Game-based learning in medical education

At present, medical education is rapidly evolving. Game-based learning (GBL) has been gradually used for education, and several innovations have emerged. The emergence of serious games and gamification provides alternative approaches for educators to improve the medical teaching process. Both serious games and gamification exert their education-promoting function by providing the possibility of combining learning activities such as feedback, testing, and spaced repetition with active participation and autonomy as well as positive experiences for students. Developing effective GBL modalities has the potential to bring immersive experiences for medical students and improve their study outcomes. Herein, we reviewed recent studies employing GBL in medical education, including serious games and gamification teaching. Furthermore, we also discussed the effectiveness and limitations of GBL to suggest future directions for the development and application of GBL in medical education.


. Introduction
With the rapid development of modern technologies and the iterations of educational concepts, the repertoire of untraditional strategies for education is becoming wider gradually. Among these novel and appealing methods, game-based learning (GBL) is fast developing as an interesting and innovative teaching approach in the field of education currently (1). Over the recent years, mounting evidence suggests that GBL can improve engagement and stimulate the motivation of students to learn, as well as promote teaching outcomes (2)(3)(4)(5)(6)(7)(8).
At present, GBL is a new trend and is extensively applied in a wide spectrum of disciplines. Given the actuality that medical students are more receptive to new things and keen on modern technologies, various interesting games are also more frequently used in medical teaching (9,10). As opposed to more traditional instructional approaches, the main modality of GBL is adding diverse game elements to other non-game areas to encourage engagement and raise the enthusiasm of participants. The scope of GBL is extensive, and it covers both non-technological and technological integration of games within the teaching activity (1). GBL is typically referred to as "serious games, " "educational games, " and "gamification" in both undergraduate courses and clinical studies. The formal definition of serious games is an interactive computer application that has a challenging goal and incorporates

. Methods
We performed a PubMed search using the following search terms: "game-based learning AND medical education, " "serious game AND medical, " "educational games AND medical, " and "gamification AND medical." We reviewed and assessed all abstracts of those searched literature carefully to select appropriate articles including original articles, meta-analyses, and reviews. Meanwhile, we excluded articles that do not belong to the field of medical education. As a result, we made summaries according to different categories in the next sections.

. Serious games in medical education
Apart from entertainment function, another purpose of serious games is to be a pedagogical tool, which provides a way of interactive learning for medical education and constitutes a balanced combination between learning activity and amusement (11). Serious games include playing elements to support educational objectives deliberately and are generally illustrated as digital games that inform, educate, and train (19). It can also be done in different formats such as digital, card, and board games (20). The benefits of serious games on learners include enhancing their collaborative awareness via multiplayer settings, providing them with opportunities for active learning to better solve clinical problems, and improving their clinical reasoning, decision-making skills, clinical performance, and the like (5,21,22). As such, serious games have potential alternatives for supplementing traditional simulation-based education and contributing to better academic performances of medical students (23). Various serious games in medical teaching activity together with their main proposes and advantages are listed in Table 1.
The primary objectives of research regarding serious games in medical education are assessing their playability, practicability, and pedagogical outcomes for some specific contexts and diseases, and widespread efforts have been put into this. In the field of surgical medical teaching, some enjoyable games have been designed and obtained good results. For example, the game "Cleft Island" was developed to test whether learners could benefit from and gain related medical knowledge from this studying format as well as measure the game experience of students (24). The game development is made up of three components including "mechanic, " "dynamic, " and "aesthetic, " which aims to give participants a better experience. The results demonstrate that this game can be used as an effective supplementary instructional material and improve students' knowledge of treatment protocol (24). Another game, named "EMERGE, " was applied to explore the implication of GBL on students' declarative and procedural knowledge, which was achieved by the design of a pretestposttest manner (25). Specifically, students were asked to complete questions concerning declarative and procedural knowledge before and after playing the "EMERGE, " respectively. The result demonstrated that this pretest-posttest comparison increased students' knowledge and yielded a positive impression of them. However, this research failed to test the long-term effects of this game (25).
Serious games are also used in the course of pediatric teaching. Recently, Gerard et al. designed a first-person serious game termed "PediatricSim" that was intended to teach and evaluate students' performances in different pediatric settings such as respiratory failure, diabetic ketoacidosis, and septic shock (26). By selecting from distant treatment options, all participants were put in the role of a code leader and direct patient management to improve their cognizance of pediatric emergencies. Furthermore, this survey also assesses the engagement of students and the educational value of "PediatricSim." It is gratified that most subjects rated the game favorably for engagement, educational value, and realism (26). Another game "NEOGAMES" aimed at promoting pediatric education to improve long-term knowledge retention of students .
/fpubh. . Improving the students' knowledge effectively (37) and successfully train students in neonatal resuscitation in a costfriendly and accessible manner (27). Limited curricular time typically hinders teaching effects of infectious diseases. As a complementary device, serious games contribute to efficaciously pedagogical outcomes by creating highly immersive experiences for users. A serious game, AntibioGame R , integrates various game techniques and elements including cartoon graphics, mascots, and avatars, which aim to improve the training of medical students in the antibiotic application and test its usability and playability. As a result, 96% of students liked it and all students said they would recommend it to others (28).
In addition to imparting expertise, serious games also play crucial roles in medical-based cultural competence education. By providing an engaging, easily accessible, and modifiable training .
/fpubh. . tool, the game "Fydlyty" is shown to be intuitive and promote medical-based cultural competence education. It incorporates a scenario editor and dialogue authoring tool as well as employs lowfidelity visuals, which enables educators and students to access it directly in a more intuitive and simple way (32). Furthermore, serious games can also be used to teach medical residents for improving their management and leadership skills, since many of them think that leadership and negotiation are two additional domains they need (38).
There are multiple serious game modalities in the type of experiences created for medical students. Different from online games that consisted of complicated elements, both card games and board games have the potential to generate ideal teaching outcomes in a low-cost and more available manner. Hage et al. designed a comprehensive and structured card game "Happy Families" that enhanced learning enjoyment and promoted the cognition of students by making learners analyze subjective and physical examinations of a given patient (33). GridlockED is a multiplayer cooperative board game designed to assist learners in understanding the concepts of prioritization and patient flow in the emergency department. The investigators also tried to identify teaching points when students are playing the GridlockED game (34). These innovative teaching formats are emerging as complementary devices and represent promising options for classes. As for their long-term efficiency and applicability in veritably clinical practices, further investigations are needed.
The epidemic of COVID-19 has reshaped public awareness and posed great challenges for the field of medical education. One of the implications on education is that COVID-19 leads to large-scale disruption of university teaching activity (39). In this context, it is necessary to develop innovative approaches for medical teaching about basic knowledge of COVID-19 because most medical students will face and treat patients with COVID-19. To enrich teaching activities and help students to acquire COVID-19 knowledge effectively, Hu et al. designed a novel game named "COVIDgame" and compared its effectiveness in improving medical students' COVID-19 knowledge with online lectures (35). The game is composed of three separate parts including choosing the right order for putting on and taking off personal protective equipment, recognizing patients with COVID-19 promptly, and assessing confirmed patients. Only when every step is right can players accomplish the game. The final test scores demonstrate that the use of serious games improves students' study outcomes and contributes to improving knowledge retention (35).
Continuing medical education (CME) is an important part of medical education, especially for general practitioners. However, limited learning strategies together with their time-consuming disadvantage usually impede the further development of CME. In some cases, the use of technology creates more realistic situations by providing subjects with immersive experiences and finally achieving improved scores. Therefore, CME games have the potential to make up traditional methods tedious and sporadic. At present, the objectives of most CME games are to verify their effectiveness and satisfaction (29-31). By comparing the game with article reading, a traditional continuing education, researchers demonstrated that serious games functioned in a more effective, pleasant, and evidence-based way (29). Even though the outcome of serious games sometimes is not encouraging as hoped, it is at least as effective as a traditional educational activity and is proposed to be a feasible option for large-scale CME (31).
The advantages of using serious games in education not only include enriching pedagogical formats, promoting students' engagement, and enhancing their learning outcomes effectively as mentioned earlier, but also have the potential to reduce expensive bedside teaching and optimize the design of medical practices (36,40,41). Despite these benefits, challenges and limitations remain. The application of serious games fails to generate ideal results in regard to transferring learners' clinical reasoning skills acquired in serious games to other cases addressing similar clinical problems (42). Furthermore, the feasibility and effects of serious games require a match between task complexity and the learner's competency level in some cases because a game may not be effective for novices but be useful for experts, which is also known as the "expertise reversal effect" (43). Therefore, measures should be taken to ensure that junior trainees learn when playing the game. Cost and efficiency are important factors that need to be considered while developing a feasible game for teaching activity since excellent software created by third-party designers even costs thousands of dollars. In addition to the economic expenditure, the time needed for training instructors as well as the need for technical support and resources are common barriers that need to be solved (1). In addition, some research designs concerning serious games in teaching activity are not following the principles of randomization and control, which makes it difficult to exclude other factors influence. Notwithstanding, we can see that some randomized controlled trials are conducted continually. These trials confirmed the positive implications of serious games on teaching knowledge (37, 44).

. Gamification in medical education
Gamification is another strategy of game-based learning, which can be described as the application of the characteristics and benefits of games to real-world problems and a process of game-thinking and game mechanics to engage users and solve problems (13,14). The field of gamification in medical teaching activity is innovative and developed constantly. Even though gamification and serious game have some analogous characteristics and conceptual overlap, there are some means to distinguish them. The easiest and most direct method is removing the game elements to see whether the learning activity still functions. Also, different from the combination of learning and game goals in serious games, gamification is a design technique that typically layers game goals on top of learning goals to motivate engagement and constructive behavior of participants (45).
It has been recognized that the use of gamification in medical education is significant and salutary. Meanwhile, the area of related study is expanding. Several published articles comprehensively summarized its advantages such as enhancing collaboration and increasing the engagement of students, improving their earning analytic and clinical decision-making capacity, as well as offering them opportunities for deliberate practice in clinical reasoning (13,46). In light of its profound influences, gamification has been widely applied in various medical disciplines and different learning stages, particularly for the millennial learner, to promote significant    (60) teaching outcomes and to further evaluate its effectiveness, which is listed in Table 2.
As an important supplement to medical curriculums, gamification has been widely used by a variety of specialties in undergraduate courses, postgraduate teaching, and resident medical education. In most cases, gamification changes traditional tedious formats of teaching activity in the undergraduate stage. Microbiology is one of the core courses in undergraduate medical education (UME) that contribute to understanding and diagnosing various clinical diseases. The application of gamification in Frontiers in Public Health frontiersin.org . /fpubh. . microbiology course is a breakthrough and an innovative attempt. By exploiting a supplemental question bank that integrates game elements and clinical pearls, Walker et al. explored the effectiveness of gamification in microbiology teaching (47). In brief, the question bank resembles "tutor mode" to deliver and provide content, and students need to answer related questions to obtain the score. The composite measures include questions answered, their accuracy, and the time of response of players. This gamification design leads to higher class exam scores and increases students' basic knowledge (47). In addition, the utilization of checkerboard games also fosters the learning process and students' cognition in microbiology courses (48). A well-designed gamification process is likewise crucial for creating a fun-filled atmosphere and platform to further enhance the learning experiences and educational performance of medical students in the anatomical curriculum (49, 50).
As for other subjects in the undergraduate stage, such as immunology and dermatology, gamification of learning shows meaningful results in terms of maintaining students' attention and keeping them in an active state throughout the course (51,52). Kahoot represents an emerging game-based learning platform that can provide timely feedback for players and is extensively applied for formative assessment during remote teaching of immunology. In the game, participants compete with each other for the correct answer and response time, and based on these performances, the overall winners will be displayed on scoreboards (51). Stud2yBuddy is a card-based board game with four categories that incorporates peer feedback and self-assessment and has the potential to offer the opportunity for improving students' content understanding (52). Moreover, gamification of learning can also shape students' satisfaction and increase their study motivation in teaching activities (53-55).
As an innovative approach for enhancing teaching effects, gamification also plays a significant role in postgraduate medical education. An online game, termed "spaced-education, " covers both preclinical and clinical domains and functions by incorporating adaptive game mechanics into an evidence-based format (56). In the game, students repeated answers to given questions according to their response accuracy to optimize longterm retention of learning. It becomes a valid and reliable tool for assessing students' knowledge and represents a well-accepted way of teaching core content (56). Furthermore, gamification together with spaced repetition studies is gradually becoming an optimal complementary method to encourage medical education and manifest obvious benefits in promoting the retention of clinical understanding (61). Likewise, the application of gamification gains well-acceptance and yields positive implications among residents (57)(58)(59)(60).
In the context of the COVID-19 pandemic, O'Connell et al. developed a novel virtual game for obstetric and gynecology teaching. The game contains a warm-up activity and several rounds of rapid-fire questions and cases, and the main purpose of each round is to test players' knowledge about obstetric and gynecological care. This gamification attempt boosts resident education and engagement due to its entertaining, effective, and educational concepts (62). In addition, some optimized suggestions and solutions have been proposed for better designing gamification in the field of medical education during the COVID-19 era. First, teaching how to play the game by dividing lessons into smaller ones is a feasible method to develop short tests for tracking students' progress. Second, educators should take into account how students work together, their true capacities, and their preferences. Third, test design is an important element that can build students' knowledge and should be carefully treated. Furthermore, the use of different game platforms can motivate better interaction of players to improve their competition sense and sociability.
Finally, future investigation also should focus on how and under what conditions gamification can maximally exert its promoting education functions effectively (63,64).
In short, the application of gamification in medical teaching activity is promising and attractive because of its potential to provide more intuitive user experiences, solve the difficulty of remote teaching, and improve learners' engagement and motivation (65)(66)(67). Nevertheless, it is worth noting that the theoretical framework specific to medical education is still lacking, and optimized strategies as mentioned earlier deserve to be considered and further evaluated.

. Discussion
Game-based learning activities can create a fascinating learning environment for students to improve their study outcomes. The benefits of GBL on learners include enhancing their collaborative awareness, providing them with opportunities for active learning to better solve clinical problems, and improving their clinical reasoning and decision-making skills. Furthermore, GBL can enable educators to explore novel and feasible teaching strategies, which contribute to the reformation of current didactical activities. Therefore, the application of serious games and gamification in medical education is meaningful.
Despite the obvious benefits, disappointing results and weaknesses remain. For example, GBL cannot yield significant outcomes in short-term gains and long-term knowledge retention sometimes (68). Therefore, how to better use recreational factors to promote teaching activity is a problem we need to solve. Moreover, there is no standardized evaluation system to measure the specific impact of GBL on students' performance and pedagogical outcomes. Many of the published works in medical education mainly converged on the engagement level and satisfaction of participants as well as the changes in knowledge score from pre-test to post-test, whereas largely ignored advanced learning objectives such as long-term knowledge gain. In the Kirkpatrick Model, the evaluation system is categorized into four levels: how participants are reacting to the program, what they can learn from the program, whether and how the program changes their practice behavior, and the profound influence of the program on participants (69, 70). In this regard, further studies should focus on assessing participants' practice behavior and the profound influence of GBL on students, which resembles the third and fourth levels of the Kirkpatrick Model. Also, most studies regarding GBL in medical education were conducted based on small sample size, and in the future, the results should be validated by further multicentric studies. As for the cost of game development, researchers should synthetically consider to best achieve the professional result of which students are used to. Finally, games are typically not considered mainstream material in medical teaching, and it is . /fpubh. . important to improve their popularizing rate and explore their potential explanatory mechanisms.

. Conclusion
At present, medical education is rapidly evolving. Meanwhile, game-based learning has been gradually used for education, and several innovations have emerged. The emergence of serious games and gamification provides alternative approaches for educators to improve the medical teaching process. In most conditions, these teaching formats are well-received by learners and can create an immersive experience for students, considered effective, engaging, easy to understand, interesting, and educational in comparison with traditional teaching activities. Multiple teaching modalities of GBL also contribute to its further application, such as card, board, and even digital games using modern technology. As such, GBL has been recognized as a potential tool for enhancing medical education.
In summary, as a novel and promising teaching method, GBL has gradually become a popular addition to medical education curricula. It functions by providing the possibility of combining learning activities such as feedback, testing, and spaced repetition with active participation and autonomy as well as positive experiences for students. Designing a more effective GBL has the potential to bring an immersive experience for medical students and improve their study outcomes.

Author contributions
HQ and XZ offered the main direction and significant guidance of this manuscript. MX and YL drafted the manuscript and made the tables for the manuscript. YZ and RX critically revised the manuscript. All authors approved the final manuscript.

Conflict of interest
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.

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