Hyperspectral imaging (HSI) provides rich spectral information for improved histopathological cancer detection. However, acquiring high-resolution HSI data for whole-slide imaging (WSI) can be time-consuming and requires a huge amount of storage space.WSI using a color camera can be achieved with fast speed, high image resolution, and excellent image quality due to the established techniques. We aim to develop an RGB-guided unsupervised hyperspectral super-resolution reconstruction method that is hypothesized to improve image quality while maintaining the spectral characteristics.High-resolution hyperspectral images of 32 histologic slides were obtained via automated WSI. High-resolution RGB histology images were registered to the hyperspectral images for RGB guidance. An unsupervised super-resolution network was trained to take the downsampled low-resolution hyperspectral patches (LR-HSI) and high-resolution RGB patches (HR-RGB) as inputs to reconstruct high-resolution hyperspectral patches (HR-HSI). Then, an Inception-based network was trained with the HR-RGB, original HR-HSI, and generated HR-HSI, respectively, for whole-slide histopathological cancer detection.Our super-resolution reconstruction network generated high-resolution hyperspectral images with well-maintained spectral characteristics and improved image quality. Image classification using the original hyperspectral data outperformed RGB because of the extra spectral information. The generated hyperspectral image patches further improved the results.The proposed method potentially reduces image acquisition time, saves storage space without compromising image quality, and improves the image classification performance. First, the size of a hyperspectral image file is large. For example, one hyperspectral image with a dimension of 3600 pixels × 2048 pixels × 150 bands saved in single precision requires about 4 GB of storage space. A whole-slide hyperspectral image acquired at a low magnification easily exceeds 100 GB. In some applications such as hematology, high magnification is necessary, which may put an extreme burden on data storage devices. Current limitations on data storage makes it difficult to establish a comprehensive hyperspectral microscopic dataset, which is essential for a thorough study of deep learning methods. Second, the acquisition of hyperspectral images can be time-consuming. Most hyperspectral microscopy studies used push-broom or spectral-scanning systems to obtain a sufficient spectral and spatial resolution. The scanning process of each image can take several seconds, which greatly increases the acquisition time of a whole-slide image. Even though a snapshot hyperspectral camera speeds up the acquisition, its intrinsic low spatial resolution would not meet the requirement of some applications in which fine structures in the slides need to be seen. Third, it is more difficult to implement autofocusing with a hyperspectral camera than a color camera. During the scanning of the histological slides, the change of slide thickness can result in unfocused images, and cellular components from different layers can become blurry. State-of-the-art microscopes and whole-slide scanners are integrated with autofocusing and extended focal imaging (EFI) algorithms to solve these problems; they are based on the acquisition of a stack of RGB images along the –,Hyperspectral image super-resolution reconstruction,–,,Since many microscopes and whole-slide scanners can have more than one camera that share the same field of view (FOV), applying the super-resolution reconstruction technique for hyperspectral microscopy and WSI is feasible. Considering the easy acquisition and wide utilization of high-quality RGB histology images, we propose using high-resolution RGB images to guide the super-resolution reconstruction of high-resolution hyperspectral images. Dey et al.Ideally, the super-resolution reconstruction of hyperspectral microscopic images should take full advantage of the superb image quality of digital histology images while maintaining the spectral features that are critical for image classification. Therefore, in this work, we develop a simple yet effective unsupervised super-resolution reconstruction network that fuses the spatial information from the high-resolution RGB images and the spectral information from the low-resolution hyperspectral images. With the proposed method, it is possible to save the acquisition time and storage space for hyperspectral images, as well as compensate for the low quality of some bands in the hyperspectral images, thus promoting the application of HSI for WSI and automatic histopathological cancer detection.22.1,In this work, we utilized 32 H&E-stained histologic slides from 16 patients with head and neck SCC.,,For the acquisition of hyperspectral images, we used the hyperspectral microscopic imaging system that has been reported in our previous works2.2Before the scanning of each slide, a white reference hyperspectral image was obtained at a blank area on the slide, and a dark current image was acquired automatically by the camera with the camera shutter closed. Afterward, each raw hyperspectral image was calibrated with the white reference and dark current images to obtain the transmittance of the tissue: For each calibrated hyperspectral image, we synthesized an RGB image using a customized HSI-to-RGB transformationIn this study, we first used a small portion of the entire dataset to train, validate, and test our proposed super-resolution reconstruction network. To make sure that the network is able to deal with the staining variation and thickness variation of different slides, which can cause the change of spectral signatures, we selected two images with minimal blank areas for each slide and used them as the “super-resolution dataset” instead of using lots of images from only one patient. In total, 22,053 patches from 64 images of 16 patients were selected, with 17,022 patches from 48 images of 12 patients used for training, 2166 patches from four images of two patients (#3 and #14) used for validation, and 2865 patches from four images of the rest two patients (#5 and #15) used for testing. Then, after the super-resolution reconstruction network was trained, high-resolution hyperspectral image patches were generated for all data using downsampled hyperspectral patches with RGB guidance, and an Inception-based CNN was trained for whole-slide image classification using (1) high-resolution RGB histology image patches, (2) original high-resolution hyperspectral image patches, and (3) generated high-resolution hyperspectral image patches, respectively. The data partition for three types of data was exactly the same. In total 181,711 images patches from 10 patients were used for training, 46,564 image patches from three patients  were used for validation, and 52,059 image patches from another three patients  were used for testing. The data that were previously used as the “super-resolution dataset” were not excluded for the image classification network to generate a classification probability map of the whole slide. Nevertheless, those data took only a small portion  of the two panchromatic images was calculated and used as the spatial loss, as Eq. (2) shows. The spectral loss calculates the MSE between the generated and input LR-HSI, as shown in Eq. (3). The loss weights of the loss functions were 0.5 and 0.5: The unsupervised super-resolution reconstruction network was implemented using Keras on a Titan XP NVIDIA GPU with 12 GB memory. We used the Adam optimizer2.4To evaluate the usefulness of our proposed super-resolution reconstruction network for image classification, we used the HR-RGB, original HR-HSI, and generated HR-HSI to train, validate, and test an Inception-based 2D CNN and compared the classification results. Specifically, reconstructed HR-HSI were generated for all image patches using the downsampled LR-HSI and the previously trained The CNN was implemented using Keras2.5To evaluate the performance of our super-resolution reconstruction network, we calculated different metrics based on the entire hypercube , grayscale image , and spectral signatures . We first used the MATLAB implementations of peak signal-to-noise-ratio (PSNR) and mean absolute error (MAE) to quantify the super-resolution reconstruction quality. PSNR measures the global intensity difference between generated HR-HSI and original HR-HSI and is calculated by averaging the PSNR value in a band-by-band basis across all 87 bands, with one band :Then, we used structural similarity index measure (SSIM)For the evaluation of whole-slide image classification, we use the area under the receiver operating characteristic (ROC) curve (AUC), as well as accuracy, sensitivity, and specificity as metrics. Accuracy is the ratio of all correctly labeled image patches to the total number of image patches. Sensitivity and specificity are determined by true positive (TP), true negative (TN), false positive (FP), and false negative (FN), where positive is cancerous and negative is normal. Sensitivity measures the percentage of correctly labeled cancerous image patches among all cancerous patches, and specificity measures how well normal image patches are detected: 3Our proposed unsupervised super-resolution reconstruction network fuses the spatial information from the high-resolution digital histology images and the spectral information from the low-resolution hyperspectral images and generates high-quality, high-resolution hyperspectral images. The reconstruction time for each To further validate the effectiveness of our proposed super-resolution reconstruction network, we acquired hyperspectral images of the same region on a histologic slide using four objective lenses with different magnifications, namely In addition to the abovementioned evaluation metrics, we implemented image classification using the original HR-HSI and generated HR-HSI to further prove the usefulness of our proposed super-resolution reconstruction network. The validation and testing results using three types of data are shown in Although the hyperspectral camera was focused by our manual adjustment, which might be subjective and dependent on the operators, it was able to acquire hyperspectral images with a very decent image quality. Regardless of the noise in a few wavelength bands and some partially unfocused images, which would have slightly compromised the spatial characters, the original high-resolution hyperspectral image patches still outperformed RGB because of the extra spectral information, with 0.93 AUC, 0.87 accuracy, 0.89 sensitivity, and 0.87 specificity in validation data, as well as 0.87 AUC, 0.82 accuracy, 0.85 sensitivity, and 0.73 specificity in the testing group. As for the generated HR-HSI, the unsupervised super-resolution reconstruction network fused the spatial components from the RGB images and the spectral information from the hyperspectral images, resulted in an improved image quality in the generated HR-HSI. One significant improvement was the removal of noise, which greatly increased the efficacy of the first and last several bands. In addition, the out-of-focus images, which were caused by the uneven thickness of slides and had fuzzy nuclei edges or blurry fiber structures, also regained sharpness. Due to the improved image quality, using generated HR-HSI made the classification performance even better.4In this work, we developed an unsupervised CNN based on a modified U-Net architecture for hyperspectral super-resolution reconstruction with the guidance of high-quality RGB digital histology images. The network fuses the spatial information from the high-resolution RGB images and the spectral information from the low-resolution hyperspectral images to generate high-resolution hyperspectral images. The generated hyperspectral images from all five super-resolution reconstruction networks with different spatial enhancement scales  for the super-resolution reconstruction network and left the remainder for the whole-slide image classification network. It is possible that, with more training data, our super-resolution reconstruction network could perform even better for spectral signature reconstructions. As for the whole-slide image classification network, 32 entire slides may not be sufficient due to the anatomical variations of SCC and the significantly increased number of features in the hyperspectral data. In addition, the tissues in all slides were either tumor or normal, which made it slightly easier to get decent image classification results. In the future, we will investigate whole-slide cancer detection in tumor-normal margin slides and see if the generated HR-HSI is able to significantly improve the outcome.Another shortcoming in this work is that we used the simulated low-resolution hyperspectral data to train the super-resolution reconstruction network, instead of acquiring a large number of hyperspectral images with a physically lower resolution as training data. It is possible that the differences between the real low-resolution hyperspectral images and simulated ones may affect the network outcome. But acquiring images with different optical resolutions and registering the high-resolution RGB images to the low-resolution hyperspectral images potentially introduces misalignment and thus minor errors during the network training. On the other hand, the way that we simulated the LR-HSI for training data (downsampling with “box” kernel) was the same as how the network output the generated LR-HSI, which could have reduced some bias. In addition, we tested the network trained with simulated LR-HSI on real LR-HSI to validate the performance of the proposed method. The results indicate that, even though the network was trained with simulated low-resolution data, it also worked well with images with actual lower resolutions. In the future, we will further investigate this by acquiring more images with physically different resolutions.With HSI getting more attention in the medical imaging field, the conflict among the acquisition speed, data storage, and resolution of hyperspectral images must be solved to apply this technology in real clinical settings. Our proposed method makes it possible to generate high-quality hyperspectral images for automatic histopathological analysis with a low-resolution HSI camera and low-magnification objective lens, hence greatly reducing the acquisition time and the file size of hyperspectral histologic images. For instance, with a In the future, we plan to develop an automatic whole-slide scanning HSI microscope with a low-resolution hyperspectral camera  and the proposed super-resolution reconstruction network built into the system. By synchronizing the color camera and the hyperspectral camera, the system will be able to acquire both data simultaneously. With the mature autofocusing and image enhancement techniques of color cameras as well as our proposed method, the image quality of both the RGB and hyperspectral images will be secured. We may be able to establish a comprehensive database of whole-slide hyperspectral histologic images, which is extremely beneficial for a thorough investigation of pathological features in hyperspectral images as well as various deep learning algorithms. In addition, the super-resolution reconstruction network and whole-slide image classification network may be combined into a single and straightforward workflow in which high-resolution hyperspectral images can be generated along with the acquisition of low-resolution hyperspectral images and high-resolution RGB images and directly fed into the image classification network, so that histopathological diagnosis can be achieved during the scanning of the slides.In conclusion, our deep learning-based hyperspectral image super-resolution reconstruction method can bring high-resolution spatial features and rich spectral information to improve pathological diagnosis, while increasing the image acquisition speed and reducing data storage requirement, which will provide wide applications in digital and computational pathology.


The coexistence of self-harm and aggression, which is referred to as dual-harm, is commonly seen in forensic population. Self-harm and aggression have often been studied separately, previous studies on risk factors of aggression or self-harm mainly focused on childhood adversities, emotional regulation, impulsivity and psychopathology, given their importance in the two behaviors. However, the factors associated with dual-harm remain unclear. This study aimed to explore potential risk factors associated with co-occurring self-harm among individuals with serious aggressive behaviors.This multi-center, cross-sectional case-control study was conducted from May 2013 to January 2016 and involved seven qualified forensic institutes located in seven provinces in China. Participants were individuals with serious aggressive behaviors and were suspected to have mental disorders. Lifetime history of self-harm was obtained by a self-report questionnaire, and serious aggressive behaviors were assessed with the use of participants’ forensic archive. Sociodemographic and clinical information were collected using a self-designed standardized data collection form, and childhood adversities was assessed using a clinician-rated scale designed by our research team. The Psychopathy Checklist-Revised (PCL-R) was used to assess psychopathic traits and the Brief Psychiatric Rating Scale (BPRS) was used to assess psychiatric symptoms of the participants. Univariate and multivariate logistic regression analyses were performed to analyze the relevant factors for dual-harm.A total of 423 individuals with serious aggressive behaviors were enrolled in the current study. Of them, 74 (17.5%) with self-harm history assigned into the dual-harm group (D-H) and 349 (82.5%) without self-harm history assigned into the aggression-only group (A-O). According to the binary logistic regression analysis, current diagnosis of mood disorder , child abuse , parental death , and the score of the affective subscale in BPRS  were significantly associated with dual-harm.Our study suggested the necessity of integrated evaluation of self-harm among individuals with serious aggressive behaviors. Childhood adversities and psychiatric symptoms in this population require special attention.The online version contains supplementary material available at 10.1186/s12888-022-04027-6. Mounting evidence suggested that some individuals engage in both self-harm and aggression during their lifetime –3. The cIndividuals engaging in dual-harm are over-represented in forensic and clinical population , 8, desp. Of note, previous studies have mainly focused on substance-related disorders due to their high incidence in forensic population [To date, risk factors of dual-harm still remained unclear. Efforts have been put into the investigations on associated factors for dual-harm in the last decade, with special attention to childhood adversities (CAs). Some studies, by distinguishing dual harmers from those who were engaged only in self-harm or aggression towards others, found that childhood adversities might be an independent risk factor for dual-harm , 11. Howpulation . Howeverpulation , it is aThe relationship between personality and self-harm or aggression has been well-established, while its relationship with dual-harm still remains unclear. A previous study revealed that dual harmers were more likely to exhibit personality traits related to emotional and interpersonal liability . PsychopThe concept of dual-harm was proposed in the last few years, and our knowledge about it remains limited. As psychiatric assessments are not routinely performed in individuals with serious aggressive behaviors due to the separation of mental health and justice systems, our knowledge is even more limited about the factors for dual-harm in individuals with serious aggressive behaviors. Based on existing empirical studies, we hypothesized that dual-harm individuals might be impacted by different factors, as compared to those who were engaged in aggression towards self or others only; and the factors for dual-harm might include childhood adversities, history of mental disorders, substance abuse, psychiatric symptoms, and psychopathy. In this case-control study, we aimed to identify associated factors for dual-harm among individuals with serious aggressive behaviors.This study is a multi-center, cross-sectional case-control study started in May 2013 and ended in January 2016. Data were obtained from seven qualified forensic institutes located in seven different provinces in China. Targeted participants were individuals with serious aggressive behaviors and were suspected to have mental disorders. In China, individuals who are engaged in serious aggressive behaviors and suspected to have a mental disorder are required to undergo a forensic psychiatric assessment in order to ascertain their mental status. More details about forensic psychiatric assessment in China can be found in previous literature . The incDual-harm was defined as the co-occurrence of self-harm and aggression during an individual’s lifetime. In this study, we defined self-harm as any self-directed injurious behavior with suicidal intent but not resulting in death . Aggression in this study was defined as any serious aggressive behaviors towards others , including homicide, assault, robbery, arson, and sexual offences.The case group included individuals with both serious aggressive behaviors and a self-harm history, and the control group included individuals with serious aggressive behaviors but without a self-harm history.Lifetime history of self-harm was obtained using a self-report questionnaire, which included questions such as “Have you ever made a suicide attempt, for example, cutting yourself or overdosing on drugs?” Serious aggressive behaviors were ascertained from the participants’ forensic archives in this study. In China, prior to a forensic assessment, the law enforcement agency needs to provide comprehensive relevant information, including demographic information, criminal files  and medical records of the individuals engaging in serious aggressive behaviors . These mDemographic and clinical information was obtained using a standardized data collection form. The demographic information included gender, age, employment status, marital status, place of residence and education levels, and the clinical information included history of mental disorders, family history of mental disorders, history of head trauma, history of alcohol and non-alcohol substance abuse, previous aggression behaviors, and lifetime treatment for mental disorders; all the above data were also obtained from the participants’ forensic archives. For analysis, the participants’ education levels were categorized into college and above (years of education > 12), middle/high school (years of education ranged 6–12), and primary school and below (illiterate or years of education < 6).Each participant was evaluated by at least two senior psychiatrists with the use of the International Classification of Diseases 10 (ICD − 10) . DiagnosA clinician-rated scale was used to assess the participants’ childhood adversities. This scale was designed by our research team based on previous studies of violence risks associated with the circumstances in China. This scale is used to assess the adversities before the age of 15 years, including child abuse, parental abandonment, parental death, parental separation, parental psychiatric disorder, parental criminal behaviors and parental alcohol/non-alcohol substance abuse. Information regarding childhood adversities was obtained from participants by asking questions such as “During the first 15 years of your life, have you ever been abused by your parents?” and “Have you lost any of your parents because he/she died?” The total number of childhood adversities that the participant had experienced were recorded and used in subsequent statistical analyses.The Chinese version of Psychopathy Checklist-Revised (PCL-R) was used to assess psychopathic personality traits in this study . The 20-The 20-item Chinese version of Brief Psychiatric Rating Scale (BPRS) was used to assess psychiatric symptoms in the participants . The BPRp < 0.05 in the univariate analysis were selected for the multivariable analysis. All analyses were two-sided, and p < 0.05 were considered as statistically significant. All data were analyzed using the SPSS software .Categorical variables were presented as number (percentage), and continuous variables were presented as mean ± standard deviation. The missing numerical and categorical values were imputed with median values and modal values, respectively. Categorical variables were analyzed using Chi-square test, and Fisher’s exact test was applied as appropriate. The one-sample Kolmogorov-Smirnov test was used to assess the normality of continuous data. Normally distributed data were analyzed using two-simple t-test and non-normally distributed data were analyzed using the Mann-Whitney U test. Binary logistic regression analysis was performed to investigate the association between dual-harm and other factors, with all the categorical variables set as dummy variables. Before the logistic analysis, we conducted Harman single-factor test to check the common method bias and collinearity statistics for all selected factors. The univariate analysis was first performed to screen potential associated factors, and then the forward stepwise (Likelihood Ratio method) procedures were used to identify independent associated factors for dual-harm. With the type of harm  set as the dependent variable, the factors with The patient recruitment process is presented in Fig. x2 = 4. 79, p = 0.046), and no significant differences were found in other demographic factors, as shown in Table p < 0.05). There was no significant difference in other clinical characteristics between the two groups. Among the seven indicators of CAs (see Method), the most prevalent childhood adverse events overall were child abuse (9.5%) and parental separation (9.0%). The D-H group exhibited a higher level of exposure to child abuse and parental death during their childhood, as compared to the A-O group . No significant inter-group difference was found in the other indicators and the total number of CAs (Table A significant difference was found in gender distribution between the two groups (p = 0.02), as well as a higher score of the affective subscale in BPRS   participants diagnosed with mental disorders, with the most common diagnoses being schizophrenia spectrum disorders, followed by mood disorders and substance-related disorders. The proportion of participants diagnosed with mood disorders and substance-related disorders was higher in the D-H group than in the A-O group (20.3 and 12.2% vs 6.3 and 7.7%), and the proportion of participants diagnosed with schizophrenia spectrum disorders and other mental disorders were lower in the D-H group than in the A-O group (48.6 and 4.1% vs 57.6 and 11.7%). Compared to those in the A-O group, participants in the D-H group had a higher score of the anti-social subscale , which was less than the critical value 40%), indicated no serious common method bias in the present study. Results of collinearity statistics showed that the VIF of candidate predictors ranged from 1.025 to 1.883, indicating no collinearity. In the final regression model, current diagnoses of mood disorders , child abuse , parental death , and the score of the affective subscale in BPRS  were independently associated with increased risk of dual-harm in individuals with serious aggressive behaviors. The Hosmer-Lemeshow test values were reported at χ2 = 6.70, 0%, indicTo our knowledge, this is the first study to investigate the independent factors for dual-harm among individuals with serious aggressive behaviors in China. In the present study, we used a case-control study design and found that current diagnoses of mood disorders, child abuse, parental death and the score of the affective subscale in BPRS were significantly associated with dual-harm among individuals with serious aggressive behaviors.Childhood adversities may contribute to the development of many maladaptive behaviors, including aggression, self-harm, and violence , 32. OurThe relationship between mental disorders and dual-harm has not been adequately studied. Our study found that dual harmers were more likely to be diagnosed with mood disorders compared to those who only engaged in aggression towards others, which was in consistent with the previous findings. Harford et al. reported that dual-harm was more strongly associated with mood disorders . FurtherAnother finding in the present study was that the dual-harm group scored higher on the affective subscale in BPRS than the aggression-only group, and this difference persisted after accounting for known risk factors. Few studies have focused on psychiatric symptoms in dual harmers, and only one study reported that individuals with dual-harm ideation had higher scores related to depression than those who had aggression ideation only . This reSome researchers proposed that a personality characterized by a predisposition to engage in harmful behaviors might be shaped by biological factors interacting with adverse early environments ; they emDespite the strength of our study, some limitations should also be noted. First, participants in our study were individuals with serious aggressive behaviors and underwent forensic psychiatric assessments, thus, the extrapolation of our findings to other populations needs further validation. Second, the definition of self-harm in this study was limited to suicide attempt, whereas aggression was limited to serious aggressive behaviors ; the relatively narrow scope of the definitions might have led to underestimation of the rate of dual-harm in the selected population. Third, another limitation of the present study is that we did not explore factors of dual-harm in males and females separately due to the relatively small number of females, thus, gender might still be a confounding factor. Fourth, an important methodological limitation is that we did not use a validated scale for CAs assessment, which may impact on the generalizability of our findings. Fifth, a self-reported scale was used to obtain self-harm information from the participants, which might lead to memory biases. Sixth, as this is a cross-sectional study, the causal relationship could not be established. Seventh, comorbidities of mental disorders were not taken into account, as only the principal diagnosis was recorded in some patient files. Eighth, due to the retrospective nature of data collection, some potentially important factors, such as emotional regulation, impulsivity, neuroticism, childhood neglect, peer, community, and collective violence, could not be included in this study. These factors need to be considered in future studies.Although some factors for dual-harm have been identified, this phenomenon has not been fully understood. In the present study, we investigated several factors known to be associated with dual-harm, such as childhood adversities, substance abuse, and history of mental disorders, and explored some potentially associated factors, such as psychopathology and psychopathy. We found that substance abuse among individuals with serious aggressive behaviors in China are different, to some extent, from those observed in other countries. Our findings suggested that a comprehensive assessment and detailed evaluation of self-harm is needed for individuals with serious aggressive behaviors, which calls for the collaborative effort of justice systems and the mental health sector. The identified risk factors suggest that effective strategies for the prevention of dual-harm among individuals with serious aggressive behaviors should include the strengthening of mental health services for this population and early intervention for children who have adverse experiences. In the future, a longitudinal design should be considered to examine the causal relationship between those variables. Future studies are also needed to explore the risk factors of dual-harm in different countries and under different jurisdictions.Additional file 1.Additional file 2.


Environmental exposure to benzene and toluene is a suspected risk factor for metabolic disorders among the general adult population. However, the effects of benzene and toluene on blood lipid profiles remain unclear. In this study, we investigated the association between urinary blood lipid profiles and metabolites of benzene and toluene in Korean adults.We analyzed the data of 3,423 adults from the Korean National Environmental Health Survey Cycle 3 (2015–2017). We used urinary trans,trans-muconic acid (ttMA) as a biomarker of benzene exposure, and urinary benzylmercapturic acid (BMA) as an indicator of toluene exposure. Multivariate logistic regression analyses were performed to explore the association between blood lipid profiles and urinary metabolites of benzene and toluene. Additionally, we examined the linear relationship and urinary metabolites of benzene and toluene between lipoprotein ratios using multivariate regression analyses.After adjusting for covariates, the fourth quartile (Q4) of ttMA [odds ratio (OR) ] and Q3 of BMA [OR (95% CI) = 1.579 ] were associated with an increased risk of hypertriglyceridemia. However, the Q4 of urinary ttMA [OR (95% CI) = 0.654 ] and Q3 of urinary BMA [OR (95% CI) = 0.619 ] decreased the risk of a high level of low-density lipoprotein cholesterol (LDL-C). Higher urinary ttMA levels were positively associated with the ratio of triglycerides to high-density lipoproteins . Higher urinary metabolite levels were negatively associated with the ratio of low-density lipoprotein to high-density lipoprotein .Benzene and toluene metabolites were significantly and positively associated with hypertriglyceridemia. However, urinary ttMA and BMA levels were negatively associated with high LDL-C levels. These findings suggest that environmental exposure to benzene and toluene disrupts lipid metabolism in humans.The online version contains supplementary material available at 10.1186/s12889-022-14319-x. Benzene and toluene are pollutants present in the atmosphere , 2. IndiThe adverse health effects of benzene and toluene on humans have been well-documented over the past few decades. Benzene was designated as ‘group 1, carcinogenic to humans’ by the International Agency for Research on Cancer , and canSeveral epidemiological studies have demonstrated a relationship between environmental exposure to benzene and metabolic diseases –15. In aThe main aim of this study was to investigate the association between blood lipid levels and urinary ttMA and BMA levels in Korean adults. Additionally, we determined whether environmental exposure to benzene and toluene affected insulin resistance and the risk of cardiovascular disease (CVD). In this study, we used urinary ttMA as an indicator of benzene exposure, and urinary BMA as an indicator of toluene exposure. Urinary ttMA is a useful biomarker for evaluating environmental exposure to benzene at concentrations below 0.1 , 17. UriThis study used cross-sectional data from the Korean National Environmental Health Survey (KoNEHS) Cycle 3 (2015–2017). This nationwide survey provides basic information for monitoring human exposure to environmental chemicals and investigating influential factors. The KoNEHS includes information from interviews, self-report questionnaires, physical examinations, and collection of biological samples. The KoNEHS uses a complex survey design stratified by residential houses, coastal regions, age, sex, and socioeconomic status. The survey was approved by the Institutional Review Board (IRB) of the National Institute of Environmental Research (NIER), Korea (IRB No. NIER-2016-Br-003-01).A total of 3,787 participants  aged ≥ 19 years were enrolled in the survey. Among them, we excluded 11 participants with missing data on the urinary metabolites of benzene or toluene, 41 with missing data on lipid profiles, and 312 taking dyslipidemia medications. Finally, 3,423 participants  were included in the analysis. The ethics review for this analysis was conducted by the IRB of Kyung Hee University Hospital (IRB No. KHUH 2021-08-002). The IRB waived the requirement for informed consent because the study was retrospective.Serum lipid profiles were collected and analyzed according to the KoNEHS guidelines . Total cWe calculated the TG to HDL-C (TG/HDL-C) ratio and LDL-C to HDL-C (LDL-C/HDL-C) ratio. The TG/HDL-C ratio was associated with insulin resistance and helpful in estimating the risk of DM in clinical practice –28. The Urine samples were collected from sterile cups and transferred to light-blocked storage containers. The container was then transferred to the laboratory in a refrigerated state (2–6 °C) . Urine sR2) of the curves was 0.995 or higher  increase in TG/HDL-C ratio Table . In contIn this study, we observed a relationship between lipid profiles and urinary metabolites of benzene and toluene in Korean adults. Urinary ttMA and BMA levels were associated with an increased risk of hypertriglyceridemia. In contrast, both urinary ttMA and BMA levels were found to be negatively correlated with serum LDL-C levels. Regarding the relationship between lipoprotein ratio and urinary ttMA and BMA, urinary ttMA was positively associated with the TG/HDL ratio, and both metabolites were inversely related to the LDL-C/HDL-C ratio.Urinary ttMA was positively associated with serum TG levels and negatively associated with serum LDL-C levels. These findings on the associations between urinary ttMA and blood lipid levels are different from those of previous animal studies , 32. MicThe effects of benzene exposure on blood lipid profiles can be explained by molecular biological mechanisms. A metabolomic study in humans reported that metabolic pathways, including carnitine shuttle, fatty acid metabolism, glycolysis, and gluconeogenesis were increased in workers exposed to benzene . BenzeneThe relationship between TG/HDL-C ratio, an indicator of insulin resistance, and urinary ttMA levels revealed in this study is in line with previous researches –15. An aInsulin resistance and hypertriglyceridemia have been studied in depth, and a complicated relationship has been identified. White adipose tissue releases free fatty acids (FFA) into the blood when the body is insulin-resistant, and skeletal muscle cells and the liver obtain increased amounts of FFA , 48. ExcTherefore, LDL-C/HDL-C is a well-known risk indicator of CVD and the progression of atherosclerosis , 52, 53.To our knowledge, this is the first study to explore the association between lipid profiles and exposure to benzene and toluene in a general population. The potential lipid metabolism-disrupting effects of benzene and toluene are supported by the mechanisms revealed in animal experiments. However, this study has several limitations. First, as this was a cross-sectional study, the findings can only be used to indicate associations and not to assess causal relationships. Second, the lifestyle behaviors and medical history of the participants were investigated through interviews and questionnaires. Self-reporting may lead to recall bias and incorrect classification . Third, This cross-sectional study suggest that human lipid metabolism may be altered by exposure to benzene and toluene. The urinary metabolites of benzene and toluene are associated with an increased risk of hypertriglyceridemia. Additionally, TG/HDL-C levels increased in individuals with high urinary ttMA levels. The urinary metabolites of benzene and toluene were negatively associated with serum LDL-C levels. Further studies in other ethnic groups are required to verify these findings.Below is the link to the electronic supplementary material.Supplementary Material 1


Previous researches have not distinguished the between-person effects from the within-person effects when exploring the relationship between self-esteem, coping styles, and anxiety symptoms among adolescents. To address this gap, this study investigated reciprocal associations among self-esteem, coping styles, and anxiety symptoms in a three-wave longitudinal panel survey, using an analytical strategy that disaggregates the within-person and the between-person variance.Data was drawn from the Longitudinal Study of Adolescents’ Mental and Behavioral Well-being Research study conducted in 10 public schools in the Guangdong province of China. All participants had a baseline visit  and follow-up interviews at 1-year intervals for 3 years. A random intercept cross-lagged panel model combined with mediation analysis was performed.At the within-person level, the following results were observed. (1) Low self-esteem and anxiety symptoms bidirectionally predicted each other. (2) Low self-esteem and negative coping style bidirectionally predicted each other. (3) Anxiety symptoms predicted subsequent negative coping style but not vice versa. At the between-person level, we obtained the following main results. (1) Significant predictive effects on the random intercept were found among all three study constructs. (2) There were sex differences regarding the association between self-esteem and anxiety symptoms and the correlation of females was stronger than that of males. (3) Self-esteem mediated the reciprocal relations between coping styles and anxiety symptoms.Overall, findings revealed a reciprocal relationship between low self-esteem and anxiety symptoms for both females and males. Besides, anxiety symptoms predict subsequent negative coping style but not vice versa. We also highlighted the mediating role of self-esteem in the reciprocal relations between coping styles and anxiety symptoms. Thus, interventions targeted at promoting self-esteem and cultivating positive coping style may help reduce adolescent anxiety.The online version contains supplementary material available at 10.1186/s13034-023-00564-4. Anxiety disorders are highly prevalent in children and adolescents, affecting approximately 117 million youth from 5 to 19 years around the world –4. It noIncreasing evidence suggests that self-esteem and coping styles may be risk factors for anxiety symptoms –9. HowevIn this study, RI-CPLM was used to determine the direction of within-person relationships between self-esteem, coping styles, and anxiety symptoms as well as the possible mechanisms between the three. Moreover, we further investigated the sex differences in these associations and tested whether these longitudinal associations remained after accounting for common risk factors.Self-esteem is defined as people’s subjective evaluation of their own worthiness as human beings . It has Despite studies investigating the relationship between self-esteem and anxiety symptoms have identified significant associations, there is little information indicating the reciprocal relations between them and giving inconsistent results. A 2-year longitudinal study of Dutch adolescents (aged 10–16 years) found that low self-esteem at baseline was predictive of relative increases in anxiety symptoms, but baseline anxiety symptoms were not associated with self-esteem at follow-up . HoweverAdolescence is a transitional period in which individuals strive to search for their own identity and to develop psychosocial competence, including strategies for coping . Coping Empirical studies have provided strong evidence supporting the relationship between self-esteem and coping styles among adolescents. On the one hand, research suggested that high levels of self-esteem as a psychological resource may help enhance individuals’ ability to cope with adversity and enable them to adopt positive coping strategies . LikewisOn the other hand, individuals who tend to use positive coping strategies are more likely to keep trying, seek support, and change the value system, so they experience positive emotions more often, including feelings of self-worth and self-confidence , 25. ThuThe potential association between coping styles and anxiety symptoms was supported in previous studies. Based on the stress-buffering model, engaging in positive coping style can buffer the negative emotion and alleviate psychosomatic symptoms . SeveralTaken together, as discussed above, there might be a bidirectional association among self-esteem, coping styles, and anxiety symptoms, respectively. In addition, there might be mediating effects between the three and the sex-specific differences in these associations might exist , 36, 37.This study was designed to evaluate the reciprocal within-person relations among self-esteem, coping styles, and anxiety symptoms over time. A three-wave RI-CLPM was employed among Chinese adolescents, making it possible to examine dynamic changes on both individual and intraindividual levels. Drawing upon previous literature, our hypotheses were as follows. (1) Low self-esteem bidirectionally and positively correlated with anxiety symptoms. (2) Low self-esteem bidirectionally and positively correlated with negative coping style. (3) Negative coping style bidirectionally and positively correlated with anxiety symptoms. Moreover, the mediating mechanisms between self-esteem, coping styles, and anxiety symptoms as well as sex differences among them were further investigated; however, no hypotheses were formulated, given the mixed and scarce findings of the existing literature.The data came from the Longitudinal Study of Adolescents’ Mental and Behavioral Well-being Research (LSAMBR), a 3-year longitudinal investigation (Registration No. ChiCTR1900022032). The LSAMBR recruited representative samples of adolescents from 69 classes of 10 public schools in Guangzhou, China. More detailed information on LSAMBR could be found elsewhere . The curStudents or their legal guardians were informed about the study details and were asked to sign an informed consent prior to the start of the study. Students were excluded if they refused to provide informed consent, were not attending school on the day of survey administration, or refused to take the survey. At each wave, an anonymous, self-administered questionnaire was designed to assess information on socio-demographic characteristics, self-esteem, coping styles, and anxiety symptoms. To avoid information bias, participants were asked to complete the self-administered questionnaires anonymously without the presence of teachers. The study received ethical approval from the Sun Yat-sen University, School of Public Health Institutional Review Board (Ethics Number: L2017060).The Chinese version of the10-item Rosenberg Self-Esteem Scale (RSES)  was usedThe Simplified Coping Style Questionnaire (SCSQ) is a 20-item self-report scale measuring individual coping styles in the context of Chinese culture, which was developed and revised by Xie  based onThe 7-item Generalized Anxiety Disorder Scale (GAD-7) was used to evaluate the severity of anxiety symptoms over the past 2 weeks. The participants grade the symptoms on a 4-point scale  . This scThe covariates were investigated at T1, including age, household socioeconomic status, living arrangement, relationships with classmates/teachers, ever smoking, and ever drinking. Household socioeconomic status was assessed by asking: “What is the financial status of your family?” . The living arrangements were measured by the question: “Who are you currently living with?” . Relationships with classmates/teachers were assessed by the question: “How would you describe your relations with your classmates/teachers?” . Ever smoking and drinking were measured by the following questions: “Have you ever smoked a whole cigarette?” and “Have you ever drunk beer, wine, or liquor?” .ICCs) indicates the proportion of within-person variance over the measurement waves. If there was substantial within-person variance , the RI-CLPM  = 140.033, p < 0.001; ΔCFI = 0.036, ΔRMSEA = 0.072). Next, we set the contemporaneous as well as cross-lagged paths to be equal across waves, and this nested model (Model 3) did not result in a decline in model fit , indicating that these path coefficients were equal across waves. Then, the models fixing the auto-regressive paths for self-esteem, coping styles, and anxiety symptoms (Model 4a–c) did not significantly degrade the fit compared with the freely estimated model . In the final model, autoregressive and cross-lagged parameters were equally constrained between adjacent waves (Model 5), which had a commensurate fit with the fully unconstrained model  exhibited good fit indices, so this model was therefore used to test the hypotheses. Table p < 0.001), indicating that low self-esteem was correlated with negative coping styles, and more severe anxiety symptoms, whereas positive coping increased, and the anxiety level decreased further.At the between-person level, the random intercepts of self-esteem, coping styles, and anxiety symptoms were significantly related to each other (p < 0.001). This indicated that within-person variations were significantly predicted by variations at the previous time point . As for the cross-lag effects, there were significant reciprocal within-person associations between self-esteem and coping styles over the three waves. That is, an increase in self-esteem in a given wave was associated with more positive coping style in the next wave . In turn, negative coping style at one-time point was related to decreases in self-esteem at the next time point . Besides, lower self-esteem in a given wave could predict anxiety symptoms in the next wave . Conversely, significant negative links from anxiety symptoms in a given wave to self-esteem were demonstrated in the next given wave . Moreover, all the paths from coping styles to anxiety symptoms were non-significant, but the paths of inverse association from anxiety symptoms to coping styles showed statistical significance from T1 to T3 . This result indicated that bidirectional within-person associations were not present between coping styles and anxiety symptoms.After separating the between-person stability, all autoregressive paths were significant , indicating a significant difference in the paths across sexes. Therefore, the unconstrained model was retained.To illustrate sex differences, a multi-group RI-CLPM was conducted. In one model, all the paths and covariances were constrained to be equal across sex , and the fit of this model was good . Another unconstrained model (model 7a) also exhibited excellent fit indices . Thus, the unconstrained model showed better fits than the constrained model  than in males . However, at the within-person level, there was no significant sex difference in the cross-lag paths , and vice versa .The results of the mediation analyses were depicted in Additional file In this study, we explored the longitudinal associations among self-esteem, coping styles, and anxiety symptoms by applying RI-CLPM  to the tThe results of RI-CLPM indicated that at the between-person level, there was a negative relationship between random intercepts of self-esteem and anxiety symptoms. These findings are supported by previous research suggesting that adolescents who reported lower levels of self-esteem tend to have a higher degree of severity of anxiety , 17, 54.The within-person variations in self-esteem exert a significant negative impact on the within-person variations of anxiety symptoms. Results from the current research further support the previous findings that low self-esteem has a significant relationship with an increased risk for anxiety symptoms in adolescents . MoreoveAt the between-person level, self-esteem is positively associated with coping styles. Adolescents with higher self-esteem are more likely to adopt the positive coping style in general, which corroborates with previous studies , 29, 56.This finding was consistent with the theory presented by Taylor and Brown , which sThere was a negative relationship between random intercepts of positive coping style and anxiety symptoms at the between-person level, which was supported by previous studies suggesting that adolescents who used more negative coping styles were more likely to have severe anxiety , 9, 35. On the other hand, our results reveal that change in coping styles may not lead to another change in anxiety symptoms at the within-person level. This is surprising, given that preliminary indications from the existing longitudinal studies that negative coping predicted increases in symptoms of anxiety , 62, 63.While all three constructs, including self-esteem, coping styles, and anxiety symptoms, are important during adolescence and inter-connected, the correlation among them has never been established. In the present study, coping styles did not act as a mediator between self-esteem and anxiety symptoms. However, the RI-CLPMs analysis demonstrated that self-esteem was a significant mediator in the reciprocal associations between coping styles and anxiety symptoms. To be more specific, alterations to coping styles predict the subsequent development of anxiety symptoms via changes in self-esteem and vice versa. Results of our study reveal that coping styles did not exert a direct effect on anxiety symptoms at the within-person level, but had an indirect effect on it through subsequent self-esteem, indicating that adolescents who applied negative coping style tend to report lower self-esteem and increased risk on the development of anxiety symptoms.These results confirm previous evidence of a positive relationship between negative coping style and low levels of self-esteem , 65. PriIn the present study, the RI-CLPM found no sex differences in any cross-lagged effects at the within-person level. That is, the association between the three study constructs was similar between the sexes at the within-person level, which showed the within-person invariance across waves. At the between-person level, we found a significant correlation between the random intercepts of each construct for both males and females, respectively. Interestingly, there was a stronger association between self-esteem and anxiety symptoms among females than in males, demonstrating that females who reported lower levels of self-esteem were more likely to report more severe anxiety symptoms, compared to their male peers. Jong et al. came to a similar conclusion that the relationship between low self-esteem and social anxiety was more evident in girls . AdolescThere were several major strengths of the present study. First, a longitudinal design using RI-CLPM was adopted to identify more precise predictive relations by accounting for time sequence as well as stability effects simultaneously. In this study, we explored how self-esteem, coping styles, and anxiety symptoms concurrently and longitudinally influenced each other over time at the within-person level. Compared with previous researches, our study design and methodology shed more light on this issue. Second, the RI-CLPMs employed in the present study differentiated within‐person from between‐person variance, which makes the results of this study more stable and reliable for within-person bidirectional relations. It will ultimately provide important practical implications for psychiatrists and policymakers working with adolescents. Specifically, between-person results determined which populations needed active intervention, and then within-person results shed light on the mechanisms by which self-esteem and coping styles contributed to anxiety, so as to provide better targets for intervention. Third, few studies have explored the direction of causal relationships among self-esteem, coping styles, and anxiety symptoms across waves among adolescents within the Asian cultural context. This study extends previous work in a unique Chinese context that finds more distributed mechanisms of stable personal characteristics  on anxiety, thus making a significant complement to existing literature.This study also presented with several limitations. First, due to data collection limitations, the status of anxiety symptoms was based on the respondents’ self-reports rather than clinical diagnoses, which though validated and widely used, may lead to a reporting bias. Second, all of our participants came from one city in southern China, which restricted the generalization of the results. Therefore, research that replicates our findings in different areas and cultural contexts would be meaningful to further validate our results. Third, though we have controlled for several important covariates, some unmeasured covariates   have notThis study contributes to addressing methodological challenges in previous literature by investigating the associations among self-esteem, coping styles, and anxiety symptoms across three waves using RI-CLPM. Overall, considering the between-person effects, both high self-esteem and positive coping style may have a significant negative effect on the random intercept of anxiety symptoms. At a within-person level, findings support that low self-esteem predicts anxiety symptoms and vice versa. Sex differences are found in this study, wherein the association between self-esteem and anxiety symptoms is stronger among females than in males. Moreover, anxiety symptoms predict subsequent negative coping style but not vice versa at a within-person level. Mediation analysis results indicate that the prospective associations between coping styles and anxiety symptoms are mediated by self-esteem. Therefore, adolescents who display a low level of self-esteem are in special need of attention, especially females. Prevention and intervention promoting the level of self-esteem and cultivating the positive coping style are likely to contribute to the reduction of anxiety symptoms.Additional file 1: Table S1. Baseline sample characteristics between follow-up and loss to follow-up participants. Table S2. The demographic characteristics of the study participants at baseline by sex. Table S3. Chi-square statistics for sex differences in specific paths of the selected models. Table S4. Significant indirect paths between self-esteem, coping styles, and anxiety symptoms for the RI-CLPM (Standardized Coefficients).


Non-precious metal-based materials play a vital role in both functional and structural materials related to various fields of practical application. Non-precious metal-based materials show many advantages, such as diversity, low cost, rich valence and abundant reserves, which thus have gained more attention in the field of electrocatalysts. However, the limited electroactive sites, sluggish reaction kinetics and poor electrochemical stability of these electrocatalysts greatly limit their extensive application. Therefore, there is an urgent need to develop new-type non-precious metal-based materials as high-performance electrocatalysts. As a typical non-precious material, magnesium alloy is the lightest structural metal, which meets the requirements for energy saving and emission reduction. Understanding the ignition mechanism of magnesium alloys during casting processes may greatly enhance the processability and applications. However, the relationship between design, fundamentals, and functionality involving non-precious metal-based materials is less covered in the literature. Therefore, this present Research Topic aims to bring together the work that links the relationship between advanced non-precious metal-based materials with fine functionality, mainly focusing on 1) innovative, high-performance and dedicated materials for energy storage devices, 2) highly efficient and stable electrocatalysts for energy conversion devices, and 3) development of structural metal materials with high ignition resistance and anti-corrosion characteristics.Wang et al. reported Cu-based multicomponent metallic compound materials M-Cu  on copper foam substrate by a facile corrosion method, which was used as an electrocatalytic material for water splitting. As we know thatcopper foam is a large surface area support for a wide range of applications. Furthermore, the unusual physicochemical properties along with the multivalence band features of Cu ions are important for increasing activity towards catalytic reactions. In this case, the introduction of the second ions can change the valence states of copper and oxygen elements, resulting in a change in the electronic structure of the materials, thus changing its catalytic activity. This research suggested the important possibility of effectively hybridizing a second metal with an appropriate transition metal support to fine-tune the electrocatalytic activity and improve the cost-effectiveness of water splitting. Li et al. investigated the effect of bimetal element doping on Mn-based catalysts for selective catalytic reduction of NOx with NH3. In the current work, a series of Zr and Co co-doped Mn-based oxides are developed by the coprecipitation method. The prepared Zr and Co co-doped Mn-based oxides exhibited greatly enhanced low-temperature denitrification performance, as well as good sulfur resistance and water resistance. Based on the analysis of various characterizations, the optimized Mn6Zr0.3Co0.7 catalyst showed the best performance, which mainly contributed to the large specific surface area and strong redox performance.Nowadays, numerous non-precious metal-based materials have been developed as electrocatalysts for water splitting. For instance, Chang et al. fabricated CeO2 with a fusiform structure by a combined microwave-ultrasonic approach. By changing the amount of H2O in the precursor system, the PVP micelle structures and resulting CeO2 surface coordination state were modified. The resulting CeO2 possessed high surface area and rich Ce3+ defects, which thus showed enhanced catalytic activity. The results confirmed that structural regulation and reaction mechanism are important for designing high-performance catalysts.In addition, the ingenious regulation of synthetic process parameters is an important means to regulate the microstructure and optimize performance. Considering the important role of imine as intermediates for biological, agricultural and pharmaceutical applications, it is important to explore high-performance catalysts for synthesizing imine. For example, Zhao et al. systemically studied the ignition behavior of magnesium alloy melts based on experiments and calculations. The underlying ignition mechanism was revealed and the corresponding ignition critical conditions were proposed. This work is helpful to the development of new ignition-proof technologies for magnesium alloy casting processes, and provides valuable instructions for the high flame-retardant design of magnesium alloys.Magnesium alloys are the lightest structural metals, which meet requirements for energy saving and emission reduction. However, the ignition of magnesium alloys during casting processes limits their processability and applications. In summary, this Research Topic discussed various non-precious metal-based materials for energy storage, energy conversion and structural applications, especially in understanding the relationship between design, fundamentals, and functionality. Owing to their key role in practical applications, engineering new high-performance non-precious metal-based materials is a vital research direction in the future.


However, there is a need for a scalable and reproducible pipeline that incorporates proper normalization between samples, correction of copy number variations, and integration of new downstream analysis tools. Here we present Containerized Bioinformatics workflow for Reproducible ChIP/ATAC-seq Analysis (CoBRA), a modularized computational workflow which quantifies ChIP-seq and ATAC-seq peak regions and performs unsupervised and supervised analyses. CoBRA provides a comprehensive state-of-the-art ChIP-seq and ATAC-seq analysis pipeline that can be used by scientists with limited computational experience. This enables researchers to gain rapid insight into protein–DNA interactions and chromatin accessibility through sample clustering, differential peak calling, motif enrichment, comparison of sites to a reference database, and pathway analysis. CoBRA is publicly available online at  A). However, analysis pipelines currently available lack useful components necessary for such analyses. For example, there is a need for better normalization between samples, adjusting copy number variations (CNVs), applying newly developed downstream annotation tools such as Cistrome DB Toolkit Chromatin immunoprecipitation sequencing (ChIP-seq) and the Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq) have become essential components of epigenetic analysis, which are employed extensively in the study of protein–DNA interactions and chromatin accessibility, respectively. ChIP-seq is a high‐throughput technology that provides unique insights into protein function by mapping genome-wide binding sites of DNA-associated proteins. ATAC-seq is a high-throughput technology that is imperative in the assessment of genome-wide chromatin accessibility. While numerous pipelines for analyzing ChIP‐seq and ATAC-seq data have been reported in the literature Figure 1In this work, we developed a modularized computational workflow, Containerized Bioinformatics workflow for Reproducible ChIP/ATAC-seq Analysis (CoBRA). CoBRA can quantify ChIP-seq and ATAC-seq peak regions, and perform unsupervised and supervised analyses. It provides sample clustering, differential peak calling, motif enrichment and clustering, annotation of differential sites by a reference database, and pathway analysis. In addition, it also provides clear, high-quality visualizations for all results.CoBRA uses Snakemake CoBRA therefore provides solutions to challenges inherent to many bioinformatics workflows: it is portable, reproducible, scalable, and easy to use. It is open source (https://bitbucket.org/cfce/cobra), well documented online. Detailed step-by-step tutorials are included, which go through all three case studies presented in this paper (https://cfce-cobra.readthedocs.io). The combination of features enables researchers to gain rapid insight into protein–DNA interactions and chromatin accessibility with comprehensive state-of-the-art ChIP-seq and ATAC-seq analysis.The CoBRA pipeline is implemented using the Snakemake workflow management system Furthermore, CoBRA is distributed as a Docker container, which can be used on any machine as long as Docker is installed. The container encapsulates all of the supporting software and libraries, eliminating the possibility of conflicting dependencies, and facilitating the installation of required software. With the built-in Snakemake reference rule, CoBRA automatically downloads all needed reference files, if they have not been downloaded before. Users specify analysis parameters in a simple human-readable configuration file A-C. A seThe pipeline calculates the reads per kilobase per million mapped reads (RPKM) using bed files and bam files provided by the user to normalize based on sequencing depth and peak size. The RPKM table is filtered through the removal of sites that have low RPKM values across multiple samples. Quantile normalization (default), z-score, and log transformation are available options to normalize the count matrix. To visualize the similarities between samples in the experiment, sample–sample correlation, principal component analysis (PCA), and sample–feature plot are automatically generated by the pipeline.r), where distance is defined as 1− r. The user can opt for using Spearman correlation, as well as selecting other distance methods  by simply changing the configuration file. The resulting correlation plot helps to determine whether the different sample types can be separated, i.e., samples of different conditions are expected to be more dissimilar to each other than replicates within the same condition. User-provided metadata are used to automatically annotate samples in all unsupervised plots.The sample–sample correlation plot illustrates the similarity between all of the samples on a pairwise basis. It also provides the clustering result based on the Pearson correlation coefficient  and samples are automatically color-coded by all user-provided annotations. The PCA plot helps the user to determine whether any patterns exist between the samples and whether outliers are present. Finally, CoBRA generates a sample–feature heatmap. The heatmap illustrates the clustering of samples based on correlation on the horizontal axis and clustering of peaks on the vertical axis. Peaks on the vertical axis can be clustered by hierarchical or A common question asked in epigenetic experiments is what are the differential sites  between sample groups. Several tools currently available can be applied to analyze differential sites, most of which are derived from RNA-seq count analysis . However, there are differences between the RNA-seq and ChIP-seq count analyses. In RNA-seq experiments, most reads are in the exome, where read count can be normalized by the total number of reads mapped to all genes. In contrast, most ChIP-seq reads are outside of peaks. The fraction of reads in peaks (FRiP) score typically ranges from 1%–40% P value cutoffs and two fold change (FC) cutoffs is displayed in a summary chart. Furthermore, the bigwig files are used to plot the peak intensity of the differential peaks in a heatmap using deepTools2 Multiple comparisons can be done within a single run. For each comparison, the number of differential peaks for two adjusted de novo motifs that are enriched in the differential peak regions compared to GC matched, randomly-selected genome background. In addition, we utilize a motif clustering algorithm to organize various motifs by similarity, making the output easier to evaluate for distinct results. By mapping the peaks to the nearest genes, CoBRA uses Gene Set Enrichment Analysis (GSEA) pre-ranked analysis to investigate the pathways that are enriched and depleted for both upregulated and downregulated peaks.The differentially enriched regions from DESeq2 for each comparison are subsequently run through HOMER The upregulated and downregulated sites are also automatically compared to a comprehensive database of ChIP/ATAC-seq and DNase l hypersensitive sites sequencing (DNase-seq) data In order to illustrate the utility of CoBRA, we applied it to three case studies with components to showcase the different capabilities of our workflow. These include a glucocorticoid receptor (GR) ChIP-seq dataset from the ENCODE project, an H3K27ac ChIP-seq data from colon cancer cell lines, and an ATAC-seq experiment on HL-60 promyelocytes differentiating into macrophages. Each example demonstrates some key functions of the CoBRA pipeline.Example 1:normalizing GR ChIP-seq data in a dose–response experimentCase studiesGSE32465) from a lung adenocarcinoma cell line (A549) at 3 different concentrations of dexamethasone, a potent GR agonist. In an analysis of this dataset vs. within treatment in the dendrogram at the top of sample–sample heatmap (A), as well as the PCA plot and higher FRiP score (9.3 vs. 0.9) than samples treated with 0.5 nM dexamethasone. Therefore, the normalization method used in DESeq2 decreases the peak intensity in the samples treated with 0.5 nM dexamethasone because the FRiP scores are higher in the samples treated with 50 nM dexamethasone, resulting in the calling of false positive differential peaks , a large, curated database of ChIP-seq and ATAC-seq data trome DB D. CoBRA al sites B, which GSM1866974, GSM2265670, GSM1224664, GSM1890746, GSM2058027, and GSM1890746).We further illustrate the advantages of CoBRA pipeline utilizing data from colorectal cancer cell lines. Microsatellite instable (MSI) and microsatellite stable (MSS) tumors are two classes used to characterize colorectal cancers. To analyze these cell lines, we selected six publicly available datasets from several experiments: three MSI samples and three MSS samples vs. MSI comparison, many peaks at the q arm of chromosome 8 are called significantly differential (A) but, following CNV correction, the number of differential peaks in this region significantly decreases . The CoBRA output includes a PCA plot (A) that demonstrates the temporal differentiation of the macrophages, with the early time point on the left side and the late time point on the right. Furthermore, the output includes a sample–feature heatmap utilizing k-means (k = 3) clustering .The application of CoBRA to these experiments demonstrates the broad capabilities of the workflow in analyzing ChIP-seq or ATAC-seq experiments. While other workflows used to analyze ChIP-seq or ATAC-seq experiments are available, they lack some of the features present in CoBRA . AdditioThe methods for installing, deploying, and using CoBRA along with a detailed tutorial are provided in the documentation available online (https://cfce-cobra.readthedocs.io/). The workflow was designed to work with Docker, which allows the user to automatically download all required software dependencies, eliminating the possibility of conflicting dependencies. This makes CoBRA easy for the user with limited computational training to install and run the workflow. Furthermore, the user does not need to prepare any reference files, as CoBRA automatically downloads all needed reference files. As a result, CoBRA is portable, reproducible, and easy to deploy. In summary, we have developed a new pipeline, CoBRA, that is fast, efficient, portable, customizable, and reproducible. The workflow is built upon the ongoing effort to make computational studies reproducible using defined workflows run inside Docker containers. CoBRA allows users with varying levels of computational skills to quickly process and analyze new data from ChIP-seq and ATAC-seq experiments. It is our hope that CoBRA can be a starting point for others to build upon and improve CoBRA as a tool and extend its ability to analyze the data in Cistrome.CoBRA ia publicly available online at https://bitbucket.org/cfce/cobra and https://cfce-cobra.readthedocs.io.The authors have declared that no competing interests exist.Available online 18 July 2021Handled by Zhihua Zhang2021 The Authors. Published by Elsevier B.V. and Science Press on behalf of Beijing Institute of Genomics, Chinese Academy of Sciences / China National Center for Bioinformation and Genetics Society of China.This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Xintao Qiu: Methodology, Software, Validation, Writing – original draft. Avery S. Feit: Methodology, Software, Validation, Writing – original draft. Ariel Feiglin: Methodology, Software, Validation. Yingtian Xie: Validation, Data curation. Nikolas Kesten: Validation. Len Taing: Software, Validation. Joseph Perkins: Software. Shengqing Gu: Validation, Investigation. Yihao Li: Validation, Investigation. Paloma Cejas: Validation, Investigation. Ningxuan Zhou: Validation, Investigation. Rinath Jeselsohn: Resources, Validation. Myles Brown: Conceptualization, Supervision, Funding acquisition. X. Shirley Liu: Supervision, Project administration. Henry W. Long: Supervision, Funding acquisition, Conceptualization, Writing – review & editing.


Polymers, due to their high molecular weight, tunable architecture, functionality, and buffering effect for endosomal escape, possess unique properties as a carrier or prophylactic agent in preventing pandemic outbreak of new viruses. Polymers are used as a carrier to reduce the minimum required dose, bioavailability, and therapeutic effectiveness of antiviral agents. Polymers are also used as multifunctional nanomaterials to, directly or indirectly, inhibit viral infections. Multifunctional polymers can interact directly with envelope glycoproteins on the viral surface to block fusion and entry of the virus in the host cell. Polymers can indirectly mobilize the immune system by activating macrophages and natural killer cells against the invading virus. This review covers natural and synthetic polymers that possess antiviral activity, their mechanism of action, and the effect of material properties like chemical composition, molecular weight, functional groups, and charge density on antiviral activity. Natural polymers like carrageenan, chitosan, fucoidan, and phosphorothioate oligonucleotides, and synthetic polymers like dendrimers and sialylated polymers are reviewed. This review discusses the steps in the viral replication cycle from binding to cell surface receptors to viral-cell fusion, replication, assembly, and release of the virus from the host cell that antiviral polymers interfere with to block viral infections. Due to their rapid mutation and evolution, viral infections have always been a global health challenge threatening both human and animal health. A virus is a nonliving microscopic structure that contains the genomic material for replication encapsulated and protected by a proteinaceous membrane. Unlike living organisms, viruses must invade a living cell, like a human or animal cell, and hijack its metabolic system for energy and nutrients to replicate and grow . Some viThe function of an antiviral agent is to block one or more of the basic steps in the viral replication cycle without affecting the normal metabolic activities of the cell . As viruPolymers, due to their tunable chemical structure and composition, high molecular weight, and their buffering effect possess unique capabilities as antiviral agents. Many polymers have been recently developed to meet the global demand for antiviral agents and to treat viral infections ,23,24,25Natural polymers or biopolymers are classified into polysaccharides, polypeptides (proteins), and nucleic acid polymers (polynucleotides) . NaturalPolysaccharides are an abundant source of renewable and biodegradable polymers. Polysaccharides are made up of more than 10 monosaccharide repeat units connected by glycosilic linkages in branched or linear chains with molecular weights ranging from tens of thousands to a few millions . Like otAuricularia auricula, Pinus massoniana, and Acanthopanax polysaccharides [Polysaccharides possess different types of functional groups including hydroxyl, amine, and carboxylic acid groups which can be used for polymer modification ,34. Thescharides . Recentlcharides . These scharides . The polcharides . This nocharides . Seaweedcharides ,53,54. Tcharides . The antcharides . In anotcharides ,57. As acharides .The cell wall of marine red seaweed contains the polysaccharides agaran and carrageenan that form approximately 50% of the dry mass of seaweed. As a high molecular weight sulfated polysaccharide, carrageenan has long been used as a gelling agent and stabilizer in food . HoweverThe negatively-charged sulfate groups of carrageenan neutralize the positive charge of the cell surface, leading to inhibition of viral attachment, penetration, and viral uncoating . The bioN-sulfonated derivatives of poly  blocked the release of human metapneumovirus (hMPV) from infected cells, which reduced viral spreading [In general, a higher degree of sulfation leads to a higher antiviral activity . It is rpreading . A nasalpreading . It shoupreading . A studypreading .Carrageenan has also been used against human papillomavirus (HPV) which is a non-enveloped small DNA virus capable of infecting mucosal membrane or skin . In one 50 value of 2.6 µg/mL [Recently, the antiviral activity of different carrageenan types against SARS-CoV-2 has been reported ,78,79. I.6 µg/mL . These sN-acetyl-D-glucosamine and D-glucosamine units, is isolated from the shell of arthropods like shrimp, lobster, crab, and insects or produced by fermentation [N-acetyl-glucosamine residues in chitosan increase the level of reactive oxygen species in macrophages after uptake, which subsequently increase the synthesis of IFN-γ by lymphocytes in the spleen, which in turn prevent translation of viral genomic RNA [Chitin and chitosan due to their biocompatibility, degradability, and non-immunogenicity are used in the development of antimicrobial wound dressing as well as other medical applications ,81. Chitentation . Chitosaentation . Althougentation . The degentation ,86. The entation . In the entation . For exaentation . In the omic RNA .N-carboxymethyl chitosan-N-O-sulfate (NCMCS), was shown to inhibit uptake and replication of human immunodeficiency virus-1 (HIV-1) in CD4+ human T-lymphoma cells, which was attributed to the interference of NCMCS with the interaction of viral GP120 envelope glycoproteins with CD4+ cell surface receptors [A sulfated derivative of chitin, namely eceptors . In anoteceptors . The suleceptors . Chitosaeceptors . In one eceptors . A deliveceptors . The teneceptors .N-(2-hydroxypropyl)-3-trimethylammonium chitosan (HTCC) and N-palmitoyl-N-monomethyl-N,N-dimethyl-N,N,N-trimethyl-6-O-glycolchitosan (GCPQ) is reported against SARS-CoV-2, as shown in Recently, the antiviral activity of quaternary ammonium modified chitosan such as Ascopbyllum nodosum, Fucus vesiculosus, Saccharina japonica, and Sargassum thunbergia. Based on molecular structure, there are two types of fucoidan, as shown in Fucoidan is a sulfated, acidic polysaccharide composed of L-fucose and galactose monosaccharides with smaller proportions of xylose and mannose . It is iKjellmaniella crassifolia fucoidan with a molecular weight of 540 kDa and 30% sulfate content was targeted to inhibition influenza A virus (IAV) [Fucus evanescens fucoidan on inhibition of hepatitis B virus (HBV) was investigated in an HBV-infected mouse model [The mechanism of action for antiviral activity of fucoidans from different sources has been recently studied ,112. Fucus (IAV) . Accordius (IAV) . In anotus (IAV) . The LMWus (IAV) . Furtherus (IAV) . In anotse model . In thisse model . The trese model . DespiteNucleic acid polymers (NAPs), as phosphorothioate oligonucleotides, possess an-tiviral activity . OligonuFollowing penetration through the cell membrane, CSFV is transported to the endoplasmic reticulum where its single-stranded RNA is released for protein translation. Following RNA translation, CSFV is replicated on the cytoplasmic membrane leading to the formation of viral particles in the Golgi apparatus. The siRNAs carried by tFNA degrade the released viral RNA to prevent its translation in the endoplasmic reticulum. List of studies on antiviral activity of NAPs are presented in Polymers are chain-like molecules formed by polymerization of small, reactive organic molecules. Polymers due to their long chain length or high molecular weight are used extensively in surface coating applications because each polymer chain can make many physical bonds to irreversibly coat the surface ,135. As ® dendrimer (SPL7013), which is used in preventing genital herpes (HSV-2) and HIV. The VivaGel® is composed of anionic G4-poly(L-lysine) dendrimer with a benzylhydramine-amide-lysine core with 32 sodium -oxyacetamide functional groups [Dendrimers due to their nanoscale size and structural uniformity are attractive as a carrier for delivery of antiviral agents . The bral groups . The funl groups .Paull and coworkers evaluated the antiviral activity of SPL7013 dendrimer against SARS-CoV-2 . CompareN-alkylated 4,4′-bipyridinium units of varying charge density were synthesized and evaluated with respect to inhibition of HIV-1 [A range of polycationic and polyanionic dendrimers have been synthesized and evaluated against viral infections . The antof HIV-1 . Resultsof HIV-1 . The PCDof HIV-1 . In anotof HIV-1 . In anotof HIV-1 . List of® and Oseltamivir® drugs, as measured by growth inhibition assay [The sialylated glycans in the protective mucin layer of the nasal cavity disrupts the entry of influenza virus (IFV) particles to host cells by complexation with viral hemagglutinin (HA) . The mucon assay . The antGlycopolymers based on sialyl oligosaccharides with a range of chain lengths and sugar densities were synthesized by reversible addition-fragmentation chain transfer polymerization (RAFT) for interaction with hemagglutinin on the surface of influenza virus . The extPolymers provide enormous opportunity to tailor antiviral activity via specific interaction with glycoproteins on the viral surface by varying molecular weight, type and degree of functionality, sequence distribution, extent of branching, and molecular architecture. Polymers can be used to increase bioavailability and therapeutic effectiveness of antiviral agents and reduce their undesired side effects. Natural biopolymers with multiple functional groups like carrageenan, chitosan, and fucoidan are used directly to bind and form irreversible complexes with envelope glycoproteins on the viral surface to block virus-host cell interaction, fusion, and entry to the host cell. Biopolymers are also used to mobilize the immune response against the invading virus by stimulating the activation of macrophages and natural killer cells. Natural nucleic acid polymers are used as antiviral agents after phosphorothioation to render them amphipathic and stabilization against nuclease degradation. Polymers deactivate the virus before cell internalization by inhibiting virus-host cell binding or after cell internalization by blocking virus replication. Synthetic dendrimers due to their symmetry, monodisperse molecular structure, and multifunctionality bind with high affinity to envelope glycoproteins on the viral surface to block virus-host cell interaction and fusion. Brush polymers modified with sialic acid groups bind with high affinity to viral hemagglutinin to form complexes that block viral infection. Research results have demonstrated that natural and synthetic polymers are useful as broad-spectrum antiviral agents to fight against many different types of viral infections. Further preclinical research in animal models and clinical trials are needed to validate the antiviral activity of polymers to fight new viral infections in the absence of vaccines.


Aligning health care spending with population needs is a goal shared by many public health and health care systems. However, most modelling approaches have proven deceptive and ineffective. We propose a novel data-driven, population-based approach to help policymakers explore the discrepancies between spending and needs in France. We leveraged several national open data sources covering demographics, social deprivation, epidemiology, environment, health-related behaviors, and all-payer health care spending . We classified the French “departements” (hereafter counties) into clusters that are homogeneous in terms of health care needs, based on a multidimensional framework. Then, we calculated all-payer per capita health care spending to analyze its within- and between-cluster variation. Based on these findings, we designed a web-based, interactive mapping tool dedicated to French policymakers and payers. The analysis shows 7 clusters of French counties differing in terms of health care needs and spending. The higher-needs/lower-spending and lower-needs/higher spending clusters suggest considerable room for improvement through a regional distribution of spending at least partially based on needs. Most interestingly, the data we used is publicly available, but policymakers lack expertise and time to undergo such analyses themselves. We plan to develop a dynamic and more granular version of the tool to allow policymakers to accurately design and evaluate health care policies.


Construct validity, convergent validity, and internal consistency were evaluated. Sex differences in EREC were evaluated using t-tests. Associations among the EREC, CCWS, and EDE-Q were evaluated using linear regression models. Sensitivity analyses were conducted in individuals below EDE-Q global score clinical cut-offs. Factor analysis suggested that all items loaded adequately onto one factor. Pearson’s correlation and Bland–Altman analyses suggested strong correlation and acceptable agreement between the EREC and CCWS (r = 0.57), but weak correlation and low agreement with the EDE-Q global score (r = 0.14). The EREC had acceptable internal consistency (α = 0.88). No sex difference was observed in the EREC in the full sample; females had a significantly higher mean score than males in sensitivity analysis. The EREC was significantly positively associated with the CCWS and EDE-Q global and shape concern scores, but not in sensitivity analysis. The EREC is a brief, validated scale that can be useful to screen for eating-related eco-concern.Eco-concern, the distress experienced relating to climate change, is associated with mental health, yet no study has examined disordered eating related to eco-concern. This study developed and validated a 10-item scale assessing Eating-Related Eco-Concern (EREC). Participants ( Climate change is defined as alterations in weather patterns and temperatures caused by both natural disasters and human activity . The worEco-concern is a general term for the distress one experiences specifically related to the climate crisis; it may include emotional disturbance due to environmental changes, symptoms of anxiety and distress , helplessness, dread, guilt, sadness, doom, and frustration ,6. Eco-cNumerous factors may influence the association between eco-concern and mental health outcomes. Age may be an important factor: eco-concern is known to impact children, adolescents, and young adults the most, particularly those with preexisting mental health conditions and lacking social support ,11,12. IThe manner in which eco-concern impacts disordered eating and the magnitude of this effect are unknown. However, studies have examined associations between specific eating behaviors related to climate change. Undergraduate students, particularly female students, may adopt behaviors such as eliminating meat, seeking organic and/or local foods, and avoiding food waste in response to climate change concerns . AlthougThe current study addressed research gaps by: (1) developing and validating the first questionnaire assessing eating behaviors related to eco-concern, the eating-related eco-concern (EREC) scale; (2) examining sex differences in climate change worry and eating-related eco-concern; and (3) examining associations among climate change worry, eating-related eco-concern, and disordered eating. In this initial study, there were three hypotheses: (1) the EREC scale would have good psychometric properties  in this sample; (2) female participants would score higher on both climate change worry and eating-related eco-concern; and (3) eating-related eco-concern would be associated with both climate change worry and disordered eating. This study provides the first questionnaire to screen for eating behaviors related to eco-concern and brings awareness to eco-concern as a potentially important contributing factor in the development of disordered eating.n = 6), those who had missing data on eating-related eco-concern (n = 24), and those with inflammatory responses (n = 3), resulting in a final sample size of 224. Compared with participants who were excluded (n = 33), the analytical sample had a higher proportion of White/Caucasian participants (82% vs. 50%), but did not differ in age or sex assigned at birth. A total of 31 participants had missing data on any EDE-Q subscales, and thus the global score. Compared with these participants, those without missing data on EDE-Q scores were significantly older , more likely to be male (22% vs. 13%), and had higher current BMI .Participants were recruited from across the United States via flyers and online recruitment strategies, including posting on social media, ResearchMatch, and University of North Carolina at Chapel Hill listservs. The only inclusion criterion for the present study was that individuals were at least 18 years old; there were no exclusion criteria. Participants provided online consent and then completed all questionnaires via an online survey. Participation was anonymous. A total of 257 adults took the survey. We excluded participants who had incorrect answers to quality assessment questions , factor structure invariance, and test–retest reliability (r = 0.91)  in the subset. In contrast to the results for the whole sample, female participants in the subset had higher levels of eating-related eco-concern than male participants (t (176) = −2.13, p = 0.0348, femalesMean = 25.01, femalesSD = 7.49, malesMean = 21.94, malesSD = 7.86).Female participants demonstrated a significantly higher level of climate change worry , which has been associated with elevated risk of disordered eating . SelflesA sensitivity analysis among individuals whose EDE-Q global scores were below clinical cut-off values was also conducted. Several differences between the sensitivity analysis and analyses in the full sample were observed. First, the EREC score did not differ significantly by sex assigned at birth in the full sample. In contrast, female participants scored significantly higher on the EREC scale than male participants in the sensitivity analysis. Indeed, the mean EREC score of females did not change significantly after excluding those who exceeded the EDE-Q cut-off value, yet the mean EREC score of males was significantly lower after excluding those who exceeded EDE-Q cut-off value. This suggest that male participants who had EDE-Q scores indicative of eating disorders were more likely to have high levels of eating-related eco-concern than female participants who meet EDE-Q cut-off values. Due to limited statistical power, we were unable to compare the strength of associations between disordered eating and eating-related eco-concern in male versus female participants. Furthermore, EDE-Q global score and shape concern subscale score were significantly associated with eating-related eco-concern, yet these associations became nonsignificant after excluding those who exceeded EDE-Q cut-off values. These results suggest that the associations between eating-related eco-concern and disordered eating were more pronounced in those whose scores on the EDE-Q were indicative of possible eating disorders. These findings raise the question of direction of causality. Do individuals with eating disorders further modify their eating behaviors due to eco-concern, and/or do individuals who change their eating behaviors due to eco-concern may develop subsequent eating disorders? A longitudinal study is needed to elucidate the causality of these relationships to provide more evidence on the prevention and/or intervention of disordered eating and eating disorders.Importantly, all questions in the EREC scale do not necessarily represent disordered eating. The goal of this study was to explore a range of behaviors that may be associated with modifications in eating behavior and attitudes related to climate change. Behaviors assessed in the EREC scale, like many healthful behaviors , when taken to an extreme, or when seen together with a more concerning degree of restrictive eating, could represent a component of a concerning behavioral pattern. Indeed, one of the challenges of treating individuals with eating disorders who have concerns about climate change is differentiating between truly health-damaging behaviors and behaviors that are sensible and deserve to remain in their eating repertoire because they are sustainable and climate-friendly while being compatible with recovery from an eating disorder.In summary, this initial study developed and validated the first scale to assess eating-related eco-concern, and is the first study to examine the association between climate change worry, eating-related eco-concern, and disordered eating. Findings from this study will raise awareness of this new topic within the field of disordered eating and eating disorders. Several limitations need to be taken into consideration. First, due to limited time and funding, we only recruited one sample where participants only completed the survey once; thus, it was not possible to examine the test–retest validity using multiple samples. Second, the sample was predominately comprised of White/Caucasian participants in the United States. This limits the generalizability of the findings. Future research should validate this scale in individuals who live in different geographical or climatic regions and in a more diverse sample. Additionally, disordered eating was evaluated via a single scale. Studies using other measures and populations  will expand understanding of the association between eco-concern with disordered eating or eating disorders. Lastly, it was not possible to examine the temporal sequence of the associations among climate change worry, eating-related eco-concern, and disordered eating due to the cross-sectional design of this study; thus, causality could not be determined. Longitudinal studies are needed to establish a potential relationship.The current study developed a 10-item scale to assess eating-related eco-concern and explored its association with disordered eating based on clinical observations in eating disorder treatment. These findings can bring awareness to the potentially new area within the fields of disordered eating, eating disorders, and climate change, which is important from both a research and clinical perspective. Healthcare providers should consider whether individuals endorse eating behaviors due to eco-concern while screening for or assessing other disordered eating behaviors. Prevention strategies, including further education about the impact of climate change and eco-concern on disordered eating, eating disorders, and mental health in general, should be incorporated into activities such as climate action clubs at schools or universities. Future studies should examine psychometric properties of the EREC scale in diverse samples, evaluate associations between eating-related eco-concern with eating disorder diagnosis and other mental health conditions, and further explore sex differences and temporal sequence of these associations.