Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Investigations on the Toxicity of CeO2 Nanoparticles after Subchronic Inhalation of Low Doses

The present research focused on the toxicology of nanomaterial. It was based on a 90day inhalation toxicity study with cerium oxide and barium sulfate nanoparticles, performed according to OECD TG 413. CeO2 is for example used as diesel fuel additive. BaSO4 is used in paintings and coatings. The project was an addition to a combined chronic inhalation toxicity and carcinogenicity study with CeO2 and BaSO4 (BASF, Ludwigshafen, Germany; NANoREG program, 8

Effects from a 90-day inhalation toxicity study with cerium oxide and barium sulfate nanoparticles in rats

Abstract Background Nanomaterials like cerium oxide and barium sulfate are frequently processed in industrial and consumer products and exposure of humans and other organisms is likely. Generally less information is given on health effects and toxicity, especially regarding long-term exposure to low nanoparticle doses. Since inhalation is still the major route of uptake the present study focused on pulmonary effects of CeO2NM-212 (0.1, 0.3, 1.0, 3.0 mg/m3) and BaSO4NM-220 nanoparticles (50.0 mg/m3) in a 90-day exposure setup. To define particle-related effects and potential mechanisms of action, observations in histopathology, bronchoalveolar lavage and immunohistochemistry were linked to pulmonary deposition and clearance rates. This further allows evaluation of potential overload related effects. Results Lung burden values increased with increasing nanoparticle dose levels and ongoing exposure. At higher doses, cerium clearance was impaired, suggesting lung overload. Barium elimination was extremely rapid and without any signs of overload. Bronchoalveolar lavage fluid analysis and histopathology revealed lung tissue inflammation with increasing severity and post-exposure persistency for CeO2. Also, marker levels for genotoxicity and cell proliferation were significantly increased. BaSO4 showed less inflammation or persistency of effects and particularly affected the nasal cavity. Conclusion CeO2 nanoparticles penetrate the alveolar space and affect the respiratory tract after inhalation mainly in terms of inflammation. Effects at low dose levels and post-exposure persistency suggest potential long-term effects and a notable relevance for human health. The generated data might be useful to improve nanoparticle risk assessment and threshold value generation. Mechanistic investigations at conditions of non-overload and absent inflammation should be further investigated in future studies

Cerium oxide and barium sulfate nanoparticle inhalation affects gene expression in alveolar epithelial cells type II

BACKGROUND: Understanding the molecular mechanisms of nanomaterial interacting with cellular systems is important for appropriate risk assessment. The identification of early biomarkers for potential (sub-)chronic effects of nanoparticles provides a promising approach towards cost-intensive and animal consuming long-term studies. As part of a 90-day inhalation toxicity study with CeO2 NM-212 and BaSO4 NM-220 the present investigations on gene expression and immunohistochemistry should reveal details on underlying mechanisms of pulmonary effects. The role of alveolar epithelial cells type II (AEII cells) is focused since its contribution to defense against inhaled particles and potentially resulting adverse effects is assumed. Low dose levels should help to specify particle-related events, including inflammation and oxidative stress. RESULTS: Rats were exposed to clean air, 0.1, 0.3, 1.0, and 3.0 mg/m(3) CeO2 NM-212 or 50.0 mg/m(3) BaSO4 NM-220 and the expression of 391 genes was analyzed in AEII cells after one, 28 and 90 days exposure. A total number of 34 genes was regulated, most of them related to inflammatory mediators. Marked changes in gene expression were measured for Ccl2, Ccl7, Ccl17, Ccl22, Ccl3, Ccl4, Il-1alpha, Il-1ss, and Il-1rn (inflammation), Lpo and Noxo1 (oxidative stress), and Mmp12 (inflammation/lung cancer). Genes related to genotoxicity and apoptosis did not display marked regulation. Although gene expression was less affected by BaSO4 compared to CeO2 the gene pattern showed great overlap. Gene expression was further analyzed in liver and kidney tissue showing inflammatory responses in both organs and marked downregulation of oxidative stress related genes in the kidney. Increases in the amount of Ce were measured in liver but not in kidney tissue. Investigation of selected genes on protein level revealed increased Ccl2 in bronchoalveolar lavage of exposed animals and increased Lpo and Mmp12 in the alveolar epithelia. CONCLUSION: AEII cells contribute to CeO2 nanoparticle caused inflammatory and oxidative stress reactions in the respiratory tract by the release of related mediators. Effects of BaSO4 exposure are low. However, overlap between both substances were detected and support identification of potential early biomarkers for nanoparticle effects on the respiratory system. Signs for long-term effects need to be further evaluated by comparison to a respective exposure setting

Approaches on MWCNT diameters and its relation to tumor development

Question: Some forms of carbon nanotubes (CNT) have been found to exhibit carcinogenic potential depending on their morphological characteristics and catalyst impurities. The use of CNTs therefore requires appropriate risk and safety assessment. Correlation of hazards of biodurable fibres to specific morphologies is an approach that has been successfully developed for microscale fibres. The derived "fibre toxicological paradigm" achieves morphology-based hazard classification for a broad class of materials. The present study aims at contributing to an extension of this paradigm to the world of nanoscale fibres. Methods: CNTs of different diameters will be compared with respect to tumor development after intraperitoneal (i.p.) injection. It will be studied whether a diameter based threshold for CNT carcinogenicity can be identified. Rats will be administered a single i.p. injection. The tumor incidence will be histopathologically approximately evaluated performed after two years post application. Additionally, an interim sacrifice will be inflammatory three month to investigate potential effects in the peritoneum. Five different types of CNT will be tested in two concentrations (0.1 and 1.0 x 109 WHO-fibers): One single-walled CNT type, one multi-walled CNT type with an average diameter of 10 nm and a length of > 5 µm, two custom-synthesized multi-walled CNTs with average diameters of 20 and of 30 nm and a length > 5 µm, and one short MWCNT (max. 4-5 µm) with a diameter of > 40 nm. Amosite will be used as positive control. All nanomaterials will be comprehensively characterized before and after dispersion to reliable determine administered diameter distributions together with other characteristics that potentially influence toxicity, including length, purity and rigidity. Conclusion: The generated data is expected to provide information on morphology induced modes-of-action of CNTs including inflammation and carcinogenicity. The data is expected to contribute to the development of a morphology-based classification approach for CNTs and other inert nanofibres. This project is funded by the German FederalInstitute for Occupational Safety and Health (F2376)

Investigations on classification and mechanisms of MWCNT-Induced carcinogenicity

Carbon nanotubes (CNT) are of great interest for toxicological research due to similarities to asbestos as shape, size, biopersistency, and toxic modes of action. It is widely accepted that fiber-specific characteristics like diameter or rigidity can affect their toxic potential. Larger diameters (> 35 nm), for instance, have been shown to contribute to tumor development. Although there are still uncertainties about the exact role of CNT thickness to carcinogenicity, a classification based on morphological characteristics could help to improve risk assessment and safe use of CNTs. This study therefore aims at providing data on the toxicity of multiwalled CNTs with narrow diameter ranges, in order to test whether a threshold for tumor development could be set for a specific fiber thickness. For this purpose, rats will be administered a single intraperitoneal injection of CNTs. Two different doses will be tested, 0.1 and 1.0 x 109 WHO-fibers, and five different types of CNT within and outside of the tumor-sensitive diameter or length range will be compared. Those include one single-walled CNT, one multiwalled CNT (MWCNT) with an average diameter of 10 nm and a length of > 5 µm, two customized MWCNT with an average diameter of 20 and 30 nm and > 5 µm in length, as well as one short MWCNT (max. 4-5 µm) with a diameter of > 40 nm. Amosite will be used as positive control. Approximately two years post-application animals will be histopathologically examined for tumors. Additionally, an interim group will be included for investigation of inflammatory reactions in the peritoneum three months after substance administration. Detailed characterization of the test materials will be presented, including determination of aspect ratios. Rigidities will be used to test whether differentiation between the five fiber types and observed responses can be achieved. The approach also aims at supporting the determination of guidelines for a standardized characterization procedure for CNTs. The project is funded by the German Federal Institute for Occupational Safety and Health (F2376)

MOESM1 of Cerium oxide and barium sulfate nanoparticle inhalation affects gene expression in alveolar epithelial cells type II

Additional file 1: Table S1. Fold regulation of regulated genes. List of fold regulation and standard deviation values of the regulated genes listed in Tables 2 and 3 of the manuscript. Values are shown for every dose group and time point