Brain Cancer Prediction Based on Novel Interpretable Ensemble Gene Selection Algorithm and Classifier.

The growth of abnormal cells in the brain causes human brain tumors. Identifying the type of tumor is crucial for the prognosis and treatment of the patient. Data from cancer microarrays typically include fewer samples with many gene expression levels as features, reflecting the curse of dimensionality and making classifying data from microarrays challenging. In most of the examined studies, cancer classification (Malignant and benign) accuracy was examined without disclosing biological information related to the classification process. A new approach was proposed to bridge the gap between cancer classification and the interpretation of the biological studies of the genes implicated in cancer. This study aims to develop a new hybrid model for cancer classification (by using feature selection mRMRe as a key step to improve the performance of classification methods and a distributed hyperparameter optimization for gradient boosting ensemble methods). To evaluate the proposed method, NB, RF, and SVM classifiers have been chosen. In terms of the AUC, sensitivity, and specificity, the optimized CatBoost classifier performed better than the optimized XGBoost in cross-validation 5, 6, 8, and 10. With an accuracy of 0.91±0.12, the optimized CatBoost classifier is more accurate than the CatBoost classifier without optimization, which is 0.81± 0.24. By using hybrid algorithms, SVM, RF, and NB automatically become more accurate. Furthermore, in terms of accuracy, SVM and RF (0.97±0.08) achieve equivalent and higher classification accuracy than NB (0.91±0.12). The findings of relevant biomedical studies confirm the findings of the selected genes.

Bone mineral density in adolescent urinary stone formers: is sex important?

Urinary stone disease (USD) is affecting a greater number of children and low bone mineral density (BMD) and increased skeletal fractures have been demonstrated in stone patients; however, the mechanism(s) driving bone disease remain unclear. This pilot study was undertaken to assess an adolescent kidney stone cohort's BMD and evaluate for an inverse correlation between BMD and urine concentration of lithogenic minerals and/or inflammatory levels. Prospective case-control study was carried out at a large pediatric center. 15 participants with USD (12-18 years of age, 8 female) were matched by age, sex, and body mass index to 15 controls. Lumbar and total body BMD z-score did not differ between groups. When stone formers were separated by sex, there was a significant difference between male stone formers vs. controls total body BMD z-score (Fig. 1). BMD z-score did not significantly correlate with urine calcium, oxalate, citrate or magnesium. Higher urine IL-13 did significantly correlate with higher total body BMD z-score (r = 0.677, p = 0.018). Total body BMD z-score did significantly correlate with body mass index (BMI) as expected for the control group (r = 0.6321, p = 0.0133). However, this relationship was not present in the USD group (r = - 0.1629, p = 0.5619). This is a small but hypothesis-generating study which demonstrates novel evidence of male-specific low BMD in adolescent stone formers. Furthermore, we demonstrated a positive association between urine IL-13 and total body BMD z-score USD patients as well as a lack of a positive BMD and BMI correlations in stone formers.

A novel regulatory role of TRAPPC9 in L-plastin-mediated osteoclast actin ring formation.

Trafficking protein particle complex 9 (TRAPPC9) is a major subunit of the TRAPPII complex. TRAPPC9 has been reported to bind nuclear factor κB kinase subunit ß (IKKß) and NF-kB-inducing kinase (NIK) where it plays a role in the canonical and noncanonical of nuclear factor-κB (NF-kB) signaling pathways, receptively. The role of TRAPPC9 in protein trafficking and cytoskeleton organization in osteoclast (OC) has not been studied yet. In this study, we examined the mRNA expression of TRAPPC9 during OC differentiation. Next, we examined the colocalization of TRAPPC9 with cathepsin-K, known to mediate OC resorption suggesting that TRAPPC9 mediates the trafficking pathway within OC. To identify TRAPPC9 protein partners important for OC-mediated cytoskeleton re-organization, we conducted immunoprecipitation of TRAPPC9 in mature OCs followed by mass spectrometry analysis. Our data showed that TRAPPC9 binds various protein partners. One protein with high recovery rate is L-plastin (LPL). LPL localizes at the podosomes and reported to play a crucial role in actin aggregation thereby actin ring formation and OC function. Although the role of LPL in OC-mediated bone resorption has not fully reported in detail. Here, first, we confirmed the binding of LPL to TRAPPC9 and, then, we investigated the potential regulatory role of TRAPPC9 in LPL-mediated OC cytoskeleton reorganization. We assessed the localization of TRAPPC9 and LPL in OC and found that TRAPPC9 is colocalized with LPL at the periphery of OC. Next, we determined the effect of TRAPPC9 overexpression on LPL recruitment to the actin ring using a viral system. Interestingly, our data showed that TRAPPC9 overexpression promotes the recruitment of LPL to the actin ring when compared with control cultures. In addition, we observed that TRAPPC9 overexpression reorganizes actin clusters/aggregates and regulates vinculin recruitment into the OC periphery to initiate podosome formation.

Autophagy plays an essential role in bone homeostasis.

Autophagy is very critical for multiple cellular processes. Autophagy plays a critical role in bone cell differentiation and function.

TRAPPC9: Novel insights into its trafficking and signaling pathways in health and disease (Review).

Trafficking protein particle complex 9 (TRAPPC9) is a protein subunit of the transport protein particle II (TRAPPII), which has been reported to be important in the trafficking of cargo from the endoplasmic reticulum (ER) to the Golgi, and in intra­Golgi and endosome­to­Golgi transport in yeast cells. In mammalian cells, TRAPPII has been shown to be important in Golgi vesicle tethering and intra­Golgi transport. TRAPPC9 is considered to be a novel molecule capable of modulating the activation of nuclear factor­κB (NF­κB). Mutations in TRAPPC9 have been linked to a rare consanguineous hereditary form of mental retardation, as part of the NF­κB pathways. In addition, TRAPPC9 has been reported to be involved in breast and colon cancer and liver diseases. The present review highlights the most recent publications on the structure, expression and function of TRAPPC9, and its association with various human diseases.