Unravelling complex associations of genetic variation and tumor microenvironments for clonal expansion in breast cancer with metastasis

Breast cancer (BrCa) is highly heterogeneous, with multiple distinct subtypes associated with variable clinical outcomes and high intra-tumor clonal diversity. This clonal diversity is caused by genomic instability, microenvironmental factors, and tumor cell plasticity. Intra-tumor clonal diversity has been linked to poor clinical outcomes including aggressive, recurrent, and treatment resistant tumors and progression to metastases. Somatic mutations that induce transcriptomic alterations and genomic instability, in combination with the harsh tumor microenvironment, shape the heterogeneity and expansion of intra-tumor clones. We identified RHAMM, which has pro-inflammatory functions in response-to-injury processes, as a contributor to BrCA cell heterogeneity. RHAMM is expressed in tumor and host cells and Rhamm-loss in these cell compartments strongly reduces clonal heterogeneity detected by single nucleotide variants used as endogenous barcodes. Our evidence predicts that a RHAMM-ve microenvironment exerts selective pressure permitting the emergence of dominant clones in lung metastases that carry specific oncogenic mutations. Our goal is to probe the interplay between clonal heterogeneity and the tumor microenvironment in the emergence of dominant intra-tumor clones. Next-generation DNA sequencing technologies now offer a two-pronged approach to the analysis of genetic heterogeneity. Long-read genome sequencing enables discovery of large structural variants and short-read, deep sequencing achieves highly accurate detection of ultra-rare single nucleotide variants. The interplay of clonal dynamics and the tumour microenvironments in the development of heterogeneous BrCa tumours can be teased apart to better understand the causative processes underlying the metastatic and treatment-resistant nature of these tumours, with discovery of potential genetic determinants relevant to cancer management

Controlling Interfacial Interactions of Amphiphilic Organic Dyes by Molecular Design

Controlling the orientation of polycyclic aromatic dyes in thin films is critical for tuning their optical, electronic, mechanical, and reactive properties. In this study, we engineered the supramolecular assembly of macrocyclic dyes by converting them into amphiphilic structures. Two octaalkylthio-substituted tetraazaporphyrins (TAPs), each with a 5-carboxypentyl chain and either a pentyl or dodecyl chain per pyrrole ring, were synthesized as statistical mixtures of four regioisomers. The unsymmetrically substituted maleodinitrile precursors were prepared in good yields using a flow reactor. Neither the tetra-ester precursors nor the tetra-acid TAPs exhibited mesomorphism, and both were classified among the rare porphyrin derivatives that form isotropic liquid phases at or near room temperature. The interfacial properties of these amphiphilic tetra-acids were investigated using Langmuir and Langmuir-Blodgett (LB) films. Langmuir films were prepared on aqueous subphases at varying pH levels and characterized by surface pressure-area isotherms, compressibility, Brewster angle microscopy, ellipsometry, and grazing incidence X-ray diffraction (GIXD). LB films were transferred to mica substrates and analyzed using atomic force microscopy (AFM). The dodecyl-substituted tetra-acid (4b) formed condensed Langmuir monolayers at 15 mN/m surface pressure and at pH values of 4.0 and 6.5, but higher surface pressures and a pH of 11 induced the formation of 3D structures. In contrast, the LB films of the pentyl-substituted tetra-acid (4a) produced a homogeneous monolayer at 15 mN/m surface pressure and pH 6.5. AFM measurements and packing correlations derived from GIXD indicated that compound 4a adopts a spider-like conformation, with its macrocycle oriented parallel to the substrate (face-on) and organized in a tightly packed hexagonal unit plane. This difference in molecular packing is attributed to intramolecular mixing of the 5-carboxypentyl and pentyl chains in 4a, which provides a better match between the footprints of the macrocycle, acid groups, and alkyl chains. In contrast, the longer dodecyl chains in 4b are either too large to fit between the 5-carboxypentyl chains or too small to fill the footprint of the TAP macrocycle. Amphiphilic dyes are technologically significant due to their tunable properties, which can be adjusted through self-organization and assembly at interfaces. Here, we report the synthesis, thermal properties, and Langmuir monolayer behavior of amphiphilic tetraazaporphyrin (TAP) derivatives, which feature four terminal carboxylic acid groups attached via pentamethylenethio spacers and four dodecylthio side chains. The metal-free tetra-ester TAP was synthesized first and subsequently metalated with Ni(II), Cu(II), Co(II), and Zn(II) acetates, yielding stable products. Hydrolysis of the esters to form the tetra-acid TAPs was achieved in moderate yields. The TAP esters are isotropic liquids at room temperature, an unusual property for porphyrins of this size, while the tetra-acid derivatives form isotropic solids with glass transitions between 40-80 °C. All tetra-acid TAPs formed Langmuir monolayers, but only the Ni(II)-containing TAP exhibited a mean molecular area consistent with a flat-on molecular orientation and could be compressed to pressures above 35 mN/m. The metal-free and Cu(II)-metalated TAPs showed similar properties, though only at pH 11, and not at pH values of 6.5 or 3. TAPs typically adopt an edge-on orientation in Langmuir films due to strong cofacial interactions between macrocycles, especially at high surface pressures. Achieving a face-on orientation is rare but would enhance applications in sensing and catalysis by improving electronic interactions with the substrate. In this study, we functionalized Ni(II)-metalated TAPs with four carboxylic acid groups via flexible aliphatic spacers and four alkyl chains, promoting face-on assembly at polar interfaces. The impact of different methylene spacers and alkyl chain lengths on monolayer formation was evaluated in Langmuir films. Di-acid NiTAP derivatives with shorter chains (C1) and longer chains (C12) were synthesized for comparison as edge-on references. The linear alkyl chains of these NiTAPs enhanced monolayer stability, with chain length and branching critically influencing interfacial behaviour. These findings contribute to the optimization of TAPs\u27 optical and electronic properties through controlled molecular orientation, with broad implications for materials science applications. Lastly, fluorescent probes are indispensable for studying membrane dynamics via fluorescence microscopy in the context of biological membranes. However, the disruption of membrane behavior by standard probes necessitates their use in low concentrations. This research introduces two diketopyrrolopyrrole (DPP) derivatives designed to mimic cholesterol, allowing for higher dye concentrations without compromising membrane integrity. DPP-1 contains one phenyl and one cyclohexyl group attached to the DPP core, while DPP-2 has two phenyl groups, simplifying its synthesis and yielding a bathochromic shift in absorption spectra. The most significant challenge in the synthesis of DPP-1 lies in the cyclic condensation reaction involving the cyano-cyclohexyl group, which is complicated by side reactions attributed to the C-H acidic proton and geminal carbocation. Subsequent studies will thoroughly examine the fluorescence properties, amphiphilicity, and interactions with the lipid membranes of DPP-1 and DPP-2

Sustainable Feedstock Planning for Renewable Natural Gas (RNG) Production via Anaerobic Digestion (AD): An Environmental Perspective with Economic Considerations

Unsustainable organic waste (OW) management significantly contributed to the global climate change crisis. Landfilling is the most widely used method to manage OW globally and in Canada as well which contributes to 2% of the country’s GHG emissions. As a response to these issues, Canada has imposed federal and provincial OW diversion targets, food waste landfilling bans, and regulations such as Clean Fuel Regulations (CFR). There is an urgent need to develop know-how and resources to aid sustainable waste management decision-making. Anaerobic digestion (AD) is a hybrid solution for two burning issues: landfilling of OW and GHG emissions from fossil fuels. Life cycle carbon intensity (CI) assessment is a tool that can be used to evaluate the environmental sustainability of RNG production. Recently registered CFR in Canada has proposed a consistent approach for life cycle assessment on clean fuels produced in Canada. This research developed feedstock planning methods for RNG production using AD in the Canadian context from a life cycle thinking-based approach. In phase 1 of the study, the environmental and economic performance of RNG production focusing on the feedstock planning stage has been conducted. According to the life cycle CI assessment results, the environmental impacts of each feedstock type were monetized using carbon credits. The net revenue was calculated considering the RNG sales, carbon credits, tipping fee revenue, and feedstock price. SSO (200 CAD/t) gives the highest net revenue followed by GHW, and WC. Feedstocks that have low energy yield (DM & SS) showed considerable credit revenue potential which will be a good incentive for them. In phase 2, a feedstock prioritizing framework was proposed for the RNG industry to rank different feedstocks for RNG production. The feedstock ranking results indicated SSO as the preferred feedstock followed by GHW and WC. The findings of this research will aid RNG producers in identifying optimal feedstocks, thereby enhancing production efficiency. Additionally, the outcomes will contribute to Canada’s commitment to achieving the United Nations Sustainable Development Goals (UNSDGs) and advancing the Federal Sustainable Development Strategy

Shaping the Future of Youth Cancer Care in Windsor-Essex Region: Insights and Recommendations based on System Strengths and Challenges

Background: Despite the advancements in oncology care, systemic barriers to care persist, affecting the experiences and outcomes of youths with cancer, their caregivers, and healthcare providers. Youth with cancer and their caregivers often report feeling underserved by healthcare systems, particularly in psychosocial support and aftercare. Healthcare providers experience parallel challenges, including limited resources and support, which hinder their ability to provide high-quality oncology care. The availability of cancer care services and experiences of youth with cancer in smaller communities remain underexplored, leaving potential gaps in support systems and healthcare accessibility. Objective: This study examined the strengths and challenges of the current oncology care practices from the viewpoints of youth with cancer, caregivers, and healthcare providers living and practicing in the Windsor-Essex region as well as explored their recommendations for development of effective care. Method: Semi-structured interviews were conducted with youths with cancer (n=2), caregivers (n=6), and local healthcare providers (n=6). Interviews were transcribed and analyzed using a qualitative thematic analysis approach. Results: The key strengths and challenges identified were: 1) the Value of holistic support services, 2) the Availability of resources, and 3) the Quality and support of youth oncology care and services. Recommendations generated from participants were: 1) Enhancing equitable supportive care for youth in oncology and 2) Strengthening cancer care capacity and collaboration. Implications: The findings highlight the need to enhance supportive services and strengthen infrastructure for sustainable, high-quality youth cancer care. Future research should focus on developing care models that integrate holistic, age-appropriate supports alongside medical treatment

Comparison of hepatic gene expression profiles between cirrhotic and non-cirrhotic HCC

Hepatocellular carcinoma (HCC) ranks among the leading causes of cancer-related deaths globally. Metabolic Associated Steatotic Liver Disease (MASLD), the most prevalent liver condition, is closely linked to a spectrum of hepatic disorders, including Metabolic Associated Steatohepatitis (MASH), liver cirrhosis, and eventually HCC. While cirrhosis is a well-established precursor to HCC, approximately 20% of HCC cases arise without prior cirrhosis, and the molecular mechanisms driving this subset of non-cirrhotic HCC remain poorly understood. This study employs a comprehensive bioinformatics approach to investigate the distinct molecular drivers of non-cirrhotic HCC compared to cirrhotic HCC. This study analyzed mRNA expression datasets to identify differentially expressed genes (DEGs) in MASLD/MASH versus normal tissue and cirrhotic and non-cirrhotic HCC versus normal tissue. GO analysis revealed that the DEGs were involved in pathways regulating lipid metabolism, cell proliferation, adhesion, migration, and immune responses, highlighting their diverse roles in tumorigenesis. Core genes involved in cell cycle regulation were identified and their expression patterns were systematically compared across MASLD/MASH, cirrhotic HCC, and non-cirrhotic HCC groups. Key genes such as CCNB1, E2F2, CDC25A, CCNE1, CDK1, CDKN2A, and CDKN2B showed significant upregulation in non-cirrhotic HCC compared to cirrhotic HCC, suggesting roles in driving tumorigenesis independent of cirrhosis. This comprehensive bioinformatics analysis identified core genes that mediate the molecular mechanisms underlying MASLD and MASH and their potential roles in non-cirrhotic HCC development. These findings provide a deeper understanding of the molecular basis of non-cirrhotic HCC and highlight promising biomarkers and therapeutic targets for diagnosing and managing this subset of HCC

The Impact of Initiating Continuous Glucose Monitoring (CGM) in Adults Diagnosed with Pre-Type 2 Diabetes

Pre-diabetes is a condition diagnosed when individuals have higher than normal blood glucose levels that are not yet in the diabetic range. The condition can occur at all different life stages but is most common in older ages and obese individuals. A commonly agreed-upon method of diagnosis is measuring glycosylated hemoglobin (HbA1c), with levels between 5.7% and 6.4% indicating pre-diabetes. The condition is considered intermediate at this stage but has a variety of comorbidities, most notably its high risk of progressing into type 2 diabetes. Methods such as monitoring, education and healthy lifestyle choices can significantly affect the outcome of pre-diabetes, potentially reducing HbA1c levels or slowing disease progression. Unfortunately, many individuals lack the proper tools and education to address and manage their disease adequately. Continuous glucose monitors (CGM) are commonly used in blood glucose monitoring for diabetes management, typically for type 1 diabetics. These devices report real-time data while identifying trends and changes, allowing users to better understand and monitor their condition. Closely monitoring blood glucose levels could aim to improve glycemic stability in pre-diabetics. However, there is a gap in existing research on the impact of CGM use in monitoring adults with pre-diabetes

Analytical methods for the rapid assessment of cannabis extract products in industrial applications

Characterization of cannabis extract in an industrial setting is required for both quality assurance (QA) and quality control (QC) purposes. More importantly, having a rapid, straightforward, and streamlined process is essential for the daily operational success of any QC and QA department. Using robust physical techniques such as polarimetry, refractometry, and densitometry, the physical properties of three distinct compositions of cannabis extract in carrier oil were characterized: Tetrahydrocannabinol (THC), cannabidiol (CBD), and a THC/CBD mixture. In addition, the shelf life of these samples was assessed using an accelerated oxidation method and were subsequently characterized by polarimetry, refractometry, and densitometry. In addition to the initial characterization of the cannabis products, a concentration dependency of these mixtures was investigated utilizing these techniques. Moreover, these quantitative methods were utilized to evaluate cannabis mixtures pre- and post-oxidation. The oxidation of mixtures largely resulted in higher density and lower refractive index values with the optical rotation values remaining unaffected by the oxidation process. These findings were supported by HPLC data providing validation of these qualitative techniques for assessment of oxidation in cannabis oil. Overall, these simple and straightforward techniques allow for the accurate and precise measurements of cannabis oil rapidly and effectively with a focus on industrial applications

Combining Carbohydrate with Semiconducting Polymers: A New Sustainable Approach in Organic Electronics

The field of technology is innovating and growing, resulting in increased production of electronics. This has a large impact on our environment, and chemists are exploring a solution to reduce these effects2,4. Researchers in our group are utilizing a new, exciting approach to conventional electronic device fabrication with organic polymers. Organic Field Effect Transistors are a type of organic electronic device that uses semiconducting materials such as polymers as an active layer1,3. OFETS have excellent mechanical and optoelectronic properties and demonstrate high performance with air stability. OFETS are lightweight, stretchable, flexible, and applicable to innovation and design in technology1, such as bioelectronics, where they can be used as sensors. Our research uses isoindigo-based semiconducting polymers with carbohydrate side chains, making them biocompatible and more environmentally friendly2,3. Previously, our group developed polymers with enhanced solubility in more environmentally friendly solvents5. Building on previous works, our current research focuses on optimizing the synthesis and electronic performance of carbohydrate-containing semiconducting polymers. Our facile new synthetic approach involves less steps, higher yields, and better performance in OFETs. This presentation will discuss various aspects of the organic device fabrication process, with an emphasis on the new synthetic approach, and ways to optimize the resulting OFETs

Exploring the application of shellac as an encapsulant for printed electronic devices

An emerging realm of technology is printed electronics. These types of electronics encompass the creation of electronic components through printing methods, offering cost-effective, mass-produced flexible, and customizable electronics. However, the manufacturing of these devices has led to substantial volumes of electronic waste due to the use of plastics and unsustainable materials resulting in adverse effects on our environment. This study focuses on the use of shellac as a green encapsulant material for printed devices, given its biodegradability, recyclability, non-toxic nature, and sourcing from sustainable materials and exploring its effectiveness by analyzing its permeability properties

Getting Past the Fork in the Road to Resolution: Investigating Self-Compassion as a Guide to Overcoming Difficult Life Events

Unresolved events (e.g., break-up, argument, loss) lack psychological closure; memories of these events demand cognitive resources, incite intense emotions, and are associated with negative mental health outcomes. To make matters worse, efforts to resolve events frequently backfire to perpetuate distress. There is a critical need to identify effective strategies to help individuals cope with these experiences. The present study experimentally examines whether a self-compassion exercise (vs. thinking as usual) influences levels of posttraumatic cognitions, posttraumatic growth, and psychological closure for negative unresolved events. Event centrality to identity and life-story is expected to moderate these effects. A total of 200 undergrads will be randomly assigned to a self-compassion or control task concerning an unresolved event of their choice, following which they will complete a series of questionnaires. This study stands to provide a practical means of helping people find closure (self-compassionate mindstate induction) in addition to informing theory and research on posttraumatic experiences