Identifying an intervention\'s core components is indispensable to gauging whether an intervention is implemented with fidelity and/or is modified; it is often a multi-stage process, starting with the first stage of identifying an initial set of core components that are gradually refined. This first stage of identifying initial core components has not been thoroughly examined. Without a clear set of steps to follow, interventions may vary in the rigor and thought applied to identifying their initial core components. We devised the CORE (Consensus on Relevant Elements) approach to synthesize opinions of intervention developers/implementers to identify an intervention\'s initial core components, particularly applicable to innovative interventions. We applied CORE to a peer-based intervention that aids military veterans with post-incarceration community reintegration. Our CORE application involved four intervention developers/implementers and two moderators to facilitate the seven CORE steps. Our CORE application had two iterations, moving through Steps 1 (individual core component suggestions) through 7 (group discussion for consensus), then repeating Steps 4 (consolidation of component definitions) through 7. This resulted in 18 consensus-reached initial core components of the peer-based intervention, down from the 60 that the developers/implementers individually suggested at Step 1. Removed components were deemed to not threaten the intervention\'s effectiveness even if absent. CORE contributes to filling a critical gap regarding identifying an intervention\'s initial core components (so that the identified components can be subsequently refined), by providing concrete steps for synthesizing the knowledge of an intervention\'s developers/implementers. Future research should examine CORE\'s utility across various interventions and implementation settings.

As the number of introduced species keeps increasing unabatedly, identifying and prioritising current and potential Invasive Alien Species (IAS) has become essential to manage them. Horizon Scanning (HS), defined as an exploration of potential threats, is considered a fundamental component of IAS management. By combining scientific knowledge on taxa with expert opinion, we identified the most relevant aquatic IAS in the Iberian Peninsula, i.e., those with the greatest geographic extent (or probability of introduction), severe ecological, economic and human health impacts, greatest difficulty and acceptability of management. We highlighted the 126 most relevant IAS already present in Iberian inland waters (i.e., Concern list) and 89 with a high probability of being introduced in the near future (i.e., Alert list), of which 24 and 10 IAS, respectively, were considered as a management priority after receiving the highest scores in the expert assessment (i.e., top-ranked IAS). In both lists, aquatic IAS belonging to the four thematic groups (plants, freshwater invertebrates, estuarine invertebrates, and vertebrates) were identified as having been introduced through various pathways from different regions of the world and classified according to their main functional feeding groups. Also, the latest update of the list of IAS of Union concern pursuant to Regulation (EU) No 1143/2014 includes only 12 top-ranked IAS identified for the Iberian Peninsula, while the national lists incorporate the vast majority of them. This fact underlines the great importance of taxa prioritisation exercises at biogeographical scales as a step prior to risk analyses and their inclusion in national lists. This HS provides a robust assessment and a cost-effective strategy for decision-makers and stakeholders to prioritise the use of limited resources for IAS prevention and management. Although applied at a transnational level in a European biodiversity hotspot, this approach is designed for potential application at any geographical or administrative scale, including the continental one.

Affitins constitute a class of small proteins belonging to Sul7d family, which, in microorganisms such as Sulfolobus acidocaldarius, bind DNA preventing its denaturation. Thanks to their stability and small size (60-66 residues in length) they have been considered as ideal candidates for engineering and have been used for more than 10 years now, for different applications. The individuation of a mutant able to recognize a specific target does not imply the knowledge of the binding geometry between the two proteins. However, its identification is of undoubted importance but not always experimentally accessible. For this reason, computational approaches such as protein-protein docking can be helpful for an initial structural characterization of the complex. This method, which produces tens of putative binding geometries ordered according to a binding score, needs to be followed by a further reranking procedure for finding the most plausible one. In the present paper, we use the server ClusPro for generating docking models of affitins with different protein partners whose experimental structures are available in the Protein Data Bank. Then, we apply two protocols for reranking the docking models. The first one investigates their stability by means of Molecular Dynamics simulations; the second one, instead, compares the docking models with the interacting residues predicted by the Matrix of Local Coupling Energies method. Results show that the more efficient way to deal with the reranking problem is to consider the information given by the two protocols together, i.e. employing a consensus approach.

To develop a consensus nomenclature for reporting OCT angiography (OCTA) findings in retinal vascular disease (e.g., diabetic retinopathy, retinal vein occlusion) by international experts.
Delphi-based survey.
Twenty-five retinal vascular disease and OCTA imaging experts.
A Delphi method of consensus development was used, comprising 2 rounds of online questionnaires, followed by a face-to-face meeting conducted virtually. Twenty-five experts in retinal vascular disease and retinal OCTA imaging were selected to constitute the OCTA Nomenclature in Delphi Study Group for retinal vascular disease. The 4 main areas of consensus were: definition of the parameters of \"wide-field (WF)\" OCTA, measurement of decreased vascular flow on conventional and WF-OCTA, nomenclature of OCTA findings, and OCTA in retinal vascular disease management and staging. The study end point was defined by the degree of consensus for each question: \"strong consensus\" was defined as ≥85% agreement, \"consensus\" as 80% to 84%, and \"near consensus\" as 70% to 79%.
Consensus and near consensus on OCTA nomenclature in retinal vascular disease.
A consensus was reached that a meaningful change in percentage of flow on WF-OCTA imaging should be an increase or decrease ≥30% of the absolute imaged area of flow signal and that a \"large area\" of WF-OCTA reduced flow signal should also be defined as ≥30% of the absolute imaged area. The presence of new vessels and intraretinal microvascular abnormalities, the foveal avascular zone parameters, the presence and amount of \"no-flow areas,\" and the assessment of vessel density in various retinal layers should be added for the staging and classification of diabetic retinopathy. Decreased flow ≥30% of the absolute imaged area should define an ischemic central retinal vein occlusion. Several other items did not meet consensus requirements or were rejected in the final discussion round.
This study provides international consensus recommendations for reporting OCTA findings in retinal vascular disease, which may help to improve the interpretability and description in clinic and clinical trials. Further validation in these settings is warranted and ongoing. Efforts are continuing to address unresolved questions.

The current practice of quantifying cerebrospinal fluid (CSF) biomarkers as an aid in the diagnosis of Alzheimer\'s disease (AD) varies from center to center. For a same biochemical profile, interpretation and reporting of results may differ, which can lead to misunderstandings and raises questions about the commutability of tests.
We obtained a description of (pre-)analytical protocols and sample reports from 40 centers worldwide. A consensus approach allowed us to propose harmonized comments corresponding to the different CSF biomarker profiles observed in patients.
The (pre-)analytical procedures were similar between centers. There was considerable heterogeneity in cutoff definitions and report comments. We therefore identified and selected by consensus the most accurate and informative comments regarding the interpretation of CSF biomarkers in the context of AD diagnosis.
This is the first time that harmonized reports are proposed across worldwide specialized laboratories involved in the biochemical diagnosis of AD.

Gene regulatory network (GRN) construction involves various steps of complex computational steps. This step-by-step procedure requires prior knowledge of programming languages such as R. Development of a web tool may reduce this complexity in the analysis steps which can be easy accessible for the user. In this study, a web tool for constructing consensus GRN by combining the outcomes obtained from four methods, namely, correlation, principal component regression, partial least square, and ridge regression, has been developed. We have designed the web tool with an interactive and user-friendly web page using the php programming language. We have used R script for the analysis steps which run in the background of the user interface. Users can upload gene expression data for constructing consensus GRN. The output obtained from analysis will be available in downloadable form in the result window of the web tool.

BACKGROUND: Enzymatic quantification of creatinine has become an essential method for clinical evaluation of renal function. Although creatinase (CR) is frequently used for this purpose, its poor thermostability severely limits industrial applications. Herein, we report a novel creatinase from Alcaligenes faecalis (afCR) with higher catalytic activity and lower KM value, than currently used creatinases. Furthermore, we developed a non-biased phylogenetic consensus method to improve the thermostability of afCR.
RESULTS: We applied a non-biased phylogenetic consensus method to identify 59 candidate consensus residues from 24 creatinase family homologs for screening afCR mutants with improved thermostability. Twenty-one amino acids of afCR were selected to mutagenesis and 11 of them exhibited improved thermostability compared to the parent enzyme (afCR-M0). Combination of single-site mutations in sequential screens resulted in a quadruple mutant D17V/T199S/L6P/T251C (M4-2) which showed ~ 1700-fold enhanced half-life at 57 °C and a 4.2 °C higher T5015 than that of afCR-M0. The mutant retained catalytic activity equivalent to afCR-M0, and thus showed strong promise for application in creatinine detection. Structural homology modeling revealed a wide range of potential molecular interactions associated with individual mutations that contributed to improving afCR thermostability.
CONCLUSIONS: Results of this study clearly demonstrated that the non-biased-phylogenetic consensus design for improvement of thermostability in afCR is effective and promising in improving the thermostability of more enzymes.

The geological conceptual model is considered a major source of uncertainty in groundwater modelling and well capture zone delineation. However, how to account for it in groundwater policy and management remains largely unresolved. We explore the drivers and barriers to account for geological conceptual uncertainty in groundwater protection amongst decision makers and stakeholders in an agricultural groundwater catchment in Denmark. Using a groundwater model, we analyze the impact of alternative geological conceptual models on capture zone delineation. A focus area, which covers multiple modelled capture zones, is defined and considered for groundwater protection. Model uncertainty and focus area are discussed at two workshops, one with local and national stakeholders and another with local farmers. The drivers to account for model uncertainty include: i) safer drinking water protection by considering a larger area for protection than identified from a single geological model; and ii) stability over time of management plans. The main barrier is the additional cost to the stakeholders for the protection of a larger area. We conclude that integration of geological uncertainty in groundwater protection plans may be improved through: i) better communication between the research community and the national water authority; ii) more constraining guidelines regarding the estimation of geological uncertainty; and iii) the development of a framework ensuring knowledge transfer to the local water authorities and detailing how to integrate uncertainty in management plans.

The European Union (EU) has recently published its first list of invasive alien species (IAS) of EU concern to which current legislation must apply. The list comprises species known to pose great threats to biodiversity and needs to be maintained and updated. Horizon scanning is seen as critical to identify the most threatening potential IAS that do not yet occur in Europe to be subsequently risk assessed for future listing. Accordingly, we present a systematic consensus horizon scanning procedure to derive a ranked list of potential IAS likely to arrive, establish, spread and have an impact on biodiversity in the region over the next decade. The approach is unique in the continental scale examined, the breadth of taxonomic groups and environments considered, and the methods and data sources used. International experts were brought together to address five broad thematic groups of potential IAS. For each thematic group the experts first independently assembled lists of potential IAS not yet established in the EU but potentially threatening biodiversity if introduced. Experts were asked to score the species within their thematic group for their separate likelihoods of i) arrival, ii) establishment, iii) spread, and iv) magnitude of the potential negative impact on biodiversity within the EU. Experts then convened for a 2-day workshop applying consensus methods to compile a ranked list of potential IAS. From an initial working list of 329 species, a list of 66 species not yet established in the EU that were considered to be very high (8 species), high (40 species) or medium (18 species) risk species was derived. Here, we present these species highlighting the potential negative impacts and the most likely biogeographic regions to be affected by these potential IAS.

Cancer immunoinformatics have led to new directions towards vaccine design from predicted potential epitope candidates, which are able to stimulate the correct cellular or humoral immune responses. They were employed to accomplish an advanced vaccine design through reverse vaccinology by replacing the whole organisms. In this review, computational tools play an essential role in evaluating multiple proteomes to identify and select the potential targeted epitopes or combinations of distinct epitopes, so that candidates may afford a rationale design competent for obtaining suitable cytotoxic T lymphocytes (CTL) or B cell-mediated immune responses. This review is a complete collection of the most beneficial online and user-friendly immunological tools, servers, and databases for the design and development of the peptide vaccine. The mechanism of major histocompatability (MHC)-restricted peptide presentation and how these tools support the vaccine development are also presented. The human papillomavirus (HPV) is taken as a model microbial strain for peptide vaccine design and its sensitization against HPV-induced cervical cancer is discussed.