Nanoscience systematic review methodology standardization

1.3.1 Example of misusing a literature review to justify a research hypothesis

Early research into the success of antioxidants, beta carotene, vitamin A, and vitamin E, for use in cancer prevention was driven by a select few studies that reported positive outcomes. However, a more comprehensive and systematic review of the literature later revealed inconsistent or contradictory findings [6]. The initial literature review, by focusing only on favorable studies, led to the mistaken assumption that antioxidants had a universally positive effect, which delayed more balanced investigations into their true efficacy.

Accordingly, it is essential to issue a strong warning regarding the practice of “vote counting” in literature reviews, [7] which is a suitable method of summarizing quantitative research results. Vote counting refers to categorizing each study into one of three outcomes (positive, negative, or no relationship) based on statistical significance. The fundamental concept is based on the idea that a research hypothesis is accepted as true when a considerable number of studies on a subject show a statistically significant impact. While appearing straightforward, vote counting is inherently problematic because it fails to account for key variables such as sample size variations, which significantly affect statistical power and the representativeness of the sample. Furthermore, “vote counting” lacks the capability to quantify the magnitude of effects, a critical aspect of interpreting research impact [8,9]. To address these limitations, more rigorous methodologies such as systematic reviews and meta-analyses have been developed. Systematic reviews provide a structured process for collecting and analyzing all relevant studies on a specific research question, thus minimizing bias in study selection. Meta-analyses, on the other hand, statistically combine the results from multiple studies, placing emphasis on factors like sample size and variance, which serve to addresses the flaws of vote counting by offering a more comprehensive and quantitative assessment of the data.

3.1.1 Formulating precise nanoscience research questions

Nanoscience sits at the vertices of many scientific fields and transcends traditional academic disciplines by encompassing biology, chemistry, physics, engineering, pharmacology, medicine, materials science, environmental science, and computational science. The formulation of precise research questions in nanoscience necessitates the utilization of a Nanoscience Research Questionnaire Matrix, NANO-RQM (Appendices 1 and 2). This structured approach prompts researchers to consider aspects such as the specific nanoscience discipline of focus, the requisite specialized knowledge, the types of nanoparticles under investigation (e.g., organic or inorganic), the implications of nanoparticle size, and the potential contribution of the study to the advancement of nanoscience. The NANO-RQM is designed to foster rigorous critical thinking and guide researchers in developing well-defined and impactful research questions within the complex landscape of nanoscience. For detailed guidelines on structuring and presenting a systematic review in nanoscience, including considerations for methodology, results, discussion, and the application of the NANO-RQM for formulating precise research questions, please refer to Appendix 3.

3.1.2 Exploring the breadth and depth of the nanoscience field

The breadth of the review is critical in the field of nanoscience, especially considering the research issues. While narrowing the scope of the study may simplify and enhance the method of review, it also introduces limitations on the conclusions that may be drawn from a study. Factors such as the specific nature of the literature, the defined research objectives, time constraints, and practical considerations all play important roles in shaping this balance. For example, students at different academic levels, from undergraduates to Ph.D. candidates, may approach the scope differently based on their available time, academic experience, and research ambitions. Whereby, the master’s student may be limited by time and experience, opting for more narrow research questions or select limited literature to ensure manageability; the doctoral student may choose more broad research issues, given more expertise, aspiration, and potential opportunities for collaboration. Incorporating systematic reviews as a prospective thesis project for nanoscience master’s students is recommended and encouraging academic advisors to explore this model is encouraged. Inspired by successful implementation in other disciplines, such as medicine, psychology, and education, systematic reviews have proven to be an effective approach for students to engage deeply with the literature. For example, in the medical field, systematic reviews are often used as a tool to critically evaluate clinical practices, guiding evidence-based medicine. In psychology, systematic reviews help synthesize findings across diverse studies to inform behavioral interventions. Similarly, in education, systematic reviews provide comprehensive evaluations of teaching methodologies, ensuring that future research is built on a solid foundation of evidence.

Incorporating this model into nanoscience research offers similar benefits. In such a dynamic and interdisciplinary field, nanoscience requires knowledge of disparate sciences (i.e., chemistry, physics, biology, engineering, etc.) to effectively navigate this complex and evolving landscape. This method enables master’s graduates to comprehensively survey the scholarly landscape and creates the foundation for their Ph.D. research, fostering the formulation of well-defined research questions and identification of critical gaps within the chosen academic domain. Moreover, the availability of resources, such as funding to engage postgraduate research assistants for a lengthy period, can substantially impact the feasibility to undertake a comprehensive and expansive literature review in nanoscience.

3.1.3 Assessing prior systematic reviews in nanoscience

An initial step in the process of writing a systematic review involves conducting a comprehensive search to determine whether there are any prior systematic reviews related to the research questions or identify if any ongoing systematic reviews have been published. This step serves several critical functions. Primary, it acquaints the researchers with the existing literature pertinent to their topic of interest. This step is also valuable toward conserving both time and resources, potentially months of effort, if a relevant and current systematic review already exists and does not require updating. Furthermore, this preliminary assessment assists in establishing a sound rationale for conducting an updated systematic review, ensuring that the research endeavor is both justified and adds value to the advancement of the field.

3.2.1 Effective nanoscience search terms

In the field of nanoscience, the deconstruction of the research questions into distinct, conceptual components are both important and challenging for establishing a foundation for generating precise search terms. The challenge arises from the transdisciplinary nature of nanoscience. Specific search terms are pivotal for capturing as all potentially relevant studies. These terms enable novice researchers to familiarize themselves with the appropriate literature, which facilitates the translation of research questions into well-defined and relevant search terms. For example, a nanoscientist investigating the use of gold nanoparticles in cancer therapy might derive search terms such as “gold nanoparticles,” “cancer therapy,” “nanoparticle applications,” “AuNPs,” and “GNPs.” Additional examples that demonstrate how a nanoscientist can refine search queries to access specific and relevant literature might include key search terms such as “quantum dots,” “solar cell efficiency,” “nanophotonics in renewable energy,” “QD-enhanced solar cells,” and “nanoscale photovoltaics” for researching the application of quantum dots in solar cell efficiency. Careful attention to this phase will ensure a comprehensive and targeted search strategy that would discover relevant studies and contribute to the advancement the field.

3.2.2 Nanoscience-specific vocabulary

The variety of terminology in nanoscience is a product of its transdisciplinary nature; recognizing the diversity of terminology is essential for comprehensive literature evaluation. Early scoping efforts have found that in the field of nanoscience, different terms often describe the same phenomena or area of study. This situation becomes particularly relevant when conducting a systematic review, where a flexible approach to terminology will reveal a broader spectrum of pertinent literature. For instance, the concept of “nanoparticle-enhanced water purification” may be expressed using alternative terminology and researchers may encounter synonymous terms like “nanoscale water remediation,” “nanoengineered water treatment,” “nanoparticulate water decontamination,” or “nanotechnology-based water treatment,” revealing the varied nomenclature that is used to describe the same area of research. Similarly, in the field of nanoparticle-based drug delivery, alternative terminologies might include “nanomedicine drug carriers,” “nanoscale pharmaceutical transport,” or “nanoparticulate drug delivery systems,” highlighting the diverse nomenclature associated within a single research area. Another field, such as nanostructured energy storage, could use diverse terms like “nanostructured batteries,” “nanoscale energy capacitors,” or “nanomaterials for energy storage,” reflecting the field’s varied nomenclature.

In nanoscience, there must be a balance between sensitivity and specificity, which, respectively, involves identifying the totality of articles that might bear relevance and subsequently ensuring that the chosen articles are genuinely pertinent to your research. To optimize search strategy, it is advised to prioritize sensitivity during this stage in order to avoid overlooking potentially valuable content. This method has the advantage of being thorough even if it may provide a wider pool of results, including both relevant and less relevant research. Subsequently, this extensive collection can be efficiently refined to ensure that crucial studies are not inadvertently omitted.

3.2.3 Inclusion and exclusion criteria

Inclusion and exclusion criteria need to be established to guide the nanoscientist in addressing their questions and delineating the boundaries of the systematic review. This process is contingent on the specific area within the broader field of nanoscience and is influenced by theoretical, methodological, and empirical considerations in the existing literature. To streamline the development of efficient criteria, a nanoscientist must create the inclusion and exclusion criteria immediately following the formulation of the research questions. This approach saves time and prevents potential influence from existing studies. Subsequently, these criteria can be consistently applied throughout the review process. Additionally, studies eligible for inclusion must align with the inclusion criteria and not contravene the exclusion criteria.

When establishing the inclusion and exclusion criteria for a systematic review, it is crucial to provide robust justification grounded in theoretical and empirical rationale. These criteria should be selected based on methodological rigor and relevance to the research question, rather than any bias against specific results or authorial perspectives. The criteria set forth influence the review’s scope, generalizability, and applicability. The inclusion and exclusion criteria play a meaningful role in shaping the interpretation and implications of the review’s findings, thereby underlining the importance of a transparent, well-reasoned approach to their determination.

The importance of inclusion and exclusion criteria is exemplified in the study of C₆₀ fullerenes (C₆₀) and their toxicity. Initially, some studies reported that C₆₀ induced oxidative stress and toxicity in fish, attributing this to reactive oxygen species (ROS) generation. However, these conclusions were later revised, as it became increasingly clear that limitations in the initial experimental techniques, specifically inadequate controls for solvent effects and light exposure, led to unintentional erroneous reports of C₆₀ ROS generation and toxicity. Current evidence and revised interpretations indicate minimal ROS production by aqueous C₆₀ and minimal toxicity in fish under controlled experimental conditions. This case demonstrates how evolving evaluation techniques can significantly alter scientific understanding, stressing the necessity of considering the methodological context and advancements when establishing inclusion criteria. Inclusion criteria should thus be sensitive to the time-dependent nature of technological advancements in nanoscience, acknowledging that earlier studies might have been constrained by the limitations of then-available analytical techniques.

In nanoscience, the following elements can be good criteria for inclusion and exclusion, which are represented in (Figure 2) to further clarify the methodology.

Figure 2

A flow chart of the inclusion and exclusion criteria in the field of nanoscience.

3.2.3.1 Timeframe

These criteria specify the time frame of the study, which may start from the beginning of the literature or stop after the most recent systematic review. However, in the context of nanoscience, authors need to define a suitable timeframe for inclusion and exclusion criteria. This is because nanoscience is a sensitive field that requires robust characterization techniques to obtain high quality results. The history of nanotechnology has been paralleled by the development of advanced imaging and characterization tools as shown in Figure 3.

Figure 3

Shows a real example of the development in the history of nanotechnology. Image Credits: The images used in this figure were selected to illustrate key milestones in the development of microscopy. We acknowledge the sources from left to right, as follows: (1) Photograph of Early Electron Microscopy: (Courtesy of Ruska, E. [1987]. The development of the electron microscope and of electron microscopy. Reviews of Modern Physics, 59(3), 627–638) (2) Bacteria image by early electron microscopy: (Courtesy of Public domain image via: Krause, F. [1937]. Bemerkungen zu der Arbeit von F. Krause: Das magnetische Elektronenmikroskop und seine Anwendung in der Biologie. Naturwissenschaften, 25(817)). (3) First image of atoms by TEM: (Courtesy of Crewe, A. V., Wall, J., & Langmore, J. [1970]. Visibility of single atoms. Science, 168(3937), 1338–1340). (4) High-resolution STM image of graphene: (Courtesy of Fuladvand, H., & Shokuhifard, R. [2011]. Review on graphene: Epitaxial graphene on insulators. International Journal of Fundamental Physical Sciences, 3(nano), 21–28). (5) Atomic force microscopy (AFM) image of palladium nanoparticles: (Courtesy of Klapetek, P., Valtr, M., Nečas, D., Salyk, O., & Dzik, P. [2011]. AFM analysis of nanoparticles in non-ideal conditions. Nanoscale Research Letters, 6(514)). (6) Cryo-EM image of an intact Bdellovibrio bacteriovorus cell: (Courtesy of Creative Commons License, ©Eikosi/en.wikipedia.org. Shared under the license). (7) SIM Super-Resolution Microscopy of HeLa cells treated with cerium dioxide NPs: (Courtesy of Guggenheim, E. J., Khan, A., Pike, J., Chang, L., Lynch, I., & Rappoport, J. Z. [2016]. Comparison of confocal and super-resolution reflectance imaging of metal oxide nanoparticles. PLOS ONE, 11(10), e0159980). All images not otherwise attributed are the property of the authors.

The first commercial scanning electron microscope was built in 1938, followed by the first commercial transmission electron microscope (TEM) in 1939. However, the resolutions of those early microscopes were not at the atomic level. After decades, high-resolution TEM was first discovered in 1970 and achieved a resolution of around 4 A. It was not until the year 2004 that a resolution of 0.6 A was achieved [18]. This advancement underscores the need for considering the evolution and progress of related technologies and methodologies that are essential for the advancement of nanoscience, a field inherently reliant on size and scale. Another notable example of technology’s impact on nanoscience research would be the development and use of AFM in studying cell mechanics. Prior to 2000, instrumentation available for such research was limited, making it challenging to obtain detailed information about the cellular mechanical properties. However, the advent and refinement of AFM have allowed research scientists to measure the forces within cells, providing greater insights into how mechanical forces affect cellular behavior, contributing to a deeper understanding in areas like cancer research, tissue engineering, and regenerative medicine. Consequently, a pertinent timeframe for systematic reviews spans from 2004 to the present, to capture the most relevant and technologically advanced research developments.

3.2.4 Borderline cases in nanoscience literature

During the process of reviewing nanoscience literature, the author may come across studies that fall into a gray area, where there is room for debate about whether they should be included or excluded. For instance, studies with preliminary data, those employing methodologies at the fringe of established scientific consensus, or manuscript preprints, necessitate careful evaluation against theoretical frameworks and empirical evidence. Such circumstances became increasingly prevalent in 2019 and 2020 during the COVID-19 pandemic to help accelerate dissemination of results, but may warrant collaborative deliberation, involving peer discussion and collective decision-making. In the context of performing a meta-analysis, it is possible to assess whether the inclusion of these borderline cases significantly influences the results. However, it is crucial to be conscious that the inclusion and exclusion criteria may have to be examined or altered if these borderline examples, which emerge throughout the literature study, signify a potential conceptual or empirical constraint in those criteria. Subsequently, it becomes important to reiterate the entire process of literature search and review, with the aim of guaranteeing the inclusion of all studies with potential relevance while excluding those that may not be pertinent.

3.3.1 Database selection

Given the rapid developments and vast, dynamic, interdisciplinary nature of this area, one must adhere to a detailed approach when designing research activities and objectives. The following section outlines essential tools, databases, and approaches for conducting effective searches in nanoscience.

3.3.2 Initial literature search strategy

Performing an in-depth literature search specific to the field of nanoscience using multiple and disparate electronic databases that relate both broadly and more specifically to the specific area (e.g., broader and more generalized scientific publications or conference proceedings) should be conducted during pre-research activities. Table 1 exemplifies a selection of generalized, yet comprehensive, databases that are particularly beneficial for researchers during these early identification phases. These databases provide a mix of broad coverage and focused insights into the field of nanoscience.

3.3.3 Advancing to specialized databases and resources

As your research progresses beyond the initial identification phases, the next step involves screening more specialized databases or journal repositories that focus specifically on nanoscience within a defined area of research. These specialized resources, which include targeted publications and conference proceedings, are crucial for aligning the research with specific experimental designs and objectives. Table 2 lists a range of such databases (across different fields of research), offering both traditional and non-traditional repositories ideal for focused nanoscience research. Early and thorough investigation of these sources is essential to uncover any gaps in the existing literature, as well as to identify potential areas of overlap or redundancy.

The strategic use of specific and specialized electronic databases, coupled with search terms that are closely aligned with nanoscience terminology and concepts is key to effectively locate relevant published and unpublished materials (discussed in the later parts of this study). It is recommended to start your in-depth search with these narrow-focus databases to ensure a targeted and subject-specific literature review. Subsequently, broadening your search to include more general databases can provide comprehensive coverage and yield interdisciplinary insights that might be missed otherwise. For a thorough literature review in your specific area of nanoscience, it is advisable to consult at least two databases. This approach, which combines both narrow and broad database searches, is considered the most effective strategy for comprehensive research in nanoscience.

3.3.4 Integration of specialized journals in research

In addition to consulting specialized databases, directly accessing specific journals dedicated to various subfields of nanoscience is beneficial during early phase research identification efforts. Table 3 provides an exemplary, albeit non-exhaustive, list of journals for specific subfields in nanoscience. Researchers should ensure their initial identification efforts are both targeted and comprehensive to avoid potential overlap or redundancy in publications. Regular consultation with these key journals ensures that all knowledge used in experimental design and plan includes latest advancements and emerging trends within their specific area of nanoscience, thereby enriching the scope and depth of their research.

3.3.5 Consulting comprehensive and advanced nanoscience tools

Research planning efforts can be supplemented by utilizing advanced nanotechnology tools and offerings that are tailored to meet the evolving needs of researchers who require access to detailed and specific information in nanoscience. One example platform that offers extensive collections of nanomaterial data, literature references, and essential resources for both established and emerging areas in nanoscience is Nano by Springer Nature. This tool, as well as other non-traditional databases like Nanowerk, provide researchers with the most up-to-date information available (Table 4). Given the dynamic nature of nanoscience, the ability to navigate and access cross-disciplinary information through a single database is significantly advantageous, as the interconnectedness of these fields necessitate a holistic approach that enables researchers to draw on a wide array of knowledge across scientific fields. For instance, in biology and biochemistry, understanding nanomaterial applications and biological interactions require insights that often overlap with chemical properties and reactions studied in chemistry and chemical engineering. This interdisciplinary approach is crucial in addressing complex research questions, where one discipline informs and enhances the understanding in another. This dual perspective is equally important in materials science and engineering which benefit from a multifaceted search strategy to better understand both the physical properties and the various applications of nanomaterials. Embracing a cross-disciplinary approach in your searches enriches the research process, ensuring that nanoscience researchers have a broad and well-rounded understanding of their field.

Many emerging tools leverage machine learning to index articles from publishers that offer daily updates and contextual insights to inform researchers about the latest developments and trends, aiding in the identification of gaps in current research. Machine learning algorithms enhance the indexing process by automatically scanning and categorizing vast volumes of scientific literature based on content, keywords, and relevance to specific fields. These algorithms can recognize patterns in the data and classify articles by subject matter and their contextual relationships, such as emerging research trends, novel methodologies, or key findings. By continuously learning from new data, these tools refine their search and filtering capabilities, providing more accurate and relevant results over time. By example, machine learning tools can highlight articles that align with a specific researcher’s area of interest, track citations, and suggest related studies that may have been missed using traditional keyword searches. Most notably, machine learning can help identify hidden connections between studies or research areas, offering deeper insights into how different pieces of research relate to one another.

To keep pace with developments, tools like the Nano platform (nano.nature.com) provide researchers with easy access to a repository of data across multiple nano-specific disciplines. The database resource serves multiple disciplines, including biology, chemistry, materials science, and more, facilitating interdisciplinary research and collaboration. Advanced filtering options and access to a wide range of resources allow researchers to refine their search results and improve the accuracy of their findings. Through the consolidation of essential information on nanomaterials, articles, and patents, Nano provides a useful platform for researchers to quickly access and assimilate relevant data that are related to their specific research area. These results include manually curated summaries that provide critical information on nanomaterials.

Nano from Springer Nature stands as a comprehensive solution for accessing a vast array of information. Researchers and institutions harness these resources to stay at the forefront of innovation, ensuring their work remains cutting-edge and well-informed. The platform provides access for researchers to the most up-to-date summaries enabling better understanding of various aspects of nanomaterials, compare different variants, and explore their applications and implications in fields ranging from medicine to environmental science. The database provides step-by-step synthesis schemes for various nanomaterials and by providing a practical guide to material synthesis this database is ideal for researchers developing new nanomaterials or replicating existing ones. Furthermore, these repositories provide information beyond traditional research publications, including nanotechnology-related patents, with easily accessible claim information that are categorized based on nano-specific classifications. Such broadening of identification efforts can expand and identify new research opportunities and enable understanding the scope of existing patents in the field.

In Table 5, an example of a specific journal search strategy, focusing on research in nanoscience-based contrast agents is provided. Different research topics within nanoscience will necessitate consulting a variety of journals or databases, tailored to the unique needs of each inquiry. Additionally, for a thorough exploration of a topic like contrast agents, integrating searches across relevant patent databases such as the United States Patent and Trademark Office (USPTO) may be beneficial to the researcher as this approach broadens the scope of the research as well as offers insights into the latest technological advancements and intellectual property developments in the field.

3.3.6 Alternative databases and access strategies in nanoscience research

Alternative databases and resources play a critical role, especially when access to data and published journals is limited. Patent databases like the USPTO, European Patent Office (EPO), and World Intellectual Property Organization (WIPO) are open access and free repositories that provide access to the latest patents and technological advancements in nanoscience. Additionally, the chemistry abstract service (CAS) offers over 100 million accessible entries of detailed chemical data, substance information, and literature references, that can benefit research in nanomaterials. While accessing necessary journals is problematic due to paywalls, researchers may overcome these barriers through various strategies. Such as leveraging subscriptions from academic institutions and utilizing or requesting articles via “interlibrary loan” systems when said material is not available at one’s institution.

Open Access Journals and Repositories (i.e., DOAJ) are becoming increasingly favorable and allow for unrestricted access to published materials within these journal systems. However, it is crucial for researchers to scrutinize the integrity, peer review nature, and ethics of these journals. Tools like Beall’s List or various predatory journal lists serve as valuable resources in this regard. They help researchers identify and avoid unscrupulous publications, ensuring the material they access is credible and accurate. Additionally, checking a journal’s inclusion in reputable indices or its impact factor can further validate its standing in the scientific community. In some cases, when information is inaccessible or supplementary data and additional information are required, researchers should consider directly contacting authors and using platforms like ResearchGate and Academia.edu for shared publications.

In instances where research developments outpace traditional publication timelines, as was recently observed during the COVID-19 pandemic, researchers might find preprint servers like ArXiv and bioRxiv beneficial. These platforms provide early access to research findings, which is particularly valuable when swift dissemination of information is necessary. However, it is important to note that most content on these servers has not undergone the peer review process typical of established journals. Consequently, while these servers offer timely access to emerging research, researchers should exercise caution and critical evaluation when considering the validity and reliability of the findings presented. Table 6 details these alternative databases and strategies.

3.3.7 Consideration of article parts for searching

The field of nanoscience evolves rapidly; thus, it is imperative to adopt a structured approach for conducting literature reviews, utilizing the database methods previously outlined. Given the breadth, volume, and dynamic nature of research in this space, researchers often encounter the challenge of navigating through an extensive volume of information, which can be overwhelming and confounding. To mitigate such issues and streamline the efficiency of the literature identification process, it is advisable to focus on specific components of scientific articles throughout the search phase. This strategy ensures that the efficiency of the search is maximized without sacrificing the precision or comprehensiveness of the overall literature review. To aid researchers in this endeavor, Table 7 has been compiled as a guideline to focus the scientist on the various sections of scientific articles.

Abstracts provide a succinct and high-level overview of the study’s aims, methods, and key findings, allowing for efficient assessment of the overall article’s relevance to the scientists. However, it is important to note that abstracts can sometimes be misleading or overly broad, offering only a partial view of the study’s actual scope or conclusions. Thus, researchers should use abstracts as an initial filter but verify key details by reviewing the full text when needed to ensure that the article’s content aligns with their research objectives.

Titles, which frequently include specific nanoscience terminology, act as concise indicators of a manuscript’s content and help guide targeted searches. However, titles may not always accurately reflect the full focus or key findings of the research presented. The sole reliance on a title alone can often lead to missing important nuances of the research. For this reason, it is essential to corroborate the title’s relevance by consulting other parts of the manuscript.

Keywords, which are usually selected by authors or required by the journal encapsulate the core content and key concepts elucidated in the manuscript and can be helpful to pinpoint specialized nanoscience terms and topics. However, in studies where key terms are obscure, examining the full text of the manuscript might be required to avoid overlooking relevant material.

The background materials offer contextual information, such as literature reviews and theoretical frameworks, aiding in determining the study’s foundation and its relation to existing knowledge. In certain circumstance, such as validation and reproducibility, consulting the methods section can provide key insights into the experimental design and procedures used in the research. Notably, the results sections, which often articulates the statistical analyses and significance of outcomes will allow for an assessment of the study’s impact and reliability within the field. Figures and graphs present complex nanoscience data visually, facilitating a quicker understanding of intricate concepts.

The bibliography or references cited within articles offer a myriad of additional context and information that can lead to the discovery of additional pertinent literature that might not have been captured in initial searches. Less recognized, but equally important are associated with disclosures of conflicts of interest, which allow the reader to evaluate research credibility and identify any potential biases. Funding sources information reveals potential influences on the research’s scope and reporting due to funding body priorities.

Finally, and probably most critically overlooked in nanoscience, the publication year will inform and indicate the recency and thus the potential relevance of methodologies and discoveries in nanoscience. Acknowledging the rapid evolution within the field, it is important to define a publication date range to capture the most current and relevant findings. For most subdisciplines within the field of nanoscience, a recommended timeframe is the last 5–10 years due to the rapid transgression of new ideas. This period likely encompasses significant technological advancements and current trends in nanoscience. There are exceptions to this general guideline (see information panel below). For instance, when investigating foundational theories or historical development of a particular technology, it will be necessary to include older seminal works. Additionally, some subfields within nanoscience may have slower rates of change, wherein older research remains highly relevant.

• Rapid technological advancements: Technologies and methodologies that were state-of-the-art a decade ago might now be obsolete or significantly advanced.

• Emergence of new materials and techniques: The past 5–10 years have witnessed the development of novel nanomaterials and fabrication techniques, which are crucial to current nanoscience research.

• Current standards and regulations: Literature from the suggested timeframe is more likely to align with the latest standards and safety regulations in nanotechnology.

• Relevance to current research questions: This period’s literature is more likely to address contemporary research questions, reflecting the latest technological capabilities and societal needs.

• Interdisciplinary integration: The recent trend toward interdisciplinary integration in nanoscience, particularly with fields like biology, medicine, and environmental science, is best captured in the most recent literature.

3.3.8 Optimizing research efficiency in nanoscience with advanced tools and technologies

In nanoscience, the body of literature is continuously expanding, thus adopting new tools and technologies is essential for researchers to efficiently organize and analyze their findings. Tools like Litmaps (https://www.litmaps.co), Connected Papers (https://www.connectedpapers.com), and Research Rabbit (https://www.researchrabbitapp.com) are useful for visualizing the expansive research landscape. These tools help authors discern where their work fits within the existing literature, identifying pivotal studies for citation and ensuring their research contributes uniquely to the field. Scite (https://scite.ai) provides insights into the citation context of existing research, a key factor in understanding the impact and reception of prior studies in nanoscience. Dimensions (https://www.dimensions.ai) extends the scope of research by providing insights into related grants, patents, and clinical trials. This broader perspective is crucial for understanding the potential applications and wider impact of nanoscience research. EndNote (formerly Kopernio; https://click.endnote.com) simplifies the process of accessing full-text articles and identifying seminal work and emerging trends in nanoscience.

During manuscript preparation and collaborative, tools such as Overleaf (https://www.overleaf.com), Rayyan (https://www.rayyan.ai), and Covidence (https://www.covidence.org) help streamline the literature review process and facilitate team alignment on relevant studies, ensuring comprehensive coverage and aiding in the identification of gaps in the literature, thereby refining research questions. For assimilating large volumes of scientific literature, reference management tools like Zotero (https://www.zotero.org) or Mendeley (https://www.mendeley.com) are useful for organizing the extensive literature. These tools can enhance the efficiency and impact of research efforts, as well as facilitate effective collaboration, rigorous literature analysis, and wider dissemination of findings in this dynamic field.

3.3.9 Search strategy for nanoscience systematic review

To ensure that a literature review is both comprehensive and focused, a tailored approach that considers the unique nature of the specific research should be adapted by the scientist. For instance, a review focusing on the toxicity of nanoparticles will use specific compound names, while a review of the biomedical applications of quantum dots might broaden the search to include synonymous terms. Filters such as publication date can be critical for emerging topics, whereby researchers might opt to include the most recent studies without date restrictions, while for more established areas, a longer timeframe could be more appropriate.

Each database and search engine may implement these operators differently, and some may not support all types. It is important to consult the help or support sections of your chosen database for specifics on how these operators can be used effectively in your nanoscience systematic review. In refining search strategies, Boolean and proximity operators and search modifiers are critical for effectively narrowing down search results and allowing researchers to pinpoint precise information in extensive databases efficiently (Tables 8–10).

Table 11 presents an illustrative example of how diverse databases can be strategically utilized to gather pertinent literature, employing tailored search terms and filters that reflect the unique aspects and current trends in nanoscience.

In conducting an effective and comprehensive literature review in nanoscience, it is essential to leverage advanced search strategies for thorough and precise literature retrieval. The use of truncation, wildcards, phrase searching, Boolean operators in parentheses, and publication year filtering may serve to improve results. However, each of these strategies should be applied thoughtfully, considering the specific needs and nuances. Similarly, it is advisable to periodically review and adjust the search strategy based on initial findings to ensure a comprehensive and relevant collection of literature.

3.3.10 Collaborative refinement of research strategies

Having established a robust foundation, the next step involves a meticulous evaluation and refinement of the gathered information. This phase ensures the relevance and comprehensiveness of your research findings and is notably highly beneficial to consider conducting this portion (as well as the previous portion) in tandem with another co-researcher, collaborator, or advisor. Such coordination can offer diverse perspectives and reduce individual bias, enhancing the accuracy of the review. Although finding flexible participants for this collaborative effort might be challenging, the value it can add in terms of reliability cannot be overstated.

In cases where collaboration is not feasible, alternative strategies can be used to improve the research process. Researchers might engage in online forums dedicated to nanoscience research or specific subfields, such as ResearchGate or discipline-specific groups on platforms like Reddit or Academia.edu can provide valuable feedback, suggestions, and insights from a broader academic community. However, caution is advised when using informal platforms, as the quality of information may vary, and advice from non-experts may not always be reliable or applicable. It is essential to cross-check any insights gained from these platforms with credible, peer-reviewed sources whenever possible. Another option is to seek external reviews from independent experts or senior researchers through academic networks or via preprint platforms, where manuscripts can be shared for early critique. These external evaluations can help identify any gaps or overlooked areas and offer an objective review of your inclusion and exclusion criteria. Additionally, leveraging tools like systematic review software (e.g., Covidence or Rayyan) can assist in organizing and refining the selection process, helping to minimize bias and ensuring that no crucial studies are missed.

This approach entails a thorough inspection of the initial search results to gauge the effectiveness of your inclusion and exclusion criteria, and to identify any potential gaps or overlooked areas in your search terms. This step goes beyond accumulating data; and focuses more so on strategically sifting through the information to extract the most pertinent and high-quality content that aligns with the specific nature of the research. This section describes the practicalities of this process, offers guidance on how to critically analyze search outcomes, and revise or expand search strategies to encompass a wider range of relevant studies, including those that might not be immediately apparent in electronic database searches.

3.3.11 Evaluating search results and criteria

Following the establishment of advanced search strategies and data collection, the initial phase of your literature review, involves a critical examination of search results. This process necessitates reviewing the most recent and high-quality articles to assess their relevance and the efficacy of your inclusion and exclusion criteria. This evaluation may indicate a need to adjust these criteria or search terms, either broadening or narrowing them to align with the scope of the research. For instance, you might expand your search to include broader concepts like “nanomaterial applications” or narrow it to specific areas such as “carbon nanotube toxicity.” This step is vital for ensuring that your review accurately reflects current trends and terminology.

3.3.12 Adapting to emerging terminologies and concepts

As you more thoroughly examine the initial search results, be prepared to discover new and previously unconsidered search terms. New concepts, methods, materials and terminologies are constantly emerging in nanoscience and adapting your search terms in response to these discoveries will provide additional literature that is relevant to your research topic. This flexibility in modifying search parameters ensures a comprehensive and current analysis that captures emerging and newly described developments and ideas.

3.3.13 Expanding research beyond electronic databases

While electronic databases provide a substantial foundation for literature review in nanoscience, they will unlikely be able to cover all pertinent literature. Additional searches, including a manual review of specific journals add to breadth and completeness of the analysis. These journals may contain valuable articles, such as letters to the editors, conference proceedings, and other works not included or indexed in most electronic databases. Exploring the reference sections of included studies often reveals significant works missed during initial searches and lead to the discovery of key journals, book chapters, and other crucial resources. In cases where published studies provide insufficient information for inclusion decisions, reaching out to authors for additional details or data is encouraged. This will aid in clarifying ambiguities and ensures a more comprehensive understanding of the research landscape. Finally, maintaining a detailed and transparent record of the entire search process, including any modifications to the search strategy and the rationale behind these changes, is paramount. This step will enhance the transparency and reproducibility of your review and serve as a valuable reference for the future. Beyond these search techniques, an in-depth systematic review in a particular nanoscience research topic should include additional methods to address often overlooked areas of research, including the unpublished works, gray literature, and publication bias. Each of these elements plays a vital role in crafting a complete and unbiased assessment of the current state of research in nanoscience.

3.3.14 Unpublished work in nanoscience

Unpublished work, often overlooked, may provide valuable insights and data for systematic reviews in nanoscience. Locating this type of work presents unique challenges. One effective approach is directly contacting researchers who have published on relevant topics to request information on unpublished data or upcoming publications. Utilizing a polite and clear communication strategy, with follow-up emails, if necessary, can yield meaningful results. It is reasonable to establish appropriate cutoff periods for responses, balancing the need for comprehensive research with time constraints. Networking within the scientific community, attending conferences, and engaging with research groups can also unveil unpublished studies and ongoing research projects. Additionally, many universities and research institutions maintain repositories of theses, dissertations, and other scholarly works, which may include unpublished research. Some databases and websites are dedicated to collecting and disseminating unpublished scientific work, such as preprint servers specific to nanoscience.

3.3.15 Gray literature in nanoscience

Gray literature including non-commercially published works is another component of a comprehensive searching for nanoscience research. Utilizing specialized databases such as OpenGrey and OpenDOAR will provide access to a vast array of gray literature, including technical reports, working papers, and dissertations. Google and Google Scholar are effective tools for locating dissertations, reports by societies and charities, and other forms of gray literature. Many government agencies and scientific organizations publish reports, working papers, and research findings relevant to nanoscience. Furthermore, important findings and research developments are often presented at conferences before publication in journals.

3.3.16 Considering publication bias in nanoscience reviews

Publication bias can significantly impact the validity of conclusions drawn from systematic reviews in nanoscience, making understanding and mitigating this bias crucial. Researchers should be aware that studies showing statistically significant results are more likely to be published than those with nonsignificant findings, which can lead to an overestimation of effect sizes and skewed conclusions. The search strategy for the review should include both published and unpublished research, focusing on the quality and relevance of the studies rather than their publication status. A critical analysis of statistical significance is necessary, considering the effect size, sample size, and the broader context of the research findings (discussed below in Section 3.4.2). Meta-analysis and systematic reviews are tools that can be used to assess overall trends and effect sizes across studies, accounting for both published and unpublished research. It is essential to document the search process transparently, including efforts to locate unpublished work and gray literature, and discuss the potential impact of publication bias on the review’s conclusions.

3.4.1 Assessing full-text articles for eligibility in nanoscience

In this phase, it is the time to move from sensitivity to specificity. The full-text versions of potentially qualified articles are presently subject to a comprehensive assessment to ascertain their suitability for incorporation in the systematic review. This phase primarily revolves around evaluating whether each published or unpublished work conforms to the predefined inclusion and exclusion criteria. Typically, this entails a focused review of the method and results sections, a practice especially pertinent when conducting a meta-analysis, instead of affording significant attention to the introduction and discussion sections.

3.4.2 Assessing statistical significance and relevance for eligibility in nanoscience

Understanding statistical significance and relevance is critical for accurately interpreting the results of nanoscience research, especially for those who may not have a strong statistical background. In systematic reviews, the ability to differentiate between a statistically significant finding and one that is practically or scientifically relevant can significantly impact the quality of the conclusions drawn. Typically, statistical significance is represented by a p-value (probability value), with a common threshold being p < 0.05. A result is considered statistically significant if the p-value is below this threshold, suggesting that the observed effect is unlikely to have occurred by chance alone. However, statistical significance does not necessarily imply that the result is practically important or relevant for applications in nanoscience. While a statistically significant result may indicate that there is an effect, it does not describe the magnitude of that effect. The effect size measures the strength of the relationship or the difference between groups, which is critical in nanoscience where even small changes at the nanoscale can have significant implications. Herein, measurements like Cohen’s d, Pearson’s r, or Odds Ratios are useful for quantifying the effect size and should be considered alongside the p-value.

Confidence intervals (CIs) provide a range within which the true value of the effect is likely to fall. A narrow CI suggests high precision, whereas a wide CI indicates greater uncertainty. By example, a 95% CI means that the scientist can be 95% confident that the interval contains the true effect. In nanoscience research, CIs are particularly meaningful for understanding the precision of measurements and outcomes. Furthermore, a statistically significant result may not always be practically relevant. For example, a new nanomaterial could show a statistically significant improvement of a given property, but the actual improvement may be too small to make a meaningful impact in real-world applications.

Sample size and statistical power are important considerations in determining the reliability of statistically significant results. Small sample sizes often lead to underpowered studies, which increase the likelihood of false negatives (failing to detect a true effect). On the other hand, extremely large sample sizes can lead to statistically significant results even for trivial effects. Researchers should ensure that studies included have appropriate sample sizes and sufficient power to detect meaningful effects. Finally, while the p-value serves as a useful tool for assessing statistical significance, nanoscientists should avoid using it as the sole criterion for determining the validity of a study. A comprehensive interpretation of study results should include a review of the effect size, CIs, and practical relevance to the respective field. To further enhance the understanding of statistical concepts and their appropriate application, readers are encouraged to consult additional resources such as Understanding Statistics and Experimental Design [22], Statistics for Experimenters: Design, Innovation, and Discovery [23], or Design and Analysis of Experiments [24]. In addition to these books, it can be beneficial to explore other statistics manuals or guides available at your university, laboratory, or as recommended by your research group. For more personalized guidance, consider consulting with a statistician or an expert in your field at your institution to ensure the correct application of statistical methods tailored to your specific research needs. Using these guides and strategies can offer clear explanations of various statistical methods and help determine when and how to apply them for accurate analysis in research contexts.