Background: The COVID-19 pandemic forced health-related organizations to rapidly launch country-wide procedures that were easy to use and inexpensive. Body temperature measurement with non-contact infrared thermometers (NCITs) is among the most common procedures, both in hospital settings and in many other entities. However, practical hospital experiences have raised great doubts about the procedure's validity.Aim: This study aimed to evaluate the validity of the body temperature measured using NCITs among oncological and transplant patients who took the polymerase chain reaction test for SARS-Cov-2 PCR+ and PCR- in a Romanian Hospital.Methods: Body temperature was measured for 5,231 inpatients using NCITs. The cutoff point for fever was equal to or above 37.3°C. Patients then completed a questionnaire about their symptoms, contact, and travel history.Findings: Fever was detected in five of 53 persons with PCR+, resulting in a sensitivity of 9.43% . No fever was verified in 5,131 of 5,171 persons with PCR-, resulting in a specificity of 99.15% . A defensive vision of NCIT procedure (maximum standard error only in favor) had a sensitivity of 15.09% .Conclusions: The use of NCITs in a triage provides little value for detection of COVID-19. Moreover, it provides a false sense of protection against the disease while possibly discriminating individuals that could present fever due to other reasons, such as oncologic treatments, where fever is a common therapeutical consequence. The consumption of qualified human resources should be considered, especially in the context of the shortage of healthcare professionals worldwide. The infectious disease COVID-19, caused by the SARS-CoV-2 virus, has been widely disseminated globally, with over 40 million infection cases and over 1.1 million deaths registered during the pandemic  are mild , it has In Romania, each hospital carries out procedures for screening, testing, and patient management , travel history, contact history, and criteria for different categories of patients or medical personal to qualify for PCR testing. Recommendations by the Center for Disease Control and Prevention (CDC) and European Centre for Disease Prevention and Control (ECDC) , 7 are iGlobally, massive non-contact temperature screening is used in hospitals, malls, office buildings, airports, and so on, as a fundamental test in the COVID-19 triage for clinical, epidemiologic, and other public health reasons. According to the U.S. Food & Drug Administration (FDA) , the norOne study reported that fever was registered in ~43% of COVID patients at the time of admission to hospital and in ~89% by the time of hospitalization . The medIn many cancer patients with fever, the symptom could be due to febrile neutropenia (FN) or even a flu-like syndrome .Cancer patients are at a higher risk of any infection due to immunosuppression, commonly caused by cancer and cancer-related treatment. Thus, they are at a higher risk of COVID-19 infection than the general population. Patients receiving active cancer treatment are at a higher risk than those in remission.Fever is also a common clinical manifestation in patients who have had a transplant, as well as for other clinical reasons not related to COVID-19. Although the purpose of hematopoietic stem cell transplant (HSCT) is curative, and the patient could suffer damage if the procedure is delayed, treatment-related toxicities and technical difficulties would be amplified and overwhelming during this pandemic. Therefore, professional societies such as the European Society for Blood and Marrow Transplantation (EBMT) have issued guidelines to help physicians during the pandemic. These include sorting and testing patients (including those without symptoms) before being admitted to a transplant ward and allocating separate areas, distinct from the transplant units, for symptomatic patients awaiting COVID-19 test results. There are also strict rules for stem cell donors.Highly immunocompromised pediatric and adult hematopoietic cell transplant (HCT) recipients frequently experience respiratory infections caused by viruses that are less virulent in immunocompetent individuals .Respiratory viral infections in allogeneic HCT recipients contribute to significant mortality rates ranging between 10 and 50% if the infection progresses to the lower respiratory tract .Another dimension that should be discussed is that fever is a non-specific, non-sensitive indicator of infection. In developing countries, infections are the major cause of a fever of unknown origin , 19.In Romania, each hospital/medical center allocates resources for screening with questionnaires and body temperature. The Clinical Institute Fundeni (CIF) is one of the few hospitals in the country doing PCR tests for all inpatients, in view of its specific oncology and transplants profile, and is aligned with similar hospitals in Europe.We aim to provide evidence for the low validity of the body temperature measurement method as it has the possibility of inducing error and stigmatizing people without COVID-19. This will allow people infected with COVID-19 to pass through the triage with a false sense of safety.The primary objective of this study was to evaluate the sensitivity of fever measurement with NCITs for positive SARS-Cov-2 test results that identified the disease in the first PCR+ testing. The secondary objective was to determine the specificity and accuracy of the fever measurement with NCITs.The study was conducted at the Clinical Institute Fundeni, a major referral hospital in Bucharest, the capital city of Romania, with core competencies on transplant  and oncology. The Clinical Institute Fundeni has had an average of 53,060 inpatients in the last 5 years, with more than 80% being oncological and transplant patients. The study was conducted in accordance with the Declaration of Helsinki, the protocol was approved by the Ethics Committee of Clinical Institute Fundeni, and the patients provided informed consent.The sample consisted of 5,231 patients with age ranging from 6 months to 91 years . The sample included both female (47%) and male (53%) individuals, and was highly representative , with CI of 95 ± 1.30% and CI of 99 ± 1.71%.All patients tested for SARS-CoV-2 from March 16 to August 30, 2020 were eligible for inclusion. Patients with non-conclusive PCR in the initial testing were not included (N-3 cases); see This was a consecutive observational study encompassing all patients admitted to the hospital from March to August 2020.Temperature was measured on the day of admission in the triage tents placed in front of the hospital entrances with NCITs held at a distance of one to five centimeters from the skin.Along with the temperature measurements, a questionnaire about symptoms, contacts, and travel history was completed by patients. Data were collected for body temperature at the time of testing, age, sex, admission department, criteria for testing measurement, symptoms, contacts, and travel history .In line with the FDA recommendation , fever wThe triage data recording system included a handwritten paper registry completed by the triage teams, trained and designated by the hospital.After the triage, all admitted patients were allocated to one of three zones according to the triage's findings for nose and throat swabs—green (no findings for COVID-19), yellow (suspicions for COVID-19), or red (possibly positive for COVID-19).Testing of nose and throat swab samples was performed using a quantitative reverse-transcription polymerase chain reaction in the CIF laboratory.® Copan Italia S.p.A., Brescia, Italy) to prevent viral RNA degradation and bacterial/fungal overgrowth. Briefly, 200 μl of the sample was processed with a Seegene Nimbus automated system, which performs both RNA extraction–using STARMag 96 × 4 Viral DNA/RNA 200 C Kit—and PCR assay setup. The RNA isolation procedure comprised four steps: sample lysis, binding nucleic acid to magnetic beads, washing debris, and purified nucleic acid elution. The Allplex 2019-nCoV Assay  is an in vitro diagnostic (IVD) real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay developed for the detection of the nucleic acids in human samples from individuals with symptoms of severe acute respiratory syndrome related to coronavirus 2 (SARS-CoV-2). This assay was designed for amplifying three viral targets: the E gene (specific to the subgenus Sarbecovirus), as well as the N and the RdRP genes (both specific to SARS-CoV-2) , European Metrology (CE) (Certificate of compliance number 4M200326.SZTDD37), and ISO13485: 2016 .Of the 5,231 individuals, 49 tested positive for fever (fever +), and 53 were PCR +. Three PCR tests were inconclusive, and the remaining 5,175 were negative. For fever or PCR, there was no significant difference between males and females. Out of the 53 PCR + cases, five registered a fever, but 48 did not. Out of the 5,175 PCR—cases, 44 registered a fever . Sensitinegative when, in fact, they would be positive—suggesting the possibility of a large number of false negatives. Consequently, the effort and cost of mobilizing staff to measure temperatures at the entrance increase all nosocomial risks since more than 90% of people with COVID-19 end up proceeding with the clinical process. The value of this NCIT method for the daily assessment of COVID-19 inpatients was not evaluated.A sensitivity value of 9.5% at the first testing of PCR+ is considered to be extremely low. This means that a significant number of SARS-CoV-2 patients would pass through the temperature triage and be admitted to the hospital as false negatives. Patients were admitted to a green, yellow, or red zone of the department, following triage findings based on symptoms, history, contact, and temperature. The internal code for this procedure was PO-MED-40. The PCR was performed within 6–24 h, depending on the status of the medical emergency. The hospital also conducted the PCR on all admitted patients, even those who did not fulfill the criteria .Our findings suggest that 48 patients, representing 90.5% of PCR + patients (1—sensitivity), were false positive (1—specificity). This implies delay in medical services for these patients, at least until the PCR tests were conducted.Specificity value was found to be very high, reaching 99.15%. Nonetheless, 44 patients out of 5,228 were It must be noted that no calculation was done for the whole hospital triage scheme in place, which also included questions about contact, symptoms, and travel history. The results may vary if these questions are added to the temperature triage. The cut-off point of 37.3°C considered for fever was another concern.Our findings are consistent with the previous literature , 22. A sAlthough body temperature measurement provides some help in identifying patients with COVID-19, its use involves some risk, as follows:The vast majority of PCR + cases are not identified. Besides providing a false sense of security, people who are not infected are set in the same space as those who are infected, possibly for hours.Most people who are referred to the red zone are false positives, generating stigmatization and great anxiety in most cases, which are harmful for patients who are already fragile due to their condition.We suggest studying screening alternatives other than NCITs in the context of COVID-19. Once the resistance to rapid testing based on the most recent bibliography  is overcome, use of rapid PCR is a possibility. Although its safety level is lower than that of serologic tests, it is much more sensitive than screening based on body temperature measurement.For future research directions, it would be interesting to use the same assessment to verify whether fevers, false positives, and false negatives occur in other types of hospital services with the same density as they do in cancer and transplant hospitals. We estimate the probability of fever results directly from concrete phases of treatment, as well as with the type of cancer. However, it would be important to verify and study patients who should always be excluded from this type of procedure. Recognizing that there is no reliable method, it would be interesting to compare the validity of fever measurement, with or without insertion in a broader protocol, by using rapid PCR tests in another sample. Finally, we believe it is of the utmost importance to complement this work with an economic study involving the direct and indirect costs of this procedure. Costs include labor, use of space and equipment, and, in particular, risk of contagion outbreaks in the hospital from unidentified COVID-19 cases.Our findings indicate that testing for fever with NCITs has a very low sensitivity to COVID-19, thus questioning NCIT use for fever screening. The issue is not about the utility of the device  but its use in clinical testing procedures (patient safety reading).Not only is the usefulness of NCIT-based testing open to question, but it might induce a false sense of security while reducing the patient's effective safety in hospital settings as it allows passage of COVID-19 patients. It also diverts attention from public health measures that are more likely to be effective uses of resources, such as self-isolation when ill, physical distancing, mask-wearing, and contact tracing.the context of the severe shortage of qualified personnel to respond to needs of the growing number of cases in the pandemic while catering to the demands of the current healthcare setting, the fever-screening procedure increases financial costs and personnel allocation needs with no apparent gain.Therefore, we recommend that body temperature measurement be eliminated from hospital admission procedures, especially in oncological hospitals or other hospitals with high immunological impairment.A possible alternative solution for screening patients for admission to hospital could be rapid low-cost testing for a first triage while serological PCR results are determined. It also allows for a quick response to the circulation of people within the hospital with a greater degree of safety than currently verified.https://osf.io/grsqh/?view_only=dc293a57a99a4d21bb0fd138e75cc7d7/.The datasets generated for this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: The studies involving human participants were reviewed and approved by Ethics Council of the Fundeni Clinical Institute. Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin.BP, FF, AT, and AC contributed to conceptualization of the study. BP, HL, FF, AT, and AC contributed toward the methodology. Software was organized by BP and validation was done by BP, HL, and FF. BP and HL performed the formal analysis, and investigation was carried out by HL, DF, AR, MS, AT, and AC. AT and AC gathered the resources, while BP, AR, and MS curated the data. The original draft was prepared by BP, HL, FF, DF, AT, and AC. HL, FF, DF, AT, and AC reviewed and edited the manuscript, while HL supervised. BP administered the project. All authors have read and agreed to the published version of the manuscript.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.


Cerebral reperfusion therapy is recommended for the treatment of acute ischemic stroke. However, the outcomes of patients receiving this therapy in middle- and low-income countries should be better defined. This study aimed to evaluate the clinical and functional outcomes of cerebral reperfusion therapy in patients with ischemic stroke.This retrospective study included patients with ischemic stroke treated with cerebral reperfusion therapy, including intravenous thrombolysis (IVT), mechanical thrombectomy (MT), and IVT with MT. The primary outcomes were death and disability, assessed using the modified Rankin scale (mRS), and stroke severity, assessed using the National Institutes of Health Stroke Scale (NIHSS), after intervention and 90 days after ictus. The association between the type of treatment and the primary outcome was assessed using binary logistic regression after adjusting for confounding variables. Furthermore, receiver operating characteristic (ROC) curves were generated to identify the cutoff point of the NIHSS score that could best discriminate the mRS score in all types of treatments.n = 291) underwent IVT only (n = 241), MT (n = 21), or IVT with MT (n = 29). In the IVT with MT group, the incidence of death within 90 days increased by five times , prevalence of disability increased by three times  and NIHSS score increased after IVT . There was no significant difference between the initial NIHSS score and that after MT (p = 0.989). Patients' NIHSS score that increased or decreased by 2.5 points had a sensitivity of 0.74 and specificity of 0.65, indicating severe disability or death in these patients.Patients (Altogether, a 2.5-point variation in NIHSS score after reperfusion is an indicator of worse outcomes. In our particular context, patients receiving the combination of IVT and MT had inferior results, which probably reflects challenges to optimize MT in LMIC. Cerebral reperfusion therapy is indicated for ischemic strokes, which account for 80% of all strokes . HoweverSeveral studies have shown the benefits of thrombolysis using tissue-type plasminogen activator (t-PA) in acute stroke –11. CurrThus, cerebral reperfusion therapy is highly recommended for the treatment of the acute phase of stroke. However, the benefits of this therapy are poorly understood in low- and middle-income countries (LMICs) due to few patients receiving cerebral reperfusion therapy in these countries. A meta-analysis reported the rates of t-PA use as 19 and 33% in LMICs and upper middle-income countries, respectively, compared to 50% in high-income countries . In LatiA critical limitation of cerebral reperfusion therapy is the need for controlled settings, which is an important inclusion criterion for studies that assess this therapy. This has fostered an important gap in knowledge. Adequate integration with prehospital services, availability of an interventional neuroradiology team, and the presence of a comprehensive stroke unit or neurointensive care unit before and after the procedure are needed to successfully execute cerebral reperfusion therapy. In view of these difficulties, both public and private hospitals must periodically analyze the treatment quality indicators of cerebral reperfusion therapy to ensure continued improvement in health services. This study aims to evaluate the clinical and functional outcomes of cerebral reperfusion therapy during hospitalization and 3 months after therapy in patients with ischemic stroke in Brazil.This was a retrospective Brazilian cohort study. All patients were treated in the acute phase of stroke at a comprehensive stroke unit center at the Botucatu Medical School. After hospitalization, patients were followed up for 90 days at the outpatient clinic between June 2012 and December 2020. Data on all patients were collected from the semi-automatic stroke databank, which was developed by our institution. The databank is integrated with the electronic medical records system to extract clinical data on patients admitted to the stroke unit and identify the main indicators of quality of care using artificial intelligence .The inclusion criteria were as follows: patients diagnosed with stroke using clinical and neuroimaging examinations, including computed tomography (CT), angiotomography, and/or magnetic resonance imaging (MRI) and had performed IV thrombolysis (IVT) alone, MT alone or IVT with MT. The IVT was indicated for strokes , within 4.5 h of symptom onset, NIHSS > 4, except aphasia; The IVT is also offered as the first option to large vessel occlusions within 4, 5 h of stroke symptoms. MT alone was indicated for stroke between 4.5 and 8 h from the onset of symptoms, NIHSS > 8 and ideally AngioCT demonstrating M1 occlusion and/or associated lesion in internal carotid artery; IVT with MT was indicated for stroke within 4.5 h of symptom onset and maintained NHISS > 8 (until 8 h of symptom onset) and AngioCT demonstrating large vessel occlusion. Participants were excluded if they presented with other neurological diseases, hemorrhagic stroke confirmed by CT or MRI scan, or stroke mimics.A standardized data extraction form created by authors was used and the following details were recorded from each patient. Two calibrated physicians extracted data from the included patients. All variables (confounding factors and outcomes) were extracted by stroke data bank of Botucatu Medical School. The database on monthly audit by the stroke unit coordinator.The variable of interest in the study was the type of treatment received by the patient, including IV thrombolysis (IVT) alone, MT alone, and IVT with MT. Patients were treated with a standard IV dose (0.9 mg/kg) and maximum total dose (90 mg) of rtPA, alteplase (Actilyse®), and 10% bolus  . MT was The primary outcomes were death and disability, assessed using the modified Rankin scale (mRS) , and strNon-categorical data are presented as mean ± standard deviation. The normality of continuous variables was assessed by Kolmogorov-Smirnov test. The patients were divided into three groups according to the type of treatment received . Non-categorical data were compared between groups using analysis of variance (parametric distribution variables) or the Kruskal–Wallis test (non-parametric distribution variables), and categorical variables were compared between groups using the chi-square test. Receiver operating characteristic (ROC) curves were generated; the variable of interest was the NIHSS score at admission and the NIHSS score variation immediately after treatment, and the outcome variable was the mRS score at all possible cutoff points. The cutoff points of the NIHSS score or the NIHSS score variation that could best discriminate the mRS score were determined by the highest sum of sensitivity and specificity (best Youden index).p < 0.05 was reached among the different modalities of treatment. Then, an automatic backward stepwise variable exclusion method (excluding variables with p ≥ 0.05 at any step) was used to select variables for the final model. The significance level was set at p < 0.05, for all analyses. Data analysis was performed using IBM SPSS Statistics® Version 21 software.The association between the type of treatment and primary outcome was assessed using binary logistic regression, with the primary outcome as the dependent variable and the type of treatment as the variable of interest. Confounding variables were selected when A flowchart of the patients included in the study is shown in p = 0.000; p = 0.009; The incidence of death within 90 days after correction for age, the ASPECTS, and the ECASS criteria was increased by five times in patients who underwent IVT with MT  and then returned to 15.9 ± 6.36 (p = 0.152). There was no significant difference between the initial NIHSS score and that after MT (p = 0.989).The study demonstrated that IVT with MT increased the risk of death and disability in patients within 90 days after ictus compared with others groups , therefore, there were differences in the clinical features at onset between the groups that received treatment with IV thrombolysis, mechanical thrombectomy, and finally those that received both treatments. A 2.5-point variation in the NIHSS score after the IVT in the IVT with MT group indicated worse outcomes with high sensitivity and specificity. However, regardless of the type of treatment, higher ASPECTS was a protective factor, and the presence of symptomatic hemorrhagic transformation increased the chance of death in patients who underwent MT alone.Our study provides a detailed overview of treatment effectiveness, mortality rate, complications, and functional outcomes of stroke in LMICs. The IVT alone group had a lower NIHSS score, higher ASPECTS, lower rates of symptomatic hemorrhage and surgical treatment, and better outcomes at 90 days. Expanding access to alteplase therapy for acute ischemic stroke is a multifaceted approach. Specific considerations based on the region, population, and healthcare resources should be considered for each strategy. Neuroimaging approaches to identify alteplase-eligible patients are a recent development in acute stroke care that holds promise for increasing alteplase treatment rates .Despite a higher NIHSS score in the MT alone group, the benefits of treatment were maintained at 90 days. Stroke severity after MT and rate of symptomatic hemorrhage were higher in the IVT with MT group. In a small Brazilian cohort, a higher rate of functional independence was observed in patients who received intra-arterial thrombolysis plus IVT than in those who received IVT alone . The DEVAccess to catheters is limited in developing countries. The main drawback of MT in everyday practice is the irregular supply of catheters and materials. Moreover, devices for neurointerventional procedures are acquired through an auction process where cheaper devices are more easily acquired but may not be of the best quality . DespiteIn our study, we observed that the majority of acute ischemic stroke patients who arrived early to the emergency department received IV thrombolysis treatment and had lower NIHSS scores. Patients who arrived late received treatment with MT and had severe neurological deficits. Severely ill and younger patients usually arrive early to the emergency department. The selection of patients for the stroke center can be via SAMU (direct access) or via the central regulation of the health system, which regulates municipalities with more than 50 km from the stroke center. However, the most serious cases that underwent thrombectomy, 60% or more were from municipalities far from Botucatu (comprehensive stroke center) and came through an alternative regulatory route. In the IVT group, most patients arrived faster due to being via SAMU from Botucatu or nearby municipalities (<50 km). This also reflects the need for better structuring and integration of the pre-hospital network across the entire range of the stroke center's area of operation.Selection of patients who undergo MT after IVT should be careful and more rigorous. In LMICs, stroke is more severe due to several risk factors, including high tobacco usage , 34; a gRecently, a randomized clinical trial  was performed to evaluate the safety and efficacy of MT in the public health system of Brazil. The authors concluded that endovascular treatment within 8 h of onset of stroke symptoms in conjunction with standard care resulted in better functional outcomes at 90 days after stroke than standard care alone. In addition, substantial reperfusion in the thrombectomy group (≥50% of the affected territory) was achieved in 91 of the 111 patients (82.0%). However, it should be noted that this positive result of endovascular treatment was achieved due to the careful selection of patients for MT—patients with an ASPECTS of <6 on CT or <5 on MRI and complete absence of leptomeningeal collaterals on CT angiography. In addition, patients needed to have a baseline infarct volume of <70 ml, a ratio of volume of ischemic tissue to baseline infarct volume of ≥1.8 ml, and an absolute volume of potentially reversible ischemia (penumbra) of ≥15 ml .There is a gap in stroke care in Brazilian public health; however, the RESILIENT study introduced expectations of better health services, cost-effectiveness, and improved care in LMICs. In the present study, substantial reperfusion (TICI 2b and 3) was achieved in 21 of the 29 patients (72.4%) in the IVT with MT group, and 16 of the 21 patients (76.2%) in the MT alone. The patients indicated for MT were considered according to the severity of stroke assessed using the NHISS; therefore, the individuals had worse neurological conditions. Based on these findings, we believe that other selection criteria should be considered for the indication of MT, such as ASPECTS, collateral circulation analysis, and CT perfusion to assess the ischemic core , 40.Despite our results showing inferior outcomes among patients receiving IVT and MT, we believe that it occurred in our particular context, which reflects the difficulties of access to MT rather than a risk of the combined therapy. In the RESILIENT trial, the median time from stroke onset to treatment was 170 min, while in our cases, it took about 220-240 min. Therefore, even though our patients were not so different from the RESILIENT's at the baseline (regarding to age and NIHSS at admission) and our recanalization rates were close to the RESILIENT's, we had more patients with complications , which may be linked to that difference on time to treatment. This difference points to the need for LMIC to expand the accessibility to MT; it is not enough to have MT available: it is needed to have it largely and promptly available in order to ensure its benefits .Limitations of cerebral intervention include the high level of procedural skills required by the operator, technical limitations associated with catheter technology in middle income countries, lengthy duration of the method, and high costs , 43. HowIn addition, prehospital procedures can improve the efficacy of acute reperfusion therapy. System-based approaches have improved in-hospital temporal parameters, maximized the utility of reperfusion therapies, and improved clinical benefits to patients . SeveralWe acknowledge the limitations of our study. First, this was a retrospective study with a small cohort. Second, this study included a convenience sample, and there was a constant learning curve since this was a university hospital. Third, the number of patients treated with the thrombectomy modality was smaller than that of patients treated with other cerebral reperfusion modalities. Fourth, we did not use collateral and perfusion imaging information to improve patient selection. CT perfusion was not available in many periods of the retrospective study due to technical failures. In addition, this research was conducted in a middle-income country with all the limitations associated with that status.The strengths of this study include its longitudinal design and the large sample size of the IVT group. Furthermore, all patients were assessed with a comprehensive neurological assessment. We believe that strategies to improve stroke care, which have been successfully implemented in high-income countries, may be useful for adaptation and implementation in LMIC settings to improve overall therapeutic outcomes. Our study does not emphasize the effectiveness of cerebral reperfusion therapies but emphasizes clinical predictors that might interfere with the neurological outcomes of individuals who have undergone such therapies.Altogether, a 2.5-point variation in NIHSS score after reperfusion in the IVT with MT is an indicator of worse outcomes. In our particular context, patients receiving the combination of IVT and MT had inferior results, which probably reflects challenges to optimize MT in LMIC.We highlight the importance of optimizing treatment in the acute phase for better outcomes in stroke patients, especially for occlusion of large vessels. In addition, there should be better integration of the pre-hospital system with in-hospital management, associated with more established thrombectomy protocols.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Institutional Review Board at Botucatu Medical School. The Ethics Committee waived the requirement of written informed consent for participation.EV, CF, LM, and RB: substantial contributions to the conception or design of the work. NEF, GL, PH, SZ, GM, NCF, LM, JS, and FW: acquisition, analysis, and interpretation of data for the work. NEF, GL, PH, LM, and RB: drafting and critical revision of the manuscript for important intellectual content. NEF, GL, PH, SZ, GM, NCF, LM, JS, FW, EV, CF, LM, and RB: final approval of the version to be published. All authors contributed to the article and approved the submitted version.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 reveal the cultural effect in the job demands-resources model, this study examined how Confucian familism, emotional labor, and work-family conflict (WFC) explain the variance in teachers’ emotional exhaustion, with a focus on the mediating roles of emotional labor and WFC. With a sample of 3,312 teachers in China, the results of this study revealed that surface acting and expression of naturally felt emotion (ENFE) and WFC mediated the relationship between familism and emotional exhaustion. Moreover, familism positively predicted deep acting, ENFE, WFC, and emotional exhaustion, while negatively predicted surface acting. These findings suggest that Confucian familism may play the dual role of motivator and stressor for Chinese teachers’ emotional labor and well-being. This study contributes to the job demands-resources theory by revealing the important role of cultural traditions and provides valuable information for interventions to sustain teacher well-being. Over the past two decades, teacher burnout, which has negative impacts on teachers’ well-being, has gained increasing attention from researchers . Based oAs defined by Previous studies found that emotional labor is significantly related to teachers’ EE, which is the key component of burnout syndrome . EE refeThere has been a growing amount of research into the emotional spillover between work and family, with more employees engaged in a dual-earner lifestyle . Thus, tAlthough the validity of JD-R model has been demonstrated in cross-cultural samples, some researchers have suggested that the impact of culture on JD-R theory should be considered . HobfollConfucianism has exerted a great influence on Chinese thinking and behavior . ConfuciWork-family conflict is defined as “a form of interrole conflict in which the role pressures from the work and family domains are mutually incompatible in some respect” , p. 77. Previous studies found that WFC mediated the relationship between SA and burnout or EE . Noor anWork-family conflict mediated the relationship between EL and EE, but different EL strategies had different effects on WFC. A few studies found that SA was positively correlated with WFC . MeanwhiConsidering the characteristics of different EL strategies, it is not surprising to find a weaker relationship between DA or ENFE and WFC than that of SA. SA expends more emotional and cognitive resources than DA because of the suppression of emotions, although they both require investment of resources . ENFE exH1: WFC mediates the relationship between EL and EE. SA is more strongly positively related to WFC than ENFE and DA.The emotions of teachers are regarded as not only an individual experience but also a sociocultural experience that conveys sociocultural messages , p. 61. Familism, as an important part of Confucianism, has a great influence on Chinese teachers . ConfuciH2: Teachers with stronger familism beliefs use more work-efficient EL strategies  and less SA.Some researchers have suggested that familism is a protective factor that strengthens the emotional connection with family members and provides familial social support in both Chinese , 2004 anConsequently, Chinese teachers with a high level of familism may experience more work-family conflict because of their high expectations of positive family involvement, which in turn leads to worse outcomes. However, previous studies on the influence of familism on WFC were mainly conducted in Latino samples  or usingH3: Familism is positively related to WFC and EE.Accordingly, in the Chinese cultural context, this study aims to examine how Confucian familism, EL, and WFC contribute to explaining variance in EE by focusing on the mediating role of EL and WFC. We developed a multivariate model to examine our hypotheses. Based on the previous studies, we hypothesize:H4: EL and WFC sequentially mediate the relationship between familism and EE.This research was approved by the Research Ethics Committee of the School of Education of Capital Normal University. Before data collection, we informed the participants about the objectives of this research and the confidentiality of data and confirmed that all data would only be accessible to the research group and used for research purposes. All data in the present study were collected anonymously.A total of 3,312 Chinese teachers from K-12 schools in Beijing, China, participated in the study . We distributed questionnaires to teachers through the teacher training department of the municipal Ministry of Education in November 2020. All participants volunteered to participate and completed the questionnaire online. The online questionnaires were administered using Survey Star. The entire procedure lasted approximately 5–10min.The years of the teaching experience ranged from 0 (new teachers) to 39years , and 1.9% (63) of the participants did not report this information. α for this subscale (11 items) was 0.96.We assessed Confucian familism using the familism subscale from the Confucian Traditional Values Scale developed by Yang . The famαs for each subscale were 0.86 (SA for students), 0.80 (DA for students), and 0.91 (ENFE for students); 0.91 (SA for parents), 0.83 (DA for students), and 0.93 (ENFE for parents); 0.94 (SA for colleagues and leaders), 0.82 (DA for colleagues and leaders), and 0.94 (ENFE for colleagues and leaders).We used the Questionnaire on Emotional Labor developed by To ensure the consistency of Chinese and English versions, the items were translated into Chinese by two translators and were then back-translated by other translators.α for this subscale was 0.96.The teachers’ emotional exhaustion was measured with the emotional exhaustion subscale from a Chinese version of the Maslach Burnout Inventory for Educators which has been revised and published in China . The subα for this scale was 0.94 .The WFC Scale was developed by The internal consistency, descriptive statistics, and correlations among the variables were analyzed using SPSS 18.0. Full information maximum likelihood procedures were applied to handle the missing data. According to the recommendation of The descriptive statistics and correlations between the variables are presented in χ2=6475.64, df=419, RMSEA=0.07, TLI=0.93, SRMR=0.03, CFI=0.93. All the factor loadings for the indicators on the latent variables were significant (ps<0.01), and the standardized factor loadings ranged from 0.66 to 0.95, indicating that all the latent factors were well-represented by their respective indicators. All the latent factors from the measurement model were significantly correlated (ps<0.01).We first evaluated the measurement model to assess whether latent variables were well-represented by indicator variables using Mplus 8.0. The confirmatory factor analysis was conducted with 6 latent factors and 31 observed variables. The latent variable familism was indexed by 11 indicators . The latent variable EE was indexed by eight indicators (eight items). The latent variable SA was indexed by three indicators . The latent variable DA was indexed by three indicators . The latent variable ENFE was indexed by three indicators . The latent variable WFC was indexed by three indicators . The estimation of the measurement model revealed a satisfactory fit to the data: ps>0.05), we only controlled the effect of years of teaching experience among SA, ENFE, and EE (ps<0.001).We applied structural equation modeling using Mplus 8.0 and the maximum likelihood estimation method to examine the hypothesized model. In the model, emotional labor strategies  and WFC sequentially mediated the effect of familism on EE after controlling for years of teaching experience . Becauseχ2=6710.261, df=446, RMSEA=0.065, TLI=0.93, SRMR=0.03, CFI=0.93). However, the standardized path coefficient from DA to WFC was non-significant , and all other path coefficients were significant , supporting H1, and the indirect effect of SA was greater than that of ENFE. In addition, the direct effect of SA on EE was significant and positive , so the mediation was complementary. However, the mediation of WFC between ENFE and EE was competitive because of the negative direct effects of ENFE on EE .As shown in ß=0.090, p<0.001; direct: ß=0.078, p<0.001), confirming H4. We added up all the positive and negative significant indirect effects of familism on EE separately. The total positive indirect effect was 0.083, and the total negative indirect effect was −0.078. The total positive effect (include indirect and direct) was 0.161.Second, the total and direct effects of familism on EE were significant and positive . ENFE and WFC also sequentially mediated the relationship between familism and EE . Moreover, this sequential mediation of SA and WFC was competitive, while the mediation of ENFE and WFC was complementary. We also found that there were competitive mediations of both SA and ENFE between familism and EE, and there was a complementary mediation of WFC between familism and EE.Third, the link between familism and EE was sequentially mediated by SA and WFC , confirming H3. The total positive indirect effect of familism on WFC was 0.039, and the total negative indirect effect was −0.035. The total positive effect (including indirect and direct effects) was 0.133.Fourth, the total and direct effects of familism on WFC were notable and positive  and EE among teachers.First, the results revealed that SA was significantly related to the EE of teachers, while DA and ENFE were negatively related to the EE of teachers. These results are consistent with many previous studies in various cultural contexts e.g., . We alsoSecond, in line with previous research , our finThird, we also found that WFC mediated the relationship between SA and EE as well as between ENFE and EE. These results are consistent with previous studies and add to a growing body of evidence that work and family spill over into each other through emotion . In addiBy examining the influence of familism on EL, WFC, and EE, we identified significant effects of cultural factors in a JD-R model from an insider’s perspective. Most studies in the field of cultural impact have only focused on the moderating role of culture and used universal cultural dimensions that attempt to describe differences between cultures. Such approaches, however, have failed to address the uniqueness and complexity of cultures. Our results provide further insights into the specificities and nuances of Chinese culture and their effects on work-related outcomes.Our findings showed that familism had positive impact on DA and ENFE and a negative impact on SA, supporting H2. Chinese teachers influenced by Confucian familism are motivated to use less SA and more DA and ENFE strategies. These results reveal the influence of cultural factors on personal variables , which is consistent with the positive effect of familism on work performance found in previous studies e.g., .Moreover, the results showed that familism was positively associated with the WFC of teachers, confirming H3. It suggested that the emphasis on familism made them more likely to experience work-family conflict. In contrast to our results, mixed evidence regarding the differences in WFC between individualistic countries and collectivistic Confucian Asian countries was previously reported: Some studies found no significant differences, while some studies found more WFC in individualistic countries  than in collectivistic countries , or vice versa . This inOur results deepened the understanding of the differences in WFC between collectivist and individualist countries that have appeared in previous studies. Eastern collectivist countries, such as China, are influenced by the Confucian culture and attach great importance to family obligations. Family members are mutually dependent and closely connected. Chinese employees even regard work as a means to improve the family’s economic well-being and fulfill family responsibilities . On the Finally, and more importantly, this study elucidated the mechanisms underlying the relationship between familism and EE by introducing EL  and WFC into the model, and familism had both a positive and negative impact on EE. These findings contribute to the JD-R theory by revealing the antecedent roles of culture and further support and enrich the JD-R theory in the Chinese context. Our findings showed that WFC and EL mediated the relationship between familism and EE among teachers: The direct effect was positive, while there were both positive and negative indirect effects. Our findings indicated that these Chinese teachers influenced by Confucian familism tended to use more work-efficient EL strategies so as to reduce EE. However, teachers with strong familism beliefs would perceive more WFC and eventually increase their EE. These findings suggest that Confucian familism may play the dual role of motivator and stressor for Chinese teachers’ emotional labor and well-being. On the one hand, Confucian familism as a cultural demand can force teachers to invest effort in their work, which leads to physical and psychological costs. On the other hand, as a cultural resource, it can also drive teachers to achieve work goals, improve work performance, and reduce the associated physiological and psychological costs .The implications of this study should be interpreted in light of its limitations. First, our study used a cross-sectional design, so we could not make any causal inferences. A longitudinal design in future research will yield more solid causal relationship evidence. Second, although we found a positive total effect of familism on EE, it is hard to be sure that familism is more of a pressure than a motivator. These results must be interpreted with caution because there may be other factors mediating the relationship between familism and EE, such as family support and family-to-work enrichment, which may have negative effects on EE . AccordiIn view of the general need to promote the well-being of teachers, it is essential to explore the factors influencing emotional exhaustion and their roles in the health impairment process. From a practical perspective, our findings suggest that DA is a health-beneficial strategy that teachers should use more, while SA is a health-detrimental strategy that teachers should use less. In addition, ENFE is a double-edged sword considering its contrasting impacts on WFC and EE, so teachers need to use this strategy carefully. Considering that teachers with more years of teaching experience will use SA less, schools can invite experienced teachers to help younger teachers learn emotion management.Moreover, given that EL can increase WFC, training and interventions for teachers need to pay attention to the contents of conflict management and relief. The finding that DA was not related to WFC suggests that training programs should help teachers understand the nature of DA and its applications in the teaching profession.Last but not least, cultural background must be taken into account in interventions in teacher burnout and teacher training. Chinese schools should consider the influence of Confucian culture when making policies and raise awareness of teachers’ needs to fulfill family responsibilities to ensure that teachers can have some balance between their work and family demands. Furthermore, the dual role of familism reveals the complexity of cultural effects, suggesting that teacher training should help teachers think dialectically about traditional values. According to our findings, the promotion of teacher well-being should not only rely on teachers’ self-regulation but should also be supported by the society, school, and family.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Research Ethics Committee of the School of Education of Capital Normal University. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.XZ, GT, HY, and WH designed the study. GT and XZ collected and analyzed data. XZ, GT, and HY wrote the manuscript. HY reviewed and revised the manuscript. All authors contributed to the article and approved the submitted version.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.


Introduction: To develop sex- and age-specific percentile curves for seven physical fitness components for Chinese Han children and adolescents aged 7–18 years based on the total and the normal weight population using a nationally representative sample.Methods: A total of 214,228 Chinese Han children and adolescents aged 7–18 years old with all nutritional status and 161,999 with normal weight were examined. Seven physical fitness components  were measured, and percentile curves for each physical fitness component at the 20th, 40th, 60th, and 80th percentiles were calculated using the general additive model for location, scale, and shape (GAMLSS).Results: Physical fitness presents different characteristics in each subgroup of sex, age, and nutritional status among children and adolescents. Sex- and age-specific percentiles for the seven physical fitness components among the Chinese Han children and adolescents aged 7–18 years based on the total and the normal weight population were provided as curves. Boys performed better than girls in FVC, SLJ, 50-m dash, GS, and ER but worse in SR. The performances of FVC, SLJ, 50-m dash, GS, BMS, and ER increased with age, but the estimates of SR were at the bottom among boys aged 12 years and girls aged 11 years. The annual increments of all components were larger in boys than girls at the peak time, which was earlier in girls than boys. The gap of physical fitness components between sexes increased with age, especially during puberty (since after 11 years old).Conclusion: The present study described the percentile curves of seven physical fitness components among the Chinese Han children and adolescents based on the total and the normal weight population at the national level, which could help to chart the level of physical fitness across age span and identify the extreme populations with either health concerns or potential talents. Physical fitness is the ability of an individual to accomplish daily tasks with vigor and alertness, without undue fatigue and with ample energy to enjoy leisure-time pursuits, and to meet unforeseen emergencies  and is u10 of the reference population for each physical fitness component. Moreover, few recent studies have produced normative-referenced percentile values for a comprehensive set of physical fitness tests in China . The CNSSCH was the largest nationally representative survey of the physical fitness of Chinese children and adolescents aged 7–18 years with a nature of cross-sectional study design, which has been conducted on a regular basis once every 5 years since 1985. It used a multistage stratified cluster sampling design as described in the previous studies . That isHeight (centimeters) and weight (kilogram) were measured by trained staff following a standardized CNSSCH procedure. While measuring, the participants were stood erect, barefoot, and at ease with only light clothing. Height was measured with a portable stadiometer to the nearest 0.1 cm, and weight was recorded in units of 0.1 kg with a standardized scale using the mean of three measurements. Both stadiometers and scales were calibrated before use and similar instruments were used at each survey site according to the requirement of the 2014 CNSSCH survey protocol. BMI was calculated as body weight (kilogram) divided by height (meters) squared (kilogram per square meter). BMI-for-age Z-score (BAZ) was calculated with the WHO 2007 references, and the reference population used here was the fixed population recommended by the WHO . ThinnesSeven physical fitness components  were measured by a team of trained field investigators following the standardized procedures. FVC, SLJ, 50-m dash, SR, and GS were measured across age of 7–18 years. BMS was assessed by oblique body pull-ups (boys aged 7–12 years), pull-ups (boys aged 13–18 years), and 1-min sit-ups (girls aged 7–18 years). ER was assessed by eight 50-m shuttle runs (both boys and girls aged 7–12 years), 1,000-m ER (boys aged 13–18 years) and 800-m ER (girls aged 13–18 years).The protocols used for physical fitness testing are described in detail below  package (version 5.2-0) with age as a covariate stratified by sex. GAMLSS is an extension of the Lambda-Mu-Sigma (LMS) method and it establishes models through four parameters of distributions: median, coefficient of variation, skewness, and kurtosis. Box-Cox power exponential (BCPE), Box-Cox power exponential orig. (BCPEo), Box-Cox t (BCT), and Box-Cox t orig. (BCTo) distributions were fitted to each fitness outcome variable stratified by sex. P-splines were used to smooth the age trend for each fitness outcome using the generalized Akaike information criterion (GAIC). The Bayesian information criterion (BIC) was used to assess the goodness of fit to compare models. Worm plots and Q-Q plots were used for visual inspection (Descriptive statistics [median and inter-quartile range (IQR)] for boys and girls among the total population and normal weight population were all calculated. Comparisons between sexes among the two studies population were performed using the Mann–Whitney spection . The modP < 0.001), and physical fitness performances were better among boys in FVC, SLJ, 50-m dash, GS, and eight 50-m shuttle runs, while better among girls in SR across all ages (P < 0.001). When compared with the total sample, the median age of the normal weight population was older (P < 0.001) as abnormal weight was distributed unevenly across age groups  and percentile values  for the seven physical fitness components based on the total and the normal weight population, respectively. Irrespective of the total population or the normal weight population, for both sexes, their performances increased with age in all components except for SR, which revealed the worst performance at P50 among boys aged 12 years and girls aged 11 years. Almost all components, such as FVC, SLJ, 50-m dash, GS, 1-min sit-ups, and ER, increased with age at each percentile, while for pull-ups, the pronounced increases occurred only in higher percentiles (P60 and above). The annual increments of all components were larger for boys than girls at the peak time, which was earlier in girls than boys, i.e., for FVC at P50, 400.0 ml/year for boys at 14 years old compared with 211.8 ml/year for girls at 12 years old among the total population, and 409.9 ml/year for boys at 14 years old compared with 212.0 ml/year for girls at 11 years old among normal weight population; for SLJ at P50, 15.7 cm/year for boys at 13 years old compared with 9.8 cm/year for girls at 8 years old among the total population and 15.2 cm/year for boys at 13 and 14 years old compared with 10.3 cm/year for girls at 8 years old among normal weight population, respectively. The total increase of each component was also higher among boys than girls in FVC , SLJ , 50-m dash , SR , GS , and eight 50-m shuttle runs , SLJ , GS , and 50-m dash . As for SR, it displayed the greatest sex difference at the age of 12  among the total and normal weight population based on a large nationally representative sample of Chinese Han children and adolescents. To the best of our knowledge, it is the first study to generate percentile values for the physical fitness components based on both the total and the normal weight population at the national level with a representative sample, which are helpful as a reference for regional comparisons and for monitoring the trends of physical fitness over time.Given that physical fitness strongly indicates current and future health outcomes for children and adolescents, it is important to assess the relative position and identify low levels of physical fitness . For insContrarily, the high percentile values could also contribute additional, i.e., they could be used by physical education teachers or coaches for sports talent identification. Some studies have suggested that children and adolescents with a score above the 95th percentile might be considered a talent for relevant sports  and coulOur study found that boys performed better than girls in FVC, SLJ, 50-m dash, GS, and ER, but worse in SR. Meanwhile, almost all performances in physical fitness components increased with age, although they appeared to plateau at a certain age. These findings are consistent with the results of previous studies from various countries , 30, 38.However, the age trend of SR showed different results across studies. We found that both boys and girls had the worst SR performance at the age of 11 or 12 years. Iglesias-Soler et al.  had simiWe observed that a substantial number of boys scored 0 in the pull-ups test, such as 40% boys aged 13 years and 30% boys aged 14 years, suggesting that this test might not finely distinguish the arm muscle strength of boys. Therefore, its usefulness and future use in Chinese children and adolescents are questionable due to the lack of sensitivity in this test, and more accurate alternative tests, such as bent-arm hang/flexed-arm hang, are widely used in some countries and regions , 45, 46 50 as an example, we found that the Chinese children and adolescents had better performance of SLJ than the European  participant data collected in the surveys can be shared with investigators whose proposed use of the data has been approved by an independent review committee identified for this purpose by contacting the corresponding author. Requests to access these datasets should be directed to The studies involving human participants were reviewed and approved by Medical Research Ethics Committee of the Peking University Health Science Center. Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin.NM conceptualized and designed the study, completed the statistical analyses, drafted the initial manuscript, and reviewed and revised the manuscript. YD and YS contributed to the conceptualization and design of the study, supervised the data collection, the statistical analyses and initial drafting of the manuscript, and reviewed and revised the manuscript. PL participated in conceiving the study design and critically reviewed and revised the manuscript from preliminary draft to submission. JD, YL, PZ, XY, JZ, and JM assisted with the data interpretation and reviewed and revised the manuscript. All authors approved the final manuscript as submitted and agreed to be accountable for all aspects of the work.This study was supported by the Humanities and Social Sciences Planning Fund Project, Ministry of Education, People's Republic of China (Grant No. 19YJA890022 to YS), and National Statistical Science Research Project (2021LY052 to YS).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.


Objective: To analyze the relationship between anxiety, self-esteem, happiness index and primary school students’ academic performance in Chilean adolescents from the Biobío province. Methodology: 733 ) public primary school students that completed the 2018 Health and School Performance Survey carried out in the Biobío province were included in this cross-sectional analysis. The BECK Anxiety Inventory (BAI) was used to measure anxiety while happiness index and self-esteem were measured using the subjective happiness scale and the Rosenberg self-esteem scale, respectively. School performance was measured by grade point average (GPA) of language, math, physical education and cumulative GPA, and behavior associated with cognition in the school context was also considered. The relationship between mental health indicators and school performance was investigated using a one-way ANOVA and Pearson correlation. Results: In comparison to students with low anxiety levels and high self-esteem and happiness levels, students with higher anxiety levels, lower self-esteem and happiness levels perceived themselves as having memory problems. They were also slower to solve math problems, had a shorter attention span in class and presented more difficulties in solving complex tasks, as well as being more nervous during testing. These students also got the lowest grade point average in math, language and physical education. Conclusions: High anxiety levels, low self-esteem and low happiness levels were associated with lower school performance and weaker behavior associated with cognition in Chilean adolescents. Implementing plans of emotional education and mental health could improve academic achievement. High-quality education is the ethical threshold by which those who work in teaching operate daily. Nowadays, new skills and knowledge demands are imposed on the educational system to prepare students to face the challenges of a complex society . Yet, haIn recent years, the students’ socio-affective competencies and emotional intelligence—particularly their impact on school performance—have been two fields of interest for educational specialists . PreviouHowever, the well-being concept is wide. In terms of educational area, this is related to the interaction of different aspects, including motivation, attitudes, decision-making, and learning tasks . RecentlAt the moment, grade point averages (GPAs) are the most stable predictor to assess the relationship between well-being and school performance ; the adeEvery day, students are exposed to several school activities for which they are demanded to develop answers, decide, create and execute the process of attention, planning, memorizing, language, and flexibility ,19,20. SEvidence reinforces the relevance of the self-perception of happiness , not onlGiven the above, more research on classroom strategies that would impact school performance and promote favorable practices is more necessary than ever. These favorable practices could improve students’ general well-being and reduce the stress level in the classroom, which, in turn, would facilitate the integration into richer school environments and allow for the development of socioemotional competencies most needed in today’s society . JonbergA recent study carried out in Chile showed how low academic performance is associated with these types of problems . One exaDespite the above, current research efforts mainly focus on the university population, with Europe and the United States leading this research field . HoweverTherefore, this study aimed to analyze the relationship between anxiety, self-esteem, happiness index and school students’ academic performance in Chilean adolescents from the Biobío province.n = 3857). From this universe, a probabilistic and stratified sample of 797 (12 ± 1.3 years) were included. After parents/legal guardians consented to be part of the study, the participants in the sample completed all the measurements. Sixty-four students were excluded for not meeting the inclusion criteria (survey or consent), so the final sample was 733 students (46.1% girls). The sample calculation considered a 5% margin of error and a 95% confidence level.This cross-sectional study used data from the Health and School Performance Survey carried out in the Biobío province in 2018. The survey included all 5th to 8th-grade students from the four public schools in one city of the Biobío providence , Spanish version was used [was used . This inwas used , and in was used Self-esteem: The Rosenberg self-esteem scale (SES), Spanish version was used to measure it [asure it . This scasure it ,45,46 anasure it . Some exasure it , being uasure it .Perception of happiness: The Subjective Happiness Scale (SHS) was used to measure it [asure it . This scasure it , being pasure it .School PerformanceBehavior associated with cognition in the school context: A survey was designed by the study’s researchers to measure this dimension, including five items from the Scale of Daily Stress was applied [ applied . The que applied .Grade point average (GPA): This included the grades on language, math, physical education subjects and the cumulative GPA of an academic semester. The Chilean grading system goes from one to seven, where four is the minimum passing grade. All the participating schools followed the same Ministry of Education curriculum and study plans, so there were no differences in the academic demands [ demands .Socio-educational data: Additionally, age, sex, school grades and special needs education participation were also elicited to better characterize the sample.p < 0.05 was used.A descriptive analysis was carried out, including both the socio-educational and mental health variables. The qualitative data were represented by frequency and percentage, while the quantitative data by the mean and standard deviation. Data distribution was established by means of normality and equality variance tests (Shapiro-Wilk and Levene). To establish the association between nominal variables, the Chi-square test was used. The difference in means between two different groups was tested with the independent samples T-Student test. To determine the effect of anxiety, self-esteem and happiness index on GPA and behavior associated with cognition in the school context were determined by one-way ANOVA. To establish significant differences between the categories of anxiety, self-esteem and happiness index, the Bonferroni Post hoc test was performed. Finally, to establish the linear relationship between anxiety, self-esteem and happiness index and the variables of school performance/cognition associated behaviors in the school context, Pearson’s correlation coefficient was used. Cohen’s d effect size (ES) was calculated and qualitatively assessed as trivial (0–0.19), small (0.20–0.49), medium (0.50–0.79), or large (0.80 and greater). The association of anxiety, self-esteem and happiness index and behavior associated with cognition in the school context and grade point average were investigated using linear regression analyses. Data are presented as β-coefficient and its 95% CI. Multivariable models were adjusted for relevant confounders. Model 0—unadjusted; and Model 1—adjusted socio-educational variables . All analyses were performed using SPSS version 25.0 software . Significance at the level of p = 0.024). In the descriptive analysis, the schoolchildren mostly reported to have good memory use in class (60.4%); be fast at solving math problems ; have a moderate attention span (40.9%); have no problems solving complex tasks (47.1%); and feel at ease during testing (52%). It is noted that 22% of schoolchildren are perceived as very nervous during tests, 19.5% have poor attention span in class and 16.5% are slow to solve math problems. When the association of behaviors associated with cognition in the school context was measured according to sex through the chi-square test, it was observed that a small proportion of boys perceived themselves slower at solving math problems, found complex tasks very difficult and felt very nervous in tests compared to girls . On the other hand, when the differences in means between boys and girls were compared through the student’s T-test, it was evidenced that girls showed better cumulative GPA and language GPA than boys .p < 0.0001; with a medium effect size); Speed to solve math problems ; Attention span ; Solution of complex tasks ; Nervousness during testing .Then, in self-esteem level ; Speed to solve math problems ; Attention span ; Solution of complex tasks (p < 0.0001); Nervousness during testing  and in happiness index, ; Speed to solve math problems ; Attention span ; Solution of complex tasks ; Nervousness during testing . Upon closer analysis, when comparing the groups with the Bonferroni test, those schoolchildren categorized as showing severe anxiety perceived themselves as having poorer memory skills than the other groups (p < 0.0001). The group with moderate to severe anxiety perceived themselves as slower to solve math problems (p < 0.0001), with greater difficulty paying attention in class (p < 0.0001), solving complex tasks (p < 0.0001) and felt more nervous when taking tests (p < 0.0001). Concerning the perception of happiness, the participants categorized as having a low perception of happiness perceived themselves as slower at solving math problems (p < 0.0001), with greater difficulty paying attention in class (p < 0.0001), solving complex tasks (p < 0.0001) and felt more nervous (p < 0.0001) when taking tests compared to the other groups. Furthermore, those participants with moderate to low perceptions of happiness perceived themselves as having poorer memory skills in class (p < 0.0001) than those with a high perception (p < 0.0001), with more difficulties when solving complex tasks (p < 0.0001), slower in solving math problems (p < 0.0001), and more nervous during tests (p < 0.0001) than the other groups ; GPA in physical education  and the cumulative GPA . Then, in self-esteem ; GPA in Language ; GPA in physical education  and the cumulative GPA  and in happiness index  and the cumulative GPA . Upon closer analysis, when comparing the groups with the Bonferroni test, the participants with moderate and severe anxiety got a lower GPA in physical education than those having very low anxiety (p = 0.008). Then, the participants with a low perception of happiness got a lower GPA in physical education and cumulative GPA compared to those with a high and moderate perception of happiness (p = 0.001). Finally, schoolchildren with a lower perception of self-esteem got a lower GPA in math (p < 0.0001) and physical education (p < 0.0001) than those who showed a moderate to a higher perception of self-esteem. Additionally, schoolchildren with a moderate-to-low perception of self-esteem got the lowest grade point average in language (p < 0.0001) and in the cumulative GPA (p < 0.0001)  .The linear association between anxiety, self-esteem and happiness index and behavior associated with cognition in the school context and GPA was analyzed with Pearson’s linear correlation coefficient and Cohen’s d effect size (ES) was calculated. Significant correlations were found in all parameters. Participants with higher levels of anxiety, lower perception of happiness and lower self-esteem perceived to have more memory problems in class, more difficulties in solving math problems, more difficulties in paying attention, felt more nervous during testing and complex tasks were harder to solve, although the effect size was trivial or small. As for the GPA, those participants with higher levels of anxiety and lower self-esteem got—on average—lower cumulative GPA and lower GPA in math, language, and physical education. Similar results were found for lower levels of happiness but math. In these cases, the effect size was also trivial or small .The association between anxiety, self-esteem and happiness index and behavior associated with cognition in the school context and GPA was estimated by linear regression analysis. For the unadjusted model, schoolchildren with very low anxiety were associated with better memory use in class, higher attention span and solution of complex tasks than schoolchildren with severe anxiety. In the same line, it was observed that schoolchildren with low and moderate perceptions of self-esteem and happiness were associated with lower memory use in class, slower to solve math problems, lower attention span, solution of complex tasks, more difficulty for resolution of complex tasks and more nervous during testing compare to schoolchildren with a high perception of self-esteem and happiness. After adjusting the model, similar associations were maintained for socio-educational variables  .In addition, in the unadjusted linear regression model, schoolchildren with very low anxiety were associated with better math and physical education GPA than schoolchildren with severe anxiety. Schoolchildren with low and moderate perceptions of self-esteem were associated with lower math, language, and cumulative GPA. Schoolchildren with a low perception of self-esteem were associated with lower physical education GPA compared to schoolchildren with a high perception of self-esteem. Additionally, schoolchildren with lower and moderate perceptions of happiness were associated with a lower cumulative GPA. Schoolchildren with a lower perception of happiness were associated with a lower physical education GPA compared with schoolchildren with a high perception of happiness. After adjusting the model, similar associations were maintained for socio-educational variables  .The main findings of this study suggest that 58.8% and 57% of the participants had low-to-moderate self-esteem and perception of happiness, respectively, while 15.6% reported having moderate-to-high anxiety levels. Participants with higher anxiety levels and lowers happiness and self-esteem levels perceived themselves as having poorer memory skills, being slower at solving math problems, having more difficulties solving complex tasks and paying attention in class. They were also more nervous during a test than participants with lower anxiety levels and higher happiness and self-esteem levels.In general, participants with higher anxiety levels and lower happiness and self-esteem levels got—on average—lower cumulative GPA and lower GPA in math, language and physical education than those with lower anxiety levels and higher happiness and self-esteem perceptions of themselves. Concerning anxiety, results showed that 84.8% of the participants presented very low anxiety levels. Previous studies have demonstrated that the higher the anxiety levels, the lower the school performance ,56,57,58This study also found that 4 out of 10 participants reported high levels of self-esteem. In this respect, previous evidence suggests that adolescents that have a heightened perception of self-esteem have better stress management, better response to failure, higher persistence in complex tasks and, in general, better response to schoolwork ,63,64. IIt has been observed that happiness’s moderating effect is a positive element for academic achievement; the greater the happiness, the higher the prediction degree of academic achievement . The preRegarding behavior associated with cognition, 39.5% of the participants judged their memory to be moderate or bad. Cognitive abilities explain teenagers’ different learning and academic performance levels in the school stage . Memory This study used a representative sample and is the most recent research in Chile giving an account of the relationship between mental health indicators such as anxiety, self-esteem and happiness and the academic performance of primary school students. There are no previous studies in Chilean adolescents that report an association between the variables described and the questionnaires used were previously validated. However, it is not exempt from limitations. Firstly, low school performance is multifaceted, and, therefore, this study’s results cannot be attributed exclusively to the participants’ mental health and/or well-being. In this sense, the present study did not analyze other intervening variables in school performance such as personal, family or contextual factors. Future studies could more closely examine the behavior or current lifestyles that may play a role in school performance, such as cell phones, low levels of physical activity, dietary habits, or sleeping routines. Finally, due to the cross-sectional nature of this study, causality cannot be inferred.The present study results show that participants with higher anxiety levels and lower happiness and self-esteem levels perceived themselves as having a bad memory, being slower at math problem solving, having a shorter attention span, having more difficulties solving complex tasks, and feeling more nervous during testing. In addition, it was also noted that participants with higher anxiety levels and lower happiness and self-esteem levels got—on average—lower grade point averages and lower average grades in math, language and physical education.These findings contribute to the local information and support existing evidence relating to lower levels of self-esteem, happiness index, higher anxiety levels, and lower school performance. Thus, it becomes the most up-to-date evidence that accounts for the relationship between anxiety, self-esteem, happiness, and schoolchildren’s school performance from Chilean public educational centers. Additionally, this study is a pioneer in Latin America in associating the perception of happiness and school performance, opening a promising research line on happiness and academic performance, which will complement the current evidence provided from the perspective of positive psychology on the relationship of these variables ,13.Moreover, this research paper sheds light on the importance of mental health studies, particularly from the perception of happiness and their implications on school performance and the behavior associated with cognition in school settings. These results can provide evidence and be used in educational centers to reflect on the importance of mental health in schoolchildren and on the potential negative impact of lower levels of self-esteem, happiness and higher anxiety levels on school performance and related behaviors with cognition in the school environment. Additionally, this study provides evidence to continue with the integration of interventions that promote better psychological health and academic performance in schoolchildren ,29,30,38Therefore, this study brings about the need to promote programs that directly impact mental health indicators and allow school students to improve their academic performance. Finally, these findings also reinforce the need to develop emotional education plans and promote general mental health in school students, as they could be directly related to school performance ,36. Base


Purpose: This study aimed to assess the prevalence, incidence, and associated factors of possible sarcopenia in a nationwide representative sample of the community-dwelling older Chinese population.Methods:This study used the data of participants aged 60 years and over from the China Health and Retirement Longitudinal Study (CHARLS). Data on participants from three waves (2011–2015) of CHARLS were extracted. Possible sarcopenia was defined as low muscle strength or low physical performance, based on the Asian Working Group for Sarcopenia 2019 consensus. We first described baseline prevalence and four-year incidence of possible sarcopenia. Then multiple logistic regression and multivariable parametric proportional hazard model with Weibull distribution were used to examine the association of risk factors with baseline prevalence and four-year incidence of possible sarcopenia, respectively.Results:The prevalence of possible sarcopenia was 46.0%. The four-year incidence of possible sarcopenia was 11.9 per 100 person-years. Multivariable analysis revealed that advanced age and depressive symptoms were associated with increased prevalence of possible sarcopenia, while receiving education and moderate or high physical activity were associated with a lower risk of possible sarcopenia prevalence. For incidence, only advanced age was associated with an increased risk of possible sarcopenia incidence.Conclusion:Our study revealed the substantial burden of possible sarcopenia and related risk factors in community-dwelling settings in China. It highlighted the importance of early detection and intervention in this subclinical group for the prevention of sarcopenia. Advancing age is accompanied by a series of physiological changes in body composition, one of which is characterized as the gradual decrease in muscle quantity and quality . When loMeasuring muscle mass is an indispensable procedure in the diagnosis of sarcopenia. However, assessing muscle mass is still a challenge in primary care settings where reliable and validated diagnostic equipment is not easily accessible. To promote early identification of people at risk of, or on the way to, sarcopenia and raise awareness of sarcopenia prevention in primary care settings, the AWGS 2019 consensus proposes a new concept named “possible sarcopenia,” which refers to poor muscle strength or low physical performance . AccordiThe epidemiological information of possible sarcopenia is limited. At present, three cross-sectional studies have reported the prevalence of possible sarcopenia based on the AWGS 2019 consensus . One wasThe purpose of this study was to estimate the prevalence and incidence of possible sarcopenia, according to the definition of the AWGS 2019 consensus, and to examine potential risk factors for both using a nationwide representative sample of community-dwelling older Chinese population aged 60 years and above. As a newly proposed concept in the updated guideline for sarcopenia, possible sarcopenia is less investigated. Epidemiological evidence of possible sarcopenia, such as prevalence and incidence, is the first step for decision-making regarding resource allocation in healthcare  and to develop preventive routines or healthcare services tailored to the growing older population. Identifying risk factors of possible sarcopenia could further help to prioritize screening and prevention programs for the particular subgroup(s).This study was the secondary analysis of the China Health and Retirement Longitudinal Study (CHARLS).This study used data from CHARLS, which is an ongoing longitudinal survey targeting a nationally representative sample of Chinese adults aged 45 years and over. Details of CHARLS have been reported elsewhere . BrieflyPossible sarcopenia, at all three waves, was defined based on the AWGS 2019 consensus, as low muscle strength or low physical performance .Muscle strength was assessed by handgrip strength. In CHARLS, handgrip strength was measured with the mechanical dynamometer . Participants were instructed to bend the elbow with 90° and squeeze the dynamometer as hard as they can for a couple of seconds. For those unable to stand unassisted, sitting was allowed. In line with AWGS 2019 recommendation, each hand was tested twice separately, and the maximum reading of four measures was used to reflect handgrip strength. Low muscle strength was defined as the handgrip strength <28 kilograms (kg) in men and <18 kg in women . The hanPhysical performance was assessed by the five-time chair stand test. Participants were instructed to sit down and keep their arms folded across the chest. Then they were asked to stand up and sit down at their fastest pace five times consecutively, without stopping and moving arms. The time needed to finish the test was recorded by the examiner. As recommended by AWGS 2019, low physical performance was defined as needing 12 s or more to complete the task . ParticiBased on previous evidence on sarcopenia, similar risk factors were considered for possible sarcopenia, including age, gender, education level, marital status, residence, smoking and drinking status, physical activity (PA), depression, body mass index (BMI), and multimorbidity , 13.Age was divided into three subgroups: 60–69, 70–79, and 80 and above. The highest education level was divided into four groups: illiterate, primary school, secondary school, and high school and above. The marital status of participants was categorized into two groups: married vs. single, divorced, or widowed. Rural or urban residence was determined based on the administrative division from the National Bureau of Statistics China .Smoking and drinking status were grouped into three categories: never, ever but quit, and current use. As for PA level, the CHARLS collected information regarding the intensity, duration, and frequency of PA in a usual week. Three types of intensity  and discrete time duration of PA were collected. In this study, we first calculated the volume of each type of PA by multiplying duration per day (minutes/day) with frequency (days), then transformed the volume into a metabolic equivalent value (MET)  . BecauseDepression was measured with the validated 10-item Center for Epidemiologic Studies Depression Scale short form , 24. Par2), overweight (23 kg/m2 ≤ BMI <25 kg/m2), normal (18.5 kg/m2 ≤ BMI <23 kg/m2), and underweight (BMI <18.5 kg/m2) (Body mass index (BMI) was calculated as the weight in kilograms divided by the square of height in meters. BMI status was categorized into four groups: obese BMI ≥ 25 kg/m kg/m2, o5 kg/m2) . At pres5 kg/m2) . Based o5 kg/m2) . Therefo5 kg/m2) . The CHADescriptive statistics on the sample characteristics were calculated for the total analytical sample. For incidence assessment, we only analyzed the data from participants who were free of possible sarcopenia at baseline. Those who lacked data to identify possible sarcopenia at both two follow-up waves (2013 and 2015) were excluded. Furthermore, to restrict interval censoring to within 2 years, we also excluded those who only lacked data on possible sarcopenia at the second wave (2013). Incidence proportion was calculated as new cases during the follow-up divided by the total number of at-risk subjects being followed. The four-year incidence rate of possible sarcopenia was calculated as new cases during 2011–2015 divided by the person-years of follow-up.For the identification of risk factors, we only analyzed data from participants without missing data in the potential risk factors at baseline. We used multivariable logistic regression to examine the adjusted association between risk factors and prevalent possible sarcopenia at baseline. Adjusted odds ratio (OR) was estimated with 95% CIs. For the incidence of possible sarcopenia, the onset time could not be exactly detected because the CHARLS collected data every 2 years. For new cases during the four-year follow-up, the onset time was only known to lie in an interval time between the last wave of free of possible sarcopenia and the wave of the new diagnosis of possible sarcopenia. Therefore, the onset time was regarded as interval censoring. For those free of possible sarcopenia until the third wave, the data were regarded as right censoring. Right censored data can be regarded as the special case of interval censoring, with the interval unbounded on the right . For intConsidering the multistage probability sampling design and non-response in the CHARLS data, individual sampling weights with non-response adjustment were taken into account in the analysis. All analyses were conducted using Stata15.0 . Signifin = 485), cancer (n = 71), and those with missing data either in handgrip strength or the five-time chair stand test  at baseline, a total of 4,866 participants were eligible for inclusion in analyzing baseline prevalence   . A totaln = 2,628). After deleting those with insufficient data to identify possible sarcopenia at the second wave (n = 874), and at both two waves (n = 0), a total of 1,754 participants were included in the incidence analysis . Adjusted associations of risk factors with prevalent and incident possible sarcopenia were shown in For risk factors analysis, we only included those free of missing data in baseline covariates  and Korea 20.1–29.2%)  and 12.1 per 100 person-years (95% CI: 11.2–13.0), respectively. The estimates were similar to the main results. Furthermore, findings from the risk factor analysis were also consistent with our main results . Third, This study examined the prevalence and incidence of possible sarcopenia as well as the associated factors in Chinese community-dwelling older adults. Advanced age, not received education, physical inactivity, and depression symptoms were associated with an increased risk of possible sarcopenia prevalence, while only advanced age was associated with an increased incidence rate of possible sarcopenia. Early screening and lifestyle intervention for these at-risk populations are encouraged in the primary care service of sarcopenia prevention.http://charls.pku.edu.cn/.Publicly available datasets were analyzed in this study. This data can be found here: The studies involving human participants were reviewed and approved by Biomedical Ethics Review Committee of Peking University. The patients/participants provided their written informed consent to participate in this study.PC, ZC, and MH: study concept and design and critical revision of the manuscript for important intellectual content. ZC: data extraction and drafting of the manuscript. ZC and PC: analysis and interpretation of data. All authors contributed to the article and approved the submitted version.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.


ETS1, TP53, E2F1, and GATA3 are highly associated with melanoma. Furthermore, our method can also be extended to other scRNA-seq data.Single-cell sequencing technology provides insights into the pathology of complex diseases like cancer. Here, we proposed a novel computational framework to explore the molecular mechanisms of cancer called melanoma. We first constructed a disease-specific cell–cell interaction network after data preprocessing and dimensionality reduction. Second, the features of cells in the cell–cell interaction network were learned by node2vec which is a graph embedding technology proposed previously. Then, consensus clusters were identified by considering different clustering algorithms. Finally, cell markers and cancer-related genes were further analyzed by integrating gene regulation pairs. We exploited our model on two independent datasets, which showed interesting results that the differences between clusters obtained by consensus clustering based on network embedding (CCNE) were observed obviously through visualization. For the KEGG pathway analysis of clusters, we found that all clusters are extremely related to MicroRNAs in cancer and HTLV-I infection, and the hub genes in cluster specific regulatory networks, i.e.,  Melanoma is a malignant tumor that develops from melanocytes and is a complex multifactorial disease caused by the interaction between genetic susceptibility factors and environmental exposure . In the There have been many significant studies based on bulk RNA-seq data of melanoma. On the other hand, network embedding is becoming a powerful way of representing the features of nodes in complex networks, and is widely used in various fields, including medicine, biology, sociology, and finance. Several state-of-art network embedding algorithms are proposed to help accomplish analysis tasks of complex networks, e.g., DeepWalk  and nodeIn this study, we applied network embedding to represent cell features, identified consensus clusters by consensus clustering, and investigated gene markers for melanoma. In the following section, we introduced the materials and methods in our model and then showed and analyzed the results. Finally, we made conclusions for our study.1  represents the Euclidean distance of the regulation pair , and max(dist) and min(dist) represent the maximum distance and the minimum distance in all regulation pairs, respectively. The larger the value, the stronger the correlation between the genes.where Then we identified the feed-forward loops (FFLs)  from theWe analyzed scRNA-seq data according to the pipeline shown in We calculated the Euclidean distance between every pair of cells in GSE72056 and filtered the pairs with the distance less than the mean distance. As a result, we obtained a cell–cell interaction network with 1,312 nodes (cells) and 444,382 edges after discarding 34 isolated cells.p = 4 and q = 0.5   .For GO enrichment analysis, we selected the top 10 items   for eachAs shown in We analyzed an independent dataset EXP0072 to verify our approach. We expressed the embedding vectors of 307 cells with 128 dimensions, which is the same as our previous experiment. The identified three clusters are shown in The numbers of genes that expressed in less than 70% of the cells in clusters were 220, 255, and 176, respectively. Then we built cluster specific gene regulatory networks accordingly. The information of cluster specific gene regulatory networks is shown in E2F1 was the hub gene in both datasets. ESR1 encodes an estrogen receptor and ligand-activated transcription factor. The protein encoded by this gene regulates the transcription of many estrogen-inducible genes and is expressed in many non-reproductive tissues. NF-kappa-B is a transcription factor formed by the combination of NFKB1 and RELA, which participates in many biological processes. E2F4 encoded by this gene is a member of the E2F family of transcription factors. The E2F family plays a crucial role in the control of cell cycle and action of tumor suppressor proteins and is also a target of the transforming proteins of small DNA tumor viruses. MYC is a proto-oncogene and encodes a nuclear phosphoprotein that plays a role in cell cycle progression, apoptosis, and cellular transformation. Amplification of this gene is frequently observed in numerous human cancers  for Kaplan–Meier survival analysis  to test  cancers .From the experiments, we found that the size of the dataset has impact on the computational cost, but not affects the network embedding, clustering, or quality of the reconstructed GRNs.ETS1, TP53, E2F1, and GATA3 are related to melanoma. At the same time, in order to verify the scalability of the method, we analyzed an independent melanoma dataset that the clusters were highly consistent, and hub genes have a great impact on melanoma.We investigated the pathology of melanoma via scRNA-seq, which revealed the significant impact of hub genes in the development of melanoma. By constructing the cell–cell interaction network and obtaining the consensus clusters, we found that the differences between clusters are obvious. Through our further analysis of each cluster, we found the hub genes http://www.ncbi.nlm.nih.gov/geo/) and CancerSEA at http://biocc.hrbmu.edu.cn/CancerSEA/goDownload.The data underlying this article are available in Gene Expression Omnibus (GQ, FL, and LD conceived and developed the framework for consensus clusters identification and wrote this manuscript. LW and GQ provided important feedback in the framework process and edited the manuscript. All authors made significant contributions to the completion and writing of this manuscript, and read and approved the final manuscript.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.