Cardiac implantable electronic device infection.

Cardiac implantable electronic device infections (CIEDI) are an important complication of device implantation associated with significant morbidity, mortality, and cost to the healthcare system. Identifying patients at high risk of device infection is paramount to improving decision making. This includes selecting appropriate devices and implementing adjunctive infection prevention measures, such as antimicrobial envelopes.

Where public health meets public opinion: Understanding political support for fluoridation in Calgary, 2021.

Objectives: To understand variables associated with support for community water fluoridation among ordinary citizens during periods of heightened issue salience, with a particular focus on how support varies on the basis of demographic characteristics, attitudes toward public health science, and political variables such as ideology, populism, and issue salience.

Methods: Statistical analysis of individual-level data from a large-scale survey of eligible voters in the City of Calgary, Alberta in 2021, collected at the time of a community water fluoridation plebiscite.

Results: Survey data (N = 1130) reveal substantively important and statistically significant relationships with fluoridation support in each of our three analysis categories (demographics, public health expertise, and politics).

Understanding Support for Municipal Political Parties: Evidence from Canada.

The province of Ontario, Canada, has a longstanding history of non-partisanship in municipal elections. In this distinctive context, we report results on citizen attitudes toward municipal partisanship using a survey of eligible voters in Canada's most populous province. Using a mixed-methods approach, we focus on three interrelated research questions.

CRISPR-Cas9 screen of E3 ubiquitin ligases identifies TRAF2 and UHRF1 as regulators of HIV latency in primary human T cells.

Unlabelled: During HIV infection of CD4+ T cells, ubiquitin pathways are essential to viral replication and host innate immune response; however, the role of specific E3 ubiquitin ligases is not well understood. Proteomics analyses identified 116 single-subunit E3 ubiquitin ligases expressed in activated primary human CD4+ T cells. Using a CRISPR-based arrayed spreading infectivity assay, we systematically knocked out 116 E3s from activated primary CD4+ T cells and infected them with NL4-3 GFP reporter HIV-1.

Comprehensive Characterization of Commercial Reverse Osmosis Membranes through High-Temperature Cross-Flow Filtration.

Developing thermally stable reverse osmosis membranes is a potential game-changer in high-temperature water treatment. In this work, the performance of three commercial reverse osmosis membranes was evaluated with a series of high-temperature filtrations. The membranes were tested with different filtration methodologies: long-term operation, cyclic tests, controlled stepwise temperature increment, and permeability tests.

The multi-lineage transcription factor ISL1 controls cardiomyocyte cell fate through interaction with NKX2.5.

Congenital heart disease often arises from perturbations of transcription factors (TFs) that guide cardiac development. ISLET1 (ISL1) is a TF that influences early cardiac cell fate, as well as differentiation of other cell types including motor neuron progenitors (MNPs) and pancreatic islet cells. While lineage specificity of ISL1 function is likely achieved through combinatorial interactions, its essential cardiac interacting partners are unknown.

Proteomic and genetic analyses of influenza A viruses identify pan-viral host targets.

Influenza A Virus (IAV) is a recurring respiratory virus with limited availability of antiviral therapies. Understanding host proteins essential for IAV infection can identify targets for alternative host-directed therapies (HDTs). Using affinity purification-mass spectrometry and global phosphoproteomic and protein abundance analyses using three IAV strains (pH1N1, H3N2, H5N1) in three human cell types (A549, NHBE, THP-1), we map 332 IAV-human protein-protein interactions and identify 13 IAV-modulated kinases.

Conceptualizing Municipal Elections: The Case of Toronto 2018.

Since Angus Campbell and colleagues first introduced the "levels of conceptualization" (LoC) framework as a measure of political sophistication, a number of scholars have applied the approach to subsequent American national elections. In this study, we present the first application of the LoC framework to a municipal election, and focus upon the 2018 Toronto mayoral race. After describing the method and data we use to adapt the framework to this new context, we replicate previous analyses, and find that LoC is related to local voter turnout and several measures of political sophistication.

A functional map of HIV-host interactions in primary human T cells.

Human Immunodeficiency Virus (HIV) relies on host molecular machinery for replication. Systematic attempts to genetically or biochemically define these host factors have yielded hundreds of candidates, but few have been functionally validated in primary cells. Here, we target 426 genes previously implicated in the HIV lifecycle through protein interaction studies for CRISPR-Cas9-mediated knock-out in primary human CD4+ T cells in order to systematically assess their functional roles in HIV replication.

Closest to the People? Incumbency Advantage and the Personal Vote in Non-Partisan Elections.

Do incumbents dominate non-partisan elections because of an especially large personal vote? This question has important implications for understanding the causes of incumbent success and the benefits or drawbacks of non-partisan elections. This paper uses a natural experiment, combined with three original datasets, to estimate the size, persistence, and consequences of the personal vote in a large non-partisan city election. We first use individual-level survey data to show that individuals assigned quasi-randomly to a new incumbent are substantially less likely to support the incumbent.

Transcription factor protein interactomes reveal genetic determinants in heart disease.

Congenital heart disease (CHD) is present in 1% of live births, yet identification of causal mutations remains challenging. We hypothesized that genetic determinants for CHDs may lie in the protein interactomes of transcription factors whose mutations cause CHDs. Defining the interactomes of two transcription factors haplo-insufficient in CHD, GATA4 and TBX5, within human cardiac progenitors, and integrating the results with nearly 9,000 exomes from proband-parent trios revealed an enrichment of de novo missense variants associated with CHD within the interactomes.

A protein network map of head and neck cancer reveals PIK3CA mutant drug sensitivity.

We outline a framework for elucidating tumor genetic complexity through multidimensional protein-protein interaction maps and apply it to enhancing our understanding of head and neck squamous cell carcinoma. This network uncovers 771 interactions from cancer and noncancerous cell states, including WT and mutant protein isoforms. Prioritization of cancer-enriched interactions reveals a previously unidentified association of the fibroblast growth factor receptor tyrosine kinase 3 with Daple, a guanine-nucleotide exchange factor, resulting in activation of Gαi- and p21-activated protein kinase 1/2 to promote cancer cell migration.

A protein interaction landscape of breast cancer.

Cancers have been associated with a diverse array of genomic alterations. To help mechanistically understand such alterations in breast-invasive carcinoma, we applied affinity purification–mass spectrometry to delineate comprehensive biophysical interaction networks for 40 frequently altered breast cancer (BC) proteins, with and without relevant mutations, across three human breast cell lines. These networks identify cancer-specific protein-protein interactions (PPIs), interconnected and enriched for common and rare cancer mutations, that are substantially rewired by the introduction of key BC mutations.

The representativeness of neighbourhood associations in Toronto and Vancouver.

Neighbourhood associations are major players in urban politics throughout North American cities and increasingly are becoming a political force in other parts of the world. However, while there is a rich and well-developed literature on the role played by neighbourhood associations in urban politics, few studies examine whether their membership reflects the socio-demographic composition and interests of the broader public. This paper addresses this gap in the literature using survey data from voters conducted during the Vancouver and Toronto 2018 municipal elections.

Efficient generation of isogenic primary human myeloid cells using CRISPR-Cas9 ribonucleoproteins.

Genome engineering of primary human cells with CRISPR-Cas9 has revolutionized experimental and therapeutic approaches to cell biology, but human myeloid-lineage cells have remained largely genetically intractable. We present a method for the delivery of CRISPR-Cas9 ribonucleoprotein (RNP) complexes by nucleofection directly into CD14 human monocytes purified from peripheral blood, leading to high rates of precise gene knockout. These cells can be efficiently differentiated into monocyte-derived macrophages or dendritic cells.

Randomized Study of Metoclopramide Plus Diphenhydramine for Acute Posttraumatic Headache.

Objective: To determine whether IV metoclopramide 20 mg + diphenhydramine 25 mg (M + D) was more efficacious than IV placebo for acute moderate or severe posttraumatic headache in the emergency room.

Methods: We conducted this randomized, double-blind, placebo-controlled, parallel-group study in 2 urban emergency departments (EDs). Participants who experienced head trauma and presented to our EDs within 10 days with a headache fulfilling criteria for acute posttraumatic headache were included.

Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms.

The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a grave threat to public health and the global economy. SARS-CoV-2 is closely related to the more lethal but less transmissible coronaviruses SARS-CoV-1 and Middle East respiratory syndrome coronavirus (MERS-CoV). Here, we have carried out comparative viral-human protein-protein interaction and viral protein localization analyses for all three viruses.

Predicting the Transition to Chronic Pain 6 Months After an Emergency Department Visit for Acute Pain: A Prospective Cohort Study.

Background: Acute pain can transition to chronic pain, a potentially debilitating illness.

Objective: We determined how often acute pain transitions to chronic pain among patients in the emergency department (ED) and whether persistent pain 1 week after the ED visit was associated with chronic pain.

Methods: An observational cohort study conducted in two EDs.

A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Repurposing.

An outbreak of the novel coronavirus SARS-CoV-2, the causative agent of COVID-19 respiratory disease, has infected over 290,000 people since the end of 2019, killed over 12,000, and caused worldwide social and economic disruption. There are currently no antiviral drugs with proven efficacy nor are there vaccines for its prevention. Unfortunately, the scientific community has little knowledge of the molecular details of SARS-CoV-2 infection.

A SARS-CoV-2 protein interaction map reveals targets for drug repurposing.

A newly described coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the causative agent of coronavirus disease 2019 (COVID-19), has infected over 2.3 million people, led to the death of more than 160,000 individuals and caused worldwide social and economic disruption. There are no antiviral drugs with proven clinical efficacy for the treatment of COVID-19, nor are there any vaccines that prevent infection with SARS-CoV-2, and efforts to develop drugs and vaccines are hampered by the limited knowledge of the molecular details of how SARS-CoV-2 infects cells.

CRISPR-Cas9 genome engineering of primary CD4 T cells for the interrogation of HIV-host factor interactions.

CRISPR-Cas9 gene-editing strategies have revolutionized our ability to engineer the human genome for robust functional interrogation of complex biological processes. We have recently adapted this technology for use in primary human CD4 T cells to create a high-throughput platform for analyzing the role of host factors in HIV infection and pathogenesis. Briefly, CRISPR-Cas9 ribonucleoproteins (crRNPs) are synthesized in vitro and delivered to activated CD4 T cells by nucleofection.