Kaplan–Meier analysis showed that IVS hypertrophy could predict CHD and MI incidence and CHD-free and MI-free survival. Multivariable Cox analysis revealed that IVS hypertrophy was correlated with CHD incidence  and MI incidence . In women, IVS hypertrophy was independently associated with CHD and MI incidence . Our prospective cohort study illustrated that IVS hypertrophy detected by echocardiography has a prognostic significance for CHD and MI. Therefore, the early detection of IVSd should be conducted to avoid adverse outcomes in further clinical practice.The aim of the present study was to evaluate the prognostic value of interventricular septum thickness (IVSd) on the incidence of cardiovascular diseases. Based on the general population in Northeast China, 10,349 participants were successfully followed up for echocardiography over a median follow-up time of 4.66 years, among which 4801 were hypertensive. Coronary heart disease (CHD) and myocardial infarction (MI) incidence were followed up. Cox proportional hazards models were used to estimate the association of the baseline IVSd with adverse outcomes. IVS hypertrophy increased incident rates of CHD and MI compared with normal IVSd in the overall population and in the female sex-stratification group. In males, IVS hypertrophy had parallel increase rates of CHD (all  Essential hypertension (EH) is one of the most common cardiovascular diseases. EH can be defined as an elevation in blood pressure for an unexplained reason that increases the risk of brain, heart, and kidney events . HyperteLeft ventricle hypertrophy (LVH) is a pathological process caused by the chronic cardiac stress load of EH . HoweverIn this study, we aimed to explore the role of IVS, regarded as the categorical variable, on the prediction of the incidence and prognostic value of CHD and MI in the total and sex-stratified analyses in the Northeast China Rural Cardiovascular Health Study (NCRCHS).The cohort was from the Northeast China Rural Cardiovascular Health Study (NCRCHS), and that study’s design, as well as inclusion and exclusion criteria, were explained in our previous work . In brieAt baseline, detailed information about the participants’ demographic characteristics, lifestyle factors, and disease and medical history was acquired by interviewing the participants using a standardized questionnaire.2), and obesity was defined as BMI ≥ 28 kg/m2 [Smoking and drinking conditions were defined as current use. Weight and height were measured with participants wearing lightweight clothing and by taking off their shoes. Family history of hypertension and family history of cardiovascular disease were self-reported and were verified by medical records. Body mass index (BMI) was calculated as weight (kilograms) divided by the square of the height (m28 kg/m2 . Blood p28 kg/m2 . The par28 kg/m2 .3 × 7.0/(2.4 + LVEDD) , and the LV end-systolic volume (LVESV) was (mL) = LVESD3 × 7.0/(2.4 + LVESD)  [Echocardiography was performed according to the previous study . In brie female) . The ech female) . During the follow up, the participants’ clinical information was collected using a face-to-face standardized questionnaire administered by village doctors. Over the median follow-up time of 4.66 years, the effective follow-up numbers were 10,349, and the follow-up rate was 86.6%. In this cohort, we defined the endpoint events as coronary heart disease (CHD) and myocardial infarction (MI), which were defined as new cases diagnosed during the follow-up period. The history of CHD and MI was excluded. CHD was defined as a diagnosis of hospitalized angina, hospitalized myocardial infarction, any revascularization procedure, or CHD-related death . MI was https://www.rstudio.com/, accessed on 1 March 2020.). Continuous variables were reported as values ± standard deviations if they had a normal distribution and were used as a nonparametric test if they had an abnormal distribution. Categorical variables were reported as numbers and percentages. This was dependent on the data type, so we chose the t-test, analysis of variance (ANOVA), nonparametric test, or χ2-test. Kaplan–Meier estimates were utilized to calculate the cumulative incidence of CHD and MI for each group, and the log-rank test was used to compare the differences between each group. Multivariable Cox proportional hazard models were adopted to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for the associations between IVS hypertrophy and CHD and MI. All of the tests were two-tailed, and p < 0.05 was considered statistically significant.All data were analyzed by R  and in keeping with the Declaration of Helsinki.p value < 0.05), as shown in According to the standard of classification, there were 4419 (92.0%) subjects with normal IVSd and 382 (8.0%) subjects with IVS hypertrophy. Apart from a family history of CVD and smoking, there were significant differences in the baseline clinical and echocardiographic characteristics between the normal IVSd group and IVS hypertrophy group . On the basis of sex, the study population was ulteriorly subdivided. Compared with the normal IVSd group, the incidence of CHD in both the male and female populations with IVS hypertrophy were statistically higher. However, only female subjects with IVS hypertrophy had an elevated incidence of CHD and MI , as in shown in Over a median follow-up of 4.66 years, 146 subjects (3.0%) developed CHD, and 67 subjects (1.4%) experienced MI. The incidences of overall CHD and MI were significantly elevated in participants with IVS hypertrophy than in the normal IVSd group  (p < 0.05).Kaplan–Meier survival estimates showed that subjects with IVS hypertrophy had higher cumulative CHD and MI incidence than those with normal IVSd in the participants overall . There w < 0.05) . As is sp < 0.01). After adjustments for sex, age, DM, BMI, Current_smoke, Current_drink, FamilyHis, Mean_SBP, Mean_DBP, GLU, and LDL_C, HDL_C as appropriate, we conducted a new analysis. In the total population, IVS hypertrophy was correlated with CHD incidence  and MI incidence . Furthermore, we stratified the subgroups by sex and found that in the female subgroup, IVS hypertrophy was independently associated with CHD incidence  and MI incidence . We carefully examined our population and found that there were four people who had acute or chronic renal insufficiency. Considering that these illnesses can result in hypertension, we eliminated these four people from our cohort and conducted a new Cox proportional hazard model analysis as shown in In this large Chinese population cohort, we showed that, in patients with hypertension, a significantly higher incidence of CHD and MI occurred in the IVS hypertrophy group compared to in the normal IVS group in the overall and female groups. This study demonstrated that abnormal IVS may be an independent prognostic factor for these adverse outcomes. Our study may help with the early intervention of hypertension-associated cardiovascular events in clinical practice.Some studies have reported that IVS was associated with an increased risk of adverse outcomes. For example, in a hypertensive population study, researchers found that diastolic left ventricular filling dysfunction and cardiac dysrhythmias were increased among patients with isolated IVS hypertrophy and normal LV mass . In a stGiven that IVSd was reported to be associated with adverse outcomes in a large number of studies, there were some explanations that may help us to understand our findings. First, IVS thickening may influence hemodynamics and activate the neurohumoral mechanism during the pathophysiology process, showing the possible links between IVS hypertrophy and adverse clinical outcomes. Second, hypertension is a risk factor of cardiovascular diseases ,24,25. IWe found that IVS is more significant in females rather than males as a predictor of CHD and MI. There are some explanations for this: first, estrogen may protect premenopausal woman from CHD risk to some extent. Endothelium-dependent vasodilation was greater in premenopausal than in postmenopausal women . The benOur study had some clinical significance. Now that IVSd has provided the prediction value of CHD and MI in adults with hypertension, we should pay attention to IVSd and avoid remodeling in the early stage. Angiotensin-converting enzyme inhibitors (ACEIs), a kind of drug used in the treatment of hypertension, have been reported to successfully reverse LV hypertrophy and myocardial fibrosis in spontaneously hypertensive rats ,39. ACEIHowever, there were some limitations in our study. First, this cohort was from a single-center study and was mainly located in the Northeast of China, and some patients were excluded in the follow-up due to the absence of ultrasonic data, which may have caused selection bias. Second, our study focused on the prognostic value of IVSd in hypertensive patients, so caution should be exercised when applying the results to the general population. Third, the follow-up time may have been too short to determine the presence of cardiovascular events. Therefore, a multi-center study and a longer follow-up time are necessary to further validate our conclusions.Our study found that hypertension patients with IVS hypertrophy were more likely to experience an elevated incidence of CHD and MI than those with normal IVSd. IVSd was associated with a parallel increased risk of incident CHD and MI in the female group. Overall, intervening measures should be put into practice to reduce further adverse cardiovascular events in the hypertension population.


In today’s business environment with high market turbulence, rapid technological change, and fierce competition, external collaboration and internal efforts in research and development (R&D) become equally important for firm growth. However, little is known about the effects of external collaboration on firm growth that generates along the path from outside to inside. Therefore, this study aims to explore the indirect effects of different types of external collaboration on firm growth capability via R&D efforts. It empirically analyzed a sample of 94 Chinese top-ranking innovative enterprises by applying hierarchical regression and mediation analysis. The results indicate that vertical collaboration, horizontal collaboration, and competitor collaboration are positively and directly related to the firm’s R&D intensity, R&D human capital, and firm growth capability. Furthermore, the firm’s R&D intensity and R&D human capital are positively and directly related to growth capability. The results of mediation analyses showed that R&D intensity mediated the relationship between external collaboration and firm growth capability. However, the results failed to support the mediating role of R&D human capital in the relationship between external collaboration and firm growth capability. This study enriches the literature on open innovation and organizational growth, and provides valuable insights for firm managers and policymakers. In the past three decades, China has developed from lagging to an emerging economy  Vertical collaboration, (b) horizontal collaboration, and (c) competitor collaboration have positive impacts on firm growth capability.Several studies have provided empirical evidence for the positive impact of external collaboration on firm growth capability. For example, Wang et al.  reportedWe argued that external collaboration stimulates the growth of R&D efforts based on the push and pull theory. From a pushing perspective, firms would feel the pressure when their collaborators expect long-term behaviors involving R&D efforts  Vertical collaboration, (b) horizontal collaboration, and (c) competitor collaboration have positive impacts on R&D efforts.Several studies have addressed the positive relationship between external collaboration and R&D efforts. Garcia Martinez et al.  argued tWith the advance of a knowledge-based economy, R&D efforts become more and more essential for firms. R&D efforts, which reflect R&D intensity and R&D human capital from an investment perspective, play an important role in the implementation of a firm’s innovation-driven development strategy. On the one hand, R&D intensity is often considered a contributor to absorptive capacity, which is an essential “ability to recognize the value of new information, assimilate it, and apply it to commercial ends”  vertical collaboration, (b) horizontal collaboration, and (c) competitor collaboration and firm growth capability.The specific affecting mechanism is as follows. First, in the modern enterprise system, R&D is a necessary function of firm growth  were selected as our sample for data analysis.Table The data collection proceeded in two stages. In the first stage, we built composite scales for measuring external collaboration and process dimensions of firm growth capability. We marked the scales based on a content analysis of the company’s disclosed information. In the second stage, the data of other variables were collected from China Stock Market & Accounting Research Database (CSMAR Database).p < 0.01). For the different scores, the two raters discussed with each other under the guidance of the professor and finally reached a consensus.Following the increasing use of panelists in research  was measured by the total score of collaboration with suppliers and customers; horizontal collaboration (HC) was measured by the total score of collaboration with governments, universities and educational institutions, consultancy firms, venture capital investment firms, trade fairs and exhibitions, and others; and competitor collaboration (CC) was measured by the score of collaboration with competitors. The score of collaboration with each type of collaborator was coded as a binary variable which was measured by 1 and 0. Among them, 1 represents that collaboration widely and deeply happens and 0 represents the reverse side.In line with previous studies , the dependent variable of our study, from a new perspective that differs from the prior studies. We realized that firm growth capability is a much more comprehensive construct than innovation performance, and so we tried to measure it from both financial and process dimensions according to the theory of balanced scorecard. We carried out a data pre-processing for the financial and process ones into  interval and measured the firm growth capability by the mean value of their scores. First, the financial dimension of firm growth capability was measured by four indexes, i.e., debt-paying ability, operating ability, profit ability and development ability. Among them, the debt-paying ability was assessed by the current ratio (current assets/current liabilities); operating ability was evaluated by inventory turnover (operating costs/average inventory); profitability was measured by operating profit ratio (operating profit/operating income); and development ability was evaluated by the operating income growth rate (current year’s operating income/last year’s operating income −1). Through principal component analysis, we calculated the weighted score of the financial dimension. Second, we independently developed a scale for measuring the process dimension of firm growth capability. Four items, i.e. “the enterprise has established a global R&D center and created a global intelligent R&D platform”, “the enterprise has advanced intelligent manufacturing system”, “the enterprise has diversified, advanced, and intelligent sales system for offline and online sales”, and “the enterprise has advanced, convenient and intelligent service system for dealing with pre-sale, sale and after-sale issues”, were developed to respectively measure research and development ability, manufacturing ability, marketing ability, and serviceability. Obviously, the firm growth capability measured in our study includes but also goes beyond the connotation of innovation performance that was concerned by predecessors  was measured by the ratio of a firm’s R&D expenditure to operating income  was measured by the percentage of highly skilled R&D workers (researchers and technicians)  and private-owned, foreign-owned, or other types of enterprises (coded as 0). Second, the age was assessed by subtracting the year of firm establishment from the year in which the survey was conducted. Third, the size was measured by the natural logarithm of the employee scale. Finally, the industry as a dummy variable was coded as 1 when a firm belongs to the industry of advanced materials, consumer discretionary, and healthcare and energy. Otherwise, it was coded as 0.Learning from the previous study , we constructed the models M1-M5. Among them, model M1 tests the effect of control variables, models M2-M4 respectively test the effects of vertical collaboration, horizontal collaboration, and competitor collaboration, and model M5 tests their combined effect.RI and RHC respectively; the models M7-M9 measure the independent effects of VC, HC, and CC on RI, and similarly the models M12-M14 measure their independent effects on RHC; and the models M10 and M15 test their combined effects on RI and RHC respectively.Second, we developed the models M6-M15 to test the effects of external collaboration on R&D efforts that were proposed by H2. Among them, M6 and M11 were set for measuring the effects of control variables on RI and RHC respectively, and in M18 we measured their combined effect.Next, we built the models M16-M18 to examine the impacts of R&D effort on firm growth capability that were proposed by H3. Among them, the models M16 and M17 measured the independent effects of RI and RHC on the relationship between external collaboration  and FGC that were proposed by H4.Controls indicate control variables, including ownership, age, size (Ln), and industry, μ indicates the random disturbance, and i denotes the number of samples.Finally, we developed the models M19-M21 to measure the mediating effects of  and competitor collaboration , but not significantly correlated with vertical collaboration . R&D human capital is significantly and positively correlated with horizontal collaboration , but not significantly correlated with vertical collaboration  and competitor collaboration . Firm growth capability is significantly and positively correlated with horizontal collaboration , competitor collaboration , R&D intensity  and R&D human capital , but is also not significantly correlated with vertical collaboration . In a word, positive correlation relationships do exist between the core variables involved in this study, since most of the correlations are significant. This provides some preliminary evidence for a part of our research hypotheses.Table In addition, the highest correlation value is 0.742, below the threshold value of 0.75 , horizontal collaboration  and competitor collaboration  have significantly positive effects on firm growth capability. Hence, hypothesis H1 is supported. However, when they work together on firm growth capability, the impact of horizontal collaboration  is still significantly positive, but the impacts of vertical collaboration  and competitor collaboration  become insignificant. It indicates that the impact of horizontal collaboration on firm growth capability is much stronger than the impacts of vertical and competitor collaborations, and would cover up their effects.Through hierarchical regression analysis, the effects of external collaboration on firm growth capability are shown in Table , horizontal collaboration , and competitor collaboration  have significantly positive effects on R&D intensity. When they work together, the impacts of horizontal collaboration  and competitor collaboration  are still significant, but the impact of vertical collaboration becomes insignificant . It reveals the importance of horizontal and competitor collaborations to the inducement of R&D financial investment. According to the results of M11-M15 models, vertical collaboration , horizontal collaboration  and competitor collaboration  have significantly positive effects on R&D human capital. When they work together, the impact of horizontal collaboration  is still significantly positive, but the impacts of vertical collaboration  and competitor collaboration  become insignificant. It demonstrates the relatively stronger impact of horizontal collaboration. In any case, the results show that hypothesis H2 is accepted.The effects of external collaboration on R&D effort are shown in Table  and R&D human capital  have significantly positive effects on firm growth capability. The results of model M18 show that R&D intensity  and R&D human capital  have concurrently significant and positive impacts on firm growth capability. Hence, hypothesis H3 is accepted.The effects of R&D effort on firm growth capability are depicted in Table , horizontal collaboration  and competitor collaboration  on firm growth capability mediated by R&D intensity are all significant. However, the indirect effects of vertical collaboration , horizontal collaboration  and competitor collaboration  on firm growth capability mediated by R&D human capital are not significant. Hypothesis H4 is therefore partially accepted.We used the bias-corrected bootstrapping method to test the indirect effects. The mediation analysis was performed at a 95% confidence interval based on 10,000 bootstrap samples. The confidence interval of the lower and upper limits was computed to check whether the indirect effects are significant. If zero is not contained in the confidence interval, it indicates that the indirect effect is significant; otherwise, the indirect effect is insignificant. The results are shown in Table The theoretical contribution of the study is threefold. First, it provides important advancements to the theory of firm growth from an external perspective. The study examines the relationships between different types of external collaboration and firm growth capability, which expands the research scope of the factors influencing firm growth. The construct of external collaboration in the study, consisting of horizontal, vertical, and competitor collaborations, attempts to go beyond the general concept of collaboration breadth and depth analyzed by Laursen and Salter . It makeSecond, it proposes and empirically tests an integrated model between various types of external collaboration and firm growth capability through the intermediary role of R&D effort. In most extant studies, both external collaboration and R&D effort have been positioned as direct predictors (Zouaghi et al., Third, the previous research on open innovation mainly centered on firms in developed economies (Chen et al., It has several important implications for managers. First, enterprises are suggested to strengthen their cooperation with external organizations. Our study shows that vertical collaboration, horizontal collaboration, and competitor collaboration are all beneficial to the advancement of firm growth capability. We recommend firms select suitable partners matching with their internal capabilities in contextual limitations to maintain sustainable growth. Managers are encouraged to take actions for stimulating external collaboration such as building online cooperation platforms and establishing cooperation alliances. Second, enterprises should attach importance to R&D investment, since both R&D intensity and R&D human capital can improve firm growth capability. Managers are also advised to make more effort on R&D activities involving the efficient exploitation of R&D resources. Third, according to the mediation role of R&D intensity, we argue that top managers should take actions to better leverage external collaboration to induce investment in R&D. We trigger the thoughts of diversified functions of external collaboration in the sustainable growth of enterprises.It also has implications for governments. For example, Chinese central and local governments have introduced many policies involving university-industry cooperation, open innovation, R&D subsidy, talent exchange, and firm sustainability. However, some of them do lack sufficiently theoretical evidence. To some extent, our study could lead governments to make better decisions about firms’ sustainable growth driven by collaborative innovation when they improve their policies.Despite valuable implications obtained from the results, some limitations do exist. First, cross-sectional data in the study can only reflect the correlations between variables, but cannot infer the causal relationships. The collection of longitudinal data is recommended in the future. Second, the fact that our study only focuses on firms in China limits the generalizability of our results. Future research should therefore conduct cross-cultural analyses to test the robustness of our findings in some other economic entities. Third, self-developed measurement of firm growth capability may be flawed and inadequate, so it needs more tests and improvements. Future empirical research can adopt questionnaire surveys or interviews with executives to capture facets of firm growth capability. Fourth, though the sample size meets the requirement of regression analysis and mediating effect test for parameter estimation, it is insufficient compared with China’s large population and numerous companies. Therefore, we need to expand the sample size in the future. Finally, although our study controls for firm ownership, age, size and industry, we believe that these variables do not cover all the possible contextual differences capable of influencing the relationships examined in our conceptual model. Thus, opportunities for future research should capture other potentially significant control variables, such as firm internationalization and firm hierarchy.Regardless of the limitations described above, our study brings out some possible future research directions. For instance, we can introduce other variables, such as technology innovation and business model innovation as mediators to further explore the outside-in mechanism of the promotion of firm growth capability. Likewise, scholars may also expand the study by introducing moderating variables, such as market dynamism, technological turbulence, and enterprise culture.Dataset 1


Performance, body composition, and processing yield are important traits in broiler production. Quantifying their association will favor making decisions and better understanding the underlying processes involved in productive and economic efficiency. This study aimed to approach this topic by modeling the relationships between these groups of variables by applying regression to data from multiple studies. The study suggests that regardless of the intervention applied and the type of broilers, the feed conversion ratio improves when the body weight gain also increases. The study’s results support the use of body composition to predict the carcass conformation of broilers and their economic value. The information provided herein may particularly be of value to point out in the right direction further modeling efforts in areas related to poultry economics and sustainability.p < 0.001) and that the changes in FCR and effects in protein-to-fat gain (PFG) are directly related (p < 0.001). The changes in PFG and the effects on carcass conformation or the market value of birds are directly related (p < 0.001). In conclusion, body composition predicts carcass conformation and its market value, supporting its use to predict the economic value of broilers.This study aims to model the relationship among performance, whole body composition, and processing yield through meta-regression. Scientific papers found in Scopus and Google Scholar were included if they reported results and variability values of an actual experiment in the three mentioned groups of variables using a single broiler genetic line. Weighted mean effect sizes were determined with a random model, the risk of bias was determined, and heterogeneity was considered an indicator of usefulness. Meta-regressions considered the effect sizes of the response variable and the percent change in one or more variables as predictors. A 78-row database was built from 14 papers, including nine factors tested on 22,256 broilers. No influencing bias was found, and the data was determined useful. Meta-regressions showed that the changes in body weight gain (BWG) are inversely related to the effects in feed conversion ratio (FCR) ( Modern broilers show increasing growth rates, improved feed conversions, and increased breast meat size and yield, which play a pivotal role in the economics and sustainability of poultry production. Indeed, across the years, broilers have become leaner , and theTo achieve this aim, operation professionals need to be able to determine, ahead of time, what the final results will be, particularly the body weight (BW) and the breast yield of the flocks. However, appropriate indicators are needed, and it is necessary to more accurately determine how likely it is for the performance to correlate to processing traits. Similarly, a correct cost-benefit balance between lowering the feed conversion ratio (FCR) and increasing breast meat production is considered by industry nutritionists to optimize the feeding cost and increase the market value of the broilers, respectively. To do so, dealing with the relationship between performance and processing yield traits is crucial.Optimum production requires the best possible diet formulation strategies, so the industry will eventually move towards a productive energy system to more accurately take into account the effective use of nutrients to produce meat . The ArkConsequently, better quantifying the association between performance, body composition, and processing yield will support production professionals, nutritionists, and researchers to make decisions and better understand the underlying processes involved in productive and economic efficiency. Most studies on the relationships between these variables have focused on comparing genetic lines  or deterThe meta-analysis was conducted and reported following the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) 2020 guidelines .A multifactorial approach ,15 was aThe scientific papers used fitted the following inclusion criteria: An study was included if it (1) was an actual experiment, (2) reported results in the three groups of variables  as the result of testing any experimental treatment using a single broiler genetic line, (3) the sample analyzed  was the whole body (including feathers), and (4) reported a variability index per response variable.breast yield} AND broilers AND {body protein} OR {protein deposition} OR {protein gain}”. The following keywords in Portuguese were also used: “peito AND frango AND {proteína corporal} OR {deposição protéica} OR {ganho de proteína}”. Only articles in English and Portuguese were included. The documents gathered were examined. Those not related to the focus of the present review, thesis or dissertations, documents that were not papers published in peer-reviewed scientific journals, and duplicates were removed. One reviewer (D.A.M.) selected the papers by inspecting the titles, abstracts, and the whole body of the manuscripts and considering the criteria mentioned earlier. The reduced set of papers was approved by a second reviewer (C.N.C.).Scientific papers were searched in Scopus  and GoogPectoralis major + P. minor) to-legs (leg quarters) ratio (BLR), and market value . One reviewer (D.A.M.) collected the data from each paper. For every response variable in each data row, the effect size was considered the difference between the means of the two treatments being compared [A database was built where each row consisted of a set of independent data and included all the data corresponding to a comparison of two treatments from the same experiment at the same age, obtaining as many datasets as non-redundant comparisons were observed. Data from different experimental periods within a paper were considered completely independent and conformed separate rows in the database . Every rcompared . PossiblTwo synthesis stages applied in the study consisted of (A) grouping the effect sizes by response variable to determine their heterogeneity and (B) including the percent (%) changes of other response variables considered as moderators to determine the relationship between the changes in the predictor  and response variables. All studies providing data were considered eligible for each synthesis.Some response variables were calculated based on the data reported in each study. The following calculations were applied:ectively , and BW reported  to clearThe grouping of the effect sizes per response variable was visually displayed as forest plots and their relationship with the changes in moderator variables as bubble plots .p < 0.01 [i-th data row  and alsoi-th data row, i-th data row, i-th data row, k was the number of data rows, being that N denoted the normal distribution of the random inter-experimental deviation . The hevariance , as follp < 0.05 [p < 0.05 [I2, defined as the portion (%) of the total variability attributed to pure heterogeneity, was also determined [The heterogeneity was estimated with the REML (Restricted Maximum Likelihood) method  and evalp < 0.05 ). The nop < 0.05 ) and thep < 0.05 . The statermined .i-th data row , and alsoi-th data row, i-th data row, j-th moderator variable , j-th moderator variable in the i-th data row, i-th data row, i-th data row, and k was the number of data rows. Furthermore, in this case p-value was <0.05, the data were re-analyzed to determine the probability associated with the slope of the moderator , as follows:erations . The PR2seudo-R2 ), defineseudo-R2 :(16)PR2=p < 0.05) [p values > 0.05 [All relationships were assessed considering simple linear meta-regressions and the models fully reported if the slopes were significant ( < 0.05) . Complem < 0.05)  and detes > 0.05 .p < 0.05) in the dataset. (3) Comparing the 95%CI of the overall effect sizes calculated with the original and adjusted datasets  to determine the existence of bias in the overall effect size. The overall effect size was considered biased if the following two criteria were met: (A) Estimates were statistically different  Funnterpart ) and (B)stats [Metafor 2.0-0 [lattice 0.20-38 [The data was analyzed using R programming language  with RStstats , the metor 2.0-0 , and the 0.20-38 .Searches conducted provided 1087 records, from which 1032 were removed due to not pertaining to the focus of the study (899), through title inspection, not being scientific papers (112), or because of duplicates (21). Fifty-five papers were screened, from which the following were excluded: two papers presenting models but not treatment mean and variability values, one observational study, and 12 not reporting results in the three target groups of response variables. After reviewing in detail 40 papers, 26 were excluded because the chemical composition was determined for the carcass (12 papers) or meat (14 papers) and did not determine the chemical composition of the whole bird . The remA widely diverse database was built, including 78 data rows from the 14 scientific papers published between 1992 and 2019 in nine scientific journals. Fifteen rows included females and 57 male birds. Both fast- and slow- growing birds were included. The database included the following factors tested: Ambient temperature (9 rows), number of feeding phases (2 rows), feed restriction (1 row), source of dietary amino acids , dietary methionine precursors (10 rows), organic trace minerals (8 rows), and dietary contents of energy (17 rows), protein (7 rows), and amino acids (18 rows).The database included 3744 protein or N analyses to determine protein gain, 2336 analyses of fat or gross energy in bomb calorimeters to determine the fat gain, 1896 birds used to determine processing traits, and 1000 independent groups including a total of 22,256 birds to determine performance.All assessed variables showed heterogeneity among rows . The taup < 0.001), and every percentage point increase in the BWG was associated with a reduction in FCR of 23.5 g less feed (95%CI: 19.4 to 27.5) per kg of body weight gain. This relationship was equivalent in slow- and fast-growing birds , but those changes in the FCR were (p < 0.001), so the reduction in FCR was associated with reductions in the PFG. This relationship was consistent in slow- and fast-growing birds .The effect sizes in CAR showed no relationship with the changes in BWG, FCR, or PFG . In addiThe data showed that the changes in the body composition were highly related to those in the carcass conformation  and the carcass market value . Broiler response was determined for the variables  in the database.In the present study, the heterogeneity of data was considered a formal verification of its usefulness to explore the influence of moderator variables on the effect sizes. Indeed, not only was the FCR (effect size SD = 35 FCR points), but most of the data used were highly diverse and heterogeneous . The widThe data demonstrates that regardless of the intervention applied to improve the performance, the higher the BWG, the better the feed efficiency . This fiInterestingly, the data showed that the better the FCR, the lower the PFG , both inp < 0.05) that were more prominent in the abdominal fat yield (−13.8%) and the breast meat yield (+6.9%) than in the whole carcass yield (+0.8%) [The analyses showed that the effect sizes observed in the carcass yield are unrelated to the changes in performance, body composition , or even (+0.8%) .Finally, the observed association of the changes in body composition, as measured by the PFG, with the effect sizes in the carcass conformation agree with the higher protein content in the breast (64.6%) compared to the legs (50.8%) and the opposite relationship in the fat content  . This coFuture research may explore the dynamics and relationships between the body protein and fat content and their ratio. The findings in the present study will support better modeling approaches to predict body energy retention, as calculated from the protein and fat gains and their corresponding caloric coefficients, and ultimately favor the determination of the net productive energy (Arkansas Net Energy). In addition, practical body composition measurements, such as the abdominal fat pad weight , may be Even though all the data utilized in the meta-regression analyses were from actual experiments, our findings do not establish formal cause-effect relationships but associations.Clostridium perfringens, or feed ingredient-associated specific enteric challenges [All data available fitting the required criteria were included in this study; however, the factors tested in the primary studies were mainly focused on nutrition. Furthermore, none of the studies included specific factors that may influence the relationships established herein, such as stress , gut micallenges . TherefoOne of the biggest challenges in mathematically modeling biological systems is that researchers need to balance three opposing criteria , where only two of them can be optimized at a time (the Levins’ Three Dimensions framework ). UsuallIn addition, it should be considered that the actual performance, body composition, and carcass values were not used in the study but the changes that resulted from experimental treatments. Therefore, the influence of uncontrolled factors was minimized. This way, the differences in performance and body composition between sexes or across the years did not influence the calculations, but their relative sensitivity did. For example, the data showed that the relationship between the changes in body weight gain and feed conversion ratio is virtually the same in fast- and slow-growing birds, even though their genetics differ. Even though performance, lean mass, and breast meat yield have evolved with genetics across the years, it is unlikely that the relationship between the percent changes in body composition and the percent changes in processing yield as the result of an experimental treatment has done so.Finally, the database available from the literature will increase if only two of the targeted areas are included  instead of including all three. If, for example, the same procedure is replicated but restricting the searches only to performance and body composition, more data will be found, and the influence of the genetics , sex, and nutrient profile of the diets may be assessed.In conclusion, the results indicate that positive changes in body weight gain are associated with improvements in the feed conversion ratio and that the body composition predicts the carcass conformation and its market value. The results of the study on the association between body weight gain and the feed conversion ratio imply the importance of maximizing broiler weight gain to support the sustainability of broiler production.


Acute stroke interventions, such as stroke units and reperfusion therapy, have the potential to improve outcomes. However, there are many disparities in patient characteristics and access to the best stroke care. Thus, we aim to compare patient-reported outcome measures (PROMs) after stroke in two stroke centers representing the public and private healthcare systems in Brazil.PROMs through the International Consortium for Health Outcomes Measures (ICHOM) were assessed at 90 days after the stroke to compare two Brazilian hospitals in southern Brazil: a public university and a private stroke center, both with stroke protocols and stroke units.n = 165), patients from the public hospital (n = 175) were younger, had poorer control of risk factors, had more frequent previous strokes, and arrived with more severe strokes. Both hospitals had a similar percentage of IV thrombolysis treatment. Only 5 patients received mechanical thrombectomy (MT), all in the private hospital. Public hospital patients presented significantly worse outcomes at 3 months, including worse quality of life and functional dependence . Poor outcome, as measured by the mRS score, was significantly associated with older age, higher NIHSS score, and the presence of heart failure. However, the public practice was a strong predictor of any self-reported disability.When compared with the private setting (Patients assisted at a good quality public stroke center with the same protocol used in the private hospital presented worse disability as measured by mRS and patient-reported outcome measures, with greater inability to communicate, dress, toilet, feed, and walk. Stroke has emerged as a major global health problem, and over 12 million people have a stroke each year and around 6.5 million people will die as a result . In LatiDisability in the post-stroke phase has a major impact on society. It is highly associated with functional dependence and the need to increase healthcare usage worldwide , besidesBrazil is a continental country with 213 million inhabitants. The public healthcare system, financed by the Ministry of Health, has universal and free healthcare coverage for the entire population , 13. TheFor 30 years, stroke was the leading cause of death in Brazil , 14. StrPorto Alegre, a city in southern Brazil, was the first to implement a stroke network in the country, initially with 3 hospitals (2 public and 1 private) and currently with 15 public and 2 private stroke centers. Since 2005, Porto Alegre has had a very well-structured network for stroke care at all healthcare levels, from pre-hospital to hospital care . In 2015PROMs are reliable indicators of quality of life after stroke . It compThus, in this study, we aim to compare the patient-reported outcomes measures from two well-structured stroke centers in Brazil that use the same stroke care protocols, but that represent distinct healthcare scenarios, public and private identifying which factors may predict outcomes for these patients.The study is based on a cohort of consecutive patients with acute ischemic stroke treated at 2 stroke centers in a city in southern Brazil: 1 private and 1 public university hospital. For this study, all consecutive patients with stroke assisted for 1 year at the private hospital (where the ICHOM strategy was implemented to measure PROMs since October 2015) and for 5 months at the public university hospital  were evaluated. Importantly, both stroke centers used exactly the same stroke code protocol for individuals suspected of AIS.1. The Public University Hospital is a tertiary hospital with 850 beds, being a regional reference for acute stroke care in the Unified Public Health System . It is a high-volume stroke center with ~600 patients with stroke per year, with an acute stroke unit inside the Emergency Department (ED) and a Stroke Rehabilitation Unit with a complete multidisciplinary team, including early in-patient rehabilitation for all patients. Since 2013, after the implementation of the National Stroke Policy, the number of public stroke centers has increased from 2 to 16 in the region. As a result of the aforementioned strategies, the number of thrombolysed patients has increased across the region, avoiding the burden on a single stroke center. Since then, the number of thrombolysed patients in this hospital is stable, between 65 and 80 patients per year. The stroke center staff is formed by a trained multidisciplinary stroke team, including 4 stroke neurologists who provide supervision and support to neurology residents onsite during the day and by telemedicine at night. Neurology residents provide onsite coverage during the day and on-call coverage from 6 pm to 8 am. So, the stroke team is available 24 h a day on a rotating schedule to give support for all stroke cases from arrival at the ED to hospital discharge. It is a Joint Commission International-accredited hospital with stroke outpatient clinic, where 80–85% of patients return for follow-up visits at least once after hospital discharge. Patients with lacunar stroke, transient ischemic attack, or minor stroke with complete etiological investigation during hospitalization are referred to primary care services. Rehabilitation after hospital discharge depends on the public healthcare system, and generally, the access is difficult with a long wait to start. In addition, the patient is often unable to pay for the transportation to go to the rehabilitation session.2. The Private Hospital is a tertiary hospital with 465 beds, which only admits private patients or patients with private health insurance. It is affiliated with Johns Hopkins Medicine International and it is also a Joint Commission International accredited hospital. It has a Neurology Residency Program, a Neurohospitalist fellowship program, and a Latu Sensu Post-Graduate in stroke. It has a well-organized Stroke Center, with a service flow of approximately 250 patients with stroke per year and a complete multidisciplinary team. Usually, the hospital has 30 IV thrombolysis and 8 to 12 thrombectomies per year. After hospital discharge, patients are referred to their physician for outpatient care, so the 3-month outcome is collected over the phone by a quality-trained stroke coordinator. Hospital Moinhos de Vento was the first to implement the ICHOM methodology to measure outcomes in Brazil and consecutively monitor patients with stroke since October 2015. After hospital discharge, patients have quick rehabilitation support through private healthcare insurance.All data regarding baseline characteristics, pre-functional stroke status measured through modified Rankin Scale (mRS) score, risk factors, last time seen well, the severity of neurological deficit assessed by the National Institute of Health Stroke Scale , key quality metrics for acute stroke care, acute treatments, complications, and mRS score at hospital discharge are prospectively collected from all patients with stroke in the routine in both hospitals. Data collection is performed by residents, fellows, nurses, research coordinators, and trained medical students. The 3-month mRS is assessed in person at the outpatient clinic or by phone. The mRS score is a 7-level scale to evaluate functional outcome. It ranges from 0 to 6, with higher values indicating a worse outcome. In this study, poor functional outcome was defined as mRs > 2 .Monitoring hospital performance indicators ensures adherence to guidelines, but it is not enough to understand what is important to patients. Therefore, in addition to the mRS, PROMs after stroke were evaluated through the International Consortium for Health Outcomes standard set . The ICHThe ICHOM standard set  outcomesThe PROMIS-10 is a 10-item instrument that assesses the general domains of health and functioning, including general physical health, mental health, social health, pain, fatigue, and overall perceived quality of life. The total is the global score, but it can also be scored on the Global Physical Health component (0–20 points) and Global Mental Health component (0–20 points). Higher scores reflect better performance. The EuroQol group index score (EQ-5D) was calculated using a transformation formula . This scp < 0.05 in the univariate comparisons between care settings (public vs. private) at baseline were also included. One model evaluated the predictors of any type of disability and another regression model for modified Rankin scale score as a continuous variable. We performed Bonferroni's correction for multiple comparisons and p-values were considered significant at <0.05. Data analysis was performed using R 3.6.2 , and variables with missing values above 9% were excluded.Frequencies and categorical variables were compared using Chi-squared tests. Continuous variables were presented as median (interquartile range-IQR), except for functional outcomes measures scores (EQ-5D and PROMIS-10). When appropriate, group comparisons between the two care settings were performed using parametric and non-parametric tests. A multivariate regression model was performed to evaluate the predictors of poor outcome. The variables in the model were based on results from other studies or clinical observation. Variables with The study protocol and cohorts from both hospitals were approved by the Ethics Committee. The consent form was waived by the ethics committees because the data are collected as part of the monitoring the quality of care and with the objective of guiding better the recommendations for post-stroke care. Patient personal data is not shared under any circumstances.n = 175) and private (n = 165) tertiary hospitals. Individuals from the public system were younger , showed a higher frequency of hypertension , diabetes , heart failure , history of drinking and smoking , previous history of stroke , and more severe neurological deficit on arrival  (p = 0.28). In addition, both hospitals had a similar percentage of ischemic patients with stroke treated with IV thrombolysis , but the door-to-needle time was lower in the private hospital . Only 5 patients received mechanical thrombectomy, all in the private hospital .The flowchart of patients included in the study is shown in  = 0.01] . Individp > 0.05, p = 0.005), either by the proportion of patients with some disability measured as mRS > 1  or by functional dependence defined as mRS > 2 .Overall mortality was similar between both hospitals (p < 0.0001), accounting for the physical and mental health subscores of the test (p < 0.01 for both). The proportion of good results for almost all PROMIS-10 items was lower in patients from the public hospital (p = 0.26).Patient-reported outcome measures were collected at a 3-month follow-up and the results are presented in hospital . Also, thospital . Figure p < 0.0001).Despite worse outcomes and higher rates of disability in the public setting, individuals with mRS > 1 received more physical therapy in the private practice when compared with public (71 vs. 54%), although it did not reach statistical significance. The post-discharge rehabilitation assessment started in May 2016, so only 36% of the private hospital patients were evaluated. The proportion of patients with stroke recurrence at 3-month follow-up was higher in the public hospital , they had more risk factors, with nearly 27% having a prior stroke compared with 16% in the private hospital, and they had more severe strokes. The two hospitals had good rates of IV thrombolysis, and nearly half of the patients arrived within 4.5 h of symptoms at both hospitals. The main findings of this study showed worse results on almost all disability and quality of life outcome measures in the public hospital: worse functional outcome measure by mRS; more patients with a disability to walk, communicate, toilet, and dress independently; and worse scores on quality of life scales, including mood, cognitive function, pain, and fatigue. Furthermore, the proportion of patients with a new stroke was much higher in the public hospital (19 vs. 2%). Interpretations should be made with caution, although they have the potential to reflect the discrepancy between high and low-health settings worldwide.Patients with stroke in resource-limited settings are generally younger –25 and hDespite similar mortality rates, patients from public and private settings presented divergent functional outcomes. The two hospitals had similarly good rates of IV thrombolysis, showing that they are organized for acute stroke care; however patient-reported outcomes were significantly worse in patients from the public setting in all categories evaluated except for the use of a feeding tube. Importantly, almost half of the patients in the public setting showed an inability to communicate in the 3-month follow-up, in contrast to the private hospital, where it was only 16%. Besides, a large number of patients remained with important limitations in motor function after 3 months of stroke, including the ability to walk, toilet, and dress independently, in addition to the greater severity of stroke at the hospital arrival, which may reflect that these patients are receiving insufficient rehabilitation after hospital discharge, both physical and speech therapy, which plays an important role in the stroke outcome . AlthougPublic health strategies aimed at predictors of functional outcomes may massively improve the quality of care in public and private practice. Evidence-based policies have dramatically improved acute stroke care in Latin America with important advances in stroke prevention, yet to be implemented worldwide , 11. HypPrivate practice was a protective factor for any type of self-reported disability. In addition to the lower number of risk factors and lower stroke severity, potential explanations include the presence of MT only in the private hospital and better assistance after hospital discharge . IndividSome limitations of this study should be taken into consideration. We selected individuals from a large public university hospital with more resources than the majority of tertiary centers in Brazil. Thus, our results may overestimate the functional outcomes in the public system across the country and, probably, in other hospitals the disparities would be greater. In both settings, stroke mortality was higher than expected, with no difference between hospitals (20 vs. 18%). This result probably occurred because all deaths were accounted for in the study, including reviewing the medical records, in addition to the fact that only 82% of patients from both services were evaluated. The strength of this study is the use of PROMs to compare stroke outcomes in both healthcare systems in Brazil. Despite a growing interest in measuring outcomes that matter to patients, there are still few randomized clinical trials evaluating PROMs, especially rehabilitation-related studies , 40. PROIn summary, patients from a good-quality public stroke center presented worse patient-reported outcome measures at follow-up, namely, the ability to walk, communicate, toilet, dress, and the quality of life. These results occurred despite similar rates of IV thrombolysis, which was an independent predictor of outcome, reducing poor outcome by 76%. Furthermore, they had significantly worse control of cardiovascular risk factors and increased stroke recurrence, but similar mortality after 3 months of follow-up when compared with patients from the private setting. In the last decade, many improvements have occurred in the organization of acute stroke care in Brazil, with the increase in the number and quality of stroke centers. However, the country still has many young patients who arrive with severe strokes, with several risk factors and poor access to rehabilitation after hospital discharge. The country needs to continue increasing the number of stroke centers, but the main strategy should be a strong national primary care program, with more access to primary and secondary prevention and rehabilitation.The raw data including the R Script will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Comitê de Ética em Pesquisa Hospital Moinhos de Vento and Comitê de Ética em Pesquisa Hospital de Clínicas de Porto Alegre. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.SM analyzed the data, prepared the first draft of the manuscript, and reviewed all drafts. WB performed the statistical analysis and prepared the first draft of the manuscript. TS provided data, reviewed and edited the first draft, and final version of the manuscript. GMan prepared the first draft of the manuscript and reviewed the final version. AP edited the first draft and reviewed the final version of the manuscript. DM, LC, AS, MM, RB, AAlm, AD, FS, AAlv, NM, GA, PM, AW, GMac, MP, and LN provided data, reviewed the result, and approved the final version of the manuscript. All authors contributed to the article and approved the submitted version.The publication of this study was funded by FIPE/HCPA.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.


Parkinson’s disease (PD) is a progressive, neurodegenerative disease with motor symptoms that are well understood, but non-motor symptoms may be present and appear at different temporal stages of the disease. Physical activity based on dance movements is emerging as a complementary therapeutic approach to a range of PD symptoms as a multidimensional activity that requires rhythmic synchronization and more neuromuscular functions.To evaluate the effects of physical activity based on dance movements on the movement, executive functions, depressive symptoms, quality of life, and severity of PD in individuals diagnosed with PD.13 individuals with PD , underwent physical activity based on dance movements (2x week for 6 months). Participants were assessed at baseline and after 6 months on movement , executive function (FAB), depressive symptoms (MADRS), quality of life (PDQ-39), and severity of PD (MDS-UPDRS TOTAL). Student’s t-test was used to compare pre and post-intervention results.p = 0.0207, executive function by the FAB test, p = 0.0074, abstract reasoning and inhibitory control by the FAB, Conceptualization test, p = 0.0062, and Inhibitory Control, p = 0.0064, depressive symptoms assessed by the MADRS test significantly reduced, p = 0.0214, and the quality of life by the PDQ-39 had a significant increase after the intervention, p = 0.0006, showed significant improvements between the pre-and post-intervention periods of physical activity based on dance movements.We observed a significant improvement in the movement  by the POMA test, Physical activity based on dance movements contributed to significant improvements in movement , executive functions, especially in cognitive flexibility and inhibitory control, and the quality of life too. Sensorimotor integration, most cognitive processing and social skills may have contributed to the results.RBR-3bhbrb5.The study was registered in the Brazilian registry of clinical trials:  Parkinson’s disease (PD) is the second most frequent neurodegenerative disease in the World and affects around 1% of the global population over 60 years old  caused bThe currently available treatments for PD are palliative, do not cover the broad symptomatic spectrum, and do not stop the disease progression . TherefoPhysical activity is one of the most widely adopted non-pharmacologic complementary therapeutic approaches for PD, and increasing evidence points to its positive effects on the symptomatic profile –9. In exAmong the therapeutic approaches based on physical activity such as, for example, physical therapy, aerobic resistance exercises, strength training, and occupational therapy have widely been tested to minimize the progressive development of PD –16. HoweThere is an increasing interest in the therapeutic applicability of physical activity based on dance movements to the management of neurodegenerative diseases, especially for individuals with PD –21. The Therefore, physical activity based on dance movements can be a suitable therapeutic approach to simultaneously address motor and non-motor symptoms of people with PD . Many stThe present study aims to evaluate the effects of physical exercise based on dance movements on the movement, executive functions, depressive symptoms, and quality of life of people with PD. We hypothesize that physical activity based on dance movements may influence the motor and nonmotor symptoms  and quality of life perception.We performed a longitudinal study aiming to analyze the effects of physical activity based on dance movements as a complementary therapy for Parkinson’s disease on the movement, executive functions, depressive symptoms, and quality of life over six months. The participants performed physical activity based on dance movements using the “Baila Parkinson” method , 33, andThe research was developed between May and December 2019. The participants were recruited through social media announcements and subscribed through the research group’s website or telephone. The participants were screened to determine if they met the following criteria: diagnosis according to the UK Parkinson’s disease Society Brain Bank, Hoehn and Yahr stage I to III, under pharmacological treatment for at least 3 years, and on physical conditions to participate in the dance classes. The participants were excluded if they were unable to perform the physical activity based on dance movements, if they had other neurologic or neuropsychiatric conditions, or some comorbidities such as osteoporosis, severe cardiopulmonary diseases, or other conditions that could represent a risk for undergoing physical activities.The participants were submitted to two weekly sessions of physical activity based on dance movements (50 minutes/session), in the afternoon for 6 (six) months. The intervention was delivered in the rooms of laboratory and for small groups of 5 to 6 subjects. The rehabilitation program of exercise based on dance movements followed a protocol based on the combination of different dance styles adapted for appropriateness and safety for individuals with PD, named the “Baila Parkinson” method , 33.The “Baila Parkinson” method consists of progressive movement sequences created by combination and adaptation of choreographic elements from different dance styles executed by people with PD in different stages of the disease. The dance styles included: tango, ballroom dance, urban dances, samba, ballet, contemporary dance, and regional dances. The methodology of dance sessions was adapted to compliance and physical limitation by the people with PD. The sessions were structured around the “work lines” of the method, focused on five aspects of the disease, corresponding to the neuropsychological functions affected by PD: cognitive, sensory, motor, emotional and social aspects .the MDS-UPDRS to evaluation the general symptomatic presentation  . The qua Movement Disorder Society—Unified Parkinson’s Disease Rating Scale (MDS-UPDRS TOTAL).First, we evaluated the people with PD before initiation of the physical activity based on dance movements sessions (pre-intervention) and within the week following completion of the six months of attendance to dance therapy sessions (post-intervention), with approximately 50 sessions performed each patient. Demographic data were collected one week before the first intervention session and included age, sex, time since PD diagnosis, and medications. All patients were tested on the day corresponding the half an hour after taking the antiparkinsonian medication, corresponding to the best ON period of the subject. The tests comprised movement, executive functions, depressive symptoms tests, quality of life assessment questionnaire, and entation . Test prWe performed statistical analysis using GraphPad Prism® 8.0 Software. First, we tested normality (Kolmogorov-Smirnov) and homogeneity (Levine test) of the data. Then we carried out parametric statistical analyses with a paired t-tests to detect differences between the pre-and post-intervention results. The interval of confidence was set in 95% .Twenty-six individuals with idiopathic PD from which eighteen met the selection criteria and were selected to attend the therapeutic sessions . We had t (12) = 2.283, p = .0207 when submitted to physical activity based on dance movements  and post-intervention , ovements . The POMt (12) = 2.840, p = .0074 (t (12) = 2.941, p = .0062 (t (12) = 2.920, p = .0064  and post-intervention ,  = .0074 . The sub = .0062 . For the = .0064 . The FABt (12) = 2.264, p = .0214  and post-intervention  intervals,  = .0214 . The MADt (12) = 4.239, p = .0006  and post-intervention ,  = .0006 . The PDQt (12) = 0.6002, p = .2798  and post-intervention  periods when submitted to physical activity based on dance movements, however these differences were not statistically significant  = .2798 . The TOTThirteen individuals from mild to moderate PD participated in 6 months of physical activity based on dance movements, and our results showed improvements in balance and gait, executive function, depressive symptoms, and quality of life. These improvements corroborate the results of previous studies , 39, 40.The POMA test results showed significant improvement in balance and gait after the physical activity based on dance movements. Previous studies have shown improvement in gait and balance but by independent protocols , 41–50. Executive functions are the most affected cognitive domain since the early stages of PD . In our Depression is the most common neuropsychiatric disorder associated with PD. However, often depressive symptoms are neglected in PD due to the difficulty in identifying them and because they overlap with other symptoms of the disease. The significant reduction in depressive symptoms detected by the MADRS test in our study is in agreement with other studies, although performed by different protocols , 58, 59.The results showed a significant improvement in the perception of quality of life, which corroborates the results presented in Albany . The conRegarding the severity of Parkinson’s disease, our results did not show significant differences in the MDS-UPDRS scores between pre-and post-intervention periods, although other studies have shown the positive results of physical activity based on dance movements approaches over PD progression evaluated by similar tests , 67, 68.Important limitations of this study must be considered. The first limitation regards the small sample size and the lack of randomization in the design of this study. The very small sample size leads to wide confidence intervals and imprecision in our estimates. The randomization is missing because i) this is a non-controlled study; and ii) participants were free to make the choice of the activity that was being offered, therefore we cannot rule out selection bias, since people with PD who proactively seek adjuvant therapies for PD symptom mitigation may experience different effects of those who are less active.Also, the use of PD medications was not monitored during the study. Finally, our sample also showed a high standard deviation of the mean scores in the MDS-UPDRS test, which reflects a high difference in PD severity among the subjects. Nonetheless, this study provides important information regarding the outcomes that are most likely to improve with physical activity based on dance movements for people with PD, and also suggests that a larger, randomized controlled trial is warranted.The present study shows some motor and non-motor benefits from physical activity-based in dance for PD’s patients with significant effects on the balance and gait, executive functions, and depressive symptoms that are positive to the quality of life of people with PD. On the other hand, there were no significant changes in functional mobility and PD severity. Characteristic elements of physical activity based on dance movements such as sensorimotor integration, most cognitive processing, and social skills may have contributed to the results obtained in this study. The paradigm we adopted may be effective in future rehabilitation.S1 Checklist(PDF)Click here for additional data file.S1 File(PDF)Click here for additional data file.S2 File(PDF)Click here for additional data file.


Cancers are the leading cause of death among people living with HIV/AIDS (PLWHA); however, nationwide studies on cancer incidence are limited. We aimed to determine the trends in the incidence rates of AIDS-defining cancers (ADCs) and non-AIDS-defining cancers (NADCs) among Korean PLWHA. Data from the National Health Insurance Sharing Service from 2004 to 2017 were collected. Age- and sex-adjusted standardized incidence ratios (SIRs) for various cancer types relative to the general population were calculated. Of the 11,737 PLWHA followed-up for 65,052 person-years (PYs), 445  developed cancer. The incidence rate of ADCs decreased, whereas that of NADCs remained unchanged. PLWHA were at an increased risk of ADCs , including Kaposi’s sarcoma, non-Hodgkin’s lymphoma, and cervical cancer, and some NADCs, including anal cancer, lung cancer, liver cancer, and oropharyngeal cancer. Of the 396 patients who received antiretroviral therapy (ART), 215 with optimal adherence had lower incidence rates for ADCs and NADCs than those with non-optimal adherence. The 5-year survival rate of PLWHA with NADCs was 57.8%. Close surveillance and routine screening of cancers and improvement in ART adherence are required to improve the clinical outcomes of PLWHA. Non-AIDS-related deaths caused by chronic illnesses related to aging, such as cancer and cardiovascular disease, are increasing in most developed countries8. A study conducted in Japan from 2005 to 2014 revealed that cancer is the leading cause of death, accounting for 47% of all cases among PLWHA7.Since the introduction of highly active antiretroviral therapy (HAART), the life expectancy of PLWHA has dramatically increased, and consequently, prolonged survival time has led to variations in the death causes11. Therefore, for long-term survival of PLWHA, early detection and treatment of cancer through active screening is important. Most of these studies have been conducted in Western countries, and studies in Asian countries have mostly focused on Taiwan, where the National Health Insurance programs and databases have been established.PLWHA have an elevated cancer risk due to non-infectious causes, such as smoking and alcohol consumption, and HIV-related immunosuppression, which impairs the control of oncogenic viruses. With the advent of HAART, the incidence rates of AIDS-defining cancers (ADCs) such as Kaposi’s sarcoma, non-Hodgkin’s lymphoma (NHL), and cervical cancer decreased, whereas the burden of non-AIDS-defining cancers (NADCs) increased. In particular, virus-related NADCs, such as Hodgkin lymphoma (Epstein Barr Virus-related), liver cancer (Hepatitis B and C virus), anogenital cancer , and oropharyngeal cancer (HPV), are considerably more prevalent in PLWHA than in the general population. PLWHA are diagnosed with cancer in advanced stages and have a higher cancer-specific mortality rate than the general population after cancer diagnosis13. According to a study published in 2017 in Korea, there was an increase in NADC incidence compared to ADC incidence, without statistically significant difference14. However, the sample size was small, and research in a single institution is not enough to represent the incidence of cancer in PLWHA in Korea. To establish an appropriate screening plan for the early detection and treatment of cancer, it is important to obtain information regarding cancer types and trends among Korean PLWHA. Therefore, this study aimed to estimate and compare the risk of cancer incidence between the general population and Korean PLWHA and to investigate the recent trends in cancer among Korean PLWHA from 2004 to 2017, using a nationwide population-based database.Three studies were conducted in Korea, of which two studies published in 2006 and 2009, reported that there was no decrease in the ADC incidence nor a relative increase in NADC incidence, and the incidence pattern of NADC varied by institutions16. The NHIS is a mandatory public medical insurance system operated by the South Korean government. Almost the entire Korean population is covered by either the NHI (97.2%) or medical aid (2.8%)17. As the NHIS database represents the entire Korean population, it can therefore be used in nationwide population-based studies of various diseases, including HIV/AIDS18.We conducted a nationwide retrospective cohort study using the 2002–2017 data from the Korea National Health Insurance Service (NHIS) database. This database includes data on patients’ sociodemographics, healthcare provider characteristics, diagnoses based on the International Classification of Disease and Related Health Problems 10th revision (ICD-10), procedures or operations, pharmacy dispensing claims, and medical care costsn = 920), patients with unknown age and sex (n = 142), and patients who did not undergo any follow-up tests  were excluded. In suspected HIV cases, that is patients who were surveillance tested, physicians sometimes used the above-mentioned ICD-10 codes in their medical records and insurance claims until they perform a confirmatory test. Therefore, we excluded patients with less than three outpatient visits or no h ospitalization to avoid false-positive cases19. To identify HIV incidence cases, 1224 patients that were considered as prevalance cases, having HIV-related codes, were deselected between 2002 and 2003. We excluded those patients in whom we could not pinpoint the time they were given their HIV diagnosis. This was done to observe all patients from the time of diagnosis of HIV to the time of cancer for the purpose of the study. After excluding 54 patients aged < 15 years from this cohort, we determined that from 2004 to 2017, there were 12,515 patients with HIV/AIDS aged ≥ 15 years in Korea.Data from all 38,205 patients who had HIV/AIDS-related codes  between 2002 and 2017 were extracted from the database  and expanded benefit coverage for patients with HIV/AIDS from 2004. Patients with HIV/AIDS registered in this program were eligible for up to 90% co-payment reduction. Because physicians only registered patients identified by confirmatory test results, data regarding RIDs are verified and reliable. Most patients register in the RID program to reduce medical expenses; however, some patients may refuse registration because they are reluctant to disclose their health status. Thus, we defined HIV infection when a patient met the above criteria rather than defining it using the RID code. We investigated the match of patients with the RID code (V103) among those who met the above criteria to check the diagnostic accuracy. Of the 12,515 patients mentioned above, 12,068 (96.4%) met the RID code (V103).21. The final number of patients was 11,737. The first date of HIV-related code registration in the database was regarded as the date of diagnosis. Patients were observed from the day of first hospital visit to the date of cancer diagnosis, death, or December 31, 2017.Of the 12,515 patients, 448 who were diagnosed with cancer before the diagnosis of HIV were excluded to avoid prevalent cancer cases. Further, 290 patients who were diagnosed with cancer within the first 90 days after the diagnosis of HIV, were considered prevalent cases and were not included in our study22. In Korea, a person diagnosed with cancer is registered with the National Cancer Registry with a specific code  to indicate cancer diagnosis and to provide special insurance benefits22. Therefore, cancer diagnoses based on claims are considered reliable. If a patient was diagnosed with multiple cancers, only the first cancer was considered.Cancer was first identified based on the ICD-10 codes, including C00–C99, and the types were subdivided according to the cancer site. Cancer was defined as the presence of the same C code more than three times within a year or inpatient hospitalization with a C code23. To evaluate cancer trends, we divided the overall observation period into three: period 1, 2004–2008; period 2, 2009–2013; and period 3, 2014–2017.According to the CDC classification criteria, NHL, Kaposi’s sarcoma, and cervical cancer were classified as AIDS-defining cancers (ADCs), whereas all other types of cancer were classified as non-AIDS-defining cancers (NADCs)Comorbidities were defined based on information obtained prior to or during HIV diagnosis. Comorbidities were evaluated using Charlson’s comorbidity index (CCI). Because HIV/AIDS and cancer were the variables of interest, we used the modified CCI to exclude these two diseases from the list of comorbidities. Covariates and ICD-10 codes used in the study included the code for chronic hepatitis B virus (HBV) infection  and chronic hepatitis C virus (HCV) infection (B182).23 , calculated as the number of days for which ART prescription was filled divided by the patient’s total follow-up time in days since ART initiation until 31 December 2017, cancer development, or death. To assess the association between cancer risk and ART adherence, we calculated standardized incidence ratios (SIRs) separately for individuals with optimal adherence. Optimal adherence to ART was defined as an MPR ≥ 95%. In the ART group, those who received only one ART regimen or two nucleoside reverse transcriptase inhibitors were excluded because they had possibly received post-exposure prophylaxis, pre-exposure prophylaxis, or treatment for other diseasesχ2 test or Fisher’s exact test, whereas non-categorical variables were tested using the Mann–Whitney U test or Kruskal–Wallis test. Cancer incidence among PLWHA was compared with that in the general Korean population between 2004 and 2017 from the Korea Central Cancer Registry (KCCR) using SIRs obtained by indirect standardization26. We calculated the ratio of observed to expected cancers in overall and site-specific cancers among PLWHA. The expected number of cancers was calculated by multiplying the age-specific cancer incidence rate in the general population for 2004–2017 and the number of person-years of PLWHA, and 95% confidence intervals (CIs) were calculated using the Poisson distribution. In addition, we compared the SIRs for optimal adherence using the Poisson regression. Kaplan–Meier curves were used to estimate the overall survival during the study period. All tests of significance were two-tailed, and statistical significance was set at P < 0.05.The SAS Enterprise Guide  was used for all statistical analyses. Categorical variables were compared using Pearson’s The study protocol was reviewed and approved by the Institutional Review Board (IRB) of the Pusan National University Hospital . Our research was performed in accordance with the relevant guidelines and regulations. Informed consent was waived by the IRB of the Pusan National University Hospital because patient information was anonymized.In total, 11,737 patients with PLWHA were followed up for 65,051.53 person-years . The total study cohort comprised of 10,911 men with a total follow-up of 60,115.89 person-years and 862 women with 4935.64 person-years. he clinical characteristics of the study population are summarized in Table p < 0.001). The prevalence of prophylactic antibiotic use was higher in the ADC group . Optimal ART adherence was higher in the NADC group, albeit not statistically significant  (Table The median age of patients with ADCs was 43 years (interquartile range [IQR]: 36–52), and that of those with NADCs was 53 years (IQR: 43–62)  were ADCs and 298 (67.0%) were NADCs  Table . Comparep < 0.001)  . However, both decreased incidence rates were not statistically significant. A similar decrease in the SIRs of ADCs was observed . There was no significant difference between the survival curves of ADC and NADC . In the overall trend, no significant difference was found between the two groups, but when they were analyzed separately for each period, probability of survivial in NADC was significantly higher at the 1st year of cancer onset, and probability of survival in ADC was signifantly higher at 7th and 8th years of onset  and 57.8% (ADC: 61.5% vs. NADC: 55.9%), respectively . The increased risk was noted for various types of cancer but was particularly high for virus-related cancers. Although the incidence of ADCs declined, that of NADCs did not.30. In a study conducted in France from 2010 to 2015, the incidence of ADC was 191 cases/100,000 person-years, the incidence of ADC showed a decreasing trend, and the incidence rate of NADC did not change28. In contrast, studies conducted in 2006, 2009, and 2017 in Korea reported no decrease in the incidence rates of ADCs among PLWHA14. As ART was established and immunity was restored, the incidence rates of Kaposi’s sarcoma and NHL decreased over time, and similarly, the risk of ADC was lower in those with optimal ART adherence. Despite the decreasing cases of ADCs, patients with poor adherence to ART remain vulnerable. A higher SIR was observed for cervical cancer among PLWHA than among the general population; however, because of the small number of cases (n = 7), a trend of decreasing incidence over time and association with ART was not confirmed.Decreasing incidence of ADCs among PLWHA has been noted in Western countries and in Taiwan34. According to the HIV/AIDS notification in Korea by the KCDC, especially since 2010, the number of young adults with HIV infection in their 20 s has rapidly increased35. This continuous influx of young adults may have slowed the rise in the cancer incidence rate over time. Some studies have shown that the SIR of NADCs decreases with time27. Previous studies included all pre-HAART periods, early HAART periods, and late HAART periods; however, this study only included late HAART periods, which may have affected the results.During the study period, no significant trends were observed in the incidence or SIR of NADC. Previous studies have reported that, as PLWHA ages, the NADC incidence tends to increase36. Additionally, previous studies have shown that enhanced immune status and early initiation of ART could reduce the incidence of virus-related NADCs37. Similarly, we found that the incidence of ADC and virus-related NADCs was reduced in the optimal ART adherence group, although it remained higher than that in the general population. Therefore, to improve cancer outcomes among PLWHA, adherence to ART and screening for and prevention of virus-related cancers should be promoted. Efforts should also be made to initiate early ART and the maintenance of enhanced immune status.Park et al. demonstrated that sustained ART, which results in long-term viral suppression, may contribute to cancer prevention, with risk reduction for ADC and virus-related NADC14. Lung cancer is the most common cancer type in Korean men aged ≥ 65 years38. These results suggest that cancer incidence patterns in Korean PLWHA are gradually becoming similar to those of the general population because of prolonged survival due to the availability of HAART14. The risk of lung cancer in PLWHA was elevated relative to that in the general population, which is consistently noted in previous studies40. In addition to the high prevalence of smoking among PLWHA, HIV infection itself, independent of smoking, was associated with an increased risk of lung cancer41. Therefore, it is necessary to encourage smoking cessation and participation in screening tests (low-dose computed tomography), which are now included in Korea’s National Cancer Screening Program (NCSP) since 2019.Risk was elevated for some virus-unrelated NADCs such as lung cancer and prostate cancer in PLWHA, compared with the general population. We found that lung cancer was second only to liver cancer in terms of NADC incidence. Lung cancer patients were not detected in two studies published in 2006 and 2009 among PLWHA in South Korea, whereas in another study published in 2017 lung and liver cancers were among the most diagnosed cancers42. In Korea, prostate cancer incidence has increased significantly compared to that in the past, partly due to the rise in average life expectancy, westernized dietary habits, and increased awareness of prostate cancer screening44. The genitourinary tract is a common vector for HIV transmission, and HIV status is a risk factor for lower urinary tract symptoms45. This may explain the high SIR of prostate cancer as PLWHA are more likely to visit the hospital regularly and get tested if they have urinary infection symptoms. Similarly, a study conducted in Taiwan has reported an increase in the SIR of prostate cancer27.In contrast to previous findings, we found a higher incidence of prostate cancer among PLWHA than among the general population47. In the general Korean population, the screening rate with recommendations for stomach cancer has consistently been > 70% since 201248. Vulnerable populations, such as those with low income, low education level, and unhealthy behaviors , were associated with lower participation in gastric cancer screening programs in South Korea49. Thus, compared with the general population, PLWHA may have an underestimated risk of cancer, especially those widely screened, owing to poor screening. In contrast, in a study of South Korean patients who received solid organ transplantation, the SIRs for thyroid, stomach, and breast cancers increased compared with those reported in the general population, which may be explained by increased surveillance rate50. Although the 5-year survival rate of cancer in Korea was 70.3%, that of PLWHA with NADCs was only 55.9%, suggesting that cancers are diagnosed at a more advanced stage among PLWHA than among the general population. Therefore, cancer screening rates should be increased for the early detection of cancer among PLWHA.Consistent with previous studies, an increase in SIR was not observed for most virus-unrelated NADC, and a decreased in SIR was observed in some cases such as stomach cancer, thyroid cancer, breast cancer. The low risk of stomach and thyroid gland cancers among PLWHA may be because of decreased surveillance. In Korea, screening for stomach, liver, colorectal, breast, cervical, and lung cancers are included in the NCSP, and that for thyroid cancer is widely available51. In addition, this immunodeficiency may have delayed the treatment of cancer, suggesting that the early initiation of ART is also important for cancer treatment. After 7 years, the survival rate of NADC interestingly showed a decrease, which may be attributed to the adverse effects of cancer treatment. When ART and antineoplastic agent are combined, enhanced and overlapping toxics effect are possible52. One study demonstrated that immunosuppression in PLWHA driven by cancer treatment, such as chemotherapy and radiotherapy, can result in an increased risk of mortality53. A cancer treatment strategy, based on the characteristics of HIV patients, is therefore warranted.No significant differences were found in overall survival between patients with ADC and patients with NADC, but there were differences in some time periods. During the first year, the survival rate of patients with ADC decreased sharply, but after one year, the survival rate did not decrease significantly. However, the survival rate of patients with NADC continued to decrease consistently for eight years. The lower survival rate in patients with ADC during the first year may be due to advanced immunodeficiency. In our study, patient with ADC were diagnosed with cancer at a younger age than patient with NADC, but they were more immunocompromised. In a previous study conducted in Korea, in spite of survival improvement in the HAART era, the early mortality was still substantial in late-HAART period, presumbably because the patients were in advanced immunodeficiency at initial presentation22. Therefore, we believe that the definitions of PLWHA and patients with cancer used in this study are reliable. Second, although we standardized age and stratified by sex to eliminate their effect on cancer incidence between PLWHA and the general population, other risk factors of cancer, such as smoking, alcohol use, and the prevalence of oncogenic viral infection, were not considered, owing to a lack of information. Third, as we had extracted data from the data from the database in 2019, we were able to retrieve data only a recent as 2017, therefore we defined our search period as between 2005 to 2017; but the trend of NADC was not clear, and the number of cancers was not sufficient to analyze the tendency for each cancer, so a study including an additional period may be necessary. Finally, as the claim data did not include clinical data in addition to laboratory test results, we were unable to extract data on CD4 count and HIV viral load, which could have helped predict the level of immune dysfunction. Therefore, we used prophylactic antibiotics and AIDS-defining illnesses as indicators of advanced immune suppression.This study had several limitations. First, HIV/AIDS and cancer incidence rates were identified through the medical insurance code and the ICD-10 code in the NHISS claims data, with potential misclassification. To address this limitation, we only included HIV/AIDS cases that had been diagnosed using the relevant diagnostic code, wherein the HIV-related test code had been prescribed, and hospitalization or at least three outpatient visits were recorded. Moreover, we confirmed that most patients (95% in PLWHA) met the RID criteria. The identification of cancer cases based on claims data is considered reliable in Korea because cancer codes are reviewed by the NHIS and provide additional benefits to patientsOverall, although cancer risk has declined in PLWHA in South Korea, the risks for ADCs and many other virus-related cancers remain. We found that cancer incidence in patients with optimal compliance with ART decreased but remained higher than that in the general population. Our findings suggest that close surveillance and routine screening of cancers and improvement in adherence to ART are required to improve the clinical outcomes of PLWHA.Supplementary Information.