Application of deep learning to understand resilience to Alzheimer's disease pathology.

People who have Alzheimer's disease neuropathologic change (ADNC) typically associated with dementia but not the associated cognitive decline can be considered to be "resilient" to the effects of ADNC. We have previously reported lower neocortical levels of hyperphosphorylated tau (pTau) and less limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) in the resilient participants compared to those with dementia and similar ADNC as determined by current NIA-AA recommendations using traditional semi-quantitative assessments of amyloid β and pathological tau burden. To better understand differences between AD-dementia and resilient participants, we developed and applied a deep learning approach to analyze the neuropathology of 14 brain donors from the Adult Changes in Thought study, including seven stringently defined resilient participants and seven age-matched AD-dementia controls.

Rapid Validation of Telepathology by an Academic Neuropathology Practice During the COVID-19 Pandemic.

Context.—: The coronavirus disease 19 (COVID-19) pandemic is placing unparalleled burdens on regional and institutional resources in medical facilities across the globe. This disruption is causing unprecedented downstream effects to traditionally established channels of patient care delivery, including those of essential anatomic pathology services.

Resistance and resilience to Alzheimer's disease pathology are associated with reduced cortical pTau and absence of limbic-predominant age-related TDP-43 encephalopathy in a community-based cohort.

Alzheimer's disease neuropathologic change (ADNC) is defined by progressive accumulation of β-amyloid plaques and hyperphosphorylated tau (pTau) neurofibrillary tangles across diverse regions of brain. Non-demented individuals who reach advanced age without significant ADNC are considered to be resistant to AD, while those burdened with ADNC are considered to be resilient. Understanding mechanisms underlying ADNC resistance and resilience may provide important clues to treating and/or preventing AD associated dementia.

Signature maps for automatic identification of prostate cancer from colorimetric analysis of H&E- and IHC-stained histopathological specimens.

Prostate cancer (PCa) is a major cause of cancer death among men. The histopathological examination of post-surgical prostate specimens and manual annotation of PCa not only allow for detailed assessment of disease characteristics and extent, but also supply the ground truth for developing of computer-aided diagnosis (CAD) systems for PCa detection before definitive treatment. As manual cancer annotation is tedious and subjective, there have been a number of publications describing methods for automating the procedure via the analysis of digitized whole-slide images (WSIs).

NDER: A Novel Web Application for Teaching Histology to Medical Students.

Medical students require a strong foundation in normal histology. However, current trends in medical school curricula have diminished time devoted to histology. Thus, there is a need for more efficient methods of teaching histology.

Safe and Effective Sarcoma Therapy through Bispecific Targeting of EGFR and uPAR.

Sarcomas differ from carcinomas in their mesenchymal origin. Therapeutic advancements have come slowly, so alternative drugs and models are urgently needed. These studies report a new drug for sarcomas that simultaneously targets both tumor and tumor neovasculature.

NDER: A novel web application using annotated whole slide images for rapid improvements in human pattern recognition.

Context: Whole-slide images (WSIs) present a rich source of information for education, training, and quality assurance. However, they are often used in a fashion similar to glass slides rather than in novel ways that leverage the advantages of WSI. We have created a pipeline to transform annotated WSI into pattern recognition training, and quality assurance web application called novel diagnostic electronic resource (NDER).

Quantitative comparison and reproducibility of pathologist scoring and digital image analysis of estrogen receptor β2 immunohistochemistry in prostate cancer.

Background: Digital image analysis offers advantages over traditional pathologist visual scoring of immunohistochemistry, although few studies examining the correlation and reproducibility of these methods have been performed in prostate cancer. We evaluated the correlation between digital image analysis (continuous variable data) and pathologist visual scoring (quasi-continuous variable data), reproducibility of each method, and association of digital image analysis methods with outcomes using prostate cancer tissue microarrays (TMAs) stained for estrogen receptor-β2 (ERβ2).

Methods: Prostate cancer TMAs were digitized and evaluated by pathologist visual scoring versus digital image analysis for ERβ2 staining within tumor epithelium.

Detection of Prostate Cancer: Quantitative Multiparametric MR Imaging Models Developed Using Registered Correlative Histopathology.

Purpose To develop multiparametric magnetic resonance (MR) imaging models to generate a quantitative, user-independent, voxel-wise composite biomarker score (CBS) for detection of prostate cancer by using coregistered correlative histopathologic results, and to compare performance of CBS-based detection with that of single quantitative MR imaging parameters. Materials and Methods Institutional review board approval and informed consent were obtained. Patients with a diagnosis of prostate cancer underwent multiparametric MR imaging before surgery for treatment.

Multisite assessment of NIA-AA guidelines for the neuropathologic evaluation of Alzheimer's disease.

Introduction: Neuropathologic assessment is the current "gold standard" for evaluating the Alzheimer's disease (AD), but there is no consensus on the methods used.

Methods: Fifteen unstained slides (8 brain regions) from each of the 14 cases were prepared and distributed to 10 different National Institute on Aging AD Centers for application of usual staining and evaluation following recently revised guidelines for AD neuropathologic change.

Results: Current practice used in the AD Centers Program achieved robustly excellent agreement for the severity score for AD neuropathologic change (average weighted κ = .

Evaluation of protein biomarkers of prostate cancer aggressiveness.

Background: Prognostic multibiomarker signatures in prostate cancer (PCa) may improve patient management and provide a bridge for developing novel therapeutics and imaging methods. Our objective was to evaluate the association between expression of 33 candidate protein biomarkers and time to biochemical failure (BF) after prostatectomy.

Methods: PCa tissue microarrays were constructed representing 160 patients for whom clinicopathologic features and follow-up data after surgery were available.

Elevated hyaluronan and hyaluronan-mediated motility receptor are associated with biochemical failure in patients with intermediate-grade prostate tumors.

Background: The clinical course of prostate cancer (PCa) measured by biochemical failure (BF) after prostatectomy remains unpredictable in many patients, particularly in intermediate Gleason score (GS) 7 tumors, suggesting that identification of molecular mechanisms associated with aggressive PCa biology may be exploited for improved prognostication or therapy. Hyaluronan (HA) is a high molecular weight polyanionic carbohydrate produced by synthases (HAS1 through HAS3) and fragmented by oxidative/nitrosative stress and hyaluronidases (HYAL1 through HYAL4, SPAM1) common in PCa microenvironments. HA and HA fragments interact with receptors CD44 and hyaluronan-mediated motility receptor (HMMR), resulting in increased tumor aggressiveness in experimental PCa models.

Expression of FAP, ADAM12, WISP1, and SOX11 is heterogeneous in aggressive fibromatosis and spatially relates to the histologic features of tumor activity.

Aggressive fibromatosis (AF) represents a group of tumors with a variable and unpredictable clinical course, characterized by a monoclonal proliferation of myofibroblastic cells. The optimal treatment for AF remains unclear. Identification and validation of genes whose expression patterns are associated with AF may elucidate biological mechanisms in AF, and aid treatment selection.

Correlation between HER2 determined by fluorescence in situ hybridization and reverse transcription-polymerase chain reaction of the oncotype DX test.

The human epidermal growth factor receptor 2 (HER2) gene is amplified and its protein product overexpressed in about 20% of invasive breast cancers. Despite more than a decade of efforts to standardize HER2 testing, controversy persists regarding the most optimal testing method. Recently, Oncotype DX reports have begun including HER2 results in addition to the previously reported Recurrence Score.

Quantitative comparison of immunohistochemical staining measured by digital image analysis versus pathologist visual scoring.

Unlabelled: Immunohistochemical (IHC) assays performed on formalin-fixed paraffin-embedded (FFPE) tissue sections traditionally have been semi-quantified by pathologist visual scoring of staining. IHC is useful for validating biomarkers discovered through genomics methods as large clinical repositories of FFPE specimens support the construction of tissue microarrays (TMAs) for high throughput studies. Due to the ubiquitous availability of IHC techniques in clinical laboratories, validated IHC biomarkers may be translated readily into clinical use.

Development of multigene expression signature maps at the protein level from digitized immunohistochemistry slides.

Molecular classification of diseases based on multigene expression signatures is increasingly used for diagnosis, prognosis, and prediction of response to therapy. Immunohistochemistry (IHC) is an optimal method for validating expression signatures obtained using high-throughput genomics techniques since IHC allows a pathologist to examine gene expression at the protein level within the context of histologically interpretable tissue sections. Additionally, validated IHC assays may be readily implemented as clinical tests since IHC is performed on routinely processed clinical tissue samples.

Time trends in fungal infections as a cause of death in hematopoietic stem cell transplant recipients: an autopsy study.

Infectious complications remain an important cause of death in hematopoietic stem cell transplant (HSCT) recipients. We undertook a 20-year (1988-2007) retrospective review of all autopsies performed on HSCT recipients in our institution, with emphasis on infections, especially fungal infections, as the cause of death. Of the 2,943 autopsies performed in our institution from 1988 to 2007, 395 (13.

Visual estimates of nucleus-to-nucleus ratios: can we trust our eyes to use the Bethesda ASCUS and LSIL size criteria?

Background: Apart from several subjective criteria, ASCUS and LSIL are defined by nuclear enlargement of 2.5x to 3x and > or = 3x the area of a normal intermediate squamous cell nucleus, respectively. The aim of this study was to assess the ability of observers with various degrees of experience to estimate nuclear area ratios.