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PurposeThe purpose of this study was to evaluate RB1 expression and survival across ovarian carcinoma histotypes and how co-occurrence of BRCA1 or BRCA2 (BRCA) alterations and RB1 loss influences survival in tubo-ovarian high-grade serous carcinoma (HGSC).Experimental designRB1 protein expression was classified by immunohistochemistry in ovarian carcinomas of 7,436 patients from the Ovarian Tumor Tissue Analysis consortium. We examined RB1 expression and germline BRCA status in a subset of 1,134 HGSC, and related genotype to overall survival (OS), tumor-infiltrating CD8+ lymphocytes, and transcriptomic subtypes. Using CRISPR-Cas9, we deleted RB1 in HGSC cells with and without BRCA1 alterations to model co-loss with treatment response. We performed whole-genome and transcriptome data analyses on 126 patients with primary HGSC to characterize tumors with concurrent BRCA deficiency and RB1 loss.ResultsRB1 loss was associated with longer OS in HGSC but with poorer prognosis in endometrioid ovarian carcinoma. Patients with HGSC harboring both RB1 loss and pathogenic germline BRCA variants had superior OS compared with patients with either alteration alone, and their median OS was three times longer than those without pathogenic BRCA variants and retained RB1 expression (9.3 vs. 3.1 years). Enhanced sensitivity to cisplatin and paclitaxel was seen in BRCA1-altered cells with RB1 knockout. Combined RB1 loss and BRCA deficiency correlated with transcriptional markers of enhanced IFN response, cell-cycle deregulation, and reduced epithelial-mesenchymal transition. CD8+ lymphocytes were most prevalent in BRCA-deficient HGSC with co-loss of RB1.ConclusionsCo-occurrence of RB1 loss and BRCA deficiency was associated with exceptionally long survival in patients with HGSC, potentially due to better treatment response and immune stimulation.

Amnon Ariel,1 Alan Altraja,2,3 Andrey Belevskiy,4 Piotr W Boros,5 Edvardas Danila,6 Matjaz Fležar,7 Vladimir Koblizek,8 Zvi G Fridlender,9 Kosta Kostov,10 Alvils Krams,11 Branislava Milenkovic,12 Attila Somfay,13 Ruzena Tkacova,14 Neven Tudoric,15 Ruxandra Ulmeanu,16 Arschang Valipour17 1Emek Medical Center, Clalit Healthcare Services, Afula, Israel; 2Department of Pulmonary Medicine, University of Tartu, 3Lung Clinic, Tartu University Hospital, Tartu, Estonia; 4Department of Pulmonology, Russian National Research Medical University, Moscow, Russia; 5Lung Pathophysiology Department, National TB and Lung Diseases Research Institute, Warsaw, Poland; 6Clinic of Infectious Chest Diseases, Dermatovenereology, and Allergology, Vilnius University, Centre of Pulmonology and Allergology, Vilnius University Hospital, Vilnius, Lithuania; 7University Clinic of Respiratory and Allergic Diseases, Golnik, Slovenia; 8Department of Pneumology, University Hospital, Hradec Králové, Czech Republic; 9Institute of Pulmonary Medicine, Hadassah Medical Center, Jerusalem, Israel; 10Clinic of Pulmonary Diseases, Military Medical Academy, Sofia, Bulgaria; 11Medical Faculty of Latvian University, Riga East University Hospital, Riga, Latvia; 12Clinic for Pulmonary Diseases, Clinical Centre of Serbia, Faculty of Medicine, University of Belgrade, Belgrade, Serbia; 13Department of Pulmonology, University of Szeged, Deszk, Hungary; 14Department of Respiratory Medicine and Tuberculosis, Faculty of Medicine, PJ Safarik University, Košice, Slovakia; 15School of Medicine, Dubrava University Hospital, Zagreb, Croatia; 16Marius Nasta Institute of Pneumology, Bucharest, Romania; 17Department of Respiratory and Critical Care Medicine, Ludwig Boltzmann Institute for COPD and Respiratory Epidemiology, Vienna, Austria Abstract: COPD is a complex, heterogeneous condition. Even in the early clinical stages, COPD carries a significant burden, with breathlessness frequently leading to a reduction in exercise capacity and changes that correlate with long-term patient outcomes and mortality. Implementation of an effective management strategy is required to reduce symptoms, preserve lung function, quality of life, and exercise capacity, and prevent exacerbations. However, current clinical practice frequently differs from published guidelines on the management of COPD. This review focuses on the current scientific evidence and expert opinion on the management of moderate COPD: the symptoms arising from moderate airflow obstruction and the burden these symptoms impose, how physical activity can improve disease outcomes, the benefits of dual bronchodilation in COPD, and the limited evidence for the benefits of inhaled corticosteroids in this disease. We emphasize the importance of maximizing bronchodilation in COPD with inhaled dual-bronchodilator treatment, enhancing patient-related outcomes, and enabling the withdrawal of inhaled corticosteroids in COPD in well-defined patient groups. Keywords: dual bronchodilation, inhaled corticosteroid, LAMA, LABA, tiotropium, anticholinergic

The topic of dark tourism emerged in the last three decades as tourism became more accessible. It allows forgotten history to be revised and transferred to the public. This study aims to restructure existing categorization regarding dark tourism and address the research gaps in dark tourism studies. We collected studies from international publication databases – Scopus, Web of Science, and Google Scholar. We pre-processed the following data for each study: topic, authors’ location of university affiliation, study area, year of publication, top-cited articles, top productive journals in publishing dark tourism studies, keywords, and internality/externality of the author from the study area. With the current paper, we analysed review articles published from 1996 to 2024 (first quarter), applying qualitative methods. Based on these, a new analytical framework was generated. Furthermore, the connections between research topics were also analysed. The results of the analysis highlight specific research gaps in the literature on dark tourism and address poorly visible research fields in international journals, e.g. terrorism-related research, social media links of dark tourism, postcolonial contexts, or commemoration of communist past and heritage. Consequently, certain countries and regions are underrepresented in the literature. This critical review offers new research areas but also gives some directions to the theoretical enrichment of the dark tourism concept.

Abstract Background During the COVID-19 pandemic, digital health solutions ensured the continuity of care especially in primary healthcare practices. COVID-19 accelerated the adoption of digital health solutions. The aim of this study is to describe the digital health-related attitudes and experiences of Hungarian Primary Care Physicians (PCPs) and also analyse the socio-demographic effects on digital health attitudes among PCPs. Methods This study used a quantitative and qualitative mixed methodological approach to examine the digital health-related attitudes and experience of Hungarian PCPs. As part of the "E-physicians and E-patients in Hungary" survey, we conducted an online survey among medical doctors working in Hungary between July 2021 to May 2022. A total of 1,774 questionnaires were received, consisting of 1,576 medical doctors and 198 dentists. Among the medical doctors there were 415 primary care physicians (PCPs). In addition to the online questionnaire survey, qualitative research in the form of semi-structured interviews with doctors was also conducted. These interviews took place between October 2021 and June 2022. A total of 62 interviews were conducted,19 with PCPs. Results Primary care physicians are more open to technologies that facilitate communication and collaboration with patients, while showing less interest in technologies that support clinical work. Of the demographic variables (age, gender, type of settlement), age was found to have the most significant effect on digital health knowledge, use and intended use. Both the interviews and the multivariate analysis indicate that individuals with greater knowledge, expertise, and experience are more likely to perceive the advantages of digital solutions. This highlights the importance of training, especially given the significant aging population among Hungarian primary care physicians, who may not be accustomed to using these tools naturally. The way PCPs perceive patient expectations regarding the use of digital health tools has a significant impact on the PCPs’ use and intended use of digital tools. When looking at perceived patient needs among PCPs the effect of age and municipality type of PCPs is significant. As age increases, the perception of patient needs decreases (from 5.02 to 4.47), and by municipality type, the average number of perceived needs decreases as one moves from larger cities to smaller municipalities (from 4.85 to 4.14). Conclusions Digital health solutions have the potential to enhance the work of PCPs, but successful implementation requires addressing specific needs, demographic differences, and challenges faced by PCPs. Development of infrastructure, education, and institutional support is necessary to ensure more efficient and higher-quality healthcare delivery through the use of digital technologies.

To harness radiometals in clinical settings, a chelator forming a stable complex with the metal of interest and targets the desired pathological site is needed. Toward this goal, we previously reported a unique set of chelators that can stably bind to both large and small metal ions, via a conformational switch. Within this chelator class, py-macrodipa is particularly promising based on its ability to stably bind several medicinally valuable radiometals including large 132/135La3+, 213Bi3+, and small 44Sc3+. Here, we report a 10-step organic synthesis of its bifunctional analogue py-macrodipa-NCS, which contains an amine-reactive -NCS group that is amenable for bioconjugation reactions to targeting vectors. The hydrolytic stability of py-macordipa-NCS was assessed, revealing a half-life of 6.0 d in pH 9.0 aqueous buffer. This bifunctional chelator was then conjugated to a prostate-specific membrane antigen (PSMA)-binding moiety, yielding the bioconjugate py-macrodipa-PSMA, which was subsequently radiolabeled with large 132/135La3+ and small 47Sc3+, revealing efficient and quantitative complex formation. The resulting radiocomplexes were injected into mice bearing both PSMA-expressing and PSMA-non-expressing tumor xenografts to determine their biodistribution patterns, revealing delivery of both 132/135La3+ and 47Sc3+ to PSMA+ tumor sites. However, partial radiometal dissociation was observed, suggesting that py-macrodipa-PSMA needs further structural optimization.

OBJECTIVES Prophylactic ankle bracing is widely used to prevent ankle sprains, but its effects on knee joint mechanics, particularly regarding ACL injury risk, are less understood. This study aimed to investigate the influence of ankle bracing on knee joint kinetics and ground reaction forces (GRFs) during a 90° side-step cutting task. METHODS Thirty physically active participants (15 males, 15 females) performed cutting trials under braced and unbraced conditions. Knee flexion, abduction, and internal rotation moments, along with mediolateral, anteroposterior, and vertical GRFs, were measured using a motion analysis system and a force plate. Paired t tests were conducted to compare the knee joint moments and GRFs between the two conditions. RESULTS The results showed that while ankle bracing did not significantly affect GRFs, it significantly increased knee internal rotation moment (p = 0.003). No significant differences were observed in knee flexion or abduction moments. CONCLUSIONS Ankle bracing, though beneficial for ankle stability, may elevate the risk of ACL injuries during dynamic activities like cutting by increasing knee internal rotation moments. Clinicians and coaches should weigh the benefits of ankle bracing against potential risks to knee health and consider alternative injury prevention strategies focused on neuromuscular control and strength training.

There are two main branches of geography at the international level and in Hungary: human and physical geography, but the relationship between these two differs significantly in different regions. Physical geography tends to use the methods adopted and applied in the natural sciences, while human geography is increasingly connected to (other) social sciences. In this study, we examined the scientific publications of authors institutionally belonging to the two branches of geography in Hungary using quantitative methods. Physical geography publications can be characterized by more authors and higher international embeddedness than human geography publications, which only started to change in the last 3–4 years. Moreover, the latter were published in a large proportion in other domestic (social science) journals, which indicates a higher degree of connection with related social sciences.

In this paper we consider a generalized polynomial f: ℝ → ℝ of degree two that satisfies the additional equation f(x)f(y) = 0 for the pairs (x, y) ∈ D, where D ⊆ ℝ2 is given by some algebraic condition. In the particular cases when there exists a positive rational m fulfilling D={(x,y)∈ℝ2|x2-my2=1},D = \left\{ {\left( {x,y} \right) \in \mathbb{R}{^2}|{x^2} - m{y^2} = 1} \right\}, we prove that f(x) = 0 for all x ∈ ℝ.

The aim of our cross-sectional study was to assess the rotational range of motion of the shoulder joint and the scapula movement of Hungarian NBII handball players, to find out how many athletes may be affected by a rotational range of motion deficit. We also wanted to gain insight into whether players with GIRD report more pain. The study was conducted between September and October 2023. We studied 31 male handball players, all of whom participated in training sessions at least 3 times a week. The survey showed that more than half of the athletes were affected by some level of range of motion deficit. Of those assessed, 29% were affected by Glenohumeral Internal Rotation Deficit (GIRD) and 55% by Total Arc of Motion Deficit (TAMD). Those who had at least 15° of internal rotation deficit during pretesting had significantly less scapula upward rotation in the neutral shoulder, 60° abduction and 90° abduction positions. No significant difference was found in the 120° shoulder abduction position. For the non-dominant upper limb, no significant difference was found between the two groups. Athletes with GIRD reported significantly greater pain on the VAS scale than those without internal rotation deficit.

IntroductionSarcopenia is associated with poor clinical outcomes in chronic diseases. Our study aimed to characterize body composition (BC) parameters in patients with inflammatory bowel disease (IBD) and compare skeletal muscle mass (SMM) parameters with the healthy pediatric population.MethodsBC of healthy controls (HC) and of patients with IBD were measured via multifrequency bioelectrical impedance (InBody 720 device) in a cross-sectional manner. The effect of sex, age, height, weight, and body mass index (BMI) on BC parameters, with a special attention to SMM, was assessed. Reference tables from SMM were generated using a maximum-likelihood curve-fitting technique for calculating Z scores.ResultsBC parameters were associated with age, body size, and sex. SMM was lower in patients with IBD (n = 57, aged 6.71 ± 8.7 years) compared to unadjusted HC (n = 307, aged 9.9–19.3 years; 143 males; SMM: 22.34 ± 8.38 vs. 24.4 ± 6.3 kg; p = 0.03). SMM showed a moderately strong correlation with age, weight, height, and BMI (R = 0.65, 0.9, 0.87, and 0.66; p

Our objective was to test whether p53 expression status is associated with survival for women diagnosed with the most common ovarian carcinoma histotypes (high-grade serous carcinoma [HGSC], endometrioid carcinoma [EC], and clear cell carcinoma [CCC]) using a large multi-institutional cohort from the Ovarian Tumor Tissue Analysis (OTTA) consortium. p53 expression was assessed on 6,678 cases represented on tissue microarrays from 25 participating OTTA study sites using a previously validated immunohistochemical (IHC) assay as a surrogate for the presence and functional effect of TP53 mutations. Three abnormal expression patterns (overexpression, complete absence, and cytoplasmic) and the normal (wild type) pattern were recorded. Survival analyses were performed by histotype. The frequency of abnormal p53 expression was 93.4% (4,630/4,957) in HGSC compared to 11.9% (116/973) in EC and 11.5% (86/748) in CCC. In HGSC, there were no differences in overall survival across the abnormal p53 expression patterns. However, in EC and CCC, abnormal p53 expression was associated with an increased risk of death for women diagnosed with EC in multivariate analysis compared to normal p53 as the reference (hazard ratio [HR] = 2.18, 95% confidence interval [CI] 1.36-3.47, p = 0.0011) and with CCC (HR = 1.57, 95% CI 1.11-2.22, p = 0.012). Abnormal p53 was also associated with shorter overall survival in The International Federation of Gynecology and Obstetrics stage I/II EC and CCC. Our study provides further evidence that functional groups of TP53 mutations assessed by abnormal surrogate p53 IHC patterns are not associated with survival in HGSC. In contrast, we validate that abnormal p53 IHC is a strong independent prognostic marker for EC and demonstrate for the first time an independent prognostic association of abnormal p53 IHC with overall survival in patients with CCC.

Radioactive isotopes are an essential part of everyday life and an expanding area of research in the fields of medicine, catalysis, and energy. Here, we describe an educational activity that introduces the concept of radioactive decay and the corresponding benefits, risks, and safe handling strategies. Specifically, we have developed an interactive card game, "Radioactivity and [superscript 235]U," as an activity which can be implemented in a fully remote setting without the need for a trained instructor or specific, previously acquired expertise. The card game consists of 72 playing cards and 50 tokens and contains links to two remotely accessible introductory videos on (1) fundamental concepts of radioactive decay and (2) instructions on gameplay. The goal of this activity is to familiarize students with the concepts of radioactive decay, shielding, and applications of radioactive isotopes. Gameplay incentivizes students to prevent, reduce, or limit exposure to a radioactive dose by collecting and using shielding cards, while also learning facts about radioactive isotopes and their stable congeners. The game was tested with undergraduate college students. Pre- and postactivity questionnaires measured the students' familiarity and opinion on the use and harm of radioactivity. The results indicate that the activity is suitable to introduce basic concepts surrounding radionuclides, radioactive decay, and shielding. We additionally observed a shift in students' opinions of nuclear chemistry and its role in the world from neutral to slightly positive after the workshop.