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The WHO Early AI-Supported Response with Social Listening (EARS) platform was developed to help inform infodemic response during the COVID-19 pandemic. There was continual monitoring and evaluation of the platform and feedback from end-users was sought on a continual basis. Iterations were made to the platform in response to user needs, including the introduction of new languages and countries, and additional features to better enable more fine-grained and rapid analysis and reporting. The platform demonstrates how a scalable, adaptable system can be iterated upon to continue to support those working in emergency preparedness and response.

Each epidemic and pandemic is accompanied by an infodemic. The infodemic during the COVID-19 pandemic was unprecedented. Accessing accurate information was difficult and misinformation harmed the pandemic response, the health of individuals and trust in science, governments and societies. WHO is building a community-centered information platform, the Hive, to deliver on the vision of ensuring that all people everywhere have access to the right information, at the right time, in the right format in order to make decisions to protect their health and the health of others. The platform provides access to credible information, a safe space for knowledge-sharing, discussion, and collaborating with others, and a forum to crowdsource solutions to problems. The platform is equipped with many collaboration features, including instant chats, event management, and data analytics tools to generate insights. The Hive platform is an innovative minimum viable product (MVP) that seeks to leverage the complex information ecosystem and the invaluable role communities play to share and access trustworthy health information during epidemics and pandemics.

The COVID-19 infodemic is an overwhelming amount of information that has challenged pandemic communication and epidemic response. WHO has produced weekly infodemic insights reports to identify questions, concerns, information voids expressed and experienced by people online. Publicly available data was collected and categorized to a public health taxonomy to enable thematic analysis. Analysis showed three key periods of narrative volume peaks. Understanding how conversations change over time can help inform future infodemic preparedness and prevention planning.

Background The infodemic accompanying the COVID-19 pandemic has led to an overwhelming amount of information, including questions, concerns and misinformation. Pandemic fatigue has been identified as a concern from early in the pandemic. With new and ongoing health emergencies in 2022, it is important to understand how pandemic fatigue is being discussed and expressed by users on digital channels. Methods This paper describes the collection of publicly available data over a 3-month period from multiple online sources using Meltwater, CrowdTangle to source data from Twitter, Facebook, Instagram, YouTube, TikTok, Pinterest, Product Reviews, Twitch, blogs & forums. A comprehensive search strategy was developed and tested. A total of 1,484,042 social media posts were identified during the time-period that included the defined search terms for pandemic fatigue. These data were initially sorted by highest levels of engagement and from this dataset, analysts reviewed the mentions to isolate and remove irrelevant content and identify dominant narratives. A thematic analysis was carried out on these narratives to identify themes related to expression of pandemic fatigue. Two researchers reviewed the data and themes. Results The thematic analysis of narratives identified six main themes relating to expression of pandemic fatigue, and one theme of counter narratives against pandemic fatigue. Data volume increased concurrent with the time of the mpox emergency announcement. Emergent themes showed the different ways users expressed pandemic fatigue and how it was interlaced with issues of trust, preventative measure acceptance and uptake, misinformation, and being overwhelmed with multiple or sustained emergencies. Conclusions This paper has identified the different ways users express pandemic fatigue on digital channels over a 3-month period. Better understanding the implications of the infodemic ecosystem on user’s perceptions, questions, and concerns regarding pandemic and more broadly emergency fatigue is vital in identifying relevant interventions and, in the longer term, strengthening the global architecture for health emergency preparedness, prevention, readiness and resilience, as evidenced in this paper. There are clear pathways for further research, including incorporating additional languages and reviewing these themes over longer time periods.

BACKGROUND Amidst the COVID-19 pandemic, there has been a need for rapid social understanding to inform infodemic management and response. While social media analysis platforms have traditionally been designed for commercial brands for marketing and sales purposes, it has been under-utilized and under-adapted for comprehensive understanding of social dynamics in areas such as public health. Traditional systems have challenges for public health usage and new tools and innovative methods are needed. The WHO Early AI-Supported Response with Social Listening (EARS) platform was developed to overcome some of these challenges. OBJECTIVE To describe the methodological approach to the development of the EARS platform, including data sourcing, development and validation of a machine learning categorization approach, as well as results from the pilot. METHODS Data for EARS is collected daily from online conversations in publicly available sources, including Twitter, Facebook public pages, online forums, news comments, and blogs in 9 languages. Public health and social media experts developed a taxonomy to categorize COVID-19 narratives to 5 relevant main categories and 41 sub-categories. We developed a semi-supervised machine learning algorithm to categorize social media posts to categories and various filters. To validate the results obtained by the machine learning-based approach we compared it to a search filters methodology applying boolean queries with the same amount of information and measured recall and precision. A Hotelling T2 was run to determine the effect of the classification method on the combined variables. RESULTS The EARS platform has been developed, validated and applied to monitor the conversation about COVID-19 since December 2020. A total of 215,469,045 social posts were collected for processing from December 2020 to February 2022. The machine learning algorithm outperformed the boolean search filters method by a large margin for precision and recall in both English and Spanish (p CONCLUSIONS The EARS platform has been specifically developed to address the changing needs of public health analysts during the COVID-19 pandemic. The application of a public health taxonomy and AI technology to a user-friendly social listening platform, accessible directly by analysts, is a significant step in better enabling understanding of global narratives. The platform was designed in a way to allow for scalability, and iterations and new countries and languages have been added. This research has shown that a machine learning approach is more accurate than using only keywords and has benefit for categorizing and understanding large amounts of digital social data during an infodemic. Further technical developments are needed and planned to provide continuous improvements and meet the challenges in generation of infodemic insights from social media faced by infodemic managers and public health professionals.

Background Vaccine hesitancy is one of the many factors impeding efforts to control the COVID-19 pandemic. Exacerbated by the COVID-19 infodemic, misinformation has undermined public trust in vaccination, led to greater polarization, and resulted in a high social cost where close social relationships have experienced conflict or disagreements about the public health response. Objective The purpose of this paper is to describe the theory behind the development of a digital behavioral science intervention—The Good Talk!—designed to target vaccine-hesitant individuals through their close contacts (eg, family, friends, and colleagues) and to describe the methodology of a research study to evaluate its efficacy. Methods The Good Talk! uses an educational serious game approach to boost the skills and competences of vaccine advocates to have open conversations about COVID-19 with their close contacts who are vaccine hesitant. The game teaches vaccine advocates evidence-based open conversation skills to help them speak with individuals who have opposing points of view or who may ascribe to nonscientifically supported beliefs while retaining trust, identifying common ground, and fostering acceptance and respect of divergent views. The game is currently under development and will be available on the web, free to access for participants worldwide, and accompanied by a promotional campaign to recruit participants through social media channels. This protocol describes the methodology for a randomized controlled trial that will compare participants who play The Good Talk! game with a control group that plays the widely known noneducational game Tetris. The study will evaluate a participant’s open conversation skills, self-efficacy, and behavioral intentions to have an open conversation with a vaccine-hesitant individual both before and after game play. Results Recruitment will commence in early 2023 and will cease once 450 participants complete the study (225 per group). The primary outcome is improvement in open conversation skills. Secondary outcomes are self-efficacy and behavioral intentions to have an open conversation with a vaccine-hesitant individual. Exploratory analyses will examine the effect of the game on implementation intentions as well as potential covariates or subgroup differences based on sociodemographic information or previous experiences with COVID-19 vaccination conversations. Conclusions The outcome of the project is to promote more open conversations regarding COVID-19 vaccination. We hope that our approach will encourage more governments and public health experts to engage in their mission to reach their citizens directly with digital health solutions and to consider such interventions as an important tool in infodemic management. International Registered Report Identifier (IRRID) PRR1-10.2196/40753

It is impossible to address the many complex needs of respiratory virus surveillance with a single system. Therefore, multiple surveillance systems and complementary studies must fit together as tiles in a “mosaic” to provide a complete picture of the risk, transmission, severity, and impact of respiratory viruses of epidemic and pandemic potential. Below we present a framework to assist national authorities to identify priority respiratory virus surveillance objectives and the best approaches to meet them; to develop implementation plans according to national context and resources; and to prioritize and target technical assistance and financial investments to meet most pressing needs.

Background: During a public health emergency, accurate and useful information can be drowned out by questions, concerns, information voids, conflicting information and misinformation. Very few studies connect information exposure and trust to health behaviours, which limits available evidence to inform when and where to act to mitigate the burden of infodemics, especially in low resource settings. In this paper, we describe the need for a toolkit that can link information exposure to health behaviours at the individual level. Methods: Most data-driven infodemiology research is designed to characterise content rather than measure associations between information exposure and health behaviours. Studies also tend to be limited to specific social media platforms, are unable to capture the breadth of individual information exposure that occur online and offline, and cannot measure differences in trust by information source or content. Studies are also designed very differently, limiting synthesis of results. To meet the needs of the research community, we propose a research toolkit that can be used in studies measuring topic-specific information exposure and health behaviours, and implements a standardised protocol so results can be combined in a meta-analysis. Other desirable features of the toolkit would include the ability to tailor studies to local contexts, ease of use for participants, and frictionless sharing of de-identified data for aggregating individual participant data. Results: We demonstrate one solution: a web-based study platform that participants use to record topic-specific information exposure in a diary application and a browser plugin for tracking access to relevant webpages, supports questionnaires, and supports incentives for participation such as visual analytics to compare trust levels with other participants. Conclusions: Our proposed solution will be able to capture detailed data about information exposure and health behaviour data, standardise study design while simultaneously supporting localisation, and make it easy to synthesise individual participant data across studies. Future research will need to evaluate the toolkit in realistic scenarios to understand the usability of the toolkit for both participants and investigators.

Background An infodemic is excess information, including false or misleading information, that spreads in digital and physical environments during a public health emergency. The COVID-19 pandemic has been accompanied by an unprecedented global infodemic that has led to confusion about the benefits of medical and public health interventions, with substantial impact on risk-taking and health-seeking behaviors, eroding trust in health authorities and compromising the effectiveness of public health responses and policies. Standardized measures are needed to quantify the harmful impacts of the infodemic in a systematic and methodologically robust manner, as well as harmonizing highly divergent approaches currently explored for this purpose. This can serve as a foundation for a systematic, evidence-based approach to monitoring, identifying, and mitigating future infodemic harms in emergency preparedness and prevention. Objective In this paper, we summarize the Fifth World Health Organization (WHO) Infodemic Management Conference structure, proceedings, outcomes, and proposed actions seeking to identify the interdisciplinary approaches and frameworks needed to enable the measurement of the burden of infodemics. Methods An iterative human-centered design (HCD) approach and concept mapping were used to facilitate focused discussions and allow for the generation of actionable outcomes and recommendations. The discussions included 86 participants representing diverse scientific disciplines and health authorities from 28 countries across all WHO regions, along with observers from civil society and global public health–implementing partners. A thematic map capturing the concepts matching the key contributing factors to the public health burden of infodemics was used throughout the conference to frame and contextualize discussions. Five key areas for immediate action were identified. Results The 5 key areas for the development of metrics to assess the burden of infodemics and associated interventions included (1) developing standardized definitions and ensuring the adoption thereof; (2) improving the map of concepts influencing the burden of infodemics; (3) conducting a review of evidence, tools, and data sources; (4) setting up a technical working group; and (5) addressing immediate priorities for postpandemic recovery and resilience building. The summary report consolidated group input toward a common vocabulary with standardized terms, concepts, study designs, measures, and tools to estimate the burden of infodemics and the effectiveness of infodemic management interventions. Conclusions Standardizing measurement is the basis for documenting the burden of infodemics on health systems and population health during emergencies. Investment is needed into the development of practical, affordable, evidence-based, and systematic methods that are legally and ethically balanced for monitoring infodemics; generating diagnostics, infodemic insights, and recommendations; and developing interventions, action-oriented guidance, policies, support options, mechanisms, and tools for infodemic managers and emergency program managers.

BACKGROUND An infodemic is excess information, including false or misleading information, that spreads in digital and physical environments during a public health emergency. The COVID-19 pandemic has been accompanied by an unprecedented global infodemic that has led to confusion about the benefits of medical and public health interventions, with substantial impact on risk-taking and health-seeking behaviors, eroding trust in health authorities and compromising the effectiveness of public health responses and policies. Standardized measures are needed to quantify the harmful impacts of the infodemic in a systematic and methodologically robust manner, as well as harmonizing highly divergent approaches currently explored for this purpose. This can serve as a foundation for a systematic, evidence-based approach to monitoring, identifying, and mitigating future infodemic harms in emergency preparedness and prevention. OBJECTIVE In this paper, we summarize the Fifth World Health Organization (WHO) Infodemic Management Conference structure, proceedings, outcomes, and proposed actions seeking to identify the interdisciplinary approaches and frameworks needed to enable the measurement of the burden of infodemics. METHODS An iterative human-centered design (HCD) approach and concept mapping were used to facilitate focused discussions and allow for the generation of actionable outcomes and recommendations. The discussions included 86 participants representing diverse scientific disciplines and health authorities from 28 countries across all WHO regions, along with observers from civil society and global public health–implementing partners. A thematic map capturing the concepts matching the key contributing factors to the public health burden of infodemics was used throughout the conference to frame and contextualize discussions. Five key areas for immediate action were identified. RESULTS The 5 key areas for the development of metrics to assess the burden of infodemics and associated interventions included (1) developing standardized definitions and ensuring the adoption thereof; (2) improving the map of concepts influencing the burden of infodemics; (3) conducting a review of evidence, tools, and data sources; (4) setting up a technical working group; and (5) addressing immediate priorities for postpandemic recovery and resilience building. The summary report consolidated group input toward a common vocabulary with standardized terms, concepts, study designs, measures, and tools to estimate the burden of infodemics and the effectiveness of infodemic management interventions. CONCLUSIONS Standardizing measurement is the basis for documenting the burden of infodemics on health systems and population health during emergencies. Investment is needed into the development of practical, affordable, evidence-based, and systematic methods that are legally and ethically balanced for monitoring infodemics; generating diagnostics, infodemic insights, and recommendations; and developing interventions, action-oriented guidance, policies, support options, mechanisms, and tools for infodemic managers and emergency program managers.

The bacterial human pathogenHelicobacter pyloriproduces a type IV secretion system (cagT4SS) to inject the oncoprotein CagA into gastric cells. ThecagT4SS external pilus mediates attachment of the apparatus to the target cell and the delivery of CagA. While the composition of the pilus is unclear, CagI is present at the surface of the bacterium and required for pilus formation. Here, we have investigated the properties of CagI by an integrative structural biology approach. Using Alpha Fold 2 and Small Angle X-ray scattering, it was found that CagI forms elongated dimers mediated by rod-shaped N-terminal domains (CagIN) and prolonged by globular C-terminal domains (CagIC). Three Designed Ankyrin Repeat Proteins (DARPins) K2, K5 and K8 selected against CagI interacted with CagICwith subnanomolar affinities. The crystal structures of the CagI:K2 and CagI:K5 complexes were solved and identified the interfaces between the molecules, thereby providing a structural explanation for the difference in affinity between the two binders. Purified CagI and CagICwere found to interact with adenocarcinoma gastric (AGS) cells, induced cell spreading and the interaction was inhibited by K2. The same DARPin inhibited CagA translocation by up to 65% in AGS cells while inhibition levels were 40% and 30% with K8 and K5, respectively. Our study suggests that CagICplays a key role incagT4SS-mediated CagA translocation and that DARPins targeting CagI represent potent inhibitors of thecagT4SS, a crucial risk factor for gastric cancer development.Author summaryHelicobacter pyloriis a bacterial pathogen that colonises the human stomach in half of the world’s population. The most virulent strains use the cag- type IV secretion system (cagT4SS), a molecular nanomachine capable of injecting the oncoprotein CagA into gastric cells. How CagA is delivered is unknown, but thecagT4SS produces an external appendage referred to as pilus, which interacts with host cell receptors, mediating CagA translocation from the cytoplasm of the bacteria to the inner membrane of the host cell. In this study we have investigated the structural and functional properties of CagI, a protein long-thought to be associated with thecagT4SS pilus but with yet unknown function. We found that CagI displays a unique dimeric structure and that its C-terminal domain is involved in interaction with the host cell. Designed Ankyrin Repeat Proteins were selected against CagI and found to interact with its C-terminal moiety with high affinity. DARPin binding was able to prevent CagI interaction with the host cell and inhibited CagA translocation byH. pylori. Our study reveals the role of CagI incagT4SS interaction with gastric cells and provides a first example of a small protein binder inhibiting thecagT4SS activity.

The first step in SARS-CoV-2 genomic surveillance is testing to identify people who are infected. However, global testing rates are falling as we emerge from the acute health emergency and remain low in many low- and middle-income countries (mean = 27 tests per 100,000 people per day). We simulated COVID-19 epidemics in a prototypical low- and middle-income country to investigate how testing rates, sampling strategies and sequencing proportions jointly impact surveillance outcomes, and showed that low testing rates and spatiotemporal biases delay time to detection of new variants by weeks to months and can lead to unreliable estimates of variant prevalence, even when the proportion of samples sequenced is increased. Accordingly, investments in wider access to diagnostics to support testing rates of approximately 100 tests per 100,000 people per day could enable more timely detection of new variants and reliable estimates of variant prevalence. The performance of global SARS-CoV-2 genomic surveillance programs is fundamentally limited by access to diagnostic testing.

Summary Viral variants of concern may emerge with dangerous resistance to the immunity generated by the current vaccines to prevent coronavirus disease 2019 (Covid-19). Moreover, if some variants of concern have increased transmissibility or virulence, the importance of efficient public health measures and vaccination programs will increase. The global response must be both timely and science based.

The bacterial human pathogen Helicobacter pylori produces a type IV secretion system (cagT4SS) to inject the oncoprotein CagA into gastric cells. The cagT4SS external pilus mediates attachment of the apparatus to the target cell and the delivery of CagA. While the composition of the pilus is unclear, CagI is present at the surface of the bacterium and required for pilus formation. Here, we have investigated the properties of CagI by an integrative structural biology approach. Using Alpha Fold 2 and Small Angle X-ray scattering, it was found that CagI forms elongated dimers mediated by rod-shape N-terminal domains (CagIN) prolonged by globular C-terminal domains (CagIC). Three Designed Ankyrin Repeat Proteins (DARPins) K2, K5 and K8 selected against CagI interacted with CagIC with subnanomolar affinities. The crystal structures of the CagI:K2 and CagI:K5 complexes were solved and identified the interfaces between the molecules, thereby providing a structural explanation for the difference in affinity between the two binders. Purified CagI and CagIC were found to interact with adenocarcinoma gastric (AGS) cells, induced cell spreading and the interaction was inhibited by K2. The same DARPin inhibited CagA translocation by up to 65% in AGS cells while inhibition levels were 40% and 30% with K8 and K5, respectively. Our study suggests that CagIC plays a key role in cagT4SS-mediated CagA translocation and that DARPins targeting CagI represent potent inhibitors of the cagT4SS, a crucial risk factor for gastric cancer development.

BACKGROUND Vaccine hesitancy is one of the many factors impeding efforts to control the COVID-19 pandemic. Exacerbated by the COVID-19 infodemic, misinformation has undermined public trust in vaccination, led to greater polarization, and resulted in a high social cost where close social relationships have experienced conflict or disagreements about the public health response. OBJECTIVE The purpose of this paper is to describe the theory behind the development of a digital behavioral science intervention—The Good Talk!—designed to target vaccine-hesitant individuals through their close contacts (eg, family, friends, and colleagues) and to describe the methodology of a research study to evaluate its efficacy. METHODS The Good Talk! uses an educational serious game approach to boost the skills and competences of vaccine advocates to have open conversations about COVID-19 with their close contacts who are vaccine hesitant. The game teaches vaccine advocates evidence-based open conversation skills to help them speak with individuals who have opposing points of view or who may ascribe to nonscientifically supported beliefs while retaining trust, identifying common ground, and fostering acceptance and respect of divergent views. The game is currently under development and will be available on the web, free to access for participants worldwide, and accompanied by a promotional campaign to recruit participants through social media channels. This protocol describes the methodology for a randomized controlled trial that will compare participants who play The Good Talk! game with a control group that plays the widely known noneducational game Tetris. The study will evaluate a participant’s open conversation skills, self-efficacy, and behavioral intentions to have an open conversation with a vaccine-hesitant individual both before and after game play. RESULTS Recruitment will commence in early 2023 and will cease once 450 participants complete the study (225 per group). The primary outcome is improvement in open conversation skills. Secondary outcomes are self-efficacy and behavioral intentions to have an open conversation with a vaccine-hesitant individual. Exploratory analyses will examine the effect of the game on implementation intentions as well as potential covariates or subgroup differences based on sociodemographic information or previous experiences with COVID-19 vaccination conversations. CONCLUSIONS The outcome of the project is to promote more open conversations regarding COVID-19 vaccination. We hope that our approach will encourage more governments and public health experts to engage in their mission to reach their citizens directly with digital health solutions and to consider such interventions as an important tool in infodemic management. INTERNATIONAL REGISTERED REPORT PRR1-10.2196/40753

International audience

Background In April 2020, the World Health Organization (WHO) Information Network for Epidemics produced an agenda for managing the COVID-19 infodemic. “Infodemic” refers to the overabundance of information—including mis- and disinformation. In this agenda it was pointed out the need to create a competency framework for infodemic management (IM). This framework was released by WHO on 20th September 2021. This paper presents the WHO framework for IM by highlighting the different investigative steps behind its development. Methods The framework was built through three steps. Step 1 included the preparatory work following the guidelines in the Guide to writing Competency Framework for WHO Academy courses. Step 2 was based on a qualitative study with participants (N = 25), identified worldwide on the basis of their academic background in relevant fields of IM or of their professional experience in IM activities at the institutional level. The interviews were conducted online between December 2020 and January 2021, they were video-recorded and analyzed using thematic analysis. In Step 3, two stakeholder panels were conducted to revise the framework. Results The competency framework contains four primary domains, each of which comprised main activities, related tasks, and knowledge and skills. It identifies competencies to manage and monitor infodemics, to design, conduct and evaluate appropriate interventions, as well as to strengthen health systems. Its main purpose is to assist institutions in reinforcing their IM capacities and implementing effective IM processes and actions according to their individual contexts and resources. Conclusion The competency framework is not intended to be a regulatory document nor a training curriculum. As a WHO initiative, it serves as a reference tool to be applied according to local priorities and needs within the different countries. This framework can assist institutions in strengthening IM capacity by hiring, staff development, and human resources planning.

Background An infodemic is an overflow of information of varying quality that surges across digital and physical environments during an acute public health event. It leads to confusion, risk-taking, and behaviors that can harm health and lead to erosion of trust in health authorities and public health responses. Owing to the global scale and high stakes of the health emergency, responding to the infodemic related to the pandemic is particularly urgent. Building on diverse research disciplines and expanding the discipline of infodemiology, more evidence-based interventions are needed to design infodemic management interventions and tools and implement them by health emergency responders. Objective The World Health Organization organized the first global infodemiology conference, entirely online, during June and July 2020, with a follow-up process from August to October 2020, to review current multidisciplinary evidence, interventions, and practices that can be applied to the COVID-19 infodemic response. This resulted in the creation of a public health research agenda for managing infodemics. Methods As part of the conference, a structured expert judgment synthesis method was used to formulate a public health research agenda. A total of 110 participants represented diverse scientific disciplines from over 35 countries and global public health implementing partners. The conference used a laddered discussion sprint methodology by rotating participant teams, and a managed follow-up process was used to assemble a research agenda based on the discussion and structured expert feedback. This resulted in a five-workstream frame of the research agenda for infodemic management and 166 suggested research questions. The participants then ranked the questions for feasibility and expected public health impact. The expert consensus was summarized in a public health research agenda that included a list of priority research questions. Results The public health research agenda for infodemic management has five workstreams: (1) measuring and continuously monitoring the impact of infodemics during health emergencies; (2) detecting signals and understanding the spread and risk of infodemics; (3) responding and deploying interventions that mitigate and protect against infodemics and their harmful effects; (4) evaluating infodemic interventions and strengthening the resilience of individuals and communities to infodemics; and (5) promoting the development, adaptation, and application of interventions and toolkits for infodemic management. Each workstream identifies research questions and highlights 49 high priority research questions. Conclusions Public health authorities need to develop, validate, implement, and adapt tools and interventions for managing infodemics in acute public health events in ways that are appropriate for their countries and contexts. Infodemiology provides a scientific foundation to make this possible. This research agenda proposes a structured framework for targeted investment for the scientific community, policy makers, implementing organizations, and other stakeholders to consider.

BACKGROUND The COVID-19 pandemic has been accompanied by an infodemic: excess information, including false or misleading information, in digital and physical environments during an acute public health event. This infodemic is leading to confusion and risk-taking behaviors that can be harmful to health, as well as to mistrust in health authorities and public health responses. The World Health Organization (WHO) is working to develop tools to provide an evidence-based response to the infodemic, enabling prioritization of health response activities. OBJECTIVE In this work, we aimed to develop a practical, structured approach to identify narratives in public online conversations on social media platforms where concerns or confusion exist or where narratives are gaining traction, thus providing actionable data to help the WHO prioritize its response efforts to address the COVID-19 infodemic. METHODS We developed a taxonomy to filter global public conversations in English and French related to COVID-19 on social media into 5 categories with 35 subcategories. The taxonomy and its implementation were validated for retrieval precision and recall, and they were reviewed and adapted as language about the pandemic in online conversations changed over time. The aggregated data for each subcategory were analyzed on a weekly basis by volume, velocity, and presence of questions to detect signals of information voids with potential for confusion or where mis- or disinformation may thrive. A human analyst reviewed and identified potential information voids and sources of confusion, and quantitative data were used to provide insights on emerging narratives, influencers, and public reactions to COVID-19–related topics. RESULTS A COVID-19 public health social listening taxonomy was developed, validated, and applied to filter relevant content for more focused analysis. A weekly analysis of public online conversations since March 23, 2020, enabled quantification of shifting interests in public health–related topics concerning the pandemic, and the analysis demonstrated recurring voids of verified health information. This approach therefore focuses on the detection of infodemic signals to generate actionable insights to rapidly inform decision-making for a more targeted and adaptive response, including risk communication. CONCLUSIONS This approach has been successfully applied to identify and analyze infodemic signals, particularly information voids, to inform the COVID-19 pandemic response. More broadly, the results have demonstrated the importance of ongoing monitoring and analysis of public online conversations, as information voids frequently recur and narratives shift over time. The approach is being piloted in individual countries and WHO regions to generate localized insights and actions; meanwhile, a pilot of an artificial intelligence–based social listening platform is using this taxonomy to aggregate and compare online conversations across 20 countries. Beyond the COVID-19 pandemic, the taxonomy and methodology may be adapted for fast deployment in future public health events, and they could form the basis of a routine social listening program for health preparedness and response planning.

As the COVID-19 pandemic evolves, the accompanying infodemic is being amplified through social media and has challenged effective response. The WHO Early AI-supported Response with Social Listening (EARS) is a platform that summarizes real-time information about how people are talking about COVID-19 in public spaces online in 20 pilot countries and in four languages. The aim of the platform is to better integrate social listening with other data sources and analyses that can inform infodemic response.

The COVID-19 pandemic is the first to unfold in the highly digitalized society of the 21st century and is therefore the first pandemic to benefit from and be threatened by a thriving real-time digital information ecosystem. For this reason, the response to the infodemic required development of a public health social listening taxonomy, a structure that can simplify the chaotic information ecosystem to enable an adaptable monitoring infrastructure that detects signals of fertile ground for misinformation and guides trusted sources of verified information to fill in information voids in a timely manner. A weekly analysis of public online conversations since 23 March 2020 has enabled the quantification of running shifts of public interest in public health-related topics concerning the pandemic and has demonstrated the frequent resumption of information voids relevant for public health interventions and risk communication in an emergency response setting.

As the COVID-19 pandemic evolves, the accompanying infodemic is being amplified through social media and has challenged effective response. The WHO Early AI-supported Response with Social Listening (EARS) is a platform that summarizes real-time information about how people are talking about COVID-19 in public spaces online in 20 pilot countries and in four languages. The aim of the platform is to better integrate social listening with other data sources and analyses that can inform infodemic response.

Background The COVID-19 pandemic has been accompanied by an infodemic: excess information, including false or misleading information, in digital and physical environments during an acute public health event. This infodemic is leading to confusion and risk-taking behaviors that can be harmful to health, as well as to mistrust in health authorities and public health responses. The World Health Organization (WHO) is working to develop tools to provide an evidence-based response to the infodemic, enabling prioritization of health response activities. Objective In this work, we aimed to develop a practical, structured approach to identify narratives in public online conversations on social media platforms where concerns or confusion exist or where narratives are gaining traction, thus providing actionable data to help the WHO prioritize its response efforts to address the COVID-19 infodemic. Methods We developed a taxonomy to filter global public conversations in English and French related to COVID-19 on social media into 5 categories with 35 subcategories. The taxonomy and its implementation were validated for retrieval precision and recall, and they were reviewed and adapted as language about the pandemic in online conversations changed over time. The aggregated data for each subcategory were analyzed on a weekly basis by volume, velocity, and presence of questions to detect signals of information voids with potential for confusion or where mis- or disinformation may thrive. A human analyst reviewed and identified potential information voids and sources of confusion, and quantitative data were used to provide insights on emerging narratives, influencers, and public reactions to COVID-19–related topics. Results A COVID-19 public health social listening taxonomy was developed, validated, and applied to filter relevant content for more focused analysis. A weekly analysis of public online conversations since March 23, 2020, enabled quantification of shifting interests in public health–related topics concerning the pandemic, and the analysis demonstrated recurring voids of verified health information. This approach therefore focuses on the detection of infodemic signals to generate actionable insights to rapidly inform decision-making for a more targeted and adaptive response, including risk communication. Conclusions This approach has been successfully applied to identify and analyze infodemic signals, particularly information voids, to inform the COVID-19 pandemic response. More broadly, the results have demonstrated the importance of ongoing monitoring and analysis of public online conversations, as information voids frequently recur and narratives shift over time. The approach is being piloted in individual countries and WHO regions to generate localized insights and actions; meanwhile, a pilot of an artificial intelligence–based social listening platform is using this taxonomy to aggregate and compare online conversations across 20 countries. Beyond the COVID-19 pandemic, the taxonomy and methodology may be adapted for fast deployment in future public health events, and they could form the basis of a routine social listening program for health preparedness and response planning.

BACKGROUND An infodemic is an overabundance of information—some accurate and some not—that occurs during an epidemic. In a similar manner to an epidemic, it spreads between humans via digital and physical information systems. It makes it hard for people to find trustworthy sources and reliable guidance when they need it. OBJECTIVE A World Health Organization (WHO) technical consultation on responding to the infodemic related to the coronavirus disease (COVID-19) pandemic was held, entirely online, to crowdsource suggested actions for a framework for infodemic management. METHODS A group of policy makers, public health professionals, researchers, students, and other concerned stakeholders was joined by representatives of the media, social media platforms, various private sector organizations, and civil society to suggest and discuss actions for all parts of society, and multiple related professional and scientific disciplines, methods, and technologies. A total of 594 ideas for actions were crowdsourced online during the discussions and consolidated into suggestions for an infodemic management framework. RESULTS The analysis team distilled the suggestions into a set of 50 proposed actions for a framework for managing infodemics in health emergencies. The consultation revealed six policy implications to consider. First, interventions and messages must be based on science and evidence, and must reach citizens and enable them to make informed decisions on how to protect themselves and their communities in a health emergency. Second, knowledge should be translated into actionable behavior-change messages, presented in ways that are understood by and accessible to all individuals in all parts of all societies. Third, governments should reach out to key communities to ensure their concerns and information needs are understood, tailoring advice and messages to address the audiences they represent. Fourth, to strengthen the analysis and amplification of information impact, strategic partnerships should be formed across all sectors, including but not limited to the social media and technology sectors, academia, and civil society. Fifth, health authorities should ensure that these actions are informed by reliable information that helps them understand the circulating narratives and changes in the flow of information, questions, and misinformation in communities. Sixth, following experiences to date in responding to the COVID-19 infodemic and the lessons from other disease outbreaks, infodemic management approaches should be further developed to support preparedness and response, and to inform risk mitigation, and be enhanced through data science and sociobehavioral and other research. CONCLUSIONS The first version of this framework proposes five action areas in which WHO Member States and actors within society can apply, according to their mandate, an infodemic management approach adapted to national contexts and practices. Responses to the COVID-19 pandemic and the related infodemic require swift, regular, systematic, and coordinated action from multiple sectors of society and government. It remains crucial that we promote trusted information and fight misinformation, thereby helping save lives.

Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is implicated in cardiovascular disease by modulating apoptosis and oxidative stress. We hypothesized that LOX-1 may be involved in pathophysiology of stroke by mediating ischaemia/reperfusion (I/R)-dependent cell death. Transient middle cerebral artery occlusion (tMCAO) was performed in wild-type (WT) mice, endothelial-specific LOX-1 transgenic mice (eLOX-1TG) and WT animals treated with LOX-1 silencing RNA (siRNA). In WT mice exposed to tMCAO, LOX-1 expression and function were increased in the MCA. Compared to WT animals, eLOX-1TG mice displayed increased stroke volumes and worsened outcome after I/R. Conversely, LOX-1-silencing decreased both stroke volume and neurological impairment. Similarly, in HBMVECs, hypoxia/reoxygenation increased LOX-1 expression, while LOX-1 overexpressing cells showed increased death following hypoxia reoxygenation. Increased caspase-3 activation was observed following LOX-1 overexpression both in vivo and in vitro, thus representing a likely mediator. Finally, monocytes from ischaemic stroke patients exhibited increased LOX-1 expression which also correlated with disease severity. Our data unequivocally demonstrate a key role for LOX-1 in determining outcome following I/R brain damage. Our findings could be corroborated in human brain endothelial cells and monocytes from patients, underscoring their translational relevance and suggesting siRNA-mediated LOX-1 knockdown as a novel therapeutic strategy for stroke patients.

The recent apparent increase in human monkeypox cases across a wide geographic area, the potential for further spread, and the lack of reliable surveillance have raised the level of concern for this emerging zoonosis. In November 2017, the World Health Organization (WHO), in collaboration with CDC, hosted an informal consultation on monkeypox with researchers, global health partners, ministries of health, and orthopoxvirus experts to review and discuss human monkeypox in African countries where cases have been recently detected and also identify components of surveillance and response that need improvement. Endemic human monkeypox has been reported from more countries in the past decade than during the previous 40 years. Since 2016, confirmed cases of monkeypox have occurred in Central African Republic, Democratic Republic of the Congo, Liberia, Nigeria, Republic of the Congo, and Sierra Leone and in captive chimpanzees in Cameroon. Many countries with endemic monkeypox lack recent experience and specific knowledge about the disease to detect cases, treat patients, and prevent further spread of the virus. Specific improvements in surveillance capacity, laboratory diagnostics, and infection control measures are needed to launch an efficient response. Further, gaps in knowledge about the epidemiology and ecology of the virus need to be addressed to design, recommend, and implement needed prevention and control measures.

Background Extracellular vesicles are released upon cellular activation and mediate inter-cellular communication. Individual species of extracellular vesicles might have divergent roles in vascular homeostasis and may show different responses to therapies such as exercise training. Aims We examine endothelial effects of medium-size and small extracellular vesicles from the same individual with or without chronic coronary syndrome, and in chronic coronary syndrome patients participating in a four-week high-intensity interval training intervention. Methods Human aortic endothelial cells were exposed to medium-size extracellular vesicles and small extracellular vesicles isolated from plasma samples of study participants. Endothelial cell survival, activation and re-endothelialisation capacity were assessed by respective staining protocols. Extracellular vesicles were quantified by nanoparticle tracking analysis and flow cytometry. Extracellular vesicle microRNA expression was quantified by realtime-quantitative polymerase chain reaction. Results In patients with chronic coronary syndrome (n = 25), plasma counts of leukocyte-derived medium-size extracellular vesicles were higher than in age-matched healthy controls (n = 25; p = 0.04) and were reduced by high-intensity interval training (n = 15; p = 0.01 vs baseline). Re-endothelialisation capacity was promoted by medium-size extracellular vesicles from controls, but not by medium-size extracellular vesicles from chronic coronary syndrome patients. High-intensity interval training for 4 weeks enhanced medium-size extracellular vesicle-mediated support of in vitro re-endothelialisation. Small extracellular vesicles from controls or chronic coronary syndrome patients increased endothelial cell death and reduced repair functions and were not affected by high-intensity interval training. Conclusion The present study demonstrates that medium-size extracellular vesicles and small extracellular vesicles differentially affect endothelial cell survival and repair responses. This equilibrium is unbalanced in patients with chronic coronary syndrome where leukocyte-derived medium-size extracellular vesicles are increased leading to a loss of medium-size extracellular vesicle-mediated endothelial repair. High-intensity interval training partially restored medium-size extracellular vesicle-mediated endothelial repair, underlining its use in cardiovascular prevention and therapy to improve endothelial function.

Dennis Carroll and colleagues call for a global early warning system to detect viruses with pandemic potential

Process mapping is a systems thinking approach used to understand, analyse and optimise processes within complex systems. We aim to demonstrate how this methodology can be applied during disease outbreaks to strengthen response and health systems. Process mapping exercises were conducted during three unique emerging disease outbreak contexts with different: mode of transmission, size, and health system infrastructure. System functioning improved considerably in each country. In Sierra Leone, laboratory testing was accelerated from 6 days to within 24 hours. In the Democratic Republic of Congo, time to suspected case notification reduced from 7 to 3 days. In Nigeria, key data reached the national level in 48 hours instead of 5 days. Our research shows that despite the chaos and complexities associated with emerging pathogen outbreaks, the implementation of a process mapping exercise can address immediate response priorities while simultaneously strengthening components of a health system.

Background: An infodemic is an overabundance of information—some accurate and some not—that occurs during an epidemic. In a similar manner to an epidemic, it spreads between humans via digital and physical information systems. It makes it hard for people to find trustworthy sources and reliable guidance when they need it. Objective: A World Health Organization (WHO) technical consultation on responding to the infodemic related to the coronavirus disease (COVID-19) pandemic was held, entirely online, to crowdsource suggested actions for a framework for infodemic management. Methods: A group of policy makers, public health professionals, researchers, students, and other concerned stakeholders was joined by representatives of the media, social media platforms, various private sector organizations, and civil society to suggest and discuss actions for all parts of society, and multiple related professional and scientific disciplines, methods, and technologies. A total of 594 ideas for actions were crowdsourced online during the discussions and consolidated into suggestions for an infodemic management framework. Results: The analysis team distilled the suggestions into a set of 50 proposed actions for a framework for managing infodemics in health emergencies. The consultation revealed six policy implications to consider. First, interventions and messages must be based on science and evidence, and must reach citizens and enable them to make informed decisions on how to protect themselves and their communities in a health emergency. Second, knowledge should be translated into actionable behavior-change messages, presented in ways that are understood by and accessible to all individuals in all parts of all societies. Third, governments should reach out to key communities to ensure their concerns and information needs are understood, tailoring advice and messages to address the audiences they represent. Fourth, to strengthen the analysis and amplification of information impact, strategic partnerships should be formed across all sectors, including but not limited to the social media and technology sectors, academia, and civil society. Fifth, health authorities should ensure that these actions are informed by reliable information that helps them understand the circulating narratives and changes in the flow of information, questions, and misinformation in communities. Sixth, following experiences to date in responding to the COVID-19 infodemic and the lessons from other disease outbreaks, infodemic management approaches should be further developed to support preparedness and response, and to inform risk mitigation, and be enhanced through data science and sociobehavioral and other research. Conclusions: The first version of this framework proposes five action areas in which WHO Member States and actors within society can apply, according to their mandate, an infodemic management approach adapted to national contexts and practices. Responses to the COVID-19 pandemic and the related infodemic require swift, regular, systematic, and coordinated action from multiple sectors of society and government. It remains crucial that we promote trusted information and fight misinformation, thereby helping save lives., peer-reviewed

Background In acute ischemic stroke (AIS) patients, impaired blood–brain barrier (BBB) integrity is associated with hemorrhagic transformation and worsened outcome. Yet, the mechanisms underlying these relationships are poorly understood and consequently therapeutic strategies are lacking. This study sought to determine whether SIRT5 contributes to BBB damage following I/R brain injury. Methods and results SIRT5 knockout ( SIRT5 −/− ) and wild type (WT) mice underwent transient middle cerebral artery (MCA) occlusion (tMCAO) followed by 48h of reperfusion. Genetic deletion of SIRT5 decreased infarct size, improved neurological function and blunted systemic inflammation following stroke. Similar effects were also achieved by in vivo SIRT5 silencing. Immunohistochemical analysis revealed decreased BBB leakage and degradation of the tight junction protein occludin in SIRT5 −/− mice exposed to tMCAO as compared to WT. In primary human brain microvascular endothelial cells (HBMVECs) exposed to hypoxia/reoxygenation (H/R), SIRT5 silencing decreased endothelial permeability and upregulated occludin and claudin-5; this effect was prevented by the PI3K inhibitor wortmannin. Lastly, SIRT5 gene expression was increased in peripheral blood monocytes (PBMCs) of AIS patients at 6h after onset of stroke compared to sex- and age-matched healthy controls. Conclusion SIRT5 is upregulated in PBMCs of AIS patients and in the MCA of WT mice exposed to tMCAO; SIRT5 mediates I/R-induced brain damage by increasing BBB permeability through degradation of occludin. This effect was reproduced in HBMVECs exposed to H/R, mediated by the PI3K/Akt pathway. Our findings shed new light on the mechanisms of I/R-dependent brain damage and suggest SIRT5 as a novel therapeutic target.

The formulation of accurate clinical case definitions is an integral part of an effective process of public health surveillance. Although such definitions should, ideally, be based on a standardized and fixed collection of defining criteria, they often require revision to reflect new knowledge of the condition involved and improvements in diagnostic testing. Optimal case definitions also need to have a balance of sensitivity and specificity that reflects their intended use. After the 2009-2010 H1N1 influenza pandemic, the World Health Organization (WHO) initiated a technical consultation on global influenza surveillance. This prompted improvements in the sensitivity and specificity of the case definition for influenza - i.e. a respiratory disease that lacks uniquely defining symptomology. The revision process not only modified the definition of influenza-like illness, to include a simplified list of the criteria shown to be most predictive of influenza infection, but also clarified the language used for the definition, to enhance interpretability. To capture severe cases of influenza that required hospitalization, a new case definition was also developed for severe acute respiratory infection in all age groups. The new definitions have been found to capture more cases without compromising specificity. Despite the challenge still posed in the clinical separation of influenza from other respiratory infections, the global use of the new WHO case definitions should help determine global trends in the characteristics and transmission of influenza viruses and the associated disease burden.La formulation de définitions précises de cas cliniques fait partie intégrante d'un processus efficace de surveillance de la santé publique. Alors que ces définitions devraient, dans l'idéal, s'appuyer sur un ensemble standardisé et fixe de critères de définition, elles nécessitent souvent une révision pour tenir compte des nouvelles connaissances relatives à la maladie concernée et des améliorations apportées aux tests diagnostiques. Pour être optimales, les définitions de cas doivent aussi établir un équilibre entre sensibilité et spécificité qui reflète leur utilisation aux fins prévues. À la suite de la pandémie de grippe H1N1 de 2009-2010, l'Organisation mondiale de la Santé (OMS) a lancé une consultation technique sur la surveillance mondiale de la grippe. Cela a conduit à des améliorations concernant la sensibilité et la spécificité de la définition de cas pour la grippe – c'est-à-dire une maladie respiratoire dont seule la symptomatologie reste à définir. Le processus de révision n'a pas seulement modifié la définition du syndrome de type grippal pour inclure une liste simplifiée des critères le mieux à même de prédire une infection grippale, il a également permis de clarifier le langage utilisé dans la définition pour en améliorer l'interprétation. Par ailleurs, afin de tenir compte des cas sévères de grippe qui nécessitaient une hospitalisation, une nouvelle définition de cas a été introduite concernant l'infection aigüe sévère des voies respiratoires dans tous les groupes d'âge. Il a été constaté que les nouvelles définitions reflétaient davantage de cas, sans pour autant compromettre la spécificité. S'il est vrai que la distinction clinique de la grippe des autres infections respiratoires continue de poser problème, l'utilisation mondiale des nouvelles définitions de cas de l'OMS devrait permettre de dégager des tendances mondiales concernant les caractéristiques et la transmission des virus grippaux ainsi que la charge de morbidité qui leur est associée.La elaboración de definiciones precisas de los casos clínicos es una parte fundamental de un proceso efectivo de la vigilancia de la salud pública. Aunque tales definiciones deberían, idealmente, estar basadas en una recopilación estandarizada y fija de criterios de definición, a menudo necesitan una revisión para reflejar el nuevo conocimiento de la enfermedad existente y las mejoras en las pruebas de diagnóstico. Las definiciones óptimas de los casos también deben tener un equilibrio entre sensibilidad y especificidad que refleje su uso previsto. Después de la pandemia de gripe H1N1 en 2009-2010, la Organización Mundial de la Salud (OMS) inició una consulta técnica para la vigilancia mundial de la gripe. Esto dio lugar a mejoras en la sensibilidad y la especificidad de las definiciones de los casos de gripe, es decir, una enfermedad respiratoria que carece de una sintomatología definitoria singular. El proceso de revisión no solo modificó la definición de las enfermedades similares a la gripe para incluir una lista simplificada de los criterios que demostraron ser más predictivos de la infección por gripe, sino que también aclaró el lenguaje utilizado para la definición, con el fin de mejorar su interpretación. Para englobar los casos graves de gripe que requirieron hospitalización, también se desarrolló una nueva definición de los casos de la infección respiratoria aguda grave en todos los grupos de edad. Se ha descubierto que las nuevas definiciones engloban más casos sin comprometer la especificidad. A pesar del desafío que todavía plantea la separación clínica de la gripe de otras infecciones respiratorias, el uso global de las nuevas definiciones de los casos de la OMS debería ayudar a determinar las tendencias mundiales en las características y transmisión de los virus de la gripe y la carga de la enfermedad asociada.إن صياغة تعريفات دقيقة للحالات من الناحية العلاجية جزء أساسي من الإجراءات الفعالة لمراقبة الصحة العامة. وبالرغم من أن مثل هذه التعريفات يجب، من الناحية النظرية، أن تقوم على مجموعة منتقاة من المعايير التعريفية الموحدة والثابتة، فغالبًا ما تحتاج تلك التعريفات إلى المراجعة لكي تعكس المعلومات التي تستجد بشأن الحالة المرتبطة بها والتطورات التي تشهدها الاختبارات التشخيصية. وتحتاج أيضًا التعريفات المثالية للحالات إلى الموازنة بين الحساسية والنوعية بما يتفق مع الاستخدام المزمع. وبعد تفشي فيروس الأنفلونزا准确制定临床病例定义是进行有效公共卫生监督进程中的一个组成部分。虽然理论上此类定义应该以标准化和固定收集的定义标准为基础，但是这些定义通常需要进行修订，以反映所涉及的新症状知识，以及诊断测试的进展。最佳病例定义还需要达到反映其预期用途敏感性与特异性的平衡。2009–2010 年 H1N1 流感大流行之后，世界卫生组织发起了一项有关全球流感监测的技术咨询。该咨询提出改进流感定义的敏感性与特异性，即呼吸道疾病缺乏独特定义的症状。修订过程不仅修改流感样疾病定义，以纳入显示最能预测流感病毒感染的简化标准列表，同时明确了定义使用的语言，以增强解释力。为了获取需要住院治疗的严重流感病例，同时为所有年龄段的严重急性呼吸道感染制定了新的病例定义。目前已经发现新定义能够囊括更多案例，并且不会影响特异性。尽管在临床上将流感与其他呼吸道感染区分开来仍然面临挑战，但是统一使用世界卫生组织的新病例定义有助于确定全球流感病毒的特征和传播趋势以及相关的疾病负担。.Формулировка точных определений клинических случаев является неотъемлемой частью эффективного эпиднадзора. Хотя в идеале такие определения должны основываться на стандартизованном и фиксированном наборе определяющих критериев, они часто требуют пересмотра с учетом новых знаний об этих состояниях и улучшениях в диагностическом тестировании. Оптимальные определения случаев также должны иметь баланс чувствительности и специфичности, который отражает их целевое назначение. После пандемии гриппа H1N1 в 2009–2010 годах Всемирная организация здравоохранения (ВОЗ) инициировала техническую консультацию по глобальному эпиднадзору за гриппом. Это привело к улучшению чувствительности и специфичности определения для гриппа, то есть респираторного заболевания, которое не имеет однозначной определяющей симптоматики. Пересмотр привел не только к изменению определения гриппоподобного заболевания, включив в него упрощенный список критериев, показавших, что гриппозная инфекция является наиболее прогностической, но и для улучшения интерпретируемости был сделан более понятным язык, используемый для этого определения. Для выявления тяжелых случаев гриппа, требующих госпитализации, было разработано новое определение для тяжелой острой респираторной инфекции во всех возрастных группах. Было обнаружено, что новые определения охватывают больше случаев без ущерба для специфичности. Несмотря на сложности, которые все еще возникают при дифференциации гриппа от других респираторных инфекций, глобальное использование новых определений ВОЗ должно помочь выявить всеобщие тенденции в характеристиках и передаче вируса гриппа, а также в связанном с ними бремени болезней.

BACKGROUND\ud \ud On March 23, 2014, the World Health Organization (WHO) was notified of an outbreak of Ebola virus disease (EVD) in Guinea. On August 8, the WHO declared the epidemic to be a "public health emergency of international concern."\ud \ud METHODS\ud \ud By September 14, 2014, a total of 4507 probable and confirmed cases, including 2296 deaths from EVD (Zaire species) had been reported from five countries in West Africa - Guinea, Liberia, Nigeria, Senegal, and Sierra Leone. We analyzed a detailed subset of data on 3343 confirmed and 667 probable Ebola cases collected in Guinea, Liberia, Nigeria, and Sierra Leone as of September 14.\ud \ud RESULTS\ud \ud The majority of patients are 15 to 44 years of age (49.9% male), and we estimate that the case fatality rate is 70.8% (95% confidence interval [CI], 69 to 73) among persons with known clinical outcome of infection. The course of infection, including signs and symptoms, incubation period (11.4 days), and serial interval (15.3 days), is similar to that reported in previous outbreaks of EVD. On the basis of the initial periods of exponential growth, the estimated basic reproduction numbers (R-0) are 1.71 (95% CI, 1.44 to 2.01) for Guinea, 1.83 (95% CI, 1.72 to 1.94) for Liberia, and 2.02 (95% CI, 1.79 to 2.26) for Sierra Leone. The estimated current reproduction numbers (R) are 1.81 (95% CI, 1.60 to 2.03) for Guinea, 1.51 (95% CI, 1.41 to 1.60) for Liberia, and 1.38 (95% CI, 1.27 to 1.51) for Sierra Leone; the corresponding doubling times are 15.7 days (95% CI, 12.9 to 20.3) for Guinea, 23.6 days (95% CI, 20.2 to 28.2) for Liberia, and 30.2 days (95% CI, 23.6 to 42.3) for Sierra Leone. Assuming no change in the control measures for this epidemic, by November 2, 2014, the cumulative reported numbers of confirmed and probable cases are predicted to be 5740 in Guinea, 9890 in Liberia, and 5000 in Sierra Leone, exceeding 20,000 in total.\ud \ud CONCLUSIONS\ud \ud These data indicate that without drastic improvements in control measures, the numbers of cases of and deaths from EVD are expected to continue increasing from hundreds to thousands per week in the coming months.

The emergence of a novel strain of coronavirus in the Arabian Peninsula raised a global health concern in 2012, partly because the majority of human infections were fatal and partly due to its presumed animal origin. An urgent meeting of scientific and public health experts was convened by WHO in January 2013 in view of the limited knowledge available on the epidemiological and natural history of infection with this novel virus. The meeting reviewed current evidence and identified critical knowledge gaps to improve better understanding of the public health risk associated with the virus so as to improve preparedness and to safeguard and protect global health.

Objective— Proangiogenic effects of mobilized bone marrow–derived stem/progenitor cells are essential for cardiac repair after myocardial infarction. MicroRNAs (miRNA/miR) are key regulators of angiogenesis. We investigated the differential regulation of angio-miRs, that is, miRNAs regulating neovascularization, in mobilized CD34 + progenitor cells obtained from patients with an acute ST-segment–elevation myocardial infarction (STEMI) as compared with those with stable coronary artery disease or healthy subjects. Approach and Results— CD34 + progenitor cells were isolated from patients with STEMI (on day 0 and day 5), stable coronary artery disease, and healthy subjects (n=27). CD34 + progenitor cells of patients with STEMI exhibited increased proangiogenic activity as compared with CD34 + cells from the other groups. Using a polymerase chain reaction–based miRNA-array and real-time polymerase chain reaction validation, we identified a profound upregulation of 2 known angio-miRs, that are, miR-378 and let-7b, in CD34 + cells of patients with STEMI. Especially, we demonstrate that miR-378 is a critical regulator of the proangiogenic capacity of CD34 + progenitor cells and its stimulatory effects on endothelial cells in vitro and in vivo, whereas let-7b upregulation in CD34 + cells failed to proof its effect on endothelial cells in vivo. Conclusions— The present study demonstrates a significant upregulation of the angio-miRs miR-378 and let-7b in mobilized CD34 + progenitor cells of patients with STEMI. The increased proangiogenic activity of these cells in patients with STEMI and the observation that in particular miR-378 regulates the angiogenic capacity of CD34 + progenitor cells in vivo suggest that this unique miRNA expression pattern represents a novel endogenous repair mechanism activated in acute myocardial infarction.

Aims MicroRNAs (miRNA) are important non-coding modulators controlling patterns of gene expression. However, profiling and validation of circulating miRNA levels related to adverse cardiovascular outcome has not been performed in patients with an acute coronary syndrome (ACS). Methods and results In a multicentre, prospective ACS cohort, 1002 out of 2168 patients presented with ST-segment elevation myocardial infarction (STEMI). Sixty-three STEMI patients experienced an adjudicated major cardiovascular event (MACE, defined as cardiac death or recurrent myocardial infarction) within 1 year of follow-up. From a miRNA profiling in a matched derivation case–control cohort, 14 miRNAs were selected for validation. Comparing 63 cases vs. 126 controls, 3 miRNAs were significantly differentially abundant. In patients with MACE, miR-26b-5p levels ( P = 0.038) were decreased, whereas miR-320a ( P = 0.047) and miR-660-5p ( P = 0.01) levels were increased. MiR-26b-5p has been suggested to prevent adverse cardiomyocyte hypertrophy, whereas miR-320a promotes cardiomyocyte death and apoptosis, and miR-660-5p has been related to active platelet production. This suggests that miR-26b-5p, miR-320a, and miR-660-5p may reflect alterations of different pathophysiological pathways involved in clinical outcome after ACS. Consistently, these three miRNAs reliably discriminated cases from controls [area under the receiver-operating characteristic curve (AUC) in age- and sex-adjusted Cox regression for miR-26b-5p = 0.707, miR-660-5p = 0.683, and miR-320a =0.672]. Combination of the three miRNAs further increased AUC to 0.718. Importantly, addition of the three miRNAs to both, the Global Registry of Acute Coronary Events (GRACE) score and a clinical model increased AUC from 0.679 to 0.720 and 0.722 to 0.732, respectively, with a net reclassification improvement of 0.20 in both cases. Conclusion This is the first study performing profiling and validation of miRNAs that are associated with adverse cardiovascular outcome in patients with STEMI. MiR-26b-5p, miR-320a, and miR-660-5p discriminated for MACE and increased risk prediction when added to the GRACE score and a clinical model. These findings suggest that the release of specific miRNAs into circulation may reflect the activation of molecular pathways that impact on clinical outcome after STEMI.

Background— MicroRNAs are key regulators of angiogenic processes. Administration of angiogenic early outgrowth cells (EOCs) or CD34 + cells has been suggested to improve cardiac function after ischemic injury, in particular by promoting neovascularization. The present study therefore examines regulation of angiomiRs, microRNAs involved in angiogenesis, in angiogenic EOCs and circulating CD34 + cells from patients with chronic heart failure (CHF) and the role for their cardiac repair capacity. Methods and Results— Angiogenic EOCs and CD34 + cells were isolated from patients with CHF caused by ischemic cardiomyopathy (n=45) and healthy subjects (n=35). In flow cytometry analyses, angiogenic EOCs were largely myeloid and positive for alternatively activated M2 macrophage markers. In vivo cardiac neovascularization and functional repair capacity were examined after transplantation into nude mice with myocardial infarction. Cardiac transplantation of angiogenic EOCs from healthy subjects markedly increased neovascularization and improved cardiac function, whereas no such effect was observed after transplantation of angiogenic EOCs from patients with CHF. Real-time polymerase chain reaction analysis of 14 candidate angiomiRs, expressed in angiogenic EOCs, revealed a pronounced loss of angiomiR-126 and -130a in angiogenic EOCs from patients with CHF that was also observed in circulating CD34 + cells. Anti–miR-126 transfection markedly impaired the capacity of angiogenic EOCs from healthy subjects to improve cardiac function. miR-126 mimic transfection increased the capacity of angiogenic EOCs from patients with CHF to improve cardiac neovascularization and function. Conclusions— The present study reveals a loss of angiomiR-126 and -130a in angiogenic EOCs and circulating CD34 + cells from patients with CHF. Reduced miR-126 expression was identified as a novel mechanism limiting their capacity to improve cardiac neovascularization and function that can be targeted by miR-126 mimic transfection.

Summary Public health research is essential for the development of effective policies and planning to address health security and risks associated with mass gatherings (MGs). Crucial research topics related to MGs and their effects on global health security are discussed in this review. The research agenda for MGs consists of a framework of five major public health research directions that address issues related to reducing the risk of public health emergencies during MGs; restricting the occurrence of non-communicable and communicable diseases; minimisation of the effect of public health events associated with MGs; optimisation of the medical services and treatment of diseases during MGs; and development and application of modern public health measures. Implementation of the proposed research topics would be expected to provide benefits over the medium to long term in planning for MGs.

Sirtuin 5 as a novel target to blunt blood-brain barrier damage induced by cerebral ischemia/reperfusion injury. [Int J Cardiol. 2018]