Nowadays, building infrastructures are pushed to become smarter in response to desires for the environmental comforts of living. Enhanced safety upgrades have begun taking advantage of new, evolving technologies. Normally, buildings are configured to respond to the safety concerns of the occupants. However, advanced Internet of Things (IoT) techniques, in combination with edge computing with lightweight virtualization technology, is being used to improve users’ comfort in their homes. It improves resource management and service isolation without affecting the deployment of heterogeneous hardware. In this research, a containerized architectural framework for support of multiple concurrent deployed IoT applications for smart buildings was proposed. The prototype developed used sensor networks as well as containerized microservices, centrally featuring the DevOps paradigm. The research proposed an occupant counting algorithm used to check occupants in and out. The proposed framework was tested in different academic buildings for data acquisition over three months. Different deployment architectures were tested to ensure the best cases based on efficiency and resource utilization. The acquired data was used for prediction purposes to aid occupant prediction for safety measures as considered by policymakers.  Software development challenges have arisen due to increases in IoT device-as-a-service, IoT infrastructure-as-a-service, and edge infrastructure-as-a-service . In IoT,The implementations are done using different platforms as services. The applicability levels of these platforms are challenged on their efficiency, performance, and variating scalabilities. This occurs in case of a system escalation, along with data analytics and resource consumption—commonly characteristics of monolithic applications . A monolNowadays, IoT devices contain embedded networking stacks, connecting directly to both publisher and subscriber service providers. The health and fire prevention domains are particularly related to the IoT reference architectures, focusing on sensors, network aspects, applications, and presentation aspects, including data analytics. IoT analytics are evolving with newer technologies, tools, and data processing, along with analytic methods. This has led to enhancements in the development of environments, with increased productivity and improved efficiency.However, there is no ownership in data management, and services escalate out of control if service charges are not clear. The other issue is the implementation of an IoT information system, which requires a high-level holistic approach. That approach must mix traditional data collection from vendor-specific cloud back ends with embedded hardware and mobile devices in real-time.IoT systems provide important, sometimes critical services, requiring uninterrupted operation or high levels of availability. Additionally, their complexity makes them difficult to integrate, while also complicating in-depth monitoring to prevent anomalies and failures .The DevOps methodology maintains system characteristics, such as availability, scalability, and fault tolerance, on a live system ,5,6,7,8.The motivation of this research was to contribute to the improvement of building safety prevention  using IoT technologies. The main question was how to integrate various IoT sensor nodes with scalable characteristics to provide a sound IoT system that provided real-time communication to the stakeholders (fire brigades) in case of a fire outbreak. The idea arose due to various challenges, such as IoT applications’ scalability, updatability, integration, and maintainability that affect performance and efficiency.This research was aimed at designing and implementing an IoT framework architecture that supported multiple concurrent deployed IoT applications in a smart building. The main objective was to develop a containerized architecture performance analysis for the IoT framework based on enhanced fire prevention, tested in Rwanda. The contributions of this research were (1) the investigation of a detailed, state-of-the-art integration of recent techniques in the IoT implementation domain; (2) the proposal of layered IoT architecture to provide central and efficient management of connected sensor nodes, data, and intervening applications, while meeting final requirements needed; (3) the application of different software engineering paradigms, including microservices and container-based virtualizations in the implementation; (4) validation of the proposed framework in a smart building scenario in which the main concern was to improve security; (5) a performance evaluation, carried out to guarantee a scalable platform.The rest of this paper was organized in the following order: The three-layer classic IoT reference architecture was extended by applying context-aware, serverless, microservices-based  cloud-ceThe three-tiered DevOps model was used to build an information system capable of providing real-time analytics . ManagemThe development of a service model structure consisted of several functions within its services. The defined hardware compatibilities  tested aRapidly developing technologies enable ubiquitous connectivity. This has resulted in the continuous growth of connected devices. On the other hand, it has also revealed challenges related to the development and architecture of information systems. The wide variety of proposed solutions enabled by interacting with devices makes it practically impossible to accurately manage the predicted ratio of data traffic patterns.In the management of a growing amount of delivered services , it is eThe initial concepts for software developments used monolithic architecture . The serDue to the wide variety of scenarios created in IoT and their different challenges , the monolithic pattern is not recommended .The microservices-based architecture proposed the distribution of the applications in a set of services in such a way that each was independent of the others. These new patterns have been used to solve specified issues with new features, such as scalability and reusability . The useMicroservices, at a high level, can be considered a black box that has been divided into layers. Depending on the tasks to be performed, the layers can be reorganized. Microservices communication is possible through interfaces exposed by the Microservices themselves. Hence, each microservices offers an application programming interface (API) to facilitate different types of connections.Microservices are useful for the development of IoT-based platforms. They allow services-oriented development, which is growing in popularity due to growing interest in parallel computation. The microservices architecture, designed and built using the Jolie programming language, was developed to work directly with a service-oriented paradigm . Here, tMost of the capabilities of containers are first executed on constrained devices with limited and relatively inexpensive storage and computing resources, like Raspberry Pi , in ordeAt this layer of the architecture, it is necessary to ascertain the performance of container schedulers or brokers, along with allocation among resources. Multiple containers, running in a cluster, support management activities. A container scheduler in a cluster has multiple goals, such as ensuring the use of resources efficiently; user access is restricted based on work and location. Additionally, it ensures that applications are quickly scheduled to avoid massive waiting times. It provides a high degree of balance between resources. It also provides an error-handling mechanism that ensures the most convenient allocation, both time-wise and power-wise . The exiThere are two key techniques used by containers to provide isolation of each container during execution environments. Those techniques are namespace and cGroup . NamespaThe implementation and administration of diverse container-based applications are rapidly developing nowadays. This development could facilitate physical or virtual host distribution, built on top of central components, such as containers’ schedulers in general, and Dockers containers’ schedulers.Among container schedulers, this research used Docker Swarm to address the problem of container management. Docker Swarm is a container management solution under the development of Docker Organization. It provides a standard Docker API, and its framework consists of two main components; first, a node that acts in the role of administrator executes an image of Swarm responsible for allocation of the containers on the remote machines ; secondly, the nodes with a remote Docker API capability are available to the administrator after the verification of its port correctness if it is open by the time the Docker daemon  starts.Docker Swarm has different major scheduling strategies that ensure the possibility of the scheduler selecting a node for executing a container. It includes strategy name or direct node selection, and selection of the node with the lower set of containers in execution spread. Regardless of the load of each container, or binpack, the selection of the most packaged node (lower available CPU/RAM) and the random selection of the node are also included. In the latter case, if the previous strategies select several nodes according to the previous criteria, the scheduler selects a target node among them randomly.The resource allocation strategy must be determined at the time of setup by the administrator or the spread strategy will be used by default. However, the spread method is the most extended scheduling strategy in most applications on the Docker Swarm Mode Cluster.In this research, apart from microservices concepts which were used together, the architecture had additional containerization mechanisms built on top to ease scalability, flexibility, and transparency. This mechanism was achieved using visualization in a container-based approach, through Docker. The proposed concept allowed for the robust development of a framework operating in a distributed way, with greater speed and increased independence over underlying operating systems.This section details the materials and methods used in the implementation of the proposed architecture in This subsection details different hardware components used during the implementation of the proposed framework architecture. The choice of criteria for each component depended on its availability and openness.ARM embedded architecture uses lower-power characteristics . The sinIn this research paper, easily obtainable off-the-shelf hardware was used to facilitate reproducible results. The setup was composed of three RPi Alarm ARMv7 for Broadcom .2, and smoke. Motion sensors were used in conjunction with obstacle sensors to detect the presence of human beings. In fire detection, prevention, and occupant detection use cases, this paper used a couple of sensors to gather specific parameters. In a specific room, sensors were used to detect the presence of fire temperature, humidity, COThe main tasks of a node were split into sensing/actuation, computation, storage, and communication, among the other nodes . The nodThe implementation used the RPi board, which allowed LAN internet connectivity. The communication used two protocols: MQTT and HTTP. MQTT operated through data messaging architecture that used the publish/subscribe paradigm to ensure that the data was sent smoothly if the sensor node was subscribed to the broker and the database. At the end-user data access, the web services used HTTP so the user could access the information through a browser application.This section details the software components used in the implementation of the proposed framework, including the Docker engine as services containers manager, server setup for web and database management, data formats, protocols for transmission, services patterns, and performance monitoring tools.Containerization is a technique used to abstract applications from the environments that they execute. Docker containers wrap up the software and its dependencies into a standardized unit for software development that includes everything it needs to run . ContainThe key advantages of using Docker for distributed applications included lower CPU overhead, version control, portability, and network performance improvement . Docker This research took advantage of Docker’s features. The idea was to combine Docker container services and microservices strategies for modular, scalable edge computing frameworks for IoT smart buildings.All sensor-generated data were periodically saved in the database, with data management conducted on the webserver. The database module was implemented using PostgreSQL over the webserver used as Nginx.Postgres was chosen as an object-relational database management system (RDBMS). It emphasized extensibility and standards compliance, and had the ability to provide replication of the database for scalability and security.Nginx is an open-source reversed proxy server for HTTPS, with a load balancer. Nginx was chosen as the web server for its security, reliability, and load balancing when there was huge traffic with connected users. Its characteristics focused on high concurrency, high performance, and low memory usage.The data exchange from sensor nodes to the cloud was formatted to allow efficient data transmission with low bandwidth. The data were converted into JSON (JavaScript Object Notation). JSON has been adopted as a standard text-based format for representing structured data.The proposed architecture in this research targeted the microservices architecture applied to the IoT framework. The architecture is made by different components including all real-time data acquisition and processing architectures in the IoT domain as shown in The proposed solutions of microservices for smart buildings in general and fire detection with occupancy detection are detailed in The concept considered allowed independent mounting and unmounting of the new nodes. Every node was considered one service for data acquisition and transmission. It allowed any connected node to be updated and integrated with the management of the services manager played by Docker Swarm. The transmission protocol, data management, web services, and visualization services were managed as microservices. This allowed services reusability without affecting the whole structure.The performance of edge computing applications followed different runtime variations depending on the running conditions. Conditions could have included the number of arrival requests and the availability of virtual resources. Additionally, the network connection quality between different interoperating application components distributed over the communication network was an additional key to consider.A mechanism to allow the aforementioned resources to be intelligently provisioned with little or no effort an application provider was required. The container manager was configured to ensure that the orchestration process of provisioning resources was done. The resources considered for provisioning in edge/cloud computing were: the usage of CPU, memory, storage, and network.There are four levels of monitoring , end-to-end link quality, and application) for self-adaptative applications to edge computing applications . Due to Docker itself had a built-in mechanism to access and convert container metrics into statistical format using Docker stats methods. Those metrics included runtime metrics and resource usage for a given container. This research proposed to use external built-in components to retrieve detailed sets of metrics by accessing exposed remote API using GET methods.-Container advisor, also known as cAdvisor, is a provided open-source platform. It was used to track, measure, aggregate, process, and display performance monitoring data for the running containers.-Prometheus is a monitoring tool relying on an open-source scheme. On top of monitoring activity, Prometheus can also store persistence time-series-based data for further processing and retrieval using PromQL language.-Grafana is a web-based open-source user interface, used to visualize large-scale performance monitoring information. It can be configured to work with the Prometheus database to visualize the time series data of the metrics.In monitoring the system behaviors, the following tools were used:The proposed framework architecture consisted of a set of services distributed across different computing sites. Each application was made of separate independent deployable components/containers, with all possible functionalities hiding their implementation details. The provision of those separate modular services enabled the services to be characteristically small and loosely coupled. This improved both testability and management, using containerization packages configured in each end device node. Those configurations provided minimum environmental capabilities for the application to run properly.Different layers of the proposed architecture are shown in The gateways worked cooperatively to ensure that the sent data were well cached and processed to reduce system response times. Additionally, the middle layer orchestrated communication between sensing nodes by providing a single-entry point to the local systems. The manager containers worked hand-in-hand with the device groups to maintain system updates of the resources. The manager containers were hosted in the cloud layer to allow multiple local domains to share data and resource status and make all resource-intensive applications run concurrently.This proposed scheme was designed such that, in highly dynamic distributed systems, the management of multiple deployed sensor nodes and their resources could be achieved efficiently. The role of the manager (Docker Swarm), shown in The communication of sensitive data generated by multiple sources occurred in high velocity at high volumes. It was managed by messaging hub techniques provided by the MQTT (message queuing telemetry transport) protocol. The aforementioned multiple layering entry allowed a manager to define communication channels for applications. It reduced the intra-service network overhead. The message broker module was included at each layer in the Docker container.2, Proximity Sensor, and IR sensor. They were all deployed to a powered RPi board connected to a LAN network. Each RPi board was configured with a Docker machine and all sensor services were deployed on it in a container-based approach.The sensing layer consisted of different sensor nodes deployed in the testing environment. The sensor nodes included, but were not limited, to: Temperature, Humidity, COThis layer was designed to manage the device groups deployed in different buildings to ensure the security and scalability of the framework. Once the new device was mounted, its corresponding gateway could update the container manager in the next layer (Fog layer) to update its discovery service, thus allowing other containers to be updated.The gateway layer ensured that all containers were running efficiently. The decisions with light computation needs were also done at this level, as this Pi board had constrained resources.In a large-scale container deployment over numerous servers, tracking all the containers and managing their life cycles is a complex task. The fog layer was composed of a configured server with a machine-learning Linux operating system (OS). On top of the OS, the Docker Swarm was installed. Its role was to ensure the proper administration of service lifecycles in massive deployments of Docker containers. The layer allowed data management as well. In order to maintain the system, the security-with-redundancy paradigm, database server, and access were all done at this layer. All deployed services in the Docker environment cooperated hand-in-hand with the Docker hub to update new versions of container images used, just in case.The research took advantage of cloud services by allowing all the public management and access to the implemented microservices resources to be managed. Main message hub services were fully managed in the cloud to control data transmission through queuing discipline. Database servers were deployed to keep persistent data for further usage. Overall web services to allow data access and user permissions at different user services were also managed at this layer. Finally, the data analytics were performed over the cloud to use cloud infrastructures that were limited at the edge node.Rwanda is an eastern African country with a fast-growing economy. Its cities have been gradually expanding, with 881,445 city dwellers in its largest cities and 8,169,341 in rural areas . IncreasA national inquiry, set up to investigate the causes of the fire outbreaks, found that 61% of fire incidents were due to short circuits, while 22% were due to unknown causes . AdditioDue to the aforementioned fire outbreaks, there was a need to address the issue by incorporating an IoT solution. Some research proposed the implementation of IoT techniques for early warning and notification, but the solution was limited by system escalation and modular reusability . Many ap2 sensors were connected in the middle of the room to maximize capture. A proximity sensor was deployed at the entry point of the room. The reason for choosing this configuration was to be sure that any captured positive value would show the moving being. The last parameter of interest was the counting of entries using two communicating infrared sensors (IR). The presence of a moving object in the office would not necessarily mean that it was a human being. All of those sensors in combination would help to improve the questions asked in [Referring to the sensor node deployment shown in asked in , for insThe management of the architecture used a distributed set of identical IoT devices deployed in different locations. Each device was configured to be part of the same group.-A New IoT device, such as a sensor or sensor node, is connected to the manager.-The connected device/sensor is identified with its unique identification.-The manager assigns the device to the device group, meaning the floor coverage of the building.-The latest device group configurations are pulled.-The manager checks for any updates from the broker (manager) map table to update the connected groups.Every time a new device was turned on or connected, there were different steps to follow:-Push a new container version, with its corresponding tags, into the configured Docker registry.Update the control API.Update the backend database with the new configuration.Update all connected IoT devices in their respective groups.Any time the admin deployed a new device or changed existing device configurations, the following steps were to be followed:For occupant presence counting, Algorithm 1 was used to synchronize two communicating IR sensors . Its deployment, shown in Algorithm 1: An Algorithm for Entry CountingInput: peopleIN, peopleOUT, IRinStatus, IRoutStatus, inPeople, outPeople, stayPeopleOutput: Number of stayPeople in a Room1Initialization of variableszero to variable peopleIN, peopleOUT: assign 2while (true) do3 Read IRinStatus4 Read IRoutStatus5 if IRinStatus == 0 then6  RETURN inPeople ← peopleIN++7 end if8 if IRoutStatus == 0 then9  RETURN outPeople ← peopleOUT++10 end if11 stayPeople = inPeople − outPeople12 if stayPeople ≤ 0 then13  No people inside // No sending process as there is null data to be sent14 else15  RETURN stayPeople16  Send stayPeople in the database // Send data to the database17 end if18end whileThe configuration and cooperation of two IR sensors were programmed using the following algorithm:2, motion, and occupants. The end nodes were equipped with various sensors  and connected to the manager  to ensure connectivity with deactivation in case of poor function.The system consisted of multiple nodes deployed in different rooms or locations to monitor selected environmental parameters, including temperature, humidity, COThe controller was configured as a Linux computer with all management capabilities. An orchestrator was installed there to manage all microservices, including the services to connect, update, and disconnect any newly connected sensor node. The evaluation of running, pending swarm of services, was monitored through the configured services Docker Swarm visualizer. The end nodes sent the data to the cloud database using publish/subscribe services. However, the management of sensor nodes’ gateways was managed by the manager through REST services. The data analytics were done in the cloud to aggregate the data and make predictions.This section details the architecture of the proposed connected modules from the device end to the human services visualization.Due to the publish and subscribe services offered by the MQTT protocol for real-time information sharing between connected devices with the central controllers, the sensor node was able to connect with predefined rules to meet the required configuration. The broker deployed in fog edge with Docker Swarm was able to work in cooperation to ensure that there was no interference. The Docker Swarm could also make sure that every device with its resources was containerized. Every container was assigned its unique identification to allow the restriction to available resources.For the client application (services) to be able to access the data generated by sensors, the services must be subscribed to the broker to allow smooth message queueing and notification sharing using the MQTT protocol. The broker used in the research implementation was EMQ. In the data management process, all generated data from the sensor nodes were saved to another service database subscriber known as the PostgreSQL server. Data could be retrieved from the database server in a different format based on the user context. In this situation, as there was a need for data for research purposes, there was no beautified user interface built. The data were kept for further use and retrieved in JSON format for preprocessing. For performance monitoring, a combination of different monitoring tools were used—cAdvisor, Prometheus and Grafana. Configuration of the services used in this research was done in layering structures. Prometheus was configured to ensure all the metrics from the cAdvisor were ingested and grabbed. To confirm the time interval of sharing the data, the scrape interval was set, including the endpoint where the cAdvisor was executing. It was forced to expose the data at port 8080.All defined services were wrapped within Docker containers to embed all required dependencies.The configurations in the Docker-compose file specified which containers were part of the installation and which ports were exposed by each container service. The configuration file focused on data ingestion from cAdvisor, Prometheus, and Grafana for simplicity.One key point to mention regarding the configuration: by configuring the specific container image, the dependency was able to ensure the direction the data took from container service one to container service two, and so on. There was also another configured time-series database (TSDB) to capture metrics parameters in real-time. In this research context, the configured storage was known as the Redis database.This section describes the results and outcomes of the implementation. It details the deployment place, along with the setup of the testbed, including the service usage visualization.This research detailed its application in the fire brigade domain. The architecture was deployed in the KALISIMBI building of the University of Rwanda (UR), as shown in The real implementation of the proposed IoT architecture system used the hardware components detailed in The system was powered by a power source and connected to the LAN network of the campus to ensure that it could sync services with Docker Hub. All data were sent by subscribed sensor nodes through the pipelined microservices up to the hosted database in the UR campus data center. Each RPi sensor was categorized into groups to manage its resources and connection capabilities. In the testbed, the computer was used where the Docker manager was configured to facilitate microservices management and scalability, referred to in The user was able to access the platform services through the developed web application under JavaScript, HTML5, Cascading Style Sheets (CSS), and ReactJS technologies. More clearly, the ReactJS framework was used to develop the web application following the responsive paradigm. For monitoring of the statuses of the containers through the container manager, Docker Swarm visualization tools were used, as shown in In a test experiment, the initial condition of the visualizer service was executed by the computer system. The Docker Swarm was configured in the board first. However, due to the limited capability of the storage, the laptop was used as a Docker Swarm manager. The RPi board was configured as the worker. It was given the IP address to be able to run independently.In summary, the system consisted of one Swarm manager (laptop), and one node worker for testing purposes. All the container services were running in the Swarm manager, while the sensor node services were running on the worker side. The Swarm manager ran all services including worker services. The reason for this configuration was so that it would be able to update the new connected worker and show the status of non-performing services, as shown in The other testing process was to measure the system availability level based on scalability capability for the system by trying to scale up and scale down all the deployed container services running in the Docker Swarm manager. The performed operation was designed to test the capability of the system availability when it came to serving an instant number of incoming requests that may affect the system overload.The scaling test was designed to observe how the system would behave in cases where there were hundreds of thousands of connected workers (sensor nodes) interacting with the services. The other concern was to see how the platform behaved when many end-users requested the services (building control units).-Reliability: the reliability of the system was measured by utilizing all the available resources to ensure that the system was running at full capacity. Those resources included CPU and active memory usage, with how many data were processed in a specific period. CPU usage metrics indicated average OS core utilization for all available CPU physical and virtual cores of the running system. Active memory showed the number of bytes stored in memory during the experiment at the time of the test.-Scalability: the measure of the prediction for extending the system to support hundreds of thousands of IoT devices publishing data with minimum system overhead to help time-critical applications. The measurement of these characteristics was indicated by the system throughput and response time metrics, showing how the system scalability was maintained.This section covers the performance evaluation of the proposed framework by following the approach and metrics discussed in The excellent performance was shown by the high throughput rate, as in principle, it should have been increased linearly as the number of devices or requests increased. The calculation of the throughput was given by the number of messages received and processed by the IoT system in one second; the lower the response time, the faster the response and processing of the system.The experiment to access the performance of the proposed framework was separated into two categories. The first was from the normal connected IoT devices’ viewpoint. The second was from the simulated requests to capture the system behaviors. For the normally connected sensor node, the measurements were also acquired. Testing was done to ensure the experimental testbed was feasible. The simulated experiment was done to test the performance while system scaling was conducted.3  to the IoT platform. In this experiment, the platform ran under the MQTT publishing operation with Quality of Service (QoS) level 0—the client simply published the message, and there was no acknowledgment by the broker. The reason for choosing level 0 was to avoid the system overhead created by acknowledgment messages. The data used for the system ingestion were simulated and represented an observation of a unique and random phenomenon. The estimated average size of each datum generated was 240 bytes. These implied the amount of data ingested to the platform backend services from sensor nodes and container controller.During the testing phase, the function of sending requests was executed to simulate virtual IoT devices published in the specified time interval. The simulated IoT devices sent requests or messages with an increment of 10The experiment aims to collect CPU, throughputs, and memory metrics usage is conducted by using cAdvisor as container resources usage analysis platform and Prometheus in combination with Grafana for monitoring the proposed platform as shown in This subsection details the performance analysis conducted given different parameters. The key concerns were related to the reliability and scalability of the system based on the changing requests. The evaluation showed that, due to the use of microservices, there was no single core overload. The graph showed that all works were distributed among the available 4 cores used in this testing, with an average of around 40% (0.4). The engagement of all cores implied an increase in system throughput.On the graph of throughput, the dominant operation was the reception as the data were being sent from the sensor node to the platform. The observed maximum value of the reception was 46,000 bytes per second. It showed a minimum of around zero at some specific period. The presence of some points with zero throughputs could depend on the sensor node device set to send data at an interval of 5 s. The maximum memory usage in this configuration was around 4600 megabytes, while the minimum was around 4200 megabytes. This implied that the average usage of 4400 megabytes of memory.The second experiment was conducted by increasing the number of nodes to track how the system behaved if it were scaled up. This experiment was conducted by setting the number of nodes to 3; the observations were measured using the same performance tools discussed (Prometheus and Grafana). In this experimental setup, the assumption was to scale up the containers to observe the system behaviors. The experiment was detailed with two entries: scaling the application, in terms of container services, and generating different requests to observe the system. In this experiment, the observations are sticking to CPU, Memory, and Traffic metrics behaviors.The performance metrics were concerned with the transmission cost of the network as shown in The network transmission at the transfer side showed tremendous changes, but it was also observed that, at one hundred requests, the graph began to go down to ten thousand, but then increased.The implementation of a comprehensive solution for the whole IoT lifecycle was presented in this research. The lifecycle presented fit into four phases: data capture, communication, analysis, and implementation. A generic framework architecture, based on the above layers, was defined in the DevOps paradigm. The architecture complied with the main system requirements of all proposed IoT solutions.The proposed IoT solutions were discussed in the building fire prevention sector, to improve building comfort and security. Different challenges were discussed concerning the scalability, updating, and performance of IoT devices with low computing capabilities. The IoT devices were installed in buildings, accessing the building’s electrical power resources.In the proposed framework for data transmission and management, the nonfunctional requirement (QoS) was considered to address all critical cases to be solved by IoT solutions. It also showed that some computation was possible at the edge side, minimizing the decision time delay.Data transmissions were considered by ensuring data transfer in real-time using MQTT-based protocols, along with data packaged in JSON format—which has been considered lightweight—to ensure low network bandwidth consumption. For services, scalability, and reusability, the container-based and microservices solution was proposed, using Docker. It satisfied the horizontal scalability of the framework. The sensor nodes, considered Docker workers for updating and easy connectivity, were under the control of the Docker Swarm manager. Data sent from sensor nodes were managed by the Nginx web server, which also acted as a load balancer in case of the huge amount of user requests coming from the front-end.The IoT framework presented in this research was validated and used in a smart building scenario to contribute to fire prevention situations. The system was deployed in the UR–KALISIMBI block site for three months to experiment with the challenges of the data capture process. The performance metrics were extracted to visualize if they were suitable for adoption by the whole University.Finally, for future work, the authors will improve the IoT interoperability for disparate and heterogeneous sensor devices, data, and the standard IoT models. Additionally, the extensions will concentrate on an advanced custom visualization layer with machine learning techniques included for decision making.


The fibroblast is one of the ideal target cell candidates for cell-based gene therapy approaches to promote tissue repair. Gene delivery to fibroblasts by viral transfection has been confirmed to have high transfection efficiency. However, in addition to immunogenic effects of viruses, the random integration of viral genes may damage the genome, affect the cell phenotype or even cause cancerous mutations in the transfected cells. Due to these potential biohazards and unknown long-term risks, the clinical use of viral transfection has been very limited. In contrast, initial non-viral transfection methods have been simple and safe to implement, with low immunogenicity, insertional mutagenesis, and risk of carcinogenesis, but their transfection efficiency has been relatively low. Nucleofection, a more recent non-viral transfection method, now combines the advantages of high transfection efficiency and direct nucleic acid delivery to the nucleus with a high safety.Here, we reviewed recent articles on fibroblast nucleofection, summarized different research points, improved methods and application scopes, and opened up ideas for promoting the further improvement and development of fibroblast nucleofection to meet the needs of a variety of disease research and clinical applications. Fibroblasts are the most common cells in connective tissue, and are differentiated from mesenchymal cells. The morphology and function of fibroblasts often undergo dynamic changes during the processes of disease development and tissue repair . FibroblGene therapy utilizing fibroblasts has been proven feasible by in vitro and in vivo experiments. For example, primary fibroblasts modified by gene nucleofection were used to treat a rat hindlimb ischemia model. They promoted the formation of collateral vessels in the lower limbs of rats and the reconstruction of circulation in the ischemic area . Lwin etMany researchers have explored the transfection efficiency of nucleofection in fibroblasts and examined the efficacy of the transgenic fibroblasts used for further cell therapy. In this article, we review the published work on fibroblasts nucleofection in recent years, and summarize the different angles of researches, advancements of methods, and evolution of applications.Due to different research purposes, different species and tissues have been selected to be used for isolating and culturing fibroblasts for experiments. Some studies have pointed out that the number of passages, confluence state, growth rate, and division phase of fibroblasts before they are used for nucleofection can affect nucleofection efficiency. Although opinions differ on the optimal number of passages for fibroblasts, most studies agree that cells should be kept in a low-passage exponential growth phase prior to transfection. Reaching high confluency should be avoided, since cells in a high confluence state are more resistant to reprogramming. In addition, the composition of the fibroblast culture medium was also indicated to correlate with the final nucleofection efficiency by affecting the proliferation rate of fibroblasts. So far, an overview over experimental design and statistical data on specific effects of these factors on fibroblasts nucleofection efficiency is missing.Fibroblasts have been successfully extracted from diverse species and tissues for research by enzymatic and explant culture methods. The enzymatic method mostly refers to the use of collagenase, dispase, hyaluronidase or trypsin to digest the chopped tissue specimens. The typical explant method consists of cutting the sample into tissue fragments of about 0.5 mm in length, planting them in a petri dish with culture medium, and letting the cells grow out of the sample. For example, we have successfully isolated fibroblasts from the dermis of the skin obtained from the back of Lewis inbred rats by the enzymatic method in previous studies. In these experiments, the first 3 passages of the cultured cells were used for subsequent experiments , 13. Som2 humidified incubators. Some of these studies added basic fibroblast growth factor (bFGF) to the culture medium, but effects on subsequent transfection were not observed. Only Kuebler et al. and Teklemariam et al. chose Iscove's Modified Dubecco's Medium (IMDM) to culture fibroblasts [Notwithstanding some studies emphasize the necessity to use cells within three to five passages in the nucleofection process , some stroblasts , 24, IMDroblasts , 36, 41 roblasts .There are a few publications reporting that the subsequent nucleofection process is significantly affected by different sources of fibroblasts. Some studies mentioned that primary fibroblasts and NIH3T3 cells are difficult to transfect –44, but Cell contamination often severely affects transfection outcomes . BacteriNucleofection is an electroporation-based transfection modality with a variety of cell-specific transfection buffers and different programs that control voltage, frequency, and pulse duration. Skrzyszowska et al. used Sacl enzyme to cut the constructed plasmid DNA into linear conformation. They added fibroblast nucleofection buffer for nucleofection of pig fibroblasts, wherein the U-20 procedure was used for pig fetal fibroblasts, U-23 procedure was used for porcine adult dermal fibroblasts. In their work, they only give numbers for different protocols , while treating the exact procedure as a trade secret. The transferred target sequence carried an enhanced green fluorescent protein (eGFP) gene. This allowed to detect transfection efficiency of the gene by observing the fluorescence intensity of eGFP . Ko et aPrevious studies have compared and found that the cuvettes provided by the manufacturer of the Nucleofector device and cuvettes from Eppendorf had no significant difference in the nucleofection process. Under certain circumstances, the transfection solution provided by the manufacturer could even be improved . It was Skrzyszowska et al. compared cell viability and proliferative activity after nucleofection and lipofection, both of which were higher in the nucleofection group. However, in PCR screening results, only in 1 of the 5 analyzed groups of nucleofection, the gene was integrated into the nuclear genome, while the transgenes of 3 of the 5 analyzed groups of lipofection were successfully integrated . TherefoThe implementation conditions and transfection results of nucleofection in related studies are summarized in Table In order to more intuitively present the relationship between the sources of fibroblasts, the nucleofection procedures used in each study with the nucleofection efficiency and cell viability in Table The composition of the nucleofection standard solution is unreported, and may have a certain negative impact on cell survival and proliferation. Most studies stated that the cell viability after nucleofection is higher than other chemical or physical transfection methods, but it is always lower than the viability of untransfected cells. Thus, some researchers recommend that 24 h after nucleofection, the standard solution of nucleofection should be replaced with DMEM, IMDM or other inducible medium according to different experimental purposes , 50. ConGene editing of fibroblasts by nuclear transfection for clinical application is a possible direction of this technology. Although it has not yet been applied to the clinic, related studies on nucleofection of fibroblasts have been carried out in various ways. For example, in research about tissue repair and reconstruction, the genes encoding VEGF165 and bFGF were transferred into fibroblasts by nucleofection, and the cells were injected into the gracilis and adductor muscles of ischemia model rat lower limbs. This significantly improved the circulation reconstruction in this model . BiodegrThe applications of nucleofection in related studies are summarized in Table Making use of the characteristics of fibroblasts, nucleofection treatment of fibroblasts has been proven to be of potential in a lot of aspects. In addition to promoting the repair and reconstruction of soft tissue or bone tissue damage, it can also be used to support the survival of adjacent cells through its exocrine function, used as a nuclear donor to produce transgenic animals, induce it into other differentiated cells or iPSCs, etc.. The diverse application modes make fibroblast nucleofection of extraordinary significance in disease research and development of novel treatments. The high efficiency of nucleofection has been well confirmed, whereas the specific and detailed way in which nucleic acids "directly" enter the nucleus is still unknown. To clarify this process in the future may allow to further improve it. Although the details of the nucleofection procedure and standard solution formula are unknown, some methods have been developed to improve the nucleofection process. This can elevate the transfection efficiency while reducing the experimental cost and ensuring cell viability, which undoubtedly paved the way for the development of fibroblast nuclear transfection-related research. However, it should be noted that nucleofection like other gene transfection methods may cause IFN and DDR, affect the level of oxidative stress in cells, and interfere with subsequent experiments. Similarly, it is necessary to study the specific mechanism of cell damage during the gene transfection process, as it can help to find a better way to minimize the negative impact on experimental cells. This can further promote the improvement and development of fibroblast nucleofection to meet the needs of various researches and clinical applications.


The development and functions of the nervous system are precisely guided and controlled by the crosstalk of molecular and cellular processes that are often revealed during pathological conditions, as defective molecular signaling and cellular interactions lie behind their cause or course. This Research Topic combines several reviews and original research articles highlighting the relevance of some of these processes, studied in different model systems, to broaden our understanding of the function of the nervous system.Dudanova, the development of biosensors to assess protein quality is a promising approach to understand pathological mechanisms and to test possible therapies in the aforementioned conditions.Proteins and RNAs are key players of the cellular systems. Protein homeostasis, i.e., proteostasis, controls the quality and the appropriated amount of functional proteins within the cell . BBSOAS is characterized by the haploinsufficiency of the transcription regulator NR2F1 (previously known as COUP-TFI), which results in intellectual disability, visual impairment, epilepsy and autistic traits.Among the proteins, the transcription factors play a central role during development due to their capacity to control gene expression. These genetic programs underlie several important processes, such as cellular proliferation, migration, or differentiation, which are essential, for instance, during nervous system development and function  are more than mere “photocopies” of the DNA to be translated into proteins or long non-coding RNAs (Lnc-RNAs) are not just junk biomolecules  to regulate food uptake and the activation of its receptor (GLP-1R) in several brain regions.Neurons are integrated in functional circuits that are mainly developed during embryonal and larval/infant stages and consolidated and refined during the adulthood. In that context, the study of small animals such as fish or rodents are of great value for the understanding of neuron connectivity. The work by Huang et al. describes the neuroprotective effect of 7,8-dihydroxyflavone (DHF) in the immature retina of P7 rats against hypoxic-ischemic injury, a major cause of acquired visual impairment in children from developing countries. DHF acts as a synthetic TrkB agonist independent of BDNF that activates Artemin upregulation and reduces gliosis in the insulted immature retina. In this Research Topic, the work by Ruff et al. uses a new inducible genetic FLRT3-CreERT2 knock-in mouse to identify a new subpopulation of RGCs with direction selective properties. These RGCs express the transmembrane protein FLRT3 and their axons specifically project to the MTN. FLRTs are multifunctional transmembrane proteins with important functions during nervous system development  is the retina. This internal layer of the eye is originated from the diencephalon and remains connected to the brain by the optic nerve, that projects to different brain areas. These projection areas include the thalamus and other accessory nuclei. Among them, the inputs to the medial terminal nucleus (MTN) in the ventral midbrain are necessary for reflex eye movements and retinal image stabilization during vision  in young rats, comparing the response of males and females. Studying sex as a biological variable is of great interest nowadays as it will help to reduce the gap in the knowledge of the health between genders.Finally, in the search for therapeutic approaches to treat neuronal dysfunctions, the work by All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Surgical disciplines are affected by an increasing shortage of young doctors. Studies show that formerly interested students decide against a career in surgical disciplines at the end of their studies or during practical year. Measures to counteract this development are urgently needed. As a joint project between gynecology, urology, and general surgery, SOCIUS mentoring was designed to prepare and encourage students for a career in surgical oncology. The structured curriculum of SOCIUS mentoring contains six modules, including surgical skills, soft skills, mentoring, theory, clinical visitation, and congress participation and runs over one year. Effects on confidence towards physician skills and plans for a future career were evaluated with questionnaires. After participation, students reported increased confidence in surgical and soft skills. In addition, participants noted that they have specified their career goals and gained more confidence in surgery, as well as seeing more development potential for a career in surgery. We describe the implementation of a novel extracurricular program for motivated students that combines individual mentoring with surgical and soft skills training. Due to its modular structure, this concept can easily be transferred to other disciplines. SOCIUS mentoring, with its combination of mentoring and skills training, is a promising measure to prepare and motivate students for their surgical career and thus counteract the shortage of young talent. The shortage of physicians is a growing challenge in all fields of medicine . SurgicaTherefore, students should be encouraged for a career in academic surgery during their undergraduate years. Courses that introduce students to hands-on surgical skills have been shown to have positive outcomes on surgical skills and confidences . OverallCurricula that combine mentoring and surgical skills training have not previously been described in the form presented in this paper. Combining the two measures could lead to increased motivation of students to pursue surgical careers. Therefore, the departments of Gynecology, Visceral Surgery, and Urology at the Hannover Medical School have launched the SOCIUS mentoring program . The aim of this program is to accompany motivated students on their way into surgical oncology training providing a curriculum optimally tailored to teach the skills required for the start of an academic career in surgery. Here, we describe the structure of the program and the results after two years.Students were informed about the program via an email, posters, and short presentations during curricular lectures. Students between their fifth and twelfth semesters  were eligible to apply. Students were selected in a two-stage process. Each participating department evaluated a one-page motivation letter and the curriculum vitae and selected 10 students. These students were then invited for an interview. Selection was based on interest and motivation for surgical oncology, research, and university career. The number of participants was limited to 10 students per year.The curriculum included approximately 100 hours of mentoring and training. An attendance rate of 80% was required for successful participation. The curriculum consisted of six modules, which are shown in After a general introduction to the rules and procedures in the operating room, the “Practical Skills” module included practical seminars on surgical instruments, a suturing course, and intensive laparoscopic surgical training on a virtual laparoscopy simulator LAP Mentor III . Furthermore, functionality of the Da-Vinci surgical robot is explained and basic skills are taught on the DaVinci-Xi simulator .The “Soft Skills” module included professional training in presentation and negotiation techniques, as well as courses on statistical literacy. In this module, participants were first introduced to established communication techniques that were not routinely taught in healthcare education. Respectful communication with all stakeholders in the hospital, effective patient presentation, presentation of scientific work, and career-enhancing self-marketing were just as much a part of the courses as asserting one’s own interests with the help of comprehensive negotiation techniques.In each of the three disciplines, there were individual clinical observations with the participating mentors to consolidate and apply what has been learned in clinical settings. Optionally, all participants had the opportunity to attend a national congress.p value <0.05 was considered significant.Before and after participation in the SOCIUS program, participants’ confidence was evaluated using a Likert-scale questionnaire, which was based on evaluations of similar programs and had been validated by experts ,13. FurtAll participants gave written consent to the scientific evaluation of the program. The data were stored in pseudonymized form. A positive ethics vote (No. 8806_BO_K_2019) by the ethics committee of the Hannover medical school was available. All methods were carried out in accordance with relevant guidelines and regulations. The implementation of the program was funded by the Dräger Foundation. The LAP Mentor III was funded by the support of the Rudolf Bartling Foundation.A total of 96 students applied to participate in the program in 2019 and 2020. Of these, 20 (20.8%) students were accepted into the program after a multi-stage selection process. The number of female participants was 80%, which represented the general population of medical students in Germany. The baseline characteristics of the participants are shown in During the peak phases of the COVID-19 pandemic, three seminars were conducted as webinars. Several seminars were held in hybrid format offering live streaming. The option for congress participation was taken by 13 (65%) of the students by attending the congress of the German Society of Gynecology and Obstetrics 2020 in Munich and the congress of the European Society of Gynaecological Oncology in Prague. Other planned congress attendances were cancelled due to the COVID-19 pandemic.A total of 17/20 (85%) participants participated in the evaluation for the program. An important goal of the mentoring was to support the students in their future career planning. Thus, high to very high agreement values were given for the items “potential for future career” , “specification of personal goals” , and “specification of career plans” . Overall mentoring was rated with the highest score  and the highest possible value regarding the recommendation of the program to friends , as illustrated in p = 0.017).The total time required to complete standard laparoscopic exercises on LAP Mentor III was significantly reduced in four out of five tasks after participation in the training see . In partAfter participation in the SOCIUS mentoring program, students reported a significant increase in confidence related to surgical techniques, safety, and demeanor in the surgical environment, and handling of statistical results see . There wAdditionally, after participation in the curriculum students reported higher interest in a career at a university hospital in general and our clinic specifically B.We describe the first implementation of an extracurricular program that combines individual mentoring with surgical and soft skills training. We demonstrated a high interest and need for such dedicated programs and that participation in this program significantly improves confidence towards the trained skills and leads to a specification of career goals.Individualized support for students appeared to be essential to address the shortage of young surgeons. According to a survey by Brundage et al. at Stanford University, 44% of the students surveyed were considering a career in surgery at the beginning of their studies. After their fourth year only 27% of the students were still interested in a surgical career . Peel etIn addition to professional qualifications, self-confident but always self-critical, situation-appropriate communication is one of the key competencies for a successful physician. Effective communication with patients can increase the effectiveness of therapeutic measures, and constructive critical discussion in the team across all hierarchical levels has positive effects on the error culture in the hospital ,19. FinaThe confidence of SOCIUS participants increased in all areas covered by the program. In particular, the most significant increase was demonstrated for the self-assessment of operative skills, which can be explained by the students’ limited prior knowledge, especially in laparoscopic surgery. Although the subjective character of the students’ assessment limits the interpretation, it could be shown that methods for the self-assessment of students correlate with the objectifiable results and are reliable survey methods ,13,20. TStatistical literacy is essential for physicians to critically and realistically evaluate scientific studies as well as their own clinical outcomes in their later medical careers. In the present study, participants reported the lowest confidence scores for statistical literacy. Regular statistical exercises with real clinical questions over a longer period of time could be suitable to anchor the basic principles more deeply. Furthermore, we plan the standardization of the candidate selection process using predefined score cards and a specific training for the mentors.Due to the modular nature of SOCIUS, adaptation or expansion of the concept to almost any surgical clinic in any surgical subdiscipline is easily possible. Furthermore, the high application numbers indicated the high level of student interest in a highly specific program. Low absenteeism and the willingness of participants to attend courses and surgical training sessions on evenings and weekends underscore the need on the one hand and the high motivation of students on the other. Whether the participants of the SOCIUS program will actually decide to pursue a surgical career in about 3–5 years and to what extent SOCIUS can thus also be considered a success for the organizing hospitals cannot be conclusively assessed today. However, the interest in an academic career and for an application at our university increased after the curriculum and that appears to be an indication for the sustainability of this project.Recruiting and motivating young students will certainly not completely solve the long-term shortage of physicians. The dissatisfaction of physicians working in surgery with their working environment and with often poorly structured postgraduate training must be brought into the focus of politics, professional societies and professional associations, irrespective of the recruitment of new physicians .Mentoring programs should be one of the basic building blocks of active and strategic human resources management at every hospital. Interdisciplinary programs, such as the SOCIUS program, represent a valuable tool for bundling the opportunities and competencies of individual departments and for generating enthusiasm among students for a surgical career.


Co-creation allows to develop tailored interventions in chronicity and to increase patients’ engagement. Considering the interacting nature of physical, psychological, and social domains in multiple sclerosis (MS), a biopsychosocial approach to care is crucial.This paper aims to present (i) an example of a co-creation process in the context of chronic diseases (ii) preferences and perspectives of young adults with multiple sclerosis  and healthcare professionals (HCPs) on the relevance, objectives, and modalities of a biopsychosocial intervention (named ESPRIMO) and on strategies/barriers to participation.n = 121) and HCPs (n = 43), online focus groups (FGs) with YawMS, consultation with an advisory board (AB) composed by YawMS, HCPs and researchers. For the survey, descriptive statistics and inductive content analysis have been used for quantitative and qualitative analysis, respectively. FGs and AB were used to deepen the understanding of the survey’s results.A participatory mixed-method approach in three consecutive steps was implemented: online surveys with YawMS . Accessibility and lack of time resulted as the main barriers to participation.The co-creation process gave valuable information on preferences and perspectives of main stakeholders on objectives, modalities, and strategies to improve participation which has been used in the design of the ESPRIMO biopsychosocial intervention. Those results might inform future intervention development in the field of chronicity. The current paper outlined a co-creation methodology which might be replicated in future research on other conditions of vulnerability. Interventions for patients with chronic disease (CD) are usually developed using a top-down approach: patients are passive users of the intervention that has been designed based on literature evidence and researchers’ experiences and perspectives. Recently participative approaches are becoming more popular and community-academic partnership is becoming a widely accepted methodology in healthcare research and in the design of interventions for health-related quality of life HRQoL; . ParticiA second core element strictly related to the management and quality of care in chronicity is the adoption of integrated models that recognizes the reciprocal impact and mediating role of different dimensions on illness beside the biological level, such as psychological and social factors. These domains compose the various dimensions that are affected by illness and that can also play a mediating role in the expression of symptomatology and more in general in the acceptance and adaptation to illness. Adjustment to chronicity requires resources in psychological and social domains as well as in the physical/rehabilitative one to maintain and/or promote an adequate HRQoL. Thus, adopting a biopsychosocial approach is highly important .However, literature on the development of integrated interventions for CDs targeting all such different domains at the same time seems still scattered. Some efforts have been made on different CDs such as, for example, chronic low back pain , stroke MS is usually first diagnosed at the age of 20–40 years . MS is cConsidering that these aspects interact one with another, a biopsychosocial approach in intervention dedicated to people with MS is needed. With the aim to fill the literature gap on integrated intervention for MS, the ESPRIMO project  started in 2019 offering a biopsychosocial approach  for young adults with MS (YawMS) aimed at improving HRQoL ,b. The pConsidering this background, the aims of the present article are:to present the approaches for the co-creation of a biopsychosocial intervention in the context of chronicity and, in particular, of multiple sclerosis;to report the preferences and perspectives of young adults with multiple sclerosis and healthcare professionals on a biopsychosocial intervention.The co-creation was implemented using a participatory mixed-methods research process  includinYoung adults with a diagnosis of multiple sclerosis (YawMS) and healthcare professionals (HCPs) with different backgrounds in healthcare setting were involved in the co-creation of the intervention together with the ESPRIMO team of researchers and clinicians .An advisory board (AB) has been established at the beginning and consulted throughout the project.The co-creation consisted of three consecutive steps : surveysTwo web-based, anonymous surveys were implemented using the software LimeSurvey and administered between October and December 2020 .The first survey was designed for YawMS meeting the following inclusion criteria: age 18–45 years, MS diagnosis, Italian speaker, and electronic informed consent. The survey was composed of closed and open questions divided into three sections aiming to collect: (section one) socio-demographic and clinical information, (section two) patients’ perspectives and preferences about the intervention, and (section three) suggestions about possible barriers/solutions to intervention participation. In section two, participants were asked to rate on a Likert scale ranging from 1 (not important) to 10 (very important) how important is that “an intervention is based on an integrated vision of mind and body” and that “an intervention aims to improve psychological and physical well-being at the same time” and on a Likert scale ranging from 1  to 10 (much), and “how much lifestyle can affect the disease.” Participants were then asked to choose a maximum of options among a list (multiple choice with the possibility to give other suggestions if they felt something was missing) about: (i) the main objectives on which an intervention should focus to promote psychological well-being and (ii) the main characteristics of an activity to promote physical well-being Additionally, multiple choice questions with one possible answer were used to investigate the ideal frequency, the ideal venue for psychological and physical activities. Two further open questions explored the limits and advantages of conducting the intervention through online modalities Section three contained two open questions asking about possible barriers to participation and possible solutions.The same rationale was used to develop the second survey designed for HCPs , with prvia email through the MS Hub and SPOKE network of Verona Province with the request of sending the survey to other colleagues . Considering that the surveys are part of a larger mixed-method data collection and according to the relevant literature in qualitative research , while for HCPs email invitations to take part in the survey were sent research , a samplThe focus group topic guide was developed to gain additional information on preferences and needs regarding psychological and physical activities, and on potential strategies to reduce barriers to participation. Aspects connected to the socio-relational contents of the intervention have been investigated. Two FGs were held in March 2021 and, applying the criteria of data saturation , were coverbatim.Patients have been recruited at the MS Center of Borgo Roma Hospital in Verona  by the treating neurologist according to the following inclusion criteria: age 18–45 years, MS diagnosis, Italian speakers, and electronic informed consent. Before participating, the participants have to fill out a brief online questionnaire to collect socio-demographic and clinical information. Focus groups have been conducted online (using Zoom) and video recorded; after the completion recordings have been transcribed The Advisory Board is composed of a clinical psychologist, a neurologist, a movement scientist, a health sociologist and four YawMS.The presentation of the ESPRIMO project and the results of the quantitative and qualitative parts to the AB were held online by the ESPRIMO researchers. Contradictory results from the surveys and the FGs or further suggestions or critical points raised by the AB were examined in an open discussion. One researcher of the team took notes of the exchanges. A final report was sent to all the members of the AB to check for completeness and correctness of the data collected.The quantitate results of the survey have been analyzed using descriptive statistics. An inductive content analysis has been applied to analyze the qualitative results of the open questions. In particular, the participants’ answers have been reported in an Excel file, and two researchers have analyzed the text and elaborated possible labels in line with the guidelines . As a fiResults of the FGs and the advisory board were used to deepen the understanding of the survey’s results and the information on the relevant topic. Each main topic was checked against the results of the survey to see if there was agreement or not and to highlight specifications.The surveys reached a sample of 121 YawMS and 43 HCPs. The majority of YawMS who responded were female and had a (self-reported) diagnosis of relapsing–remitting multiple sclerosis; the mean age was 33 ± 7 years.Neurologists (53%), psychologists (23%), physiatrists (14%), physiotherapists (5%), and nurses (5%) filled out the survey dedicated to HCPs; the mean age was 40 ± 10 years.Most of the participants thought that an intervention based on an integrated mind–body vision is extremely relevant , and that is highly important to simultaneously improve psychological and physical well-being , psychological benefits (N = 14), adjustment to the disease (N = 7), social benefits (N = 7), global benefits (N = 6), and physical benefits (N = 2).When specifically asked how beneficial an integrated biopsychosocial intervention can be for the care process, HCPs answered positively (mean 8.4 ± 1.6). Moreover, the following perceived benefits were added: benefits in the care path, HCPs hypothesized an improved treatment adherence, more realistic expectations regarding treatments, and enhanced HCPs-patients relationships and trust. In the words of a participant “putting the person at the center with their specific physical, emotional, cultural, and social characteristics allows the doctor to better understand their needs and to establish a more effective care relationship.” Regarding the adjustment to the disease, HCPs highlighted that an integrated intervention might foster a better understanding of the symptoms, an acceptance of MS and promote a more favorable concept of disability also improving its acceptance within the family. According to HCPs, an integrated intervention might reduce the risk of relapses  and could improve interpersonal relationships and foster social inclusion and stigma reduction . Global benefits are also expected . As far as psychological benefits, HCPs considered an improvement in mood and self-efficacy and reduction of stress, increased awareness of one’s functioning, increased ability to cope with difficulties and disability, all of which might also have a positive impact on relapses.As regards the Regarding the main objectives to promote psychological well-being, among the listed options the most rated both by YawMS and HCPs were helping to accept the disease and providing stress management strategies. The third most rated by YawMS was supporting the expression of emotions and concerns, while the HCPs indicated “increase self-efficacy in managing the disease” .Thirty-one YawMS indicated other potentially relevant objectives; the following are the main categories emerged: increase independence, manage anger and negative emotions, develop a positive approach, help to go back to normal life, work on self-esteem, coping with difficulties, receiving support in a delicate period of time , handling the psychological effects of taking medications, understanding how to communicate the diagnosis and how to react to judgment, dealing with stigma and feelings of being a burden, sharing experiences with others YawMS.Regarding the preference on the main characteristics of an activity to promote physical well-being, having tangible benefits on the body, being tailored to each individual’s physical needs, fostering relationships with others YawMS and encouraging to continue after the intervention were reported more frequently .N = 17) included: becoming independent, improving balance, and endurance, strengthening the muscles and resistance to fatigue; experimenting dynamic activities; reducing stress. Additionally, one HCP stated that the intervention should improve the perception of one’s body, its potentialities, and its limits.Other aspects that were added by YawMS . No YawMS participating in the FGs had significant limitations, while 23% had partial limitations, and 77% had no limitations.And then [after the diagnosis]at that point many things come out, in short: about you, how you are, what you do, how you act in certain situations and moments or in the workplace).” As an adjunction, single comments regarded that it is important to: “let things emerge and think about them” not to be overwhelmed; increase motivation to act positive change; improve self-efficacy in the management of the disease, because of his personal difficulties in adapting to a new lifestyle.Regarding the main psychological objectives of the intervention, all participants agreed on the ones most frequently reported in the surveys. Regarding the acceptance of the disease, receiving practical suggestions, for example, on how to deal with a specific symptom or with uncertainty, should be considered in the delivery of the intervention. Having to deal with the disease made YawMS realize their functioning and other difficulties because the disease is connected to all areas of their lives: accepting the disease is the first step that also helps to intervene on other aspects . Dance has been considered a good way to mix all these elements, also helping to create social connections and prevent social isolation linked to diagnosis. Moreover, dance might help to express oneself in a more effective way, “allowing to express even emotions.” Nevertheless each individual impairment such as balance should be acknowledged, and one participant suggested to offer different types of dances. One participant cited the possibility to organize evening events based on dance activities.In addition, getting to know people dealing with the same condition and doing physical activities together has been considered a way of increasing motivation. Interaction with other people and music are a way, according to participants, to have fun while also doing something useful for the body  in order to enrich and deepen the data collected.Involving patients in research and valuing their opinion as experts can inform the design of services starting from the experience and needs of people that will use them . ProgramThe value of the biopsychosocial approach was confirmed by results throughout all steps of the co-creation, with a clear recommendation, as all parties involved might benefit from it. Specifically, the responses of YawMS and HCPs highlighted the importance of developing interventions using an integrated vision of mind and body, that simultaneously target physical and psychological well-being. HCPs highlighted possible benefits for patients, for the course of the disease and for the general process of care, including the improvement of doctor-patient relationships which represent a valuable aspect according to the literature .Moreover, the results suggest that each activity should not only target one specific component but that the bio-psycho-social domains are highly integrated. For example, some answers regarding physical activity encompassed themes pertaining social or psychological domains. In fact, according to participants, physical activity should also aim to reduce stress and foster relationships with others YawMS, once again reinforcing the importance of a biopsychosocial approach in the design of the intervention. However, the interaction between different components must be acknowledged all throughout the intervention design and should be targeted as a specific aim and should not be just a collateral result.Regarding the psychological domain, the main objectives highlighted by YawMS, and also supported by HCPs, regarded acceptance of the disease, stress management and emotional expression. This is in line with previous results in which YawMS stressed the importance of reducing unpleasant emotions and promoting strategies to accept MS as the most relevant aim of a psychological intervention  and withRegarding the physical activity domain, the main characteristics, according to stakeholders, are that it should have tangible benefits on the body, be tailored to each individual’s physical needs, and encourage to continue after the intervention. During the focus group, the main results of the survey in the area of physical activity were confirmed, such as the relevance of an activity that should be beneficial and adapted to the level of the individual. In line with the literature in this field  participRegarding the socio-relational domain of the intervention, doing the intervention with other young people that share the experience of living with MS emerged as a positive element that can help people to prevent social isolation and to foster meaningful interaction with alike people. Having to share a path with people that can easily comprehend the struggles of living with MS can help to build a positive environment, however, the broader social context should not be forgotten. Indeed, participants highlighted the need to learn specific skills to interact with their personal friends, family, or colleagues and the importance of diminishing stigma-related aspects in the general population. In fact, stigma is a social factor that can affect mental health in MS; however social resources  might protect people from stigma’s negative consequences .The co-creation phase made it possible to inform the choice of the intervention on practical aspects which are fundamental to maximize the results and the feasibility of the intervention.Regarding the timing, the intervention should have modalities that have low interference on the person’s life and be sustainable while also being pleasant and enjoyable for the person. This is particularly relevant considering the target population (young adults) that often works or studies, has low levels of disability and has an active personal  and social life  potentially making them busier and also already involved in other psychological, physical or social activities. In general, an intervention dedicated to young adults should fit in their busy daily schedule and should consider strategies to reduce psychological barriers to participation, including different types of fear in interacting with other people .Linked to the previous aspect, different insights on the limits and advantages of conducting the intervention online emerged and could be considered in future research in this field. To sum up, online modalities could be accessible to a wider public and could lower the risk of COVID-19 infections; however, reduced sense of belonging and social connections  and increased feelings of isolation have been stressed as the main limits of this modality. Some aspects regarding the facilitation/limitation in personal expression, the level of motivation and the technical aspects of the online modalities were more controversial; however, a slight prevalence of negative considerations.In-person encounters should also consider an easily accessible venue. The relevance of a non-medical venue for the intervention was strongly recommended by YawMS. Recent literature supports this suggestion; for example, an external de-medicalized venue was preferred for physical intervention for stroke patients .Based on the suggestions regarding possible barriers to participation, the ESPRIMO program has been designed to maximize the effects on wellbeing while also considering accessibility and people’s difficulties in participating in too many encounters due to personal reasons.Considering also the AB suggestions and previous literature recommendation for incorporation of at least one booster session to extend the length of the intervention to a minimum of 3 months in psychological interventions for adolescents and young adults living with chronic illnesses  the inteThree different timeframes  have been offered to foster participation. Psychological sessions focused mainly on the preferred objectives that emerged in the co-creation; for the physical activity, swing dance sessions were held by trained specialists that could adapt the activities based on the participants’ physical abilities. One psychologist was always present during each session to motivate the participation and to serve as a reference person during the intervention in order to potentially manage the psychological barriers.Even if contrasting opinions were collected during the different co-creation steps regarding the modalities of the intervention, in-person encounters were chosen given the lifting of preventative measures during the period of the start of the intervention and to account for the desire of human contact after a long period of social distancing. However, personal protective equipment was mandatory during in-person encounters to increase patient safety. Moreover, in addition to the group psychological and physical group face-to-face activities, to foster independence and give the possibility to practice in the most convenient moment of the day (as suggested by participants), YawMS are invited to do some short psychological and physical exercises that were guided by a manual and videos/audios shared on a dedicated Telegram channel. The Telegram channel also allows for informal communication between participants as a space to share thoughts, doubts, or improvements.All group activities were held in a neutral venue not connected with the health services: a villa managed by a non-profit association that pursues civic, solidarity and social utility purposes by hosting different projects dedicated to the community, young people, and vulnerable people. The building is surrounded by nature, based on participants’ suggestions and the literature on the positive effect of nature on wellbeing . In ordeTo the best of our knowledge, no previous study investigated the needs and preferences of YawMS regarding a biopsychosocial intervention and involved those patients in the co-creation process, making the paper particularly innovative in this field. Moreover, due to the COVID-19 scenario, an adaptation of the methods used for the co-creation process has been implemented, with online modalities for the surveys, FGs and AB discussion. As a further strength, representatives for each psychological, physical, and social domain have been included as stakeholders in the different steps of the co-creation process, together with YawMS representatives. Moreover, a representative of MS patients was also involved in the design of the manual and the revision of this manuscript.The majority of YawMS included in the surveys and focus groups were female, which, however, is in line with the higher frequency of MS diagnosis in females. The paper presents some limits; a relevant limit is that almost all respondents reported a diagnosis of relapsing–remitting MS, and patients with other types of MS and higher disability were less represented. The preferences and perspectives of those patients should be further explored in future research.The co-creation process described in the current paper allowed to integrate evidence from the literature and the clinical expertise of the researchers from the ESPRIMO project with the perspective of the MS main stakeholders (YawMS and HCPs) and to inform the design of the ESPRIMO intervention. Moreover, engaging patients in a meaningful way and fostering an alliance between researchers and patients  might have empowered patients and reduced the power imbalance between them and researchers.Preferences and perspectives of YawMS on the relevance, the objectives, modalities, and timing of the intervention but even on strategies to promote participation have been described and might enrich with insights future interventions development and research in the chronicity field. Moreover, the current paper outlined in detail a participative methodology as a model of co-creation in practice which might be replicated in future research on other CDs.The raw data supporting the conclusions of this article will be made available by the authors upon reasonable request.The studies involving human participants were reviewed and approved by the Ethical Committee of the Verona Hospital (Prog 2676CESC). The patients/participants provided their electronic informed consent to participate in this study.VD and MR: conceptualization. VD, SP, and MR: data collection and curation. VD, SP, MR, FG, and AG: participant recruitment. SP and VD: formal analysis. SP, MR, and VD: methodology and writing—original draft. AG, MM, FG, VB, LP, and FS: writing—review and editing. All authors contributed to the article and approved the submitted version.Italian Ministry of Research and University (MIUR) 5-year special funding to strengthen and enhance the excellence in research and teaching (Department of Excellence—Dipartimento di Eccellenza). The present study has been partially supported by this programme.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.