A multi-scale feature extraction and fusion-based model for retinal vessel segmentation in fundus images.

In response to the challenge of low accuracy in retinal vessel segmentation attributed to the minute nature of the vessels, this paper proposes a retinal vessel segmentation model based on an improved U-Net, which combines multi-scale feature extraction and fusion techniques. An improved dilated residual module was first used to replace the original convolutional layer of U-Net, and this module, coupled with a dual attention mechanism and diverse expansion rates, facilitates the extraction of multi-scale vascular features. Moreover, an adaptive feature fusion module was added at the skip connections of the model to improve vessel connectivity. To further optimize network training, a hybrid loss function is employed to mitigate the class imbalance between vessels and the background. Experimental results on the DRIVE dataset and CHASE_DB1 dataset show that the proposed model has an accuracy of 96.27% and 96.96%, sensitivity of 81.32% and 82.59%, and AUC of 98.34% and 98.70%, respectively, demonstrating superior segmentation performance.

Chemical hazard assessment toward safer electrolytes for lithium-ion batteries.

Commercialization of rechargeable lithium-ion (Li-ion) batteries has revolutionized the design of portable electronic devices and is facilitating the current transition to electric vehicles. The technological specifications of Li-ion batteries continue to evolve through the introduction of various high-risk liquid electrolyte chemicals, yet critical evaluation of the physical, environmental, and human health hazards of these substances is lacking. Using the GreenScreen for Safer Chemicals approach, we conducted a chemical hazard assessment (CHA) of 103 electrolyte chemicals categorized into seven chemical groups: salts, carbonates, esters, ethers, sulfoxides-sulfites-sulfones, overcharge protection additives, and flame-retardant additives. To minimize data gaps, we focused on six toxicity and hazard data sources, including three empirical and three nonempirical predictive data sources. Furthermore, we investigated the structural similarities among selected electrolyte chemicals using the ChemMine tool and the simplified molecular input line entry system inputs from PubChem to evaluate whether chemicals with similar structures exhibit similar toxicity. The results demonstrate that salts, overcharge protection additives, and flame-retardant additives contain the most toxic components in the electrolyte solutions. Furthermore, carbonates, esters, and ethers account for most flammability hazards in Li-ion batteries. This study supports the complementary use of quantitative structure-activity relationship models to minimize data gaps and inconsistencies in CHA. Integr Environ Assess Manag 2024;20:2231-2244. © 2024 The Author(s). Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Comparative life cycle assessment of copper and gold recovery from waste printed circuit boards: Pyrometallurgy, chemical leaching and bioleaching.

Printed circuit boards (PCBs) make up a substantial amount of electronic waste (e-waste) generated annually. Waste PCBs contain high quantities of copper and gold in comparison to natural ores. As such, "urban mining" of waste PCBs to recover these metals is of commercial interest. In this work, we used life cycle assessment to compare the environmental impact of four copper and gold recovery processes. We evaluated pyrometallurgy, chemical leaching, and bioleaching, as well as a hybrid leaching process that uses bioleaching to recover copper and chemical leaching to recover gold. Furthermore, we considered differences in environmental impact based on differences in electricity sources. If electricity comes from fossil fuels, the pyrometallurgical process results in the lowest environmental impact in all impact categories studied. If electricity comes from carbon-free sources, the pyrometallurgical process results in the lowest environmental impact in all categories studied except global warming, where the hybrid leaching process results in the lowest impact. In all cases, metal recovery from waste PCBs leads to lower environmental impact than primary metal production. Our goal is to guide e-waste recyclers towards more environmentally sustainable metal recovery processes and to provide knowledge gaps in the field to guide future research.

Meta-Attention Network Based Spectral Reconstruction with Snapshot Near-Infrared Metasurface.

Near-infrared (NIR) spectral information is important for detecting and analyzing material compositions. However, snapshot NIR spectral imaging systems still pose significant challenges owing to the lack of high-performance NIR filters and bulky setups, preventing effective encoding and integration with mobile devices. This study introduces a snapshot spectral imaging system that employs a compact NIR metasurface featuring 25 distinct C4 symmetry structures. Benefitting from the sufficient spectral variety and low correlation coefficient among these structures, center-wavelength accuracy of 0.05 nm and full width at half maximum accuracy of 0.13 nm are realized. The system maintains good performance within an incident angle of 1°. A novel meta-attention network prior iterative denoising reconstruction (MAN-IDR) algorithm is developed to achieve high-quality NIR spectral imaging. By leveraging the designed metasurface and MAN-IDR, the NIR spectral images, exhibiting precise textures, minimal artifacts in the spatial dimension, and little crosstalk between spectral channels, are reconstructed from a single grayscale recording image. The proposed NIR metasurface and MAN-IDR hold great promise for further integration with smartphones and drones, guaranteeing the adoption of NIR spectral imaging in real-world scenarios such as aerospace, health diagnostics, and machine vision.

The association between weight-adjusted-waist index and stress urinary incontinence in female adults: a population-based study.

INTRODUCTION: Obesity has a significant impact on female stress urinary incontinence. The weight-adjusted-waist index (WWI), a newly explored metric for measuring physical obesity and stress urine incontinence, has not been investigated. METHODS: Cross-sectional data were obtained from the 2011 to 2018 National Health and Nutrition Examination Survey (NHANES) of participants with complete data for WWI and SUI. The independent connection between WWI and SUI was examined using weighted multivariable logistic regression analyses. Smoothed curve fitting was used to study their relationship. In addition, subgroup analyses were performed, and interaction tests were undertaken. RESULTS: In 2,361 female participants over 20, WWI and SUI showed a positive association. Model 3 found that for each one-unit increase in WWI, SUI prevalence increased by 38% [1.38 (1.20, 1.59)]. The prevalence of SUI was 84% higher among participants in the highest quartile of WWI compared to those in the lowest quartile [1.84 (1.32, 2.57)]. Observed nonlinear positive correlation between WWI and SUI was revealed through smoothed curve fitting. In addition, we found that WWI was more strongly associated with SUI than traditional indicators of obesity, including BMI and weight. CONCLUSIONS: Females with higher weight-adjusted waist index levels were more likely to develop stress urinary incontinence and have a stronger correlation than traditional indicators of obesity. According to our research, WWI may help detect women's stress urinary incontinence (SUI), and managing obesity through the WWI index may reduce SUI prevalence rates.

Restricted reaction of layered double hydroxide nanoparticles with phosphate in a confined microsphere space.

Over the past decades, considerable efforts have been made to find useful solutions for phosphate pollution control. The state transition of nanomaterials from freely dispersed to encapsulated provides a realizable route for their application in phosphate elimination. The separation convenience offered by encapsulation has been widely recognized, however, the unique binding mode of nanostructures and phosphate in the confined space remains unclear, limiting its further development. Here, carboxymethyl cellulose (CMC) microspheres were used as hosts to deploy layered double hydroxide (LDH) nanoparticles. On this basis, we described an attempt to explore the adsorption behavior of LDH and phosphate in the microsphere space. Compared to their freely dispersed analogues, LDH particles exhibited higher structural stability, wider pH adaptability, and better phosphate selectivity when spatially confined in the CMC microsphere. Nevertheless, the kinetic process was severely inhibited by three orders of magnitude. Besides, the saturated phosphate adsorption capacity was also reduced to 74.6 % of the freely dispersed system. A combinative characterization revealed that the highly electronegative CMC host not only causes electrostatic repulsion to phosphate, but also extracts the electron density of the metal center of LDH, weakening its ability to act as a Lewis acid site for phosphate binding. Meanwhile, the microsphere encapsulation also hinders the ion exchange function of interlayer anions and phosphate. This study offers an objective insight into the reaction of LDH and phosphate in the confined microsphere space, which may contribute to the advanced design of encapsulation strategies for nanoparticles.

The leucine-responsive regulatory protein SCAB_Lrp modulates thaxtomin biosynthesis, pathogenicity, and morphological development in Streptomyces scabies.

Streptomyces scabies is the best-characterized plant-pathogenic streptomycete, which is a special species among the large genus Streptomyces. The pathogenicity of S. scabies relies on the production of the secondary metabolite thaxtomin A. Little is known about the molecular mechanisms underlying the regulation of thaxtomin biosynthesis in S. scabies beyond the pathway-specific activator TxtR and the cellulose utilization repressor CebR. The leucine-responsive regulatory protein (Lrp) family modulates secondary metabolism in nonpathogenic streptomycetes. However, the regulatory relationship between the Lrp and pathogenic streptomycetes remains unknown. In this study, we demonstrated that SCAB_Lrp (SCAB_77931) from S. scabies significantly affects thaxtomin biosynthesis, pathogenicity, and morphological development. SCAB_Lrp deletion resulted in a dramatic decline in thaxtomin A production and a low-virulence phenotype of S. scabies. An in-depth dissection of the regulatory mechanism of SCAB_Lrp revealed that it positively regulates the transcription of the thaxtomin biosynthetic gene cluster by directly binding to the promoter of the cluster-situated regulator gene txtR. SCAB_Lrp also controls the morphological development of S. scabies by directly activating the transcription of amfC, whiB, and ssgB. SCAB_Lrp directly controls the transcription of its own gene by binding a specific sequence (5'-GGACAGTCGCCGTGCTACG-3'). Moreover, phenylalanine and methionine have been characterized as SCAB_Lrp effectors by strengthening the binding affinity and complex status between SCAB_Lrp and DNA. Our findings characterize a multifunctional regulatory protein, SCAB_Lrp, that controls secondary metabolism, pathogenicity, and sporulation in S. scabies and provide new insights into the complex regulatory network that modulates thaxtomin phytotoxins in pathogenic Streptomyces.

A SERS-Fluorescence dual-signal aptasensor for sensitive and robust determination of AFB1 in nut samples based on Apt-Cy5 and MNP@Ag-PEI.

Food aflatoxin B1 (AFB1) contamination greatly threatens human health and its sensitive determination is imperative. In this study, a surface-enhanced Raman scattering (SERS) and fluorescence dual-signal aptasensor was constructed for sensitive AFB1 detection in peanuts, walnuts, and almonds samples. Fluorescent dye cy5 was used as fluorophore and Raman reporter, while polyethyleneimine modified Ag coating magnetic nanoparticles (MNP@Ag-PEI) were utilized to absorb the cy5 modified aptamer (apt-cy5). Results indicated that linear ranges of 0.001-1000 ng/mL and 0.2-20,000 ng/mL with detection limits of 0.45 pg/mL and 0.135 ng/mL for the SERS and fluorescence methods were obtained, respectively, and AFB1 detection in the nut samples using the aptasensor achieved satisfactory recoveries of 95.2%-108.6% for SERS and 94.7%-109.7% for fluorescence. Compared with other mono signal detection, the established aptasensor facilely fused the merits of the two signals and improved the detection accuracy and flexibility.

CHALLENGES AND OPPORTUNITIES OF INCREASING MATERIALS CIRCULARITY: A Focus on Critical Metal Recovery from Electronic Waste.

This article is a summary of the authors' response to the 2023 Circular Economy Request for Information: Challenges and Opportunities of Increasing Materials Circularity, a call for information issued by the U.S. Department of Energy's Advanced Materials & Manufacturing Technologies Office (AMMTO) in March 2023. Information can be found at www.energy.gov/eere/ammto/2023-circular-economy-request-information-challenges-and-opportunities-increasing.

Identification and validation of transferrin receptor protein 1 for predicting prognosis and immune infiltration in lower grade glioma.

Introduction: Transferrin receptor protein 1 (TFRC), an ananda molecule associated with ferroptosis, has been identified as affecting a wide spectrum of pathological processes in various cancers, but the prognostic value correlates with the tumor microenvironment of TFRC in lower-grade glioma (LGG) is still unclear. Materials and methods: Clinical pathological information and gene expression data of patients with LGG come from The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), GTEx, Oncomine, UCSC Xena, and GEO databases. We then used various bioinformatics methods and mathematical models to analyze those data, aiming to investigate the clinical significance of TFRC in LGG and illustrate its association with tumor immunity. In addition, the molecular function and mechanisms of TFRC were revealed by gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA). Immunohistochemical experiments and single-cell analysis have been performed. Results: TFRC expression was highly expressed in many tumors and showed a poor prognosis. Including gliomas, it was significantly associated with several poor clinical prognostic variables, tumor immune microenvironment, tumor mutational burden (TMB), m6a modification, and ferroptosis in LGG. TFRC as a key factor was further used to build a prediction nomogram. The C-index, calibration curve, and decision curve analysis showed the nomogram was clinically useful and calibration was accurate. At the same time, we also demonstrated that promoter hypomethylation of DNA upstream of TFRC could lead to high TFRC expression and poor overall survival. There is a significant correlation between TFRC and CD8 + T cell, macrophage cell infiltration, and several immune checkpoints, such as PD-L1(cd274), CTLA4, and PD1, suggesting a novel direction for future clinical application. Functional and molecular mechanism analysis showed an association of TFRC expression with immune-related pathways through GSEA, GO, and KEGG analysis. Finally, immunohistochemical experiments and single-cell analysis confirmed the expression of TFRC in glioma. Conclusion: TFRC may be a potential prognostic biomarker and an immunotherapeutic target for glioma.

Spectrum dispersion element based on the metasurface with parabolic phase.

New kinds of dispersion elements are required for the minimization of the spectrometers. Metasurfaces offer new methods for a novel type of spectrometers due to their ultra-thin property and great ability to manipulate the electromagnetic field. Here, we propose and demonstrate a spectral modulated metasurface as a miniaturized dispersion element that possesses parabolic phase profile. Different wavelengths of the incident light can be dispersed to different spatial positions due to the accumulation of the dynamic phase varies with the wavelengths from metasurface. Detailed theoretical spectrum dispersion ability is analyzed and experimental demonstration is achieved. The polarization conversion efficiency is high, which is promising to be used in practical applications. Such metasurface provides a new and simple way to design dispersion devices and has the potential to be used in spectrometers, variable filters, spectrum tomography, etc.

A deep learning based multimodal fusion model for skin lesion diagnosis using smartphone collected clinical images and metadata.

Introduction: Skin cancer is one of the most common types of cancer. An accessible tool to the public can help screening for malign lesion. We aimed to develop a deep learning model to classify skin lesion using clinical images and meta information collected from smartphones. Methods: A deep neural network was developed with two encoders for extracting information from image data and metadata. A multimodal fusion module with intra-modality self-attention and inter-modality cross-attention was proposed to effectively combine image features and meta features. The model was trained on tested on a public dataset and compared with other state-of-the-art methods using five-fold cross-validation. Results: Including metadata is shown to significantly improve a model's performance. Our model outperformed other metadata fusion methods in terms of accuracy, balanced accuracy and area under the receiver-operating characteristic curve, with an averaged value of 0.768±0.022, 0.775±0.022 and 0.947±0.007. Conclusion: A deep learning model using smartphone collected images and metadata for skin lesion diagnosis was successfully developed. The proposed model showed promising performance and could be a potential tool for skin cancer screening.

Advancing chemical hazard assessment with decision analysis: A case study on lithium-ion and redox flow batteries used for energy storage.

Batteries are important for promoting renewable energy, but, like most engineered products, they contain multiple hazardous materials. The purpose of this study is to evaluate industrial-scale batteries using GreenScreen® for Safer Chemicals, an established chemical hazard assessment (CHA) framework, and to develop a systematic, transparent methodology to quantify the CHA results, harmonize them, and aggregate them into single-value hazard scores, which can facilitate quantitative comparison and a robust evaluation of data gaps, inconsistencies, and uncertainty through the implementation of carefully selected scenarios and stochastic multicriteria acceptability analysis (SMAA). Using multiple authoritative toxicity data sources, six battery products are evaluated: three lithium-ion batteries (lithium iron phosphate, lithium nickel cobalt manganese hydroxide, and lithium manganese oxide), and three redox flow batteries (vanadium redox, zinc-bromine, and all-iron). The CHA results indicate that many materials in these batteries, including reagents and intermediates, inherently exhibit high hazard; therefore, safer materials should be identified and considered in future designs. The scenario analysis and SMAA, combined, provide a quantitative evaluation framework to support the decision-making needed to compare alternative technologies. Thus, this study highlights specific strategies to reduce the use of hazardous materials in complex engineered products before they are widely used in this rapidly-expanding industry sector.

Development of software enabling Chinese medicine-based precision treatment for osteoporosis at the gene and pathway levels.

BACKGROUND: Precision medicine aims to address the demand for precise therapy at the gene and pathway levels. We aimed to design software to allow precise treatment of osteoporosis (OP) with Chinese medicines (CMs) at the gene and pathway levels. METHODS: PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP database), and the Wanfang database were searched to identify studies treating osteoporosis with CMs. The TCMSP was used to identify bioactive ingredients and related genes for each CM. Gene expression omnibus (GEO) database and the limma package were used to identify differentially expressed genes in osteoporosis. Perl software was used to identify the shared genes between the bioactive components in CM and osteoporosis. R packages and bioconductor packages were used to define the target relationship between shared genes and their related pathways. Third-party Python libraries were used to write program codes. Pyinstaller library was used to create an executable program file. RESULTS: Data mining: a total of 164 CMs were included, but Drynariae Rhizoma (gusuibu) was used to present this process. We obtained 44 precise relationships among the bioactive ingredients of Drynariae Rhizoma, shared genes, and pathways. Python programming: we developed the software to show the precise relationship among bioactive ingredients, shared genes, and pathways for each CM, including Drynariae Rhizoma. CONCLUSIONS: This study could increase the precision of CM, and could provide a valuable and convenient software for searching precise relationships among bioactive ingredients, shared genes, and pathways.

Modification and Targeted Design of N-Terminal Truncates Derived from Brevinin with Improved Therapeutic Efficacy.

Antimicrobial peptides (AMPs) are a class of molecules that play an essential role in innate immune regulation. The Brevinin-1 family are AMPs that show strong pharmacological and antimicrobial potential. A novel peptide, B1A, was designed based on the primary structure of brevinin-1PLb and brevinin-1PLc. Subsequently, a synthesised replicate was subjected to a series of bioassays and was found to display antimicrobial activity. However, it also displayed high levels of haemolysis in a horse red blood cell haemolytic assay, suggesting potential toxicity. Therefore, we rationally designed a number of B1A analogues with aim of retaining antimicrobial activity, lowering toxicity, and to explore the structure-activity relationship of its N-terminus. B1A and its analogues still retained the "Rana Box" and the FLP-motif, which is a feature of this subfamily. However, the introduction of Lys and Trp residues into the peptide sequences revealed that antimicrobial activity of these analogues remained unchanged once the hydrophobicity and the charge reached the threshold. Hence, the idea that the hydrophobicity saturation in different situations is related to antimicrobial activity can be understood via the structure-activity relationship. Meanwhile, it could also be the starting point for the generation of peptides with specific antimicrobial activity.

A Novel Antimicrobial Peptide (Kassinatuerin-3) Isolated from the Skin Secretion of the African Frog, Kassina senegalensis.

Amphibian skin secretions are remarkable sources of novel bioactive peptides. Among these, antimicrobial peptides have demonstrated an outstanding efficacy in killing microorganisms via a general membranolytic mechanism, which may offer the prospect of solving specific target-driven antibiotic resistance. Here, the discovery of a novel defensive peptide is described from the skin secretion of the African frog, Kassina senegalensis. Named kassinatuerin-3, it was identified through a combination of "shot-gun" cloning and MS/MS fragmentation sequencing. Subsequently, a synthetic replicate was subjected to biofunctional evaluation. The results indicated that kassinatuerin-3 possessed antimicrobial activity against Gram-positive bacteria but no effect against Gram-negative bacteria. Additionally, it was active in biofilm eradication on S. aureus and MRSA and in the antiproliferation of selected cancer cell lines. Moreover, it had a very mild hemolytic effect, which demonstrated a high therapeutic index for kassinatuerin-3. Collectively, although kassinatuerin-3 did not demonstrate remarkable bioactivities compared with other natural or synthetic antimicrobial peptides (AMPs), it offered a new insight into the design of antimicrobial derivatives.

Simple fiber-optic sensor for simultaneous and sensitive measurement of high pressure and high temperature based on the silica capillary tube.

A simple fiber-optic sensor for simultaneous measurement of high pressure and high temperature was proposed. The sensor was simply fabricated by splicing two sections of silica capillary tubes (SCTs) with different inner diameters to the single-mode fiber. The thick core SCT functions as a Fabry-Perot (FP) micro-cavity and an anti-resonant reflecting waveguide at the same time. The two different sensing mechanisms lead to the high contrast sensitivity values of pressure and temperature (‒3.76 nm/MPa, 27.7 pm/°C and 4.24 nm/MPa, 0.82 pm/°C). We also proposed a simple and effective method to evaluate the actual sensitivities of two-parameter sensors by using linear programming, which shows that our sensor is more sensitive than others in high pressure and high temperature simultaneous detection. Besides, low cost, good mechanical property and convenient reflective probe make the sensor more competitive in actual application.

Multicriteria Decision Analysis Characterization of Chemical Hazard Assessment Data Sources.

Chemical hazard assessment (CHA), which aims to investigate the inherent hazard potential of chemicals, has been developed with the purpose of promoting safer consumer products. Despite the increasing use of CHA in recent years, finding adequate and reliable toxicity data required for CHA is still challenging due to issues regarding data completeness and data quality. Also, collecting data from primary toxicity reports or literature can be time consuming, which promotes the use of secondary data sources instead. In this study, we evaluate and characterize numerous secondary data sources on the basis of 5 performance attributes: reliability, adequacy, transparency, volume, and ease of use. We use GreenScreen for Safer Chemicals v1.4 as the CHA framework, which defines the endpoints of interest used in this analysis. We focused upon 34 data sources that reflect 3 types of secondary data: chemical-oriented data sources, hazard-trait-oriented data sources, and predictive data sources. To integrate and analyze the evaluation results, we applied 2 multicriteria decision analysis (MCDA) methodologies: multiattribute utility theory (MAUT) and stochastic multiobjective acceptability analysis (SMAA). Overall, the findings in this research program allow us to explore the relative importance of performance criteria and the data source quality for effectively conducting CHA. Integr Environ Assess Manag 2019;00:1-14. © 2019 SETAC.

A Hylarana latouchii Skin Secretion-Derived Novel Bombesin-Related Pentadecapeptide (Ranatensin-HLa) Evoke Myotropic Effects on the in vitro Rat Smooth Muscles.

Amphibians have developed successful defensive strategies for combating predators and invasive microorganisms encountered in their broad range of environments, which involve secretion of complex cocktails of noxious, toxic and diverse bioactive molecules from the skins. In recent years, amphibian skin secretions have been considered as an extraordinary warehouse for the discovery of therapeutic medicines. In this study, through bioactivity screening of the Hylarana latouchii skin secretion-derived fractions, a novel peptide belonging to ranatensin subfamily (ranatensin-HLa) was discovered, and structurally and pharmacologically-characterised. It consists of 15 amino acid residues, pGlu-NGDRAPQWAVGHFM-NH2, and its synthetic replicate was found to exhibit pharmacological activities on increasing the contraction of the in vitro rat bladder and uterus smooth muscles. Corresponding characteristic sigmoidal dose-response curves with EC50 values of 7.1 nM and 5.5 nM were produced, respectively, in bladder and uterus. Moreover, the precursor of ranatensin-HLa showed a high degree of similarity to those of bombesin-like peptides from Odorrana grahami and Odorrana schmackeri. Hylarana latouchii skin continues to serve as a storehouse with diverse lead compounds for the development of therapeutically effective medicines.

The role of data source selection in chemical hazard assessment: A case study on organic photovoltaics.

Chemical hazard assessment (CHA), designed to evaluate the inherent hazard of chemicals used in everyday consumer products, is gaining in popularity and rigor. Although CHA is being more commonly used by industry and government organizations, there is limited information in the academic literature on the merits and limitations of CHA methods. In the current study, the significance of the need to use multiple data sources to successfully complete a CHA is explored. Specifically, a case study approach is used in which more than one hundred organic substances used in the synthesis of organic solar cells are evaluated using the GreenScreen® for Safer Chemicals framework as the basis for the CHA. Seven data sources, including three chemical-oriented, two hazard-trait-oriented, and two predictive data sources, are utilized to minimize data gaps and allow for complete assessments for most of the chemicals of interest. Findings from sensitivity analysis using single data sources and combinations of data sources highlight that the CHA outcomes can vary considerably as a function of data sources used, which highlights the importance of identifying and/or creating more comprehensive and standardized data sources.