Predicting cancer content in tiles of lung squamous cell carcinoma tumours with validation against pathologist labels.

Background: A growing body of research is using deep learning to explore the relationship between treatment biomarkers for lung cancer patients and cancer tissue morphology on digitized whole slide images (WSIs) of tumour resections. However, these WSIs typically contain non-cancer tissue, introducing noise during model training. As digital pathology models typically start with splitting WSIs into tiles, we propose a model that can be used to exclude non-cancer tiles from the WSIs of lung squamous cell carcinoma (SqCC) tumours.

Substituents' Effect on the Photophysics of Trinuclear Copper(I) and Silver(I) Pyrazolate-Phosphine Cages.

A series of structurally similar trinuclear macrocyclic copper(I) and silver(I) pyrazolate complexes bearing various short-bite diphosphine RPCH(R')PR ligands are reported. Upon diphosphine coordination, the planar geometry of the initial complexes undergoes bending along the line between two metal atoms coordinated to the phosphorus moieties. The complexes based on dcpm ligands (R = cyclohexyl, R' = H, Ph) do not exhibit dynamic behavior in solution at room temperature on the P NMR time scale as it was previously observed for similar trinuclear copper complexes bearing the dppm (R = Ph, R' = H) scaffold.

Neuroadaptive Biochemical Mechanisms of Remote Ischemic Conditioning.

This review summarizes the currently known biochemical neuroadaptive mechanisms of remote ischemic conditioning. In particular, it focuses on the significance of the pro-adaptive effects of remote ischemic conditioning which allow for the prevention of the neurological and cognitive impairments associated with hippocampal dysregulation after brain damage. The neuroimmunohumoral pathway transmitting a conditioning stimulus, as well as the molecular basis of the early and delayed phases of neuroprotection, including anti-apoptotic, anti-oxidant, and anti-inflammatory components, are also outlined.

Staying Online in Uncertain Times: A Nationwide Canadian Survey of Pathology Resident Uses of and Adaptations to Online Learning During COVID-19.

Context.—: Because of restrictions as a result of the COVID-19 pandemic, medical educators rapidly transitioned to an online curriculum for pathology resident education. The benefits and challenges of the shift to online learning, as well as strategies to maximize learning, are yet to be fully elucidated.

Differences in the Autophagy Response to Hypoxia in the Hippocampus and Neocortex of Rats.

Autophagy is a regulated mechanism of degradation of misfolded proteins and organelles in the cell. Neurons are highly differentiated cells with extended projections, and therefore, their functioning largely depends on the mechanisms of autophagy. For the first time in an animal model using immunohistochemistry, dot analysis, and qRT-PCR, the autophagy (macroautophagy) activity in neurons of two brain regions (hippocampus and neocortex) under normoxia and after exposure to hypoxia was studied.

Intermittent Hypoxic Training as an Effective Tool for Increasing the Adaptive Potential, Endurance and Working Capacity of the Brain.

This review is devoted to the phenomenon of intermittent hypoxic training and is aimed at drawing the attention of researchers to the necessity of studying the mechanisms mediating the positive, particularly neuroprotective, effects of hypoxic training at the molecular level. The review briefly describes the historical aspects of studying the beneficial effects of mild hypoxia, as well as the use of hypoxic training in medicine and sports. The physiological mechanisms of hypoxic adaptation, models of hypoxic training and their effectiveness are summarized, giving examples of their beneficial effects in various organs including the brain.

A Case of Li-Fraumeni Associated Thymoma.

Thymomas are among the most common cancers of the anterior mediastinum. They rarely occur in patients with Li-Fraumeni syndrome (LFS), a hereditary syndrome that predisposes individuals to cancer and is characterized by mutations in the tumor suppressor encoding gene . Here we describe a case of primary thymoma in a woman diagnosed with LFS.

A Survey on Changes to the Canadian Anatomical Pathology Certification Examination Due to Coronavirus Disease 2019 and Implications for Competency-Based Medical Education.

The coronavirus disease 2019 pandemic resulted in a dramatic change in the Royal College of Physicians and Surgeons of Canada assessment process through elimination of the oral and practical components of the 2020 Anatomical Pathology examination. Our study sought to determine stakeholder opinions and experiences on these changes in the context of the 2019 implementation of competency-based medical education. Surveys were designed for residents and practicing pathologists.

Mononuclear Copper(I) 3-(2-pyridyl)pyrazole Complexes: The Crucial Role of Phosphine on Photoluminescence.

A series of emissive Cu(I) cationic complexes with 3-(2-pyridyl)-5-phenyl-pyrazole and various phosphines: dppbz (), Xantphos (), DPEPhos (), PPh (), and BINAP () were designed and characterized. Complexes obtained exhibit bright yellow-green emission (ca. 520-650 nm) in the solid state with a wide range of QYs (1-78%) and lifetimes (19-119 µs) at 298 K.

Evaluation of an open-source machine-learning tool to quantify bone marrow plasma cells.

Aims: The objective of this study was to develop and validate an open-source digital pathology tool, QuPath, to automatically quantify CD138-positive bone marrow plasma cells (BMPCs).

Methods: We analysed CD138-scanned slides in QuPath. In the initial training phase, manual positive and negative cell counts were performed in representative areas of 10 bone marrow biopsies.

Long-Term Effects of Prenatal Severe Hypoxia on Central and Peripheral Components of the Glucocorticoid System in Rats.

Introduction: Prenatal hypoxia is a risk factor for the development of numerous neurological disorders. It is known that the maternal stress response to hypoxia determines the epigenetic impairment of the perinatal expression of glucocorticoid receptors (GR) in the hippocampus of the progeny, but so far no detailed study of how this affects the functional state of the glucocorticoid system during further ontogenesis has been performed.

Objective: The goal of the present study was to examine the long-term effects of the prenatal hypoxia on the functioning of the glucocorticoid system throughout life.

A Case of Synchronous Malignant and Benign Granular Cell Tumor of the Vulva.

Granular cell tumors (GCT) are rare soft tissue neoplasms, which seldom occur in the vulva. They are more commonly benign, but malignant GCT do occur. We report a case of a 50-yr-old postmenopausal woman who presented with a vulvar lesion that was diagnosed as GCT on biopsy.

Overexpression of Long Noncoding RNA HOTAIR Is a Unique Epigenetic Characteristic of Myxopapillary Ependymoma.

Ependymomas are a heterogeneous group of central nervous system tumors. Despite the recent advances, there are no specific biomarkers for ependymomas. In this study, we explored the role of homeobox (HOX) genes and long noncoding RNA (LncRNA) HOTAIR in ependymomas along the neural axis.

Explicit Dialogue About the Purpose of Hospital Admission Is Essential: How Different Perspectives Affect Teamwork, Trust, and Patient Care.

Purpose: The authors previously found that attending physicians conceptualize hospital admission purpose according to 3 perspectives: one focused dominantly on discharge, one on monitoring and managing chronic conditions, and one on optimizing overall patient health. Given implications of varying perspectives for patient care and team collaboration, this study explored how purpose of admission is negotiated and enacted within clinical teaching teams.

Method: Direct observations and field interviews took place in 2 internal medicine teaching units at 2 teaching hospitals in Ontario, Canada, in summer 2017.

[Applying remote ischemic pre- and postconditioning for the correction of experimental depression].

Aim: To assess antidepressant properties of remote ischemic limb pre- and post-conditioning.

Material And Methods: The study was performed with rats that were subjected to unavoidable aversive stress in the 'learned helplessness' paradigm for developing experimental depression, or were additional exposed to three brief episodes of ischemia/reperfusion of the limb before or after stressing.

Results: Remote ischemic preconditioning completely prevented depressive-like behavior and caused hyperactivation of the pituitary-adrenal hormonal axis.

Is It Time to Be More Explicit About the Purpose of a Hospital Admission?

Purpose: Patient care suffers when teaching teams fail to achieve a shared understanding of problems to be addressed during a hospital admission. In academic contexts where attending physicians take turns supervising, practice variability may contribute to undermining this shared understanding. Exploring variability around what constitutes the purpose of the hospital admission was the focus of this study.

Pathogenetic Role of the Stress-induced Release of Glucocorticoid Hormones in the Development of Post-traumatic Stress Disorder: An Experimental Study.

In the rat experimental model of posttraumatic stress disorder (PTSD), the level of blood corticosterone was at least eight-fold increased (an overrelease). The use of hypobaric hypoxic preconditioning or short-term inhibition of glucocorticoid synthesis by metyrapone injection prevented development of the experimental PTSD.

Predicting Outcomes of Hormone and Chemotherapy in the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) Study by Biochemically-inspired Machine Learning.

Genomic aberrations and gene expression-defined subtypes in the large METABRIC patient cohort have been used to stratify and predict survival. The present study used normalized gene expression signatures of paclitaxel drug response to predict outcome for different survival times in METABRIC patients receiving hormone (HT) and, in some cases, chemotherapy (CT) agents. This machine learning method, which distinguishes sensitivity vs.

Genomic signatures for paclitaxel and gemcitabine resistance in breast cancer derived by machine learning.

Increasingly, the effectiveness of adjuvant chemotherapy agents for breast cancer has been related to changes in the genomic profile of tumors. We investigated correspondence between growth inhibitory concentrations of paclitaxel and gemcitabine (GI50) and gene copy number, mutation, and expression first in breast cancer cell lines and then in patients. Genes encoding direct targets of these drugs, metabolizing enzymes, transporters, and those previously associated with chemoresistance to paclitaxel (n = 31 genes) or gemcitabine (n = 18) were analyzed.

[Pattern of neuronal expression of transcription factors NF-kappaB under different modes of hypobaric hypoxia].

Transcription factor NF-kappaB plays a pivotal role in mechanisms of brain neuron survival and degeneration under injurious stimuli, first of all different types of hypoxia. In the present work, using quantitative immunohystochemistry, we provide analysis of expression of different subunits of NF-kappaB (p65 and c-Rel) in the rat neocortex in response to severe injurious hypobaric hypoxia (HH) or after a single or multiple sessions of mild protective HH. Severe hypoxia (SH), resulting in loss of brain neurons, has no effect on the level of expression of p65 but suppresses expression of c-Rel.

[Involvement of transcriptional factor induced by hypoxia in the neuronal mechanisms of adaptation to psychoemotional and hypoxic stress].

Using quantitative immunohistochemistry, neuronal expression of alpha-subunit of the transcriptional factor HIF-1 in hippocampus and neocortex of rats in response to pathogenic psychoemotional (model of posttraumatic stress disorder, PTSD) and hypoxic (severe hypobaric hypoxia, 180 Torr, 3 h), as well as to neuroprotective exposures to hypoxic pre- and postconditioning has been studied. Elongated overexpression of HIF-1alpha in hippocampus and neocortex of rats in response to the psychoemotional stress in PTSD paradigm, but not hypoxic stress, has been observed. Hypoxic pre- and postconditioning with mild hypobaric hypoxia (360 Torr, 2 h, 3 trials spaced at 24 h), those induced adaptation to the psychoemotional stress, abolished the elongated HIF-1alpha overexpression.

Antidepressant effect of hypoxic preconditioning is associated with modification of expression of transcription factor c-Fos in rat brain in response to unavoidable stress.

Development of post-stress depression in rats was accompanied by long-term moderate activation of the expression of transcription factor c-Fos in the neocortex, hippocampus, and paraventricular nucleus of the hypothalamus. Hypoxic preconditioning preventing depressive state in rats under conditions of unavoidable stress considerably enhanced c-Fos expression in the studied brain regions during the early stages of stress response (days 1-5) and promoted its normalization at later terms (10 days). Disturbances in the wavy dynamics of c-Fos expression can contribute to the pathogenic mechanisms of depression, in particular and induce hyperproduction of hypothalamic neurohormone corticoliberin, whereas potentiation of early expression of this factor in response to stress is obviously necessary for prevention of post-stress disorders.

Effects of hypoxic preconditioning on expression of transcription factor NGFI-A in the rat brain after unavoidable stress in the "learned helplessness" model.

We report here our immunocytochemical studies establishing that the development of a depression-like state in rats following unavoidable stress in a "learned helplessness" model is accompanied by stable activation of the expression of transcription factor NGFI-A in the dorsal hippocampus (field CA1) and the magnocellular paraventricular nucleus of the hypothalamus, along with an early wave of post-stress expression, which died down rapidly, in the ventral hippocampus (the dentate gyrus) and a long period of up to five days of high-level expression in the neocortex. In rats subjected to three sessions of preconditioning consisting of moderate hypobaric hypoxia (360 mmHg, 2 h, with intervals of 24 h), which did not form depression in these circumstances, there were significant changes in the dynamics of immunoreactive protein content in the hippocampus, with a stable increase in expression in the ventral hippocampus and only transient and delayed (by five days) expression in field CA1. In the neocortex (layer II), preconditioning eliminated the effects of stress, preventing prolongation of the first wave of NGFI-A expression to five days, while in the magnocellular hypothalamus, conversely, preconditioning stimulated a second (delayed) wave of the expression of this transcription factor.

Mild hypobaric hypoxia preconditioning up-regulates expression of transcription factors c-Fos and NGFI-A in rat neocortex and hippocampus.

Transcription factors c-Fos and NGFI-A encoded by immediate early genes largely participate in the biochemical cascade leading to genomically driven lasting adaptation by neurons to injurious exposures including hypoxia/ischemia. Present study was designed to examine the involvement of c-Fos and NGFI-A in the development of brain hypoxic tolerance induced by mild hypoxic preconditioning. Earlier we have reported that preconditioning by repetitive mild hypobaric hypoxia (MHH) considerably increases neuronal resistance to subsequent severe injurious exposures.

[The hypoxic preconditioning effect upon expression of the NGFI-A transcription factor in the rat brain following an unavoidable stess in the "learned helpnessness" model].

In this study, by an immunocytochemistry it is established that development of the depression after an inescapable stress in the learned helplessness model in rats is associated with stable induction of the transcription factor NGFI-A in the dorsal hippocampus (CA1 field) and in the paraventricular hypothalamic magnocellular nucleus (PVNm), as well as with rapid and transient stress-induced expression of NGFI-A in the dentate gyrus and, supported on high level till 5 days, in the neocortex. Hypoxic preconditioning using mild repetitive hypobaric hypoxia (360 Torr for 2 hrs each of 3 days) prevented development of the depressive state in rats, and considerably changed the dynamics of the NGFI-A immunoreactivity in the hippocampus: the stable increase of an expression in the dentate gyrus and only transitory and delayed (for 5 day) in the CA1 field was detected. In the neocortex (Layer II) the stress influence was levelled with preconditioning by preventing the prolongation of the first wave of expression NGFI-A untill 5 days, and in PVNm, on the contrary, was stimulated the second (delayed) wave of an expression of this transcription factor.