Machine learning-based monosaccharide profiling for tissue-specific classification of Wolfiporia extensa samples.

Machine learning (ML) has been used for many clinical decision-making processes and diagnostic procedures in bioinformatics applications. We examined eight algorithms, including linear discriminant analysis (LDA), logistic regression (LR), k-nearest neighbor (KNN), random forest (RF), gradient boosting machine (GBM), support vector machine (SVM), Naïve Bayes classifier (NB), and artificial neural network (ANN) models, to evaluate their classification and prediction capabilities for four tissue types in Wolfiporia extensa using their monosaccharide composition profiles. All 8 ML-based models were assessed as exemplary models with AUC exceeding 0.

Critical role of lncEPAT in coupling dysregulated EGFR pathway and histone H2A deubiquitination during glioblastoma tumorigenesis.

Histone 2A (H2A) monoubiquitination is a fundamental epigenetics mechanism of gene expression, which plays a critical role in regulating cell fate. However, it is unknown if H2A ubiquitination is involved in EGFR-driven tumorigenesis. In the current study, we have characterized a previously unidentified oncogenic lncRNA (lncEPAT) that mediates the integration of the dysregulated EGFR pathway with H2A deubiquitination in tumorigenesis.

tRNA Function and Dysregulation in Cancer.

Transfer RNA (tRNA) is a central component of protein synthesis and plays important roles in epigenetic regulation of gene expression in tumors. tRNAs are also involved in many cell processes including cell proliferation, cell signaling pathways and stress response, implicating a role in tumorigenesis and cancer progression. The complex role of tRNA in cell regulation implies that an understanding of tRNA function and dysregulation can be used to develop treatments for many cancers including breast cancer, colon cancer, and glioblastoma.

Robust Aggregation for Federated Learning by Minimum -Divergence Estimation.

Federated learning is a framework for multiple devices or institutions, called local clients, to collaboratively train a global model without sharing their data. For federated learning with a central server, an aggregation algorithm integrates model information sent from local clients to update the parameters for a global model. Sample mean is the simplest and most commonly used aggregation method.

Alteration of power law scaling of spontaneous brain activity in schizophrenia.

Nonlinear dynamical analysis has been used to quantify the complexity of brain signal at temporal scales. Power law scaling is a well-validated method in physics that has been used to describe the dynamics of a system in the frequency domain, ranging from noisy oscillation to complex fluctuations. In this research, we investigated the power-law characteristics in a large-scale resting-state fMRI data of schizophrenia and healthy participants derived from Taiwan Aging and Mental Illness cohort.

Radiomic Features at CT Can Distinguish Pancreatic Cancer from Noncancerous Pancreas.

Purpose To identify distinguishing CT radiomic features of pancreatic ductal adenocarcinoma (PDAC) and to investigate whether radiomic analysis with machine learning can distinguish between patients who have PDAC and those who do not. Materials and Methods This retrospective study included contrast material-enhanced CT images in 436 patients with PDAC and 479 healthy controls from 2012 to 2018 from Taiwan that were randomly divided for training and testing. Another 100 patients with PDAC (enriched for small PDACs) and 100 controls from Taiwan were identified for testing (from 2004 to 2011).

EGFR/SRC/ERK-stabilized YTHDF2 promotes cholesterol dysregulation and invasive growth of glioblastoma.

Glioblastoma (GBM) is the most common type of adult malignant brain tumor, but its molecular mechanisms are not well understood. In addition, the knowledge of the disease-associated expression and function of YTHDF2 remains very limited. Here, we show that YTHDF2 overexpression clinically correlates with poor glioma patient prognosis.

YTHDF3 Induces the Translation of mA-Enriched Gene Transcripts to Promote Breast Cancer Brain Metastasis.

Brain metastasis is a major cause of cancer mortality, but its molecular mechanisms are severely understudied. In addition, little is known regarding the role of mA reader YTHDF3 in human diseases. Here, we show that YTHDF3 overexpression clinically correlates with brain metastases in breast cancer patients.

Epigenetic regulation of cancer stem cell and tumorigenesis.

As a unique subpopulation of cancer cells, cancer stem cells (CSCs) acquire the resistance to conventional therapies and appear to be the prime cause of cancer recurrence. Like their normal counterparts, CSCs can renew themselves and generate differentiated progenies. Cancer stem cells are distinguished among heterogenous cancer cells by molecular markers and their capacity of efficiently forming new tumors composed of diverse and heterogenous cancer cells.

Wnt-Induced Stabilization of KDM4C Is Required for Wnt/β-Catenin Target Gene Expression and Glioblastoma Tumorigenesis.

Wnt/β-catenin signaling activates the transcription of target genes to regulate stem cells and cancer development. However, the contribution of epigenetic regulation to this process is unknown. Here, we report that Wnt activation stabilizes the epigenetic regulator KDM4C that promotes tumorigenesis and survival of human glioblastoma cells by epigenetically activating the transcription of Wnt target genes.

Aberrant Activation of β-Catenin Signaling Drives Glioma Tumorigenesis via USP1-Mediated Stabilization of EZH2.

Aberrant activation of β-catenin signaling is a critical driver for tumorigenesis, but the mechanism underlying this activation is not completely understood. In this study, we demonstrate a critical role of β-catenin signaling in stabilization of enhancer of zeste homolog 2 (EZH2) and control of EZH2-mediated gene repression in oncogenesis. β-Catenin/TCF4 activated the transcription of the deubiquitinase USP1, which then interacted with and deubiquitinated EZH2 directly.

A peptide encoded by circular form of LINC-PINT suppresses oncogenic transcriptional elongation in glioblastoma.

Circular RNAs (circRNAs) are a large class of transcripts in the mammalian genome. Although the translation of circRNAs was reported, additional coding circRNAs and the functions of their translated products remain elusive. Here, we demonstrate that an endogenous circRNA generated from a long noncoding RNA encodes regulatory peptides.

Sufficient dimension reduction via random-partitions for the large-p-small-n problem.

Sufficient dimension reduction (SDR) continues to be an active field of research. When estimating the central subspace (CS), inverse regression based SDR methods involve solving a generalized eigenvalue problem, which can be problematic under the large-p-small-n situation. In recent years, new techniques have emerged in numerical linear algebra, called randomized algorithms or random sketching, for high-dimensional and large scale problems.

Methylation of RNA N-methyladenosine in modulation of cytokine responses and tumorigenesis.

Among myriads of distinct chemical modification in RNAs, the dynamic, reversible and fine-tuned methylation of N-methyladenosine (mA) is the most prevalent modification in eukaryotic mRNAs. This RNA mark is generated by proteins that act as mA writers and can be reversed by proteins that act as mA erasers. The RNA mA modification is also mediated by another group of proteins capable of recognizing mA that act as mA readers.

The Role of Fibrinogen-Like Protein 2 on Immunosuppression and Malignant Progression in Glioma.

Background: Virtually all low-grade gliomas (LGGs) will progress to high-grade gliomas (HGGs), including glioblastoma, the most common malignant primary brain tumor in adults. A key regulator of immunosuppression, fibrinogen-like protein 2 (FGL2), may play an important role in the malignant transformation of LGG to HGG. We sought to determine the mechanism of FGL2 on tumor progression and to show that inhibiting FGL2 expression had a therapeutic effect.

Profiles of brain metastases: Prioritization of therapeutic targets.

We sought to compare the tumor profiles of brain metastases from common cancers with those of primary tumors and extracranial metastases in order to identify potential targets and prioritize rational treatment strategies. Tumor samples were collected from both the primary and metastatic sites of nonsmall cell lung cancer, breast cancer and melanoma from patients in locations worldwide, and these were submitted to Caris Life Sciences for tumor multiplatform analysis, including gene sequencing (Sanger and next-generation sequencing with a targeted 47-gene panel), protein expression (assayed by immunohistochemistry) and gene amplification (assayed by in situ hybridization). The data analysis considered differential protein expression, gene amplification and mutations among brain metastases, extracranial metastases and primary tumors.

JAK2-binding long noncoding RNA promotes breast cancer brain metastasis.

Conventional therapies for breast cancer brain metastases (BCBMs) have been largely ineffective because of chemoresistance and impermeability of the blood-brain barrier. A comprehensive understanding of the underlying mechanism that allows breast cancer cells to infiltrate the brain is necessary to circumvent treatment resistance of BCBMs. Here, we determined that expression of a long noncoding RNA (lncRNA) that we have named lncRNA associated with BCBM (Lnc-BM) is prognostic of the progression of brain metastasis in breast cancer patients.

Novel Role of FBXW7 Circular RNA in Repressing Glioma Tumorigenesis.

Background: Circular RNAs (circRNAs) are RNA transcripts that are widespread in the eukaryotic genome. Recent evidence indicates that circRNAs play important roles in tissue development, gene regulation, and carcinogenesis. However, whether circRNAs encode functional proteins remains elusive, although translation of several circRNAs was recently reported.

Gli1-induced deubiquitinase USP48 aids glioblastoma tumorigenesis by stabilizing Gli1.

Aberrant activation of the Hedgehog (Hh) signaling pathway drives the tumorigenesis of multiple cancers. In this study, we screened a panel of deubiquitinases that may regulate the Hh pathway. We find that deubiquitinase USP48 activates Gli-dependent transcription by stabilizing Gli1 protein.

Robust mislabel logistic regression without modeling mislabel probabilities.

Logistic regression is among the most widely used statistical methods for linear discriminant analysis. In many applications, we only observe possibly mislabeled responses. Fitting a conventional logistic regression can then lead to biased estimation.

mA Demethylase ALKBH5 Maintains Tumorigenicity of Glioblastoma Stem-like Cells by Sustaining FOXM1 Expression and Cell Proliferation Program.

The dynamic and reversible N-methyladenosine (mA) RNA modification installed and erased by N-methyltransferases and demethylases regulates gene expression and cell fate. We show that the mA demethylase ALKBH5 is highly expressed in glioblastoma stem-like cells (GSCs). Silencing ALKBH5 suppresses the proliferation of patient-derived GSCs.

Neuroprotective effects of adjunctive treatments for acute stroke thrombolysis: a review of clinical evidence.

The narrow therapeutic time window and risk of intracranial hemorrhage largely restrict the clinical application of thrombolysis in acute ischemic stroke. Adjunctive treatments added to rt-PA may be beneficial to improve the capacity of neural cell to withstand ischemia, and to reduce the hemorrhage risk as well. This review aims to evaluate the neuroprotective effects of adjunctive treatments in combination with thrombolytic therapy for acute ischemic stroke.