Abstract Mitosis is a critical criterion for meningioma grading. However, pathologists’ assessment of mitoses subject to significant inter-observer variation due challenges in locating mitosis hotspots and accurately detecting mitotic figures. To address this issue, we leverage digital pathology propose computational strategy enhance assessment. The has two components: (1) A depth-first search algorithm that quantifies the mathematically maximum count 10 consecutive high-power fields, which...

Photoreceptors are compartmentalized neurons in which all proteins responsible for evoking visual signals confined to the outer segment. Yet, mechanisms establishing and maintaining photoreceptor compartmentalization poorly understood. Here we investigated targeting of two related membrane proteins, R9AP syntaxin 3, one residing within other excluded from Surprisingly, have found that only 3 has information encoded its sequence removal redirects this protein Furthermore, endoplasmic...

Mutations in rhodopsin cause retinitis pigmentosa humans and retinal degeneration a multitude of other animals. We utilized high-resolution live imaging the large rod photoreceptors from transgenic frogs (Xenopus) to compare properties fluorescently tagged rhodopsin, Rho-EGFP, RhoP23H-EGFP. The mutant was abnormally distributed both inner outer segments (OS), accumulating OS concentration ∼0.1% compared endogenous opsin. RhoP23H-EGFP formed dense fluorescent foci, with concentrations protein...

Artificial Intelligence (AI) brings advancements to support pathologists in navigating high-resolution tumor images search for pathology patterns of interest. However, existing AI-assisted tools have not realized this promised potential due a lack insight into and HCI considerations pathologists' navigation workflows practice. We first conducted formative study with six medical professionals capture their strategies. By incorporating our observations along the domain knowledge, we designed...

Aging increases the risk for Alzheimer's disease (AD), driving pathological changes like amyloid-β (Aβ) buildup, inflammation, and oxidative stress, especially in prefrontal cortex (PFC). We present first subcellular-resolution spatial transcriptome atlas of human (PFC), generated with Stereo-seq from six male AD cases at varying neuropathological stages age-matched controls. Our analyses revealed distinct transcriptional alterations across PFC layers, highlighted disruptions laminar...

Z-stack scanning is an emerging whole slide imaging technology that captures multiple focal planes alongside the z-axis of a glass slide. Because z-stacking can offer enhanced depth information compared to single-layer imaging, this be particularly useful in analyzing small-scaled histopathological patterns. However, its actual clinical impact remains debated with mixed results. To clarify this, we investigate effect z-stack on artificial intelligence (AI) mitosis detection meningiomas. With...

Alzheimer's disease (AD) is characterized by the progressive spread of tau pathology throughout brain. Inflammation has been demonstrated to be present in state as well changes endocytic trafficking. Here we identify Rab7 effector RILP, a protein at intersection inflammatory states and trafficking, novel player propagation. We show that RILP cleaved AD brain this cleavage correlates increases hyperphosphorylated tau. Cleavage can induced both BE(2) neuron-like cells microglia cell line when...

Recent developments in AI have provided assisting tools to support pathologists’ diagnoses. However, it remains challenging incorporate such into practice; one main concern is AI’s insufficient workflow integration with medical decisions. We observed examination and discovered that the hindering factor integrate its incompatibility workflow. To bridge gap between pathologists AI, we developed a human-AI collaborative diagnosis tool— xPath —that shares similar process of pathologists, which...

Mitochondrial dysfunction is observed in Alzheimer's disease (AD). However, the relationship between functional mitochondrial deficits and AD pathologies not well established human subjects.Post-mortem brain tissue from 11 non-demented (ND) 12 subjects was used to examine electron transport chain (ETC) function. Data were analyzed by neuropathology diagnosis Apolipoprotein E (APOE) genotype. Relationships pathology function determined.AD had reductions cytochrome oxidase (COX) complex II...

The retina is among the most metabolically active tissues in body, requiring a constant supply of blood glucose to sustain function. We assessed impact low on vision C57BL/6J mice rendered hypoglycemic by null mutation glucagon receptor gene, Gcgr. Metabolic stress from moderate hypoglycemia led late-onset loss retinal function Gcgr(-/-) mice, visual acuity, and eventual death cells. Retinal measured electroretinogram b-wave threshold declined >100-fold age 9 13 months, whereas decreases...

Background: Alzheimer’s disease (AD) brains accumulate DNA double-strand breaks (DSBs), which could contribute to neurodegeneration and dysfunction. The genomic distribution of AD brain DSBs is unclear. Objective: To map genome-wide DSB distributions in age-matched control brains. Methods: We obtained autopsy tissue from 3 individuals. donors were men between the ages 78 91. Nuclei extracted frontal cortex subjected Cleavage Under Targets & Release Using Nuclease (CUT&RUN) assay with...

Background: DNA breaks accumulate in Alzheimer’s disease (AD) brains. While their role as true genomic lesions is recognized, also support cognitive function by facilitating the expression of activity-dependent immediate early genes. This process involves TOP2B, a topoisomerase that catalyzes formation double-strand breaks. Objective: To characterize how AD impacts adaptive at nervous system Methods: We leveraged ability single- and to activate poly(ADP-ribose) polymerases (PARPs) conjugate...

The P23H mutation in rhodopsin (Rho(P23H)) is a prevalent cause of autosomal dominant retinitis pigmentosa. We examined the role ER stress proteins, Chop and Ask1, regulating death rod photoreceptors mouse line harboring Rho(P23H) transgene (GHL(+)). used knockout mice models to determine whether Ask1 regulate survival or retinal degeneration. Electrophysiological recordings showed similar responses sensitivities for GHL(+), GHL(+)/Chop(-/-) GHL(+)/Ask1(-/-) animals between 4-28 weeks, by...

Objective To evaluate the ability of contrast sensitivity (CS) to discriminate loss visual function in diabetic subjects with no clinical signs retinopathy relative that normal subjects. Research design and methods In this prospective cross-sectional study, we measured CS 46 a mean age 48±6 years, best-corrected acuity 20/20 retinopathy. The these was compared measurements control at four spatial frequencies (3, 6, 12, 18 cycles per degree) under moderate (500 lux) dim (less than 2...

PDE6 (phosphodiesterase-6) is the effector molecule in vertebrate phototransduction cascade. Progress understanding structure and function of has been hindered by lack an expression system enzyme. Here we report ectopic analysis compartmentalization membrane dynamics enhanced green fluorescent protein (EGFP) fusion human cone PDE6C rods transgenic Xenopus laevis. EGFP-PDE6C correctly targeted to rod outer segments Xenopus, where it displayed a characteristic striated pattern EGFP...

G protein–coupled receptor (GPCR) cascades rely on membrane protein diffusion for signaling and are generally found in spatially constrained subcellular microcompartments. How the geometry of these microcompartments impacts cascade activities, however, is not understood, primarily because inability current live cell–imaging technologies to resolve small structures. Here, we examine dynamics GPCR rhodopsin within discrete photoreceptors using a novel high resolution approach. Rhodopsin fused...

We examined the impact of an APOE ε4 genotype on Alzheimer's disease (AD) subject platelet and lymphocyte metabolism. Mean mitochondrial cytochrome oxidase Vmax activity was lower in carriers Annexin V, a marker apoptosis, significantly higher. Proteins that mediate mitophagy energy sensing were higher lymphocytes which could represent compensatory changes recapitulate phenomena observed post-mortem AD brains. Analysis lipid synthesis pathway found AceCSI, ATP CL, phosphorylated ACC levels...

Mitochondrial dysfunction is observed in Alzheimer's disease (AD). Altered mitochondrial respiration, cytochrome oxidase (COX) Vmax, and mitophagy are human subjects animal models of AD. Models derived from induced pluripotent stem cells (iPSCs) may not recapitulate these phenotypes after reprogramming differentiated adult cells.We examined function across iPSC including cerebral organoids, forebrain neurons, astrocytes. iPSCs were reprogrammed fibroblasts either the University Kansas...

Pathology is a fundamental element of modern medicine that determines the final diagnosis medical conditions, leads decisions, and portrays prognosis. Due to continuous improvements in AI capabilities (e.g., object recognition image processing), intelligent systems are bound play key role augmenting pathology research clinical practices. Despite pervasive deployment computational approaches similar fields such as radiology, there has been less success integrating practices histopathological...

Cavernous angiomas (CAs) are benign vascular malformations predominantly seen in the brain parenchyma and therefore referred to as intra-axial. Extra-axial dural-based cavernous angiomas, on other hand, rare lesions found outside of parenchyma. They occur middle fossa may be easily misdiagnosed meningiomas due their extra-axial location. In addition, CAs that located fossa, such convexity, have a better prognosis since they more surgically accessible. Surgical resection is main treatment...

This demo presents a human-AI collaborative system to assist pathologists in examining the pathological pattern of mitosis, critical factor tumor diagnosis. Traditionally, face challenges assessing mitoses due task's inherent complexity. The demonstrated aims address problem by designing an enhanced human-artificial intelligence workflow. Firstly, it can guide pathologist user regions interest that have flexible morphologies. Then, inside each region interest, highlights AI-detected mitosis...

Recent studies have explored the spatial transcriptomics patterns of Alzheimer's disease (AD) brain by sequencing in mouse models, enabling identification unique genome-wide transcriptomic features associated with different regions and pathological status. However, dynamics gene interactions that occur during amyloid-β accumulation remain largely unknown. In this study, we performed analyses on ligand-receptor communication, transcription factor regulatory network, spot-specific network to...