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Rotylenchus is a widely distributed, economically important plant-parasitic nematode group whose species-level identification relies largely on limited morphological characters, including character-based tabular keys and molecular data of ribosomal and mitochondrial genes. In this study, a combined morphological and molecular analysis of three populations of Rotylenchus goodeyi from Belgium, Poland, and the Netherlands revealed important character variations of this species, leading to synonymization of R. rhomboides with R. goodeyi and a high nucleotide variation within cox1 gene sequences in these populations. Additional Illumina sequencing of DNA from individuals of the Dutch population revealed two variants of mitogenomes, each approximately 23 Kb in size, differing by approximately 9% and containing 11 protein-coding genes, 2 ribosomal RNA genes, and as many as 29 transfer RNA genes. In addition to the first representative whole-genome shotgun sequence datasets of the genus Rotylenchus, this study also provides the full-length mitogenome and the ribosomal DNA sequences of R. goodeyi.

The aim of the research presented in the article is to analyse the term “prostitution” and “sexual service” and an attempt to transfer the results of this analysis to the ground of the so-called prostitution-related crimes in the Polish criminal code. Therefore, the article analyses the content of Articles 203 and 204 CC. The method used was mainly the dogamtic-legal method and the derivational concept of legal interpretation. The main thesis that has been formulated in the article is the lack of a coherent view of the doctrine and jurisprudence of criminal law as to the scope of the concept of “prostitution”. The article also presents the phenomenon of the so-called soft prostitution and doubts that may arise on the basis of prostitution-related crimes in connection with this form of sexual services.

IntroductionThere are gaps in the evidence base of tumour classification despite being essential for cancer diagnosis, treatment and patient care. The WHO in charge of the production of an updated international classification, the WHO Classification of Tumours (WCT), aims to adapt evidence gap map (EGM) methodology to inform future editions of the WCT, by providing a visual summary of the existing evidence.Methods and analysisBibliographical references used in the WCT fifth edition of Tumours of the Lung (Thoracic Tumours volume) will be used as search results of a literature search. A descriptive analysis of the cited evidence for tumour types and descriptors will be drafted and plotted in EPPI-Reviewer to develop a visual evidence map. The resulting EGM will reflect the number of cited studies in the size of the spheres, and the level of evidence by applying a four-colour code (red=low level evidence, orange=moderate level, green=high level and blue=unclassifiable). Overview of the findings will be provided in narrative form and a report will discuss the overall stage of cited research in the WCT and will include analysis of gaps, under-researched categories of tumour descriptors and pockets of low-level evidence.Ethics and disseminationNo ethics approval will be required as this is a study of previously published material. Findings of the EGM will be published and used to guide editors, stakeholders and researchers for future research planning and related decision-making, especially for the development of future editions of the WCT.PROSPERO registration numberCRD42022302327.

Introduction Perinatal period is characterized by an increased risk of thrombosis due to low resources and limited compensatory capacity of the coagulation system in early stages of life. Case report We report a case of a second pregnancy female infant born at 39 weeks by caesarean section, due to pre-labor rupture of membranes, with body weight of 3,570 γ and Apgar score 10. The pregnancy was complicated by hypothyroidism, uterine myoma, urinary tract infections, and mother's appendectomy at 16 Hbd. At 3 months, the girl was admitted to our hospital due to kidney calcifications, which were incidentally found during ultrasound scan. In laboratory workup, no abnormalities in calcium and phosphate homeostasis were detected. However, in ultrasound scan, linear calcifications along pyramids were visualized in both kidneys. Due to atypical location of nephrocalcinosis, Doppler scan was performed, showing lack of visible blood flow from renal veins to inferior vena cava (IVC), with compensatory flow from renal veins to paravertebral plexuses, and IVC obliteration with a massive calcification in the hepatic section. Magnetic resonance confirmed obliteration of IVC and common iliac veins, segmental dilatation of IVC, and compensatory blood flow from kidneys and lower limbs to paravertebral plexuses. Clinical picture and formation of collateral circulation suggested intrauterine thrombosis. Congenital thrombophilia was excluded in laboratory examination. Conclusions The differential diagnosis of calcifications in renal parenchyma (nephrocalcinosis) should include renal vein thrombosis. Massive fetal and perinatal thrombosis can be asymptomatic due to high ability to form collateral circulation at the early stage of life.

Urinary tract infections (UTIs) are one of childhood’s most common bacterial infections. The study aimed to determine the clinical symptoms, laboratory tests, risk factors, and etiology of different UTIs in children admitted to pediatric hospitals for three years. Methods: Patients with positive urine cultures diagnosed with acute pyelonephritis (APN) or cystitis (CYS) were analyzed for clinical symptoms, laboratory tests, risk factors, and etiology, depending on their age and sex. Results: We studied 948 children with UTIs (531 girls and 417 boys), with a median age of 12 (IQR 5–48 months). A total of 789 children had clinical symptoms; the main symptom was fever (63.4% of patients). Specific symptoms of UTIs were presented only in 16.3% of patients. Children with APN had shown significantly more frequent loss of appetite, vomiting, lethargy, seizures, and less frequent dysuria and haematuria than children with CYS. We found significantly higher median WBC, CRP, and leukocyturia in children with APN than with CYS. The risk factors of UTIs were presented in 46.6% of patients, of which 35.6% were children with APN and 61.7% with CYS. The main risk factor was CAKUT, more frequently diagnosed in children with CYS than APN, mainly in children

Vulvar squamous cell carcinoma (VSCC) develops from high-grade squamous intraepithelial lesions (HSIL) and differentiated vulvar intraepithelial neoplasia (dVIN). This study aimed to assess the diagnostic value of circulating hsa-miR-431-5p in vulvar precancers and VSCC. Expression levels of hsa-miR-431-5p were analyzed by quantitative RT-PCR in plasma samples of 29 patients with vulvar precancers (HSIL or dVIN), 107 with VSCC as well as 15 healthy blood donors. We used hsa-miR-93-5p and hsa-miR-425-5p as normalizers. The levels of miR-431-5p were increased in the blood of patients with VSCC compared to those with vulvar precancers. Statistically significant differences in the survival rates (time to progression) were revealed for VSCC patients categorized by miR-431-5p levels. Low levels of circulating miR-431-5p were found to be indicative of unfavorable survival rates. In summary, our data reveal the diagnostic potential of circulating miR-431-5p in patients with vulvar precancers and VSCC.

Simple Summary Our study aimed to advance the understanding of vulvar squamous cell carcinoma (VSCC) biology by recognizing biological pathways that drive the progression of this disease. We applied the experimental path from global proteomic analysis of vulvar tumors to the targeted and quantitative assessment of specific proteins both in the tumors and blood of VSCC patients. The proteomic analysis has advanced the knowledge on VSCC biology by pointing at inflammation as a driver of progression and by providing grounds for the hypothesis of vulvovaginal microflora disturbances as a trigger for the inflammatory response. The study results indicate prognostic protein markers and potential therapeutic targets for improved and personalized management of VSCC. Abstract Current knowledge on the biology of squamous cell vulvar carcinoma (VSCC) is limited. We aimed to identify protein markers of VSCC tumors that would permit to stratify patients by progression risk. Early-stage tumors from patients who progressed (progVSCC) and from those who were disease-free (d-fVSCC) during follow-up, along with normal vulvar tissues were examined by mass spectrometry-based proteomics. Differentially expressed proteins (DEPs) were then verified in solid tissues and blood samples of patients with VSCC tumors and vulvar premalignant lesions. In progVSCC vs. d-fVSCC tumors, the immune response was the most over-represented Gene Ontology category for the identified DEPs. Pathway profiling suggested bacterial infections to be linked to aggressive VSCC phenotypes. High Mobility Group AT-Hook 2 (HMGA2) and Proteinase 3 (PRTN3) were revealed as proteins predicting VSCC progression. HMGA2 and PRTN3 abundances are associated with an aggressive phenotype, and hold promise as markers for VSCC patient stratification. It appears that vulvovaginal microflora disturbances trigger an inflammatory response contributing to cancer progression, suggesting that bacterial rather than viral infection status should be considered in the development of targeted therapies in VSCC.

AimsVulvar squamous cell carcinoma (VSCC) spreads early and mainly locally via direct expansion into adjacent structures, followed by lymphatic metastasis to the regional lymph nodes (LNs). In the lymphatic metastasis, cancer cells bearing CXCR4 and ACKR3 (CXCR7) receptors are recruited to the LNs that produce the CXCL12 ligand. Our study aimed to assess the role of the CXCR4/ACKR3/CXCL12 axis in VSCC progression.MethodsTumour and LN tissue samples were obtained from 46 patients with VSCC and 51 patients with premalignant vulvar lesions. We assessed CXCR4, ACKR3 and CXCL12 by immunohistochemistry (IHC) in the tissue samples. Additionally, CXCL12 levels were determined by ELISA in the sera of 23 patients with premalignant lesions, 37 with VSCC and 16 healthy volunteers.ResultsCXCR4 and ACKR3 proteins were virtually absent in vulvar precancers, while in VSCC samples the IHC staining was strong. In the LNs of patients with VSCC, 98% of metastatic cells expressed CXCR4 and 85% expressed ACKR3. Neither CXCR4 nor ACKR3 presence was correlated with tumour human papilloma virus status. Few CXCL12-positive cells were found in the analysed tissue samples, but serum CXCL12 levels were significantly increased in both patients with premalignant vulvar lesions and with VSCC compared with healthy volunteers.ConclusionsIt appears that during progression and lymphatic spread of VSCC, the CXCR4/ACKR3/CXCL12 axis is activated. Moreover, our data suggest that CXCR4 antagonists merit further attention as a possible therapeutic option in patients with VSCC.

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Background A knowledge on the biology of squamous cell vulvar carcinoma (VSCC) is limited. We aimed to identify protein markers of VSCC tumors stratifying patients by progression risk. Early stage VSCC tumors from patients who progressed (progVSCC) and from those who were disease-free (d-fVSCC) during follow-up, along with normal vulvar tissues were examined by mass spectrometry-based proteomics.Results In progVSCC vs d-fVSCC tumors, the immune response was the most over-represented Gene Ontology category for the identified DEPs. Interestingly, pathway profiling suggested bacterial infections to be linked to aggressive VSCC phenotypes. Differentially expressed proteins (DEPs) were verified in solid tissues and blood samples of patients with VSCC tumors and vulvar premalignant lesions. High Mobility Group AT-Hook 2 (HMGA2) and Proteinase 3 (PRTN3) were revealed as protein markers predicting VSCC progression.Conclusions HMGA2 and PRTN3 abundances are associated with aggressive VSCC phenotype, and hold promise as markers for patient stratification. It appears that vulvovaginal microflora disturbances trigger inflammatory response contributing to cancer progression.

This paper summarises the research project titled ‘Criminal court diagnostics in granting parole and releasing on parole in judicial theory and practice’ implemented by the Institute of Justice. The aim of the project, including in particular the empirical study it comprised, was (among others) to validate the statement that the work of administrative staff of penitentiary establishments and penitentiary courts is lacking in terms of professional and in-depth criminological prognosis. The empirical study involved an analysis of 540 cases from the second quarter of 2013, in which cases inmates’ applications for parole were granted. One of the findings from the study was that the courts’ statements of reasons for decisions to grant parole (which seem to reflect the process whereby the court reaches the conclusion that it is justified to grant the given person parole) were inadequate (especially in the light of requirements provided for in Article 77(1) of the Criminal Code). This observation holds true for a large number of decisions.

In this review, we summarize the existing literature on next generation sequencing (NGS) studies in vulvar squamous cell carcinoma (VSCC). A total of 201 VSCC tumor samples were investigated in five studies published between 2017 and 2019. Findings on somatic mutations in human papillomavirus (HPV)-DNA positive (HPV+) and HPV-DNA negative (HPV-) disease were extracted and submitted to pathway and drug candidate analyses. The general genetic findings show cell cycle activity aberrations common to both HPV+ and HPV- VSCC. In silico analyses of somatic mutations detected in NGS studies pointed to PI3K-Akt pathway as the main pathway dysregulated in both HPV+ and HPV- VSCC tumors. In addition, pathways specific for HPV+ VSCC, i.e. AMPK, Prolactin, mTOR and Chemokine pathways as well as pathways unique for HPV- disease, i.e. GnRH, Neurotrophin, Oxytocin, Notch pathways were identified. These observations provide a rationale for incorporating novel specific therapeutic strategies in vulvar cancer. In this review, based on the Drug Gene Interaction database analysis of the NGS data, we listed potential drugs for this disease. The candidates revealed in our analysis provide new therapeutic opportunities in VSCC.

Background Vulvar squamous cell carcinoma (VSCC) constitutes over 90% of vulvar cancer. Its pathogenesis can follow two different pathways; high risk human papillomavirus (hrHPV)-dependent and HPV-independent. Due to the rarity of VSCC, molecular mechanisms underlying VSCC development remain largely unknown. The study aimed to identify pathogenic mutations implicated in the two pathways of VSCC development. Methods Using next generation sequencing, 81 VSCC tumors, 52 hrHPV(+) and 29 hrHPV(−), were screened for hotspot mutations in 50 genes covered by the Ion AmpliSeq Cancer Hotspot Panel v2 Kit (Thermo Fisher Scientific). Results Mutations of TP53 (46% and 41%, of hrHPV(+) and hrHPV(−) cases respectively) and CDKN2A (p16) (25% and 21%, of hrHPV(+) and hrHPV(−) cases respectively) were the most common genetic alterations identified in VSCC tumors. Further mutations were identified in PIK3CA, FBXW7, HRAS, FGFR3, STK11, AKT1, SMAD4, FLT3, JAK3, GNAQ, and PTEN, albeit at low frequencies. Some of the identified mutations may activate the PI3K/AKT/mTOR pathway. The activation of mTOR was confirmed in the vast majority of VSCC samples by immunohistochemical staining. Conclusions Detecting pathogenic mutations in 13/50 genes examined at comparable frequencies in hrHPV(+) and hrHPV(−) tumors suggest that genetic mechanisms of the two routes of VSCC pathogenesis may be similar, despite being initiated from different premalignant lesions. Importantly, our data provide a rationale for new anti-VSCC therapies targeting the PI3K/AKT/mTOR pathway.

Technetium (99mTc)-radiolabeled colloids are popular tracers used to map lymphatic vessels and regional lymph nodes (LNs). The regional LN status is a significant determinant of cancer stage and patient prognosis, and strongly influences treatment. Regional LN dissection has become a part of surgical treatment. However, not all patients with LN involvement benefit from extensive lymphadenectomy in terms of prolonged survival. Moreover, overtreatment of patients with localized disease carries the unnecessary risk of complications. It is believed that sentinel LN biopsy (SLNB) allows to assess the involvement of the most representative LN of the lymphatic basin and to decide on radical LN dissection.99mTc is an easily available radionuclide emitting gamma rays. The value of 99mTc for diagnostic procedures is associated with its relatively short half-life that makes it safe both for patients and medical personnel. A colloid presenting specific physical and biological properties, including optimal particle size, is a carrier for the radionuclide. When administered at the tumor site, a radiocolloid is absorbed by the lymphatics, and the first LN that it gets trapped in is referred to as the sentinel LN (SLN). The radiopharmaceutical must reach the SLN relatively quickly, but its storage within the SLN, and the radionuclide’s half-life must be long enough to enable intraoperative imaging and evaluation. SLNB is currently the gold standard in breast cancer and malignant melanoma diagnosis, and is under extensive investigation in gynecological cancers. Here, we provide a historical perspective of the SLN concept and the clinical relevance of SLNB in gynecologic oncology. Moreover, we review the technical aspects of the application of 99mTc-based radiopharmaceuticals in lymphoscintigraphy and intraoperative lymphatic mapping.

Background Recent advancements in understanding β-escin action provide basis for new therapeutic claims for the drug. β-escin-evoked attenuation of NF-κB-dependent signaling, increase in MMP-14 and decrease in COUP-TFII content and a rise in cholesterol biosynthesis could be beneficial in alleviating muscle-damaging processes. Purpose The aim of this study was to investigate the effect of β-escin on skeletal muscle regeneration. Methods Rat model of cardiotoxin-induced injury of fast-twich extensor digitorum longus (EDL) and slow-twich soleus (SOL) muscles and C2C12 myoblast cells were used in the study. We evaluated muscles obtained on day 3 and 14 post-injury by histological analyses of muscle fibers, connective tissue, and mononuclear infiltrate, by immunolocalization of macrophages and by qPCR to quantify the expression of muscle regeneration-related genes. Mechanism of drug action was investigated in vitro by assessing cell viability, NF-κB activation, MMP-2 and MMP-9 secretion, and ALDH activity. Results In rat model, β-escin rescues regenerating muscles from atrophy. The drug reduces inflammatory infiltration, increases the number of muscle fibers and decreases fibrosis. β-escin reduces macrophage infiltration into injured muscles and promotes their M2 polarization. It also alters transcription of muscle regeneration-related genes: Myf5, Myh2, Myh3, Myh8, Myod1, Pax3 and Pax7, and Pcna. In C2C12 myoblasts in vitro, β-escin inhibits TNF-α-induced activation of NF-κB, reduces secretion of MMP-9 and increases ALDH activity. Conclusions The data reveal beneficial role of β-escin in muscle regeneration, particularly in poorly regenerating slow-twitch muscles. The findings provide rationale for further studies on β-escin repositioning into conditions associated with muscle damage such as strenuous exercise, drug-induced myotoxicity or age-related disuse atrophy.

Upregulation of interleukin 15 (IL-15) contributes directly i.a. to the development of inflammatory and autoimmune diseases. Selective blockade of IL-15 aimed to treat rheumatoid arthritis, psoriasis and other IL-15-related disorders has been recognized as an efficient therapeutic method. The aim of the study was to identify small molecules which would interact with IL-15 or its receptor IL-15Rα and inhibit the cytokine's activity. Based on the crystal structure of IL-15Rα·IL-15, we created pharmacophore models to screen the ZINC database of chemical compounds for potential IL-15 and IL-15Rα inhibitors. Twenty compounds with the highest predicted binding affinities were subjected to in vitro analysis using human peripheral blood mononuclear cells to validate in silico data. Twelve molecules efficiently reduced IL-15-dependent TNF-α and IL-17 synthesis. Among these, cefazolin - a safe first-generation cephalosporin antibiotic - holds the highest promise for IL-15-directed therapeutic applications.

Intellectual capital has become a fundamental source for enterprises, but its measurement and reporting remain a major challenge for managers and researchers. The purpose of this paper is to examine and report the differences in the Intellectual Capital (IC) Market Value (MV) to Book Value (BV) of the Polish WIG 20 indexed companies from Warsaw Stock Exchange. The data necessary to perform the calculations in accordance with the MV/PV method came from the financial statements for the period 2010-2014 of 20 Polish companies. The MV/BV method provides the means to measure intellectual capital in a precise and timely calculation and is particularly useful for the companies that are listed on the stock market. Results are presented and followed by discussion and implication for future research.

Vulvar squamous cell carcinoma (VSCC) originates from the progression of either a high-grade squamous intraepithelial lesion (HSIL) or differentiated-type vulvar intraepithelial neoplasia (dVIN), often in a background of lichen sclerosus (LS). The mechanisms leading to the progression of these premalignant lesions to VSCC are elusive. This study aims to identify pathogenic mutations implicated in VSCC development. Using next-generation sequencing, 38 HSIL, 19 dVIN, 20 LS, of which 10 were solitary lesions and 10 with adjacent VSCC, and 10 VSCC adjacent to LS, were screened for hotspot mutations in 50 genes covered by the Ion AmpliSeq Cancer Hotspot Panel v2 Kit (Thermo Fisher Scientific). Pathogenic mutations of TP53 were the most common genetic alterations identified in 53% and 24% of dVIN and HSIL cases, respectively, followed by CDKN2A (p16) mutated in 42% and 0% of dVIN and HSIL, respectively. Seven (70%) and three (30%) of 10 cases of VSCC associated with LS carried TP53 and CDKN2A mutations, respectively, whereas neither solitary LS nor LS associated with VSCC cases harbored mutations in these genes. It appears that TP53 mutations are early events during VSCC carcinogenesis, being present in both HSIL and dVIN lesions. Our preliminary data do not support a genetic background for the notion of LS as the VSCC premalignant lesion.

A continuing quest for specific inhibitors of proinflammatory cytokines brings promise for effective therapies designed for inflammatory and autoimmune disorders. Cefazolin, a safe, first-generation cephalosporin antibiotic, has been recently shown to specifically interact with interleukin 15 (IL-15) receptor subunit α (IL-15Rα) and to inhibit IL-15-dependent TNF-α and IL-17 synthesis. The aim of this study was to elucidate cefazolin activity against IL-2, IL-4, IL-15 and IL-21, i.e. four cytokines sharing the common cytokine receptor γ chain (γc). In silico, molecular docking unveiled two potential cefazolin binding sites within the IL-2/IL-15Rβ subunit and two within the γc subunit. In vitro, cefazolin decreased proliferation of PBMC (peripheral blood mononuclear cells) following IL-2, IL-4 and IL-15 stimulation, reduced production of IFN-γ, IL-17 and TNF-α in IL-2- and IL-15-treated PBMC and in IL-15 stimulated natural killer (NK) cells, attenuated IL-4-dependent expression of CD11c in monocyte-derived dendritic cells and suppressed phosphorylation of JAK3 in response to IL-2 and IL-15 in PBMC, to IL-4 in TF-1 (erythroleukemic cell line) and to IL-21 in NK-92 (NK cell line). The results of the study suggest that cefazolin may exert inhibitory activity against all of the γc receptor-dependent cytokines, i.e. IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21.

Introduction/Background Vulvar squamous cell carcinoma (VSCC) develops from vulvar squamous intraepithelial lesions (VIN). VIN is subdivided into two types, high grade-squamous intraepithelial lesion (HSIL) and differentiated vulvar intraepithelial neoplasia (dVIN), which differ by pathogenesis and clinical course. No molecular markers allowing precise and non-invasive diagnosis and/or differentiation of malignant and premalignant lesions of the vulva have been developed to date. This study aimed to identify circulating microRNAs as markers for differential diagnostics of VIN and VSCC. Methodology Expression levels of 20 microRNAs were analyzed by quantitative RT-PCR in the plasma samples of 19 patients with VIN (HSIL and dVIN), 41 patients with VSCC and 15 healthy female donors (control group). The microRNA levels were normalized to hsa-miR-93-5p and hsa-miR-425-5p. Results The levels of three microRNA molecules, namely miR-7-5p, miR-630 and miR-23b-3p were found to differentiate plasma samples of obtained from healthy donors, VIN and VSCC patients. The levels of miR-7-5p and miR-630 were decreased in blood of patients with VSCC as compared to VIN and controls. In contrary, the levels of miR-23b-3p were decreased in the blood of VSCC patients as compared to VIN and healthy donor samples. These differences were statistically significant. Conclusion Our data reveal high diagnostic potential of the assessment of levels of circulating miR-7-5p, miR-23b-3p and miR-630 in VIN and VSCC patients. Disclosure Nothing to disclose

The skeletal muscle regeneration occurs due to the presence of tissue specific stem cells - satellite cells. These cells, localized between sarcolemma and basal lamina, are bound to muscle fibers and remain quiescent until their activation upon muscle injury. Due to pathological conditions, such as extensive injury or dystrophy, skeletal muscle regeneration is diminished. Among the therapies aiming to ameliorate skeletal muscle diseases are transplantations of the stem cells. In our previous studies we showed that Sdf-1 (stromal derived factor −1) increased migration of stem cells and their fusion with myoblasts in vitro. Importantly, we identified that Sdf-1 caused an increase in the expression of tetraspanin CD9 - adhesion protein involved in myoblasts fusion. In the current study we aimed to uncover the details of molecular mechanism of Sdf-1 action. We focused at the Sdf-1 receptors - Cxcr4 and Cxcr7, as well as signaling pathways induced by these molecules in primary myoblasts, as well as various stem cells - mesenchymal stem cells and embryonic stem cells, i.e. the cells of different migration and myogenic potential. We showed that Sdf-1 altered actin organization via FAK (focal adhesion kinase), Cdc42 (cell division control protein 42), and Rac-1 (Ras-Related C3 Botulinum Toxin Substrate 1). Moreover, we showed that Sdf-1 modified the transcription profile of genes encoding factors engaged in cells adhesion and migration. As the result, cells such as primary myoblasts or embryonic stem cells, became characterized by more effective migration when transplanted into regenerating muscle.

This article provides new morphological data about Mesocriconema involutum (Loof, 1987) Loof, 1989, a very rare European nematode species. This is the first report on its occurrence in Poland and the third record in Europe. Specimens of M. involutum described in this article were collected from the rhizosphere of grass on the bank of Lake Kielno (northern part of Poland). The research allowed to determine the presence of two projections on the anterior vulval lip, which previously had not been described for this species. A detailed description of the tail's terminal annulus is also given.

Niniejszy artykul przedstawia rozwoj porozumien procesowych w polskim postepowaniu karnym. Ukazuje kolejne liczne nowelizacje przepisow regulujących instytucje skazania bez rozprawy i dobrowolnego poddania sie karze. Artykul stanowi tez probe oceny obecnego znaczenia porozumien procesowych w polskim wymiarze sprawiedliwości. W artykule zaakcentowane wiec zostaly zalety konsensualizmu, ale naświetlono w nim takze mozliwe koszty i zagrozenia z nim związane.

Endometrial stromal sarcomas (ESSs) are mesenchymal uterine tumors characterized by recurrent genetic events, most commonly chromosomal rearrangements, that create oncogenic gene fusions. High-grade endometrial stromal sarcomas (HG-ESSs), as defined in the 2014 World Health Organization Classification, typically contain oncogenic YWHAE-NUTM2 fusions; however, although not well characterized, there are tumors morphologically overlapping with HG-ESS that do not contain the YWHAE-NUTM2 fusions. These fusions are also found in certain pediatric primitive sarcomas, including clear cell sarcoma of the kidney and soft tissue undifferentiated round cell sarcoma of infancy. A subset of these same pediatric sarcomas lack YWHAE-NUTM2 fusions and instead have internal tandem duplications (ITDs) involving exon 15 of BCOR (BCOR ITD). We investigated the presence of BCOR ITD by targeted sequencing in a series of 31 uterine sarcomas, comprising 5 low-grade ESS, 13 uterine sarcomas diagnosed as HG-ESS, and 13 undifferentiated uterine sarcomas. BCOR ITD were present in 1 uterine sarcoma diagnosed as HG-ESS and 2 undifferentiated sarcomas with uniform nuclear features, all of which lacked any of the recurrent chromosome translocations known to occur in ESS. These 3 high-grade sarcomas with BCOR ITD affected young patients (average age, 24) and morphologically were composed of nonpleomorphic spindle cells admixed with epithelioid and round cell areas. Focal myxoid stroma was present in 2 cases. Mitotic activity was brisk, necrosis was present, and there was lymphovascular involvement in all cases. The 3 uterine sarcomas with BCOR ITD exhibited diffuse cyclin D1 immunohistochemical expression and there was diffuse BCOR expression in the 2 cases tested. Long-term follow-up in 2 patients revealed 1 to be tumor-free after 22 years and the other to die of disease after 8 years. In conclusion, BCOR ITD is an oncogenic alternative to YWHAE-NUTM2 fusion in high-grade uterine sarcomas with uniform nuclear features. We propose that neoplasms with the morphology described and BCOR ITD be regarded as a unique subtype of high-grade uterine sarcoma, possibly within the family of endometrial stromal neoplasia. ispartof: The American Journal of Surgical Pathology vol:42 issue:3 pages:335-341 ispartof: location:United States status: published

The purpose of the article was to present the essence of competitiveness and human capital from the macroeconomic perspective, as well as to present human capital as a source of competitiveness of the European Union member states. In order to assess the human capital of the member states, the level of education of residents, as well as calculated synthetic indicator of human capital were analysed. In addition, relationship between the level of the indicator of human capital and competitiveness of the member states, measured by GDP per capita was examined.

Endometrial stromal tumors include translocation-associated low- and high-grade endometrial stromal sarcomas (ESS) and highly malignant undifferentiated uterine sarcomas (UUS). UUS is considered a poorly defined group of aggressive tumors and is often seen as a diagnosis of exclusion after ESS and leiomyosarcoma (LMS) have been ruled out. We performed a comprehensive analysis of gene expression, copy number variation, point mutations, and immune cell infiltrates in the largest series to date of all major types of uterine sarcomas to shed light on the biology of UUS and to identify potential novel therapeutic targets. We show that UUS tumors have a distinct molecular profile from LMS and ESS. Gene expression and immunohistochemical analyses revealed the presence of high numbers of tumor-associated macrophages (TAMs) in UUS, which makes UUS patients suitable candidates for therapies targeting TAMs. Our results show a high genomic instability of UUS and downregulation of several TP53-mediated tumor suppressor genes, such as NDN, CDH11, and NDRG4. Moreover, we demonstrate that UUS carry somatic mutations in several oncogenes and tumor suppressor genes implicated in RAS/PI3K/AKT/mTOR, ERBB3, and Hedgehog signaling.