Efficient manufacturing of CAR-T cells from whole blood: a scalable approach to reduce costs and enhance accessibility in cancer therapy.

Background: Chimeric antigen receptor T (CAR-T) cells have significantly advanced the treatment of cancers such as leukemia and lymphoma. Traditionally, T cells are collected from patients through leukapheresis, an expensive and potentially invasive process that requires specialized equipment and trained personnel. Although whole blood collections are much more technically straightforward, whole blood starting material has not been widely utilized for clinical CAR-T cell manufacturing, in part due to lack of manufacturing processes designed for use in a good manufacturing practice (GMP) environment.

Successful control of an outbreak of Panton-Valentine leucocidin positive meticillin resistant in a National Burns Unit through early detection by whole genome sequencing.

We report an outbreak of PVL-producing MRSA in the Irish National Burns Unit in 2022 involving seven patients, two staff members and two positive environmental samples. This outbreak was successfully controlled using a range of measures including staff screening, environmental screening and enhanced cleaning. The use of real time whole genome sequencing (WGS) allowed for rapid identification of relatedness and for a rapid outbreak response.

CAR-T cell expansion platforms yield distinct T cell differentiation states.

With investigators looking to expand engineered T cell therapies such as CAR-T to new tumor targets and patient populations, a variety of cell manufacturing platforms have been developed to scale manufacturing capacity using closed and/or automated systems. Such platforms are particularly useful for solid tumor targets, which typically require higher CAR-T cell doses. Although T cell phenotype and function are key attributes that often correlate with therapeutic efficacy, how manufacturing platforms influence the final CAR-T cell product is currently unknown.

Strategies to implement evidence-informed decision making at the organizational level: a rapid systematic review.

Background: Achievement of evidence-informed decision making (EIDM) requires the integration of evidence into all practice decisions by identifying and synthesizing evidence, then developing and executing plans to implement and evaluate changes to practice. This rapid systematic review synthesizes evidence for strategies for the implementation of EIDM across organizations, mapping facilitators and barriers to the COM-B (capability, opportunity, motivation, behaviour) model for behaviour change. The review was conducted to support leadership at organizations delivering public health services (health promotion, communicable disease prevention) to drive change toward evidence-informed public health.

Design and high-throughput implementation of MALDI-TOF/MS-based assays for Parkin E3 ligase activity.

Parkinson's disease (PD) is a progressive neurological disorder that manifests clinically as alterations in movement as well as multiple non-motor symptoms including but not limited to cognitive and autonomic abnormalities. Loss-of-function mutations in the gene encoding the ubiquitin E3 ligase Parkin are causal for familial and juvenile PD. Among several therapeutic approaches being explored to treat or improve the prognosis of patients with PD, the use of small molecules able to reinstate or boost Parkin activity represents a potential pharmacological treatment strategy.

What is the specific role of schools and daycares in COVID-19 transmission? A final report from a living rapid review.

Due to rapidly evolving conditions, the question of how to safely operate schools and daycares remained a top priority throughout the COVID-19 pandemic. In response to growing and changing evidence, the National Collaborating Centre for Methods and Tools in Canada maintained a living rapid review on the role of schools and daycares in COVID-19 transmission to guide evidence-informed decision making. This Review presents the final iteration of this living rapid review.

Methods to support evidence-informed decision-making in the midst of COVID-19: creation and evolution of a rapid review service from the National Collaborating Centre for Methods and Tools.

Background: The COVID-19 public health crisis has produced an immense and quickly evolving body of evidence. This research speed and volume, along with variability in quality, could overwhelm public health decision-makers striving to make timely decisions based on the best available evidence. In response to this challenge, the National Collaborating Centre for Methods and Tools developed a Rapid Evidence Service, building on internationally accepted rapid review methodologies, to address priority COVID-19 public health questions.

Exploring parity in female authorship of pharmacoepidemiology articles: A case study of the Canadian Network for Observational Drug Effect Studies and its citing articles.

Purpose: The Canadian Network for Observational Drug Effect Studies (CNODES) studies the benefits and risks of post-market drugs and evaluates its research mobilization efforts for accountability, demonstrating value, and learning. As part of these evaluation efforts, and acknowledging gender disparity in authorship across many academic disciplines, CNODES examined the relationship between gender and authorship in its own journal articles and the literature citing them.

Methods: CNODES articles (published 2012-2017) and all citing articles were identified and extracted using Scopus.

Generation of a chemical genetic model for JAK3.

Janus Kinases (JAKs) have emerged as an important drug target for the treatment of a number of immune disorders due to the central role that they play in cytokine signalling. 4 isoforms of JAKs exist in mammalian cells and the ideal isoform profile of a JAK inhibitor has been the subject of much debate. JAK3 has been proposed as an ideal target due to its expression being largely restricted to the immune system and its requirement for signalling by cytokine receptors using the common γ-chain.

High-throughput matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry-based deubiquitylating enzyme assay for drug discovery.

Deubiquitylating enzymes (DUBs) play a vital role in the ubiquitin pathway by editing or removing ubiquitin from their substrate. As breakthroughs within the ubiquitin field continue to highlight the potential of deubiquitylating enzymes as drug targets, there is increasing demand for versatile high-throughput (HT) tools for the identification of potent and selective DUB modulators. Here we present the HT adaptation of the previously published MALDI-TOF-based DUB assay method.

Correction: Using Natural Language Processing to Examine the Uptake, Content, and Readability of Media Coverage of a Pan-Canadian Drug Safety Research Project: Cross-Sectional Observational Study.

[This corrects the article DOI: 10.2196/13296.].

Using Natural Language Processing to Examine the Uptake, Content, and Readability of Media Coverage of a Pan-Canadian Drug Safety Research Project: Cross-Sectional Observational Study.

Background: Isotretinoin, for treating cystic acne, increases the risk of miscarriage and fetal abnormalities when taken during pregnancy. The Health Canada-approved product monograph for isotretinoin includes pregnancy prevention guidelines. A recent study by the Canadian Network for Observational Drug Effect Studies (CNODES) on the occurrence of pregnancy and pregnancy outcomes during isotretinoin therapy estimated poor adherence to these guidelines.

A description of a tailored knowledge translation intervention delivered by knowledge brokers within public health departments in Canada.

Background: While there is an expectation to demonstrate evidence-informed public health there is an ongoing need for capacity development. The purpose of this paper is to provide a description of a tailored knowledge translation intervention implemented by knowledge brokers (KBs), and reflections on the factors that facilitated or hindered its implementation.

Methods: The 22-month knowledge translation intervention, implemented by two KBs, sought to facilitate evidence-informed public health decision-making.

Are district nurses well placed to provide equitable end-of-life care to individuals who are homeless?

This literature review aimed to answer the focus question: are district nurses well placed to provide equitable end of life care (EOL) for homeless individuals? It focused on 10 primary research studies, from which two themes emerged and subsequently formed the basis of the discussion: (1) the difficulty in predicting disease trajectory in people who are homeless and (2) the gaps in existing systems. The main findings from these themes were a lack of education on the recognition of the dying and a general lack of knowledge of the complex challenges faced by and health needs of homeless people, which cause stigma from both the general public and health professionals towards these marginalised individuals. Further, there is certainly a lack of suitable places to deliver palliative and EOL care for people who are homeless.

Building a framework for the evaluation of knowledge translation for the Canadian Network for Observational Drug Effect Studies.

Purpose: The Canadian Network for Observational Drug Effect Studies (CNODES), a network of pharmacoepidemiologists and other researchers from seven provincial sites, provides evidence on the benefits and risks of drugs used by Canadians. The Knowledge Translation Team, one of CNODES' four main teams, evaluates the impact of its efforts using an iterative and emergent approach. This article shares key lessons from early evaluation phases, including identifying stakeholders and their evaluation needs, choosing evaluation theories and approaches, and developing evaluation questions, designs, and methods appropriate for the CNODES context.

Impact of an organization-wide knowledge translation strategy to support evidence-informed public health decision making.

Background: The public health sector is moving toward adopting evidence-informed decision making into practice, but effort is still required to effectively develop capacity and promote contextual factors that advance and sustain it. This paper describes the impact of an organization-wide knowledge translation intervention delivered by knowledge brokers on evidence-informed decision making knowledge, skills and behaviour.

Methods: A case study design was implemented with the intervention and data collection tailored to the unique needs of each case (health department).

Measuring the impact of pharmacoepidemiologic research using altmetrics: A case study of a CNODES drug-safety article.

Purpose: To provide an overview of altmetrics, including their potential benefits and limitations, how they may be obtained, and their role in assessing pharmacoepidemiologic research impact.

Methods: Our review was informed by compiling relevant literature identified through searching multiple health research databases (PubMed, Embase, and CIHNAHL) and grey literature sources (websites, blogs, and reports). We demonstrate how pharmacoepidemiologists, in particular, may use altmetrics to understand scholarly impact and knowledge translation by providing a case study of a drug-safety study conducted by the Canadian Network of Observational Drug Effect Studies.

Temporal Consistency and Movement Effort of Repetitive Reaching During Continuation in Children and Adults.

The ability to match one's movements to an external beat and maintain that rhythm in the absence of the beat suggests sophisticated, well-developed neural control. Children (aged 5-10 years) were compared with adults (aged 18-30 years) during a repetitive reaching task to determine development of this control. Children as young as 5 years exhibited this control.

Tools to support evidence-informed public health decision making.

Background: Public health professionals are increasingly expected to engage in evidence-informed decision making to inform practice and policy decisions. Evidence-informed decision making involves the use of research evidence along with expertise, existing public health resources, knowledge about community health issues, the local context and community, and the political climate. The National Collaborating Centre for Methods and Tools has identified a seven step process for evidence-informed decision making.

Knowledge brokering in public health: a tale of two studies.

Objectives: A Knowledge Broker is one approach for facilitating the integration of evidence-informed decision making in public health practice. In this paper, the findings from two studies investigating a Knowledge Broker intervention as a means of enhancing capacity for evidence-informed decision making are presented. Contextual factors that facilitate this strategy are also identified.

Kinome-wide selectivity profiling of ATP-competitive mammalian target of rapamycin (mTOR) inhibitors and characterization of their binding kinetics.

An intensive recent effort to develop ATP-competitive mTOR inhibitors has resulted in several potent and selective molecules such as Torin1, PP242, KU63794, and WYE354. These inhibitors are being widely used as pharmacological probes of mTOR-dependent biology. To determine the potency and specificity of these agents, we have undertaken a systematic kinome-wide effort to profile their selectivity and potency using chemical proteomics and assays for enzymatic activity, protein binding, and disruption of cellular signaling.