Aiming to inform the development of effective teacher preparation programs that harness artificial intelligence's (AI) power and ultimately contribute to the broader goal of equitable education, this study investigates preservice teachers’ experiences and perceptions related to AI focusing on social learning. Specifically, it examines preservice teachers’ familiarity with AI, their views on its potential to enhance social learning and their perspectives on designing AI-supported environments to foster social learning. The analyses of data collected from 197 preservice teachers show that about one-third of preservice teachers have no or limited familiarity with AI, and a majority of them expressed hesitations about using AI to foster social learning. Overall, they found AI to be more beneficial for designing virtual learning practices compared to its potential in supporting student social learning, among other findings.

The aim of this study was to synthesize thiolated chitosan derivative and evaluated its antioxidant activity. Thiol groups were introduced into chitosan and hydroxypropyl trimethylammonium chloride chitosan quaternary ammonium salt (HACC) by microwave reaction, respectively. At the same time, a series of compounds containing thiol groups were introduced at the amino site. The structure of the chitosan derivatives was identified by FTIR and 1H NMR. The thiol groups content, thermal stability, water solubility and cytotoxicity of the chitosan derivative were evaluated. The antioxidant activity of chitosan derivatives was evaluated using superoxide anion radical scavenging activity assay, DPPH radical scavenging activity assay, hydroxyl radical scavenging activity assay and reducing power assay. The results showed that the thiolated chitosan derivatives obtained in this study possessed excellent antioxidant activity, which provides a new idea for the further study of chitosan antioxidants.

Preservice teachers' beliefs regarding technology integration significantly influence their future teaching practices. This qualitative study examines the beliefs and intentions of 51 preservice teachers within the context of technology integration in their envisioned teaching scenarios. Thematic analysis identified three primary themes. Firstly, participants expressed their intentions to integrate technology into teaching, with 74% exhibiting a high intention, 22% moderate, and 4% low. Secondly, value beliefs encompassed positive perceptions supported by interest and usefulness, including eight roles of technology (e.g., facilitators, quality enhancers) and four concerns (e.g., equity, safety). Negative beliefs such as distraction were also identified. Thirdly, pedagogical beliefs varied, with 49% holding student-centered views, 37% being teacher-centered, and 14% balanced perspectives. Crosstab analysis explored relationships between technology integration intention levels, value beliefs, and pedagogical beliefs. These findings offer insights into preservice teachers' beliefs on technology integration, informing teacher education programs and strategies to enhance technology integration in classrooms.

Pluripotent stem cell-derived small extracellular vesicles (PSC-sEVs) have demonstrated great clinical translational potential in multiple aging-related degenerative diseases. Characterizing the PSC-sEVs is crucial for their clinical applications. However, the specific marker pattern of PSC-sEVs remains unknown. Here, the sEVs derived from two typical types of PSCs including induced pluripotent stem cells (iPSC-sEVs) and embryonic stem cells (ESC-sEVs) were analysed using proteomic analysis by liquid chromatography with tandem mass spectrometry (LC-MS/MS), and surface marker phenotyping analysis by nanoparticle flow cytometry (NanoFCM). A group of pluripotency-related proteins were found to be enriched in PSC-sEVs by LC-MS/MS and then validated by Western Blot analysis. To investigate whether these proteins were specifically expressed in PSC-sEVs, sEVs derived from seven types of non-PSCs (non-PSC-sEVs) were adopted for analysis. The results showed that PODXL, OCT4, Dnmt3a, and LIN28A were specifically enriched in PSC-sEVs but not in non-PSC-sEVs. Then, commonly used surface antigens for PSC identification (SSEA4, Tra-1-60 and Tra-1-81) and PODXL were gauged at single-particle resolution by NanoFCM for surface marker identification. The results showed that the positive rates of PODXL (>50%) and SSEA4 (>70%) in PSC-sEVs were much higher than those in non-PSC-sEVs (<10%). These results were further verified with samples purified by density gradient ultracentrifugation. Taken together, this study for the first time identified a cohort of specific markers for PSC-sEVs, among which PODXL, OCT4, Dnmt3a and LIN28A can be detected with Western Blot analysis, and PODXL and SSEA4 can be detected with NanoFCM analysis. The application of these specific markers for PSC-sEVs identification may advance the clinical translation of PSCs-sEVs.

Aiming to promote equity in computing, this study proposes an educational model that offers an alternative approach to inspire K-12 students to become interested in CS and develop their computational thinking (CT) skills. It also examines the experience of marginalized students during the COVID pandemic in a learning environment grounded in the model. Adopting a mixed methods case study, this work focused on the experience of 82 girls enrolled in a free after school program. The results show that access to the opportunities is critical to promote equity. The experience allows the underrepresented population, i.e. the girls, to gain deepened understanding of not only CT/CS, but also other topics like work ethics, digital citizenship, and how to work with peers to achieve goals. The girls have also broadened their views of computing related fields by working on meaningful projects that demonstrated the value of abstract concepts of coding and programming. A combination of human facilitators and well-constructed tutorials has the potential of improving girls’ self-study skills and preparing them to become more independent learners.

Tendinopathy is a common musculoskeletal disorder which results in chronic pain and reduced performance. The therapeutic effect of stem cell derived-small extracellular vesicles (sEVs) for tendinopathy has been validated in recent years. However, whether large extracellular vesicles (lEVs), another subset of extracellular vesicles, possesses the ability for the improvement of tendinopathy remains unknown. Here, we showed that lEVs secreted from iPSC-derived MSCs (iMSC-lEVs) significantly mitigated pain derived from tendinopathy in rats. Immunohistochemical analysis showed that iMSC-lEVs regulated the heterogeneity of infiltrated macrophages and several inflammatory cytokines in rat tendon tissue. Meanwhile, in vitro experiments revealed that the M1 pro-inflammatory macrophages were repolarized towards M2 anti-inflammatory macrophages by iMSC-lEVs, and this effect was mediated by regulating p38 MAPK pathway. Moreover, liquid chromatography-tandem mass spectrometry analysis identified 2208 proteins encapsulated in iMSC-lEVs, including 134 new-found proteins beyond current Vesiclepedia database. By bioinformatics and Western blot analyses, we showed that DUSP2 and DUSP3, the negative regulator of p38 phosphorylation, were enriched in iMSC-lEVs and could be transported to macrophages. Further, the immunomodulatory effect of iMSC-lEVs on macrophages was validated in explant tendon tissue from tendinopathy patients. Taken together, our results demonstrate that iMSC-lEVs could reduce inflammation in tendinopathy by regulating macrophage heterogeneity, which is mediated via the p38 MAPK pathway by delivery of DUSP2 and DUSP3, and might be a promising candidate for tendinopathy therapy.

Objectives Fragmentation of cancer care (FC) occurs when patients receive treatment across several different hospitals. Patients with high-grade endometrial cancer often require adjuvant treatment after surgery, and it is unknown if change of location during treatment impacts patient outcomes. Methods This population-based retrospective cohort study included patients diagnosed between 2003–2017 with high-grade endometrial cancer who received adjuvant treatment post-operatively. Non-fragmented care (NFC) was defined as receiving surgery and adjuvant treatment at the same institution. The primary outcome was overall survival (OS). Results We identified 1,795 patients, of whom 583 (32.5%) had FC. Patients with NFC were more likely to have had surgery by a Gynecologic Oncologist (92.4 vs 58.8%, p<0.001), surgical staging (66.6 vs 44.8%, p<0.001), and less travel for surgery (mean 30.8 km vs 93.7 km, p<0.001). They were less likely to receive chemotherapy (26.3 vs 30%, p<0.001) and chemoradiation (38.4 vs 41.3%, p<0.001). Median survival was 9 years. There was no significant difference in OS between patients who received FC and NFC. 92.4 and 93.5% of the patients in the FC and NFC groups were treated at a specialized gynecologic oncology centre for at least part of their treatment (surgery, adjuvant treatment or both). Conclusions We have previously shown that regionalization of surgery in high-grade endometrial cancer is associated with improved survival. Fragmentation of surgery and adjuvant treatment in this population does not have an adverse effect on survival. After receiving surgical treatment with a Gynecologic Oncologist, these patients may receive adjuvant treatment closer to home to decrease financial and travel burden.

Innate lymphoid cells (ILCs) are a newly identified heterogeneous family of innate immune cells. We conducted this study to investigate the frequency of circulating ILC subsets in various chronic kidney diseases (CKD). In DN, the proportion of total ILCs and certain ILC subgroups increased significantly. Positive correlations between proportion of total ILCs, ILC1s and body mass index, glycated hemoglobin were observed in DN. In LN, a significantly increased proportion of ILC1s was found in parallel with a reduced proportion of ILC2s. The proportions of total ILCs and ILC1s were correlated with WBC count and the level of C3. In all enrolled patients, the proportion of total ILCs and ILC1s was significantly correlated with the levels of ACR and GFR. In the present study, the proportion of circulating ILC subsets increased significantly in various types of CKD and correlated with clinico-pathological features, which suggests a possible role for ILCs in CKD.

Abstract: This study explores an online learning world where game development was a center piece and social learning was an inherent feature rather than imposed. Grounded in enactivism, this paper examines the affordances of this environment, focusing on sociocultural perspectives. This qualitative case study involved 35 participating educators. Data included educators’ online interactions and written work. The results showed that the learning environment afforded ample opportunities for social learning, as reflected in the extent and ways the educators interacted and collaborated with each other. A total of nine categories of interactions were identified, illustrating the diverse types of social communication. Culture of learning, trauma, and games contributing to the formation of a culture were some major themes identified in educators’ reflections.

The paper shares the results of the process of forming a cross-disciplinary collaborative team and using a user-centered design framework to co-create a self-directed, self-paced, personalized, flexible learning environment as an alternative

Background Patients diagnosed with cancer often experience considerable challenges with mental health, and those who had more intense psychiatric care prior to their cancer diagnosis have a higher risk of mortality. As prior research demonstrated a survival benefit among patients screened for symptoms using the Edmonton symptom assessment system (ESAS), this study aims to examine the association between being ESAS-screened and the risk of mortality across varying intensity levels of pre-diagnosis psychiatric care utilization. Methods We conducted a retrospective matched cohort study using population-wide administrative databases. All patients diagnosed with cancer in Ontario, Canada, from January 2007 to December 2015 were identified. Propensity score matching was used to pair ESAS-screened individuals to those not screened. Pairs were also hard matched on a pre-diagnosis psychiatric care utilization gradient. A multivariable Cox proportional hazards regression model was implemented to estimate the association between ESAS and mortality, for each intensity level of pre-diagnosis psychiatric care. Results The matched cohort consisted of 119,806 patient pairs (ESAS-screened and not screened), of whom 54,468 (45.5%) pairs had prior outpatient psychiatric care and 2249 (1.8%) pairs had experienced emergency department visits or had been hospitalized for psychiatric care. Overall being exposed to ESAS was significantly associated with a 51% decrease in the hazard of mortality (HR 0.49, 95%CI 0.48-0.50, p-value <0.0001). This association was similar across all levels of prior psychiatric use, however, there was no evidence of a differential impact. Conclusion In addition to routinely monitoring symptom severity, including depression, among patients with cancer, it is also important to identify those with preexisting psychiatric comorbidities at the time of diagnosis. This information can be used to ensure that timely and appropriate psycho-oncology services and psycho-social supports are offered to help the patient and their family cope during the cancer disease trajectory.

OBJECTIVE:Practice guidelines advocating for regionalization of endometrial cancer surgery to gynecologic oncologists practicing in designated gynecologic oncology centres were published in Ontario in June 2013. Our objectives were to determine whether this policy affected surgical wait times, and whether longer wait time to surgery is a predictor of survival in high grade endometrial cancer patients. METHODS:This was a population-based retrospective cohort study, which included patients diagnosed with high-grade non-endometrioid endometrial cancer who had a hysterectomy between 2003 and 2017. Multivariable Cox proportional hazards regression with a spline function was used to model the relationship between surgical wait time and overall survival (OS). RESULTS:We identified 3518 patients who underwent hysterectomy for high-grade non-endometrioid endometrial cancer. Patients who had surgery with a gynecologic oncologist had a median surgical wait time from diagnosis to hysterectomy of 53 days compared to 57 days pre-regionalization (p = 0.0007), and from first gynecologic oncology consultation to hysterectomy of 29 days compared to 32 days pre-regionalization (p = 0.0006). Survival was inferior for patients who had surgery within 14 days of diagnosis (HR death 2.7 for 1-7 days, 95% CI 1.61-4.51, and HR death 1.96 for 8-14 days, 95% CI 1.50-2.57), reflective of disease severity. Decreased survival occurred with surgical wait times of more than 45 days from the patient's first gynecologic oncology appointment (HR death 1.19 for 46-60 days, 95% CI 1.04-1.36, and HR death 1.42 for 61-75 days, 95% CI 1.11-1.83). CONCLUSIONS:Regionalization of surgery for high-grade endometrial cancer has not had an impact on surgical wait times. Patients who have surgery more than 45 days after surgical consultation have reduced survival.

The success of transcriptome-wide association studies (TWAS) has led to substantial research toward improving the predictive accuracy of its core component of genetically regulated expression (GReX). GReX links expression information with genotype and phenotype by playing two roles simultaneously: it acts as both the outcome of the genotype-based predictive models (for predicting expressions) and the linear combination of genotypes (as the predicted expressions) for association tests. From the perspective of machine learning (considering SNPs as features), these are actually two separable steps-feature selection and feature aggregation-which can be independently conducted. In this study, we show that the single approach of GReX limits the adaptability of TWAS methodology and practice. By conducting simulations and real data analysis, we demonstrate that disentangled protocols adapting straightforward approaches for feature selection (e.g., simple marker test) and aggregation (e.g., kernel machines) outperform the standard TWAS protocols that rely on GReX. Our development provides more powerful novel tools for conducting TWAS. More importantly, our characterization of the exact nature of TWAS suggests that, instead of questionably binding two distinct steps into the same statistical form (GReX), methodological research focusing on optimal combinations of feature selection and aggregation approaches will bring higher power to TWAS protocols.

12101 Background: Symptom control is prioritized by cancer patients and may improve overall survival. Several jurisdictions have thus launched population-wide initiatives to assess symptoms at regular intervals. In Ontario, Canada, for example, all cancer patients are screened using the Edmonton Symptom Assessment System (ESAS) at every outpatient visit. Few studies have examined symptom burdens in adolescents and young adults (AYA). Previous work suggests that AYA symptoms differ from those in older patients, and that general screening tools may not be appropriate. Despite this, whether current symptom screening initiatives reach AYA with cancer are unknown. We therefore determined 1) Whether AYA with cancer were participating in ESAS screening, and 2) Which AYA were at highest risk of not being screened. Methods: We identified all Ontario AYA diagnosed with cancer at age 15-29 years between 2010-2018 and treated in adult centers. Patients were linked to population-based databases to identify all cancer-related outpatient visits in the year following diagnosis and whether visits involved completion of an ESAS form. Each patient’s first year was divided into two-week periods. For each period, AYA were considered either “unscreened” if they had a cancer-related visit but no ESAS score, or “screened” if they had a cancer-related visit with at least one ESAS score. Periods without cancer-related visits were not considered, given no potential for ESAS screening during such periods. Covariates included age at diagnosis, sex, cancer type, neighbourhood income quintile, and institution type [regional cancer centre (RCC) vs. community]. Multivariable logistic regression models were implemented under a generalized estimating equations approach to account for individual-level correlation. Results: The final cohort included 5,435 AYA. Within any given two-week period, only 36-45% of AYA attending cancer-related outpatient visits were screened. In adjusted analyses, age and sex were not associated with being screened. However, AYA living in the lowest income quintile neighbourhood were less likely to be screened [odds ratio (OR) 0.86, 95th confidence interval (95CI) 0.77-0.97; p = 0.01] compared to those in the highest. Patients with hematologic malignancies were least likely to be screened (OR 0.77, 95CI 0.67-0.88; p < 0.001), as were AYA attending community centers (OR 0.48, 95CI 0.42-0.55; p < 0.001). Conclusions: Despite a population-wide symptom assessment program, only a minority of AYA are screened. Though patients with hematologic cancers suffer from particularly high symptom burdens, they were less likely to be screened. Interventions targeting AYA are required to increase uptake, particularly among those in disadvantaged neighborhoods or attending community hospitals. Studies of AYA-specific symptom assessment tools are also warranted.

Preeclampsia is the main reason for maternal and fetal deaths during the second half of pregnancy. Trophoblast cells play a pivotal role in preeclampsia progression. Circular RNA (circRNA) circ_0111277 has been reported to be related to the development of trophoblast cells. This study is designed to explore the role and mechanism of circ_0111277 on trophoblast cell behavior in preeclampsia. Circ_0111277, microRNA-424-5p (miR-424-5p), and nuclear factor of activated T-cell 5 (NFAT5) levels were measured by real-time quantitative polymerase chain reaction (RT-qPCR). Cell viability, migration, invasion, and angiogenesis were measured by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) assay, transwell assay, tube formation assay, and wound healing assay. Protein levels of matrix metallopeptidase 2 (MMP2), vascular endothelial growth factor-A (VEGF-A), NFAT5, phospho-phosphatidylinositol 3 kinase (p-PI3K), PI3K, phospho-protein kinase B (p-AKT), and AKT were examined by western blot assay. The binding relationship between miR-424-5p and circ_0111277 or NFAT5 was predicted by circBank or starBase and then verified by a dual-luciferase reporter assay. Circ_0111277 and NFAT5 expression were increased in placenta tissues of preeclampsia patients, and miR-424-5p was decreased. Moreover, circ_0111277 knockdown could boost cell viability, migration, invasion, and angiogenesis in trophoblast cells. The mechanical analysis discovered that circ_0111277 acted as a sponge of miR-424-5p to regulate NFAT5 expression. Besides, circ_0111277 silencing promoted the PI3K/AKT signaling pathway in trophoblast cells. Circ_0111277 downregulation could facilitate cell growth and metastasis in trophoblast cells partly by regulating the miR-424-5p/NFAT5 axis, providing an underlying circRNA-targeted therapy for preeclampsia.

The transcriptome-wide association study (TWAS) has emerged as one of several promising techniques for integrating multi-scale 'omics' data into traditional genome-wide association studies (GWAS). Unlike GWAS, which associates phenotypic variance directly with genetic variants, TWAS uses a reference dataset to train a predictive model for gene expressions, which allows it to associate phenotype with variants through the mediating effect of expressions. Although effective, this core innovation of TWAS is poorly understood, since the predictive accuracy of the genotype-expression model is generally low and further bounded by expression heritability. This raises the question: to what degree does the accuracy of the expression model affect the power of TWAS? Furthermore, would replacing predictions with actual, experimentally determined expressions improve power? To answer these questions, we compared the power of GWAS, TWAS, and a hypothetical protocol utilizing real expression data. We derived non-centrality parameters (NCPs) for linear mixed models (LMMs) to enable closed-form calculations of statistical power that do not rely on specific protocol implementations. We examined two representative scenarios: causality (genotype contributes to phenotype through expression) and pleiotropy (genotype contributes directly to both phenotype and expression), and also tested the effects of various properties including expression heritability. Our analysis reveals two main outcomes: (1) Under pleiotropy, the use of predicted expressions in TWAS is superior to actual expressions. This explains why TWAS can function with weak expression models, and shows that TWAS remains relevant even when real expressions are available. (2) GWAS outperforms TWAS when expression heritability is below a threshold of 0.04 under causality, or 0.06 under pleiotropy. Analysis of existing publications suggests that TWAS has been misapplied in place of GWAS, in situations where expression heritability is low.

Computational thinking (CT) is increasingly being recognized as a fundamental skill, like math, for all students. This need to equip every student with competent CT skills calls for CT education in K-12 schools and teachers with adequate content and pedagogical knowledge to integrate CT. This study elicits and synthesis what top leaders in CT education know and experience about best practices of CT in K-12 schools and educator preparation. It also examines experts' views about distinctive challenges, useful strategies, and practical models related to CT education. Adopting an expert interview approach, the participants are five leaders with diverse background and extensive experience in the field of CT education. The qualitative analysis of the data points to two guidelines to teach CT in K-12 context, namely age level appropriateness and good design. It also indicates three main challenges and specific strategies to establish CT-integrated teacher education programs.