Toronto Public Health

There is now clear evidence, from a variety of studies, that galactic bars contribute to and/or accelerate processes which quench galaxies. However, bars have a variety of strengths and pattern speeds, and previous work has suggested that slow and strong bars impact their hosts the most. In this paper, we continue to investigate the impact of bar strength and bar speed on host galaxy evolution in a sample of barred galaxies identified via classifications from Galaxy Zoo. We perform a comprehensive assessment of star-formation tracers spanning a variety of timescales, based on spatially resolved spectroscopic information from the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey. Specifically, we examine the radial distributions of EW[Halpha], HdeltaA, Hbeta, and Dn4000; spectral data that trace star-formation on current, intermediate, and much longer timescales. We investigate how these star-formation tracers vary with respect to each other in diagnostic evolutionary planes for eight categories of barred galaxies (combinations of star forming or quenching; strong and weak; fast and slow). We continue to find that slow-strong bars drive the quenching of their hosts the most by triggering active star-formation throughout the barred region; however, we note some additional complexity: we observe that stronger bars boost star-formation at the bar centre while slower bars have increased star-formation along the bar. This work adds to the growing evidence that galactic bars have both global and local impacts on their host galaxies.

Abstract Cathodic protection (CP) systems are vital to mitigating external corrosion on buried pipelines. However, a critical gap remains in the frequency and coverage of pipe-to-soil (P/S) potential measurements, which are central to compliance and CP performance assessment. While remote monitoring units (RMUs) have successfully automated rectifier and bond monitoring, the industry has yet to fully embrace year-round, remote P/S potential data acquisition due to concerns over reference electrode longevity and accuracy. This project focuses on a North American pipeline operator's experience in evaluating the long-term performance of permanent reference electrodes installed alongside RMUs, which is a subset of a group of operators that have deployed similar systems. Each site includes seven or eight reference electrodes with various chemistries and manufacturers to evaluate variability and drift. The RMU’s capabilities enable high-resolution monitoring, and ON/OFF cycling to approximate interrupted readings. The study also integrates traditional manual surveys, soil sampling and analysis, and electrode placement benchmarking to calibrate remote readings. Data is aggregated through the Mobiltex CorView platform to allow anonymized analysis and comparison across environments, installation practices, and product types. The intent is that this methodology and findings contribute to broader regulatory acceptance of permanent reference electrodes for compliance-grade monitoring. Preliminary insights suggest measurable trends in stability and accuracy among electrode types and provide early validation for their use in continuous monitoring frameworks. This paper will share lessons learned through the installation process and data trends observed over the first two years of operation at one location, establishing a platform for future follow-on analyses, and opening the discussion for recommendations across the industry.

Abstract Background Inflammatory injury to the intestine triggers a reprogramming of the intestinal epithelium to a fetal-like state that drives rapid restoration of the epithelial barrier. Although the intestinal microbiota is a key modulator of inflammation, its role in influencing epithelial fetal-like stem cell reprogramming and consequent restitution remains unclear. Aims We aim to identify how host-microbiota interactions regulate intestinal epithelial restitution following damage. Our hypothesis is that intestinal epithelial NOD2 signaling accelerates epithelial fetal-like stem cell reprogramming to promote tissue repair following intestinal injury. Methods Mice were irradiated (IR, 12Gγ) to induce synchronous inflammatory injury to small intestine. Intestinal restitution kinetics were assessed transcriptionally (scRNA-Seq, qPCR), histologically, and by flow cytometry. In vivo observations were supported with in vitro small intestinal organoid models of inflammatory injury. Results We demonstrated that the intestinal microbiota accelerated epithelial restitution through an amplified inflammation-associated repair response that promoted the emergence of fetal-like intestinal epithelial cells (IECs) expressing Ly6a and Clu. NOD2, a sensor of bacterial peptidoglycan, whose gene has mutations associated with CD, was expressed in fetal-like IECs following injury. In ileal organoids, NOD2 stimulation potentiated an inflammatory gene signature associated with interferon (IFN) signaling, which was concomitant with enterocyte recovery. Deficiency in NOD2 exacerbated epithelial apoptosis following IR injury, while epithelial-specific NOD2 signaling increased the emergence of fetal-like IECs and consequently, increased epithelial proliferation. Conclusions These findings identify a critical role for NOD2-dependent microbial detection in regulating the expansion of fetal-like IECs following injury, which contributes to the protective effect of this microbial sensor in resolving intestinal inflammation. Funding Agencies CIHR

The semi-random hypergraph process is a natural generalisation of the semi-random graph process, which can be thought of as a one player game. For fixed $r < s$, starting with an empty hypergraph on $n$ vertices, in each round a set of $r$ vertices $U$ is presented to the player independently and uniformly at random. The player then selects a set of $s-r$ vertices $V$ and adds the hyperedge $U \cup V$ to the $s$-uniform hypergraph. For a fixed (monotone) increasing graph property, the player's objective is to force the graph to satisfy this property with high probability in as few rounds as possible. We focus on the case where the player's objective is to construct a subgraph isomorphic to an arbitrary, fixed hypergraph $H$. In the case $r=1$ the threshold for the number of rounds required was already known in terms of the degeneracy of $H$. In the case $2 \le r < s$, we give upper and lower bounds on this threshold for general $H$, and find further improved upper bounds for cliques in particular. We identify cases where the upper and lower bounds match. We also demonstrate that the lower bounds are not always tight by finding exact thresholds for various paths and cycles.

Intratumoural heterogeneity remains one of the most formidable challenges in oncology, driving treatment resistance, disease progression, and poor patient outcomes. To uncover the cellular programs that define tumour composition and diversity, we interrogated over 3.6 million single cells derived from more than 1,000 primary and metastatic tumours spanning 14 diverse cancer types. Through the identification and quantification of coordinated gene expression programs, we delineated heterogeneous cancer cell states, exhibiting unique and clinically significant associations with patient survival. Integration with high-resolution spatial transcriptomics identified prognostic cancer cell states marked by aggressive transcriptional programs, co-localizing with invasive histological features and significantly enriched in metastatic settings. Functional drug perturbation screening uncovered drug vulnerabilities specific to distinct cancer cell states, supporting both direct targeting strategies and therapeutic reprogramming toward less aggressive cellular phenotypes. Collectively, this study offers novel insights into the relationship between intratumoural transcriptional heterogeneity, spatial organization, clinical outcomes, and therapeutic vulnerabilities.

BackgroundTwo decades of research have highlighted persistent income-related health inequities in Canada across municipal, provincial, and national levels. While there is broad consensus among researchers, advocates, and health professionals that social determinants are the primary drivers of health, the empirical foundation supporting this remains relatively limited. A current renaissance in health system data access offers an opportunity to assess the multilevel impact of social factors on health inequalities, yet this potential remains underused.ObjectiveThis project aims to examine how social, economic, and political conditions shape health inequalities and investigate how structural and intermediate determinants explain disparities across national, provincial, city, neighborhood, and individual levels.MethodsWe will create the Canadian Social Determinants Urban Laboratory (CSDUL), a multilevel, longitudinal, virtual data environment that integrates 15 existing databases from Statistics Canada, the Canadian Institute for Health Information, the Canadian Urban Environmental Health Research Consortium, and DMTI Spatial. Guided by the World Health Organization social determinants of health framework, CSDUL will initially cover 2011 to 2015 due to data completeness and expand as additional years become available. CSDUL builds on Statistics Canada’s Canadian Population Health Survey and will link survey data to administrative and health records, including hospital discharges, ambulatory care, mortality, cancer registries, and longitudinal tax files. Area-level indicators will be added using historical postal codes and geospatial boundaries. Organized through a hub-and-node model, CSDUL includes a central hub and 5 research nodes. We will develop and validate area-based indicators to study social determinants at micro (individual), meso (neighborhood, city, and province), and macro (national) levels. A core deliverable is to assess the strengths and limitations of survey and administrative data for health research and derive variables accordingly. After developing CSDUL, we will replicate World Health Organization Regional Office for Europe income-related health inequality analysis for urban Canada and analyze the impact of social determinants on outcomes. We will apply a 2-fold Oaxaca-Blinder decomposition between the lowest and highest urban income quintiles. A major strength of CSDUL is its capacity to analyze how diverse determinants shape health across subgroups (eg, gender), identifying key drivers of health outcomes.ResultsThe indicators to be used in CSDUL are being developed and validated by the contributing nodes. In collaboration with node 3, we are constructing measures of social capital using DMTI Spatial Points of Interest data. A prototype version of CSDUL incorporating a limited set of indicators has been developed in Statistics Canada’s Research Data Centre. We anticipate receiving the finalized indicators from the nodes by August 2025 to September 2025 and aim to complete the decomposition analysis by December 2025.ConclusionsMultisectoral interventions are most effective when they are customized to meet the unique needs of specific subpopulations using robust and multilevel data sources such as CSDUL.International Registered Report Identifier (IRRID)DERR1-10.2196/71929

Abstract INTRODUCTION Recurrent IDH-mutant gliomas pose a significant therapeutic challenge, with limited treatment options following progression after standard therapy. Combining PARP inhibitors with immune checkpoint blockade has been proposed as a synergistic strategy in IDH-mutant high-grade gliomas, leveraging vulnerabilities in homologous recombination repair and increased PD-L1 expression following PARP inhibition. OBJECTIVE This phase II trial (NCT03991832) evaluated the combination of the PARP inhibitor olaparib and the PD-L1 inhibitor durvalumab in patients with recurrent IDH-mutant glioma. We also investigated the potential of the plasma tumor methylome as a non-invasive biomarker of treatment response. METHODS Twenty-nine patients (median age 40.5 years; 41% female) were enrolled between January 2020 and February 2023. All patients received olaparib (300 mg twice daily) and durvalumab (1,500 mg IV every four weeks) until radiographic or clinical progression. Plasma samples were collected at baseline and monthly, and cell-free methylated DNA immunoprecipitation sequencing (cfMeDIP-seq) was performed. RESULTS The objective response rate was 10%, and median overall survival was 9.3 months. Longitudinal cfMeDIP-seq profiling enabled development of a circulating methylome classifier that accurately distinguished responders from non-responders. Integration with matched tumor transcriptomic and methylation data revealed enrichment of immune and DNA repair pathways in responders. Whole-exome sequencing identified no consistent mutational correlates. Spatial transcriptomic analysis demonstrated a more interactive, immune-rich tumor microenvironment and reduced malignant cell state diversity in responders. CONCLUSION This study supports the safety of combined PARP and PD-L1 blockade in recurrent IDH-mutant glioma and highlights the plasma methylome as a promising non-invasive biomarker of therapeutic response.