Publications by authors named "Macaulay R"

Glioblastoma (GBM) is a highly aggressive brain tumor characterized by its ability to evade the immune system, hindering the efficacy of current immunotherapies. Recent research has highlighted the important role of immunosuppressive macrophages in the tumor microenvironment (TME) in driving this immune evasion. In this study, we are the first to identify as a key regulator of tumor-associated macrophage (TAM)-mediated immunosuppression in GBM.

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There is a growing interest in how exposure to biodiversity influences mental health and wellbeing; however, few studies have focused on children. The aim of this review was to identify studies that used components of biodiversity and children's health outcomes to assess if there were any themes that could be used to inform urban design and understand the mechanisms behind associations. We used a PROSPERO registered protocol to identify eligible studies following pre-defined inclusion criteria.

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Objective: Cognitive function may contribute to variability in older adults' ability to cope with chronic stress; however, limited research has evaluated this relationship. This study investigated the relationship between theoretically derived coping domains and cognitive function in 165 middle-to-older adults during the Omicron stage of COVID-19.

Method: Participants completed a clinical interview and self-report measures of health.

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Bovine mastitis is an inflammation of the mammary gland, and it is the most common infectious disease in dairy cattle. Mastitis reduces milk yield and quality, costing dairy farmers millions of dollars each year. The aim of this study was to develop a point-of-need test for identifying mastitis pathogens that is field portable, cost-effective and can be used with minimal training.

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Glioblastoma (GBM) is the most common yet uniformly fatal adult brain cancer. Intra-tumoral molecular and cellular heterogeneities are major contributory factors to therapeutic refractoriness and futility in GBM. Molecular heterogeneity is represented through molecular subtype clusters whereby the proneural (PN) subtype is associated with significantly increased long-term survival compared to the highly resistant mesenchymal (MES) subtype.

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Leptomeningeal disease (LMD) remains a rapidly lethal complication for late-stage melanoma patients. Here, we characterize the tumor microenvironment of LMD and patient-matched extra-cranial metastases using spatial transcriptomics in a small number of clinical specimens (nine tissues from two patients) with extensive in vitro and in vivo validation. The spatial landscape of melanoma LMD is characterized by a lack of immune infiltration and instead exhibits a higher level of stromal involvement.

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Objectives: Contextually driven decision making is multidimensional, as individuals need to contend with prioritizing both competing and complementary demands. However, data is limited as to whether temporal discounting rates vary as a function of framing (gains vs loss) and domain (monetary vs social) in middle-to-older aged adults. It is also unclear whether socioaffective characteristics like social isolation and loneliness are associated with temporal discounting.

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Article Synopsis
  • Leptomeningeal disease (LMD) is a severe complication in late-stage melanoma, posing challenges for effective treatment due to its hidden location and unclear biology.
  • Research identifies that the tumor microenvironment in LMD has low immune response but high stromal activity, promoting tumor survival and resistance to therapies.
  • Targeting the stroma via SERPINA3 and its signaling pathways can resensitize melanoma cells to MAPK inhibitors, offering potential new strategies for treatment.
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Melanomas can adopt multiple transcriptional states. Little is known about the epigenetic drivers of these cell states, limiting our ability to regulate melanoma heterogeneity. Here, we identify stress-induced HDAC8 activity as driving melanoma brain metastasis development.

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Purpose: There is a growing body of literature documenting glioma heterogeneity in terms of radiographic, histologic, molecular, and genetic characteristics. Incomplete spatial specification of intraoperative tumor samples may contribute to variability in the results of pathological and biological investigations. We have developed a system, termed geo-tagging, for routine intraoperative linkage of each tumor sample to its location via neuronavigation.

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Objective: Loneliness is linked to interleukin 6 (IL-6), a marker of systemic inflammation, which chronically has deleterious effects on physical and mental health across the adult life span. This study investigated cross-sectional relationships among loneliness, IL-6, demographics, multimorbidity, depression, obesity, friendship quantity, and slowed gait.

Methods: Data from the Midlife Development in the United States Biomarker Project, a national adult sample ( N = 822; age range, 26-78 years) was used for this study.

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Temozolomide (TMZ) is an important first-line treatment for glioblastoma (GBM), but there are limitations to TMZ response in terms of durability and dependence on the promoter methylation status of the DNA repair gene O-methylguanine DNA methyltransferase (). MGMT-promoter-hypermethylated (MGMT-M) GBMs are more sensitive to TMZ than MGMT-promoter-hypomethylated (MGMT-UM) GBMs. Moreover, TMZ resistance is inevitable even in TMZ-sensitive MGMT-M GBMs.

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Introduction: Radiation necrosis (RN) is caused by vascular damage and brain parenchymal injury resulting in inflammation following radiotherapy (RT) for brain metastases. The impact of immunotherapy (IO) on the immune cellular microenvironment in patients' brain metastases is unknown. The objective of this study was to characterize the inflammatory microenvironment in the setting of RN compared to recurrent metastasis and determine whether IO treatment affects the cellular infiltrates.

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Background: Providing feedback is a key aspect of simulated participants' (SPs) educational work. In teaching contexts, the ability to provide feedback to learners is central to their role. Suboptimal feedback practices may deny learners the valuable feedback they need to learn and improve.

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Article Synopsis
  • Patients with primary central nervous system lymphoma (PCNSL) often show non-focal neurological symptoms and may have distinctive MRI findings, but deviations can complicate diagnosis.
  • A case study of a 68-year-old man with a history of infections and myasthenia gravis highlighted the challenge of diagnosing lymphoma when faced with atypical symptoms; he initially presented with vision changes and memory deficits, later diagnosed with EBV-induced diffuse large B-cell lymphoma after symptom progression.
  • Treatment included steroids, rituximab, and high-dose methotrexate, leading to complications such as kidney disease, but ultimately he achieved complete remission after receiving whole-brain radiation therapy.
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Background: Schwannomas are common peripheral nerve sheath tumors that can cause severe morbidity given their stereotypic intracranial and paraspinal locations. Similar to many solid tumors, schwannomas and other nerve sheath tumors are primarily thought to arise due to aberrant hyperactivation of the RAS growth factor signaling pathway. Here, we sought to further define the molecular pathogenesis of schwannomas.

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Background: Student burnout can be defined as the negative reactions that occur because of prolonged academic stress, which can result in emotional exhaustion/exhaustion (EE/EX), depersonalization/cynicism, and diminished personal accomplishment/reduced academic efficacy (DPA/RAE).

Objective: The purpose of this scoping review is to determine if burnout is prevalent in oral health students (OHS); identify the factors that are shown to be predicators of burnout in OHS; determine the preventive and coping strategies OHS used to mitigate the effects of burnout; and identify gaps in the literature on burnout in OHS.

Methods: A systematic search was completed using the following databases: PubMed, CINAHL, EBSCO, and ERIC.

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Background: Gangliogliomas are well-differentiated, slow-growing glioneuronal neoplasms frequently reported to harbor upregulating alterations in the mitogen-activated protein kinase pathway, particularly serine-threonine protein kinase B-RAF alterations. Fusions involving neurotrophin tyrosine receptor kinase (NTRK) genes have rarely been reported in ganglioglioma. Similarly, echinoderm microtubule-associated protein-like (EML) 4 gene fusion has been described in lung cancer, but none has been reported in ganglioglioma.

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Meningiomas are the most common intracranial primary tumor in adults. Surgery is the predominant therapeutic modality for symptomatic meningiomas. Although the majority of meningiomas are benign, there exists a subset of meningiomas that are clinically aggressive.

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Objectives: Age-related variations in emotional, physical, and cognitive health are poorly understood. This multimethod study extends previous work by investigating mechanistic models by which trait mindfulness, perceived stress, and negative affect (NA) influence health outcomes in adults aged 57-87 years old.

Method: In this cross-sectional study, 119 adults completed clinical interviews, cognitive and gait assessments, the Mindful Attention and Awareness Scale, Positive and Negative Affect Schedule, and Perceived Stress Scale.

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Objectives: Sleep health and executive function are multifaceted constructs that decline with age. Some evidence suggests that poor sleep health may underlie declines in executive function, but this relationship is not consistently found in cognitively normal older adults. The authors systematically investigated distinct sleep health domain associations with specific aspects of executive function.

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Background: Leptomeningeal disease (LMD) occurs as a late complication of several human cancers and has no rationally designed treatment options. A major barrier to developing effective therapies for LMD is the lack of cell-based or preclinical models that recapitulate human disease. Here, we describe the development of in vitro and in vivo cultures of patient-derived cerebrospinal fluid circulating tumor cells (PD-CSF-CTCs) from patients with melanoma as a preclinical model to identify exploitable vulnerabilities in melanoma LMD.

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Background: Leptomeningeal disease (LMD) is a devastating complication of systemic malignancy, of which there is an unclear etiology. The aim of this study is to determine if surgical or anatomic factors can predict LMD in patients with metastatic melanoma.

Methods: A retrospective chart review was performed of 1162 patients treated at single institution for melanoma brain metastases (MBM).

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Stemness reprogramming remains a largely unaddressed principal cause of lethality in glioblastoma (GBM). It is therefore of utmost importance to identify and target mechanisms that are essential for GBM stemness and self-renewal. Previously, we implicated BIRC3 as an essential mediator of therapeutic resistance and survival adaptation in GBM.

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