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Thyroid disease presents a significant health risk, lowering the quality of life and increasing treatment costs. The diagnosis of thyroid disease can be challenging, especially for inexperienced practitioners. Machine learning has been established as one of the methods for disease diagnosis based on previous studies. This research introduces a novel and more effective technique for predicting thyroid disease by utilizing machine learning methodologies, surpassing the performance of previous studies in this field. This study utilizes the UCI thyroid disease dataset, which consists of 9172 samples and 30 features, and exhibits a highly imbalanced target class distribution. However, machine learning algorithms trained on imbalanced thyroid disease data face challenges in reliably detecting minority data and disease. To address this issue, re-sampling is employed, which modifies the ratio between target classes to balance the data. In this study, the down-sampling approach is utilized to achieve a balanced distribution of target classes. A novel RF-based self-stacking classifier is presented in this research for efficient thyroid disease detection. The proposed approach demonstrates the ability to diagnose primary hypothyroidism, increased binding protein, compensated hypothyroidism, and concurrent non-thyroidal illness with an accuracy of 99.5%. The recommended model exhibits state-of-the-art performance, achieving 100% macro precision, 100% macro recall, and 100% macro F1-score. A thorough comparative assessment is conducted to demonstrate the viability of the proposed approach, including several machine learning classifiers, deep neural networks, and ensemble voting classifiers. The results of K-fold cross-validation provide further support for the efficacy of the proposed self-stacking classifier. [ABSTRACT FROM AUTHOR]

With the development of Australian schools and secondary education, there is an expectation by the public and authorities that students will receive a high-quality education. However, in socio-economically disadvantaged areas, schools are unable to sufficiently develop learning experiences for students from culturally and linguistically diverse (CALD) backgrounds due to problems with funding, management, and stakeholders. Further, school leaders are unable to provide high-quality educational resources for students. The aim of this autoethnographic study is to reveal the vulnerability that a pre-service teacher, Author1—who is also from a CALD background—experienced during his placement in a school in a socio-economically disadvantaged area with many students from CALD backgrounds. The negative situations these students faced and the hardship of changing the educational structure, which has been ongoing for years, were disheartening. [ABSTRACT FROM AUTHOR]

Impairment of neurogenesis in the hippocampus following whole‑brain irradiation is the most important mechanism of radiation‑induced cognitive dysfunction. However, the underlying mechanism remains obscure, meaning an ideal therapeutic target has not been identified. Evidence indicates that DNA methylation in neurons regulates synaptic plasticity and neuronal network activity. In the present study, the expression of DNA methyltransferases (DNMTs) in the hippocampus was analyzed to investigate their potential function in radiation‑induced neurogenesis impairment. Sprague‑Dawley rats were used throughout the present study, apportioned to the following groups: Control, radiation only, zebularine (a DNMT inhibitor) only, and radiation and zebularine together. Immunofluorescence staining revealed that radiation inhibited cellular proliferation and dendritic growth within new neurons of the hippocampus. In addition, western blot analysis demonstrated lower expression levels of DNMT1 and DNMT3A protein following radiation treatment compared with that in the non‑irradiated control. Furthermore, compared with the radiation‑only group, the radiation and zebularine group had significantly lower cell proliferative abilities, dendritic growth, and DNMT1 and DNMT3A protein levels. The results of the present study indicated that DNMT1 and DNMT3A may be involved in the pathogenesis of whole‑brain radiation‑induced neurogenesis impairment. [ABSTRACT FROM AUTHOR]

To clarify what is the major control over aboveground biomass in a premature grassland under a condition of rainfall fluctuation, we conducted a 2-year experiment in a grassland of northern China. We manipulated species richness (4, 8 and 14 species) nested within a simulated rainfall gradient and we examined the relationships at different community organization levels. Previous experimental studies showed that species richness influenced aboveground biomass positively. Our results were not quite consistent with those revealed in mature grasslands. We found that, instead of species richness, plant coverage tended to be a critical factor that enhanced aboveground biomass at both the community level and the plant functional group level. In addition, different plant functional groups demonstrated different patterns in terms of the relationship. Our results also indicated that, in a premature grassland, plant communities with higher species richness were more stable, in terms of aboveground biomass, than those with lower species richness, offering an agreement with those revealed in mature grasslands. Our findings shed light on the development of man-made grasslands: higher plant coverage in a newly established grassland can significantly improve aboveground biomass. [Copyright &y& Elsevier]

This investigation aimed to develop and validate a novel oxidative stress score for prognostic prediction in locally advanced cervical cancer (LACC) patients receiving chemoradiotherapy. A total of 301 LACC patients were enrolled and randomly divided into a training and a validation set. The association between oxidative stress parameters and prognosis was analyzed for oxidative stress score (OSS) establishment. A Cox regression model was conducted for overall survival (OS) and progression-free survival (PFS). A nomogram prediction model was developed using independent prognostic factors from the training set and validated in the validation set. A novel OSS was established with four oxidative stress parameters, including albumin, total bilirubin, blood urea nitrogen, and lactate dehydrogenase. Multivariate regression analysis identified OSS as an independent prognostic factor for OS (p = 0.001) and PFS (p < 0.001). A predictive nomogram based on the OSS was established and validated. The C-indexes of the nomogram in the training set were 0.772 for OS and 0.781 for PFS, while in the validation set the C-indexes were 0.642 for OS and 0.621 for PFS. This study confirmed that preoperative OSS could serve as a useful independent prognostic factor in LACC patients who received CCRT. [ABSTRACT FROM AUTHOR]

Fatty acid metabolism has been identified as an emerging hallmark of cancer, which was closely associated with cancer prognosis. Whether fatty acid metabolism-related genes (FMGs) signature play a more crucial role in biological behavior of esophageal squamous cell carcinoma (ESCC) prognosis remains unknown. Thus, we aimed to identify a reliable FMGs signature for assisting treatment decisions and prognosis evaluation of ESCC. In the present study, we conducted consensus clustering analysis on 259 publicly available ESCC samples. The clinical information was downloaded from The Cancer Genome Atlas (TCGA, 80 ESCC samples) and Gene Expression Omnibus (GEO) database (GSE53625, 179 ESCC samples). A consensus clustering arithmetic was used to determine the FMGs molecular subtypes, and survival outcomes and immune features were evaluated among the different subtypes. Kaplan–Meier analysis and the receiver operating characteristic (ROC) was applied to evaluate the reliability of the risk model in training cohort, validation cohort and all cohorts. A nomogram to predict patients' 1-year, 3-year and 5-year survival rate was also studied. Finally, CCK-8 assay, wound healing assay, and transwell assay were implemented to evaluate the inherent mechanisms of FMGs for tumorigenesis in ESCC. Two subtypes were identified by consensus clustering, of which cluster 2 is preferentially associated with poor prognosis, lower immune cell infiltration. A fatty acid (FA) metabolism-related risk model containing eight genes (FZD10, TACSTD2, MUC4, PDLIM1, PRSS12, BAALC, DNAJA2 and ALOX12B) was established. High-risk group patients displayed worse survival, higher stromal, immune and ESTIMATE scores than in the low-risk group. Moreover, a nomogram revealed good predictive ability of clinical outcomes in ESCC patients. The results of qRT-PCR analysis revealed that the MUC4 and BAALC had high expression level, and FZD10, PDLIM1, TACSTD2, ALOX12B had low expression level in ESCC cells. In vitro, silencing MUC4 remarkably inhibited ESCC cell proliferation, invasion and migration. Our study fills the gap of FMGs signature in predicting the prognosis of ESCC patients. These findings revealed that cluster subtypes and risk model of FMGs had effects on survival prediction, and were expected to be the potential promising targets for ESCC. [ABSTRACT FROM AUTHOR]

Background: Cisplatin-based chemoradiation is the standard of care for patients with locally advanced cervical cancer. Nevertheless, an increasing number of radio-resistant tumors still recur.Methods and Design: Three hundred cervical cancer patients with FIGO stages IB2-IVA and no para-aortic lymphadenopathy (> 10 mm) will be enrolled. All patients will be randomly divided into four arms to receive either (1) intensity modulated radiation therapy (IMRT), (2) RapidArc, (3) positron emission tomography/computed tomography (PET/CT) with F-18 fluorodeoxyglucose (FDG), or (4) Comet assay-guided IMRT, PET/CT, and Comet assay-guided RapidArc. All patients will receive definitive radiotherapy consisting of external beam whole pelvic radiation therapy and high-dose rate intracavitary brachytherapy. Cisplatin 30 mg/m2 weekly will be administered concurrently for five courses. Two to four cycles of TP (Taxol 135 mg/m2, D1, and DDP 75 mg/m2, D1-3) sequential chemotherapy will be performed according to MRI or PET/CT after cisplatin-based chemoradiation. The primary outcome measure is progression-free survival, and the second outcome measures are overall survival and time to progression.Discussion: RapidArc has an obvious advantage in improving the degree of target coverage, improving organs at risk, sparing healthy tissue, and significantly reducing the treatment time. FDG-PET/CT can increase the agreement between biopsies and delineated tumor volume and has the potential to positively impact the course of treatment. The Comet assay is attractive as a potential clinical test of tumor radiosensitivity. During radiotherapy, accurately defining disease areas is critical to avoid the unnecessary irradiation of normal tissue. Based on FDG-PET/CT and Comet assay, higher doses can be safely delivered to accurate tumor volumes, while the doses to the bladder and rectum are relatively low.Trial Registration: ClinicalTrials.gov Protocol Registration and Results System Receipt Release Date: May 21, 2017 - Retrospectively registered. NCT03163979 . [ABSTRACT FROM AUTHOR]

Background: Conventional nutritional metrics are closely associated with the prognosis of patients with radically resected esophageal squamous cell carcinoma (ESCC). Nevertheless, the prognostic implications of muscle and adipose tissue composite indexes in ESCC remain unknown. Methods: We retrospectively analyzed clinicopathological data of 304 patients who underwent resected ESCC. To obtain measurements of the muscle and adipose indexes, preoperative computed tomography (CT) images were used to quantify skeletal-muscle adipose tissue. The diagnostic threshold for muscle-adipose imbalance was determined using X-tile software and used to analyze the association between the muscle-adipose index (MAI) and survival. Instantaneous risk of recurrence was assessed using a hazard function. We constructed a nomogram based on the MAI and other clinical characteristics and established a novel predictive model with independent prognostic factors. The prognostic capabilities of these nomograms were evaluated using calibration curves, receiver operating characteristic (ROC) curves, and decision-curve analysis (DCA). Results: The overall survival (OS) and disease-free survival (DFS) rates in the muscle-adipose-balanced group were significantly better than those in the muscle-adipose-imbalanced group. Multivariate analyses revealed that the MAI, prognostic nutritional index (PNI), tumor stage, and tumor differentiation were independent prognostic factors for OS and DFS in patients with resected ESCC (P < 0.05). The nuclear density curve indicated a lower risk of recurrence for patients in the muscle-adipose-balanced group than that for their imbalanced counterparts. Conversely, the nuclear density curve for PNI was confounded. Postoperative radiotherapy- (RT) benefit analysis demonstrated that patients with ESCC in the muscle-adipose-balanced group could benefit from adjuvant RT. Conclusion: This study confirmed that preoperative MAI could serve as a useful independent prognostic factor in patients with resected ESCC. A nomogram based on the MAI and other clinical characteristics could provide individualized survival prediction for patients receiving radical resection. Timely and appropriate nutritional supplements may improve treatment efficacy. [ABSTRACT FROM AUTHOR]

A series of novel 7-arylaminopyrazolo[1,5-a]pyrimidine derivatives containing the hydrazone moiety has been synthesized by a five-step procedure including cyclization, chlorination, animation, hydrazinolysis, and condensation. Structures of the products have been characterized by IR, 1H NMR and MS spectra, and single-crystal X-ray diffraction. The bioassay results indicate most of the compounds as potentially antiproliferation agents against A549 and HT-29 cell lines. Among those, compounds 6e and 6f exhibit remarkable inhibitory activity against HT-29 cell lines, that are comparable with that of the positive control sorafenib. Preliminary structure-activity relationship is considered. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) is the most commonly diagnosed cancer and second leading cause of cancer-related death in women worldwide. Ferroptosis, an iron-dependent newly discovered mode of cell death, can be induced by lenaltinib and plays an important role in the biological behaviors of BC. Therefore, the prognostic value of ferroptosis-related genes (FRGs) in BC warrants further investigation. FRG expression profiles and clinical data were downloaded from The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO). Immune-related pathways were found in the functional analysis. Significant differences in enrichment scores for immune cells were observed. Some patients from TCGA-BRCA were included as the training cohort. A six-gene prediction signature was constructed with the least absolute shrinkage and selection operator Cox regression. This model was validated in the rest of the TCGA-BRCA and GEO cohort. The expressions of the six FRGs were verified with real-time quantitative polymerase chain reaction and immunohistochemistry in the Human Protein Atlas. Relapse or metastasis was more likely in the high-risk group. Risk score was an independent predictor of disease-free survival. Collectively, the ferroptosis-related risk model established in this study may serve as an effective tool to predict the prognosis in BC. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) is the most commonly diagnosed cancer and second leading cause of cancer-related death in women worldwide. Ferroptosis, an iron-dependent newly discovered mode of cell death, can be induced by lenaltinib and plays an important role in the biological behaviors of BC. Therefore, the prognostic value of ferroptosis-related genes (FRGs) in BC warrants further investigation. FRG expression profiles and clinical data were downloaded from The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO). Immune-related pathways were found in the functional analysis. Significant differences in enrichment scores for immune cells were observed. Some patients from TCGA-BRCA were included as the training cohort. A six-gene prediction signature was constructed with the least absolute shrinkage and selection operator Cox regression. This model was validated in the rest of the TCGA-BRCA and GEO cohort. The expressions of the six FRGs were verified with real-time quantitative polymerase chain reaction and immunohistochemistry in the Human Protein Atlas. Relapse or metastasis was more likely in the high-risk group. Risk score was an independent predictor of disease-free survival. Collectively, the ferroptosis-related risk model established in this study may serve as an effective tool to predict the prognosis in BC. [ABSTRACT FROM AUTHOR]

Background. As a parameter integrating platelet (P), neutrophil (N), and lymphocyte (L) levels, the systemic immune-inflammation index (SII) has been used as a prognostic marker for patient survival in various types of solid malignant tumors. However, there is no in-depth study in non-small-cell lung cancer (NSCLC) patients with brain metastases after stereotactic radiotherapy. Therefore, we performed a retrospective analysis to determine the clinical and prognostic value of the SII in NSCLC patients with brain metastases who underwent stereotactic radiotherapy. Materials and Methods. We enrolled 124 NSCLC patients with brain metastases treated with stereotactic radiotherapy in our hospital between May 2015 and June 2018. We obtained all baseline blood samples within one week prior to stereotactic radiotherapy. The SII was calculated by the following formula: neutrophil counts × platelet counts / lymphocyte counts. The optimal cutoff value of the SII for predicting prognosis was assessed by receiver operating characteristic (ROC) curves with the maximum log-rank values. The discriminative ability of predicting prognosis was calculated and compared using the Kaplan–Meier method and log-rank test. The hazard ratio (HR) and 95% confidence interval (CI) were combined to evaluate the prognostic impact of the blood index on overall survival (OS) and progression-free survival (PFS). Only those parameters that proved to be associated with statistically significant differences in clinical outcomes were compared in multivariate analysis using a multiple Cox proportional hazard regression model to identify independent prognostic factors. Results. Of the total enrolled patients, 53.2% and 46.8% have high SII and low SII, respectively. In this study, Kaplan–Meier curve analysis revealed that the median PFS was 9 months (range: 2–22 months) and the median OS was 18 months (range: 4–37 months). Applying an optimal cutoff of 480 (SII), the median PFS was better in the low SII group patients (11.5 vs. 9 months), and the median OS was significantly longer in the low SII group patients (20 vs. 18 months). A SII > 480 was significantly associated with worse OS (HR: 2.196; 95% CI 1.259–3.832; P = 0.006) and PFS (HR: 2.471; 95% CI 1.488–4.104; P < 0.001) according to univariate analysis. In multivariate analysis, only age (HR: 2.159; 95% CI 1.205–3.869; P = 0.010), KPS (HR: 1.887; 95% CI 1.114–3.198; P = 0.018), and SII (HR: 1.938; 95% CI 1.046–3.589; P = 0.035) were independently correlated with OS, and SII (HR: 2.224; 95% CI 1.298–3.810; P = 0.004) was an independent prognostic predictor of PFS, whereas we found that other inflammation-based indices lost their independent value. Conclusions. The SII, which is an integrated blood parameter based on platelet, neutrophil, and lymphocyte counts, may be an independent prognostic indicator and may be useful for the identification of NSCLC patients with brain metastases after stereotactic radiotherapy at high risk for recurrence. [ABSTRACT FROM AUTHOR]

Background: Brain metastases (BM) are severe incidents among patients with non-small cell lung cancer (NSCLC) and have been associated with significant morbidity and decreased survival; thus, new methods are required to improve clinical management. Magnetic resonance spectroscopy (MRS) allows noninvasive measurements of biochemical information from tumor tissue, providing clinically useful imaging biomarkers. The primary aim of this study was to explore the application of MRS in the assessment of tumor prognosis after stereotactic radiotherapy in NSCLC patients with BM. Patients and Methods: MRS was performed on NSCLC patients attending Qingdao Center Hospital with suspected BM, and 68 patients were included in the survival analysis. The qualitative and quantitative parameters of MRS metabolites, such as choline (Cho), creatine (Cr), and N-acetyl-aspartate (NAA), were recorded. To select a cutoff for MRS metabolite parameters in the tumor and to distinguish patients who had recurrence, we performed an ROC curve analysis. Univariate and multivariate Cox regression analyses were used to assess the association between MRS metabolite parameters and clinical cancer prognosis. Results: The average age was 56 years. A total of 68 NSCLC patients underwent metabolic evaluation with single voxel proton MRS and were selected for retrospective analysis. According to the area under the curve (AUC) to predict recurrence, the MRS metabolite parameters were determined as Cho (AUC=0.550), Cr (AUC=0.415), NAA (AUC=0.524), NAA/Cr (AUC=0.600), Cho/Cr (AUC=0.723), and Cho/NAA (AUC=0.543). Cho and Cr predicted poor survival while Cho/Cr and NAA/Cr predicted improved survival (P< 0.05). In the multivariate model with adjustment to establish the potential role of MRS metabolite parameters, Cho/Cr showed a significant association with OS (P=0.009) and PFS (P=0.006) after stereotactic radiotherapy. Conclusion: The positive results of this study indicate the predictive value of metabolic characteristics of BM detected with MRS for the outcome after stereotactic radiotherapy. [ABSTRACT FROM AUTHOR]

Background. The systemic immune-inflammation index (SII) has an important role in predicting survival in some solid tumors. However, little information is available concerning the change of the SII (∆SII) in colorectal cancer (CRC) after curative resection. This study was designed to evaluate the role of ∆SII in CRC patients who received surgery. Methods. A total 206 patients were enrolled in this study. Clinicopathologic characteristics and survival were assessed. The relationships between overall survival (OS), disease-free survival (DFS), and ∆SII were analyzed with both univariate Kaplan-Meier and multivariate Cox regression methods. Results. Based on the patient data, the receiver operating characteristic (ROC) optimal cutoff value of ∆SII was 127.7 for OS prediction. The 3-year and 5-year OS rates, respectively, were 60.4% and 36.7% in the high-∆SII group (>127.7) and 87.6% and 79.8% in the low-∆SII group (≤127.7). The 3-year and 5-year DFS rates, respectively, were 54.1% and 34.1% in the high-∆SII group and 80.3% and 78.5% in the low-∆SII group. In the univariate analysis, smoking, pathological stages III-IV, high-middle degree of differentiation, lymphatic invasion, vascular invasion, and the high-ΔSII group were associated with poor OS. Adjuvant therapy, pathological stages III-IV, vascular invasion, and ΔSII were able to predict DFS. Multivariate analysis revealed that pathological stages III-IV (HR = 0.442 , 95% CI = 0.236 -0.827, p = 0.011), vascular invasion (HR = 2.182 , 95% CI = 1.243 -3.829, p = 0.007), and the high-ΔSII group (HR = 4.301 , 95% CI = 2.517 -7.350, p < 0.001) were independent predictors for OS. Adjuvant therapy (HR = 0.415 , 95% CI = 0.250 -0.687, p = 0.001), vascular invasion (HR = 3.305 , 95% CI = 1.944 -5.620, p < 0.001), and the high-ΔSII group (HR = 4.924 , 95% CI = 2.992 -8.102, p < 0.001) were significant prognostic factors for DFS. Conclusions. The present study demonstrated that ∆SII was associated with the clinical outcome in CRC patients undergoing curative resection, supporting the role of ∆SII as a prognostic biomarker. [ABSTRACT FROM AUTHOR]

Irradiation to developing brains results in progressive cognitive dysfunction. Changes in the morphology of mature neurons are thought to be related to impairments of cognitive function. However, little is known about the effects of radiation on neurite outgrowth of immature neurons. Therefore, we sought to evaluate the structural alterations of immature neurons following X-ray irradiation and determine potential strategies to reverse it. Our data revealed damage to the neurite outgrowths of cultured neurons after 2 Gy and 8 Gy irradiation at 1 d and 3 d, respectively. De-phosphorylation of nuclear factor of activated T-cells c4/3 (NFATc4/3) was inhibited post-irradiation. Extraneous brain-derived neurotrophic factor (BDNF) ameliorated impairment of neurite growth and activated the NFATc4/3 signaling pathway. These data indicate that BDNF confers neuroprotective effects against irradiation by modulating the NFATc4/3 pathway. [ABSTRACT FROM AUTHOR]

Question: Can species richness be a predictor for above-ground biomass in natural grasslands at a regional scale? Location: A total of 647 sites across temperate natural grasslands of northern China. Methods: Structural equation modelling (SEM) was used to examine the effect of species richness on above-ground biomass. Asymptotically distribution-free estimation was selected for parameter estimation. The SEM process was performed at five sample sizes ( n=50, 100, 200, 300 and 647). Spatial structure in the original data was examined by calculating Moran's I. Results: SEM run at n=647 revealed a positive effect of species richness on above-ground biomass after controlling for the influences of bioclimatic factors and grazing. At the four reduced sample size levels, the positive effect held true for most cases in 400 observations (>92%). Conclusions: Contrary to observations in previous studies in natural grasslands, our data showed a positive effect of species richness on above-ground biomass. This suggests that, as a short-term effect of diversity on productivity, niche complementarity among coexisting species tends to be an important process in arid and semi-arid natural grasslands. We hold that biodiversity conservation is among the fundamental approaches required to maintain productivity of grasslands in arid and semi-arid areas. [ABSTRACT FROM AUTHOR]