Radioresistant Pulmonary Oligometastatic and Oligoprogressive Lesions From Nonlung Primaries: Impact of Histology and Dose-Fractionation on Local Control After Radiation Therapy.

Purpose: We investigated whether pulmonary metastases from historically considered radioresistant primaries would have inferior local control after radiation therapy than those from nonradioresistant nonlung primaries, and whether higher biologically effective dose assuming alpha/beta=10 (BED10) would be associated with superior local control.

Methods And Materials: We identified patients treated with radiation therapy for oligometastatic or oligoprogressive pulmonary disease to 1 to 5 lung metastases from nonlung primaries in 2013 to 2020 at a single health care system. Radioresistant primary cancers included colorectal carcinoma, endometrial carcinoma, renal cell carcinoma, melanoma, and sarcoma.

Dose-Volume Predictors of Radiation Pneumonitis After Thoracic Hypofractionated Radiation Therapy.

Purpose: Hypofractionated radiation therapy (HFRT) is a common treatment for thoracic tumors, typically delivered as 60 Gy in 15 fractions. We aimed to identify dosimetric risk factors associated with radiation pneumonitis in patients receiving HFRT at 4 Gy per fraction, focusing on lung V20, mean lung dose (MLD), and lung V5 as potential predictors of grade ≥2 pneumonitis.

Methods And Materials: All patients were treated with thoracic HFRT to 60 Gy in 15 fractions or 72 Gy in 18 fractions at a single health care system from 2013 to 2020.

The Rat Genome Database: Genetic, Genomic, and Phenotypic Data Across Multiple Species.

The laboratory rat, Rattus norvegicus, is an important model of human health and disease, and experimental findings in the rat have relevance to human physiology and disease. The Rat Genome Database (RGD, https://rgd.mcw.

Rare disease research resources at the Rat Genome Database.

Rare diseases individually affect relatively few people, but as a group they impact considerable numbers of people. The Rat Genome Database (https://rgd.mcw.

2022 updates to the Rat Genome Database: a Findable, Accessible, Interoperable, and Reusable (FAIR) resource.

The Rat Genome Database (RGD, https://rgd.mcw.edu) has evolved from simply a resource for rat genetic markers, maps, and genes, by adding multiple genomic data types and extensive disease and phenotype annotations and developing tools to effectively mine, analyze, and visualize the available data, to empower investigators in their hypothesis-driven research.

The Gene Ontology knowledgebase in 2023.

The Gene Ontology (GO) knowledgebase (http://geneontology.org) is a comprehensive resource concerning the functions of genes and gene products (proteins and noncoding RNAs). GO annotations cover genes from organisms across the tree of life as well as viruses, though most gene function knowledge currently derives from experiments carried out in a relatively small number of model organisms.

Ontological Analysis of Coronavirus Associated Human Genes at the COVID-19 Disease Portal.

The COVID-19 pandemic stemmed a parallel upsurge in the scientific literature about SARS-CoV-2 infection and its health burden. The Rat Genome Database (RGD) created a COVID-19 Disease Portal to leverage information from the scientific literature. In the COVID-19 Portal, gene-disease associations are established by manual curation of PubMed literature.

STING Agonists in Head and Neck Squamous Cell Carcinoma.

Despite the development of new treatment paradigms and improved biologic understanding of head and neck squamous cell carcinoma (HNSCC), therapeutic resistance remains a substantial problem, and novel treatment approaches are needed. Stimulator of interferon genes (STING) is a critical regulator of the antitumor response through regulation of both immune-dependent and tumor-intrinsic mechanisms. As such, the STING pathway has emerged as a rational pharmacologic target leading to the development of multiple STING agonists.

MOET: a web-based gene set enrichment tool at the Rat Genome Database for multiontology and multispecies analyses.

Biological interpretation of a large amount of gene or protein data is complex. Ontology analysis tools are imperative in finding functional similarities through overrepresentation or enrichment of terms associated with the input gene or protein lists. However, most tools are limited by their ability to do ontology-specific and species-limited analyses.

Combinations of immunotherapy and radiation therapy in head and neck squamous cell carcinoma: a narrative review.

Radiation therapy and systemic therapy are the primary non-surgical treatment modalities for head and neck squamous cell carcinoma (HNSCC). Despite advances in our biologic understanding of this disease and the development of novel therapeutics, treatment resistance remains a significant problem. It has become increasingly evident that the innate and adaptive immune systems play a significant role in the modulation of anti-tumor responses to traditional cancer-directed therapies.

Regulation of the Cell-Intrinsic DNA Damage Response by the Innate Immune Machinery.

Maintenance of genomic integrity is crucial for cell survival. As such, elegant DNA damage response (DDR) systems have evolved to ensure proper repair of DNA double-strand breaks (DSBs) and other lesions that threaten genomic integrity. Towards this end, most therapeutic studies have focused on understanding of the canonical DNA DSB repair pathways to enhance the efficacy of DNA-damaging therapies.

Zinc Supplementation with or without Additional Micronutrients Does Not Affect Peripheral Blood Gene Expression or Serum Cytokine Level in Bangladeshi Children.

Preventive zinc supplementation provided as a stand-alone dispersible tablet, or via home fortification as multiple micronutrient powders (MNPs), has been considered a potential strategy to prevent zinc deficiency and improve health (including immune) outcomes among children in low- and middle-income countries. However, the impact of zinc supplementation on immune profiles has not been well characterized. We sought to define the effect of zinc supplementation on peripheral blood gene expression and cytokine levels among young children in Dhaka, Bangladesh.

NECo: A node embedding algorithm for multiplex heterogeneous networks.

Complex diseases such as hypertension, cancer, and diabetes cause nearly 70% of the deaths in the U.S. and involve multiple genes and their interactions with environmental factors.

STING enhances cell death through regulation of reactive oxygen species and DNA damage.

Resistance to DNA-damaging agents is a significant cause of treatment failure and poor outcomes in oncology. To identify unrecognized regulators of cell survival we performed a whole-genome CRISPR-Cas9 screen using treatment with ionizing radiation as a selective pressure, and identified STING (stimulator of interferon genes) as an intrinsic regulator of tumor cell survival. We show that STING regulates a transcriptional program that controls the generation of reactive oxygen species (ROS), and that STING loss alters ROS homeostasis to reduce DNA damage and to cause therapeutic resistance.

The translocon-associated protein (TRAP) complex regulates quality control of N-linked glycosylation during ER stress.

Asparagine (N)-linked glycosylation is required for endoplasmic reticulum (ER) homeostasis, but how this co- and posttranslational modification is maintained during ER stress is unknown. Here, we introduce a fluorescence-based strategy to detect aberrant N-glycosylation in individual cells and identify a regulatory role for the heterotetrameric translocon-associated protein (TRAP) complex. Unexpectedly, cells with knockout of SSR3 or SSR4 subunits restore N-glycosylation over time concurrent with a diminished ER stress transcriptional signature.

The Year of the Rat: The Rat Genome Database at 20: a multi-species knowledgebase and analysis platform.

Formed in late 1999, the Rat Genome Database (RGD, https://rgd.mcw.edu) will be 20 in 2020, the Year of the Rat.

RIPLET, and not TRIM25, is required for endogenous RIG-I-dependent antiviral responses.

The innate immune system is our first line of defense against viral pathogens. Host cell pattern recognition receptors sense viral components and initiate immune signaling cascades that result in the production of an array of cytokines to combat infection. Retinoic acid-inducible gene-I (RIG-I) is a pattern recognition receptor that recognizes viral RNA and, when activated, results in the production of type I and III interferons (IFNs) and the upregulation of IFN-stimulated genes.

Rat Genome Databases, Repositories, and Tools.

Resources for rat researchers are extensive, including strain repositories and databases all around the world. The Rat Genome Database (RGD) serves as the primary rat data repository, providing both manual and computationally collected data from other databases.

Predicting instances of pathway ontology classes for pathway integration.

Background: To improve the outcomes of biological pathway analysis, a better way of integrating pathway data is needed. Ontologies can be used to organize data from disparate sources, and we leverage the Pathway Ontology as a unifying ontology for organizing pathway data. We aim to associate pathway instances from different databases to the appropriate class in the Pathway Ontology.

Integrated curation and data mining for disease and phenotype models at the Rat Genome Database.

Rats have been used as research models in biomedical research for over 150 years. These disease models arise from naturally occurring mutations, selective breeding and, more recently, genome manipulation. Through the innovation of genome-editing technologies, genome-modified rats provide precision models of disease by disrupting or complementing targeted genes.

A Primer for the Rat Genome Database (RGD).

The laboratory rat, Rattus norvegicus, is an important model of human health and disease, and experimental findings in the rat have relevance to human physiology and disease. The Rat Genome Database (RGD, http://rgd.mcw.

CDKN2A Copy Number Loss Is an Independent Prognostic Factor in HPV-Negative Head and Neck Squamous Cell Carcinoma.

Background: HPV infection is associated with high p16 expression and good prognosis in head and neck squamous cell carcinomas (HNSCCs). Analysis of CDKN2A, the gene encoding p16, may further elucidate the association between p16 expression and prognosis. We sought to determine whether CDKN2A copy number loss was associated with poor survival in HPV-negative HNSCCs.

Identification of a second binding site on the TRIM25 B30.2 domain.

The etinoic acid-nducible ene- (RIG-I) receptor recognizes short 5'-di- and triphosphate base-paired viral RNA and is a critical mediator of the innate immune response against viruses such as influenza A, Ebola, HIV and hepatitis C. This response is reported to require an orchestrated interaction with the partite otif 25 (TRIM25) B30.2 protein-interaction domain.