The labour market of Russia's Kaliningrad exclave amid COVID-19

The COVID-19 pandemic, which has swept across the globe, is a serious challenge to the Russian labour market. This article examines the consequences of COVID-19 for Russia’s Kaliningrad exclave and how its territorially isolated and lockdownaffected small labour market responds to drastic changes in employment, income, and consumption. Another question is how the immigrant-rich labour market will rebalance the supply-demand equation. Official statistics from the regional government and its subordinate bodies show that the Kaliningrad regional labour market has been severely battered by shutdown measures. This particularly applies to organisations operating in the most sensitive industries: manufacturing, hospitality, tourism, estate, transport, and warehousing. The unemployment has gone up, reaching a level above the national average; the number of vacancies is dwindling. Keeping the proportion of out-of-the-region workforce at the usual level may aggravate the situation. Although effective, the measures taken by the regional authorities seem insufficient for an isolated regional labour market

Gene Expression Analysis Identifies Novel Targets for Cervical Cancer Therapy

Although there has been significant progress in prevention and treatment of cervical cancer, this malignancy is still a leading cause of cancer death for women. Anti-angiogenesis and immunotherapy approaches have been providing survival benefits, however, response rates and durability of response need to be improved. There is a clear need for combination therapies that increase effectiveness of these agents and further improve patient outcome. Previous studies have largely focused on gene expression and molecular pathways in untreated cervix cancer. The goal of this study was to evaluate cancer-specific molecular pathways and their correlation with tumor immune profile in recurrent cervical cancer. Tumor and adjacent normal tissues were used to identify potential combination therapy targets. We found that DNA damage repair pathway genes were significantly overexpressed in the tumor. Based on our results and other recent investigations, we suggest that combination immune checkpoint and PARP inhibitor therapy is a high priority consideration for patients with recurrent, previously treated cervical cancer. We also show that multiple epithelial-mesenchymal transition-related genes, including MAP2K4, ID2, JAK1, FGF2, PIK3R1, AKT3, FGF13, and STAT3 may be potential targets. Interestingly, high-throughput analysis of Cancer Genome Atlas data identified distinct targets, including Fatty acid synthase FASN and Matrix Metallopeptidase 1 MMP1 as novel, promising combination therapy partners

International Society of Gynecological Pathologists (ISGyP) Endometrial Cancer Project : Guidelines From the Special Techniques and Ancillary Studies Group:Guidelines From the Special Techniques and Ancillary Studies Group

The aim of this article is to propose guidelines and recommendations in problematic areas in pathologic reporting of endometrial carcinoma (EC) regarding special techniques and ancillary studies. An organizing committee designed a comprehensive survey with different questions related to pathologic features, diagnosis, and prognosis of EC that was sent to all members of the International Society of Gynecological Pathologists. The special techniques/ancillary studies group received 4 different questions to be addressed. Five members of the group reviewed the literature and came up with recommendations and an accompanying text which were discussed and agreed upon by all members of the group. Twelve different recommendations are made. They address the value of immunohistochemistry, ploidy, and molecular analysis for assessing prognosis in EC, the value of steroid hormone receptor analysis to predict response to hormone therapy, and parameters regarding applying immunohistochemistry and molecular tests for assessing mismatch deficiency in EC

Low-Grade Serous Carcinoma of the Ovary Displaying a Macropapillary Pattern of Invasion

Invasive micropapillary serous carcinoma (MPSC) also designated "low- grade serous carcinoma" (LGSC) of the ovary is characterized by small micropapillae that infiltrate underlying tissue (ovarian stroma). On occasion these tumors in addition to the micropapillae contain large macropapillae lined by bland epithelium. In rare cases, the entire tumor is composed of macropapillae. at these cases, the question of whether this is ail invasive carcinoma or an unusual type of adenofibroma has been raised. The goal of this study was to describe this unusual macropapillary pattern of invasion in LGSC. Cases of LGSC containing macropapillae were retrieved from the files of the Johns Hopkins Hospital. In addition to a detailed morphologic analysis, the mutational status of KRAS and BRAF in the macropapillary, noninvasive, and invasive MPSC components was analyzed by nucleotide sequencing. There were 14 cases containing macropapillae ( 11 cases of LGSC, 2 cases of atypical proliferative serous tumor (APST) with microinvasion, and I case of APST with a focus of LGSC with macropapillae in perivaginal soft tissue). In 3 cases, extraovarian metastases contained macropapillae. Molecular analysis of the primary tumor components (macropapillary, noninvasive, and invasive MPSC and/or APST) was performed in 7 cases and of a lymph node metastasis with macropapillae in I case. The identical KRAS mutation was detected in all of the analyzed components of the primary ovarian tumors in 4 cases. In one of these cases, macropapillae in the lymph node metastasis contained a KRAS mutation identical to the primary tumor. The BRAF mutation identified in I case was identical in all components of the ovarian tumor. The identical mutations in the macropapillae and the other tumor components in each case indicate that they are clonally related. The finding of macropapillae within lymph nodes Supports the interpretation that the macropapillary component is another manifestation of invasion in LGSC. The recognition of this pattern is important, especially in cases when a tumor is composed entirely of macropapillae

Knowledge control of higher school students majoring in Physics in General Physics and Profession-oriented English by means of testing

One of the important problems of the methodology of teaching any discipline is the effective identification of the objective level of students’ knowledge, acquired skills and abilities in the study of a discipline. Traditional methods of testing and assessing knowledge contain some drawbacks: excessive time spent on the exam; elements of teacher’s subjectivity that may occur; inability to clarify clear criteria for assessing knowledge, etc. Based on this, and the prospects for the reform of higher education in Ukraine, such methods of knowledge control are needed, which would allow teachers not only to establish an objective level of students’ knowledge, but also to identify (diagnose) the causes of gaps in student learning so that they could on its basis help the student to overcome the identified gaps. This method, devoid of most of the above shortcomings, is computer testing, the use of which for a long time as a means of monitoring and evaluating students’ achievements in studying the course of General Physics and Profession-oriented English at the Department of Materials Science and New Technologies (State higher educational institution "Vasyl Stefanyk Precarpathian National University"), at the Department of Physics and the Department of Western and Oriental Languages and their Teaching Methods (The State Institution“ South Ukrainian National Pedagogical University named after K. D. Ushynsky”) has shown that the use of computer testing in the study of Physics and foreign languages in the professional field should be subject to certain reservations, since this method has some advantages alongside disadvantages that can distort the results of monitoring and evaluation of students’ achievements. Based on the analysis of the authors' experience as well as the analysis of pedagogical, psychological and scientific-methodological literature devoted to this problem, an attempt is made to establish the conditions and limits of computer testing in the organization of the learning platform (courses) in the fields of General Physics and foreign languages for the students majoring in Physics at institutes of higher education. The article states that computer testing, on condition that tests meet the quality requirements, should be used only for the current (thematic) control of knowledge during each semester. This method is at the same time an express control method aimed at testing students' knowledge in the process of studying General Physics and foreign languages; it is also a “sensitive” diagnostic method which allows you to identify shortcomings of a student in time in the process of learning, giving the teacher the opportunity to timely influence its course. The learning progress control (testing in theoretical modules) can be carried out by means of computer testing but with the use of certain additional precautionary methodological measures. It is more expedient to carry out the final control in the form of a quality written-oral examination

A Rare PDGFRA Exon 15 Germline Mutation Identified in a Patient With Phenotypic Manifestations Concerning for GIST-Plus Syndrome: A Case Report and Review of Literature

Molecular alterations in PDGFRA are well-described as drivers of sporadic gastrointestinal stromal tumors (GISTs) and inflammatory fibroid polyps (IFPs). However, a small number of families with germline PDGFRA mutations in exons 12, 14, and 18 have been reported, forming the basis of an autosomal dominant inherited disorder with incomplete penetrance and variable expressivity, now referred to as PDGFRA-mutant syndrome or GIST-plus syndrome. Phenotypic manifestations of this rare syndrome include multiple gastrointestinal GISTS, IFPs, fibrous tumors, and other variable features. Herein, we report the case of a 58-year-old female who presented with a gastric GIST and numerous small intestinal IFPs, found to harbor a previously undescribed germline PDGFRA exon 15 p.G680R mutation. Somatic tumor testing was performed on the GIST, a duodenal IFP, and an ileal IFP utilizing a targeted next-generation sequencing panel, revealing additional and distinct secondary PDGFRA exon 12 somatic mutations in each of the 3 tumors. Our findings raise important considerations regarding mechanisms of tumor development in patients with underlying germline PDGFRA alterations and highlight the potential utility of expanding currently available germline and somatic testing panels to include exons outside the typical hotspot regions

Early and consistent overexpression of ADRM1 in ovarian high-grade serous carcinoma

Abstract Background Ovarian carcinoma is highly dependent on the ubiquitin proteasome system (UPS), but its clinical response to treatment with the proteasome inhibitor bortezomib has been disappointing. This has driven exploration of alternate approaches to target the UPS in ovarian cancer. Recently, proteasome inhibitors targeting the 19S regulatory particle-associated RPN13 protein have been described, such as RA190. RPN13, which is encoded by ADRM1, facilitates the recognition by the proteasome of its polyubiquinated substrates. Inhibition of RPN13 produces a rapid, toxic accumulation of polyubiquitinated proteins in ovarian and other cancer cells, triggering apoptosis. Here, we sought to determine if RPN13 is available as a target in precursors of ovarian/fallopian tube cancer as well as all advanced cases, and the impact of increased ADRM1 gene copy number on sensitivity of ovarian cancer to RA190. Methods ADRM1 mRNA was quantified by RNAscope in situ hybridization and RPN13 protein detected by immunohistochemistry in high grade serous carcinoma (HGSC) of the ovary and serous tubal intraepithelial carcinoma (STIC). Amplification of ADRM1 and sensitivity to RA190 were determined in ovarian cancer cell lines. Results Here, we demonstrate that expression of ADRM1mRNA is significantly elevated in STIC and HGSC as compared to normal fallopian tube epithelium. ADRM1 mRNA and RPN13 were ubiquitously and robustly expressed in ovarian carcinoma tissue and cell lines. No correlation was found between ADRM1 amplification and sensitivity of ovarian cancer cell lines to RA190, but all were susceptible. Conclusions RPN13 can potentially be targeted by RA190 in both in situ and metastatic ovarian carcinoma. Ovarian cancer cell lines are sensitive to RA190 regardless of whether the ADRM1 gene is amplified

Additional file 6: Figure S6. of Early and consistent overexpression of ADRM1 in ovarian high-grade serous carcinoma

Consistent RPN13 protein expression in TMA HGSC (Part 1). TMA HGSC samples were assessed for RPN13 mRNA and protein expression. mRNA levels varied between samples however, protein levels remained similar between samples. (TIFF 6401 kb