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.

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).

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.

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.

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.