Publications by authors named "Mack S"

Introduction: There is a high prevalence of type 2 diabetes (T2D) in First Nations populations worldwide, increasingly at younger ages. This review aims to identify interventions for the prevention of T2D in First Nations children and young people aged 4-25 years.

Methods: A systematic search of both published and unpublished literature until March 2024 was performed using 15 electronic databases, including MEDLINE, CINAHL, EMBASE, Scopus, Cochrane Library, ATSIHealth, OpenGrey and specific First Nations databases.

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Background: Medicaid expansion under the Affordable Care Act aimed to expand healthcare access, improve quality, and reduce costs. The effects of Medicaid expansion on receipt of local therapy for lung cancer are unknown.

Methods: We utilized the National Cancer Database to conduct a retrospective analysis of patients with clinical T1-2, N0, M0 non-small cell lung cancer (NSCLC) without neoadjuvant treatment.

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Background: Depression associated with occupational stress is highly prevalent, causing high rates of sick leave and thus posing significant societal and economic burden. Meta-analyses of the few studies on psychological and work-focused interventions for common mental disorders including depression report small effects on depressive symptomatology and occupational outcomes. There is an urgent need for more controlled studies on work-directed interventions assessing work outcomes.

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Distinguishing tumor maintenance genes from initiation, progression, and passenger genes is critical for developing effective therapies. We employed a functional genomic approach using the Lazy Piggy transposon to identify tumor maintenance genes in vivo and applied this to sonic hedgehog (SHH) medulloblastoma (MB). Combining Lazy Piggy screening in mice and transcriptomic profiling of human MB, we identified the voltage-gated potassium channel KCNB2 as a candidate maintenance driver.

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Ependymoma (EPN) is a common form of brain tumor in children, often resistant to available cytotoxic therapies. Molecular profiling studies have led to a better understanding of EPN subtypes and revealed a critical role of oncogenes ZFTA-RELA fusion and EPHB2 in supratentorial ependymoma (ST-EPN). However, the immune system's role in tumor progression and response to therapy remains poorly understood.

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Background: As value-based care models continue to gain emphasis, along with the need for improved profiling across the continuum of lung cancer care, a better understanding of geographic variation in utilization of services surrounding episodes of care is needed.

Methods: In this retrospective cohort study of patients undergoing lung cancer resection from 2017 to 2019, we examined geographic variation in utilization of services surrounding episodes of lung cancer resection. We utilized hierarchical logistic regression models to determine risk-adjusted utilization of services.

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Background: Pectus excavatum (PE) is the most common congenital chest wall defect and is characterized by the inward displacement of the sternum and costal cartilages. To date, there are limited data on adult patients undergoing the Nuss procedure for PE. This study aimed to assess the complication rate between the pediatric and adult populations and assess the trends in demographics.

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Background: The real-world safety of robotic resections after neoadjuvant chemoimmunotherapy remains poorly defined in patients with non-small cell lung cancer. Due to reported increased operative challenges after neoadjuvant immunotherapy, we aim to describe our early institutional experience and outcomes after robotic resection in this clinical context.

Methods: We performed a retrospective chart review of patients with non-small cell lung cancer who underwent a robotic lobectomy, comparing patients from June 1, 2022, through October 31, 2023, who were treated with neoadjuvant chemoimmunotherapy consistent with the Checkmate-816 protocol and a control group with upfront resection.

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Transcription factors are frequent cancer driver genes, exhibiting noted specificity based on the precise cell of origin. We demonstrate that ZIC1 exhibits loss-of-function (LOF) somatic events in group 4 (G4) medulloblastoma through recurrent point mutations, subchromosomal deletions and mono-allelic epigenetic repression (60% of G4 medulloblastoma). In contrast, highly similar SHH medulloblastoma exhibits distinct and diametrically opposed gain-of-function mutations and copy number gains (20% of SHH medulloblastoma).

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Glioblastoma is a highly aggressive primary brain tumor with glioblastoma stem cells (GSCs) enforcing the intra-tumoral hierarchy. Plasma cells (PCs) are critical effectors of the B-lineage immune system, but their roles in glioblastoma remain largely unexplored. Here, we leverage single-cell RNA and B cell receptor sequencing of tumor-infiltrating B-lineage cells and reveal that PCs are aberrantly enriched in the glioblastoma-infiltrating B-lineage population, experience low level of somatic hypermutation, and are associated with poor prognosis.

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Objective: The purpose of this study is to utilize a representative national sample to compare survival outcomes of patients with visceral pleural invasion (VPI) who underwent either a lobectomy or a segmentectomy.

Methods: National Cancer Database from 2010 to 2019 was utilized. Patients with tumor size ≤ 2 cm, with VPI, non-small cell lung cancer (NSCLC), with a known vital status were included in the study.

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Article Synopsis
  • Medulloblastoma and ependymoma are common types of brain tumors in children, and this study analyzes their molecular differences using bulk RNA sequencing data from a large number of tumor samples.
  • The researchers processed the data to create a unified landscape, identifying distinct gene expression profiles and molecular characteristics within the tumors, particularly highlighting two compartments in ependymoma and subtypes in medulloblastoma.
  • The findings provide a valuable resource for discovering new biomarkers and improving diagnostic accuracy, and the data can be explored using the interactive platform Oncoscape for better patient classification in future research.
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Immune synapse (IS) formation determines T cell antitumor activity. Here, we present a protocol for characterizing the IS formation between chimeric antigen receptor (CAR) T cells and tumor cells by measuring the IS size and calcium flux by live-cell imaging. We describe steps for CAR T cell manufacturing, sample preparation, image acquisition, and data analysis.

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Article Synopsis
  • The DPB1 locus shows allele frequencies influenced by genetic drift, but specific amino acids at this locus are shaped by balancing selection, suggesting a complex relationship between drift and selection in genetic diversity.
  • Using Ewens-Watterson and asymmetric Linkage Disequilibrium analyses across 136 global populations, researchers found strong evidence of balancing selection affecting DP serologic categories (SCs), while no similar selection was observed for T-cell epitopes or supertypes.
  • The distribution of different SCs varies globally, with specific SCs prevalent in distinct regions, and the study highlights consistent associations between DPA1 and DP SC haplotypes, indicating that natural selection is primarily acting to preserve diversity in DP SCs rather than DPB1 alle
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  • The study aimed to analyze how Medicaid expansion impacted the receipt of adjuvant chemotherapy among eligible cancer patients using a national database.
  • Researchers reviewed data from nearly 10,000 patients treated in states that expanded Medicaid, finding a significant increase in chemotherapy receipt post-expansion (70.2% vs. 62.3%).
  • The results suggest that Medicaid expansion improved access to care and potentially led to better survival outcomes for patients receiving adjuvant therapy.
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Article Synopsis
  • - Although most HLA loci show signs of balancing selection at the allele level, the DPB1 locus appears to follow neutral evolution or directional selection in many populations, despite evidence of balancing selection at the nucleotide and amino acid levels.
  • - The study introduces methods to analyze the global distribution of DPB1 alleles and their amino acid sequences, allowing for a detailed investigation of natural selection's role in DPB1 diversity.
  • - Findings reveal significant evidence of balancing selection at specific amino acid positions (56, 85-87, 36, 55, and 84), but not at the allele level for DPB1.
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MYC promotes tumor growth through multiple mechanisms. Here, we show that, in human glioblastomas, the variant transcript encodes a 114-amino acid peptide, MYC pre-mRNA encoded protein (MPEP), from the upstream open reading frame (uORF) . Secreted MPEP promotes patient-derived xenograft tumor growth in vivo, independent of MYC through direct binding, and activation of tropomyosin receptor kinase B (TRKB), which induces downstream AKT-mTOR signaling.

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  • Fractional laser therapy is effective for improving skin texture and quality of life for patients with traumatic scars, but there are concerns about its declining insurance coverage.
  • A study examined policies from 60 major American health insurers and found only a minority (18.3%) covered scar revision with laser therapy, while 13.8% of claims from one institution were denied.
  • Over the study period from 2017 to 2022, there was a 14.5% annual decrease in the likelihood of getting reimbursement for this treatment, highlighting the need for better strategies to maintain patient access.
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Article Synopsis
  • * Annual CH fluxes averaged around 26g CH/m²/year; the highest emissions were linked with certain temperature and salinity conditions, particularly in fresh-oligohaline marshes.
  • * The research found that salinity was the main factor affecting annual CH fluxes, while temperature, gross primary productivity, and tidal height influenced shorter-term variability, providing crucial data for better estimating methane emissions in these ecosystems.
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Unlabelled: ZFTA-RELA is the most recurrent genetic alteration seen in pediatric supratentorial ependymoma (EPN) and is sufficient to initiate tumors in mice. Despite ZFTA-RELA's potent oncogenic potential, gene fusions are observed exclusively in childhood EPN, with tumors located distinctly in the supratentorial region of the central nervous system (CNS). We hypothesized that specific chromatin modules accessible during brain development would render distinct cell lineage programs at direct risk of transformation by ZFTA-RELA.

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  • The study investigates the outcomes of minimally invasive surgery (MIS) compared to open surgery for repairing esophageal atresia/tracheoesophageal fistula (EA/TEF) in neonates, utilizing data from 2013 to 2020.
  • A total of 1,738 neonates were analyzed, revealing that although MIS use increased over time, it was linked to longer surgical times and higher rates of overall postoperative interventions.
  • Despite these findings, there was no significant difference in overall morbidity between the two surgical approaches, suggesting a need for further research to assess the long-term effects of MIS on EA/TEF repairs.
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Bidirectional communication between tumours and neurons has emerged as a key facet of the tumour microenvironment that drives malignancy. Another hallmark feature of cancer is epigenomic dysregulation, in which alterations in gene expression influence cell states and interactions with the tumour microenvironment. Ependymoma (EPN) is a paediatric brain tumour that relies on epigenomic remodelling to engender malignancy; however, how these epigenetic mechanisms intersect with extrinsic neuronal signalling during EPN tumour progression is unknown.

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