The impact of limited sucrose intake on perineuronal nets of parvalbumin interneurons in the basolateral amygdala: A potential role in stress resilience.

Natural rewards like regular sucrose consumption can buffer physiological and behavioral stress responses, likely mediated, at least in part, by increased plasticity in parvalbumin-positive (PV+) interneurons in the basolateral amygdala (BLA). As PV+ interneuron plasticity is tightly regulated by specialized extracellular matrix structures called perineuronal nets (PNNs), this study investigated the impact of regular sucrose consumption vs. repetitive stress on the PNNs that surround PV+ interneurons in the BLA, as well as the number of glutamatergic (vGLUT1) and GABAergic (vGAT) appositions that PV+ cells receive.

Brief Report: Phase II Clinical Trial of Atezolizumab in Advanced Nonsmall Cell Lung Cancer Patients Previously Treated With PD-1-Directed Therapy.

Background:: Prospective data of sequencing PD-L1 inhibition after PD-1 inhibition is limited in non-small cell lung cancer (NSCLC). We report a phase II clinical trial of atezolizumab following PD-1 directed therapy (NCT03014648).

Methods:: Previously treated advanced NSCLC patients were enrolled in cohorts based on response to prior nivolumab or pembrolizumab therapy; progressive disease (Cohort 1); stable disease (Cohort 2), or partial or complete response (Cohort 3).

Multiplex digital profiling of DNA methylation heterogeneity for sensitive and cost-effective cancer detection in low-volume liquid biopsies.

Molecular alterations in cancerous tissues exhibit intercellular genetic and epigenetic heterogeneity, complicating the performance of diagnostic assays, particularly for early cancer detection. Conventional liquid biopsy methods have limited sensitivity and/or ability to assess epigenetic heterogeneity of rare epiallelic variants cost-effectively. We report an approach, named REM-DREAMing (Ratiometric-Encoded Multiplex Discrimination of Rare EpiAlleles by Melt), which leverages a digital microfluidic platform that incorporates a ratiometric fluorescence multiplex detection scheme and precise digital high-resolution melt analysis to enable low-cost, parallelized analysis of heterogeneous methylation patterns on a molecule-by-molecule basis for the detection of cancer in liquid biopsies.

Body composition as a biomarker for assessing future lung cancer risk.

Purpose: To investigate if body composition is a biomarker for assessing the risk of developing lung cancer.

Materials And Methods: Low-dose computed tomography (LDCT) scans from the Pittsburgh Lung Screening Study (PLuSS) (n=3,635, 22 follow-up years) and NLST-ACRIN (n=16,435, 8 follow-up years) cohorts were used in the study. Artificial intelligence (AI) algorithms were developed to automatically segment and quantify subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), intramuscular adipose tissue (IMAT), skeletal muscle (SM), and bone.

Vascular Biomarkers for Pulmonary Nodule Malignancy: Arteries vs. Veins.

Objective: This study aims to investigate the association between the arteries and veins surrounding a pulmonary nodule and its malignancy.

Methods: A dataset of 146 subjects from a LDCT lung cancer screening program was used in this study. AI algorithms were used to automatically segment and quantify nodules and their surrounding macro-vasculature.

The influence of paraventricular nucleus of the hypothalamus soluble guanylate cyclase on autonomic and neuroendocrine responses to acute restraint stress in rats.

The paraventricular nucleus of the hypothalamus (PVN) regulates physiological and behavioural responses evoked by stressful stimuli, but the local neurochemical and signalling mechanisms involved are not completely understood. The soluble guanylate cyclase (sGC) within the PVN is implicated in autonomic and cardiovascular control in rodents under resting conditions. However, the involvement of PVN sGC-mediated signalling in stress responses is unknown.

Neighborhood-level deprivation and survival in lung cancer.

Background: Despite recent advances in lung cancer therapeutics and improving overall survival, disparities persist among socially disadvantaged populations. This study aims to determine the effects of neighborhood deprivation indices (NDI) on lung cancer mortality. This is a multicenter retrospective cohort study assessing the relationship between NDI and overall survival adjusted for age, disease stage, and DNA methylation among biopsy-proven lung cancer patients.

Methylation of is a synthetic lethal marker for ATR/CHK1 inhibitors in pancreatic cancer.

Background And Objectives: Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignancies. An epigenetic-based synthetic lethal strategy provides a novel opportunity for PDAC treatment. Finding more DNA damage repair (DDR)-related or cell fate-related molecules with aberrant epigenetic changes is becoming very important.

Epigenetic silencing of promotes hepatocellular carcinoma growth by activating PI3K/AKT signaling.

The aim of current study is to explore the epigenetic changes and function of KCTD8 in human hepatocellular carcinoma (HCC). HCC cell lines and tissue samples were employed. Methylation specific PCR, flow cytometry, immunoprecipitation and xenograft mouse models were used.

Inhibition of prefrontal cortex parvalbumin interneurons mitigates behavioral and physiological sequelae of chronic stress in male mice.

Chronic stress leads to hypofunction of the medial prefrontal cortex (mPFC), mechanisms of which remain to be determined. Enhanced activation of GABAergic of parvalbumin (PV) expressing interneurons (INs) is thought to play a role in stress-induced prefrontal inhibition. In this study, we tested whether chemogenetic inhibition of mPFC PV INs after chronic stress can rescue chronic stress-related behavioral and physiological phenotypes.

Epigenetic silencing of BEND4, a novel DNA damage repair gene, is a synthetic lethal marker for ATM inhibitor in pancreatic cancer.

Synthetic lethality is a novel model for cancer therapy. To understand the function and mechanism of BEN domain-containing protein 4 (BEND4) in pancreatic cancer, eight cell lines and a total of 492 cases of pancreatic neoplasia samples were included in this study. Methylation-specific polymerase chain reaction, CRISPR/Cas9, immunoprecipitation assay, comet assay, and xenograft mouse model were used.

Epigenetic silencing schlafen-11 sensitizes esophageal cancer to ATM inhibitor.

Background: Targeting DNA damage response (DDR) pathway is a cutting-edge strategy. It has been reported that Schlafen-11 (SLFN11) contributes to increase chemosensitivity by participating in DDR. However, the detailed mechanism is unclear.

Phase 2 study of epigenetic priming with decitabine followed by cytarabine for acute myeloid leukemia in older patients.

Acute myeloid leukemia (AML) in older patients has a poor prognosis, low complete remission (CR) rates, and poor overall survival (OS). Preclinical studies have shown synergistic effects of epigenetic priming with hypomethylating agents followed by cytarabine. Based on these data, we hypothesized that an induction regimen using epigenetic priming with decitabine, followed by cytarabine would be effective and safe in older patients with previously untreated AML.

Methylation of NRIP3 Is a Synthetic Lethal Marker for Combined PI3K and ATR/ATM Inhibitors in Colorectal Cancer.

Introduction: The aim of this study was to investigate the epigenetic regulation and underlying mechanism of NRIP3 in colorectal cancer (CRC).

Methods: Eight cell lines (SW480, SW620, DKO, LOVO, HT29, HCT116, DLD1, and RKO), 187 resected margin samples from colorectal cancer tissue, 146 cases with colorectal adenomatous polyps, and 308 colorectal cancer samples were used. Methylation-specific PCR, Western blotting, RNA interference assay, and a xenograft mouse model were used.

Pulmonary circulatory system characteristics are associated with future lung cancer risk.

Background: Most of the subjects eligible for annual low-dose computed tomography (LDCT) lung screening will not develop lung cancer for their life. It is important to identify novel biomarkers that can help identify those at risk of developing lung cancer and improve the efficiency of LDCT screening programs.

Objective: This study aims to investigate the association between the morphology of the pulmonary circulatory system (PCS) and lung cancer development using LDCT scans acquired in the screening setting.

RASSF1A promotes ATM signaling and methylation is a synthetic lethal marker for ATR inhibitors.

The mechanism of RASSF1A in DNA damage repair remains to be further clarified for applying to synthetic lethal strategy. Eight esophageal cancer cell lines, 181 cases of esophageal dysplasia and 1066 cases of primary esophageal squamous cell carcinoma (ESCC) were employed. Methylation-specific PCR, the CRISPR/Cas9 technique, immunoprecipitation assay and a xenograft mouse model were used.

Molecular neurobiology of loss: a role for basolateral amygdala extracellular matrix.

Psychological loss is a common experience that erodes well-being and negatively impacts quality of life. The molecular underpinnings of loss are poorly understood. Here, we investigate the mechanisms of loss using an environmental enrichment removal (ER) paradigm in male rats.

Correlated variability in primate superior colliculus depends on functional class.

Correlated variability in neuronal activity (spike count correlations, r) can constrain how information is read out from populations of neurons. Traditionally, r is reported as a single value summarizing a brain area. However, single values, like summary statistics, stand to obscure underlying features of the constituent elements.

Multiplex Digital Methylation-Specific PCR for Noninvasive Screening of Lung Cancer.

There remains tremendous interest in developing liquid biopsy assays for detection of cancer-specific alterations, such as mutations and DNA methylation, in cell-free DNA (cfDNA) obtained through noninvasive blood draws. However, liquid biopsy analysis is often challenging due to exceedingly low fractions of circulating tumor DNA (ctDNA), necessitating the use of extended tumor biomarker panels. While multiplexed PCR strategies provide advantages such as higher throughput, their implementation is often hindered by challenges such as primer-dimers and PCR competition.

Improving lung cancer diagnosis with cancer, fungal, and imaging biomarkers.

Objective: Indeterminate pulmonary nodules (IPNs) represent a significant diagnostic burden in health care. We aimed to compare a combination clinical prediction model (Mayo Clinic model), fungal (histoplasmosis serology), imaging (computed tomography [CT] radiomics), and cancer (high-sensitivity cytokeratin fraction 21; hsCYFRA 21-1) biomarker approach to a validated prediction model in diagnosing lung cancer.

Methods: A prospective specimen collection, retrospective blinded evaluation study was performed in 3 independent cohorts with 6- to 30-mm IPNs (n = 281).

Hippocampal glucocorticoid receptors modulate status epilepticus severity.

Status epilepticus (SE) is a life-threatening medical emergency with significant morbidity and mortality. SE is associated with a robust and sustained increase in serum glucocorticoids, reaching concentrations sufficient to activate the dense population of glucocorticoid receptors (GRs) expressed among hippocampal excitatory neurons. Glucocorticoid exposure can increase hippocampal neuron excitability; however, whether activation of hippocampal GRs during SE exacerbates seizure severity remains unknown.

Preclinical Models of Chronic Stress: Adaptation or Pathology?

The experience of prolonged stress changes how individuals interact with their environment and process interoceptive cues, with the end goal of optimizing survival and well-being in the face of a now-hostile world. The chronic stress response includes numerous changes consistent with limiting further damage to the organism, including development of passive or active behavioral strategies and metabolic adjustments to alter energy mobilization. These changes are consistent with symptoms of pathology in humans, and as a result, chronic stress has been used as a translational model for diseases such as depression.

Response to Neoadjuvant Targeted Therapy in Operable Head and Neck Cancer Confers Survival Benefit.

Purpose: Neoadjuvant targeted therapy provides a brief, preoperative window of opportunity that can be exploited to individualize cancer care based on treatment response. We investigated whether response to neoadjuvant therapy during the preoperative window confers survival benefit in patients with operable head and neck squamous cell carcinoma (HNSCC).

Patients And Methods: A pooled analysis of treatment-naïve patients with operable HNSCC enrolled in one of three clinical trials from 2009 to 2020 (NCT00779389, NCT01218048, NCT02473731).

Epigenetic silencing of JAM3 promotes esophageal cancer development by activating Wnt signaling.

Background: The role of JAM3 in different tumors is controversial. The epigenetic regulation and the mechanism of JAM3 remain to be elucidated in human esophageal cancer (EC).

Methods: Eleven EC cell lines, 49 cases of esophageal intraepithelial neoplasia (EIN) and 760 cases of primary EC samples were employed.

Genome Sequences of Two Gordonia rubripertincta Cluster DJ Bacteriophages, Pherobrine and Burley.

Pherobrine and Burley are siphoviruses infecting Gordonia rubripertincta. Pherobrine has a 60,305-bp genome with 89 predicted protein-coding genes, and Burley has a 60,111-bp genome with 90 predicted protein-coding genes. Both phages are assigned to cluster DJ, where they share 78% gene content similarity with each other.