Outbreak.info Research Library: a standardized, searchable platform to discover and explore COVID-19 resources.

Outbreak.info Research Library is a standardized, searchable interface of coronavirus disease 2019 (COVID-19) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) publications, clinical trials, datasets, protocols and other resources, built with a reusable framework. We developed a rigorous schema to enforce consistency across different sources and resource types and linked related resources. Researchers can quickly search the latest research across data repositories, regardless of resource type or repository location, via a search interface, public application programming interface (API) and R package.

Outbreak.info genomic reports: scalable and dynamic surveillance of SARS-CoV-2 variants and mutations.

In response to the emergence of SARS-CoV-2 variants of concern, the global scientific community, through unprecedented effort, has sequenced and shared over 11 million genomes through GISAID, as of May 2022. This extraordinarily high sampling rate provides a unique opportunity to track the evolution of the virus in near real-time. Here, we present outbreak.info , a platform that currently tracks over 40 million combinations of Pango lineages and individual mutations, across over 7,000 locations, to provide insights for researchers, public health officials and the general public. We describe the interpretable visualizations available in our web application, the pipelines that enable the scalable ingestion of heterogeneous sources of SARS-CoV-2 variant data and the server infrastructure that enables widespread data dissemination via a high-performance API that can be accessed using an R package. We show how outbreak.info can be used for genomic surveillance and as a hypothesis-generation tool to understand the ongoing pandemic at varying geographic and temporal scales.

MyGeneset.info: an interactive and programmatic platform for community-curated and user-created collections of genes.

Gene definitions and identifiers can be painful to manage-more so when trying to include gene function annotations as this can be highly context-dependent. Creating groups of genes or gene sets can help provide such context, but it compounds the issue as each gene within the gene set can map to multiple identifiers and have annotations derived from multiple sources. We developed MyGeneset.info to provide an API for integrated annotations for gene sets suitable for use in analytical pipelines or web servers. Leveraging our previous work with MyGene.info (a server that provides gene-centric annotations and identifiers), MyGeneset.info addresses the challenge of managing gene sets from multiple resources. With our API, users readily have read-only access to gene sets imported from commonly-used resources such as Wikipathways, CTD, Reactome, SMPDB, MSigDB, GO, and DO. In addition to supporting the access and reuse of approximately 180k gene sets from humans, common model organisms (mice, yeast, etc.), and less-common ones (e.g. black cottonwood tree), MyGeneset.info supports user-created gene sets, providing an important means for making gene sets more FAIR. User-created gene sets can serve as a way to store and manage collections for analysis or easy dissemination through a consistent API.

Schema Playground: a tool for authoring, extending, and using metadata schemas to improve FAIRness of biomedical data.

BACKGROUND: Biomedical researchers are strongly encouraged to make their research outputs more Findable, Accessible, Interoperable, and Reusable (FAIR). While many biomedical research outputs are more readily accessible through open data efforts, finding relevant outputs remains a significant challenge. Schema.org is a metadata vocabulary standardization project that enables web content creators to make their content more FAIR. Leveraging Schema.org could benefit biomedical research resource providers, but it can be challenging to apply Schema.org standards to biomedical research outputs. We created an online browser-based tool that empowers researchers and repository developers to utilize Schema.org or other biomedical schema projects. RESULTS: Our browser-based tool includes features which can help address many of the barriers towards Schema.org-compliance such as: The ability to easily browse for relevant Schema.org classes, the ability to extend and customize a class to be more suitable for biomedical research outputs, the ability to create data validation to ensure adherence of a research output to a customized class, and the ability to register a custom class to our schema registry enabling others to search and re-use it. We demonstrate the use of our tool with the creation of the Outbreak.info schema-a large multi-class schema for harmonizing various COVID-19 related resources. CONCLUSIONS: We have created a browser-based tool to empower biomedical research resource providers to leverage Schema.org classes to make their research outputs more FAIR.

BioThings SDK: a toolkit for building high-performance data APIs in biomedical research.

SUMMARY: To meet the increased need of making biomedical resources more accessible and reusable, Web Application Programming Interfaces (APIs) or web services have become a common way to disseminate knowledge sources. The BioThings APIs are a collection of high-performance, scalable, annotation as a service APIs that automate the integration of biological annotations from disparate data sources. This collection of APIs currently includes MyGene.info, MyVariant.info and MyChem.info for integrating annotations on genes, variants and chemical compounds, respectively. These APIs are used by both individual researchers and application developers to simplify the process of annotation retrieval and identifier mapping. Here, we describe the BioThings Software Development Kit (SDK), a generalizable and reusable toolkit for integrating data from multiple disparate data sources and creating high-performance APIs. This toolkit allows users to easily create their own BioThings APIs for any data type of interest to them, as well as keep APIs up-to-date with their underlying data sources. AVAILABILITY AND IMPLEMENTATION: The BioThings SDK is built in Python and released via PyPI (https://pypi.org/project/biothings/). Its source code is hosted at its github repository (https://github.com/biothings/biothings.api). SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Health-promoting properties of barley: A review of nutrient and nutraceutical composition, functionality, bioprocessing, and health benefits.

Barley is one of the world's oldest cereal crops forming an important component of many traditional diets. Barley is rich in a variety of bioactive phytochemicals with potentially health-promoting effects. However, its beneficial nutritional attributes are not being fully realized because of the limited number of foods it is currently utilized in. It is therefore crucial for the food industry to produce novel barley-based foods that are healthy and cater to customers' tastes. This article reviews the nutritional and functional characteristics of barley, with an emphasis on its ability to improve glucose/lipid metabolism. Then, recent trends in barley product development are discussed. Finally, current limitations and future research directions in glucolipid modulation mechanisms and barley bioprocessing are discussed.

Effect of infrared irradiation combined with mannitol and kinesiology tape on postoperative swelling and pain in patients with a periarticular ankle fracture.

Objectives: To explore the effect of infrared irradiation combined with mannitol and Kinesiology tape on postoperative swelling and pain in patients with a periarticular ankle fracture. Methods: The research subjects of this study were 88 patients with periarticular ankle fracture treated by surgery in the Department of Orthopedics of Baoding No.1 Central Hospital from October, 2019 to May, 2021. They were randomly divided into the observation group and the control group based on the random number table method, with 44 cases in each group. All patients were treated after the operation. Patients in the control group were treated with conventional drugs; while those in the observation group were provided with infrared irradiation combined with mannitol and Kinesiology tape. Further comparison was conducted on the degree of swelling, pain and satisfaction after treatment at three, five and seven days after operation. Results: At three, five and seven days after operation, the cross-section diameter of the injured limb was significantly smaller in the observation group than that in the control group, and the difference was statistically significant (p<0. 05). The degree of pain in both groups was significantly lower at three, five and seven days after operation than that before treatment; moreover, the degree of pain in the observation group was significantly lower than that in the control group, and the difference was statistically significant (p<0. 05). Besides, the comparison of posttreatment satisfaction in both groups after treatment revealed that the total satisfaction of patients in the observation group (97.73%) was higher than that in the control group (79.55%), with a statistically significant difference (p<0.05). Conclusion: Infrared irradiation combined with mannitol and Kinesiology tape can effectively alleviate postoperative swelling and pain of patients with a periarticular ankle fracture.

Development of a colloidal gold immunochromatographic strip for the rapid detection of pefloxacin in grass carp with a novel pretreatment method.

A rapid colloidal gold immunochromatography assay (GICA) for the detection of pefloxacin (PEF) was established and optimized. The anti-PEF monoclonal antibody (mAb) was used to target PEF as a colloidal gold-mAb conjugate. The mAb belonged to the IgG2b subtype, lambda light chain, the affinity constant (Ka) was 5.21 × 109 L·mol-1, and its half maximal inhibitory concentration (IC50) was 0.23 ng·mL-1. No obvious cross-reactivity (CR) was observed with other common fluoroquinolone antibiotics, including ciprofloxacin (CIP), norfloxacin (NOR), lomefloxacin (LOM) and ofloxacin (OFL). The visual limit of detection (vLOD) of the optimized GICA was 2 ng·g-1 under the conventional pretreatment method, and the assay was completed in 15 min. Liquid chromatography tandem-mass spectrometry (LC-MS/MS) was employed to confirm the performance of the strip. In addition, a novel pretreatment was established and compared with conventional pretreatment. Without the removal of organic solvents, the novel pretreatment method reduced the sample pretreatment time (more than 10 min). The vLOD of the optimized GICA was also 2 ng·g-1 when applying the novel pretreatment method. In conclusion, the proposed PEF-GICA could detect samples containing PEF rapidly and accurately, and the novel pretreatment method saved the time of sample pretreatment and improved the efficiency of detection.

Regulatory effect of LncRNA DRAIC/miR-149-5p/NFIB molecular network on autophagy of esophageal cancer cells and its biological behavior.

OBJECTIVE: This experiment will explore the effect of LncRNA DRAIC/miR-149-5p/NFIB molecular network on esophageal cancer (EC) cells' biological behavior and autophagy. METHODS: We bought human EC cells and normal esophageal epithelial cells HEEC. DRAIC, miR-149-5p and NFIB protein expression were tested. The low expression plasmid of DRAIC and empty vector of DRAIC, miR-149-5p miR-mimics, miR-149-5p inhibitors and negative control groups, NFIB high expression plasmid, NFIB low expression plasmid and empty vector were transfected into EC cells (Eca-109 and EC9706) to detect changes in cell biological behavior and autophagy protein expression. The targeted relationship between DRAIC/miR-149-5p/NFIB was verified through dual-luciferase report and pull-down experiment. RESULTS: DRAIC and NFIB showed high expression in EC cells, while miR-149-5p showed low expression. Down-regulating DRAIC, NFIB and over-expressing miR-149-5p can inhibit EC cells' proliferation and invasion, and improve apoptosis and autophagy. Dual-luciferase report and pull-down experiment confirmed that DRAIC targeted miR-149-5p regulation, and down-regulating DRAIC could reverse miR-149-5p inhibitor's effect on the biological behavior of EC cells. However, dual-luciferase report revealed that miR-149-5p directly targeted NFIB, and miR-149-5p inhibitor could weaken the effect of down-regulating NFIB on apoptosis and autophagy of EC cells. Moreover, DRAIC has an effect on the autophagy of EC cells through miR-149-5p/NFIB. CONCLUSION: LncRNA DRAIC is relevant to cell biology and autophagy of EC. In the future, DRAIC may be developed as a key gene for EC diagnosis and treatment.

Fermented barley ß-glucan regulates fat deposition in Caenorhabditis elegans.

BACKGROUND: Barley contains a relatively high concentration of the mixed-linkage (1 → 3) (1 → 4) ß-glucan, which has been reported to be a functional food with prebiotic potential. In the current study we compared the properties of two neutral barley ß-glucans, obtained from raw barley: raw barley ß-glucan (RBG) and Lactobacillus plantarum dy-1-fermented barley (FBG). RESULTS: Molecular characteristics revealed that the molecular weight of barley ß-glucan decreased from 1.13 × 105 D to 6.35 × 104 D after fermentation. Fermentation also improved the water / oil holding capacity, solubility, and swelling capacity of barley ß-glucan. Both RBG and FBG significantly improved the locomotive behavior of nematodes, thereby increasing their energy consumption and reducing fat deposition - the effect was more significant with FBG. These effects could potentially depend on nhr-49, TGF-daf-7 mediated pathways and so on, in which nhr-49 factor is particularly required. CONCLUSION: These results suggested that fermentation may enhance in vitro physiological activities of barley ß-glucan, thereby altering the effects on the lipid metabolism in vivo. © 2020 Society of Chemical Industry.

Fermented barley extracts with Lactobacillus plantarum dy-1 changes serum metabolomic profiles in rats with high-fat diet-induced obesity.

We have previously reported an aqueous extract of fermented barley with Lactobacillus plantarum dy-1 (LFBE) has more efficient anti-obesity effect compared with that of Saccharomyces cerevisiae. To further explore associated effects of LFBE on body weight and body fat distribution, and lipid profiles related metabolic outcomes, serum metabolites were analysed using LC-MS-MS and partial least-squares-discriminant analysis (PLS-DA). Obese and lean groups were clearly discriminated from each other on PLS-DA score plot and major metabolites contributing to the discrimination were assigned as lipid metabolites (fatty acids), lipid metabolism intermediates (choline, betaine, carnitine and butyryl-carnitine), amino acids and citric acid. A high-fat diet increased lipid metabolites and decreased lipid metabolism intermediates, indicating that abnormal lipid metabolism induced by a high-fat diet resulted in fat accumulation via decreased ß-oxidation. But LFBE can inhibit fat accumulation by reducing lipid metabolites and increasing lipid metabolism intermediates. Furthermore, the level changes of these metabolites can be used to assess the risk of obesity and the therapeutic effect of obesity management.

Single-Molecule Flow Platform for the Quantification of Biomolecules Attached to Single Nanoparticles.

We describe here a flow platform for quantifying the number of biomolecules on individual fluorescent nanoparticles. The platform combines line-confocal fluorescence detection with near nanoscale channels (1-2 µm in width and height) to achieve high single-molecule detection sensitivity and throughput. The number of biomolecules present on each nanoparticle was determined by deconvolving the fluorescence intensity distribution of single-nanoparticle-biomolecule complexes with the intensity distribution of single biomolecules. We demonstrate this approach by quantifying the number of streptavidins on individual semiconducting polymer dots (Pdots); streptavidin was rendered fluorescent using biotin-Alexa647. This flow platform has high-throughput (hundreds to thousands of nanoparticles detected per second) and requires minute amounts of sample (∼5 µL at a dilute concentration of 10 pM). This measurement method is an additional tool for characterizing synthetic or biological nanoparticles.

Efficient Synthesis of Dimeric Oxazoles, Piperidines and Tetrahydroisoquinolines from N-Substituted 2-Oxazolones.

A mild and practical method for the construction of heterocycles from N-substituted 2-oxazolones through cascade, BF3 ⋅Et2 O/H2 O-catalyzed reactions involving iminium ion generation and trapping by external or internal olefinic and aryl moieties is described. Mechanistic and computational studies revealed the strong protic acid HBF4 as the initiating catalyst for these cascade reactions. Providing access to novel molecular diversity, these processes may facilitate chemical biology studies, drug discovery efforts and natural products synthesis.

Combined ultrasound-guided cutting-needle biopsy and standard pleural biopsy for diagnosis of malignant pleural effusions.

BACKGROUND: The most efficient approach to diagnose malignant pleural effusions (MPEs) is still controversial and uncertain. This study aimed to evaluate the utility of a combined approach using ultrasound (US)-guided cutting-needle biopsy (CNB) and standard pleural biopsy (SPB) for diagnosing MPE. METHODS: Pleural effusions were collected from 172 patients for biochemical and microbiological analyses. US-guided CNB and SPB were performed in the same operation sequentially to obtain specimens for histological analysis. RESULTS: US-guided CNB and SPB procedures provided adequate material for histological analysis in 90.7 and 93.0% of cases, respectively, while a combination of the 2 techniques was in 96.5% of cases. The sensitivity, specificity, positive-predictive value (PPV), negative-predictive value (NPV) and diagnostic accuracy of US-guided CNB versus SPB were: 51.2 vs 63.4%, 100 vs 100%, 100 vs 100%, 64.9 vs 72.2% and 74.4 vs 81.3%, respectively. When CNB was combined with SPB, the corresponding values were 88.6, 100, 100, 88.6 and 93.9%, respectively. Whereas sensitivity, NPV and diagnostic accuracy were not significantly different between CNB and SPB, the combination of CNB and SPB significantly improved the sensitivity, NPV and diagnostic accuracy versus each technique alone (p < 0.05). Significant pain (eight patients), moderate haemoptysis (two patients) and chest wall haematomas (two patients) were observed following CNB, while syncope (four patients) and a slight pneumothorax (four patients) were observed following SPB. CONCLUSIONS: Use of a combination of US-guided CNB and SPB afforded a high sensitivity to diagnose MPEs, it is a convenient and safe approach.

Squaraine-based polymer dots with narrow, bright near-infrared fluorescence for biological applications.

This article describes the design and development of squaraine-based semiconducting polymer dots (Pdots) that show large Stokes shifts and narrow-band emissions in the near-infrared (NIR) region. Fluorescent copolymers containing fluorene and squaraine units were synthesized and used as precursors for preparing the Pdots, where exciton diffusion and likely through-bond energy transfer led to highly bright and narrow-band NIR emissions. The resulting Pdots exhibit the emission full width at half-maximum of ∼36 nm, which is ∼2 times narrower than those of inorganic quantum dots in the same wavelength region (∼66 nm for Qdot705). The squaraine-based Pdots show a high fluorescence quantum yield (QY) of 0.30 and a large Stokes shift of ∼340 nm. Single-particle analysis indicates that the average per-particle brightness of the Pdots is ∼6 times higher than that of Qdot705. We demonstrate bioconjugation of the squaraine Pdots and employ the Pdot bioconjugates in flow cytometry and cellular imaging applications. Our results suggest that the narrow bandwidth, high QY, and large Stokes shift are promising for multiplexed biological detections.

Reconsideration and Reflection on Spinal Disorders Through the Study of Intervertebral Discs in Patients with Lumbar Spondylolisthesis.

OBJECTIVE: This study analyzed and explored the relationship between isthmic spondylolisthesis and disc degeneration by comparing the degree of disc degeneration in patients with isthmic spondylolisthesis, lumbar disc herniation, and asymptomatic healthy individuals. METHODS: This study included a total of 138 cases, consisting of L5-S1 single segment lesion patients and a normal lumbar spine population. The cases were divided into 3 groups based on the type of disease: fifty eight cases in the isthmic spondylolisthesis (IS) group, 50 cases in the lumbar disc herniation (LDH) group, and 30 cases in the normal lumbar vertebrae (NLV) group. RESULTS: The research findings indicate that the proportion of intervertebral disc degeneration in the LDH group is significantly higher than that in the IS group and NLV group (65.3% vs. 33.3% vs. 25.8%, P < 0.05). The Pfirrmann grades of lumbar intervertebral discs (L1-L4) in the LDH group are significantly higher than those in the IS group and NLV group (P < 0.05), and the intervertebral height index (IHI) (L1-L4) of lumbar vertebrae in the LDH group is significantly lower than that in the IS group and NLV group (P < 0.05). CONCLUSIONS: The results showed that the degree of intervertebral disc degeneration in patients with isthmic spondylolisthesis was lighter than that in patients with LDH, and even similar to that in healthy individuals. The occurrence of IS may have slowed down the degeneration of nonaffected segment intervertebral discs through certain factors.

Osthole inhibits malignant phenotypes and induces ferroptosis in KRAS-mutant colorectal cancer cells via suppressing AMPK/Akt signaling.

PURPOSE: Ferroptosis is a form of cell death driven by iron-dependent lipid peroxidation. Intriguingly, KRAS-mutant cancers are particularly vulnerable to ferroptosis. Osthole is a natural coumarin extracted from Cnidium spp. and other Apiaceous plants. In the present study, we explored the antitumor potential of osthole in KRAS-mutant colorectal cancer (CRC) cells. METHODS: Cell viability assay, EdU incorporation assay, flow cytometry, tumor xenograft model, western blot, immunochemistry staining, immunofluorescence, transcriptome RNA sequencing and quantitative reverse transcription-PCR were performed to evaluate the influence of osthole treatment on KRAS-mutant CRC cells. RESULTS: We found that osthole treatment suppressed proliferation and tumor growth of KRAS-mutant CRC cell lines HCT116 and SW480. Moreover, osthole treatment increased ROS production and induced ferroptosis. Osthole treatment also promoted autophagy, but inhibition of autophagy by ATG7 knockdown or 3-MA showed no influence on osthole-induced ferroptosis. In comparison, osthole increased lysosomal activation, and co-treatment with lysosome inhibitor Baf-A1 attenuated osthole-induced ferroptosis. Besides, osthole treatment reduced the phosphorylation of AMPK, Akt and mTOR in HCT116 and SW480 cells, while restored AMPK signaling by AMPK agonist AICAR partially abrogated ferroptosis induced by osthole treatment. Finally, co-treatment with osthole increased the cytotoxicity of cetuximab in KRAS-mutant CRC cells in vitro and in vivo. CONCLUSION: Our results suggested that the natural product osthole exerted its anticancer effects in KRAS-mutant CRC cells via inducing ferroptosis, and this was partially through inhibiting AMPK/Akt/mTOR signaling. Our results may expand our current knowledge for the use of osthole as an anticancer agent.

STAM-binding Protein-like 1 Promotes Growth and Migration of Colorectal Cancer by NF-κB Pathway.

BACKGROUND: STAM-binding protein-like 1 (STAMBPL1) functions as a deubiquitinase to cleave Lys63 ubiquitin linkage, and is associated with cancer dissemination and progression. The role of STAMBPL1 in colorectal cancer (CRC) remains unclear. METHODS: STAMBPL1 expression was determined by western blot and qRT-PCR. Cell proliferation was detected by colony formation and MTT assays, and apoptosis was assessed by flow cytometry. The metastasis was evaluated by transwell and wound healing assays. An animal xenograft experiment was used to investigate the effect of STAMBPL1 on tumor growth. RESULTS: The expression of STAMBPL1 was elevated in CRC cells. Knockdown of STAMBPL1 reduced cell viability of CRC and suppressed the proliferation, invasion, and migration. Apoptosis of CRC was induced by silence of STAMBPL1. Tumor growth of CRC was also suppressed by the silence of STAMBPL1. Knockdown of STAMBPL1 increased IκB and decreased phosphorylation of IκB to reduce p65 phosphorylation. CONCLUSION: Knockdown of STAMBPL1 inhibited cell growth and metastasis of CRC through inactivation of the NF-κB pathway.

Development of Indirect Competitive ELISA and Colloidal Gold Immunochromatographic Strip for Endosulfan Detection Based on a Monoclonal Antibody.

Endosulfan, as an effective broad-spectrum insecticide, has been banned in agricultural areas because of the potential harmful effects on human health. This study aimed to develop an indirect competitive enzyme-linked immunosorbent assay (ic-ELISA) and colloidal gold immunochromatographic (ICA) strip based on a prepared monoclonal antibody (mAb) for quantitative and qualitative detection of endosulfan. A new mAb with high sensitivity and affinity was designed and screened. The ic-ELISA showed a 50% inhibition concentration (IC50) value of 5.16 ng/mL for endosulfan. Under optimum conditions, the limit of detection (LOD) was determined to be 1.14 ng/mL. The average recoveries of endosulfan in spiked pear and apple samples ranged from 91.48-113.45% and 92.39-106.12% with an average coefficient of variation (CV) of less than 7%, respectively. The analysis of colloidal gold ICA strip could be completed within 15 min by naked eye and the visual limit of detection (vLOD) was both 40 ng/mL in pear and apple samples. In conclusion, both developed immunological methods were suitable and reliable for the on-site detection of endosulfan in real samples at trace levels.

Transcriptome Analysis and Functional Characterization Reveal That Peclg Gene Contributes to the Virulence of Penicillium expansum on Apple Fruits.

Penicillium expansum is the causal agent of blue mold decay on apple fruits and is also known to be the major producer of patulin, a mycotoxin that represents serious hazard to human health. Several mechanisms have been suggested to explain the pathogenesis of P. expansum in host plants. Secreted effector proteins are vital for the pathogenicity of many fungal pathogens through manipulating their hosts for efficient colonization. In this study, we performed a RNA-Seq analysis followed by computational prediction of effector proteins from P. expansum during infection of the host apple fruits, and a total of 212 and 268 candidate effector protein genes were identified at 6 and 9 h after inoculation (hai), respectively. One of the candidate effector protein genes was identified as a concanavalin A-like lectin/glucanase (Peclg), which was dramatically induced during the pathogen-host interaction. Targeted knockout of Peclg resulted in significant reduction in conidial production and germination relative to the wild type. Further studies showed that in addition to salt stress, the mutant was much more sensitive to SDS and Congo red, suggesting a defect in cell wall integrity. Pathogenicity assays revealed that the ΔPeclg mutant showed significant decrease in virulence and infectious growth on apple fruits. All these results suggest that Peclg is required for fungal growth, stress response, and the virulence of P. expansum.