This study was designed to explore learning experiences of university students with dyslexia and factors that could contribute to their success in the university career. Although, great efforts have been made to diagnose dyslexia and to mitigate its effects at primary and secondary school, little has been done at the university level in particular in the Italian context. Indeed in the university context, the availability and possibility to use of support tools, that enable the student to achieve educational success, is still not sufficiently adequate. In this paper we used bivariate association tests and cluster analysis, in order to identify the most suitable compensatory tools and support strategies that can facilitate the students’ performance in higher education. The data were obtained through the voluntary participation of Italian students, enrolled in a bachelor degree course, with certified diagnosis of dyslexia. Six groups of students were identified from the cluster analysis, defining specific support tools and learning strategies for each group. Furthermore, through the creation of these six groups, it was possible to describe “profiles” that highlight the risk factors (late diagnosis) and-or protection factors  in analyzing the academic career of students with dyslexia. Therefore, starting from these data, through artificial intelligence it will be possible to identify and suggest study methodologies and create specific support tools for each student that can enable her/him to achieve educational success in her/his academic career. Adults with dyslexia experience significant difficulty in adjusting to the academic demands of higher education2. Indeed, students with dyslexia often experience problems with information processing, note-taking, organization of essays and expressing ideas in writing4. Dyslexics students try to compensate for reading and writing disorders by using a variety of compensatory strategies including memory aids, advocacy strategies and digital tools5. Moreover, a lack of confidence can affect students’ performance, especially in social situations, such as reading and writing in front of others. Thus, enhancing learning potential of students with dyslexia is still an open challenge for academic staff6. Internationally, the number of students with disabilities enrolled in higher education is on the rise7. Students with dyslexia compile the largest subgroup8. In Italy, a survey conducted by ANVUR  together with CNUDD  during 2020, reveals that between 2017 and 2020, students with SLD increased from 6500 to 16,084.Dyslexia is a specific learning disorder (SLD), in that makes affected people continue to experience significant reading and writing related problems throughout their adult lives, which has been generally explained in terms of phonological deficits9; (3) realize of an online shared repository of learning and teaching materials; (4) create training paths for both students, based on the enhancement of the entrepreneurial mindset, and teachers, for improving the dyslexia awareness and (5) a sketching a memorandum of understanding to spread common inclusion strategies among higher education institutions. The remainder of the paper is structured as follows: “Starting from Goal 4 of the Sustainable Development Goals, which calls for equal access to tertiary education, including university, as part of the promotion of lifelong learning opportunities for all and in particular for the vulnerable people, the aim of this paper is to identify a set of approaches to deal with the difficulties encountered by dyslexic students in terms of homogeneity in socio-demographic characteristics, the difficulties encountered during university experience with the ultimate goal to provide appropriate treatment and support needed for successful functioning in and out of school. In this paper we used bivariate association tests and cluster analysis, which is a multivariate statistical analysis tool, in order to understand the most suitable compensatory tools and support strategies that can facilitate the students’ performance. An insight into their lives and experiences with an overview of their past is evaluated. The sample includes students that are studying or complete the career less than five years agos, in Italian universities, plus students enrolled in the last 2 years of High School. Data has been collected by using a self-reported questionnaire method. In our study we only considered certified dyslexic students, for whom the clinical diagnosis of dyslexia is based on the elements that foresee and comply with the recommendations of the Consensus Conference (2007–2009 and subsequent updates) and the Consensus Conference of the ISS . The volunteers of this study were undergraduate and postgraduate dyslexic students studying for a degree in Higher Education. The study is within an European project, named as VRAIlexia, that aims at providing tools and services for supporting the academic life of dyslexic students. More specifically, the tangible outcomes of the project can be summarized as follows: (1) a battery of virtual reality test useful to both collect in real-time the skills of dyslexic students through quantitative scores and enhance the awareness of teachers; (2) an artificial intelligence-based platform for the identification of the most appropriate supporting methodologies based on student-specific needs, whose proof of concept is presented in9. Despite these fundamental guidelines that emerged, the Italian community of clinicians highlighted that there are some critical aspects and started a debate on the matter as early as 2014 “the criteria adopted in general for the diagnosis of SLD must be respected, such as the absence of a decisive role of environmental and educational factors, and other exclusion factors such as sensory and intellectual handicap and severe emotional problems”10. In recent years the debate around the issues concerning the modality of the diagnosis of dyslexia has been further animated also at the international level. One of the most debated issues is the IQ-achievement discrepancy model that it does not assess or inform the quality of instruction received by students. Some students may be identified as having learning disabilities when, in reality, they simply have not experienced classroom instruction that meets their learning needs. A new approach to the diagnosis of dyslexia has been proposed by11. Otherwise as concluded by12, it’s very important that clinicians, schools and researchers cooperate in developing tools with good psychometric properties and based on recent research on dyslexia. In Italy, Law no. 170/2010 (New Rules on Specific Learning Disorders in schools) recognizes dyslexia, dysgraphia, dysorthography and dyscalculia as as SLD. The 170/2010 law has the purpose of: (a) guarantee the right to education; foster academic success, (b) including through educational support measures, ensure adequate training and promote the development of potential; (c) reduce relational and emotional discomfort; (d) adopt forms of verification and evaluation adequate to the training needs of students; (e) prepare teachers and raise parents’ awareness of problems related to learning difficulties; (f) to favor early diagnosis and rehabilitation didactic paths; (g) to increase communication and collaboration between family, school and health services during the education and training process; (h) ensure equal opportunities for the development of social and professional skills. The operating profile ascertains: cognitive skills; Linguistic and metaphonological skills; Visual-spatial skills; Motor-praxic skills; Attentional skills; Memory skills; School skills: reading, writing , reading comprehension, calculation, study method; Affective-relational situation . The diagnostic evaluation can only take place in the structures of the national health system or those accredited by it. It has a multidisciplinary character, in fact, the team is made up of a child neuropsychiatrist, a psychologist and a speech therapist or psychomotor specialist. The clinical diagnosis is based on the elements that foresee and comply with the recommendations of the Consensus Conference (2007–2009 and subsequent updates) and the Consensus Conference of the ISS . In the diagnosis, explicit reference is made to the nosographic criterion as indicated by the ICD-10: F81, also specifying whether reading and-or calculation and-or writing disorder is thus configured as a mixed disorder. The certification contains the information necessary to draw up an individualized and personalized educational and didactic program, where the dispensatory measures and the compensatory tools useful to the student for his educational path are explained. In fact, an operating profile is formulated that highlights the student’s weaknesses and strengths. The certification is always updated through a reassessment at the authorized structures at each change of school cycle and not earlier than 3 years from the previous one. Or upon notification by the school or family where an update is necessary. Specifically, Law no.170/2010 set methods, including medical history, clinical interview, school report, teacher evaluation, rating scales, and psychometric assessment to be considered for the dyslexia evaluation13. Finally, it is important to specify that in Italy there are no schools or special classes for students with dyslexia, but that an inclusive path is favored thanks to the law 170/2010 that provides dyslexic students with the necessary tools to achieve educational success. Law 170/2010 was the first specific regulatory intervention in Italy on SLD which ensures that students with SLD can benefit from special compensatory measures of didactic flexibility during the course of education and training and in university studies. Moreover, it requires that school institutions guarantee “the introduction of compensatory tools, including alternative means of learning and information technologies, as well as dispensing measures from some non-essential services for purposes of the quality of the concepts to be learned”. Compensatory tools are devices that raise the student from the performance made hard by the disorder, allowing him/her to focus on more complex cognitive tasks. On the other hand, dispensary measures are interventions that allow the pupil or student not to perform certain services that, due to the disorder, are particularly difficult and that do not improve learning. Law 170 provides that the assessment of dyslexia takes into account neuropsychological, psychological and speech therapy aspects. After the diagnosis evaluation, the family role is of the utmost importance l since parents are involved in the establishment of an educational plan with the school, by defining their rights and duties, as well as providing the authorization to apply suitable compensatory instruments and dispensatory strategies14. Moreover, family support can be a protective factor that may positively impact self-esteem15. Confirmation of the diagnosis is required at every change in school level and whenever it is deemed useful to modify it, to take into account the possible fluctuations of the problems and possible significant recoveries10.Since Dyslexia, as SLD, tends to persist throughout life and constitute a potential factor of vulnerability, there is a recognition of the need for a range of support over time and the importance of early diagnosis. The assessment of SLD must be a process guided by criteria as well-defined as possible, according to standards contained in the diagnostic manuals. Over the years, a lot has been done to diagnose dyslexia. Diagnosis has usually relied on some specific tests that aim to quantify reading difficulties, jointly with clinical tools that measure cognitive abilities16. It is worth noting that in Italy dyslexia is not recognized in almost two out of three children at the age of 8–10 years, when the disorder should be clearly expressed and identified. The non-recognition of two-thirds (or more) of the cases of dyslexia and the lack of adequate and timely interventions lead to anxiety and depressive behaviors17, low self-esteem and a low academic self-concept with school failure and drop out18. Focusing on high school students, academic assignments can have an impact on self-esteem and self-confidence, particularly when written assignments attract criticism for their poor presentation and weaknesses of grammar, punctuation and spelling19. Moreover, children with specific learning disorders are often subject to stigmatization by families, teachers and peers, which can lead to increased self-stigma and reduced motivation to learn20.Dyslexia is one of the most common conditions experienced by school-age children23, and24 found that students with dyslexia experience high levels of stress, strong negative emotions such as fear and loneliness, due to their interactions with teachers. Other dyslexic students report feelings of lack of confidence, inferiority25 and anxiety26. Moreover, other studies reported that students with dyslexia have a significantly lower level of self-esteem and more negative self-concept when compared to other students28.To the author’s knowledge, only few studies have focused on identifying emotions among dyslexic students. Among them29. Indeed, the earlier the intervention, the better the expectations of effectiveness. The management of SLD requires rehabilitative and educational care. The rehabilitation process is carried out as early as possible. Effectiveness is linked to the precociousness, intensity and frequency of interventions, for which the rehabilitation can rely on the collaboration of the family and the school. The earlier the intervention, the more likely it is that the procedures to help children with difficulties meet the normal teaching procedures of the class. A study carried out in Italy, revealed that the late diagnosis of dyslexia (in adulthood) is associated with negative effects, such as a sense of shame and incompetence, whereas in the case of early diagnosis or when parents and/or friends supported them adequately, this enabled students to cope with their dyslexia30. Another factor that negatively affects the academic lives of students with dyslexia is the number and severity of difficulties encountered31.It is worth noting that facing the diagnosis of dyslexia can be emotionally and psychologically challenging: recognizing it early, especially before the beginning of school, is crucial to help affected people fill their learning gap27. A few previous studies have nonetheless demonstrated that this permanent disorder can cause undergraduates and other adults a number of difficulties when they have to cope with tasks and activities that involve reading and writing33.University students with dyslexia have been inadequately investigated to date, especially in ItalyThe biggest problem, in Italy, is the inadequacy of diagnosis tools for post-school age. Indeed, when students with a late diagnosis arrive at university, these difficulties are overlooked and it is no longer possible to see improvements in the disorder but only refinement of the study method with the aim to compensate for the problems, thus making explicit the importance of identifying the appropriate support methods. To date, very few studies have explored day-to-day learning experiences of university students with dyslexia. For this reason, the aim of this work is to analyze a representative sample of the Italian population of students affected by dyslexia in order to identify the socio-demographic characteristics, the perceived difficulties and supports needs useful for each “type” of diagnosed-dyslexic student entering the university pathway ho have been diagnosed with dyslexia.The collection of the data needed to achieve the goal of the study was carried out through a questionnaire that was administered to Italian students with dyslexia, who were at least 18 years old and who were attending university or left it at most 5 years earlier. Our questionnaire was subjected to a double conformity check. Indeed, after an internal validation of the questionnaire by the ethics committee of the University of Tuscia, we sent our research proposal to the National University Conference of Disability Delegates (CNUD)—which is a body to represent the policy and activities of Italian universities towards students with SLD and disability. The attached questionnaire was validated in accordance with CNUD’s ethical principles and guidelines. The Italian Universities that have taken part in the survey are only those that have responded favorably to the CNUD’s invitation, thus ensuring that the ethical principles of their respective Universities are respected. In total, 66 Italian universities took part in the survey. Moreover, the data collection was conducted according to the ethical standards outlined in the 1964 Declaration of Helsinki. After that the Italian Universities have taken part in the survey, the students who completed the questionnaire were recruited by the Rector’s delegates for Inclusion at each University on the basis of the certification submitted at the time of enrolment at the university. The certificate is accepted by the University if the clinical diagnosis is based on the elements that foresee and comply with the recommendations of the Consensus Conference (2007–2009 and subsequent updates) and the Consensus Conference of the ISS . If a student has been diagnosed with a specific learning disorder (SLD) and present a certificate  or by a specialist or by an health care facility recognized by the Italian system) the Special Needs Unit will make sure that, once he/she is enrolled at University, get the necessary arrangements in order to: facilitate his/her academic progress and success; ensure a proper educational path;—develop his/her potential; reduce the causes of educational and emotional discomfort. The following services are offered by the Universities to the SLD students: support for prospective students who want to take the admission test; tutoring service to provide information and advice, promote integration at the university and suggest a method of study for core subjects; opportunities for interaction with the teaching staff in order to identify the best ways to attend courses and take exams. The participation in the questionnaire was voluntary and all the data has been recorded, collected and analyzed by guaranteeing anonymity and the respect of the General Data Protection Regulation guidelines. All the participants were informed about the aims of the study and asked to digitally sign an informed consent. The questionnaire is basically divided into three sections as sketched in Fig. The first one comprises demographic questions, such as age, gender, attended degree course and/or school and year of the program. The second section investigates the dyslexia status and history of the students. It includes questions about co-morbidity with other SLDs, type of support received, year of the diagnosis and presence of relatives with dyslexia. For each question, some answers are suggested. Suggestions are based on the corpus of knowledge about dyslexia and cover quite exhaustively all the possible answers. However, a blank space where to add possible missing alternatives has been inserted, in order not to neglect any useful information and not to bias the test. The third section, instead, is focused on the issues experienced by the students during their learning process and on the support tools and strategies that they found particularly useful or useless. This section is in turn divided into three groups, which survey issues, support tools and support strategies, respectively. For each group, a long list of items is presented. The participants must give a score from 0 to 5  to each item, where 0 stands for not experienced issue or useless tool/strategy, 5 stands for very strong issue or very useful tool/strategy and the marks in the middle stand for intermediate levels of importance of the issue or usefulness of the tool/strategy. The options “unknown” and “never tried” have been added in the support tools group, in order to differentiate such cases from the 0 mark, which means “tried and considered useless”, instead. The three lists of items have been created from face-to-face interviews made to 25 dyslexic students, by including all the issues they experienced, also if partially or just for a brief period of their life, and all the support tools/strategies they tried or they would like to have tried. This allowed having an exhaustive overview. However, again, a blank space has been left to give the opportunity to the participants to indicate possible missing issues/tools/strategies. It is worth noting that completing the questionnaire takes less than 10 min. In fact, it was specifically designed to be light and not too time-consuming, since performing large and repetitive tasks is one of the problems that most severely affects people with dyslexia. This allows participants to be more engaged, so as to provide answers unbiased by lack of concentration or hurry and, thus, more reliable data. We adopted a stratified probabilistic sample. The primary sampling units are represented by universities, while the secondary sampling units are students. We considered a sample with a sampling fraction equal to 10% of the total population. In this way we obtained a sample population that best represents the entire population being studied. The questionnaire was hosted online and 1.261 students with dyslexia from across Italy answered it. 72 answers were discarded since the participants were either outside the age range, or did not have a dyslexia clinical report, or completed the questionnaire more than once. The remaining 1.189 answers constitute the database of the analysis performed in this study.34. In our study, the units of analysis were students who participated in the survey. Agglomerative hierarchical clustering techniques proceed by a series of successive mergers. It starts with the individual units, thus there are initially as many clusters as units. The most similar units are first grouped, and these initial groups are merged according to their similarities. Eventually, as the similarities decrease, all subgroups are fused into a single cluster. Concerning the measure of similarity, we used the Gower distance35. The Gower distance is a metric that measures the dissimilarity of two items with mixed numeric and non-numeric data. Gower distance is also called Gower dissimilarity. This is the most popular distance for mixed-type variables; it is appealing because ranges between 0 and 1, being an average of the scaled distances calculated variable by variable. The Gower’s distance can be defined as the complement to one of the Gower’s similarity coefficient: We here adopted an agglomerative algorithm in order to apply a cluster analysis, which is a multivariate statistical tool aimed at grouping a set of units in such a way that units in the same group  are more similar to each other than to those in other groups (clusters). This method is the most common type of hierarchical clustering used to group units in clusters based on their similarity since it is suitable for constructing and identifying typological groupings that can be both distinct from each other and internally homogeneous36 between unit i and unit j, where 34 is considered hierarchical clustering procedures based on minimizing the “loss of information” from joining two groups. This method is usually implemented with loss of information taken to be an increase in an error sum of squares (ESS) criterion. Firstly for a given cluster k, let It is a dissimilarity or distance measureThis analysis considers a representative sample of 1.189 adulthood students with dyslexia. Dyslexia represents the most frequent self-declared disorder in higher education. Participants varied in terms of age, gender, level of study and age of diagnosis reflecting diversity within the students population. We start our analysis by considering some socio-demographic aspects of the sample. Table From Fig. Indeed, Fig. From this consideration, in Fig. 37: better access to relevant information, lobbying activity and access to a self-care network. Belonging to an association that deals with dyslexia guarantees students access to a network of opportunities and relationships that also have a significant impact on the student’s self-esteem. A recent research on dyslexic university students38 confirms the need of students in helping to create a community of support and support for dyslexic students within universities. Even at the level of micro-groups, social capital has a powerful balancing effect, both in terms of results and the self-esteem of students.By considering the type of support in each student’s type, significant relationships emerge from Fig. In this section, we report the results from the cluster analysis. As shown earlier, we used a hierarchical agglomerative method via Gower’s distance measure. We relied on agglomerative coefficient analysis to choose the link type. Indeed, this indicator measures the dissimilarity of a unit with respect to the first cluster to which it joins, divided by the dissimilarity of the final merger in the cluster analysis, averaged over all samples, we chose the best criterion among those presented above. Low values of the agglomerative coefficient reflect clustering of units that are “heterogeneous” with each other, larger values indicate well-formed clusters with “homogeneous” units in each cluster. From the analysis of the agglomerative coefficient, we chose to use Ward’s method, a hierarchical method that is based on the decomposition of total deviance into deviance within groups and deviance between groups; at each interaction the pair that gives rise to the lowest variance within groups is merged. The process of aggregation can be represented by using the dendrogram, which reports on the x-axis the units that participate in the process of aggregation and in the y-axis the level of distance at which the aggregation occurs between different groups that are being formed for successive agglomerations. From Fig. In order to proceed with the clustering process, we considered in the analysis the issue that students have encountered during their university career and the socio-demographic characteristics, based on the questionnaire answers. In the following table we report the six groups identified by the cluster analysis according to year of birth.39 in order to increase reading accessibility for those who struggle the most, text simplification might be used as an efficient rehabilitation tool and daily reading assistive technology, fostering overall reading ability and fluency through increased practice.As we can see from Table 40. In addition, interactive discussions and classroom activities can increase self-esteem in students with SLD41.Participation into study groups may have a positive effect on the well-being of dyslexics students, this participation could enable favorable relations, reciprocal acceptance, and pleasant involvement in group activities. On the other hand, it is important to remember the importance of social partner interventions aimed at improving self-image, greater development of communication skills and increased motivation to learn7. University students with dyslexia have disparate and complex needs that may require a mix of supporting tools. Students with SLD experience feelings of failure within the school education system, in particular if their problem is not recognized and adequate support is not provided. Providing appropriate support can fulfill the reading and writing requirements in higher education. The aim of this study was to explore the lives and experiences of dyslexic students studying at Italian Universities in order to provide appropriate support tools and strategies that can facilitate the students’ performance. The research took place between March and May 2021 by collecting 1.189 questionnaires. In this paper we used bivariate association tests and cluster analysis, which is a multivariate statistical analysis tool. Our results from descriptive statistics reveal the importance of an earlier diagnosis and treatment for dyslexia with specific help, in particular help from association of dyslexic students. Earlier diagnosis, treatment for dyslexia with specific help from speech language therapists, psychologists and association and being able to compensate for dyslexia, by providing appropriate equipment can be keys to success in university studies in order to help dyslexic students to feel in control of their learning. In this context, it is important to note that from our results emerges a positive association between help from associations and friends and the probability of success in university studies. Belonging to an association that deals with dyslexia guarantees students access to a network of opportunities and relationships that also have a significant impact on the student’s self-esteem. A recent research on dyslexic university students38 confirms the need of students in helping to create a community of support and support for dyslexic students within universities. Even at the level of micro-groups, social capital has a powerful balancing effect, both in terms of results and the self-esteem of girls and guys. Moreover, our data, international scientific literature and recent research at national level confirm that it would be essential to support and implement macro, meso and micro support networks for dyslexic students with ad hoc policies and strategies, formal or informal. Finally, results from cluster analysis suggest a variety of internal challenges associated with attending higher educational institutions: universities are to actively promote students’ equal rights and prevent direct or indirect discrimination and they should guarantee individualized and personalized didactic plan. In Italy, awareness of SLD issues is very recent, as the first law recognizing dyslexia was introduced in 2010. For this reason it is necessary an extra effort on the part of universities to make their institutions more dyslexia-friendly across the board. This can include everything from using dyslexia-friendly fonts, stricter guidelines for teaching staff regarding monitoring student action plans and social skills interventions should be a popular adjunct treatment for students with SLD. In the light of the results obtained from the survey carried out over 1.189 certified Italian dyslexic students, this study intended to identify, through the statistical cluster analysis, which tools may be beneficial to the development and adaptation of educational methods to support students with dyslexia in order to overcome all the main difficulties encountered. Indeed, as already reported in9 dyslexic university students often see their academic career slowed down or even spoiled. Starting from the necessity to untap dyslexic students’ potential and enhance their strengths, the results of this research will be used to develop learning tools and services to ensure to dyslexic students equal access and opportunity of success during their career and their lifelong learning experience. The results of this research will be part of the project VRAIlexia , i.e. the output of the cluster analysis survey-based proposed will be part of BESPECIAL AI -based platform. Indeed, the AI solution we propose is a software platform able to provide dyslexic students at university with customized digital supporting tools and personal learning strategies. The kernel of the platform consists in an AI-based module that is capable of predicting the specific support needed by each user, from his/her dyslexia clinical report and, the answers to a self-evaluation questionnaire about the difficulties faced during the studies and the solutions they deem to be helpful , and a battery of psychometric tests. AI is trained on a large database of clinical reports of dyslexic students and on questionnaires and psychometric tests performed by them. The output of BESPECIAL  are digital tools  and best practices  that are estimated to be more useful for each student. Digital tools will improve the students’ study material and adapting it, using AI, based on students’ needs, whereas the services will be provided to the higher institutions, in order to define standard strategies for inclusive education. In fact, well-known techniques like NLP, OCR, GANs etc. are employed to adapt the material to the specific needs of each student. The above-described AI solution has been conceived within a European project, named VRAIlexia (www.vrailexia.eu), which aims at overcoming all the main difficulties encountered by dyslexic student at university and reducing the gap with respect to non-dyslexic students. In addition to BESPECIAL development, VRAIlexia will lead to: (1) implement a battery of virtual reality test to collect in real-time the skills score of dyslexic students; (2) realize of an online shared repository; (3) create a training path for dyslexia awareness and (4) a memorandum of understanding to spread common inclusion strategies among higher education institutions. Among the several activities provided by VRAIlexia project, the main one consists of providing dyslexic students at university with digital supporting tools that are specific for each of them and, thus, much more effective, in order to decisively reduce the problems they usually encounter and facilitate their academic career. VRAIlexia project aims at changing the perception and developing a model of tools to overcome dyslexic’s main difficulties empowering their motivation and self-esteem. The perspective is to let that Universities can develop strategies for inclusion for fostering all students to discover and point on one’s strengths and values. A further future objective of the Vrailexia project will be to translate the questionnaire into other languages to be administered in other European countries in order to perform a similar clustering approach, permitting to compare the dyslexic profiles based on different languages.The number of dyslexic students in need of support is increasing at many universities


Human infection studies (HIS) involve deliberately infecting healthy volunteers with disease-causing pathogens under controlled conditions. These studies are “controlled” by way of using specific types of pathogens, including dose, and the availability of emergency medical facilities to research volunteers. Most HIS involve diseases whose treatment is known and are done to accelerate the development of novel therapeutics such as vaccines, to address emerging and existing infectious diseases. Traditionally, HIS have been conducted primarily in high-income countries (HICs) but are now increasingly being conducted in low-and-middle income countries (LMICs). In LMICs settings, HIS are likely to raise concerns among various stakeholders including participating populations and regulatory bodies, that are unfamiliar with this type of research. Deliberately infecting a healthy individual with a disease-causing pathogen seems to go against the normal practice of medicine of “do no harm”. Such types of studies can give rise to increased rumors and jeopardize research participation in study activities, including non-HIS research. Community engagement can be one approach to address particular issues that HIS studies raise through meaningfully engaging with communities, where views and voices inform the conduct of HIS studies. In addition, engagement can inform the ethical conduct and acceptability of HIS studies in LMICs settings and provide opportunities for sharing information, listening to, and responding to concerns and views from potential participants, and the larger community in which the study would be conducted. Despite community engagement being an important aspect to consider, very few published and gray literature cover the types of approaches that have been used, and lessons learnt in engagement for HIS. This article outlinesthe community engagement approaches that were used to engage stakeholders and communities for malaria HIS-controlled human malaria infection (CHMI), undertaken in Kilifi, Kenya. It outlines the engagement activities across the research cycle, from activities conducted during protocol development, to planning, and implementation of the study. We discuss the challenges experienced, lessons learnt, and provide some recommendations for engagement around HIS. Human infection studies (HIS), otherwise known as controlled human infection studies, challenge studies, and human challenge trials, involve deliberate infection of healthy volunteers through administering pathogens under controlled conditions . ControlTraditionally, HIS have been conducted primarily in high-income countries (HICs) but many target infectious diseases occurring mostly in low-and-middle-income countries (LMICs). Some of the reasons why this has been the case include limited (but rapidly growing) infrastructure, skills/training to undertake such studies, and inadequate legal, ethical, and regulatory systems in LMICs. Community understanding and acceptability of such studies can also be a reason why these studies have taken time to be conducted in LMICs settings. In recent years, capacity building initiatives targeting LMICs have significantly addressed some of these gaps, which has also contributed to an increasing number of HIS conducted in these settings .While conducting HIS in LMICs is a welcome idea, these types of studies require careful development of research approaches that support both scientific and ethical conduct. The idea of deliberately infecting a healthy individual with a pathogen goes against the ethical norm in clinical practice and research of “do no harm” . Safety The HIS can raise concerns among communities and the broader public if appropriate steps to engage communities are not taken. Such concerns can be around: the type of pathogen involved ; the experience and implications of requirements for residency away from home during the study where this is a requirement; discomfort or health risks related to the study procedures (such as frequent blood sampling); perceptions around treatability of disease following deliberate infection (including possibilities of third party risks); and limits to the right to withdraw that may be in place to protect the volunteer . TherefoSeveral published works have demonstrated the importance of community and stakeholder engagement for HIS. In a recent study that assessed the acceptability of SARS-COV-2 HIS, conducted in the UK among 20 to 57-year-olds, volunteers suggested that due to the ethical complexities and public interest in such studies, it was important to ensure transparency to the public and broader scientific communities . SimilarIn India, workshop participants identified important considerations for HIS, including the role of ethics review committees in safeguarding the rights of research volunteers, considerations of legal implications on deliberate infection of healthy people, and other social considerations such as engaging the media . ReviewiStudies have also shown the importance of community engagement for HIS in LMIC settings, especially among populations with either little research experience or where this type of study is implemented for the first time . CommuniEven though the importance of careful community and stakeholder engagement is emphasized in the literature, there is the little emphasis given to the approaches used or their value. Here, we aim to share our experiences, including challenges and lessons learnt during the development and implementation of engagement activities for malaria HIS conducted in Kilifi Kenya, to provide a resource for researchers and engagement practitioners in other LMIC contexts.Over the last 6 years, a program of HIS on falciparum malaria involving over 160 volunteers has been conducted at the Kenya Medical Research Institute (KEMRI)-Wellcome Trust Research Programme (KWTRP) and Center for Geographic Medicine Research Coast (CGMR-C), in Kilifi , under a program titled “Controlled Human Malaria Infection in Semi-Immune Kenyan Adults” (CHMI–SIKA) .The CHMI–SIKA program of work in Kilifi followed an initial “proof of principle” HIS on falciparum malaria at the KEMRI Center for Clinical Research in Nairobi , involving 28 healthy semi-immune adults, recruited mainly from medical colleges and those living within the vicinity of the research center in Nairobi in 2013 . Given tPlasmodium falciparum  sporozoites following successful recruitment and screening to ensure healthy status. These volunteers were admitted to a residential facility a day before infection and monitored for the development of any signs and symptoms of malaria. The study outcomes and procedures have been described previously  Measure correlations between antibody levels to defined and well-characterized malaria antigens and growth rates of (b) Confirm the safety of CHMI administered by direct venous inoculation in semi-immune volunteers.(c) Measure parasite growth rates in semi-immune volunteers.(d) Establish a sample set for the study of immunity to malaria and its effect on parasite growth following CHMI in semi-immune volunteers.(e) Explore the understanding, motivations for participation, and experiences of volunteers and other stakeholders.The implementation of this study in a different setting outside of the initial setting of Nairobi provided an opportunity for a context-specific undertaking of community engagement activities with a clearly outlined strategy to inform practice. This community case study focuses on local engagement approaches for the CHMI–SIKA study in Kilifi, which was made possible by the early buy-in of national-level stakeholders.The KWTRP has its headquarters in Kilifi, with 2 other research hubs in Nairobi and Mbale (Eastern Uganda). Kilifi County is one of the 47 Counties in the devolved government system of Kenya, located in the Coastal part of the country, bordering the Indian Ocean. It is a rural County, with fast-rising peri-urban towns. The residents of the county are predominantly from the Mijikenda community. The population of Kilifi has low-literacy levels, and the main economic activities include tourism, farming, and fishing.The KWTRP Kilifi hub hosts a range of international and national collaborative research projects, including epidemiological, social, laboratory and clinical research, to inform local, national, and international health policy. The research activities at KWTRP are supported by a strategic community, public and policy engagement platform, with specific experienced engagement staff  responsible for implementing engagement activities . The proCommunity engagement at the Kilifi hub of KWTRP is supported by a network of around 200 community representatives , elected by residents living within the KHDSS . The KCRP. falciparum sporozoites and were required to be full-time residents in a study facility for up to 25 days for close clinical and research monitoring. Study procedures and stakeholder experiences are detailed in a series of clinical trial and social science publications (The CHMI–SIKA study began in 2016 with volunteer recruitment and was conducted over 3 years (2016–2018). Healthy adults aged between 18 and 45 years were injected with ications , includiications .Planning for community and stakeholder engagement for CHMI–SIKA began early, as part of the development and preparation of the study protocol for scientific and ethical approval. The flow chart in Community engagement Advice for STudies) team was formed and deliberated on all aspects of community and stakeholder engagement throughout the planning, review, and implementation of the CHMI–SIKA study  healthy volunteers would be deliberately infected with malaria parasites; (ii) volunteers would be required to stay in full residency during a prolonged period (up to 25 days) during the study; and (iii) volunteers from Ahero, in Western Kenya (about 850 km from Kilifi) would travel to join their Kilifi counterparts participating in the study. This design ensured that healthy adults with a range of levels of prior malaria exposure were included since malaria has high endemicity in Western Kenya and low-to-moderate endemicity across Kilifi. Through their deliberations, the CAST team identified the stakeholders to be engaged and engagement approaches to be used  and deveThe CHMI–SIKA study team were allocated time to present this study to Kilifi County department of health stakeholders during one of their routine County health management team (CHMT) meetings. The Head of Engagement worked with the coordinator of CHMT meetings to identify a suitable date and time, and then the study investigator was informed. A member of the research team (often the PI or study coordinator) gave a 10-min presentation, and then took questions, comments, and recommendations from the health managers, including discussion and approval of the strategies developed by the study CAST team.Study sensitization meetings with members of a network of community representatives  drawn from 3 locations where study volunteers were going to be recruited from , were conducted. The community representatives shared their concerns as community members, and concerns that could come from those they represented in their respective villages. Giving them information about the CHMI–SIKA study and responding to their concerns, meant that they were better equipped to respond to questions from community members whom they represented.barazas, which are large meetings of community members. Chiefs are responsible for calling the baraza. Community members are mobilized from their homes by word of mouth, through village elders (these elders work under instruction from a Chief). Meetings cannot begin without the presence of a local Chief. During the meeting, the Chief makes opening remarks, before inviting guests to make their presentation to community members. At the end of the engagement meeting, it is again the responsibility of the Chief to close and disperse the audience. In some instances, the Chief may summarize his/her learning or understanding of the study as part of closing remarks. Barazas are typically attended by 100–200 community members if well mobilized and they usually take place during mid-morning hours. These meetings provided a forum for directly engaging community members on the CHMI-SIKA study. Between 70 and 150 community members from sub-locations of the 3 main locations named earlier were reached with CHMI-SIKA study messaging. The meetings began with a member of the CLG giving a general overview of KWTRP and research activities conducted by scientists at the center, and then a CHMI–SIKA study team member was invited to talk about the study. This was followed by a question-and-answer session.KWTRP has a well-established relationship with local area Chiefs, their assistants and village elders within the KHDSS. In Kenya, Chiefs form part of the national administrative arm of the government responsible for interior security. As such, part of their responsibility includes maintaining security at the community level and disseminating or enforcing relevant government policies within their localities. Chiefs are considered important gatekeepers in the community and approve activities that involve community members to happen at the community level. Important information is communicated to the general public through organizing community Important gaps in a wider understanding of the research context were highlighted through more general questions asked about how KWTRP conducts research activities. For example, community members wanted to understand why KWTRP focuses mainly on certain diseases such as malaria, and not other common illnesses affecting the community such as filariasis or hypertension. These questions were responded to by a CLG staff and CHMI–SIKA study team present in the sessions who explained the process of arriving at a research question, including the review of hospital mortality data.From routine engagement activities, we have come to understand that KWTRP staff are important gatekeepers in the community as they are often asked many questions about the work of the Programme. To ensure that all the staff in the Programme were aware of this study and that any concerns/questions they had were addressed appropriately, the CLG staff organized a series of seminars where the CHMI–SIKA team presented the study and responded to questions that were raised refer to .The study team came up with the idea of engaging the study volunteers, as a way of keeping them busy during their in-patient stay and improving their understanding of health research during residency. After administration of malaria parasites (between days 2 and 5 post-infection), the research volunteers had a workshop in-residency and then were invited into the research institution for a tour of the research facilities  and interaction with scientists. The study team also took this opportunity to further respond to questions from the volunteers, concerning the CHMI–SIKA study. Volunteers were picked in groups from the in-patient facility in a bus and immediately transported back after the engagement meeting. This was done to ensure that all volunteers got back to the in-patient facility without breaking study protocols and going home to visit family/friends. The open days also provided an opportunity for CLG staff to discuss with the study volunteers more broadly about KEMRI as an organization and provide a holistic view of the research conducted.The CHMI–SIKA study team participated in a media engagement workshop organized by KWTRP's communications team for researchers at the Programme. During the workshop, scientists shared a round table with one or two journalists and discussed with them their research areas of interest, including ongoing or planned work. Through this workshop, the study was explained to journalists who were present.An important feature of the engagement activities undertaken was that CHMI–SIKA study team members  attended and participated in all the engagement sessions alongside experienced members of the community engagement team. When the scientists participate in engagement activities, they can hear first-hand, issues that are of concern to potential research volunteers. They are also able to learn about and consider social and cultural aspects that are important to the community where a study is being conducted . In addiThe CHMI–SIKA research study was the first of its kind in Kilifi. It was also the first time that the study volunteers were drawn from different parts of the country and put together in one site. Thus, the experience of the CLG staff in systematic planning for research studies helped us prepare for this unique study. At first, having a structure such as the CAST group that is set up for every study involving human subjects was important as it aided in carefully thinking through important points of consideration for engagement, using an engagement template. The engagement template has a section for sensitivities in a study; here, unique features of CHMI–SIKA were listed. From this list, key messages were developed to aid in correct and consistent messaging. Secondly, going out into the community gave potential volunteers an opportunity to (i) meet the CHMI–SIKA team, (ii) hear first-hand about the study, and (iii) have their concerns about the study responded to. Having researchers directly interact with community members and discuss planned research is one way to build respectful relations and provide opportunities to discuss areas that worry the community as was the case with CHMI–SIKA and can contribute to building trust. Finally, using a combination of approaches ensured that many different stakeholders were reached with engagement activities and had opportunities to have their concerns responded to. Systematic engagement is very involving and time-consuming; thereby requiring ample planning time so as not to interfere with study timelines.At the end of every engagement session, conducting what the CLG calls “debrief meetings” in all engagement activities helped to review what worked well and what did not. For every CHMI–SIKA engagement activity, the engagement team met to discuss and formulate strategies for improving what did not work well. Emerging new concerns not captured in earlier developed key messages were shared with the study team and responses fed back to the stakeholder or community group engaged. Such meetings are helpful as the implementing teams can review what works and what does not work well, and how challenges faced can be mitigated in future engagement sessions. To support learnings in engagement, embedding empirical social science work within ongoing HIS has built a better understanding of study benefits and risks , and higThe social science team was able to draw on some of the similarities and differences in engagement approaches, between Kilifi  and Ahero (Western Kenya). Some similarities included large community meetings, while differences included working with community health volunteers in engagement, which was done in Ahero but not in Kilifi. In addition, in Kilifi, field staff training on communication and consenting forms part of engagement activities. Field workers are often the face of the institution in the community and encounter challenging questions about research being conducted by the organization, as they visit homes to give study information and refer potential volunteers for screening. As such, the CHMI–SIKA field workers went through a communications and consent training before carrying out study activities, as is done for all studies undertaken in the Programme. In addition, the field workers had extensive training including role plays on how to effectively communicate the key messages of the study. This allowed for an internal evaluation and feedback based on the role plays conducted. The role plays involved selected members of the field team acting as potential volunteers who would be approached for information giving about the study with feedback on how the information was relayed and whether reflective of the key messages. The key messages document was useful in ensuring that during the training, field workers understood how to frame messages around the study uniqueness, thereby, ensuring that what they said was consistent with the information shared through engagement activities. Based on sentiments shared by community members in routine engagement activities, consistency in messaging is a key marker for trust. Conflicting messages coming from members of the same institution are considered to be a flag for dishonesty with the potential for breaking trust.Throughout the CHMI–SIKA study, the community engagement and study teams worked together to address a range of challenges. For example, engagement activities were conducted around April/May, which in the Coastal part of Kenya, is the long rainy period. Often, meetings had to be postponed either due to heavy rains or because community members were busy in their farms. The CHMI–SIKA study team appreciated these challenges and were willing to be flexible. However, the CLG staff understood the tight study timelines and made efforts to negotiate with community leaders to continue with some of the meetings through sourcing for in-door venues where residents would be sheltered from the rain. In planning for community engagement activities, research teams must be cognizant of community socio-cultural norms and practices, as these can sometimes have a direct impact on engagement, recruitment, and study timelines.Another challenge that faced the CHMI–SIKA study was that after the first cohort of participants had been successfully enrolled and completed follow-up with the publishing of the embedded social science study , a news Determining engagement effectiveness is a complex task that involves having first outlined goals and objectives for evaluation. However, we think that our engagement was useful in some ways as the CHMI–SIKA study was conducted successfully from beginning to end without major interruptions. KWTRP's long-standing relationship with the community members in the KHDSS might have helped make engagement sessions smoother. The community is aware and expects that every new study recruiting human volunteers will be brought to a community meeting for dialogue before the study commences. This has helped to build trust with this community, which is critical when conducting research such as HIS.In addition, the engagement process as well as on-going study interactions and embedded social science studies helped to identify key areas of concerns early on in the study, which helped in addressing these and initial fears, questions about the research design, safety concerns . This we think might have contributed to allaying initial fears and hesitation among potential volunteers.Administering informed consent took account of views from the community; it was a process with several interactions with study team members, and extended time for discussions with family members, as was requested by community members in engagement activities . We postFollowing successful completion of the first cohort in 2016 which enrolled 37 volunteers, the majority of these volunteers became self-appointed “study ambassadors” and communicated their experiences of participation as well as information about the study in the community. Taken together, the initiation of in-residence workshops  and embedded social science and empirical ethics work, allowed for a volunteer-centered engagement approach for direct feedback into the processes and procedures of the study conduct. This for instance resulted in a better understanding of the need to stay in residence. There was a co-adaption of learnings from each engagement process from one cohort to the other.Despite HIS being relatively new in Kenya, the high-level stakeholder engagement meetings held in Nairobi during the very first “challenge” study paved the way for successfully carrying out the study in Kilifi. In addition, conducting a broad range of engagement activities, right from the protocol development stage to the formation of a CAST, developing key messages and using these for consistent and correct messaging during engagement implementation, minimized the chances of raising rumors about the study. These approaches also provided a forum where multiple stakeholders raised concerns and questions related to CHMI–SIKA and HIS in general and had these responded to. Research and engagement teams can draw on these approaches including lessons that have been learnt as a reference for future HIS engagement planning and implementation.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.NM, PN, PB, DK, and MK contributed to the conception and design of the work. NM, PN, CM, SM, JM, MM, BK, HA, JW, PB, and MK conducted engagement activities. NM wrote the first draft of the manuscript. MK, DK, PB, MH, VM, EA, CM, and PC contributed to manuscript revision, read, and approved the submitted version. All authors contributed to the article and approved the submitted version.This work was funded by the Wellcome Trust (Grant Number: 107499). The funder had no role in the design, analysis, write up, or decision to submit 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.


Boredom is a common emotional experience in daily life adversely affecting individual physical health, mental health, and social functioning. Therefore, it is an important issue to improve the quality of life by ameliorating individuals’ state of boredom. We used a longitudinal research approach. First, we tested 728 participants with the Multidimensional State Boredom Scale (MSBS). Then, after 3 months, the participants filled out the Cognitive Flexibility Inventory (CFI), Perceived Social Support Scale (PSSS), and Meaning of Life Questionnaire (MILQ); 715 valid questionnaires were obtained. Results showed that cognitive flexibility played a mediating role between boredom and the presence of meaning in life, but social support did not. The total effect of boredom on the presence of meaning in life was significant. Cognitive flexibility and social support played a mediating role between boredom and the search for meaning in life, respectively, but the overall effect of boredom on the search for meaning in life was not significant. This study found that boredom has different effects on the presence of meaning in life and the search for meaning in life. It can improve individuals’ sense of meaning in life by reducing boredom and improving cognitive flexibility and social support. Previous research has mainly interpreted boredom in terms of emotional, cognitive, physiological, and motivational aspects. Although a unified conclusion has not been reached, it is universally agreed that boredom is an unpleasant emotional experience  that is Boredom is a negative emotion in which individuals experience a loss of attention, lack of interest, poor self-control, and reduced well-being, which in turn affects their perception of their current situation and experience of the meaning of life ,8. In moMeaning in life is defined as people understanding and appreciating life, discovering the importance of their own lives, and recognizing the purpose and mission of life . On the The Five “A”s of Meaning Maintenance Model focuses on the intrinsic resources of individuals and theorizes on the mechanisms by which boredom affects meaning in life. It proposes that assimilation and accommodation, important concepts of Piaget’s cognitive development theory, are among the compensation strategies for individuals’ loss of meaning and arousal of disgust. Although the functions of the two are different, assimilation and accommodation both enrich the existing schemas of individuals and promote the development of cognitive structures. Piaget believes that to achieve adaptation, individuals need to constantly adjust their cognitive structures due to environmental constraints as a way to obtain a balanced process of internal cognition and external environment . Cognitive flexibility is an important part of executive functioning as an individual’s ability to adopt flexible cognitive strategies, which reflects cognitive adaptability and plays an important role in individual ability development and environmental adaptation . Martin To cope with boredom, individuals must mobilize their intrinsic resources. Cognitive flexibility, as a functional expression of assimilation and accommodation, can help individuals recognize and understand dilemmas from different perspectives and solve problems in multiple ways , thus enAlthough the Five “A”s Meaning Maintenance Model focuses on intrinsic resources and theorizes on the mechanisms by which boredom affects the meaning in life, the role of extrinsic resources remains to be explored. Developmental resource theory suggests that adolescents cannot develop without intrinsic and extrinsic resources. Social support is an important extrinsic resource for individuals and is closely related to psychological well−being. Cassel argued that social support has a protective function and can act as a buffer or protector when individuals are under stress . MoreoveTo sum up, this study aims to examine the predictive effect of boredom on the two dimensions of meaning in life through a longitudinal study and to test the mediating effects of cognitive flexibility and social support between boredom and meaning in life. It expands the understanding of meaning in life and lays the theoretical foundation for an in−depth investigation of the mechanism of boredom’s influence on meaning in life.A total of 728 university students from a Chinese university participated in this longitudinal study, in which 13 participants who did not wish to continue to participate in the survey and did not fill out all the questionnaires seriously were removed. Altogether 715 valid participants were obtained, among which 420 (58.74%) were men and 295 (41.26%) were women. The mean age was 19.48 ± 1.31 years.Longitudinal measurements were taken at 2 time points. The first, in September, examined participants’ state of boredom; the second, in November, examined participants’ cognitive flexibility, social support, and meaning in life. A pre−trained administrator was in the classroom to organize each test, who also informed the participants that participation was completely voluntary and that they could quit at any stage of the study. Those who completed all tests were given a small gift as a token of appreciation.The Multidimensional State Boredom Scale was developed by Fahlman et al. (2013) . This stThe Meaning in Life Questionnaire developed by Steger et al. (2006)  is a briThe Cognitive Flexibility Questionnaire was developed by Dennis et al. (2010) . It contThe Scale of Perceived Supports, developed by Blumenthal et al. (1987)  and reviThis study adopted SPSS 26.0  for descriptive statistics analysis and correlation analysis. Mplus 8.3  was used to construct the structural equation model.Descriptive tests and Pearson correlation analysis were conducted concerning the five variables to obtain the means, standard deviations, and variable correlation matrices. Detailed dimensional scores are shown in p < 0.01) and did not correlate with the search for meaning in life at T2 (p > 0.05). The presence of meaning in life was significantly related to the search for meaning in life (p < 0.05). It suggests that there may be differences in the mechanisms of effects of state boredom on the two dimensions of meaning in life. State boredom at T1 significantly negatively correlated with social support (p < 0.01) and cognitive flexibility (p < 0.01) at T2.As shown in The measurement model included five latent variables . Results showed that the measurement fits well: CFI = 0.95, TLI = 0.94, RMSEA = 0.05, and SRMR = 0.06, indicating that a subsequent structural model analysis could be conducted.p > 0.05, 95% CI = ). The intrinsic resource (cognitive flexibility) could mediate between state boredom and the presence of meaning in life ; the extrinsic resource  could not mediate between state boredom and the presence of meaning in life . The total effect of state boredom on the presence of meaning in life is significant . The results indicated that state boredom played a destructive role in the presence of meaning in life.The constructed structural equation model with grade and gender being controlled as well as the presence of and search for meaning being dependent variables, is shown in p < 0.05, 95% CI = ). The intrinsic resource (cognitive flexibility) could mediate between state boredom and the search for meaning in life ; the extrinsic resource  could play a mediating role between state boredom and the search for meaning in life . However, the total effect of state boredom on the search for meaning in life is not significant . The results indicated that state boredom has no significant role in the search for meaning in life.The direct path between state boredom and the search for meaning in life was significant  and extrinsic resources  between state boredom and the presence of meaning in life and between state boredom and the search for meaning in life, respectively. First, the findings showed that state boredom did not directly affect the presence of meaning in life. Instead, it mediated the presence of meaning in life through cognitive flexibility, i.e., the higher the level of state boredom, the lower the level of cognitive flexibility, and the lower the level of the presence of meaning in life. Although social support did not mediate between state boredom and the presence of meaning in life, the total effect of state boredom was significant, reducing an individual’s level of the presence of meaning in life in the long run. Second, state boredom had a significantly positive direct effect on the search for meaning in life, with cognitive flexibility and social support mediating between state boredom and the search for meaning in life. The higher the level of boredom, the lower the level of cognitive flexibility and social support, and the lower the search for meaning in life. However, the total effect of state boredom on the search for meaning is not significant, indicating that the overall effect of state boredom is largely insignificant.This study added to and complemented the empirical research literature on the relationship between boredom and meaning in life, expanding the scope of related research. Unlike previous studies, which have used meaning in life as an antecedent variable, this study has used state boredom as an antecedent variable to explore the relationship between boredom and meaning in life. Most prior studies have used existentialist theories as a starting point, treating meaning in life as an antecedent variable and boredom as an outcome variable while exploring the relationship between these two variables. Although a study conducted by Fahlman et al. found a negative predictive effect of boredom on meaning in life, it did not separately examine the effect of boredom on the two dimensions of meaning in life . The preThis study also explored the mechanisms through which state boredom acted on two dimensions of meaning in life. First, our findings confirmed that state boredom could act through intrinsic resources (cognitive flexibility) on the presence of meaning in life. In this, our findings were inconsistent with the mediating pathway of the five “A”s in the meaning maintenance model because they did not show that boredom aroused the compensatory effect of cognitive flexibility; instead, boredom actually reduced an individual’s cognitive flexibility. According to prior studies, negative emotional states are negatively associated with an individual’s cognitive flexibility ; this fiAdditionally, our findings confirm that state boredom can act on the search for meaning in life through both intrinsic resources (cognitive flexibility) and extrinsic resources . It is worth noting, however, that the total effect of state boredom on the search for meaning in life was not significant. Although the direct effect of boredom on the search for meaning in life was positively significant, the effects of the two indirect paths from state boredom to the search for meaning in life were negatively significant, and a suppression effect was observed. We, therefore, see the total effect of state boredom on the search for meaning in life as insignificant. This suggests that, although state boredom has the effect of motivating individuals to seek new stimuli and escape boredom , it can In summary, the effect of state boredom on meaning in life revealed that when individuals, especially college students, fall into a state of boredom for a long period of time, boredom diminished their cognitive flexibility and social support. Individuals could not escape this dilemma by relying solely on their own ability to self−regulate. For this reason, high school and university educators should work to enhance the support provided by internal and external resources, for example, by providing college students with methods of alleviating boredom, such as mindfulness training. At the same time, educators should aim to make the learning environment more stimulating and enrich the form and content of teaching and learning, thereby increasing student engagement. Such steps could help students improve their ability to deal with boredom and thus gain more meaningful experiences.However, it should be acknowledged there are shortcomings in this study. Firstly, in terms of the participants, although it was confirmed that boredom effected the meaning of life, the participants were confined to college students in general higher education institutions. Therefore, future studies can explore the relationship between boredom and meaning in life in other groups to advance the representativeness of the study results. Secondly, in terms of research methods, this study mainly used self−reported measures, which can be advanced in further studies by adding behavioral observations or others’ evaluations to examine individuals’ boredom and meaning in life from multiple perspectives. In the process of follow−up measurements, college students also experienced different learning stages at the beginning of the school year versus midterm with various stressful events, which might have an impact on their experience of boredom and meaning in life. Thirdly, in terms of the research contents, this study explored the mechanism of the role of boredom in influencing the meaning in life in terms of intrinsic and extrinsic resources orientation. The role of cognitive flexibility in intrinsic resources and social support in extrinsic resources are examined, while other resource factors still remain to be investigated. This study used a combination of questionnaires as well as a longitudinal design to conduct an exploratory study of the relationship between boredom and meaning in life, taking college students as research participants. This study found that boredom has different effects on the presence of meaning in life and the search of meaning in life. Cognitive flexibility played a mediating role between boredom and the presence of meaning in life, but social support did not. The total effect of boredom on the presence of meaning in life was significant. Cognitive flexibility and social support played a mediating role between boredom and the search for meaning in life, respectively, but the overall effect of boredom on the search for meaning in life was not significant. Findings revealed that individuals’ sense of meaning in life could be enhanced by reducing boredom and increasing cognitive flexibility and social support.


Background: Colorectal cancer (CRC) is the third most common cancer worldwide. Colonoscopy is the gold standard examination that reduces the morbidity and mortality of CRC. Artificial intelligence (AI) could be useful in reducing the errors of the specialist and in drawing attention to the suspicious area. Methods: A prospective single-center randomized controlled study was conducted in an outpatient endoscopy unit with the aim of evaluating the usefulness of AI-assisted colonoscopy in PDR and ADR during the day time. It is important to understand how already available CADe systems improve the detection of polyps and adenomas in order to make a decision about their routine use in practice. In the period from October 2021 to February 2022, 400 examinations (patients) were included in the study. One hundred and ninety-four patients were examined using the ENDO-AID CADe artificial intelligence device (study group), and 206 patients were examined without the artificial intelligence (control group). Results: None of the analyzed indicators (PDR and ADR during morning and afternoon colonoscopies) showed differences between the study and control groups. There was an increase in PDR during afternoon colonoscopies, as well as ADR during morning and afternoon colonoscopies. Conclusions: Based on our results, the use of AI systems in colonoscopies is recommended, especially in circumstances of an increase of examinations. Additional studies with larger groups of patients at night are needed to confirm the already available data. Colorectal cancer (CRC) is the third most common cancer type worldwide ,2. EpideA colonoscopy with the discovery and appropriate removal of adenomatous polyps is considered the gold standard examination that reduces the morbidity and mortality of CRC ,5,6.It is known that colorectal adenocarcinoma mainly develops by the adenoma–carcinoma pathway from benign adenomatous polyps of the colon. This type of cancer mostly develops from the normal, intact colon mucosa, when polyps form on its surface; these are considered as precursor lesions of CRC. Such pathological changes in the colon mucosa are formed under the influence of several factors. These include both genetic and epigenetic processes, resulting in the silencing of several tumor-suppressor genes, activation of oncogenes, and development of chromosomal instability .Usually, CRC is treated surgically and, if necessary, chemotherapy is added to the treatment; however, several studies are available on drug therapy for metastatic CRC. For example, Regorafenib, which is a multi-kinase inhibitor, targets angiogenic, stromal and oncogenic receptor tyrosine kinase (RTK) . SimilarCRC is considered a suitable type of cancer for the applicability of screening, as most polyps detected during colonoscopy (including adenomas and sessile serrated lesions) can be successfully removed endoscopically, thus ensuring CRC prevention .Timely detection and elimination of such polyps by polypectomy protect patients from developing CRC .It is known that for every 1.0% increase in the adenoma detection rate (ADR), interval CRC risks can be reduced by up to 3.0% .It is known that the time of day when a colonoscopy is performed can affect the quality of the examination. This is related to the medical doctor’s fatigue, the number of examinations that he has performed during the day, as well as the medical doctor’s experience. These factors can affect the adenoma detection rate, thus also the therapy tactics, and contribute to the development of interval cancer . Polyp dPolyps and adenomas may not be noticed during colonoscopy due to the anatomy of the colon, the lack of experience and the fatigue of the endoscopist. The number of unnoticed polyps can reach up to 27% for various reasons . The proAs one of the options for increasing PDR and ADR, the presence of a second researcher during the screening colonoscopy could be considered, but such a strategy requires additional staff time resources, which would not be acceptable with the current shortage of medical personnel. Moreover, the research results show that such an approach is not fully effective in the context of ADR .In recent years, multiple systems have been developed for automatic polyp detection assistance ; howeverA system to be used daily during routine examinations should be one that, in terms of efficiency, is comparable to the productivity of a high-quality endoscopist (endoscopist with a high ADR). The system should be able to improve both the endoscopist’s PDR and ADR, regardless of the time of day, the endoscopist’s fatigue, and the number of examinations already performed during the day.Artificial intelligence (AI) could be useful in reducing the possible errors of the colonoscopy specialist, to draw the medical doctor’s attention to the suspicious area of the colon mucosa ,20.AI-powered endoscopic systems have the potential to improve the accuracy and efficiency of diagnostic and therapeutic procedures, such as identifying and classifying polyps and other lesions. Some examples of AI-powered endoscopic systems include those that use computer vision algorithms to analyze images and videos of the gastrointestinal tract to detect and classify lesions, and those that use machine learning algorithms to assist in the interpretation of endoscopic images and videos. Additionally, AI-powered endoscopic systems can also assist in real-time during the procedure, guiding the endoscopist to the targeted area, and providing information about the tissue being examined.The aim of this study was to compare polyp detection rate (PDR) and adenoma detection rate (ADR) in examinations performed with and without AI in the morning and afternoon hours.This was a prospective single center randomized controlled study conducted in an outpatient endoscopy unit at Health Center 4, Riga, Latvia, with the aim of evaluating the usefulness of AI-assisted colonoscopy in PDR and ADR during daytime in the period from October 2021 to February 2022.From October 2021 to February 2022, 837 colonoscopy examinations were performed, and colonoscopies from 400 patients were included in the study. To be eligible for participation in the study, participants had to meet the following inclusion criteria: age of at least 18, and they had to have signed the informed consent form. Informed consent was obtained from all subjects involved in the study. Patients were sent for a colonoscopy examination by the family doctor; therefore the preparation schemes were different for each individual.In turn, the exclusion criteria were: 1, a previously undergone colonoscopy examination; 2, inflammatory bowel diseases; 3, hereditary polyposis syndrome; 4, known CRC; 5, previously undergone colorectal surgery; 6, contraindications for polypectomy; 7, bad bowel preparation on a Boston-Bowel-Preparation-Scale (BBPS) of 0 to 1 in any of the three bowel segments; 8, patients with standard contraindications to colonoscopy such as acute diverticulitis and known or suspected perforation. Incomplete colonoscopies  were excluded from the primary analysis.All eligible patients were randomized for ENDO-AID CADe AI + (study group) and ENDO-AID CADe AI—(control group). Prior to the colonoscopy procedures, patients were divided into groups. Patients were blinded to the group allocation results.Colonoscopy examinations were performed with the Olympus Evis X1 video endoscopy system and the ENDO-AID CADe AI device.The examinations were performed by two endoscopists, who perform an average of 2000 colonoscopy examinations per year; one endoscopist has more than 15 years of experience, and the other one has eight years.A total of 400 patients were included in the study and randomly divided into two groups. One hundred and ninety-four patients were examined using the ENDO-AID CADe AI device (study group) and 206 patients were examined without the ENDO-AID CADe AI device (control group).The ENDO-AID CADe AI device system works in real-time; the CADe AI was used during the evacuation of the instrument from the caecum, marking the found polyp on the main monitor with a green outline , drawingDue to patient data security concerns, endoscopic images were obtained through Olympus.It was assumed that morning examinations are carried out between 8.00 and 13.00, and afternoon examinations are between 13.00 and 18.30.Colonoscopy examinations were performed with the Olympus EVIS V1 video endoscopy system and the ENDO-AID CADe artificial intelligence device. All colonoscopy examinations were performed under anesthesiologist supervision under short-term intravenous isolated propofol sedation. The dose of medicine was determined by the anesthesiologist.Bowel cleanliness was assessed by an endoscopist using the BPPS scale. Six subjects were excluded from the study due to poor bowel preparation (0–1 in any of the three bowel sections).The time of evacuation of the instrument from the cecum for each performed colonoscopy was not less than 7 min and was monitored by the endoscopist’s assistant.Any detected polyp was described in the colonoscopy report according to the Paris  and NICEThe biopsied or ablated polyp was sent for morphological examination. If a polyp was found, at least two pieces from the lesion were taken before polypectomy; in the event that the removed polyp disappeared in the colon fluid, the tissue was available for morphological evaluation.The examination begins by inspecting the anal canal and the rectum, performing an examination in retroversion to evaluate the mucosa above the “Z” line and evaluate the condition of internal hemorrhoidal nodes. When the mucosa of the anal canal is viewed in retroversion, the endoscope is advanced proximally into the sigmoid, descending, transverse, and ascending the colon until the dome of the cecum is reached. By moving the endoscope proximally into the colon, the residual contents are evacuated from the colon. A mandatory requirement for a high-quality colonoscopy examination is photo-documentation of the opening of the appendix. If technically possible, a retroversion examination was also performed in the cecum.The right side of the colon was examined twice, returning distally from the cecum to the transverse colon, inspecting the mucosa in NBI mode, and again proximal to the cecum.In order to detect flat polyps of the right colon, after evacuating the instrument from the caecum for the second time, staining of the mucosa with methylene blue solution was performed.Further inspection of the mucosa of the colon was performed by gradually evacuating the endoscope, also carefully inspecting the mucosa behind the folds.All removed polyps and specimens from biopsied lesions were transmitted to the Academic Histology laboratory  for morphological diagnostics. All samples were analyzed by expert pathologists. All removed and biopsied lesions were analyzed and characterized according to the World Health Organization criteria, depending on morphological characteristics . All lesp-value of less than 0.05 was considered to signify statistical significance. Statistical analysis was performed using IBM SPSS (version 20) [For baseline sociodemographic and clinical characteristics and colonoscopy quality parameters, comparison between the two groups was performed using the Mann-Whitney-U-test for continuous variables and the Chi-square test for categorical variables. A sion 20) .During the study period, two gastroenterologists performed and analyzed 400 colonoscopies. Participant age ranged from 18–84 years. Our results showed that there are no statistical differences regarding age and gender between the two groups . First doctor (DR1) performed 98 non-AI-assisted colonoscopies (42 in the morning and 56 in the afternoon) and 91 AI-assisted colonoscopies (43 in the morning and 48 in the afternoon); while the second doctor (DR2) performed 108 non-AI-assisted colonoscopies (62 in the morning and 46 in the afternoon) and 103 AI-assisted colonoscopies (57 in the morning and 46 in the afternoon). In total, the study group had 194 colonoscopies, while the control group had 206 colonoscopies .p = 0.939), while in the afternoon PDR without AI was 28.50% and with AI 37.50% (p = 0.333), which indicates that adding AI during afternoon colonoscopies for (DR1) improves PDR, but not statistically significantly . Similarly to DR 1, PDR in morning colonoscopies for DR 2 without AI was also higher, but not statistically significantly; however, afternoon PDR without AI was 39.10%, while with AI assistance it increased to 50% (p = 0.256), which indicates that PDR increases significantly when using AI, but not statistically significantly , which confirms the beneficial effects of AI in increasing ADR for this doctor also during morning colonoscopies, but not statistically significantly , indicating that adding AI during afternoon colonoscopies also improves ADR for DR 1, but not statistically significantly , while in the afternoon ADR without AI was 21.70%. Using the AI function, it increased to 34.8% (p = 0.165), which indicates that the use of AI during afternoon colonoscopies significantly improves ADR for DR 2, but not statistically significantly  , CRC is Considering that the realization of the adenoma-carcinoma pathway requires a relatively long time, as well as the fact that early-stage CRC remains mostly asymptomatic, it is possible to treat it preventively with the help of polypectomies and to apply highly effective treatment in the early stages of an already known oncological disease. Current knowledge about the pathogenesis of CRC and the natural course of the disease suggests that CRC and precancerous changes in the bowel are suitable conditions for screening .To ensure the highest possible quality of the colonoscopy examination, the preparation of the colon before the examination with a split regimen is still relevant. Sufficient time, not less than 6 min, but preferably at least 8 min, should also be devoted to the evacuation of the instrument from the caecum. If retroflection on the right side of the colon is not possible, then this area should be examined twice—going from the caecum to the transversum, then again to the caecum, and then evacuating the instrument completely, devoting time to other segments of the colon as well. This approach improves ADR scores .In recent years, the method of colonoscopy has progressed significantly. Endoscopists can improve colonoscopy quality and ADR by using specific tools during routine examinations—for example, various endo cuffs for expanding the field of view of the mucosa and straightening folds of the colon, digital chromoendoscopy options for more successful detection of flat polyps and determination of borders, so that the result of a polypectomy achieves maximum value. Full spectrum colonoscopy options are also available, as are devices that assist retrograde examination during a colonoscopy .All the previously described methods allow the colonoscopy examination to become as effective as possible, thus contributing to the 5-year survival rate in CRC .Even using all the methods described above to improve PDR and ADR, some polyps remain undetected and unremoved. More often, undetected polyps hide behind the folds of the bowel and are not in the field of view of the endoscopist. However, other data reveal that in some cases, especially if the polyp is flat or serrated, it can go unnoticed even when it lies in the field of view of the endoscopist .Such errors can be observed when the colonoscopy is performed by an endoscopist without sufficient experience and qualifications, as well as when the endoscopist’s attention is diverted from the screen for unclear reasons .Similarly, errors during colonoscopy should be discussed in the context of the researcher’s fatigue, burnout, and the time of the working day when the examination is performed.To contribute to the further reduction of CRC incidence and mortality, the implementation of an automatic polyp detection system in daily practice should be considered. However, it should have very high sensitivity and specificity in real time to maintain a sufficiently high ADR and avoid false positives .The results of research conducted in 2019 showed a significant increase in ADR, PDR, and mean number of polyps and adenomas per colonoscopy in the CADe group compared to the control group. However, it should be recognized that this increase was mainly due to an increase in the number of adenomas smaller than 5 mm. It is known that these diminutive lesions are often the most difficult to find endoscopically. It is also known that small adenomas are associated with a lower risk of developing a malignant tumor. Therefore, one would think that such findings could lead to additional unnecessary polypectomies and an increased workload. However, finding and eliminating any adenoma during colonoscopy could reduce the risks of developing CRC.It should be noted that polyps that are not in the doctor’s field of view during the colonoscopy are still a major drawback of the current CADe system. Additional technologies that would able to deal with the detection of polyps behind the folds of the colon, in hard-to-see areas of the mucosa, are needed .The functioning of the brain and the subsequent provision of all body functions is still not fully understood. Currently, people mainly use their visual recognition functions in the context of endoscopic image perception, but this type of image perception has its limitations .So far, data have been obtained that the human brain and its vision and image recognition functions are not fully capable of processing when compared to computer image perception capabilities . In addiArtificial intelligence (AI) is currently an assistive device in a constant learning process, which provides solutions that are tied to human intelligence by storing and processing the acquired data. Basically, types of artificial intelligence are designed to analyze visual images; however, there are also developments that recognize and process data related to audio, voice and various languages .Currently available methods mainly use Deep Neural Networks (DNN) and Convolutional Neural Networks (CNN). These networks have the ability to independently derive data from, for example, available healthcare data and thereby augment their work capabilities and functions .It is in the context of colonoscopies that two important roles of artificial intelligence in maintaining the quality of the examination have crystallized. The first is the detection of polyps during the examination (CADe), when the device informs the endoscopist about the presence of a mucosal lesion with both an audible and a visual signal, encircling the suspicious mucosal area with a green border. The use of this function would have the potential to contribute to an increase in ADRs for each endoscopist, and it is likely that the CADe function would make the greatest contribution during afternoon examinations.The second feature of the artificial intelligence device that could be used during routine examinations is polyp characterization (CADx). The use of this function would allow the endoscopist to improve the accuracy of the optical diagnosis and to navigate the morphological structures of a particular polyp already during the examination, thus predicting whether the detected polyp is adenomatous or not. This would allow the examiner to avoid performing unnecessary non-adenomatous polypectomies, thereby avoiding the development of additional complications, as well as saving significant amounts of the health care budget. It is known that avoiding the removal of unnecessary non-adenomatous masses could save up to $33 million annually in the US .The results of our study indicate that in afternoon colonoscopies, both PDR and ADR are lower for both endoscopists compared to morning colonoscopies. Most likely, this finding could be related to the doctor’s fatigue and reduced ability to concentrate in the second half of the working day.It is known that having long working hours and performing many examinations during the day can reduce the cognitive abilities of the doctor and contribute to the frequency of the development of medical errors .The results of our study could also be applied to endoscopic examinations; that is, the quality of performed colonoscopies could also be related to the doctor’s fatigue during the day.Scientists have tried to measure the degree of fatigue in the context of colonoscopy examinations by using the time spent at work  but alsoOverwork of doctors has been a hot topic in recent years .It is known that, for example, the demand for colonoscopy examinations has grown significantly in China, and thus the fatigue of endoscopists due to work overload is also increasing .Several studies have not shown a negative effect of a higher number of examinations on ADRs ,42. HoweAvailable research  also indWhen using AI-assisted colonoscopies in the morning examinations for both doctors, the PDR was lower than in colonoscopies without AI. However, this does not apply to ADR morning colonoscopies. These results could indicate higher concentration abilities of doctors in the morning.Considering that the development of CRC is mainly associated directly with adenomatous polyps, ADR is clearly a more important indicator, and it increases in both morning and afternoon colonoscopy examinations for both doctors, but not statistically significantly.Future studies could consider analyzing the degree of physician fatigue using other objective, independent tools, which could provide more reliable information on the association of endoscopist fatigue with the reduction of ADRs during the day.Considering that there are data showing that an additional expert participating in the endoscopy procedure improves both PDR and ADR , the daiData from other studies on ADR exposure during weekday afternoons are also available .However, there are also reports that colonoscopies performed in the afternoon were of better quality, specifically in the context of ADR . It is tThe limitations of our work include the fact that the study was conducted in one center, and the colonoscopies were performed by only two endoscopists. It should also be considered that if the number of patients included in the study were larger, statistically reliable differences in the results between the study and control groups could be expected.In addition to the already existing information, data on colonoscope evacuation time, which is also known to be a significant factor in the raising of ADR, would probably be useful.Based on the results of our study, the use of AI systems in routine screening colonoscopies is considered justified and recommended, especially in circumstances where there is an increase in the number of diagnostic examinations. In the future, however, attention should be paid to the problem of the lack of endoscopists, the workload of doctors, and whether colonoscopies are performed within endoscopy departments’ quality requirements. Additional studies with larger groups of patients during the working day are needed to confirm the already available data.The results of this study indicate that, although there is no statistically significant difference between groups, the real-time CADe-assisted system increases the PDR during afternoon colonoscopies for both physicians, as well as the ADR during both morning and afternoon colonoscopies for both physicians. Thus, CADe-assisted systems should be considered for use during colonoscopies in routine work.