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Many cities are currently planning and building new large-scale active transport networks to achieve a wide array of environmental, economic, and social equity goals. This is often combined with developing public campaigns to increase public awareness of their plans and introduced infrastructure to build a culture that celebrates and supports using them. While several studies explored the impacts of active transport infrastructure on users perception and travel behaviour, very little has been done to explore the factors associated with people’s awareness of such infrastructure at an early stage of their introduction. Accordingly, this study examines the factors affecting people’s likelihood of being aware of a new flagship cycling network in Montréal known as Réseau Express Vélo (REV), while understanding equity of awareness across gender identities. To achieve this goal, the study uses summary statistics and weighted multilevel logistic regressions to analyze data collected from a large-scale survey. The results of the paper show that various socioeconomic factors including age, ethnicity, income, language, as well as individuals’ travel behaviour and lifestyle are associated with being familiar with such a large bike network. Significant differences between women and men can also be observed, in which women are less likely to be aware of REV. Younger women in their 20 s tend to know much less about the project in comparison with men in the same age group. Women who identify as non-white only and used English to complete the survey are the group with the lowest probability of being aware of the project. Findings from this research unmask key aspects related to the likelihood of being aware of a new large-scale cycling network, offering important insights to transport planners, policy makers, and researchers.

Asian American school leaders in K-20 schools and universities remain underrepresented in the field. As such, it is imperative that we study the experience of Asian American women (AAW) leaders to understand the racialized experiences of this specific group, particularly when they enact innovative leadership. We, the authors, argue that behind these racialized experiences are white emotionalities that are imposed upon AAW in uniquely raced and gendered ways. This conceptual paper addresses the following question: “how do white emotionalities thwart the innovative social justice efforts of female Asian American leaders in K-20 education?” To answer, we drew on the “kuwentos” of two AAW school leaders: one from K-12 administration and one from higher education administration. Kuwentos is derived from the Pinay concept of storytelling; thus, it is a befitting methodology to explicate these two women’s particular racial experiences. To critically interpret invisible operations of whiteness, we employed critical race hermeneutics (CRH) to reveal what is often left to the unconscious when examining the impact of whiteness on people of Color. To reveal how these seemingly natural presumptions are not so natural, CRH must be used. In drawing attention to how white emotionalities impact the innovative leadership of AAWs, the authors first use kuwentos to tell our own stories of experiencing white emotionalities. We then analyze these kuwentos through a CRH lens and end with implications and recommendations to positively impact AAW educational leaders.

The eicosanoid lipoxin A4 (LXA4) has emerging roles in lymphocyte-driven diseases. We identified reduced LXA4 levels in posterior segment uveitis patients and investigated the role of LXA4 in the pathogenesis of experimental autoimmune uveitis (EAU). Immunization for EAU with a retinal self-antigen caused selective downregulation of LXA4 in lymph nodes draining the site of immunization, while at the same time amplifying LXA4 in the inflamed target tissue. T cell effector function, migration and glycolytic responses were amplified in LXA4-deficient mice, which correlated with more severe pathology, whereas LXA4 treatment attenuated disease. In vivo deletion or supplementation of LXA4 identified modulation of CC-chemokine receptor 7 (CCR7) and sphingosine 1- phosphate receptor-1 (S1PR1) expression and glucose metabolism in CD4+ T cells as potential mechanisms for LXA4 regulation of T cell effector function and trafficking. Our results demonstrate the intrinsic lymph node LXA4 pathway as a significant checkpoint in the development and severity of adaptive immunity.

Background: There has been a push toward implementation of electronic health records (EHRs) in federally-funded hospitals under the current policies initiated by the Indian government, with a lack of evidence supporting their adoption. We analyzed data from the American College of Cardiology’s PINNACLE (Practice Innovation and Clinical Excellence) India Quality Improvement Program (PIQIP) to evaluate the association between EHR use and quality of cardiovascular disease care in India. Methods and Results: Between 2011–2016, we collected data on performance measures for patients with coronary artery disease (CAD), heart failure (HF) and atrial fibrillation (AF) among 17 participating practices in PIQIP. There were 19,035 patients with CAD, 9,373 patients with HF, and 1,127 patients with AF. Documentation of co-morbidity burden in patients with CAD was lower among practices with EHR—hypertension (49.8% vs. 52.1%, p = 0.003), diabetes (34.9% vs. 38.3%, p

Chronic itch remains a highly prevalent disorder with limited treatment options. Most chronic itch diseases are thought to be driven by both the nervous and immune systems, but the fundamental molecular and cellular interactions that trigger the development of itch and the acute-to-chronic itch transition remain unknown. Here, we show that skin-infiltrating neutrophils are key initiators of itch in atopic dermatitis, the most prevalent chronic itch disorder. Neutrophil depletion significantly attenuated itch-evoked scratching in a mouse model of atopic dermatitis. Neutrophils were also required for several key hallmarks of chronic itch, including skin hyperinnervation, enhanced expression of itch signaling molecules, and upregulation of inflammatory cytokines, activity-induced genes, and markers of neuropathic itch. Finally, we demonstrate that neutrophils are required for induction of CXCL10, a ligand of the CXCR3 receptor that promotes itch via activation of sensory neurons, and we find that that CXCR3 antagonism attenuates chronic itch.

RNAi has potential for therapeutically downregulating the expression of dominantly inherited genes in a variety of human genetic disorders. Here we used the ROSA26 mouse, which constitutively expresses the bacterial lacZ gene in tissues body wide, as a model to test the ability to downregulate gene expression in striated muscles. Recombinant adeno-associated viral vectors (rAAVs) were generated that express short hairpin RNAs (shRNAs) able to target the lacZ mRNA. Systemic delivery of these rAAV6 vectors led to a decrease of β-galactosidase expression of 30-50-fold in the striated muscles of ROSA26 mice. However, high doses of vectors expressing 21 nucleotide shRNA sequences were associated with significant toxicity in both liver and cardiac muscle. This toxicity was reduced in cardiac muscle using lower vector doses. Furthermore, improved knockdown in the absence of toxicity was obtained by using a shorter (19 nucleotide) shRNA guide sequence. These results support the possibility of using rAAV vectors to deliver RNAi sequences systemically to treat dominantly inherited disorders of striated muscle.

Asian American school leaders in K-20 schools and universities remain underrepresented in the field. As such, it is imperative that we study the experience of Asian American women (AAW) leaders to understand the racialized experiences of this specific group, particularly when they enact innovative leadership. We, the authors, argue that behind these racialized experiences are white emotionalities that are imposed upon AAW in uniquely raced and gendered ways. This conceptual paper addresses the following question: "how do white emotionalities thwart the innovative social justice efforts of female Asian American leaders in K-20 education?" To answer, we drew on the "kuwentos" of two AAW school leaders: one from K-12 administration and one from higher education administration. Kuwentos is derived from the Pinay concept of storytelling; thus, it is a befitting methodology to explicate these two women's particular racial experiences. To critically interpret invisible operations of whiteness, we employed critical race hermeneutics (CRH) to reveal what is often left to the unconscious when examining the impact of whiteness on people of Color. To reveal how these seemingly natural presumptions are not so natural, CRH must be used. In drawing attention to how white emotionalities impact the innovative leadership of AAWs, the authors first use kuwentos to tell our own stories of experiencing white emotionalities. We then analyze these kuwentos through a CRH lens and end with implications and recommendations to positively impact AAW educational leaders. [ABSTRACT FROM AUTHOR]

Abstract Extracellular vesicles (EVs) are associated with intercellular communications, immune responses, viral pathogenicity, cardiovascular diseases, neurological disorders, and cancer progression. EVs deliver proteins, metabolites, and nucleic acids into recipient cells to effectively alter their physiological and biological response. During their transportation from the donor to the recipient cell EVs face differential ionic concentrations, which can be detrimental to their integrity and impact their cargo content. EVs are known to possess ion channels and transporters in their membrane but neither the function nor the role of these channels in EVs is known. In this study, we discover a functional calcium-activated large-conductance potassium channel (BKCa) in the membrane of EVs. Furthermore, we establish that BKCa is essential for the structural and functional integrity of EVs. Together, these findings establish the critical role of ion channels such as BKCa in functioning as gatekeepers and maintaining EV-mediated signaling.

The aim of this study was to evaluate soil properties and Eragrostis tef (teff) growth on Technosols produced from coarse and fine coal wastes from Moatize Mine, Mozambique. The experiment was performed in triplicate in 30 L containers filled with different substrate conditions, composed of fine coal waste, coarse coal waste, agricultural soil, and sewage sludge as an organic matter source. The soil analyses included bulk density, available water capacity, permeability, and fertility. Plant growth was monitored for biomass production and plant tissue composition. All the substrates presented a good available water capacity and a proper drainage condition. Regarding soil fertility, there were shortages of potassium and boron in the substrates composed exclusively of coal wastes, which was reflected in the composition of the plant tissue. Even so, plant growth was statistically equivalent to the control in all conditions, except for the substrate produced exclusively with fine coal waste and sewage sludge, which presented a better performance. Technosols are an alternative for reducing the final mine waste volume, and Eragrostis tef is used as a means for land use after the mining process, with social gains, and as a tool in an ecological process for restoring coal mining sites.

ABSTRACT Background There remains significant variability in the surgical management of thick melanoma patients with clinically node‐negative disease. We evaluated factors influencing overall survival (OS) in these patients, focusing on the surgical management of the primary tumor and nodal basin. Methods Using the National Cancer Database, we identified 7647 patients diagnosed between 2012 and 2017 with thick melanoma (> 4 mm, T4) and clinically node‐negative disease. 4332 patients had complete data and met all inclusion criteria. These patients were stratified into three groups based on nodal assessment: sentinel lymph node biopsy (SLNB), elective lymphadenectomy (ELND), or no nodal evaluation (NNE). OS was compared using Kaplan–Meier analyses and multivariable Cox proportional hazard regression. Results In the cohort, 2851 (65.8%) had a SLNB, 799 (18.4%) had an ELND, and 682 (15.7%) had NNE. OS significantly decreased for each millimeter of increasing Breslow thickness. Ulceration, lymphovascular invasion, and tumor‐positive SLN (+SLN) were associated with worse OS (all p

Abstract Background Hereditary angioedema with normal C1-inhibitor function (HAE nC1-INH) and idiopathic angioedema of unknown etiology (AE-UNK) are rare conditions that cause recurrent subcutaneous and submucosal swelling. The characteristics and clinical outcomes of patients with these conditions in Canada have not been studied. Methods The aim of this study was to extract real-world evidence from the electronic health records of patients with HAE nC1-INH or AE-UNK who were managed in selected practices of Canadian HAE-treating specialist physicians between 01-Jan-2012 and 01-Jan-2022, to examine case numbers, treatment, clinical outcomes, and healthcare utilization. Results Of 60 patients (37 with HAE nC1-INH, 23 with AE-UNK), median (range) age at symptom onset was 21.5 (5.0–57.0) and 23.0 (10.0–54.0) years, respectively. Time to diagnosis from onset of symptoms was 7.0 (0.0–43.0) and 2.0 (− 10.0 to 50.0) years. Significant differences were observed in terms of the predominant triggers for angioedema attacks between patients with HAE nC1-INH and AE-UNK: stress (65% vs. 26%, p = 0.007) and estrogen therapy (35% vs. 9%, p = 0.031). Before diagnosis, most patients received antihistamines (50% of HAE nC1-INH and 61% of AE-UNK patients). Post-diagnosis, 73% and 74% of HAE nC1-INH and AE-UNK patients received long-term prophylaxis (LTP), with the most common LTP treatments being subcutaneous pdC1-INH (43% of HAE nC1-INH patients and 39% of AE-UNK patients) and tranexamic acid (41% of HAE nC1-INH patients and 35% of AE-UNK patients). Of patients with HAE nC1-INH, and patients with AE-UNK, 22% and 13%, respectively, were taking more than one LTP treatment concurrently. Before HAE treatment initiation, significantly fewer patients with AE-UNK compared to patients with HAE nC1-INH had angioedema attacks affecting their extremities (13% vs. 38%, p = 0.045) and GI system (22% vs. 57%, p = 0.015). In the three months following treatment initiation, patients with AE-UNK experienced significantly fewer angioedema attacks compared to patients with HAE nC1-INH (median 2.0 attacks [0.0–48.0] vs. 6.0 attacks [0.0–60.0], p = 0.044). Additionally, fewer patients with AE-UNK compared to HAE nC1-INH experienced attacks affecting their GI system (26% vs. 57%, p = 0.032). Attack duration and frequency significantly decreased for patients with HAE nC1-INH from a median of 1.00 day (range: 0.00–7.00) to 0.29 day (range: 0.02–4.00; p = 0.001) and from 10.50 attacks (range: 0.00–90.00) to 6.00 attacks (range: 0.00–60.00; p = 0.004) in the three months following HAE treatment initiation. Conclusions Using Canadian real-world evidence, these data demonstrate differing clinical trajectories between patients with HAE nC1-INH and AE-UNK, including diagnostic delays, varied attack characteristics, treatment responses and healthcare utilization. Despite treatment response, many patients still experienced frequent angioedema attacks. These results suggest an unmet need for treatment guidelines and therapies specifically for patients with HAE nC1-INH and AE-UNK and better understanding of the pathophysiology accounting for the reported differences between the two.

Abstract This paper evaluates how the contribution of scientific publications on climate change from the University of São Paulo (USP) evolved between 1989 and 2022. The study conducted a bibliometric analysis of 2874 research articles collected from the Web of Science and Scopus databases to explore main trend topics and reveal influential journals and collaboration networks using the Bibliometrix software. The study shows an increasing and more significant temporal publication distribution from 2010 onwards. Based on the author’s affiliations, results indicate that the most important partnerships are national (67%), while the international co-authorships are predominantly with research collaborators of the Global North (North America and Europe). Several papers published in the period are in high-impact factor journals, evidence on climate change from USP. Environmental services, Atlantic Forest, Tropical Forest, Amazon, biodiversity, and Land use are the hotspot research topics to which USP researchers contribute. The evolution of three thematic groups was identified: (i) physical science, (ii) causes and effects, and (iii) strategies, discussed in themes such as organic matter, deforestation, and mitigation, respectively. This research is helpful to get insights into the current research development trends, to show the broadness of the scientific production, and the importance of the USP role in the climate change theme. Ultimately, it provides valuable information for further studies and suggests the possibility of advancing the research agenda on climate change with the Global South. Graphical Abstract

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) are widely used in patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2 negative (HER2−) advanced/metastatic breast cancer (ABC/MBC) in first line (1L), but little is known about their real-world use and clinical outcomes long-term, in Canada. This study used Pentavere’s previously validated artificial intelligence (AI) to extract real-world data on the treatment patterns and outcomes of patients receiving CDK4/6i+endocrine therapy (ET) for HR+/HER2− ABC/MBC at Sinai Health in Toronto, Canada. Between 1 January 2016 and 1 July 2021, 48 patients were diagnosed with HR+/HER2− ABC/MBC and received CDK4/6i + ET. A total of 38 out of 48 patients received CDK4/6i + ET in 1L, of which 34 of the 38 (89.5%) received palbociclib + ET. In 2L, 12 of the 21 (57.1%) patients received CDK4/6i + ET, of which 58.3% received abemaciclib. In 3L, most patients received chemotherapy (10/12, 83.3%). For the patients receiving CDK4/6i in 1L, the median (95% CI) time to the next treatment was 42.3 (41.2, NA) months. The median (95% CI) time to chemotherapy was 46.5 (41.4, NA) months. The two-year overall survival (95% CI) was 97.4% (92.4, 100.0), and the median (range) follow-up was 28.7 (3.4–67.6) months. Despite the limitations inherent in real-world studies and a limited number of patients, these AI-extracted data complement previous studies, demonstrating the effectiveness of CDK4/6i + ET in the Canadian real-world 1L, with most patients receiving palbociclib as CDK4/6i in 1L.

Real-world evidence for patients with advanced EGFR-mutated non-small cell lung cancer (NSCLC) in Canada is limited. This study’s objective was to use previously validated DARWENTM artificial intelligence (AI) to extract data from electronic heath records of patients with non-squamous NSCLC at University Health Network (UHN) to describe EGFR mutation prevalence, treatment patterns, and outcomes. Of 2154 patients with NSCLC, 613 had advanced disease. Of these, 136 (22%) had common sensitizing EGFR mutations (cEGFRm; ex19del, L858R), 8 (1%) had exon 20 insertions (ex20ins), and 338 (55%) had EGFR wild type. One-year overall survival (OS) (95% CI) for patients with cEGFRm, ex20ins, and EGFR wild type tumours was 88% (83, 94), 100% (100, 100), and 59% (53, 65), respectively. In total, 38% patients with ex20ins received experimental ex20ins targeting treatment as their first-line therapy. A total of 57 patients (36%) with cEGFRm received osimertinib as their first-line treatment, and 61 (39%) received it as their second-line treatment. One-year OS (95% CI) following the discontinuation of osimertinib was 35% (17, 75) post-first-line and 20% (9, 44) post-second-line. In this real-world AI-generated dataset, survival post-osimertinib was poor in patients with cEGFR mutations. Patients with ex20ins in this cohort had improved outcomes, possibly due to ex20ins targeting treatment, highlighting the need for more effective treatments for patients with advanced EGFRm NSCLC.

An unexpected strategy for [beta]-catenin-dependent regulation of cell-lineage determination based on interactions between [beta]-catenin and a specific homeodomain factor, Prop1, is presented. A novel transcriptional strategy that underlies [beta]-catenin control of cell-lineage determination in organogenesis is discovered during the study.

BackgroundCurrent preoperative imaging is insufficient to predict survival and tumor recurrence in endometrial cancer (EC), necessitating invasive procedures for risk stratification.PurposeTo establish a multiparametric MRI radiomics model for predicting disease-free survival (DFS) and high-risk histopathologic features in EC.MethodsThis retrospective study included 71 patients with histopathology-proven EC and preoperative MRI over a 10-year period. Clinicopathology data were extracted from health records. Manual MRI segmentation was performed on T2-weighted (T2W), apparent diffusion coefficient (ADC) maps and dynamic contrast-enhanced T1-weighted images (DCE T1WI). Radiomic feature (RF) extraction was performed with PyRadiomics. Associations between RF and histopathologic features were assessed using logistic regression. Associations between DFS and RF or clinicopathologic features were assessed using the Cox proportional hazards model. All RF with univariate analysis p-value < 0.2 were included in elastic net analysis to build radiomic signatures.ResultsThe 3-year DFS rate was 68% (95% CI = 57%-80%). There were no significant clinicopathologic predictors for DFS, whilst the radiomics signature was a strong predictor of DFS (p

Introduction: Lepidic growth is considered noninvasive in lung nonmucinous adenocarcinoma, whereas other patterns are invasive. Considerable interobserver variability in assessing “invasion” has been reported. We assessed the utility of cytokeratin 7 (CK7) stain and recently proposed International Association for the Study of Lung Cancer criteria to improve assessment of noninvasion in lung adenocarcinoma. Methods: Four pathologists (two staff, two trainees) assessed 158 hematoxylin and eosin (HE)- and CK7-stained slides of 108 pT1N0-2 nonmucinous lung adenocarcinoma cases. Scoring took place in four rounds. First, sections were independently scored for percentage of noninvasive or probable noninvasive and invasive or probable invasive patterns. Second, after a consensus scoring algorithm for CK7 was formulated, the slides were rescored. Subsequent third-round scoring was conducted only on HE slides using the 2023 International Association for the Study of Lung Cancer proposed criteria, and fourth-round scoring on both HE and CK7 slides simultaneously. Intraclass correlation coefficient (ICC) was calculated for each round. Recurrence-free survival was assessed using Cox proportional hazards regression methods. Results: In the first two rounds, interobserver concordance was consistently higher with CK7 (ICC range = 0.44–0.6) than HE (range = 0.24–0.49) scores. The IASLC proposed algorithm improved ICC of HE scores to 0.60 (95% confidence interval: 0.52–0.67), and round 4 HE and CK7 combined improved ICC to 0.75 (95% confidence interval: 0.70–0.80). Continuous measures of averaged noninvasive and probable noninvasive scores on HE were associated with improved recurrence-free survival (hazard ratio: 0.83–0.86). Conclusions: CK7 staining consistently increased interobserver concordance in assessment of invasive versus noninvasive patterns than HE. Combining CK7 with the 2023 IASLC criteria for morphologic features of invasion may further improve the interobservers’ concordance for the recognition of lepidic growth in nonmucinous lung adenocarcinoma.

Abstract Aims Whether sex affects selection for and outcomes after heart transplantation (HTx) remains unclear. We aimed to show sex differences in pre‐transplant characteristics and outcomes after HTx. Methods and results From 1995 to 2019, 49 200 HTx recipients were prospectively enrolled in the Organ Procurement and Transplantation Network. Logistic regression models were used to evaluate clinical characteristics by sex. Multivariable Cox regression models were fitted to assess sex differences in all‐cause mortality, cardiovascular mortality, graft failure, cardiac allograft vasculopathy (CAV), and malignancy. In 49 200 patients (median age 55 years, interquartile range 46–62; 24.6% women), 49 732 events occurred during a median follow‐up of 8.1 years. Men were older than women, had more often ischaemic cardiomyopathy (odds ratio [OR] 3.26, 95% confidence interval [CI] 3.11–3.42; P

Background: Stereotactic radiosurgery (SRS) has supplanted whole brain radiotherapy (WBRT) as standard-of-care adjuvant treatment following surgery for brain metastasis (BrM). Concomitant with the adoption of adjuvant SRS, a new pattern of failure termed “Pachymeningeal failure” (PMF) has emerged. Methods: We reviewed a prospective registry of 264 BrM patients; 145 and 119 were treated adjuvantly with WBRT and SRS, respectively. The Cox proportional hazards model was used to identify variables correlating to outcomes. Outcomes were calculated using the cumulative incidence (CI) method. Univariate (UVA) and multivariate analyses (MVA) were done to identify factors associated with PMF. Results: CI of PMF was 2 % and 18 % at 12 months, and 2 % and 23 % at 24 months for WRBT and SRS, respectively (p