Linking and GenBank to the National Clinical Cohort Collaborative.

Objective: This project demonstrates the feasibility of connecting medical imaging data and features, SARS-CoV-2 genome variants, with clinical data in the National Clinical Cohort Collaborative (N3C) repository to accelerate integrative research on detection, diagnosis, and treatment of COVID-19-related morbidities. The N3C curated a rich collection of aggregated and de-identified electronic health records (EHR) data of over 18 million patients, including 7.5 million COVID-positive patients, seen at hospitals across the United States.

Targeting undruggable phosphatase overcomes trastuzumab resistance by inhibiting multi-oncogenic kinases.

Aims: Resistance to targeted therapy is one of the critical obstacles in cancer management. Resistance to trastuzumab frequently develops in the treatment for HER2 cancers. The role of protein tyrosine phosphatases (PTPs) in trastuzumab resistance is not well understood.

The cytoplasmic phosphate level has a central regulatory role in the phosphate starvation response of Caulobacter crescentus.

In bacteria, the availability of environmental inorganic phosphate is typically sensed by the conserved PhoR-PhoB two-component signal transduction pathway, which uses the flux through the PstSCAB phosphate transporter as a readout of the extracellular phosphate level to control phosphate-responsive genes. While the sensing of environmental phosphate is well-investigated, the regulatory effects of cytoplasmic phosphate are unclear. Here, we disentangle the physiological and transcriptional responses of Caulobacter crescentus to changes in the environmental and cytoplasmic phosphate levels by uncoupling phosphate uptake from the activity of the PstSCAB system, using an additional, heterologously produced phosphate transporter.

An Evaluation of the Sharing Dance Public School Program on Physical Literacy.

Physical literacy (PL) is a multidimensional concept that includes the domains of movement competence, positive affect, social participation, and the confidence, motivation, and knowledge and understanding necessary for regular engagement in physical activity. The was created by Canada's National Ballet School specifically designed to promote PL through dance. The objective of this study was to evaluate the effectiveness of the program to improve PL in grade 4 to 6 children over the course of a school year.

VISTA drives macrophages towards a pro-tumoral phenotype that promotes cancer cell phagocytosis yet down-regulates T cell responses.

Background: VISTA is a well-known immune checkpoint in T cell biology, but its role in innate immunity is less established. Here, we investigated the role of VISTA on anticancer macrophage immunity, with a focus on phagocytosis, macrophage polarization and concomitant T cell activation.

Methods: Macrophages, differentiated from VISTA overexpressed THP-1 cells and cord blood CD34 cell-derived monocytes, were used in phagocytosis assay using B lymphoma target cells opsonized with Rituximab.

Novel high-yield potato protease inhibitor panels block a wide array of proteases involved in viral infection and crucial tissue damage.

Viruses critically rely on various proteases to ensure host cell entry and replication. In response to viral infection, the host will induce acute tissue inflammation pulled by granulocytes. Upon hyperactivation, neutrophil granulocytes may cause undue tissue damage through proteolytic degradation of the extracellular matrix.

Direct Functionalization of Polysaccharide-Based Xylan Phenyl Carbonate Nanoparticles with Tumor Cell Specific Antibodies.

An efficient and easy-to-use approach is presented for obtaining biocompatible polysaccharide-based nanoparticles (NP) that can act as tumor-specific drug delivery agents. Two antibodies are directly immobilized onto reactive xylan phenyl carbonate (XPC) NP; namely Cetuximab (CTX) that binds to human epidermal growth factor receptor (EGFR) and Atezolizumab (ATZ) that binds to programmed death-ligand 1 (PD-L1). High coupling efficiency (up to 100 %) are achieved without any pre-activation and no aggregation occurs during antibody immobilization.

Open and reusable deep learning for pathology with WSInfer and QuPath.

Digital pathology has seen a proliferation of deep learning models in recent years, but many models are not readily reusable. To address this challenge, we developed WSInfer: an open-source software ecosystem designed to streamline the sharing and reuse of deep learning models for digital pathology. The increased access to trained models can augment research on the diagnostic, prognostic, and predictive capabilities of digital pathology.

Basics of advanced therapy medicinal product development in academic pharma and the role of a GMP simulation unit.

Following successes of authorized chimeric antigen receptor T-cell products being commercially marketed in the United States and European Union, product development of T-cell-based cancer immunotherapy consisting of cell-based advanced therapy medicinal products (ATMPs) has gained further momentum. Due to their complex characteristics, pharmacological properties of living cell products are, in contrast to classical biological drugs such as small molecules, more difficult to define. Despite the availability of many new advanced technologies that facilitate ATMP manufacturing, translation from research-grade to clinical-grade manufacturing in accordance with Good Manufacturing Practices (cGMP) needs a thorough product development process in order to maintain the same product characteristics and activity of the therapeutic product after full-scale clinical GMP production as originally developed within a research setting.

Signal regulatory protein beta 2 is a novel positive regulator of innate anticancer immunity.

In recent years, the therapeutic (re)activation of innate anticancer immunity has gained prominence, with therapeutic blocking of the interaction of Signal Regulatory Protein (SIRP)-α with its ligand CD47 yielding complete responses in refractory and relapsed B cell lymphoma patients. SIRP-α has as crucial inhibitory role on phagocytes, with e.g.

A luminescence-based method to assess antigen presentation and antigen-specific T cell responses for screening of immunomodulatory checkpoints and therapeutics.

Investigations into the strength of antigen-specific responses is becoming increasingly relevant for decision making in early-phase research of novel immunotherapeutic approaches, including adoptive cell but also immune checkpoint inhibitor (ICI)-based therapies. In the latter, antigen-specific rapid and high throughput tools to investigate MHC/antigen-specific T cell receptor (TCR) activation haven't been implemented yet. Here, we present a simple and rapid luminescence-based approach using the human papillomavirus 16 (HPV16) E7 peptide as model antigen and E7-TCR transgenic Jurkat.

EGFR-selective activation of CD27 co-stimulatory signaling by a bispecific antibody enhances anti-tumor activity of T cells.

A higher density of tumor infiltrating lymphocytes (TILs) in the tumor microenvironment, particularly cytotoxic CD8 T cells, is associated with improved clinical outcome in various cancers. However, local inhibitory factors can suppress T cell activity and hinder anti-tumor immunity. Notably, TILs from various cancer types express the co-stimulatory Tumor Necrosis Factor receptor CD27, making it a potential target for co-stimulation and re-activation of tumor-infiltrated and tumor-reactive T cells.

Galectin-9 has non-apoptotic cytotoxic activity toward acute myeloid leukemia independent of cytarabine resistance.

Acute myeloid leukemia (AML) is a malignancy still associated with poor survival rates, among others, due to frequent occurrence of therapy-resistant relapse after standard-of-care treatment with cytarabine (AraC). AraC triggers apoptotic cell death, a type of cell death to which AML cells often become resistant. Therefore, therapeutic options that trigger an alternate type of cell death are of particular interest.

Salivary Extracellular MicroRNAs for Early Detection and Prognostication of Esophageal Cancer: A Clinical Study.

Background & Aims: Early detection of esophageal squamous cell carcinoma (ESCC) will facilitate curative treatment. We aimed to establish a microRNA (miRNA) signature derived from salivary extracellular vesicles and particles (EVPs) for early ESCC detection and prognostication.

Methods: Salivary EVP miRNA expression was profiled in a pilot cohort (n = 54) using microarray.

Notch1 promotes resistance to cisplatin by up-regulating Ecto-5'-nucleotidase (CD73) in triple-negative breast cancer cells.

Triple-negative breast cancer (TNBC) is an aggressive molecular subtype that due to lack of druggable targets is treated with chemotherapy as standard of care. However, TNBC is prone to chemoresistance and associates with poor survival. The aim of this study was to explore the molecular mechanisms of chemoresistance in TNBC.

Feasibility and Utility of a Fitbit Tracker Among Ambulatory Children and Youth With Disabilities.

Purpose: To examine the feasibility and utility of the Fitbit Charge HR to estimate physical activity among ambulatory children and youth with disabilities.

Method: Participants (4-17 y old) with disabilities were recruited and asked to wear a Fitbit for 28 days. Feasibility was assessed as the number of participants who adhered to the 28-day protocol.

Program evaluation of a virtual physical activity program for individuals with disabilities.

Introduction: Regular physical activity is important for positive health outcomes yet, most individuals do not meet physical activity guidelines. Recent studies show that one in five Canadians aged 15 or older have one or more disabilities, yet as a population, individuals with disabilities are 16%-62% less likely to meet physical activity guidelines. The COVID-19 pandemic created additional barriers to physical activity participation as lockdowns prevented in-person programming.

A cross-sectional study of Canadian children's valuation of literacies across social contexts.

Background: Children, on average, do not engage in sufficient physical activity to reap the physical, mental, and social health benefits. Understanding the value that children place on movement across social contexts, and the relative ranking of this valuation, may help us to understand and intervene on activity levels.

Method: This exploratory study examined the valuation of reading/writing, math, and movement across three social contexts (school, home, with friends) among children 6-13 years of age (= 7,845; 51.

A model industrial workhorse: Bacillus subtilis strain 168 and its genome after a quarter of a century.

The vast majority of genomic sequences are automatically annotated using various software programs. The accuracy of these annotations depends heavily on the very few manual annotation efforts that combine verified experimental data with genomic sequences from model organisms. Here, we summarize the updated functional annotation of Bacillus subtilis strain 168, a quarter century after its genome sequence was first made public.

The DNA damage response pathway regulates the expression of the immune checkpoint CD47.

CD47 is a cell surface ligand expressed on all nucleated cells. It is a unique immune checkpoint protein acting as "don't eat me" signal to prevent phagocytosis and is constitutively overexpressed in many tumors. However, the underlying mechanism(s) for CD47 overexpression is not clear.

Tumor infiltrating CD8/CD103/TIM-3-expressing lymphocytes in epithelial ovarian cancer co-express CXCL13 and associate with improved survival.

Reactivation of tumor infiltrating T lymphocytes (TILs) with immune checkpoint inhibitors or co-stimulators has proven to be an effective anti-cancer strategy for a broad range of malignancies. However, epithelial ovarian cancer (EOC) remains largely refractory to current T cell-targeting immunotherapeutics. Therefore, identification of novel immune checkpoint targets and biomarkers with prognostic value for EOC is warranted.

Guilty by association: Importers, exporters and MscS-type mechanosensitive channels encoded in biosynthetic gene clusters for the stress-protectant ectoine.

Ectoine and its derivative hydroxyectoine are widely synthesized or imported by bacteria to fend off the detrimental effects of high osmolarity on cellular hydration and growth. Genes that are connected to a particular physiological process are often found in the same genomic context. We exploited this feature in a comprehensive bioinformatical analysis of 1103 ectoine biosynthetic gene clusters from Bacteria and Archaea through which we identified 415 ect operons that colocalize with genes encoding potential osmolyte transporters.