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Saliva-based Testing Model to Combat the COVID-19 Pandemic: Innovation and Future Applications

***Introduction***

The COVID-19 pandemic revealed deep vulnerabilities in global health systems, leading to an urgent need for new and effective models for testing and diagnosing the SARS-CoV-2 virus. This article focuses on the development of a new testing technology known as “SalivaDirect,” which has demonstrated innovative effectiveness by using patient saliva as a test sample without the need for complex extraction procedures. This technology has managed to address the significant challenges faced by global efforts to diagnose infections, including material shortages and healthcare system responses. We will explore the benefits that “SalivaDirect” offers, how it has contributed to improving the capacity for rapid and effective testing, and expanding access to testing in the United States and beyond. We will also discuss the new regulatory frameworks and innovative practices that have been developed to ensure the continuity of this strategy in the face of future pandemics.

The Evolution of COVID-19 Diagnostic Strategies

The COVID-19 pandemic posed unprecedented challenges to health systems around the world, with research showing that the world was unprepared to deal with this outbreak. This called for an urgent need to implement large-scale testing, resulting in the rapid and effective evolution of diagnostic strategies to meet the high demand for tests. There were many obstacles that slowed this process, such as regulatory delays, workforce shortages, lab bottlenecks, and supply chain disruptions. To achieve these changes, and given the critical need, new strategies for testing SARS-CoV-2 were developed, focusing on the use of saliva as a diagnostic sample.

Instead of relying on traditional methods that require nasopharyngeal swabs, saliva was used, which is a less painful and easier sample to collect, helping to alleviate pressure on medical staff. Saliva has been shown to provide accurate and reliable results for COVID-19 diagnosis, facilitating broader access to testing for various segments of the community, thus allowing for faster and more effective identification of infection cases.

The use of saliva became possible due to a series of studies proving its effectiveness as a reliable indicator of viral presence. Research has shown that there is a higher concentration of viral RNA in saliva during the early stages of infection compared to nasal swabs, making saliva a standard methodology for diagnosis. Studies have also confirmed that saliva can be collected without the need for specialized personnel, contributing to the acceleration of testing.

SalivaDirect Protocol

The SalivaDirect protocol was developed in response to the challenges faced by traditional testing methods. The main goal was to facilitate access to COVID-19 testing by providing a protocol that could be easily adopted and at a reasonable cost. Unlike traditional tests that require RNA extraction, the new protocol simplified this process by using saliva as a direct sample material, thus reducing time and costs.

The protocol was designed to work with materials available on the market, allowing laboratories to use reliable materials sourced from multiple providers, thus easing pressure on the supply chain. The estimated cost per test using SalivaDirect ranged from $1.21 to $4.39, making it an economical option for various health laboratories.

Taking into account multiple studies and careful monitoring of performance, SalivaDirect confirmed its effectiveness by achieving positive rates of up to 94% when compared to traditional testing methods, making it highly reliable, cost-effective, and adaptable to the needs of different laboratories. This protocol also enabled the testing of asymptomatic individuals, thereby increasing the ability to screen and identify infected cases across various populations.

Framework

New Organization and Series of Laboratories

To ensure the successful dissemination of the protocol, a new organizational framework has been established to align with the requirements of the U.S. Food and Drug Administration (FDA). Yale University received authorization to collaborate with the FDA to offer the SalivaDirect test to complex diagnostic laboratories. This procedure was groundbreaking as it delegated responsibility to certain laboratories to enhance technology transfer and immediately increase testing capacity, which was vital amid the health crisis.

Thanks to this collaboration, a network of over 200 laboratories across the United States was formed, leading to more than 6.5 million tests for SARS-CoV-2 by May 2024. This network addresses innovation in public health and provides communities with effective tools to manage future epidemics or seasonal illnesses. Additionally, this network facilitated immediate exchanges to solve problems and collaborate on establishing best health practices in various communities.

These collaborative models are essential for responding to future epidemics, as they provide a replicable pathway in any potential health crisis. These systems and methods offer an ideal framework for managing tests, resulting in improved overall safety and increased capacity to provide healthcare during times of crisis. The SalivaDirect protocol serves as a model for various global health systems to expand testing and facilitate access.

Development of the SalivaDirect Protocol and Its Interactions with Laboratories

The development of the SalivaDirect protocol required close collaboration among multiple laboratories and institutions. Technical and administrative support was provided to designated laboratories to ensure compliance with usage instructions, as there was a need to equip laboratories based on approved tools and materials for use in COVID-19 testing. Collecting data on performance was critical, and this data was sent to Yale University, which analyzed it and forwarded it to the FDA. This collaboration simplified resource sharing required for verification and the development of competent testing protocols.

Lessons learned from this collaboration include the importance of continuous analysis and communication with laboratories once the launch process began. By creating a network of interconnected laboratories, it became possible to share necessary verification materials, while regular video meetings provided a platform to discuss any challenges or needs related to the protocol. For example, more than 25 modifications to the base protocol were adopted to expand its use and facilitate wider adoption, including the introduction of new mechanisms to support high-throughput testing and reduce costs.

Sample Collection Strategies and Unsupervised Needs

Initially, it was necessary for saliva collection to be supervised by trained professionals to ensure quality. However, with the increasing demand for testing, it became essential to seek more cost-effective methods to expand sampling usage. This led to collaboration with the FDA to develop a protocol allowing trainable individuals to supervise saliva collection.

The initiatives successfully demonstrated the ability to collect saliva samples reliably without supervision. This allowed individuals to collect their samples in various locations, whether in clinics or at home, increasing access to testing. This development was supported by providing clear instructions for collecting quality saliva samples, reducing the burden associated with collecting and transporting samples.

With the FDA allowing laboratories to implement unsupervised protocols, saliva collection kits could be developed based on these protocols, helping to remove barriers and increase the number of available tests.

Increasing Capacity and Achieving Bulk Testing

As the U.S. economy reopened, there was an urgent need to implement mass screening programs to ensure that schools and public places were safe. To ensure the sustainability of these efforts, it was essential for testing methods to be less expensive and more efficient. The SalivaDirect method had already met appropriate standards, but there was a need to explore other solutions such as batch sampling, which provided a more economical approach.

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Despite concerns about the impact of pooling on test sensitivity, pooling protocols were developed and successfully tested, showing significant agreement with individual test results. This development has proven effective in cost savings and increasing laboratories’ capacity to process a larger number of samples.

The success stories of laboratories that used SalivaDirect for population-level testing highlight the importance of this process. Laboratories, supported by clear and streamlined protocols, have been able to enhance testing capabilities in their communities while also meeting the growing demands for screening support in education, healthcare, and workplace settings.

The Extensive Network of SalivaDirect Laboratories

Since August 2020, more than 200 high-complexity CLIA-certified laboratories across the United States have become part of the SalivaDirect network. These laboratories have not only contributed to expanding testing capacity but also to developing new screening methods and effectively serving communities. The total recorded tests exceeded 6.5 million, with a positivity and negativity rate of less than 0.01%.

Laboratories contribute to providing reliable testing in diverse settings such as schools and healthcare centers. Many laboratories come from academic institutions or private entities, reflecting a rapid response to the pandemic. With the increasing demand, the network’s capacity remains high, ready to face any sudden increase in demand.

The swift response and adaptability to variants have helped network laboratories meet the growing needs, demonstrating the protocol’s resilience. Laboratories have agreed on several goals, such as saving time and reducing the need for closed testing tools, which has facilitated their ability to deliver accurate and rapid results in their communities.

The Role of SalivaDirect in SARS-CoV-2 Testing

The SalivaDirect model was established as a pioneering initiative in the testing of the SARS-CoV-2 virus, providing a comprehensive network of CLIA-certified laboratories. This initiative has contributed to enhancing access to virus testing among individuals, especially in the context of the COVID-19 pandemic. The model allows for the adoption of simple and effective testing protocols, facilitating testing without the need for complex procedures. Many group calls and individual conversations have taken place between laboratory teams and the SalivaDirect team, helping clarify technical aspects and facilitating the overall adoption of tests.

Since its launch, there has been an increasing recognition of the importance of having scalable and monitored protocols to address changing public health needs. For instance, simple and non-complex protocols have been implemented to provide consistent testing across multiple sites, which can enhance the quality of future data and monitoring purposes. The success of this initiative shows that a standardized testing process can effectively be applied in different countries and networks.

The Importance of Network and Collaboration Among Laboratories

The SalivaDirect initiative features a network of highly competent laboratories, enhancing opportunities for collaboration and knowledge exchange among these laboratories. Even in the face of a decline in COVID-19 testing cases, the network remains active and cooperative, providing technical support and seeking new collaboration opportunities. This network is essential for building on the successes achieved during the pandemic and preparing for a rapid and effective response to future health challenges.

Collaboration among laboratories includes resource and information exchange, virus testing coordination, and these laboratories serve as a sentinel to track virus spread and the emergence of new variants, which is a vital component of effective health response. These laboratories also contribute new suggestions for future diagnostic targets, requiring the scientific community to focus more on closely preparing laboratories and interpreting results.

Developing Innovative Diagnostic Solutions

Continuing from the achievements of the SalivaDirect model, there are ongoing efforts to develop and deploy new diagnostic solutions. SalivaDirect, Inc., a nonprofit organization supporting public health, focuses on creating mobile testing programs that remove barriers preventing communities from accessing tests. These solutions allow vulnerable communities to reduce health service gaps and increase access to testing that may be vital for identifying and treating emerging health issues.

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One of the prominent aspects of the development carried out by SalivaDirect is the establishment of webinars that bring together scientists and researchers from various countries, facilitating the exchange of ideas and experiences. These activities emphasize the importance of building a strong knowledge network that aids in enhancing public health and improving responses to future pandemics.

Strategic Design for Pandemic Response

The SalivaDirect model is a benchmark for pandemic response, providing a framework that allows for effective interaction with future health challenges. By utilizing flexible protocols and adaptable reproductions, testing can be expanded to better meet community needs. The need for rapid responses to pandemics also requires methods for easy sample collection, such as saliva collection, opening the door for greater access to clinical trials.

Increasing evidence suggests that viral and bacterial diseases can be identified in saliva with clinical sensitivities similar to those in nasal samples, reflecting the great potential of the SalivaDirect method and its rapid adaptations for testing other pathogens. For instance, studies have shown that the model can be adjusted to study diseases such as influenza, RSV, and mpox virus, making it possible to effectively respond to emerging infection threats.

The Importance of Collaboration and Innovation in Addressing Upcoming Health Challenges

The SalivaDirect initiative underscores the importance of collaboration among countries and health organizations to tackle global challenges in public health. With a cohesive regulatory framework, the SalivaDirect model has improved access to SARS-CoV-2 testing. Success relies on innovation in regulation and the application of open protocols that meet quality standards set by developers. This model serves as a roadmap for addressing a broader scope of tests for new respiratory diseases, opening new avenues for improving global public health.

Through this collaboration and innovation, we can enhance our collective readiness to face future health challenges and improve our competencies in dealing with pandemics. The importance of investment in research and studies based on lessons learned from the COVID-19 period is highlighted as a means to strengthen public health infrastructure and empower communities to face pandemics more effectively.

Challenges in SARS-CoV-2 Diagnosis

The COVID-19 pandemic significantly impacted healthcare systems worldwide, revealing how unprepared we were to tackle pandemics. One of the main challenges was in the testing for SARS-CoV-2 infection, which imposed tremendous pressure on healthcare services. Before the virus, many health systems relied on traditional diagnostic techniques and practices that depended on samples like nasopharyngeal swabs for respiratory infections. However, as the virus spread, these systems faced serious obstacles including resource shortages, inadequate laboratory capacities, and a lack of necessary equipment such as personal protective equipment. For example, the COVID-19 crisis led to a reduction in the availability of swabs and medications, impacting laboratories’ ability to conduct necessary tests quickly and efficiently.

Nasopharyngeal swabs became the standard samples, even though they faced challenges in being painful experiences that might deter patients from undergoing testing. Furthermore, collecting those samples required trained health professionals, adding cost and time to the testing process. This situation prompted researchers to consider alternatives such as saliva, leading to new opportunities for expanding our testing capabilities in a simpler and more cost-effective manner. There should be greater preparedness to face future pandemics through more flexible testing strategies and the use of readily available materials.

Innovations in Using Saliva for COVID-19 Diagnosis

The pandemic witnessed a radical shift in how diagnostic testing was conceived. Research’s focus on using saliva as an alternative model for testing SARS-CoV-2 has paved the way for promising results. Studies like those reported by Wright and others (2020) have shown that saliva can be more suitable than traditional swabs, as it is less painful and easier to collect. Additionally, saliva analysis requires less complex equipment, facilitating the testing process in local communities like schools and kindergartens. This recent trend could simplify testing significantly and enhance public confidence in testing programs.

An example

One of the keys to the success of the SalivaDirect program is the collaboration between Yale University and various institutions and organizations. This partnership has enabled the rapid development and deployment of the testing protocol. In addition to academic institutions, collaboration with local health departments, schools, and community organizations has played a significant role in ensuring that the testing process is accessible to as many individuals as possible. The collective efforts of these partnerships demonstrate the importance of collaboration in addressing public health challenges effectively.

Conclusion

The SalivaDirect program, with its innovative approach and collaborative efforts, represents a significant advancement in the testing landscape for SARS-CoV-2. The use of saliva as a testing medium not only improves accessibility but also highlights the potential for similar strategies in future public health crises. By learning from both the successes and challenges faced during the COVID-19 pandemic, we can build more resilient health systems capable of swiftly addressing emerging infectious diseases.

With the U.S. Food and Drug Administration (FDA)

The SalivaDirect initiative developed an innovative regulatory framework in partnership with the U.S. Food and Drug Administration. Yale University obtained an emergency use authorization, allowing participating laboratories to implement the protocol under our supervision. The process included meticulous monitoring of protocol performance, as laboratories had to confirm the effectiveness of the protocols before they were approved, helping to build a reliable diagnostic system. Additionally, subsequent modifications to the protocol, which exceeded 25 adjustments, improved performance and enhanced access to testing.

Creating a Laboratory Network across the United States

A network of clinical laboratories was established across the United States to use the SalivaDirect protocol. The primary goal was to develop a support mechanism for laboratories to assist them in easily implementing the protocol. Through collaboration with laboratories, we were able to provide technical support and assist in sharing the necessary resources to validate performance. Regular video conferences and information exchange via communication channels helped laboratories enhance efficiency and improve test quality. This network played a vital role in facilitating the rapid distribution of tests during the peak of the pandemic.

Global Response to Future Health Challenges

The impact of the SalivaDirect protocol was not limited to addressing COVID-19; it has become a model that can be developed to meet future global health challenges. With a focus on accessibility and effectiveness, the approach used in the development of the protocol could be ideal for application to other forms of viruses such as influenza and other respiratory viruses. By June 2024, we continued to seek additional FDA approvals and gain further confidence in performance through reference material testing and ensuring compliance with regulatory requirements.

Conclusion of Efforts and Future Prospects

Work has continued to improve the SalivaDirect protocol and expand its scope to include new capabilities such as at-home self-sampling, which will enable access to testing in a wide range of environments. Efforts continue to address the challenges of non-invasive testing, and we will continue to push the boundaries of what can be achieved in diagnostic fields using open and adaptable models. By enhancing networks among laboratories and disseminating knowledge, we have positioned ourselves to tackle any global health challenges that may arise in the future.

Developing Saliva Sampling Methods

The SalivaDirect initiative has achieved significant success in developing saliva sampling methods, contributing to the acceleration and improvement of screening processes for detecting the SARS-CoV-2 virus. This method represents an important advancement in the healthcare system, making sample collection simple and uncomplicated, thereby reducing the need for trained health personnel to supervise the process. Initially, saliva was collected under the supervision of health staff, but with the increasing demand for testing, we worked with the U.S. Food and Drug Administration (FDA) to develop new protocols that allow individuals to collect their samples independently in an unsupervised manner. Clear and comprehensive guidelines were provided to individuals to ensure high-quality sample collection, helping to establish practical solutions to alleviate the burden of sample transportation and testing, thus broadening the public’s base for conducting tests.

Increasing Testing Capacity Using SalivaDirect

With the resumption of economic activity, schools, and sporting events in the United States, continuous mass testing for COVID-19 has become essential. SalivaDirect has developed new methods that enable laboratories to achieve this efficiently. One key strategy was to conduct pooled sample testing, allowing laboratories to save time and costs while maintaining test accuracy. After tests and analyses, it was confirmed that this method does not adversely affect test sensitivity. Although many laboratories preferred to continue testing individual samples, some recognized the economic benefits of the pooled testing approach.

Network

SalivaDirect Laboratories and Their Contributions to Testing

Since 2020, a network of over 200 CLIA-certified laboratories has been established across 42 U.S. states to provide testing services using SalivaDirect protocols. This network has enabled the conduct of over 6.5 million tests for individuals suspected of having the coronavirus, with reported rates of false positives and false negatives of less than 0.01%, reflecting the system’s effectiveness. These laboratories rely on a variety of available resources and chemicals, allowing them to meet testing needs rapidly and on a large scale. Additionally, this network has demonstrated significant flexibility in adapting to local and health requirements, contributing to the success of testing operations during the pandemic.

Strategies for Response and Planning for Future Health Disasters

The experience of SalivaDirect serves as a model for effective pandemic response and planning for future health crises. One of the lessons learned is the importance of the rapid implementation of sample collection protocols, which can help overcome many challenges when a new pandemic emerges. By providing saliva-based sample collection options, access to testing has been significantly expanded. There is also a highlighted need to develop a flexible and user-friendly system that enables laboratories to respond quickly to community demands. The study addressed the importance of providing open-source protocols, allowing for rapid application by a diverse network of laboratories.

Future Trends and Innovation Opportunities in Health Testing

As efforts continue to improve testing services, those behind SalivaDirect are looking to develop new and innovative specialized protocols. Recently, SalivaDirect, Inc. was established as a non-profit public health organization aiming to enhance innovations in public health. With ongoing work on existing networks and the development of new partnerships, this initiative seeks to improve the quality of testing and maintain the continuity of services provided to communities. Utilizing these models not only serves in critical times but also reflects a commitment to achieving long-term qualitative improvements in public health systems.

SalivaDirect Methodology and Its Use in Respiratory Disease Diagnosis

SalivaDirect methodology is considered one of the most important modern approaches used in diagnosing respiratory diseases, including SARS-CoV-2 virus. This methodology was developed to facilitate the sample collection process and simplify testing procedures, relying on saliva as a means of sample collection instead of traditional methods such as nasal swabs. This innovation has not only expedited the detection of viruses but also made it less expensive and more accessible, enhancing access to testing in resource-limited communities.

In previous studies, SalivaDirect has proven effective not only in detecting the coronavirus but also in monitoring several other respiratory pathogens such as influenza, respiratory syncytial virus, and pneumococci. Researchers have indicated that this method is easily adaptable for the detection of these viruses, suggesting enormous potential for the scalability of this methodology and improvement of the public health community’s response to emerging health threats. The results obtained using SalivaDirect provide a strong infrastructure for collaboration and education among laboratories, enhancing the ability to coordinate testing during epidemics.

For instance, laboratories participating in the SalivaDirect network have increased access to testing across the United States, meeting the needs of diverse populations. This collaboration is also beneficial in monitoring the spread of emerging viruses and can therefore be used as a tool for predicting the emergence of new virus variants. Additionally, the implementation of this methodology helps build a unified knowledge base that supports addressing health crises at a global level.

The Framework

Regulatory and Quality Metrics in the SalivaDirect Model

Studies indicate that one of the reasons for the success of the SalivaDirect model is the strong regulatory framework established to set quality standards for handling tests and diagnoses. Innovative methods have been utilized in collaboration with the U.S. Food and Drug Administration (FDA) to establish reliable standards that ensure the safety and efficacy of the tests used. Moreover, this framework includes a mechanism for quality verification of tests using open-source protocols, allowing laboratories to develop new methods while adhering to high-quality standards.

This degree of collaboration between private companies and regulatory agencies helps provide an environment that fosters sustainable innovation and effective responses to pandemics. This success can be considered a model to emulate in efforts to enhance the healthcare system’s capacity to deal with future health emergencies. Specifically, pandemic outbreaks require rapid responses, and the effectiveness of this response depends on the availability of reliable diagnostic tools.

Additionally, the model involves collaboration between scientists and laboratories to create a continuous innovation environment. Research teams can leverage shared resources and previous research findings to achieve ongoing improvement. Providing cost-effective and efficient solutions is a significant challenge, especially in resource-limited communities. By relying on this regulatory framework, it is possible to achieve greater objectives in combating diseases and improving public health on a large scale.

Future Applications of the SalivaDirect Model and Social Testing Challenges

The SalivaDirect model is expected to continue influencing the public health sector in the future. With the technologies developed, this methodology can be applied in other fields such as the diagnosis of infectious diseases or chronic diseases. As the pandemic surpasses the COVID-19 crisis, the scalability of SalivaDirect is needed to address new global health challenges. Leveraging data collected during the pandemic can help enhance and adapt testing models to the potential emergence of new pathogens.

In the future, the scientific community must develop strategies that focus on social relationships and community components to ensure that health solutions encompass the diverse needs of individuals. Education and awareness about how to conduct self-tests and utilize new technologies are essential aspects for achieving success. Furthermore, providing the necessary physical means and knowledge to support such initiatives in communities is crucial.

When considering how to address potential future pandemics, it is essential to strengthen the SalivaDirect network to enhance coordination and collaboration among different laboratories. Continuous improvement in sample collection and analysis techniques will contribute to strengthening the resilience of the healthcare system. Moreover, good preparedness and the ability to respond quickly to emerging pathogens are key factors that will enable us to incorporate the model into global public health strategies in the future.

Evolution of COVID-19 Testing Methods Using Saliva

In recent years, the focus in medical and scientific research has shifted to using saliva as a means of combining efficacy and convenience in detecting the novel coronavirus (SARS-CoV-2). Traditional methods for virus testing have relied on nasal swabs, which require a certain skill to execute and sometimes cause discomfort or pain for patients. However, with advancements in genetic technologies, saliva tests have become an attractive and more convenient alternative. Saliva tests are characterized by their ease of collection and the lack of need for complex equipment compared to traditional methods.

The main benefit of using saliva is that it can be easily collected, making it ideal for mass testing, such as in schools and daycare centers. Some studies, such as those conducted by a team of scientists from a medical research institute, have shown that the results obtained from saliva tests were consistent with those from nasal swabs. In those contexts, saliva tests are a cost-effective option, particularly in low- and middle-income countries where resources and funding remain limited.

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One prominent example of this is the COVID detection program implemented in primary schools in Abu Dhabi, which relied on saliva tests as a primary tool for detecting the virus among students. The results were encouraging, as they helped reduce the spread of the virus in that environment. Additionally, the use of saliva reduces contact between individuals and supports general health safety principles.

Challenges of Saliva Testing and Future Research

Despite the numerous benefits of saliva testing, several challenges still remain. The accuracy of the test is one of the most important elements to consider when relying on this method. For example, researchers need to ensure that the sensitivity of saliva tests is not less than that of traditional swab tests. While many preliminary studies show promising results, the need for broader agreement within the scientific community remains urgent.

Some research suggests that in certain cases, the sensitivity of saliva testing may be lower in detecting the virus due to the amount of virus present in saliva compared to nasal swabs. Thus, there may be a need to develop new protocols to improve performance, including concentration and processing techniques before performing the test.

Furthermore, economic analyses play a significant role in determining the widespread adoption of saliva testing. Health programs and systems need to ensure that the cost and maintenance of these tests can fit their budgets without compromising the quality of healthcare provided.

Impacts of Saliva Testing on Community and Health Awareness

The use of saliva tests in public health significantly affects health awareness in communities. These tests help alleviate fear and anxiety related to the COVID pandemic, enhancing community responses to the virus. Establishing saliva testing programs provides individuals in the community the opportunity to assess their health in a non-invasive and low-cost manner.

The educational system and care centers that adopt these tests learn how to better manage health crises, thereby enhancing their resilience and capacity to deal with similar health situations in the future. Providing rapid and easy tests helps boost parents’ and the community’s confidence in educational institutions.

Moreover, this type of testing leads to better health behaviors, as individuals become more cautious and aware of the importance of preventive assessments. Community-driven research and healthcare help create a health culture aimed at promoting prevention and early detection of diseases.

Source link: https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2024.1446514/full

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