Brief Report: Methylation-Based ctDNA Serial Monitoring Correlates With Immunotherapy Response in NSCLC.

Purpose: Circulating tumor DNA (ctDNA) can reflect the genetic and epigenetic composition of malignancies and can serve as a noninvasive biomarker for cancer diagnostics and monitoring. This study aimed to evaluate the utility of a methylation-based ctDNA assay as a predictive tool in non-small cell lung cancer (NSCLC) anti-PD1 based immunotherapy monitoring.

Methods: We evaluated a cohort of 20 patients with NSCLC treated with anti-PD1 based immunotherapy that had both baseline and follow-up blood draws as well as outcome data available.

BRCA1 frameshift variants leading to extended incorrect protein C termini.

Carriers of BRCA1 germline pathogenic variants are at substantially higher risk of developing breast and ovarian cancer than the general population. Accurate identification of at-risk individuals is crucial for risk stratification and the implementation of targeted preventive and therapeutic interventions. Despite significant progress in variant classification efforts, a sizable portion of reported BRCA1 variants remain as variants of uncertain clinical significance (VUSs).

An Immune-Related Gene Expression Signature Predicts Benefit from Adding Atezolizumab to FOLFOXIRI plus Bevacizumab in Metastatic Colorectal Cancer.

Purpose: AtezoTRIBE phase II randomized study demonstrated that adding atezolizumab to first-line FOLFOXIRI (5-fluorouracil, oxaliplatin, irinotecan) plus bevacizumab prolongs progression-free survival (PFS) of patients with metastatic colorectal cancer (mCRC), with a modest benefit among proficient mismatch repair (pMMR). DetermaIO is an immune-related 27-gene expression signature able to predict benefit from immune checkpoint inhibition in triple-negative breast cancer. In this analysis of AtezoTRIBE, we investigated the predictive impact of DetermaIO in mCRC.

The 27-gene IO score is associated with efficacy of PD-1/L1 inhibitors independent of FGFR expression in a real-world metastatic urothelial carcinoma cohort.

Multiple targeted therapeutics have been approved by the FDA for mUC, including immune checkpoint inhibitors (ICIs) and more recently targeted agents for both FGFR and Nectin-4. FGFR3-aberrant and Nectin-4 expressing cells have been associated with an immunosuppressed phenotype. Given that less than half of all patients respond to these agents as monotherapies and less than 20% are eligible to receive salvage therapy, effective personalized treatment plans are critical.

27-gene Immuno-Oncology (IO) Score is Associated With Efficacy of Checkpoint Immunotherapy in Advanced NSCLC: A Retrospective BC Cancer Study.

Background: Immune checkpoint inhibitors (ICI) are standard of care in advanced non-small cell lung cancer (NSCLC). However, not all patients benefit, even among PD-L1 tumor proportional score (TPS) ≥50%, indicating an unmet need for additional biomarkers such as those assessing the tumor immune microenvironment (TIME). DetermaIO is a 27-gene assay that classifies TIME and has previously demonstrated association with ICI response.

Translation of the 27-gene immuno-oncology test (IO score) to predict outcomes in immune checkpoint inhibitor treated metastatic urothelial cancer patients.

Background: The IO Score is a 27-gene immuno-oncology (IO) classifier that has previously predicted benefit to immune checkpoint inhibitor (ICI) therapy in triple negative breast cancer (TNBC) and non-small cell lung cancer (NSCLC). It generates both a continuous score and a binary result using a defined threshold that is conserved between breast and lung. Herein, we aimed to evaluate the IO Score's binary threshold in ICI-naïve TCGA bladder cancer patients (TCGA-BLCA) and assess its clinical utility in metastatic urothelial cancer (mUC) using the IMvigor210 clinical trial treated with the ICI, atezolizumab.

Intestinal Alkaline Phosphatase Prevents Sulfate Reducing Bacteria-Induced Increased Tight Junction Permeability by Inhibiting Snail Pathway.

Tight junctions (TJs) are essential components of intestinal barrier integrity and protect the epithelium against passive paracellular flux and microbial translocation. Dysfunctional TJ leads to leaky gut, a condition associated with diseases including inflammatory bowel disease (IBD). Sulfate-Reducing Bacteria (SRB) are minor residents of the gut.

Norepinephrine induces growth of Desulfovibrio vulgaris in an iron dependent manner.

Unlabelled: Desulfovibrio spp. is a commensal sulfate reducing bacterium that is present in small numbers in the gastrointestinal tract. Increased concentrations of Desulfovibrio spp.

Association of a novel 27-gene immuno-oncology assay with efficacy of immune checkpoint inhibitors in advanced non-small cell lung cancer.

Background: Immune checkpoint inhibitor (ICI) therapies represent a major advance in treating a variety of advanced-stage malignancies. Nevertheless, only a subset of patients benefit, even when selected based on approved biomarkers such as PD-L1 and tumor mutational burden. New biomarkers are needed to maximize the therapeutic ratio of these therapies.

Serum antibodies to selected antigens are associated with active gastritis in patients seen at the University Teaching Hospital in Lusaka, Zambia.

Introduction: Little is known about specific bacterial characteristics of () infection influencing gastric carcinogenesis in Zambia. The aim of this study was to evaluate the associations between pre-selected antibodies with gastric cancer, premalignant lesions and active gastritis.

Methods: This was cross-sectional study with multiple comparisons of patients with gastric cancer (GC), gastric premalignant (GP) lesions and active or chronic gastritis.

Notch Signaling Pathway Is Activated by Sulfate Reducing Bacteria.

Sulfate Reducing Bacteria (SRB), usually rare residents of the gut, are often found in increased numbers (called a SRB bloom) in inflammatory conditions such as Inflammatory Bowel Disease (IBD), pouchitis, and periodontitis. However, the underlying mechanisms of this association remain largely unknown. Notch signaling, a conserved cell-cell communication pathway, is usually involved in tissue development and differentiation.

Thermodynamics and Free Energy Landscape of BAR-Domain Dimerization from Molecular Simulations.

Proteins with BAR domains function to bind to and remodel biological membranes, where the dimerization of BAR domains is a key step in this function. These domains can dimerize in solution or after localizing to the membrane surface. Here, we characterize the binding thermodynamics of homodimerization between the LSP1 BAR domain proteins in solution, using molecular dynamics (MD) simulations.

Standard Bacteriophage Purification Procedures Cause Loss in Numbers and Activity.

For decades, bacteriophage purification has followed structured protocols focused on generating high concentrations of phage in manageable volumes. As research moves toward understanding complex phage populations, purification needs have shifted to maximize the amount of phage while maintaining diversity and activity. The effects of standard phage purification procedures such as polyethylene glycol (PEG) precipitation and cesium chloride (CsCl) density gradients on both diversity and activity of a phage population are not known.

Immunostimulatory membrane proteins potentiate -induced carcinogenesis by enabling CagA translocation.

Infection with is the single greatest risk factor for developing gastric adenocarcinoma. In prospective, population-based studies, seropositivity to the uncharacterized proteins Hp0305 and Hp1564 was significantly associated with cancer risk in East Asia. However, the mechanism underlying this observation has not been elucidated.

The Holistic Grief Effects of Bereaved Black Female College Students.

This study examined the holistic grief effects of Black female college students. A total of 105 participants from two universities, who identified as Black or African American females, completed a questionnaire regarding death losses and grief effects they experienced. Descriptive statistics and ANOVAs examined between-group differences based on loss experiences.

Racial Differences in CagA Sero-prevalence in a Consortium of Adult Cohorts in the United States.

Background: Prevalence of () infection, the main risk factor for gastric cancer, has been decreasing in the United States; however, there remains a substantial racial disparity. Moreover, the time-trends for prevalence of CagA-positive infection, the most virulent form, are unknown in the U.S.

NERDSS: A Nonequilibrium Simulator for Multibody Self-Assembly at the Cellular Scale.

Currently, a significant barrier to building predictive models of cellular self-assembly processes is that molecular models cannot capture minutes-long dynamics that couple distinct components with active processes, whereas reaction-diffusion models cannot capture structures of molecular assembly. Here, we introduce the nonequilibrium reaction-diffusion self-assembly simulator (NERDSS), which addresses this spatiotemporal resolution gap. NERDSS integrates efficient reaction-diffusion algorithms into generalized software that operates on user-defined molecules through diffusion, binding and orientation, unbinding, chemical transformations, and spatial localization.

Performance of multiplex serology in discriminating active vs past Helicobacter pylori infection in a primarily African American population in the southeastern United States.

Purpose: To feasibly analyze associations of Helicobacter pylori (H. pylori) with disease in large cohort studies, assays are needed to assess H. pylori prevalence in existing biospecimens.

Use of Letermovir for Salvage Therapy for Resistant Cytomegalovirus in a Pediatric Hematopoietic Stem Cell Transplant Recipient.

We present here the first published use of letermovir for the treatment of resistant cytomegalovirus (CMV) in a pediatric patient. A 14-year-old girl underwent a double unrelated umbilical cord blood transplantation to treat her sickle cell disease (hemoglobin SS) and developed ganciclovir-resistant CMV DNAemia with end-organ involvement that was treated successfully with a combination of foscarnet and letermovir. After she was transitioned to letermovir monotherapy for secondary prophylaxis, she developed recurrent DNAemia with laboratory-confirmed ganciclovir, foscarnet, and letermovir resistance.

Smoking, Serology, and Gastric Cancer Risk in Prospective Studies from China, Japan, and Korea.

Smoking is an established risk factor for gastric cancer development. In this study, we aimed to assess prospectively the association of smoking with gastric cancer risk in 1,446 non-cardia gastric cancer cases and 1,796 controls from China, Japan, and Korea with consideration of infection as a potential effect modifier. Applying logistic regression models stratified by study and adjusted for age and sex we found that current, but not former, smoking was significantly associated with gastric cancer risk [OR = 1.

Modification of the Gastric Mucosal Microbiota by a Strain-Specific Helicobacter pylori Oncoprotein and Carcinogenic Histologic Phenotype.

is the strongest risk factor for gastric adenocarcinoma; however, most infected individuals never develop this malignancy. Strain-specific microbial factors, such as the oncoprotein CagA, as well as environmental conditions, such as iron deficiency, augment cancer risk. Importantly, dysbiosis of the gastric microbiota is also associated with gastric cancer.

Epstein-Barr virus, but not human cytomegalovirus, is associated with a high-grade human papillomavirus-associated cervical lesions among women in North Carolina.

Statement Of The Problem: Human papillomavirus (HPV) infection is known to contribute to cervical carcinogenesis, yet other cofactors that may contribute to oncogenesis are poorly understood. Herein, we examine whether the Epstein-Barr virus (EBV) and human cytomegalovirus (CMV), two oncomodulatory viruses, are associated with HPV-mediated cervical neoplastic progression.

Methods: Sixty patient cervical brush samples from a study of North Carolina women were obtained.

Serologic Response to Helicobacter pylori Proteins Associated With Risk of Colorectal Cancer Among Diverse Populations in the United States.

Background & Aims: Previous studies reported an association of the bacteria Helicobacter pylori, the primary cause of gastric cancer, and risk of colorectal cancer (CRC). However, these findings have been inconsistent, appear to vary with population characteristics, and may be specific for virulence factor VacA. To more thoroughly evaluate the potential association of H pylori antibodies with CRC risk, we assembled a large consortium of cohorts representing diverse populations in the United States.