TarIKGC: A Target Identification Tool Using Semantics-Enhanced Knowledge Graph Completion with Application to CDK2 Inhibitor Discovery.

Target identification is a critical stage in the drug discovery pipeline. Various computational methodologies have been dedicated to enhancing the classification performance of compound-target interactions, yet significant room remains for improving the recommendation performance. To address this challenge, we developed TarIKGC, a tool for target prioritization that leverages semantics enhanced knowledge graph (KG) completion.

[Enhancement algorithm for surface electromyographic-based gesture recognition based on real-time fusion of muscle fatigue features].

This study aims to optimize surface electromyography-based gesture recognition technique, focusing on the impact of muscle fatigue on the recognition performance. An innovative real-time analysis algorithm is proposed in the paper, which can extract muscle fatigue features in real time and fuse them into the hand gesture recognition process. Based on self-collected data, this paper applies algorithms such as convolutional neural networks and long short-term memory networks to provide an in-depth analysis of the feature extraction method of muscle fatigue, and compares the impact of muscle fatigue features on the performance of surface electromyography-based gesture recognition tasks.

Partisan divide and Racial/Ethnic disparities in COVID-19 vaccine hesitancy among Parents/Guardians and vaccine uptake among children in the U.S.

Objectives: We undertook an observational study to assess the impact of state-level partisanship and parents'/guardians' race/ethnicity on their degree of COVID-19 vaccine hesitancy.

Material And Methods: We observed a pooled cross-section of 59,280 U.S.

A multidimensional platform of patient-derived tumors identifies drug susceptibilities for clinical lenvatinib resistance.

Lenvatinib, a second-generation multi-receptor tyrosine kinase inhibitor approved by the FDA for first-line treatment of advanced liver cancer, facing limitations due to drug resistance. Here, we applied a multidimensional, high-throughput screening platform comprising patient-derived resistant liver tumor cells (PDCs), organoids (PDOs), and xenografts (PDXs) to identify drug susceptibilities for conquering lenvatinib resistance in clinically relevant settings. Expansion and passaging of PDCs and PDOs from resistant patient liver tumors retained functional fidelity to lenvatinib treatment, expediting drug repurposing screens.

Integrating External Controls by Regression Calibration for Genome-Wide Association Study.

Genome-wide association studies (GWAS) have successfully revealed many disease-associated genetic variants. For a case-control study, the adequate power of an association test can be achieved with a large sample size, although genotyping large samples is expensive. A cost-effective strategy to boost power is to integrate external control samples with publicly available genotyped data.

Galectin-7 Induction by EHMT2 Inhibition Enhances Immunity in Microsatellite Stability Colorectal Cancer.

Background & Aims: Although immunotherapy shows substantial advancement in colorectal cancer (CRC) with microsatellite instability high, it has limited efficacy for CRC with microsatellite stability (MSS). Identifying combinations that reverse immune suppression and prime MSS tumors for current immunotherapy approaches remains an urgent need.

Methods: An in vitro CRISPR screen was performed using coculture models of primary tumor cells and autologous immune cells from MSS CRC patients to identify epigenetic targets that could enhance immunotherapy efficacy in MSS tumors.

Gene-Based Association Tests Using New Polygenic Risk Scores and Incorporating Gene Expression Data.

Recently, gene-based association studies have shown that integrating genome-wide association studies (GWAS) with expression quantitative trait locus (eQTL) data can boost statistical power and that the genetic liability of traits can be captured by polygenic risk scores (PRSs). In this paper, we propose a new gene-based statistical method that leverages gene-expression measurements and new PRSs to identify genes that are associated with phenotypes of interest. We used a generalized linear model to associate phenotypes with gene expression and PRSs and used a score-test statistic to test the association between phenotypes and genes.

Control for population stratification in genetic association studies based on GWAS summary statistics.

Over the past years, genome-wide association studies (GWAS) have generated a wealth of new information. Summary data from many GWAS are now publicly available, promoting the development of many statistical methods for association studies based on GWAS summary statistics, which avoids the increasing challenges associated with individual-level genotype and phenotype data sharing. However, for population-based association studies such as GWAS, it has been long recognized that population stratification can seriously confound association results.

Loss-of-Function Genetic Screening Identifies Aldolase A as an Essential Driver for Liver Cancer Cell Growth Under Hypoxia.

Background And Aims: Hypoxia is a common feature of the tumor microenvironment (TME), which promotes tumor progression, metastasis, and therapeutic drug resistance through a myriad of cell activities in tumor and stroma cells. While targeting hypoxic TME is emerging as a promising strategy for treating solid tumors, preclinical development of this approach is lacking in the study of HCC.

Approach And Results: From a genome-wide CRISPR/CRISPR-associated 9 gene knockout screening, we identified aldolase A (ALDOA), a key enzyme in glycolysis and gluconeogenesis, as an essential driver for HCC cell growth under hypoxia.

Tumor-associated macrophages in immunotherapy.

Tumor-associated macrophages (TAMs) are essential components of the tumor microenvironment involved in the progression and metastasis of cancer. They are intimately involved in angiogenesis and immunosuppression in normal and malignant tissues, as well as pro-fibrotic activities. With the development of immunotherapy, eradication of cancer cells through activation of the innate immune system has achieved inspiring results, whereas only a handful of patients show a durable response.

RNA-binding protein RALY reprogrammes mitochondrial metabolism via mediating miRNA processing in colorectal cancer.

Objective: Dysregulated cellular metabolism is a distinct hallmark of human colorectal cancer (CRC). However, metabolic programme rewiring during tumour progression has yet to be fully understood.

Design: We analysed altered gene signatures during colorectal tumour progression, and used a complex of molecular and metabolic assays to study the regulation of metabolism in CRC cell lines, human patient-derived xenograft mouse models and tumour organoid models.

Children's Non-symbolic and Symbolic Numerical Representations and Their Associations With Mathematical Ability.

Most empirical evidence supports the view that non-symbolic and symbolic representations are foundations for advanced mathematical ability. However, the detailed development trajectories of these two types of representations in childhood are not very clear, nor are the different effects of non-symbolic and symbolic representations on the development of mathematical ability. We assessed 253 4- to 8-year-old children's non-symbolic and symbolic numerical representations, mapping skills, and mathematical ability, aiming to investigate the developmental trajectories and associations between these skills.

Children's Non-symbolic, Symbolic Addition and Their Mapping Capacity at 4-7 Years Old.

The study aimed to examine the developmental trajectories of non-symbolic and symbolic addition capacities in children and the mapping ability between these two. We assessed 106 4- to 7-year-old children and found that 4-year-olds were able to do non-symbolic addition but not symbolic addition. Five-year-olds and older were able to do symbolic addition and their performance in symbolic addition exceeded non-symbolic addition in grade 1 (approximate age 7).