In recent years, it has become clear that artificial intelligence (AI) models can achieve high accuracy in specific pathology-related tasks. An example is our deep-learning model, designed to automatically detect serous tubal intraepithelial carcinoma (STIC), the precursor lesion to high-grade serous ovarian carcinoma, found in the fallopian tube. However, the standalone performance of a model is insufficient to determine its value in the diagnostic setting.
View Article and Find Full Text PDFThe visual perception provided by retinal prostheses is limited by the overlapping current spread of adjacent electrodes. This reduces the spatial resolution attainable with unipolar stimulation. Conversely, simultaneous multipolar stimulation guided by the measured neural responses-neural activity shaping (NAS)-can attenuate excessive spread of excitation allowing for more precise control over the pattern of neural activation.
View Article and Find Full Text PDFBackground: Expansion of the scope of pharmacists' activities in hospital is associated with reductions in adverse events and drug-related readmissions. However, the breadth of hospital pharmacists' clinical activities varies widely across Ontario due to provisions in the provincial . Few data exist defining expanded scope in institutions across Ontario.
View Article and Find Full Text PDFPurpose: Shallow whole-genome sequencing (sWGS) can detect copy-number (CN) aberrations. In high-grade serous ovarian cancer (HGSOC) sWGS identified CN signatures such as homologous recombination deficiency (HRD) to direct therapy. We applied sWGS with targeted sequencing to p53abn endometrial cancers to identify additional prognostic stratification and therapeutic opportunities.
View Article and Find Full Text PDFVulvovaginal melanoma (VVM) is a rare but deadly disease, accounting for 5% of all vulvar malignancies, with a 5-yr survival rate of only 47% for all stages of the disease. VVM is a distinct subset of melanoma, with a unique genomic profile and underlying pathogenesis unassociated with sun exposure. Distinguishing these rare malignancies from very common pigmented lesions of the vulva and vagina is challenging as histologic features often overlap between entities.
View Article and Find Full Text PDFImmune checkpoint inhibitor (ICI) therapy has revolutionized renal cell carcinoma treatment. Patients previously thought to be palliative now occasionally achieve complete cures from ICI. However, since immunotherapies stimulate the immune system to induce anti-tumor immunity, they often lead to adverse autoimmunity.
View Article and Find Full Text PDFHow cell-to-cell copy number alterations that underpin genomic instability in human cancers drive genomic and phenotypic variation, and consequently the evolution of cancer, remains understudied. Here, by applying scaled single-cell whole-genome sequencing to wild-type, TP53-deficient and TP53-deficient;BRCA1-deficient or TP53-deficient;BRCA2-deficient mammary epithelial cells (13,818 genomes), and to primary triple-negative breast cancer (TNBC) and high-grade serous ovarian cancer (HGSC) cells (22,057 genomes), we identify three distinct 'foreground' mutational patterns that are defined by cell-to-cell structural variation. Cell- and clone-specific high-level amplifications, parallel haplotype-specific copy number alterations and copy number segment length variation (serrate structural variations) had measurable phenotypic and evolutionary consequences.
View Article and Find Full Text PDFVisual prostheses currently restore only limited vision. More research and pre-clinical work are required to improve the devices and stimulation strategies that are used to induce neural activity that results in visual perception. Evaluation of candidate strategies and devices requires an objective way to convert measured and modelled patterns of neural activity into a quantitative measure of visual acuity.
View Article and Find Full Text PDFObjectives: Thrombotic thrombocytopenic purpura (TTP) is a rare thrombotic microangiopathy (TMA) caused by ADAMTS13 deficiency with mortality of up to 90% in the absence of treatment, typically therapeutic plasma exchange (TPE). TTP presents similarly to other TMAs in which TPE is ineffective and associated with morbidity and additional costs. Thus, we sought to assess clinical and laboratory parameters differentiating TTP from other TMAs in our institution's catchment population.
View Article and Find Full Text PDFElectrical stimulation of neural tissue is used in both clinical and experimental devices to evoke a desired spatiotemporal pattern of neural activity. These devices induce a local field that drives neural activation, referred to as an activating function or generator signal. In visual prostheses, the spread of generator signal from each electrode within the neural tissue results in a spread of visual perception, referred to as a phosphene.
View Article and Find Full Text PDFThe tumour immune microenvironment is a crucial mediator of lung tumourigenesis, and characterizing the immune landscape of patient tumours may guide immunotherapy treatment regimens and uncover novel intervention points. We sought to identify the landscape of tumour-infiltrating immune cells in the context of long non-coding RNA (lncRNAs), known regulators of gene expression. We examined the lncRNA profiles of lung adenocarcinoma (LUAD) tumours by interrogating RNA sequencing data from microdissected and non-microdissected samples (BCCRC and TCGA).
View Article and Find Full Text PDFBackground And Aims: The Psychoactive Surveillance Consortium and Analysis Network (PSCAN) is a national network of academic emergency departments (ED), analytical toxicologists and pharmacologists that collects clinical data paired with biological samples to identify and improve treatments of medical conditions arising from use of new psychoactive substances (NPS). The aim of this study was to gather clinical data with paired drug identification from NPS users who presented to EDs within PSCAN during its first year (2016-17).
Design: Observational study involving patient records and biological samples.
Objective: Kidney Donor Profile Index (KDPI) and cold ischemic time (CIT) independently influence recipient outcomes after kidney transplantation; however, the compound effect of these variables on posttransplant outcomes is unknown.
Design: The Scientific Registry of Transplant Recipients database of deceased-donor kidney transplant recipients between January 2012 and December 2016 was reviewed. Recipients were stratified based on their KDPI (0%-20%, 21%-85%, 86%-100%) and then based on CIT (0-12, 13-24, 25-30, 31-36, ≥ 37 hours).
Background: Historically, there is perceived pressure to achieve therapeutic levels of tacrolimus quickly after heart transplant (HT). We evaluated the association between time within therapeutic tacrolimus range and time to therapeutic trough and rejection in the 30 days following HT.
Methods: This is a single-center retrospective cohort study of consecutive adult HT patients receiving immunosuppression.
Background: The tumor microenvironment (TME) is a complex mixture of tumor epithelium, stroma and immune cells, and the immune component of the TME is highly prognostic for tumor progression and patient outcome. In lung cancer, anti-PD-1 therapy significantly improves patient survival through activation of T cell cytotoxicity against tumor cells. Direct contact between CD8+ T cells and target cells is necessary for CD8+ T cell activity, indicating that spatial organization of immune cells within the TME reflects a critical process in anti-tumor immunity.
View Article and Find Full Text PDFT follicular helper cells (Tfh) play crucial roles in the development of humoral immunity. In the B cell-rich germinal center of lymphoid organs, they select for high-affinity B cells and aid in their maturation. While Tfh have known roles in B cell malignancies and have prognostic value in some epithelial cancers, their role in lung tumour initiation and development is unknown.
View Article and Find Full Text PDFObjective: Retinal prostheses provide visual perception via electrical stimulation of the retina using an implanted array of electrodes. The retinal activation resulting from each electrode is not point-like; instead each electrode introduces a spread of retinal activation that may overlap with activations from other electrodes. With most conventional stimulation strategies this overlap leads to image blur.
View Article and Find Full Text PDF20 years ago, accidental bisphenol A (BPA) exposure caused a sudden increase in chromosomally abnormal eggs from our control mice [1]. Subsequent rodent studies demonstrated developmental effects of exposure with repercussions on adult health and fertility (e.g.
View Article and Find Full Text PDFIntroduction: BK polyomavirus (BKPyV) continues to impact renal transplant recipients (RTR). The New England BK Consortium aims to jointly optimize screening and management of BKPyV.
Methods: Our first project was to survey centers' BKPyV screening protocols and compare them to consensus guidelines.
This work aims to characterize the performance of an improved 4DCT technique aiming to overcome irregular breathing-related image artifacts. To address this, we have developed respiratory motion guided (RMG) 4DCT, which uses real-time breathing motion analysis to prospectively gate scans based on detection of irregular breathing. This is the first investigation of RMG-4DCT using a real-time software prototype, testing the hypothesis that it can reduce breathing irregularities during imaging, reduce image oversampling and improve image quality compared to a 'conventional' 4DCT protocol without breathing guidance.
View Article and Find Full Text PDFAsynchrony among synaptic inputs may prevent a neuron from responding to behaviorally relevant sensory stimuli. For example, "octopus cells" are monaural neurons in the auditory brainstem of mammals that receive input from auditory nerve fibers (ANFs) representing a broad band of sound frequencies. Octopus cells are known to respond with finely timed action potentials at the onset of sounds despite the fact that due to the traveling wave delay in the cochlea, synaptic input from the auditory nerve is temporally diffuse.
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