Gas supply system risk assessment is a serious and important problem in cities. Existing methods tend to manually build mathematical models to predict risk value from single-modal information, i.e., pipeline parameters. In this paper, we attempt to consider this problem from a deep-learning perspective and define a novel task, Urban Gas Supply System Risk Assessment (GSS-RA). To drive deep-learning techniques into this task, we collect and build a domain-specific dataset GSS-20K containing multi-modal data. Accompanying the dataset, we design a new deep-learning framework named GSS-RiskAsser to learn risk prediction. In our method, we design a parallel-transformers Vision Embedding Transformer (VET) and Score Matrix Transformer (SMT) to process multi-modal information, and then propose a Multi-Modal Fusion (MMF) module to fuse the features with a cross-attention mechanism. Experiments show that GSS-RiskAsser could work well on GSS-RA task and facilitate practical applications. Our data and code will be made publicly available. The advantages and the increasing demand of natural gas for urban life and industry has led to the rapid growth of the buried gas pipeline network . HoweverTo efficiently assess the gas supply system risk, existing methods attempt to build mathematical models to predict risk possibility in cities ,8. In thHowever, this strategy largely relies on expert consensus that might lead to various weight combinations for these factors. On the other hand, in the current gas supply system risk assessment community, researchers have not made the agreement of what kind of factors or features are expected to be considered into the risk assessment model. This results in inconsistent solution directions. In this context, deep learning has been rapidly developing since the success of ImageNet  in the cIn general, there are three issues when employing deep-learning techniques into the urban gas supply system risk assessment system. First, it is well known that a large-scale dataset plays a key role in driving efficient models and enables powerful feature representation. When we re-define the GSS-RA task, there are few datasets targeted at solving this problem. In the field of natural gas supply systems, the major challenge lies in how to select the types of information that might be significant for risk assessment. Secondly, the various kinds of data shown in different distributions and the feature vectors or embeddings extracted from these multi-modal data might not be represented in the similar latent space. So how to design a deep-learning model that could deal with multi-modal data might be a serious issue. Finally, in the newly formatted gas supply system risk task, it is necessary to build a proper evaluation system to validate the performance of our model.In this paper, our main work is to solve the GSS-RA task from the above aspects. To tackle the data problem, we present a novel data collection with an analysis system. We collect information about its natural gas supply system with both visual and non-visual modals. In brief, we adopt an image–language pair as input (represented by a gas supply system image and a gas usage score matrix) that indicates the gas supply system situation for each user in our city environment. In this way, we build the first dataset for GSS-RA task, named GSS-20K. In terms of deep-learning architecture designing, we propose a novel framework GSS-RiskAsser for dealing with the multi-modal input data. In our GSS-RiskAsser, we encode the image and score matrix in two types of one-dimensional vector. Then we build a parallel transformer-like neural network to separately extract the feature embedding. To deal with the multi-modal input problem, we propose a cross-attention mechanism into these two branches that achieves multi-modal information exchange and fusion, so we can jointly obtain the final feature embedding that considers different types of information at the same time. Finally, we employ our GSS-RiskAsser into two practical applications: Gas Supply System Risk Heatmap Monitoring and User Gas Supply System Relationship Graph. We believe that our efforts could benefit future city gas supply system monitoring and warning systems. The overall pipeline of our work is illustrated in To the best of our knowledge, we are the first to consider urban gas supply system risk assessment as a deep-learning problem. We analyze and attempt to solve the challenges when employing deep-learning techniques in this field. We re-format and define a novel task Urban Natural Gas Supply System Risk Assessment (GSS-RA). To drive the model, we publish a dataset GSS-20K that uses both image and language types of data for GSS-RA task.Accompanying the GSS-RA task and GSS-20K dataset, we build a practical gas supply system risk assessment system, and design a parallel transformer to process image and score matrix input for each sample. To deal with the multi-modal data problem, we propose a cross-attention mechanism into these two branches that achieves multi-modal information exchange and fusion.To properly evaluate our work, we employ our GSS-RiskAsser into two practical applications: Gas Supply System Risk Heatmap Monitoring and User Gas Supply System Relationship Graph. We believe that our efforts provide a feasible benchmark, which serves as a strong baseline for the GSS-RA task, and in the future could facilitate research and practical applications on city gas supply system monitoring and warning. Our dataset and code will be made publicly available.The major contributions of this paper are three-fold:Early works for gas risk assessment consider it as a mathematical problem. On the contrary, these works try to solve this task by defining their own evaluation metrics to assess the gas risk from qualitative and quantitative aspects . Jo et aThe methods mentioned above tend to manually build mathematical models to predict urban gas risk. With the development of artificial intelligence, more and more researchers pay their attention to constructing machine learning or neural network models. Li et al. proposes a unified framework for the new application in the vulnerability assessment of urban gas using Support Vector Machine (SVM) and Artificial Neural Network (ANN), and compares the two methods in performance . In addiMulti-modal fusion is one of the key topics in multi-modal research, which aims to integrate information extracted from different modalities into a stable multi-modal representation. Currently, the total deep learning-based multi-modal representation methods could be summarized into two families. One of those is proposed to fuse information from various sensors by tensor operations, such as concatenation ,26 or weAs is mentioned earlier, we re-format the gas supply system risk assessment as a new GSS-RA task. In contrast to current approaches for tackling this problem, the GSS-RA problem setting advances them in these aspects: (1) we consider the gas supply system risk on a user level while most works investigate it at urban plot level. (2) we exploit both visual and non-visual information to define a multi-modal task for this problem. (3) we build a hierarchical risk evaluation system where the final gas supply system risk I that describes the user’s gas supply system and a pipeline situation score matrix M from several experts’ judgement, a GSS-RA model will learn to predict the three gas supply system risk metrics In the GSS-RA problem, given a 2D single static RGB image As few works focus on dealing with a gas supply system risk assessment with deep-learning methods and there exists no dataset to fully support our GSS-RA task, we construct the GSS-20K dataset by manual acquisition and annotation. First, we acquire gas supply system images for each user to build the visual subset . Then, wCurrent deep-learning datasets, such as MS COCO , usuallyIn many deep-learning tasks, such as agricultural pest detection , visual Accident-related factors: We first consider what factors might cause gas supply system accidents. (1) Hose defect. (2) Burning appliance defect. (3) User misconduct. (4) Pipeline and equipment defects. (4) Management. Consequence related factors: Secondly, we also consider the loss of life and property when an accident happens. (1) Difficulty of repair. (2) Safety interlocking device. (3) Gas environment. The details of these factors and the scoring paradigm are shown in To obtain the final score matrix, we adopt one-hot encoding function to build the score related to each factor into a 1-dimensional vector (containing 10 elements) and concatenate these vectors into our score matrix with Compared with image collection for visual tasks, e.g., image classification , it is fOur SCMMG method includes the following steps. For visual data generation, we build a complex data augmentation pipeline that adopts mix-up, rotate, noise, blur and some popular strategies to generate an image that is an unseen and positive sample in the original dataset. Moreover, we also randomly sample a positive score matrix and generate a new score matrix by clustering neighbor sampling as well as Gaussian noise. Finally, we randomly combine the generated visual and non-visual information to obtain the expanded multi-modal data. In this way, we build our GSS-20K dataset with enough positive samples.To further motivate the construction and usage of our dataset, we compare GSS-20K with several existing datasets from two aspects, i.e., comparison with datasets for some popular deep-learning tasks and comparison with datasets that are related to the task of gas supply system risk assessment. The comparison is illustrated in As can be observed, image classification and object detection are the key topics in the computer vision and deep-learning community, where many researchers participate in building large-scale datasets as their benchmarks. Thus, ImageNet  or MS COWe propose a framework GSS-RiskAsser to address GSS-RA task, whose structure in The great success of transformers in NLP has sparked particular interest from the computer vision community in introducing transformer architectures into processing 2D images . In our The structure of VET is shown in Next, given the patch sequence lth encoder, the input sequence Each transformer encoder is composed of a Multi-head Self-Attention (MSA) module and a Multi-Layer Perceptron (MLP). For Thus, the MSA output is the sum of these self-attention outputs. Finally, we further adopt MLP and short-cut mechanism to obtain the transformer encoder output Finally, we use Similar to VET, we also build a transformer-like architecture to process score matrix data, named Score Matrix Transformer (SMT). First, we flatten the score matrix into a patch sequence Next, we build several transformer encoders to process this sequence Please note that due to the fact that score matrix is not in the same distribution of images, the transformer encoders in SMT do not share any weights with those in VET. Finally, we use In GSS-RiskAsser, we aim to tackle the multi-modal information problem. Therefore, we design a Multi-Modal Fusion (MMF) module to achieve reasonable and effective feature fusion from VET and SMT. The architecture of MMF is shown in lth layer, the Query Taking the CLS token lth layer on VET branch:In this way, by combining several cross-attention modules, we could build a Multi-head Cross-Attention (MCA) module to compute the final fusion output at In the same way, we could obtain the output for SMT Implementation Details We train our model for 300 epochs on 8 Titan X GPUs with a batch size of 1024. In terms of optimizer, we use cosine linear-rate scheduler with the initial learning rate of 0.001 and a weight decay of 0.005. During training and inference, we resize all the images into Baselines Since GSS-RA is a novel task and no existing baseline methods could work in this task. We compare our GSS-RiskAsser with the following popular deep-learning models: (1) CNN-based methods. We only apply CNN architecture to process visual information and predict gas supply system risk. The models we compare are ResNet50 and ResNet101. (2) RNN-based methods. In these baselines, we only exploit score matrix by DNN, GRU or LSTM to predict risk value. (3) CNN-RNN fusion methods. We extract multi-modal features by CNN and RNN separately and concatenate them to predict risk. Apart from these methods, we also compare our GSS-RiskAsser with its ablated versions such as VET only and SMT only. Moreover, we report ablation studies on various GSS-RiskAsser versions, e.g., single-head self-attention, single attention for multi-modal fusion and different image/patch sizes.Evaluation Metrics For three different types of risks, we use Mean Absolute Error (MAE) and Mean Square Error (MSE) as evaluation metrics.N is the number of testing samples. 0.054, 0.040 and 0.036 MAE on the possibility risk, consequence risk and final risk assessment. Therefore, we can conclude that multi-modal features could play a complementary role in our task.70%, 80% and 70% on three types of risks in MAE. Among these accuracy curves, our GSS-RiskAsser is the best method and obtain a larger improvement compared to others.We also report accuracy on various MAE and MSE thresholds. We built some ablation experiments on investigating the effects of architecture parameters, fusion strategy and image/patch sizes. In these experiments, we use MAE as metrics and set several different parameter combinations.Effect of architecture parameters.0.065 to 0.055 on MAE of possibility risk. On the contrary, our method is more robust to the number of SMT encoders, in which there is only around 0.001 decline. This could be attributed to the reason that score matrix input is already in a high semantic space so SMT could easily learn the high-quality features from it.Effect of fusion strategy. As discussed earlier, multi-modal information fusion is one of the major challenges in processing different types of features. In 0.007 and 0.006 MAE improvements compared to concatenation fusion and sum fusion. In addition, under the multi-level cross-attention strategy, our GSS-RiskAsser could achieve higher performance on our task.Effect of image/patch sizes. In GSS-RiskAsser, we use image as visual information input, so here we discuss how to resize the image shape and how to tokenize the image into patch sequence. In Gas Supply System Risk Heatmap Monitoring. We deploy our GSS-RiskAsser into practical urban natural gas pipeline applications. The first one is gas supply system risk heatmap monitoring, as shwon in Gas Supply System Risk Relationship Graph. To further investigate the gas supply system risk distribution as well as the potential accident reasons. We deploy our GSS-RiskAsser and draw the gas supply system risk relationship graph in In this work, we study the urban gas supply system risk assessment problem from a deep-learning perspective, and define a novel task GSS-RA. To further investigate the GSS-RA task and provide a proper method as baseline, we collect and build a domain-specific dataset GSS-20K that contains multi-modal data. To the best of our knowledge, we are the first to adopt a deep-learning approach to this problem and publish the corresponding dataset. In addition, we propose a new gas supply system risk assessment framework, and design parallel transformers to process multi-modal information at the same time. To properly fuse them, we propose a cross-attention mechanism to achieve multi-modal information exchange and fusion. Experiments show that our method could work well on the GSS-RA task and in the future could promote practical applications in the real world.


Background: The high prevalence of mental disorders related to posttraumatic stress among Syrian refugees is often in contrast with their low utilization of mental health care in the host countries. Mental health self-stigma, i.e., internalized stigma of having a mental disorder, could prevent individuals from seeking mental health care. Therefore, we aimed to provide evidence on different aspects of mental health self-stigmatization among adult Syrian refugees with posttraumatic stress symptoms residing in Germany. Moreover, we investigated associations with sociodemographic and psychopathological variables in order to identify those at higher risk of self-stigmatization.Material and Methods: Overall, 133 participants with mild to moderate posttraumatic stress symptoms were recruited in the metropolitan areas of Leipzig, Dresden and Halle, Germany, using a multimodal approach. Mental health self-stigma was assessed using the Self-Stigma of Mental Illness Scale – Short Form (SSMIS-SF), consisting of four subscales , each scoring from 5 (low) to 45 (high) points. Linear regression analysis was used to test associations of sociodemographic and psychopathological variables with self-stigma subscales.Results: On average, self-stigma ratings ranged from 16.5 (SD = 6.6) points on Application to self to 28.3 (SD = 7.5) points on Stereotype awareness. Results showed higher scores on Application to self for individuals who were younger  and single . Regression analyses yielded statistically significant associations between having multiple comorbidities and a higher Application to self stigma , controlling for sociodemographic covariates.Discussion: Mental health self-stigma was increased among Syrian refugees in Germany. Correlates of increased self-stigma could inform efforts to improve access to mental health care among Syrian refugees with mental ill-health. Longitudinal studies following an intersectional approach by concurrently examining multiple forms of public and internalized stigma could provide helpful insights for developing tailored stigma reduction efforts in this context. Around the globe, the number of individuals forcibly displaced from their homes due to persecution, violence, conflict and human rights violations has risen to 79.5 million by the end of 2019 . Upon arSociologist Erving Goffman defined stigma as an “attribute that is deeply discrediting,” resulting in the “situation of the individual who is disqualified from full social acceptance” . DepartiThe process of internalizing negative views among individuals with mental ill-health can have detrimental psychosocial effects see . For exaAs for Syrian individuals with mental ill-health, the few existing studies suggest a high level of stigma related to undergoing specialized mental health treatments and receiving a mental disorder diagnosis. For example, Hassan and colleagues  have poiSanadak trial  to describe the level of mental health self-stigma among Syrian refugees according to the progressive model of self-stigma, (II) to investigate possible differences in mental health self-stigma according to age, gender, education and family status, and (III) to determine whether individuals were more prone to self-stigmatization if they had more psychopathological comorbidities. Based on our findings, we aimed to inform the development of adapted stigma reduction efforts and of urgently needed multidisciplinary  support options for refugees in Germany and other host countries  between October 2018 and December 2019. A detailed description of recruitment procedures is given elsewhere (Participants of the lsewhere . Potentilsewhere  and (IV)lsewhere , (III) alsewhere , (IV) cuSanadak trial and the procedure of translation to Arabic (if measures were not available in Arabic) is provided in the study protocol  (strongly disagree) to 9 (strongly agree). There are four subscales, each consisting of four 5-items, which represent consecutive stages in the stigma internalization process: stereotype awareness (Aware), stereotype agreement (Agree), application to self (Apply), and harm to self-esteem (Harm). Examples of items are “I think the public believes … most people with mental illness are to blame for their problems” , “I think … most people with a mental illness cannot take care of themselves” , “Because I have a mental illness … I am dangerous” , or “I currently respect myself less because … I am unpredictable” . Sum scores were calculated for each of the subscales, with a possible range of 5 (low level of self-stigma) to 45 (high level of self-stigma). Good reliability and validity have been demonstrated for the SSMIS-SF (SMIS-SF) . The SSMSSMIS-SF .Psychopathological comorbidities  were determined according to scores of the Patient Health Questionnaire – Depression Module (PHQ-9) ( (PHQ-9) , the Gen (PHQ-9)  and the  (PHQ-9) . We used (PHQ-9) , 31, 32.r bivariate correlation coefficients using pairwise complete observations. Differences between the four self-stigma subscales were tested using one-way repeated measures analysis of variance (ANOVA), which is in line with previous investigations of the progressive model of self-stigmatization based on cross-sectional data . The majority of participants were male, single, had a high degree of school education and not more than one psychopathological comorbidity. The age of participants in the analysis sample ranged from 18 to 64 years. Mean posttraumatic stress symptom level (PDS-5) according to the screening assessment was 24.4 (SD = 11.1).F = 73.526, p < 0.001, Post-hoc tests with Bonferroni-corrected p-values yielded significantly higher scores on Stereotype awareness than the other three subscales (p < 0.001), and significant differences between higher Stereotype agreement and lower Application to self (p = 0.007). Correlations between self-stigma subscales are shown in Application to self scores for older vs. younger individuals (Cohen's d = 0.53). Testing for gender and education differences on self-stigma yielded no significant results. Post-hoc tests with Bonferroni-adjusted p-values yielded significantly higher Application to self scores for single vs. married participants (p = 0.003).Univariate comparisons of mental health self-stigma scores across age groups, gender, education and family status are displayed in Stereotype awareness and Harm to self-esteem. Being married (in reference to being single) was significantly associated with lower scores on Stereotype agreement. In addition, higher age was significantly associated with lower scores on Application to self , whereas having ≥2 psychopathological comorbidities (in reference to ≤ 1 comorbidity) was significantly associated with higher scores on that subscale.Self-stigma subscales between individuals with different numbers of comorbidities see  were notApplication to self for individuals who were younger and single, respectively. Moreover, regression analyses yielded significant associations between having multiple comorbidities and higher Application to self , controlling for sociodemographic covariates .The study aim was to investigate mental health self-stigma and to investigate its associations with sociodemographic and psychopathological characteristics in a sample of adult Syrian refugees with mild to moderate posttraumatic stress symptoms residing in Germany. Forty-four percent of participants in our sample had multiple psychopathological comorbidities. Our results showed higher scores on Brief Version of the Internalized Stigma of Mental Illness Scale (ISMI-10)  might be more difficult to interpret in the case of refugees who have left the societal context that they grew up in and have entered a different cultural and societal sphere in the host country.The scores on the four subscales of mental health self-stigma in the current sample broadly aligned with results from clinical non-refugee samples based on the same measure , 16, 36.ISMI-10) , a recenISMI-10) . The autStereotype awareness, our results showed significantly lower scores for the three subsequent stages  in the self-stigmatization process (see Stereotype agreement (higher) and Application to self (lower). However, scores for Harm to self-esteem were not significantly different compared to the preceding two stages. Similar to our findings, previous examinations of the model have yielded inconsistent patterns. For example, Corrigan et al.  and weakest between the most distant stages (Stereotype awareness – Harm to self-esteem).Compared to cess see . Anothern et al.  reportedn et al. . Other rn et al. . Yet, itn et al. . In linen et al. , 13, 15,Similar to existing studies, our findings indicated a differentiation between higher perceived public stigma and lower self-stigma, as well as higher correlations between more proximal stages of self-stigmatization. In light of inconclusive evidence, the assumption of a trickle-down process with decreasing self-stigma along the postulated four stages requires further empirical testing and corresponding refinement. The underlying idea of stigma internalization as a progression from public stigma to self-stigma is, however, substantiated by longitudinal empirical evidence , 40. NotStereotype agreement, when adjusting for the other sociodemographics and the number of comorbidities. Given the lack of reported sociodemographic characteristics of mental health self-stigma in refugees from Syria, we draw upon a systematic review on mental health stigma in individuals in different Arabic cultural contexts (Our results showed that being married (vs. single) was associated with less contexts . This stcontexts ] reportecontexts . This coApplication to self ) for younger vs. older individuals. This is in line with results from a Canadian population-based survey which reported significantly lower self-stigma of depression for older adults . We found no such associations for the remaining three self-stigma subscales . Stronger self-stigma for higher symptom severity has been reported before, both in Western samples and in Arabic refugee samples  and was conducted in accordance with the Declaration of Helsinki  and the ICH guidelines for Good Clinical Practice (GCP). The patients/participants provided their written informed consent to participate in this study.JB contributed to acquisition of the data, formulated the research question, wrote the statistical analysis plan, conducted the statistical analyses, interpreted the data, wrote the manuscript, and gave final approval of the version to be published. AP was the trial statistician, contributed to acquisition of the data, supported in analysis of the data, interpreting the results, and drafting the manuscript, and gave final approval of the version to be published. SR substantially contributed to acquisition of the data, supported in drafting the manuscript, and gave final approval of the version to be published. ML, AR, MN, JD, TG, AK, and H-HK contributed to acquisition of the data, revised the manuscript critically for important intellectual content, and gave final approval of the version to be published. SR-H conceptualized and designed the study, supported in interpreting the data, revised the manuscript critically for important intellectual content, and gave final approval of the version to be published. 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.


To develop and evaluate the prognostic value of a comprehensive inflammatory biomarker for postoperative colorectal cancer (CRC) patients.A total of 646 CRC patients were recruited between August 2017 and December 2019 from Fujian Medical University Union Hospital, with follow-up data up to 2021. The least absolute shrinkage and selection operator method (LASSO) was used to select inflammation indicators in order to construct a comprehensive biomarker (named NSAP). The Cox regression model was utilized to analyze the association between the NSAP and the disease-free survival (DFS) of CRC. Predictive performance and clinical utility of prognostic models were evaluated by area under the curve (AUC) and decision curve analyses (DCAs).P < 0.05). DCAs also demonstrated that the established nomogram had better utility for decision making.During a median follow-up of 23 months, 95 clinical outcomes were observed, with a 1-year survival rate is 89.47%. A comprehensive inflammatory biomarker (NSAP) was established based on four blood indicators (including neutrophil-to-lymphocyte ratio (NLR), neutrophil×monocyte-to-lymphocyte ratio (SIRI), albumin-to-globulin ratio (AGR), and platelet-to-lymphocytes ratio (PLR)). Patients with a lower NSAP had significantly associated with better DFS of CRC . Moreover, compared to a previously established model, the traditional TNM staging system or/and tumor markers, the nomogram based on NSAP displayed more excellent predictive ability (0.752 vs 0.597, 0.711 and 0.735, Our study suggests that NSAP may be a useful comprehensive prognostic biomarker for predicting the DFS of CRC patients. The nomogram based on NSAP can be considered a valuable tool to estimate the prognosis of patients with CRC.The online version contains supplementary material available at 10.1186/s12957-022-02550-0. Colorectal cancer (CRC) is the third most common malignant tumor and the second leading cause of death worldwide . To dateAccumulating studies have shown that the host immune system may have a dual role in tumor promotion and suppression –10. WhenTherefore, the purpose of this study is to comprehensively explore the roles of various blood indicators in the disease-free survival (DFS) of CRC patients and to develop a novel inflammation-related comprehensive biomarker using the LASSO algorithm, with a goal to provide research evidence for individual prediction and decision-making.From August 2017 to December 2019, a total of 646 CRC patients who underwent surgical resection were consecutively enrolled at Fujian Medical University Union Hospital . Patients were eligible if they met the following criteria: (1) newly pathologically diagnosed with primary CRC, (2) no receipt of any treatment that affected blood indicators, and (3) without neoadjuvant radiotherapy or radiochemotherapy prior to surgery. The exclusion criteria were as follows: (1) patients with a history of blood disease or infection and autoimmune disease and (2) patients who suffered from other cancers or emergency surgery before being included in the study. All patients provided written informed consent and fully understood the study. The research protocol has been approved by the institutional review board of Fujian Medical University (No.2020KY007) and followed the ethical standards of the Helsinki Declaration.The patient’s demographic and clinical characteristics were abstracted from the hospital medical record system. The relevant preoperative laboratory parameters for blood indicators were measured on the day of admission, including the tests of blood routine , blood biochemical , and tumor markers including alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9 (CA19-9). Then, eight blood indicators were calculated accordingly: neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), neutrophil×monocyte-to-lymphocyte ratio , albumin-to-globulin ratio (AGR), platelet-to-lymphocyte ratio (PLR), serum albumin + 5×total lymphocyte , monocyte-to-high-density lipoprotein ratio (MHR), and monocyte-to-lymphocyte ratio (MLR). In addition, we also compared the prognosis of colorectal cancer with a newly developed nomogram in previous literatures , includiAll patients were followed up by trained study interviewers through telephone inter at 3-month intervals for the first 2 years postoperatively and every 6 months for the next years. DFS was defined as the time from initial surgery to recurrence, metastasis, death (for any reason), or the last follow-up . The overall loss of follow-up rate was 4.3%. During follow-up, 28 cases were dead, 82 patients occurred recurrence and metastasis (19 subjects were identified before death), and 551 subjects were still alive at the last follow-up.P-value less than 0.05 was statistical significance.The cutoff points for NLR, LMR, SIRI, AGR, PLR, OPNI, MHR, and MLR were determined by the X-tile program . Reverse Kaplan-Meier method was used to calculate median follow-up time. A heat map was used to reveal the degree of correlation among the eight blood indicators. Then, the LASSO algorithm was utilized to develop a comprehensive blood indicator. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated based on the univariate and multivariate Cox regression model for exploring independent prognostic factors of CRC. Three prediction models were established using a generalized linear model (GLM), receiver operating characteristic (ROC) methods, and the predictive ability that were compared through the area under the curve (AUC). Decision curve analysis (DCA) was plotted to further assess the clinical usefulness of the models. All statistical analysis was performed using R software (version 4.0.5). Of the 646 CRC cases included in the final analysis Table , 403 62. During The heat map provided the correlation between eight blood indicators, reflecting in the area of the circle and the shade of the color Fig. A. SeveraP < 0.001, Fig. P<0.001), and 1.89 , respectively. Additionally, tumor stage , AFP , and CEA  were found to be independent prognostic factors for DFS in the multivariate analysis  based on a combination of four inflammation-related parameters using the LASSO method. Our study demonstrated that NSAP was an independent prognostic factor for CRC, and the high-NSAP was associated with poor DFS. The nomogram based on NSAP and the TNM staging system and tumor markers displayed a high predictive performance and clinical decision value.A large number of studies have shown that systemic inflammation has become an essential part of tumorigenesis, proliferation, survival, and migration and is likely to become a new direction for cancer treatment and monitoring –20. To dAlthough a single inflammatory index was proved to have predictive ability, the comprehensiveness and accuracy are not satisfactory. In the current study, varying degrees of correlation among the eight indicators were also observed. Therefore, we employed the LASSO method to solve these problems instead of the traditional Cox model. The most prominent advantage of the LASSO algorithm is that the relatively unimportant coefficients of independent variables become 0 and are excluded from modeling through penalized regression on all variable coefficients . It is pThe exact underlying mechanism of the close correlation between the high NSAP and the poor DFS is not yet clear. We found that three of the four indicators included in NSAP are related to lymphocyte count, except for AGR. Previous studies showed that the local control of metastatic invasion by the immune system might be critical to survival. The presence of lymphocytes in the tumor may be a favorable prognostic sign . For exaNevertheless, the current research has some limitations that should be considered. First of all, although we have collected complete follow-up data of 646 patients, the findings of this study were still limited by the lack of external verification and a relatively small sample size. Second, as a single-center study, it will inevitably bring about potential selection bias. Future multi-center studies with larger sample sizes are warranted to confirm our findings further. Third, the 3-year follow-up time has affected the tracking of more outcome events and limited the observation of the survival rate of CRC for a longer time. It is necessary to continue the follow-up visit according to the established follow-up plan in the future.This study developed a novel comprehensive inflammatory biomarker (NSAP) and suggested that NSAP is strongly associated with the DFS in CRC patients. Compared with the previously established model, the traditional TNM staging system, and tumor markers, NASP can effectively improve the predictive ability of the prognostic model. More prospective multi-center data sets are still needed to confirm our findings and the practicality of clinical decision-making in the future.Additional file 1: Table S1. Baseline tumor markers and inflammation index of patients with colorectal cancer. Fig.S1. Coefficients deviance of the LASSO analysis. Fig. S2. A, B, C X-tile analysis on the optimal cutoff points of NSAP. Fig. S3. A Kaplan-Meier curves for disease-free survival of CRC patients. according to the stage; B according to alpha-fetoprotein (AFP); C according to carcinoembryonic antigen (CEA). Fig. S4. A Calibration curve of nomogram of 1-Year DFS. B Calibration curve of nomogram of 2-Year DFS.


More powerful prognostic and diagnostic tools are urgently needed for identifying and treating ovarian cancer (OC), which is the most fatal malignancy in women in developed countries. Circular RNAs (circRNAs) are conservative and stable looped molecules that can regulate gene expression by competing with other endogenous microRNA sponges. This discovery provided new insight into novel methods for regulating genes that are involved in many disorders and cancers. This review focuses on the dysregulated expression of circRNAs as well as their diagnostic and prognostic values in OC. We found that studies have identified twenty-one downregulated circRNAs and fifty-seven upregulated ones. The results of these studies confirm that circRNAs might be potent biomarkers with diagnostic, prognostic and therapeutic target value for OC. We also consider the connection between circRNAs and OC cell proliferation, apoptosis, metastasis, and chemotherapy resistance and sensitivity.The online version contains supplementary material available at 10.1186/s11658-021-00284-7. Ovarian cancer (OC) is the most fatal malignancy among women . One in The incomplete understanding of the genetic alterations and molecular pathways of OC means treatments cannot be properly targeted. Thus, despite the relatively rapid development of diagnostic and therapeutic techniques, the prognosis for patients with OC is still unsatisfactory. Elucidating its pathogenesis could reveal novel and promising biomarkers and targeted therapy sites , 5.Non-coding RNAs (ncRNAs) comprise more than 98% of the human genome. They are transcribed from DNA without being translated into a protein and play essential roles in gene translation and regulation . ImportaCircular RNA (circRNA), a large class of non-coding regulatory RNA, was first discovered in 1976 . More thhttps://joannabriggs.org/systematic-review-register) and its protocol has been registered on PRISMA flow diagram [This study focuses on the identification and expression of dysregulated circRNAs. It also assesses their importance in the diagnosis of OC and estimation of patient prognosis. The study was performed in accordance with the JBI methodology for systematic scoping reviews . The pro diagram .Question: What role do circRNA expression levels play in patients with ovarian cancer (OC)?Participant type: Cisgender women with OC and related OC cell lines.Concept: Circular RNA expression as biomarkers with prognostic and diagnostic functions.Context: Not applicable and special.Based on the reporting objects used in systematic scoping reviews, our searches were performed using Web of Science, PubMed, Embase and Scopus. The keywords were "circular RNA", "CircRNA", "Ovarian Cancer" and "OC", as well as other synonyms for circRNAs. The latest date of publication was April 2021 and the publication language was English. The search results were combined and de-duplicated.EndNote X9 software was used to find and remove duplicates. References were arranged by number and exported to Microsoft Word for screening. The study process was summarized in a PRISMA flow diagram , the list of circRNAs and the study design being expressed differentially. Related supplementary information, including samples or cell lines, the related mRNA, and their expressions, functions and potential targets were extracted from relevant online databases, including Circad, CircNet, CircBase, and PubMed Table . The limWe extracted 487 articles from Web of Science, PubMed, Embase and Scopus. The results were merged and de-duplicated. After removing irrelevant articles, 78 abstracts were reviewed. The selection procedure is shown in the flowchart in Fig. As with other non-coding RNAs (ncRNAs), circRNAs can adjust gene expression by sponging protein or RNA. The most-reported way involves regulating miRNA activity by acting as competition for endogenous miRNA sponge elements. This allows mRNA to escape from miRNA suppression post-transcriptionally . The sizCircRNAs are specific miRNA reservoirs or sponges.CircRNAs interact with RNA-binding proteins (RBPs), which play a central function in transcription and translation of genes.CircRNAs act as protein or peptide translators.CircRNAs act as regulators of gene transcription and expression Fig. .Notable characteristics of circRNAs include their prevalence and specificity , 24, higConsiderable evidence has shown that circRNAs can affect the aggressive properties of tumors. For example, they compete with miRNAs, translate into proteins, act as miRNA reservoirs, and form fusion circRNAs (f-circRNAs) , 29. TheAccording to the information we have about the importance of these circRNAs, their effect on various organs is not negligible. One of the organs that can be affected by these circRNAs is the ovaries. Ovaries play a fundamental role in the female reproductive system with the basic functions of producing oocytes under the stimulation of gonadotropic hormones secreted from the pituitary gland to guarantee the evolution of follicles, estrous cycles, and post-pregnancy hormonal levels. The risk factors for OC include age, a family history of the disease, and unremitting ovulation in carriers of the heredity mutation of BRCA1 . The occInvasive therapies, such as surgery, and drug therapies have not sufficiently reduced OC mortality. Finding new biomarkers and targets may help with earlier diagnosis and more effective treatment. The relationships between circRNAs and OC have considerable potential because of their regulatory roles. It is known that abnormalities in the regulation of signaling pathways and cellular mechanisms cause cancer formation, progression, and metastasis. In the past few years, multiple studies have focused on differentially expressed circRNAs in OC, indicating that circRNAs could be therapeutic targets and novel biomarkers for this disease .Various internal and external factors are involved in cancer pathogenesis. Genetic and epigenetic factors are the main ones , 39. MulAhmed et al. were the first to conduct an expression analysis on circRNAs in ovarian tumors. They found that a great number of circRNAs are differentially expressed in tumors . They alMultiple circRNAs, such as circ-0051240, circ-EPSTI1, circ-PIP5K1A and circ-GFRA1, cause malignant behavior of OC cells by acting as miRNA sponges –55. circCirc-UBAP2 promotes the expression of N-cadherin in OC cells by sponging miR-144 as well as exerting conservative effects on OC cell proliferation and invasion. Overexpression of miR-144 has a reverse effect on Circ-UBAP2 tumorigenesis . AnotherSilencing circ-102958 significantly inhibits OC cell proliferation and invasion and its upregulation is associated with a poor prognosis in OC patients. It promotes OC cell proliferation and migration by increasing the expression of SH2D3A through influence on the activity of miR-1205 as a competing endogenous RNA (ceRNA) .The circ-MYLK level in patients with OC has been found to be significantly higher in cancer tissues than that in adjacent ones. Circ-MYLK can be targeted by microRNA-652 . Li et aHsa-Circ-0026123 inhibits OC progression by mediating the miR‑124‑3p/EZH2 candidate biomarker for the diagnosis and therapeutic target of OC . In 2019Multiple studies are showing that circRNAs are significant in EOC. Circ-PGAM1 was found to be an oncogenic circRNA in EOC tissues and cells by Zhang et al. They silenced it and showed inhibition of progression in EOC tissues and cells. A related miRNA, miR-542-3p, was found to be downregulated in EOC tissues and cells. Its overexpression suppressed the formation of tumors in related tissues and cells .As mentioned before, circRNAs have other functions and can play a crucial role in tumor cell proliferation, apoptosis, metastasis and invasion. Here are some of the studies that investigate possible mechanisms by which circRNAs take part in OC development. Chen et al. found high distribution of circ-ASH2L in the cytoplasm, where it competes with vascular endothelial growth factor A (VEGFA) to absorb miR-665. This evidence justifies the role of circ-ASH2L in tumorigenesis and angiogenesis via the miR-665/VEGFA pathway . The incThere is a high expression of circ-PUM1 in normal ovarian tissues. There is also a direct relationship between its high expression and advanced stages of OC as defined using the FIGO scale from the International Federation of Gynecology and Obstetrics. Cell line-based studies revealed that circ-PUM1 increases cell invasiveness and proliferation by sponging miR-6753-5p and miR-615-5p to upregulate MMP2 and NF-κB expression. Guan et al. found that Circ-PUM1, on the one hand, causes rapid OC cell growth, invasion and metastasis, and on the other hand, by acting on the peritoneum, contributes to cancer metastasis via the formation of cancerous exosomes .Many circRNAs, such as circ-RhoC, promote angiogenesis in OC. High expression of circ-RhoC promotes tumor formation and metastasis. However, this circRNAs sponging of miR-302 upregulates VEGFA expression, which is involved in metastasis and angiogenesis .Zhang et al. discovered that one of the functions of circRNAs is to attenuate the inhibitory effects of miRNAs on protein translation by competing with them and interfering with target mRNAs. As an example, circ-S-7 has 74 conserved binding sites that can attach to the targeted miRNA. Meanwhile, it can also interact with miRNAs by attaching to argonaute proteins. Circ-S-7 expression is significantly higher in OC tissues and cells, indicating an association with the lymph node metastasis status, tumor node metastasis (TNM) classification of malignant tumor stages, and overall survivorship rates in patients with OC. Its silencing inhibited the growth and metastasis of OC cells [Circ-NOLC1 is another circRNA that is more highly expressed in EOC tissues than in normal tissues and is positively related to the FIGO-defined stage. Its overexpression in cell lines is proven to increase cell growth, migration and invasion. It plays an oncogenic role by attacking to ESPR1 and RhoA, and by modulating CDK1 levels .The next circRNA with diagnostic potential in EOC patient serum and tissues is circ-0049116, which is generated from a cell surface-associated protein named mucin 16. Increased expression of the circ-MUC16/miR-199a-5p axis positively correlates with the degree of tumorigenesis in EOC patients . The expOf all the circRNAs known to be involved in EOC, circ-ABCB10 is associated with the worst overall survival rate (OS). According to the in vitro experiments done by Chen et al., circ-ABCB10 showed negative regulation of miR-203, miR-1271 and miR-1252 in EOC cells as well as an association with increased cell proliferation and decreased apoptosis rate. Thus, circ-ABCB10 expression is associated with weak differentiation, progressive FIGO stages, and large tumor size. This is known to be due to its guiding of the mir1271-mediated Capn4/Wnt/β-catenin signaling pathway , 84.Circ-0072995 increases malignancy through its influence on the miR-147a/CDK6 axis. Circ-EEF2 and circ-RAB11FIP1 facilitate autophagy by sponging mir-6881-3p and miR-129 in EOC –82. AnotSome CircRNAs have potential as biomarkers because their abnormal regulation is associated with pathological and clinical outcomes in OC patients. In 2020, Wang et al. conducted a comprehensive study using the serum of patients with OC instead of tissue samples. Using bioinformatics analyses of data and studying miRNA-binding sites, they identified 5 important upregulated circRNAs: circ-0002711; Chr5:170610175-170632616+; circ-0001756; Chr4:147227078-147230127-; and Chr16:53,175091-53191453+. They all showed an association with dysregulation in OC and were considered potential diagnostic biomarkers .Numerous studies have shown that circ-0015756, circ-0002711, hsa-circ-0015326, circ-0001068, circ-0025033 and circ-KIF4A are oncogenic circRNAs with diagnostic and prognostic value in OC –94. TheiCirc-0004390, which is derived from LPAR3 gene, is significantly upregulated in OC cells and tissues. Its knockdown can markedly reduce OC cell proliferation. By sponging miR-198, circ-0004390 increases cell proliferation to regulate the expression of hepatocyte growth factor receptor in OC cells. Xu et al. expressed that the level of circ-0004390 was closely related to the overall survivor level in patients with OC and found that it regulates OC proliferation via miR-198. The axis provides an important target in therapy .One of the most valid and effective treatments for patients with cancer is chemotherapy. However, the chemical resistance resulting from the constant use of this method has gradually become a concern. In recent years, circRNAs have been considered significant targets and markers for the prognosis, diagnosis and treatment of many diseases, especially cancer . In 2012Three other studies affirmed a high expression of circRNAs in PTX-resistant cells and tissues in OC patients –102. TheThe findings of Li et al. provide novel information for overcoming chemotherapy resistance in OC. They confirmed the inhibitory mechanism of miR-211-5p against drug resistance in PTX-resistant OC cells. However, circ-NRIP1 hinders this action by sponging miR-211-5p and decreasing its expression. Simultaneously, HOXC8 expression increases and leas tumorigenesis .As mentioned above, EOC is the most significant pathological subtype of OC, accounting for more than 90% of cases. Amongst the subtypes of EOC, SOC (high-grade serous ovarian cancer) accounts for 60–70% . Some evThere is a group of circRNAs that play inhibitory roles in OC tumorigenesis and thus have tumor-suppressive effects. Cancer cells have the ability to avoid anti-growth signals via suppression of the expression of tumor suppressor genes. The anti-growth signals are key through arresting of the cell cycle. These circRNAs, like oncogenic ones, sponge miRNA to manage the malignancy of OC cells. CDR1as may be the best example of a tumor-suppressive circRNA , 109. ItCirc-BNC2, circ-EXOC6B, circ-FAM13B, circ-N4BP2L2, circ-RHOBTB3, circ-CELSR1, circ-ITCH and circ1656 are involved in EOC in a tumor-suppressive capacity. They could also potentially act as novel diagnostic biomarkers –112. CirIt has been shown that the expression of Circ-ITCH decreases in EOC cell lines in comparison to normal ones and is associated with tumor size, decreasing FIGO stage, and inhibition of cell proliferation . HoweverUsing RT-qPCR, Yalan et al. established that circ-RHOBTB3 downregulation induces OC formation with the inactivation of the PI3K/AKT signaling pathway . AnotherCirc-ANKRD12 locates in the cytoplasm and is a potential clinical biomarker. It is involved in various functions, including invasion, cell cycle arrest, cancer metabolism alteration, and immune system modulation . The expLike other tumor suppressor circRNAs, circ-0078607 downregulation leads to OC formation. Zhang et al. indicated that inducing Fas expression via oncogenic miR-518a-5p suppresses OC. This circRNA is suggested as a new effective therapeutic target in OC treatment . Circ-00Circ-MTO1/miR-182-5p/KLF15 also inhibits OC progression . Circ-10In recent years, broad research on circRNA biogenesis has been conducted. At first, it was believed that circRNAs were just a transcriptional derangement from the RNA splicing process, but further study has fully authenticated their strictly regulated biosynthesis. However, that biogenesis is not yet fully elucidated, leaving more space for research. It is currently known that circRNAs are single-stranded, looped RNA molecules that are generated from pre-mRNAs via a back-splicing process expressed under particular situations. They principally reside in the cytoplasm where they have various functions associated with binding to other molecules such as proteins and miRNAs .Mounting evidence shows that circRNAs are dysregulated in cancerous tissues and can intercede in diverse signaling pathways, resulting in tumorigenesis, invasion and metastasis . ImpairmOne of the most important needs in medical science is to have methods for the early detection and non-invasive treatment of cancer. CircRNAs have attracted considerable attention. Thanks to the rapid development in the fields of biotechnology and bioinformatics data analysis, a large number of these RNAs have been identified in different organisms. Due to their unusual expression and their effect on cancer cell growth, proliferation, apoptosis and metastasis, they can be an appropriate option for use as diagnostic biomarkers and therapeutic targets , 133. ToAlthough sponging miRNAs is a substantial function of circRNAs, many do not have binding sites for miRNAs. Therefore, there may be other means of action besides sponging miRNAs. More studies are needed to elucidate the relationships and pathways relevant for miRNAs, circRNAs and proteins.Many recent studies into circRNAs and their role in tumor resistance to chemotherapy indicate the involvement of regulatory pathway mechanisms, such as EMT processing, apoptosis, ceRNA regulation and autophagy . AlthougAll the descriptions in this paper form just a small part of the capabilities and potential of these unique molecules in the prognosis and diagnosis of OC. Further comprehensive studies are needed to decipher the numerous aspects of circRNA behavior and use them in future clinical procedures.Additional file 1. PRISMA Checklist


Background: Recent emerging evidence has highlighted the potential critical role of cerebrospinal fluid (CSF) in cerebral waste clearance and immunomodulation. It is already very well-established that the central nervous system (CNS) is completely submerged in CSF on a macro-level; but to what extent is this true on a micro-level? Specifically, within the peri-neural and peri-vascular spaces within the CNS parenchyma. Therefore, the objective of this study was to use magnetic resonance imaging (MRI) to simultaneously map the presence of CSF within all peri-neural  and peri-vascular spaces in vivo in humans. Four MRI protocols each with five participants were used to image the CSF in the brain and spinal cord. Our findings indicated that all CNS neuro- and vascular-communication channels are surrounded with CSF. In other words, all peri-neural spaces surrounding the cranial and spinal nerves as well as all peri-vascular spaces surrounding MRI-visible vasculature were filled with CSF. These findings suggest that anatomically, substance exchange between the brain parenchyma and outside tissues including lymphatic ones can only occur through CSF pathways and/or vascular pathways, warranting further investigation into its implications in cerebral waste clearance and immunity. The critical involvement of cerebrospinal fluid (CSF) in metabolic cerebral waste clearance (CWC) has gained a lot of momentum lately. Our traditional understanding of CSF circulation is that it is produced by the choroid plexus and circulates through the ventricles and subarachnoid spaces, exiting directly into the dural venous sinuses via arachnoid granulations/villi –5. RecenIn light of the importance of CSF physiology, researchers have focused their attention on investigating CWC CSF outflow pathways, out of the central nervous system (CNS). The traditional outflow pathway via the arachnoid granulations/villi is becoming increasingly unpopular due to the lack of physiological evidence to support it , 21. Thiin vivo imaging methods. Therefore, the objective of this study was to use magnetic resonance imaging (MRI) to simultaneously map the presence of CSF within all peri-neural  and peri-vascular spaces in vivo in humans.Although our understanding of CSF physiology remains relatively rudimentary and is still very much under investigation, one concept has become increasingly apparent: all CNS neuro- and vascular-communication channels are surrounded with CSF. It is already very well-established that the CNS is completely submerged in CSF on a macro-level; but now we know that this is true even on a micro-level, specifically within the peri-neural and peri-vascular spaces within the CNS parenchyma. Most studies have asynchronously investigated these spaces and these investigations have been mainly conducted in animals and human cadavers. Moreover, although CSF-filled peri-vascular spaces in several brain regions have been illustrated in several studies, to our knowledge, there is no systematic study focusing on whether all cerebral vasculature (with the exception of capillaries) are surrounded with CSF, and this can only be revealed using To prove the concept, we designed four types of experiments each with five healthy participants . Each protocol was tailored to a specific area of investigation and anatomical structures, such as cranial nerves and their corresponding perineural spaces, cerebral vasculature and their corresponding perivascular spaces, and different segments of the spinal cord. The study was approved by local Institutional Review Board. Written consent was obtained prior to each MRI experiment. Various sequences were used to image CSF in the brain and spinal cord at 3T .Sampling Perfection with Application optimized Contrasts using different flip angle Evolution” (T2W-SPACE) sequence to image the CSF and cranial nerves with hyperintense CSF signal and hypointense signal for cranial nerves and blood vessels , as well as the diameter ratio of the cranial nerve diameter over the total diameter , for all 12 cranial nerves in healthy humans (The first experiment employed a 3D T2-weighted (T2W) “ vessels . This sey humans , 2.STrategically Acquired Gradient Echo” (STAGE) imaging to simultaneously obtain bright-blood and dark-blood images  and bright-blood (T1W) which were used to visualize the blood vessels and perivascular spaces in the order of 100 μm. In addition, to acquire a pure CSF image with suppressed blood signals, we used a 3D turbo-spin echo (TSE) sequence with TR/TE = 2,000/345 ms and an isotropic voxel size of 0.5 mm. With such a long echo time, the images were heavily T2-weighted such that all tissues other than CSF (very long T2) were suppressed. Given the long TR/TE and high-resolution 3D sampling scheme, the sequence took half an hour covering the central half of the brain in the sagittal plane.For the second experiment, in order to image CSF in peri-vascular spaces and to demonstrate that all MRI-visible cerebral blood vessels were surrounded by CSF, we used high-resolution “d images –41. The * weighted spoiled gradient echo sequence  was used to acquire images with hyperintense CSF and blood vessels, and hypointense nerves. This sequence is one of the clinical sequences for cervical protocol. Imaging parameters were: TR = 587 ms, TE = 17 ms, flip angle = 30°, in-plane resolution = 0.5 × 0.5 mm2, slice thickness = 3 mm, scanning time = 3 min.The third experiment was performed on the cervical spinal cord at the C4/C5 level. A 2D T22, slice thickness = 4 mm, scanning time = 2 min. This sequence, with sub-millimeter in-plane resolution, provided high nerve-to-CSF contrast. The 12 pairs of cranial nerves and spinal nerves were labeled by experienced neuroradiologist on images from the first, third and fourth experiments.The fourth and final experiment was for imaging the lumbar spinal nerves at L3/L4 level. A regular T2W-TSE sequence was used with the following imaging parameters: TR = 5,490 ms, TE = 87 ms, in-plane resolution = 0.6 × 0.6 mmAll MRI data were first visually evaluated to label nerves and vessels on representative images. Representative images of the first experiment are shown in The CNS neuro-communication channels consist of 12 pairs of cranial nerves and 31 pairs of spinal nerves. Images from the first experiment were used to visualize all 12 pairs of the cranial nerves , 2. As iThe spinal nerves were visualized on the images from the third and fourth experiments . SimilarThe high-resolution (in the order of 100 μm) sT2W . Once agin vivo in humans; as opposed to previous studies that have asynchronously investigated this, mainly in animals and human cadavers. Our findings indicate that all brain parenchyma and spinal cord communication channels, both neuro- and vascular-communication channels, are encased in CSF. The diameter ratios, nerve diameter over total diameter , ranged from 0.6–0.8. It logically follows that CSF must play a critical role in substance exchange between the brain parenchyma/spinal cord and its communication channels as well as its surrounding environment/tissue—a role that has been historically underestimated and understudied. Our findings are consistent with previous literature that have asynchronously investigated CSF-filled peri-neural spaces, mostly in the context of CWC lymphatic-associated CSF outflow pathways, as well as peri-vascular spaces , in the peri-neural spaces. Therefore, CSF must play a critical role in regulating the communication between the cranial nerves and their surroundings. One such type of communication regulation is with the lymphatic system. In fact, the interaction of CSF with the lymphatic system is only beginning to be understood. There is a growing body of evidence to suggest that CSF tracer eventually makes it into the deep cervical lymph nodes , 36, 37.Our findings also drive home the point that all MRI-visible vasculature is surrounded with CSF-filled peri-vascular spaces. Therefore, CSF must play a critical role in regulating the communication between the blood and the brain parenchyma, as well as CWC at large. In 1985, Rennels et al. introduced the idea of a fluid circulation system throughout the CNS via peri-vascular spaces . But it Starting 6 years ago, gadolinium-based contrast agent (GCA) residual deposition in the brain parenchyma with chronic administration has been documented , 62. GCAin vivo in humans. Third, our study utilized MRI which is minimally invasive and therefore caused minimal disruption to the biological system. In the past, most MRI studies of the peri-neural and peri-vascular spaces have been mainly conducted in animals , all MRI-visible vasculature and spinal nerves. Second, our study was performed  animals , 68.On the other hand, the major limitation of our study is that we did not investigate the underlying mechanisms of how CSF made it into or out of these peri-vascular and peri-neural spaces. Although this has been a topic-of-interest as of late, and several strides have been made to address this topic, the latest of which has been the establishment of the glymphatic pathway, the CSF efflux mechanisms remain unclear. One current question of interest is: “What is the underlying pathway/mechanism by which CSF drains into the meningeal lymphatics, and how is this pathway/mechanism related to CSF-filled peri-vascular and peri-neural spaces?” Another major limitation is that we did not investigate if and how CSF communicates with the CNS neuro- and vascular-communication channels themselves , nor a quantitative morphometric measurement of the arterial and venous blood vessels and their corresponding peri-vascular spaces. There is growing evidence to suggest that CSF in peri-vascular spaces might be involved in the direct transport of cerebral waste into the parenchymal vasculature, perhaps through transcellular mechanisms , 69, 70.In conclusion, our findings indicate that all CNS neuro- and vascular-communication channels are surrounded with CSF. In other words, all peri-neural spaces surrounding the cranial and spinal nerves as well as all peri-vascular spaces surrounding MRI-visible vasculature were filled with CSF. These findings highlight the extent to which CSF infiltrates the parenchyma and its importance, therefore, warranting further investigation into its potential implications.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 Wayne State University Institutional Review Board. The patients/participants provided their written informed consent to participate in this study.LF participated in conceptualization, data acquisition, data analysis, manuscript writing, and manuscript editing. YC participated in conceptualization, investigation, data acquisition, data analysis, manuscript writing, and manuscript editing. SX participated in data acquisition, data analysis, and manuscript editing. EH participated in methodology, data analysis, and manuscript editing. JH participated in conceptualization, methodology, data analysis, and manuscript editing. QJ participated in conceptualization, methodology, data analysis, and manuscript editing. 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.


Our results also strongly indicate that individual use of HA or rhEGF slightly decreased the inflammation and restored the destructive joint structure, but was not as drastic as seen in the HA/Me-rhEGF. Moreover, HA/Me-rhEGF profoundly reduced cartilage destruction and proteoglycan loss and downregulated matrix metalloproteinase expressions. These findings reveal that the treatment of HA/Me-rhEGF could be more beneficial than the use of single HA or rhEGF in reliving osteoarthritis and demonstrate the therapeutic application of microencapsulation technology in difficult joint disorders. In essence, we believe that the Me-rhEGF could be promising for further research and development as a clinical treatment against osteoarthritis.Osteoarthritis, a highly age-related and chronic inflammatory disorder with cartilage loss, causes patients difficultly in movement; there is no efficient and sustainable remedy for osteoarthritis currently. Although hyaluronic acid (HA) and platelet-rich plasma (PRP) have been used to alleviate osteoarthritis, the effects could be short and multiple injections might be required. To address this issue, we exploited the property of chitosan to encapsulate recombinant human epidermal growth factor and obtained microencapsulated rhEGF (Me-rhEGF). In the current study, we induced the osteoarthritis-like symptoms with monosodium iodoacetate (MIA) in rats and investigated the therapeutic effects of Me-rhEGF. Following administration of HA/Me-rhEGF  Osteoarthritis (OA) is a chronic, inflammatory, and degenerative joint disease, resulting in progressive cartilage damage. OA ultimately leads to cartilage loss, osteophyte formation (bone spurs), and bone thickening which in turn results in remodeling of affected joints. OA is more likely associated with patients that are elderly or obese. Estimably, there could be as high as 10–20% of people aged over 65 afflicted by OA .In response to the lack of effective treatment, new remedies have been investigated for administration to OA patients, such as hyaluronic acid (HA). In 1997, the US Food and Drug Administration approved the use of HA by intra-articular injection to treat OA patients . HA is oβ (TGF-β), insulin-like growth factor-1 (IGF-1), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and hepatocyte growth factor (HGF) in addition to various cytokines, chemokines, and coagulation factors . De. Deβ andIn conclusion, OA is a chronic inflammatory disease that is difficult to be completely treated. However, our study provides insight and promising results for the prompt delivery of HA/Me-rhEGF. Our novel therapeutic approach ensures a steady and consistent release of rhEGF coordinating with HA to ameliorate the symptoms of MIA-induced OA in rats. That is evidenced by significantly reduced inflammatory cytokines and mediators. Overall, chitosan-microencapsulated rhEGF exhibited higher stability in preservation and provided better anti-inflammatory effect than nonencapsulated rhEGF. As a result, we believe that this HA/Me-rhEGF has promising potential as an OA treatment in the clinical field.


Introduction: Previous research delivers strong indications that inflammatory activation leads to treatment resistance in a subgroup of patients with Major Depressive Disorder (MDD). Thus, tailored interventions are needed. The present study aimed to find potential biomarkers that may enable patients to be stratified according to immune activation.Methods: A phase IIa randomized placebo-controlled trial was performed to assess levels of inflammatory compounds in responders/remitters and non-responders/non-remitters to sertraline plus celecoxib (n = 20) and sertraline plus placebo (n = 23). Levels of macrophage migration inhibitory factor, neopterin, and tumor necrosis factor alpha were determined by enzyme-linked immunosorbent assay; response and remission were measured by reduction of the Montgomery Åsberg Depression Rating Scale score.Results: Both treatment groups showed a significant decline in depression symptoms, but no difference was found between groups. A clear pattern emerged only for macrophage migration inhibitory factor: placebo remitters showed significantly lower baseline levels than non-remitters (a similar trend was seen in responders and non-responders) while celecoxib responders showed a trend for higher baseline levels than non-responders.Conclusion: Small subsample sizes are a notable limitation, wherefore results are preliminary. However, the present study provides novel insights by suggesting macrophage migration inhibitory factor as a promising biomarker for treatment choice.https://www.clinicaltrialsregister.eu/ctr-search/trial/2009-011990-34/DE, EudraCT-No.: 2009-011990-34.The trial was registered in EU Clinical Trials Register (EU-CTR):  In clinical practice, patients' response to antidepressant treatment often remains unsatisfactory. Around 20% up to 50% of depressed patients show non-response to at least two standard antidepressant drug trials , 2. Furt2 (PGE2), which acts as a stimulator of indoleamine-2,3-dioxygenase  score oSerum levels of MIF, neopterin, and TNFα were assessed at baseline and endpoint (week 6). Blood was drawn in fasting condition. All parameters were determined by enzyme-linked immunosorbent assay (ELISA) with standard curve by using the quantitative sandwich enzyme immunoassay technique  and competitive enzyme immunoassay technique (neopterin), according to the instruction of the kit manufacturer  and analyzed using MARS data analysis software . BMI was calculated as body weight (in kg) divided by the square of body height (in m). Depression severity was assessed by trained raters at baseline and endpoint (6 weeks) with the MADRS , 51. ResAll patients who were taking antidepressant medication prior to the study underwent a 3-day wash-out period before the start of trial treatment. In case of premedication with long half-life, a longer period since the last treatment was necessary to be included see . If needt-test for continuous data that met the criteria for parametric testing , or linear regression. To compare levels of inflammatory compounds between subgroups, Mann-Whitney-U-test for independent samples and Wilcoxon signed-rank test for dependent samples were used if data did not meet assumptions for parametric testing and/or small subsamples were tested. The significance level was set at 5% (two-sided) for all tests. As analyses were exploratory and subsamples were small, adjustment for multiple testing and correction for possible confounding variables were neglected in the primary analyses. Hence, the data reported here are preliminary. Due to statistical power limitations, trends are also reported (p < 0.10). The flow chart is given in SPSS software (IBM SPSS Statistics 25) was for statistical analyses used. The trial data presented here were planned as secondary per-protocol analyses. In this report, the primary outcomes were response and remission independently of inflammatory status and cytokine serum levels according to the response and remission status. Secondary analyses, investigated the role of BMI, age, sex, and smoking status. Endpoint parameter values were subtracted from baseline parameter values to reflect the change of values over time. Therefore, positive values represent a decrease and negative values represent an increase of levels over time. Descriptive analyses are given as mean and standard deviation or median and interquartile range for continuous variables, and as frequencies (percentages) for categorical variables. Testing for significances was performed using Chi-square test for categorical data , Student's 2 = 0.62; p = 0.43) or remission rates  between the two treatment groups. Both treatment groups showed a significant decline of MADRS scores over time . In responders, the MADRS score decreased slightly more in the celecoxib group than in the placebo group, although the difference was not significant . In non-responders, the MADRS score decreased slightly more in the placebo group than in the celecoxib group, but this difference was also not significant .Z = −1.86; p = 0.06), but no differences of MIF change between placebo responders and non-responders were found. However, the celecoxib group showed a trend for differential change of MIF levels over time: Remitters showed a decrease while non-remitters showed an increase . Furthermore, the change in MIF levels was significantly different in non-responders and non-remitters to celecoxib (increase) compared with non-responders and non-remitters to placebo .Regarding the change of MIF levels over time, in the placebo group non-responders showed a trend for a decrease to endpoint .No significant differences in neopterin levels emerged at baseline and endpoint between responders and non-responders as well as remitters and non-remitters in either treatment arm see , C.2. InZ = −1.86; p = 0.06). In contrast, celecoxib non-responders showed a decrease of TNFα levels over time . In the celecoxib group, responders showed differential course over time (increase) compared with non-responders . In non-responders, celecoxib-treated patients showed a decrease of TNF α levels over time whereas placebo-treated patients showed an increase .No significances emerged for TNFα levels at baseline. At endpoint, only lower levels were found in placebo responders compared with placebo non-responders. For further details, see The most interesting and relevant results were obtained for MIF. Therefore, possible confounders were further investigated.Rho = 0.23; p = 0.16). We found no difference in the change of BMI over time according to treatment  or response/ remission status across treatments  occurred. However, in the placebo group a decrease in BMI over time significantly predicted a lower response (% MADRS score reduction) .No significant correlation was found between BMI and MIF baseline levels  at baseline. No difference emerged in age according to response/ remission status  across treatments. However, higher age significantly predicted a lower response (% MADRS score reduction) in the placebo group .We found a significant positive correlation between age and MIF levels  at baseline than women. Response/remission status were independent from sex . Response status was also statistically independent from sex in the placebo and celecoxib subgroups . However, in the celecoxib group men showed a numerically lower reduction in MADRS score than women. Regarding changes in biomarker level over time, women as compared to men showed a significantly different course of MIF levels . This difference emerged only in the placebo group  and was seen in responders as a trend .Men had significantly higher MIF levels . Furthermore, response/remission status were independent from smoking status . Response status was also independent from smoking status in the placebo and celecoxib subgroups .No significant differences in baseline MIF levels emerged between smokers and non-smokers  = 2.82; p = 0.07]. For remission, a significant model was obtained . Similarly, the model predicting MIF levels at endpoint was significant . In the celecoxib group, a trend emerged for the prediction of MIF levels at baseline by response status, age, and sex . Data on the individual predictors are given in R2 but partly lacking significance of single predictors, collinearity diagnostics were performed. No indication for multicollinearity was present in any of the models. Thus, this effect may result from the collective impact of more or less nearly significant predictors.Because MIF levels were associated with age and sex, we performed preliminary regression analyses with age and sex as covariates to further investigate the predictive capability of response status on the expression of MIF levels. In the placebo group, a trend emerged for predicting of MIF levels at baseline by response status, age, and sex [Overall, no difference in response or remission rates between the two treatment arms were found. One reason for this result might be that celecoxib add-on to sertraline is not superior to sertraline plus placebo. In contrast to our findings, a meta-analysis of previous trials found a superior effect of add-on celecoxib to standard antidepressant treatment over add-on placebo without taking inflammatory status into account , 54. NotOur study goes beyond the current state of knowledge by looking into response status in subgroups. A dependency of inflammatory biomarker levels and response/remission to different treatment becomes apparent, at baseline and during the course of treatment. However, a clear pattern was only observed for MIF, which is consistent with previous literature. Non-responders to sertraline plus placebo showed a trend for higher baseline levels as compared with sertraline responders. This was especially and significantly evident in non-remitters compared with remitters pointing to the well-known treatment resistance to standard serotonergic agents when pro-inflammatory levels are increased . Vice veRegarding relevant patient characteristics, MIF levels were found to be related to age and sex but not to BMI. In the placebo group, weight loss and higher age were associated with treatment resistance. Since age was positively associated with both, MIF levels and treatment failure, the concept of immunosenscence presents a suitable explanation. Immunosenscence describes the changes of the immune system which, among others, is characterized by low-grade inflammation and all of which increase during aging . It is tAs for neopterin, baseline levels did not discriminate between responders/remitters and non-responders/non-remitters to either treatment. Previous research found that higher neopterin levels were associated with depression and the number of depressive episodes , 60 indiThe involvement of the kynurenine pathway in MDD pathophysiology has been receiving growing attention. In fact, pro-inflammatory cytokines such as IFNγ, TNFα, IL-1, and the hormone PGE2, which is stimulated by MIF via COX-2-upregulation, stimulate the activity of the enzyme IDO and consequently the breakdown of tryptophan into potentially neurotoxic kynurenine metabolites , 65–68. p-value should be treated as a strict cut-off, and many scientists favor a non-categorical use today . The patients/participants provided their written informed consent to participate in this study.MS has prepared the data and conducted the analysis, evaluation, and interpretation of the present work, as well has drafted the present manuscript. BB and GA-H have conducted data acquisition. EW has contributed to planning the study and conducted data acquistion. PZ has conducted the laboratory analyses. RM has contributed to the interpretation of data. HD has contributed to design and planning the study and data interpretation. NM has contributed to design and planning the study, data acquisition, and evaluation. BB, EW, GA-H, PZ, RM, HD, and NM have critically reviewed and revized the content. All authors contributed to the manuscript and approved submission.This present work was funded by the EU 7th Framework program (grant number EU-FP7-CP-IP-2008-222963/EU-FP7-PEOPLE-2009-IAPP-MarieCurie-286334) and Horizon 2020 (grant number H2020-SC1-2016-2017/H2020-SC1-2017-Two-Stage-RTD). Further, part of this work was supported by the foundation Immunität und Seele. The funders had no role in the study design, data collection and analysis, or decision to publish.RM declares personal fees from Otsuka/Lundbeck outside the submitted work. HD is the coordinator of the project funded by the EU. The remaining 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.


Background: Diffuse leptomeningeal glioneuronal tumor (DL-GNT) is a new entity described in the 2016 World Health Organization (WHO) classification of brain tumors. While DL-GNT is predominantly an indolent tumor that affects young boys, high-grade DL-GNT is unusual and seldom reported in children.Case Presentation: In this report, we describe the challenges and pitfalls associated with diagnosing this high-grade variant in a tuberculosis-endemic region. We highlight the importance of identifying non-typical imaging findings, i.e., non-enhancing cystic lesions with high T2 signal along the leptomeningeal surface, that may expedite the diagnosis of this condition. Histopathologic correlations with MR spectroscopy findings are also discussed.Conclusion: We provide the first clinical imaging report of utilizing MR spectroscopy to distinguish DL-GNT from tuberculosis with histopathologic correlation. Diffuse leptomeningeal glioneuronal tumor (DL-GNT) is a new entity described in the 2016 World Health Organization (WHO) classification of brain tumors . On the The diagnosis of DL-GNT is challenging, as patients present with non-specific symptoms of raised intracranial pressure and focal neurology. Additionally, cerebrospinal fluid analysis is often misleading with patients having elevated protein and normal glucose levels, which is compatible with tuberculous meningitis. The difficult task of distinguishing this tumor from a granulomatous process is further compounded when DL-GNT presents in regions where tuberculosis (TB) is endemic.A characteristic imaging finding of DL-GNT is diffuse enhancing nodular thickening of the meninges at the basal cisterns . Cystic In this report, we describe the clinical presentation, laboratory results, imaging characteristics, and histopathologic findings of DL-GNT in a patient from a TB-endemic region.A 5-year-old boy initially presented with headache, right eye pain, and vomiting, to a rural district hospital in the State of Sabah, East Malaysia on Borneo island. The boy also experienced difficulty in walking, blurring of vision, and fluctuating consciousness 1 month before admission. There was a significant (but unquantified) loss of weight and anorexia. He completed his bacille Calmette-Guerin (BCG) vaccination but missed all scheduled shots after his first birthday because of poor family support. On examination, a Glasgow Coma Scale (GCS) of 9 was documented (E2V2M5) with left lateral strabismus. The pupils were unequal (4 mm/3 mm) and sluggish. Power in all four limbs was 4/5  with normal reflexes. Babinski was downgoing, and Kernig's sign was not elicited.The boy was transferred to our center for further evaluation and treatment. Non-contrast CT brain showed acute hydrocephalus with cerebral edema. Subsequently, an external ventricular drain was inserted. Intra-operatively, the opening pressure was high, and outflowing cerebrospinal fluid (CSF) was clear and colorless.streptococcus Group B, haemophilus influenzae, streptococcus pneumoniae, neisseria meningitidis, and escherichia coli. Both gastric lavage for acid fast bacilli stain and gastric lavage for GeneXpert were negative.Magnetic resonance imaging of the brain revealed diffuse enhancing nodular leptomeningeal thickening, especially at the basal cisterns . No intrprobable TB  criteria, this child was classified as bable TB . A standThe boy's condition improved considerably after 14 days, and he was well enough to undergo a comprehensive ophthalmology examination. He had a visual acuity of 1/60 in the right eye, and there was no light perception in the left eye. A positive right afferent pupillary defect was detected. Ophthalmoscopy showed normal macula bilaterally.Both his parents were screened and found to be negative for TB. He was discharged well after a 4-week hospital stay.via the Burr hole just prior to the shunt revision.One month later, he presented again with vomiting, unsteady gait, and anorexia. The follow-up MR brain study revealed exuberant nodular leptomeningeal enhancement that was more extensive than the initial study . Also, tHistopathological examination (HPE) revealed a moderately cellular neoplastic proliferation with background desmoplastic and myxoid changes seen from the hematoxylin and eosin (H&E) stain slides . The celA family conference was held to counsel the parents on possible treatment options. The parents decided to opt for palliative treatment. The patient succumbed to the illness 3 months later, 22 weeks in total, after diagnosis.probable TB given the clinical symptoms, imaging findings, and other supporting laboratory investigation results , a molecule that is usually not present in high-grade tumors . Also, tHistologically, three criteria need to be met to diagnose DL-GNT: (1) glial cell proliferation without extension into the brain parenchyma, (2) absence of intra-axial lesions, and 3) demonstrable leptomeningeal encapsulation. In our case, leptomeningeal encapsulation could not be demonstrated, as the biopsy did not include tumoral tissue from the periphery. Nevertheless, the patient was diagnosed with DL-GNT, because the lesion was essentially within the leptomeningeal region with no primary brain parenchymal lesion. Furthermore, the positive immunohistochemistry S100 and synaptophysin staining are specific for DL-GNT .The datasets presented in this article are not readily available because they contain identifiable protected health information. Requests to access the datasets should be directed to Yong Guang Teh  was funded by Universiti Malaysia Sabah.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.


To investigate the feasibility of a fast liver magnetic resonance imaging (MRI) protocol for lesion detection in adults using 3.0-T MRI.A fast liver MRI exam protocol was proposed. The protocol included motion-resistant coronal T2-w sequence, axial T2-w fast spin echo sequence with fat suppression, axial in-op phase gradient recalled echo (GRE) T1, axial diffusion weighted imaging (DWI), and axial contrast-enhanced T1 sequences. To evaluate the diagnostic capacity of the proposed protocol, 31 consecutive patients  underwent a liver MRI exam with conventional sequences, including the proposed protocol as a subset. Images from the conventional protocol and extracted abbreviated protocol were independently read, and the diagnostic concordance rate was assessed for each patient. The concordance analysis is presented as the proportion of concordant cases between the two protocols.The net measurement time of the fast liver MRI protocol without adjustment and waiting time were 4 min and 28 s. In the 31 patients included in this study, 139 suspicious findings were found from both the conventional liver MR protocol and the fast liver MRI protocol. The diagnostic concordance rate was 96.4%.The fast liver MRI protocol is feasible at 3.0-T, with a shorter exam time and high diagnostic concordance compared to the conventional liver MRI workflow. Magnetic resonance imaging (MRI) is a well-established liver imaging modality in clinical practice, with the advantages of higher soft-tissue contrast and a lack of ionizing radiation exposure –4. By muHowever, MRI has several constraints including a higher cost, longer scanning time, and a higher demand for patient cooperation . Due to With the improvement of both hardware and software, the speed of MRI and the simplicity of operation have significantly improved within the past decades. Various parallel imaging techniques, including sensitivity encoding (SENSE), array spatial sensitivity encoding technique (ASSET), generalized auto-calibrating partially parallel acquisitions (GRAPPA), and controlled aliasing in parallel imaging results in higher acceleration (CAIPIRINHA) were proposed , 6. ThesThis study was approved by the institutional review board, and written informed consent was obtained from each enrolled patient. Thirty-one patients  were consecutively enrolled between August 2017 and September 2017. The clinical characteristics of all the 31 patients are summarized and presented in MRI exams were performed on a 3.0-T scanner  with a phased-array 18-channel body coil. For MRI examinations of the 31 patients, conventional liver MRI protocol was used in the study, and the detailed acquisition parameters of MRI sequences are summarized in 2; and three-phase  contrast-enhanced T1-weighted FS VIBE. The proposed fast liver MRI protocol, which was extracted from conventional protocol, included the following core sequences: localizer with three orthogonal orientations in one breath-hold; coronal T2-weighted half-Fourier single shot turbo-spin echo (HASTE) in one breath-hold; axial T2-weighted fat-saturated (FS) rotating blade-like k-space covering (BLADE) with respiratory triggering; T1-weighted volumetric interpolated breath-hold examination (VIBE) with two echoes and water-fat Dixon reconstruction in one breath-hold, acting in two roles, including the in-and-opposed phase T1-weighted, and pre-contrast T1-weighted fat-saturated scan (Dixon water image); Echo-planar-imaging (EPI) diffusion-weighted sequence with b = 1000 s/mmThe diagnostic concordance between the abbreviated protocol used in the fast liver workflow and the conventional protocol was evaluated using the following steps:In step 1, the images from the whole conventional liver MRI scans were sent to the picture archiving and communication system (PACS) system and read using routine clinical procedure, i.e., a randomly assigned radiologist read the images and made a diagnostic report for each case. Another senior radiologist was randomly assigned to verify the report. In the study, liver reporting & data system (LI-RADS) assessment system 2017) was used for assigning suspicion categories of liver lesions  measurement might be a valuable diagnostic tool for the characterization of focal liver lesions (FLLs)  , 15, oths (FLLs) –22. In ts (FLLs) –26.The high diagnostic concordance rate of the abbreviated protocol used in the fast liver MRI workflow revealed that the abbreviated protocol could provide enough diagnostic information for most of the abdominal lesions. Besides shortening the exam time, the use of the abbreviated protocol could also increase the patient’s comfort, because fewer breath-holds were needed. Moreover, as four redundant image sets were excluded , fewer images had to be read. Thus, the time spent on image reading for radiologists could be reduced, and the throughput of the diagnosis work could be improved.Some limitations of our study should be noted. First, due to the lack of a biopsy or surgical pathology as a gold standard to assess the diagnostic efficiency, we only evaluated the diagnostic concordance between the abbreviated protocol used in the fast liver MRI workflow and the conventional MRI protocol. Second, radiologists who read the two group images in the diagnostic concordance step were randomly assigned according to daily schedule, which might have caused additional discordance due to the readers’ different experience or knowledge. Although we conducted two levels of the concordance analysis to minimize human error, unwanted discordance might have still existed. Third, our study was carried out in a single institution with a small sample size, resulting in the heterogeneity of the patient population and the absence of a separate analysis of patients with diffuse liver disease such as cirrhosis. Further study should be performed to demonstrate the efficiency of the fast protocol with larger sample size.The results show that the proposed fast liver MRI protocol is feasible in clinical practice at 3.0-T. This modality could serve to accelerate abdominal MRI in daily clinical practice, without significantly impacting diagnostic value.The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding authors.The studies involving human participants were reviewed and approved by Changhai Hospital Ethics committee. The patients/participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.The conception and design of the study: CM, JL, and CF. Acquisition of data: JL, YC, XW, and QY. Analysis and interpretation of data: JL, CF, JPL, XW, and BK. Drafting the article: CM and JL. Final approval of the version to be submitted: JL, CM, YC, CF, BK, XW, and JPL. All authors contributed to the article and approved the submitted version.This work was supported by the Key junior college of national clinical of China; National Natural Science Foundation of China (81601468); Project of precision medical transformation application of SMMU (2017JZ42); Science and Technology Innovation Foundation of Shanghai (17411952200).Author CF was employed by the company Siemens Shenzhen Magnetic Resonance Ltd. Author BK was employed by the company Siemens Healthcare.The remaining 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.