The purpose of this study is to investigate the characteristics, relationships and mechanisms underlying the psychological capital, career commitment, gratitude and career well-being of teachers in ethnic areas. In total, 573 primary school and secondary school teachers in Sichuan Province (including 402 teachers in ethnic regions and 171 teachers in non-ethnic areas) were investigated. Following questionnaires were used to investigate these questions: “Psychological Capital Questionnaire for Primary and Secondary School Teachers,” “Gratitude Questionnaire,” “Teacher Career Well-being Questionnaire” and “Career Commitment Questionnaire for Primary and Secondary School Teachers.” The results show that the psychological capital of teachers in ethnic areas is higher than that of teachers in non-ethnic areas. Teachers in ethnic areas have lower levels of career well-being and lower levels of gratitude than teachers in non-ethnic areas. There was no significant difference in career commitment between teachers in ethnic areas and teachers in non-ethnic areas. There were significant positive correlations among psychological capital, gratitude, career well-being and career commitment. Psychological capital can predict career commitment significantly and positively. The mediating effect of career well-being between teachers’ psychological capital and career commitment was significant in both ethnic areas and non-ethnic areas. The chain of mediating effects between gratitude and career well-being was significant in non-ethnic areas. In conclusion, psychological capital can predict teacher career commitment effectively, and the prediction mechanism in ethnic areas is different from that in non-ethnic areas. However, due to the limitations of living conditions, working conditions and economic treatment in ethnic areas, some teachers exhibit negative work attitudes, a sense of powerlessness with regard to their work and a lower sense of career well-being , 288 teachers with a college degree or below, and 3 teachers whose educational status was unrecorded; and 486 teachers in the fields of language, mathematics and foreign affairs, 486 teachers in the fields of political science, history and geography, and 3 teachers whose area of teaching was unrecorded. Questionnaires were returned by 285 teachers (5 teachers with a graduate degree and 280 teachers with a bachelor’s degree), 288 teachers with a college degree or less, and 3 teachers whose educational data was unrecorded; 486 teachers in the fields of language, mathematics and foreign languages, 49 teachers in the fields of science, history, geography and chemistry, 30 teachers in the fields of music, sports and aesthetic education, and 8 teachers whose area of teaching was unrecorded; and 402 primary school teachers, 168 secondary school teachers (152 middle school teachers and 16 high school teachers), and 3 teachers whose level of teaching was unrecorded.x2/df = 4.32, GFI = 0.91, AGFI = 0.86, CFI = 0.88, NFI = 0.85, IFI = 0.88, and RMSEA = 0.08. The α coefficient of this questionnaire in the present study was 0.76, and the α coefficient of each dimension ranged from 0.60 to 0.62. This fact indicates that the questionnaire has acceptable letter validity in this study.This study used the Psychological Capital Questionnaire for Primary and Secondary School Teachers developed by x2/df = 2.44, GFI = 0.92, CFI = 0.91, NNFI = 0.90, and RMSEA = 0.05. The α coefficient of the questionnaire in this study was 0.85, and the α coefficients of the dimensions ranged from 0.65 to 0.76. This fact indicates that the questionnaire has good reliability and validity.This study used the Career Commitment Questionnaire for Primary and Secondary School Teachers developed by x2/df = 2.91, GFI = 0.73, CFI = 0.96, NFI = 0.95, NNFI = 0.96, and RMSEA = 0.09. The α coefficient of the questionnaire in this study was 0.94, and the α coefficients of the dimensions ranged from 0.71–0.92, indicating the high reliability of the questionnaire in this study.This study used the Teacher Career Well-being Questionnaire developed by This study used the Gratitude Questionnaire (GQ-6) developed by The questionnaire was administered to the subject group in the classroom of a teacher training class, and the time required was approximately 25 min. The main test was administered by a trained psychology graduate student, and before the questionnaire was administered, the main test subject read the instructions and the principles of anonymity and confidentiality for the test to the subjects. Microsoft Excel 2007, IBM SPSS 25.0, IBM AMOS 21.0, and Mplus 7.4 were used for statistical processing of the data.Since this study used a questionnaire method to collect data and all data were obtained from subjects’ self-reports, common method bias may exist in the measurements. Common method bias is often controlled in two ways: procedural control and statistical control . The pron = 2), the differences in the main variables among teachers of different ethnicities were not compared in the analysis of non-ethnic areas.Descriptive statistics were conducted for all teachers’ scores on psychological capital, gratitude, career well-being, and career commitment measures, and differences in each of the main variables were examined for demographic variables such as ethnicity, gender, and education. The results are presented in p = 0.065). The gratitude and career well-being of teachers in non-ethnic areas were significantly higher than those of teachers in ethnic areas (p < 0.01). t = −2.12, p < 0.05, Cohen’s d = −0.21), career well-being , and career commitment  scores of male teachers from ethnic areas were significantly lower than those of female teachers; the career well-being of primary school teachers in ethnic areas was significantly higher than that of secondary school teachers ; teachers who taught different subjects in ethnic areas had significant variations in career well-being  and teachers of language arts and mathematics having higher career commitment than teachers of political science, history, geography, science and chemistry (p < 0.01). t = −2.12, p < 0.01, Cohen’s d = −0.46). Furthermore, there were significant differences in psychological capital among different teaching subjects in non-ethnic areas .As seen from Pearson product-difference correlation analysis was conducted on psychological capital, career well-being, gratitude and career commitment, and the results are shown in This study adopts the single-factor method as part of the balance method for packaging the gratitude questionnaire  to avoidBecause the dependent variables differed significantly in terms of teacher gender, school level, and teaching subject, these variables needed to be controlled for in the structural equation model. Gender , school level (based on primary school), and teaching subject  were transformed into dummy variables with codings 0 and 1.p > 0.05, 95% CI = ) and career well-being to gratitude  for teachers in ethnic areas were too small and were insignificant; the regression coefficients of career commitment to psychological capital  and gratitude  had small regression coefficients with p values greater than 0.05 and 95% CI including 0, all of which were non-significant paths. Therefore, these paths were removed from the modified model. The chi-square difference between the hypothetical model and the modified model was Δx2(1) = 1.20, p > 0.05 and Δx2(2) = 0.23, p > 0.05 for ethnic areas and non-ethnic areas, respectively. The hypothetical paths were verified using structural equation modeling and the BC bootstrap method . The results of the operations are shown in The regression coefficients of career commitment to gratitude  aThis study investigated the basic conditions, relationships, and mechanisms of psychological capital, gratitude, career well-being, and career commitment for 402 primary and secondary school teachers in ethnic areas and another 171 teachers in non-ethnic areas. The findings indicated that the psychological capital of teachers in ethnic areas was slightly higher than that of teachers in non-ethnic areas, possibly because schools in ethnic areas are mostly located in more remote, non-central cities and have relatively poor conditions of school operation and social resources , given tg = 0.067). This fact indicate that there is no substantial difference between the psychological capital of male and female teachers in general, while female teachers in ethnic areas have significantly higher psychological capital than male teachers. This result reflects the difference between the career characteristics and career psychological states of teachers in ethnic areas and those of other teachers. Teachers in ethnic areas had significantly lower career well-being than teachers in non-ethnic areas, which is a result of the objective conditions in ethnic areas , which depends more on the individual’s self-fulfillment in his or her career and is a sense of eudemonic well-being . MeanwhiIn summary, the hypotheses tested in this study were the predictive role of psychological capital on career commitment (Hypothesis 1) and the mediating role of career well-being on psychological capital and career commitment (Hypothesis 2). One hypotheses that could not be tested was the mediating role of gratitude on psychological capital and career commitment (Hypothesis 3). The sequential mediating role of gratitude on career well-being (Hypothesis 4) was tested only among teachers in non-ethnic areas but not among teachers in ethnic areas.This study found that psychological capital had a significant positive predictive effect on teachers’ career commitment in both ethnic and non-ethnic areas, validating psychological capital theory. However, the direct effect of psychological capital on career commitment did not reach the significance level in non-ethnic areas. This result suggests that there are significant differences in the mechanisms by which teachers’ psychological capital works in ethnic and non-ethnic areas, and future research can explore the reasons for this fact further. Moreover, the effect of psychological capital in ethnic areas was slightly larger than in non-ethnic areas. This result is in line with the results of the mean comparison above. That is, teachers in ethnic areas require more psychological resources to maintain the same career commitment as other teachers. This fact suggests, on the one hand, that psychological capital is crucial to teachers in ethnic areas. On the other hand, it suggests that there may be some kind of compensatory mechanism that substitutes psychological capital for real resources. Future research can explore and verify this property of psychological capital from that perspective further.In addition, psychological capital can act indirectly on career commitment through career well-being, validating the extended and constructed models. However, gratitude did not act directly on career commitment and could act indirectly on career commitment through enhanced career well-being only among non-ethnic teachers. This finding refutes the common speculation that perceived gratitude traits enhance employees’ gratitude toward the organization, increases employee loyalty, and thus enhances career commitment. A more plausible explanation is that gratitude traits enhance individual well-being, increase positive experiences at work, and thus enhance career commitment. Therefore, perhaps focusing on enhancing each teacher’s happiness and satisfaction is a more effective way of securing his or her career commitment as opposed to merely requiring teachers to be grateful and loyal to their profession.There are certain shortcomings and limitations in this study that need to be supplemented and developed by future studies. First, this study tries to explain the effect of psychological capital on career commitment in ethnic areas from the perspective of gratitude and career well-being, but the effect of gratitude has not been verified in the sample of teachers in ethnic areas, which is inconsistent with the research hypothesis, and future research can analyze the reasons for this fact further through more empirical studies. Second, the sample of this study is mainly concentrated in Sichuan Province, which does not reflect the entire picture of ethnic areas in China. Future research can cover a wider range of ethnic areas to increase the diversity and representativeness of the sample. Finally, this study is only a cross-sectional survey study, and the causal relationship between variables needs to be verified further. Future research can verify further the causal relationship between variables through follow-up surveys and experimental studies .The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation, to any qualified researcher.DH: the acquisition, analysis, or interpretation of data for the work and drafting the work or revising it critically for important intellectual content. TZ: substantial contributions to the conception or design of the work and final approval of the version to be published. KZ: the acquisition, analysis, or interpretation of data for the work, drafting the work or revising it critically for important intellectual content, and final approval of the version to be published. FD: drafting the work or revising it critically for important intellectual content. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.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.


In a follow-up sample of 48 patients with IGE-GTCS and 48 matched normal controls (NCs), high-resolution 3D T1WI was performed at baseline. After 1 year of follow-up, 31 patients were classified as seizure free (SF) and 17 as drug resistant (DR). The volumes of subcortical structures were extracted, and vertex-based shape analysis was performed using FSL-Integrated Registration and Segmentation Toolbox (FSL-FIRST). Comparisons among groups were calculated adjusting for covariates . Analysis of the relationships among imaging biomarkers along with frequency and duration was assessed using partial correlations. The differential imaging indicators were used as features in a linear support vector machine (LSVM). The DR group displayed significant regional atrophy in the volume of the left amygdala compared with NCs  and SF patients . Meanwhile, vertex-based shape analysis showed focal inward deformation in the basolateral subregion of the left amygdala in DR compared with the results for SF and NC . There were significant correlations between the volume changes and seizure frequency  and between shape  changes and seizure frequency. Moreover, the volume of the left thalamus in the DR group was significantly correlated with seizure frequency . The SVM results revealed areas under the receiver operating characteristic curve of 0.82, 0.68, and 0.88 for the classification between SF and DR, between SF and NC, and between DR and NC, respectively. This study indicates the presence of focal atrophy in the basolateral region of the left amygdala in patients with IGE drug resistance; this finding may help predict drug responses and suggests a potential therapeutic target.We aimed to determine the alterations in the subcortical structures of patients with idiopathic generalized epilepsy with tonic–clonic seizures (IGE-GTCS)  Idiopathic generalized epilepsy (IGE) with tonic–clonic seizures (GTCS), one of the main genetic generalized epilepsy syndromes, representing approximately 15–20% of all epilepsies , typicalvia volumetric and voxel-based morphology (VBM) analysis  play a crucial role in the generation and propagation of epilepsy . Some stanalysis . Some stanalysis . Some fuanalysis ,b. DespiComplementary to VBM, vertex-based shape analysis is an automatic method that provides useful information about the location and pattern of morphological changes in subcortical structures. Shape analysis is now widely used to evaluate the regional atrophy of subcortical structures in various neurological and psychiatric disorders . MoreoveIn the present study, we hypothesized that IGE-GTCS patients with different drug responses would have diverse changes in the subcortical nuclei, and the structural alteration of subcortical nuclei may be potential biomarkers of drug responses in IGE patients. To verify this hypothesis, we conducted both volume and morphology analyses of subcortical structures with FSL-Integrated Registration and Segmentation Toolbox (FSL-FIRST) software in IGE-GTCS patients to determine specific patterns that might be a biomarker to predict which patients will develop drug resistance.1WI results were necessary for inclusion.In order to make it easier for readers to understand, we made a schematic figure of the analytical methods . Forty-evia the ILAE criteria  were enrolled during the same recruitment period. They underwent the same image scanning with the same quality control standards as the patients. Prior to the study, all subjects (patients and NCs) gave written informed consent, and this study was approved by the Research Ethics Committee of Nanjing Drum Tower Hospital.1WI was conducted using a 3D turbo field echo sequence . During the examination, the subjects were ordered to close their eyes and remain motionless.Brain scanning of all the subjects was performed on a Philips Healthcare  3 T MR imaging scanner with an eight-channel head coil. High-resolution 3D T1 to preprocess each anatomical image to perform intensity correction and skull dissection. A Bayesian model-based segmentation tool in FSL-FIRST2 was used to segment subcortical nuclei , cerebrospinal fluid (CSF), gray matter (GM), and white matter (WM). No participant was excluded owing to poor structural segmentation, following FSL-FIRST guidelines3. Then, we calculated the volumes of the individual subcortical nuclei and the intracranial volume (ICV). For the subcortical nuclei of all subjects, the vertex index was calculated using the FSL vertex analysis script, first_utils script, which is based on the signed vertical distance from the corresponding surface mesh  in the Montreal Neurological Institute (MNI) template. A positive index indicated outward deformation or expansion of the surface of a given structure, whereas a negative index indicated inward deformation or atrophy of the surface of the structure. Finally, the degree of deformation value for all participants was computed and then used for statistical analysis.To investigate the alterations in subcortical structures, we first applied the DARTEL algorithm in the SPM12 toolboxa priori determination of the significance level at p < 0.05 was considered statistically significant, false discovery rate corrected (FDR corrected). The volume difference between the left and right amygdala was compared by using paired t-test in the three groups  separately. Intergroup differences in subcortical shape were assessed using a method based on a non-parametric approach for seven pairs of nuclei using the FSL randomization procedure and adjusting the covariates (age and sex). The findings were corrected for multiple comparisons using threshold-free cluster enhancement (TFCE) with a familywise error (FWE) rate of p < 0.05 by running 5,000 random permutations. Then, after controlling for age, sex, and ICV, the relationship between the volume and shape of the structures with seizure frequency and disease duration was analyzed by partial correlation.This study used IBM SPSS Statistics, Version 23.0, to determine a statistical description and make statistical inferences. A chi-square test was used to assess the classification variables. Analysis of variance (ANOVA) was performed to evaluate continuous variables. ANOVA was used for between-group comparisons  of the volume of subcortical nuclei after adjusting the covariates . An analysis with 4. LSVM is one of the most widely used supervised machine learning methods  of the classifier in the classification of test set data in each test were recorded. Then, the area under the curve (AUC) of the ROC was statistically compared based on the DeLong method. To test the sample size imbalance effect on the classification, a control analysis to select the same sample size of DR (n = 17) from NC (n = 48) was performed.To explore whether imaging indicators can be used to classify including SF vs. DR, DR vs. NC, SF vs. NC, we applied the LIBSVM toolbox for MATLAB to implement the linear support vector machine (LSVM) classification methods . Its purp > 0.05) were generally well balanced. Patients who were not SF indeed had a higher seizure frequency  and had a longer illness duration  than SF patients. However, there was no significant difference in onset age between the two groups .Anatomical MRI data from 96 participants were included in the study, consisting of 31 SF patients, 17 DR patients, and 48 NCs. The demographic and clinical characteristics of the subjects are listed in p = 0.008, uncorrected) . There was no difference in the volume between SF patients and NCs (p > 0.05). Additionally, there was no significant difference in bilateral amygdala volume in NCs (p = 0.100) and SF patients (p = 0.164), but the volume of the left amygdala was smaller than that of the right amygdala in the DR group (p = 0.031) (p > 0.05) and volume (p = 0.372) of the left amygdala between the medication group and the non-medication group.We analyzed seven pairs of subcortical nuclei, including the bilateral thalamus, hippocampus, amygdala, nucleus accumbens, putamen, caudate, and palladium. The subcortical nuclei schematic is shown in rrected) . Compare= 0.031) . Interesp < 0.05, FWE corrected), which was located in the basolateral region   showed slight inward deformation (atrophy) in the DR group compared with that of NCs. Furthermore, compared with controls, SF patients had minor inward deformation in the shape of the left pallidum .Compared with NCs, DR patients showed significant regional atrophy in the shape of the left amygdala  . In addir = −0.438, p = 0.003, uncorrected) and volume  , but a correlation was not found in all patients. No correlation was found for the disease duration in either patient group. On the other hand, left amygdala volume was positively correlated with right amygdala volume in the NC group  and SF , but this correlation was not found in the DR group   . In the = 0.140) .p > 0.05) was generally well balanced, but the age of our subjects (IGE patients) ranged from 12 to 57 years old. Therefore, age was regarded as a feature in this study. The characteristics that identify SF patients from NCs are age, the shape of the left amygdala and palladium, and volume of the left amygdala; those that differentiate DR patients from NCs are age, the shape of the left amygdala and putamen, and volume of the left amygdala; and those that discriminate SF patients and DR patients include age, shape, and volume of the left amygdala and palladium. LSVM distinguished DR patients from NCs with an accuracy of 84.62%, sensitivity of 58.82%, specificity of 87.50%, and AUC of 0.88, whereas the accuracy, sensitivity, specificity, and AUC for differentiating SF patients from NCs were 70.89, 41.94, 89.58%, and 0.68, respectively. In terms of distinguishing DR patients from SF patients, the accuracy, sensitivity, specificity, and AUC were 77.08, 90.32, 52.94%, and 0.82, respectively. Furthermore, LSVM distinguished DR patients (n = 17) from NCs (n = 17) with an accuracy of 82.35%, sensitivity of 82.35%, specificity of 82.35%, and AUC of 0.90, and the classification features are the same as above  is vital to the maintenance and propagation of seizures explained by its extensive connections . The ANTWe explored the classification results of drug responses in IGE-GTCS patients using LSVM with imaging indicators. Although the results are not very satisfactory, they provided us with an opportunity to judge the efficacy of the drug clinically. This is a brave attempt in the study of prognostic biomarkers in DR epilepsy. In the future, this needs to be verified in animal experiments and brain connectomics studies. The mediocre performance may have been due to the following reasons. First, our sample size was not large enough though it was essential for classification performance, and the sample size imbalance effect was also a source of poor classification results. In addition, amygdala atrophy may have a complex pathophysiological mechanism and may not be suitable for classification. Our findings support the clinical validity of left amygdala contraction as a potential means for clinicians to predict the efficacy of a drug in IGE patients who have no obvious lesions on conventional MRI.The main limitation of our study is that the sample size of the patients in the DR group was small. This may cause the statistical effect to be erroneously low. For example, the difference in the left amygdala volume between the DR group and the SF group was not corrected for multiple comparisons. Clinical and imaging indicators had related trends, but no significant difference was found. Moreover, a larger sample size can provide more representative features for obtaining a more stable and reliable classification performance. However, the recruitment of DR subjects is still challenging owing to the low incidence and the demands of follow-up work. Second, although the mechanism of the effect of AEDs on brain structure is unclear, we cannot eliminate this drug effect. Some subjects had already taken AEDs before the study began. Some studies have shown that AEDs can affect a person’s brain structure, resulting in pseudoatrophy of the brain or neurogenesis . On the The findings from this study suggested the presence of focal atrophy of the left amygdala located in the basolateral region, which may help predict drug response and suggest a potential therapeutic target such as DBS.The original contributions presented in the study are included in the article/The studies involving human participants were reviewed and approved by the Research Ethics Committee of Nanjing Drum Tower Hospital. Written informed consent to participate in this study was provided by the participants’ legal guardian/next of kin.XL, ZYW, and QC contributed to the design and manuscript preparation. JW and JLi were responsible for collecting data. XW, ZQ, and WZ were involved in analyzing the imaging data. JLu and XZ executed the experimental work. ZGW, BL, and BZ guided the design of the study protocol and reviewed and critiqued the manuscript. All authors have read and approved the manuscript.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.


To establish a non-invasive diagnostic model based on convolutional neural networks (CNNs) to distinguish benign from malignant lesions manifesting as a solid, indeterminate solitary pulmonary nodule (SPN) or mass (SPM) on computed tomography (CT).A total of 459 patients with solid indeterminate SPNs/SPMs on CT were ultimately included in this retrospective study and assigned to the train (n=366), validation (n=46), and test (n=47) sets. Histopathologic analysis was available for each patient. An end-to-end CNN model was proposed to predict the natural history of solid indeterminate SPN/SPMs on CT. Receiver operating characteristic curves were plotted to evaluate the predictive performance of the proposed CNN model. The accuracy, sensitivity, and specificity of diagnoses by radiologists alone were compared with those of diagnoses by radiologists by using the CNN model to assess its clinical utility.vs. 66%, P<0.01; 87 vs. 61%, P<0.01; 85 vs. 66%, P=0.03, in the train, validation, and test sets, respectively). In addition, while there was a slight increase in sensitivity, the specificity improved significantly by an average of 42% .For the CNN model, the AUC was 91%  in the test set. The diagnostic accuracy of radiologists with the CNN model was significantly higher than that without the model (89 The CNN model could be a valuable tool in non-invasively differentiating benign from malignant lesions manifesting as solid, indeterminate SPNs/SPMs on CT. With the use of thoracic low-dose computed tomography (CT) for lung cancer screening, an increasing number of solitary pulmonary nodules (SPNs) or masses (SPMs) are deliberately or incidentally discovered. Solid SPNs are extremely common, and malignancy account for approximately 60% range: 55–66%) , 2. Data5–66% , 2High-resolution computed tomography (HRCT) can non-invasively provide specific information about pulmonary lesions . HoweverRecently, machine learning has shown outstanding capabilities as one of the most promising tools for the detection, diagnosis, and differentiation of lung lesions. Over the years, two computational strategies have been developed to predict the malignancy of lung lesions on CT images: radiomics based on quantitative radiological image features and deep learning methods such as those based on cascade convolutional neural networks (CNNs). The extraction of radiomics features relies heavily on accurate lesions boundary outline, and predictive models are built based on a prior knowledge of which features are significant. Whereas CNNs could automatically extract potential features beyond human perception from medical images to predict whether a lesion is benign or malignant by amplifying aspects of the input images that are important for discrimination and suppressing irrelevant variations . When suThe retrospective study was approved by the ethics committee of “Shanghai Pulmonary” Hospital. The informed consent requirement was waived.We retrospectively included 459 consecutive patients with solid, indeterminate SPNs or SPMs on CT between January 2018 and December 2018. Patients who met the following criteria were included: (1) presence of a primary intrapulmonary lesion; (2) the diameter of an existing lesion of >8 mm , and the result was further linearly mapped to the value interval . Each 3×224×224 tensor represented one patient in the network pipeline. The preprocessing was shown in The voxel spatial resolution of all patients’ raw CT were standardized on all three axes, to 0.6 × 0.6 × 0.6 mmhttps://github.com/DrIsDr/TJU_Chen_SK.The train dataset was used to train the deep learning algorithm, a separate validation dataset to tune parameter, and the test dataset to assess the final model. During the training stage, only weight parameters in the last two fully connected layers and all batch normalization layers in the network were trained for 1 epoch, and others remained unchanged. This can be considered as a warm-up training. Then the entire model was trained for additional 60 epochs. This process simultaneously optimized all network layers, making the lower convolutional layer more suitable for edge and corner features in CT data, as well as for the specific data distribution resulting from our combination of orthogonal slices. The weights corresponding to the epoch with the lowest validation loss were chosen as the optimal model and saved. The model used Adam as weights optimizer and cross-entropy as loss function . The leaThe CNN models were often referred to “black-box” technology due to lack of interpretability, making it difficult for users to understand the inference procedure. We used the class activation map (CAM) to visualize the discriminative process of the neural network , and theAs can be seen in the Baseline characteristics and image information of the participants were summarized as mean ± standard deviations (SD) values for continuous variables, and as frequency and percentage for categorical variables. Statistical significance was tested using Student’s t-test, Welch’s t-test, Mann-Whitney U-test, and Kruskal-Wallis for continuous variables as appropriate, and Chi-square test for categorical variables. A p-value < 0.05 was considered to be statistically significant. The predictive results of CNN model were compared with the pathological gold standard. The diagnostic performance of the CNN model was described using the area under the receiver operating characteristic (ROC) curve (AUC) with 95% CI. The mean value of accuracy, sensitivity, and specificity of diagnoses by radiologists alone were compared with those of diagnoses by radiologists with the assistance of the CNN model to evaluate its clinical utility. All statistical analyses are based on SPSS 20.0 software  and R version 3.6.3 .A total of 459 patients with solid, indeterminate SPNs or SPMs were included. Of the 459 patients, 183 had benign disease  and 276 had malignant disease . Among the 183 benign cases, there were 124, 55, and 4 granulomas, pulmonary sclerosing pneumocytomas (PSPs), and focal organizing pneumonia (FOP), respectively. The subtype of malignancy only included lung adenocarcinomas.The clinical baseline characteristics and image features are listed in The model demonstrated superior performance in the train set ; the results in the validation and test sets showed slightly lower but still satisfactory differentiation performance  Figure 6vs. 87%, P<0.01; validation set: 61 vs. 83%, P=0.02; test set: 66 vs. 83%, P=0.06). When radiologists used the CNN model, their diagnostic accuracy was higher than that achieved by radiologists alone    Table 3.Deep CNN is a type of deep learning approach in which computers are not explicitly programmed but can perform tasks by analyzing relationships of existing data. In this retrospective study, our CNN model achieved better accuracy than three radiologists in differentiation between benignity and malignancy for solid, indeterminate SPNs or SPMs. When radiologists used the CNN model, the mean accuracy was 87%, and the specificity improved by 42%, which would have facilitated timely diagnosis and treatment for lung cancer and avoided unnecessary excision for benign cases by a non-invasive, highly efficient, and reproducible method. Furthermore, to enhance interpretability, we used visualization techniques to analyze the process of the CNN model classification. To the best of our knowledge, this is the first attempt to differentiate radiographically solid, indeterminate lesions using interpretable CNN technology based on thin-section CT scans.The solid SPN is an extremely common type of tumor, and approximately 60% of solid SPNs are malignant , 2. PublChest CT examinations can provide specific information about morphological and density characteristics and are helpful to estimate the probability of malignancy for pulmonary solid lesions. Multiple studies have revealed that spiculation, lobulation, irregular shape, and pleural retraction are associated with malignancy, whereas lesions with a regular shape and the smooth margin are more likely to be benign , 29. HowThus, it is very pivotal to differentiate benign from malignant solid, indeterminate SPNs or SPMs by using a new approach to overcome the naked limitation. However, some studies revealed and exploited the massive potential of image features that may be visually imperceptible to even very experienced thoracic radiologists and can be extracted from CT scans by using (1) radiomics methods or (2) deep learning approaches based on CNNs –34. BothAdditionally, the CNN model is highly efficient in distinguishing benignity from malignancy for solid, indeterminate lesions. Radiologists spent an average of 3 min to read and interpret a set of CT images of one patient, while the CNN model could process the 366 patient images in just 5 s. Moreover, in routine clinical practice, radiologists usually need to review and compare prior CT images to make a diagnosis, which would require more time despite yielding higher accuracy. In our model, on the basis of coordinate information, we adopted a supervised learning method, guided the neural network model to extract features layer-by-layer from CT images of interest, constantly enhanced the intensity of feature abstraction, and finally output the result of the prediction. Thus, we used an end-to-end computational method that could greatly simplify the traditional workflow.A limitation of our model is the overfitting issue caused by the single-institute small data size. To compensate for this limitation, we utilized the pretrained network on ImageNet that included millions of natural images, in a process termed transfer learning. Although there is no intuitive approach for using a pretrained model with non-medical images for differentiation of medical images, some features including the edges, corners, orientations, and textures are generic. We compared the performance of the CNN model with or without pretrained procedure using the same experimental parameters, and the results showed the pretrained CNN model performed much better than the untrained one  currently provided. At present, the design of CNN algorithms and the abundance of clinical data are mutually reinforcing. In the future, as more data become available and finer-level annotation information becomes more widespread, CNNs can be more useful for clinical applications. Considering actual clinical limitations, the design of our cohort was restricted to allow differentiation between adenocarcinomas and benign diseases including granulomas, PSP, and FOP. Actually, it makes sense to use CNN model to further predict the results of benign lesions for subclassification. However, in our study, we did not perform this task. Understandably, the multi-classification tasks for benign lesions are difficult due to the disparity in sample distribution of benign subtypes , as a well-performing model requires a large number of sample data of each type of disease. We plan to conduct a more in-depth evaluation of the application of CNN model to multi-classification tasks based on large samples in the upcoming studies.In conclusion, we established a CNN model based on CT images that can serve as a valuable tool for radiologists to differentiate radiographic solid, indeterminate SPNs or SPMs. Moreover, a visualization procedure was presented to enhance interpretability of CNN model.https://github.com/DrIsDr/TJU_Chen_SK.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 below: KS: Conception and design, data analysis and interpretation, manuscript writing, final approval of manuscript. SC: Data analysis and interpretation, manuscript writing, final approval of manuscript. JZ: Collection and assembly of data, manuscript writing, final approval of manuscript. BW: Manuscript writing, final approval of manuscript. YY: Manuscript writing, final approval of manuscript. YW: Data analysis and interpretation, manuscript writing, final approval of manuscript. CW: Provision of study materials or patients, manuscript writing, final approval of manuscript. XS: Conception and design, administrative support, manuscript writing, final approval of manuscript. All authors contributed to the article and approved the submitted version.This work was supported by the Natural Science Foundation of Shanghai (grant Number 21Y11910400). The funders had no role in the study design, data collection, data analysis, and writing the manuscripts.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.


Ambio is a leading journal in environmental science and policy, sustainable development, and human-environment interactions. The paper at hand aims to run a bibliometric analysis to inspect the main publications features of Ambio in Science Citation Index Expanded SCI-EXPANDED. For this scope, a bibliometric survey has been carried out to investigate the journal’s historic characteristics in the Web of Science (WoS) categories of environmental sciences and environmental engineering for Ambio from 1980 to 2019. These are the categories for which the journal has been indexed throughout the indexed time frame. The paper proposes technical and methodological innovations, including improvements in the methods and original characteristics analyzed. Documents published in Ambio were searched out from SCI-EXPANDED. Six publication indicators were applied to evaluate the publication performance of countries, institutes, and authors. Three citation indicators were used to compare publications. As a parameter, the journal impact factor contributor was applied to compare the most frequently cited publications. The journal impact factor contributing publications were also discussed. Results show that Sweden ranked top in six publication indicators and that the top three productive institutes were located in Sweden. A low percentage of productive authors emerged as a journal impact factor contributor. Similarly, a low relationship between the IF contributing publications and the highly cited publications was also found. Less than half of the top 100 highly cited publications in Ambio did not lie within the high impact in most the recent year of 2019. Three members of the advisory board in Ambio were the main productive authors. T.V. Callaghan contributed to most of the publications while papers published by J. Rockstrom as first and corresponding author contributed the most to the journal impact factor. An article authored by Steffen et al. (n et al.  scored t Ambio is a primary source for environmental scientists and policy analysts, as well as for scholars interested in sustainable development, ecosystem functioning and human-environment interactions. The journal is published by The Royal Swedish Academy of Sciences and was founded in 1971.Ambio has been indexed in the Science Citation Index Expanded (SCI-EXPANDED) in 1977 and classified in the Web of Science (WoS) categories of environmental engineering and environmental sciences, performing an impact factor of 4.778 in 2019. Currently, Ambio is indexed in four WoS categories: ecology; environmental chemistry; geography, planning and development; medicine.Sustainable development, sustainability studies and, more broadly, ecological and resource policy are ascending multidimensional disciplines that deserve devoted research, classification and data . All document information from SCI-EXPANDED and each year’s citation times for every publication sorting from the Web of Science Core Collection was checked and downloaded into Microsoft Excel 2016. Additional coding was manually performed.The documents used in this study were derived from the SCI-EXPANDED of the WoS Core Collection, Clarivate Analytics. The searching keyword phrase “The SCI-EXPANDED database was originally designed for researchers to find documents, but it cannot be directly used for bibliometric research Ho . TherefoThe performed research has been undertaken through a brand-new set of feature analysis that has been completed by the traditional key publication features explorations. This includes taking into account: (i) selected characteristics percentages and ranks together; (ii) independent studies; (iii) international collaborations; (iv) most performative first authors and corresponding authors; (v) characteristics of the most productive countries; (vi) characteristics of the most productive institutions; (viii) most recurrent words within the publication’s title.The collaboration type, country and institution were determined by the authors’ affiliation. In the SCI-EXPANDED database, the corresponding author is designated as the “reprint author”. This study uses the term “corresponding author” instead. In a single author publication where the authorship is unspecified, the single author was considered both as first author and corresponding author. Similarly, in a singly institutional publication, the institution is classified as the first-author institution and the corresponding-author institution. In multi-corresponding-author articles, only the last corresponding author, institute, and country were considered see Ho .The affiliations that originated in England, Scotland, Northern Ireland and Wales were reclassified as UK (United Kingdom). For publications that occurred before 1997, Hong Kong affiliates were included in China. The affiliations in Trinid & Tabago were included in Trinidad Tobago. The affiliates of Fed Rep Ger  and Ger Dem Rep (German Democratic Republic) were also included in Germany. France includes the affiliation of French Guiana. The affiliations in Greenland were included in Denmark. The affiliation of Czechoslovakia was checked and reclassified as the Czech Republic. The affiliation in the USSR  were checked and reclassified as in Russia and Estonia—depending on the institution’s nationality. The members of W Ind Assoc St (West Indies Associated States) were reclassified as St Lucia (Saint Lucia) affiliates. Similarly, Geol Survey Czechoslovakia  was checked and reclassified as Czech Geol Survey . Acad Sci USSR (the Academy of Sciences of the Soviet Union) was checked and reclassified as Russian Acad Sci (the Russian Academy of Sciences). The same applied to the Acad Med Sci USSR —it was checked and reclassified as Russian Acad Med Sci . Publications by Stockholm Univ and Univ Stockholm were also reclassified as pertaining to Stockholm Univ (Stockholm University in Sweden).Ambio published 4154 documents in 10 Web of Science document types.From 1980 to 2019, APP) of 3.3. It is worth noting that the documents in the Web of Science Core Collection can be divided into two document types. Among those, 137 documents are classified as conference papers and articles. Therefore, the total percentage is higher than 100%.Table APP of 7.0 followed by reviews with 5.8. The average number of authors per publication in the journal was 3.2, and the maximum number of authors was 53.Document type of discussions with one document had the highest CPP2019 of the proceedings paper was much higher than other document types, at 65. Reviews had similar CPP2019 than articles. A review entitled “Coupled human and natural systems” ”  is defined as in the Journal Citation Reports (JCR) year—i.e., the average number of citations of a journal article published in the past two years. The denominator includes document types of articles or reviews. Some categories of documents that are not normally cited, for example, letters, editorial materials, and other document types are not included in the denominator of the impact factor. Due to the definition of the journal impact factor, only the following document types were considered for further analysis: articles, reviews, and proceedings papers.According to the Web of Science’s definition,IF) is defined as the sum of all the citations coming from articles published by the journal in the previous two years in the selected JCR year, divided by the total number of academic articles published by the journal . Periodicals of the first two years have observed the following: .According to the 2019 Journal Citation Reports (JCR), JCR used 178 Web of Science categories in SCI-EXPANDED to index 9381 journals. The journal impact factor  that means the citation number of Cyear-1 + Cyear-2. The denominator is made of three document types such as reviews, articles, and proceedings papers. A research product pertaining to any other document type is excluded from the denominator.IF) contributing papers were listed in Table IF contributing papers were ranked top 20 in terms of CN (Cyear-2 + Cyear-1), respectively. However, only 25% and 50% of them were ranked as top 20 in terms of TC2019 and C2019, respectively. Only five of the top 20 most contributing papers for the journal impact factor (IF) contributing papers including four articles by Mergler et al.  is a paper-level metric. It does not apply to individual papers or subgroups of papers that appeared in the publication. Additionally, it does not apply to authors of papers, research groups, institutions, or universities.The top 20 journal impact factor  fluctuated and slightly increased in the long run, reaching a minimum of 0.929 in 1999 to a maximum of 4.778 in 2019. The ranking of Ambio in the Web of Science subject categories of environmental sciences and environmental engineering were not improved, especially in the last five years. The journal had a higher ranking in the category of environmental engineering with respect to environmental sciences since 2012. In 2014, notable changes occurred in Ambio’s policies, including the enclosure of six major new features  with the peak year in the 7th year  in the 4th year  in the 5th year   and their citations per publication (CPP2019 = TC2019/TP) have been proposed to discover the development of a journal , country independent papers (IP), internationally collaborative papers (CP), first-author papers (FP), corresponding-author papers (RP), and single-author papers (SP) have been applied as criteria to compare the publication’s performance of countries and institutes for a research topic  were single country papers from 87 countries, while 1019 (31%) were internationally collaborative papers from 117 countries. Six publication indicators: number total of papers , an IP of 639 papers (29% of 2242 country independent papers), a CP of 441 papers , an FP of 879 papers (27% of 3261 first-author papers), an RP of 872 papers (27% of 3227 corresponding-author papers), and an SP of 186 papers (22% of 838 single-author papers).Table CPP2019 of 25 and 1814 papers (56%) from inter-institutional collaborations with a CPP2019 of 34. The percentage of the inter-institutional collaboration rate of the Ambio (56%) was found higher than that of J. Membr. Sci. (38%) (Fu and Ho Pol. J. Environ. Stud. (31%)   came from independent institutions with a TP of 308 papers (9.4% of 3261 papers), an IP of 68 papers , a CP of 240 papers , an FP of 159 papers (4.9% of 3261 first-author papers), and an RP of 157 papers (4.9% of 3227 corresponding-author papers) while the Swedish University of Agricultural Sciences in Sweden took the leading position with an SP of 27 papers (3.2% of 838 single-author papers).The characteristics of the top 10 productive institutions with the six publication indicators were listed in Table TP), first-author papers (FP), corresponding-author papers (RP), and single-author papers (SP) were applied for the analysis of authors’ characteristics for papers in a research field.With the exception of seven anonymous papers , 3398 papers were published by 8431 authors including 2798 authors who published first-author papers, 2733 authors who published corresponding-author papers, and 834 authors who published single-author papers. The first author and the corresponding author are the most significant author positions Gaeta . Three bAmbio. T.V. Callaghan , who is a member of the advisory board in Ambio, affiliated to the Royal Swedish Academy of Sciences in Sweden, was the largest contributor with 40 papers including seven reviews and 33 articles. Callaghan also ranked top in first-author papers with 20 items and corresponding-author papers with 19 publications. F. Barnaby  ranked the top in single-author papers with 12. M. Johansson  with 27 papers ranked second in total papers and T.R. Christensen  with 22 papers ranked third, both of Johansson and Christensen were from Lund University in Sweden. C. Folke  with 20 papers from the Stockholm University in Sweden and T.D. Prowse  with 18 papers from the University of Victoria in Canada were also sitting in the advisory board of Ambio.Table CPP2019 = 424; CN = 100) from Stockholm University in Sweden was the most productive associate editor in Ambio, and published seven articles. Comparing the top 24 most productive authors, an advisory board member—C. Folke—with one review and 19 articles, had the highest CPP2019 of 227, followed by T. Elmqvist  and F. Wulff  from Stockholm University, respectively. T. Elmqvist from Stockholm University was the journal impact factor best contributor with the highest CN (Cyear-1 + Cyear-2) of 290, followed by C. Folke from the same university with a CN of 278, and T.V. Callaghan from Royal Swedish Academy of Sciences with a CN of 247. The most productive authors, C. Folke and T. Elmqvist also published the top largest number of papers falling within the 100 journal impact factor contributing papers with five contributions, respectively. A.D. Fox, C. Folke, J.N. Galloway, T.V. Callaghan, and W. Steffen published two first-author papers and corresponding-author papers in the top 100 journal impact factor contributing papers.E. Andersson  of 3405 papers were highly cited papers including one classic article with a TC2019 of 1126. The 202 highly cited papers were published by 836 highly cited authors from 412 institutions in 45 countries. The USA had 86 highly cited papers (43% of 200 highly cited papers with affiliation information in SCI-EXPANDED) followed by Sweden , Canada , the UK , and Germany . Stockholm University in Sweden published 32 of 202 highly cited papers  followed by the Swedish University of Agricultural Sciences, Royal Swedish Academy of Sciences, and Lund University in Sweden with 10 papers. C. Folke published the most cited papers in the Ambio with 12 papers including the most four first-author and corresponding-author papers, respectively.In CN (Cyear-2 + Cyear-1), respectively while five and 10 of them were ranked top 20 in terms of CN and C2019, respectively. The five of the top 20 most frequently cited papers including four articles by Lindberg et al. , followed by “ecosystem services” , “Baltic sea” , “eutrophication” , “sustainability” , “biodiversity” , “governance” , “phosphorus” , “conservation” , and “arctic” . The results of the analysis considered the author’s keywords and words in the paper title. Papers having the topics of “Baltic sea” and “climate change” were the most popular in Ambio, with respective scores of 231 and 345.Several scholars proposed the distribution of words in article titles, abstracts, author keywords, and Ambio is a top journal in environmental sciences and policy and sustainability studies. Several investigations have conducted bibliometric analyses on journals’ publications performances over the years. These facts motivated this paper’s rationale in scrutinizing the main publication features of Ambio for the time span 1980–2019. This time frame is the available indexing period for the journal and refer to the Web of Science categories of environmental sciences and environmental engineering—the two original categories for which the journal has been historically indexed.Research in environmental policy and sustainable development is on the rise. This trend calls for accurate mapping of existing publications in these domains (Gatto et al. Ambio from 1980 to 2019 was analyzed. The peak year of citations per publication was found to be the 3rd full year since its publication. The papers published in 2007 and 2002 had a higher impact on the journal. Sweden dominated the performance indicators, ranking first in six publication indicators. Stockholm University and the Swedish University of Agricultural Sciences in Sweden were the best performers. T.V. Callaghan did not only publish the largest number of papers in Ambio but was also the best performer for the categories of first-author paper and corresponding-author papers. The less productive author, J. Rockstrom was, however, the largest journal impact factor contributor.A total of 3405 papers including 3263 articles and 142 reviews in IF contributing papers were found in the top 100 highly cited papers. Only 45% of the top 100 most impactful papers in 2019 were listed within the top 100 highly cited papers. Three members of the advisory board in the Ambio—T.V. Callaghan, C. Folke, and T.D. Prowse—were ranked as productive authors. One article published by Rockstrom et al. in 2017 was the top journal impact factor contributing article. An article by Steffen et al. in 2007 was not only the most frequently cited article but also the most impactful publication in 2019. The results show that the journal impact factor contributing papers were not the highly cited papers or the highly impactful publications in Ambio in the most recent available year—2019.One-third of the top 100 The results in the study provided some initial evidence that highly cited papers in a journal might not necessarily greatly contribute to the journal impact factor. This observation leads to a striking conclusion: it is not always appropriate to use the journal impact factor as an indicator to evaluate the publication performance of institutes and authors. This conclusion may lead to important research, policy, and practical implications in the field of bibliometrics, scientometrics, information science, and publications studies that may be carried on in other papers.This work also attempted to provide some technical and analytical innovations with respect to the existing scholarship. Some of the novelties proposed in this study are the procedural improvements performed with the scope to render more solid and reliable outputs and avoid overlappings and errors. Additionally, the paper benefited from an enlarged set of new characteristics—that has been investigated along with traditional publication features. These distinct elements allowed for increased precision in the analyses and for broadening the investigation spectrum, returning more accountable results.Bibliometric analyses can offer a bird’s eye perspective on specific timely subjects. This includes specific journals’ characteristics and publications trends, as well as quantitative indications on the analyzed literature. However, bibliometrics is unable to yield recommendations on germane publications features, including papers’ contents, indications and quality. This is why bibliometrics suggests for integration of qualitative studies on the same bodies of research and mixed methods. In this regard, the paper at hand makes no exception. Future papers may address this issue, disentangling selected characteristics of the examined works. Furthermore, other studies may target different environmental policy and science and sustainability studies journals, as well as further disciplines. Alternative bibliometric techniques, publications databases, papers characteristics, software, and time frames could also be considered. Differentiating the data and the analyses would contribute to better assess the trends and determinants of the sorting sectoral publications.


To evaluate the efficacy and/or safety of acupuncture therapy (AT) in quitting smoking.  Randomized controlled trials (RCTs) were searched in PubMed, Cochrane Library, Embase, Web of Science, and Chinese Biomedical Database (CBM). We used Cochrane Collaborative Quality Assessment to assess the risk of bias. Bayesian network meta-analysis was utilized to evaluate the efficacy and safety of different interventions. Data analyses were conducted using WinBUGS 1.4.3, Stata 14, and RevMan 5.3.5 software.  A total of 2706 patients from 23 studies were included, involving 6 treatment arms. Network meta-analysis demonstrated that there was no significant difference in short-term abstinence rates or changes in Fagerstrom test for nicotine dependence (FTND) scores and daily smoking among these groups , auricular acupressure (AA), sham auricular acupressure (SAA), acupuncture plus auricular acupressure (APAA), and nicotine replacement therapy (NRT)). However, there was a significant difference between SAA and AA with risk ratio (RR) of 2.49  in long-term abstinence rate. The probabilistic ranking results showed that APAA and AA were superior to other interventions in the comparison of abstinence rates. There was no obvious inconsistency between the direct comparison and indirect comparison, using the consistency test. CRD42020164712. AA was superior to SAA in smoke quitting, but there was no difference among other interventions in long-term truncation rates. There was no difference in short-term abstinence rates among these selected groups. We need large sample RCTs to clarify the advantages of interventions such as APAA and AA. In addition, reporting of adverse events that may occur during treatment also should be enhanced to complement evidence-based medicine. The trial is registered with PROSPERO  Tobacco dependence is one of the major public health problems , which iThe most internationally recognized standard therapy is nicotine replacement with the objective quantification of abstinence rate , 8. Howehttps://www.crd.york.ac.uk/PROSPERO/.Our study has been registered on the International Prospective Register of Systematic Reviews (PROSPERO) and the registered number is CRD42020164712 which is available at Five electronic databases were searched from inception to March 2021 for RCTs: PubMed, the Cochrane Library, Embase, Web of Science, and Chinese Biomedical Database (CBM). Forward and reverse citation screening through a systematic review of citation and bibliography were also conducted. We used the following search terms: smoking cessation, nicotine replacement therapy, acupuncture, and auricular acupressure, as well as synonyms and derivatives of these words. There are no language restrictions. Search strategies were demonstrated for searching the English and the Chinese e-libraries (Supplementary We included RCTs with acupuncture therapy (AT), auricular acupressure (AA), and acupuncture combined with auricular acupressure (APAA) as intervention measures for smokers who voluntarily quit smoking. The controls included in the study were sham acupuncture therapy (SAT), sham auricular acupressure (SAA), nicotine replacement therapy (NRT), or AA alone. The literature published in Chinese and/or English languages was included. To minimize heterogeneity, the smokers who received two or more treatment combinations (except auricular acupoint combination acupuncture) or any acupuncture with electrical or laser stimulation were excluded. Furthermore, articles with duplicate data, incomplete data, or no access to the full text were excluded.We imported the retrieved literature into Endnote X9. Two independent reviewers screened and included studies according to the eligibility criteria. For any disagreements between these two reviewers, a third senior researcher was consulted, and a conclusion was reached after the discussion. For articles with duplicate data, we only included one with a larger sample size or a longer follow-up period.We used a predesigned Excel sheet to extract data from included studies. The main information includes the first author, year of publication, sample size, interventions, methods, and outcomes. When data were reported for multiple time periods, data at each time period were recorded.We selected short-term and long-term abstinence rates as primary outcome measures. We preferred the sustained abstinence rates, and if the article did not report the results of sustained abstinence outcome, we chose the point abstinence rate. As stated above, the golden standard of abstinence rate is breath carbon monoxide, urinary cotinine, or both. We have adopted the principle of this standard in the current network meta-analysis accordingly . MoreoveUsing the Cochrane Collaborative Quality Assessment tool, two independent reviewers evaluated the methodology quality of each included study . AssessmOur study combined direct and indirect evidence from all available RCTs. Bayesian network meta-analysis was performed, using WinBUGS  software, and Stata  was used to draw the network diagram, while the Review Manager Software  was used to produce funnel plot to assess the risk of publication bias. We applied visual evaluation to evaluate the small size effect of test funnel plot asymmetry.χ2 statistics and I2 statistics. When the P value was ≤0.05 and I2 was ≥50%, statistical heterogeneity existed, and the random effect model was adopted. The fitting degree of the model was judged by comparing the Deviance Information Criterion (DIC) values of the random effect model and the fixed effect model. When the difference value of DIC < 5, the fitting degree of the two models is consistent, and if DIC > 5, the model with a smaller DIC value is adopted. The model convergence was evaluated by the Potential Scale Reduction Factors (PSRF), and the closer the PSRF value was to 1, the better the convergence of the model was. Finally, two independent reviewers evaluated the quality of direct and indirect evidence using the recommended rating, development, and rating methods [To measure the effects, weighted mean difference (WMD) was calculated for continuous data with 95% CI ; risk ratio (RR) for short-term and long-term abstinence rates with 95% CI was calculated. We carried out a consistency model analysis on the main efficacy indicators. We calculated the probability of the lower surface of the cumulative sequencing curve (SUCRA) , ranked  methods .n = 5), not RCTs (n = 28), masters' thesis (n = 5), not English or Chinese articles (n = 1), duplicate publications (n = 4), and laser/electroacupuncture interventions or control interventions not meeting inclusion criteria (n = 51). Finally, 23 RCTs [A total of 7,733 references were identified from the five electronic databases with 6 records from other sources. We retrieved 117 articles for further evaluation after screening them by title and abstract. Furthermore, 94 articles were excluded for the following reasons: unable to access full text  , 33–36 o3 , 33–36We analyzed the consistency of the four outcome measures separately. The results show that the PSRF is 1, which indicates good data convergence. The heterogeneity test results showed that the heterogeneity was small in the short-term and long-term abstinence rates and daily smoking without significant difference. The random effect model was chosen because there was greater heterogeneity in the FTND score . We tested the model fitting degree of each outcome index under the random effect model, and the ratio value was all close to 1, which proved that the model fitting degree was good.We collected 18 RCTs on short-term abstinence rates. Direct pairwise randomized effect meta-analysis illustrated that there was no significant difference when AA, APAA, AT, NRT, or SAA was compared to placebo SAT, showing RR and 95% CI was 2.07 , 2.09 , 1.37 , 1.36 , or 1.37 , respectively . NetworkData on long-term abstinence rates were available from 8 RCTs, reporting a total of 696 participants with events. The results of the pairwise random effect meta-analyses showed that RRs were low and without a significant difference, showing that AA versus SAT was 2.57 , APAA versus SAT was 1.96 , NRT versus SAT was 1.80 , AT versus SAT was 1.44 , and SAA versus SAT was 1.03  . NetworkData on FTND scores were obtained from 6 RCTs; the direct meta-analysis showed that there was no significant difference in comparison between SAT and AA, APAA, AT, NRT, or SAA, showing that WMDs were −1.11 , 1.22 , 1.00 , 0.907 , or −0.324  , respectSeven studies reported changes in daily smoking. A total of four interventions were involved, including APAA, AA, SAA, and SAT. No significant difference was observed among these four groups . In addiOf the 23 studies we included, 17 of them show , 37–41 nP=0.75), AT and AA (P=0.74), NRT and AA (P=0.17), AT and APAA (P=0.18), NRT and AT (P=0.74), and SAT and AT (P=0.92). The results of direct comparison and indirect comparison were consistent (Supplementary Because only the network graph with short-term abstinence rates became a closed loop, we only performed node-splitting analysis, and node-splitting analysis showed no inconsistency between APAA and AA (We used short-term abstinence rates, long-term abstinence rates, and daily smoking as indicators of sensitivity analysis. The clinical similarity and methodological similarity of the included studies were good, and the analytical results were reliable. Thus, our data were robust and reliable.P=0.82, meaning that publication bias was relatively low (A funnel plot was performed for short-term abstinence rates, involving 18 studies, including a four arms study. It was divided into three separate studies. Funnel plots illustrated that scatters were almost visually symmetrical, and the result of Begg's test was vely low .It is well accepted that tobacco smoking is one of the most challenge public health problems nowadays, which also attracts enormous attention from medical and social points of view . QuittinIn addition to other sources of bias, most studies are not clear about whether the implementation of allocation concealment and blind method is correct, and the criteria are not clear, which may compromise the validity of the results. Particularly in the Chinese studies, most of them are subjective, which is more susceptible to affect the experimental outcomes objectively. We also consider that, due to the particularity of acupuncture and auricular acupressure, it may be difficult to treat blindness for doctors, but it is necessary to blind patients . HoweverMost of the results of the Bayesian network meta-analysis were not statistically different, but the rank probability showed that AA and APAA were superior to other intervention indicators. It is worth noting that our estimates of the efficacy of these interventions are not accurate, which can be seen from the broad confidence interval. Moreover, the number of the included studies was relatively small. Some pairwise comparisons only involve one study. Therefore, more trials with a larger sample size are needed to establish more accurate efficient comparison. On the plus side, our paired meta-analysis results were consistent with the network meta-analysis results, which also improved the quality of our evidence. However, since most treatments do not have data on adverse events, the extent of their differences in safety is uncertain.AT was not superior to other treatments such as SAT and NRT in the long-term abstinence rates, but there was a difference between AA and SAA, which was consistent with the previous research results. However, in terms of short-term abstinence rate, we did not conclude that AT or AA was superior to other therapies, which was consistent with the results of White et al., but different from those of Wang et al. , 44. ThiThere were some limitations to our network meta-analysis. First, the course of treatment in the RCTs we included varied from 10 days to 8 weeks and the follow-up time was also quite different. Thus, it would be best to determine the collected data from a similar period. However, it would reduce the power of significance if a specific treatment period was selected in the current study. We will collect the data from larger data based which probably will enable us to test a more specific period. If the later clinical study can unify the treatment cycle and follow-up time, it may have been more convincing. Second, although the selected points of the studies we included are almost the same, there are also subtle differences. Although existing studies have shown that there is no direct linkage between acupoint selection and curative effect , acupuncOur analysis shows that a larger sample size, more consistent intervention methods, and treatment follow-up time are needed for future RCTs of acupuncture, auricular acupressure, and other traditional Chinese medicine methods for smoking cessation, so as to improve the quality of research and clarify the advantages of such methods in smoking cessation effect. In addition, we should pay more attention to the possible adverse events of these intervention processes and strengthen the evidence-based medical evaluation of safety evaluation. However, there is a lack of sufficient data from the included studies in the current network meta-analysis to offer an objectively dose-dependent value. This will be performed in our future study.AA was superior to SAA in long-term abstinence rate comparison. The probability rankings of AA and APAA were also better than other interventions. RCTs with larger sample size, more consistent intervention methods, and longer treatment follow-up time will be investigated in future to further clarify the advantages of treatment methods such as APAA and AA. In addition, more attention should also be paid to the possible adverse events during the treatment of TCM methods such as acupuncture, which should be reported to supplement the evidence-based medical evidence in this area.


To investigate the prognostic significance of extranodal extension (ENE) in papillary thyroid cancer (PTC).Seven hundred forty-three PTC patients were enrolled in the study from January 2014 to December 2017. The patients were dichotomized according to the presence of ENE. Logistic analysis was used to compare differences between the two groups. Kaplan–Meier (K-M) curve and propensity score matching (PSM) analyses were used for recurrence-free survival (RFS) comparisons. Cox regression was performed to analyze the effects of ENE on RFS in PTC.Thirty-four patients (4.58%) had ENE. Univariate analysis showed that age, tumor size, extrathyroidal extension, and nodal stage were associated with ENE. Further logistic regression analysis showed that age, extrathyroidal extension, and nodal stage remained statistically significant. Evaluation of K-M curves showed a statistically significant difference between the two groups before and after PSM. Cox regression showed that tumor size and ENE were independent risk factors for RFS.Age ≥55 years, extrathyroidal extension, and lateral cervical lymph node metastasis were identified as independent risk factors for ENE. ENE is an independent prognostic factor in PTC. With the rapid development of medical technology, the demand for evidence-based clinical practice and decision-making has progressively increased. Recent studies using real-world data (RWD) are increasingly high profile and have received increasing attention in the medical field . Within In previous studies on PTC, approximately 20%–80% of patients have cervical lymph node metastasis when diagnosed , 4. HoweHowever, the above studies were all retrospective studies conducted under natural conditions, and confounding factors on the prognostic significance of ENE were not eliminated. Therefore, the purpose of this study was to evaluate the prognostic significance of ENE in PTC using the propensity score matching (PSM) method, which will provide more updated, comprehensive evidence for clinical decision-making.We retrospectively reviewed the electronic medical records of 2,094 PTC patients in the Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, from January 2014 to December 2017. Then, patients were selected according to the following inclusion criteria: 1) PTC and cervical lymph node metastasis were confirmed by pathologic examination and 2) the clinical and pathological data were complete. The exclusion criteria were as follows: 1) the patient had other malignant tumors and 2) the patient had a history of cervical radiotherapy or trauma. All the patients who underwent surgery signed informed consent forms, and all the study contents were approved. The process of patient enrollment to the study cohort is shown in All clinical data were available through the electronic medical records, and patients with macroscopic ENE and macroscopic extrathyroidal extension were included in this study. ENE was defined as follows: intraoperative findings indicating that the organ had gross invasion by lymph node metastasis. As showed in During follow-up, the endpoint was recurrence-free survival (RFS) . All patients were regularly followed up by clinical evaluation, serum thyroglobulin level measurement, and ultrasound examinations 6 months after surgery. Recurrence was defined as structural recurrence and pathologically confirmed by fine-needle aspiration biopsy (FNAB) or distant recurrence. If the patient was lost to follow-up, their data were censored.All patients underwent open surgery. Thyroidectomy and cervical lymph node dissection were performed concurrently. Central lymph nodes were routinely dissected. Lateral cervical dissection was performed in patients with evidence of lateral cervical lymph node metastases through FNAB or preoperative imaging evidence. Important structures, such as the internal jugular arteriovenous, sternocleidomastoid muscle, and spinal accessory nerve, were spared. The therapeutic strategy for PTC with ENE was no residual resection or iodine 131 treatment. All PTC patients continued thyroid-stimulating hormone (TSH) suppression therapy after surgical treatment.P < 0.05 was considered statistically significant.Statistical analysis was performed with R Studio (Version 1.3.1093). Normally distributed data are expressed as the mean ± standard deviation (SD), and skewed data are expressed as the interquartile range. Univariate and multivariable logistic regression analyses were used to compare two groups. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. The log-rank test and Kaplan–Meier (K-M) curves were used for prognosis comparisons. Cox regression was performed to calculate the hazard ratios (HRs) and 95% CIs to determine the effects of ENE on RFS in PTC. PSM analysis was conducted to minimize the effects of potential confounders on selection bias. PSM was performed with 1:1 matching and a caliper value of 0.02.During the study period, 743 PTC patients were included. Among them, 220 were male and 523 were female. The age range of the patients was 18–76 years, with a mean of 42.84 years and an SD of 12.75 years. The baseline features of the PTC patients are presented in Thirty-four patients  with ENE were enrolled. The invaded organs were classified according to their location in the central neck compartment or lateral neck compartment. Thirty patients showed ENE of the central lymph nodes, and the median tumor size was 17.76 ± 13.66 mm. Lymph nodes mainly invaded the recurrent laryngeal nerve, followed by the surrounding adipose tissue and parathyroid gland. Twenty-two patients showed ENE of the lateral lymph nodes, and the median tumor size was 15.27 ± 10.87 mm. The internal jugular vein was the most frequently invaded of the cervical artery, followed by the adipose tissue, accessory nerve, and common carotid artery Table 2.Univariate analysis showed that age, tumor size, extrathyroidal extension, and nodal stage were associated with ENE, whereas sex, multifocality, and Hashimoto’s thyroiditis were not. We conducted multivariate analysis to further verify whether risk factors affected PTC patients with ENE. Our results showed that age, extrathyroidal extension, and nodal stage remained significantly different, but tumor size did not Table 3.P < 0.001; Twenty-three patients were lost to follow-up during the study period. The median follow-up time was 40.46 ± 15.51 months, and 15 of 720 PTC patients in this study experienced relapse. A comparison of the prognosis of the patients in the two groups indicated that the RFS of patients with ENE was lower than that of patients without ENE, and there was a significant difference between the two groups  were compared, and RFS was subsequently compared Table 4.We further conducted Cox regression analysis to determine the effects of ENE on RFS in PTC. Our results showed that age, tumor size, and ENE were independent risk factors for RFS before PSM. Then, we balanced the confounding factors, and tumor size and ENE still showed statistical significance after PSM Table 5.In recent years, thyroid carcinoma has exhibited the most rapid increase in incidence among solid tumors, and PTC is the most common malignant thyroid cancer . PreviouPrevious studies, including a meta-analysis, suggest that the presence of ENE is a significant poor prognostic factor in PTC . Wu et aThe relationship between ENE and prognosis was further analyzed using PSM. PSM is an effective statistical method that can process nonrandomized study data (such as RWD) and effectively reduce the confounding factors to fully equalize differences between the study groups . For PSMThis study also showed a significant association between ENE and the clinicopathological features of PTC, such as age, tumor size, extrathyroidal extension, and nodal stage. Roh et al.  found thIn the central neck compartment, the recurrent laryngeal nerve was most frequently infiltrated by lymph nodes with ENE. Moritani  found thThere are still some shortcomings in this study. 1) The follow-up time of this study is brief, and we will continue to follow-up this group of patients to further compare the difference in the long-term survival of patients. 2) This study focused on the prognostic significance of patients with macroscopic ENE. Further comprehensive studies on the prognostic significance of microscopic ENE are expected.In summary, ENE is relatively uncommon in thyroid carcinoma, accounting for only 4.58% of all cases of lymph node metastasis in this study. Age ≥55 years, extrathyroidal extension, and lateral cervical lymph node metastasis have been identified as independent risk factors for ENE. ENE is an independent prognostic factor in PTC.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 Hangzhou First People’s Hospital. The patients/participants provided their written informed consent to participate in this study.D-CL and T-HZ: drafted the work, designed the work, collected and analyzed data, revised the article for important content, final approval of the article to be published, agreement to be accountable for the work. FW: drafted the work, designed the work, collected and analyzed data, wrote the article, revised the article for important content, final approval of the article to be published, agreement to be accountable for the work. K-NL: designed the work, collected and analyzed data, revised the article for important content, final approval of the article to be published, and agreement to be accountable for the work. L-LM: collected and analyzed data, revised the article for important content, final approval of the article to be published, and agreement to be accountable for the work. L-QZ: collected and analyzed data, final approval of the article to be published, and agreement to be accountable for the work. K-CJ: collected and analyzed data, final approval of the article to be published, and agreement to be accountable for the work. YZ: drafted the work, designed the work, revised the article for important content, final approval of the article to be published, and agreement to be accountable for the work. BL and W-JZ: Statistical analysis and data processing, final approval of the article to be published, and agreement to be accountable for the work. All authors contributed to the article and approved the submitted version.This work was supported by the Medical Health Science and Technology Project of Zhejiang Provincial Health Commission (Grant numbers 0020190490 and 0020190151), the Medical and Health Technology Project of Hangzhou (Grant number A20200432), and the Zhejiang Provincial Medical and Health Technology Project (Grant number 2019RC240).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.


Low socioeconomic position (SEP) is associated with a high incidence of diabetic foot ulcers (DFUs). However, reports on the association between SEP and DFU outcomes are limited. Therefore, in this study, we investigated this association and determined the prognostic factors of DFU outcomes.The total cohort comprised 976,252 individuals. Using probability sampling, we randomly selected a sample of patients by reviewing the data from the Health Insurance Review and Assessment Service database of South Korea during 2011–2015. Residence, household income, and insurance type represented SEP. The primary outcome was amputation, and the secondary outcome was mortality. A multivariate model was applied to identify the predictive factors. Amputation-free survival and overall survival were calculated using the Kaplan-Meier method.p < 0.01), low SEP , ophthalmopathy , circulatory complications , and institutional type  were prognostic factors for amputation. Old age , low SEP , ophthalmopathy , circulatory complications , and institution type  were predictors of mortality.Among 976,252 individuals in the cohort, 1362 had DFUs . Overall amputation and mortality rates were 4.7 and 12.3%, respectively. Male sex (hazard ratio [HR], 2.41; DFU patients with a low SEP are strongly associated with increased amputation and mortality rates. Along with age and comorbidities, SEP could provide the basis for risk assessment of adverse outcomes in DFU. Providing targeted care for this population considering SEP may improve the prognosis. Diabetic foot ulcers (DFUs) are one of the major complications of neuropathy and microvascular disease in patients with diabetes. The annual incidence and prevalence rates of DFU are 1–4% and 5–10%, respectively, while the lifetime risk of developing DFUs is 15% in diabetic patients . DFUs, tSeveral medical factors including atherosclerosis with multiple stenosis, nephropathy, and uncontrolled diabetes have been reported as predictive factors for amputation and mortality, which are the major outcomes of DFUs , 8. HoweEquality in health care according to the need has been an important goal for health care policy in South Korea. All citizens of South Korea are covered by a mandatory health insurance system from birth to death. People are designated as National Health Insurance (NHI) or medical aid (MA) beneficiaries according to their insurance status. Most people who are covered under the NHI are associated with a low SEP and are recipients of the National Basic Livelihood Security System in South Korea. Understanding the association between amputation and mortality rate of DFUs with low SEP can lead to the development of health policies that can ameliorate the inequalities among the different SEPs.This study aimed to determine the association between SEP and DFU outcomes, namely, amputation and mortality, and identify prognostic factors for these outcomes in a South Korean population.We investigated amputation and mortality rates among patients with DFUs in the South Korean population using the database of the National Health Insurance Sharing Service-National Sample Cohort (NHIS-NSC). The amputation and mortality rates based on residence, type of health insurance, type of medical institution, and income status were examined and the comorbidities associated with diabetes were also considered.Data for the period 2011–2015 were extracted from the database of the NHIS-NSC, a population-based cohort established by the NHIS in South Korea. The NHIS collects data on the diagnosis, treatment, prescription, healthcare utilization, and inpatient and outpatient records . Death rThe disease code for DFU was created in 2011 in South Korea. Until 2010, only disease codes indicating wounds such as gangrene and ulcers were used. Therefore, these patients with DFUs could have been overlooked and not identified. Therefore, to reduce bias, only data from 2011 onward was selected.The cohort comprised 976,252 people  who were randomly selected to represent the entire South Korean population. Using probability sampling, this random cohort sample was generated representing an individual’s total annual medical expenses within each stratum defined by age, sex, eligibility status (employed or self-employed), and income level (10 quartiles for each eligibility status and MA recipients) combinations using the proportional allocations of the 49,936,638 Korean residents in 2011.DFU was defined using the Korean Classification of Diseases-6th (KCD-6th) and KCD-7th versions for the period 2011–2012 and after 2013, respectively. Diabetic foot was defined using the KCD code, indicating diabetic foot complications . Patients with events within 1 year of the first diagnosis were excluded to reduce the possibility of reverse causation.The data assessed in our study included demographic information such as age, sex, type of health insurance, residence regions, type of medical institutions at first diagnosis, household income, and other diabetes-related complications. The type of health insurance was divided into NHI and MA. The NHI covers approximately 96% of the total South Korean population, while the remaining 4% is covered by the MA program, which receives additional public assistance . The hosand the cause of death data from the Statistics Korea database. Hypertensive disease , coronary heart disease (ICD-10 codes I20–I25), cerebrovascular disease (ICD-10 codes I60–I69), and dyslipidemia (ICD-10 code E78) were considered comorbidities.The primary outcome was amputation, and the secondary outcome was mortality. Amputation was defined following the operation codes . The NHIS-NSC database was merged with death records n for dichotomous variables and means with standard deviations for continuous variables. Fisher’s exact test or Pearson’s χ2 test was used for categorical variables, and Student’s t-test was used for continuous variables. We used the Cox proportional-hazards model to evaluate the association of possible risk factors with amputation or mortality. Multivariate analysis was performed using Cox regression with factors that showed p < 0.1 in the univariate analyses. For censored cases, the follow-up duration was calculated from the date of the first diagnosis to the date of amputation or death. For cases not censored, we set the end of the follow-up point as the last date of medical care utilization . Amputation-free survival and overall survival were calculated using the Kaplan-Meier method. All statistical analyses were performed using SAS enterprise guide version 7.1  and R studio version 3.3.3 with p < 0.05 considered statistically significant.Descriptive statistics are presented as The Institutional Review Board of Seoul National University Boramae Medical Center (No. 07–2019-25) granted this study an exemption with regards ethical approval. We did not obtain informed consent because the patients’ records and information were anonymized and de-identified before the analyses. The criteria of informed consent is approved by the the Institutional Review Board of Seoul National University Boramae Medical Center. All methods were carried out in accordance with relevant guidelines and regulations. The data used in this study is not publicly available.A total of 1289 subjects were identified during the study period from the randomized cohort sample  underwent amputation during the follow-up duration of 656 days. Kaplan-Meier curves were generated for overall amputation-free survival Fig. a, and th.7% underIn total, 158 patients 12.3%) died during the follow-up duration of 880 days. Kaplan-Meier curves were generated for overall survival (Fig. .3% died Our study results indicate that a low SEP, reflected by area residence, income level, and type of insurance, is associated with poor outcomes in patients with DFU. Both amputation and mortality rates showed significant differences between the lowest and highest SEP groups. This association was significant after considering age, sex, and comorbidities. Similarly, association between lower SEP and high rate of lower extremity amputation has been reported in peripheral vascular disease –26. WhilWe investigated factors representing biological mediators for amputation including neuropathy and vasculopathy, and disease severity of diabetes including nephropathy ophthalmopathy. Between the biological mediators, the main etiologies of DFU , vasculoWe suggest that poor access to care, processes and quality of care, and health behaviors associated with patient education  are poteThe strength of this study is that its target sample group was randomly selected which can represent the total South Korean population. Although South Korea provides health insurance coverage for all citizens, blind spots exist, especially for diseases that require meticulous care. The findings from investigations into the prevalence of DFUs and the predictive factors for its prognosis, can guide the rational development of appropriate health care policies. According to our study, the low SEP group may be considered a high-risk group for poor DFU outcomes. While DFUs are associated with high health-related costs in persons with diabetes, patients with a low SEP are more likely to be neglected, which makes it a vicious cycle. DFUs, with amputation as the outcome, are associated with higher health-related costs caused by hospitalization, rehabilitation, home care, and social services for the disabled. Therefore, prevention of amputation through appropriate wound care can be the most important step for cost reduction in these patients. Management health programs will be useful for DFU patients with a low SEP, if provided by the society. Many studies have reported that prevention and screening programs for DFUs can reduce the rates of amputation, re-ulceration, and hospitalization –39. PatoOur study has some limitations. First, our data did not include lifestyle, smoking, or health-related clinical factors such as hemoglobin A1c level and body mass index, which could have influenced the outcomes. Second, although the claims data were available from the year 2002, our study only targeted data from the year 2011 onwards because this was the year when the specific disease code for the diabetic foot was generated. This inevitably reduced the total sample size. Third, major and minor amputation was not separately considered but was analyzed together as amputation event. First amputation event, major or minor, has its value but cannot reflect the severity of the outcome. Forth, death was not investigated in a disease specific manner and further investigation would be required. Lastly, this is a population-based study conducted in South Korea, and its findings may not necessarily be generalizable to the people of other countries with different medical insurance systems. Future studies that consider a more comprehensive range of factors including medication, laboratory data, and lifestyles are recommended to validate the findings of this study.In conclusion, our results suggest that DFU patients with a low SEP are strongly associated with an increased rate of amputation and mortality. Hence, more attention needs to be given to such patients. Addressing SEP in patients with DFUs and providing targeted care for them may improve the prognosis.