Enhancing stroke risk and prognostic timeframe assessment with deep learning and a broad range of retinal biomarkers.

Stroke stands as a major global health issue, causing high death and disability rates and significant social and economic burdens. The effectiveness of existing stroke risk assessment methods is questionable due to their use of inconsistent and varying biomarkers, which may lead to unpredictable risk evaluations. This study introduces an automatic deep learning-based system for predicting stroke risk (both ischemic and hemorrhagic) and estimating the time frame of its occurrence, utilizing a comprehensive set of known retinal biomarkers from fundus images.

Microglia promote anti-tumour immunity and suppress breast cancer brain metastasis.

Breast cancer brain metastasis (BCBM) is a lethal disease with no effective treatments. Prior work has shown that brain cancers and metastases are densely infiltrated with anti-inflammatory, protumourigenic tumour-associated macrophages, but the role of brain-resident microglia remains controversial because they are challenging to discriminate from other tumour-associated macrophages. Using single-cell RNA sequencing, genetic and humanized mouse models, we specifically identify microglia and find that they play a distinct pro-inflammatory and tumour-suppressive role in BCBM.

Characterization of extracellular vesicles in COVID-19 infection during pregnancy.

SARS-CoV-2 infection may cause a severe inflammatory response, inflicting severe morbidity and mortality. This risk is modestly increased in pregnant patients. Despite the hypercoagulability and immunosuppression associated with pregnancy, most pregnant women experience a mild COVID-19 infection.

A spatially resolved single-cell genomic atlas of the adult human breast.

The adult human breast is comprised of an intricate network of epithelial ducts and lobules that are embedded in connective and adipose tissue. Although most previous studies have focused on the breast epithelial system, many of the non-epithelial cell types remain understudied. Here we constructed the comprehensive Human Breast Cell Atlas (HBCA) at single-cell and spatial resolution.

The Role of Extracellular Vesicles (EVs) in Chronic Graft vs. Host Disease, and the Potential Function of Placental Cell-Derived EVs as a Therapeutic Tool.

Chronic graft-versus-host disease (cGVHD) presents with dermal inflammation and fibrosis. We investigated the characteristics of extracellular vesicles (EVs) obtained from cGVHD patients, and their potential effects on human dermal fibroblast (NHDF) cells. The anti-inflammatory and anti-fibrotic effects of placental EVs were also explored given their known anti-inflammatory properties.

Extracellular Vesicles of COVID-19 Patients Reflect Inflammation, Thrombogenicity, and Disease Severity.

Severe COVID-19 infections present with cytokine storms, hypercoagulation, and acute respiratory distress syndrome, with extracellular vesicles (EVs) being involved in coagulation and inflammation. This study aimed to determine whether coagulation profiles and EVs reflect COVID-19 disease severity. Thirty-six patients with symptomatic COVID-19 infection with mild/moderate/severe disease (12 in each group) were analyzed.

Associations of maternal and placental extracellular vesicle miRNA with preeclampsia.

Gestational vascular complications (GVCs), including gestational hypertension and preeclampsia, are leading causes of maternal morbidity and mortality. Elevated levels of extracellular vesicles (EVs), in GVC have been linked to vascular injury. This study aims to characterize placental and circulating EV miRNA in GVCs, and explores the involvement of EV-miRNA in GVC, and whether they may be used to distinguish between placental and maternal pathologies.

Characterization of alternative mRNA splicing in cultured cell populations representing progressive stages of human fetal kidney development.

Nephrons are the functional units of the kidney. During kidney development, cells from the cap mesenchyme-a transient kidney-specific progenitor state-undergo a mesenchymal to epithelial transition (MET) and subsequently differentiate into the various epithelial cell types that create the tubular structures of the nephron. Faults in this transition can lead to a pediatric malignancy of the kidney called Wilms' tumor that mimics normal kidney development.

Evaluation of a New Neural Network Classifier for Diabetic Retinopathy.

Background: Medical image segmentation is a well-studied subject within the field of image processing. The goal of this research is to create an AI retinal screening grading system that is both accurate and fast. We introduce a new segmentation network which achieves state-of-the-art results on semantic segmentation of color fundus photographs.

Extracellular Vesicles Derived from Chimeric Antigen Receptor-T Cells: A Potential Therapy for Cancer.

Chimeric antigen receptor (CAR)-T cells are genetically engineered T cells, directed against a tumor-associated antigen. Extracellular vesicles (EVs) derived from CAR-T cells (CAR-T EVs) may preserve CAR-T activity and overcome one of the major obstacles responsible for CAR-T cell failure in patients with solid tumors. This study aimed to compare CAR-T EVs with their parental cells and explore their cell penetration and cytotoxic activity.

Thyroid doses in Ukraine due to I intake after the Chornobyl accident. Report II: dose estimates for the Ukrainian population.

This paper describes the revision of the thyroid dosimetry system in Ukraine using new, recently available data on (i) revised I thyroid activities derived from direct thyroid measurements done in May and June 1986 in 146,425 individuals; (ii) revised estimates of I ground deposition density in each Ukrainian settlement; and (iii) estimates of age- and gender-specific thyroid masses for the Ukrainian population. The revised dosimetry system estimates the thyroid doses for the residents of the settlements divided into three levels depending on the availability of measurements of I thyroid activity among their residents. Thyroid doses due to I intake were estimated in this study for different age and gender groups of residents of 30,353 settlements in 24 oblasts of Ukraine, Autonomous Republic Krym, and cities of Kyiv and Sevastopol.

Humoral response rate and predictors of response to BNT162b2 mRNA COVID19 vaccine in patients with multiple myeloma.

Multiple myeloma (MM) patients are at excess risk for clinically significant COVID19 infection. BNT162b2 mRNA COVID19 (BNT162b2) vaccine provides effective protection against COVID19 for the general population, yet its effect in MM patients may be compromised due to disease and therapy-related factors and was not yet evaluated. This single-centre prospective study included MM patients tested for serological response 14-21 days post second vaccine.

Mesencephalic astrocyte-derived neurotrophic factor is secreted from interferon-γ-activated tumor cells through ER calcium depletion.

The most successful immunotherapeutic agents are blocking antibodies to either programmed cell death-1 (PD-1), an inhibitory receptor expressed on T lymphocytes, or to its ligand, programmed cell death-ligand 1 (PD-L1). Nevertheless, many patients do not respond, and additional approaches, specifically blocking other inhibitory receptors on T cells, are being explored. Importantly, the source of the ligands for these receptors are often the tumor cells.

Thyroid doses in Ukraine due to I intake after the Chornobyl accident. Report I: revision of direct thyroid measurements.

The increased risk of thyroid cancer among individuals exposed during childhood and adolescence to Iodine-131 (I) is the main statistically significant long-term effect of the Chornobyl accident. Several radiation epidemiological studies have been carried out or are currently in progress in Ukraine, to assess the risk of radiation-related health effects in exposed populations. About 150,000 measurements of I thyroid activity, so-called 'direct thyroid measurements', performed in May-June 1986 in the Ukrainian population served as the main sources of data used to estimate thyroid doses to the individuals of these studies.

State-based targeted vaccination.

Vaccination has become one of the most prominent measures for preventing the spread of infectious diseases in modern times. However, mass vaccination of the population may not always be possible due to high costs, severe side effects, or shortage. Therefore, identifying individuals with a high potential of spreading the disease and targeted vaccination of these individuals is of high importance.

RECONSTRUCTION OF THE RADIOACTIVE CONTAMINATION OF THE TERRITORY OF UKRAINE BY IODINE-131 DURING INITIAL PERIOD OF THE CHORNOBYL ACCIDENT USING THE RESULTS FROM NUMERICAL MODEL WRF.

Objective: To reconstruct the 131I activity concentrations in air and 131I ground deposition densities from 26 April to7 May 1986 from the radioactivity release after the Chornobyl accident in the settlements of Ukraine using themesoscale radionuclides atmospheric transport model LEDI and meteorological information from the numericalweather forecast model WRF and to compare the obtained results with those calculated previously as well as withavailable measurements of 131I activity in soil.Object of research: the near-ground layer of the atmosphere and the surface of the territory of Ukraine radioactively contaminated as a result of the Chornobyl accident.Materials and methods of research.

Single-Cell RNA Sequencing Reveals mRNA Splice Isoform Switching during Kidney Development.

Background: During mammalian kidney development, nephron progenitors undergo a mesenchymal-to-epithelial transition and eventually differentiate into the various tubular segments of the nephron. Recently, Drop-seq single-cell RNA sequencing technology for measuring gene expression from thousands of individual cells identified the different cell types in the developing kidney. However, that analysis did not include the additional layer of heterogeneity that alternative mRNA splicing creates.

Preventive radioecological assessment of territory for optimization of monitoring and countermeasures after radiation accidents.

A methodology of a preventive radioecological assessment of the territory has been developed for optimizing post-emergency monitoring and countermeasure implementation in an event of a severe radiation accident. Approaches and main stages of integrated radioecological zoning of the territory are described. An algorithm for the assessment of the potential radioecological criticality (sensitivity) of the area is presented.

A brief review of single-cell transcriptomic technologies.

In recent years, there has been an effort to develop new technologies for measuring gene expression and sequence information from thousands of individual cells. Large data sets that were obtained using these 'single cell' technologies have allowed scientists to address fundamental questions in biomedicine ranging from stems cells and development to cancer and immunology. Here, we provide a brief review of recent developments in single-cell technology.

Role of PI4K and PI3K-AKT in ERK1/2 activation by GnRH in the pituitary gonadotropes.

The role of PI4K and PI3K-AKT in ERK1/2 activation by GnRH was examined. A relatively long preincubation (60 min) with wortmannin (10 nM and 10 μM), and LY294002 (10 μM and 100 μM) (doses known to inhibit PI3K and PI4K, respectively), were required to inhibit GnRH-and PMA-stimulated ERK1/2 activity in αT3-1 and LβT2 gonadotrope cells. A similar preincubation protocol was required to demonstrate inhibition of IGF-1-stimulated AKT activation lending support for the need of prolonged incubation (60 min) with wortmannin in contrast to other cellular systems.

Differential signaling of the GnRH receptor in pituitary gonadotrope cell lines and prostate cancer cell lines.

The GnRH receptor (GnRHR) mediates the pituitary functions of GnRH, as well as its anti-proliferative effects in sex hormone-dependent cancer cells. Here we compare the signaling of GnRHR in pituitary gonadotrope cell lines vs. prostate cancer cell lines.

Parkin promotes degradation of the mitochondrial pro-apoptotic ARTS protein.

Parkinson's disease (PD) is associated with excessive cell death causing selective loss of dopaminergic neurons. Dysfunction of the Ubiquitin Proteasome System (UPS) is associated with the pathophysiology of PD. Mutations in Parkin which impair its E3-ligase activity play a major role in the pathogenesis of inherited PD.

Peptides mimicking the unique ARTS-XIAP binding site promote apoptotic cell death in cultured cancer cells.

Purpose: XIAP [X-linked inhibitor of apoptosis (IAP) protein] is the best characterized mammalian caspase inhibitor. XIAP is frequently overexpressed in a variety of human tumors, and genetic inactivation of XIAP in mice protects against lymphoma. Therefore, XIAP is an attractive target for anticancer therapy.

X-linked Inhibitor of Apoptosis Protein promotes the degradation of its antagonist, the pro-apoptotic ARTS protein.

ARTS (Sept4_i2) is a mitochondrial pro-apoptotic tumor suppressor protein. In response to apoptotic signals, ARTS translocates to the cytosol where it promotes caspase activation through caspase de-repression and proteasome mediated degradation of X-linked Inhibitor of Apoptosis Protein (XIAP). Here we show that XIAP regulates the levels of ARTS by serving as its ubiquitin ligase, thereby providing a potential feedback mechanism to protect against unwanted apoptosis.

The IAP-antagonist ARTS initiates caspase activation upstream of cytochrome C and SMAC/Diablo.

ARTS (Sept4_i2) is a pro-apoptotic tumor suppressor protein that functions as an antagonist of X-linked IAP (XIAP) to promote apoptosis. It is generally thought that mitochondrial outer membrane permeabilization (MOMP) occurs before activation of caspases and is required for it. Here, we show that ARTS initiates caspase activation upstream of MOMP.