PHARAOH: A collaborative crowdsourcing platform for phenotyping and regional analysis of histology.

Deep learning has proven capable of automating key aspects of histopathologic analysis. However, its context-specific nature and continued reliance on large expert-annotated training datasets hinders the development of a critical mass of applications to garner widespread adoption in clinical/research workflows. Here, we present an online collaborative platform that streamlines tissue image annotation to promote the development and sharing of custom computer vision models for PHenotyping And Regional Analysis Of Histology (PHARAOH; https://www.

The Unholy Grail of cancer screening: or is it just about the Benjamins?

The biotechnology company Grail developed a non-invasive blood test (Galleri test) which is claimed to detect 50 types of cancer at early and potentially curable stages. The initially promising results from prospective studies, and the anticipated financial success of Grail led the sequencing giant Illumina to purchase Grail for $8 billion (2021). Following this event, Grail collaborated with the UK National Health System to further clarify the test's capability, in a 3-year prospective trial, along with the standard of care.

Antiviral activity of pyrazole derivatives bearing a hydroxyquinoline scaffold against SARS-CoV-2, HCoV-229E, MERS-CoV, and IBV propagation.

The ongoing global threat posed by coronaviruses necessitates the urgent development of effective antiviral agents. In this study, we investigated the potential of hydroxyquinoline-pyrazole candidates as antiviral agents against a range of coronaviruses, including SARS-CoV-2, MERS-CoV, and HCoV-229E. Molecular docking studies were conducted to assess the binding affinity of the synthesized compounds to key viral proteins.

Professional Master of Health Science in Laboratory Medicine: Training Clinical Laboratory Scientists in an Integrated Program at a Research-Intensive University.

A 2-year professional master of health science program at the University of Toronto provides a unique integrated educational program to train allied health science personnel to practice as physician extenders and health care professionals in two high-demand clinical laboratory disciplines, Pathologists' Assistant (PA) and Clinical Embryologist (CE). This report describes an integrated graduate program developed and delivered in a research-intensive laboratory medicine department. The core courses in fundamental biomedical science and in general medical laboratory function and operations formed the foundation on which the requisite clinical skills required to practice as a PA or CE were subsequently delivered as comprehensive CE and PA specialty courses and practicums.

Guidance for securing approvals for new biomarkers: from discovery to clinical implementation.

The journey of translating a molecular discovery into the clinic involves multiple steps and requires planning, time, effort, and money. In this review, we provide a quick guide on the technical and clinical validation parameters that are necessary for successful commercialization of molecular and other markers. We also briefly address the different options for regulatory approvals.

Glial fibrillary acidic protein, neurofilament light, matrix metalloprotease 3 and fatty acid binding protein 4 as non-invasive brain tumor biomarkers.

Background: Gliomas are aggressive malignant tumors, with poor prognosis. There is an unmet need for the discovery of new, non-invasive biomarkers for differential diagnosis, prognosis, and management of brain tumors. Our objective is to validate four plasma biomarkers - glial fibrillary acidic protein (GFAP), neurofilament light (NEFL), matrix metalloprotease 3 (MMP3) and fatty acid binding protein 4 (FABP4) - and compare them with established brain tumor molecular markers and survival.

Pathologist workload, burnout, and wellness: connecting the dots.

No standard tool to measure pathologist workload currently exists. An accurate measure of workload is needed for determining the number of pathologists to be hired, distributing the workload fairly among pathologists, and assessing the overall cost of pathology consults. Initially, simple tools such as counting cases or slides were used to give an estimate of the workload.

Computational pathology: an evolving concept.

The initial enthusiasm about computational pathology (CP) and artificial intelligence (AI) was that they will replace pathologists entirely on the way to fully automated diagnostics. It is becoming clear that currently this is not the immediate model to pursue. On top of the legal and regulatory complexities surrounding its implementation, the majority of tested machine learning (ML)-based predictive algorithms do not display the exquisite performance needed to render them unequivocal, standalone decision makers for matters with direct implications to human health.

Transforming diagnostics: The implementation of digital pathology in clinical laboratories.

Digital pathology (DP) has emerged as a cutting-edge technology that promises to revolutionise diagnostics in clinical laboratories. This perspective article explores the implementation planning and considerations of DP in a single multicentre institution in Canada, the University Health Network, discussing benefits, challenges, potential implications and considerations for future adopters. We examine the transition from traditional microscopy to digital slide scanning and its impact on pathology practice, patient care and medical research.

Evaluating the Effect of Lactobacillus casei FEGY 9973 and Curcumin on Experimental Giardiasis.

Background And Objective: Giardia is a parasitic hard protozoan that causes a variety of parasitological and pathological changes in gastrointestinal epithelial cells and is resistant to a variety of disinfectants and treatments. This study used experimental animals infected with Giardia Lamblia to assess the potential therapeutic effect of Lactobacillus casei, Lactobacillus bulgaricus (Lactobacillus in yoghurt) and curcumin in comparison to one of the commonly used drugs (metronidazole).

Methods: The study included 54 Syrian hamsters (Mesocricetus auratus) that ranged in weight from 80 to 100 g and were divided into six groups: The effect of the used preparations was assessed in terms of parasitological and histopathological aspects in Group I non-infected healthy control, Group II infected non-treated, Group III infected treated with metronidazole MTZ, Group IV infected treated with Lactobacillus casei, Group V infected treated with curcumin, and Group VI infected treated with, Lactobacillus bulgaricus (Lactobacillus in yoghurt).

ABCC2 brush-border expression predicts outcome in papillary renal cell carcinoma: a multi-institutional study of 254 cases.

Aims: Papillary renal cell carcinoma (PRCC) histologic subtyping is no longer recommended in the 2022 WHO classification. Currently, WHO/ISUP nucleolar grade is the only accepted prognostic histologic parameter for PRCC. ABCC2, a renal drug transporter, has been shown to significantly predict outcomes in PRCC.

Protective Effects of Polyphenol-Rich Extracts against Neurotoxicity Elicited by Paraquat or Rotenone in Cellular Models of Parkinson's Disease.

Parkinson's disease (PD) is a neurodegenerative disorder involving motor symptoms caused by a loss of dopaminergic neurons in the substantia nigra region of the brain. Epidemiological evidence suggests that anthocyanin (ANC) intake is associated with a low risk of PD. Previously, we reported that extracts enriched with ANC and proanthocyanidins (PAC) suppressed dopaminergic neuron death elicited by the PD-related toxin rotenone in a primary midbrain culture model.

Protective effects of polyphenol-rich extracts against neurotoxicity elicited by paraquat or rotenone in cellular models of Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder involving motor symptoms caused by a loss of dopaminergic neurons in the substantia nigra region of the brain. Epidemiological evidence suggests that anthocyanin (ANC) intake is associated with a low risk of PD. Previously, we reported that extracts enriched with ANC and proanthocyanidins (PAC) suppressed dopaminergic neuron death elicited by the PD-related toxin rotenone in a primary midbrain culture model.

Doxorubicin-Induced Platelet Activation and Clearance Relieved by Salvianolic Acid Compound: Novel Mechanism and Potential Therapy for Chemotherapy-Associated Thrombosis and Thrombocytopenia.

Doxorubicin (Dox) is a widely utilized chemotherapeutic; however, it carries side effects, including drug-induced immune thrombocytopenia (DITP) and increased risk of venous thromboembolism (VTE). Currently, the mechanisms for Dox-associated DITP and VTE are poorly understood, and an effective inhibitor to relieve these complications remains to be developed. In this study, we found that Dox significantly induced platelet activation and enhanced platelet phagocytosis by macrophages and accelerated platelet clearance.

CAP-ACP Workload Model for Advanced Diagnostics in Precision Medicine.

Objectives: In precision medicine, where oncologic management is tailored to the individual's clinical and genetic profiles, advanced diagnostic testing provides prognostic information and guides management in a growing number of malignancies. There is a need to capture the work pathologists perform to meet this demand by providing medically relevant, timely, and accurate testing results. This work includes not only direct patient consults (interpretation of results and issuing reports) but the administrative and medical oversight as well as the research needed to provide the necessary quality assurance, quality control, direction, and framework for the laboratory.

The Impact of Modifying Sunitinib Treatment Scheduling on Renal Cancer Tumor Biology and Resistance.

With sunitinib treatment of metastatic renal cell carcinoma, most patients end up developing resistance over time. Recent clinical trials have shown that individualizing treatment protocols could delay resistance and result in better outcomes. We developed an in vivo xenograft tumor model and compared tumor growth rate, morphological, and transcriptomic differences between alternative and traditional treatment schedules.

ABCC2 expression in papillary renal cell carcinoma provides better prognostic stratification than WHO/ISUP nucleolar grade.

Papillary renal cell carcinoma (PRCC) classification has traditionally been divided into two histologic types, type 1 and type 2. A new biological stratification system has recently been proposed based on comprehensive morphologic and genomic analysis. The predominant molecular marker in this 4-tiered stratification is the renal drug transporter ABCC2.

Disruptive innovations in the clinical laboratory: catching the wave of precision diagnostics.

Disruptive innovation is an invention that disrupts an existing market and creates a new one by providing a different set of values, which ultimately overtakes the existing market. Typically, when disruptive innovations are introduced, their performance is initially less than existing standard technologies, but because of their ability to bring the cost down, and with gradual improvement, they end up replacing established service standards.Disruptive technologies have their fingerprints in health care.

Addressing the Diagnostic Miscommunication in Pathology.

Objectives: The pathology report serves as a crucial communication tool among a number of stakeholders. It can sometimes be challenging to understand. A communication barrier exists among pathologists, other clinicians, and patients when interpreting the pathology report, leaving both clinicians and patients less empowered when making treatment decisions.

Percutaneous deep vein arterialization: An emerging technique for no-option chronic limb-threatening ischemia patients.

Chronic limb-threatening ischemia (CLTI), with characteristic ischemic rest pain, non-healing ulcers, or gangrene attributable to arterial occlusive disease, requires successful revascularization to minimize tissue loss. End-stage CLTI in particular, with occlusion of the pedal arteries, results in a lack of suitable targets for bypass and can result in failure of endovascular revascularization procedures, leaving no option for treatment other than amputation. With limb salvage as the primary goal, nontraditional revascularization techniques such as percutaneous deep vein arterialization (pDVA) may help minimize incidence of amputation.

Necessity and Challenges of Sample Preconcentration in Analysis of Multiple MicroRNAs by Capillary Electrophoresis.

Thousands of putative microRNA (miRNA)-based cancer biomarkers have been reported, but none has been validated for approval by the Food and Drug Administration. One of the reasons for this alarming discrepancy is the lack of a method that is sufficiently robust for carrying out validation studies, which may require analysis of samples from hundreds of patients across multiple institutions and pooling the results together. The capillary electrophoresis (CE)-based hybridization assay proved to be more robust than reversed transcription polymerase chain reaction (the current standard), but its limit of quantification (LOQ) exceeds 10 pM while miRNA concentrations in cell lysates are below 1 pM.

Reassessment of p53 immunohistochemistry thresholds in invasive high grade bladder cancer shows a better correlation with TP53 and FGFR3 mutations.

FGFR3 mutations are frequently mutually exclusive of TP53 mutations in invasive high grade urothelial carcinoma (HGUC) and p53 immunohistochemistry is often used as a surrogate for TP53 mutations. A 10 % staining cut off has been used in HGUC for designation as p53 positive or negative however, a novel contemporary method we have previously proposed (0% or >50 % - abnormal vs. 1-49 % - wild type) has shown significant correlation with oncologic outcome as well.

A Framework for Optimizing Technology-Enabled Diabetes and Cardiometabolic Care and Education: The Role of the Diabetes Care and Education Specialist.

Purpose: The purpose of this article is to present a framework for optimizing technology-enabled diabetes and cardiometabolic care and education using a standardized approach. This approach leverages the expertise of the diabetes care and education specialist, the multiplicity of technologies, and integration with the care team. Technology can offer increased opportunity to improve health outcomes while also offering conveniences for people with diabetes and cardiometabolic conditions.

Knowledge Translation in Oncology: The Bumpy Ride From Bench to Bedside.

Objectives: Knowledge translation (KT) is the dynamic process of mobilizing best-practice evidence to guide health care decisions.

Methods: Using a PubMed search, challenges were identified and milestones defined.

Results: Substantial challenges exist in integrating discoveries into patient care, including technical limitations related to genomic testing like turnaround time, standardization, reproducibility, and results interpretation.

Identification of Prognostic Biomarkers in the Urinary Peptidome of the Small Renal Mass.

Renal cell carcinoma (RCC) is often diagnosed incidentally as a small renal mass (SRM; pT1a, ≤4 cm). Increasing concerns surrounding the overtreatment of patients with benign or clinically silent SRMs has resulted in a recent shift in treatment recommendations, especially in elderly and infirm patients. There are currently no biomarkers that can predict progression.