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Transplanted lungs suffer worse outcomes than other organ transplants with many developing chronic lung allograft dysfunction (CLAD), diagnosed by physiologic changes. Histology of transbronchial biopsies (TBB) yields little insight, and the molecular basis of CLAD is not defined. We hypothesized that gene expression in TBBs would reveal the nature of CLAD and distinguish CLAD from changes due simply to time posttransplant. Whole-genome mRNA profiling was performed with microarrays in 498 prospectively collected TBBs from the INTERLUNG study, 90 diagnosed as CLAD. Time was associated with increased expression of inflammation genes e.g. CD1E and immunoglobulins. After correcting for time, CLAD manifested not as inflammation but as parenchymal response-to-wounding, with increased expression of genes such as HIF1A, SERPINE2, and IGF1 that are increased in many injury and disease states and cancers, associated with development, angiogenesis, and epithelial response-to-wounding in pathway analysis. Fibrillar collagen genes were increased in CLAD, indicating matrix changes, and normal transcripts were decreased - dedifferentiation. Gene-based classifiers predicted CLAD with AUC 0.70 (no time-correction) and 0.87 (time-corrected). CLAD related gene sets and classifiers were strongly prognostic for graft failure and correlated with CLAD stage. Thus, in TBBs molecular changes indicate that CLAD primarily reflects severe parenchymal injury-induced changes and dedifferentiation.

Fatty acid binding protein A (A-FABP) is one of FABPs isoforms found mainly in adipose tissue and macrophages. It works through many integrated pathways, regulating inflammation and lipid metabolism, promoting glucose production, impairing insulin function, and contributing to diseases such as atherosclerosis and diabetes. A-FABP is upregulated in the adipose tissue of obese patients and its increased release into the bloodstream is positively associated with body mass index. Consequently, A-FABP plays a key role in regulating metabolism in obese people. Recent studies in mouse models and humans demonstrated the role of A-FABP in increasing the risk of obesity-related cancers. Here we summarized the state of research on the link between obesity, cancer and A-FABP as a new potential therapeutic target for the treatment of obesity - associated cancers.

The aim of our study was to explore organizational innovations made in hospitals in years 2017-2019 in Europe in accordance with the Scoping Review procedure. The analysis of the indicated years resulted from the need to identify organizational innovations before the Covid-19 pandemic. We selected articles in four databases: MEDLINE/PUBMED, Embase, Cochrane Collaboration, Web of Science. To explore all fields of organizational innovations in healthcare the following research questions were formulated: Q1: How do the organizational innovations presented in this Scoping Review affect the functioning of hospital facilities? Q2: How do the innovations presented in the Scoping Review contribute to increasing patients’ safety? Q3: How does the research presented in the Scoping Review affect the organization of healthcare facilities? Q4: How do the organizational innovations presented in the Scoping Review change selected hospitals? Q5: How does the research presented in the Scoping Review combine medical innovations with organizational innovations? Methods A scoping review methodology was chosen in order to deepen research activity in the field of organizational technologies in hospitals without impact of Covid-19 pandemic crisis. The scoping review approach was used as it allows for various study designs to be included and their findings synthetized. During the study, methodological stages outlined by Arksey and O’Malley and further defined by Levac et. al. were followed. They include: 1. Identifying research questions. 2. Identifying relevant studies. 3. Study selections. 4. Charting the data. 5. Collating, summarizing, and reporting the results. The analysis of articles was conducted by phrases related to health technologies: Hospital innovations AND hospital investment AND Hospital New Technologies in Europe in four databases: PUBMED/Medline, Embase, Cochrane Collaboration, Web of Science (WoS). The research were conducted in November 2022 by search in three databases (PUBMED/Medline, Embase, Cochrane Collaboration) with adding the studies from Web of Science database in February 2023. The study was minimized to years 2017-2019 and restricted only to English language. The articles regarding organizational change in hospitals, specific departments, improvement into those departments, innovations and investments in hospitals, as well as research based on interviews with hospital management/healthcare professionals, management changes, research related to quality, patients’ safety, mhealth applications at the hospitals (ehealth solutions at the hospital care), patients’ diagnostics pathways, the role of medical staff on organizational changes, new treatment methods regarding organizational issues were taken into account. Discussion The organizational change introduced in hospitals can positively affect patient safety, for example, by improving the ergonomics of medical staff, thereby reducing the risk of occupational accidents. Hospitals that invest in modern solutions can increase work efficiency while minimizing costs and the risk of medical errors. Innovative organizational changes in hospitals also have a major impact on improving patient flow. Implementing new solutions and procedures allows better management of healthcare processes, resulting in shorter waiting times for hospital admissions, shorter hospital stays and faster access to appropriate specialists. As a result, patients receive faster and more efficient care, and the process is more organized and safer . Organizational changes in hospitals have a significant impact on improving patient pathways. With new solutions and procedures, medical staff can operate more efficiently and effectively, resulting in better quality of patient care. Innovative approaches to work organization allow better coordination between different medical staff enabling faster and more comprehensive patient care . Organisational change means that not only the physical environment is altered, but also the behavioural operations, structural relationships and roles, and the hospital organisational culture may transform. For example, changing the physical health care environment can affect job satisfaction, stress, intention to leave, and the way staff work together. Ethics and dissemination Ethical approval will be not required (primary data will not be gathered in this research). The results will be published in a peer-reviewed journal. The article will be disseminated via appropriate mailing lists and social media, as well as various research platforms.

PURPOSE For patients with surgically resected disease, multiple studies suggest a benefit of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in delaying cancer recurrence. The necessary duration of therapy for benefit is unknown. MATERIALS AND METHODS This randomized phase II study enrolled patients with completely resected stage IA-IIIB EGFR-mutant non–small-cell lung cancer (American Joint Committee on Cancer 7th edition) after stage-appropriate standard-of-care adjuvant therapy. Patients were randomly assigned 1:1 to 3 months or 2 years of adjuvant afatinib starting at 30 mg by mouth daily. Computed tomography imaging was performed every 6 months for 3 years and then annually. The primary study end point for this planned 92-patient trial was recurrence rate at 2 years from randomization. A 20% improvement (from 70% with 3 months to 90% with 2 years) was targeted. RESULTS Forty-six patients enrolled and 45 were treated. The assigned course of afatinib treatment was completed by 96% (22/23) of patients in the 3-month group and only 41% (9/22) in the 2-year group. The 2-year recurrence-free survival (RFS) rates were 70% in the 3-month group and 81% in the 2-year group ( P = .55). The median RFS was 42.8 months in the 3-month group and 58.6 months in the 2-year group. Side effects were consistent with those previously described for afatinib. CONCLUSION Recurrences at 2 years were 11% less common with 2 years versus 3 months of adjuvant afatinib. This difference did not meet the 20% primary study target, likely because of underaccrual and early drug discontinuation on the 2-year group. With the availability of osimertinib with better efficacy and tolerability than earlier-generation agents, the optimal duration of adjuvant EGFR TKI therapy remains an important question.

This research aimed to investigate how health behaviors changed during the COVID-19 pandemic and to identify the economic factors influencing these changes. There were considered income situation and labor market situation as the potential economic factors. Additionally, in the analysis, there were included other characteristics: age, gender, and education level. Health condition was considered through the prism of certain unhealthy characteristics: alcohol consumption, smoking cigarettes, lack of physical activity, and unfavorable eating habits. The study was carried out on the stratified sample of adult inhabitants of Poland (N=1067) in November 2020. To achieve the aim multiple correspondence analysis was used. The results show that the pandemic has changed health behaviors. The negative changes mainly concerned physical activity and eating habits, and only one-sixth reported an increase in alcohol use and cigarette smoking. An increase in negative health behavior was mostly associated with the following characteristics: male, lower age (between 30 and 59), employed persons, tertiary education, and higher income (the fourth and the fifth income quintile group). The exception was a physical activity, where all changes (both negative and positive) were associated with females, people with basic vocational and secondary education, the second and third quintile group, pensioners and retirees, 60 and above age.

COVID-19 disease, which highly affected global life in 2020, led to a rapid scientific response. Versatile optimization methods found their application in scientific studies related to COVID-19 pandemic. Differential Evolution (DE) and Particle Swarm Optimization (PSO) are two metaheuristics that for over two decades have been widely researched and used in various fields of science. In this paper a survey of DE and PSO applications for problems related with COVID-19 pandemic that were rapidly published in 2020 is presented from two different points of view: 1. practitioners seeking the appropriate method to solve particular problem, 2. experts in metaheuristics that are interested in methodological details, inter comparisons between different methods, and the ways for improvement. The effectiveness and popularity of DE and PSO is analyzed in the context of other metaheuristics used against COVID-19. It is found that in COVID-19 related studies: 1. DE and PSO are most frequently used for calibration of epidemiological models and image-based classification of patients or symptoms, but applications are versatile, even interconnecting the pandemic and humanities; 2. reporting on DE or PSO methodological details is often scarce, and the choices made are not necessarily appropriate for the particular algorithm or problem; 3. mainly the basic variants of DE and PSO that were proposed in the late XX century are applied, and research performed in recent two decades is rather ignored; 4. the number of citations and the availability of codes in various programming languages seems to be the main factors for choosing metaheuristics that are finally used.

Approximately 10% of EGFR-activating mutations occur as in-frame insertion mutations in exon 20 of the EGFR kinase domain (EGFR ins20). EGFR ins20 mutations have not demonstrated the same sensitivity to early generations of EGFR tyrosine kinase inhibitors (TKI) as canonical activating EGFR mutations such as del19 and L858R. Development of effective therapies for this subset of patients has been challenging, but recent years have seen more rapid progress in these efforts. In this review, we describe the molecular and clinicopathologic features of EGFR ins20 mutations and summarize recent data on emerging therapies for patients with this subtype of EGFR-mutant non–small cell lung cancer (NSCLC).Significance:When activating mutations in EGFR were first discovered in lung cancer, the lack of sensitivity of tumors harboring EGFR ins20 mutations to early-generation EGFR TKIs resulted in this subset of EGFR-mutant tumors being initially classified as an untargetable or intrinsically resistant subpopulation. In addition, the diversity of mutations within EGFR exon 20 and resultant challenges identifying them on routine clinical genotyping tests led to underestimation of their frequency. However, recent scientific progress in targeting EGFR ins20 mutations as well as more effective identification of this clinical cohort has enhanced our ability to develop effective therapies for patients with this subtype of EGFR-mutant NSCLC.

The approach proposed in this study includes methods specifically dedicated to the detection of allophonic variation in English. This study aims to find an efficient method for automatic evaluation of aspiration in the case of Polish second-language (L2) English speakers' pronunciation when whole words are analyzed instead of particular allophones extracted from words. Sample words including aspirated and unaspirated allophones were prepared by experts in English phonetics and phonology. The datasets created include recordings of words pronounced by nine native English speakers of standard southern British accent and 20 Polish L2 English users. Complete unedited words are treated as input data for feature extraction and classification algorithms such as k-nearest neighbors, naive Bayes method, long-short term memory, and convolutional neural network (CNN). Various signal representations, including low-level audio features, the so-called mid-term and feature trajectory, and spectrograms, are tested in the context of their usability for the detection of aspiration. The results obtained show high potential for an automated evaluation of pronunciation focused on a particular phonological feature (aspiration) when classifiers analyze whole words. Additionally, CNN returns satisfying results for the automated classification of words containing aspirated and unaspirated allophones produced by Polish L2 speakers.

Purpose: This study investigates the determinants of audit committee (AC) formation in a semi-mandatory setting of a European economy, in which ownership and control are predominantly in the hands of families and business groups, and the voluntary practice of forming an AC has not been widely accepted. Methodology: This research uses a sample of Polish nonfinancial firms listed on the Warsaw Stock Exchange (WSE) in 2008–2015. The study implemented logistic regression to test the role of the supervisory board (SB) and companies’ compositional characteristics in AC creation. Findings: Primary analysis provided evidence of an inverted association between commonly accepted determinants of AC formation – such as the number of independent members on the supervisory board (SB) – and accounting and finance expertise of the SB members. The study also revealed that companies with foreign ownership are more likely to have an AC. Originality: This study indicates an important relationship between the existence of other SB committees as a meaningful determinant of AC formation. This article is valuable for supervisory bodies and regulators as they provide insights into factors that influence audit committee formation.

The aim of the study was to determine the influence of the size and form of Artemia sp. feed on the rearing indices of Atlantic sturgeon larvae. In the experiment, the nauplius sizes used were 480 µm (group AD), 430 µm (group AM), and 430 µm frozen nauplii (group AI). After three weeks of rearing, the sturgeon from group AD had the highest mean body weight of 0.131 g that was statistically significantly different from groups AM (0.071 g) and AI (0.033 g). The longest total length was noted in group AD (2.8 cm) and was statistically different from the others (P ≤ 0.05). Specific growth rate in groups AD and AM was 14.7 and 11.8% d−1, respectively, and these values differed statistically from those in group AI at 7.8% d−1. The highest survival rate was recorded in group AD at 60.6%, while the lowest was noted in group AI at 15.6%, and the differences between these two groups were statistically significant. The results of the experiment indicated that a feed of live 480 µm Artemia sp. nauplius significantly accelerated the growth rates and increased the survival rates of Atlantic sturgeon larvae.

Introduction. The BRCA1 and BRCA2 genes belong to suppressor genes that control the mechanisms of repairing various damages of the DNA double helix, regulate cell division, and the cell cycle. Mutations within these genes are associated with the hereditary ovarian and breast cancers. Aim. Assessment of the frequency of testing BRCA1 and BRCA2 gene mutation in the population of women living in urban and rural environments with diagnosed ovarian cancer. Material and methods. The study was conducted among 300 women seeking treatment or consulting a doctor from the Wielkopolska Oncology Center in Poznań, and patients treated in a home hospice in the Rawicz district in Wielkopolska province over the period 2016-2018. Results. Among the respondents, the most were women aged from 36 to 40 (53.3%). The age of developing ovarian cancer for the women from cities is between 41 and 45. In the vast majority of women, i.e. 247 (82.3%), epithelial cancer was diagnosed. A marker that could indicate ovarian cancer, i.e. CA 125 antigen, was determined in more than half of 165 (55.0%). However, only in a few cases, in a total of 25 (8.3%) patients a test confirming the presence of BRCA1 and BRCA2 gene mutation was performed. Conclusions. The possibility of testing for BRCA1 and BRCA2 gene mutation in all sick women and their closest family should be considered. Regardless of the age of women, it is important to raise awareness of the risk of ovarian cancer, encourage them to keep regular medical appointments, and perform diagnostic tests.

The article addresses issues related to the civil system of democratic supervision and control over special services in Poland since the political transformation. The system is based on the supervision of the executive authority, which also sets the directions of activities, Parliamentary control – mainly with the help of the Committee for Special Services, judiciary supervision assessing their actions in terms of possible abuse of powers or failure to fulfill their obligations. The functionality of some legal solutions in the field of supervision and control over the services was assessed. The dominant role of the Prime Minister in exercising supervision over the special services was pointed out.

Introduction Systemic cryotherapy is a popular treatment involving a short stay in a cryogenic chamber at a temperature below −100 °C. This leads to a number of physiological reactions, some of them also observed in the skin. The aim of the study was to analyze the effect of a single cryogenic treatment on selected skin characteristics (skin pH, level of hydration and TEWL – Transepidermal Water Loss) in young, healthy people. Materials and methods Skin characteristics in 77 young people (23.63 ± 1.36 years) were assessed. In the study, 43 women and 33 men who took part in a one-time treatment (−120 °C) lasting 3 min. Measurements were made on the forearm skin and (in men) on the face twice: before and immediately after the procedure. Results: Initial differences in hydration of the stratum corneum and TEWL were observed between the group of women and men. After one treatment, the examined characteristics of the forearm skin did not change, and an unfavorable increase in TEWL in men was indicated in the facial area. Conclusions A single stay in the cryogenic chamber, while maintaining the correct methodology of the treatment, is safe for the skin. The changes taking place depend on the body surface area tested, which indicates that the skin on the limbs and on the face reacts differently to the cryogenic stimulus.

We present a novel quantitative approach for classification of authors' stylistics and gender differences based on extraction of word collocation. The proposed algorithm attenuates previously described issues of text processing using the vector models. We demonstrate the approach by analyzing a corpus of Russian prose. We discuss different approaches for classification and identification of the author's style implemented by currently-available software solutions and libraries of morphological analysis, methods of parameterization, indexing of texts, artificial intelligence algorithms and knowledge extraction. Our results demonstrate the efficiency and relative advantage of regression decision tree methods in identifying informative frequency indexes in a way that lends itself to their logical interpretation. We develop a toolkit for conducting comparative experiments to assess the effectiveness of classification of natural language text data, using vector, set-theoretic and the author's set-theoretic with collocation extraction models of text representation. Comparing the ability of different methods to identify the style and gender differences of authors of fiction works, we find that the proposed approach incorporating collocation information alleviates some of the previously identified deficiencies and yields overall improvements in the classification accuracy.

Introduction Capmatinib is approved for MET exon 14–altered NSCLC on the basis of activity in targeted therapy–naive patients. We conducted a phase 2 study to assess the efficacy of capmatinib in patients previously treated with a MET inhibitor. Methods Patients with advanced NSCLC harboring MET amplification or MET exon 14 skipping alterations received capmatinib 400 mg twice daily. The primary end point was the objective response rate. Secondary end points included progression-free survival, disease control rate (DCR), intracranial response rate, and overall survival. Circulating tumor DNA was analyzed to identify capmatinib resistance mechanisms. Results A total of 20 patients were enrolled between May 2016 and November 2019, including 15 patients with MET skipping alterations and five patients with MET amplification. All patients had received crizotinib; three had also received other MET-directed therapies. The median interval between crizotinib and capmatinib was 22 days (range: 4–374). Two patients (10%) achieved an objective response to capmatinib and 14 had stable disease, yielding a DCR of 80%. Among five patients who discontinued crizotinib for intolerance, the DCR was 83%, including two patients with the best tumor shrinkage of −25% and −28%. Intracranial DCR among four patients with measurable brain metastases was 100%, with no observed intracranial objective responses. Overall, the median progression-free survival and overall survival were 5.5 (95% confidence interval: 1.3–11.0) and 11.3 (95% confidence interval: 5.5–not reached) months, respectively. MET D1228 and Y1230 mutations and MAPK alterations were recurrently detected in postcrizotinib, precapmatinib plasma. New and persistent MET mutations and MAPK pathway alterations were detected in plasma at progression on capmatinib. Conclusions Capmatinib has modest activity in crizotinib-pretreated MET-altered NSCLC, potentially owing to overlapping resistance mechanisms.

Background Osimertinib is a third-generation EGFR tyrosine kinase inhibitor that has improved survival and central nervous system (CNS) outcomes in patients with non–small cell lung cancer (NSCLC) with activating EGFR mutations. However, little is known about the efficacy and safety of combining osimertinib with chemotherapy. Methods This was a retrospective study performed at 3 institutions. Patients with advanced EGFR-mutated NSCLC who received concurrent osimertinib with chemotherapy in the third-line or beyond were identified by chart review. Efficacy outcomes including duration on treatment (DOT), overall survival (OS), and CNS outcomes were assessed. Safety outcomes were also evaluated. Results A total of 44 patients met inclusion criteria. Median DOT with osimertinib plus platinum doublet (n = 28) was 6.1 months (95% CI 4.1 months–not reached), and with osimertinib plus single-agent chemotherapy (n = 29) was 2.6 months (95% CI 1.8-4.8 months). Median OS from the start of osimertinib plus chemotherapy was 10.4 months (95% CI 7.0-13.2 months). At initiation of osimertinib plus chemotherapy, 37 patients (84%) had CNS metastases; 9 of these (24%) had CNS disease progression on osimertinib plus chemotherapy. Chemotherapy was delayed or dose reduced due to toxicity in 8 patients (18%); osimertinib was discontinued in 1 patient (2%) for reduced cardiac ejection fraction, and dose reduced in 2 patients (5%). Conclusions The combination of osimertinib plus chemotherapy appeared safe and showed favorable control of CNS disease in this cohort of patients who had progressed systemically with multiple prior lines of therapy, with DOT and survival outcomes similar to historical chemotherapy controls.

Cardiovascular risk factors, biomarkers, and diseases are associated with poor prognosis in COVID-19 infections. Significant progress in artificial intelligence (AI) applied to cardiac imaging has recently been made. We assessed the utility of AI analytic software EchoGo in COVID-19 inpatients. Fifty consecutive COVID-19+ inpatients (age 66 ± 13 years, 22 women) who had echocardiography in 4/17/2020–8/5/2020 were analyzed with EchoGo software, with output correlated against standard echocardiography measurements. After adjustment for the APACHE-4 score, associations with clinical outcomes were assessed. Mean EchoGo outputs were left ventricular end-diastolic volume (LVEDV) 121 ± 42 mL, end-systolic volume (LVESV) 53 ± 30 mL, ejection fraction (LVEF) 58 ± 11%, and global longitudinal strain (GLS) −16.1 ± 5.1%. Pearson correlation coefficients (p-value) with standard measurements were 0.810 (

Composite full-thickness nasal defects that include adjacent facial units still remain a challenge for reconstructive surgeons. The commonly used auricular free flap (AFF) might not be sufficient for full coverage of a defect, and radial forearm free flap (RFFF) lacks the rigid component for nasal framework. Therefore, the authors present a chimeric flap combined of both AFF and RFFF for the reconstruction of extended nasal defects. Auricular free flap enables the restoration of the exact contour of nose, and it preserves similar texture and color of the skin. Moreover, its harvesting results in minimal deformity of donor site. Radial forearm free flap gives the possibility of covering extensive defects of the facial units thanks to its elasticity and long vascular pedicle. The combination of both flaps seems to be an optimal solution for the reconstruction of extended nasal defects, giving satisfactory aesthetic results. Also, it might not require any further corrections, remaining a one-stage procedure.

[Abstract] Aims. This study aimed to assess age‐ and sex‐related differences in management and 1‐year risk for all‐cause mortality and hospitalization in chronic heart failure (HF) patients. Methods and results. Of 16 354 patients included in the European Society of Cardiology Heart Failure Long‐Term Registry, 9428 chronic HF patients were analysed [median age: 66 years; 28.5% women; mean left ventricular ejection fraction (LVEF) 37%]. Rates of use of guideline‐directed medical therapy (GDMT) were high (angiotensin‐converting enzyme inhibitors/angiotensin receptor blockers, beta‐blockers and mineralocorticoid receptor antagonists: 85.7%, 88.7% and 58.8%, respectively). Crude GDMT utilization rates were lower in women than in men (all differences: P ≤ 0.001), and GDMT use became lower with ageing in both sexes, at baseline and at 1‐year follow‐up. Sex was not an independent predictor of GDMT prescription; however, age >75 years was a significant predictor of GDMT underutilization. Rates of all‐cause mortality were lower in women than in men (7.1% vs. 8.7%; P = 0.015), as were rates of all‐cause hospitalization (21.9% vs. 27.3%; P < 0.001) and there were no differences in causes of death. All‐cause mortality and all‐cause hospitalization increased with greater age in both sexes. Sex was not an independent predictor of 1‐year all‐cause mortality (restricted to patients with LVEF ≤45%). Mortality risk was significantly lower in patients of younger age, compared to patients aged >75 years. Conclusions. There was a decline in GDMT use with advanced age in both sexes. Sex was not an independent predictor of GDMT or adverse outcomes. However, age >75 years independently predicted lower GDMT use and higher all‐cause mortality in patients with LVEF ≤45%.

Introduction. Anastrozole is a chemotherapeutic drug used to treat breast cancer in postmenopausal women. The condition for success of this type of treatment is the presence of estrogen receptors in cancer cells. Anastrozole belongs to strong-acting, nonsteroidal inhibitors of aromatase, which is responsible for androgen-estrogen conversion process. The metabolism of this drug is based on biotransformation both in phase I and II. Initially it metabolizes in the liver with cytochrome P450 isoenzymes, followed by a glucuronidation reaction catalyzed by the UGT1A4 enzyme. Material and method. In order to minimize the side effects, new therapeutic approaches are sought to increase the success of the therapy. Conclusions. Biodegradable nano-tools that deliver anastrozole to the target site with an increase in its half-life to 144 hours are a promising method. A similar effect can be achieved by using a transdermal anastrozole administration system, which is a completely non-invasive method of treatment.

Mobocertinib, an oral epidermal growth factor receptor (EGFR) inhibitor targeting EGFR gene mutations, including exon 20 insertions (EGFRex20ins), in non–small cell lung cancer, was evaluated in a phase I/II dose-escalation/expansion trial (ClinicalTrials.gov NCT02716116). Dose escalation identified 160 mg/d as the recommended phase 2 dose and maximum tolerated dose. Among 136 patients treated with 160 mg/d, the most common any-grade treatment-related adverse events (TRAE; >25%) were diarrhea (83%), nausea (43%), rash (33%), and vomiting (26%), with diarrhea (21%) the only grade ≥3 TRAE >5%. Among 28 EGFRex20ins patients treated at 160 mg/d, the investigator-assessed confirmed response rate was 43% (12/28; 95% confidence interval, 24%–63%) with median duration of response of 14 months (5.0–not reached) and median progression-free survival of 7.3 months (4.4–15.6). Mobocertinib demonstrated antitumor activity in patients with diverse EGFRex20ins variants with a safety profile consistent with other EGFR inhibitors. Significance: No oral EGFR-targeted therapies are currently approved for patients with EGFRex20ins NSCLC. Mobocertinib demonstrated antitumor activity with manageable toxicity in patients with advanced EGFRex20ins NSCLC in this study, supporting additional development of mobocertinib in this patient population. See related commentary by Pacheco, p. 1617. This article is highlighted in the In This Issue feature, p. 1601

Acute pancreatitis (AP) is a frequent hospitalization cause of patients suffering from gastrointestinal disorders. Gelsolin has an ability to bind bioactive lipids including different sphingolipids engaged in inflammatory response. Importantly, hypogelsolinemia was observed in patients with different states of acute and chronic inflammation. The aim of the present study was to assess the interplay of blood plasma gelsolin and blood plasma sphingosine-1-phosphate (S1P) concentration in patients diagnosed with acute pancreatitis. To assess the concentration of gelsolin and S1P, immunoblotting and HPLC technique were employed, respectively. Additionally, the concentrations of amylase, lipase, C-reactive protein (CRP), procalcitonin (PCT) and the number of white blood cells (WBC) and platelet (PLT) were recorded. We found that both pGSN and S1P concentrations in the plasma of the AP patients were significantly lower (pGSN ~ 15–165 mg/L; S1P ~ 100–360 pmol/mL) when compared to the levels of pGSN and S1P in a control group (pGSN ~ 130–240 mg/L; S1P ~ 260–400 pmol/mL). Additionally, higher concentrations of CRP, WBC, amylase and lipase were associated with low level of gelsolin in the blood of AP patients. No correlations between the level of PCT and PLT with gelsolin concentration were noticed. Plasma gelsolin and S1P levels decrease during severe acute pancreatitis. Simultaneous assessment of pGSN and S1P can be useful in development of more accurate diagnostic strategies for patients with severe acute pancreatitis.

A total of 94 patients with colorectal cancer (CRC) were included in this study. Lymphocytic infiltration of CD45+ cells in the normal colon was more pronounced than that in the paired tumor stroma (p = 0.0008). The mean immunoscore of CD45+TILs was decreased in CRC compared with the controls (p = 0.0010). The percentage of CD3+ cells was higher in stage II than in stage IV (p = 0.0218) and showed a negative correlation with the TNM classification (r = -0.2867, p = 0.0109). The number of stromal CD4+TILs was higher in stage I than in stage III (p = 0.0116) and IV (p = 0.0104), and there was a negative correlation between this number and the stage (r = -0.3708, p = 0.0008). There was a positive correlation between the Ki-67 and CD45+ (r = 0.2468, p = 0.0294), CD3+ (r = 0.3822, p = 0.0006), and CD4+ cells (r = 0.5465, p + cells was also dependent on the TNM stage (p = 0.0444) and tumor budding (p = 0.0324). These findings suggest a suppressive impact of CRC on the adaptive immune response and emphasize the importance of CAFs in regulating tumor immunity.

Objectives: In obesity, there is a shift in the pro-oxidative-antioxidant balance towards the oxidationreactions. However, it has been shown that in people with normal body composition, after a series of whole-body cryotherapy (WBC), the balance shifts in the opposite direction. Design: The aim of the study was to assess the impact of 20 WBC treatments on blood pro-oxidative-antioxidant balance. Interventions: Study included 14 obese (BMI > 35) and 10 non-obese volunteers. Methods: The total antioxidative (TAS/TAC) and pro-oxidative status (TOS/TOC) in serum and activity of antioxidant enzymes in erythrocytes were determined before the first and 2 hours after the last cryostimulation. Results: In the obese group, a significantly higher level of TOS/TOC, and its significant decrease after the WBC series, was observed. Cryotherapy had no influence on TAS/TAC level which was similar in both groups. Changes in activity of antioxidant enzymes were multidirectional. An increase in CAT activity in the obese group was observed. OSI, both before and after a series of treatments, was significantly higher in obese subjects. Conclusions: A beneficial effect on the level of TOS/TOC and CAT activity was indicated, but the proposed number of treatments for patients with class II obesity turned out to be insufficient. Trial registration: Australian New Zealand Clinical Trials Registry identifier: ACTRN12619000524190.

Purpose: Osimertinib is an effective therapy in EGFR-mutant non–small cell lung cancer (NSCLC), but resistance invariably develops. Navitoclax is an oral inhibitor of BCL-2/BCL-xL that has exhibited synergy with osimertinib in preclinical models of EGFR-mutant NSCLC. In hematologic malignancies, BCL-2 family inhibitors in combination therapy effectively increase cellular apoptosis and decrease drug resistance. Patients and Methods: This single-arm phase Ib study evaluated safety, tolerability, and feasibility of osimertinib and navitoclax, including dose expansion in T790M-positive patients at the recommended phase II dose (RP2D). Eligible patients had advanced EGFR-mutant NSCLC with prior tyrosine kinase inhibitor exposure. Five dose levels were planned with osimertinib from 40 to 80 mg orally daily and navitoclax from 150 to 325 mg orally daily. Results: A total of 27 patients were enrolled (18 in the dose-escalation cohort and nine in the dose-expansion cohort): median age 65, 67% female, 48% exon 19 del, and 37% L858R, median one prior line of therapy. The most common adverse events were lymphopenia (37%), fatigue (22%), nausea (22%), and thrombocytopenia (37%). No dose-limiting toxicities were seen in dose-escalation cohort; osimertinib 80 mg, navitoclax 150 mg was chosen as the RP2D. Most patients (78%) received >95% of planned doses through three cycles. In expansion cohort, objective response rate was 100% and median progression-free survival was 16.8 months. A proapoptotic effect from navitoclax was demonstrated by early-onset thrombocytopenia. Conclusions: Oral combination therapy with navitoclax and osimertinib was safe and feasible at RP2D with clinical efficacy. Early thrombocytopenia was common, supporting an target engagement by navitoclax. Further study of BCL-2/BCL-xL inhibition to enhance osimertinib activity is warranted.

This paper reports the characteristics of ferrochrome slag and its feasibility as aggregate in refractories aiming to substitute virgin refractory raw materials. Refractory castable specimens were formulated with ferrochrome slag as an aggregate and commercial calcium aluminate cement as a binder. Objective was to prepare refractory specimens with a maximum slag utilization but simultaneously to sustain good properties, comparable to those of virgin raw material refractory products. Mechanical and thermo-physical properties of the cured, dried and sintered specimens were characterized. Cold crushing strengths of best performing ferrochrome slag containing specimens were higher than 90 MPa and compressive strength values measured at 1200 °C were over 9 MPa. Thermal insulation properties were even better than those of commercial refractory reference, showing thermal conductivity values as low as λRT−1000 °C = 1.3 − 0.9 W/m K. The liquid phase formation above 1200 °C limits the ferrochrome slag use for refractory applications. Results suggest ferrochrome slag’s feasibility as an aggregate raw material for refractory materials up to temperatures of 1200 °C in air and up to temperatures of 700 °C in acidic gaseous atmosphere. Possible applications for this kind of novel refractory materials are, e.g., insulating secondary layers or bottom zones in metallurgical processes to substitute virgin refractories. A direct contact to molten metal must be avoided, but they are applicable as, e.g. floorings when exposed only to occasional melt droplets. Graphic Abstract

BACKGROUND We previously developed molecular assessment systems for lung transplant transbronchial biopsies (TBBs) with high surfactant and bronchial mucosal biopsies, identifying T-cell‒mediated rejection (TCMR) on the basis of the expression of rejection-associated transcripts, but the relationship of rejection to graft loss is unknown. This study aimed to develop molecular assessments for TBBs and mucosal biopsies and to establish the impact of molecular TCMR on graft survival. METHODS We used microarrays and machine learning to assign TCMR scores to an expanded cohort of 457 TBBs (367 high surfactant plus 90 low surfactant) and 314 mucosal biopsies. We tested the score agreement between TBB–TBB, mucosal–mucosal, and TBB–mucosal biopsy pairs in the same patient. We also assessed the association of molecular TCMR scores with graft loss (death or retransplantation) and compared it with the prognostic associations for histology and donor-specific antibodies. RESULTS The molecular TCMR scores assigned in all the TBBs performed similarly to those in high-surfactant TBBs, indicating that variation in alveolation in TBBs does not prevent the detection of TCMR. Mucosal biopsy pieces showed less piece-to-piece variation than TBBs. TCMR scores in TBBs agreed with those in mucosal biopsies. In both TBBs and mucosal biopsies, molecular TCMR was associated with graft loss, whereas histologic rejection and donor-specific antibodies were not. CONCLUSIONS Molecular TCMR can be detected in TBBs regardless of surfactant and in mucosal biopsies, which show less variability in the sampled tissue than TBBs. On the basis of these findings, molecular TCMR appears to be an important predictor of the risk of future graft failure. Trial registration ClinicalTrials.gov NCT02812290.

Repeated bolus injections are associated with higher costs and poor compliance and can hinder the implementation of global immunization campaigns. Here, we report the development and preclinical testing of patches of transdermal core-shell microneedles-which were fabricated by the micromoulding and alignment of vaccine cores and shells made from poly(lactic-co-glycolic acid) with varying degradability kinetics-for the preprogrammed burst release of vaccine payloads over a period of a few days to more than a month from a single administration. In rats, microneedles loaded with a clinically available vaccine (Prevnar-13) against the bacterium Streptococcus pneumoniae induced immune responses that were similar to immune responses observed after multiple subcutaneous bolus injections, and led to immune protection against a lethal bacterial dose. Microneedle patches delivering preprogrammed doses may offer an alternative strategy to prophylactic and therapeutic protocols that require multiple injections.

WstępOśrodkowe zaburzenia słuchu (ang. central auditory processing disorders – CAPD) to niejednorodne dysfunkcje, w których nieprawidłowej realizacji wyższych funkcji słuchowych współtowarzyszą zaburzenia procesów poznawczych. Zakładając, że u dzieci z CAPD realizacja tych procesów może mieć wpływ na analizę informacji akustycznej, poprawa funkcji poznawczych za pomocą metody jaką jest terapia Neurofeedback powinna przynieść korzystny wpływ także na przetwarzanie słuchowe.CelCelem pracy była ocena wpływu terapii Neurofeedback na poprawę wyższych funkcji słuchowych i poznawczych u dzieci z CAPD.MetodaBadania przeprowadzono na grupie trzech dzieci z zaburzeniami wyższych funkcji słuchowych oraz procesu uwagi. W trakcie treningu Neurofeedback tłumiono wolną czynność mózgową oraz wzmacniano czynność szybką. Wpływ treningu na funkcje słuchowe i funkcje poznawcze oceniano na podstawie wyników trzech testów wyższych funkcji słuchowych oraz komputerowych testów uwagi.WynikiAnaliza współczynników odzwierciedlających stosunki wybranych fal mózgowych wykazała, obniżenie po treningach nadmiernie wyrażonej czynności wolnej oraz wzmocnienia zaniżonej czynności szybkiej u wszystkich trenowanych dzieci. Normalizacji relacji pomiędzy falami mózgowymi towarzyszyła poprawa wyników testów wyższych funkcji słuchowych. Lepsze wyniki po terapii odnotowano także w komputerowych testach uwagi.PodsumowanieUzyskane wyniki wskazują, że trening Neurofeedback może korzystnie wpływać na poprawę przetwarzania słuchowego na wyższych piętrach układu nerwowego oraz funkcji poznawczych.

W pracy przedstawiono historię implantów ślimakowych, począwszy od pierwszych prób zastosowania stymulacji elektrycznej po czasy współczesne.

WstępDążenie do optymalnego wykorzystania okresu krytycznego dla rozwoju słuchowego dziecka z niedosłuchem rodzi potrzebę opracowania odpowiednich narzędzi, dostosowanych do oceny tego rozwoju u małych dzieci. Kluczowe znaczenie ma możliwość dokonywania pomiarów i porównywania wyników uzyskiwanych od pierwszych miesięcy życia.CelCelem pracy jest ocena rozwoju słuchowego dzieci z głębokim niedosłuchem, którym wszczepiono implant ślimakowy przed ukończeniem drugiego roku życia.Materiał i metodyMateriał badawczy stanowiło 122 dzieci, których średni wiek w chwili aktywacji implantu wynosił 14,3 miesiąca. Oceny rozwoju słuchowego dokonano na podstawie wyniku badania kwestionariuszem LittlEARS. Kwestionariusz wypełniali rodzice lub opiekunowie dzieci z badanej grupy. Badania przeprowadzono w dniu aktywacji implantu ślimakowego, dokonując tym samym oceny rozwoju słuchowego osiągniętego przed wszczepieniem implantu, oraz po około 5 miesiącach użytkowania systemu. Dodatkowo, na podstawie co najmniej rocznej obserwacji, przeprowadzono ocenę tempa rozwoju słuchowego dzieci, u których aktywacja systemu implantu ślimakowego nastąpiła przed ukończeniem pierwszego roku życia.WynikiNieadekwatny do wieku poziom rozwoju słuchowego przed aktywacją implantu stwierdzono u 86% dzieci z badanej grupy. Natomiast po około 5 miesiącach korzystania z implantu ślimakowego adekwatny do wieku poziom rozwoju słuchowego osiągnęło 72% dzieci. Wyniki co najmniej rocznej obserwacji dzieci, którym wszczepiono implant ślimakowy przed ukończeniem pierwszego roku życia, wskazują, że dzieci te uzyskują poziom rozwoju słuchowego odpowiadający normie słuchowej po około 10 miesiącach korzystania z implantu.WnioskiTempo rozwoju słuchowego dzieci z głębokim niedosłuchem, implantowanych we wczesnym okresie życia jest szybsze od tempa tego rozwoju u dzieci ze słuchem prawidłowym. Umożliwia to większości dzieci „nadrobienie” zaległości w rozwoju słuchowym, powstałych na skutek głębokiego niedosłuchu w pierwszych miesiącach życia. Implant ślimakowy pozwala dzieciom z głębokim niedosłuchem na zrównanie stopnia rozwoju słuchowego ze stopniem tego rozwoju u dzieci prawidłowo słyszących. Zrównanie to u większości dzieci następuje przed ukończeniem drugiego roku życia.

Purpose: The aim of this article is to determine how the local governments of medium-sized cities see a military unit located on their territory in the context of its participation in social and economic processes. Design/Methodology/Approach: The article presents the results of a research carried out using the diagnostic survey method, utilising the interview technique. For the analysis of the collected material and presentation of the results, the methods of Text mining as well as R v.3.6.1 program and RStudio editor were used. Findings: The use of text mining for the analysis of links between military units and local government units allowed to deepen the knowledge on the significance given by local government representatives to the presence of the army and its impact on socio-economic processes in specific territorial units. Practical Implications: The results of the research can be used in designing local development strategies and creating conditions for local agents to work together for development. In addition, they can be used to better understand the links between local governments and military units, by decision makers at the central level. Originality/Value: The results of the research indicate the possibility of using text mining for the analysis of complex links identified between entities on the territory of communes. Text mining allows to combine a qualitative and quantitative approach, in the context of identifying the impact of individual entities on the development of the commune and creating meanings in the process of interaction between entities located on its territory., peer-reviewed

Purpose: The article deals with the issue of sources and changes in the structure of financing for higher education institutions (HEIs) in Poland. Design/Methodology/Approach: Revenues gained by HEIs outside the public support system and fees paid by students are referred to as the so-called third stream. As a result of global changes occurring in higher education systems, these revenues are increasingly important for the functioning of these organizations. The article, based on official statistical data, analyses the structure of revenues for the years 1995–2017 of the HEIs in Poland from operating activities, the dynamics of changes in revenues from research activities, revenues from sales of other works as well as research and development services, and revenues from separate economic activities. Findings: The analysis shows that the change in orientation of Polish HEIs towards activation of relations with the social and economic environment is clearly reflected in the changing structure and dynamics of revenues., peer-reviewed

WstępImplant pniowy (ABI) to obecnie jedyna proteza słuchu dla osób z uszkodzeniem nerwów słuchowych. Wszczepiany jest on głównie pacjentom ze zdiagnozowaną neurofibromatozą typu 2 (NF2), w przebiegu której na nerwie słuchowym tworzą się guzy, co nieuchronnie prowadzi do całkowitej głuchoty. Pacjenci korzystający z systemu implantu pniowego uzyskują w badaniach niski poziom rozumienia dźwięków mowy. Jednym z czynników składających się na prawidłowy przebieg tego procesu jest słuch fonematyczny. Jest to umiejętność odbioru przez układ słuchowy cech dystynktywnych fonemów w danym języku, co pozwala na różnicowanie dźwięków mowy. Zaburzenia słuchu fonematycznego są przyczyną problemów z rozumieniem mowy i uniemożliwiają sprawną komunikację.CelCelem pracy jest ocena stanu słuchu fonematycznego u pacjenta z dwoma implantami pniowymi, w tym ocena możliwości dyskryminacji głosek opozycyjnych, co jest jednym z warunków umożliwiających prawidłowy odbiór mowy.Materiał i metodyOceny stanu słuchu fonematycznego dokonano u użytkownika dwóch implantów pniowych. Do badania wykorzystano „Test do badania słuchu fonematycznego” autorstwa E. Szeląg i A. Szymaszek. Test przeprowadzono w warunkach ciszy.Wyniki i wnioskiStymulacja elektryczna realizowana przez dwa systemy implantu pniowego pozwala pacjentowi – w sprzyjających akustycznie warunkach – na odbiór i różnicowanie opozycyjnych głosek oraz paronimów bez posiłkowania się kontekstem wypowiedzi. Zatem stosowanie słuchowych implantów pniowych może być skuteczną metodą kompensacji utraconego, w przebiegu NF2, słuchu. W celu uogólnienia wniosków z badania wskazane byłoby przeprowadzanie podobnych badań u innych użytkowników implantów pniowych. Pomocne dla dalszego rozwoju programu rehabilitacji i wspomagania pacjentów w uzyskiwaniu jak największych korzyści z implantu pniowego byłoby przeprowadzenie badań dotyczących wpływu treningu słuchowego na rozwój kompetencji słuchowych dotyczących rozumienia mowy u pacjentów z ABI. Przeprowadzenie testu słuchu fonematycznego przed treningiem słuchowym i po takim treningu umożliwiłoby ocenę skuteczności podjętej interwencji.

Badania audiometryczne są często wykorzystywane podczas masowych programów badań przesiewowych słuchu u dzieci w wieku szkolnym. Wykonuje się je za pomocą urządzeń zwanych audiometrami, które ze względu na dokładność pomiaru można podzielić na kliniczne, diagnostyczne i skriningowe. Celem niniejszej pracy jest przedstawienie rozwiązań technicznych i technologicznych zastosowanych w 14 wybranych urządzeniach do audiometrycznych badań przesiewowych słuchu u dzieci w wieku szkolnym. Prezentacja została dokonana pod kątem przydatności tych rozwiązań w realizacji programów badań masowych.

Celem niniejszego artykułu jest analiza sektorowej polityki ochrony zdrowia w świetle zabezpieczenia interesu obywateli poprzez przybliżenie perspektywy zorganizowanych interesów organizacji pacjentów. Tekst jest próbą uzupełnienia dyskusji nt. roli tej szczególnej grupy interesariuszy w procesie podejmowania decyzji w sektorze ochrony zdrowia. Odwołując się do przykładów empirycznych, założono, że cały polski system ochrony zdrowia nie służy dobrze interesom pacjentów z powodu niedoborów organizacyjnych, finansowych i personalnych, a konstytucyjna obietnica równego dostępu do świadczeń ochrony zdrowia jest paradoksalnie skuteczną barierą dla wszelkich zmian zmierzających do poprawy sposobu funkcjonowania tego systemu. Pomimo wrażenia "zwrotu pacjento-centrycznego" w ochronie zdrowia w Polsce zorganizowane interesy pacjentów skupione wokół rzeczniczych organizacji pacjentów wciąż mają niewielki udział w procesie formułowania i wdrażania ważnych zmian w tej polityce sektorowej.

Purpose: The objective of the paper is to review historical developments and the current setup of healthcare financing models in Central Europe. Methodology: A systematic narrative approach has been taken with the research emphasis on a critical literature review and analyses of healthcare spending statistical data. Findings: A comparison between different models currently in place seems to suggest the existence of patterns leading to improved quality of the healthcare service proposition that is critically impacted by a financing model. Implications: The findings have practical implications since different results have been achieved in countries choosing different models but starting from practically the same point. That realisation should serve as a foundation for further work on this subject, potentially leading to adjustments to financing models chosen by some countries. Value: The paper offers a comparative analysis of the healthcare system financing evolution in four Central European Countries and an overview of their current state.

WójcikJustyna, Obuchowska Aleksandra, Ozga Alicja, Standyło Arkadiusz, Obuchowska Karolina, Piotrowska Paulina. Polycystic ovary syndrome (PCOS) - risk factor, diagnostic and current treatment. Journal of Education, Health and Sport.2020;10(9):556-560. eISSN 2391-8306. DOI http://dx.doi.org/10.12775/JEHS.2020.10.09.067 https://apcz.umk.pl/czasopisma/index.php/JEHS/article/view/JEHS.2020.10.09.067 https://zenodo.org/record/4043733 The journal has had 5 points in Ministry of Science and Higher Education parametric evaluation. § 8. 2) and § 12. 1. 2) 22.02.2019. © The Authors 2020; This article is published with open access at Licensee Open Journal Systems of Nicolaus Copernicus University in Torun, Poland Open Access. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author (s) and source are credited. This is an open access article licensed under the terms of the Creative Commons Attribution Non commercial license Share alike. (http://creativecommons.org/licenses/by-nc-sa/4.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited. The authors declare that there is no conflict of interests regarding the publication of this paper. Received: 16.09.2020. Revised: 21.09.2020. Accepted: 22.09.2020. Polycystic ovary syndrome (PCOS) - risk factor, diagnostic and current treatment Justyna Wójcik1a, Aleksandra Obuchowska1b, Alicja Ozga1c, Arkadiusz Standyło1d, Karolina Obuchowska1e, Paulina Piotrowska1f ajustynawojcik455@gmail.com; https://orcid.org/0000-0001-7163-6784 baobuchowska12@gmail.com; https://orcid.org/0000-0003-0464-2695 caozga1@gmail.com; https://orcid.org/0000-0003-1291-905X da.standylo@gmail.com; https://orcid.org/0000-0002-5154-4759 ekarolinaobuchowska99@gmail.com; https://orcid.org/0000-0003-4519-8236 fpaulina.piotrowska222@gmail.com; https://orcid.org/0000-0002-5516-952X 1Faculty of Medicine, Medical University of Lublin, Chodźki Street 19, 20-093 Lublin, Poland Corresponding author: Justyna Wójcik Medical University of Lublin, Chodźki Street 19 20-953 Lublin, Poland e-mail: justynawojcik455@gmail.com Abstract Introduction: Polycystic ovary syndrome (PCOS) is one of the most common endocrine and metabolic disorders in women in reproductive age, defined as a combination of signs and symptoms resulting from androgen excess and ovarian dysfunction in the absence of other specific diagnoses. PCOS is often associated with an increased risk of obesity, insulin resistance, metabolic disorders and cardiovascular events. The aim of the study: The purpose of this systemic review was to collect and analyze materials about risk factors, diagnostics, and the current treatment of polycystic ovary syndrome. Material and method: Review of the literature published in 2004-2018. Description of the state of knowledge: PCOS is characterized by an excessive secretion of androgens from the ovaries and / or adrenal glands. Intrinsic ovarian factors, such as altered steroidogenesis, and factors external to the ovary, such as hyperinsulinemia, contribute to the ovarian overproduction of androgens. PCOS requires careful selection of an appropriate diagnostic method and therapeutic approach to combat hyperandrogenism, a consequence of ovarian dysfunction and related metabolic disorders. Treatment of both women at risk of PCOS and those with a confirmed diagnosis of PCOS includes education, healthy lifestyle interventions and symptomatic therapeutic interventions. Summary: PCOS is a complex disorder involving many organs and affecting many body functions. It is important to diagnose this disease as soon as possible in order to implement appropriately selected therapeutic treatment aimed at eliminating disease symptoms and reducing the systemic consequences of hyperandrogenism in patients. Key words: polycystic ovary syndrome, PCOS, diagnostics of PCOS, personalized therapy

Since its approval in April 2018, osimertinib has been widely adopted as first-line therapy for patients with advanced EGFR-mutant non -small cell lung cancer (NSCLC). Understanding osimertinib resistance mechanisms and currently available treatment options are essential to selecting optimal second line therapy for patients whose disease progresses during front-line osimertinib. Using data compiled from 6 osimertinib-resistance series, we describe here the heterogeneous profile of EGFR-dependent and independent mechanisms of osimertinib treatment failure. We identified MET alterations (7%-24%), EGFR C797X (0%-29%), SCLC transformation (2%-15%), and oncogene fusions (1%-10%) as the most common mechanisms of resistance. This review provides an evidence-based, algorithmic approach to the evaluation and management of post-osimertinib progression as well as a compendium of active, enrolling clinical trials for this population.

Introduction: Cervical cancer (CC) is currently the eight most common cancer among women and the seventh leading cause of cancer-related death in women in Poland. Early, non-invasive cervical cancer may develop over the years without clinical symptoms. Also, given the fact that early forms are treatable effectively, it's important to get preventive examinations. It is especially important in the group of women at high risk of developing CC. Purpose: The aim of the study is to assess women's knowledge of the risk factors for cervical cancer.Material and method: Women's knowledge of cervical cancer risk factors was verified with an anonymous online questionnaire. The obtained results were analysed and checked on the basis of scientific literature.Results: The vast majority of respondents consider family history of cancer as a risk factor for CC. 75.9% of women consider infection with HPV a risk factor. Chronic vaginal infections were chosen by over half of the women. The onset of intercourse at an early age was considered a risk factor by only 24.6%, while a large number of sexual partners by 45.4%.Conclusions: The results of the conducted research indicate that the knowledge of women from the studied group about the risk factors for cervical cancer and methods of prevention is average. In order to improve the epidemiological situation of cervical cancer in Poland, efforts should be intensified to increase the education of women in this field.

Lung cancer remains the leading cause of cancer-related deaths worldwide. The treatment of non-small cell lung cancer (NSCLC), which accounts for a vast majority of lung cancers, has shifted to personalized, targeted therapy following discoveries of several targetable oncogenic mutations. Targeting of specific mutations has improved outcomes in many patients. This success has led to several target-specific agents replacing chemotherapy as first-line treatment in certain mutated NSCLC. Several researchers have reported that there may be imaging biomarkers that may be predictive of the presence of these mutations. These features, when present, have the potential in triaging patients into the most appropriate diagnostic and treatment algorithms. Distinct imaging features and patterns of metastases that have been associated with NSCLC with various targetable oncogenic mutations are presented in this review.

The aim of the study is to analyse the phenomenon that can be described as “administration of dialogue”. Legal norms introduce competences to a dialogue with the entrepreneur in order to joint-ly develop the most effective solutions to implement the public interest. This is possible by using a policy of voluntary exercising of the law. This dialogue is an alternative to traditional formalised (legalistic) methods of administration. Digitisation enables this change due to the possibility of indi-vidualising the supervisory and regulatory impact. Dialogue as a method of administration is an ex-pression of the humanisation of administrative law (introducing a more partnership approach to the entrepreneur) and of the economisation of law (taking into account economic factors in the process of applying the law). This includes negotiating enforcement of competition law (e.g. commitment decisions), but also cases where the entrepreneur may have an impact on exercising (enforcement) of public law obligations, although the entrepreneur’s position versus the public authority is not equivalent.

OBJECTIVES Dyssynergic defecation is a common disorder in children with functional constipation (FC) because of relaxation disorders of the sphincter apparatus and intra-rectal pressure during defecation. The aim of the study was to determine frequency and type of dyssynergic defecation and to assess pressure in the anal canal poles during simulated evacuation and function of puborectalis muscle in defecation in children with FC. METHODS Three-dimensional (3D) high-resolution anorectal manometries (3D HRAM) were performed in 131 children with FC. In the manometric test, resting pressure measurements were assessed in 4 measuring poles of the anal canal. RESULTS One hundred thirty-one children ages 5 to 17 years (mean age 10.2; SD ± 3.8; median 10) were involved in the study (69 girls and 62 boys). Dyssynergic defecation was shown in 106/131 (80.9%) examined children. A statistically significant difference between the age of examined children (P

Low rates of adult patient participation have been a persistent problem in cancer clinical trials and have continued to be a barrier to efficient drug development. The routine use of significant exclusion criteria has contributed to this problem by limiting participation in studies and creating significant clinical differences between the study cohorts and the real-world cancer patient populations. These routine exclusions also unnecessarily restrict opportunities for many patients to access potentially promising new therapies during clinical development. Multiple efforts are underway to broaden eligibility criteria, allowing more patients to enroll in studies and generating more robust data regarding the effect of novel therapies in the population at large. Focusing specifically on lung cancer as an example, a multistakeholder working group empaneled by the LUNGevity Foundation identified 14 restrictive and potentially outdated exclusion criteria that appear frequently in lung cancer clinical trials. As a part of the project, the group evaluated data from multiple recent lung cancer studies to ascertain the extent to which these 14 criteria appeared in study protocols and played a role in excluding patients (screen failures). The present report describes the working group's efforts to limit the use of these routine exclusions and presents clinical justifications for reducing the use of 14 criteria as routine exclusions in lung cancer studies, potentially expanding trial eligibility and improving the generalizability of the results from lung cancer trials.

In recent years, the prevalence of obesity has increased dramatically and has become a 21st century epidemic. Obesity is associated with the development of many diseases, and therefore treatments that can reduce body mass are actively sought. The aim of this study was to examine the effect of 20 cryostimulation sessions on body composition in obese/high body mass (HBM, n = 12) males and normal body mass (NBM, n = 9) controls. The HBM group had a mean age = 29.08 ± 4.19 years, body fat percentage = 32.08 ± 6.16%, body mass index = 36.23 ± 8.13 kg/m2) and NBM group had a mean age = 22.00 ± 2.45 years, body fat percentage = 12.14 ± 4.93%, body mass index = 23.58 ± 2.00 kg/m2. Kilocalorie intake was similar for both groups. All participants received 20 sessions of systemic cryostimulation at −120°C for 2–3 min in a cryochamber. Blood samples were collected before the first session, 1 h after the 10th session, and 1 h after the 20th cryostimulation session. C-reactive protein (CRP) plasma concentrations, and expression of the heat shock protein genes (HSPA1A, HSPB1) and CRP mRNA in leukocytes were evaluated after 10 and 20 cryostimulation sessions. In both groups, 20 sessions were associated with a significant decrease in body mass, fat mass and the percentage of body fat. CRP concentrations were significantly higher in obese people before the first session and after 10 treatments, but not at the end of study. Expression of HSPA1A and HSPB1 mRNA gradually decreased with the number of cryostimulation sessions. A significant difference in HSPA1A expression was found after 20 sessions (NBM > HBM) and for HSPB1 at baseline and after 20 sessions (HBM > NBM). Our results show that cryostimulation influences body composition and that cryostimulation-induced HSP genes expression depends on the number of cryosessions and baseline body mass, and is differentially altered in HBM individuals. Further research on the interaction between body mass and cold adaptation is warranted.

How does access to foreign or independent media affect the operation of a state security apparatus? This article answers this question concentrating on two characteristics of the informant network of the East German Stasi: the number of informants and their “price.” Exposure to West German TV (WGTV) had the potential to decrease the supply of informants and increase the demand for them, pushing up the value of the payments the informants received, but leaving their quantity theoretically ambiguous. I verify this reasoning using a rare original data set of Stasi informants. Results show that informants were given approximately 70 East German marks worth of rewards more per year in the areas that had access to WGTV, as compared with areas with no reception—ironically an amount roughly equivalent to the cost of an annual East German TV subscription. These findings demonstrate how an authoritarian state can counteract the potentially destabilizing effect of foreign media.

Objectives Vestibular rehabilitation leads to a gradual diminution of the subjective and objective symptoms that accompany the vestibular disorders. The aim of the study was to compare the impact of 2 different types of vestibular rehabilitation on vestibular compensation in patients with chronic unilateral vestibular dysfunction. Material and Methods The study was conducted on a group of 58 subjects (43 females and 15 males) aged 40–64 years, who presented with chronic unilateral vestibular dysfunction and were hospitalized. The patients were randomly assigned to either of the 2 groups established. The study was conducted in a 6-week period. Group 1 consisted of patients who underwent customized group vestibular rehabilitation in an outpatient setting. The program was performed once a week for 1 h 30 min, under the supervision of a physiotherapist and a physiatrist. Group 2 was instructed to perform Cawthorne–Cooksey exercises and simple balance exercises twice a day for 15 min. Results An improvement in the outcomes of the Dynamic Gait Index as well as the Berg Balance Scale was statistically significant for group 1. The time for fulfilling the task in the Timed Up and Go Test improved in both groups (p < 0.05). The subjective estimation of the symptoms evaluated with the use of the Dizziness Handicap Inventory and the Visual Analogue Scale revealed a statistically significant improvement in both groups, yet it was higher in group 1. Conclusions The compensation achieved after 6 weeks of the customized, supervised outpatient rehabilitation program in group 1 was superior to the results of the home-based unsupervised Cawthorne–Cooksey and balance exercises. Int J Occup Med Environ Health. 2020;33(3):273–82