Sex differences in the molecular profile of adult diffuse glioma are shaped by IDH status and tumor microenvironment.

Background: Sex differences in adult diffuse glioma (ADG) are well-established clinically, yet the underlying molecular mechanisms remain inadequately understood. Here, we aim to reveal molecular features and cellular compositions unique to each sex in ADG to comprehend the role of sex in disease etiology.

Methods: We quantified sex differences in transcriptome of ADG using multiple independent glioma patient datasets.

Construction of An Orthotopic Xenograft Model of Non-small Cell Lung Cancer Mimicking Disease Progression and Predicting Drug Activities.

Non-small cell lung cancer (NSCLC) is a highly lethal disease with a complex and heterogeneous tumor microenvironment. Currently, common animal models based on subcutaneous inoculation of cancer cell suspensions do not recapitulate the tumor microenvironment in NSCLC. Herein we describe a murine orthotopic lung cancer xenograft model that employs the intrapulmonary inoculation of three-dimensional multicellular spheroids (MCS).

Integration of Pan-Cancer Cell Line and Single-Cell Transcriptomic Profiles Enables Inference of Therapeutic Vulnerabilities in Heterogeneous Tumors.

Unlabelled: Single-cell RNA sequencing (scRNA-seq) greatly advanced the understanding of intratumoral heterogeneity by identifying distinct cancer cell subpopulations. However, translating biological differences into treatment strategies is challenging due to a lack of tools to facilitate efficient drug discovery that tackles heterogeneous tumors. Developing such approaches requires accurate prediction of drug response at the single-cell level to offer therapeutic options to specific cell subpopulations.

A Web Application for Predicting Drug Combination Efficacy Using Monotherapy Data and IDACombo.

We recently reported a computational method (IDACombo) designed to predict the efficacy of cancer drug combinations using monotherapy response data and the assumptions of independent drug action. Given the strong agreement between IDACombo predictions and measured drug combination efficacy in vitro and in clinical trials, we believe IDACombo can be of immediate use to researchers who are working to develop novel drug combinations. While we previously released our method as an R package, we have now created an R Shiny application to allow researchers without programming experience to easily utilize this method.

Sex-related differences in delayed doxorubicin-induced cardiac dysfunction in C57BL/6 mice.

Cancer survivors may experience long-term cardiovascular complications due to chemotherapeutic drugs such as doxorubicin (DOX). The exact mechanism of delayed DOX-induced cardiotoxicity has not been fully elucidated. Sex is an important risk factor for DOX-induced cardiotoxicity.

A review of computational methods for predicting cancer drug response at the single-cell level through integration with bulk RNAseq data.

Cancer treatment failure is often attributed to tumor heterogeneity, where diverse malignant cell clones exist within a patient. Despite a growing understanding of heterogeneous tumor cells depicted by single-cell RNA sequencing (scRNA-seq), there is still a gap in the translation of such knowledge into treatment strategies tackling the pervasive issue of therapy resistance. In this review, we survey methods leveraging large-scale drug screens to generate cellular sensitivities to various therapeutics.

Adaptive neural identification and non-singular control of pure-feedback nonlinear systems.

This paper proposes a new constructive identification and adaptive control method for nonlinear pure-feedback systems, which remedies the 'explosion of complexity' and potential control singularity encountered in the traditional adaptive backstepping controllers. First, to avoid using the backstepping recursive design, alternative state variables and the corresponding coordinate transformation are introduced to reformulate the pure-feedback system into an equivalent canonical model. Then, a high-order sliding mode (HOSM) observer is used to reconstruct the unknown states for this canonical model.

Inferring therapeutic vulnerability within tumors through integration of pan-cancer cell line and single-cell transcriptomic profiles.

Single-cell RNA sequencing greatly advanced our understanding of intratumoral heterogeneity through identifying tumor subpopulations with distinct biologies. However, translating biological differences into treatment strategies is challenging, as we still lack tools to facilitate efficient drug discovery that tackles heterogeneous tumors. One key component of such approaches tackles accurate prediction of drug response at the single-cell level to offer therapeutic options to specific cell subpopulations.

Simplicity: web-based visualization and analysis of high-throughput cancer cell line screens.

High-throughput drug screens are a powerful tool for cancer drug development. However, the results of such screens are often made available only as raw data, which is intractable for researchers without informatic skills, or as highly processed summary statistics, which can lack essential information for translating screening results into clinically meaningful discoveries. To improve the usability of these datasets, we developed Simplicity, a robust and user-friendly web interface for visualizing, exploring, and summarizing raw and processed data from high-throughput drug screens.

Understanding Statin-Roxadustat Drug-Drug-Disease Interaction Using Physiologically-Based Pharmacokinetic Modeling.

A different drug-drug interaction (DDI) scenario may exist in patients with chronic kidney disease (CKD) compared with healthy volunteers (HVs), depending on the interplay between drug-drug and disease (drug-drug-disease interaction (DDDI)). Physiologically-based pharmacokinetic (PBPK) modeling, in lieu of a clinical trial, is a promising tool for evaluating these complex DDDIs in patients. However, the prediction confidence of PBPK modeling in the severe CKD population is still low when nonrenal pathways are involved.

A systematic review on sex differences in adverse drug reactions related to psychotropic, cardiovascular, and analgesic medications.

Adverse drug reactions (ADRs) are the main safety concerns of clinically used medications. Accumulating evidence has shown that ADRs can affect men and women differently, which suggests sex as a biological predictor in the risk of ADRs. This review aims to summarize the current state of knowledge on sex differences in ADRs with the focus on the commonly used psychotropic, cardiovascular, and analgesic medications, and to aid clinical decision making and future mechanistic investigations on this topic.

Computational drug discovery for castration-resistant prostate cancers through in vitro drug response modeling.

Prostate cancer (PC) is the most frequently diagnosed malignancy and a leading cause of cancer deaths in US men. Many PC cases metastasize and develop resistance to systemic hormonal therapy, a stage known as castration-resistant prostate cancer (CRPC). Therefore, there is an urgent need to develop effective therapeutic strategies for CRPC.

Deciphering genetic causes for sex differences in human health through drug metabolism and transporter genes.

Sex differences have been widely observed in human health. However, little is known about the underlying mechanism behind these observed sex differences. We hypothesize that sex-differentiated genetic effects are contributors of these phenotypic differences.

Simplicity: Web-Based Visualization and Analysis of High-Throughput Cancer Cell Line Screens.

High-throughput drug screens are a powerful tool for cancer drug development. However, the results of such screens are often made available only as raw data, which is intractable for researchers without informatics skills, or as highly processed summary statistics, which can lack essential information for translating screening results into clinically meaningful discoveries. To improve the usability of these datasets, we developed Simplicity, a robust and user-friendly web interface for visualizing, exploring, and summarizing raw and processed data from high- throughput drug screens.

Sex dimorphism in response to targeted therapy and immunotherapy in non-small cell lung cancer patients: a narrative review.

Background And Objective: Multiple agents have been developed for treating non-small cell lung cancer (NSCLC). However, patients' response to these therapies vary drastically, which indicates a need to tailor therapy. Sex is a readily usable clinical characteristic that has been shown to impact patients' response to drugs.

Multi-H∞ Controls for Unknown Input-Interference Nonlinear System With Reinforcement Learning.

This article studies the multi- [Formula: see text] controls for the input-interference nonlinear systems via adaptive dynamic programming (ADP) method, which allows for multiple inputs to have the individual selfish component of the strategy to resist weighted interference. In this line, the ADP scheme is used to learn the Nash-optimization solutions of the input-interference nonlinear system such that multiple [Formula: see text] performance indices can reach the defined Nash equilibrium. First, the input-interference nonlinear system is given and the Nash equilibrium is defined.

A Long Noncoding RNA, GAS5 Can Be a Biomarker for Docetaxel Response in Castration Resistant Prostate Cancer.

While functional studies of long noncoding RNAs (lncRNAs) have mostly focused on how they influence disease diagnosis and prognosis, the pharmacogenomic relevance of lncRNAs remains largely unknown. Here, we test the hypothesis that the expression of a lncRNA, grow arrest-specific 5 () can be a biomarker for docetaxel response in castration resistant prostate cancer (CRPC) using both prostate cancer (PCa) cell lines and CRPC patient datasets. Our results suggest that lower expression is associated with docetaxel resistance in both PCa cell lines and CRPC patients.

Unknown System Dynamics Estimator for Active Vehicle Suspension Control Systems With Time-Varying Delay.

This article proposes a novel control method for vehicle active suspension systems in the presence of time-varying input delay and unknown nonlinearities. An unknown system dynamics estimator (USDE), which employs first-order low-pass filter operations and has only one tuning parameter, is constructed to deal with unknown nonlinearities. With this USDE, the widely used function approximators (e.

Oncogene or tumor suppressor? Long noncoding RNAs role in patient's prognosis varies depending on disease type.

Functional studies of long noncoding RNAs (lncRNAs) are often performed in the context of only a single cancer type. However, the tissue-specific expression patterns of lncRNAs raise the question of whether lncRNA associations identified in one cancer type are relevant to other cancer types. Here, we examine the relationships between the expression levels of 50 cancer-related lncRNAs and survival data from 24 types of cancer in The Cancer Genome Atlas (TCGA) with the goal of identifying prognosis related lncRNAs.

Intrapulmonary inoculation of multicellular spheroids to construct an orthotopic lung cancer xenograft model that mimics four clinical stages of non-small cell lung cancer.

Introduction: Lung cancer leads in mortality among all types of cancer in US and Non-small cell lung cancer (NSCLC) is the major type of lung cancer. Mice models of lung cancer based on subcutaneous or orthotopic inoculation of cancer cell suspension do not adequately mimic the progression of lung cancer in clinic.

Methods: A549-iRFP cells (human NSCLC adenocarcinoma) were cultured to form multicellular spheroids (MCS), which were then inoculated intrapulmonarily into male athymic nude mice.

Lipid-Coated, pH-Sensitive Magnesium Phosphate Particles for Intracellular Protein Delivery.

Purpose: To develop cationic lipid-coated magnesium phosphate nanoparticles (LPP) for intracellular catalase (CAT) delivery.

Methods: Magnesium phosphate nanoparticles (MgP NP) were prepared by micro-emulsion precipitation and mixed with catalase-loaded cationic liposomes (DOTAP/cholesterol) to yield LPP formulation of catalase (LPP-CAT). The size and ζ-potential of LPP-CAT were measured by dynamic light scattering.

Adaptive Finite-Time Fuzzy Control of Nonlinear Active Suspension Systems With Input Delay.

This paper presents a new adaptive fuzzy control scheme for active suspension systems subject to control input time delay and unknown nonlinear dynamics. First, a predictor-based compensation scheme is constructed to address the effect of input delay in the closed-loop system. Then, a fuzzy logic system (FLS) is employed as the function approximator to address the unknown nonlinearities.

Finite-Time Convergence Adaptive Neural Network Control for Nonlinear Servo Systems.

Although adaptive control design with function approximators, for example, neural networks (NNs) and fuzzy logic systems, has been studied for various nonlinear systems, the classical adaptive laws derived based on the gradient descent algorithm with σ -modification or e -modification cannot guarantee the parameter estimation convergence. These nonconvergent learning methods may lead to sluggish response in the control system and make the parameter tuning complex. The aim of this paper is to propose a new learning strategy driven by the estimation error to design the alternative adaptive laws for adaptive control of nonlinear servo systems.

Evaluation of bone mass in children and young adults with juvenile idiopathic arthritis.

Objectives: To examine bone mineral density (BMD) in the spines of patients with juvenile idiopathic arthritis (JIA), and to identify the main predictors of spine BMD.

Methods: 160 patients with JIA (82 female, 78 male; median age, 8.7±3.