Software implementation of the main cluster analysis tools

This article discusses an approach to creating a complex of programs for the implementation of cluster analysis methods. A number of cluster analysis tools for processing the initial data set and their software implementation are analyzed, as well as the complexity of the application of cluster data analysis. An approach to data is generalized from the point of view of factual material that supplies information for the problem under study and is the basis for discussion, analysis and decision-making. Cluster analysis is a procedure that combines objects or variables into groups based on a given rule. The work provides a grouping of multivariate data using proximity measures such as sample correlation coefficient and its module, cosine of the angle between vectors and Euclidean distance. The authors proposed a method for grouping by centers, by the nearest neighbor and by selected standards. The results can be used by analysts in the process of creating a data analysis structure and will improve the efficiency of clustering algorithms. The practical significance of the results of the application of the developed algorithms is expressed in the software package created by means of the C ++ language in the VS environment

Scientific, institutional and personal rivalries among Soviet geographers in the late Stalin era

Scientific, institutional and personal rivalries between three key centres of geographical research and scholarship (the Academy of Sciences Institute of Geography and the Faculties of Geography at Moscow and Leningrad State Universities) are surveyed for the period from 1945 to the early 1950s. It is argued that the debates and rivalries between members of the three institutions appear to have been motivated by a variety of scientific, ideological, institutional and personal factors, but that genuine scientific disagreements were at least as important as political and ideological factors in influencing the course of the debates and in determining their final outcome

Comparative assessment of the diagnostic value of echocardiography and magnetic resonance imaging in determining myocardial viability

Aim. To compare myocardial imaging methods in patients with complicated coronary artery disease with significantly decreased myocardial contractility.Material and methods. This single-center retrospective study included 109 patients with complicated coronary artery disease who underwent surgical treatment between 2014 and 2020. All patients had indications for delayed contrast-enhanced cardiac magnetic resonance imaging (MRI) in order to determine myocardial viability due to a pronounced decrease in left ventricular contractility according to echocardiography (ejection fraction (EF) ≤30%).Results. Impairment of local contractility according to MRI and echocardiography significantly correlates with depth of contrast accumulation (p=0,0000000018 and p=0,0000034, respectively). Delayed contrast-enhanced cardiac MRI with cine sequences allows to determine higher number of impaired contractility cases compared with echocardiography (p=0,000006).Conclusion. MRI with cine sequence allowed to determine higher number of impaired contractility cases compared with echocardiography. Delayed contrastenhanced MRI is a reliably more sensitive method than electrocardiography in detecting left ventricular scarring. The depth of contrast agent accumulation correlates with local contractility impairment detected by echocardiography and delayed contrast-enhanced cardiac MRI

Cystatin C Deficiency Promotes Epidermal Dysplasia in K14-HPV16 Transgenic Mice

Cysteine protease cathepsins are important in extracellular matrix protein degradation, cell apoptosis, and angiogenesis. Mice lacking cathepsins are protected from tumor progression in several animal models, suggesting that the regulation of cathepsin activities controls the growth of various malignant tumors.We tested the role of cathepsins using a mouse model of multistage epithelial carcinogenesis, in which the human keratin-14 promoter/enhancer drove the expression of human papillomavirus type 16 (HPV16) early region E6/E7 transgenes. During the progression of premalignant dysplasia, we observed increased expression of cysteine protease cathepsin S, but concomitantly reduced expression of cathepsin endogenous inhibitor cystatin C in the skin tissue extract. Absence of cystatin C in these transgenic mice resulted in more progression of dysplasia to carcinoma in situ on the face, ear, chest, and tail. Chest and ear skin extract real time PCR and immunoblot analysis, mouse serum sample ELISA, tissue immunohistological analysis, and tissue extract-mediated in vitro elastinolysis and collagenolysis assays demonstrated that cystatin C deficiency significantly increased cathepsin expression and activity. In skin from both the chest and ear, we found that the absence of cystatin C reduced epithelial cell apoptosis but increased proliferation. From the same tissue preparations, we detected significantly higher levels of pro-angiogenic laminin 5-derived γ2 peptides and concurrently increased neovascularization in cystatin C-deficient mice, compared to those from wild-type control mice.Enhanced cathepsin expression and activity in cystatin C-deficient mice contributed to the progression of dysplasia by altering premalignant tissue epithelial proliferation, apoptosis, and neovascularization

Human macrophage foam cells degrade atherosclerotic plaques through cathepsin K mediated processes

<p>Abstract</p> <p>Background</p> <p>Proteolytic degradation of Type I Collagen by proteases may play an important role in remodeling of atherosclerotic plaques, contributing to increased risk of plaque rupture.</p> <p>The aim of the current study was to investigate whether human macrophage foam cells degrade the extracellular matrix (ECM) of atherosclerotic plaques by cathepsin K mediated processes.</p> <p>Methods</p> <p>We 1) cultured human macrophages on ECM and measured cathepsin K generated fragments of type I collagen (C-terminal fragments of Type I collagen (CTX-I) 2) investigated the presence of CTX-I in human coronary arteries and 3) finally investigated the clinical potential by measuring circulating CTX-I in women with and without radiographic evidence of aortic calcified atherosclerosis.</p> <p>Results</p> <p>Immune-histochemistry of early and advanced lesions of coronary arteries demonstrated co-localization of Cathepsin-K and CTX-I in areas of intimal hyperplasia and in shoulder regions of advanced plaques. Treatment of human monocytes with M-CSF or M-CSF+LDL generated macrophages and foam cells producing CTX-I when cultured on type I collagen enriched matrix. Circulating levels of CTX-I were not significantly different in women with aortic calcifications compared to those without.</p> <p>Conclusions</p> <p>Human macrophage foam cells degrade the atherosclerotic plaques though cathepsin K mediated processes, resulting in increase in levels of CTX-I. Serum CTX-I was not elevated in women with aortic calcification, likely due to the contribution of CTX-I from osteoclastic bone resorption which involves Cathepsin-K. The human macrophage model system may be used to identify important pathway leading to excessive proteolytic plaque remodeling and plaque rupture.</p

Viral emissions into the air and environment after SARS-CoV-2 human challenge: a phase 1, open label, first-in-human study

Background Effectively implementing strategies to curb SARS-CoV-2 transmission requires understanding who is contagious and when. Although viral load on upper respiratory swabs has commonly been used to infer contagiousness, measuring viral emissions might be more accurate to indicate the chance of onward transmission and identify likely routes. We aimed to correlate viral emissions, viral load in the upper respiratory tract, and symptoms, longitudinally, in participants who were experimentally infected with SARS-CoV-2. Methods In this phase 1, open label, first-in-human SARS-CoV-2 experimental infection study at quarantine unit at the Royal Free London NHS Foundation Trust, London, UK, healthy adults aged 18–30 years who were unvaccinated for SARS-CoV-2, not previously known to have been infected with SARS-CoV-2, and seronegative at screening were recruited. Participants were inoculated with 10 50% tissue culture infectious dose of pre-alpha wild-type SARS-CoV-2 (Asp614Gly) by intranasal drops and remained in individual negative pressure rooms for a minimum of 14 days. Nose and throat swabs were collected daily. Emissions were collected daily from the air (using a Coriolis μ air sampler and directly into facemasks) and the surrounding environment (via surface and hand swabs). All samples were collected by researchers, and tested by using PCR, plaque assay, or lateral flow antigen test. Symptom scores were collected using self-reported symptom diaries three times daily. The study is registered with ClinicalTrials.gov, NCT04865237. Findings Between March 6 and July 8, 2021, 36 participants (ten female and 26 male) were recruited and 18 (53%) of 34 participants became infected, resulting in protracted high viral loads in the nose and throat following a short incubation period, with mild-to-moderate symptoms. Two participants were excluded from the per-protocol analysis owing to seroconversion between screening and inoculation, identified post hoc. Viral RNA was detected in 63 (25%) of 252 Coriolis air samples from 16 participants, 109 (43%) of 252 mask samples from 17 participants, 67 (27%) of 252 hand swabs from 16 participants, and 371 (29%) of 1260 surface swabs from 18 participants. Viable SARS-CoV-2 was collected from breath captured in 16 masks and from 13 surfaces, including four small frequently touched surfaces and nine larger surfaces where airborne virus could deposit. Viral emissions correlated more strongly with viral load in nasal swabs than throat swabs. Two individuals emitted 86% of airborne virus, and the majority of airborne virus collected was released on 3 days. Individuals who reported the highest total symptom scores were not those who emitted most virus. Very few emissions occurred before the first reported symptom (7%) and hardly any before the first positive lateral flow antigen test (2%). Interpretation After controlled experimental inoculation, the timing, extent, and routes of viral emissions was heterogeneous. We observed that a minority of participants were high airborne virus emitters, giving support to the notion of superspreading individuals or events. Our data implicates the nose as the most important source of emissions. Frequent self-testing coupled with isolation upon awareness of first symptoms could reduce onward transmissions. Funding UK Vaccine Taskforce of the Department for Business, Energy and Industrial Strategy of Her Majesty's Government

Применение фотодинамической терапии при лечении кератоакантомы

The review is on treatment of keratoacanthomas using photodynamic therapy. The defining characteristic of keratoacanthoma among epithelial tumors is a rapid spontaneous regression in the case of typical keratoacanthoma and long-term persistence, recurrence and common malignant transformation to squamous cell carcinoma in the case of atypical keratoacanthoma. In recent years, photodynamic therapy which is an effective method of treatment of different types of cancer and pre-cancer diseases of the skin including actinic keratosis, Bowen’s disease, basal cell carcinoma, is increasingly used in clinical practice. There are few data for photodynamic therapy in the treatment of keratoacanthoma. The analysis of the literature shows that using of photodynamic therapy in the set of treatment modalities in patients with keratoacanthoma improves the efficacy and reduces the terms of the therapy. In all investigations except one there was complete tumor regression in 100% patients with keratoacanthoma who underwent photodynamic therapy. In one study complete tumor regression was observed in 66.7% of patients with atypical keratoacanthoma after photodynamic therapy. The follow-up of patients in all analyzed studies accounted for at least 2-3 years. During this time none of the patients had evidence for recurrence. This approach has minimal restrictions for application. Thus, photodynamic therapy may become a therapeutic alternative to surgical treatment of keratoacanthoma with good clinical and cosmetic results.Обзор посвящен проблеме лечения кератоакантомы методом фотодинамической терапии. Отличительной особенностью кератоакантомы среди эпителиальных опухолей кожи является быстрый спонтанный регресс в случае типичной кератоакантомы и длительное персистирование, рецидивирование и нередкая трансформация в плоскоклеточный рак в случае атипичной кератоакантомы. В последние годы в клинической практике все чаще применяют фотодинамическую терапию, которая является эффективным методом лечения различных видов рака и предраковых заболеваний кожи, в том числе актинического кератоза, болезни Боуэна, базальноклеточного рака. Опубликованы немногочисленные данные о применении фотодинамической терапии при лечении кератоакантомы. Анализ данных литературы показывает, что применение фотодинамической терапии в комплексе лечебных мероприятий у больных кератоакантомой повышает эффективность и сокращает сроки ее лечения. Во всех исследованиях, кроме одного, у 100% пациентов с кератоакантомами, прошедших лечение фотодинамической терапией, была получена полная регрессия опухолей. В одном исследовании у пациентов с атипичной формой кератоакантомы после фотодинамической терапии полная регрессия получена в 66,7% наблюдений. Продолжительность наблюдения за пациентами во всех проанализированных работах составила не менее 2-3 лет. В течение этого срока ни у одного из пациентов не получено данных о рецидивировании заболевания. Данная технология имеет минимальное количество ограничений к использованию. Таким образом, фотодинамическая терапия может стать терапевтической альтернативой хирургическому лечению кератоакантомы с хорошими клиническими и косметическими результатами

Assessment of proteolytic degradation of the basement membrane: a fragment of type IV collagen as a biochemical marker for liver fibrosis

<p>Abstract</p> <p>Background</p> <p>Collagen deposition and an altered matrix metalloproteinase (MMP) expression profile are hallmarks of fibrosis. Type IV collagen is the most abundant structural basement membrane component of tissue, which increases 14-fold during fibrogenesis in the liver. Proteolytic degradation of collagens by proteases produces small fragments, so-called neoepitopes, which are released systemically. Technologies investigating MMP-generated fragments of collagens may provide more useful information than traditional serological assays that crudely measure total protein. In the present study, we developed an ELISA for the quantification of a neoepitope generated by MMP degradation of type IV collagen and evaluated the association of this neoepitope with liver fibrosis in two animal models.</p> <p>Methods</p> <p>Type IV collagen was degraded <it>in vitro </it>by a variety of proteases. Mass spectrometric analysis revealed more than 200 different degradation fragments. A specific peptide sequence, 1438'GTPSVDHGFL'1447 (CO4-MMP), in the α1 chain of type IV collagen generated by MMP-9 was selected for ELISA development. ELISA was used to determine serum levels of the CO4-MMP neoepitope in two rat models of liver fibrosis: inhalation of carbon tetrachloride (CCl₄) and bile duct ligation (BDL). The levels were correlated to histological findings using Sirius red staining.</p> <p>Results</p> <p>A technically robust assay was produced that is specific to the type IV degradation fragment, GTPSVDHGFL. CO4-MMP serum levels increased significantly in all BDL groups compared to baseline, with a maximum increase of 248% seen two weeks after BDL. There were no changes in CO4-MMP levels in sham-operated rats. In the CCl₄model, levels of CO4-MMP were significantly elevated at weeks 12, 16 and 20 compared to baseline levels, with a maximum increase of 88% after 20 weeks. CO4-MMP levels correlated to Sirius red staining results.</p> <p>Conclusion</p> <p>This ELISA is the first assay developed for assessment of proteolytic degraded type IV collagen, which, by enabling quantification of basement membrane degradation, could be relevant in investigating various fibrogenic pathologies. The CO4-MMP degradation fragment was highly associated with liver fibrosis in the two animal models studied.</p