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Rok Gorenšek,1,2,* Martin Kresnik,1,3,* Iztok Takač,1,4 Tomaž Rojko,1,5 Monika Sobočan1,4 1Faculty of Medicine, University of Maribor, Maribor, Slovenia; 2Department of Oncology, University Medical Centre Maribor, Maribor, Slovenia; 3Department of Emergency Medicine, University Medical Centre Maribor, Maribor, Slovenia; 4Division of Gynecology and Perinatology, University Medical Centre Maribor, Maribor, Slovenia; 5Department of Pathology, University Medical Centre Maribor, Maribor, Slovenia*These authors contributed equally to this workCorrespondence: Monika Sobočan, University Medical Centre Maribor, Division for Gynecology and Perinatology, Ljubljanska ulica 5, Maribor, 2000, Slovenia, Tel +386 2 321 2195, Email monika.sobocan@gmail.comAbstract: Triple negative breast cancer (TNBC) is a subtype of breast cancer which does not express or expresses a minimum amount of estrogen receptors (ER), progesterone receptors (PR) and human epidermal growth factor receptor 2 (HER2) protein. TNBCs include a heterogenic group of cancers that are aggressive, grow rapidly and are associated with poor prognosis and overall survival, mainly attributed to a lack of effective therapeutic targets. For a long time, a major issue with predicting the outcome and prognosis of TNBCs was the lack of an accurate biomarker, a molecule that helps us objectively assess a patient’s health status. In recent times, defining the presence of tumor-infiltrating lymphocytes (TIL) is becoming an indispensable method of determining a patient’s prognosis. TILs are found in tumor tissue and the surrounding stroma and carry a prognostic value. Furthermore, they are known to improve the effect of systemic therapy. With the rise of immunotherapy, the role of TIL in this newer therapeutic option is a topic of increased importance. The goal behind this research article is a comprehensive review of the current literature on the importance of tumor-infiltrating lymphocytes in the prognosis of TNBC.Keywords: tumor-infiltrating lymphocytes, immunotherapy, prognosis, dysfunction/exhaustion, microenvironment, immunometabolism

Gestational trophoblastic disease (GTD) is a heterogeneous group of rare tumours characterised by abnormal proliferation of trophoblastic tissue. It consists of benign or premalignant conditions, such as complete and partial molar pregnancy and variants of malignant diseases. The malignant tumours specifically are commonly referred to as gestational trophoblastic neoplasia (GTN). They consist of invasive mole, choriocarcinoma, placental-site trophoblastic tumour (PSTT) and epithelioid trophoblastic tumour (ETT).

The aim of this study was to evaluate changes in prognostic risk profiles of women with endometrial cancer by comparing the clinical risk assessment with the integrated molecular risk assessment profiling.

Background: Breast cancer (BC) comprises multiple subtypes with distinct molecular features, which differ in their interplay with host immunity, prognosis, and treatment. Non-invasive blood analyses can provide valuable insights into systemic immunity during cancer. The aim of this study was to analyze the expression of transcriptional isoforms in peripheral blood mononuclear cells (PBMCs) from BC patients and healthy women to identify potential BC immune biomarkers. Methods: RNA sequencing and isoform-level bioinformatics were performed on PBMCs from 12 triple-negative and 13 luminal A patients. Isoform expression validation by qRT-PCR and clinicopathological correlations were performed in a larger cohort (156 BC patients and 32 healthy women). Results: Transcriptional analyses showed a significant ( p < 0.001) decrease in the ENST00000374459 RASGEF1A isoform in PBMCs of BC compared to healthy subjects, indicating disease-related expression changes. The decrease was associated with higher ctDNA and Ki-67 values. Conclusions: The levels of the RASGEF1A transcriptional isoform ENST00000374459 may have the potential to distinguish between BC and healthy subjects. The downregulation of ENST00000374459 in breast cancer is associated with higher proliferation and ctDNA shedding. Specialized bioinformatics analyses such as isoform analyses hold significant promise in the detection of biomarkers, since standard RNA sequencing analyses may overlook specific transcriptional changes that may be disease-associated and biologically important.

BRCA genetic testing is available for UK Jewish individuals but the provision of information online for BRCA is unknown. We aimed to evaluate online provision of BRCA information by UK organisations (UKO), UK Jewish community organisations (JCO), and genetic testing providers (GTP). Google searches for organisations offering BRCA information were performed using relevant sets of keywords. The first 100 website links were categorised into UKOs/JCOs/GTPs; additional JCOs were supplemented through community experts. Websites were reviewed using customised questionnaires for BRCA information. Information provision was assessed for five domains: accessibility, scope, depth, accuracy, and quality. These domains were combined to provide a composite score (maximum score = 5). Results were screened ( n = 6856) and 45 UKOs, 16 JCOs, and 18 GTPs provided BRCA information. Accessibility was high (84%,66/79). Scope was lacking with 35% (28/79) addressing >50% items. Most (82%, 65/79) described BRCA -associated cancers: breast and/or ovarian cancer was mentioned by 78%(62/79), but only 34% (27/79) mentioned ≥1 pancreatic, prostate, melanoma. Few websites provided carrier frequencies in the general (24%,19/79) and Jewish populations (20%,16/79). Only 15% (12/79) had quality information with some/minimal shortcomings. Overall information provision was low-to-moderate: median scores UKO = 2.1 (IQR = 1), JCO = 1.6 (IQR = 0.9), and GTP = 2.3 (IQR = 1) (maximum-score = 5). There is a scarcity of high-quality BRCA information online. These findings have implications for UK Jewish BRCA programmes and those considering BRCA testing.

Background and Objectives : Gestational trophoblastic disease (GTD) is a group of pregnancy-related malignant and premalignant diseases. The aim of this study was to assess the prognostic value of clinical characteristics to predict treatment outcomes in women with GTD. Materials and Methods : In this retrospective study, 34 patients treated for GTD at the Division of Gynaecology and Perinatology, University Medical Centre Maribor, between 2008 and 2022 were identified. Clinical and pathological characteristics were obtained by analysing patient data records. Results : Within the cohort of 34 patients with GTD, 29 patients (85.3%) had a partial hydatidiform mole (HM) and five patients545 (14.7%) had a complete HM. Two patients with a complete HM developed a postmolar gestational trophoblastic neoplasia (GTN), which represents 5.8% of all cases. Conclusions : GTD is a rare disease that is frequently asymptomatic. The subsequent consequences of GTD, which can lead to malignant transformation, as well life-threatening disease complications, warrant training for early recognition of HMs and timely treatment and surveillance.

Endometrial and cervical cancers are the two most common gynaecological malignancies and among the leading causes of death worldwide. The extracellular matrix (ECM) is an important component of the cellular microenvironment and plays an important role in developing and regulating normal tissues and homeostasis. The pathological dynamics of the ECM contribute to several different processes such as endometriosis, infertility, cancer, and metastasis. Identifying changes in components of ECM is crucial for understanding the mechanisms of cancer development and its progression. We performed a systematic analysis of publications on the topic of changes in the extracellular matrix in cervical and endometrial cancer. The findings of this systematic review show that matrix metalloproteinases (MMP) play an important role impacting tumour growth in both types of cancer. MMPs degrade various specific substrates (collagen, elastin, fibronectin, aggrecan, fibulin, laminin, tenascin, vitronectin, versican, nidogen) and play a crucial role in the basal membrane degradation and ECM components. Similar types of MMPs were found to be increased in both cancers, namely, MMP-1, MMP-2, MMP-9, and MMP-11. Elevated concentrations of MMP-2 and MMP-9 were correlated with the FIGO stage and are associated with poor prognosis in endometrial cancer, whereas in cervical cancer, elevated concentrations of MMP-9 have been associated with a better outcome. Elevated ADAMTS levels were found in cervical cancer tissues. Elevated disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) levels were also found in endometrial cancer, but their role is still unclear. Following these findings, this review reports on tissue inhibitors of ECM enzymes, MMPs, and ADAMTS. The present review demonstrates changes in the extracellular matrix in cervical and endometrial cancers and compared their effect on cancer development, progression, and patient prognosis.

Endometrial cancer is the most common gynecologic malignancy in the developed world. Risk stratification and treatment approaches are changing due to better understanding of tumor biology. Upregulated Wnt signaling plays an important role in cancer initiation and progression with promising potential for development of specific Wnt inhibitor therapy. One of the ways in which Wnt signaling contributes to progression of cancer, is by activating epithelial-to-mesenchymal transition (EMT) in tumor cells, causing the expression of mesenchymal markers, and enabling tumor cells to dissociate and migrate. This study analyzed the expression of Wnt signaling and EMT markers in endometrial cancer. Wnt signaling and EMT markers were significantly correlated with hormone receptors status in EC, but not with other clinico-pathological characteristics. Expression of Wnt antagonist, Dkk1 was significantly different between the ESGO-ESTRO-ESP patient risk assessment categories using integrated molecular risk assessment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ledinek, Sobočan, Sisinger, Hojnik, Büdefeld, Potočnik and Knez.)

The role of estrogens and progesterone in the development and progression of endometrial cancer is well-established, but there are very little data about the role of androgens. There are five different androgens produced in women: dehydroepiandrosterone sulphate (DHEAS), dehydroepiandrosterone (DHEA), androstenedione (A 4 ), testosterone (T) and dihydrotestosterone (DHT). The most potent hormones are T and DHT, the latter being mainly produced from T in peripheral tissues, including endometrium. Although they are considered to exert antiproliferative effects in many settings and the expression of their receptors is more often associated with a good prognosis in EC, it is still unknown in which specific settings androgens have carcinogenic or protective effects in EC.

The overall survival of women with endometrial cancer is excellent after management. Different management strategies are associated with variable patient-reported outcomes (PROs). Evaluating PROs in the follow-up period can aid in better counseling and intervention for PRO improvement. This study aimed to evaluate the properties of the Slovenian translation of the EORTC QLQ-EN24 assessment scale. Women treated at the University Medical Centre Maribor, Slovenia, between January 2016 and December 2019 were invited to report their symptoms using the EORTC QLQ-EN24 questionnaire. Data were correlated with treatment modalities and clinical characteristics. The median age of participants in our study was 61 years old. PROs were not specific to therapy or clinical characteristics. Overall, women who more frequently reported gastrointestinal symptoms, muscular pain, or back pain also had statistically more frequently decreased levels of PROs in other assessed areas. Women who reported sexual or vaginal problems more often reported significantly poorer body images. Sexual activity within 4 weeks prior to completing the scale was reported by 39% of women. Sexual functioning assessments also showed important correlations between sexual interest, enjoyment, and activity. Individualized follow-ups addressing PROs should be offered to better address concerns and improve long-term outcomes in women with endometrial cancer.

High grade epithelial ovarian cancer (EOC) represents a diagnostic and therapeutic challenge due to its aggressive features and short recurrence free survival (RFS) after primary treatment. Novel targets to inform our understanding of the EOC carcinogenesis in the translational machinery can provide us with independent prognostic markers and provide drugable targets. We have identified candidate eukaryotic initiation factors (eIF) and eukaryotic elongation factors (eEF) in the translational machinery for differential expression in EOC through in-silico analysis. We present the analysis of 150 ovarian tissue microarray (TMA) samples on the expression of the translational markers eIF2α, eIF2G, eIF5 (eIF5A and eIF5B), eIF6 and eEF1A1. All translational markers were differentially expressed among non-neoplastic ovarian samples and tumour samples (borderline tumours and EOC). In EOC, expression of eIF5A was found to be significantly correlated with recurrence free survival (RFS) and expression of eIF2G and eEF1A1 with overall survival (OS). Expression correlation among factor subunits showed that the correlation of eEF1A1, eIF2G, EIF2α and eIF5A were significantly interconnected. eIF5A was also correlated with eIF5B and eIF6. Our study demonstrates that EOCs have different translational profile compared to benign ovarian tissue and that eIF5A is a central dysregulated factor of the translation machinery., (© 2022. The Author(s).)

Endometrial cancer (EC) is the most common gynaecologic malignancy in the developed countries. Recent evidence suggests that histopathological subtyping together with molecular subgrouping can lead to more accurate assessment of the risk profile for the patient. Clinical studies suggest the currently used molecular classification improves the risk assessment of women with endometrial cancer but does not explain the differences in recurrence profiles clearly. This could be improved by novel markers. One of such are mutations in the β -catenin ( CTNNB1 ) gene, a frequently mutated gene in endometrial cancer. This shows mutations mostly at phosphorylation sites of the β -catenin and almost exclusively in the endometrial subgroup of no specific molecular profile. CTNNB1 mutations lead to alterations in the Wnt/ β -catenin signalling pathway, involved in the carcinogenesis and progression of EC by inducing transcription of target genes, whose function is to regulate the cell cycle. Although tumours with mutations in CTNNB1 tend to have low-risk characteristics, they are related to worse outcomes with significantly increased rate of disease recurrence and lower overall survival., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Živa Ledinek et al.)

Adenomyosis, endometriosis, endometritis, and typical endometrial hyperplasia are common non-cancerous diseases of the endometrium that afflict many women with life-impacting consequences. The mammalian target of the rapamycin (mTOR) pathway interacts with estrogen signaling and is known to be dysregulated in endometrial cancer. Based on this knowledge, we attempt to investigate the role of mTOR signaling in benign endometrial diseases while focusing on how the interplay between mTOR and eukaryotic translation initiation factors (eIFs) affects their development. In fact, mTOR overactivity is apparent in adenomyosis, endometriosis, and typical endometrial hyperplasia, where it promotes endometrial cell proliferation and invasiveness. Recent data show aberrant expression of various components of the mTOR pathway in both eutopic and ectopic endometrium of patients with adenomyosis or endometriosis and in hyperplastic endometrium as well. Moreover, studies on endometritis show that derangement of mTOR signaling is linked to the establishment of endometrial dysfunction caused by chronic inflammation. This review shows that inhibition of the mTOR pathway has a promising therapeutic effect in benign endometrial conditions, concluding that mTOR signaling dysregulation plays a critical part in their pathogenesis.

Triple-negative breast cancer (TNBC) is a breast cancer (BC) subtype that accounts for approximately 15-20% of all BC cases. Cancer cell lines (CLs) provide an efficient way to model the disease. We have recently isolated a patient-derived triple-negative BC CL MFUM-BrTNBC-1 and performed a detailed morphological and molecular characterisation and a comprehensive comparison with three commercial BC CLs (MCF-7, MDA-MB-231, MDA-MB-453). Light and fluorescence microscopy were used for morphological studies; immunocytochemical staining for hormone receptor, p53 and Ki67 status; RNA sequencing, qRT-PCR and STR analysis for molecular characterisation; and biomedical image analysis for comparative phenotypical analysis. The patient tissue-derived MFUM-BrTNBC-1 maintained the primary triple-negative receptor status. STR analysis showed a stable and unique STR profile up to the 6th passage. MFUM-BrTNBC-1 expressed EMT transition markers and displayed changes in several cancer-related pathways (MAPK, Wnt and PI3K signalling; nucleotide excision repair; and SWI/SNF chromatin remodelling). Morphologically, MFUM-BrTNBC-1 differed from the commercial TNBC CL MDA-MB-231. The advantages of MFUM-BrTNBC-1 are its isolation from a primary tumour, rather than a metastatic site; good growth characteristics; phenotype identical to primary tissue; complete records of origin; a unique identifier; complete, unique STR profile; quantifiable morphological properties; and genetic stability up to (at least) the 6th passage.

Background: Effective clinical reasoning is a core competency of health professionals that is necessary to assure patients' safety. Unfortunately, adoption of longitudinal clinical reasoning curricula is still infrequent. This study explores the barriers that hinder the explicit teaching of clinical reasoning from a new international perspective., Methods: The context of this study was a European project whose aim is to develop a longitudinal clinical reasoning curriculum. We collected data in semi-structured interviews with responders from several European countries who represent various health professions and have different backgrounds, roles and experience. We performed a qualitative content analysis of the gathered data and constructed a coding frame using a combined deductive/inductive approach. The identified themes were validated by parallel coding and in group discussions among project members., Results: A total of 29 respondents from five European countries participated in the interviews; the majority of them represent medicine and nursing sciences. We grouped the identified barriers into eight general themes: Time, Culture, Motivation, Clinical Reasoning as a Concept, Teaching, Assessment, Infrastructure and Others. Subthemes included issues with discussing errors and providing feedback, awareness of clinical reasoning teaching methods, and tensions between the groups of professionals involved., Conclusions: This study provides an in-depth analysis of the barriers that hinder the teaching of explicit clinical reasoning. The opinions are presented from the perspective of several European higher education institutions. The identified barriers are complex and should be treated holistically due to the many interconnections between the identified barriers. Progress in implementation is hampered by the presence of reciprocal causal chains that aggravate this situation. Further research could investigate the perceptual differences between health professions regarding the barriers to clinical reasoning. The collected insights on the complexity and diversity of these barriers will help when rolling out a long-term agenda for overcoming the factors that inhibit the implementation of clinical reasoning curricula., (© 2021. The Author(s).)

This review summarizes the recent findings of a vast array of studies conducted on androgen receptor-positive triple-negative breast cancer (AR-positive TNBC) to provide a better understanding of this specific breast cancer subgroup. AR expression is correlated with higher age, lower histological grade, lower proliferation index Ki-67, spiculated masses, and calcifications on mammography. Studies investigating the correlation between AR expression and lymph node metastasis are highly discordant. In addition, results regarding prognosis are highly contradictory. AR antagonists are a promising novel therapeutic approach in AR-positive TNBC. However, AR signaling pathways should be more investigated in order to understand the influence of AR expression on TNBC more thoroughly.

Cell lines are widely used for various research purposes including cancer and drug research. Recently, there have been studies that pointed to discrepancies in the literature and usage of cell lines. That is why we have prepared a comprehensive overview of the most common gynaecological cancer cell lines, their literature, a list of currently available cell lines, and new findings compared with the original studies. A literature review was conducted via MEDLINE, PubMed and ScienceDirect for reviews in the last 5 years to identify research and other studies related to gynaecological cancer cell lines. We present an overview of the current literature with reference to the original studies and pointed to certain inconsistencies in the literature. The adherence to culturing rulesets and the international guidelines helps in minimizing replication failure between institutions. Evidence from the latest research suggests that despite certain drawbacks, variations of cancer cell lines can also be useful in regard to a more diverse genomic landscape., (© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Objective: To determine the prevalence of lower urinary tract symptoms (LUTS) in female adolescent population., Study Design: We performed a questionnaire-based study in nine randomly selected high schools in our country. Our primary aim was to evaluate the prevalence of certain LUTS in adolescent girls: frequency, urgency, nocturia, feeling of incomplete bladder emptying, dysuria, and urinary incontinence. The secondary aim was to investigate the effect of some possible risk factors on LUTS prevalence. Statistical analysis was performed using SPSS Statistics Programme. Descriptive statistics were calculated. Non-parametric test was used for comparison of numerical and Pearson's Chi-square test for categorical data. Logistic regression was performed to identify the independent prognosticators for LUTS presence. Statistical significance was set at p < 0.05., Results: We included 2745 adolescent girls. Their average age was 16.8 ± 1.2 years and 17.8 % of them regularly experienced at least one LUTS. The frequency of occasional LUTS was even higher. The most common symptom was urinary incontinence (5.9 %), followed by frequency (5.1 %), feeling of incomplete bladder emptying (4.8 %), urgency (3.1 %), and nocturia (2.6 %). Risk factors for LUTS presence were girls' school success, frequent pelvic pain, previous cystitis, history of night enuresis in childhood, and sexual intercourses in the last three months., Conclusions: According to our results, the prevalence of LUTS amongst female adolescents is high and can be associated with certain risk factors. In our opinion, further research should be directed into determining the effect of LUTS on adolescents' quality of life., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Endometrial cancer is the most common gynecological cancer in developed countries. The disease is diagnosed with increasing frequency in younger women, commonly also in their reproductive age. The standard treatment of endometrial cancer is surgical in the form of hysterectomy and bilateral salpingo-oophorectomy, and this precludes future fertility in younger women. The current challenge is to identify the group of women with endometrial cancer and low-risk features that would benefit from more conservative treatment options. More focus in management needs to be aimed towards the preservation of quality of life, without jeopardizing oncological outcomes. In this review, we analyze the current approaches to identification of women for conservative management and evaluate the success of different medical options for treatment and surgical techniques that are fertility sparing. We also elaborate on the future perspectives, focusing on the incorporation of molecular characterization of endometrial cancer to fertility preservation algorithms. Future studies should focus specifically on identifying reliable clinical and molecular predictive markers in this group of young women. With improved knowledge and better risk assessment, the precision medicine is the path towards improved understanding of the disease and possibly widening the group of women that could benefit from treatment methods preserving their fertility.

Introduction: Endometrial cancer (EC) is the most common gynaecological malignancy in developed countries. Early and accurate diagnostic assessment is crucial for appropriate treatment planning. Information obtained by pre-operative imaging with transvaginal ultrasound (TVUS) and histological endometrial biopsy assessment is often the cornerstone for further management planning. This study aimed to analyse the accuracy of this diagnostic approach for patient management decisions., Materials and Methods: This single-centre retrospective analysis included all patients with endometrial cancer treated between 2015 and 2019. Pre-operative TVUS staging assessment and histopathological endometrial biopsy examination were compared with the final surgical stage and histopathological diagnosis., Results: Pre-operative and surgical pathological assessment of Type I and Type II tumours was in agreement in 95 % (174/184) and 54 % (12/22) of cases, respectively. The sensitivity and specificity of TVUS assessment of myometrial invasion were 76 % [95 % confidence interval (CI) 66.3-84.2 %] and 81.7 % [95 % CI 73.0-88.6 %], respectively. Diagnostic accuracy was higher for Type I EC (95 %) than Type II EC (54 %). Only presumed ESMO/ESGO/ESTRO risk classification (p < 0.000) and deep myometrial invasion (p < 0.000) were significant for the prediction of lymph node involvement., Conclusion: Pre-operative TVUS examination and pathological endometrial biopsy evaluation enable moderately accurate assessment of the risk of EC. Efforts should be aimed towards the development of novel and more reproducible methods, such as molecular tumour characterization, to improve the pre-operative assessment of risk in patients with EC., Competing Interests: Declaration of Competing Interest The author declare no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Identifying women at risk for small-for-gestational-age newborns (SGA) is an important challenge in obstetrics. Several different risk factors have been suggested to contribute to the development of SGA. Previous research is inconclusive on the role selenium (Se) plays in the development of SGA. The aim of the study was therefore to explore the role of Se concentrations in amniotic fluid in order to understand its possible role in the development of SGA., Study Design: This prospective, single center study investigated the relationships between Se concentrations in amniotic fluid and pregnancy outcomes. Amniotic fluid was collected from pregnant women during amniocentesis at 16/17 weeks of pregnancy. Se values were determined using the electrothermal atomic absorption spectrometry and expressed in µg/L. Characteristics of mothers and newborns were obtained from women and delivery records., Results: 327 samples of amniotic fluid were evaluated. Patients with SGA newborns had significantly lower mean values of amniotic fluid concentrations of Se compared to appropriate-for-gestational-age (AGA) newborns (4.8 ± 1.9 µg/L versus 5.6 ± 2.5 µg/L ( p = 0.017)). Adjusting for different risk factors, Se remained the only significant factor impacting the outcome of a newborn (b = -0.152, s.e. = 0.077; p < 0.048). Se levels in amniotic fluid did not correlate with pre-eclampsia or preterm delivery., Conclusion: Amniotic fluid Se levels represent a viable root of further investigation and assessment in order to identify women with low birth weight newborns early. Women with decreased Se levels had a statistically significant chance of developing SGA. Further research is needed to elucidate the link between Se, other trace elements, and other risk factors and their impact on the development of SGA newborns.

Endometrial cancer (EC) is a common gynecologic malignancy which continues to have a poor prognosis in advanced stages due to current therapeutic limitations. A significant mechanism of chemoresistance in EC has been shown to also be the enhancement of epithelial to mesenchymal transition (EMT) and the subsequent obtainment of stem cell-like characteristics of EC. Current evidence on EMT in EC however fails to explain the relationship leading to an EMT signaling enhancement. Our review therefore focuses on understanding eukaryotic translation initiation factors (eIFs) as key regulators of the translational process in enhancing EMT and subsequently impacting higher chemoresistance of EC. We identified pathways connected to the development of a microenvironment for EMT, inducers of the process specifically related to estrogen receptors as well as their interplay with eIFs. In the future, investigation elucidating the translational biology of EC in EMT may therefore focus on the signaling between protein kinase RNA-like ER kinase (PERK) and eIF2alpha as well as eIF3B.

Objective: Clinical and pathological characteristics of triple negative breast cancer (TNBC) treatment are required for escalation or de-escalation of treatment because of a lack of druggable targets. This study aimed to identify the factors affecting the risk of disease recurrence and disease-related death in patients with TNBC., Methods: Patients with TNBC who were treated at the University Medical Centre Maribor between January 2010 and December 2017 were studied. Clinical and pathological data were analyzed using multivariate analysis and non-parametric tests. Subgroup analysis was performed to examine additional factors that affect 5-year overall survival (OS) and recurrence-free survival., Results: Multivariate analysis showed that tumor size and the lymph node ratio (LNR) were significant risks in our population. Better discrimination of patients at risk of a shorter recurrence-free survival and OS was achieved by using the LNR. Only lymphovascular invasion was significant for predicting 5-year OS., Conclusion: For risk-based decision-making systems, the LNR is useful for discriminating between high- and low-risk patients with TNBC.

Studies of the mechanistic (mammalian) target of rapamycin inhibitors (mTOR) represent a step towards the targeted treatment of gynecological cancers. It has been shown that women with increased levels of mTOR signaling pathway targets have worse prognosis compared to women with normal mTOR levels. Yet, targeting mTOR alone has led to unsatisfactory outcomes in gynecological cancer. The aim of our review was therefore to provide an overview of the most recent clinical results and basic findings on the interplay of mTOR signaling and cold shock proteins in gynecological malignancies. Due to their oncogenic activity, there are promising data showing that mTOR and Y-box-protein 1 (YB-1) dual targeting improves the inhibition of carcinogenic activity. Although several components differentially expressed in patients with ovarian, endometrial, and cervical cancer of the mTOR were identified, there are only a few investigated downstream actors in gynecological cancer connecting them with YB-1. Our analysis shows that YB-1 is an important player impacting AKT as well as the downstream actors interacting with mTOR such as epidermal growth factor receptor (EGFR), Snail or E-cadherin., Competing Interests: The authors declare no conflict of interest.

Nowadays, women want a more intimate and familiar atmosphere during labour, which results in increased planned home birth rates. Every woman has the autonomy to decide where she will give birth; however, it is important that she is informed of risks and advantages beforehand. Home births can be distinguished between planned and unplanned home births. Planned home births can be conducted by professional birth attendants (licensed midwives) or birth assistants (doulas, etc). The rates of Slovenian women who decided to deliver at home are increasing year by year. Researches on home births still present discordant data about home birth safety. Their findings have shown that the main advantage of home birth is a spontaneous birth without medical interventions, especially in multiparous low-risk women. The main disadvantage, however, is a higher risk for neonatal death, in particular on occurrence of complications requiring a transfer to hospital and surgical intervention. Global guidelines emphasize careful selection of candidates suitable for home birth, well-informed pregnant women, education of birth attendants, and strict formation of transfer indications., (© 2019 John Wiley & Sons, Ltd.)

Background: Student engagement (SE) in the curriculum is a positive indicator in the development of students deeply involved in their learning. It also has several benefits for the schools' level of educational innovation and quality assurance., Method: In order to identify the most important pearls from the last decade of educational developments within the field of SE at the Faculty of Medicine University of Maribor, we searched through our school's archives, publications and research in the field of medical education., Results: Three areas were identified as the most important SE complements: (i) peer teaching, (ii) school governance, and (iii) extracurricular activities. The paper highlights how many student-driven initiatives move from informal frameworks toward a formal structure, elective courses, and, in the end, compulsory components of the curriculum., Discussion: As demonstrated by the three educational achievements at our school, fostering a high level of SE can lead to innovative curricular changes, benefit the whole school and enable students to deliver highly impactful extracurricular projects.

Objective: An increasing number of breast-conserving surgeries (BCS) has lead clinicians to the dilemma how to provide patients with the best pathological, short-term and long-term outcomes, while at the same time improving the cosmetic outcome and the patients' quality of life. A proposed solution is the use of intraoperative ultrasound (IOUS) for lesion resection in palpable as well as non-palpable breast cancer., Methods: This review identifies and compares evidence on palpation-guided/wire-guided vs. US-guided localization as well as stand-alone observational IOUS studies published between June 2001 and July 2017, indexed in Medline. A cornerstone of this review is the discussion on technology advancement as well as alternative IOUS approaches and their feasibility in treatment of patients with calcifications and multifocal lesions currently not treated with IOUS localization., Results: In comparison to other available methods, IOUS provided in most studies better rates of clear margins, lower rates of re-excisions as well as better cosmetic outcomes. Currently, there is a lack of available multicenter data on method comparisons as well as several limitations to the use of IOUS., Conclusions: With a comparable follow-up rate of loco-regional recurrences and a higher reported long-term quality of life, IOUS should be a highly regarded method of localization in the planning of BCS., (Copyright © 2017 Elsevier B.V. All rights reserved.)