Understanding the cross-cultural adaptation of students studying in foreign countries by exploring acculturative stress factors is crucial to ensure the smooth academic performance of the students and, in turn, to enhance the global reputation of their universities. Therefore, it is an area of interest for the authorities (Ministry) and the corresponding management of universities. Using a random sample of 138 international students in China, descriptive and logistic regressions were conducted to assess the levels and influence of acculturative stress factors on cross-cultural adaptation, specifically on international students’ sense of security and belonging during the COVID-19 pandemic outbreak. The results revealed that students were most concerned about homesickness, which obtained the highest mean score. The regression results indicated that the perception of fear and discrimination significantly impacted international students’ sense of security. The perception of fear, guilt, and how long the student stayed in China also significantly affected the sense of belonging. We argue that the reflections provided herein are essential for universities to improve how they manage and handle international students to mitigate the effects of acculturative stress, particularly when additional stressful conditions are present, such as the COVID-19 pandemic. The study of acculturation has gone through several stages of evolution. In particular, dimensions evolved from Berry’s two-dimensional model addressed the degrees of orientation on majority and cultural heritage ,2,3 to eAs one of the main groups of sojourners, international students attending higher education outside their native countries are more likely to struggle with acculturative stress due to the difficulties inherent in adjusting to their living conditions in a foreign country, which has attracted continuous scholarly attention. With limited exposure to the host country’s culture and lifestyle, university students are prone to experience higher levels of stress and depression ,15,16. TInternational higher education in China has been lucrative to many universities, with international education growing in size in our increasingly connected world. According to the statistics released by China’s Ministry of Education, 397,635 international students from 202 countries and regions had studied in 811 higher education institutions and scientific research in 31 provinces by 2019. These students created a complex and culturally diversified society by providing varied cultural values, mental outlooks, and social norms. Research on acculturative stress in international students in China is more representative and useful since the country welcomes students from both developed countries and developing countries . PreviouThe COVID-19 pandemic has brought questions about individuals’ psychosocial well-being into focus. Studies have documented increases in depression , anxietySimilarly, results from undergraduate and postgraduate students from Malaysia show that instructor performance, course evaluation, student characteristics, and system quality are four factors that influence students’ satisfaction with e-learning . The eviThis will be the case until the COVID-19 outbreak slows down; however, there are no signs of it happening soon as more waves and cases of Virus Mutations Variants rise in different parts of China and the world . The unique context of international student groups in foreign countries during the pandemic is an interesting area of research to investigate how acculturative stress affects emotional perception. Therefore, this study explores acculturative stress perception and the relationship between acculturative stress, and the sense of security and belonging the international students in China feel. We hope to provide suggestions to institutions and universities to improve their management of international students.Although early studies on cross-cultural adaptation mainly focused on using qualitative methods to determine the influencing factors of acculturative stress ,44,45, iThis study utilized a web-based, semi-structured survey questionnaire to collect information regarding cross-cultural adaptation before the outbreak of COVID-19, changes since the outbreak and to measure acculturative stress. The respondents were informed that participation was voluntary and that all collected information would be kept confidential and used for research purposes only.The survey began by qualifying the respondents by determining if the respondent had the time to complete the survey and if they were in China during the COVID-19 pandemic outbreak from January 2020 to March 2020. The questionnaire included four parts: (1) conventional questions regarding the adaptation of international students, including how long they had been in China, their level of proficiency in Chinese, their rationale for studying in China, and their satisfaction with their institution; (2) perceptions and adaptation during the COVID-19 epidemic period; (3) acculturative stress in the four dimensions of homesickness, fear, guilt, and discrimination during the pandemic period; and (4) demographic information including gender, age, marital status, course, scholarship type, and country of origin. Based on the logistic regression model, this study analyzed the relationship between the two binary variables and the other factors.The survey started with the international students of Nanjing Agricultural University and adopted the snowball sampling method to distribute the questionnaire widely through WeChat groups of international students and on other social network applications. International students completely filled a total of 150 questionnaires with a valid sample of 138 responses that passed the screening test, which met the sample size requirements of logistic regression. Excluding a very small number of samples from the three continents of America, Europe, and Oceania, this study focused on international students from Asia and Africa, with a final valid sample size of 133. The data preparation process included questionnaire checking, editing, coding, transcribing, cleaning the data, and selecting a data analysis strategy. The research used STATA 16.0 software for the analysis.We used a binary logistic regression model to analyze two psychological feelings that international students may have experienced during the pandemic period in China. Empirically, the model is expressed as follows:p: the probability of the occurrence of the dependent variable;n: independent variables;X1 Security = F2 Prefer back = FSpecifically, the examined logistic regression model could be defined as:1, which equaled one if the respondents chose Yes as the answer and zero otherwise. In addition, we also asked the respondents whether they would prefer to be back at their home to investigate their sense of belonging, denoted as Y2, which equaled one if the respondents chose Yes as the answer and zero otherwise.For the dependent variable, we first investigated whether the respondents thought they were safe in China and understood this as the sense of security, denoted as YFor the explanatory variables, we used acculturative stress levels. Each dimension of the acculturative stress was further extended to encompass several particular items—i.e., subscales—which were adjusted to produce expressions that could better correspond to the student’s current situation based on the Acculturative Stress Scale for International Students developed by Sandhu and Asrabadi : homesicIn Additionally, with the epidemic situation overseas becoming more serious, families may not have been able to help. Compulsory blockade measures also made it more difficult for international students to earn income from part-time jobs. For multiple reasons, more attention was paid to the financial aspect of the fear item. Regarding guilt, the highest mean was obtained by the following item: I feel guilty about leaving my family and friends behind. Adjusting to the host culture is generally conceived as infidelity and a betrayal of their own culture. The need for international students to adjust to another culture seems insincere to their culture and people, which may cause a sense of guilt. Unexpectedly, international students were least concerned about discrimination during the COVID-19 pandemic. This is contrary to the results of many studies ,50, indi1 had a mean of 0.89, indicating that approximately 89% of international students felt safe in China during the outbreak. Similarly, it could be seen from the mean of Y2 that only approximately 36% of international students would have preferred to go back to their home country during the pandemic. The two binary variables together constituted the dependent variable of this study. According to the simple comparison of the means of acculturative stress, perceived homesickness obtained the highest score, with a mean of 2.98, indicating that many international students suffered from homesickness. All four means of the acculturative stress factors were under 3, showing that stress levels were low. The mean value of Howlong was 3.36, indicating that most international students had been in China for at least 1 year.p-values are displayed in The regression results with each variable’s estimated coefficients and Drawing insights from the research on the acculturation of immigrants and sojourners, the main purpose of the present study was to investigate the acculturative stress levels of international students who were in China during the outbreak of the COVID-19 pandemic and the relationship between acculturative stress and their sense of security and belonging. The findings indicated that international students did experience the stress of cultural adaptability to some extent, and the mean of homesickness was the highest. Furthermore, we found that the perception of fear was positively related to the sense of security, while the coefficient of the perception of discrimination was negative and statistically significant. At the same time, the results of the other analyses on the sense of belonging were different: the length of time that international students had been in China was negatively associated with the sense of belonging, while the perception of guilt was positively associated with it.This study found that international students often struggled with immigration and visa extension issues due to traveling restrictions . The panMany studies have focused on the relationship between acculturative stress and emotional stress. International students were reported to have a relatively high rate of depression compared to normal Chinese people , which wWith the normalization of COVID-19, the post-epidemic era has put forward more empirical requirements for managing international students. It is necessary to strengthen the education of international students in China in daily health and safety measures and to improve their health awareness. Using our findings as a starting point, we should pay attention to the emotional state of international students in China and provide cross-cultural adaptation counseling services. If the acculturative stresses are not resolved for a long time, their study, work, and life will be affected. Therefore, a special counseling office can be set up to hire counselors with relevant professional knowledge and experience to provide “one-to-one” or “one-to-many” services for foreign students in China. We can also invite psychological experts to hold lectures on mental health in colleges and universities.In addition, awareness of the social environment’s safety and stability helps attract international students to study in China, highlighting the importance of propaganda and ideological work. As the “home” of international students in China, colleges and universities should establish an effective working mechanism to convey accurate and useful information in time. At the same time, we should pay close attention to the negative information that international students easily misunderstand, take the initiative to understand the situation from their point of view and provide them with both sociological and psychological support services to calm their emotions and control their thoughts.Moreover, strengthening these students’ language and cultural training can improve their environmental adaptability in China. Language adaptability is closely related to an individual’s sense of belonging and security in a foreign environment. Colleges and universities should improve international students’ ability to read, speak, and write Chinese in various ways to enhance communication skills by opening Chinese language teaching courses and organizing interesting activities related to Chinese culture.Finally, to reduce the effects of acculturative stress on international students, there is a need to improve the support and counseling services available to enhance their sense of belonging and safety, especially during difficult situations such as the one brought about by the COVID-19 pandemic. In , the autThis study has some limitations. First, the sample size was relatively small and not representative of all the international students in China. Caution should be exercised in generalizing the findings to a larger population. Therefore, further research could broaden the scope of this study by recruiting large and representative samples. Secondly, the quantitative study relied on self-reported survey responses, which can be influenced by a social desirability bias. Thirdly, this study used only two perceptual, cognitive variables—binary variables—to investigate and measure the psychological conditions of international students, which might not be sufficient. Thus, future research should enrich the expression of relevant psychological conditions to make the results more accurate and focus more on exploring the impact mechanisms of acculturation on international students’ more diversified perceptions to permit causal inferences.With the acceleration of the process of economic globalization and the increasing scale of international education, China, as an important host country in Asia, has attracted many international students from all around the world, which puts forward higher requirements for the shaping of a good learning environment and the management of international students. From the research results, the acculturative stress levels of international students in China were relatively low, showing a high average satisfaction. Meanwhile, the relationship between psychological feelings and acculturative stress gave university administrators and policymakers new ideas to improve their management levels. The results are also of value for researchers interested in exploring acculturation among international students in different contexts of higher education.


Neuro-developmental delay (NDD) is when a child's reflexes and nervous system are underdeveloped or immature at a given stage of child development. Neurodevelopmental delays account for delayed skill development surrounding speech, social, emotional, behavioral, motor, and cognitive delays. NDD might affect the child's psychological and physical well-being, resulting in chronic disease and disabilities throughout adulthood. This review sought to investigate the implication of early diagnosis and intervention of NDD in children. In this regard, this research opted for a systematic meta-analysis that used keywords and Boolean operators to search through main databases, including the Web of Science, JStor, PsychINFO, Science Direct, Cochrane, Scopus, and ASSIA. The result identified that telehealth interventions improved the management of NDD in children. Also, the Early Start Denver Model (ESDM) model was determined to improve the quality of life for NDD children. Another model was LEAP (Learning Experience and Alternative Program for Preschoolers and Their Parents) and Leap , which improved behavioral, education, and social interventions in NDD children. The study identified that technology could revolutionize NDD interventions in children, possibly improving the quality of life. The parent-children relationship was shown to enhance the management of this condition; thus, it is recommended as one of the best ways to intervene in the management of NDD. Most importantly, the integration of machine learning algorithms and technology can create models; while this may not be significant in the treatment of childhood NDD but instead might be ideal in improving the quality of life for NDD children. Moreover, their social and communication skills along with academic achievements will improve. The study proposes further research in order to understand the different types of NDDs and their intervention strategies to help the researchers identify the most accurate models to improve the conditions and support the parents and guardians in the management. Development delay (DD) refers to a child’s delayed pace of skills development compared to others within the age group . GeneralNDD potentially impairs the child’s psychological and physical health, and its effects can carry on to adulthood, creating chronic disabilities . The maiThe NDD management process incorporates the role of many individuals in the child’s life . The parSearch strategyThis review applied a literature search procedure to identify credible sources about the diagnosis and intervention of NDD in children. The aim was to examine the implications of the diagnosis and intervention of NDD in children’s development and parent/guardian interactions. The review applied inclusion and exclusion criteria to determine the most accurate sources reflecting the research aims and objectives . In thisThe keywords were applied in the following databases to help identify accurate and verifiable journal articles to create table characteristics and substantiate the findings . The datData extractionData extraction involved transcribing information from the sources to qualify for the review. Reviewing data before extraction aimed to increase accuracy and reduce bias. This research conducted a robust data extraction process involving much paper, including RevMan 5.4 software . This research investigated the implication of early diagnosis and intervention in managing NDD in children. Therefore, data extraction applied the keywords and the Boolean operators to analyze the participant numbers and characteristics. In this respect, the intervention and the control group participants were recorded for the randomized clinical trials to improve the analysis. In addition, the extraction process captured the research objective, the comparison, and the outcome, which also included the comments on the implications of this study.Quality assessmentQuality was of the essence in this review, which entailed systematically and carefully examining the research to identify its relevance, value, and trustworthiness . The folAnalysisThe included data were analyzed using RevMan 5.4 software, where risk difference, a test of heterogeneity, forest plot, and funnel plot is discussed in length concerning the table characteristics. PRISMA flowchartPRISMA flowchart is used in systematic meta-analysis reviews to support the transparent and easy-to-understand search strategy . The incStudy characteristicsThe characteristics in Table Meta-analysisThe following section provides a meta-analysis to establish the implications of early diagnosis and intervention in managing neurodevelopmental delays in children. The subsequent studies were the most influential in showing the results during the intervention and the outcome. Forest plotThe forest plot as shown in Figure Risk differenceThe diamond box shows the averaged combination of studies within the 95% confidence interval, which means that the studies fall within the vertical line and, thus, no statistical difference between the intervention and the control group, although Table Figure Funnel plotThe funnel in meta-analysis is used in estimating the risk of publication bias within the study . The scaRisk of biasAnother critical measure is the risk of bias in randomized controlled trials . The risDiscussionThis study aimed to investigate the implications of early diagnosis and treatment on managing NDD in children. A study was conducted to compare standard clinical treatment with dialogical family guidance in diagnosing and managing NDD . The effTechnological advancement has revolutionized different sectors of the globe, and healthcare is one of the most affected by the technologies. The rise of pandemics and instabilities surrounding the health sector has strengthened the use and adoption of technology to address prevalent and emerging conditions. As a result, this study witnessed telehealth’s help in improving and managing NDD conditions. For instance, a recent review showed effective improvement in ND monitoring through telehealth . MoreoveNeurodevelopmental delays are among the most challenging conditions affecting many children globally. The study has shown that delays can be managed using assistive models and technology and that none of the applications can effectively reverse the conditions. Therefore, future research on neurodevelopmental delays can help inform the field of medicine on interventions parents can make to prevent future neurodevelopment conditions. The use of screening tools in the population requires careful complementary and multidisciplinary clinical evaluation to enable early detection and intervention to optimize normal functioning.The current systematic review offers a narrative summary of the available evidence in this area. Studies have shown that early diagnosis and intervention of neurodevelopmental delays in children can have significant implications for their long-term outcomes. Early diagnosis and intervention through methods such as developmental screening and early intervention services can help children receive the support and therapies needed to improve their outcomes. The study has shown that the delays can be improved using assistive models and technology, but none of the applications can effectively fully reverse the conditions.


Background. Physical activity is a potential parameter to assess the severity or prognosis of lung disease. However, the differences in physical activity between healthy individuals and patients with lung disease remain unclear. Methods. The analyses in this report are a combined analysis of four cohorts, including a healthy control cohort, in a prospective study designed to evaluate wearable device-estimated physical activity in three cohorts: the lung cancer cohort, the interstitial pneumonia cohort, and the COPD cohort (UMIN000047834). In this report, physical activity in the lung disease cohort was compared with that in the healthy cohort. Subgroup analyses were performed based on age, sex, duration of wearable device use, and lung disease subtype. Results. A total of 238 cases were analyzed, including 216 patients with lung disease and 22 healthy cases. Distance walked and number of steps were significantly lower in the patient group compared to the healthy control group. ROC analysis for the diagnostic value of lung disease by mean distance walked and mean number of steps showed AUC of 0.764  and 0.822 , respectively. There was a significant difference in physical activity by age, but not by gender nor by duration based on the threshold of 7 days of wearing the device. Conclusions. Lung disease decreases physical activity compared to healthy subjects, and aging may bias the estimation of physical activity. The distance walked or number of steps is recommended as a measure of physical activity, with a period of approximately one week and adjusted for age for future investigation. Physical activity is an important parameter to evaluate an individual’s general health status. Some reports have indicated the importance of physical activity in patients with lung diseases, especially COPD ,2,3,4,5.The results of this report are from exploratory analysis of the main study, which was designed to assess disease severity in three disease cohorts using a wearable device (UMIN000047834), and the aim of this analysis was to compare physical activity between healthy cases and patients with lung disease.The main study is a prospective observational study at a single-institution, and the inclusion criteria included (1) patients diagnosed with advanced lung cancer, interstitial pneumonia or COPD, and (2) outpatients for treatment or observation at a single institution. Patients with interstitial pneumonia were enrolled regardless of the type of interstitial pneumonia, from interstitial pulmonary fibrosis to collagen-disease-related interstitial pneumonia, and patients with COPD were diagnosed in clinical practice based on pulmonary function testing. The exclusion criteria included (1) patients with unstable gait due to lower limb disease. Healthy controls without lung disease were recruited from the medical staff. The healthy group was enrolled as an exploratory group, separate from the other three cohorts in this analysis, for the purpose of exploratory validation as an exploratory study group.We used the wearable device, amue link , which is equipped with a GPS system that can monitor real time movements without any other device, such as smart phone. To estimate the distance walked, this device adopts a unique algorithm to distinguish the method of travel, such as by vehicle or on foot. This device is also expected to calculate the actual walked distance. In this study, this device measured a total of 6 physical activity values as follows: sum and mean of (1) METS, (2) distance walked, and (3) number of steps. All patients were instructed to wear the wearable device on their wrist, following the company’s recommendation that the device on the wrist can adequately measure distance walked and steps taken. The duration of measurement was from wake-up to bedtime, with the exception of special situations such as bath time. All participants were instructed to wear the fitness tracker device for up to 14 days. The data were sent to the data center via the Internet and stored in real time with the reservation of privacy.The wearable device measurements were compared between the healthy and lung disease groups, and we estimated the AUC to discriminate the healthy from lung disease groups by physical activity in the ROC analysis. Although the aim was not to discriminate disease by physical activity, we assumed that the high accuracy of discriminating disease by physical activity, represented by a higher AUC, means that physical activity is associated with the presence or absence of respiratory disease. Comparisons of physical activity were made between patients with lung disease and healthy controls, and between the different types of lung disease. We hypothesized that the factors of age, sex, and the duration the device is worn may bias the estimation of physical activity and subgroup analyses performed based on these factors.As described above, physical activity, as continuous values, were compared between patients with lung disease and healthy controls, and between different types of lung disease. The physical activity values were compared between the healthy group and lung disease using the Kruskal–Wallis test, and the multiple comparison tests across groups were performed using the Dunn–Bonferroni method. Statistical comparisons of the continuous values were tested with 0.05 representing a significant difference. ROC analyses were performed, and the 95% confidential intervals were calculated by SPSS version 28.0. As this is an exploratory study, sample size calculations were not performed. We obtained written informed consent from all enrolled cases and followed them prospectively in this study. The study was conducted in accordance with the principles of the Declaration of Helsinki.p < 0.001). The failure rate for physical activity assessment in the whole population is 5.5%. The physical activities measured by the wearable device showed a stronger correlation with each other, except for METS.A total of 238 cases were analyzed, including 22 healthy cases, 119 patients with lung cancer, 51 patients with interstitial pneumonia, and 46 patients with COPD . WrittenNonparametric test was performed for the measured value estimated by the wearable device between groups. As a result, the distance walked and the number of steps walked were candidate parameters as physical activities for diagnosis of lung disease. The physical activities in the patient group were statistically significantly lower compared with the healthy control group, with p value of 0.05 or less for the sum of METS, sum and mean of the distance walked, and sum and mean of the number of steps walked . ROC anaThere was significant difference in physical activity in except with METS between healthy control group and each lung disease group . For allSubgroup analysis by age showed that patients aged 75 years or older had less physical activity in all disease subtypes, and distance and steps walked were significantly different between younger and older patients . There wThe analyses in this study indicated the following three important clinical questions: (1) which measurement among wearable device is appropriate to assess physical activity, (2) which factor should be adjusted, and (3) how long of a term is required to estimate physical activity? Our data showed a significant difference in physical activity between the patients with lung disease and healthy cases. In previous reports, Fabio Pitta et al. reported that patients with COPD were inactive compared with healthy elderly patients , and BenA greater difference was found in the lung cancer group followed by interstitial pneumonia group among three cohort, from which we expect that an measurement of physical activity will be of clinical significance, especially in the two pulmonary diseases. Sofie Breuls et al. showed that the patients with interstitial pneumonia were less active compared with the patients with COPD in their propensity score analysis. This study used the daily steps to evaluate the physical activity . As we cThere was a significant difference in the distance walked and the number of steps walked between each disease cohort and the healthy group, and these two measurements seemed to be the candidate parameters of physical activities in our study. In our study, METS is not a better candidate to evaluate the physical activity, however, the formula for estimating METS is specified for the device, therefore, the results in our study do not mean that METS is not completely excluded as a parameter of physical activity when using the other device. The previous study, as mentioned above, assessed physical activity using steps, and our data also showed that the number of steps walked was a better predictor of lower physical activity due to lung disease. Meanwhile, our data showed that mean distance walked also had potential as a candidate measure of physical activity in the lung disease population. In particular, this device, amue link, was designed to calculate the distance by using a unique algorithm to identify movement on foot, which may be the reason why the distance walked was a better predictor of physical activity in this study.The subgroup analyses based on age, sex, or duration of device wear showed that age may be a bias for physical activity, suggesting that these measured activities require adjustment based on age but not sex. Therefore, we performed an additional subgroup analysis of cases of individuals aged 69 or younger, in which the difference in physical activity between patients and healthy controls has remained consistent, and the AUC in this subgroup is 0.732 , which is not as inferior compared to that in all cases ). The decrease in physical activity with age has been reported in the previous reports ,11, whicThis study has some limitations. Failure to measure physical activity was calculated to occur at 5.5%, which may bias the analysis. There are some outliers in the data, which are assumed to be caused by errors with the device in estimating physical activity. The analyses were not prospectively designed, and the sample size of the healthy control group is small, although the sample size of the pulmonary disease group is sufficiently large, which may be a limitation. In addition, it is inevitable that the variation across disease will be a limitation of the analysis.The lung disease decreased the physical activity compared with healthy cases in our study. Considering the fact that the difference in physical activity between healthy case and lung disease patients, the physical activity had potential to be reflected on the severity of the disease. We are preparing to report the association between the lung disease severity and physical activity in the next report of this study, which is the primary endpoint of the main study. Our data showed that age should be adjusted for when assessing physical activity, but the reduced physical activity in patients with lung disease was found even in the younger population. The subtype of lung disease seems to be associated with reduced physical activity. The number of steps walked was a good parameter of physical activity in our study, as shown in the previous study indicated. In addition, the distance walked was also a good indicator of daily activity when calculated by the device used in our study. We recommend using the distance or steps walked as a measure of physical activity with the period of about one week while adjusting for age for future investigations.


Biomedical experts are facing challenges in keeping up with the vast amount of biomedical knowledge published daily. With millions of citations added to databases like MEDLINE/PubMed each year, efficiently accessing relevant information becomes crucial. Traditional term-based searches may lead to irrelevant or missed documents due to homonyms, synonyms, abbreviations, or term mismatch. To address this, semantic search approaches employing predefined concepts with associated synonyms and relations have been used to expand query terms and improve information retrieval. The National Library of Medicine (NLM) plays a significant role in this area, indexing citations in the MEDLINE database with topic descriptors from the Medical Subject Headings (MeSH) thesaurus, enabling advanced semantic search strategies to retrieve relevant citations, despite synonymy, and polysemy of biomedical terms. Over time, advancements in semantic indexing have been made, with Machine Learning facilitating the transition from manual to automatic semantic indexing in the biomedical literature. The paper highlights the journey of this transition, starting with manual semantic indexing and the initial efforts toward automatic indexing. The BioASQ challenge has served as a catalyst in revolutionizing the domain of semantic indexing, further pushing the boundaries of efficient knowledge retrieval in the biomedical field. A vast amount of biomedical knowledge is published every day in the literature and in structured resources like biomedical ontologies. It is a challenge for biomedical experts to identify and process all the available knowledge. For example, 1.3 million citations were added to MEDLINE/PubMed during 2018,During the last years important advancements have been achieved in the area of semantic indexing. In particular, the use of Machine Learning has helped to move gradually from manual to automatic semantic indexing in the biomedical literature. Since 2012, BioASQ has initiated a shared task for semantic indexing, allowing leading teams in the field to advance their approaches and improve significantly their performance. This performance improvement has led to the adoption of fully automated indexing by NLM since 2022. In this paper, the road of this transition is presented: how manual semantic indexing has started, the first efforts toward automatic indexing, and how the BioASQ challenge has helped in the revolution of the domain.A History of the National Library of Medicine: The Nation's Treasury of Medical Knowledge by Miles  and the average time to index for articles fully indexed by humans was 145 days in FY 2021 , or systems that aim to match queries to relevant documents or snippets by using resources with formally defined semantics as a mediator  by producing better rankings of relevant information, for example by matching queries to results at the conceptual level; (ii) by reducing redundant results, for example by aggregating results that express the same concepts; (iii) by increasing the coverage of the results, for example by expanding queries with semantically related terms; (iv) by presenting the results in a more comprehensible manner, for example by allowing the results to be grouped by the concepts of the query. In the biomedical domain, search engines such as GoPubMed  established the Indexing Initiative project back in 1996  combines human NLM Index Section expertise and Natural Language Processing technology to curate the biomedical literature more efficiently and consistently. In 2002, MTI started being used to provide indexing recommendations to the NLM indexers . The indexers noticed that for a small set of journals, MTI performed very well, and these journals were the first to be processed by MTIFL. In Task a, on large-scale semantic indexing of biomedical literature, and Task b, on biomedical semantic information retrieval, question answering, and summarization.Since 2012 a dedicated shared task has been organized for the automated semantic indexing of biomedical literature, in the context of the annual BioASQ challenge , as each article belongs to only some of the several thousand classes provided by MeSH. The classes are also hierarchically organized and the systems were required to assign the narrower labels applicable to each document, as done by the MEDLINE curators.Task a was structured into several weekly testsets, distributed over a period of about 4 months, February to May, annually. The testset, consisting of new, unclassified documents, was released each Monday, and the participants had about twenty-four hours to produce their predictions and submit their responses before some manual annotations become available by the MEDLINE curators. The weekly testsets were organized into three batches, running for several weeks each, in total. In particular, in the first version of Task a, each batch consisted of six testsets. For the remaining nine annual versions, each batch consisted of five weekly testsets as presented in Task a, considering the four best positions achieved by a team in any of the testsets of that batch. The classification performance of the systems participating in Task a was assessed with a range of evaluation measures. These include variants of standard information retrieval measures for multi-label classification problems , as well as measures that use the MeSH hierarchy to provide a more refined estimate of the systems' performance. The official measures for identifying the winners of the task were the micro-averaged F-measure (MiF) and the Lowest Common Ancestor F-measure  architectures. For example, u et al.  succeedeThe most recent participating systems along with their corresponding approaches are listed in BioASQ offered the opportunity to the respective research community to compete against each other as well as against strong baselines, and hence helped to push the performance of the participating systems significantly. The different variants of MTI indicate the methodical progression toward fully automatic indexing. MTI First Line Indexer (MTIFL) was in use from 2011 to 2020 and is shown in purple with F1 going from 0.6399 to 0.7712. The MTIFL variant started when indexers noticed that MTI performed very well on a small subset of journals . For the first time, MTI was treated the same as a junior indexer where the MTI indexing was reviewed by a more senior indexer. MTI Comment On (MTIC) started in 2017 but statistics were not tracked until 2020. It is shown in light green with F1 0.9742–0.9931. MTIC included the title of the article being commented on to enrich the usually terse text of articles commenting on another article. MTIC replaced the practice of just copying over the indexing from the originating article. MTI Review (MTIR) was in use from 2017 to 2022 and is shown in light blue with F1 of 0.8874–0.8752. MTIR was the staging area to see how journals performed using the MTI Automatic indexing algorithm (described next). Indexers would review every article indexed by MTIR only using the title and abstract  to evaluate the MTIR indexing. This provided a realistic review of how the automatic indexing would perform for each journal. Finally, MTI Automatic (MTIA) started in late 2019 and is shown in light red with F1 going from 0.9924 to 0.9871. MTIA is like MTIR except that for MTIA, there is no complete indexer review of the articles. For MTIA, indexers only review a small sample of the articles to ensure quality and completeness of the indexing. MTIR provided the most accurate measure of how well MTI performed since the vast majority of MTIA results are not manually reviewed. This small sampling of the MTIA results likely contributes to the false boost in performance of MTIA over MTIR that we see in In 2013, the first BioASQ Challenge—Large-scale Online Biomedical Semantic Indexing  subject headings to MeSH Headings NLM, . The updThe NLM Medical Text Indexer (MTI) continues to be improved and expanded using the latest technology. The next generation of MTI (MTIX) has been developed from the beginning as a Machine Learning/Deep Learning program, presented by Rae et al.  at the 2Despite the important advancements achieved in semantic indexing so far, there is still a lot of room for improvement in terms of specific challenges still persisting in the field. For example, new MeSH descriptors, introduced during the extension of the MeSH thesaurus through annual updates  to train groups of like journals, so new journals will by default be indexed based on their journal descriptor training group until the next time MTIX is fully retrained. Both new MeSH terms and any MeSH term that has drifted from its meaning would be handled in the same way. NLM has established a team of experienced in-house curators that will manually index a small set of articles that involve new MeSH terms (or drifted terms) to provide MTIX with a set of validated indexed articles to train with. The new training sets will include both true positive occurrences of the new/drifted MeSH terms and any false positive examples the curators can identify, so that MTIX has a more balanced training set to work with. Experiments are ongoing to determine exactly how many examples of each new/drifted MeSH term are needed to ensure the best training for MTIX.To ensure that MeSH indexing continues to be the quality product that it is, NLM has the team of experienced curators review and re-index specific types of articles and random samples of the automatic indexing. Any corrections made by the curators are fed back into improving MTIA and corrected on any affected articles. Journals where chemicals, genes, and proteins are more frequently found are targeted in this review due to MTIA not doing as well with them. The random sample of 100 (at time of writing) daily articles is chosen from any remaining articles from across the daily processing. This set of 100 articles statistically provides an adequate random sampling for daily review. NLM is continuing to evaluate this number to ensure that we cover the literature and will adjust as the results of these evaluations and user feedback dictate.Still, the ever-expanding information needs of domain experts suggest that further extensions of semantic indexing would be useful in several directions, even beyond scientific literature and/or MeSH descriptors. This includes indexing other types of documents such as clinical trials, healthcare-project summaries, biomedical patents, and clinical reports, as well as indexing in other languages beyond English  can be found at: AK and GP originated the BioASQ Challenge. AN was co-organizing the BioASQ challenge since 2017. JM provided the MTI tool for the challenge and has supported the BioASQ challenge since the beginning. AK, JM, and AN drafted the manuscript. All authors reviewed the manuscript. All authors contributed to the article and approved the submitted version.


Understanding the type and frequency of current neonatal intensive care unit (NICU) therapy services and predictors of referral for therapy services is a crucial first step to supporting positive long-term outcomes in very preterm infants. This study enrolled 83 very preterm infants  from a longitudinal clinical trial. Race, neonatal medical index, neuroimaging, and frequency of therapy sessions were extracted from medical records. The Test of Infant Motor Performance and the General Movement Assessment were administered. Average weekly sessions of occupational therapy, physical therapy, and speech therapy were significantly different by type, but the magnitude and direction of the difference depended upon the discharge week. Infants at high risk for cerebral palsy based on their baseline General Movements Assessment scores received more therapy sessions than infants at low risk for cerebral palsy. Baseline General Movements Assessment was related to the mean number of occupational therapy sessions but not physical therapy or speech therapy sessions. Neonatal Medical Index scores and Test of Infant Motor Performance scores were not predictive of combined therapy services. Medical and developmental risk factors, as well as outcomes from therapy assessments, should be the basis for referral for therapy services in the neonatal intensive care unit. In 2020, the incidence of preterm birth (before 37 weeks of gestation) impacted one in every ten infants born in the United States . CompareTherapies consisting of physical, occupational, or speech–language therapies in the NICU aim to improve the neurobehavioral, sensory, feeding behavior, state regulation, and neuromotor function of infants who were born less than 37 weeks of gestational age . The AmeGiven the short and long-term developmental challenges associated with preterm birth, there is increased emphasis on training therapists to deliver interventions to preterm infants. Research on the effectiveness of targeted early interventions in the NICU is needed but should be considered when compared with the current standard of practice. Understanding the current state of therapy in the NICU, the type and amount of therapy being administered as usual care, and which demographic, behavioral, and medical risk factors are associated with access to therapy services will help with intervention research and public policy. Despite the importance of these questions, to the best of our knowledge, only one study to date has examined the type and frequency of therapy services provided for preterm infants in a single-level IV NICU . They foHere, we aim to add to this literature by using primary medical data that documented the frequency of therapy visits between baseline assessment and NICU discharge for infants born <32 weeks gestational age and who were part of the Supporting Play Exploration and Early Development Intervention (SPEEDI2) clinical trial (NCT03518736). SPEEDI is a three-arm randomized clinical trial, with participants enrolled at three sites. One arm (SPEEDI_Early) provides an intervention that starts in the NICU and aims to provide an enriched environment and increased opportunities for infant-initiated movements through collaborative parent, therapist, and infant interactions during the first months of life .The objectives of this paper are to (1) describe the therapy services that very preterm infants received in the NICUs and evaluate if the frequency or type of services changed over time as infants moved closer to NICU discharge, and (2) evaluate if medical, behavioral, and sociodemographic infant risk factors  influenced amount or type of therapy services received in the NICU.Every infant admitted to participating Level IV NICUs during the enrollment period was screened for eligibility. Initially, only infants <29 weeks of gestation were enrolled from one of two hospitals; however, following the COVID-19 pandemic, the inclusion criteria were changed to <32 weeks of gestation and a NICU stay of greater than 28 days. These criteria are consistent with the state criteria for automatic eligibility for early intervention ensuring all infants were eligible for the same early intervention services. In addition, a community hospital with a level III NICU was added as an enrollment site, but all infants enrolled were counted toward the primary site’s enrollment as all study visits were completed by the primary hospital’s research team. Infants were offered enrollment if they were between 35 and 42 weeks of gestation, medically stable, off invasive or non-invasive ventilation, lived within 100 miles of the hospital, and spoke English. Exclusion criteria included a diagnosis of a genetic syndrome or musculoskeletal deformity.Participants included 83 infants  weeks) enrolled in a therapeutic clinical trial and were randomly assigned to one of 3 groups, Usual Care, SPEEDI_early, and SPEEDI_Late (NCT02153736). While only the infants in SPEEDI_Early were receiving NICU-based intervention visits, all 3 groups were monitored, and able to continue their usual clinical care including therapy services . The usuAll outcome measures used in this analysis were part of the research protocol and completed by highly trained research therapists. At baseline, the Test of Infant Motor Performance (TIMP), General Movement Assessment, and an initial medical record review were completed. Ongoing medical record reviews were completed by the site’s clinical research coordinator who was familiar with the site’s medical record system. Each hospital had similar policies for therapy documentation of any completed therapy visit.Test of Infant Motor Performance (TIMP). The TIMP is an assessment of posture and movement for infants from 32 weeks of gestational age to 4 months of corrected age . The GMA is a standardized, noninvasive method of observation of spontaneous, complex movements to evaluate the typical maturation of the nervous system . Prior sMedical Record. Electronic medical records were reviewed weekly from the time of enrollment to NICU discharge. Weeks were considered Sunday to Saturday and thus the last Saturday the infant was in the NICU ended the final week of data extraction. If babies were given a baseline assessment and discharged within 24 h, their data were not included in the analysis. Data from full weeks were considered in all analyses. The length of NICU stay after the baseline assessment ranged from 0 days to more than 100 days . However, only 2 infants were still in the hospital 10 weeks after baseline; therefore, data provided in this paper are presented by week post baseline, including the infants who were in the hospital the entire week . The frep = 0.9999).Service Type Over Time. To describe the therapy services that very preterm infants received in the NICU, we fit a generalized linear model to the data for each week post baseline in which the infant was in the NICU, utilizing a Poisson distribution to model the mean number of services. The model included an effect for service Type , the number of weeks since baseline (1 to 9), and the interaction between Type and Week as well as a random effect for participant. We tested to see if we could treat Week as a continuous variable (with the built-in assumption of linearity), as opposed to treating Week as categorical (and thus a non-linear effect), and found that the less complex model using Week as a continuous variable was sufficient .Service Type Before Discharge. To specifically explore the weeks leading up to hospital discharge, we fit a generalized linear model to the data for the three weeks prior to discharge, utilizing a Poisson distribution to model the mean number of services. The model included an effect for service Type , Discharge Relative Week , and the interaction between Type and Discharge Relative Week as well as a random effect for participant. We tested to see if we could treat Week as a continuous variable (with the built-in assumption of linearity), as opposed to treating Week as categorical (and thus a non-linear effect), and found that similar to the above, the less complex model was sufficient  described above and added in fixed effects for race (Caucasian yes/no), baseline NMI, and GMA .Predictors of Individual Services. In order to determine if medical risk or standardized therapy assessment results influenced the frequency of individual therapy service, we repeated the analysis by adding the TIMP, which is typically completed by therapists and for each therapy service, rather than aggregate. We used three separate generalized linear models  of the data for the frequency of therapy services from baseline through discharge or 9 weeks post baseline, whichever was shorter, utilizing a Poisson distribution to model the mean number of services. The models included a fixed effect for  as well as a random effect for participant. Parameter estimates were examined and post hoc tests performed with a Tukey HSD correction were calculated when relevant for pairwise comparisons .1,729 = 7.6, p = 0.0005). This significant interaction indicates that services provided were significantly different, but the magnitude and significance of the difference depend upon the discharge week , Week (one to nine), and the interaction between Type and Week as well as a random effect for participant. The interaction effect for Type by Week was significant  and the model was refit to exclude the interaction effect. The Service Type effect was significant  but the Week effect was not significant . Post hoc tests revealed that ST services are significantly different from both OT  and PT  services, but there was no difference between OT and PT  in terms of the frequency of services  received an average of 0.12 more therapy sessions than did infants at low risk for CP . In addi54 = 2.86, p = 0.006). Examination of the parameter estimate for GMA indicates that infants who had an abnormal baseline GMA had a higher mean number of OT sessions (0.51 more). The baseline GMA score was not statistically significantly associated with PT sessions  or ST sessions .Baseline GMA was related to the mean number of OT sessions over the 9 weeks of NICU time . Examination of the parameter estimate for NMI indicates that as the baseline NMI score increases, the mean number of OT sessions increases. With regards to the mean number of PT sessions, the baseline NMI score is not statistically significantly associated with PT sessions . With regards to the mean number of ST sessions, we see that baseline NMI is related to the mean number of ST sessions over the 9 weeks of NICU time . Examination of the parameter estimate for NMI indicates that as the baseline NMI score increases, the mean number of ST sessions decreases.Baseline NMI was related to the mean number of OT sessions over the nine weeks of NICU time , the mean number of PT sessions , or the mean number of ST sessions .The baseline TIMP score was not associated with the mean number of OT sessions . Further, we did not document therapy coverage for the NICUs , or the individual hospital distribution of roles and responsibilities between therapy disciplines. Moreover, we did not collect the recommended frequency of therapy services by each discipline, and staffing may have impacted the actual frequency, which may not have been consistent with the recommended amount in each case. This study also did not track parent presence in therapy sessions, which impacts the efficacy and carryover of therapy services. We did not record the duration of therapy sessions, or exactly what a therapist did in any given session. Data were not collected regarding the timing to full oral feeds, which is likely highly related to the need and timing of therapy services. These data may not be representative of other types of NICU settings or for samples with different socio-demographic compositions. Future work may compare referral practices to elucidate optimal referral protocols for the best service outcomes. Our work highlights that improvement is still needed in utilizing medical and developmental risk factors, as well as outcomes from therapy assessments, as the basis for referral for therapy services in the NICU.This study found that services provided in the NICU were significantly different by type, but the magnitude and significance of the difference depended upon the time since enrollment week. Our study adds to previous research by demonstrating that an abnormal GMA  is associated with more therapy services in the NICU, and that NMI and TIMP scores are not. These results highlight the lack of valuable clinical and developmental information being used to guide therapy referrals. The clinical impact of this work recommends that medical and developmental risk factors, as well as outcomes from therapy assessments, should be the basis for referral for therapy services in the neonatal intensive care unit.


Journal of General Microbiology was first published in 1947, two years after the founding of the Society for General Microbiology. Although both names have changed, to Microbiology and the Microbiology Society, respectively, the former names capture a key aspect of the journal, in that it is inclusive of all microbes, from viruses through to fungi, protozoa and algae. Except for animal and plant virology, which branched off in 1967 to create the Journal of General Virology, this ambition continues to this day. The word ‘general’ was a counterpoint to the many specific applied microbiology journals that existed in this period, in the diary and brewing industries, for example. Whilst the Society was founded to bring together diverse groups of researchers, doing more fundamental research, the journal encompasses both fundamental and applied research, which can be seen from articles published right from its first issue to the current day.The In this two-part celebratory article, the team of senior editors associated with the journal at the start of our anniversary year have reviewed highly cited and influential papers published in the journal's 75 year history. The 40 or so selected papers, which date from 1956 to 2014, highlight some favourite themes, under a number of broader topic areas. While not comprehensive, we hope it will highlight of areas where the journal has championed important work and will encourage continued submission of strong research as the journal as it continues beyond its 75th year.The ability to culture microbes in the laboratory in controlled and reproducible ways was integral to the work of the early pioneers of our subject. This enabled experiments to tease apart how they resource food, convert this to energy and then build new biomass. We start with a series of early fundamental papers, focused on microbial physiology and growth.Aerobacter cloacae  was popular for such studies. This work was followed shortly by two other important papers. The first, from Schaechter and colleagues in 1958, determined the influence of media composition and temperature on cell size [Enterococcus faecalis when grown on glucose as the sole energy source and only using substrate-level phosphorylation for energy production. Using this system, they established a direct relationship between the amount of energy source and biomass. Knowing how ATP was generated from glucose they derived a measure for growth yield, termed YATP [Our earliest highlighted paper from 1956 is a classic on the use of continuous culture for the growth of bacteria, from scientists at the Microbiological Research Department at Porton Down, Wiltshire, an important research centre for microbiology in the UK from this period [ell size . The secell size . The claed YATP . This asSaccharomyces cerevisiae [S. cerevisiae during anaerobic glucose-limited culture, another growth mode that is available to this metabolically flexible class of microbes [Yeast physiology and metabolism also featured in early classic papers. De Deken in 1966 elucidated the generality of a process called the ‘Crabtree effect’, which is when yeast growing on certain sugars in the presence of oxygen use fermentative metabolism rather aerobic respiration. De Deken determined that this was due to a regulatory system that resulted in repression of the respiratory system when growing on selected sugars, and that this occurred in many yeasts in addition to the model brewer’s yeast microbes . This unEscherichia coli has often served as the model system, as being a facultative anaerobe it can grow easily in the laboratory either with or without oxygen and can quickly transition between these modes. An elegant paper in the early days of molecular genetics described a mutant of E. coli that cannot grow in anaerobic conditions using fumarate as the sole electron acceptor for respiration [nirA. This was later found to be identical to fnr [fnr twice!This transition between aerobic and anaerobic growth has also been the topic of many other papers in the journal. Here piration . The mutl to fnr , so the in vivo, as metals that are essential at low concentrations can be toxic at higher concentrations, and bacteria have evolved many ways to control the intracellular levels of potentially toxic metals such as copper, for example using the CopAB system in the plant pathogen Xanthomonas axonopodis [Pseudomonas aeruginosa acquires iron from organic sources was described in an important paper from 2000, where an elegant genetic study revealed two distinct uptake routes for iron capture via haem [As well as the regulatory mechanisms involved in this aerobic–anaerobic transition, the biochemical and physiological changes in the presence and absence of oxygen also highlight the use of metals in enzymes, where the journal has also published important papers. The use of metals in respiratory enzymes, but also more widely in many other enzymes, has prompted important reviews by Hughes and Poole  and Gaddopodis . Iron nevia haem , both of2). The appreciation that ROS are generated constantly during aerobic growth, through electron leakage from respiratory enzymes and by host organisms to kill invading microbes, triggered many studies from the mid-1990s onwards. Particularly strong contributions to Microbiology have shed light on adaptive strategies that allow obligate anaerobes to tolerate O2 and to scavenge ROS. Anaerobes are ubiquitous and include bacteria of environmental, medical or biotechnological interest, as well as commensals and pathogens of the gut microbiota. Consequently, they have been well studied by microbiologists from the outset of both the Society and the journal.One consequence of high concentrations of metals such as iron is the generation of reactive oxygen species or ROS from molecular oxygen H-dependent O2 reductase to protect against oxidative stress [Clostridioides difficile [Most anaerobes, despite their name, can tolerate transient exposure to air, low-Orobiosis . A similricans . The O2  journal , and man purpose . In anotficile .2 directly, microbes have diverse ways to handle ROS in complex adaptive responses. While Clostridium perfringens has surprisingly classical (in non-obligate anaerobes) enzymes of ROS detoxification, such as superoxide dismutase, catalase and hydroxyperoxide reductase [2 as a by-product. These mechanisms are not restricted to anaerobic bacteria either, and the role of a copper- and zinc-containing superoxide dismutase in the pathogenic fungus Candida albicans was established in a paper published in the journal [C. difficile confers a high level of resistance against peroxide via the secretion of a glutamate dehydrogenase-like enzyme through an unknown mechanism [2, eliminate endogenously produced ROS in aerated cultures, adapt their metabolism and efficiently repair damaged molecules.As well as dealing with Oeductase , other a journal . An appaechanism  and confC. albicans. This tool was used mainly as a reporter of gene expression, although it later became invaluable for protein localization and/or morphology studies in many yeast species.The interesting behaviours in which microbes engage often involve processes at the cell envelope or within organelles, where microscopy with direct visualization of microbial cells has been a key experimental tool. An important paper published in the journal was the first optimization of green fluorescent protein (yEGFP) for use in yeast , initialE. coli. In essence, a capillary is loaded with a defined buffer containing an attractant chemostimulus. One end of the capillary is then placed into a suspension of E. coli cells. As the attractant diffuses out of the capillary, a gradient is generated and the bacteria move up that gradient and into the capillary. After a predetermined amount of time, the capillary contents  are assayed. This simple assay allowed Adler to define the best conditions for assaying bacterial chemotaxis and set the scene for almost all subsequent work in the field and consequently has been (and continues to be) cited many times.One fascinating cellular process, well studied in many different microbes, is chemotaxis, the understanding of which has led to in-depth understanding of sensing and signal transduction pathways. A significant early methodological paper was published in the journal in 1973 by Julius Adler, considered by many to be the pioneer in this field . Adler aE. coli has a complex cell envelope comprising both an outer and inner membrane. One controversial paper, which was discounted for many years by the community, was published by Bayer in 1968 [E. coli were examined by transmission electron microscopy. Plasmolysis occurs when bacteria are placed in hypo-osmotic medium, with shrinkage of the cytoplasm leading to separation of the cytoplasmic membrane from the cell wall and outer membrane. The micrographs revealed areas where, unexpectedly, the two membranes remained in contact despite cytoplasmic shrinkage. Bayer and others proposed that these contact sites functioned in the export of lipopolysaccharides. These sites of membrane contact became known as ‘Bayer junctions’ or ‘Bayer patches’, although for many years they were dismissed as an artefact arising from the chemical fixation process used to prepare the cells for electron microscopy. Recently structural and biochemical analysis of the lipopolysaccharide transport machinery (LPT) have shown that it forms a transenvelope machine that connects both membranes. Since the structure formed during this process is resistant to plasmolysis, it likely gives rise to the contact sites seen in Bayer’s original images.As a Gram-negative organism,  in 1968 . In thisBacillus subtilis and P. aeruginosa. The formation of biofilms requires some matrix or ‘glue molecules’ to be secreted to hold the structure together, which is often a secreted polysaccharide. However, an important paper in the journal discovered that in the pathogen Acinetobacter baumannii, there is an essential role for the cell surface pili in this process and that biofilm development is abolished when biosynthesis of the pili, via a novel chaperone-usher system, is disrupted [While we considered growth of bacteria in liquid culture in the previous section, microbes can also be grown on surfaces as colonies, the kinetic study of which was described by Pirt in a classic paper in 1967 . Much moisrupted .The implications of life in biofilms was the subject of another classic paper from Jan-Ulrich Kreft in 2004, where he used mathematical modelling to argue that bacteria within biofilms are behaving altruistically . Unlike In part 2 we will continue our journey and look a papers based around the broader themes of microbial communities and evolution as we complete our journey through 75 years of the journal’s most impactful papers.


Health promotion programs are most beneficial in chronic diseases such as diabetes and morbid obesity, which can be positively affected by changes in attitudes, beliefs, and lifestyle.This study aimed to develop an internet-based modern Health Promotion model using interactive online applications through continuing education and participation.The goal was to positively impact knowledge, behavior, and quality of life for patients with obesity and/or diabetes. This is a prospective interventional study on patients with obesity or type 2 diabetes. Seventeen two patients who met the inclusion criteria were distributed randomly into two groups (control and intervention) from 2019 to 2021 in Greece. All the participants were given questionaries concerning quality of life anxiety and depression (HADS) attitudes and beliefs, knowledge about their condition and general questions to establish a baseline. A traditional health promotion model was followed for the control group. For participants in the intervention group, a web-based health promotion program was created according to the goals of the research. Participants were instructed to log on 1–2 times a week for 5–15 min, with the understanding that the research team would be monitoring their activities. The website included two knowledge games and personalized educational material based on their needs.The sample comprised 72 patients (36 in control and 36 in the intervention groups). The mean age was 47.8 years for the control group and 42.7 years for the intervention group (p = 0.293). Both study groups had a significant increase in knowledge score on diabetes  and obesity  along with a positive attitude score towards fighting obesity . Still, the overall change was more remarkable for the intervention group, as indicated by the significant interaction effect of the analysis. Anxiety was decreased only in the intervention group . Analysis for QOL during follow-up showed that Physical Health and Level of Independence was improved in both study groups but the degree of improvement was more significant in the intervention group . Psychological Health was improved only in the intervention group, with better scores at 6 and 12 months compared to controls . Furthermore, Social relationships were improved only in the intervention group .The results of the present study showed that the participants in the intervention group showed significant improvement in knowledge, attitudes, and beliefs after using the internet as a learning tool. The intervention group also showed significantly reduced anxiety and depression arising from chronic illness. All of this resulted in an improved quality of life regarding physical Health, mental Health, and social relationships. Technology and online-based health promotion programs can revolutionize how we approach the prevention and management of chronic and terminal illnesses by improving accessibility, personalizing care, increasing engagement and motivation, improving data analysis, and disease management. The development of the World Wide Web and the Information and Communication Technologies in the 1990s helped spread the Internet from one side of the globe to the other. This enabled people to develop applications, to directly access a wide range of information, and to communicate more easily  is considered of primary importance so that patients can first understand the nature of their disease and then be empowered with knowledge and skills to manage their symptoms, especially in chronic conditions .Health promotion interventions are considered effective in preventing and improving the overall health of the target population. However, their range could be made more effective through internet-based programs from authorized agencies, taking into account users’ actual needs and expectations . A largeEvidence for the impact of these applications on users’ lifestyles is compelling, according to a 2019 Xinghan et al. meta-analysis of more than 23 studies .These applications could improve health promotion by facilitating interdisciplinary collaboration, better doctor and patient communication, exchange of ideas between patients and targeted information . This islearning map for continuous training. It showed that educating, and changing attitudes and beliefs in the intervention group led to better outcomes, compared to the control group that had the classical educational approach [The aim of this study was to provide targeted and personalized information to participants according to their knowledge deficiencies. Participants answered a series of questions through interactive games and depending on the wrong answers they received the corresponding information. Using this model, a significant improvement in their knowledge scales was recorded compared to the traditional model of health promotion used in the control group. In Garrett et al. published a randomized study in people with diabetes using a approach . Active,approach .The importance of the interactive educational process that takes place through these applications is great and is highlighted by research such as a systematic review of Norris et al., in 2001. This study focused on diabetes self-management education through patients collaborating with others in the same group . In contThe development of various applications that are used daily by millions of users enables direct communication between people of different age groups but who have something in common, such as a health condition. Indeed, a meta-analysis by Laranjo et al. in 2015 showed that, with widespread social media such as Twitter and Facebook, the effect on behavior modification was greater since these networks make it easier to communicate in private groups . GreaterPositive attitudes towards chronic illnesses can help to alleviate anxiety and depression, which are major factors influencing quality of life.  A study Providing information and encouraging optimism in patients with chronic diseases, such as diabetes, also helps to change their attitudes and beliefs and consequently to improve the compliance with the treatment. In giving patients more control over their treatment, we can reduce potential complications from the disease . In the In 2004, Wassenberg et al. showed that positive attitudes in people with hypertension towards their chronic disease resulted in better regulation of the disease, as participants had more consistent monitoring of blood pressure . In addiAnother study by Baranowski et al. in 2016, in collaboration with many organizations, identified the most beneficial features for health education games: that they be interactive, have feedback, allow for agency and control, identity, and immersion .In the present research these elements were included in the development of the two online knowledge games. Greater knowledge resulting in behavior modification was observed since the participants received direct information about their performance (score) as well as customized information depending on their incorrect answers. Indeed, the value of this approach can also be seen in publications such as a study by Espinosa-Curiel et al. in 2020, which developed an online knowledge game aimed at changing children’s eating habits. In just 6 weeks there was an improvement in the level of knowledge as well as a more positive attitude towards a healthier diet. The children’s parents agreed that the game had a positive effect on them as they could now recognize more than 10 unhealthy foods .Like most studies performed with questionaries, the present study has some limitations that should be considered. Apart from the limited sample size, limited depth of information, and possible misunderstandings or interpretation errors from the participants, mainly due to language barriers. The main limitation is the self-report bias. Questionnaires rely on self-reported data, and sometimes the participants may not always be honest or accurate in their responses. In addition, they may be influenced by social desirability bias or other factors affecting their answers, so researchers have limited control over variables that could affect the results. While questionnaires can provide valuable insights into participants’ knowledge, attitudes, and beliefs, they are not without limitations, and their findings should always be considered in the context of their limitations.It appears that the study was conducted during the COVID-19 pandemic, which posed significant challenges due to government restrictions. Diabetes was one of the comorbidities with increased incidence in COVID-19 patients as the virus is related to glucose dysregulation or hyperglycemic hyperosmotic state . AdditioThe present intervention was a challenge for the participants as they were unfamiliar with such programs. However, the personalized approach, the online material, and the monitoring from the research team through Google Analytics, delivered targeted feedback and encouraged participation in a healthier lifestyle, better monitoring of glucose levels, etc. The final analysis of the research results showed that the participants in the intervention group showed significant improvement in knowledge, attitudes, and beliefs after using the internet as a learning tool, particularly compared to the control group which used a traditional health promotion approach. The intervention group also showed a significant reduction of anxiety and depression arising from chronic illness. All of this resulted in an improved quality of life in regards to physical health, mental health, and social relationships. Those involved in health education and promotion not only must integrate modern tools into their existing programs, but also must design new interventions using the philosophy of the internet and social media, through the growing potentials of smart phones. Using these technologies, and looking into the future with the artificial intelligence, we can allow users to benefit from both traditional and experiential methods. Practically, the internet allows health promotion providers to easily and quickly customize health education to fit the individual need.Technology and online-based health promotion programs have the potential to play a significant role in addressing a wide range of chronic and terminal illnesses. Some potential future implications are improved accessibility by allowing patients to access information and support from their homes. This can be particularly important for patients who have difficulty traveling or live in rural or remote areas. Another significant implication is the personalization of care. Technology can help health promotion programs better tailor their care to individual patients, considering factors such as age, gender, health status, and lifestyle. This can help to make care more effective and engaging for patients and increase motivation for example development of games that can also be used to make health promotion programs more engaging and fun. Also, online programs are cost-effective by reducing the need for face-to-face consultations and other traditional healthcare services.In conclusion, technology and online-based health promotion programs have the potential to revolutionize the way we approach the prevention and management of chronic and terminal illnesses. By improving accessibility, personalizing care, increasing engagement and motivation, improving data analysis, and improving disease management, these programs can help to improve health outcomes and reduce the burden of illness on individuals and society.