Prognostic significance of serum complement activation, neutrophil extracellular traps and extracellular DNA in newly diagnosed epithelial ovarian cancer.

Purpose: We observed that the tumor microenvironment (TME) in metastatic epithelial ovarian cancer (EOC) and in other solid tumors can reprogram normal neutrophils to acquire a complement-dependent suppressor phenotype characterized by inhibition of stimulated T cell activation. This study aims to evaluate whether serum markers of neutrophil activation and complement at diagnosis of EOC would be associated with clinical outcomes.

Experimental Design: We conducted a two-center prospective study of patients with newly diagnosed EOC (N = 188).

Cost-Effectiveness of Breast Cancer Screening Using Digital Mammography in Canada.

Importance: Evolving breast cancer treatments have led to improved outcomes but carry a substantial financial burden. The association of treatment costs with the cost-effectiveness of screening mammography is unknown.

Objective: To determine the cost-effectiveness of population-based breast cancer screening in the context of current treatment standards.

Screening for breast cancer: a systematic review update to inform the Canadian Task Force on Preventive Health Care guideline.

Objective: This systematic review update synthesized recent evidence on the benefits and harms of breast cancer screening in women aged ≥ 40 years and aims to inform the Canadian Task Force on Preventive Health Care's (CTFPHC) guideline update.

Methods: We searched Ovid MEDLINE® ALL, Embase Classic + Embase and Cochrane Central Register of Controlled Trials to update our searches to July 8, 2023. Search results for observational studies were limited to publication dates from 2014 to capture more relevant studies.

A Modified Bleaching Method for Multiplex Immunofluorescence Staining of FFPE Tissue Sections.

Multiplex immunofluorescence (mIF) staining plays an important role in profiling biomarkers and allows investigation of co-relationships between multiple biomarkers in the same tissue section. The Cell DIVE mIF platform (Leica Microsystems) employs an alkaline solution of hydrogen peroxide as a fluorophore inactivation reagent in the sequential staining, imaging, and bleaching protocol for use on FFPE sections. Suboptimal bleaching efficiency, degradation of tissue structure, and loss of antigen immunogenicity occasionally are encountered with the standard bleaching process.

Signal amplification by cyclic extension enables high-sensitivity single-cell mass cytometry.

Mass cytometry uses metal-isotope-tagged antibodies to label targets of interest, which enables simultaneous measurements of ~50 proteins or protein modifications in millions of single cells, but its sensitivity is limited. Here, we present a signal amplification technology, termed Amplification by Cyclic Extension (ACE), implementing thermal-cycling-based DNA in situ concatenation in combination with 3-cyanovinylcarbazole phosphoramidite-based DNA crosslinking to enable signal amplification simultaneously on >30 protein epitopes. We demonstrate the utility of ACE in low-abundance protein quantification with suspension mass cytometry to characterize molecular reprogramming during the epithelial-to-mesenchymal transition as well as the mesenchymal-to-epithelial transition.

Onvansertib treatment overcomes olaparib resistance in high-grade ovarian carcinomas.

Occurrence of resistance to olaparib, a poly(ADP-ribose) polymerase (PARP) inhibitor (PARPi) approved in ovarian carcinoma, has already been shown in clinical settings. Identifying combination treatments to sensitize tumor cells and/or overcome resistance to olaparib is critical. Polo-like kinase 1 (PLK1), a master regulator of mitosis, is also involved in the DNA damage response promoting homologous recombination (HR)-mediated DNA repair and in the recovery from the G2/M checkpoint.

Primary care physicians' perceptions of artificial intelligence systems in the care of adolescents' mental health.

Background: Given that mental health problems in adolescence may have lifelong impacts, the role of primary care physicians (PCPs) in identifying and managing these issues is important. Artificial Intelligence (AI) may offer solutions to the current challenges involved in mental health care. We therefore explored PCPs' challenges in addressing adolescents' mental health, along with their attitudes towards using AI to assist them in their tasks.

The intrinsic substrate specificity of the human tyrosine kinome.

Phosphorylation of proteins on tyrosine (Tyr) residues evolved in metazoan organisms as a mechanism of coordinating tissue growth. Multicellular eukaryotes typically have more than 50 distinct protein Tyr kinases that catalyse the phosphorylation of thousands of Tyr residues throughout the proteome. How a given Tyr kinase can phosphorylate a specific subset of proteins at unique Tyr sites is only partially understood.

Neutrophil-Mediated Inflammatory Plasminogen Degradation, Rather Than High Plasminogen-Activator Inhibitor-1, May Underly Failures and Inefficiencies of Intrapleural Fibrinolysis.

Background: Complex pleural space infections often require treatment with multiple doses of intrapleural tissue plasminogen activator (tPA) and deoxyribonuclease, with treatment failure frequently necessitating surgery. Pleural infections are rich in neutrophils, and neutrophil elastase degrades plasminogen, the target substrate of tPA, that is required to generate fibrinolysis. We hypothesized that pleural fluid from patients with pleural space infection would show high elastase activity, evidence of inflammatory plasminogen degradation, and low fibrinolytic potential in response to tPA that could be rescued with plasminogen supplementation.

Socially Assistive Robots for patients with Alzheimer's Disease: A scoping review.

Background: The most common form of dementia, Alzheimer's Disease (AD), is challenging for both those affected as well as for their care providers, and caregivers. Socially assistive robots (SARs) offer promising supportive care to assist in the complex management associated with AD.

Objectives: To conduct a scoping review of published articles that proposed, discussed, developed or tested SAR for interacting with AD patients.

Self-care interventions to assist family physicians with mental health care of older patients during the COVID-19 pandemic: Feasibility, acceptability, and outcomes of a pilot randomized controlled trial.

Background: The COVID-19 pandemic has required family physicians to rapidly address increasing mental health problems with limited resources. Vulnerable home-based seniors with chronic physical conditions and commonly undermanaged symptoms of anxiety and depression were recruited in this pilot study to compare two brief self-care intervention strategies for the management of symptoms of depression and/or anxiety.

Methods: We conducted a pilot RCT to compare two tele-health strategies to address mental health symptoms either with 1) validated CBT self-care tools plus up to three telephone calls from a trained lay coach vs.

Activation of GPR3-β-arrestin2-PKM2 pathway in Kupffer cells stimulates glycolysis and inhibits obesity and liver pathogenesis.

Kupffer cells are liver resident macrophages and play critical role in fatty liver disease, yet the underlying mechanisms remain unclear. Here, we show that activation of G-protein coupled receptor 3 (GPR3) in Kupffer cells stimulates glycolysis and protects mice from obesity and fatty liver disease. GPR3 activation induces a rapid increase in glycolysis via formation of complexes between β-arrestin2 and key glycolytic enzymes as well as sustained increase in glycolysis through transcription of glycolytic genes.

Effect of Breast Screening Regimen on Breast Cancer Outcomes: A Modeling Study.

Guidelines vary for the age at which to begin breast cancer screening and the interval between examinations. A validated computer model was used to compare estimated outcomes between various screening regimens. The OncoSim-Breast microsimulation model (Canadian Partnership Against Cancer) was used to simulate a cohort of 1.

Quality control for digital tomosynthesis in the ECOG-ACRIN EA1151 TMIST trial.

Background: The Tomosynthesis Mammography Imaging Screening Trial (TMIST), EA1151 conducted by the Eastern Cooperative Oncology Group (ECOG)/American College of Radiology Imaging Network (ACRIN) is a randomized clinical trial designed to assess the effectiveness for breast cancer screening of digital breast tomosynthesis (TM) compared to digital mammography (DM). Equipment from multiple vendors is being used in the study.

Purpose: For the findings of the study to be valid and capture the true capacities of the two technology types, it is important that all equipment is operated within appropriate parameters with regard to image quality and dose.

Audit of data from examination image headers collected for quality assurance in the ECOG-ACRIN EA1151 tomosynthesis mammographic imaging screening trial (TMIST).

Purpose: A comprehensive, centrally-monitored physics quality control (QC) program was developed for the Tomosynthesis Imaging Screening Trial (TMIST), a randomized controlled trial of digital breast tomosynthesis (TM) versus digital mammography (DM) for cancer screening. As part of the program, in addition to a set of phantom-based tests, de-identified data on image acquisition and processing parameters were captured from the DICOM headers of all individual patient images in the trial. These data were analyzed to assess the potential usefulness of header data from digital mammograms and tomosynthesis images of patients for quality assurance in breast imaging.

Adaptation and outcomes of a lay-guided mental health self-care model: Results of six trials.

Objective: To synthesize results of six controlled trials of self-care interventions for depression and/or anxiety, focusing on five trials in which lay guidance was compared to self-directed use of the same self-care tools.

Methods: The trials were conducted in Canada in different target populations. Self-care tools were adapted to each population.

Correction for Self-Selection in Breast Cancer Screening. Comment on Dibden et al. Worldwide Review and Meta-Analysis of Cohort Studies Measuring the Effect of Mammography Screening Programmes on Incidence-Based Breast Cancer Mortality. 2020, , 976.

Observational studies of cancer screening are subject to bias associated with the self-selection of screening participants for whom the underlying probability of cancer death may be different from those who do not participate. Dibden et al. reviewed data on mortality reduction from 27 observational studies of mammography screening expressed in terms of relative risk for women who were screened versus not screened.

Capturing the True Cost of Breast Cancer Treatment: Molecular Subtype and Stage-Specific per-Case Activity-Based Costing.

Background: Breast cancer (BC) treatment is rapidly evolving with new and costly therapeutics. Existing costing models have a limited ability to capture current treatment costs. We used an Activity-Based Costing (ABC) method to determine a per-case cost for BC treatment by stage and molecular subtype.

Early Immune Changes Support Signet Ring Cell Dormancy in CDH1-Driven Hereditary Diffuse Gastric Carcinogenesis.

Unlabelled: Stage IA gastric adenocarcinoma, characterized by foci of intramucosal signet ring cells (SRC), is found in nearly all asymptomatic patients with germline pathogenic CDH1 variants and hereditary diffuse gastric cancer syndrome (HDGC). The molecular steps involved in initiating malignant transformation and promoting SRC dormancy in HDGC are unknown. Here, whole-exome bulk RNA sequencing (RNA-seq) of SRCs and adjacent non-SRC epithelium (NEP) was performed on laser-capture microdissected (LCM) regions of interest found in risk-reducing total gastrectomy specimens from patients with HDGC (Clinicaltrials.

Development of a transdiagnostic digital interactive application for eating disorders: psychometric properties, satisfaction, and perceptions on implementation in clinical practice.

Background: Given limited availability of informed treatments for people affected by eating disorders (EDs), there has been increasing interest in developing self-administered, technology-based ED interventions. However, many available interventions are limited to a specific ED diagnosis or assume that participants are ready to change. We developed a digital self-help application (called ASTrA) that was explicitly designed to be transdiagnostic and to help increase motivation for change.

Cytomegalovirus durably primes neutrophil oxidative burst.

Cytomegalovirus (CMV) is a ubiquitous herpes virus that infects most humans, thereafter persisting lifelong in tissues of the host. It is a known pathogen in immunosuppressed patients, but its impact on immunocompetent hosts remains less understood. Recent data have shown that CMV leaves a significant and long-lasting imprint in host immunity that may confer some protection against subsequent bacterial infection.

Examination of fully automated mammographic density measures using LIBRA and breast cancer risk in a cohort of 21,000 non-Hispanic white women.

Background: Breast density is strongly associated with breast cancer risk. Fully automated quantitative density assessment methods have recently been developed that could facilitate large-scale studies, although data on associations with long-term breast cancer risk are limited. We examined LIBRA assessments and breast cancer risk and compared results to prior assessments using Cumulus, an established computer-assisted method requiring manual thresholding.