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

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Immunoglobulin, glucocorticoid, or combination therapy for multisystem inflammatory syndrome in children: a propensity-weighted cohort study.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C), a hyperinflammatory condition associated with SARS-CoV-2 infection, has emerged as a serious illness in children worldwide. Immunoglobulin or glucocorticoids, or both, are currently recommended treatments. METHODS: The Best Available Treatment Study evaluated immunomodulatory treatments for MIS-C in an international observational cohort. Analysis of the first 614 patients was previously reported. In this propensity-weighted cohort study, clinical and outcome data from children with suspected or proven MIS-C were collected onto a web-based Research Electronic Data Capture database. After excluding neonates and incomplete or duplicate records, inverse probability weighting was used to compare primary treatments with intravenous immunoglobulin, intravenous immunoglobulin plus glucocorticoids, or glucocorticoids alone, using intravenous immunoglobulin as the reference treatment. Primary outcomes were a composite of inotropic or ventilator support from the second day after treatment initiation, or death, and time to improvement on an ordinal clinical severity scale. Secondary outcomes included treatment escalation, clinical deterioration, fever, and coronary artery aneurysm occurrence and resolution. This study is registered with the ISRCTN registry, ISRCTN69546370. FINDINGS: We enrolled 2101 children (aged 0 months to 19 years) with clinically diagnosed MIS-C from 39 countries between June 14, 2020, and April 25, 2022, and, following exclusions, 2009 patients were included for analysis (median age 8·0 years [IQR 4·2-11·4], 1191 [59·3%] male and 818 [40·7%] female, and 825 [41·1%] White). 680 (33·8%) patients received primary treatment with intravenous immunoglobulin, 698 (34·7%) with intravenous immunoglobulin plus glucocorticoids, 487 (24·2%) with glucocorticoids alone; 59 (2·9%) patients received other combinations, including biologicals, and 85 (4·2%) patients received no immunomodulators. There were no significant differences between treatments for primary outcomes for the 1586 patients with complete baseline and outcome data that were considered for primary analysis. Adjusted odds ratios for ventilation, inotropic support, or death were 1·09 (95% CI 0·75-1·58; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids and 0·93 (0·58-1·47; corrected p value=1·00) for glucocorticoids alone, versus intravenous immunoglobulin alone. Adjusted average hazard ratios for time to improvement were 1·04 (95% CI 0·91-1·20; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids, and 0·84 (0·70-1·00; corrected p value=0·22) for glucocorticoids alone, versus intravenous immunoglobulin alone. Treatment escalation was less frequent for intravenous immunoglobulin plus glucocorticoids (OR 0·15 [95% CI 0·11-0·20]; p<0·0001) and glucocorticoids alone (0·68 [0·50-0·93]; p=0·014) versus intravenous immunoglobulin alone. Persistent fever (from day 2 onward) was less common with intravenous immunoglobulin plus glucocorticoids compared with either intravenous immunoglobulin alone (OR 0·50 [95% CI 0·38-0·67]; p<0·0001) or glucocorticoids alone (0·63 [0·45-0·88]; p=0·0058). Coronary artery aneurysm occurrence and resolution did not differ significantly between treatment groups. INTERPRETATION: Recovery rates, including occurrence and resolution of coronary artery aneurysms, were similar for primary treatment with intravenous immunoglobulin when compared to glucocorticoids or intravenous immunoglobulin plus glucocorticoids. Initial treatment with glucocorticoids appears to be a safe alternative to immunoglobulin or combined therapy, and might be advantageous in view of the cost and limited availability of intravenous immunoglobulin in many countries. FUNDING: Imperial College London, the European Union's Horizon 2020, Wellcome Trust, the Medical Research Foundation, UK National Institute for Health and Care Research, and National Institutes of Health

PFAS-Contaminated Pesticides Applied near Public Supply Wells Disproportionately Impact Communities of Color in California

Contaminated drinking water from widespread environmental pollutants such as perfluoroalkyl and polyfluoroalkyl substances (PFAS) poses a rising threat to public health. PFAS monitoring in groundwater is limited and fails to consider pesticides found to contain PFAS as a potential contamination source. Given previous findings on the disproportionate exposure of communities of Color to both pesticides and PFAS, we investigated disparities in PFAS-contaminated pesticide applications in California based on community-level sociodemographic characteristics. We utilized statewide pesticide application data from the California Department of Pesticide Regulation and recently reported concentrations of PFAS chemicals detected in eight pesticide products to calculate the areal density of PFAS applied within 1 km of individual community water systems' (CWSs) supply wells. Spatial regression analyses suggest that statewide, CWSs that serve a greater proportion of Latinx and non-Latinx People of Color residents experience a greater areal density of PFAS applied and greater likelihood of PFAS application near their public supply wells. These results highlight agroecosystems as potentially important sources of PFAS in drinking water and identify areas that may be at risk of PFAS contamination and warrant additional PFAS monitoring and remediation

Evaluating harm associated with anti-malarial drugs: a survey of methods used by clinical researchers to elicit, assess and record participant-reported adverse events and related data.

BACKGROUND: Participant reports of medical histories, adverse events (AE) and non-study drugs are integral to evaluating harm in clinical research. However, interpreting or synthesizing results is complicated if studies use different methods for ascertaining and assessing these data. To explore how these data are obtained in malaria drug studies, a descriptive online survey of clinical researchers was conducted during 2012 and 2013. METHODS: The survey was advertised through e-mails, collaborators and at conferences. Questions aimed to capture the detail, rationale and application of methods used to obtain relevant data within various study designs and populations. Closed responses were analysed using proportions, open responses through identifying repeating ideas and underlying concepts. RESULTS: Of fifty-two respondents from 25 counties, 87% worked at an investigational site and 75% reported about an interventional study. Studies employed a range of methods to elicit, assess and record participant-reported AEs and related data. Questioning about AEs in 31% of interventional studies was a combination of general (open questions about health) and structured (reference to specific health-related items), 26% used structured only and 18% general only. No observational studies used general questioning alone. A minority incorporated pictorial tools. Rationales for the questioning approach included: standardization of assessment or data capture, specificity or comprehensiveness of data sought, avoidance of suggestion, feasibility, and understanding participants' perceptions. Most respondents considered the approach they reported was optimal, though several reconsidered this. Four AE grading, and three causality assessment approaches were reported. Combining general and structured questions about non-study drug use were considered useful for revealing and identifying specific medicines, while pictures could enhance reports, particularly in areas of low literacy. CONCLUSIONS: It is critical to evaluate the safety of anti-malarial drugs being deployed in large, diverse populations. Many studies would be suitable for contributing to a larger body of evidence for answering questions on harm. However this survey showed that various methods are used to obtain relevant data, which could influence study results. As the best practices for obtaining such data are unclear, anti-malarial clinical researchers should work towards consensus about the selection and/or design of optimal methods

Atomic spectrometry update: review of advances in atomic spectrometry and related techniques

This review covers developments in ‘Atomic Spectrometry’. It covers atomic emission, absorption, fluorescence and mass spectrometry, but excludes material on speciation and coupled techniques which is included in a separate review. It should be read in conjunction with the other related reviews in the series.1–6 A critical approach to the selection of material has been adopted, with only novel developments in instrumentation, techniques and methodology being included. Developments worthy of note include photochemical and electrochemical methods of vapour generation, single particle analysis using ICP-MS and the development of new methods for direct plasma generation in liquid samples. The use of MC-ICP-MS continues to grow in importance for isotope ratio measurements in fields as diverse as geochronology, nuclear forensics and biomedical research. Laser-based methods are also important in many fields, particularly for direct and stand-off analysis of solid samples