Automated data analysis of unstructured grey literature in health research: A mapping review.

The amount of grey literature and 'softer' intelligence from social media or websites is vast. Given the long lead-times of producing high-quality peer-reviewed health information, this is causing a demand for new ways to provide prompt input for secondary research. To our knowledge, this is the first review of automated data extraction methods or tools for health-related grey literature and soft data, with a focus on (semi)automating horizon scans, health technology assessments (HTA), evidence maps, or other literature reviews. We searched six databases to cover both health- and computer-science literature. After deduplication, 10% of the search results were screened by two reviewers, the remainder was single-screened up to an estimated 95% sensitivity; screening was stopped early after screening an additional 1000 results with no new includes. All full texts were retrieved, screened, and extracted by a single reviewer and 10% were checked in duplicate. We included 84 papers covering automation for health-related social media, internet fora, news, patents, government agencies and charities, or trial registers. From each paper, we extracted data about important functionalities for users of the tool or method; information about the level of support and reliability; and about practical challenges and research gaps. Poor availability of code, data, and usable tools leads to low transparency regarding performance and duplication of work. Financial implications, scalability, integration into downstream workflows, and meaningful evaluations should be carefully planned before starting to develop a tool, given the vast amounts of data and opportunities those tools offer to expedite research.

A narrative review of recent tools and innovations toward automating living systematic reviews and evidence syntheses.

Living reviews are an increasingly popular research paradigm. The purpose of a 'living' approach is to allow rapid collation, appraisal and synthesis of evolving evidence on an important research topic, enabling timely influence on patient care and public health policy. However, living reviews are time- and resource-intensive. The accumulation of new evidence and the possibility of developments within the review's research topic can introduce unique challenges into the living review workflow. To investigate the potential of software tools to support living systematic or rapid reviews, we present a narrative review informed by an examination of tools contained on the Systematic Review Toolbox website. We identified 11 tools with relevant functionalities and discuss the important features of these tools with respect to different steps of the living review workflow. Four tools (NestedKnowledge, SWIFT-ActiveScreener, DistillerSR, EPPI-Reviewer) covered multiple, successive steps of the review process, and the remaining tools addressed specific components of the workflow, including scoping and protocol formulation, reference retrieval, automated data extraction, write-up and dissemination of data. We identify several ways in which living reviews can be made more efficient and practical. Most of these focus on general workflow management, or automation through artificial intelligence and machine-learning, in the screening process. More sophisticated uses of automation mostly target living rapid reviews to increase the speed of production or evidence maps to broaden the scope of the map. We use a case study to highlight some of the barriers and challenges to incorporating tools into the living review workflow and processes. These include increased workload, the need for organisation, ensuring timely dissemination and challenges related to the development of bespoke automation tools to facilitate the review process. We describe how current end-user tools address these challenges, and which knowledge gaps remain that could be addressed by future tool development. Dedicated web presences for automatic dissemination of in-progress evidence updates, rather than solely relying on peer-reviewed journal publications, help to make the effort of a living evidence synthesis worthwhile. Despite offering basic living review functionalities, existing end-user tools could be further developed to be interoperable with other tools to support multiple workflow steps seamlessly, to address broader automatic evidence retrieval from a larger variety of sources, and to improve dissemination of evidence between review updates.

Provisioning Australian Seed Carrot Agroecosystems with Non-Floral Habitat Provides Oviposition Sites for Crop-Pollinating Diptera.

The addition of floral resources is a common intervention to support the adult life stages of key crop pollinators. Fly (Diptera) crop pollinators, however, typically do not require floral resources in their immature life stages and are likely not supported by this management intervention. Here, we deployed portable pools filled with habitat (decaying plant materials, soil, water) in seed carrot agroecosystems with the intention of providing reproduction sites for beneficial syrphid (tribe Eristalini) fly pollinators. Within 12 to 21 days after the pools were deployed, we found that the habitat pools supported the oviposition and larval development of two species of eristaline syrphid flies, Eristalis tenax (Linnaeus, 1758) and Eristalinus punctulatus (Macquart, 1847). Each habitat pool contained an average (±S.E.) of 547 ± 117 eristaline fly eggs and 50 ± 17 eristaline fly larvae. Additionally, we found significantly more eggs were laid on decaying plant stems and carrot roots compared to other locations within the pool habitat (e.g., on decaying carrot umbels, leaves, etc.). These results suggest that deploying habitat pools in agroecosystems can be a successful management intervention that rapidly facilitates fly pollinator reproduction. This method can be used to support future studies to determine if the addition of habitat resources on intensively cultivated farms increases flower visitation and crop pollination success by flies.

Anti-inflammatory IL-8 Regulation via an Advanced Drug Delivery System at the Oral Mucosa.

Oral inflammatory diseases are highly prevalent in the worldwide population. Topical treatment of inflammation is challenging due to dilution effects of saliva and crevicular fluid. Thus, there is a great medical need to develop smart anti-inflammatory drug delivery systems for mucosa treatment. We compared two promising anti-inflammatory dendritic poly(glycerol-caprolactone) sulfate (dPGS-PCL) polymers for their applicability to the oral mucosa. Using an ex vivo porcine tissue model, cell monolayers, and full-thickness 3D oral mucosal organoids, the polymers were evaluated for muco-adhesion, penetration, and anti-inflammatory properties. The biodegradable dPGS-PCL97 polymers adhered to and penetrated the masticatory mucosa within seconds. No effects on metabolic activity and cell proliferation were found. dPGS-PCL97 revealed a significant downregulation of pro-inflammatory cytokines with a clear preference for IL-8 in cell monolayers and mucosal organoids. Thus, dPGS-PCL97 exhibits excellent properties for topical anti-inflammatory therapy, suggesting new therapeutic avenues in the treatment of oral inflammatory diseases.

Has the COVID-19 pandemic influenced suicide rates differentially according to socioeconomic indices and ethnicity? More evidence is needed globally.

The COVID-19 pandemic has harmed many people's mental health globally. Whilst the evidence generated thus far from high-income countries regarding the pandemic's impact on suicide rates is generally reassuring, we know little about its influence on this outcome in lower- and middle-income countries or among marginalised and disadvantaged people. There are some signals for concern regarding the pandemic's potentially unequal impact on suicide rates, with some of the affected demographic subgroups and regions being at elevated risk before the pandemic began. However, the evidence-base for this topic is currently sparse, and studies conducted to date have generally not taken account of pre-pandemic temporal trends. The collection of accurate, complete and comparable data on suicide rate trends in ethnic minority and low-income groups should be prioritised. The vulnerability of low-income groups will likely be exacerbated further by the current energy supply and cost-of-living crises in many countries. It is therefore crucial that reassuring messaging highlighting the stability of suicide rates during the pandemic does not lead to complacency among policymakers.

The impact of the COVID-19 pandemic on presentations to health services following self-harm: systematic review.

BACKGROUND: Evidence on the impact of the pandemic on healthcare presentations for self-harm has accumulated rapidly. However, existing reviews do not include studies published beyond 2020. AIMS: To systematically review evidence on presentations to health services following self-harm during the COVID-19 pandemic. METHOD: A comprehensive search of databases (WHO COVID-19 database; Medline; medRxiv; Scopus; PsyRxiv; SocArXiv; bioRxiv; COVID-19 Open Research Dataset, PubMed) was conducted. Studies published from 1 January 2020 to 7 September 2021 were included. Study quality was assessed with a critical appraisal tool. RESULTS: Fifty-one studies were included: 57% (29/51) were rated as 'low' quality, 31% (16/51) as 'moderate' and 12% (6/51) as 'high-moderate'. Most evidence (84%, 43/51) was from high-income countries. A total of 47% (24/51) of studies reported reductions in presentation frequency, including all six rated as high-moderate quality, which reported reductions of 17-56%. Settings treating higher lethality self-harm were overrepresented among studies reporting increased demand. Two of the three higher-quality studies including study observation months from 2021 reported reductions in self-harm presentations. Evidence from 2021 suggests increased numbers of presentations among adolescents, particularly girls. CONCLUSIONS: Sustained reductions in numbers of self-harm presentations were seen into the first half of 2021, although this evidence is based on a relatively small number of higher-quality studies. Evidence from low- and middle-income countries is lacking. Increased numbers of presentations among adolescents, particularly girls, into 2021 is concerning. Findings may reflect changes in thresholds for help-seeking, use of alternative sources of support and variable effects of the pandemic across groups.

SARS-CoV-2 Infection and the Risk of Suicidal and Self-Harm Thoughts and Behaviour: A Systematic Review.

OBJECTIVE: The COVID-19 pandemic has had a complex impact on risks of suicide and non-fatal self-harm worldwide with some evidence of increased risk in specific populations including women, young people, and people from ethnic minority backgrounds. This review aims to systematically address whether SARS-CoV-2 infection and/or COVID-19 disease confer elevated risk directly. METHOD: As part of a larger Living Systematic Review examining self-harm and suicide during the pandemic, automated daily searches using a broad list of keywords were performed on a comprehensive set of databases with data from relevant articles published between January 1, 2020 and July 18, 2021. Eligibility criteria for our present review included studies investigating suicide and/or self-harm in people infected with SARS-CoV-2 with or without manifestations of COVID-19 disease with a comparator group who did not have infection or disease. Suicidal and self-harm thoughts and behaviour (STBs) were outcomes of interest. Studies were excluded if they reported data for people who only had potential infection/disease without a confirmed exposure, clinical/molecular diagnosis or self-report of a positive SARS-CoV-2 test result. Studies of news reports, treatment studies, and ecological studies examining rates of both SARS-CoV-2 infections and suicide/self-harm rates across a region were also excluded. RESULTS: We identified 12 studies examining STBs in nine distinct samples of people with SARS-CoV-2. These studies, which investigated STBs in the general population and in subpopulations, including healthcare workers, generally found positive associations between SARS-CoV-2 infection and/or COVID-19 disease and subsequent suicidal/self-harm thoughts and suicidal/self-harm behaviour. CONCLUSIONS: This review identified some evidence that infection with SARS-CoV-2 and/or COVID-19 disease may be associated with increased risks for suicidal and self-harm thoughts and behaviours but a causal link cannot be inferred. Further research with longer follow-up periods is required to confirm these findings and to establish whether these associations are causal.

Diagnostic test accuracy and cost-effectiveness of tests for codeletion of chromosomal arms 1p and 19q in people with glioma.

BACKGROUND: Complete deletion of both the short arm of chromosome 1 (1p) and the long arm of chromosome 19 (19q), known as 1p/19q codeletion, is a mutation that can occur in gliomas. It occurs in a type of glioma known as oligodendroglioma and its higher grade counterpart known as anaplastic oligodendroglioma. Detection of 1p/19q codeletion in gliomas is important because, together with another mutation in an enzyme known as isocitrate dehydrogenase, it is needed to make the diagnosis of an oligodendroglioma. Presence of 1p/19q codeletion also informs patient prognosis and prediction of the best drug treatment. The main two tests in use are fluorescent in situ hybridisation (FISH) and polymerase chain reaction (PCR)-based loss of heterozygosity (LOH) assays (also known as PCR-based short tandem repeat or microsatellite analysis). Many other tests are available. None of the tests is perfect, although PCR-based LOH is expected to have very high sensitivity. OBJECTIVES: To estimate the sensitivity and specificity and cost-effectiveness of different deoxyribonucleic acid (DNA)-based techniques for determining 1p/19q codeletion status in glioma. SEARCH METHODS: We searched MEDLINE, Embase and BIOSIS up to July 2019. There were no restrictions based on language or date of publication. We sought economic evaluation studies from the results of this search and using the National Health Service Economic Evaluation Database. SELECTION CRITERIA: We included cross-sectional studies in adults with glioma or any subtype of glioma, presenting raw data or cross-tabulations of two or more DNA-based tests for 1p/19q codeletion. We also sought economic evaluations of these tests. DATA COLLECTION AND ANALYSIS: We followed procedures outlined in the Cochrane Handbook for Diagnostic Test Accuracy Reviews. Two review authors independently screened titles/abstracts/full texts, performed data extraction, and undertook applicability and risk of bias assessments using QUADAS-2. Meta-analyses used the hierarchical summary ROC model to estimate and compare test accuracy. We used FISH and PCR-based LOH as alternate reference standards to examine how tests compared with those in common use, and conducted a latent class analysis comparing FISH and PCR-based LOH. We constructed an economic model to evaluate cost-effectiveness. MAIN RESULTS: We included 53 studies examining: PCR-based LOH, FISH, single nucleotide polymorphism (SNP) array, next-generation sequencing (NGS), comparative genomic hybridisation (CGH), array comparative genomic hybridisation (aCGH), multiplex-ligation-dependent probe amplification (MLPA), real-time PCR, chromogenic in situ hybridisation (CISH), mass spectrometry (MS), restriction fragment length polymorphism (RFLP) analysis, G-banding, methylation array and NanoString. Risk of bias was low for only one study; most gave us concerns about how patients were selected or about missing data. We had applicability concerns about many of the studies because only patients with specific subtypes of glioma were included. 1520 participants contributed to analyses using FISH as the reference, 1304 participants to analyses involving PCR-based LOH as the reference and 262 participants to analyses of comparisons between methods from studies not including FISH or PCR-based LOH. Most evidence was available for comparison of FISH with PCR-based LOH (15 studies, 915 participants): PCR-based LOH detected 94% of FISH-determined codeletions (95% credible interval (CrI) 83% to 98%) and FISH detected 91% of codeletions determined by PCR-based LOH (CrI 78% to 97%). Of tumours determined not to have a deletion by FISH, 94% (CrI 87% to 98%) had a deletion detected by PCR-based LOH, and of those determined not to have a deletion by PCR-based LOH, 96% (CrI 90% to 99%) had a deletion detected by FISH. The latent class analysis suggested that PCR-based LOH may be slightly more accurate than FISH. Most other techniques appeared to have high sensitivity (i.e. produced few false-negative results) for detection of 1p/19q codeletion when either FISH or PCR-based LOH was considered as the reference standard, although there was limited evidence. There was some indication of differences in specificity (false-positive rate) with some techniques. Both NGS and SNP array had high specificity when considered against FISH as the reference standard (NGS: 6 studies, 243 participants; SNP: 6 studies, 111 participants), although we rated certainty in the evidence as low or very low. NGS and SNP array also had high specificity when PCR-based LOH was considered the reference standard, although with much more uncertainty as these results were based on fewer studies (just one study with 49 participants for NGS and two studies with 33 participants for SNP array). G-banding had low sensitivity and specificity when PCR-based LOH was the reference standard. Although MS had very high sensitivity and specificity when both FISH and PCR-based LOH were considered the reference standard, these results were based on only one study with a small number of participants. Real-time PCR also showed high specificity with FISH as a reference standard, although there were only two studies including 40 participants. We found no relevant economic evaluations. Our economic model using FISH as the reference standard suggested that the resource-optimising test depends on which measure of diagnostic accuracy is most important. With FISH as the reference standard, MLPA is likely to be cost-effective if society was willing to pay GBP 1000 or less for a true positive detected. However, as the value placed on a true positive increased, CISH was most cost-effective. Findings differed when the outcome measure changed to either true negative detected or correct diagnosis. When PCR-based LOH was used as the reference standard, MLPA was likely to be cost-effective for all measures of diagnostic accuracy at lower threshold values for willingness to pay. However, as the threshold values increased, none of the tests were clearly more likely to be considered cost-effective. AUTHORS' CONCLUSIONS: In our review, most techniques (except G-banding) appeared to have good sensitivity (few false negatives) for detection of 1p/19q codeletions in glioma against both FISH and PCR-based LOH as a reference standard. However, we judged the certainty of the evidence low or very low for all the tests. There are possible differences in specificity, with both NGS and SNP array having high specificity (fewer false positives) for 1p/19q codeletion when considered against FISH as the reference standard. The economic analysis should be interpreted with caution due to the small number of studies.

Diagnostic accuracy of 1p/19q codeletion tests in oligodendroglioma: A comprehensive meta-analysis based on a Cochrane systematic review.

Codeletion of chromosomal arms 1p and 19q, in conjunction with a mutation in the isocitrate dehydrogenase 1 or 2 gene, is the molecular diagnostic criterion for oligodendroglioma, IDH mutant and 1p/19q codeleted. 1p/19q codeletion is a diagnostic marker and allows prognostication and prediction of the best drug response within IDH-mutant tumours. We performed a Cochrane review and simple economic analysis to establish the most sensitive, specific and cost-effective techniques for determining 1p/19q codeletion status. Fluorescent in situ hybridisation (FISH) and polymerase chain reaction (PCR)-based loss of heterozygosity (LOH) test methods were considered as reference standard. Most techniques (FISH, chromogenic in situ hybridisation [CISH], PCR, real-time PCR, multiplex ligation-dependent probe amplification [MLPA], single nucleotide polymorphism [SNP] array, comparative genomic hybridisation [CGH], array CGH, next-generation sequencing [NGS], mass spectrometry and NanoString) showed good sensitivity (few false negatives) for detection of 1p/19q codeletions in glioma, irrespective of whether FISH or PCR-based LOH was used as the reference standard. Both NGS and SNP array had a high specificity (fewer false positives) for 1p/19q codeletion when considered against FISH as the reference standard. Our findings suggest that G banding is not a suitable test for 1p/19q analysis. Within these limits, considering cost per diagnosis and using FISH as a reference, MLPA was marginally more cost-effective than other tests, although these economic analyses were limited by the range of available parameters, time horizon and data from multiple healthcare organisations.

Suicide and self-harm in low- and middle- income countries during the COVID-19 pandemic: A systematic review.

There is widespread concern over the potential impact of the COVID-19 pandemic on suicide and self-harm globally, particularly in low- and middle-income countries (LMIC) where the burden of these behaviours is greatest. We synthesised the evidence from the published literature on the impact of the pandemic on suicide and self-harm in LMIC. This review is nested within a living systematic review (PROSPERO ID CRD42020183326) that continuously identifies published evidence (all languages) through a comprehensive automated search of multiple databases (PubMed; Scopus; medRxiv, PsyArXiv; SocArXiv; bioRxiv; the WHO COVID-19 database; and the COVID-19 Open Research Dataset by Semantic Scholar (up to 11/2020), including data from Microsoft Academic, Elsevier, arXiv and PubMed Central.) All articles identified by the 4th August 2021 were screened. Papers reporting on data from a LMIC and presenting evidence on the impact of the pandemic on suicide or self-harm were included. Methodological quality was assessed using an appropriate tool, and a narrative synthesis presented. A total of 22 studies from LMIC were identified representing data from 12 countries. There was an absence of data from Africa, the Pacific, and the Caribbean. The reviewed studies mostly report on the early months of COVID-19 and were generally methodologically poor. Few studies directly assessed the impact of the pandemic. The most robust evidence, from time-series studies, indicate either a reduction or no change in suicide and self-harm behaviour. As LMIC continue to experience repeated waves of the virus and increased associated mortality, against a backdrop of vaccine inaccessibility and limited welfare support, continued efforts are needed to track the indirect impact of the pandemic on suicide and self-harm in these countries.

Systematic review of the impact of the COVID-19 pandemic on suicidal behaviour amongst health and social care workers across the world.

BACKGROUND: The COVID-19 pandemic has had an impact on the mental health of healthcare and social care workers, and its potential effect on suicidal thoughts and behaviour is of particular concern. METHODS: This systematic review identified and appraised the published literature that has reported on the impact of COVID-19 on suicidal thoughts and behaviour and self-harm amongst healthcare and social care workers worldwide up to May 31, 2021. RESULTS: Out of 37 potentially relevant papers identified, ten met our eligibility criteria. Our review has highlighted that the impact of COVID-19 has varied as a function of setting, working relationships, occupational roles, and psychiatric comorbidities. LIMITATIONS: There have been no completed cohort studies comparing pre- and post-pandemic suicidal thoughts and behaviours. It is possible some papers may have been missed in the search. CONCLUSIONS: The current quality of evidence pertaining to suicidal behaviour in healthcare workers is poor, and evidence is entirely absent for those working in social care. The clinical relevance of this work is to bring attention to what evidence exists, and to encourage, in practice, proactive approaches to interventions for improving healthcare and social care worker mental health.

MGMT promoter methylation testing to predict overall survival in people with glioblastoma treated with temozolomide: a comprehensive meta-analysis based on a Cochrane Systematic Review.

BACKGROUND: The DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) causes resistance of tumor cells to alkylating agents. It is a predictive biomarker in high-grade gliomas treated with temozolomide, however, there is no consensus on which test method, methylation sites, and cutoff values to use. METHODS: We performed a Cochrane Review to examine studies using different techniques to measure MGMT and predict survival in glioblastoma patients treated with temozolomide. Eligible longitudinal studies included (i) adults with glioblastoma treated with temozolomide with or without radiotherapy, or surgery; (ii) where MGMT status was determined in tumor tissue, and assessed by 1 or more technique; and (iii) where overall survival was an outcome parameter, with sufficient information to estimate hazard ratios (HRs). Two or more methods were compared in 32 independent cohorts with 3474 patients. RESULTS: Methylation-specific PCR (MSP) and pyrosequencing (PSQ) techniques were more prognostic than immunohistochemistry for MGMT protein, and PSQ is a slightly better predictor than MSP. CONCLUSIONS: We cannot draw strong conclusions about use of frozen tissue vs formalin-fixed paraffin-embedded in MSP and PSQ. Also, our meta-analysis does not provide strong evidence about the best CpG sites or threshold. MSP has been studied mainly for CpG sites 76-80 and 84-87 and PSQ at CpG sites ranging from 72 to 95. A cutoff threshold of 9% for CpG sites 74-78 performed better than higher thresholds of 28% or 29% in 2 of the 3 good-quality studies. About 190 studies were identified presenting HRs from survival analysis in patients in which MGMT methylation was measured by 1 technique only.

Prognostic value of test(s) for O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation for predicting overall survival in people with glioblastoma treated with temozolomide.

BACKGROUND: Glioblastoma is an aggressive form of brain cancer. Approximately five in 100 people with glioblastoma survive for five years past diagnosis. Glioblastomas that have a particular modification to their DNA (called methylation) in a particular region (the O6-methylguanine-DNA methyltransferase (MGMT) promoter) respond better to treatment with chemotherapy using a drug called temozolomide. OBJECTIVES: To determine which method for assessing MGMT methylation status best predicts overall survival in people diagnosed with glioblastoma who are treated with temozolomide. SEARCH METHODS: We searched MEDLINE, Embase, BIOSIS, Web of Science Conference Proceedings Citation Index to December 2018, and examined reference lists. For economic evaluation studies, we additionally searched NHS Economic Evaluation Database (EED) up to December 2014. SELECTION CRITERIA: Eligible studies were longitudinal (cohort) studies of adults with diagnosed glioblastoma treated with temozolomide with/without radiotherapy/surgery. Studies had to have related MGMT status in tumour tissue (assessed by one or more method) with overall survival and presented results as hazard ratios or with sufficient information (e.g. Kaplan-Meier curves) for us to estimate hazard ratios. We focused mainly on studies comparing two or more methods, and listed brief details of articles that examined a single method of measuring MGMT promoter methylation. We also sought economic evaluations conducted alongside trials, modelling studies and cost analysis. DATA COLLECTION AND ANALYSIS: Two review authors independently undertook all steps of the identification and data extraction process for multiple-method studies. We assessed risk of bias and applicability using our own modified and extended version of the QUality In Prognosis Studies (QUIPS) tool. We compared different techniques, exact promoter regions (5'-cytosine-phosphate-guanine-3' (CpG) sites) and thresholds for interpretation within studies by examining hazard ratios. We performed meta-analyses for comparisons of the three most commonly examined methods (immunohistochemistry (IHC), methylation-specific polymerase chain reaction (MSP) and pyrosequencing (PSQ)), with ratios of hazard ratios (RHR), using an imputed value of the correlation between results based on the same individuals. MAIN RESULTS: We included 32 independent cohorts involving 3474 people that compared two or more methods. We found evidence that MSP (CpG sites 76 to 80 and 84 to 87) is more prognostic than IHC for MGMT protein at varying thresholds (RHR 1.31, 95% confidence interval (CI) 1.01 to 1.71). We also found evidence that PSQ is more prognostic than IHC for MGMT protein at various thresholds (RHR 1.36, 95% CI 1.01 to 1.84). The data suggest that PSQ (mainly at CpG sites 74 to 78, using various thresholds) is slightly more prognostic than MSP at sites 76 to 80 and 84 to 87 (RHR 1.14, 95% CI 0.87 to 1.48). Many variants of PSQ have been compared, although we did not see any strong and consistent messages from the results. Targeting multiple CpG sites is likely to be more prognostic than targeting just one. In addition, we identified and summarised 190 articles describing a single method for measuring MGMT promoter methylation status. AUTHORS' CONCLUSIONS: PSQ and MSP appear more prognostic for overall survival than IHC. Strong evidence is not available to draw conclusions with confidence about the best CpG sites or thresholds for quantitative methods. MSP has been studied mainly for CpG sites 76 to 80 and 84 to 87 and PSQ at CpG sites ranging from 72 to 95. A threshold of 9% for CpG sites 74 to 78 performed better than higher thresholds of 28% or 29% in two of three good-quality studies making such comparisons.

High-throughput planar solid-phase extraction coupled to orbitrap high-resolution mass spectrometry via the autoTLC-MS interface for screening of 66 multi-class antibiotic residues in food of animal origin.

Antibiotic residues in food pose a major threat to the health of humans and animals worldwide. Their trace-level analysis is still too time- and cost-intensive to be adequately covered in routine analysis. Thus, a new high-throughput planar solid-phase extraction method has been developed for rapid screening of 66 antibiotics. Via simple clicks on the image, the autoTLC-MS interface automatically eluted the target analyte zones directly into an orbitrap high-resolution mass spectrometer operated in the variable data-independent acquisition mode. Muscle tissue, cow milk and chicken eggs were analyzed regarding nine different antibiotic classes, including sulfonamides, diaminopyrimidines, lincosamides, pleuromutilins, macrolides, cephalosporins, penicillins, amphenicols and nitroimidazoles. The planar clean-up took 7 min per sample, which is 5-fold faster than the routine state-of-the-art. The screening method has been validated for one representative of each class according to the European Commission Decision 2002/657/EC. Most analytes were successfully detected at half of their required maximum residue limit.

Data extraction methods for systematic review (semi)automation: Update of a living systematic review.

Background: The reliable and usable (semi)automation of data extraction can support the field of systematic review by reducing the workload required to gather information about the conduct and results of the included studies. This living systematic review examines published approaches for data extraction from reports of clinical studies. Methods: We systematically and continually search PubMed, ACL Anthology, arXiv, OpenAlex via EPPI-Reviewer, and the  dblp computer science bibliography. Full text screening and data extraction are conducted within an open-source living systematic review application created for the purpose of this review. This living review update includes publications up to December 2022 and OpenAlex content up to March 2023. Results: 76 publications are included in this review. Of these, 64 (84%) of the publications addressed extraction of data from abstracts, while 19 (25%) used full texts. A total of 71 (93%) publications developed classifiers for randomised controlled trials. Over 30 entities were extracted, with PICOs (population, intervention, comparator, outcome) being the most frequently extracted. Data are available from 25 (33%), and code from 30 (39%) publications. Six (8%) implemented publicly available tools Conclusions: This living systematic review presents an overview of (semi)automated data-extraction literature of interest to different types of literature review. We identified a broad evidence base of publications describing data extraction for interventional reviews and a small number of publications extracting epidemiological or diagnostic accuracy data. Between review updates, trends for sharing data and code increased strongly: in the base-review, data and code were available for 13 and 19% respectively, these numbers increased to 78 and 87% within the 23 new publications. Compared with the base-review, we observed another research trend, away from straightforward data extraction and towards additionally extracting relations between entities or automatic text summarisation. With this living review we aim to review the literature continually.

Improving plant drought tolerance and growth under water limitation through combinatorial engineering of signalling networks.

Agriculture is by far the biggest water consumer on our planet, accounting for 70 per cent of all freshwater withdrawals. Climate change and a growing world population increase pressure on agriculture to use water more efficiently ('more crop per drop'). Water-use efficiency (WUE) and drought tolerance of crops are complex traits that are determined by many physiological processes whose interplay is not well understood. Here, we describe a combinatorial engineering approach to optimize signalling networks involved in the control of stress tolerance. Screening a large population of combinatorially transformed plant lines, we identified a combination of calcium-dependent protein kinase genes that confers enhanced drought stress tolerance and improved growth under water-limiting conditions. Targeted introduction of this gene combination into plants increased plant survival under drought and enhanced growth under water-limited conditions. Our work provides an efficient strategy for engineering complex signalling networks to improve plant performance under adverse environmental conditions, which does not depend on prior understanding of network function.

Risk and Protective Factors in the COVID-19 Pandemic: A Rapid Evidence Map.

Background: Given the worldwide spread of the 2019 Novel Coronavirus (COVID-19), there is an urgent need to identify risk and protective factors and expose areas of insufficient understanding. Emerging tools, such as the Rapid Evidence Map (rEM), are being developed to systematically characterize large collections of scientific literature. We sought to generate an rEM of risk and protective factors to comprehensively inform areas that impact COVID-19 outcomes for different sub-populations in order to better protect the public. Methods: We developed a protocol that includes a study goal, study questions, a PECO statement, and a process for screening literature by combining semi-automated machine learning with the expertise of our review team. We applied this protocol to reports within the COVID-19 Open Research Dataset (CORD-19) that were published in early 2020. SWIFT-Active Screener was used to prioritize records according to pre-defined inclusion criteria. Relevant studies were categorized by risk and protective status; susceptibility category (Behavioral, Physiological, Demographic, and Environmental); and affected sub-populations. Using tagged studies, we created an rEM for COVID-19 susceptibility that reveals: (1) current lines of evidence; (2) knowledge gaps; and (3) areas that may benefit from systematic review. Results: We imported 4,330 titles and abstracts from CORD-19. After screening 3,521 of these to achieve 99% estimated recall, 217 relevant studies were identified. Most included studies concerned the impact of underlying comorbidities (Physiological); age and gender (Demographic); and social factors (Environmental) on COVID-19 outcomes. Among the relevant studies, older males with comorbidities were commonly reported to have the poorest outcomes. We noted a paucity of COVID-19 studies among children and susceptible sub-groups, including pregnant women, racial minorities, refugees/migrants, and healthcare workers, with few studies examining protective factors. Conclusion: Using rEM analysis, we synthesized the recent body of evidence related to COVID-19 risk and protective factors. The results provide a comprehensive tool for rapidly elucidating COVID-19 susceptibility patterns and identifying resource-rich/resource-poor areas of research that may benefit from future investigation as the pandemic evolves.

Data extraction methods for systematic review (semi)automation: A living review protocol.

Background: Researchers in evidence-based medicine cannot keep up with the amounts of both old and newly published primary research articles. Conducting and updating of systematic reviews is time-consuming. In practice, data extraction is one of the most complex tasks in this process. Exponential improvements in computational processing speed and data storage are fostering the development of data extraction models and algorithms. This, in combination with quicker pathways to publication, led to a large landscape of tools and methods for data extraction tasks. Objective: To review published methods and tools for data extraction to (semi)automate the systematic reviewing process. Methods: We propose to conduct a living review. With this methodology we aim to do monthly search updates, as well as bi-annual review updates if new evidence permits it. In a cross-sectional analysis we will extract methodological characteristics and assess the quality of reporting in our included papers. Conclusions: We aim to increase transparency in the reporting and assessment of machine learning technologies to the benefit of data scientists, systematic reviewers and funders of health research. This living review will help to reduce duplicate efforts by data scientists who develop data extraction methods. It will also serve to inform systematic reviewers about possibilities to support their data extraction.

Adding evidence of the effects of treatments into relevant Wikipedia pages: a randomised trial.

OBJECTIVES: To investigate the effects of adding high-grade quantitative evidence of outcomes of treatments into relevant Wikipedia pages on further information-seeking behaviour by the use of routinely collected data. SETTING: Wikipedia, Cochrane summary pages and the Cochrane Library. DESIGN: Randomised trial. PARTICIPANTS: Wikipedia pages which were highly relevant to up-to-date Cochrane Schizophrenia systematic reviews that contained a Summary of Findings table. INTERVENTIONS: Eligible Wikipedia pages in the intervention group were seeded with tables of best evidence of the effects of care and hyperlinks to the source Cochrane review. Eligible Wikipedia pages in the control group were left unchanged. MAIN OUTCOME MEASURES: Routinely collected data on access to the full text and summary web page (after 12 months). RESULTS: We randomised 70 Wikipedia pages (100% follow-up). Six of the 35 Wikipedia pages in the intervention group had the tabular format deleted during the study but all pages continued to report the same data within the text. There was no evidence of effect on either of the coprimary outcomes: full-text access adjusted ratio of geometric means 1.30, 95% CI: 0.71 to 2.38; page views 1.14, 95% CI: 0.6 to 2.13. Results were similar for all other outcomes, with exception of Altmetric score for which there was some evidence of clear effect (1.36, 95% CI: 1.05 to 1.78). CONCLUSIONS: The pursuit of fair balance within Wikipedia healthcare pages is impressive and its reach unsurpassed. For every person who sought and clicked the reference on the 'intervention' Wikipedia page to seek more information (the primary outcome), many more are likely to have been informed by the page alone. Enriching Wikipedia content is, potentially, a powerful way to improve health literacy and it is possible to test the effects of seeding pages with evidence. This trial should be replicated, expanded and developed. TRIAL REGISTRATION NUMBER: IRCT2017070330407N2.

The impact of the COVID-19 pandemic on self-harm and suicidal behaviour: update of living systematic review.

Background: The COVID-19 pandemic has caused considerable morbidity, mortality and disruption to people's lives around the world. There are concerns that rates of suicide and suicidal behaviour may rise during and in its aftermath. Our living systematic review synthesises findings from emerging literature on incidence and prevalence of suicidal behaviour as well as suicide prevention efforts in relation to COVID-19, with this iteration synthesising relevant evidence up to 19 th October 2020. Method:  Automated daily searches feed into a web-based database with screening and data extraction functionalities. Eligibility criteria include incidence/prevalence of suicidal behaviour, exposure-outcome relationships and effects of interventions in relation to the COVID-19 pandemic. Outcomes of interest are suicide, self-harm or attempted suicide and suicidal thoughts. No restrictions are placed on language or study type, except for single-person case reports. We exclude one-off cross-sectional studies without either pre-pandemic measures or comparisons of COVID-19 positive vs. unaffected individuals. Results: Searches identified 6,226 articles. Seventy-eight articles met our inclusion criteria. We identified a further 64 relevant cross-sectional studies that did not meet our revised inclusion criteria. Thirty-four articles were not peer-reviewed (e.g. research letters, pre-prints). All articles were based on observational studies. There was no consistent evidence of a rise in suicide but many studies noted adverse economic effects were evolving. There was evidence of a rise in community distress, fall in hospital presentation for suicidal behaviour and early evidence of an increased frequency of suicidal thoughts in those who had become infected with COVID-19. Conclusions:  Research evidence of the impact of COVID-19 on suicidal behaviour is accumulating rapidly. This living review provides a regular synthesis of the most up-to-date research evidence to guide public health and clinical policy to mitigate the impact of COVID-19 on suicide risk as the longer term impacts of the pandemic on suicide risk are researched.