Systematic reviews and systematic maps represent powerful tools to identify, collect, evaluate and summarise primary research pertinent to a specific research question or topic in a highly standardised and reproducible manner. Even though they are seen as the "gold standard" when synthesising primary research, systematic reviews and maps are typically resource-intensive and complex activities. Thus, managing the conduct and reporting of such reviews can become a time consuming and challenging task. This paper introduces the open access online tool CADIMA, which was developed through a collaboration between the Julius Kühn-Institut and the Collaboration for Environmental Evidence, in order to increase the efficiency of the evidence synthesis process and facilitate reporting of all activities to maximise methodological rigour. Furthermore, we analyse how CADIMA compares with other available tools by providing a comprehensive summary of existing software designed for the purposes of systematic review management. We show that CADIMA is the only available open access tool that is designed to: (1) assist throughout the systematic review/map process; (2) be suited to reviews broader than medical sciences; (3) allow for offline data extraction; and, (4) support working as a review team.

Background: Within the last decades, genome-editing techniques such as CRISPR/Cas, TALENs, Zinc-Finger Nucleases, Meganucleases, Oligonucleotide-Directed Mutagenesis and base editing have been developed enabling a precise modification of DNA sequences. Such techniques provide options for simple, time-saving and cost-effective applications compared to other breeding techniques and hence genome editing has already been promoted for a wide range of plant species. Although the application of genome-editing induces less unintended modifications (off-targets) in the genome compared to classical mutagenesis techniques, off-target effects are a prominent point of criticism as they are supposed to cause unintended effects, e.g. genomic instability or cell death. To address these aspects, this map aims to answer the following question: What is the available evidence for the range of applications of genome-editing as a new tool for plant trait modification and the potential occurrence of associated off-target effects? This primary question will be considered by two secondary questions: One aims to overview the market-oriented traits being modified by genome-editing in plants and the other explores the occurrence of off-target effects. Methods: A literature search in nine bibliographic databases, Google Scholar, and 47 web pages of companies and governmental agencies was conducted using predefined and tested search strings in English language. Articles were screened on title/abstract and full text level for relevance based on pre-defined inclusion criteria. The relevant information of included studies were mapped using a pre-defined data extraction strategy. Besides a descriptive summary of the relevant literature, a spreadsheet containing all extracted data is provided. Results: Altogether, 555 relevant articles from journals, company web pages and web pages of governmental agencies were identified containing 1328 studies/applications of genome-editing in model plants and agricultural crops in the period January 1996 to May 2018. Most of the studies were conducted in China followed by the USA. Genomeediting was already applied in 68 different plants. Although most of the studies were basic research, 99 different market-oriented applications were identified in 28 different crops leading to plants with improved food and feed quality, agronomic value like growth characteristics or increased yield, tolerance to biotic and abiotic stress, herbicide tolerance or industrial benefits. 252 studies explored off-target effects. Most of the studies were conducted using CRISPR/ Cas. Several studies firstly investigated whether sites in the genome show similarity to the target sequence and secondly analyzed these potential off-target sites by sequencing. In around 3% of the analyzed potential off-target

People have a stake in conservation and environmental management both for their own interests and the sake of the environment itself. Environmental decision-making has changed somewhat in recent decades to account for unintentional impacts on human wellbeing. The involvement of stakeholders in environmental projects has been recognised as critical for ensuring their success and equally for the syntheses of evidence of what works, where, and for whom, providing key benefits and challenges. As a result of increased interest in systematic reviews of complex management issues, there is a need for guidance in best practices for stakeholder engagement. Here, we propose a framework for stakeholder engagement in systematic reviews/systematic maps, highlighting recommendations and advice that are critical for effective, efficient and meaningful engagement of stakeholders. The discussion herein aims to provide a toolbox of stakeholder engagement activities, whilst also recommending approaches from stakeholder engagement research that may prove to be particularly useful for systematic reviews and systematic maps.

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CRISPR/Cas enables a targeted modification of DNA sequences. Despite their ease and efficient use, one limitation is the potential occurrence of associated off-target effects. This systematic review aims to answer the following research question: Which factors affect the occurrence of off-target effects caused by the use of CRISPR/Cas in plants? Literature published until March 2019 was considered for this review. Articles were screened for relevance based on pre-defined inclusion criteria. Relevant studies were subject to critical appraisal. All studies included in the systematic review were synthesized in a narrative report, but studies rated as high and medium/high validity were reported separately from studies rated as low and medium/low or unclear validity. In addition, we ran a binary logistic regression analysis to verify five factors that may affect the occurrence of off-target effects: (1) Number of mismatches (2) Position of mismatches (3) GC-content of the targeting sequence (4) Altered nuclease variants (5) Delivery methods. In total, 180 relevant articles were included in this review containing 468 studies therein. Seventy nine percentage of these studies were rated as having high or medium/high validity. Within these studies, 6,416 potential off-target sequences were assessed for the occurrence of off-target effects. Results clearly indicate that an increased number of mismatches between the on-target and potential off-target sequence steeply decreases the likelihood of off-target effects. The observed rate of off-target effects decreased from 59% when there is one mismatch between the on-target and off-target sequences toward 0% when four or more mismatches exist. In addition, mismatch/es located within the first eight nucleotides proximal to the PAM significantly decreased the occurrence of off-target effects. There is no evidence that the GC-content significantly affects off-target effects. The database regarding the impact of the nuclease variant and the delivery method is very poor as the majority of studies applied the standard nuclease SpCas9 and the CRISPR/Cas system was stably delivered in the genome. Hence, a general significant impact of these two factors on the occurrence of off-target effects cannot be proved. This identified evidence gap needs to be filled by systematic studies exploring these individual factors in sufficient numbers.