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The twenties are typically considered the prime reproductive years for women. However, in today’s modern world, many women are choosing to delay family planning, resulting in an increase of females in their forties seeking fertility treatment. Althoughin vitrofertilization (IVF) with donated oocytes and preimplantation genetic testing may help to address the impact of maternal age, the success rate for IVF treatment in this age group is still significantly lower. While endometrial changes, such as abnormal endometrial thickness, inflammatory background, and altered hormone response signaling, are associated with aging, little is known about the molecular features of endometrial aging and their impact on the ability to support embryo implantation. To better understand age-specific changes, we performed endometrial transcriptome profiling of young and advanced age females, undergoing hormonal replacement therapy (HRT) before frozen embryo transfer, followed by immunohistology analysis and single-cell-based deconvolution. Here, we identified 491 differentially expressed genes pointing to the effect of aging on decidualization, cell signaling, inflammation and endometrial receptivity. Our results indicate that p16INK4amay be involved in cellular senescence and the suppression of metabolic and inflammatory processes essential for endometrial preparation for embryo implantation. We have also shown that the proportion of ciliated cells along with ciliary processes is affected by endometrial aging. These findings have important implications for future strategies aimed at improving infertility treatment in women of advanced reproductive age.

For the clinicians with non-pathology background, first encountering the patients with pleural or peritoneal effusions, mesothelioma is only one statistically rare but clinically significant option of many differential diagnoses. This review aims to help the clinicians and broad life science audiences to understand step by step the possibilities and shortcomings of pathological diagnosing of mesothelioma, including the basic technical requirements. The first cytomorphology evaluation of pleural and peritoneal effusions in routinely stained smears enables in most cases only to identify cells suspicious for malignancy. The recent guidelines of epithelioid mesothelioma cytologic diagnosis and reporting emphasize immunochemistry (IC) in the cell blocks is mandatory whenever a diagnosis of malignancy is clinically entertained and/or cytologically suspected. The IC workup is challenging, since there is no fixed antibody panel, but multiple questions must be solved, such as 1) confirm the mesothelial or epithelial origin of isolated atypical cells and cell clusters; 2) delineate their benign or malignant nature; and 3) discriminate mesothelioma from other malignancies and metastatic disease. The rationale of the most widely clinically used IC markers is given and illustrated by the examples. The final confirmation of mesothelioma diagnosis and establishing its subtype and grade is possible only in the histological samples.

Prostate adenocarcinoma (PCa) stromal markers have recently gained attention as complementary diagnostic tools. The DNA reparation complex protein FANCM has been shown to express in the normal prostate stroma and FANCM gene alterations to be associated with PCa susceptibility; this has led to the hypothesis that an insufficient level of FANCM expression may provide additional information for the evaluation of PCa. The study cohort comprised 60 radical prostatectomy specimens. The controls involved 11 autopsies (CTRL) and non-cancerous tissue (NCT) areas from the prostatectomy specimen. The samples were stained with the FANCM antibody. The quantification of the stromal staining index (SSI) was made using ImageJ and QuPath. Overall, 655 regions of interest (ROI) were analyzed. FANCM expression appeared equally intense and stroma specific in both CTRL and NCT, indicating the absence of underlying baseline alterations. Within the age span of the cohort 47-89 years, no significant effect of the age of the patients on the FANCM expression was seen. FANCM demonstrated Gleason grade (G) dependent decline in PCa, being statistically significant in controls versus G1 and G2 versus G3. In other adjacent International Society of Urological Pathology (ISUP) groups, it remained insignificant, still being meaningful between high and low-grade cancers.

Immunotherapy using immune checkpoint inhibitors has demonstrated durable responses and has significantly improved survival in patients with non-small cell lung cancer (NSCLC). Moreover, immunotherapy is increasingly used in combination with cytotoxic treatments such as chemotherapy and radiotherapy. Although the combined treatments are more effective, the underling mechanisms that lead to higher antitumor activity are not fully understood. Therefore, the aim of the current retrospective study was to determine the relationship between expression of immune checkpoints [programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1)] and the enzyme DNA-dependent protein kinase (DNA-PK), which is part of a key pathway involved in the repair of cytotoxic cancer therapy induced damage. Surgically excised NSCLC tissues (n=121) were histologically examined for overall extent of inflammation (score 0-3). Expression levels of PD-1 (number of PD-1 positive cells), PD-L1 [tumor proportion score (TPS); %] and DNA-PK (proportion of DNA-PK positive tumor cells; %) were determined using immunohistochemistry. Expressions of these markers were compared in different clinicopathological subgroups and later used for nonparametric Spearman correlation analysis to determine associations. In patients with NSCLC, PD-1 was significantly expressed in males (P=0.030) and in patients with no or trivial inflammation scores (P=0.030). PD-L1 expression was also significantly higher in current smokers (P=0.025). Correlation analysis was based on the individual values of patients and revealed a significant association between one of the targets of immune checkpoint inhibitors and tumor cell DNA-PK. Tumors with higher numbers of PD-1 positive cells also demonstrated higher tumor cell DNA-PK expressions (P=0.027). The results demonstrated a significant positive correlation between the PD-1/PD-L1 axis and tumor cell DNA-PK expression in patients with NSCLC. Further studies are required to clarify the significance of this correlation and its effect on the efficacy of immunotherapy and cytotoxic cancer therapy combinations.

The diagnostic value of stromal changes in carcinomas, including prostate, is under debate; in terms of limited sample tissue of biopsy, in addition to glandular alterations, the stromal changes could have additional diagnostic value, but the results in clinical settings are controversial. The research aims to evaluate the potential of stromal changes as a supplementary tool to predict the presence of higher grade carcinomas in the prostate using Masson's trichrome and Fanconi anemia complementation group M (FANCM) antibody stainings. 385 biopsies and corresponding radical prostatectomy specimens were analyzed to evaluate the rates of the diversity of ISUP grades. Of 128 upgraded prostatectomy cases, 82 were diagnosed with ISUP Gleason Grade 1 (GG1) in a biopsy. All 82 cancerous samples were stained with Masson's trichrome and FACNM antibody and compared with 82 samples without cancer to see if there was a difference in stromal composition. Additionally, 50 GG1 samples without the upgrade were stained to demonstrate if stromal changes can predict less differentiated carcinomas in the prostate. In FANCM stained samples, the average percentage of positively staining stroma over the total in non-upgraded GG1 biopsies was 36 % (13-59 %, SD = 11); 34 % (9-58, SD = 13) in samples from the upgraded cancerous group, and 44 % (22-69, SD = 11) in samples without cancer. In Masson's trichrome stained samples, with collagen quantified, the percentage in non-upgraded GG1 biopsies was 41 % (20-78 %, SD = 11); 44 % (23-89, SD = 15) in samples from upgraded cancerous group and 37 % (15-57, SD = 9) in samples without cancer. In both FANCM and Masson's trichrome, no statistical significance was found between upgraded and non-upgraded groups (p = 0.84 and p = 0.5, respectively), although some upgrades from GG1 to GG4 showed extreme values. The statistical significance was found in cancerous vs. benign samples with both FANCM (p 0.01) and Masson's trichrome (p = 0.012). The main limiting factor is a significant overlap in staining intensity between cancerous and cancer-free groups.

Eesti Arst 2020; 99(5):320–321, Eesti Arst, 2020: Mai

Pathadin ( https://gitlab.com/Digipathology/Pathadin ) was designed as a WSI oriented open-source set of tools for beginners to experience the advantages of computer-assisted image analysis and cover essential features, frequently strenuous to access with the alternative programs. It is mainly oriented to work with histology slides but also includes a significant part of modern image formats. Introducing Pathadin, the manuscript aims to improve understanding of contemporary image analysis components, resolve technophobia and misbeliefs in the computational field, simplifying pathology research work, and shifting it into a quantitative paradigm. Despite being easy to use, Pathadin includes both basic and advanced analytical algorithms, as the application of machine learning. The functionality of Pathadin is demonstrated by AI-enhanced quantification of epithelial and stromal changes in prostate carcinoma, and their dependence on ISUP grade. The material included 5 radical prostatectomy samples for training and 83 (including 11 autopsies) samples for analysis. The analytical material was stained with Masson’s trichrome and Ki67, as widely available and potentially prognostic markers. An integrated solution by HistomicsTK for Ki67 evaluation was used. A U-net model for separating glands and stroma was trained, simplifying the independent analysis of these components. During the process, the model successfully highlighted glands and stroma. Masson’s trichrome stain demonstrated a gradual increase in collagen expression, being statistically significant between controls vs. G1, and G3 vs. G4. Although there was considerable overlap between adjacent groups, there was only a minor overlap in collagen amount between high- and low-grade carcinomas, affirming that with further research, stroma could be an additional diagnostic marker in prostate adenocarcinoma. Ki67 showed a statistically significant gradual increase in all groups except G1 vs. G2 and G4 vs. G5. Pathadin demonstrates that there is no need for significant resources to experience the advantages of modern computer-assisted analysis.

Bakalaura darbā tiek izveidots matemātikas teorētisks apraksts priekš sākumskolas skolotājiem, kas grib pasniegt matemātiku 5. un 6. klasē, ar piemēriem no reālas dzīves, uzdevumiem un ieteikumiem. Bakalaura darba autore: Elīna Minajeva. Darba mērķis: izveidot palīgmateriālus matemātikā sākumskolas skolotājiem, kas grib pasniegt matemātiku 5. un 6. klasē., The Bachelor thesis presents the mathematics theoretical materials for primary school teachers who want to master Maths for Grade 5 and 6. The paper includes real-life examples, tasks and recommendations. The author of the paper: Elīna Minajeva. The goal of the study: to create a mathematics curriculum for primary school teachers who want to master Maths for Grade 5 and 6.

For the clinicians with non-pathology background, first encountering the patients with pleural or peritoneal effusions, mesothelioma is only one statistically rare but clinically significant option of many differential diagnoses. This review aims to help the clinicians and broad life science audiences to understand step by step the possibilities and shortcomings of pathological diagnosing of mesothelioma, including the basic technical requirements. The first cytomorphology evaluation of pleural and peritoneal effusions in routinely stained smears enables in most cases only to identify cells suspicious for malignancy. The recent guidelines of epithelioid mesothelioma cytologic diagnosis and reporting emphasize immunochemistry (IC) in the cell blocks is mandatory whenever a diagnosis of malignancy is clinically entertained and/or cytologically suspected. The IC workup is challenging, since there is no fixed antibody panel, but multiple questions must be solved, such as 1) confirm the mesothelial or epithelial origin of isolated atypical cells and cell clusters; 2) delineate their benign or malignant nature; and 3) discriminate mesothelioma from other malignancies and metastatic disease. The rationale of the most widely clinically used IC markers is given and illustrated by the examples. The final confirmation of mesothelioma diagnosis and establishing its subtype and grade is possible only in the histological samples.

Decreased tillage intensity can contribute to a reduced agro-technological footprint and stabilise the negative impact of climate change, especially in leguminous crop cultivation. For this reason, a long-term (since 1988) stationary field experiment has been performed on silty loam Planosol (in Lithuania). The main objective of this study was to establish the influence of sustainable tillage and no-tillage systems on soil aggregate stability to water, penetration resistance, enzymatic activity, abundance of earthworm and faba bean grain yield. Five different tillage systems were investigated: conventional deep and shallow mouldboard ploughing, deep chiselling, shallow disking and no-tillage. No-tillage in faba bean cultivation significantly increased soil structural stability by 40–97%, saccharase content by 0.7–2.0 times, urease activity by 3–4 times, the average quantity of earthworm by 55% and the biomass by 3.6 times. The impact of other ploughless tillage systems on soil properties was positive but not as significant. Faba bean grain yield was more influenced by growing seasons than by different tillage methods.

“Feminisma reprezentācija vērtību kontekstā Latvijas medijos” ir pētījums, kura mērķis ir iegūt priekšstatu par feminisma tēmas atspoguļojumu, kādos kontekstos mediji reprezentē feminismu un kādas vērtības tiek paustas. Bakalaura darba teorētiskais pamats tiek balstīts uz feminisma tēmas izpēti, konkrēti aprakstot tā izplatītākos veidus un feminisma tēmas atspoguļojumu saistībā ar medijiem, līdz ar to teorijā tiek iekļauts arī reprezentācijas termina skaidrojums un apkopota informācija par mediju efektu teoriju. Kā metodoloģija šajā pētījumā tiek izmantota kvantitatīvā un kvalitatīvā kontentanalīze, ar kuras palīdzību 2017. gada 9 populārākajos Latvijas medijos, pēc trīs atslēgas vārdiem - feminisms, feminists un feminsite, tiek atlasīti un kategorizēti 128 raksti. Rakstu analīze tiek veikta pēc trīs kategorijām - adjektīvi, dihotomiju izmantojums un personas/autora pozicionējums - identifikācija ar feminismu. Pētījumā tiek izpētītas 128 mediju publikācijas, kuras ir gan informējoša satura, gan viedokļu raksti, gan intervijas ar dažādām sabiedrībā pazīstamām personām. Pētījuma rezultāti liecina, ka mūsdienās feminisma kustība kļūst populārāka, jo medijos parādās daudz informācijas saistībā ar to, kā arī mūsdienās cilvēki sevi vairāk sāk pozicionēt kā feministi vai feministu un pozitīvi vērtē šo kustību. Atslēgas vārdi: feminisms, mediji, reprezentācija, vērtības, "Representation of Feminism in the Context of Values in Latvian Media" is a study aimed at gaining an idea of the reflection of the theme of feminism, in what context the media represents feminism and what values are expressed. The theoretical basis of the Bachelor's paper is based on the study of the topic of feminism, in particular describing its most common types and the presentation of the topic of feminism in relation to the media; therefore, the explanation of the term of representation and information on the theory of media effects are also included in the theory. As a methodology in this study, quantitative and qualitative analysis of the content is used, with which, in the nineteen most popular Latvian media in 2017, after key words - feminism, feminist, 128 articles are selected and categorized. The analysis of the articles is carried out in three categories - adjectives, the use of dichotomies and the positioning of the person / author - identification with feminism. The study examines 128 media publications, which contain both informative content, opinion articles and interviews with various public figures. The results of the research show that today, the movement of feminism is becoming more popular, as there is a lot of information in the media about it, and nowadays people are beginning to position themselves as feminists, and positively evaluate this movement. Keywords: feminism, media, representation, values

Dairy cattle breeding is one of the main suppliers of protein and animal fat, it is one of the most important branches of agriculture and plays a primary role in providing adequate nutrition for the population. During the purposeful work on harmonization of the national regulatory framework with international legislation, special attention is paid to scientific developments in the way of full implementation of Russian livestock production in the global trading system. The recommendations of the International Committee for Registration of Animals (ICAR) (Global Standard…, 2017; Trukhachev et al., 2017) are the methodological basis for the introduction of the generally accepted organizational principles for the recording and evaluation of the productive qualities of animals. One of the stages of this process was implementation in 2015-2017. in the Stavropol State Agrarian University of research projects, especially significant for the agro-industrial complex of the Russian Federation in the direction of ensuring import substitution in animal husbandry (genetic material), which envisage the development of a regional model for the formation and management of highly productive genetic resources for dairy cattle. The object of the research was cattle (cows) of the North Caucasian population of the Ayrshire breed (n = 550), from which, based on the analysis of the materials of the primary zooveterinary records, groups of cows with 3-fold milking were formed to study the daily dynamics of fat and protein content in raw milk samples I, II and III milking, n = 240) and 2-fold milking (I and II milking - 180 cows). In the process of performing monthly analyzes of the quality of individual milk samples obtained from pedigree cows taken for 2- or 3-fold milking, it was found that a certain pattern is observed in the diurnal dynamics of fat and protein content in milk, which probably has a general biological nature and largely depends on the technological factor - the multiplicity of milking cows, which coincides, basically, with the regularities described in the methodology of the International Committee for Registration of Animals (ICAR). The nature of the dynamics of the concentration of fat in milk at 2- and 3-fold milking has, though a different mathematical form, but they have a general tendency: the fat in milk for milking cows, as a rule, is 10.77–10.98 % lower, than II and III milking. The variability of the protein concentration in milk during the day is the same as the fat dynamics, though it is less expressed than of fat and accounts 0.88%. Keywords: milk cows, milk quality, Ayrshire cattle Article DOI: http://doi.org/10.15544/RD.2017.068

Background. The aim of the study was to assess the impact of CD133-positive (CD133+) cancer stem cell proportions on treatment results of glioblastoma multiforme (GBM) patients.Patients and methods. Patients with GBM (n = 42) received postoperative radiotherapy (± chemotherapy). Surgically excised GBM tissue sections were immunohistochemically examined for CD133 expression. The proportions of CD133+ GBM cells were determined (%). The proportion of CD133+ GBM stem cells was established by 2 independent researchers whose results were in good accordance (R = 0.8, p < 0.01). Additionally, CD133 expression levels were correlated with patients overall survival.Results. The proportion of CD133+ cells varied between patients, being from 0.5% to 82%. Mean and median proportions of CD133+ cells of the entire study group were 33% ± 24% (mean ± SD) and 28%, respectively. Clinical data do not support the association between higher proportion of stem cells and the aggressiveness of GBM. Median survival time of the study group was 10.0 months (95% CI 9.0-11.0). The survival time clearly depended on the proportion of CD133+ cells (log rank test, p = 0.02). Median survival times for patients with low (< median) and high (≥ median) proportion of CD133+ cells were 9.0 months (95% CI 7.6-10.5) and 12.0 months (95% CI 9.3-14.7), respectively. In multivariate analysis, the proportion of CD133+ cells emerged as a significant independent predictor for longer overall survival (HR 2.0, 95% CI 1.0-3.8, p = 0.04).Conclusions. In patients with higher stem cell proportion, significantly longer survival times after postoperative radiotherapy were achieved. Underlying reasons and possible higher sensitivity of GBM stem cells to fractionated radiotherapy should be clarified in further studies.