Carson M

We previously reported that the DNA alkylator and transcriptional-blocking chemotherapeutic agent trabectedin enhances oncolytic herpes simplex viroimmunotherapy in human sarcoma xenograft models, though the mechanism remained to be elucidated. Here we report trabectedin disrupts the intrinsic cellular anti-viral response which increases viral transcript spread throughout the human tumor cells. We also extended our synergy findings to syngeneic murine sarcoma models, which are poorly susceptible to virus infection...

INTRODUCTION: The COVID-19 pandemic posed a significant lifecourse rupture, not least to those who had specific physical vulnerabilities to the virus, but also to those who were suffering with mental ill health. Women and birthing people who were pregnant, experienced a perinatal bereavement, or were in the first post-partum year (i.e., perinatal) were exposed to a number of risk factors for mental ill health, including alterations to the way in which their perinatal care was delivered...

BACKGROUND: Cystic fibrosis associated liver disease (CFLD) carries a significant disease burden with no effective preventive therapies. According to the gut-liver axis hypothesis for CFLD pathogenesis, dysbiosis and increased intestinal inflammation and permeability permit pathogenic bacterial translocation into the portal circulation, leading to hepatic inflammation and fibrosis. Evaluating the effect of CFTR (cystic fibrosis transmembrane conductance regulator) modulation with elexacaftor/tezacaftor/ivacaftor (ETI) may help determine the role of CFTR in CFLD and increase understanding of CFLD pathogenesis, which is critical for developing therapies...

GRP170 ( Hyou1 ) is required for mouse embryonic development, and its ablation in kidney nephrons leads to renal failure. Unlike most chaperones, GRP170 is the lone member of its chaperone family in the ER lumen. However, the cellular requirement for GRP170, which both binds non-native proteins and acts as nucleotide exchange factor for BiP, is poorly understood. Here, we report on the isolation of mouse embryonic fibroblasts obtained from mice in which LoxP sites were engineered in the Hyou1 loci ( Hyou1LoxP/ LoxP )...

BACKGROUND: To address the shortage of oncologists in the wake of the rapidly increasing global cancer burden, general practitioners of oncology (GPOs) have been added to cancer care teams worldwide. GPOs are family physicians with additional training in oncology and their roles differ by both country and region. In this study, we aimed to learn about the roles and expectations of GPOs from the perspective of oncologists in Canada and Nepal. METHODS: A survey was designed and administered to Canadian and Nepali Oncologists between February and November 2022 using Research Electronic Data Capture, a secure web-based software platform hosted at Queen's University in Kingston, Ontario, Canada...

Skills on Wheels, a 5-week pediatric wheelchair skills training program implemented over 2 years, was developed to address confidence, social participation, and mobility for wheelchair-using children. This study tests the hypothesis that pediatric wheelchair skills training will increase wheelchair skill ability, confidence, and participation of wheelchair-using children. Individualized instruction was delivered by occupational ( N  = 50) and physical ( N  = 12) therapy practitioners and doctoral students...

No abstract text is available yet for this article.

No abstract text is available yet for this article.

BACKGROUND: Large introductory lecture courses are frequently post-secondary students' first formal interaction with science, technology, engineering, and mathematics (STEM) disciplines. Grade outcomes in these courses are often disparate across student populations, which, in turn, has implications for student retention. This study positions such disparities as a manifestation of systemic inequities along the dimensions of sex, race/ethnicity, income, and first-generation status and investigates the extent to which they are similar across peer institutions...

INTRODUCTION: Congenital dermal sinus (CDS) is an open neural tube defect (NTD) that occurs in 1 in 2500 births a year and often goes undetected until patients present with complications like infection and neurological deficits. Early diagnosis and repair of CDS may prevent formation of these complications. In utero diagnosis of these lesions may improve long-term outcomes by enabling referral to specialty services and planned postnatal repair, however only two such cases have been reported in the literature...

Preclinical and clinical data suggest that androgen receptor signaling strongly contributes to bladder cancer development. The roles of the androgen receptor in bladder carcinogenesis have obvious implications for understanding the strong male sex bias in this disease and for potential therapeutic strategies as well. In this review, we summarize what is known about androgen receptor signaling in urothelial carcinoma as well as in tumor-infiltrating immune cells, reviewing preclinical and clinical data. We also highlight clinical trial efforts in this area...

OBJECTIVES: Among patients with severe acute kidney injury (AKI) admitted to the ICU in high-income countries, regional practice variations for fluid balance (FB) management, timing, and choice of renal replacement therapy (RRT) modality may be significant. DESIGN: Secondary post hoc analysis of the STandard vs. Accelerated initiation of Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial (ClinicalTrials.gov number NCT02568722). SETTING: One hundred-fifty-three ICUs in 13 countries...

No abstract text is available yet for this article.

PURPOSE: To report a series of three patients with von Hippel-Lindau (VHL) disease who demonstrated regression of their retinal hemangioblastomas (RH) using belzutifan in conjunction with photocoagulation therapy. OBSERVATIONS: Patient 1, a 23-year-old female, presented with multiple RHs in her right eye (OD) that were lasered. Her left eye (OS) revealed a large inferotemporal RH that measured approximately 2.1 mm2 . Systemic belzutifan was administered. Four months after initiation of treatment, the lesion regressed to 1...

PURPOSE: Adverse neighborhood contextual factors may affect breast cancer outcomes through environmental, psychosocial, and biological pathways. The objective of this study is to examine the relationship between allostatic load (AL), neighborhood opportunity, and all-cause mortality among patients with breast cancer. METHODS: Women age 18 years and older with newly diagnosed stage I-III breast cancer who received surgical treatment between January 1, 2012, and December 31, 2020, at a National Cancer Institute Comprehensive Cancer Center were identified...

UNLABELLED: Understanding the effects of genetic variants is crucial for accurately predicting traits and functional outcomes. Recent approaches have utilized artificial intelligence and protein language models to score all possible missense variant effects at the proteome level for a single genome, but a reliable tool is needed to explore these effects at the pan-genome level. To address this gap, we introduce a new tool called PanEffect. We implemented PanEffect at MaizeGDB to enable a comprehensive examination of the potential effects of coding variants across 50 maize genomes...

OBJECTIVES: To examine whether higher weight status is associated with increased eating disorder risk in athletes. DESIGN: Study 1 used cross-sectional (N = 942) and longitudinal (N = 483) data collected over a five-year period from Division I athletes at a Midwestern university. Study 2 used cross-sectional data from athletes competing at various levels at universities across the United States (N = 825). METHODS: Weight and height were measured in Study 1 and self-reported in Study 2; higher weight was defined as body mass index ≥ 25 kg/m2 ...

BACKGROUND: Heart failure (HF) affects >6 million US adults, with recent increases in HF hospitalizations. We aimed to investigate the association between neighborhood disadvantage and incident HF events and potential differences by diabetes status. METHODS: We included 23 645 participants from the REGARDS study (Reasons for Geographic and Racial Differences in Stroke), a prospective cohort of Black and White adults aged ≥45 years living in the continental United States (baseline 2005-2007)...

BACKGROUND: To assess whether changes in breakfast and water consumption during the first full school year after the emergence of the COVID-19 pandemic varied based on sex/gender, race/ethnicity, and socioeconomic status among Canadian adolescents. METHODS: Prospective annual survey data collected pre- (October 2019-March 2020) and post-COVID-19 onset (November 2020-June 2021) the Cannabis, Obesity, Mental health, Physical activity, Alcohol, Smoking, and Sedentary behaviour (COMPASS) study...

BACKGROUND: Ionizing radiation and alkylating chemotherapies increase secondary malignancy risk in patients with cancer predisposition syndromes (CPSs), such as Li-Fraumeni syndrome. Laser interstitial thermal therapy (LITT) is a minimally invasive ablation technique that has not been associated with mutagenic risks. We describe the case of a child with LFS and a history of treated choroid plexus carcinoma (CPC) who developed a second primary glial tumor that was safely treated with magnetic resonance imaging (MRI)-guided LITT...