Diabetes mellitus is related to variable dental and oral complications like xerostomia and periodontal problems. Therefore, diabetes can affect the oral status and oral health-related quality of life (OHRQoL). A systematic review of evidence can determine the association between diabetes and OHRQoL. so, this study aimed to evaluate the effects of diabetes on OHRQoL.After determining the PECO and eligible criteria, a comprehensive search was conducted in PubMed, Scopus, Web of Science, and Embase without any restriction. Further searches were performed in Google Scholar and reference lists of selected articles. Two independent reviewers carried out paper selection, data extraction, and quality assessment. A meta-analysis was conducted using a “random effect model” and the standardized mean difference of OHRQoL with a 95% confidence interval (CI) was reported as estimating pooled effect size.After screening 237 identified records, three case-control and ten cross-sectional studies met eligibility criteria. Two cross-sectional studies were excluded in the quality assessment phase and the rest of the studies have a low or moderate risk of bias. The pooled standardized mean difference between the case and the control groups was 0.148 (95% CI: −0.045 to 0.340).Diabetes mellitus has no statistical significant association with OHRQoL. Nevertheless, based on the articles' review, it seems that diabetes can lead to functional limitations, physical pain, and psychological discomfort. Also, complications of diabetes adversely affect wellbeing. Hence dentists can play an essential role in the awareness of persons with diabetes about these problems and improve their OHRQoL.https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022303038, identifier CRD42022303038. Diabetes mellitus is a chronic disease caused by insulin dysfunction and deficiency characterized by hyperglycemia (high blood glucose) , 2. ChroInternational Diabetes Federation (IDF) estimated that in 2021, 536.6 million adults had diabetes in 215 countries. It also stated that by 2,045, approximately 783.2 million people worldwide will have diabetes mellitus  that examined diabetes mellitus as the exposure and OHRQoL as the outcome (determined by OHIP or GOHAI questionnaire) and also studied individuals over 18 years of age were included. Studies in which participants had received periodontal treatment in the past 6 months were excluded, along with case reports, reviews, and review protocols. In addition, no restrictions on language or year of publication were considered.*”[All Fields] OR “diabet*”[All Fields] OR “Diabetes Mellitus”[MeSH Terms] OR “Diabetes Mellitus”[All Fields] OR “diabetes mellitus, type 1”[MeSH Terms] OR “diabetes mellitus type 1”[All Fields] OR “diabetes mellitus, type 2”[MeSH Terms] OR “diabetes mellitus type 2”[All Fields] OR “T1DM”[All Fields] OR “T2DM”[All Fields]) AND . The search strategies of other databases are also presented in Two independent reviewers (YMH and KA) carried out a systematic literature search using PubMed, ISI Web of Science, EMBASE, and Scopus without any restriction on language or other limitations until April 2022. Further searches were conducted in Google Scholar (gray literature) and reference lists of selected articles until May 2022. We used following search query in PubMed:  screened the title and abstract of studies according to eligibility criteria. Dubious studies were kept for the next stage. Then, the remaining full-text articles were evaluated according to inclusion and exclusion criteria, and relevant reports were selected. Any disagreements about the selection of articles between two reviewers were resolved by consulting the third reviewer (YMH).The same two reviewers (KM and ST) independently evaluated the quality of studies using NIH quality assessment tools for Observational Cohort and Cross-Sectional Studies and Case-Control Studies . For thep-values).A data extraction spreadsheet was designed, and the following information was independently extracted by two reviewers (KM and ST): first author's name, year of publication, country, study design , participant characteristics , type of questionnaire and statistical summaries related to OHRQoL . The standardized mean difference (SMD) of OHRQoL with a 95% confidence interval (CI) was reported as estimating pooled effect size. Due to the small number of studies, a “random effect model” was used. Heterogeneity across included studies assessed by the Cochran Q test and I-square index. If the stantial . PublicaDue to the lack of a clear cutoff to determine the effect of OHRQoL on different variables such as diabetes, only the standardized mean difference (SMD) of OHRQoL between the case and control groups was used for meta-analysis.This research was approved by the Research Ethics Committees of Vice-Chancellor in Research Affairs -Medical University of Isfahan .Initially, 237 records were identified from searching in electronic databases and manual search. After removing duplicates, the title and abstract of 103 articles were screened separately by two reviewers. Based on predetermined eligibility criteria, 29 articles were selected for the full-text stage. After scanning the full-text of articles, 16 records were excluded for the following reasons: the outcome wasn't OHRQoL; the age range wasn't appropriate; Insufficient data to investigate the relationship between diabetes and OHRQoL, and periodontal treatments. In addition, two records were excluded during the quality assessment phase , 29. Finn = 7), OHIP 20 (n = 3), GOHAI (n = 2), and both the OHIP 14 and GOHAI (n = 1) for measuring the OHRQoL. The sample size varied between included studies, and the age of the diabetic patients ranged from 18 to 86 years old. Three studies included controlled diabetic patients with type 1 and 2 diabetes [62, 66, and 80% of the participants in Azogui-Lévy et al.   , 3.The funnel plot showed a symmetric distribution of the data in each study . Begg's The present study systematically reviewed the evidence on the impact of diabetes mellitus on oral health-related quality of life and Related variables affecting OHRQoL. Our meta-analysis of three case-control studies , 19, 34 Among the included studies, nine studies used the OHIP questionnaire to assess OHRQoL, of which five studies examined each domain of the OHIP questionnaire separately. All five studies reported a high impact of diabetes on three domains of Functional limitation, psychological discomfort, and physical pain than on other domains. The study of Ravindranath et al.  and MohsThe studies included in this research demonstrated that diabetes mellitus reduced OHRQoL in different ways. Ravindranath et al.  and NikbMohsen et al.  suggesteAzogui-Lévy et al. showed that age is directly associated with better OHRQoL. The importance of aesthetic demand in younger patients and the greater adaptation of older people to diabetes after years of suffering from it were among the reasons they stated for this association .Like any research, study limitations must be identified to deduce the finding correctly. Participants in most included studies were gathered from diabetic patients who were referred to hospitals or clinics. In other words, most of the studies were hospital-based. Also, the findings were mainly based on the questionnaire results, and patients were not clinically examined. On the other hand, the small number of case-control studies did not allow for performed meta-analyses with a larger population. Hence, we suggest conducting case-control studies in a large-scale, randomized, and community setting. We also recommend that more dependent variables be carefully examined to determine the confounders and the effect of these variables on OHRQoL.Given the finding of this literature, diabetes mellitus has no statistically significant association with oral health-related quality of life. Nevertheless, based on the articles' review, it seems that diabetes can lead to functional limitations as well as physical pain and psychological discomfort. On the other hand, complications of diabetes such as xerostomia and periodontal problems adversely affect wellbeing. Therefore, due to the relationship between some variables related to diabetes and OHRQoL, dentists can play an essential role in the awareness of diabetic patients about these problems and improve their quality of life. In addition, we recommend that visiting a dentist be part of the care protocol for diabetic patients.f_nilchian@dnt.mui.ac.ir.The datasets presented in this article are not readily available because this article is a systematic review and does not have any dataset. Requests to access the datasets should be directed to YM, KA, ST, MT, and FN researched data, designed the study, reviewed, and edited the manuscript. KA and ST screened, evaluated the quality of the studies, and extract a data spreadsheet. YM checked the data as the third reviewer. Statistical analysis was performed by MT, YM, and FN wrote the first draft of the manuscript. FN is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data, and the accuracy of the data analysis. All authors approved the final version of the manuscript.


To investigate whether radiomics based on ultrasound images can predict lymphovascular invasion (LVI) of rectal cancer (RC) before surgery.A total of 203 patients with RC were enrolled retrospectively, and they were divided into a training set (143 patients) and a validation set (60 patients). We extracted the radiomic features from the largest gray ultrasound image of the RC lesion. The intraclass correlation coefficient (ICC) was applied to test the repeatability of the radiomic features. The least absolute shrinkage and selection operator (LASSO) was used to reduce the data dimension and select significant features. Logistic regression (LR) analysis was applied to establish the radiomics model. The receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) were used to evaluate the comprehensive performance of the model.Among the 203 patients, 33 (16.7%) were LVI positive and 170 (83.7%) were LVI negative. A total of 5350 (90.1%) radiomic features with ICC values of ≥ 0.75 were reported, which were subsequently subjected to hypothesis testing and LASSO regression dimension reduction analysis. Finally, 15 selected features were used to construct the radiomics model. The area under the curve (AUC) of the training set was 0.849, and the AUC of the validation set was 0.781. The calibration curve indicated that the radiomics model had good calibration, and DCA demonstrated that the model had clinical benefits.The proposed endorectal ultrasound-based radiomics model has the potential to predict LVI preoperatively in RC.The online version contains supplementary material available at 10.1186/s12880-022-00813-6. According to global cancer statistics in 2020, rectal cancer (RC) is a major threat to humans. The RC has the third-highest recorded incidence of cancer, which is listed after lung cancer and breast cancer, and the cancer-related mortality rate of RC is ranked second after lung cancer . Early dThe poor prognosis of RC is related to various factors, including lesion size, stage, lymphovascular invasion (LVI) status, tumor marker status, immune indicators that are positive, RC’s sensitivity to radiotherapy and chemotherapy, and so on .Previous studies have shown that vascular invasion is an independent risk factor for poor prognosis of RC , 8. Now,There are numerous means of preoperative examination for RC. Colonoscopy can observe the general surface of the mass and perform the biopsy; however, the disadvantage is that the depth of infiltration and extraintestinal invasion could not be observed. Magnetic resonance imaging (MRI), especially high-resolution MRI, is the first choice for preoperative imaging diagnosis and postoperative follow-up review, which can accurately perform tumor node matastasis (TNM) staging, but its high cost makes it difficult to repeat multiple examinations, and it is always difficult to distinguish the T2 stage from the T3 stage , 10. EndIn recent years, radiomics has been introduced and has the potential to provide help for the above clinical challenges. Radiomics, using computers to excavate the data of medical images  to discover the intrinsic relationship between medical images and features, such as diagnostic localization, biological behavior, and treatment outcome of diseases, could provide a reference for clinical decision-making. Several recent reviews systematically reviewed artificial intelligence (AI) models and machine learning about radiomics based on high-resolution MRI which could be used to predict the response of chemotherapy and distant metastasis of RC, and the results showed that this novel imaging technology might be helpful to clinical decision-making –16. ChinThe Ethics Committee of our hospital approved this retrospective study. Informed consent was waived. Patients with RC who underwent surgery in our hospital from January 2018 to February 2021, were included in this study. Inclusion criteria were the following: (1) RC that was confirmed by postoperative pathology, (2) TRUS examination that was conducted before surgery, (3) the biggest section of the RC lesion image that was clear and complete , and (4) the required clinicopathological data that were complete. The exclusion criteria were as follows: (1) previous history of RC, (2) unclear diagnosis of LVI, and (3) neoadjuvant chemoradiotherapy if performed before ultrasound examination.First, the patient was asked to lie on the examination bed with a left lateral coxa and knee bending position, take off pants, and fully expose the anus. Before the TRUS examination, a digital rectal examination (DRE) was conducted to judge whether anal stenosis exists and the distance between the lower edge of the lesion and the anus, the lesion’s size, and its position. Then, a 50-ml mixture of water and starch was instilled into the rectal cavity through the anus, and the TRUS probe was wrapped in a condom for isolation when the probe was extended into the anal canal for examination. A convex or line array probe was selected according to the lesion’s size and distance between the lower edge of the lesion and the anus. An experienced sonographer performed a comprehensive scan of the lesion to assess the lesion’s size, shape, margin, and internal echogenicity, the distance between the lower edge of the lesion and the anus, and whether muscularis, serosal layer, internal anal sphincter, and external anal sphincter invasion existed. The images were stored for future use.Esaote MyLab Class C and General Electric Company (GE) LOGIQ E9 ultrasound diagnostic instruments were used to acquire ultrasound images of the lesions. The frequency of the probe was 6–15 MHz, and the images were recorded and saved in the Digital Imaging and Communications in Medicine (DICOM) format.Clinical and pathological data, such as the patient’s gender, age, tumor size, stage, vascular invasion, and serum CEA, CA125, CA199, CA242, CA742, etc., were collected.In this study, the ROIs of the lesions were outlined using the image software application ITK-SNAP(3.8.0), which is an open source for medical image segmentation Fig.  24]. Th. Th24]. In this study, we used the Cart package in R language (version 4.3.0) to stratify all patients in a 7:3 ratio by the computer randomization method, with 70% of patients entering the training set for model construction and 30% of patients entering the validation set for model verification. Different evaluation metrics (radiomic features) often had different scales and scale units. To increase the comparability of quantitative radiomic features, we performed Z-score normalization for quantitative features in training and validation sets, respectively. Subsequently, to select the radiomic features associated with LVI in RC from the numerous image features, we performed a hypothesis test on all features in the training set and retained the features with statistically significant significance in the hypothesis test for the multifactor regression analysis. The massive number of radiomic features constructed in the model easily led to model overfitting, and to reduce the influence of high-dimensional features on the model, we used LASSO regression for feature downscaling and tenfold cross-validation to filter the optimal subset of features to predict LVI in RC from radiomic features. Meanwhile, we performed a correlation analysis of all features to optimize the covariance effect of the subset of features. We considered a correlation coefficient of ≥ 0.8 to be a high correlation.To construct the radiomics model, we performed multifactor logistic regression modeling using the optimal subset of features in the training set. Meanwhile, we used the area under the curve (AUC) of the receiver operating characteristic (ROC) curve of both training and validation sets to evaluate the comprehensive discrimination ability of the radiomics model. We also used calibration curves to calculate the agreement between the predicted and observed probabilities. We used decision curve analysis (DCA) to estimate the outcome of the prediction model under different threshold probabilities.SPSS 22.0 and R language (version 4.3.0) were used for the analysis. For statistical analysis of clinical parameters and hypothesis testing of radiomics characteristics, the chi-square test or Fisher’s exact probability method was used for statistical analysis of count data, and an independent samples t-test or Mann–Whitney U test was performed for measurement data. Means ± standard deviations were used for measures that conformed to a normal distribution and medians for those abnormal distributions. A P-value of < 0.05 was considered statistically significant.According to the above-mentioned inclusion and exclusion criteria, 203 patients with RC were finally included Fig. . The ageThe Intelligence Foundry software was used to extract the features of the outlined ROIs Fig. , and a tWe used logistic regression on the optimal subset of features to build a radiomics model in this training set, and we also applied the validation set for model evaluation. The ROC curves Fig.  showed tRC has a high incidence and poor prognosis. Microvascular invasion is an important factor in the residual and recurrence of RC . At thisRadiomics is useful in the diagnosis, staging, treatment response, and prognosis of many solid tumors. For example, radiomics can be applied to the differential diagnosis of HCC , the assUltrasound is an inexpensive, quick, and noninvasive examination, which reflects its worth in offering TNM stage information of RC. Patients may gain benefits if this examination combining radiomics is used to predict the LVI of RC noninvasively before resection.There have been some studies of radiomics predicting vascular invasion in RC. Zhang et al. . appliedNevertheless, radiomics has limitations, especially in its operator dependence on manual outlining of the ROIs and the generalizability of the model . For exaThis study has the following limitations. First, the case selection bias may exist in our retrospective study, which should be avoided by prospective studies in the future. Second, the ultrasound images used in this study were from different operators using different machines, and these confounding factors could potentially affect the predictive performance of the model, so the next step requires a prospective cohort study with strictly controlled variables . Third, ultrasound images only take the largest section for analysis. Although it can represent a lesion, it still cannot represent the whole lesion, and information may still be missed. Future studies need to analyze the overall lesions by forming three-dimensional images. Four, the limit number of cases is also one of our limitations. We need further research with large samples and multicenter data in the future.In summary, we have developed a prediction model for endorectal ultrasound-based radiomics, which is expected to be used to predict the presence of RC LVI. This method can be promoted in clinical practice because it can noninvasively predict the presence or absence of LVI before surgery and thus influence clinical decision-making.Additional file 1: CLAIM .


Background: Intelligence scores in males with Duchenne Muscular Dystrophy (DMD) and Becker Muscular Dystrophy (BMD) remain a major issue in clinical practice. We performed a literature review and meta-analysis to further delineate the intellectual functioning of dystrophinopathies. Method: Published, peer-reviewed articles assessing intelligence, using Wechsler Scales, of males with DMD or BMD were searched from 1960 to 2022. Meta-analysis with random-effects models was conducted, assessing weighted, mean effect sizes of full-scale IQ (FSIQ) scores relative to normative data . Post hoc we analysed differences between performance and verbal intelligence scores. Results: 43 studies were included, reporting data on 1472 males with dystrophinopathies; with FSIQ scores available for 1234 DMD (k = 32) and 101 BMD (k = 7). DMD males score, on average, one standard deviation below average (FSIQ = 84.76) and significantly lower than BMD (FSIQ = 92.11). Compared to a previous meta-analysis published in 2001, we find, on average, significantly higher FSIQ scores in DMD. Conclusion: Males with Duchenne have, on average, significantly lower FSIQ scores than BMD males and the general population. Clinicians must consider lower intelligence in dystrophinopathies to ensure good clinical practice. Dystrophinopathies are X-linked recessive progressive neuromuscular disorders caused by mutations in the dystrophin gene. Due to dystrophin deficiency in muscles, patients with dystrophinopathies show progressive muscular weakness, cardiomyopathy, motor delay, and respiratory impairment . The mosDystrophin can be found in the central nervous system (CNS), muscle cells, and endothelial cells. In the brain, dystrophin is found in regions such as the hippocampus, amygdala, cerebral cortex, prefrontal cortex, and in the Purkinje cells of the cerebellum ,5,6,7,8.In contrast to DMD, less research was conducted on measuring intelligence in BMD boys. A recent review by Ferrero and Rossi (2022)  reportedg-factor) that determines an individual’s “general” abilities level and (2) specific cognitive functions (s-factors) that are used to solve specific problems, tasks, and (sub)tests. The current paper aims to review the results of the Wechsler Intelligence Scales administered to males with dystrophinopathies. To our knowledge, this will be the first meta-analysis on Wechsler test scores in BMD. In research and clinical practice, Wechsler Intelligence Scales are internationally the most frequently used tests to determine intelligence , even inr = 0.55) [The main reason to focus on Wechsler Intelligence Scales alone is to ensure consistency of test scores and therefore minimalizing variation of methods/instruments used. For example, some instruments, e.g., the Raven Standard Progressive Matrices, show only moderate correlation with the Wechsler Intelligence Scales  . Analysig-factor), the WISC-V and WPPSI-IV administer five index scores (s-factors): verbal comprehension, visuospatial functioning, fluid reasoning, working memory, and information processing speed, and the WAIS-IV four factors: verbal comprehension, perceptual reasoning, working memory, and processing speed. Additionally, subtests have been removed and introduced in the updated versions. Despite the variability between the structure of the different Wechsler Intelligence scales, correlations between FSIQ scores of different versions , WISC-III and WISC-V (r = 0.87), WISC-V and WPPSI-III (r = 0.78)) are high, indicating that scores on different versions are strongly related within the general population [Nonetheless, it should be noted that the Wechsler Intelligence scales have been revised and updated with new subtests and new normative data several times, resulting in a variability of versions since the first (adult) version of this test was published in 1955. There is a separate Wechsler Intelligence scales version for adults , children , and preschoolers   ,36,37, cDespite the abandonment of the PIQ-VIQ split in the newest versions of the Wechsler scales, we decided to do a tentative analysis of PIQ and VIQ in our sample of studies. Cotton et al. (2001)  reportedDespite the current sizable literature (on mainly DMD), intelligence scores in dystrophinopathies are still a matter of debate. The main purpose of this meta-analysis is to evaluate the intelligence scores of patients with DMD and BMD, through a systematic review and meta-analysis of published scientific articles over the last decades. To provide better insight into the intelligence scores distribution of the different phenotypes, test scores of, respectively the DMD and BMD population will be compared to normative data of the typically developing population. We will take the mean age of the participants, the publication year of the study, the continent where the study took place, the type of Wechsler Intelligence scale used , and the version of Wechsler Intelligence scale  into account as possible moderator effects. Results from this review will also be compared to a meta-analysis in 2001  to give A research PROSPERO protocol was submitted (CRD42020194365). We searched for studies that examined or described standardized intelligence scores of boys and young men with Duchenne Muscular Dystrophy (DMD) and Becker Muscular Dystrophy (BMD) on the Wechsler Intelligence scales, published from 1960 through 2022, and written in the English language. Non-peer-reviewed articles, single case studies, dissertations/thesis, or proceedings of the conference were excluded. To address the risk of bias at the study level: solely Wechsler Intelligence scales were compared and all studies with a biased study sample were excluded . Studies that did not use Wechsler Intelligence scales to determine intelligence scores or studies that did not publish standardized intelligence scores were excluded. Relevant studies were identified by searching the electronic database PubMed/Medline, Embase, PsychInfo, and Web of Science. Articles were identified by search terms ‘Duchenne’; ‘Muscular Dystrophy, Duchenne’; ‘Becker Muscular Dystrophy’; ‘intelligence’ OR ‘IQ’; ‘intelligence tests’; ‘Wechsler’; ‘WAIS; ‘WPPSI; ‘WISC; ‘TIQ’, ‘FSIQ’. Each search was limited to ‘English’. The first search was set from 1960 to 2020. As there was a delay in our study, we did a second search with the same search strategy from 1960 to March 2022. All identified articles were independently reviewed by the first authors  using the Rayyan app  for systematic reviews . Full-ten), age , location , Wechsler Intelligence scale being used . Additionally, results of intelligence testing that were reported as an intelligence quotient  were searched for. Range, mean, and standard deviation of scores were reported for full-scale (FSIQ), verbal (VIQ), and performance intelligence quotients (PIQ). The first author (PW) checked the extracted data to maximize reliability. To reduce the risk of bias and increase the directness of evidence, in- and exclusion criteria of the individual study samples were assessed. Inclusion criteria that selected a biased sample of the dystrophinopathies were eliminated from our statistical analyses. For example, studies that reported intelligence quotient scores of only a subgroup of the DMD population, such as boys with DMD with comorbid Autism Spectrum Disorder (ASD), were excluded.The first author (EM) extracted data from included studies using a standardized form. Data were collected on population , sample size  with “The Joanna Briggs Institute (JBI) Critical Appraisal Tool for Analytical Cross Sectional Studies . The stuI2 value and Cochran’s Q tests were performed for all six models to check for significant between-study heterogeneity. Besides 95% confidence intervals (95% CI), also 95% prediction intervals (95% PI) are reported. The 95% prediction interval reflects the range of expected IQ scores in future DMD and BMD patients [Descriptive statistics were calculated using IBM SPSS statistics 27 . Meta-analyses were performed in RStudio   using thpatients .Only a few included studies (k = 9) assessed the FSIQ of both healthy controls and males with DMD or BMD. To analyse a possible deviation of the FSIQ scores in dystrophinopathies from the standardization sample, for each included study Cohen’s d was calculated based on the difference between the reported mean FSIQ score and the mean FSIQ score of 100 (SD = 15) as reported for the standardization sample in the manuals of the Wechsler scales ,36,37. As mentioned above, the newest versions of the Wechsler scales report next to FSIQ, scores on five/four index scores. However, as only two studies made use of a newer version  we did not further analyse these index scores of males with dystrophinopathies.t-test was performed to check whether the reported mean FSIQ scores significantly deviated from the mean FSIQ scores reported by Cotton et al. (2001). Post hoc meta-regression analyses were used to perform moderator analyses for the continent the study took place  to consider possible cross-cultural differences [Next, post hoc subgroup analyses were conducted using Q-tests for subgroup differences to analyse possible differences in FSIQ between included DMD and BMD studies and possible differences between reported VIQ and PIQ outcomes within both the DMD and BMD subgroups separately. A post hoc independent samples ferences ,49, the p < 0.05.Publication bias was assessed by visual inspection of funnel plots and was statistically assessed using Egger’s tests for funnel plot asymmetry . Lastly,The initial data search identified 325 articles, the second 42 . Of the n = 1107) and six BMD studies (n = 91). Data on PIQ were available in 32 studies for DMD (n= 1075) and six BMD studies (n = 91). The 43 studies provided data on 1472 patients with dystrophinopathies, 1354 of them with DMD (91.98%), 118 with BMD (8.20%). Sample sizes differed from 3 to 148. Data on FSIQ were available for 1234 patients with DMD (k = 32) and 101 patients with BMD (k = 7). Data on VIQ were available in 35 studies for DMD (Seven studies described a FSIQ of the WPPSI and the WISC (16.30%), three studies of the WPPSI, the WISC, and the WAIS (7.00%), eight studies the WISC and the WAIS (18.60%), twenty-two studies the WISC (51.20%), and three studies the WAIS (7.00%). Different Wechsler versions were used: the WPPSI , the WISC , and the WAIS . Notation of age data differed per study, 34 studies provided a mean age, age range, and/or SD; therefore, weighted means are reported. The mean age for the total dystrophinopathy group was 11.65 years  based on 34 studies, for DMD 10.13 years  and for BMD 27.54 years . The overall quality of evidence of the 32 included DMD studies was moderate, and for the 7 BMD studies strong. Details of the evaluation results are presented in p < 0.001), this translates into an average FSIQ of 84.76 points for individuals with DMD  .Boys and men with DMD (k = 32) had, on average, a significantly lower FSIQ score compared to the means reported for the standardization sample  . Heterogp = 0.12, I2 = 40.50%) (Boys and men with BMD (k = 7) also had, on average, a significantly lower FSIQ compared to the means reported for the standardization sample , this translates into an average FSIQ of 92.11 points  . Heterog 40.50%) .Q = 6.31, on 1 degrees of freedom, p = 0.01).Our results for the random effect model showed that the FSIQ scores of boys and men with BMD were, on average, significantly higher compared to boys and men with DMD (k = 35) was, on average, significantly lower compared to the means reported for the standardization sample, this translates into an average VIQ of 84.21 points , see Q = 51.27, p = 0.03, I2 = 33.70%).The VIQ in DMD (k = 6) was also, on average, significantly lower compared to normative data . This translates into an average VIQ of 90.81  .The average VIQ in BMD ( 114.87) . Heterogk = 32) were, on average, significantly lower compared to the normal population . This translates into an average PIQ of 88.82. , see Q = 58.88, p < 0.01, I2 = 47.30%). PIQ scores in BMD (k = 6) were, on average, significantly lower compared to the normal population . This translates into an average PIQ of 89.18  .PIQ scores in DMD ( 113.07) . Heterog2 = 60.27). Studies taking place in South America showed significantly lower average FSIQ scores compared to studies from Europe , Asia , North America , and Oceania . FSIQ scores from the other continents did not significantly differ between one another, p > 0.05. No significant moderator effect was found for the continent where the study took place when studying the FSIQ data of the BMD group (p > 0.05). In de BMD group, a significant moderator effect was found on FSIQ for the WISC version used : FSIQ scores on WISC-III are, on average, significantly higher than those scores on WISC-R, in BMD. No significant moderator effect was found on FSIQ for the other used versions  and the version of the Wechsler Intelligence scale ) in the BMD group (p > 0.05). No type and version effects were found in the DMD sample (p > 0.05).For DMD, significant moderator effects were found in the FSIQ data regarding the continent where the study took place (Rp > 0.05).The other moderator effects being analysed were: the mean age of the participants and the publication year of the study. Both were also not significant in both groups . As p > 0.05, an additional trim-and-fill analysis was not conducted. See Egger’s regression did not indicate a publication bias concerning FSIQ scores in DMD   , by defa = 0.79) .p = 0.034) nor in BMD . No significant missing clinical values were indicated for FSIQ scores in DMD . The FSIQ in our DMD sample  was significantly higher than reported by Cotton , (n = 148). However, we did not observe any differences in study methodology to explain this. We found that European studies were overrepresented in this review, which seems to be an overall trend in literature on DMD [The aim of the current study was to conduct a meta-analysis on the Wechsler Intelligence scale scores of boys and men diagnosed with DMD and BMD. As there is a growing scientific and clinical interest in brain-related comorbidities of DMD and BMD , we felte on DMD . This is the first study analysing the intelligence scores of in a total of 101 boys and men with BMD in 7 studies using Wechsler Intelligence scales. Results indicate that BMD boys and men have a mean FSIQ of 92.11, an average intelligence score. The reliability interval of the intelligence scores of boys and men with BMD predicts that there is 95% chance a male with BMD will have a FSIQ on the Wechsler Intelligence scales between 79.63 and 104.59. The mean FSIQ scores of the BMD population were statistically significantly higher than those of boys and men with DMD. Where males with BMD score on average 7.35 FSIQ points more. However, it should be noted that the mean age of males with BMD was higher (27.54 years) than of our DMD population (10.13 years). Previous research has shown intelligence scores to stabilize from the age of 11–12 years ,123,124,Earlier research reported a statistically significant discrepancy between verbal IQ and performance IQ scores in boys and young men with DMD ,99,110. One important moderator factor, that has not been considered in both our review and the Cotton review, is the degree of (fine) motor impairment in boys and young men as some of the subtests of the Wechsler Intelligence scales require motor function and speed of (fine) motor function. Patients with dystrophinopathies may be hindered by progressive muscular weakness and motor delay. Different studies show that patients with impaired motor function are at a disadvantage on some of the subtests of the Wechsler Intelligence scales in which motor skills are required, leading to an underestimation of their intelligence scores ,127. TheAn important limitation of our work is the variability in versions of Wechsler scales, i.e., some children were assessed with WISC-R and other children with the WISC-V. Therefore, there may be some differences in intelligence scores that are subsequent to the varying versions that are based on different subtests. Our tentative analysis suggests that there are no confounding effects from the variability in versions, except in the BMD sample, the WISC-III (k = 2) differed from the WISC-R . However, all other versions  did not differ in both samples. Therefore, we believe our overall intelligence scores are representative for our population. This analyses of moderator effects learns us that there were no significant moderator effect for the different versions of the Wechsler scales being used until now (paragraph 3.5). Therefore, it may be expected that the recent conversions into the WISC-V and WPPI-IV will not result in different intelligence scores for the dystrophinopathy populations.The overall methodological quality of the included studies is for the DMD studies moderate and for the BMD studies strong, Although some included studies did not have a strong quality of evidence, we included all of the studies in our analysis. Considering that multiple studies received a weak or moderate rating because the authors did not identify or deal with confounding factors. However, intelligence scores were most of the time reported as a descriptive and not part of an intervention or manipulation in the reviewed studies. Nonetheless, it should be noted that some available studies did have limitations that could affect our results. In some cases, small sample sizes affect the precision of the estimated estimates and power of the included study. Secondly, in multiple studies information is missing. It was, often unclear in the reviewed studies whether the intelligence testing was carried out by a trained psychologist or not, which may lead to a ‘moderate’ score. Consequently, the study quality might have been under- of overestimated. Especially within the dystrophinopathy population, it should be taken in account by whom intelligence was assessed as the testing of men with dystrophinopathy may require more than average testing skills due to the complexity of their functioning caused by the brain related comorbidities .In conclusion, our systematic review and meta-analysis demonstrated that males with DMD may manifest clinically and statistically meaningful reductions in overall intelligence compared to normative data. The mean FSIQ score found in DMD is 4.46 points higher in comparison to the review of the Cotton. On the one hand, our data confirm the findings of the Cotton review; on the other hand, our data further refine and elaborate on intelligence in DMD and BMD. The gap between performance IQ and verbal IQ in boys and men with DMD was not found in the seven studies published on BMD. Males with BMD have average intelligence scores. We recommend to routinely offer intelligence and cognitive functioning screening to patients with DMD and BMD and that the Wechsler Intelligence scales provide a solid instrument to measure intelligence in individuals with dystrophinopathies. These data may contribute to help patients achieve optimal participation in society .


High-quality human capital (HC) development has a strong influence on achieving a win-win target of economic growth and energy consumption mitigation based on the background of the contemporary “carbon neutrality” constraints in China. We here aim to empirically assess the effect of HC on energy consumption (EC) in 30 provinces of China from 2000 to 2019. Moreover, we broaden the literature by discussing the effect of HC in terms of impact mechanism and nonlinear relationship. Based on methods of the augmented mean group (AMG), the estimation of long-term impacts indicates that the improvement of HC significantly discourages the increase in EC. The intrinsic mechanism shows that the accumulation of HC significantly promotes the decline of EC through economic structure adjustment and technological innovation. Moreover, the threshold model indicates that income equality lifts the inhibitory impact of HC on EC. Accordingly, the development of HC should be involved in the policy preference of China’s provincial and national development strategies considering its effectiveness in stimulating the reduction of energy consumption. Since−1 ,6. Moreo−1 . China’s−1 ,9. China in 2021 . Therefo in 2021 . Further in 2021 ,13,14. TThe existing literature has examined the linkage between HC and EC in China. From the perspective of micro, some studies found that households with high education levels prefer to select environmental-friendly household appliances in China ,16,17. HNevertheless, China’s HC has risen since 2010. Approval rates of tertiary education grew by 85% during 1977–2020 . AdditioHere, using the augmented mean group (AMG) and pooled mean group (PMG) estimators, the relevant theoretical models of HC and EC are constructed, which proves the long-term impact of HC on EC. Then we come up with multi-dimensional paths through which HC impacts energy consumption. Among them, economic structure, economic growth, and technological innovation are involved. In order to provide policy support for the realization of sustainable development, we effectively assess the influence of HC on EC. We make the following contributions: First, we build a theoretical analysis framework according to HC accumulation characteristics. This framework can help explore the long-run direct effect of HC development on EC as well as the indirect transmission channels from three viewpoints of scale, structural and technical impacts. Moreover, for the purpose of identifying the nonlinear linkage between HC and EC, here we creatively use income inequality as a threshold variable. This provides important empirical evidence for China’s EC reduction action plans, considering that China’s income inequality has increased significantly, which may lead to great inequality in HC.The remaining structure of this article is as follows. Most of the current studies used education experience as an estimated indicator for HC ,34,35. SPrevious studies have analyzed the influence of economic growth on EC through a series of theoretical hypotheses  , and a lHere, we provide the influence mechanism as to why EC is affected by HC. From the consumption perspective, households with higher education attainment levels would like to choose energy-efficient products, thus reducing EC ,17. FromFirst, the expansion of HC has a pivotal impact on helping China converge to the economic development of advanced nations. The relationship between HC and economic growth has been well-established by previous studies ,67. The Next, HC investment promotes technological innovation ,72,73. PThird, HC can lead to economic structure upgrading by improving enterprises’ innovation capacities, instructing the flow of advanced ideas to high-value-added sectors, and optimizing resource allocation . Using tHypothesis I.Improved HC reduces energy consumption.Hypothesis II.The intermediary mechanisms of the HC–EC nexus are economic growth, economic structure shifts, and technological innovation.Income inequality might produce a threshold effect when investigating the impact of HC on EC. Income inequality is closely linked to HC , which dHypothesis III.With the change in income inequality, HC has a nonlinear effect on EC.ec), which is expressed in tons of standard coal equivalent and from CEADs database. The independent variable is human capital (hc). There is currently no authoritative measurement of the HC. Most of the current literature measured HC employing traditional statistics  [China Human Capital Index Report 2020 published by the Central University of Finance and Economics.The dependent variable here is energy consumption (ainment) ,101,102.ainment) ,103,104.ainment) . China Hainment)  has provgdp), capital stock (cs), economic structure (is), financial development (fd), population (pop), trade liberalization (tra), energy intensity (ei), and technological progress (rd) as control variables for our study as these variables have been shown to be able to impact regional energy consumption obviously. Moreover, we test the nonlinear impact of HC on EC using income inequality (that is Gini coefficient) as the threshold variable; note that it is not available for provincial data on income inequality in China. Referring to Hu [gini) using the average income of the top and bottom 20% of the total population in each province as:T is the total population; China Statistical Yearbook and Provincial Statistical Yearbook. The technological innovation data are from China National Intellectual Property Administration. Additionally, we consider economic growth  is an indicator function with a value of 1 or 0. Equation (3) shows the single threshold case, and it allows the effect of HC to vary with multi-threshold values.We analyze the nonlinear linkage of HC and EC by employing the panel threshold regression model, which is specifically shown as follows:ec and hc are EC and HC, respectively, and M is an intermediary variable. We here consider three intermediary effects, which are clarified below.We develop an intermediary effect model to investigate the transmission mechanism for the effect of HC on EC, which is shown as:Scale effect: economic growth. Many researchers found that economic growth can bring scale effect [e effect . Thus, wStructural effect: economic structure. HC improvement can affect the labor share in different industries. Moreover, some articles used labor composition to measure the structural change in economic development [elopment . Thus, wTechnical effect: technological innovation. Several scholars employed the quantity of green technology patents, which is generally accepted as a proxy for technological innovation [novation . Thus, hFirst, using the fixed-effect and AMG estimators, we examine the potential impact of HC on the EC, which is used to verify Hypothesis I. Then we conduct an impact mechanism analysis to analyze the scale and technological and structural effects of HC on the EC, which is employed to test the Hypothesis II. Finally, we study the nonlinear effect of HC on the EC using income inequality as the threshold variable, which is applied to examine Hypothesis III.We first perform a cross-sectional dependence (CD) test for methodology selection, as ignoring the CD test can cause inconsistencies in the results. We use Pesaran’s CD test to perform cross-sectional correlation. As can be seen in We then perform a stationary panel unit root test to evaluate the integration order of the variables. Due to the existence of cross-sectional dependence, we use the cross-sectional augmented Shin unit root test   and the Finally, we conduct panel cointegration analysis to test the presence of long-run linkage between variables. The ADF panel cointegration test proposed by Kao  allows fWith the fixed effect model, HC has a significant negative impact on EC (see column (1) in Regarding control variables, the results show that economic development positively affects EC. A 1% increase in economic development increases EC by 1.04% and 0.887% with the fixed effect and AMG methods, respectively. This is similar to the conclusion that per capita income growth is a primary driving factor for EC . In addiWe use Dumitrescu–Hurlin panel causality test to explore the direction of causality between variables, as the existence of reverse causality will lead to erroneous empirical conclusions. In addition, this causality test method is applicable to panel data with cross-sectional dependence heterogeneity, which can avoid providing biased results caused by cross-sectional dependence and heterogeneity. The null hypothesis of this test is that there is no causal relationship between variables. From the results of the causality test, we can see that both W-stat and Z-stat are significant at the 10% level, which means that there is bidirectional causality between independent variables and dependent variables . In partMoreover, we use multiple approaches to ensure the robustness of the results. First, we use the approach of removing extreme values to check the robustness see . After eFinally, the choice of samples often impacts the estimated results. To test whether the impact of the HC on energy varies by region, we split China’s 30 provinces into coastal and inland regions and calculated the long-term impact of HC on energy consumption. We find that the impact of HC on EC presents great heterogeneity see . Even moWe examine the influence mechanism of HC on EC by analyzing the scale effect, structural effect, and technical effect. First, columns (1) and (2) of Second, columns (3) and (4) of Third, columns (5) and (6) of In summary, we have confirmed Hypothesis III, which posits that HC has a nonlinear effect on EC with the change in income inequality. When the income Gini coefficient rises, the impact of HC on reducing EC decreases and become insignificant. This implies the relationship between HC and EC does not change monotonically. A significant shift in their relationship may depend on equal income distribution as a necessary condition. Thomas et al.  justifieWe investigated the impact of HC on EC in China from 2000 to 2019 using the fixed effect, AMG, and PMG estimators. Moreover, we analyzed how HC affects EC by distinguishing three transmission channels . Primarily, we used income inequality as a threshold variable, exploring whether there is a nonlinear relationship between HC and EC. Finally, we discussed the heterogeneous impact of HC on EC between inland and coastal regions.We found that the HC improvement reduces EC with the fixed effect, AMG, and PMG estimators. This conclusion supports previous studies that suggest HC enhances environment quality by improving management efficiency . HoweverWe have several policy implications according to our results. First, our results, which showed a negative relationship between HC and EC, suggest that in order to reduce China’s energy consumption, policymakers should foster the accumulation of HC by involving more investments in education and health systems and improving the share of higher education levels. This means that China’s climate mitigation goal is consistent with current educational strategies and policies, such as the “Education Modernization 2035 Plan”, which stipulates enhancing the quantity of HC.Next, our results showed that income equality could strengthen the inhibitory impact of HC on EC. Thus, policymakers should smooth the income gap between poor and rich households by initiating poverty reduction programs and living standard guarantee programs. Moreover, many other dimensions of development, especially improving public services for poor households, are important. For example, the government should promote industrialization and encourage technology transfer in rural areas, considering most poor Chinese households are from rural areas. Moreover, policymakers should implement a redistribution policy to further protect the rights of health care and education for poor households. Finally, the government should adopt various financial measures to ease credit imperfections faced by poor households, especially by providing poor households with more diverse financial assistance to access education .Third, since the improvement of inequality has no negative influence on EC in the inland region, policymakers should further optimize the allocation of HC resources between developed coastal and less developed inland regions, especially strengthening the education investment in the inland region. This means that China should make efforts to promote convergence in HC while encouraging the construction of a sustainable development economic system in the inland region. Various policies, such as reform aimed at expanding the coverage of compulsory education in rural areas  and the It is necessary to highlight that although our results are useful for investigating the relationship between HC and EC, the dataset has a limited competitive advantage because of its inaccessibility to sectoral-level or even firm-level data. We hope to further analyze the related issues  based on a competitively advantaged dataset. This can provide policymakers with a comprehensive interpretation of the energy impact of HC. Moreover, human capital development is involved in a systematical economic–energy analysis framework, which not only provides an interesting viewpoint for China’s energy consumption mitigation but also extends the research range in the subject of energy economics for emerging countries, considering that China is the top energy consumer. Further related studies can be applied to other emerging regions.


To establish an easy and widely applicable prognostic prediction model for uveal melanoma (UM) based on a Chinese population.A total of 295 consecutive cases treated at the Eye & ENT Hospital of Fudan University were included as the primary cohort, and 256 cases were included in the validation cohorts from two external Caucasian databases. Clinicopathological data were collected retrospectively, and nomogram models were formulated based on multivariable analysis. The concordance index (C-index), AUC , and Brier score were calculated and compared.Based on the training cohort, a nomogram model was established with five relevant variables: age, tumor size, ciliary body involvement, non-spindle cell type and extra-scleral extension. The C-index was 0.737, the 3- and 5-year AUCs were 0.767 and 0.742, and the Brier scores for 3- and 5-year survival were 0.082 and 0.129, respectively, which showed superior prediction compared to that of the Tumor, Node and Metastasis staging system. The model also displayed good discrimination and calibration in the external validation cohorts. By risk stratification, patients could be divided into low- and high-risk groups, and the overall survival curves displayed significant differences in the training and validation cohorts.Our nomogram model was simple and accurate at predicting the overall survival of patients with UM. It was established based on Asian patients and proved suitable for Caucasian patients; thus, it has a wide range of potential applications, especially for patients living in less medically developed countries and regions. Uveal melanoma (UM) is the most common intraocular primary malignancy in adults involving the choroid, iris and ciliary body, and has a high tendency to metastasize, resulting in high mortality –3. ApproWorse prognostic indicators for UM include 1) clinical factors, such as older age at presentation, male sex, larger basal tumor diameter, high tumor thickness, ciliary body involvement, and extraocular spread , 8; 2) hTo our knowledge, no prognostic models have been analyzed and established based on Asian patients. Asian patients, compared to the Caucasian population, have some unique features, such as a lower incidence probability, earlier onset age, and larger tumor diameter , 21. TheBased on the long-term follow-up results of the patients in our hospital, we established a novel and simple nomogram prediction model to predict the survival of UM patients. Two public databases from Western countries were analyzed for external verification.We retrospectively and consecutively reviewed all patients with UM who were treated between January 2002 and October 2017 at the Eye & ENT Hospital of Fudan University in Shanghai, one of the three largest tertiary eye centers in China. All patients were diagnosed by experienced ocular surgeons. All patients received enucleation or proton radiotherapy during this time period. Informed consent was obtained from the subjects after explanation of the nature and possible consequences of the study. Institutional Review Board (IRB)/Ethics Committee approval was obtained, and all data for the study were collected and analyzed in accordance with the tenets set forth in the Declaration of Helsinki.Patients’ clinical data included age at diagnosis, sex, laterality, best corrected visual acuity (BCVA), tumor location, largest basal tumor diameter and thickness determined by type B ultrasonography and survival status. The tumor classification of each patient was recorded according to the seventh edition of the Tumor, Node and Metastasis (TNM) staging system. All tumor specimens stained with hematoxylin and eosin (H&E) were examined by one experienced pathologist to identify the cell type, tumor location and extraocular spread  pathologically. Based on the modifications of Callender’s classification of UM , cell tyth edition of the TNM classification.The external validation data came from The Cancer Genome Atlas (TCGA) database and the Surveillance, Epidemiology, and End Results (SEER) database. From the SEER database, we selected all patients diagnosed with “ciliary body melanoma”, “choroid melanoma” or “iris melanoma”, together with the 7Quantitative variables are expressed as the means ± standard deviations. Frequency counts and percentages of participants within each category were calculated for categorical data. Kaplan–Meier curves were used to analyze the survival data. Univariate and multivariate Cox proportional hazards regression was performed to assess factors related to patient survival. Hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) were derived from Cox models. The proportionality assumption of the Cox model was assessed by testing the correlation of the Schoenfeld residuals and the logarithm of time using the cox-zph test in R.We searched for predictors of OS that were repeatedly reported in studies or systematic reviews and can be easily ascertained in different settings with various levels of clinical experience. As described herein, 14 variables shown in We assessed the predictive accuracy of the prognostic nomogram in the internal testing set and two external validation cohorts with discrimination and calibration. Discrimination for predicting outcome was evaluated by calculating the Harrell concordance index (C-index) , togethehttp://www.rproject.org). The results are reported in compliance with the Transparent Reporting of a multivariable prediction model for Individual Prognosis or Diagnosis (TRIPOD) criteria . All analyses were performed using R version 4.0.1  and patients treated by proton radiotherapy lacking pathological data (2.8%) were excluded. Thus, 295 patients, all treated by enucleation, with a mean follow-up time of 70.4 ± 47.5 months  were included in the training cohort. The patients included and excluded were comparable  were included. In the SEER database, patients with incomplete or ambiguous TNM stage or patients without exact pathological data were excluded, and a total of 179 patients with a mean follow-up time of 44.0 ± 21.6 months  were analyzed , the HR markedly increased with tumor size, indicating that it could also serve as a predictor in the prediction model  and thus make different follow-up plans accordingly. For example, we could reduce unnecessary invasive examinations and testing expenses for low-risk patients, and give close follow-ups or preventive treatments, such as clinical drug trials, to patients with high risk. In this way, the model is simple to operate and will contribute to rational allocation of medical resources.In conclusion, we developed a simple and easy-to-promote nomogram model to predict the OS of patients with UM based on our Chinese population, and it was more accurate than the TNM staging system. Our prediction model also showed high discrimination and good calibration when verified by two Caucasian databases, suggesting that the model is suitable for a wide population.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Ethics Committee of Eye & ENT Hospital of Fudan University. The patients/participants provided their written informed consent to participate in this study.Conception and design (HY and JQ); Data collection ; Data analysis and interpretation (JGa.); Manuscript preparation ; Obtained funding (KX). All authors contributed to the article and approved the submitted version.Project supported by the Shanghai Committee of Science and Technology, China (Grand No. 20Y11911200). The funding had no role in the design or conduct of this research.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.


Severe acquired brain injury (SABI) is a major global public health problem and a source of disability. A major contributor to disability after SABI is limited access to multidisciplinary rehabilitation, despite evidence of sustained functional gains, improved quality of life, increased return to work, and reduced need for long-term care. Twelve patients with a diagnosis of SABI were enrolled and equally divided into two groups: experimental and control. Patients in both groups underwent intensive neurorehabilitation according to the severity of their disabilities . However, in the experimental group, the treatment was performed by using a humanoid robot. At baseline, the two groups differed significantly only in Severe Impairment Battery (SIB) scores. Results showed that the experimental treatment had a higher effect than the traditional one on quality of life and mood. In conclusion, this pilot study provides evidence of the possible effects of relational and cognitive stimulation in more severely brain-injured patients. Severe acquired brain injury (SABI) is a neurological condition due to severe brain damage followed by a coma of at least 24 h, a Glasgow Coma Scale of eight or less, and/or complex neurological disabilities treatable only in high specialty neurorehabilitation units . SABI inThe main cognitive consequences of SABI include neuropsychological and psychological symptoms such as spatial–temporal disorientation, a deficit in attention and memory, judgment and abstract thinking, language disorders, personality changes, and alteration in behavioral and emotional functioning  . SABI imOver the last years, the development of new technologies in the field of cognitive rehabilitation has led to the increasing use of computer-based cognitive tools in patients with SABI . RecentlRobots can be used in various daily scenarios or to support motor functions, training, and rehabilitation. There are two main categories of robotic rehabilitation systems, namely therapy robots  and assistive robots  . RecentlAccording to the literature, humanoid robots, known as social robots, have a humanlike appearance in that they have human bodies and behavioral characteristics that mimic human behavior: verbal and non-verbal behavioral cues such as gaze and gestures, body postures, facial emotions, proxemics, etc. . MeanwhiIn this study, we have described the effects of neurocognitive training performed by using the humanoid robot PEPPER on cognitive and emotive processes, communication, and social skills, in comparison with traditional cognitive treatment, in a cohort of SABI patients.This pilot study included twelve patients with a diagnosis of SABI who were admitted to the Rehabilitation Unit for SABI of the IRCCS Centro Neurolesi “Bonino-Pulejo” of Messina  from December 2020 to December 2021. The diagnosis of SABI referred to an episode of traumatic or vascular etiology, with a variety of neurologic symptoms related to alterations in cognition, affectivity, and sensorimotor ability, as well as deficits in the domains of attention and memory.Subjects were selected according to the following inclusion criteria: (i) SABI diagnosis; (ii) age over 17 years; (iii) level of cognitive functioning (LCF) ≥ 3; Mini-Mental Status Examination (MMSE ≥ 16 ≤24). Exclusion criteria were as follows: (1) vision/hearing loss that limits the participant’s understanding of instructions, or; (2) global aphasia.All patients were taking drug therapy with antiepileptic, antihemorrhagic, and antihypertensive medications. However, patients were not subjected to further experimental treatments during the study .n = 6, submitted to a robotic rehabilitation) and control group . Patients did not receive any other cognitive treatment. A more detailed description of the two groups is in Participants performed a long-term intensive rehabilitative treatment. Before beginning, the sample of enrolled patients was randomly assigned to two groups: experimental group , after 1 month (T1), and after an additional 2 months (T2), i.e., one month after the end of the rehabilitative treatment. The specific psychometric battery was administered by a skilled neuropsychologist, and it included: Level of Cognitive Functioning Scale (LCF); scores ranging from 1 (non-responders) to 8 (purposeful-appropriate person) ; MMSE toPEPPER is an industrially produced humanoid robot able to exhibit body language, perceive and interact with its surroundings, and move around. It can also analyze people’s expressions and voice tones, using the latest advances and proprietary algorithms in voice and emotion recognition to trigger interactions. The robot is equipped with features and high-level interfaces for multimodal communication with the humans around it. The touch screen on his chest displays content to highlight messages and support speech. The robot provides feedback by a combination of verbal response and visual feedback, which is displayed on the robot’s tablet screen. The robot’s responses are further accompanied by head and arm gestures .Each cognitive session  of the experimental treatment included the stimulation of specific cognitive domains: memory, attention, language, spatiotemporal orientation, planning, reasoning, and other executive functions, calculation, and practice. Exercises were parameterized by setting certain robot parameters such as level of difficulty, duration, etc.The results of each exercise were aggregated according to the objective and stored within a “cloud” service, in a database also containing the patient’s biographical data, the rehabilitation objectives defined by the practitioner, and the results of the related exercises. Patient’s information was only accessed by the operator via tablet.In most cases, the exercises included an initial phase of exposition of the topic through the robot and a series of successive quizzes, whose possible answers were displayed on the tablet. The robot acquired the answers (right or wrong), the response time, the time of execution of the entire exercise, and the number of attempts (if the exercise provides for it). By starting from this information, an evaluation in percentage was deduced.The traditional rehabilitative program was planned according to a predefined scheme. Each rehabilitative session was composed as follows: space–time orientation exercises (20 min), attention exercises (30 min), rest (10 min), and memory exercises (30 min). Concerning memory, internal and external aids such as a clock, city maps , diaries, notebooks, family photographs for recovering crucial events of the patient’s life (episodic memory), image–word associations to facilitate semantic memory, auditory and visual barrage tasks for visual sustained attention recovery were used. On the whole, exercise difficulty gradually increased during the rehabilitative sessions.p < 0.05 as statistically significant. Because of the reduced sample dimensionality, a no-parametric approach was performed. Thus, differences between groups at baseline were assessed by the Mann–Whitney U test, whereas proportions by the Chi-squared test.Data were analyzed using the R version 4.0.5 at a 95% confidence level and considered a p-values were obtained by likelihood ratio tests of the full model (full model) compared to the model without ‘group’ as fixed effect (WG model). A random effects analysis of variance model was used to estimate the Intraclass correlation (ICC).The Levene test was used to assess homoscedasticity before using the lme4 package of R to perform a linear mixed effects analysis of the relationship between clinical outcome and treatment. We included in the model the two levels variable ‘group’  and the three-level variable ‘evaluation time’  as fixed effects. Subject’s variability was considered as a random effect by including correlated intercepts and slopes for the fixed factors. The interaction between the fixed effects was also considered. p = 0.04), as visible in At baseline, the two groups significantly differed only in SIB scores (p < 0.001), EQ-5D (X2(3) = 101.27 p < 0.001), and BDI-II (X2(3) = 57.99; p < 0.001). In addition, for these measures, the full models had lower AIC and BIC values and considerably reduced deviations than the WG models, as shown in Significant differences between the WG models and the full models were found for the following outcomes: HAM-A (X2(3) = 53.62; p < 0.001) and BDI-II ; whereas from baseline to T2, the interaction significantly affected the patients’ scores of all these three outcomes, indicating that changes between the two groups increased over time in such measures. Results of the mixed effects model reported in p = 0.04).The ICCs of any model showed a high correlation between two evaluations on the same patient and at the same time: 0.76 for HAM-A, 0.87 for EQ-5D, and 0.84 for BDI-II . Indeed,p < 0.001) and BDI-II  scores, as visible in Moreover, the experimental treatment significantly affected the mood of EG patients, by decreasing from baseline to T2 both the HAM-A (−12.33 ± 1.37, t = 8.98, The results of this preliminary study were very surprising, as unlike what might have been expected, patients in the experimental group did not improve their cognitive performance after the rehabilitation program with the humanoid robot, but they perceived better quality of life and better mood than the control group.We can hypothesize that the use of the robot has contributed substantially for several reasons. First, the robot lightens the burden of cognitive rehabilitation and decreases frustration levels. Second, the reactions of the robot are directly related to the input provided by the patient. Thus, the relational aspect requires a greater effort. Finally, the play-therapeutic aspect plays an important role in mood. Unfortunately, to date, there is not enough literature to support our hypothesis because studies have focused on patients with different neurological disorders. Indeed, in , the autCifuentes et al.  exploredThis study has some limitations, including the small sample size, lack of design control for the presence of pharmacological treatments, and lack of unambiguous training assessments and uncontrollable factors. On the other hand, the small number of participants is the most common challenge facing cognitive training researchers in this field. This challenges the generalization and reliability of the experimental results reported in this study and may account for the significant difference in SIB scores at baseline between the two groups.Robotic rehabilitation has provided promising assistive approaches to mitigate cognitive deficits. The field of SABI is still being studied because there are no standardized protocols . In this


Plastic pollution is widespread in each type of ecosystems. However, the colonization events of microorganisms on plastics seem to be neglected in inland waters. Therefore, in this study we analyze the possible colonization on the surface (hereafter epiplastic microhabitats) of two typology of plastic supports by diatom community. Specifically, we located 20 supports in expanded polystyrene and 20 in polyethylene terephthalate both floating and dipped (~ 1 m) in a central Italian shallow water pond, in order to evaluate the diachronic colonization of diatoms from November 2019 to August 2020. Our result showed the tendency in colonizing both epiplastic microhabitats without significant differences in number of species; additionally, depth does not appear to affect the number of species. As regard the temporal colonization, the number of species tends to increase over time from autumn-winter to spring-summer in both types of epiplastic microhabitats and depth. Instead, increase in dominance of some species over time has been demonstrated: only a few species keep a high number of individuals compared to the others; therefore, the number of individuals within the species is not uniformly distributed. These results suggest the tendency of diatom community to colonize plastic supports in lentic waters, and this evidence can be very important because artificial supports can increase the surface available for the settlement of the algae community with an increase of productivity and the colonization of new communities of different taxa. Further studies are mandatory to investigate the possible effects on the epiplastic community and the ecological implications in freshwater environments.The online version contains supplementary material available at 10.1007/s11356-022-23335-8. In addition, diatoms are important primary producers at the base of food webs; it is estimated that they are responsible for the production of about 25% of all the oxygen produced on Earth ISPRA . The diaAs regards the biofilm that forms on plastic supports in marine water, diatoms represent the most abundant type of eukaryotes Caruso . PreviouHow does the type of plastic polymers affect the diatom species assemblage?How does the depth of plastic polymers affect the diatom species assemblage?Does the diatom species assemblage on plastic substrates show a temporal trend?The largest number of studies on this issue has been developed in marine waters, while only a few in running waters. In fact, this topic in inland waters and in particular in wetland habitats has been neglected to date. For this reason, we want to evaluate the colonization of diatom species in inland shallow water habitats depending on the type of plastic substrate. Sintered expanded polystyrene (PS) and polyethylene terephthalate (PE) were chosen as plastic supports as they are two of the most widely produced and used plastic materials . The Torre Flavia Wetland is a Special Protection Zone , identified on the basis of European Bird Directive (147/2009/EC). In the study area, there is also a Site of Community Importance . Since the 1970s, the area has been progressively reclaimed, and this has led to the creation of a swamp in the rear dune area, made of many linked channels Gustin .Echinophora spinosa , Cakile maritima , Pancratium maritimum  regarding vegetal component and Bufo bufo , Emys orbicularis , Charadrius dubius , or Charadrius alexandrinus , regarding animal component  and the trampling of dunes. Some of these issues could become a threat for the many species present, like t Gustin .The sampling sites were placed within one of the numerous artificial canals that form a connecting network in the wetland area behind the dunes Fig. . The entThe study was conducted from November 2019 to August 2020. Ten plastic supports were created, each constituted by two PS structures and two PE structures Fig. .Samples were transported to the laboratory where oxidation of diatoms was carried out according to Italian protocol for inland water ISPRA . After hQualitative and quantitative analyses were carried out regarding the diatom community. The diatoms were classified at the species level, and following the temporal frequencies of the species most founded were calculated. The species most frequent were considered those that were found at least >50% during the samplings (5/10) for each type of plastic support.A chi-square test was carried out to analyze the differences in the distribution of the number of individuals of the most abundant species in relation to the different types of substrates and to the different depths.Then, we analyzed the number of diatom species in different supports and depths by the Kruskal-Wallis test (H).t tests for paired data were performed.To evaluate possible differences between the number of diatom species found on different types of supports (PS and PE) and different depths (floating and dipped), the Diversity indexes were calculated to test differences in the species distribution in function of the time by Mann-Kendall test. The data were transformed by log (x+1).pj is the proportion of characters belonging to the jth type of letter in the string of interest);Shannon diversity index, calculated as R is richness and pi the proportional abundances);Simpson index, calculated as evenness, calculated as N).number of species . In Table We found 97 species of diatoms overall on the 39 supports recovered  Table Table 3Vat test performed between the number of diatom species on PS and PE did not show significant differences in their distribution . Moreover, the differences in the number of diatom species found on floating and dipped supports were not significance . Therefore, the results highlighted that colonization of diatoms was independent of depth and substrate type.The paired The results of the diversity indices  calculated for each support are shown in Fig. p = ns), while showed a significant correlation with time for the Shannon index as regards the floating PS and PE supports   Fig. .R2 = 0.565, p = 0.012; fPE: R2 = 0.51, p = 0.020)  Fig. .Fig. 4PlR2 = 0.5823, p = 0.0102; dPS: R2 = 0.695, p = 0.0052; fPE: R2 = 0.619, p = 0.0068; dPE: R2 = 0.507, p = 0.02)  = 0.89, and a probability p1′ (observed ≥ expected) = 0.11.From the analysis of the co-occurrence, applied to the species found on plastic and polystyrene supports, regardless of depth, through presence/absence matrices, an observed index = 0.05434 was found, with a probability p2 (observed ≤ expected) = 0.95, and a probability p2′ (observed ≥ expected) = 0.05.From the analysis of the co-occurrence, applied to the species found on the floating and dipped supports, regardless of the type of substrate, through presence/absence matrices, an observed index = 0.04897 was found, with a probability The results obtained in this study show a tendency of diatom species to colonize plastic artificial supports placed in lentic environments, contributing to investigate a topic little-known in these types of freshwater ecosystems. In particular, this study represent the first investigation of plastic colonization by freshwater microalgae in a wetland habitat. According to Lagarde et al. , a solidThe diatom colonization was observed on both types of plastic supports, PS and PE, and both on floating and dipped supports. The most frequently encountered diatom species are characteristic of waters with a medium-high trophic level, also populating environments from β to α meso-saprobic and medium-high electrolyte content ISPRA . These rBacillaria paxillifera, Cyclotella comta, Cymbella compacta, Gomphonema pumilum, Gomphonema zellense, Navicula cryptocephala, Navicula tripunctata, allowed the settlement of other species over time, increasing the number of species in the composition of diatomic community constant permanently. The number of species increased during the sampling period in all four cases of supports, as highlighted by the significant results of diversity indices. The Navicula, together with other genera, represent a genus very widespread and abundant on plastic debris in aquatic systems  and not by inter-specific interactions. Anyway, it is evident that the diatom community colonizes plastic substrates regardless of the type of polymer in a relatively short time; therefore, we hypothesize that any plastic waste can be colonized by diatoms. It is important to highlight that a similar condition could be temporary because, according to Khan et al. , the litThe findings emerged by this study can have positive but also negative implications on the ecosystem. In fact, plastic can represent a new habitat for diatom and form as substrate for the colonization of primary producers, supporting the biodiversity. However, the fragmentation of plastic in smaller size and the exposure to environmental factors and pollutants can modify the chemical-physical properties of plastics. Some studies highlight that the presence of plastic can reduce the pollutants available in the environment. In fact, plastics could adsorb hydrophobic organic contaminants from contaminated water and reduce the concentrations available to microalgae, which could be the mechanism of minimizing toxicity when organic contaminants are exposed to microalgae in combination with microplastics The online version contains


Previous studies have demonstrated that trimethylamine N-oxide (TMAO) and its precursors, including choline, betaine, and carnitine, are closely associated with blood pressure (BP) changes. Nevertheless, with the limitation of reverse causality and confounder in observational studies, such a relationship remains unclear. We aimed to assess the causal relationship of TMAO and its precursors with BP by the Mendelian Randomization (MR) approach.In this study, two-sample MR was used to reveal the causal effect of TMAO and its precursors on BP. Pooled data of TMAO and its precursors was from genome-wide association studies (GWAS) which includes summary data of human metabolome in 2,076 European participants from Framingham Heart Study. Summary-level data for BP was extracted from the International Consortium of Blood Pressure-Genome Wide Association Studies. Inverse variance weighted (IVW), MR Egger regression, Maximum likelihood, Weighted median, and MR pleiotropy residual sum and outlier test (MR-PRESSO) were used in this MR analysis.p = 0.020). Additionally, our findings also indicated that a 1 unit increase in carnitine should be associated with a 1SD increase in systolic BP mmHg . This result was also confirmed by sensitivity analysis methods such as Maximum likelihood, MR-PRESSO, and Weighted median. No effects of betaine or choline on systolic or diastolic BP were observed in the present study.A total of 160 independent SNP loci were associated with TMAO and three precursors, including 58 associated with TMAO, 29 associated with choline, 44 associated with betaine, and 29 associated with carnitine, were selected. MR results suggested that a 1 unit increase in TMAO should be associated with a 1SD increase in systolic BP mmHg (beta: 0.039, SE, 0.072, Our study provides evidence of a causal relationship of TMAO and its precursors with BP, suggesting that mediating the generation of TMAO would be beneficial for lowering BP. Hypertension is the most common chronic disease and an independent risk factor for cardiovascular diseases including heart failure, coronary heart disease, and myocardial infarction. Accumulating evidence has indicated that for every 5 mmHg increase in systolic blood pressure (BP), the risk of myocardial infarction rises by 5% and mortality by 10% . At presP < 0.0001)  . These f 0.0001) –11, and  0.0001) . However 0.0001) , 11.These observational studies addressed the association of TMAO and its precursors with BP, but the findings are often controversial due to the potential confounders and reverse causation in epidemiological studies. Randomized controlled trials (RCTs) are the most reliable way to make causal inferences in epidemiological studies. Nevertheless, it is often not easy to directly investigate the etiology of disease because of the difficulty of design and implementation in RCT and the medical ethical issues that must be considered. Mendelian randomization (MR) studies infer the causality of exposure factor on the outcome using genetic variants that have strong associations with the exposure factor as instrumental variables (IVs) . AccordiThis study analyzed the causal effect of TMAO and its precursors on BP using a 2-sample MR analysis. TMAO and its precursors were used as exposure factors, and BP was used as an outcome indicator in our analysis.P < 5 × 10−5) were selected as IVs in this study  IVs were significantly associated with TMAO and its precursors: (2) IVs were not associated with BP; (3) Only TMAO and its precursors affected BP. Only SNPs that simultaneously met the above criteria were included as IVs .P < 5 * 10−5; (2) Linkage disequilibrium parameters r2 < 0.01; (3) Gene distances = 10,000 kb. Furthermore, TMAO and its precursors could not be indirectly linked to BP via confounding factors in the MR; (4) SNPs with incompatible alleles and palindromic SNPs with minor allele frequencies close to 0.5 were removed from the analysis.We extracted SNPs from the gut metabolite database using Plink software with the following criteria: (1) P-values, and standard errors, were collected.Based on the above principles, we utilized Catalog and Phenoscanner to explore whether the included SNPs were associated with confounders and, if not associated, the SNP was included  . FurtherThis study mainly used the inverse variance weighted (IVW) method to evaluate the relationship of TMAO and precursors with systolic and diastolic BP. The outcomes of IVW were the major indicators of this study, which used random-effects model if there was heterogeneity; otherwise, the fixed effects model . In addiFirst, we used the MR-PRESSO method to detect outliers and reanalyze them after removing them . The “leP-value < 0.05 being a statistically significant difference.Statistical analysis was performed using the TwoSampleMR package in R software, and all results were expressed as OR and its 95% CI, with a Included SNP locus information is provided in the p = 0.039) (p = 0.020), MR-PRESSO . Additionally, our findings also indicated that a 1 unit increase in carnitine should be associated with a 1 SD increase in systolic BP mmHg  (p = 0.017)  . This re= 0.039) . This re= 0.017) . No effeThe results of horizontal pleiotropy and heterogeneity suggested the absence of horizontal pleiotropy but heterogeneity . ConsideBased on the 2-sample MR analysis, our results showed that TMAO and carnitine were associated with systolic BP. Each 1 unit increase in TMAO and carnitine was associated with an increase in systolic BP. However, there was not statistically significance of TMAO/carnitine for systolic BP in MR Egger, indicating that our results may be affected by potential deviation. In addition, we also found no evidence of causal effects of betaine and choline on BP.P < 0.0001) , is a metabolite of choline, lecithin, and carnitine , 10. Die 0.0001) . In addi 0.0001) –30. For  0.0001) , and som 0.0001) , 30. OveAdditional studies have also found a relationship between precursors of TMAO such as carnitine, choline, and betaine and BP –12. HoweThe mechanism by which TMAO and its precursors affect BP is currently unknown. Limited evidence has demonstrated that TMAO infusion can prolong the effects of hypertension in a model of angiotensin II-induced hypertension , suggestThis is the first MR study to explore the effect of TMAO and its precursors on BP. Our study has some advantages. For example, data on intestinal metabolites and BP in the study were obtained from the largest sample in the GWAS study; besides, in order to explain the potential factors, four MR methods (MR-PRESSO), Weighted median, MR Egger and Maximum likelihood were conducted for sensitivity analysis of IVW result. However, our study also has some weaknesses. First, this study used pooled data from the GWAS studies and could not evaluate the non-linear relationship between TMAO and BP, and also, due to the limitations of data, we were unable to perform subgroup analyses. Second, the inclusion of populations of European ancestry in this study may limit the application of the results to other ethnic people. Thirdly, since this is a cross-sectional design, it may have some impact on the reliability of our results. Fourthly, MR Egger reported that there was not statistically significance of TMAO/carnitine for systolic BP, indicating that our results may be affected by potential deviation. Fifthly, because we did not have access to raw data, therefore, we could only estimate the causality of the two, and at the same time, we could not conclude a detailed causal relationship of TMAO and the high systolic BP. Finally, we can only make a preliminary judgment about this causality of TMAO and carnitine with systolic BP by the MR approach, and the underlying biological mechanisms of the two are still not fully clarified. Therefore, more studies were still needed to prove the relationship between them.In summary, we found a positive causal relationship of TMAO and carnitine with systolic BP, which was also confirmed by several previous studies. Further investigation of the mechanism between the two is suggested, and in addition, trials of targeted agents against TMAO need to be carried out.The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Ethical review and approval was not required for the study on human participants in accordance with the local legislation and institutional requirements. The patients/participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.Study design and drafting manuscript: HW and ZZ. Data collection and data analysis: HW and QL. Data interpretation: XD and LC. All authors take responsibility for the integrity of the data analysis and participated and approved the final version of manuscript.This work was supported by National Natural Science Foundation of China [Grant 81300243], Sichuan Administration of Traditional Chinese Medicine [2020JC0010], Chengdu Health Commission Medical Research Project [2021206], Project of Sichuan Science and Technology Department [19YYJC0580]. Chengdu High-level Key Clinical Specialty Construction Project. Chengdu Science and Technology Bureau Technology Innovation Project [2019-YF05-00523-SN].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.


The purpose of the study was to test whether primary lifestyles mediate associations of SES with incidence of dyslipidemia and to explore interaction relations of lifestyles and SES with incidence of dyslipidemia.We included 9,901 individuals at baseline from January 2018 to November 2019, and incidence data were updated to 31 December 2020. Dyslipidemia was defined as total cholesterol (TC) 6.2 mmol/L TC ≥ or triglycerides (TG) ≥2.3 mmol/L or low-density lipoprotein cholesterol (LDL-C) ≥4.1 mmol/L or high-density lipoprotein cholesterol (HDL-C) <1.0 mmol/L; or physician diagnosed dyslipidemia or lipid-lowering drugs use. Lifestyles, socioeconomic factors, and personal characteristics were collected by a questionnaire. A latent class analysis based on education, family income, and occupational position was used to assess the SES. Lifestyle score was calculated using cigarette smoking, alcohol consumption, physical activity, and diet. Cox proportional hazard models and multivariate analyses were used to explore the associations. The mediation effect was evaluated using bootstrap method.Participant mean age was 36.5 years (SD = 0.11). The cumulative incidence of dyslipidemia was 11.0% over a mean follow-up of 13.4 months. Compared with participants of high SES, those with low SES had higher risk of incidence of dyslipidemia , after adjusting for lifestyle scores and other covariates. The proportion mediated by lifestyles was 5.41% (95%CI: 4.17–7.11). A significant additive interaction was found between lifestyles and SES, whereas association between lifestyle and incidence of dyslipidemia was stronger among those of high SES. Additionally, individuals with low SES and no or one healthy lifestyle behavior had a higher risk of developing dyslipidemia than those with high SES and 3 or 4 healthy lifestyles.Unhealthy lifestyles play a small moderating role in socioeconomic inequity in incidence of dyslipidemia among Chinese governmental employees, suggesting that promoting healthy lifestyles alone may not significantly reduce socioeconomic inequalities in health, and measures to address other social determinants of health should also be considered alongside. Globally, dyslipidemia, generally characterized by an elevated level of blood lipids, including low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglycerides (TG), or a decreased level of high-density lipoprotein cholesterol (HDL-C), has been considered as an independent preventable risk factor of cardiovascular disease (CVD) –4. For iSocioeconomic status (SES) has been commonly defined as the combination of education, income level, and occupation . SES wasNumerous epidemiological studies have established that lifestyle factors are the main risk factors associated with dyslipidemia , 15. LifThe aims of this study are as follows: (1) to assess whether SES is associated with the incidence of dyslipidemia in Chinese governmental employee population; and (2) if such association exists, to explore the mediating role of potentially modifiable lifestyle behaviors in it.n = 876). Overall, 6,617 participants were eligible for the longitudinal analyses  of Hunan Province, China. Detailed information on study design of this cohort has been described in our previous study . Brieflyanalyses .Baseline self-reported education level, family income level, and occupational position were used to measure SES, and each factor was divided into three levels . Total family income was obtained through a digital self-reported questionnaire platform, which was applied in our previous study , and we We assessed lifestyle factors at baseline with reference to questionnaires applied in previous large prospective studies , 25. We 2]. Sleep quality was evaluated using items of the Pittsburgh sleep quality index (PSQI)  and family history of above common chronic diseases. Bodyweight and height were measured at baseline, with BMI calculated as weight (kg)/ when individuals with low SES were compared with those of high SES . There wp <0.05) . In modehigh SES .p-value <0.001). The mediation proportion by lifestyles on above relationship was 10.3% . There were no differences of the mean levels of TC, LDL-C, and HDL-C between low and high SES groups .A positively additive interaction was observed between lifestyle score and SES on incidence of dyslipidemia  in a subgroup analysis and found that those individuals with overweight or obesity were more prone to be a stronger association between low SES and incidence of dyslipidemia than those with normal BMI. Obesity is associated with diet- and exercise-related behaviors that control the balance of energy intake and expenditure  as the mediators of the SES-dyslipidemia association and cannot comment on the relative importance of health behaviors in relation to other mediators. Additionally, although SES was evaluated as a composite index  in our study, it cannot sufficiently capture SES because other additional SES aspects  were not considered. Second, participants in our study were from Hunan Province, China, although the sample of this special population is considered large, the results of the study may not be generalizable to other regions of China. Thus, future multiprovince or multinational monitoring studies are necessary to confirm our findings. Third, the follow-up duration is relatively short, and participants diagnosed during the study period were likely to have severe illness at baseline. SES and lifestyles might be influenced by health conditions. In this study, we adjusted the self-report comorbidities in main analysis to obtain robust results. Fourth, participants excluded from this study owing to missing information were younger, of high SES, and more likely to be women, which would lead to selection bias. Finally, although we controlled for key covariates in our Cox and mediation analysis, residual confounding by variables that are unknown or not included in the analysis may contribute to an overestimation of the role of lifestyles in the association between SES and incidence of dyslipidemia.In this large Chinese Governmental Employee Cohort, low SES was found to be significantly associated with higher risks of incidence of dyslipidemia, and the association was slightly mediated by lifestyle behaviors. Thus, for significantly reducing socioeconomic inequalities in dyslipidemia, other social determinants of health are considered alongside the promotion of healthy lifestyles. Notably, those with disadvantaged SES and unhealthy lifestyles had the highest risks of incidence, which emphasizes the importance of lifestyle modification to reduce the burden of disease for governmental employees, especially those with low SES in China.The original contributions presented in the study are included in the article/The studies involving human participants were reviewed and approved by The Ethics Committee of Xiangya School of Public Health, Central South University, China (No. XYGW-2016-10). The patients/participants provided their written informed consent to participate in this study.LL was responsible for the study design, data analyses and interpretation, and manuscript writing and revision. FO, JH, and DQ were responsible for the data acquisition, interpretation, and manuscript revision. LL and DL were responsible for the manuscript revision. SX was responsible for the study conceptualization, data acquisition and interpretation, and manuscript revision. All of the authors approved the final content of this manuscript.This work was supported by the Ministry of Science and Technology of China (grant no. 2016YFC0900802).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.