Explore the vast range of titles available.

The adoption of the maker-centered method is gaining popularity in K-12 school curricula. However, a unified consensus on its effectiveness in enhancing K-12 students' learning outcomes remains elusive. Therefore, the purpose of this meta-analysis was to synthesize the findings on the overall effects of the maker-centered learning method on K-12 students' learning outcomes. We reviewed the literature published between 2010 and 2022 and identified 34 empirical studies on the maker-centered learning method that met inclusion criteria. The combined effect size was then calculated using a random effects model (REM). Results showed that the maker-centered learning method has a small effect on K-12 students' learning outcomes with an overall effect size of 0.369. The outcome measure was also coded to study the potential moderating effects of various characteristics of the studies, including learning stages, research design, experimental duration, testing instruments, measuring moment, disciplines, learning outcomes, and educational resources. The moderator analysis revealed that the maker-centered learning method was more effective for (a) high school students, (b) mathematics, (c) a learning duration of 1 to 3 months, (d) with the assistance of traditional educational resources, and (e) in the psychomotor performance. These findings provide insights for future studies and practical applications of the maker-centered learning method for K-12 students' academic development.

FOXM1 , a known transcription factor, promotes cell proliferation in a variety of cancer cells. Here we show that Foxm1 is required for survival, quiescence and self-renewal of MLL-AF9 (MA9)-transformed leukemia stem cells (LSCs) in vivo. Mechanistically, Foxm1 upregulation activates the Wnt/β-catenin signaling pathways by directly binding to β-catenin and stabilizing β-catenin protein through inhibiting its degradation, thereby preserving LSC quiescence, and promoting LSC self-renewal in MLL-rearranged AML. More importantly, inhibition of FOXM1 markedly suppresses leukemogenic potential and induces apoptosis of primary LSCs from MLL-rearranged AML patients in vitro and in vivo in xenograft mice. Thus, our study shows a critical role and mechanisms of Foxm1 in MA9-LSCs, and indicates that FOXM1 is a potential therapeutic target for selectively eliminating LSCs in MLL-rearranged AML. FOXM1 is a known transcription factor which promotes cell proliferation in cancer cells. Here, the authors show that FOXM1 is required for the maintenance of quiescence and self-renewal of leukemia stem cells in MLL-AF9-rearranged acute myeloid leukemia patient and mouse models.

Myelodysplastic syndromes (MDS) are age-related myeloid neoplasms with Increased risk of progression to acute myeloid leukemia (AML). The mechanisms of transformation of MDS to AML are poorly understood, especially in relation to the aging microenvironment. We previously established an mDia1/miR-146a double knockout (DKO) mouse model phenocopying MDS. These mice develop age-related pancytopenia with oversecretion of proinflammatory cytokines. Here, we found that most of the DKO mice underwent leukemic transformation at 12-14 months of age. These mice showed myeloblast replacement of fibrotic bone marrow and widespread leukemic infiltration. Strikingly, depletion of IL-6 in these mice largely rescued the leukemic transformation and markedly extended survival. Single-cell RNA sequencing analyses revealed that DKO leukemic mice had increased monocytic blasts that were reduced with IL-6 knockout. We further revealed that the levels of surface and soluble IL-6 receptor (IL-6R) in the bone marrow were significantly increased in high-risk MDS patients. Similarly, IL-6R was also highly expressed in older DKO mice. Blocking of IL-6 signaling significantly ameliorated AML progression in the DKO model and clonogenicity of CD34-positive cells from MDS patients. Our study establishes a mouse model of progression of age-related MDS to AML and indicates the clinical significance of targeting IL-6 signaling in treating high-risk MDS.

Purpose Among malignant tumors, non-small cell lung cancer (NSCLC) remains a major threat to human life and health. Studies have illustrated that minichromosome maintenance protein 4 (MCM4) has complex interactions with the progression of many cancers, yet the role and mechanism of MCM4 in NSCLC remain to be elucidated. Methods MCM4 expression in NSCLC tissues was assessed using the TCGA database. MCM4 levels in NSCLC cells and tissues was validated utilizing qRT-PCR and western blot. Cell proliferation, metastasis and EMT were measured by CCK-8, transwell, and western blot assays. Subsequently, E2F1 bound with the promoter of MCM4 was predicted via JASPAR database. Luciferase assay and chromatin immunoprecipitation (ChIP) were utilized to evaluate the binding relationship between the two. Finally, rescue experiments were performed to demonstrate the mechanism of MCM4 regulating NSCLC progression. Xenograft model was utilized to prove the role of MCM4 and E2F1 in NSCLC in vivo. Results MCM4 was markedly elevated in NSCLC tumor samples and intimately linked to poor patient prognosis. Silencing of MCM4 repressed growth, migration, invasion, and EMT of cells. In vivo test findings displayed that knockdown of MCM4 suppressed changes in tumor volume and weight in mice. Moreover, E2F1 bound with the promoter of MCM4 was predicted by JASPAR database. E2F1 was heightened in NSCLC tissues and cells. Then, the outcome of rescue assays confirmed that E2F1 introduction attenuated the depressing influence of MCM4 knockdown on NSCLC. Moreover, E2F1/MCM4 promoted the progression of NSCLC by activating the PI3K/AKT signaling pathway. Conclusions E2F1 accelerated NSCLC progression by activating the PI3K/AKT pathway through MCM4. Our outcomes confirmed that MCM4 is a potential target for the treatment of NSCLC patients.

Background There is some evidence in the literature that older adults with cognitive impairments have a higher risk for falls and osteoporotic hip fractures. Currently, the associations between bone health and cognitive health have not been extensively studied. Thus, the present cross-sectional study aims to investigate the relationship between markers of bone loss and cognitive performance in older adults with and without osteopenia as well as older adults with cognitive impairments (i.e., Alzheimer’s disease [AD]). Methods Sixty-two non-osteopenia participants and one hundred three osteopenia participants as the cohort 1 and 33 cognitively normal non-AD participants and 39 AD participants as the cohort 2 were recruited. To assess cognitive and bone health, hip bone mineral density (BMD) and cognitive performance (via Minimal Mental State Examination [MMSE] and/or Auditory Verbal Learning Test-delayed recall [AVLT-DR]) were assessed. Furthermore, in cohort 1, plasma amyloid-β (Aβ) levels, and in cohort 2, cerebrospinal fluid (CSF) Aβ levels were determined. Results We observed that (1) compared with non-osteopenia participants, BMD values (t = − 22.806; 95%CI: − 1.801, − 1.484; p  < 0.001), MMSE scores (t = − 5.392; 95%CI: − 3.260, − 1.698; p  < 0.001), and AVLT-DR scores (t = − 4.142; 95%CI: − 2.181, − 0.804; p  < 0.001), plasma Aβ42 levels (t = − 2.821; 95%CI: − 1.737, − 0.305; p  = 0.01), and Aβ42/40 ratio (t = − 2.020; 95%CI: − 0.009, − 0.001; p  = 0.04) were significantly lower in osteopenia participants; (2) plasma Aβ42/40 ratio showed a mediate effect for the association between BMD values and the performance of cognitive function in osteopenia participants by mediation analysis, adjusting age, sex, years of education, and body mass index (BMI); (3) BMD values (95%CI: − 1.085, 0.478; p  < 0.001) were significantly reduced in AD participants as compared with cognitively normal non-AD participants; (4) in AD participants, the interactive effects of BMD and CSF Aβ42/40 ratio on MMSE scores was found by regression analysis, controlling age, sex, years of education, and BMI; (5) BMD can distinguish AD participants from cognitively normal non-AD participants with AUC of 0.816 and distinguish participants with the cognitive impairment from cognitively normal participants with AUC of 0.794. Conclusion Our findings suggest a relationship between bone health and cognitive health. Given the correlations between BMD and important markers of cognitive health (e.g. , central and peripheral pathological change of Aβ), BMD might serve as a promising and easy-accessible biomarker. However, more research is needed to further substantiate our findings.

ObjectiveTo examine the effects of lifestyle interventions, including dietary guidance, health education and weight management, on pregnancy outcomes in women at high risk of gestational diabetes mellitus (GDM).MethodsOur study included 251 women at high risk of GDM and 128 randomized to lifestyle interventions (dietary guidance, health education, and weight management); One hundred and twenty-three people were randomly assigned to a control group (regular pregnancy check-ups). Counts between groups were compared using either chi-square test or Fisher’s exact test.ResultsCompared with the control group, the risk of GDM was reduced by 46.9% (16.4% vs 30.9%, P = 0.007) and the risk of pregnancy induced hypertension (PIH) was reduced by 74.2% (2.3% vs 8.9%, P = 0.034) in the intervention group. There were no significant differences in macrosomia, cesarean section, or preterm birth ( P >0.05).ConclusionThe lifestyle intervention in this study helped pregnant women to better understand knowledge related to pregnancy, reduce stress and anxiety, and increase intake of adequate prenatal nutrition. This intervention prevented metabolic abnormalities that may occur due to inadequate nutrient intake during pregnancy. In addition, it helped women to control weight gain, maintain appropriate weight gain during pregnancy, and reduce the risk of excessive or insufficient weight gain, ultimately lowering the incidence of GDM and PIH. This highlights the importance of early screening and intervention for high-risk pregnant women.Clinical Trial Registrationhttps://www.chictr.org.cn, identifier ChiCTR2300073766.

BackgroundThe research aims to observe the difference in the effect of preoperative doxorubicin curcumin co-loaded lipid nanoparticles (DOX+CUR LPNs) and doxorubicin (VAD) in the treatment of osteosarcoma. Methods68 patients with osteosarcoma who visited the hospital from January 2020 to December 2022 are chosen. They are separated into VAD group and DOX+CUR LPNs group, with 34 cases in each group. VAD and DOX+CUR LPNs groups VAD chemotherapy, and DOX+CUR LPNs treatment, respectively. All patients receive tumor resection. Comparison is made between the two groups before chemotherapy, at the end of chemotherapy and 1 week after surgery on the changes of vascular endothelial growth factor (VEGF), angiopoietin-2 (Ang-2), galectin-3 (Gal-3), renal function indicators cystatin-C (Cys-C), serum creatinine (Scr), blood urea nitrogen (BUN) in the peripheral blood. The clinical efficacy and adverse reactions are determined by observation and follow-up for 1 month. ResultsThe VEGF, Ang-2, and Gal-3 in both groups were significantly lower at 1 week after chemotherapy and surgery compared to before chemotherapy (P < 0.05). The VEGF and Gal-3 in the DOX+CUR LPNs group were lower than those in the VAD group in the same period, with P < 0.05. The Cys-C, Scr, and BUN in both groups of patients after chemotherapy and surgery increased compared to before chemotherapy, with P < 0.05. The Cys-C, Scr, and BUN in the DOX+CUR LPNs group were lower than those in the VAD group during the same period, with P < 0.05. Following up for 1 month, the ORR of the DOX+CUR LPNs group was 94.12% (32/34) higher than that of the VAD group, with P < 0.05. The incidence of adverse reactions in the DOX+CUR LPNs group was 47.05% lower than that in the VAD group, with P < 0.05. ConclusionPreoperative application of DOX+CUR LPNs enables effective drug delivery to the tumor section by combining the antibacterial, antioxidant and anti-inflammatory effects of curcumin, which is co-wrapped in nanoparticles. It has the effect of promoting angiogenesis and damage repair, inhibiting inflammation-related factors, and protecting renal function, while adriamycin alone has drug resistance problems and toxic side effects, which can damage the patient's liver and kidney. Therefore, DOX+CUR LPNs are more effective than adriamycin alone, indicating that it can improve the therapeutic effect of the drug and reduce the side effects, which is of great significance for improving the survival rate and quality of life of patients.

Background Pulmonary embolism (PE) is a significant cause of death in cancer patients. Although there are many reports on the clinical features and In-hospital prognosis for PE, but few studies on malignant tumors combined with pulmonary embolism. Early identification of high-risk populations, enhanced monitoring, and targeted therapeutic measures are crucial for improving patient prognosis. We conducted this study to identify reliable prognostic indicators through the analysis of real-world data. Methods A total of 471 patients of malignant tumors complicated with PE were divided into two groups: (1) PE with poor prognosis group ( n  = 146). (2) PE without poor prognosis group ( n  = 325). Clinical characteristics, laboratory parameters and adverse prognostic events were recorded and analyzed. Results High diastolic blood pressure (Odds Ratio [OR] = 1.819, 95% confidence interval [CI]: 1.144–2.893, p  = 0.011), myoglobin (MYO) (OR = 3.283, 95% CI: 2.016–5.347, p  < 0.001), procalcitonin (PCT) (OR = 2.530, 95% CI: 1.581–4.049, p  < 0.001), pleural effusion (OR = 1.618, 95% CI: 1.013–2.584, p  = 0.044) and invasive surgery (OR = 2.339, 95% CI: 1.471–3.719, p  < 0.001) were found to be independent risk factors for poor prognosis in malignant tumor patients with PE. The ROC curve analysis showed that the area under the curve (AUC) for MYO and PCT were 0.683 and 0.657, respectively. The combined predictive value of MYO and PCT was 0.704. Conclusion High diastolic blood pressure, MYO, PCT, pleural effusion, invasive surgery were proved to be independent risk factors for poor prognosis in malignant tumor patients with PE. In biomarkers, the indicator of MYO combined with PCT shows the highest predictive value.

Uterine leiomyosarcoma (LMS) is a rare but deadly disease. Due to poor understanding of the molecular and genetic causes of the disease, the diagnosis of LMS has been based primarily on histology. Nuclear atypia is one of hallmarks in LMS, however, it also occurs in 2 clinically benign variants, including smooth muscle tumors with fumarate hydratase alteration (SMT‐FH) and leiomyoma with bizarre nuclei (LM‐BN). In addition to nuclear atypia, many well recognized biomarkers used for LMS are also frequently overexpressed in LM‐BN, and the histogenesis and molecular natures for LM‐BN and LMS remain largely unknown. To characterize the molecular profiling of LMS, SMT‐FH, and LM‐BN, we performed integrated comprehensive genomic profiling including whole‐genome sequencing (WGS) and RNA sequencing and genomic microarray analyses to assess genome‐wide copy number alterations (CNAs) and immunohistochemistry (IHC) in all 3 tumor types. We found that both LM‐BN and LMS showed genomic instability and harbored extensive CNAs throughout the whole genome. By contrast, the SMT‐FH presented its characteristic 1q43‐44 deletions in all cases tested, with minimal CNAs in the rest of genomic regions. Further analyses revealed that LMS and LM‐BN groups showed similar patterns of CNAs that are tended to cluster together and separated from the SMT‐FH group. The integrated molecular profiling enabled the detection of novel and traditional biomarkers and showed excellent discrimination between LM‐BN and LMS. Our study suggests that LM‐BN, despite having similar nuclear atypia to SMT‐FH, showed similar genomic instability but distinct genomic alterations with its malignant counterpart of LMS. The integrated molecular profiling is of clinical importance in characterizing these rare uterine smooth muscle tumors. Leiomyosarcoma and 2 benign mimics (leiomyoma with FH alteration [SMT‐FH] and leiomyoma with bizarre nuclei [LM‐BN]) have characteristic nuclear atypia and often cause diagnostic challenge. LM‐BN and LMS are highly genomically unstable and harbor extensive CNAs in the genome, whereas SMT‐FH shows simple 1q43‐44 deletions. Integrated molecular profiling enabled the detection of novel and traditional biomarkers and showed excellent discrimination between LM‐BN and LMS.

Recurrence is frequent in pediatric ependymoma (EPN). Our longitudinal integrated analysis of 30 patient-matched repeated relapses (3.67 ± 1.76 times) over 13 years (5.8 ± 3.8) reveals stable molecular subtypes (RELA and PFA) and convergent DNA methylation reprogramming during serial relapses accompanied by increased orthotopic patient derived xenograft (PDX) (13/27) formation in the late recurrences. A set of differentially methylated CpGs (DMCs) and DNA methylation regions (DMRs) are found to persist in primary and relapse tumors (potential driver DMCs) and are acquired exclusively in the relapses (potential booster DMCs). Integrating with RNAseq reveals differentially expressed genes regulated by potential driver DMRs ( CACNA1H, SLC12A7, RARA in RELA and HSPB8, GMPR, ITGB4 in PFA) and potential booster DMRs ( PLEKHG1 in RELA and NOTCH, EPHA2, SUFU, FOXJ1 in PFA tumors). DMCs predicators of relapse are also identified in the primary tumors. This study provides a high-resolution epigenetic roadmap of serial EPN relapses and 13 orthotopic PDX models to facilitate biological and preclinical studies. While recurrence is frequent in ependymoma, the underlying molecular mechanisms remain to be explored. Here, the authors investigate epigenetic, genetic and tumorigenic changes in 30 patient-matched repeated relapses over 13 years and identify distinct patterns of DNA methylation.