Genomic analysis of surgical patients to identify patients at risk for postoperative sepsis and surgical site infection.

Background: Early and accurate diagnosis of sepsis and the ensuing organ dysfunction remain a challenge in the postoperative setting. Susceptibility to infections, as well as the subsequent immunological response, are driven to some extent by the genetic predisposition of the patient. The purpose of this study was to identify novel genetic variants associated with postoperative sepsis (POS) and surgical site infections (SSIs).

The Hallmarks of Predictive Oncology.

As the field of artificial intelligence evolves rapidly, these hallmarks are intended to capture fundamental, complementary concepts necessary for the progress and timely adoption of predictive modeling in precision oncology. Through these hallmarks, we hope to establish standards and guidelines that enable the symbiotic development of artificial intelligence and precision oncology.

Mutation in and a Variant Linked to a Severe Sporadic Infant Dilated Cardiomyopathy Case.

Structural or electrophysiologic cardiac anomalies may compromise cardiac function, leading to sudden cardiac death (SCD). Genetic screening of families with severe cardiomyopathies underlines the role of genetic variations in cardiac-specific genes. The present study details the clinical and genetic characterization of a malignant dilated cardiomyopathy (DCM) case in a 1-year-old Mexican child who presented a severe left ventricular dilation and dysfunction that led to SCD.

Changing Treatment and Metastatic Disease Patterns in Patients with EGFR Mutated NSCLC: An Academic Thoracic Medical Investigator's Consortium Registry Analysis.

Introduction: Osimertinib is now a standard first-line (1L) therapy for EGFR-mutated (EGFRm) advanced NSCLC. We aimed to characterize patterns of therapy and longitudinal risk of brain and liver metastasis in a cohort of EGFRm NSCLC.

Methods: Patients with metastatic EGFRm NSCLC who received 1L systemic therapy at sites within the Academic Thoracic Medical Investigator's Consortium were included; demographic and clinical data including treatment patterns were described.

Egg shape and color mediate acceptance thresholds in diverse avian host species with different rates of antiparasitic egg rejection.

Eggshell recognition in parental birds is vital for nest management, defense against brood parasitism, optimal embryonic development, and minimizing disease and predation risks. This process relies on acceptance thresholds balancing the risk of rejecting own eggs against the benefit of excluding foreign ones, following signal detection theory. We investigated the role of object shape in egg rejection decisions among three host species of the brown-headed cowbird (Molothrus ater), each with a varying known response to parasitic eggs.

Genomic and Transcriptomic Profiling of Digital Papillary Adenocarcinomas Reveals Alterations in Matrix Remodeling and Metabolic Genes.

Background: Digital papillary adenocarcinoma (DPAC) is a rare but aggressive cutaneous malignant sweat gland neoplasm that occurs on acral sites. Despite its clinical significance, the cellular and genetic characteristics of DPAC remain incompletely understood.

Methods: We conducted a comprehensive genomic and transcriptomic analysis of DPAC (n = 14) using targeted next-generation DNA and RNA sequencing, along with gene expression profiling employing the Nanostring Technologies nCounter IO 360 Panel.

Biologically-targeted discovery-replication scan identifies G×G interaction in relation to risk of Barrett's esophagus and esophageal adenocarcinoma.

Inherited genetics represents an important contributor to risk of esophageal adenocarcinoma (EAC), and its precursor Barrett's esophagus (BE). Genome-wide association studies have identified ∼30 susceptibility variants for BE/EAC, yet genetic interactions remain unexamined. To address challenges in large-scale G×G scans, we combined knowledge-guided filtering and machine learning approaches, focusing on genes with (A) known/plausible links to BE/EAC pathogenesis (n=493) or (B) prior evidence of biological interactions (n=4,196).

Comparative species delimitation of a biological conservation icon.

The United States Endangered Species Act (ESA) of 1973 set a precedent for biodiversity conservation across the globe. A key requirement of protections afforded by the ESA is the accurate delimitation of imperiled species. We present a comparative reference-based taxonomic approach to species delimitation that integrates genomic and morphological data for objectively assessing the distinctiveness of species targeted for protection by governmental agencies.

Glutathione accelerates the cell cycle and cellular reprogramming in plant regeneration.

The plasticity of plant cells underlies their wide capacity to regenerate, with increasing evidence in plants and animals implicating cell-cycle dynamics in cellular reprogramming. To investigate the cell cycle during cellular reprogramming, we developed a comprehensive set of cell-cycle-phase markers in the Arabidopsis root. Using single-cell RNA sequencing profiles and live imaging during regeneration, we found that a subset of cells near an ablation injury dramatically increases division rate by truncating G1 phase.

Enhancing chemotherapy response prediction via matched colorectal tumor-organoid gene expression analysis and network-based biomarker selection.

Background: Colorectal cancer (CRC) presents significant challenges in chemotherapy response prediction due to its molecular heterogeneity. Current methods often fail to account for the complexity and variability inherent in individual tumors.

Methods: We developed a novel approach using matched CRC tumor and organoid gene expression data.

Clinicogenomic landscape of pancreatic adenocarcinoma identifies KRAS mutant dosage as prognostic of overall survival.

Nearly all pancreatic adenocarcinomas (PDAC) are genomically characterized by KRAS exon 2 mutations. Most patients with PDAC present with advanced disease and are treated with cytotoxic therapy. Genomic biomarkers prognostic of disease outcomes have been challenging to identify.

Refining breast cancer genetic risk and biology through multi-ancestry fine-mapping analyses of 192 risk regions.

Genome-wide association studies have identified approximately 200 genetic risk loci for breast cancer, but the causal variants and target genes are mostly unknown. We sought to fine-map all known breast cancer risk loci using genome-wide association study data from 172,737 female breast cancer cases and 242,009 controls of African, Asian and European ancestry. We identified 332 independent association signals for breast cancer risk, including 131 signals not reported previously, and for 50 of them, we narrowed the credible causal variants down to a single variant.

Deeper response predicts better outcomes in high-risk-smoldering-myeloma: results of the I-PRISM phase II clinical trial.

Early therapeutic intervention in high-risk smoldering multiple myeloma (HR-SMM) has shown benefits, however, no studies have assessed whether biochemical progression or response depth predicts long-term outcomes. The single-arm I-PRISM phase II trial (NCT02916771) evaluated ixazomib, lenalidomide, and dexamethasone in 55 patients with HR-SMM. The primary endpoint, median progression-free survival (PFS), was not reached (NR) (95% CI: 57.

Finding functional microproteins.

Genome-wide translational profiling has uncovered the synthesis in human cells of thousands of microproteins, a class of proteins traditionally overlooked in functional studies. Although an increasing number of these microproteins have been found to play critical roles in cellular processes, the functional relevance of the majority remains poorly understood. Studying these low-abundance, often unstable proteins is further complicated by the challenge of disentangling their functions from the noncoding roles of the associated DNA, RNA, and the act of translation.

Infiltrating plasma cells maintain glioblastoma stem cells through IgG-Tumor binding.

Glioblastoma is a highly aggressive primary brain tumor with glioblastoma stem cells (GSCs) enforcing the intra-tumoral hierarchy. Plasma cells (PCs) are critical effectors of the B-lineage immune system, but their roles in glioblastoma remain largely unexplored. Here, we leverage single-cell RNA and B cell receptor sequencing of tumor-infiltrating B-lineage cells and reveal that PCs are aberrantly enriched in the glioblastoma-infiltrating B-lineage population, experience low level of somatic hypermutation, and are associated with poor prognosis.

CIROZ is dispensable in ancestral vertebrates but essential for left-right patterning in humans.

Four genes-DAND5, PKD1L1, MMP21, and CIROP-form a genetic module that has specifically evolved in vertebrate species that harbor motile cilia in their left-right organizer (LRO). We find here that CIROZ (previously known as C1orf127) is also specifically expressed in the LRO of mice, frogs, and fish, where it encodes a protein with a signal peptide followed by 3 zona pellucida N domains, consistent with extracellular localization. We report 16 individuals from 10 families with bi-allelic CIROZ inactivation variants, which cause heterotaxy with congenital heart defects.

Deriving a genetic regulatory network from an optimization principle.

Many biological systems operate near the physical limits to their performance, suggesting that aspects of their behavior and underlying mechanisms could be derived from optimization principles. However, such principles have often been applied only in simplified models. Here, we explore a detailed mechanistic model of the gap gene network in the embryo, optimizing its 50+ parameters to maximize the information that gene expression levels provide about nuclear positions.

Evolutionary and Functional Analysis of Monoamine Oxidase F (MAO F): A Novel Member of the MAO Gene Family.

The monoamine oxidase (MAO) gene family encodes for enzymes that perform the oxidative deamination of monoamines, a process required to degrade norepinephrine, serotonin, dopamine, and other amines. While mammalian MAO enzymes, MAO A and MAO B, have been extensively studied, the molecular properties of the other family members are only partly uncovered. This study aims to explore the evolution of monoamine oxidases, emphasizing understanding the MAO gene repertoire among vertebrates.

Genetic and Phenotypic Intra-Clade Variation in Candida auris Isolated from Critically Ill Patients in a New York City Tertiary Care Center.

Background: Candida auris is an emerging multidrug-resistant pathogen. Interpretation of susceptibility testing can be difficult since minimum inhibitory concentration (MIC) breakpoints have not been fully established.

Methods: All C.

Standardization of Genomic Nomenclature across a Diverse Ecosystem of Stakeholders: Evolution and Challenges.

Background: Genetic testing has traditionally been divided into molecular genetics and cytogenetics, originally driven by the use of different assays and their associated limitations. Cytogenetic technologies such as karyotyping, fluorescent in situ hybridization or chromosomal microarrays are used to detect large "megabase level" copy number variants and other structural variants such as inversions or translocations. In contrast, molecular methodologies are heavily biased toward subgenic "small variants" such as single nucleotide variants, insertions/deletions, and targeted detection of intragenic, exon level deletions or duplications.

Maximizing the clinical utility and performance of cytology samples for comprehensive genetic profiling.

Comprehensive molecular profiling by next-generation sequencing has revolutionized tumor classification and biomarker evaluation. However, routine implementation is challenged by the scant nature of diagnostic material obtained through minimally invasive procedures. Here, we describe our long-term experience in profiling cytology samples with an in-depth assessment of the performance, quality metrics, biomarker identification capabilities, and potential pitfalls.