Novel trial designs in neuro-oncology.

Purpose Of Review: An important factor contributing to the low rate of success in identifying effective therapies for brain tumor patients is the slow, inefficient, and expensive process of drug development, as well as small patient numbers, low patient participation in clinical trials, and reluctance of patients to enroll in ineffective control arms. In recent years, a number of novel trial designs have been developed to try to address some of these issues.

Recent Findings: Surgical 'window-of-opportunity' trials that evaluate tumor drug concentrations and pharmacodynamic effects provide invaluable early data early guiding the development of novel therapies.

Liquid biopsy epigenomic profiling for cancer subtyping.

Although circulating tumor DNA (ctDNA) assays are increasingly used to inform clinical decisions in cancer care, they have limited ability to identify the transcriptional programs that govern cancer phenotypes and their dynamic changes during the course of disease. To address these limitations, we developed a method for comprehensive epigenomic profiling of cancer from 1 ml of patient plasma. Using an immunoprecipitation-based approach targeting histone modifications and DNA methylation, we measured 1,268 epigenomic profiles in plasma from 433 individuals with one of 15 cancers.

Activity of a first-in-class oral HIF2-alpha inhibitor, PT2385, in patients with first recurrence of glioblastoma.

Introduction: Hypoxia inducible factor 2-alpha (HIF2α) mediates cellular responses to hypoxia and is over-expressed in glioblastoma (GBM). PT2385 is an oral HIF2α inhibitor with in vivo activity against GBM.

Methods: A two-stage single-arm open-label phase II study of adults with GBM at first recurrence following chemoradiation with measurable disease was conducted through the Adult Brain Tumor Consortium.

Machine learning-enabled constrained multi-objective design of architected materials.

Architected materials that consist of multiple subelements arranged in particular orders can demonstrate a much broader range of properties than their constituent materials. However, the rational design of these materials generally relies on experts' prior knowledge and requires painstaking effort. Here, we present a data-efficient method for the high-dimensional multi-property optimization of 3D-printed architected materials utilizing a machine learning (ML) cycle consisting of the finite element method (FEM) and 3D neural networks.

Clinical trial links oncolytic immunoactivation to survival in glioblastoma.

Immunotherapy failures can result from the highly suppressive tumour microenvironment that characterizes aggressive forms of cancer such as recurrent glioblastoma (rGBM). Here we report the results of a first-in-human phase I trial in 41 patients with rGBM who were injected with CAN-3110-an oncolytic herpes virus (oHSV). In contrast to other clinical oHSVs, CAN-3110 retains the viral neurovirulence ICP34.

Sequencing polymers to enable solid-state lithium batteries.

Rational designs of solid polymer electrolytes with high ion conduction are critical in enabling the creation of advanced lithium batteries. However, known polymer electrolytes have much lower ionic conductivity than liquid/ceramics at room temperature, which limits their practical use in batteries. Here we show that precise positioning of designed repeating units in alternating polymer sequences lays the foundation for homogenized Li distribution, non-aggregated Li-anion solvation and sequence-assisted site-to-site ion migration, facilitating the tuning of Li conductivity by up to three orders of magnitude.

Chinese family care partners of older adults in Canada have grit: A qualitative study.

Aim: To explain the process taken by Chinese family care partners of older adults in the Greater Toronto Area, Canada, to access health and social services in their communities. The research question was: What mechanisms and structures impact the agency of Chinese family care partners of older adults, in the process of assisting them to access health and social services?

Design: This qualitative study was informed by critical realism.

Methods: Chinese family care partners of older adults in the Greater Toronto Area, Canada, were interviewed from August 2020 to June 2021.

Pyruvate kinase M2 regulates mitochondrial homeostasis in cisplatin-induced acute kidney injury.

An important pathophysiological process of acute kidney injury (AKI) is mitochondrial fragmentation in renal tubular epithelial cells, which leads to cell death. Pyruvate kinase M2 (PKM2) is an active protein with various biological functions that participates in regulating glycolysis and plays a key role in regulating cell survival. However, the role and mechanism of PKM2 in regulating cell survival during AKI remain unclear.

Effects of different high-temperature conduction modes on the ovalbumin-glucose model: AGEs production and regulation of glycated ovalbumin on gut microbiota.

Food high-temperature processing frequently induces the production of advanced glycation end products (AGEs) in the food industry. In this study, the effects of three high-temperature conduction modes on the AGEs production derived from ovalbumin (OVA)-glucose model and the regulation of glycated OVA on gut microbiota were investigated. The peak time of OVA shifted maximally from 13.

A systematic knowledge graph-based smart management method for operations: A case study of standardized management.

Standardized routine operation management (SROM) has been widely accepted and applied by kinds of enterprises and played a key supporting role. With full use of the emerging knowledge-based smart management technology, SROM will further increase comprehensive efficiency and save human resources greatly at the same time, especially for small and medium enterprises (SMEs). Hence, we propose a systematic knowledge-based smart management method to transfer SROM activities from human operations to automatic response by means of knowledge explicitation, organization, sharing and reusing, which can be further achieved by employing knowledge graph.

RANO 2.0: Update to the Response Assessment in Neuro-Oncology Criteria for High- and Low-Grade Gliomas in Adults.

Purpose: The Response Assessment in Neuro-Oncology (RANO) criteria for high-grade gliomas (RANO-HGG) and low-grade gliomas (RANO-LGG) were developed to improve reliability of response assessment in glioma trials. Over time, some limitations of these criteria were identified, and challenges emerged regarding integrating features of the modified RANO (mRANO) or the immunotherapy RANO (iRANO) criteria.

Methods: Informed by data from studies evaluating the different criteria, updates to the RANO criteria are proposed (RANO 2.

Characterization and Functional Analysis of Genes in Highbush Blueberry ().

Chalcone synthase (CHS) is the first key enzyme-catalyzing plant flavonoid biosynthesis. Until now, however, the blueberry CHS gene family has not been systematically characterized and studied. In this study, we identified 22 genes that could be further classified into four subfamilies from the highbush blueberry () genome.

Photo-induced scandium-catalyzed biomimetic skeleton conversion of lathyrane to naturally rare eupholathone diterpenes.

The naturally scarce eupholathone-type euphornin E (1) was efficiently prepared from abundant lathyrane-type factor L a visible-light-induced Sc(OTf)-catalyzed tandem process. Eupholathones 2 and 3 were also smoothly obtained by changing the reaction solvent. This route provides a convenient method for easily constructing scarce eupholathone- from lathyrane-type diterpenes, and confirms the biogenetic relationship between them from a chemical standpoint.

Positive-Unlabeled Learning With Label Distribution Alignment.

Positive-Unlabeled (PU) data arise frequently in a wide range of fields such as medical diagnosis, anomaly analysis and personalized advertising. The absence of any known negative labels makes it very challenging to learn binary classifiers from such data. Many state-of-the-art methods reformulate the original classification risk with individual risks over positive and unlabeled data, and explicitly minimize the risk of classifying unlabeled data as negative.

Experimental and finite element analysis of the generation mechanism of high impulse noise overpressure (caused by a recoilless weapon) at the bottom of the ear.

The intense impulse noise may damage the soldiers' hearing organs during a weapon's firing. It is essential to find out the generation mechanism of the overpressure at the bottom of the ear. The experiments of measuring the overpressure at the bottom of the ear were conducted through a rotating human head model at a recoilless weapon firing platform.

Brain tumor-related epilepsy management: A Society for Neuro-oncology (SNO) consensus review on current management.

Tumor-related epilepsy (TRE) is a frequent and major consequence of brain tumors. Management of TRE is required throughout the course of disease and a deep understanding of diagnosis and treatment is key to improving quality of life. Gross total resection is favored from both an oncologic and epilepsy perspective.

Insight into the molecular mechanism underlying the enhancement of antioxidant activity in ovalbumin by high-energy electron beam irradiation.

The effects of high-energy electron beam irradiation (HE-EBI) at various doses (0, 25, 50, 75, and 100 kGy) on the antioxidant activity of ovalbumin (OVA) were studied, and the molecular mechanism was investigated. The results showed that the antioxidant activity of HE-EBI-treated OVA was significantly enhanced in a dose-dependent manner. The irradiated OVA structure gradually unfolded to form a "honeycomb" structure, exposing the buried hydrophobic and free sulfhydryl groups inside the molecule.

Intratumoral drug-releasing microdevices allow in situ high-throughput pharmaco phenotyping in patients with gliomas.

The lack of reliable predictive biomarkers to guide effective therapy is a major obstacle to the advancement of therapy for high-grade gliomas, particularly glioblastoma (GBM), one of the few cancers whose prognosis has not improved over the past several decades. With this pilot clinical trial (number NCT04135807), we provide first-in-human evidence that drug-releasing intratumoral microdevices (IMDs) can be safely and effectively used to obtain patient-specific, high-throughput molecular and histopathological drug response profiling. These data can complement other strategies to inform the selection of drugs based on their observed antitumor effect in situ.