), Ministry of Culture, Sports and Tourism (235), Amendment (232), etc.The TF-IDF is as follows: Game (1021.64), Content industry (819.231), Game industry (805.568), Korea (790.339), Assemblyman (749.254), Korea Association of Game Industry (689.621), COVID-19 (646.248), Amendment (544.657), Content (505.219), Ministry of Culture, Sports and Tourism (502.333), etc.The degree of centrality shows the following: Game (0.148), Game industry (0.101), Content industry (0.095), Korea (0.062), COVID-19 (0.039), Content (0.034), Assemblyman (0.03), Ministry of Culture, Sports and Tourism (0.028), Korea Association of Game Industry (0.027), Global (0.026), etc.In summary, it was found that Game, Game industry, Content industry, Assemblyman, and COVID-19 are the important keywords. The overall results are depicted in By using the CONCOR analysis and UCINET6 program, its visualization is illustrated in As a result of CONCOR analysis, Group 1 (red circle) includes Game, Game industry, Content industry, Korea, Game business, and Growth, thus, it is named ‘Game industry’. Group 2 (pink circle) includes Assemblyman, Regulation, Ministry of Culture, Sports and Tourism, thus, it is named ‘Game regulations’. Group 3 (sky blue circle) includes Policy enforcement and Support, thus, it is named ‘Industrial expansion’. Group 4 (yellow circle) includes Announcement, Strategy, and E-sports, thus, it is named ‘E-sports’. Group 5 (green circle) includes Game law and Amendment, thus, it is named ‘Game law amendment’. Group 6 (orange color circle) includes game festival and open, thus, it is named ‘Game festival’. The details are depicted in The keywords in 2020 can be classified into a total of six groups such as Game industry, Game regulations, Industrial expansion, E-sports, Game law amendment, and Game Festival. Those groups indicate that the national game industry of 2020 in South Korea continued to be in a growth trend and the Korean government planned to reduce the regulatory impediments to the game industry and rigid game rating system. The changes included changing the market policies, online game shutdown policy, lasting from 12:00 to 6:00 am, as a means of preventing game addiction in adolescents aged 15 or below, and investment in e-sports and online game infrastructure, eventually in order to expand the size of the game industry itself.To clearly see the impact of the COVID 19 pandemic on online game issues in South Korea, the keywords between 2019 and 2020 were compared as indicated in In the list of 2019 keywords, the words such as Disease code, Game addiction, and WHO  were placed on the top 10 and their frequency was relatively higher than 70. These negative terms arose in association with the WHO declaration that gaming addiction would be listed as a mental health condition for the first time in May 2019. In contrast, the top-listed keywords of 2020 were contact-free, online, and digital, which indicates that the online game and its users had been greatly influenced by the COVID 19 pandemic, and what should be noticed was that the governmental support for the game law and E-sports market was much more being enforced.In comparing the game industry issues between 2019 and 2020 based on the big data analysis of news data, the following implications were identified. Firstly, there was a great change in attitudes toward online gaming in the public and the government policies. When the world-renown health organization WHO designated and conditioned abnormal gaming behaviours as a mental illness, gaming became more associated with public health issues and family social problems. Thus, the game industry was also got negatively affected and the additional regulatory policies were enforced by the government.However, after the COVID 19 outbreak, the restrictions and worries suddenly decreased but issues revolving around economic investment and the profitable market in the game industry gained an attention. Compared the sudden change in attitude and policies, the government should be careful not to be polarized in terms of public opinions and the policy-making towards the gaming and game industry. Rather, it is necessary to have in-depth discussions with business enterprises and academic circles regularly so that the overall content industry including the game industry can continue to grow in POST-COVID era.Secondly, relevant government agencies need to make a sustained effort to maintain the growth trend in the game industry. The video games industry is immensely large and related to several industries such as computing, arts, music, and story content and experts to make it keep on. Thus, it requires newly trained game-related designers, programmers, technicians, artists, and researchers. In this regard, for the sustainable development of the domestic game industry, laws and regulations related to the game industry need to be reliable and planned on a long-term base.Accordingly, it is necessary to build an industrial ecology through which business enterprises can grow by constructing cluster complexes specializing in developing startups and small and medium-sized businesses along with political support.The game industry has continued to grow and its growth rate increases more rapidly due to the great influence of COVID-19 on the person’s lifestyle and entertainment activities. This is a general trend in the overall content industry including animation, broadcasting, and online education. The comparative analysis between the ongoing game industry issues in 2019 and 2020 has indicated that there were significant changes in the society’s attitude towards gaming. That is, in 2019, negative keywords arose including disease code and game addiction as associated with the WHO declaration to include gaming addiction to mental illness. In 2020, during the COVID-19 pandemic, the top keywords that arose includes contact-free, online, and digital, which signifies that the game industry was influenced by the pandemic, and users tend to move towards online gaming. These results are significantly important to understand the ongoing trend in the gaming industry, to guide the establishment of public game policies, and predict future gaming trends for the better improvement of the entire game industry in South Korea.The limitations in this paper have two aspects. First, one-year difference in this study is quite short to make a general conclusion about how the COVID-19 pandemic has influenced on the entire game industry in South Korea so further study will be necessary to conduct with an expanded data collection period and amount. Second, recent studies use various text mining techniques besides CONCOR or SNA that this paper applied. Thus, it requires to apply different methodology of text mining such as Topic Modeling, which is a machine learning technique that is capable of discovering the patterns within a set of documents, to check the analysis results to deduce more accurate and different aspects of meanings associated with the relationship between Covid-19 pandemic and game industry.


It has been shown that pentosidine and reactive free amine contents are significantly higher in elderly patients with ischemic heart disease. Pentosidine is also significantly higher in patients with arterial hypertension. Malondialdehyde turned out to be higher in patients with diabetes mellitus type 2 that was not treated with insulin or metformin than in those treated with both medications (p = 0.052). GAL3 was found to be lower both in persons without diabetes and in diabetics treated with metformin (p = 0.005). LOX-1 was higher in diabetic patients not treated with metformin or insulin, and lowest in diabetics treated with both insulin and metformin, with the effect of metformin reducing LOX-1 levels (p = 0.039). Our results were the basis for a discussion about the diagnostic value in the clinical practice of LOX-1 and GAL3 in geriatric patients with diabetes and also provide grounds for inferring the therapeutic benefits of insulin and metformin treatment.Medical care for geriatric patients is a great challenge, mainly due to various overlapping deficits relevant to numerous coexisting diseases, of which the most common are diabetes mellitus and atherosclerosis. In the case of diabetes, the glycation process is intensified, which accelerates atherosclerosis development and diabetic complications. Our goal was to investigate the relationship between the classical biochemical parameters of diabetes and atherosclerosis, as well as parameters which may indicate a nephropathy, and the parameters strictly related to glycation, taking into account the pharmacological treatment of patients. Methods: We analyzed the patients’ serum concentrations of fluorescent glycation product—pentosidine, concentrations of soluble receptors for advanced glycation products (sRAGE), lipoprotein receptor-1 (LOX-1), galectin 3 (GAL3), scavenger receptor class A (SR-A), and scavenger receptor class B (SR-BI), as well as the level of lipid peroxidation and free amine content. Among the identified correlations, the most interesting are the following: sRAGE with triglycerides (r = 0.47,  In 1909, the Viennese doctor Ignatz Leo Nascher introduced the term “geriatrics”, which meant “old age medicine” . In 2004The number and proportion of people aged 60 years and older in the global population is increasing. In 2019, the number of elderly people was 1 billion, and this number will increase to 1.4 billion by 2030 and 2.1 billion by 2050 [Clinical manifestations of diseases affecting elderly persons include a lot of somatic and mental problems. This applies to atherosclerotic cardiovascular disease, diabetes, arterial hypertension, osteoarthritis, urinary incontinence, hearing problems, and visual impairment, as well as osteoporosis and sarcopenia. Moreover, dementia, including Alzheimer’s disease and depression, cannot be omitted . FurtherDiabetes mellitus (DM), in particular type 2 diabetes (T2DM), is the most common disease in older adults. It is estimated that T2DM affects up to 40 percent of people over 65 years old in developed and even in developing countries . ApproxiChronically sustained high blood sugar levels lead to the damage and abnormal function of many organs, especially, the heart, blood vessels, kidneys, nerves, and eyesight ,14. DiabIn diabetes mellitus, the theory of oxidative stress is associated with autooxidation of glucose (glycoxidation), which produces reactive ketoaldehydes. This intensifies the process of non-enzymatic protein glycation leading to formation of advanced glycation end products (AGEs). During this process, due to the strong dependence on oxygen, many toxic oxygen derivatives are formed. In people with diabetes, the serum concentrations of pentosidine, pyraline, or carboxymethyl lysine are increased. The severity of the production of reactive oxygen species (ROS) depends on the degree of protein glycation and thus on glycemia. Many proteins in the body undergo the process of glycation, including proteins of the basement membrane and blood proteins .In the present study, a focus was placed not only on AGEs but also on their receptors. Glycation products are ligands for numerous proteins, the most important of which appear to be: receptor for advanced glycation end products , scavenger receptors class A  and class B, type I , lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1), and galectin 3 (GAL3) ,19,20,21Gaining detailed knowledge about the factors leading to the aging process and the course of diseases occurring in the elderly (including diabetes) makes it possible to develop a way to delay the decline in the functionality of the human body and at the same time extend life. Our goal was to investigate the relationship between the classical biochemical parameters of diabetes and atherosclerosis and the parameters strictly related to glycation, taking into account the hypoglycemic treatment of patients. This work can be called a preliminary study, allowing to identify directions for further research promising to demonstrate cause−effect relationships in geriatric diseases.The study group consisted of patients hospitalized at the Department of Geriatrics, University Teaching Hospital, in Wrocław. Included in this observational prospective study were blood samples of 79 consecutive patients, who gave conscious permission and fulfilled the inclusion criteria. The inclusion criteria for the study group were: age over 60 and the ability to express informed consent in the study. The exclusion criteria were: acute conditions in the 4 weeks prior to study participation, such as myocardial infarction, venous thromboembolism, stroke; as well as cancer. In total, 79 patients who were qualified for the scientific project gave written permission for participation in the study and taking biological materials. The Bioethical Commission at Wroclaw Medical University gave written permission (opinion number KB-344/2017). The results of routine laboratory tests, such as serum levels of: glucose, total protein, hemoglobin, glycated hemoglobin (HbA1c), C-reactive protein (CRP), cholesterol, HDL, LDL, triglycerides, creatinine, and uric acid, as well estimated glomerular filtration rate , were uPentosidine is a ribose-derived glyco-oxidation product of arginine and lysine residues and is one of the fluorescent forms of AGEs. The methodology of pentosidine determination was a slight modification of that of Leszek et al. . Serum sDetermination of the glutathione (one of main factors responsible for the antioxidative mechanism in the body) concentration is usually performed as a measure of thiol groups content using Ellman’s reagent ; DTNB). The method was developed in 1991 by Diplock  et al. T−1·L·cm−1.A method of estimation of lipid peroxidation intensity is based on the reaction of malondialdehyde with thiobarbituric acid (TBA). The pink product obtained was later determined by spectrophotometry . The reaThe procedure is described in the work of Fracasso et al. . Serum s® . The manufacturer’s instructions were followed.The concentration of GAL3 and LOX1 in serum samples was performed using human immunoassay ELISA kits from ElabscienceThe concentration of sRAGE, SCRAB1, and MSR1 in serum samples was performed using human immunoassay ELISA kits from ELK Biotechnology (ELK (Wuhan) Biotechnology CO., Ltd., Wuhan, China). The manufacturer’s instructions were followed.2 test. For comparison of all the variables between groups /without IHD; etc.), the Mann−Whitney U test was used. A Kruskal–Wallis test with post-hoc median test was used when comparing more than two continuous variables. All calculated p-values were two-sided, and the statistical significance level was set at p < 0.05. Spearman rank correlation analysis was used to determine associations between oxidative and inflammatory markers with selected parameters. To determine the most important predictors of AGE, pentosidine, and SR-BI levels, modeling with Generalized Linear Models (GLM) was used. As covariates in the models, all those variables which showed significant relationship with the dependent variable were introduced in the univariate analysis. The variables were fitted using Gaussian distribution with the identity link function. The models were constructed in a two-way step procedure based on the Wald test results with the significance level increased to 20% and Akaike information criterion (AIC). Statistics for the variables rejected during modeling, which are given in the tables, were obtained after their independent inclusion in the final model.Statistical analysis was conducted using the data analysis software system Statistica . Normality of distribution and homogeneity variance of parameters were checked, and if the parameters were not normal in distribution, a nonparametric test was chosen. Frequency analysis was conducted using Fisher’s exact test or χThe studied geriatric group is heterogeneous due to various disease states that affect individual patients . Therefop < 0.005 and are relatively little or not described in the literature on the subject, are emphasized, as given below:p = 0.031, p < 0.0001, p < 0.0001), with triglycerides , and negatively with GFR . The latter additionally correlates with HDL  (p = 0.0491) (p = 0.003) (Pentosidine has been shown to be higher in people with ischemic heart disease (IHD) ( 0.0018) A. Likewi 0.0491) B. It was= 0.003) C.p = 0.009)  D.p = 0.0047), and in the diabetic group it is lower in subjects treated with metformin as compared with diabetics treated with insulin or treated with drugs other than metformin and insulin (p = 0.0268) (Serum GAL3 content is found to be lower in nondiabetic subjects ( 0.0268) A,B.p = 0.0398)  C. The mep = 0.052) (MDA is higher in diabetic patients not treated with insulin or metformin than those treated with metformin and insulin simultaneously (= 0.052) D. The me2 6.60; df 1; p = 0.01).In the multivariate analysis of SR-BI levels based on HDL and uric acid, as the variables, only HDL turned out to be a significant predictor .The following variables were used in the multivariate analysis of pentosidine levels: IHD, hypertension, GFR, creatinine, and HbA1c. The best model included three predictors: IHD, hypertension, and GFR, of which the first two were barely significant  is the only marker of glycation that is routinely used in diagnostics. It is considered as the gold standard in the estimation of long-term glycemia because it is considered to reflect a weighted measure of the average blood glucose levels during the past 120 days and has been shown to correlate with adverse outcomes in diabetics, especially related to microvascular complications ,28. The The expected result was the observation of a correlation between pentosidine and HbA1c. This effect has not been observed. Instead, we found a correlation between parameter pairs: HbA1c-GAL3 and HbA1c-BMI. Lack of correlation between serum pentosidine and HbA1c was reported previously by, for example, Hashimoto et al. or Sato et al. ,31. It cGalectin-3 is a protein from the group of β-galactoside binding lectins with pro-inflammatory properties, presented as a novel biomarker of pathological conditions, such as various types of cancer, especially thyroid cancer , acute aThe correlation of galectin-3 with BMI values has been demonstrated repeatedly in different study groups ,37,38. OAccording to our observations, galectin-3 inversely correlates with GFR, indicating a relationship with kidney damage. Many studies have already concluded that galectin-3 strongly affects this organ’s fibrosis, and it has even been suggested that its measurement will allow to predict renal failure and patients’ survival ,42.Moreover, galectin 3 affects fibrosis of many other organs, including the heart after myocardial infarction (MI), hence the need to lower the level of this glycoprotein in order to avoid heart failure after MI . Our stuAnother issue is the previously proven thrombogenic effect of galectin-3 ,46. The In our study, galectin 3 is significantly higher in elderly patients with diabetes type 2 compared with patients without diabetes. It would seem that galectin 3 is a very interesting diagnostic tool. Many authors present it as a novel biomarker—for example, Hrynchyshyn et al. and Kanukurti et al. present it as a new biomarker for the diagnosis, analysis, and prognosis of acute and chronic heart failure ,33; KingHowever, doubts as to its diagnostic value are raised by the multitude of pathological conditions associated with an elevated level of this protein. When determining its elevated level, the geriatricians cannot state whether the cause is diabetes, heart failure, pancreatitis, cancer, or depression. It seems that this parameter is not specific, thus is of little diagnostic value.The second of the analyzed receptors for AGE, i.e., receptor for advanced glycation end products (RAGE), is the protein responsible for inflammation, apoptosis, reactive oxygen species (ROS) signaling, proliferation, and autophagy . sRAGE iIn our study group, the negative correlation between SR-BI and HDL was also observed. This is an expected result, as it has been proven that elevating SR-BI expression causes an increase in HDL clearance, a reduction in plasma HDL levels, and an increase in biliary cholesterol levels .The analysis revealed also that SR-BI correlates with one more parameter—Lectin-type oxidized LDL receptor 1. In the latest publications (2020 and 2021), LOX-1 is presented as a promising target for early diagnosis and cardiovascular risk prediction ,50,51. SThrough modeling, we found that for SR-BI, HDL is a good predictor. West reported this relationship for subjects with hyperalphalipoproteinemia . This isMetformin is the most prescribed glucose-lowering medicine worldwide and has been used to treat diabetes since 1957 . In the Numerous data from in vitro experiments indicate that metformin inhibits the expression of LOX-1. This is evidenced, for example, by the data of Hung et al., who studied this dependence in human umbilical vein endothelial cells (HUVECs) ; by ShiuFree amine groups are potentially available to react with a reducing sugar; therefore, this is an important parameter regarding the potential for glycation. In addition, Valencia et al. found that free amine content measured using OPA correlates strongly with RAGE binding affinity to AGE . FracessIn addition to free amine content, we also observe higher pentosidine values in patients with ischemic heart disease. This was an expected result, as it was previously reported that circulating fluorescent AGE and pentosidine levels have been associated with cardiovascular disease ,63,64,65It is stated that the kidney normally clears circulating AGEs, but these products accumulate both in diabetic and not-diabetic nephropathy . PentosiWe do not try to present fluorescence of pentosidine as a diagnostic tool, but we want to pay attention to the low cost, speed, and simplicity of AGEs determination by measuring fluorescence compared to other methods, such as enzyme immunoassay or liquid chromatography with tandem mass spectrometry (LC-MS/MS). For research purposes, this method seems to be sufficient.The glycation pathway is associated with reactive oxidative species (ROS) and with peroxidation. ROS peroxidize membrane unsaturated fatty acids, leading to the generation of reactive aldehydes as advanced lipid peroxidation end products (ALE). Resulting reactive aldehydes react with proteins to cause an alteration of protein structure to exacerbate the complication of diseases such as diabetes and atherosclerosis . One of The diagnosis of diseases of old age is constantly developing. Today, we have the ability to use parameters that were unavailable even several or several dozen years ago, because basic sciences discovered their importance only relatively recently. The mentioned glycated hemoglobin came into use at the end of the 20th century , and nowIn this project, it was shown that glutathione and SR-A have no noticeable value as indicators of typical geriatric diseases, but other parameters appear to be interestingly related to pathologies of old age. According to the study, pentosidine is significantly increased in ischemic heart disease and arterial hypertension and is also associated with kidney function. We also found indications that sRAGE and SR-BI have anti-atherogenic effects. The role of galectin 3 and LOX-1 in the pathomechanism of senile diseases is still under investigation. In our study, we observed a difference in the concentration of these proteins depending on the treatment. Combined treatment with insulin and metformin seems to be particularly beneficial as it reduces the intensity of lipid peroxidation and probably influences the expression of the protein responsible for lipoprotein binding, thus having the potential to inhibit atherosclerosis. Metformin alone results in a decrease in galectin 3, which may protect against fibrosis and organ failure, such as the kidneys and the heart.As emphasized several times in the discussion, this research should be repeated on a larger geriatric population. However, this is likely a great value in this research direction due to the possibility of finding a parameter that allowed for an even earlier diagnosis of prediabetic conditions or other numerous diseases of old age, as well as the possibility of monitoring the treatment of metabolic diseases typical of the elderly.


No similar correlations were observed in the NE group, except for the mean amplitude EO p = 0.033 and sway area EO p = 0.030. There was one difference between the BL and the NE group for the mean amplitude parameter, p = 0.018, in a solid surface test with open eyes. The results were higher in the BL group. Conclusions: The present study showed no worse balance in the BL group than in the NE group but worse performance on the foam than without it. It indicates the need to develop body balance skills in blind people by improving their proprioceptive sensitivity. In everyday life and training, blind people should experience exteroceptive stimuli, different textures, and unstable surfaces as much as possible.Aim: The study was designed to assess the effects of surface instability in the response of the balance control system in children and youths with visual impairment (BL) and in normally sighted controls (NE). Materials and Methods: The empirical research study involved 80 individuals, aged from 6 to 20 years, with a mean age of 14.37 (±4.68), including 40 blind individuals and a randomly selected control group 40 normally sighted. Stabilometric measurements were performed with the use of the Platform CQ Stab 2P, with eyes open (EO) and closed (EC) on the solid surface, and then, the same procedure was performed on the platform covered with 1-centimetre-thick foam. Results: Statistical analyses  of the results identified during the trials reveal the following findings in the BL group in the EO and EC tests. The results of the foam surface test were higher and the differences were statistically significant in the BL group (sway path EO  The organ of vision plays a role in maintaining balance, as shown by numerous studies ,4,5,6,7.Sipko and Skolimowski  report tIn individuals with visual impairments, the interaction of the somatosensory and vestibular systems may be augmented, as a result of which these functions play the main role in balance maintenance, and they compensate for insufficient visual input. Schwesig et al.  point ou3), and 1 cm thick. The feet in both trials were positioned in free stride, allowing for repeatability of measurement.Literature review shows a scarcity of research reports discussing dynamic balance and the effects of proprioception in postural control in individuals with visual impairments ,15. ThisThe study was designed to assess the effects of surface instability in the response of the balance control system in blind children and youths compared to sighted controls. The hypothesis was that blind individuals would have worse balance characteristics.After applying the inclusion and exclusion criterion, the analysis contained 80 people who did not meet the criteria for physical activity, according to the index classification of Moderate-to-Vigorous Physical Activity—MVPA. Participants came from the Subcarpathian region of Poland, were aged 6 to 20 years, with a mean age of 14.37 (±4.68) years, a mean body height of 151.52 cm (±19.99), and a body weight of 51.81 kg (±20.67). In this study, there were 40 participants in the blind group (BL) and 40 participants in the control group ), including 20 women and 20 men in each group, aged 6 to 20 years. The mean body height BL was 150.84 cm (±20.59) and NE 152.2 (±19.38), and the body weight BL was 51.40 kg (±21.13) and NE 22.20 kg (±20.21). According to the WHO classification, the study population is children and youths ,17,18.The study was divided into three phases. In the first stage, declarations related to participation in the study were submitted by the parents of the children and the adult persons, aged 6–20, who were members of the Polish Association of the Blind’s Podkarpackie Region Branch (250 subjects). In the second stage, the parents or adult participants completed questionnaires, based on which, subjects qualified for the next stage . During the third stage, the subjects were examined for the essential anthropometric characteristics, body height and mass, and took part in a balance test . The statistical power of our study was 0.80, the same as the recommended power of 0.8, and the required number of people per group was 40. The eligibility criteria are shown in Ultimately, all the study stages were completed by 40 blind individuals (BL)—who had certificates of congenital visual impairment ICD 10—H54 and blindness was defined as visual acuity of less than 3/60 (0.05) or corresponding visual field loss in the better eye with best possible correction ,20. All Physically active people are physically active for 7 days per week, with cumulative physical activity for a minimum of 1 h per day. Physical activity includes all activities that accelerate breathing and heart rate, e.g., cycling, sports game, and physical education at school.After eligibility criteria were met, the control group , matched for age and gender to the study group) was randomly selected from among 500 students, inactive by the index MVPA classification, and attending schools in the Podkarpackie Region, Poland. All the persons recruited for the study could walk unassisted and did not use any orthopaedic aids . All the subjects were able to assume the standing position for the assessment. Individuals with neurological disorders or motor deficits, impairing their ability to maintain balance in a standing position without aid, and/or those using any orthopaedic tools were excluded. The eligibility criteria were as follows: absence of injuries or musculoskeletal pain in the previous six months, because it has been proven in experimental studies that muscle tissue is completely regenerated after about 3 to 6 months ,24; and The local bioethics commission approved the study.All the measurements were performed on the same day, starting with anthropometric measurements. Body height was measured with a Seca 213 mobile stadiometer, with an accuracy of 0.1 cm. Body mass was measured using the electronic scale, OMRON BF 500, with an accuracy of 0.1 kg. The measurements were performed under standard conditions; children were in underwear and barefoot, stood upright, without bending knees.Sway path (SP) (mm)—the total length of the path in the sagittal and frontal plane;Mean amplitude (MA) (mm)—mean deflection of the COP;Mean velocity (MV) (mm/s)—mean speed of COP excursions along the sagittal and frontal plane;2)—area delineated by the COP;Sway area (SA)  ,27,28,29p < 0.05.The acquired material was subjected to statistical analyses, computed using Statistica 12.5. The normality of distributions was verified with the Shapiro–Wilk W test, and equality of variances was assessed with Levene’s test. A nonparametric Mann–Whitney U test for independent samples was used to assess the differences in the mean values of the balance parameters between the blind subjects and the controls. Intragroup variability for the same subjects was examined using a Wilcoxon matched-pairs test in two measurements on the solid surface and the foam surface. Statistical significance was assumed at p = 0.009), mean velocity MV-EO , sway area SA-EO (p = 0.017), and number of COP deflections along the sagittal plane LWAP-EO (p = 0.004) (p = 0.006), mean amplitude MA-EC (p = 0.030), mean velocity MV-EC (p = 0.006), and sway area SA-EC (p = 0.009)  . Higher = 0.009) . Higher p = 0.033), and SA-EO (p = 0.030) (p = 0.052), SA-EC (p = 0.052), and MA-EC (p = 0.067) were approaching the threshold of statistical significance  . The resificance .Statistical analyses using the Mann–Whitney U test showed no significant differences between the results acquired by subjects in the BL and the NE groups, in trials with eyes open on the foam surface . Similarp = 0.018)  . No sign= 0.018) .This study investigated the effects of surface instability on the response of the balance control system in people with visual impairment (BL) and normally sighted controls (NE). The significant findings of the present study did not show poorer balance in the BL group compared to the NE group. However, in the tests on the unstable surface, considerable sensitivity to the interfering factor’s effects was observed in the BL group. Therefore, the results do not support the hypothesis that blind children and youths have poorer balance characteristics than sighted peers.We took up this subject matter in our study because balance-related problems resulting from proprioceptive disturbances  in people with visual impairments and normally sighted controls are under-researched ,15. FurtThe present study’s findings show no differences in balance parameters between the BL and NE groups in the trials on the foam surface, with eyes open or closed. It is likely that proprioception, the primary source of information for BL subjects, makes it possible for them to perform stabilometric tests as effectively as NE subjects. We are aware that the participants of our study represent a wide range of age groups, making it difficult to compare our results to other studies. Because of this, we discuss our findings separately by reference to studies involving only adults or children. As regards the former, Nakata and Yabe, in their study, compared the automatic postural responses in congenitally blind and sighted male subjects aged 19–24 years. During the trials, four types of perturbations (forward and backward translations and toe up and down rotations) were randomly applied to induce postural responses in the subjects. The authors reported no differences between the postural responses of blind and sighted subjects to platform displacements, and as a result, they postulated that the ability to control postural balance during perturbations of this type was not affected by vision loss from birth. Hence, it seems that the absence of vision from birth in humans does not affect the automatic postural response systems .On the other hand, Rogge et al. carried out a study in which balance training was provided to blind adult individuals as well as age- and gender-matched sighted controls. Assessment of the effects showed similar balance performance improvement in both groups . FurtherOther researchers, however, have reported poorer functioning of the balance system in blind or partially sighted populations. Houwen et al.  conducteThe present study shows a relationship between the type of floor surface and balance control parameters in BL subjects compared to NE individuals. In the BL group, there were differences in the values measured during trials with eyes open on stable versus unstable surfaces. In the NE group, the results did not differ similarly: the differences were only observed in the mean amplitude and the sway area in trials with eyes open, with higher values measured on the foam surface compared to the solid surface. This observation gains significance in light of the evidence suggesting that up until 12 or even 15 years of age, children cannot fully use vestibular and visual stimuli in the process of balance control. According to Paszko-Patej et al. , blind oIn summary, it can be stipulated that proprioception plays an essential role in balance control, given the fact that higher balance parameters are observed in BL subjects on an unstable surface. This information may be helpful for therapists working with BL individuals. It should be taken into account by those designing therapeutic programs for this population. Foam mats and other unstable surfaces should be used in training pro-grammes. In everyday life, blind people should experience as many exteroceptive stimuli, different textures, and unstable surfaces as possible. Consequently, further research is needed to investigate this issue in more detail to facilitate a more accurate assessment of postural stability in BL individuals.The presented study has some limitations. The most significant is the wide age deviation of the respondents. We surveyed all willing persons who applied from the Polish Association of the Blind, Podkarpackie Branch. To partially offset this deviation, we matched the group 1:1, considering the age and gender. In addition, to ensure homogeneity of the study group, only people blind from birth qualified; all participants were physically inactive. We also recognise that balance and proprioception can vary significantly with age. Therefore, further research is needed that includes the division into age groups: children, adolescents, adults, and older people with BL. We think it would be interesting to compare balance in these age groups since involutionary changes occur in all systems of the human body, including those responsible for balance. A lack of clear-cut differences between the groups may be associated with the subject’s age and the related balance system immaturity and lability, characteristic of children and adolescents up to 15–16 years of age. This may also be associated with the less important roles of the vestibular and visual systems in balance control.On the other hand, the data suggest that proprioception is the primary source of afferent input in balance control in BL subjects. As mentioned above, the group studied is individuals who have been blind since birth, that is, those who do not respond to all visual stimuli. It would also be worthwhile to conduct further studies on balance assessment according to the severity of the visual impairment and consider the impairment of monocular and binocular vision. In our study, all the participants were physically inactive, so it is necessary to continue the study with a consideration of physically active people with BL, taking into account the level or type of physical activity practised.The present study’s findings did not show poorer balance in the BL group compared to the NE group. However, in the tests on the unstable surface, considerable sensitivity to the effects of the interfering factor was observed in the BL group. Proprioception plays an important role in balance control, given that a change in the surface leads to increased balance parameters in subjects with visual dysfunction. This explicitly shows it is necessary to develop body balance skills in blind subjects, by improving their proprioceptive sensibility and by building their spatial awareness of the body location. Foam mats and other unstable surfaces should be used in the training programme. In everyday life, blind people should experience as many exteroceptive stimuli, different textures, and unstable surfaces as possible.


Investigating psychological characteristics through self-reported measures  and dynamic behaviors through objective measures  may allow us to better understand the behavior of at-risk drivers. To assess drivers’ motivation, the theoretical framework of achievement goals has been studied recently. These achievement goals can influence the decision-making and behaviors of individuals engaged in driving. The four achievement goals in driving are: seeking to improve or to drive as well as possible (mastery-approach), to outperform other drivers (performance-approach), to avoid driving badly (mastery-avoidance), and to avoid being the worst driver (performance-avoidance). Naturalistic Driving Studies (NDS) provide access to the objective measurements of data not accessible through self-reported measurements . Three dynamic criteria have been developed to characterize the behavior of motorists objectively: driving events, time spent above acceleration thresholds , and the extent of dynamic demands. All these criteria have been measured in different road contexts . The aim of this study was to examine the predictive role of the four achievement goals on these objective driving behaviors. 266 drivers  took part in the study, and 4 242 482 km was recorded during 8 months. Simultaneously, they completed the Achievement Goals in Driving Questionnaire. The main results highlighted that mastery-approach goals negatively predicted hard braking and the extent of dynamic demands on plain and hilly roads. Mastery-approach goals seem to be the most protective goals in driving. Future research on the promotion of mastery-approach goals in driving may be able to modify the behavior of at-risk drivers. In Europe, 80 559 people died on the road in 2016  estimateThe achievement goal theory has been widely used in the literature to assess the motivations of individuals engaged in an achievement context. The work of Maehr and Nicholls  and DwecIn the 1980s, the first researchers at the origin of this theoretical framework , 13, 16 The driving behavior variables related to achievement goals in Mascret et al. , 11 studInitially in the 1970s , drivingFrom the objective data collected in the NDS, variables have been developed to characterize driver behavior, such as driving incidents, extent of dynamic demands, and percentages of time spent above acceleration thresholds.In general, it is difficult to assess driver behavior during crashes because of the rarity of these events. Therefore, near-crashes and incidents are often studied . Wu et a2 intervals. The number of different crossings reached (the area of the 2D graph) gives an indication of the dynamic load levels and, in particular, the extreme values reached at least once by the driver. The more a driver explores the high dynamic capabilities of his vehicle load, the larger the area of the acceleration crossing will be. Liu et al. [To study the dynamic demands generated by drivers with their vehicle , Lechner and Naude  developeu et al.  used a bTo assess high acceleration, braking and cornering demands, Lechner and Perrin , and NauTo investigate driving behavior, it may be relevant to consider the driving environment, and more particularly the type of road , but also the relief on which the road is situated . Indeed, Lechner and Perrin  observedRecently, real-world driver behavior has been studied in relation to personality traits or characteristics, such as anger , opennesVan Yperen et al.  in theirIn the meta-analysis of Van Yperen et al. , performIn education, sport, and work, mastery-approach goals are the most adaptative goals  and theyageM = 42.08 years, SD = 11.38, range = 22–77 years) voluntarily and anonymously participated in the study. Only drivers with a category B license  were included , with an average of 649 trips per drivers (SD = 377), an average driving time of 202 hours per drivers (SD = 100), and with a total mileage of 4 242 482 kilometers .266 French drivers  developed by DDI (Driving Data to Intelligence), a subsidiary of Michelin that exploits mobility data. This data collection system includes a GPS with a frequency of 1 Hertz, and a three-dimension accelerometer  with an acquisition frequency of 5 Hertz. Driving data were collected continuously during 8 months, representing a total of approximately 53 730 hours of driving. Individuals commit to being the only ones to drive their equipped vehicle during the recording period. Participants also filled out the questionnaire assessing achievement goals in driving, after the 8-month recording period. They gave informed consent and were not made aware of the purpose of the study. The study met the requirements of the institutional board of Aix-Marseille University and of the Commission Nationale de l’Informatique et des Libertés (n˚2004–801). The consent was requested and obtained in written form. The data were collected and analyzed completely anonymously.When driving, my goal is to drive better and better”), performance-approach goals , mastery-avoidance goals , and performance-avoidance goals  were assessed using a Likert scale ranging from 1 (completely disagree) to 5 (completely agree). Results of the confirmatory factor analysis were acceptable [χ2  = 124.43, p < .001, CFI = .936, TLI = .912, SRMR = .053, RMSEA = .073. Using McDonald’s omegas, a good level of internal consistency [ω = .712) and performance-approach goals (ω = .837). The internal consistency of mastery-approach (ω = .693) and performance-avoidance goals (ω = .697) was somewhat low, but the value is very close to .700, which can be considered acceptable.The four achievement goals in driving were assessed using the Achievement Goals in Driving Questionnaire . Masterceptable , 50: χ2 sistency  was foun2 was then obtained. Finally, the percentage of time during which each driver exceeded a longitudinal acceleration of 3 m/s2 was calculated. A high percentage indicates that the driver often performed high accelerations. The percentage of time each driver spent below -3 m/s2 longitudinal acceleration, indicating hard braking, was also calculated. A high percentage indicates that the driver was often performing hard braking. This threshold was used in the 100-Car study by Klauer et al. [Longitudinal accelerations were recorded continuously for each vehicle during the data collection period with a frequency of 5 Hertz. A distribution of longitudinal accelerations every 1 m/sr et al.  and alsor et al.  to asses2 was calculated. This threshold has been used in various studies [Lateral accelerations, representing the centrifugal force pushing the vehicle outward when cornering, were also recorded at a frequency of 5 Hertz and the percentage of time during which each driver exceeded a lateral acceleration of 3 m/s studies , 52 to aIncidents are critical driving situations considered risky because the vehicle reaches high dynamic demands in the longitudinal lateral or combined directions. Incident detection is based on the work of Naude et al. . We consThe acquisition frequency in the present study is 5 Hz whereas Naude et al.  developeThe thresholds used by Naude et al.  are:2 and Jerk > 2 m/s3,Speed < 80 km/h, and Acceleration norm (x and y) > 6 m/s2 and Jerk > 2 m/s3,Speed > 80 km/h and Acceleration norm (x and y) > 5 m/s2 and Jerk > 2 m/s3.Speed > 100 km/h and Acceleration norm (x and y) > 4 m/sThe thresholds used in the study are:2 & Jerk norm (x and y) > 3 m/s3Acceleration norm (x and y) > 6 m/sThe number of incidents for a driver depends on his or her mileage. To get a representative indicator of driving style, the total driving time (in minutes) was divided by the total number of incidents. A high ratio indicates that the driver has a relatively calm driving style. A low ratio indicates sporty or riskier driving style .This variable consists in crossing the lateral and longitudinal accelerations in a 2d matrix. The indicator used to characterize this extent is the percentage of filling of the matrix. A high value represents a driver who has strongly stressed his vehicle in acceleration, braking, and/or combined demands. For an illustration, see Using the methodology developed by Michelin, we were able to know the type of road  and the topography  at each instant of driving. All the variables which objectively characterize the driving behavior  have been measured in all these contexts.χ2 (9) = 27.88, p < .001) was calculated to detect outliers [Mahalanobis distance at the multivariate level  generally brake less, and use the vehicle less dynamically. Performance-approach goals are positive predictors of longitudinal acceleration above 3 m/s2. This means that drivers who want to outperform other drivers generally accelerate more. Performance-avoidance goals are positive predictors of global extent of dynamics demands. In other terms, drivers who want to avoid being worse drivers than others generally use the vehicle more dynamically. The detailed results are presented in After controlling for gender, age, years of driving license, and driving time, the results of the regression analysis showed that mastery-approach goals are negative predictors of braking lower than -3 m/s2 in plain and also on hilly roads, and finally of right turn above 3 m/s2 on hilly roads , particularly on plain and hilly roads. Feeling in control of the driving task does not result in hard braking on plain and hilly roads nor in erratic dynamic demands of one’s vehicle on plain roads. All these results confirm our hypotheses, and relations observed in other domains [This study is the first to relate achievement goals to objective measures of driving behavior. It improves and expands the understanding of drivers’ psychological characteristics and driving behavior. This study showed the predictive role of achievement goals on some objective driving behaviors: incidents, percentage of time spent over an acceleration threshold, and extent of dynamic demands. In general, mastery-approach goals were found to be negative predictors of the extent of dynamic demands. By focusing on the road context, this relationship is also observed in plain. These goals are also negative predictors of heavy braking . This relationship is confirmed on hilly and plain roads. They are also positive predictors of heavy transversal accelerations on left turns on plain roads. For these individuals, making strong accelerations on hilly and plain roads and taking left turns quickly on plain roads is a way of showing their superiority to others. This is consistent with our hypothesis and with findings in other domains , in which performance-approach goals positively predict cheating and aggressive behaviors [Our study also showed that performance-approach goals are significant positive predictors of high longitudinal acceleration , whereas in the driving literature  and in oOur study also showed that performance-avoidance goals are positive predictors of the extent of dynamic demands in general, and more specifically on plain, urban and extra-urban roads. Higher dynamic demands can generate more risky driving situations. In the literature on achievement goals in work and education, these goals are often linked to negative outcomes such as anxiety, negative affect, and low performance , 61. SimMastery-avoidance goals were found to be positive predictors of the extent of dynamic demands on plain roads, and negative predictors of important accelerations on mountains roads. These goals are linked to a negative consequence (important dynamic demands on plain roads) and a positive consequence (low acceleration in the mountains). These results are consistent with our hypotheses and with the protective role observed in driving with self-reported measured , 11. MorIn addition, no significant relationship was found between incidents and achievement goals. This result can be explained by the fact that an incident is not only related to the driver’s behavior, but also to the other road users’ behaviors, and by the state of road infrastructure, which were not assessed in this study.The study has several limitations that open up perspectives for future studies. First, the study was conducted in a single country (France), yet Hulleman et al.  showed tAchievement goals theory has been widely studied since the 1980s , 72, 73 S1 File(XLSX)Click here for additional data file.