Descriptive statistics methods, Wilcoxon W-test, and multiple regression analysis were used for statistical analysis in the R software environment, version 3.5.2. The findings of our research showed that Nationalistic and Patriotic ENA are the strongest predictors of studied ICC scales and have an opposite negative impact on Acceptance and Absolutization in both male and female students. This fact should be taken into account in the context of ICC developments.The search for predictors of intercultural competence (ICC) development is one of the important challenges of modern psychology in connection with globalization in all the spheres of modern life, including university education. The purpose of the present research is to show that the ethno-national attitudes (ENA), which Khukhlaev et al. consider as an individual’s predisposition to assess the nationality/ethnicity can determine the severity of ICC features in male and female university students. The sample includes 219  first–third year Russian university students. ICC was measured with the author’s modification of the intercultural sensitivity scale (ISS) by Khuhlaev and Chibisova. ISS is based on the Developmental Model of Intercultural Sensitivity, (DMIS) by Bennett and includes 4 subscales: Minimization, Absolutization, Ambivalence, Acceptance. ENA  were determined with the  The development of intercultural competence (ICC) is one of the most important theoretical, applied, and practical psychological problems in the changing and globalizing world ,2,3,4. Tintercultural communicative competence [intercultural sensitivity [cultural intelligence [multicultural effectiveness [intercultural competence (ICC) in the broadest sense, as a generalizing definition of the phenomenon characterizing the personality activity in a multicultural environment towards the different aspects of intercultural diversity and dialogue [Western and Russian scientists have developed more than 60 different models of the ICC ,4,6,7,8 mpetence ,10, intesitivity ,11,12, clligence ,14, multtiveness , and somtiveness . The ICCdialogue ,18,19,20denial of cultural differences, creating the defense from the differences and minimizing their influence. The following three ethnorelativistic stages imply acceptance of cultural differences, adaptation to their influence and integration of another worldview with one’s own [The Development Model of Intercultural Sensitivity (DMIS) by Bennett ,21 is onne’s own .intercultural sensitivity scale (ISS) for ICC diagnostics based on the DMIS, which includes 4 subscales: Minimization, Absolutization, Ambivalence, and Acceptance. Minimization and Absolutization correspond to ethnocentric orientations according to the DMIS. Ambivalence is a transitional orientation from ethnocentrism to ethnorelativism. Acceptance corresponds to ethnorelative orientations according to the DMIS [Russian psychologists Khukhlaev and Chibisova developed a Russian-language technique called the the DMIS ,23.socio-cultural, social-psychological, personality, and individual determinants [socio-cultural factors of ICC  are fairly well studied on the basis of different models [Numerous empirical studies revealed that the development of ICC is associated with various rminants ,15,16,23t models ,28,29,30socio-psychological factors of the ICC, various social attitudes are primarily studied [Among the  studied ,32,33. W studied , a lot o studied ,36 as we studied ,38, whicIn Russian psychology, ethnic attitudes are actively studied in connection with the problem of nationalism and extremism. Khuhlaev proposes to consider “ethno-national attitudes” (ENA) as attitudes towards the phenomenon of “nationality” , which ipersonality and individual determinants of ICC are less studied than socio-cultural and socio-psychological factors, especially in Russian psychology. Recently, in Western psychology, the influence of different personality traits on the ICC and related concepts has been actively studied [Acceptance; extraversion and agreeableness with Ambivalence; and agreeableness with Absolutization in university students [consciousness: it has a positive impact on Minimization in school students, a positive impact on Acceptance in university students, and a weak but negative impact on Absolutization  in both groups of students [In our opinion,  studied ,44,45,46 studied ,18,19,20 studied ,48. We f studied ,18,19. Nstudents ,19. FFM individual predictors of the ICC include age and gender, which both are poorly researched. Most studies of the ICC problem have been performed on student and adult samples, while the characteristics of ICC in adolescents have not been sufficiently studied [Absolutization scale: women are more confident than men in their ability to control the influence of cultural differences on the communication process [Absolutization scale, and also found gender differences on the Acceptance scale  [Possible  studied . Insuffi studied . However studied . The opp studied . Using t process . In our  process ,50, we ctudents) ,50.In summary, we emphasize once again that ICC development is determined by a combination of factors: socio-cultural, socio-psychological, personality, and individual, which must be studied together. Due to the fact that there are so few studies of the ICC based on the DMIS and its Russian modifications in Russian psychology, the research of any ICC predictors of different levels, for example socio-psychological (ENA) and individual (gender differences), is relevant.Thus, the purpose of the present study is to consider the ethno-national attitudes as ICC predictors based on the DMIS and compare their impacts in male and female university students. Patriotic ethno-national attitudes will have a positive impact on the ICC development . Although Khukhlaev et al. [Nationalist ethno-national attitudes, on the contrary, can become a barrier to the ICC development , because they are based on hostility to other cultures. The impact of Neutral and Negativistic ethno-national attitudes may be ambiguous, since, on the one hand, they reduce the probability of a conflict comparison of one’s own and other ethnic groups and therefore can positively influence the ICC development, but on the other hand, an indifferent and negative attitude to the nationality (ethnicity) can interfere with intercultural differences perception, which, in turn, reduces the possibility of ICC development. Based on our previous research of ICC [Based on the ethno-national attitudes definition and the results of its research in the context of intercultural relations ,42,51,52v et al. ,41,42,52h of ICC , we alsoA total of 219  university students, aged 17 to 24 (the mean is 19.06 ± 1.57 years) took part in the research. All of them were first-, second- and third-year students of different departments of two large Moscow universities . The students represent different regions of Russia, as well as the republics of the former USSR. All of them are ethnically Russian, speak Russian as a native language and study in Russian. They participated in the study during classes in psychological and pedagogical disciplines, as one of the elective tasks, for which they received additional points. They were advised that participation would be free and voluntary. All subjects gave their informed consent for inclusion before they participated in the study. The study was conducted in accordance with the APA Ethical Standards and the Code of Ethics of the RPS , and the protocol was approved by the Ethics Committee of RUDN University (# 050422-0-015).Intercultural Sensitivity Scale (ISS) by Khukhlaev and Chibisova [Minimization, Absolutization, Ambivalence, Acceptance), described in detail above. We used the author’s modifications of this technique with the following changes [The hibisova  in Logashibisova  contains changes ,18,19,20(1) We asked respondents to express their degree of consent with items using a direct response Likert scale: from 0  to 10 (“absolutely agree”), instead of a reverse scale that was used in the previous modification by Logashchenko;α and McDonald’s hω. All subscales of the ISS modified by us have acceptable Cronbach α coefficients (0.60–0.78) and McDonald hω coefficients (0.47–0.76), which indicates their acceptable internal consistency [(2) We reduced the number of items on each subscale to 8 based on a psychometric study using factor analysis, and the coefficients Cronbach’ sistency ,54. In tethno-national attitudes scale (ENAS) by Khukhlaev, Kuznetsov, and Tkachenko [The kachenko  consistsNationalistic Attitudes subscale are: (1) There are such nationalities, among which almost all people are bad; (2) I don’t like it if a person near me starts to speak a native (not our) language. Sample items from the Patriotic Attitudes subscale are: (1) When I think about my nationality, I feel pride and love; (2) I feel a kinship with people of my nationality. Some items from the Neutral Attitudes subscale include: (1) For me, my nationality plays no role in everyday life; (2) Nationality exists, but it is not very important. Finally, example items from the Negativistic Attitudes subscale are: (1) Separation of nationalities harms society; (2) It’s not very right to separate people according to nationality.Subscales have good internal consistency, as well as configurational and measurement invariance . Exampleα and McDonald’s ω, Wilcoxon rank sum test with continuity correction, Fisher F-test, and the multiple regression analysis were used for statistical analysis. The regression analysis by the method of “backward” stepwise search was used. Independent variables were the ethno-national attitudes  and dependent variables were the ICC features . In a first step, the full regression models with all possible predictors for each ISS subscale were constructed separately for male and female students. The next step involved analyzing all the input models by the method of search of all possible predictor combinations with evaluating the informational contribution of each set using the Akaike information criterion (AIC). Models having the highest information load at the smallest quantity of predictors (“a best predictor model”) were selected for further analysis. Statistical processing was carried out in the R software environment for statistical computing and graphics, version 3.5.2 [The descriptive statistics methods, coefficients Cronbach’ on 3.5.2 .W-test in male and female students. Significant differences exist only between Neutral attitudes, which are higher in male students (p = 0.049). F-test, which confirms that there is a significant impact of the ethno-national attitudes (ENA) on the ICC indicators. At the same time, there is a large range of the determination coefficients (R2), which reflects the different degree of the ENA influence on different ISS subscales.The results of the multiple regression analysis (best predictor models) are presented in Acceptance predicts 10.4% of the variance in the general sample, 18.1% in male students and only 8.3% in female students. The significant predictors of Acceptance  in all studied samples are Nationalistic and Patriotic ENA, but its influence is opposite: Nationalistic ENA has a negative impact, while Patriotic ENA has a positive one. The revealed impacts completely correspond to our hypothesis and to the definition of Nationalistic and Patriotic ENA. It can be noted that both predictors have a stronger impact in male than in female students and this fact is also consistent with our assumptions. Ambivalence (transition stage from ethnocentrism to ethno-relativism) predict only by 3%–4% of the variance in the all samples. Differences between samples are that Patriotic ENA as a positive predictor is not significant in male students, while a significant model in female students includes Neutral ENA with negative impact. Absolutization  the regression models with the highest determination coefficients were obtained (R2 = 0.336–0.356) in all studied samples. As expected, Nationalistic ENA have a strong positive impact on Absolutization that manifests itself in an exaggeration of the significance of cultural differences, in the attribution to the cultural characteristics of a stronger influence than they actually have, and in a purposeful search for cultural or ethnic attributes that favorably distinguish their own ethno-cultural group from others. Neutral (indifferent) ENA, on the contrary, have a negative impact on Absolutization and prevent the overestimation of cultural characteristics and differences. The only difference in the regression models between the studied samples is that Neutral ENA are not significant predictors in male students, despite the fact that they are higher in this group.Minimization  was obtained only in the general sample of university students and in female students. These models include Nationalistic and Patriotic ENA with weak negative impacts (R2 = 0.050–0.062).The purpose of the present study is to consider ethno-national attitudes as ICC predictors based on the DMIS, and compare their impacts in male and female university students. We surmise that ENA, especially Patriotic and Nationalistic, can predict the features of ICC in opposite ways and that their influence varies in male and female samples. Summarizing the results of the study, we can conclude that our hypothesis was mainly confirmed regarding the ENA impact on ICC, but less confirmed regarding gender differences.Absolutization  and a negative impact on Acceptance , and Patriotic ENA has a reverse effect in these cases. These ENA have the same impact on ICC in the general sample and in male and female students groups. Thirdly, minor differences in ENA impact on ICC features were identified between male and female university students, but they are not as significant as we expected. Regarding the lack of significant gender differences between the ICC scales, our data are consistent with the findings of Hammer et al. [Firstly, it was found that the ENA can explain from 3.1% to 35.6% of the ICC variance on the basis of the DMIS. Such determination coefficients are considered to be a not very high, yet the result can be deemed satisfactory, given the huge quantity of external and internal factors influencing the ICC indicators. Secondly, it was shown that most significant predictors for the ICC features are Nationalistic and Patriotic ENA with opposite impacts. As was expected, Nationalistic ENA has a positive impact on r et al. . Thus, we can conclude that ENA are important predictors of ICC development stages from absolutization to acceptance of cultural differences. According to our data, ENA have a stronger impact on ICC than FFM personality traits . TherefoThere are several limitations to our study that should be taken into account when conducting future research in this area. Firstly, one limitation is the sample size and its female-to-male ratio. Secondly, only ethnically Russian students were involved in our study. We understand that both ethnic origin and ethnic identity are important factors of the ICC development, which must be taken into consideration in further studies. Another possible limitation of this study is the measure used to collect the data. The ICC can be measured with various tools, the most popular being self-questionnaires. However, there is a need to use more objective methods, including expert assessments and quasi-experiments. The next limitation is a certain lack of prior research studies on this topic in Russian psychology, so it is difficult to compare our results with other researchers’ and provide a more comprehensive outlook on the problem.Summing up all the findings and limitations of our research, we can determine its future prospects: (1) the complex study of different ICC predictors ; (2) a sample expansion and its balancing by the female-to-male ratio; (3) using of additional measurement methods for both ENA and ICC, as well as other methods of statistical analysis; (4) the development of the programs to improve the ICC in university students in a multicultural educational environment, taking into account the ICC predictors of different levels .


Purpose: The aim of this study was to analyze the incidence of intrarenal reflux (IRR) among vesicoureteral refluxes (VURs), diagnosed by contrast-enhanced voiding urosonography (ceVUS), to define VURs which are positive to IRR and their locations in the kidney.Materials and Methods: Seventy patients with VURs, including 103 uretero-renal units (URUs) with VURs of grades II–V  were examined with ceVUS due to recurrent febrile UTI or first febrile UTI accompanied by abnormalities on renal ultrasonography. Patients were examined on GE Logiq S8 ultrasound machine, using second generation of ultrasound contrast agent.Results: Out of 103 VURs, 51 (49.51%) had IRR regardless the grade of VUR, showing increase in IRR incidence with VUR severity (p < 0.0001). The median age at the time of IRR diagnosis was 5 months , whereas in patients without IRR, it was 15.5 months , (p = 0.0069). IRR was most common in superior pole (80%), followed by inferior pole (62.7%), and middle segments (37%), and to all segments (27%) (p < 0.0001).Conclusion: In the present study, patients with IRR-associated VUR showed earlier clinical presentation. The distribution of IRRs corresponded to the natural distribution of composed papillae types II and III, while the incidence of IRR increased with severity of VUR. Further clinical studies may point to the importance of considering IRR in the future classification of VUR. Vesicoureteral reflux (VUR) is defined as a backflow of urine from the urinary bladder to the proximal part of the urinary system, including the kidney parenchyma. It is usually diagnosed by voiding cystourethrography (VCUG), direct radionuclide cystography (DRNC), and contrast-enhanced voiding urosonography (ceVUS). It may be associated with an increased incidence of urinary tract infection (UTIs), functional abnormalities of the lower urinary tract (LUT) and bowel, scarring of the kidney parenchyma, and other congenital anomalies of the kidney and urinary tract (CAKUT). Despite a large number of studies, which support the theory that VUR is a very important risk factor for kidney scarring, and the decrease of kidney function, some studies reported opposite results , 2. MorePatients with IRR usually had UTIs and renal scars more frequently than those without IRR . Some auThe incidence of IRR is ~1–11% in patients with VUR if VCUG is used as the diagnostic method , 7–9. AlThe second case study was reported on four patients with VUR and IRR by ceVUS, describing IRR by second generation of UCA . The newIn this retrospective study, patients with recurrent febrile UTIs or with first febrile UTIs, accompanied with abnormal findings on renal ultrasonography underwent ceVUS, regadless the sex, according to the current recommendations , 19–21. via a 6F−8F feeding tube or a hydrophilic catheter through the urethra under the pressure of a 70–100-cm column of water until functional bladder capacity was reached or until the child showed the urge to void. The procedure lasts usually 10–20 min, and can be repeated, especially in very young patients. The second generation of UCA is stable and allows the performing of the procedure, without refilling. The additional guaranty for UCA stability is the setting of the US machine to low mechanical index and shift of the US focus out of the observed object. Patients were examined by two experienced pediatric nephrologists on GE Logiq S8 ultrasound machine by probes C 2–9 and 9L, using B-mode and harmonic imaging with mechanical index of 0.06–0.08. The kidneys and bladder were inspected approximately every 10 s and frames were recorded. Some sequences were recorded by video clips. The results were concluded consensually. The IRR appearance is a “smoke-like” extension of UCA, spreading from the renal calyces through the renal parenchyma to the renal periphery  was prepared by instilling 0.5 ml of UCA into 250 ml of saline bag. Then UCA was introduced into the bladder, immediately after preparation eriphery .Seventy patients  with VUR, with expected 140 ureter-renal units (URU) were examined by ceVUS. Out of that number of expected URUs, 37 were excluded from the study due to the following: renal agenesis (1 URU), multicystic dysplasia (2 URUs), duplex channel system (5 URUs), and absence of VUR (29 URUs). Altogether, we analyzed 103 URUs with VURs of grades II–V. Grades I–II were considered non-dilated VURs, grade III as moderately dilated VURs, and grades IV–V as highly dilated VURs. Forty-seven of VURs were right sided, while 56 were left sided. We also recorded the exact locations of IRR in the kidney, distinguishing the occurrence of IRRs in upper, middle, and lower zone, or in combined locations.2 (Cochrain-Armitage) test for trend was used. To assess differences between continuous variables, the Mann-Whitney-test was used.Data are presented as percentages or fractions with 95% confidence intervals when describing a categorical variable or as a median and interquartile range (IQR), as well as range, when presenting a continuous variable. To test trends between ordered categories χp-value was interpreted according to ASA Statement on p-value from 2016.p = 0.0069). The oldest patient was 7 years and 4 months old when diagnosed with IRR.The median age at the diagnosis of VUR was 10 months, . There were 38 (54.2%) patients with IRR and 32 (45.7%) patients with VUR without IRR. At the time of diagnosis, children with IRR had a median age of 5 months , whereas those without IRR had a median age of 15.5 months ,  were of grade II. Eight of them  had IRR. Thirty-one (30.09%) were of grade III. Twenty-six of them (25.24%) had IRR, while 17 (16.5%) were of grades IV and V, and all of them (16.5%) had IRR.Fifty-one of that number (49.51%) had IRR, regardless of the grade of VUR.The appearance of IRR in different grades of VURs is given in The significant difference was noticed regarding the occurrence of IRR in renal segments. IRR appeared most frequently in the superior pole, then in the inferior pole, and in the middle segment, while in the all segments together, IRR was noticed less frequently .p < 0.0001)  .p = 0.0139 and p = 0.0104). On the other hand, for superior and inferior pole parenchyma, existence of the trend was more uncertain   .CeVUS is a sensitive method for the detection of VUR in both sexes. There are some opinions that ceVUS should be applied as a first diagnostic method for VUR only in girls, but not in young boys because of the real possibility of overlooking posterior urethral valve. We share the opinion with some other authors that the posterior urethral valve can be easily diagnosed by ultrasonography as well as by characteristic clinical appearance , 24. HowSeveral studies from the literature, which have been done only by VCUG, reported 1–11% of IRR-associated VURs , 12, 14,Thus far, IRR has been referred as a condition which is characteristic for children younger than 4 years, diagnosed mostly after recurrent UTI, and only occasionally diagnosed after that age , 9. Our The entire genesis of the IRR is explained through animal models. According to the results of the study done on piglets, simple papillae and compound papillae type I have not had IRR, while the group of compound papillae types II and III had IRR in 77.66% of cases. The reason for that is specific anatomy of renal papillae and its area cribrosa, as well as inclination of orifices of papillary ducts. While papillary ducts in simple papillae or in type I papillae are opened obliquely through small, slit-like orifices, in compound papillae types II and III orifices are widely opened directly into surface, forming flat, even concave area cribrosa . That meSince we know that IRR is based on refluxing papillae, it should not be dependent on VUR grade.However, it was shown that the number of IRRs rises with the grade of VUR, as it was in our study , 9, 13. At the end, we have to note that this study has some limitations including its retrospective nature, relatively small number of patients, and lack of clinical correlation with findings of ceVUS, but we are convinced that we still have representative results, based on sufficient number of data which can improve the diagnosis of VUR.In summary, we can say that IRR is one developmental variation, which became highly detectable by ceVUS, which was clearly shown in this study. Based on our study, we can divide VURs in two groups: those with IRR and those without IRR. The distribution of IRRs corresponded to the natural distribution of composed papillae types II and III, while the incidence of IRR increased with severity of VUR. Patients with IRR-associated VUR showed earlier clinical presentation. The results of this study showed that only a minority of non-dilating VURs and majority of dilating VURs would have IRR. We consider IRR as a very significant diagnostic sign. Therefore, further clinical studies may point to the importance of considering IRR in the future classification of VURThe raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Ethical Committee University Hospital of Split. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.AS: conceptualization, data curation, formal analysis, investigation, methodology, supervision, validation, visualization, and writing—original draft. AA and MS-B: data curation, formal analysis, investigation, visualization, and writing—original draft. KV: formal analysis, supervision, and writing—original draft. BB: data curation, formal analysis, investigation, and writing—original draft. AP: conceptualization, data curation, investigation, and writing—original draft. MS: conceptualization, data curation, formal analysis, methodology, validation, writing—original draft. All authors contributed to the article and approved the submitted version.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.


Purpose: To explore the effects of physical activity (PA) intervention on executive function (EF) and motor skills (MS) among children with attention deficit hyperactivity disorder and/or autism spectrum disorder (ASD).Methods: Relevant studies were sourced from PubMed, Web of Science, EMBASE, Cochrane Library, CNKI and Wanfang Data. Only randomized controlled trials (RCT) were included based upon the following criteria: (1) participants were children and clinically diagnosed with ADHD/ASD, (2) intervention strategies were identified as chronic physical activity, and (3) EF  and/or MS  were measured at baseline and post-intervention and compared with an eligible control group.Results: Eleven studies involving 346 participants were finally identified. PA elicited significant improvements in EF and MS in children with ADHD/ASD. Regarding changes in the EF of participants, PA showed a great improvement in overall EF , inhibitory control  and cognitive flexibility , but no significant improvement in working memory . Significant improvements were also found with respect to gross motor skills , but no significant changes were found in fine motor skills .Conclusion: Chronic PA interventions may promote EF and MS in children with ADHD/ASD, especially in inhibitory control, cognitive flexibility, and gross motor skills. However, PA interventions seemed to have insignificant effects on working memory and fine motor skills to children with ADHD/ASD.PROSPERO registration number: CRD42019118622 Attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are the most common neurodevelopmental disorders in children . This study is registered with PROSPERO (CRD42019118622) and the protocol has been published in a peer-reviewed journal.physical activity, exercise, executive function, cognitive function, inhibitory control, inhibition, working memory, cognitive flexibility, motor skill, gross motor skill, fine motor skill, motor behaviors, motor functions, ADHD, ADD, and ASD. In addition, the reference lists of included studies were examined for other potentially eligible studies.We performed a search of PubMed, Web of Science, EMBASE, Cochrane Library, CNKI and Wanfang Data from inception to August 2020. We considered all the English and Chinese studies. We used key phrases and Medical Subject Heading (MeSH) terms as follows: Articles were eligible for inclusion if the study design was a randomized controlled trial (RCT); if the participants were children and adolescents with ADHD and/or ASD; if the studies reported at least one outcome of interest measured at pre- and post-intervention. In these studies, the experimental group received a chronic PA intervention program with no limitation on the types, frequency, and intensity, while the control group was treated by sedentary resting or received no treatment. The outcomes of interest consisted of three subfunctions of EF  and two subtypes of motor skills .The titles and abstracts of studies were initially screened by two independent review authors. Related studies were recorded and managed using Endnote software. Following this, the two authors put their screened studies together and determined suitable studies with the inclusion criteria. When a disagreement happened, a third author participated to solve the problem by discussion to make a final consensus. For the studies that met the inclusion criteria, full articles were obtained for further analysis. The two authors separately extracted data from the published works using standard data extraction forms. Any inconsistencies in the process of data extraction were solved by checking original texts and reaching an agreement through discussion. Information on trial design, characteristics of the subjects, PA protocol, and relevant results were noted according to a redesigned form. We recorded the name of the first author and the year of publication for each article; the sample sizes, the ages, and gender of participants; the measurements; and the interventions for each group. When data were insufficient or inapplicable, we attempted to contact the authors by e-mail. A total of two authors were contacted (Yazd and Liu), and only Liu replied.The Cochrane Collaboration's tools were used to check the random sequence generation, allocation concealment, blinding, incomplete outcome data, selective reporting and other bias. Each item was determined as a high-risk, low-risk, or unclear grade by the two authors. The grading of evidence quality and risk of bias by two authors were compared, and the third reviewer was consulted if the consensus was not attained.We used Revman 5.3  to conduct the data analysis. The continuous outcomes were expressed as mean difference (MD) with 95% Confidence Intervals (CIs). When the MD of the outcomes is large or the unit is different, the standardized mean difference (SMD) was used. The SMD and 95% CI were calculated and then interpreted as suggested by Cohen : 0.00–0.p > 0.10, I2 < 50%, it will be considered that heterogeneity is low enough and a meta-analysis can be conducted with a fixed-effect model. If p < 0.10, I2 > 50%, it will be considered as a high level of heterogeneity, and a random effect model will be used.If The flow diagram illustrating the search and screening process is shown in A total of 346 participants were included in the analysis, of which 174 (about 50.28%) participants underwent a PA intervention. The characteristics of subjects, type of intervention, intensity and duration, and measurements from the included studies were described in The evaluation results are shown in p < 0.0001), with high heterogeneity . Regarding the subfunctions of EF, the SMD was 0.28  for working memory, with moderate heterogeneity ; 1.30  for inhibitory control, with large heterogeneity ; and 0.85  for cognitive flexibility, with low heterogeneity .Eight studies with 329 subjects assessed executive function as outcomes . The poop = 0.04), with moderate heterogeneity . Regarding the subfunctions of MS, the pooled SMD was 0.80  for gross motor skills, with small heterogeneity ; and the SMD was 0.30  for fine motor skills, with large heterogeneity . Unfortunately, there was no significant change in fine motor skills as compared with control groups.Six studies with 161 subjects assessed motor skills as outcomes . The pooThe present meta-analysis revealed that PA could significantly improve EF and MS of ADHD/ASD children in terms of cognitive flexibility, inhibitory control, and gross motor skills. However, our analysis did not provide strong evidence to the effectiveness of PA on working memory and fine motor skills in ADHD/ASD children.Our findings are aligned with previous studies on the efficacy of PA on improving some aspects of cognition of individuals with ASD/ADHD  have demonstrated positive effects on fine motor skills in children with ADHD/ASD by modulating neurotransmitters, fine motor skills could be improved with increasing neurotransmitter levels. Moderate to high-intensity PA has also been recognized as an effective way to enhance the level of neurotransmitters  and MS  in children with ADHD/ASD. One strength of the study is the strict inclusion principles, which could increase the validity of causal inferences. Also, subgroup analysis was conducted to explore the detailed changes of physical activity on motor skills and executive functions in children with ADHD/ASD might be another important feature of the study.However, some limitations were still present in the evaluation. First, the different measurements of the included studies may lead to high heterogeneity in this meta-analysis. Second, a relatively small number of studies in motor skills in comparison to EF studies included in the review may affect the findings of our analysis. As a result, the effects of PA on MS remain to be determined and further explored. Third, the results of the meta-analysis might be limited by the lack of large sample, multi-center and long-term studies in the included studies, which may have some limitations in guiding clinical applications.In conclusion, the present meta-analysis supports the positive effects of PA on EF and MS in children with ADHD/ASD, especially in inhibitory control, cognitive flexibility, and gross motor skills. These findings indicate that PA can be implemented in children with ADHD/ASD as an alternative training modality. However, we found insignificant effects of PA interventions on working memory and fine motor skills in children with ADHD/ASD. Future studies should investigate the effects of PA in ADHD/ASD longitudinally through multicenter RCT with large sample sizes.All datasets generated for this study are included in the article/supplementary material.This study was conceptualized by MZ, ZL, HM, and DS. DS contributed to collecting data. Analyzing data and drafting the manuscript was by MZ and ZL. HM contributed to revising and approving the final version of the manuscript. All authors contributed to the article and approved the submitted version.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.


Objectives: Herpes zoster (HZ) infection has been associated with disease burdens such as infection and depression. However, the relationship between chronic interstitial cystitis (CIC) and HZ is unknown. This study investigated HZ risk in patients with CIC. Patients and Methods: The Longitudinal Health Insurance Database, which is a subset of the Taiwan National Health Insurance Research Database, was used in the study. The case cohort consisted of patients with newly diagnosed CIC between 2000 and 2012. Each patient with CIC was matched to four controls by age and index year. All participants were traced from the index date to HZ diagnosis, and loss to follow-up or death, or to the end of the study (31 December 2013). Results: A total of 1096 patients with CIC and 4384 controls were enrolled. The incidence rate of HZ in patients with CIC was 10.8 per 1000 person-years, whereas that for controls was 7.25 per 1000 person-years. HZ risk for the case cohort was 1.48 times that for the control cohort. Among participants aged ≤49 years, patients with CIC had a 1.91-fold-increased HZ risk compared to those without CIC. Conclusion: Patients with CIC had a higher risk of HZ than those without CIC. CIC should not be ignored, particularly in young adults. Chronic interstitial cystitis (CIC) is also known as bladder pain syndrome. According to the definition given by the National Institute of Diabetes and Digestive and Kidney Diseases, it is a chronic condition that causes a painful urinary syndrome. The cause of CIC is still poorly understood. The syndromes of CIC are urgency, nocturia, and pain in the pelvic area .CIC is more prevalent in women  than in men  . A multiHerpes zoster (HZ) is caused by the reactivation of the varicella-zoster virus, and is characterized by painful vesicular rashes with a dermatomal distribution. Through a systematic review, Kawai et al. observed that HZ incidence was 3–5 per 1000 person-years in North America, Europe, and the Asia Pacific region. Furthermore, they found that HZ incidence increased with age, with 6–8 and 8–12 cases per 1000 person-years at 60 and 80 years old, respectively [The relationship between HZ and disease burdens, such as infection and depression, has been identified ,7,8. HowThe Taiwanese government initiated a National Health Insurance (NHI) program in 1995. Most residents of Taiwan are included in the program. The medical claims of insured patients are recorded in the National Health Insurance Research Database (NHRID). In this study, we used the Longitudinal Health Insurance Database, which is a subset of the NHRID and contains the medical information, such as outpatient visits, hospitalization records, and medication usage, of 1 million randomly selected beneficiaries from the NHI program. The diagnostic codes, such as CIC or HZ, were defined according to the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM). All identification data were encrypted for ethical reasons.Patients with newly diagnosed CIC (ICD-9-CM: 595.1) between 2000 and 2012 were assigned to the case cohort. Patients aged less than 20 years or with a history of HZ were excluded. Each CIC patient was matched with 4 controls according to age and index year. The index year of the case cohort was the year of CIC diagnosis, and that of the control cohort was randomly assigned. We traced all participants from the index date to HZ diagnosis, and loss to follow-up or death, or to the end of the study (31 December 2013).The primary event of this study was HZ (ICD-9-CM: 053). Chronic kidney disease , obesity (ICD-9-CM: 278), diabetes (ICD-9-CM: 250), coronary artery disease , depression , and cancer (ICD-9-CM: 140–208) were considered comorbidities.t test for continuous variables. The hazard ratio was estimated using the Cox proportional hazard regression model and then adjusted for age, sex, and CAD in a multivariable model. We assessed the cumulative incidence curve using the Kaplan–Meier method and examined it by using the log-rank test.To compare the distribution of the baseline characteristics of the two cohorts, we used the chi-square test for categorical variables and the A total of 1096 patients with CIC and 4384 controls were enrolled in this study. They were observed for approximately 6 years. The effects of CIC on HZ depending on age, gender, and the presence of comorbidities are listed in To our knowledge, this is the first population-based study to identify the association between CIC and HZ. Patients with CIC were found to have a higher risk of HZ than those without CIC, particularly in those aged ≤49 years.The prevalence rate of CIC is between 2% and 17.3% in the general population . The majAn association between CIC and depression has been identified. Cepeda et al. reported that compared with 0.06% of the general population, 0.13% of patients with depression developed CIC within 2 years. The incidence of CIC is higher in patients with depression than in the general population . CIC oftWomen with CIC and depression have a high likelihood of experiencing abdominal or bladder pain . Rabin eA strong association exists between depression and HZ. Chen et al. found that compared with controls, patients with HZ had a considerably higher incidence of major depression (2.2% vs. 1.4%) and any depressive disorder (4.3% vs. 3.2%) . PatientEvidence indicates that HZ risk increases with age due to the decrease in immune system robustness. We proved this relationship , and we This study analyzed a subset of the Taiwanese NHIRD. The NHIRD has a large sample size and is highly representative of the population. This study, being retrospective, has several limitations. First, biases regarding CIC or HZ diagnosis may exist among medical specialists due to the diagnostic criteria. However, all insurance claims are sent to the National Health Insurance Administration and are reviewed by reimbursement experts. Therefore, diagnostic codes assigned are reliable. Second, disease severity is not recorded in the NHIRD. The severity of IC and HZ might cause different outcomes. Third, lifestyle is not recorded in the NHIRD. A balanced diet and moderate exercise are good for health and might influence the immunity of participants. Despite these potential limitations, the large sample size of this study yielded a powerful statistical analysis. Participants with CIC were found to have a higher risk of developing HZ than those without CIC.Patients with CIC have a higher HZ risk than healthy individuals. Hence, CIC burden should not be ignored, particularly in young adults.


Alzheimer’s disease (AD) is a disease of a heterogeneous nature, which can be disentangled by exploring the characteristics of each AD subtype in the brain structure, neuropathology, and cognition. In this study, a total of 192 AD and 228 cognitively normal (CN) subjects were obtained from the Alzheimer’s disease Neuroimaging Initiative database. Based on the cortical thickness patterns, the mixture of experts method (MOE) was applied to the implicit model spectrum of transforms lined with each AD subtype, then their neuropsychological and neuropathological characteristics were analyzed. Furthermore, the piecewise linear classifiers composed of each AD subtype and CN were resolved, and each subtype was comprehensively explained. The following four distinct AD subtypes were discovered: bilateral parietal, frontal, and temporal atrophy AD subtype , 29.2%), left temporal dominant atrophy AD subtype , minimal atrophy AD subtype , and diffuse atrophy AD subtype . These four subtypes display their own characteristics in atrophy pattern, cognition, and neuropathology. Compared with the previous studies, our study found that some AD subjects showed obvious asymmetrical atrophy in left lateral temporal-parietal cortex, OSAD presented the worst cerebrospinal fluid levels, and MAD had the highest proportions of APOE ε4 and APOE ε2. The subtype characteristics were further revealed from the aspect of the model, making it easier for clinicians to understand. The results offer an effective support for individual diagnosis and prognosis. Alzheimer’s disease (AD) is a heterogeneous disease. Memory impairment is a common characteristic among AD patients; some, however, suffer from other obvious cognitive deficits, such as executive function impairment or language impairment . A post-The cortical atrophy features acquired from sMRI have been applied to the research on early-stage AD subtypes . In someThe mixture of experts (MOE) that integrates the fuzzy clustering (mixture) with piece-wise linear SVM (expert) . In thiswww.adni.loni.usc.edu) (accessed on 23 February 2021) [The data used in this study were acquired from the Alzheimer’s disease Neuroimaging Initiative (ADNI) database (ry 2021) . ADNI, wry 2021) .3) from 192 AD and 188 CN participants of the ADNI-1 baseline sample were considered in this study [http://freesurfer.net/) (accessed on 23 February 2021) [T1-weighted structural MR scans , and ADNI-composite scores. Among them, the first mainly includes Mini-Mental State Exam (MMSE), Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB), and AD Assessment Scale-Cognitive Subscale (ADAS-Cog), and the last includes four sub-domains: memory, executive function, language, and visuospatial. Gibbons et al. derived the composite scores for memory (ADNI-MEM) and executive function (ADNI-EF) according to the ADNI neuropsychological battery using item response theory (IRT) methods in 2012 ,23,24, aAll subjects contained the apolipoprotein E (APOE) information with two alleles, and the cerebrospinal fluid (CSF) data was acquired from about half of the subjects. Of 228 CN participants, 111 had CSF data available. Of 192 AD participants, 98 had their CSF beta-amyloid 1–42 (Aβ1–42) and phosphorylated tau (p-tau) data available, and CSF total tau (t-tau) data was discovered in 96 ones ,26.Sixty-eight regional cortical thickness features were obtained from the Desikan–Killiany Atlas for defining the AD subtypes in each subject. In order to minimize the effects of individual differences, the age, sex, years of education and intracranial volume (ICV) were termed as extraneous variables. For each feature, the regression coefficient of CN :The algorithm flowchart of MOE is shown in ex (BPC) . C and tAfter the AD subtypes were defined, the cross-validation , and CSF biomarker levels were compared among the AD subtypes. The quantitative variables were compared via the analysis of variance (ANOVA), and pairwise comparison via the Dunnett’s test. On this basis, the significant difference between two AD subtype groups were reported. The differences among the qualitative variables were calculated using the chi-square tests, and the abnormal proportions were figured out after the missing data were excluded. Next, the longitudinal analysis was conducted for AD subjects. In each subtype, the cortical thickness data of 68 ROIs were used to calculate the annual rate of change. The cortical thickness data were input into the hyperplanes and parameters of the MOE model, which were generated in the definition of AD subtypes, and then the time-varying subtype attribution of each subject was calculated. The longitudinal scores of each subtype on the global cognition scales, FAQ and the ADNI-composite scores in 4 sub-domains were also calculated. In all longitudinal analyses, the data used were sampled at 12 months or 24 months.n = 56, 29.2%), a group showed prominent bilateral parietal and frontal atrophy, mainly including bilateral lateral parietal lobes, precuneus, bilateral superior frontal, middle and inferior temporal. (2) Left temporal dominant atrophy AD subtype , a group displayed the prominent atrophy in the left lateral parietal, middle, and inferior temporal. (3) Minimal atrophy AD subtype , a group presented the least extent and amount of atrophy among 4 groups, only suffering from sporadic atrophy in the inferior temporal of the whole cortical cortex. (4) Diffuse atrophy AD subtype , a group with atrophy in nearly all cortical regions except for postcentral, paracentral lingual, and pericalcarine areas. The AD subjects were divided into 4 subtypes using the MOE method. The 4 subgroups from the CN group manifested a reasonable classification and separation, with the average accuracy of 83.1 ± 4.8%, the BPC of 0.63 ± 0.02, and the maximum pair-wise inner product equal for 0.29 ± 0.07. Each subtype was named after its statistical characteristic—cortical thickness atrophy pattern—found in comparison with the CN cohort . The subThe demographic information of the four AD subtypes and the CN group were compared . The LTASome AD subjects were not involved in the longitudinal data collection. The number of subjects was counted in the longitudinal analysis . The ave1–42, the concentration of Aβ1–42 in MAD was significantly higher than those in OSAD and DAD. The average Aβ1–42 in OSAD was the minimum, and their abnormality ratio was the highest among the four subtypes. The normal tau ratio in MAD was highest in all four subtypes, the abnormality ratios of t-tau and p-tau in OSAD seemed to be the highest in AD subtype, and they were significantly different from those in MAD through the qualitative analysis  exceeded 75% in Murray et al.’s study ,28, but The LTAD was manifested by obvious asymmetrical atrophy in left lateral hemisphere. In previous studies, the subtypes were named directly by the regions of atrophy like the left hemisphere, but through the hierarchical clustering in a study, the left-right asymmetrical cerebral atrophy was discovered in the HSAD , while aThe disease duration of LTAD was significantly different from those of DAD and OSAD. In the longitudinal analysis, it appeared found that LTAD had a higher rate of change in the thickness of the occipital cortex. Therefore, some LTAD subjects may convert to DAD. As proved by the previous studies, it is in the left hemisphere that the atrophy will take place firstly, followed by the diffusion atrophy throughout the brain during the disease duration ,34. This1–42 and tau carried in OSAD were the highest, and abnormal CSF levels could accelerate the disease process [The proportions of APOE ε4 and APOE ε2 carried in MAD were the highest. According to a recent study, it is speculated that APOE ε2 has protective effects on the brain structure and cognition and may retard the cortical atrophy and cognitive degradation from APOE ε4 . However process . Accordi process ,6. No diThe four subtypes showed no significant differences in age or education level. Nevertheless, such differences have been found in some of the previous studies ,28. OSADVarious significant differences were reflected among the subtypes in the ADNI composite scores, but significant differences appeared only in few subitems. Therefore, the composite score was more sensitive than the subitems in our subtype results. In our study, the difference was significant in FAQ, which, however, was not included into the ADNI composite score. The non-negligible problem is that both composite score and other cognitive scales  are mainly used to investigate the differences among CN, MCI, and AD , but theAccording to the baseline data of ADNI, it was found in our study that most AD subjects followed a certain subtype, which would not be changed with the duration of disease, indicating that each subtype defined in our study does not simply refer to a stage of the disease course. However, other subjects would be altered into other subtypes, which might be ascribed to different underlying pathophysiological factors among the subjects, leading to a certain subtype tendency during the data collection. This also coincides with the soft classification of fuzzy clustering in MOE. Given this, the AD heterogeneity can be more comprehensively explored in the future study from the perspective of multi-subtype attribution by mining the potential factors among the subjects.In the SVM analysis of MOE, the classification accuracy was the highest for DAD and CN with the most serious atrophy, and the lowest for MAD. The specificity of the DAD was very low. A side effect of clustering was that SVM might be confounded with MOE, and, from the angle of classification model, it was not as complicated as the specialized model in the research on AD subtype classification. However, it could be seen from the results of four SVMs, the heterogeneity indeed existed among the AD samples. In most of the research on AD classification and recognition, AD has been regarded as a single pattern. It is anticipated that applying the study results of AD subtypes to AD classification research may provide a clue for improving the precision of AD classification model and enhancing the interpretability, this, however, has not been verified in other studies of AD subtypes.Some limitations still exist in our study. First, the voxel-by-voxel whole brain voxel-based morphometry (VBM) measurements, which have been widely used in the studies of AD. Both methods provide different types of information and should thus be used in tandem. In future study, the MOE can be used to define AD subtypes based on the features of VBM, which can further compare with the conclusions of this study. Second, more and more studies have shown that the brain diseases of the aged are complicated, and multiple comorbid pathologies are quite common ,39. In aThe atrophy patterns of gray matter from sMRI were input into MOE to simulate the heterogeneous cerebral cortex change process from CN to AD. Four AD subtypes were identified, and their structural, neuropathological, and neuropsychological characteristics were analyzed. Subsequently, the differences of each AD subtype and CN linear classifier were compared and interpreted in the heterogeneous models. The results of our study show that substantial heterogeneity exists among the AD subjects. An asymmetrical atrophy pattern was discovered in the AD cohorts, the extreme proportions of APOE were carried, and the highest CSF characteristics were manifested in OSAD. It has been discovered through the cognitive assessment that the composite scores may be of high sensitivity for the AD subtypes. The differences between the conversion models can be obtained in the aspect of the atrophy pattern, thus better expounding the potential physiological processes in the development of AD and improving the personalized diagnosis.


While numerous comparative works on the magnitude of health inequalities in Europe have been conducted, there is a paucity of research that encompasses non-European nations such as Asian countries. This study was conducted to compare Europe and Korea in terms of educational health inequalities, with poor self-rated health (SRH) as the outcome variable. The European Union Statistics on Income and Living Conditions and the Korea National Health and Nutrition Examination Survey in 2017 were used (31 countries). Adult men and women aged 20+ years were included . The age-standardized, sex-specific prevalence of poor SRH by educational level was computed. The slope index of inequality (SII) and relative index of inequality (RII) were calculated. The prevalence of poor SRH was higher in Korea than in other countries for both low/middle- and highly educated individuals. Among highly educated Koreans, the proportion of less healthy women was higher than that of less healthy men. Korea’s SII was the highest for men (15.7%) and the ninth-highest for women (10.4%). In contrast, Korea’s RII was the third-lowest for men (3.27), and the lowest among women (1.98). This high-SII–low-RII mix seems to have been generated by the high level of baseline poor SRH. Health inequalities have been observed in most of the world ,2,3. In Despite the consistent findings on the association between SEP and health, there has been a crucial question with regard to the causality of the association: do differences in SEP cause differences in health? ,10,11. CInternational comparative studies on the magnitude of socioeconomic health inequalities may have very important implications. Based on the investigations on mortality inequalities by education and occupation among European countries, Mackenbach and colleagues concluded that countries whose social, economic, and healthcare policies have been more influenced by egalitarian principles were not successful in reducing relative mortality inequalities than other Southern European countries ,19. StudWhile numerous comparative works on health inequalities in European countries have been conducted ,3,21,22,As health inequalities in Korea as compared to European countries remain under-investigated, this study was conducted to compare the magnitude of educational inequalities in poor self-rated health in Europe and Korea. This study will aid in understanding the international patterns of the educational health inequalities in poor self-rated health.This article does not present information from any studies with human participants performed by any of the authors. This study was approved by the Seoul National University Hospital Institutional Review Board (IRB No. E-1901-021-999).The European Union Statistics on Income and Living Conditions (EU-SILC) and the Korea National Health and Nutrition Examination Survey (KNHANES) in 2017 were used. A total of 31 countries were examined. These two datasets are known for their high quality and reliability: nationally representative, used as core data sources for producing OECD health statistics across European countries and Korea , and areSRH was rated with a question, “How is your health in general?” in Europe, and “In general, what do you think that your health is?” in Korea. In both datasets, there were five responses: “very good”, “good”, “fair”, “poor”, and “very poor.” To make the meaning clearer, responses were dichotomized as poor SRH (“poor” + “very poor”) and fair/good SRH (“fair” + “good” + “very good”), following prior studies which compared self-rated health across countries ,22,25,28SEP was measured by the highest educational level attained. Among the many variables that can be used to quantify SEP, education is known to be the most reliable in terms of minimizing the likelihood of reverse causality and having high comparability across nations . For anaAge was calculated by subtracting the year of birth plus a year from 2017 based on the guideline by Eurostat . As in tThe first step of the statistical analysis involved age-standardization of the prevalence of poor SRH (“poor” + “very poor”) by educational level (elementary/secondary and tertiary) for men and women in the 31 countries . Age-staY) is a link function, Y is 1 for poor health and 0 for fair/good health, and the error term follows a binomial distribution. The SII and RII can be calculated as β1 for the model with the identity-link function and exp(β1) for the model with the log-link function. The SII is interpreted as the prevalence difference (%) between the hypothetically lowest and highest educational groups. In a similar vein, the RII refers to the prevalence ratio (unitless) of poor SRH between the two extreme educational groups. Confidence intervals (CIs) at 95% were estimated. More details about the calculation of the SII and RII can be found elsewhere [The second step was the calculation of the slope index of inequality  and the relative index of inequality . These two measures are succinct and effective summary indicators of health inequality cross-nationally, as well as within society ,35,36. Tlsewhere ,39.We used PROC SURVEYREG for age-standardized prevalence and PROC GENMOD for SII/RII in SAS version 9.4 for Windows . The comprehensive SAS syntax can be found in prior papers ,41. As tThe age-standardized prevalence of poor SRH among low/middle-educated women was 21.3% in Korea, followed by 17.5% in Serbia and 13.8% in Croatia . For higThe absolute educational inequality in SRH in men, measured by the SII, was highest in Korea , followed immediately by Croatia  and Serbia , following Spain  and Greece , among adult men and women. Two nationally representative datasets (EU-SILC and KNHANES), which are used to generate major OECD statistics, were utilized.p = 0.006) for men and 0.500 (p = 0.029) for women. Differences in the survey period (2015 versus circa 2000), the data  and outcome variables (poor SRH versus a weighted SRH variable) might have resulted in the less than excellent between-study correlations for educational inequalities in SRH.The results of this study revealed that educational inequalities in SRH existed in all 31 countries, including Korea, and in both men and women. These results are in line with prior investigations in that lower SEP corresponds to poorer SRH in most of the world ,21,22,25Prior comparative studies on educational mortality inequalities among European countries presented geographic patterns . The magIn terms of the age-standardized prevalence of poor SRH, Korea ranked highest among all educational groups for both men and women out of the 31 countries. Korea is well-known to have generally high levels of poor SRH, one of the highest among OECD nations . In addiThe point made above is closely related to the next point: Korea’s absolute differences (SIIs) in poor SRH were comparatively high, while the relative inequalities (RIIs) of poor SRH were on the lower side for both men and women. Among the countries studied, the SII in Korea was the highest among men and the ninth-highest among women. In contrast, the RII was the third-lowest among men and the lowest among women. This high-SII–low-RII mix seems to have been generated by the high baseline prevalence of poor SRH, as discussed earlier. As the prevalence of poor SRH in Korea is high, regardless of sex and SEP, it is likely that the SII, as a kind of weighted difference in rates, is largely due to the large absolute numbers, whereas the RII, as a sort of weighted ratio of rates, is small due to the large denominators. Other countries with high SII also exhibit a low RII .A similar comparison based on income level reported that the difference in the percentage of respondents with self-rated good health among the fifth quintile (highest 20% of income) and the first quintile (lowest 20%) in Korea was 10.6% in 2013, which was one of the lowest differences among OECD countries . As the As for the reason why health inequalities in SRH have emerged and become amplified in Korea, studies have suggested that the expansion of the national health insurance system has enabled less-educated individuals to detect illnesses and diseases more easily . Korea’sA different composition of prevalent diseases may have resulted in the differences between Korea with Europe. According to the literature, cardiovascular disease is the leading contributor to inequalities in mortality in Europe, whereas cancer is the most important contributor in Korea . It is wSelf-rated health consists of two dimensions: objective health problems and the perception and reporting styles on those health problems. Studies using “anchoring vignettes” provided evidence on the differences between objective measurements and self-reports of health problems ,44,45,46This study provides a more comprehensive picture of educational health inequalities in Korea by juxtaposing Korean and European data. However, although maximum efforts were exerted to synchronize the two datasets, some comparability issues remain. For instance, the 31 countries in this study contain different numbers of respondents and slightly dissimilar age spans. The survey method also has limitations. In particular, as surveys do not include the entire population and depend on self-reporting, they can be less accurate than administrative data. Cross-cultural comparisons based on more robust data sources such as census, death certificates, or big data are encouraged. In addition, in further studies, it will be more informative to include more varied types of variables  other than age. Considering that Korea’s health inequalities have been increasing ,47, crosIn conclusion, educational inequalities in poor SRH were evident in all 31 countries, including Korea. The absolute magnitude of educational inequalities in poor SRH, measured by the SII, was highest for Korean men and the ninth-highest for Korean women. However, the relative magnitude of educational inequalities was relatively small for Korean men and women. Further international comparative studies across high-income countries, including Korea, are required to provide additional information on the magnitude and ranking of health inequalities and associated determinants.


The topics of serious leisure and subjective well-being have been discussed extensively in previous research. It is generally acknowledged that people prefer to experience deeper satisfaction and happiness through serious participation in leisure-time physical activities. However, it is essential to examine the relationship between serious leisure and subjective well-being in an urban setting as well as the mediating effect of leisure satisfaction. Data were collected from 447 recreational runners at the 2018 Wuxi International Marathon event in China. The study results showed that serious leisure was positively associated with leisure satisfaction and subjective well-being, that leisure satisfaction was positively associated with subjective well-being, and that leisure satisfaction completely mediated the relationship between serious leisure and subjective well-being. Running group membership significantly affected the path from serious leisure to leisure satisfaction, while other demographic variables  did not moderate any paths. These results help explain the intricate relationship between serious leisure and subjective well-being and offer theoretical and managerial implications for serious leisure. Due to rapid economic development and improvements in living conditions, leisure has become an essential part of life for urban residents in China. People are no longer satisfied with experiencing short-term, monotonous rewards; instead, they prefer pursuing the long-lasting and multidimensional benefits achieved as they progress in leisure participation . PreviouThe concept of serious leisure (SL) was first proposed by The existing literature provides sufficient evidence supporting the role of SL on leisure satisfaction (LS) and subjective well-being (SWB). SL has been defined as “The systematic pursuit of an amateur, hobbyist, or volunteer activity that is sufficiently substantial and interesting for the participant to find a career there in the acquisition and expression of its special skills and knowledge” . StebbinExtensive evidence indicates that endurance sports are connected to the qualities of SL. Distance running , which is considered an endurance sport, fits the definition of SL because it requires a time commitment for training, the acquisition of knowledge and skills, and is usually challenging in nature . PreviouSWB is defined as an individual’s overall state of subjective wellness and usually includes two primary components: cognitive and affective . Over thSeveral researchers have recognized SL as a significant predictor of SWB. A quantitative study revealed that demographic variables and the qualities of SL can positively predict SWB, and the significant indicators included level of education, self-enrichment, self-expression, and self-gratification (enjoyment) . AnotherHypothesis 1: Serious leisure is positively associated with subjective well-being.Studies of LS began in the 1980s and aimed to examine individuals’ positive perceptions of leisure participation and overall satisfaction with leisure experiences. Existing studies have examined the differences in LS among participants with different degrees of leisure involvement. For example, Hypothesis 2: Serious leisure is positively associated with leisure satisfaction.Some scholars have made great effort to explore the relationship between LS and SWB, and their results have shown that LS is significantly positively associated with SWB. For example, Hypothesis 3: Leisure satisfaction is positively associated with subjective well-being.Previous research has provided an important background for exploring the relationship among SL, LS, and SWB. Previous research suggests that LS significantly improves as the degree of leisure involvement increases and that SWB improves as LS increases. However, LS may play an important role in the relationship between SL and SWB, and the relationship among the three variables must be re-examined, especially based on the context of a distance running event in China. To address these gaps in the existing literature, this study proposes a mediating model to explore the influence of LS on SL and SWB. Thus, the following hypothesis is proposed see :Hypothesis 4: Leisure satisfaction can mediate the relationship between serious leisure and subjective well-being.The data analyzed in this study were collected at the Wuxi International Marathon Event held on March 25, 2018, in Wuxi, a medium-sized city in Southeast China. This event was certified as a gold label event by the China Athletics Association (CAA) in 2015 and has successfully attracted nearly 30,000 participants since 2014. During the questionnaires collection process, the participants were informed about the consent and purpose of the survey, and ethical approval was not required according to the local legislation and institutional requirements. In total, 480 paper questionnaires were randomly  delivered to half marathon (21.095 km) and full marathon (42.195 km) runners near the finish area. In order to ensure the seriousness of the marathon runners, this study investigated marathon runners who reported running more than three times a week, had run in the past 6 months, and had run more than 5 km once, based on the operational definition suggested in existing studies . As a reIBM SPSS 22.0 was first used to calculate the descriptive statistics , Cronbach’s alpha (CA), and correlation analysis. Then, confirmatory factor analysis (CFA) was conducted using AMOS 21 to evaluate the reliability and validity of each construct in the hypothesis model. Third, a linear regression was used to examine Hypothesis 1 and Hypothesis 3, and SL was measured by the Serious Leisure Inventory and Scale (SLIM) proposed by LS was measured by a scale developed by Based on research conducted by Concerning the applicability of the measures above in the Chinese context, first, the measures in English were translated into simplified Chinese by one researcher. Then, another researcher translated the measures back into English. The original meaning of the measures was retained based on a comparison of the two English versions. Second, the final measures were perfected before the formal investigation based on suggestions by three professors who mainly focus on leisure sport studies.Previous studies have confirmed that SL, LS, and SWB are associated with related sociodemographic variables . ConcernThe respondents included 131 female runners (29.3% of the sample). Most marathon runners were married (61.3%) and ranged in age from 20 to 44 years (76.9%). Most respondents held a college or postgraduate degree (84.4%), and most respondents had an annual income greater than US $7,500 (72.9%), which is higher than the average income level in the region . Moreover, most runners were members of a running group (57.9%) see .M = 4.29; SD = 0.69) and personal effort  were the qualities on which the marathon runners agreed the most, and the average score of the SL was M = 4.11, SD = 0.62. Similarly, the marathon runners exhibited high scores on LS, ranging from 4.13 to 4.33. The relaxation  and physiological  dimensions were the two dimensions on which the marathon runners agreed the most, and the average score of LS was M = 4.22, SD = 0.53. SWLS 2  and SWLS 3  were scored relatively high, and the average score of SWB was M = 5.33, SD = 1.03  verified that all observed variables could be effectively used to evaluate the latent construct in the hypothesized model. Previous research suggests that indicators with factor loadings higher than 0.70 are acceptable , with a r = 0.79, p < 0.01) and SWB ; LS was positively correlated with SWB ; SL, LS, and SWB were correlated with most of the demographic variables, except for the correlations between gender and SL , LS , and SWB , between marriage and LS  and between income and LS  and SWB .P < 0.001) and age  were positively associated with SWB; LS , age , and marriage  were positively associated with SWB. Thus, hypotheses 1 and 3 were supported in this study.Step 1 and Step 3 in P < 0.001) and RG  were positively associated with LS. LS , age , and marriage  were positively associated with SWB. However, SL  was not associated with SWB. Concerning the results of step 1, step 4 indicates that LS had a complete mediating effect between SL and SWB. The value of the mediating effect was 0.357 . Thus, hypothesis 2 and hypothesis 4 were supported.Step 2 and Step 4 in This study further examined the effects of demographic variables  on the model path through a series of z-tests. This study mainly examined the interrelationships among SL, LS, and SWB through a regression analysis and Process macro V3.3 for IBM SPSS. First, involvement in a distance running event had a positive influence on the individuals’ life satisfaction . The resConsistent with the hypotheses in this study, SL was positively associated with LS in marathon running. This result filled the gap between SL and LS and expanded the quantitative findings reported by Another finding from this study is that the LS of marathon runners positively influenced their SWB. The current study enriches the previous literature  by examiThe results of Process macro V3.3 indicated that LS had a mediation effect on the relationship between SL and SWB. This finding indicates that SL is more likely to influence individuals’ LS with running, thereby increasing their SWB. This finding extends the existing literature  by introIn addition, this study examined the impact of demographic variables  on the path of the theoretical model. The study results indicated that marathon runners differed significantly on the path from SL to LS in the model based on their membership in a running group. As This study further extends the application of the SL framework to the leisure sports context among Chinese distance running event participants. A recent study confirmed that SL qualities were positively associated with marathon running participation behaviors, such as the number of running years, running frequency per week, and longest marathon event . Based oFour research hypotheses were proposed in this study. First, consistent with previous studies , the finThis study has several limitations. First, this study examined the relationship among SL, LS, and SWB based on marathon running in China. Future research should be applied to other leisure sports activities and should further examine the hypothetical model. Second, this study verified the mediation effect of LS on the relationship between SL and SWB. Other variables  should be explored via the mediation model in subsequent studies. Third, this study examined the mediation effect of LS using the total SL, LS, and SWB scores; future studies should explore the relationship among the subdimensions of the three variables and consider the mediation effect of other variables  in the model in this study.These results have theoretical and practical implications for the field of leisure activities. First, many variables may mediate or moderate the influence of SL on SWB. Scholars should focus on exploring these variables through both quantitative and qualitative methods to discover the potential framework that affects participants’ well-being. Second, organizers of marathon events should cater to the various needs of participants  and provide high-quality service in various aspects, such as security, energy supply, and route design. The more LS marathon runners acquire, the higher their SWB, and the more likely they are to participate in marathons again in the future. Third, government agencies  should provide more support to people, such as perfecting the running route, strengthening the construction of running groups, and optimizing relevant policies. These changes could promote individuals’ serious participation in running activities and offer a deeper degree of LS and SWB.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.Ethical review and approval was not required for the study on human participants in accordance with the local legislation and institutional requirements. Written informed consent from the participants was not required to participate in this study in accordance with the national legislation in the host country and the institutional requirements.HT wrote this manuscript. YQ was responsible for research design and ideas. YL was responsible for research revision. WZ and CF were responsible for collecting questionnaire and analyzing the data. All authors contributed to the article and approved the submitted version.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.


High glucose , NLR HR 1.54, p = 0.002), PLR , and SII  were associated with an increase of cancer incidence. After adjusting for clinical covariates  SII, PLR, and NLR remained independent prognostic factors for the prediction of cancer incidence. Conclusions: Inflammatory indices are promising, easy to perform, and inexpensive tools for identifying patients with higher risk of cancer in cancer-free population.Background: Despite the robust data available on inflammatory indices (neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), and systemic immune-inflammation index (SII)) and clinical outcome in oncological patients, their utility as a predictor of cancer incidence in the general population has not been reported in literature. Methods: The Bagnacavallo study was performed between October 2005 and March 2009. All citizens of Bagnacavallo  aged 30–60 years as of January 2005 were eligible and were invited by written letter to participate to the study. All participants underwent a detailed clinical history and physical examination following the model of the Dionysos Study. All blood values included in the analysis were obtained the day of physical examination. Cancer incidence data were obtained from the population-based Romagna Cancer Registry, which operates according to standard methods. The aim of this analysis was to examine the association between metabolic syndrome and baseline SII, NLR, and PLR levels, and the diagnosis of an invasive cancer in the Bagnacavallo study cohort. Results: At univariate analysis, metabolic syndrome was not associated with an increase of cancer incidence (HR 1.30;  In the era of immunotherapy, attention to the immune system and its interplay with cancer development and spread is growing day by day. Several data suggest that a systemic inflammatory response is associated with cancer development, angiogenesis promotion, apoptosis inhibition, and damage of DNA, thus resulting in cancer progression and metastasis . In partTherefore, on the one hand, the immune system detects and targets non-self agents (including mutated cells) by the activation of the innate immune system in the attempt to protect the organism. On the other hand, the immune cells involved in innate immune system are one of the major sources of the angiogenic, epithelial and stromal growth factors, which contribute to the neoplastic progression. Based on this relationship between systemic inflammation and cancer progression, several inflammation-based indices have been used as available and inexpensive surrogates of the immunological microenvironment and systemic inflammation. The main scores include the neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), and systemic immune-inflammation index (SII), and they showed to have prognostic and predictive value in many types of invasive solid cancers, such as colorectal ,3, gastrDespite the robust data available on inflammatory indices  as prognostic predictors for many types of oncological patients, their utility as predictors of tumor incidence in a cancer-free population has not been already reported in literature.Concurrently, in the last decade the link between immune disequilibrium and MS has been highlighted . MS is aHowever, MS is now recognized to be a pro-inflammatory condition ,12, and Trying to deepen the significance of MS and its possible outcomes in the general population, Foschi et al. conducted the Bagnacavallo Study by collecting data about liver function in 3933 citizens from Bagnacavallo , in order to evaluate potential risk factors and health outcomes of fatty liver (FL) in general population. In particular, the authors recollected data about lipid assessment, liver function, and glucose metabolism, and a liver ultrasound was performed in order to investigate the presence of FL ,20.In this study Foschi et al. concluded that FL is highly prevalent in Northern Italy and more frequent in citizens with liver transaminases alteration compared to those with normal values (74% vs. 35%). They also found that all components of the metabolic syndrome were associated to FL independently of altered liver enzymes, gender, age, and alcohol consumption.Starting from the same population of Bagnacavallo study, this study aims at evaluating the predictive value of metabolic syndrome and immune-inflammation indicators in order to identify the risk of cancer among a general population.The Bagnacavallo study was performed between October 2005 and March 2009. All citizens of Bagnacavallo  aged 30–60 years as of January 2005 were eligible and were invited by written letter to participate in the study. Public encounters were also held to promote participation in the study [All participants underwent a detailed clinical history and physical examination following the model of the Dionysos Study . Weight All blood values included in the analysis were obtained the day of physical examination.Cancer incidence data were obtained from population-based Romagna Cancer Registry, which operates according to standard methods . We searThe study was approved by the Ethical Committee of Area Vasta Romagna—IRST (reference number 112). All citizens gave written informed consent before they started with the clinical history, physical examination, and performed blood tests.The aim of this analysis was to examine the association between metabolic syndrome and baseline SII, NLR, and PLR levels and the diagnosis of an invasive cancer in the Bagnacavallo Study cohort.Cancers were coded according to the International Code Disease classification version 10 (ICD-10). Eligible cancers had the following codes: C00–43, C45–96. The codes, by the tumor site, are shown in Table S1The cohort was cross-checked with the files of the cancer registry. Cancer-free survival (CFS) was calculated as the time from the date of the physical examination to the date of cancer diagnosis or death from any cause or the date of end of follow-up (31 December 2016), whichever occurred first. CFS curves were estimated using the Kaplan–Meier method and compared with the log-rank test. Hazard ratios (HR) and 95% confidence intervals (95% CI) were calculated using the Cox proportional hazards analysis starting from a crude model (with no covariates). The HRs were subsequently adjusted for patients age, gender, smoking, physical activity and education. Model 1 was adjusted for patient age. Model 2 was adjusted for patient age, gender, smoker, physical activity, and education. All variables were forced into the models.The SII was calculated as platelet count × neutrophil count/lymphocyte count, NLR was obtained by dividing the absolute neutrophil count by the absolute lymphocyte count, and the PLR was calculated by as the ratio of the absolute platelet count to the absolute lymphocyte count.MS was diagnosed using the harmonized international definition . In detap-value less than 0.05 was considered statistically significant.For continuous predictors, such as NLR, PLR, and SII, we identified the best cut-off using the ROC curve and Youden′s test . STATA vThe dataset from the Bagnacavallo study included 4026 subjects that accepted to take part in the analysis. A total of 3810 of them were eligible for our analysis , and 884At the time of database lock in 31 December 2016, after a median follow-up time of 10 years, 203 invasive cancer have been diagnosed (5.3%). Of these, 20.6% were breast cancers, 15.3% prostate cancers, 6.9% lung and colon rectal cancers, 6.4% hematological cancers, 4.9% cervical or endometrium or ovarian cancer, and 3.9% were gastric cancers.The main characteristics of the study population were summarized in A), PLR (B), and SII (C).p-value of 0.0359 and returned 1.5 as a cutoff point value. For PLR, the area under the curve in the ROC analysis was 0.5420. Youden′s test was equal to 0.115 with a p-value of 0.036 and returned 110.6 as a cutoff point value. For SII, the area under the curve in the ROC analysis was 0.5438. Youden′s test was equal to 0.099 with a p-value of 0.0359 and returned 365,776 as a cutoff point value. So, SII ≥ 365,776, NLR ≥ 1.5 and PLR ≥ 110.6 were considered as elevated levels.For NLR, the area under the curve in the ROC analysis was substantially low, 0.5506. Youden′s test was equal to 0.110 with a p-value = 0.155. An additional analysis was performed to evaluate the single components of metabolic syndrome and cancer incidence. With univariate analysis, Subjects with high glucose showed an increased risk of developing cancer   . No othep-value = 0.002; HR 1.58 95% CI 1.20–2.07 log-rank test p-value = 0.001; HR 1.47 95% CI 1.11–1.94 log-rank test p-value = 0.006; respectively)  .In this era of interest toward the immune system and its interplay with chronic ailments, including cancer, this is the first study performed in a healthy population that focuses on the possible predictive role of inflammatory indices and MS on cancer incidence.Our analysis proves that inflammatory indices  are actual risk factors for cancer development in the general population. No data exists in the literature about the role of inflammatory indices in the general population, while several epidemiologic data have established an association between chronic inflammation and the development and progression of some kinds of cancers, including gastric, esophageal, colorectal, liver, pancreatic, bladder, and lung tumors ,27,28,29The role of chronic inflammation as a promotor of carcinogenesis was first proposed by Rudolf Virchow in 1863, who detected leucocytes within cancer tissue ,30. SincNowadays, inflammation is recognized as a hallmark feature of cancer development and progression . The molStarting from these considerations, measurable blood parameters that reflect systemic inflammatory response have been incorporated in prognostic scores for several types of cancer . NLR conPLR is an inflammatory index that considers both the role of platelets and lymphocytes in the cancer-inflammatory response interplay. Evidence shows that tissue injury induced by cancer-related inflammation leads to platelet activation and aggregation, at the same time stimulating the coagulation cascade; thrombocytosis is very common in patients with solid tumors, indeed ,47. The The SII, defined as platelets X neutrophils/lymphocytes, is a combination of the PLR and NLR and has been demonstrated to have a high prognostic value in some invasive cancers ,54,55,56A previous meta-analysis performed on 13 studies indicated that elevated SII is associated with poor overall survival, progression free survival, cancer-specific survival, and time to recurrence .Considering the link between chronic inflammation and cancer, and all the data supporting a prognostic role of inflammation biomarkers in many types of solid tumors, it is reasonable to assume that the inflammatory indices could be clinically useful to recognize an increased cancer risk in a cancer-free population. Our data support this hypothesis, but only conducting further investigations on a larger scale it will be possible to understand the best clinical use of inflammation parameters in a screening context.In addition to cancer, another condition of chronic inflammation has been the object of study in recent decades: MS. Starting from the amount of evidence about the close relationship between obesity, insulin resistance, and innate immune activation, we investigated the possible connection between MS and cancer: unfortunately, our analysis showed no significant correlation between the diagnosis of metabolic syndrome and the development of malignancies.In the last several years, many studies investigated the association between cancer risk and the different components of metabolic syndrome, but epidemiologic evidence is still scarce.In a large population-based study conducted on a sample of 16,677 subjects on medications for hyperlipidemia, diabetes, and hypertension, an increased risk of pancreatic cancer in males and colorectal cancer in females was detected .In a meta-analysis that evaluated 38,940 cancer cases, despite differences concerning sample characteristics and MS definition used in cohorts, the presence of MS has been shown to be in association with liver, colorectal, and bladder cancer in men and endometrial, pancreas, postmenopausal breast, rectal, and colorectal cancer in women . HoweverThe biological mechanisms that link MS and cancer are far from being fully understood. It has been proposed that obesity and insulin resistance can constitute the main factors of the MS-cancer link. The insulin resistance stimulates the bioavailability of insulin-like growth factor-1 (IGF-1); the interaction between IGF-1 and its receptors induces the downstream activation of the Ras-Raf-MAPK and PI3K/Akt pathways, thus leading to increased cancer cell proliferation, and inhibition of apoptosis ,18,19,61In our analysis, the reason behind the lack of correlation between MS, its components and cancer development could reside in the follow-up time. There are no data available concerning the time of exposure to MS that confers a higher risk of cancer onset, but it is likely that a follow-up time longer than the 3.5 years considered in our analysis might be necessary.Furthermore, our dataset recollects data about 4026 citizens from the population of Bagnacavallo; thus, we considered a homogeneous population from the same geographic area, where citizens are supposed to have similar behavior and similar nutrition habits. On the other hand, only 203 citizens developed invasive cancers in our study follow-up, a small sample that does not allow further stratification analysis  that could make the correlation more evident and specific.In conclusion, Inflammatory indices are promising, easy to perform and inexpensive tools for identifying patients with higher risk of cancer in general population; no significant correlation was found between MS, its components, and cancer incidence, but these results could be affected by the short time of follow up and small sample of invasive cancers developed. Inflammatory indices could be part of risk stratification criterions in the general population.