Exploring the impact of corporate social responsibility (CSR) fulfillment and disclosure on enterprises’ sustainable innovation capacity can not only expand the research boundary of factors of sustainable innovation and the impact of CSR, but it can also serve as a reference for the decision-making of listed companies in increasing pollution problems. Using a sample of 224 Chinese A-share businesses in the heavy pollution industry listed between 2016 and 2020 and employing an ordinary least square regression, the results provide empirical evidence that CSR is positively associated with sustainable innovation. Second, the business environment can serve as a moderator of the relationship between CSR and sustainable innovation, and the positive relationship between CSR and sustainable innovation is more pronounced in regions with better macroeconomic conditions. Additionally, the improvement of CSR for sustainable innovation is more clear in state-owned firms than in non-state-owned enterprises. After a series of robustness tests that eliminate marketization, law enforcement, and macro-political unpredictability, the results still hold. This study broadens the scope of CSR and sustainable innovation research. In addition, the theoretical and practical significance of this study’s findings is referenced in this paper. Environmental and climate concerns caused by the intensification of global industrialization are irreversible. Corporate social responsibility (CSR) is a successful approach that encourages businesses to take on additional duties to support social and sustainable development, given the growing consensus in modern global business on the value of sustainable development . InnovatEconomy , legislaAs a fundamental aspect of sustainable development, the importance of sustainable innovation is self-evident . Prior rIt is common knowledge that significantly polluting companies have a far greater detrimental influence on the ecological environment than others do . BecauseThis article picks Chinese A-share listed firms from 2016 to 2020 as its research object and empirically examines the impact of CSR on enterprises’ sustainable innovation capacity. The findings show that the output of green innovation considerably enhances business sustainability. Given the sustainable development of businesses, the following questions are posed in this study. How can CSR foster innovation and sustainability? Does the influence of CSR on the capacity for sustainable innovation vary by corporate environment? What is the state of CSR in the Chinese heavy polluting industry?The following are the primary contributions of this work. First, it expands the literature on sustainable innovation and CSR, which contributes to the development of a fresh perspective for the study of the factors influencing the sustainable innovation capacity of businesses. Existing studies have investigated more CSR-influencing aspects, however, there remains a dearth of studies on CSR’s role. As opposed to undertaking a standard analysis at the firm or national level, this study focuses on publicly traded enterprises in China’s heavy pollution industry. This study can therefore serve as a substantial contribution to the research on the sustainable development of the heavy pollution sector and give theoretical support for the heavy pollution industry to realize its low-carbon transformation goals. Third, most previous research has ignored the societal dimensions of CSR in general . In thisThe organization of this investigation is as follows: The literature review and research hypotheses are provided in Section “Literature Reviews and Research Hypotheses”. The third section of this study describes the research design, including the variables, sample, and model selection. The section “Robustness Tests” consists of empirical analysis, findings reporting, and comments. Section “Conclusions and Policy Recommendations” highlights the theoretical and practical implications’ conclusions and policy recommendations.According to the stakeholder theory, (CSR) entails that the development of businesses should include stakeholders, including employees, consumers, suppliers, and communities . By adheEverything related to CSR can have a favorable effect on shareholder profitability . CSR proMany researchers have conducted studies on sustainable innovation. Sustainable innovation is described as an innovation model with sustainable innovation goals in the creative development process . It exemH1: The output of CSR can significantly enhance the corporate sustainable innovation performance.Environment and resources limit the development and operation of heavy pollution industries, which are specialized sectors. In other words, high pollution businesses operate in an environment that is dynamic and constantly changing. Instead of operating in a vacuum, organizations are formed by their surroundings . The envBased on the preceding study, the following is the second hypothesis:H2: The promotion effect of the output of CSR on sustainable innovation performance is more significant when the business environment is poor.*ST, suspended listing, and delisting between 2016 and 2020 were omitted from this study. Second, we eliminate samples devoid of CSR and other variable values. Third, to prevent the influence of extreme values, we eliminate the samples from 2016-to 2020 for which the value of sustainable innovation is zero. The CSR statistics are from the social responsibility reports of HeXun Net-listed enterprises. The data on sustainable innovation comes from the National Intellectual Property Patent Database and the Green List of International Patent Classification maintained by the World Intellectual Property Organization (WIPO). Other data sources include the China Statistical Yearbook, the China Environmental Statistical Yearbook, the annual reports of publicly traded enterprises, and the RESSET database.This study focuses on the Chinese A-share firms involved in severe pollution industries from 2016 to 2020. Two thousand sixteen is the most recent year for which we have comprehensive data. Given that some data are unavailable at the time of this study, 2020 has been chosen as the conclusion date. The scope of sample selection refers to the CSMAR database and the classification standards of heavily polluting industries in The Guidelines for Environmental Information Disclosure of Listed Companies by the Chinese Ministry of Environmental Protection. To assure the validity of the empirical research, the sample is treated as follows. First, to avoid the influence of outliers, firms with anomalous financial status, ST, According to the current body of research, there are no accepted criteria for measuring the sustainable innovation of businesses. The patent data of an enterprise directly reflects its technological innovation accomplishments, and the number of patents can be used to gauge an enterprise’s innovation level . This stThe social responsibility assessment system of HeXun Net comprises fifty subdivision indicators. The entire system is based on shareholder responsibility, employee accountability, supplier, customer, consumer responsibility, environmental responsibility, and social responsibility. The findings represent CSR compliance and transparency.per capita GDP, average salary level, consumption rate, per capita fixed asset investment, and GDP growth rate as indicators and takes into consideration disparities in economic development level and human capital from the standpoint of the macroeconomic environment.The business environment is selected as the moderating variable in this study. The concept of conducting business is derived from the World Bank’s Doing Business Report. The World Bank evaluates the business climate from a national and regional standpoint. This study requires more granular indicators for provincial regions. Consequently, this article utilizes the research on the evaluation index system of the business environment  to objecDrawing on the previous empirical research on CSR , this stThe definitions and interpretations of all variables are shown in Based on the previous studies , this stThe variables’ descriptive statistics for the entire sample are presented in The Pearson correlation coefficients between the variables are displayed in In general, if the correlation coefficients between independent variables are less than or equal to 0.80, the model may not have significant multicollinearity issues. All correlation coefficients between independent variables in this model are less than 0.454. There is hence no multicollinearity issue. The findings of the univariate correlation analysis are shown above, and the results of the multivariate regression analysis will be presented below.F-value shows that the models as a whole are significant (18.506). Model (1)'s regression output comprises independent variables and control variables. CSR has a significantly positive impact on sustainable innovation , as shown in the table. This positive correlation implies that hypothesis H1 proposed in this paper’s research hypothesis section has been confirmed by the empirical study. The findings suggest that organizations that prioritize CSR fulfillment and disclosure have a greater capability for sustainable innovation. Since the existing research has identified the influencing factors of CSR, we choose several representative corporate management variables as control variables, and the regression results of the control variables in Model (1) are most consistent with expectations. Among the control variables, the SIZE, AGE, CASH, SOE, and INDEP regression coefficients are significantly positive. A greater number of independent directors, a larger asset size, a longer listing period, more asset liquidity, and more stable equity are all correlated with a higher ability for sustainable innovation. Significantly negative regression coefficients for PB can be observed. The lower the price-to-book ratio, the greater the company’s investment value and growth prospects, and hence its emphasis on sustainable innovation. Several research has previously investigated and proven the inherent positive impact of CSR, innovation, and sustainable development  CSR significantly improves the sustainable innovation capacity of businesses and (2) when a business is in a region with a more favorable macroeconomic environment, the effect of CSR on sustainable innovation capacity is more pronounced. Additionally, the improvement of CSR for sustainable innovation is more clear in state-owned firms than in non-state-owned enterprises. CSR has a more favorable effect on sustainable innovation when the board is more independent. These results also indicate that the government and independent directors can serve as a check, a balance, and a supervisor to encourage stakeholders to prioritize CSR and promote sustainable innovation capacity from the sidelines, particularly in China’s heavy pollution industry.This study’s findings have the following implications for businesses, their managers, and legislators. In the first place, our empirical findings demonstrate that CSR greatly improves sustainable innovation potential. Therefore, corporate managers must acknowledge the significance of CSR. They should place a greater emphasis on the outcomes of sustainable innovation and realize the sustainable development of businesses through sustainable innovation. Due to the stimulation of macroeconomic environmental conditions, firms in the heavy polluting industry will pay greater attention to the fulfillment and disclosure of CSR and support the strengthening of their capacity for sustainable innovation. Currently, heavy polluting industries, particularly manufacturing, are shifting from China’s economically developed eastern areas to the economically depressed center and western regions. If the government does not prioritize local economic growth, it may negatively affect the local ecology. Moreover, by addressing internal governance characteristics, businesses can mitigate the detrimental impact of the regional transfer on sustainable innovation. Thirdly, green human resource management methods can improve the environmental performance and sustainability of businesses . IncorpoThis study has limitations that necessitate more investigation. Due to the availability of data, this report only includes information from 2016 to 2020. Due to China’s ongoing efforts in energy saving and emission reduction during the past few years, results may vary over time. In addition, this article examined the impact of CSR on sustainable innovation from the standpoint of CSR. In future, we can also examine the effects of the many components of CSR. Lastly, the proportion of highly educated employees and research and development professionals might be viewed as elements that influence the sustainable innovation capacity of businesses.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.XL: investigation, data curation, modeling and experiment. RY: methodology, supervision, and writing. XZ: review and editing. All authors contributed to the article and approved the submitted version.The work was supported by the National Natural Science Foundation of China , Beijing Natural Science Foundation (no. 9184023), Beijing Municipal Education Commission Foundation , the Fundamental Research Funds for the Central Universities  and Beijing Philosophy and Social Science Planning Project (no. 21JCC089).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.


To verify the presence in the literature of other possible implantation sites, we performed a systematic review of the literature on Pubmed, Google scholar and Scopus from 2000 to 2021 using different combinations of the following terms: (Nexplanon), (contraceptive implant), (insertion). Two manuscripts with three cases were detected. Nexplanon® was implanted in the upper back. In all cases, there were no complications during the insertions and the follow up demonstrated no side effects with contraceptive efficacy. Our report and review is a further confirmation that the scapular region can become a valid insertion site, maintaining good efficacy and safety of the subcutaneous device.The etonogestrel (ENG) implant is among the most effective reversible contraceptives. It can be a good option for patients with different chronic diseases due to no clinically significant effects on lipid metabolism or liver function. Some limitations in the use of this type of device are represented by social and psychiatric disorders, where the easy accessibility of the device becomes a negative feature. In these patients several cases of self-removal or damage to the device have been reported. We report the successful insertion of the Nexplanon It contains 68 mg of ENG implant that is slowly released for three years; it is not impacted by individual characteristics and genetic variantsNexplanonThe ENG implant is among the most effective reversible contraceptives available, with efficacy as good or better than the sterilization procedures, but without the risk of invasive surgery ,2,3.Implant contraceptives can be a good option for patients with chronic diseases because, beyond their need for highly effective contraception, there are no clinically significant effects on lipid metabolism or liver function. According to the criteria of eligibility of contraception ,5, theirWe report the successful insertion of the subcutaneous device in the scapular region in a young woman with chronic psychiatric disorder. To verify the presence in the literature of other possible implantation sites, we performed a systematic review of the literature on Pubmed, Google scholar and Scopus.®. Because of the patient’s psychiatric illness, the typical site at arm level was not recommended due to the high risk of self-removal or damage.A 16-year-old girl presented to our hospital, accompanied by her mother, for a menstrual disorder: she reported long periods of amenorrhea over the last years. The patient suffered from borderline personality disorder with marked affective instability and impulsivity with self-harm, which had caused multiple superficial cuts along the forearms bilaterally and on the right thigh. The patient was on chronic lithium therapy with poor control of psychiatric symptoms. Options were discussed and the mother, the legal administrator, refused the intrauterine device (IUD) because of the maidenhood status of the daughter, and the estrogen-progestogen pills due to the difficulty of ensuring daily intake. Additionally, the vaginal ring and transdermal contraceptive patch were inappropriate due to low adherence to treatment. For these reasons, the best option was the insertion of the subcutaneous device, Nexplanon® placement in a different unreachable body site.The risks and benefits of the subcutaneous device were explained to the mother and the patient, underlining that in the literature there are very few cases of alternative insertion site. They gave the consent for Nexplanon® was placed in the right scapular region without any complications , the patient reported normalization of the menstrual cycle without any side effects or discomfort related to the implant such as headaches, acne, pain, breast pain or depression. The implant remained superficial and palpable in the same position. However, she did not seem to pay attention to the implant and did not try to remove it.This research was approved by our Institutional Review Board (RC 08/2020).MEDLINE (PubMed), Google Scholar and Scopus databases were searched up to December 2021. The manuscripts considered were published from 2000 up to December 2021.Only articles in English were included in the search. The research strategy adopted included different combinations of the following terms: (Nexplanon) AND (contraceptive implant) AND (insertion).® implant, the procedure and the follow up.For the selection of the papers, we included articles that focused on cases of alternative sites of Nexplanon implantation. We examined in our review, the age and the history of patients, symptoms, the medical reason for a different NexplanonWe excluded from the review studies with different topics like aberrations from procedure for insertion and removal, and case complications such as infections, migrations, embolism, lipoatrophy and adverse reactions.All studies identified were examined for year, citation, title, authors, abstract and their full texts. Duplicates were identified through manual screening performed by one researcher and then removed. PRISMA guidelines were followed. The PRISMA flow diagram of the selection process is provided in Because this contraceptive method is cutting edge, the studies included are all case reports. For this reason, we present the data in a descriptive manner.n = 244 from MEDLINE; n = 48 from Scopus; n = 4750 from Google Scholar). We removed duplicates (n = 292) and others written in non-English (n = 15). After screening and exclusion of all records on different topics, two manuscripts were detected as eligible in our review  that suffer from chronic neurological diseases and psychotic symptoms, and that frequently self-inflict lacerations on their skin. For this reason, Nexplanon® implant is a 4 cm rod-shaped barium sulphate, containing 68 mg ENG.The NexplanonPeak serum concentration (266 pg/mL) of ENG is achieved within 1 day after insertion, suppressing ovulation, which requires only 90 or more pg/mL . BioavaiTo date, the common site of insertion is at the level of the medial face of the non-dominant arm with local anesthesia, 8 to 10 cm above the medial epicondyle of the non-dominant arm, 3–5 cm away from the sulcus between the biceps and triceps muscles that contains a large neurovascular bundle ,14. ThisComplications are rare; they are reported in 0.3–1% of insertions and 0.2–1.75 of removals ,16. ThesIn the literature, there are very few cases of insertion in other regions  because of the presence of vulnerable nerves and vessels in the inner arm . The sca® in other sites could be a good possibility in patients with social problems  or with skin and neuromuscular diseases of the upper limbs.We report the three cases described in the literature of insertion localized at the back and the results were good for compliance by the patient and contraceptive efficacy as demonstrated by the estrogen levels. In these cases, including the case from our institute, all patients shared similar diseases with psychiatric and neurological symptoms. In general, insertion of NexplanonThe strength of our study is the novelty and the presentation of a very rare case (only three others present in the literature) and the long period of time reviewed in the literature: we analysed the cases of alternative sites of implantation of contraceptive device from over the last 21 years. All the studies selected during the eligibility phase were further evaluated by manual comparison of populations, study settings and authors to avoid overlapping cases.The limitation of our study is the retrospective nature of it and the main risk of bias is represented by the presence of all case reports among the papers selected, due to the rarity of this complication.There are a significant number of psychiatric and social conditions that would benefit from the possibility of having an effective and safe contraceptive device, not easily accessible by the user. It becomes imperative to think of an alternative insertion site in order to meet all the needs of patients. As demonstrated by the previous cases described in the literature, our case report is a further confirmation that the scapular region can become a valid insertion site, because this anatomical region does not reduce the efficacy and safety of the subcutaneous device and does not lead to an increased risk of complications. Unfortunately, we do not know what the removal of the device will look like. For this reason, it is necessary to carry out a study that can systematically test this anatomical region as a possible alternative insertion site, evaluating the insertion, removal and associated complications compared to the common site.


It aimed to compare the use of the tele-objective structured clinical examination (teleOSCE) with in-person assessment in high-stakes clinical examination so as to determine the impact of the teleOSCE on the assessment undertaken. Discussion follows regarding what skills and domains can effectively be assessed in a teleOSCE.This study is a retrospective observational analysis. It compares the results achieved by final year medical students in their clinical examination, assessed using the teleOSCE in 2020 (n=285), with those who were examined using the traditional in-person format in 2019 (n=280). The study was undertaken at the University of New South Wales, Australia.In the domain of physical examination, students in 2020 scored 0.277 points higher than those in 2019 . Across all other domains, there was no significant difference in mean scores between 2019 and 2020.The teleOSCE does not negatively impact assessment in clinical examination in all domains except physical examination. If the teleOSCE is the future of clinical skills examination, assessment of physical examination will require concomitant workplace-based assessment. The coronavirus disease 2019 (COVID-19) pandemic has forced healthcare education across the globe to adapt to the unique and challenging scenario of facilitating performance-based examinations under strict social distancing requirements. Many “pivoted” to online platforms with minimal guidance from the literature, to implement these assessments . TheoretThe challenging year of 2020 has offered an unprecedented and valuable opportunity for data collection on the online assessment process. The University of New South Wales in Sydney, Australia is one of many medical schools that was forced to use an online “electronic” OSCE (teleOSCE) with minimal guidance. Final year students underwent their summative OSCE assessments using this online format to comply with COVID-19 restrictions.The following study aims to establish whether the use of the teleOSCE has impacted assessment outcomes. Ultimately, the study aims to facilitate discussion on what skills and domains can effectively be assessed in a teleOSCE to guide future development and use of online clinical examinations.The research was conducted under the ethics approval granted by the Human Research Ethics Committee of the University of New South Wales . Complying with the ethics approval we used administrative assessment data held by the University of New South Wales which required no consent from participants.This study is an observational study which compares the results achieved by the students examined in 2020 via the teleOSCE, with those who were examined under the traditional OSCE format in 2019.In-person clinical OSCEs have been run for many years and staff are familiar with the requirements for implementation. Conversion of this to an online format required several steps. The prime amongst these was the technology aspect  which was entirely novel in this setting. Thereafter, adaptation of the station was required, i.e., to suit an online format. In conjunction, personnel and procedural changes were required, before various stages of testing. The clinical stations are described below, with the technological, personnel, procedural, testing, and training aspects described in The traditional in-person OSCE, as run in 2019, consisted of 9 stations from 7 disciplines  of 12 minutes duration. For each station students are provided with a short summary of a clinical scenario, from which they are expected to take a brief targeted history, and conduct a physical examination, before attempting to diagnose the patient, suggest relevant investigations and management, and answer questions from the examiner. Each station is preceded by 2 minutes reading time and followed by a short period to allow transition to the subsequent station. Within stations students are assessed on their clinical skills in relation to the specific station content, but also on generic aspects such as communication and physical examination skills. To ensure comparability between the teleOSCE, and the in-person OSCE, core features from the latter were maintained in the online version wherever possible. For the most part, this was relatively straightforward since initiation of the consultation with the patient, collection of the history, interpretation of clinical information and summarization of the case by the student could all be easily achieved in the online format . HoweverFor the teleOSCE in 2020, 285 senior students participated in the assessment; while, for the traditional in-person format evaluation of OSCE in 2019, 280 senior students participated. All target students participated in the examinations.Scores of the teleOSCE examination and that of the traditional in-person OSCE.The results of teleOSCE and traditional in-person OSCE for 2 years. The data used in this analysis were the raw scores given by the examiners before modifications made by the post examination standard setting process implemented by the medicine program ,12. ThisThere was no sampling bias because all target students participated in the OSCE and all data was included in the study.The sample size of this study was determined by the availability of participants, all of which were included in the study . Because the study used all available data and the study had no impact on the participants it was unnecessary to limit the number of study participants nor undertake a priori sample size and power calculation . The resIndependent t-test analysis was used to compare the mean scores of student assessment results between 2019 (in-person OSCE) and 2020 (teleOSCE). The comparison was made by disciplines  and separately by domains . This analysis was chosen to identify the impact of the assessment mode on different medical disciplines as well as assessment domains, respectively. Bonferroni correction was undertaken to correct for alpha inflation.In 2019, 280 students undertook the in-person examinations, while in 2020, there were 285 examinees in the teleOSCE. All students completed the entirety of their examinations, and all of their unidentified raw scores were eligible for use in this study. Demographic data was not available for inclusion in this study.In the domain of physical examination, students in 2020 scored 0.277 points higher than those in 2019 . Across all other domains, there was no significant difference in mean scores between 2019 and 2020. These results are illustrated in When analyzing the results by discipline, compared to the 2019 (in-person) students the 2020 (teleOSCE) students scored 0.216 points higher in medicine  and 0.390 points higher in emergency medicine  respectively. Across all other disciplines, there was no significant difference between the mean scores in 2019 compared to 2020. These results are depicted in The cohorts in this study were of comparable size (280 versus 285) and no significant difference were seen in the outcomes of almost all domains  and disciplines. This suggests that the change to an online platform did not influence the performance of students, or the information available to assessors in these areas. However, significant differences are noted in the disciplines of medicine and emergency medicine, and the domain of physical examination.The method of performance assessment utilized in 2019 has been in practice at the University of New South Wales for many years and minor adaptations in methodology have previously been well-described in the literature . There aExploring adjustments made to the method of examination provides insights into why the physical examination domain results may have changed . In bothAdditionally, the information available to the examiner is less in the teleOSCE. Previously, the in-person format permitted an examiner a single observation of the student, with multiple facets, including witnessing the students carry out the steps of an examination. By removing this specific data point, examiners simply have less information with which to make a judgement, a well-established hindrance to validity . ObservaLooking more broadly at performance examination, the observation of the performance of a single skill in a single environment during an assessment has poor generalizability due to case specificity . For insUtilizing student marks to compare the impact of the in-person and teleOSCE has its limitations in that more than simply the student performance and the assessment modality will contribute to this result. Such confounders were not controlled for in this observational study. Furthermore, the in-person and teleOSCE assess different aspects of competence in the domain of physical examination and this may limit scope for comparison in this domain. Of note, the in-person OSCE requires a student to elicit findings by physical examination whereas the teleOSCE requires a student to describe this process . The teleOSCE does impact assessment of physical examination competence; however, this may be due to the inherent constraints of the online format of assessment in this particular domain rather than solely ascribable to differences in student performance between 2019 and 2020.Research on teleOSCE is still in its infancy. Evaluating the method used by the University of New South Wales for performance examination in 2020 has demonstrated that the transition from the in-person performance assessment to a teleOSCE platform was very successful. Bar physical examination, comparing traditional in-person OSCE outcomes with those of the teleOSCE shows no significant changes across the various domains. As such, these online summative examinations can continue to play a role in the broader multimodal assessment system, providing valuable data to examiners when making an accurate judgement about a student’s competency in those domains. However, this study also revealed the need for careful consideration of the way we assess physical examination using teleOSCE. Students can no longer execute the actions of a physical examination on a patient, and as such, examiners have less information with which to make an assessment and this may account for an increase in scores in this domain. With the increased likelihood of utilizing teleOSCE more frequently in the future, we need to identify the physical examination skills that cannot be accurately assessed via teleOSCE and make sure these skills are assessed via workplace-based assessment tools.


Cancer genomic studies often include data collected from several omics platforms. Each omics data source contributes to the understanding of the underlying biological process via source specific  patterns of variability. At the same time, statistical associations and potential interactions among the different data sources can reveal signals from common biological processes that might not be identified by single source analyses. These common patterns of variability are referred to as “shared” or “joint”. In this work, we show how the use of joint and individual components can lead to better predictive models, and to a deeper understanding of the biological process at hand. We identify joint and individual contributions of DNA methylation, miRNA and mRNA expression collected from blood samples in a lung cancer case–control study nested within the Norwegian Women and Cancer (NOWAC) cohort study, and we use such components to build prediction models for case–control and metastatic status. To assess the quality of predictions, we compare models based on simultaneous, integrative analysis of multi-source omics data to a standard non-integrative analysis of each single omics dataset, and to penalized regression models. Additionally, we apply the proposed approach to a breast cancer dataset from The Cancer Genome Atlas.Our results show how an integrative analysis that preserves both components of variation is more appropriate than standard multi-omics analyses that are not based on such a distinction. Both joint and individual components are shown to contribute to a better quality of model predictions, and facilitate the interpretation of the underlying biological processes in lung cancer development.In the presence of multiple omics data sources, we recommend the use of data integration techniques that preserve the joint and individual components across the omics sources. We show how the inclusion of such components increases the quality of model predictions of clinical outcomes.The online version contains supplementary material available at 10.1186/s12859-021-04296-0. Cancer studies benefit from the availability of genomic data, also known as omics. The dimensionality of omics data is extremely high, suggesting the application of dimension reduction techniques. Additionally, omics are available across multiple sources (or ‘blocks’) of data, collected on the same organisms or tissues, and measured on different platforms. A comprehensive understanding of the key underlying biological process relies on an integrative approach able to combine the information arising from such multi-source data. To this end, a large number of statistical methods for the simultaneous analysis of multi-omics data have recently been proposed. Multiple reviews of such methods are available, for example in –3.Data integration techniques are often used to identify ‘joint’  contributions of the data sources to the observed variation, and their simultaneous effect on the biological process under study. Such patterns of variation arise from the interaction among different omics sources, and may not be detected by a separate analysis of each single source. However, the different data sources do not only contain the joint information, but also independent contributions. The separate analysis of each data source has so far been the most common approach used in the omics context, and knowledge about the individual contributions of each omics source is relevant to the understanding of the biological processes of interest. As a consequence, considering only the joint patterns might also prove insufficient, as it overlooks the heterogeneity among single data sources, and their individual signals from the underlying relevant biological process. An example of this can be seen in genomic studies collecting DNA methylation and gene expression data. It is known that methylation regulates gene expression and that this can cause a non-negligible joint structure across the different data sources. For example, they have been shown to contribute together and jointly relate to the occurrence and characteristics of lung cancer , 5. On tSeveral methods that have recently been proposed to address this problem are based on matrix factorization. In this framework, each data block is decomposed into three matrices modeling different types of variation, specifically joint variation across the blocks, individual variation for each data block, and residual variation. One such method is JIVE. JIVE stands for Joint and Individual Variance Explained, it was formulated by  and, alsOther dimension reduction methods have been extended to the case of multi-source data, as for example canonical correlation analysis (CCA)  or partiAdditionally, Principal Component Analysis (PCA) based techniques have been expanded to the case of multi-source data. For example, consensus PCA  consistsIn this work, we focus on prediction models for lung cancer development using both joint and individual components arising from different sources of omics data. We show how the inclusion of both joint and individual components in predictive models leads to a better quality of predictions. The combination of joint and individual components can also facilitate the biological interpretation of the underlying process, although this might still fail as the dimension reduction itself bears the risk of obscuring some relevant information.We use aJIVE to formulate integrative prediction models in a real data set on lung cancer, identifying individual and joint components across three sources of omics data. We chose to use aJIVE because it inherits a good subspace recovery in comparison to other methods , as wellThe data we use stem from a lung cancer case–control study nested within the Norwegian Women and Cancer (NOWAC) cohort study . The assTo further evaluate this approach, we provide an application to a publicly available dataset on breast cancer from The Cancer Genome Atlas (TCGA).K is the number of data sources used in the study. Each block is a matrix with n columns, where n is the number of study subjects. The kth matrix k. The overall dimensionality is denoted as k, Throughout the manuscript, we will denote each data block with Angle based Joint and Individual Variation Explained (aJIVE) is a variant of the JIVE method, based on perturbation of row subspaces. JIVE aims to minimize the squared residual components The first step is based on the choice of the initial ranks for each data block, which are used as a threshold value in the first SVD decomposition of the data blocks. This choice is rather subjective and involves taking into account some bias variance trade-off in the joint signals representation. Although  provide From the aJIVE decomposition, it is possible to obtain the full matrix representation of the original features, as well as the block specific decompositions of each data source and the common normalized scores. The aJIVE implementation is available in Matlab  and R 3.The data used in the following analyses stems from blood samples in a lung cancer case–control study nested within the Norwegian Women and Cancer Study (NOWAC) . All parLaboratory processing and microarray analyses for DNA methylation and mRNA expression are described in . For miRPreprocessing and quality control of methylation data accounted for missing values and intensities below detection thresholds, and included background subtraction and dye bias correction . For mRNBecause of the high computational requirements, we reduced the number of mRNA expressions to |>3, see , 34). Thhylation . We accoWe performed aJIVE on the three levels of omics data. The initial ranks were selected by maximizing the profile likelihood , but difJoint and individual components were used in prediction models. The outcomes of interest were the occurrence of lung cancer (yes/no) and metastasis (yes/no).We fitted logistic models on each outcome using joint and individual components as explanatory variables, in addition to age, BMI and smoking. These models were compared in terms of AUC with the respective models with only age, BMI and smoking as covariates. To assess the performance of the models, we measured the average AUC in a 10-fold cross-validation. We compared these with a non-integrative analysis, obtained by performing PCA separately on each single data source. We fitted a model on the first principal components (PCs) of each data source, and on the same clinical covariates. We chose to include five PCs for each data source, based on the variance explained by the first PCs and on the analysis of screeplots. We included the same numbers of individual components in the integrative model described above.To provide a comparison with a standard supervised prediction method, we ran a lasso procedure that selects signals from all three omics layers and used it to predict the two outcomes of interest. We used 10-fold cross-validation on 2/3 of the data points to select the optimal penalty parameter and we used the fitted lasso model to predict case–control status and metastasis. We ensured the inclusion of the clinical covariates in the lasso models by fixing the corresponding penalty parameters to 0 for age, BMI and smoking status. We compared the quality of model prediction in terms of average AUC across 50 repeats of this procedure.In addition, we used a random forest of 1000 trees to predict case versus control on the basis of joint and individual components, and patient covariates as above . We extracted the AUCs and the out of the bag (OOB) classification errors from the random forest, and we ranked all the variables in importance on the basis of their mean decrease in gini index .https://www.cancer.gov/tcga), and used in the mixOmics project [To assess the predictive performance also in another dataset, we illustrate an application to a subset of data generated by The Cancer Genome Atlas  and the results are similar.Prediction models are validated in a 10-fold cross-validation framework, and such results are further confirmed by random forests. From the cross-validation study, we see that for case–control status, the integrative analysis provides better prediction than non-integrative analysis.As an additional comparison, we use supervised variable selection and fit a lasso model on the three omics layers. Although we would expect that a supervised method, by using information from the response variable in fitting the model itself, results in better predictions, the aJIVE models used here perform similarly (for case vs. control), and substantially better (for metastasis).A possible explanation of generally low AUCs is that prediction models for the NOWAC dataset might also be affected by the time between blood sampling and cancer diagnosis, and we expect the quality of predictions to be higher in subjects with a shorter time to diagnosis. We stratified cases into two subgroups based on time to diagnosis (higher vs. lower than the median time) and obtained higher in-sample AUCs for the classification of case versus control in subjects with a closer time to diagnosis. For the classification of metastasis, the sample size in the two time to diagnosis classes is not enough to draw conclusions. In the application to the NOWAC dataset, it is interesting to observe that one genomic component identified from aJIVE, specifically one individual component from the methylation data, ranks above smoking in importance for case–control classification Fig. , smokingIn the TCGA example, the high prediction quality of the non-integrative model is likely to arise from the definition of subtypes, which is based on levels of mRNA expression. In the non-integrative models, the mRNA principal components highly contribute to the prediction quality . Although we use multiclass ROC curves in this example, a dichotomous classification of the tumor classes could provide a deeper understanding of the models and easier comparison with the logistic case.While this work provides preliminary evidence of the importance of an integrative analysis of the omics sources, a more thorough investigation of the joint and individual components could help identifying relevant biological patterns for future research. An example can be given by the underlying biological processes involving smoking and lung cancer: the omics signals that are dominating the components could be important risk factors for lung cancer, in addition to being informative about present or past smoking, and their interaction could shed light on the relevant underlying biological processes. Although a functional interpretation of such processes and of their link to the clinical outcomes is not straightforward, an investigation of the aJIVE components could provide further information that would not be identified by a non-integrative analysis of the separate omics sources.The chosen approach for variable filtering is based on variance for mRNA, and on genomic location and variance for methylation. Specifically, the top 5000 most variable mRNAs are selected and CpGs are then selected based on their location on genes, by including CpGs located on the same genes as filtered mRNAs. The top 10,000 most variable CpGs are included in addition to these. We expect that choosing signals that are on the same gene locations, and therefore naturally associated, will result in very relevant joint contributions and possibly obscure the individual components associated with methylation. The inclusion of the most variable CpGs, independently from their gene locations, solves this issue. Varying the proportions of CpGs that are selected based on their variance and on their gene location can give rise to different joint and individual contributions, and this aspect needs to be fully considered in the interpretation of the results. In the supplementary material (Additional file One of the main issues in aJIVE is the selection of initial ranks. The most common method for the choice of initial ranks in aJIVE is the visualization of screeplots, which is subjective and highly sensitive to noise in the data. The profile likelihood idea suggested by  partly aThe high dimensionality of the data motivates the use of sparse methods, which reduce the number of variables included in the model and provide an easier interpretation of the results. A sparse version of the aJIVE method could be used for this purpose, by introducing a penalty term in the decomposition to induce variable sparsity. This has not been specifically implemented for aJIVE, but  discuss Finally, one aspect that is not accounted for in aJIVE is the presence of partially shared components. When joint components are only shared by, for example, two out of the three data sources, they will not be identified by aJIVE. This is a limitation of most data integration methods, and we expect partially shared components to result in even better prediction models. A way to investigate partially shared patterns is provided in the SLIDE method by , and is Our study shows how integrative models that include both joint and individual contribution of multiple datasets lead to more accurate model predictions, and facilitate the interpretation of the underlying biological processes. We use joint and individual contributions of DNA methylation, miRNA and mRNA expression to predict cancer development in a lung cancer case–control study, and breast cancer subtype in a dataset from The Cancer Genome Atlas. We show that the use of joint and individual components leads to better prediction models, and to a deeper understanding of the biological process in hand.Additional file 1. Different filtering methods on the NOWAC dataset.Additional file 2. Effect of initial ranks on the proportion of variance explained.


In 2018, the government of China decided to develop Hainan Province as the country's first free trade port operating within the country's socialist system. Based on this strategy, Hainan reformed its medical laws and policies to make it freer and more open. For example, Hainan formulated policies for more rapid and convenient access of foreign medicine and sanitary equipment (MSE), allowed manufacturers to register MSE in China with real-world data (RWD), and provided legal and visa conveniences for international medical teams to carry out various activities, including: diagnosis, treatment and scientific research. Hainan's reforms are not only conducive to the improvement of local medical and public health levels, but also provide opportunities for international MSE manufacturers and medical research institutions swiftly to enter China's huge medical market. However, with opportunity comes risk: Hainan should be on guard against public health risks associated with medical tourism, and decide how to strike a reasonable balance between protecting local MSE enterprises and improving the accessibility of imported MSE through policies and legislation. Finally, the paper recommends that Hainan should improve the regulatory system as soon as possible to ensure the quality of diagnosis and treatment in its new hospitals, and deal with data and information security risks in the RWD research. China is now the world's largest exporter and commodity trader . As an eEarlier, China had put forward two cooperation initiatives: “Silk Road Economic Belt” and “21st Century Maritime Silk Road” in 2013  . This neIn 2018, China's President Xi Jinping announced that the country would build its first socialist system-based free trade port in Hainan Province. The aim was to develop it as a pilot zone for China's exploration of further reform and the opening-up of various fields . The cenHainan Free Trade Port Law of the People's Republic of China on June 10, 2021. The law granted Hainan Free Trade Port (HFTP) a high degree of legislative autonomy. According to Article 10 of the law, HFTP can suspend application of some national laws and regulations in the region and gained the right to formulate local laws in relation to special policies which are only applicable within the region  before it can be imported  . AnnuallMSE is the cornerstone for promoting good public health. Clinical evidence of evidence-based medicine, a new model of modern clinical practice and research, mainly comes from large-sample RCTs and meta-analyses . HoweverRCTs are currently the recognized standard for evaluating the efficacy of MSE in countries around the world . RCT res21st Century Cures Act was passed in the USA, which authorized the US Food and Drug Administration to use RWD, where appropriate, as the approval evidence for post-market research and new indication development of MSE  has attracted increasing attention. RWS is based on the premise of non-intervention, that is, where treatment measures are non-randomly selected according to the actual condition and wishes of patients. Data related to the MSE used and the health status of patients  is then collected and analyzed. Conclusions are drawn from evidence from large samples, long-term evaluation and statistical analysis, so as to obtain data on evidence-based medicine for MSE. The purpose is to ascertain its medical effectiveness, that is, sufficient real-world evidence (RWE) . In 2016t of MSE .Regulations for the Supervision and Administration of Medical Devices in the region. Hainan has promulgated the Implementation Plan of the Pilot Work of Clinical Real-World Data Application in Hainan Boao-Lecheng Pilot Zone of International Medical Tourism. According to this policy, MSE without registration in China can be imported and used on a small scale in the region after being licensed. The clinical data generated during the use of licensed MSE can be converted into RWD and RWE for registration and approval in China after scientific and strict design, collection, processing, analysis and evaluation  were allowed to travel to other regions for treatment on a personal basis. However, the central government discovered that this regime of diagnosis and treatment bred medical corruption. For example, some physicians began to neglect their duties and sought to practice medicine under their own names so as to generate higher incomes . In respIn response, HFTP experimented in becoming a platform provider which “does not ask for ownership, but for use” rather than a resource owner. HFTP also established a new type of “shared hospital” , responsIn general, HFTP has quickly carried out a large number of reforms in the medical field, providing increased convenience and preferential policies for medical resources from other regions or countries to enter China. This has also had positive impacts on the public health status of HFTP. On the other hand, HFTP's reforms also face significant challenges.HFTP has limited local medical resources with a per capita gross domestic product of fewer than 10,000 US dollars . This maSuch openness offers HFTP residents the opportunity to enjoy the latest MSE in line with the international market and the expertise and resources of advanced medical teams from other countries and regions. Due to the high-level of tariff autonomy in HFTP and the good quality and low cost of medical infrastructure in the region, the prices of related MSE and diagnosis and treatment services has been significantly reduced, effectively lowering patients' treatment costs. For example, the cost of Boston keratoprothesis in HFTP is roughly 14% of that of similar operations abroad .HFTP's openness is also conducive to the improvement of the health status of some disabled people. For example, the specific MSE urgently needed by some disabled people with rare diseases (such as multiple sclerosis) is not produced in the Chinese mainland. To enter China's market , this tyIn addition, the reform of HFTP also offers good opportunities for international pharmaceutical enterprises. China's total health spending reached ¥6.5196 trillion in 2019 (about US$1.0073 trillion based on the current exchange rate) , making The reform of HFTP faces many challenges. In the current stage, medical tourism-associated public health risk is the major challenge facing the fields of medical and public health. HFTP has established nine new hospitals in Boao Lecheng, including two stem cell hospitals whose main business is anti-aging treatment . Due to Second, the acceleration of foreign MSE imports has also brought new challenges to the field of intellectual property management of HFTP. From 2012, China promised to implement stricter intellectual property protection, rapidly revise a series of laws and regulations such as the patent law, and establish new specialized intellectual property courts, one of which is located in HFTP  Thanks tThird, the operation mode of shared hospital may have a negative impact on its diagnosis and treatment quality. A shared hospital provides a new hospital business model. It also means that a shared hospital will be composed of dozens of non-resident teams that do not necessarily relate easily to each other. For example, teams and hospitals will have less experience in daily cooperation and work docking than traditional hospitals. Unfamiliar cooperation and differences in work habits may lead to an amplification of avoidable medical mistakes. For example, in January 2021, a patient died while undergoing cochlear implantation surgery in a shared hospital. His family then pointed out that there were a series of avoidable low-level technical errors in the diagnosis and treatment process at the hospital, including the wrong recording of the patient's age and medical history . PerhapsFourth, the collection and application of RWD brings new regulatory challenges for HFTP in terms of data and information security. HFTP approved the reform measures of RWD, which have greatly improved the registration and listing speed of MSE. However, compared with the mature regulatory system of RCT in China, the regulatory system for RWD in HFTP is still not perfect. In terms of data and information security, HFTP requires all parties involved in RWD research to conduct security processing on data  and establish a robust data security management system . HoweverAnother concern is that the rapid introduction of foreign MSE may impact on local enterprises' R&D and production. Currently, there is still a big gap in MSE R&D and production capacity between Chinese enterprises and western counterparts . AlthougHowever, we believe that HFTP's reform policy of accelerating the import process may have deepened the inferior position of Chinese enterprises in some areas, but this may be within the country's previous plans. At present, HFTP is mainly licensed to import MSE that is difficult for China to achieve domestic substitution in a short time. Most are specific drugs for the treatment of cancer and rare diseases. China Customs has previously reduced the tariff rate of these two types of MSE to 0% . It seemOverall Plan for the Construction of Hainan Free Trade Port (OPCHFTP) issued by the central government, although OPCHFTP makes a few principled provisions, such as:Overall, the reform of HFTP in the medical field is still in its infancy and faces many challenges. This paper has argued that HFTP's reforms in the medical field face more institutional challenges than reforms in various areas, including finance and taxation. This may relate to the lack of a mature domestic system template for HFTP's reform in this field. China has not yet formulated a systematic health law. The current health legal system is composed of more than 30 old and new laws. The lack of coordination between laws and sometimes conflicting situations still occurs, making it difficult to provide a systematic legal template for the reform of HFTP . In addi“We should support Hainan in introducing high quality foreign medical resources from abroad. We must draw from the trial experience of regional medical centers to explore and support the building of regional medical centers in Hainan” .–Article 12, Section 1,Chapter III, OPCHFTPIn the absence of a systemic template, HFTP must try to construct a new institutional concept and framework for its medical reforms. While this implies that HFTP's reform may face additional unexpected challenges, as stated in OPCHETP, HFTP's reform experience and lessons in this field will still become an important reference for national reforms .HFTP is called “the pilot zone of national reform and opening up” by the Chinese government . This meThe original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.All authors made a significant contribution to this work, in relation to the conception, study design, execution, acquisition of data, analysis, and interpretation. All authors were involved in drafting, revising or critically reviewing the article, and gave final approval to the current version. Finally, all agreed on which journal the article should be submitted to and are accountable for all aspects of the work.This article is an outcome of the Hainan Provincial Philosophy and Social Science 2020 Planning Projects [Grant Number: HNSK(YB) 20-04].FQ is a Fellow of the Royal Society of Arts (UK). YW is employed by Danzhou City Construction Investment Co., Ltd. QW is the Dean of Hainan University Law School. He is also a council member of the China Law Society, executive director of China Civil Procedure Law Research Institute, chairman of China Pacific Society Natural Resources Law Research Branch. The remaining author declares 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.


Concern regarding the reliability and accuracy of the health-related information provided by online newspaper articles has increased. Numerous criteria and items have been proposed and published regarding the quality assessment of online information, but there is no standard quality assessment tool available for online newspapers.This study aimed to develop the Health Information Quality Assessment Tool (HIQUAL) for online newspaper articles.We reviewed previous health information quality assessment tools and related studies and accordingly developed and customized new criteria. The interrater agreement for the new assessment tool was assessed for 3 newspaper articles on different subjects  using the Fleiss κ and Gwet agreement coefficient. To compare the quality scores generated by each pair of tools, convergent validity was measured using the Kendall τ ranked correlation.Overall, the HIQUAL for newspaper articles comprised 10 items across 5 domains: reliability, usefulness, understandability, sufficiency, and transparency. The interrater agreement for the article on colorectal cancer was in the moderate to substantial range , while for the article introducing obesity genetic testing it was in the substantial range, with values of 0.63 (SE 0.28) and 0.86 (SE 0.10) for the two measures, respectively. There was relatively low agreement for the article on hypertension diagnostic criteria at 0.20 (SE 0.10) and 0.75 (SE 0.13), respectively. Validity of the correlation assessed with the Kendall τ showed good correlation between tools .We developed a new assessment tool to evaluate the quality of health information in online newspaper articles, to help consumers discern accurate sources of health information. The HIQUAL can help increase the accuracy and quality of online health information in Korea. With advancements in technology, public interest toward health has increased. This has led to the public actively seeking health-related information and enhancing their medical expertise beyond simply managing their diseases , which hThere are various tools used to assess the quality of health-related information, including the DISCERN instrument, created by the University of Oxford ; the HeaWith the increased use of the internet for information dissemination, the numbers of online newspaper articles and users have rapidly increased. According to a survey conducted in 2018, 63% of 3425 participants indicated that they preferred using the web to receive news, while only 17% of them chose print newspapers . The resAccording to the Korea Press Foundation, this trend can be seen in Korea as well, where 80.8% of the total population read newspaper articles via a mobile device . As the This study can be divided into four steps . First, intrinsic, contextual, representational, and accessibility—and presented in a hierarchical framework to understand DQ from a consumer's perspective. Intrinsic DQ means that facts have quality in their own right; contextual DQ emphasizes the situations that must be considered to assess the context of the information; representational DQ emphasizes a format that is concise and consistent and data whose meaning is understandable and interpretable; and accessibility DQ emphasizes the significance of the parts of the framework. Our study also used this category to organize domains of various previously developed evaluation tools.A review of existing literature was conducted to select the domains that correspond to the content of the questions guiding the development of the HIQUAL. A study by Wang and Strong was used to classify various dimensions included in existing assessment tools . In thisDeveloped by Oxford University, the DISCERN instrument evaluates information on disease and treatment under 3 domains, including 8 reliability items, 7 quality of information items, and 1 comprehensive evaluation, and has established feasibility and reliability ,26. The In Korea, Lee et al classified the common domains presented in previous studies as representation, contents, usage, and connection . A studyThe dimensions of the existing tools were classified according to the categories used by Wang and Strong  25]. Th. Th25]. We analyzed the interrater agreement to ensure the consistency of the evaluation tool. A total of 3 interrater agreement analyses were performed in the process of revising the HIQUAL. The first and second evaluations were performed in a pilot study using a nonfinalized version of the tool with 3 articles, while the third evaluation was performed using the final version of the tool. News articles used in the assessment were randomly selected from among the most-viewed articles of the month in the health section of a portal website, which was the most popular online search engine in Korea ; the finThe interrater agreement used two methods (Fleiss κ coefficient and Gwet agreement coefficient [AC]). Fleiss κ is a method used to measure the degree of agreement between two or more raters ,35, wherThe validity was verified by comparing the results of 3 tools: DISCERN, QUEST, and HIQUAL. The Kendall rank correlation coefficient (τ) proposed by Kendall measures the association and strength between paired observations . The KenThe final version of the HIQUAL is presented in a table format. The newly developed tool consists of the five domains of reliability, usefulness, understandability, sufficiency, and transparency, and has 10 questions . The evaUsing the HIQUAL, 5 raters evaluated 3 online newspaper articles. The interrater agreement was then analyzed . AgreemeIn terms of the statistical values of agreement, the coefficients for Fleiss κ were lower than those for Gwet AC. However, the overall percentage of agreements, including that of the third article with the lowest interrater agreement, was higher than 0.70. Fleiss κ is a model developed in Cohen κ, which may show the kappa paradox . Gwet ACThe results of the validity tests are shown in In this study, we developed a novel tool to evaluate the quality of health information in online newspaper articles by reviewing previous studies and existing tools. The HIQUAL consists of 5 domains, namely reliability, usefulness, ease of understanding, sufficiency, and transparency. We found the HIQUAL to have high interrater agreement. After evaluating a total of 16 online newspaper articles, the HIQUAL was highly correlated with two other tools—DISCERN and QUEST. The results of the analysis, divided into treatment articles and diagnosis and prevention articles, also showed similar results to the overall analysis.In the process of developing the HIQUAL, a variety of previously developed quality assessment tools were compared. Among them was the DISCERN instrument, which consists of 16 questions and assesses the quality of treatment information for diseases; several studies have demonstrated its validity and reliability ,46. In KSince the number of consumers using internet health information has increased in Korea, Son presented criteria for quality evaluation based on prior studies that reviewed domestic and foreign health information websites . This stA variety of tools have been used, but most of them are limited in the purpose and objective of evaluation and may not be suitable for evaluating online newspaper articles. Newspaper articles cover a wide range of content, ranging from diagnosing, treating, and preventing diseases to health care and new scientific discoveries. It should be considered that insufficient information, as well as information supported by scant evidence, can be communicated to an unspecified number of people in this process. Additionally, it is also necessary to convey sufficient information from an objective and independent perspective, as well as an appropriate understanding of the uncertainty of scientific research . HoweverThere are points to consider when applying the HIQUAL. First, it is aimed at health-related online newspaper articles, so it is difficult to apply it to other forms of media or information. A tool that can cover a variety of evaluation targets may degrade its own accuracy and value, and well-made existing tools such as DISCERN and HONcode also limit their evaluation targets. Consequently, a tool developed in accordance with the characteristics and purpose of the evaluation target can be determined well in advance to evaluate the evaluation medium. Furthermore, it can be used more effectively when applied to articles that require neutral and sufficient information delivery, such as new medical findings or treatments, than to articles that convey well-known universal knowledge. With the evolution of technology over time, the issues of inaccurate online information will continue to arise, so our tool can be useful in targeting online newspaper readers.The second limitation is the problem of the users. The result of the interrater agreement of the third article, which had a lower level of agreement than the other articles, was analyzed. We confirmed that the level of agreement increased when we examined the results of 4 medical specialists. To use this tool properly, judgment on medical validity or errors is necessary, and considering this, it is desirable for medical doctors or professionals in the field of health care to participate in the evaluation. In addition, as the results of the interrater agreement show, there may be some differences in the results of the assessment among raters. Therefore, in such a case, quality evaluation may be considered by two or more evaluators individually, and a final evaluation may be derived through consultation. During the actual application, it may also be useful to train the raters in advance to fully understand the assessment tools or to organize and operate an evaluation group where raters who are familiar with the tools can continue to participate.Third, although the criteria and tools have been revised and identified by repeating the process of verifying reliability, the fact that the confirmation of the reliability and validity of the final completed tool was made using a relatively small number of articles may constitute another limitation. The fact that the final evaluation was made by a small number of experts and that they were not a representative group could also be a limitation of this study.This study developed a new evaluation tool, the HIQUAL, for performing quality assessment of health-related online newspaper articles. For more effective use of the tool, it is desirable to establish a system that continuously monitors and evaluates health-related articles and delivers evaluation results to consumers so that they can make accurate judgments. Moreover, this tool could help information producers, such as journalists or reporters, produce quality health-related information articles. With the quality assessment tool, data producers can provide accurate and understandable information for online health-related articles. Using the HIQUAL, it will be possible to establish a platform that conducts continuous evaluations and regularly publishes the results, giving audiences access to high-quality health-related online newspaper articles. In addition, this tool will guide practitioners in the medical field in advancing sound strategies for disseminating health information among the general public and promote collaboration between experienced medical practitioners and news sites. Against the backdrop of the increasing number of health-related newspaper articles, as well as concerns about their quality and accuracy, this tool may be useful for assessing the quality of online health information in Korea.


The Drone Forensics (DRFs) field is a branch of digital forensics, which involves the identification, capture, preservation, reconstruction, analysis, and documentation of drone incidents. Several models have been proposed in the literature for the DRF field, which generally discusses DRF from a reactive forensic perspective; however, the proactive forensic perspective is missing. Therefore, this paper proposes a novel forensic readiness framework called Drone Forensics Readiness Framework (DRFRF) using the design science method. It consists of two stages: (i) proactive forensic stage and (ii) reactive forensic stage. It considers centralized logging of all events of all the applicants within the drone device in preparation for an examination. It will speed up gathering data when an investigation is needed, permitting the forensic investigators to handle the examination and analysis directly. Additionally, digital forensics analysts can increase the possible use of digital evidence while decreasing the charge of performing forensic readiness. Thus, both the time and cost required to perform forensic readiness could be saved. The completeness, logicalness, and usefulness of DRFRF were compared to those of other models already existing in the DRF domain. The results showed the novelty and efficiency of DRFRF and its applicability to the situations before and after drone incidents. Digital forensics is a significant domain that involves capturing and analyzing cybercrimes. It has many branches: database forensics, IoT forensics, cloud forensics, drone forensics, wireless forensics, malware forensics, mobile forensics, network forensics, and data forensics. These branches have numerous and redundant forensics models, frameworks, approaches, policies, procedures, and tasks. However, the digital forensics domain suffers from the absence of a standardized forensic framework to deal with all these branches. To deal with all cybercrimes, the digital forensics field consists of two stages: proactive forensics and reactive forensics. Proactive forensics refers to forensic readiness before a crime happens; this stage prepares and collects digital evidence to avoid any future risk or disaster. On the other hand, the reactive forensics stage refers to the process after the occurrence of the crime. The main aim of this stage is to identify, capture, preserve, analyze, and document cybercrime. Therefore, all digital forensics branches are categorized under these two stages. Studies on the proactive forensics approach have mainly explored forensic readiness within the context of the ISO/IEC 27043:2015 standard [The rest of the article is structured as follows: Several models and frameworks have been proposed for the DRF field in the literature. These models and frameworks have discussed DRF from four perspectives: (1) forensic analysis, (2) nonforensic analysis, (3) forensic framework, and (4) application in the forensic analysis . For exaSimilarly, in , the DJIThe authors in  attempteA forensic framework comprising 12 phases was designed in  to introFindings reported in  showed tIn another project , a forenIn , the resThe authors in  proposedIn , a captuIn , an inclIn another research , a new DFurthermore, the authors in  conducteMoreover, in , the resThe electromagnetic watermarking concept was introduced in  as a tecIn , the autIn , drone aThe researchers in  proposedIn , the secThe overall legal process to gather and examine any drones from the crime scene and examine inside the lab has been discussed by .Also,  proposedThe review of the literature revealed that the DRF field lacks a forensic readiness framework to structure, organize, and unify the DRF field from a readiness perspective. Thus, this study proposes a comprehensive readiness forensic framework applicable to the DRF field.This paper adopted a Design Science Research (DSR) method to develop a drone forensic readiness framework. DSR is a method used to generate original and insistent objects for a particular problem area that allows analytics to be studied . For thiIdentifying Search Engines: seven common search engines are used in this study to collect data: IEEE Explorer, Web of Science, Scopus, Springer, ACM, Science Direct, and Google Scholar.Collecting drone forensic models: to collect data, the authors identified keywords . Based on the keywords, 132 articles were collected from the literature, as shown in Filtering data: regarding the time scope, the search was confined to the studies published between 2000 and January 2021. For the purpose of the present paper, documents such as research articles, conference papers, dissertations, books, and book chapters were considered, and the other types of documents were excluded. In addition, the duplicates and screening of the topic and abstracts were ignored. Stage I: searching stage: this stage involves conducting a literature review and collecting data. It consists of three steps:Identifying the development models: this step aims to identify the development and validation models used to develop and validate the forensic readiness framework. Extracting common concepts and processesCommon processes and concepts were execrated from 32 identified models. The extraction criteria were adopted from : the proCombining extracted processes and conceptsthe common concepts or processes with similar meaning or functioning regardless of their names or synonyms were combined into the same category, as presented in Identifying relationshipsthis step identifies the relationships among proposed drone forensic processes and concepts. A survey of drone forensic models showed various UML relationships amongst the concepts and processes that were common among all such models. Three kinds of common UML relationships were discovered: Association, Specialization/Generalization, and Aggregation.Proposing a drone forensic readiness framework:  the relationships identified in the above step were used to create the drone forensic readiness framework applicable to the drone forensics field see . It consStage 1: Before the Occurrence of Drone Crime. This stage represents the main stage of the proposed framework. The main aim of this stage is to monitor and capture the whole drones' activities before any crime or incident happens. It is called the proactive forensics stage. It consists of two phases: the monitoring & capturing phase and the preservation phase.Monitoring and Capturing Phase. The purpose of this phase is to observe and secure the flight paths of the drone and capture the whole streaming activities . For security purposes, the monitoring component uses a firewall to filter both incoming and outcoming wireless traffic. “Filtering” is defined as the process of controlling access by examining all the packets based on the content of their headers. However, a firewall cannot detect all the misconduct data since some laptop/mobile devices may make their identities unclear to appear as legitimate users of the network. For that reason, our proposed framework employs a component called the Capture Component (CC), which records or logs all the monitored data sent from the drone. CC gathers all the volatile and nonvolatile data monitored to gather potential digital evidence. Each drone has its associated CC that captures/logs the data passing through that laptop/mobile. CC captures/logs the data in log files, as depicted in Preservation Phase. The primary goal of evidence preservation is to ensure that absolutely no changes are made to the captured/logged data after collection [llection . Figure Stage2: After the Occurrence of Drone Crime. This is the second stage of the proposed framework. It involves conducting a normal digital forensic investigation process to reveal the evidence of the drone crime. It is called the reactive forensic stage. It consists of two processes: examination and analysis process, and documentation and reporting process. The examination process is used to check the authenticity of the gathered data against any tampering through rehashing the captured data. Thus, if the captured data are not authentic, the investigation team should return to the preservation stage to take another original copy. If the captured information is correct and has not been tampered with, the data will move to the analysis phase. The main purpose of the analysis phase of the proposed framework is to mine and extract the data from ES to come up with evidence that can associate a particular adversary with a criminal activity committed on the drone device. The analyzed data are next passed on to the documentation and reporting phase. Although it is not within the scope of this study to discuss data mining in detail, the use of data-mining techniques should not be overlooked during the process of conducting a digital forensic investigation.During the reporting phase, the final evidence is prepared for the entire digital forensic investigation. The data are used by cyber forensic experts when they testify in a court of law that an intruder should be found guilty based on the evidence that they have gathered in their digital forensics investigation. The prosecutor in a court of law has to decide whether the intruder is guilty or not, based on the evidence presented by the cyber forensic experts concerned.Validating Drone Forensic Readiness Framework. This is the sixth step of the development and validation process of the drone forensic readiness framework. It is used to validate the proposed framework's completeness, logicalness, and usefulness through a validation technique, namely a comparison of its performance with other models [r models . This coStage II: Development and Validation Stage: this stage involves developing and validating DRFRF. It consists of several steps:Through this study, DRF field has suffered from lacking a forensic readiness framework to structure, organize, and unify the DRF field from a readiness perspective, as revealed previously in Without discounting the aforementioned capabilities of DRFRF, the authors of this paper take a step to explore the advantages of DRFRF that supersedes the existing models and the limitations. It is important to note that the limitations that have been identified have carefully been analyzed and positioned to be relevant for inclusion as future work beforehand.The DRFRF has been juxtaposed as a comprehensive framework that has major inclusion and integration of processes and concepts that have been suggested by existing drone investigation models. While it is important to acknowledge that these models have offered very significant insights towards the development of DRFRF, we put across one core advantage that DRFRF holds. DRFRF is able to cover preincident preparation that has explicitly been presented at a readiness phase. This phase not only is able to shorten the process of conducting an investigation in drones but also saves time due to the availability of forensic evidence when needed. Additionally, the scope of the major phases in the proposed DRFRF  have been described well based on their functionalities, where DRFRF hold an advantage of leveraging the prescribed guidelines for information technologies, incident investigation techniques, and processes that explicitly are adapted verbatim from ISO7IEC 27043. Next, the DRFRF has room for further integration, which means it is easy to incorporate other suitable processes because of how the different phases have been classified and as a result, the DRFRF activities accept other processes that can be deemed as essential during integration.At the time of writing this paper, there currently does not exist specific guidelines or standards that address incident response categorically and as such, incident response can only be encapsulated in ISO/IEC 27043 investigative process classes from a generic perspective. This is a current limitation of this framework. However, an inclusion or adoption of these (standardized) guidelines will be inevitable.Drone forensics has grown tremendous care from academics working in this field. Drone Forensics (DRF) is a significant field that encompasses the investigations for identifying and discovering drone crimes. Several models and techniques have been proposed for the DRF field. These techniques and models use the interior logs of devices and their controllers to recognize any malicious action. They can duplicate the flight routes that can be used by experts during forensic investigates. The verification and security of drones have also been improved to avoid intrusion. However, the literature lacks a standardized forensics model/framework to deal with different drone crimes. Therefore, this study provided a novel forensic readiness framework that can be applied to the DRF field to deal with drone crimes from both preincident and after-incident perspectives. The proposed DRFRF consists of two stages: (I) proactive forensics stage and (II) reactive forensics stage. The production from Stage I is mainly well-defined as the input to Stage II where chain-of-custody and chain-of-evidence are guaranteed correspondingly. Frequently, the postincident process is referred to as an afterthought which, theoretically, leads a frequent drone crime. Thus, the proposed framework can be defined as a comprehensive framework that could be used to preempt, prepare for, and prevent a drone incident occurrence. The proposed framework DRFRF was validated through a comparison with other existing models. To demonstrate the effectiveness of the proposed DRFRF, a real scenario is required; thus, the future work of this study will focus on the implementation of the DRFRF in a real case.


Asthma is the most common inflammatory disease affecting the lungs, which can be caused by intrauterine or postnatal insults depending on the exposure to environmental factors. During early life, the exposure to different risk factors can influence the microbiome leading to undesired changes to the immune system. The modulations of the immunity, caused by dysbiosis during development, can increase the susceptibility to allergic diseases. On the other hand, immune training approaches during pregnancy can prevent allergic inflammatory diseases of the airways. In this review, we focus on evidence of risk factors in early life that can alter the development of lung immunity associated with dysbiosis, that leads to asthma and affect childhood and adult life. Furthermore, we discuss new ideas for potential prevention strategies that can be applied during pregnancy and postnatal period. Asthma is the most common heterogeneous inflammatory lung disease appearing generally in childhood. Adults are also affected, and more than 339 million people of all ages are living with asthma worldwide. Over 80% of asthma-related deaths occur in low-and lower-middle income countries . The patIn this sense, there is not a unique cause or major determinant risk factor that contributes to the development of asthma. Apparently, the combination of several factors in early life and inflammatory response due to it in a period of rapid growth and development of the lung causes structural and immune impairments that leading to asthma . TherefoAs above mentioned, asthma is developed due to several risk factors and can be linked with prenatal or early life events, causing it to appear specially in childhood. During early life, asthma can be associated with factors  such as In the recent years there were many advances in gene sequencing technology, expanding the knowledge on lung and gut microbiome, and on the significant role of the interactions between these two niches in the development and incidence of chronic airway disease. The airways are composed by a resident microbiota that develops after birth and interacts with different body sites, such as the gut, and its composition changes in health and disease .Escherichia coli at age 1 week while colonization by Citrobacter freundii, Clostridium species, Enterobacter cloacae, Enterococcus faecalis, Klebsiella oxytoca, Klebsiella pneumoniae, and Staphylococcus aureus were associated with cesarean section. However, at age 1 year this gut microbial perturbations were not apparent. Therefore, the same group conducted a cohort prospectively study with 700 children to investigate a risk of developing asthma in the first 6 years of life  that can presents food sensitization in the early life , incentive for breastfeeding and enhancing other microbial exposure through the “farm effect,” as endorsed by the hygiene hypothesis , 40. BeyLactobacillus rhamnosus- on postnatal period, showed a reduced risk of childhood asthma  and metabolites, dietary derivatives and helminthic compounds in order to prevent the disease development .Moreover, The Finnish Allergy prevention program  describedysbiosis. Understanding its roles and the immune responses due to this imbalance in asthma are promising both to comprehend the disease pathophysiology and to elaborate preventive strategies. Dietary interventions are considered safe and promising to boost the immune system and attenuate asthma symptomatology in children. Nevertheless, tackling asthma prevention is challenging because of the existing knowledge gap on the immune pathways that predispose some infants to develop asthma and not others. It seems that the beneficial effects resulting from prevention approaches are due to the combination of them, instead of just one strategy. However, further research is needed on observational studies and clinical trials on the effects of using different combined strategies vs. a sole intervention for asthma prevention.The changes in microbiome composition due to diseases is called LG, JA, AF, AS, GS, DM, and LO conceived the design and concepts. RP, AC, VO, and IC wrote the manuscript. All authors contributed to the editing and revision of the manuscript and approved the submission.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.