NITRC NITRC Community Forum: community-blog

Unlocking the Full Potential of Brain Imaging: The Power of Proper Data Annotation

Abby Paulson — Wed, 20 Nov 2024 19:42:03 GMT

This article is a collaboration among Dr. Giorgio Ascoli, Dr. David Kennedy, and Dr. Angie Laird.
In the rapidly evolving field of neuroimaging, a crucial yet often overlooked aspect is gaining recognition: the importance of data annotation. This process of systematically documenting and characterizing datasets is essential for maximizing the value and reusability of neuroimaging data. There is a growing understanding that proper annotation is not just an administrative task, but a fundamental component of findable, accessible, interoperable, and reusable (FAIR) research.
The Subjectivity of "High-Quality" Data
One of the key insights emerging from the neuroimaging community is that the concept of "high-quality" data is far more nuanced than previously thought. What constitutes high-quality for one analysis may be insufficient for another. 
For instance, a dataset meticulously collected to study dendritic complexity in various brain regions might include thousands of cell traces from young animals exposed to different doses of nicotine in utero. The researchers, focusing primarily on branch numbers, might have opted for 2D projections without recording branch diameters. This choice allows for faster tracing and a larger sample size, perfectly suiting their research goals. However, the same dataset might be deemed "low-quality" by computational modelers interested in dendritic self-repulsion (requiring 3D data) or synaptic integration (requiring diameter measures). This scenario illustrates how the same data can be simultaneously high and low quality, depending on the research question. This realization challenges the traditional notion that data quality is an absolute measure.
The Responsibility of Data Users
The subjective nature of data quality shifts responsibility to data users, requiring researchers to thoroughly understand the strengths and limitations of shared datasets based on their annotations. Users must determine if a dataset suits their specific research question, rather than dismissing it outright as "low-quality." Once this distinction is appreciated, we strongly recommend avoiding "low quality" when referring to publicly shared datasets. Instead, researchers should explain why certain datasets may be unsuitable for a specific application given well-defined inclusion criteria. This approach helps prevent discouraging data owners from sharing their data in the future due to fears of criticism outside the proper scientific context.
The Importance of Comprehensive Annotation
To facilitate this understanding, comprehensive and clear annotation is essential. Datasets should be annotated across multiple dimensions of metadata. While the importance of annotation is clear, the process comes with several challenges such as terminology reconciliation, scaling, contributor engagement, and the cultural perception that data annotation is valued work.
Addressing Challenges
The neuroimaging community is making significant progress in addressing the challenges of data annotation. Advanced computational tools, including deep learning technologies, are being integrated into annotation workflows to improve efficiency and consistency. Simultaneously, there's a growing emphasis on educational initiatives, with efforts to train students, even at the undergraduate level, in data annotation practices. This approach not only helps meet current annotation needs but also prepares the next generation of researchers to work effectively with complex datasets.
Furthermore, a cultural shift is underway, with increasing recognition of the value of annotation work and efforts to properly acknowledge and reward those who contribute to this crucial task. Standardization efforts, spearheaded by initiatives like NITRC, promote best practices in data curation and annotation across the field. These combined efforts are paving the way for more robust, reusable, and valuable neuroimaging datasets in the future.
The Benefits of Proper Annotation
The benefits of thorough data annotation in neuroimaging research are far-reaching and substantial. Well-annotated datasets can be more easily repurposed for new research questions, improving data reusability and maximizing the value of each study. Clear metadata enhances reproducibility by allowing other researchers to better understand and potentially replicate studies. Standardized annotations facilitate easier data sharing and collaboration across research groups, while also accelerating scientific discovery by making it easier to find and use relevant data. Moreover, engaging in annotation work provides students with invaluable hands-on experience, deepening their understanding of complex scientific concepts and methodologies. This educational aspect of data annotation further underscores its importance in the field, contributing to the development of skilled researchers who appreciate the nuances of data quality and annotation.
Moving in the Right Direction
As the field of neuroimaging advances, the importance of proper data annotation cannot be overstated. It is a crucial component in unlocking the full potential of brain scans and other neuroimaging data. While challenges remain, the neuroimaging community is moving in the right direction, recognizing that the future of neuroscience research depends not just on collecting data, but on documenting it in a way that maximizes its long-term value and reusability. Through continued efforts in education, tool development, and cultural shift, the field is paving the way for a future where data annotation is recognized as the vital scientific contribution it truly is. This recognition is key to fostering an environment where researchers are encouraged to share their data, knowing that it will be evaluated fairly and used appropriately based on its specific strengths and limitations.
Join our conversation about annotations by completing our <a href="https://form.typeform.com/to/PU15Xtcz">Data Annotation Survey</a>.

A Neuroimager's Perspective on the ABCD Study and AIIM 2024

Angie Laird — Wed, 22 May 2024 15:26:36 GMT

By: Angie Laird, PhD, NITRC Domain Expert

Hi! I’m sitting at the airport in Washington DC, waiting for a flight to take me back home to Miami. The inaugural ABCD Insights and Innovations Meeting (AIIM) has just ended and I’m so excited to talk about the amazing research I’ve heard about over the past two days.

AIIM was hosted at the NIH Campus in Bethesda, Maryland, on March 4-5, 2024. The meeting was designed for researchers to share innovative findings and emerging insights about adolescent development through use of data generated by the Adolescent Brain Cognitive Development (ABCD) Study. AIIM was intended to foster collaboration among scientists from multiple disciplines and career stages and provide opportunities for sharing novel perspectives through data presentations, roundtable discussions, and interactive poster sessions. The meeting also provided opportunities for attendees to connect with members of the ABCD consortium and NIH program staff.

What an incredible meeting! There were so many inspiring and exciting presentations on the schedule. I saw lots of interesting applications of ABCD data on cognition, psychopathology, and substance use, as well as cool new methodological advances.

Throughout the meeting, I connected with many graduate students, postdoctoral fellows, and early career faculty and was truly impressed by these thoughtful and talented researchers. There were panel discussions, flash talks, and an “Ask The Experts” session. The first afternoon included an informative session with NIH program officers from NIDA, NIMH, NIAAA, NIMHD, and NIHLBI, while the second day included a series of outstanding presentations from members of the START cohort - if you’re not familiar with the START ABCD Training Program, you should definitely take a look!

As a neuroimager, I tend to think of ABCD as a data resource for neuroimagers about adolescent brain development. So, I found it interesting that this wasn’t a typical “neuroimaging conference”. Sure, many researchers are incorporating brain-based phenotypes into their work, but many others are not. What *is* trending? Well, researchers are collectively leveraging ABCD's rich data that contextualizes the adolescent experience, including variables related to the structural and social determinants of health. These include variables at the individual, family, and community levels. ABCD is a unique resource that has captured many socioenvironmental variables not addresssed in other population-based neuroimaging studies. Moreover, ABCD includes a demographically diverse cohort. As an ABCD site PI, it’s quite gratifying to see so many scholars take advantage of these data and ask societally meaningful questions related to the impacts of childhood poverty, gender diversity, and neighborhood disadvantage. There was also a lot of compelling work centered around sleep, which plays such a critical role during adolescent development. Overall, ABCD presents a novel opportunity to look beyond simple trends in race and ethnicity and consider persons in their lived environments, using linked datasets and allowing for the consideration of different theoretical approaches. Such work will help us all better understand pathways to prevention and intervention, as well as policies for societal level factors that cause health inequities.

It’s not often that you attend a meeting in which everyone is working with the same dataset, yet in such different ways! I’m told that the AIIM website will be updated in the next few days with more information on presentations and resources.

Special thanks to Traci Murray, Caitlin Dudevoir, Susan Holbrook, and many others at NIH who did a fantastic job organizing the meeting and making it so successful. I am returning home energized with new ideas and I’m ready to tackle more ABCD data projects.

The plan is for AIIM to be an annual event, so I will see you there next year!

The Multiverse Approach in Neuroimaging and EEG

Arnaud Delorme — Thu, 15 Feb 2024 17:58:58 GMT

By: Arnaud Delorme, PhD, NITRC Domain Expert (https://doi.org/10.18116/7cg8-4951)

The "multiverse" approach in the context of Neuroscience analysis is a concept borrowed from statistical analysis and research methodologies, particularly in the fields of psychology and neuroscience. While specific to Neuroscience, the technique can be applied to the processing of fMRI, and EEG, MEG, and other physiological signals. In this article, we will focus on EEG as an example application.

In research, a multiverse analysis refers to exploring multiple analytical scenarios for the same dataset. Instead of committing to a single method of analysis, researchers explore a range of different analytical choices to understand how these choices affect the study's outcomes. This approach acknowledges that different analytical paths can lead to different results, and it aims to provide a more comprehensive view of the data. For example, is it better to high-pass filter the data at 0.1 Hz or 0.5 Hz (see figure).

Why multiverse?

EEG data is complex and multidimensional, with many potential ways to preprocess, analyze, and interpret the signals. This includes choices like filtering methods, artifact rejection strategies, feature extraction techniques, and statistical analyses. In a multiverse approach, an EEG researcher might explore various preprocessing steps (e.g., different ways of handling artifacts like eye blinks or muscle movements), different methods of segmenting the data (e.g., time windows), and different statistical tests or machine learning algorithms for interpretation. By examining the outcomes across these different scenarios, researchers can better understand the robustness of their findings. If an outcome is consistent across many different analytical paths, it can be considered more reliable. If the outcome varies significantly with different methods, this variability needs to be understood and reported.

The importance of defining good metric

Defining good metrics is crucial because metrics are how we quantify the success, effectiveness, or quality of an experiment, model, or method. Taking the example from the paper titled "EEG is better left alone," (Delorme, 2022), where the authors used 'the number of significant channels' as a metric, we can understand the rationale behind selecting this specific metric. In EEG (Electroencephalography) studies, data is collected from multiple channels placed across the scalp. Each channel records electrical activity from different regions of the brain. The choice of using the number of significant channels as a metric likely stems from the goal of the study, which is to maximize significance. Other metrics could involve the amplitude of some ERPs or the deviation from the mean response (Clayson et al., 2021). Another metric could be how close automated data rejection and cleaning are to human rejection (Delorme and Martin, 2021).

Cross-validation

Cross-validation is a vital technique in statistical modeling, particularly in fields like machine learning, where the performance of a model must be accurately assessed. At its core, cross-validation is about evaluating how well a model generalizes to an independent dataset. Traditionally, when a model is trained on a particular set of data, there's always the risk that it will overfit - that is, it becomes too tailored to the specific quirks of that data and fails to perform well on new, unseen data. Cross-validation addresses this problem by using different portions of the data to train and test the model in multiple rounds, ensuring that the model is robust and performs consistently across different data samples.

What does it mean in the context of a multiverse analysis? Cross-validation helps in tuning hyperparameters, which are the configuration settings used to optimize data processing performance. By evaluating the model's performance for various hyperparameters across multiple folds, one can find the most optimal set of hyperparameters that provide the best generalization performance. Concretely, it means that we will optimize processing on one set of data (the training data) and assess performance on another set of data (the testing data).

Conclusion

Multiverse analyses, when done properly with cross-validation, offer multiple advantages:

Transparency and robustness: This approach increases the transparency of the research process and helps identify the most robust and reproducible findings.

Reduces the risk of cherry-picking parameters or falling prey to confirmation biases, as researchers are not just presenting the analysis that worked best but are showing a range of possible outcomes.

It does present some challenges, as conducting a multiverse analysis can be time-consuming and computationally intensive.

In summary, the multiverse approach in EEG analysis explores a wide range of analytical choices to understand how these choices impact the results. This approach ensures that the conclusions drawn from EEG data are robust and not overly dependent on specific analytical decisions.

References

A. Delorme and J. A. Martin, "Automated Data Cleaning for the Muse EEG," 2021 IEEE International Conference on Bioinformatics and Biomedicine (BIBM), Houston, TX, USA, 2021, pp. 1-5, doi: 10.1109/BIBM52615.2021.9669415.

Delorme A. (2023). EEG is better left alone. Scientific reports, 13(1), 2372. https://doi.org/10.1038/s41598-023-27528-0

Clayson, P. E., Baldwin, S. A., Rocha, H. A., & Larson, M. J. (2021). The data-processing multiverse of event-related potentials (ERPs): A roadmap for the optimization and standardization of ERP processing and reduction pipelines. NeuroImage, 245, 118712. https://doi.org/10.1016/j.neuroimage.2021.118712

Quarterly Newsletter Article from February 2024

A New Era of Data Sharing

Abby Paulson — Thu, 15 Feb 2024 17:54:20 GMT

By: The NITRC Team (https://doi.org/10.18116/8ah0-8116)

The scientific research community has entered a new era of data curation, management, and access. This is due to recent efforts to encourage open data practices including the the NIH's new Data Management and Sharing Policy. The policy emphasizes the need for consistent and transparent data management practices, including accuracy, preservation, and efficient storage. Additionally, it requires data to be open and FAIR (Findable, Accessible, Interoperable, and Re-usable), and demands consistent and transparent data management and curation practices like accuracy, preservation, and high-performance storage.

So, what does this mean for you? Choosing the proper data repository is more critical than ever before. Beyond that, establishing a process within your laboratory for curating data for public access can be one of the most daunting yet essential aspects of data management for investigative science. We can help be part of your solution and help you easily navigate this exciting new landscape.

Quarterly Newsletter Article from October 26, 2023

Characteristics of Quality Data Repositories

NITRC Moderator — Thu, 15 Feb 2024 17:52:19 GMT

By: The NITRC Team (https://doi.org/10.18116/yd0f-2q69)

It is wonderful, exciting news when a researcher learns they have been awarded funding for their research proposal. And then the work begins.

Sometimes funding requirements name a particular data repository (or sets of repositories) to be used to preserve and share data. But if a specific data repository is not identified, choosing which one to share data with is important. With the 2023 NIH Data Management and Sharing Policy officially in place, selecting the right repository for your particular data is a decision that NIH-funded researchers have to make, and non-NIH-funded researchers interested in open data are choosing to make as well.

Fortunately, many resources have become available to help with this decision-making process. NIH provides guidance for Selecting a Data Repository, including a list of desirable characteristics of data repositories and a list of NIH-Approved Repositories for Sharing Scientific Data – on which NITRC is listed for neuroimaging data. Another resource is Nine Best Practices for Research Software Registries and Repositories: A Concise Guide. Here the authors describe an environment most conducive to researchers using software registries and repositories. In response, the NITRC team recently completed a gap analysis between these recommended best practices and what we offer, making adjustments to better meet their objectives. You can read our response in the NITRC User Guide here.

If you or your colleagues have neuroimaging data needing a repository home, please consider using NITRC and contact moderator@nitrc.org for more details.

Quarterly Newsletter Article from May 11, 2023

Providing Performance Information about Tools and Resources

Christian Haselgrove — Thu, 15 Feb 2024 17:50:56 GMT

By: Christian Haselgrove, NITRC Co-PI (https://doi.org/10.18116/k53j-8480)

Since its inception, NITRC has provided answers to basic questions to help with the selection of neuroimaging software: What does this tool do? What platforms does it run on? What license is it released under? NITRC now takes a step further by providing performance information about tools: How long does it take to run? How well does it perform a given function? Exposing this information before software is downloaded and installed, let alone run, will save time when selecting a tool for a given analysis and will provide insights on the best tool for a task.

NITRC now reports performance data for image segmentation. For segmentation tools, we report run time, accuracy compared to Internet Brain Segmentation Repository data, and test-retest stability using Brain Segmentation Testing Protocol data. Sample images of segmentation results are also provided for qualitative analysis of results.

While much of this data can be used to compare tools, care should be taken not to jump from narrowly defined metrics to broad judgements of quality. Indeed, most metrics, even if they can be expressed quantitatively, do not map simply to quality. By the same token, these metrics express nuanced functional performance that can help distinguish tools and select the best option for a given analysis.

Find performance data by following the Performance Data menu item at the left on a tool's main page. (See, for example, FreeSurfer.) Stay tuned as we expand performance data to other functions in the future and send any feedback you have to moderator@nitrc.org.

Quarterly Newsletter Article from October 13, 2022

Responsible Use of Large-Scale Neuroimaging Datasets

Angie Laird — Thu, 15 Feb 2024 17:47:47 GMT

By: Angie Laird, PhD, Florida International University (https://doi.org/10.18116/18b3-1v85)

Large, open datasets have emerged as important neuroimaging resources that offer exciting opportunities for innovative discoveries. Before engaging in secondary data analyses, it is essential that researchers consider relevant ethical issues for responsible data use.

Training Considerations for Responsible Conduct of Research

Training in responsible conduct of research typically emphasizes important topics related to the protection of human subjects, animal welfare, and laboratory safety. However, responsible conduct of research also extends to data management, sharing and ownership, scientific rigor and reproducibility, and responsible authorship and publication.

Increased sharing of large, open datasets must be accompanied by heightened attention to ensuring the protection of participant identity, including individuals from more vulnerable populations, such as patients with clinical disorders and/or from historically underrepresented groups.

Responsible Data Analyses Require Advance Planning

Beyond concerns about participant privacy, responsible data analyses require advance planning, becoming familiar with the data acquisition protocols, and understanding the limitations of the acquired data.

Generally, when planning to collect study data, scientists can choose the research instrument that best addresses their research question. However, when working with existing data, the study design cannot be manipulated. Consequently, the scientific process is reversed, and the research question must be designed based on the appropriateness of the available instrument. Secondary data analysis projects can be conducted relatively quickly - the data are already collected and available for download. But responsible data use requires that researchers pause before engaging with the data and think carefully to ensure that research questions are suitable for the given dataset.

Preventing Stigmatizing Research

Finally, prior to any data analysis or interpretation, researchers must engage responsibly and fully consider the psychological, social, economic, and any other potentially harmful impacts their research could have on individuals, communities, and society. Specifically, this means that responsible use of variables related to race, ethnicity, gender, and sex must be thoughtfully considered prior to conducting analyses of neuroimaging data. Comparisons across participants who are grouped by race and/or ethnicity can potentially be interpreted as evidence of biomarkers that explain neurobiological mechanisms through which some communities experience lower rates of achievement and poorer life outcomes. To discourage continuation of this biological deficits framework, it is imperative that data analysts recognize that ethical conduct in research includes ensuring that analyses prevent further stigmatization, marginalization, and injustice toward individuals because of racial, ethnic, or gender status.

Additional discussion of these issues can be found in two recent publications, including a review article and a practical guide for analyzing data from the ABCD Study.

Guidelines for Preventing Stigmatizing Research have been adapted from the Responsible Conduct of Research developed by All of Us, the NIH’s Precision Medicine Initiative.

Quarterly Newsletter Article from June 14, 2022

Leverage AWS Cloud Computing for your Neuroimaging Data with NeuroStack

Hailey D''Silva — Thu, 15 Feb 2024 17:44:16 GMT

By: Hailey D'Silva, Neuroimaging Data Analyst, Yale School of Medicine (https://doi.org/10.18116/c4rt-aj48)

Cloud computing allows you to borrow compute resources on a pay-as-you-go basis. Research groups who were previously limited to running their analyses on their local or institutional systems can now choose a cloud platform to flexibly and scalably borrow the compute resources they need. Neuroimaging datasets are getting larger, creating greater storage and compute demands, and many of the largest neuroimaging datasets are already hosted on cloud platforms. This has prompted some researchers to wonder how they can work with data in the cloud, but migrating workflows and building data pipelines from scratch on a cloud platform can present a significant challenge.

We are proud to present NeuroStack, built through a collaboration between researchers at the Yale School of Medicine and the University of Massachusetts Medical School. NeuroStack is a tool to aid researchers working with neuroimaging data using AWS cloud computing. Little to no AWS experience is needed to use NeuroStack, and it is freely available to the research community on the NITRC website. When you download NeuroStack, you build a pipeline of AWS resources optimized for neuroimaging workflows into your AWS account. Researchers who previously would have needed to spend hours learning about and building AWS services from scratch can now use NeuroStack to immediately begin working with their data. To use NeuroStack, simply modify and upload a template script to fit your needs and upload your data. Your uploaded data will immediately begin processing according to your script.

What types of workflows can you use NeuroStack for? NeuroStack contains the NITRC computational environment (NITRC-CE), which means you can use NeuroStack to work with any of the software available in the NITRC-CE. This includes FSL, SPM, AFNI, FreeSurfer, PLINK, 3D Slicer, MRIcron, DTIPrep, scikit-learn, NEURON, and more.

You can download NeuroStack and find detailed instructions here. Watch the NeuroStack introduction video here.

Quarterly Newsletter Article from March 15, 2022

Creating Longevity for Scientific Projects

David Kennedy — Thu, 15 Feb 2024 17:40:09 GMT

By: David Kennedy, PhD (https://doi.org/10.18116/t5nq-ey18)

Scientific researchers often discuss the long-term sustainability of projects that initially receive grant funding. If orphaned, projects can become obsolete in the fast-paced scientific research environment, yet often sustaining them requires a considerable expense of time, money, and more often than not, both.

We sat down with our team and discussed these topics, drawing from the 14 years and counting that NITRC has served the neuroimaging community.

Q. Concerning longevity, are all projects the same?

No. At NITRC, we host many projects: software tools, data, data repositories, community interest groups, etc. These different types of projects have different perspectives on considering project longevity. Here we will review high-level considerations for longevity for software and data projects separately. Software longevity requires active development and support to keep up with the advances in underlying computational infrastructure (hardware and operating system evolution) and to sustain user support and bug tracking. Data longevity requires the persistence of the requisite data storage space. If best practices and standards of data sharing are followed, users’ long-term support can be fairly self-sustaining. If best practices and standards of data sharing are not followed, continued support for facilitating data use would be required, or else the utility of the data will diminish over time as the data becomes unintelligible to users without assistance.

Q. Can you share some of the keys to ensure a scientific project has a foundation for longevity?

Several factors can play a role in promoting the longevity of a project. Some include integration with other initiatives and leveraging cost efficiency options when possible (e.g., bulk cloud computing discounts via NIH STRIDES Initiative). One of the most important factors to encourage longevity is to follow ‘best practices for project management. Nine Best Practices for Research Software Registries and Repositories: A Concise Guide provides valuable direction. This is an output from a Task Force of the FORCE11 Software Citation Implementation Working Group. In it, the authors suggest nine best practices for scientific projects incorporating repositories. They include the following, though the source provides much more detailed content:

Provide guidance for users

Provide guidance to software contributors

Establish an authorship policy

Share your metadata schema

Stipulate conditions of use

State a privacy policy

Provide a retention policy

Disclose your end-of-life policy

The active maintenance of a scientific project requires sustainable funding year-over-year. The National Institutes of Health (NIH) often requires grantees and contractors to propose a sustainability plan for projects that provide infrastructure. Most specific funding is time-limited, and its scope can change; scientific projects that provide infrastructure should have diversification in their set of funding avenues. Sustainability can be as simple as having more than one NIH Institute or Center or other government entity supporting it, like Substance Abuse and Mental Health Services Administration (SAMSHA) or the National Science Foundation (NSF), being tapped to fund various portions of the program. Longer-term and sustainable funding can also come from licensing, usage, and other fee-based service models.

Q. What happens when funding eventually runs out?

All good things do, unfortunately, come to an end. ‘End of Life’ and ‘sunsetting’ options should be anticipated and planned to facilitate users' ordered transition to seek alternate solutions. In most cases, good and valuable ‘products’ are replaced by even better ‘products’. The community then advances in the technology, capabilities, and knowledge provided by the past.

Q. Can you recommend some other resources?

For further reading, consider the following:

https://www.nap.edu/resource/25639/biomed_public_webinar_0717.pdf

https://pubmed.ncbi.nlm.nih.gov/25349910/

https://www.nationalacademies.org/our-work/forecasting-costs-for-preserving-archiving-and-promoting-access-to-biomedical-data

Quarterly Newsletter Article from December 21, 2021

Kicking Off NITRC Week

Abby Paulson — Thu, 15 Feb 2024 17:37:51 GMT

https://doi.org/10.18116/epj4-xs64

Instead of hosting a Town Hall, we want to provide our community with value that we are making available all week: expert panel discussions on several neuroimaging domains, a demonstration using NITRC Image Repository data on the NITRC Computational Environment, information about the State of Neuroimaging, and more. All of that is available right here on NITRC.

We use community guidance to make plans for NITRC’s future, so in exchange, we are asking for you to give us your feedback about how NITRC can better serve you in the coming years. Please take five minutes to provide us with your Community Feedback for our future direction. Most of us have spent enough time on scheduled video calls this year, so we are leaving this content available for you to enjoy at your convenience during NITRC Week.

We are glad to have you as part of our neuroimaging community!

Domain Experts Share Expertise

To celebrate NITRC Week, our team sat down with experts to learn more about EEG/MEG, Imaging Genomics, Computational Neuroscience, and Educational Resources in neuroimaging. Each of these domains (and more!) are searchable on NITRC. View the Panel Discussions >

Quarterly Newsletter Article from May 5, 2021