The power of personas: Exploring an innovative model for understanding stakeholder perspectives in an oncology learning health network.

Introduction: Learning health networks (LHNs) improve clinical outcomes by applying core tenets of continuous quality improvements (QI) to reach community-defined outcomes, data-sharing, and empowered interdisciplinary teams including patients and caregivers. LHNs provide an ideal environment for the rapid adoption of evidence-based guidelines and translation of research and best practices at scale. When an LHN is established, it is critical to understand the needs of all stakeholders.

House Mice in the Atlantic Region: Genetic Signals of Their Human Transport.

Background/objectives: The colonization history of house mice reflects the maritime history of humans that passively transported them worldwide. We investigated western house mouse colonization in the Atlantic region through studies of mitochondrial D-loop DNA sequences from modern specimens.

Methods: We assembled a dataset of 758 haplotypes derived from 2765 mice from 47 countries/oceanic archipelagos (a combination of new and published data).

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.

Co-infusion of mesenchymal stromal cells to prevent GVHD after allogeneic hematopoietic cell transplantation from HLA-mismatched unrelated donors after reduced-intensity conditioning: a double-blind randomized study and literature review.

Background: Mesenchymal stromal cells (MSC) have immunomodulatory and hematopoiesis-supporting properties that could potentially benefit hematopoietic stem cell (HSC) engraftment and decrease the incidence and/or severity of graft-versus-host disease (GVHD).

Methods: Based on our previous pilot study, we established a multicenter, prospective, randomized, double-blind trial evaluating the efficacy of co-infusing third-party MSC (1.5-3 × 10/kg) versus placebo on the day of HSC transplantation (HCT) to prevent GVHD in recipients of HLA-mismatched unrelated donors after reduced-intensity conditioning.

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.

Phase 1 Study of Adjuvant Allogeneic Granulocyte-Macrophage Colony-Stimulating Factor-Transduced Pancreatic Tumor Cell Vaccine, Low-Dose Cyclophosphamide, and Stereotactic Body Radiation Therapy Followed by FOLFIRINOX in High-Risk Resected Pancreatic Ductal Adenocarcinoma.

Purpose: Local and distant progression remains common following resection of resectable pancreatic ductal adenocarcinoma (PDAC) despite adjuvant multiagent chemotherapy. We report a prospective institutional phase 1 trial incorporating adjuvant GVAX vaccine, low-dose cyclophosphamide (Cy), and stereotactic body radiation therapy (SBRT) followed by FOLFIRINOX (FFX) among patients who underwent resection of high-risk PDAC.

Patients And Methods: The study design was a modified 3+3.

NRG Oncology International Consensus Contouring Atlas on Target Volumes and Dosing Strategies for Dose-Escalated Pancreatic Cancer Radiation Therapy.

Purpose: Dose-escalated radiation therapy is increasingly used in the treatment of pancreatic cancer; however, approaches to target delineation vary widely. We present the first North American cooperative group consensus contouring atlas for dose-escalated pancreatic cancer radiation therapy.

Methods And Materials: An expert international panel comprising 15 radiation oncologists, 2 surgeons, and 1 radiologist was recruited.

3-nitropyridine analogues as novel microtubule-targeting agents.

Microtubule-targeting agents are an important class of anti-cancer drugs; their full potential is however not realized because of significant myelotoxicity and neurotoxicity. We here report 3-nitropyridine analogues as a novel group of microtubule-targeting agents with potent anti-cancer effects against a broad range of cancer types. We show that these 3-nitropyridines induce cell cycle arrest in the G2-M phase and inhibit tubulin polymerization by interacting with tubulin.

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.

Digital Light Process 3D Printing of Magnetically Aligned Liquid Crystalline Elastomer Free-forms.

Liquid crystalline elastomers (LCEs) are anisotropic soft materials capable of large dimensional changes when subjected to a stimulus. The magnitude and directionality of the stimuli-induced thermomechanical response is associated with the alignment of the LCE. Recent reports detail the preparation of LCEs by additive manufacturing (AM) techniques, predominately using direct ink write printing.

Molecular Dynamics, Dielectric Properties, and Textures of Protonated and Selectively Deuterated 4'-Pentyl-4-biphenylcarbonitrile Liquid Crystal.

Using liquid crystals in near-infrared applications suffers from effects related to processes like parasitic absorption and high sensitivity to UV-light exposure. One way of managing these disadvantages is to use deuterated systems. The combined H and H nuclear magnetic resonance relaxometry method (FFC NMR), dielectric spectroscopy (DS), optical microscopy (POM), and differential scanning calorimetry (DSC) approach was applied to investigate the influence of selective deuteration on the molecular dynamics, thermal properties, self-organization, and electric-field responsiveness to a 4'-pentyl-4-biphenylcarbonitrile (5CB) liquid crystal.

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.

Immune modulatory effects of tulathromycin, gamithromycin, and oxytetracycline in cattle.

Certain classes of antibiotics, including tetracyclines and macrolides, are known to exert immune suppressive effects in other species but the immune modulatory effects of these antibiotics have not been previously studied in cattle. To address this question, we investigated the effects of oxytetracycline, gamithromycin, and tulathromycin on T cell and macrophage responses to activation, using in vitro assays. In addition, we assessed the impact of these antibiotics on T cell responses in vivo following treatment of healthy cattle with currently recommended doses of each of the three antibiotics.

Quasi-periodic X-ray eruptions years after a nearby tidal disruption event.

Quasi-periodic eruptions (QPEs) are luminous bursts of soft X-rays from the nuclei of galaxies, repeating on timescales of hours to weeks. The mechanism behind these rare systems is uncertain, but most theories involve accretion disks around supermassive black holes (SMBHs) undergoing instabilities or interacting with a stellar object in a close orbit. It has been suggested that this disk could be created when the SMBH disrupts a passing star, implying that many QPEs should be preceded by observable tidal disruption events (TDEs).

Joint testing of rare variant burden scores using non-negative least squares.

Gene-based burden tests are a popular and powerful approach for analysis of exome-wide association studies. These approaches combine sets of variants within a gene into a single burden score that is then tested for association. Typically, a range of burden scores are calculated and tested across a range of annotation classes and frequency bins.

Outcomes with non-small cell lung cancer and brain-only metastasis.

Background: We evaluated outcomes in non-small cell lung cancer (NSCLC) patients who presented with brain-only metastatic (BOM) disease overall and by EGFR/ALK mutation status.

Methods: We analyzed clinico-demographic, treatment and survival data for all NSCLC patients who presented to our center between 2014 and 2016 with BOM as their first presentation of metastatic disease. Differences in overall survival (OS) were evaluated using log-rank tests for NSCLC wildtype (NSCLCwt NSCLC with an ALK-rearrangement/EGFR-mutation (NSCLCmut+).

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.

Ventricular-subventricular zone stem cell niche adaptations in a mouse model of post-infectious hydrocephalus.

Congenital post-infectious hydrocephalus (PIH) is a condition characterized by enlargement of the ventricular system, consequently imposing a burden on the associated stem cell niche, the ventricular-subventricular zone (V-SVZ). To investigate how the V-SVZ adapts in PIH, we developed a mouse model of influenza virus-induced PIH based on direct intracerebroventricular injection of mouse-adapted influenza virus at two distinct time points: embryonic day 16 (E16), when stem cells line the ventricle, and postnatal day 4 (P4), when an ependymal monolayer covers the ventricle surface and stem cells retain only a thin ventricle-contacting process. Global hydrocephalus with associated regions of astrogliosis along the lateral ventricle was found in 82% of the mice infected at P4.

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.

Variation in outcomes and practice patterns among patients with localized pancreatic cancer: the impact of the pancreatic cancer multidisciplinary clinic.

Introduction: Patients with localized pancreatic adenocarcinoma (PDAC) benefit from multi-modality therapy. Whether care patterns and oncologic outcomes vary if a patient was seen through a pancreatic multi-disciplinary clinic (PMDC) versus only individual specialty clinics is unclear.

Methods: Using institutional Pancreatic Cancer Registry, we identified patients with localized PDAC from 2019- 2022 who eventually underwent resection.

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.