The Tracking Cancer Evolution Through Therapy (TRACERx) program represents the most comprehensive effort to characterize tumor evolution in real time. Through longitudinal, multiregion, and multiomic profiling of tumors—and particularly of non-small-cell lung cancer and clear cell renal cell carcinoma—TRACERx has illuminated the dynamic interplay between genetic, nongenetic, and (micro)environmental factors that drive cancer progression, immune evasion, and therapeutic resistance. A central insight from TRACERx has been that not all tumor evolution is genomic: Transcriptomic diversity, epigenetic alterations, RNA editing, and changes in cell–cell interactions also drive adaptation. Methodological innovations—including tumor-informed and ultrasensitive circulating tumor DNA assays, representative sequencing, and integrative immune–genomic analyses—have yielded biomarkers resistant to sampling bias and/or predictive of recurrence, metastasis, and treatment response. By demonstrating that intratumor heterogeneity is a key determinant of clinical outcome and revealing its molecular, transcriptional, and ecosystem-level drivers, TRACERx has established a framework for linking evolutionary dynamics to patient care. As both a scientific framework and a clinical paradigm, TRACERx demonstrates how adaptive, iterative research can refine evolutionary models, improve patient risk stratification, and inspire next-generation cancer evolution studies across malignancies.

Purpose: To emphasize the diagnostic role of magnetic resonance imaging (MRI) in identifying Fitz-Hugh–Curtis syndrome (FHCS) in an adolescent patient with a subtleclinical presentation. Methods: A 17-year-old female presented with acute onset right upper quadrant and right shoulder pain. The initial diagnostic workup, including ultrasound (US), computedtomography (CT), and laboratory testing was inconclusive. Due to persistent symptoms and elevated inflammatory markers, MRI of the abdomen and pelvis was subsequentlyperformed. Results: MRI demonstrated a bilateral pyosalpinx with restricted diffusion, free fluid in the pelvis and subhepatic region, and linear adhesions between the hepatic capsule and peritoneum, which was consistentwith pelvic inflammatory disease (PID) complicated by FHCS. Microbiologic analysis confirmed a Chlamydia trachomatis infection. The patient received targeted antibiotic therapy with clinical improvement. Conclusion: FHCS represents a rare but importantcomplication of PID that may present with non-specificor extra-pelvic symptoms. MRI is the modality of choicefor confirming PID-related complications and perihepatic inflammation, offering high sensitivity and the advantage of radiation-free imaging, which is especially relevant in the adolescent population.

Lemon essential oil is widely used in both commercial and domestic products. It consists of a mixture of volatile, liposoluble compounds responsible for its characteristic fragrance and bioactive properties, including antimicrobial, anti-inflammatory and antioxidant activities. The importance of lemon essential oil is even more significant when considering the increasing interest in natural products that promote human health. In this study, domestically grown lemons were used. The essential oil was extracted from the peel using the hydrodistillation method, an environmentally friendly process. The composition of the resulting essential oil was analysed using gas chromatography coupled with mass spectrometry (GC-MS). The analysis revealed that d-limonene, β-pinene, and γ-terpinene are the predominant components found in lemon essential oil. The antimicrobial activity of the essential oil was tested and found to be effective against Staphylococcus aureus. Molecular docking analysis revealed that all three principal compounds were able to bind to the DNA gyrase enzyme, with d-limonene exhibiting the lowest binding energy. The essential oil also exhibited significant DPPH radical scavenging activity, highlighting its antioxidant potential. The results indicate that both concentration and incubation time affect the antioxidant capacity of the essential oil.

Aim: This study aimed to determine the basic epidemiological characteristics of patients with stroke who were hospitalised at the General Hospital and the Hospital for Homeland War Veterans in Ogulin over a ten-year period.Materials and methods: A retrospective analysis ofdata from the hospital information system was conducted, encompassing all patients diagnosed with stroke at Ogulin General Hospital between January 1, 2014, and December 31, 2023.Results: A total of 1521 patients were diagnosed witha stroke. Of these, 81.7% were diagnosed with an ischaemic stroke. No statistically significant difference was found in the frequency of strokes between men andwomen (p = 0.233). The highest proportion of patients,39.7%, was in the 70- to 80-year age group. Most strokeswere recorded in January (147), while the fewest occurred in April (107). A total of 13.7% of patients diagnosed with a stroke were transferred to another hospital facility.Discussion: The study highlights stroke as a significantproblem in the rural region of Ogulin, primarily due tolimited resources. Early interventions, improved infrastructure, and standardised protocols are needed to reduce mortality and disability.

The development of advanced macromolecular systems with tailored structural and functional properties is a key objective in modern materials science, particularly for biomedical applications such as targeted drug delivery. In this study, hydrogel (HG), a polymer-based formulation, was investigated as a functional carrier for the enhanced intradermal and transdermal delivery of propranolol hydrochloride (PRO-HCl), a highly water-soluble model compound, and its potential was compared to other vehicles easily obtained by pharmacists: ointment (OM), liposomal cream (LCR), and microemulsion (ME). The formulations were characterized by their physicochemical and rheological characteristics, and evaluated in vitro and ex vivo using vertical diffusion cells equipped with synthetic membranes, intact porcine skin, and skin pretreated with solid microneedles (MNs). The HG formulation exhibited superior release performance (2396.85 ± 48.18 μg/cm2) and the highest intradermal drug deposition (19.87 ± 4.12 μg/cm2), while its combination with MNs significantly enhanced transdermal permeation (p = 0.0017). In contrast, the synergistic effect of MNs and ME led to a pronounced increase in drug accumulation within the skin (up to 60.3-fold). These findings highlight the crucial role of matrix composition and properties in modulating molecular transport through biological barriers. The study demonstrates that polymeric HGs represent versatile, functional materials with tunable structural and mechanical features, suitable for controlled release and potential systemic delivery applications.

Background: Advances in computational pathology using deep learning have enabled the prediction of molecular biomarkers and therapy response directly from hematoxylin and eosin (H&E) whole slide images (WSIs), offering a potential complement to molecular assays. Methods: Following PRISMA guidelines, we searched Embase, Web of Science, and PubMed (01/2020–04/2025) for studies applying H&E-based WSI computational analysis to predict prognosis or treatment response in solid tumors, with molecular pathology comparators. Data extraction and quality assessment with a 7-item QUADAS-2/PROBAST-adapted tool was performed. Results: Of 322 records screened, 64 met inclusion. Many studies focused on breast, colorectal, lung, gastric, or prostate cancer. Targets included Microsatellite Instability, mutations (e.g., EGFR, TP53), protein biomarkers (e.g., PD-L1, HER2), and gene expression profiles. Convolutional neural networks were most common, alongside Vision Transformers and foundation models. Median dataset size for model development was 509 cases (range: 13–12,592); 64% used independent external validation. AUROCs ranged from 0.58 to 0.97. Clinical readiness varied: 41% were proof-of-concept only, while 30% had multi-cohort validation. Median quality score was 71.4%, with frequent gaps in cohort representativeness and method reporting. Conclusions: H&E-based WSI computational analysis can accurately predict diverse biomarkers and therapy-relevant endpoints, sometimes nearing molecular assay performance. Dataset quality, external validation, and reporting variability currently limit clinical adoption; standardized benchmarking and multi-institutional validation are needed for integration into precision oncology workflows.

Copy number variations (CNVs) play a crucial role in cancer diagnostics and prognostics, potentially impacting treatment decisions. Ultra‐low‐pass whole‐genome sequencing (ULP‐WGS) has emerged as a promising alternative to array‐based methods for CNV detection, especially in formalin‐fixed paraffin‐embedded (FFPE) samples. However, sequencing biases and sample heterogeneity necessitate the optimization of CNV detection tools for FFPE sample‐derived data. This study evaluates three open‐source CNV callers (CNVpytor, ichorCNA, and WisecondorX) using ULP‐WGS and compares their performance against a single nucleotide polymorphism (SNP) array. Our results demonstrate that under optimal experimental conditions, ichorCNA and WisecondorX achieved equal detection of true positive results, with reduced false positive results compared to the SNP array. The SNP array detection pattern differed somewhat from that of the CNV callers, while ichorCNA and WisecondorX had the most comparable detection pattern. We highlight the importance of (pre‐)analytical parameters such as neoplastic cell content, sequencing coverage, and bin size selection on CNV detection accuracy. Our findings support the adoption of ULP‐WGS‐based CNV detection as a robust alternative to SNP arrays, with WisecondorX emerging as the most suitable tool for clinical implementation.

Previous studies show that interventions to improve attitudes toward stuttering yield inconsistent results on the Public Opinion Survey of Human Attributes–Stuttering (POSHA–S). Comparisons of pre- and post-intervention samples indicate that success depends on the percentage of respondents who improved rather than the magnitude of change. A “crossover” effect emerged: respondents with the most positive pre-test attitudes showed lower post-test ratings, whereas those with the most negative pre-test attitudes showed the greatest improvement; respondents with intermediate attitudes showed little change. Similar patterns appeared in non-intervention samples, where one-third fell into positive, minimal, or negative change groups. The study analyzed 943 respondents from 29 intervention samples classified as unsuccessful (U), marginally successful (MS), successful (S), or very successful (VS), plus 345 respondents from 12 non-intervention samples. Using non-intervention data as a baseline, we calculated percentages shifting among the three change groups. In the VS category, interventions moved people from the negative and minimal change groups into the positive change group. In the S category, gains in the positive change group came from the negative change group. In the MS category, all intervention-related changes began in the negative change group, yielding modest growth in the positive and minimal change group. The U category showed shifts into both the positive and negative change group, mainly reducing the minimal change group. These findings suggest that interventions to improve attitudes toward stuttering should apply strategies tailored to individuals in positive, minimal, and negative change groups.

Ovaj rad pruža (sveobuhvatnu) analizu razvoja rimskog kaznenog (krivičnog) postupka od kraljevskog doba do kraja Republike. Autor istražuje kako je rano rimsko društvo prešlo sa privatne osvete na državno provođenje pravde, naglašavajući nerazdvojivost prava, religije i politike. Kroz detaljno razmatranje institucija kao što su quaestores parricidii, quaestiones perpetuae, te reformi koje su sproveli Sula, Ciceron i Pompej, tekst prikazuje sve veću formalizaciju, specijalizaciju i politizaciju krivičnog prava. Posebna pažnja posvećena je procesnim principima, uključujući pretpostavku nevinosti, akuzatorni model i pravila dokazivanja. Zaključno, rimsko krivično pravo – iako često zapostavljeno u korist privatnog prava – imalo je značajan uticaj na temeljne koncepte savremenih evropskih  krivičnopravnih sistema.

Activin A and B share the same downstream signalling pathway (activation of SMAD2/3) as TGF-β and consequently elicit many of the same functional responses as TGF-β, including immune suppression, activation of cancer-associated fibroblasts (CAFs) and extracellular matrix production and remodelling. However, activin’s role in tumourigenesis has been relatively overlooked compared to TGF-β’s. We generated and characterized a dual specificity human antibody that recognizes both activin A and B and compared its activity in syngeneic mouse models of breast cancer and pancreatic ductal adenocarcinoma (PDAC) with an activin A-specific antibody. We demonstrate that activin A and B are central to the function of CAFs and therapeutic inhibition of activin results in a reduction of collagen rich desmoplastic barriers, enabling the infiltration of cytotoxic T cells. This is correlated with an upregulation of the T cell chemoattractant CXCL10, which is normally repressed by activin signalling. Interestingly, despite greater T cell infiltration, activin A inhibition resulted in poorer survival in the KPC mouse model of PDAC and slightly larger tumours in the breast cancer model, indicating a tumour suppressive role of activin A-rich CAFs. Strikingly, however, treatment with the same anti-activin A antibody of PDAC tumours where SMAD4 is deleted in the tumour cells, resulted in increased survival, which was potentiated with additional treatment with immune checkpoint inhibitors. These results suggest that anti-activin therapy has potential for the cohort of PDAC patients exhibiting inactivation of SMAD4.

Background: The symptoms of COPD differ based on the stage of the disease, becoming more noticeable in its severe stages and during exacerbations. They are associated with temporary incapacity for work and cause a decrease in working capacity. Also, occupations with special working conditions and exposure to pollutants at work cause increased bronchial secretion and cough. This research aims to identify the most common symptoms in COPD patients and evaluate their work capacity based on symptom prevalence. Methods: 200 subjects were included in the prospective study. Participants were divided into two groups: a study group and a control group. Within each group, subgroups were created based on smoking habits, a key risk factor for COPD development. Results: The dominant symptom in both groups was cough, with 34.67%. In subjects with preserved working capacity, the most common symptoms are chest pressure with 13.33% and shortness of breath with 9.33%, while in the group with reduced working capacity, fatigue (30%) and dyspnea with 26%. In the control group, most subjects had obstructive bronchitis, asthma and chronic simplex bronchitis. Conclusion: According to the GOLD classification, modified working capacity decreased by 51.33%, while retained working capacity declined by 48.67% in relation to disease severity. Cough was the dominant symptom in both groups, while other symptoms varied independently of the stage of the disease.

Dear editor,We would like to express our sincere gratitude for the attention given to our published scientific paper, as well as for the positive comments, valuable suggestions, and thoughtful questions in the Comment on the article by Bajpai. We consider his contribution extremely important for improving the quality of future research in this field.

Workplace behaviors and employee outcomes, such as team functioning, job satisfaction, and intentions to leave, are crucial for healthcare quality and safety. It highlights the substantial productivity, societal, and economic costs of worker well-being. Against this backdrop, this study examines how two dimensions of organizational culture: ethical climate and perceived managerial competence, together with team support, relate to job satisfaction and turnover intention among healthcare professionals. A quantitative, cross-sectional survey was conducted with 430 physicians, nurses, and other clinical staff in public and private institutions across the Federation of Bosnia and Herzegovina. Using established scales and structural equation modeling (SEM) in AMOS, we first verified satisfactory reliability and construct validity via exploratory and confirmatory factor analyses. The structural model showed that ethical organizational culture and managerial competence are positively related to team support and, directly or indirectly, to higher job satisfaction and lower turnover intention. Team support was positively related to job satisfaction and negatively related to turnover intention and significantly mediated the effects of both ethical climate and managerial competence on these outcomes. In addition, job satisfaction was strongly and negatively correlated with turnover intention, underscoring its central role in retention.

The aim of this study was to investigate the effectiveness, tolerability and safety of using lisinopril tablets in the treatment of essential hypertension for a period of 12 weeks.Methods:A multicenter, observational, non-interventional, postmarketing clinical trial was conducted on adult patients older than 30 years with a diagnosis of hypertension and blood pressure values ≥ 140/90 mmHg. Patients taking lisinopril were monitored for 12 weeks, during one initial and three control examinations.Main findings: The study included 334 patients:group A-aged 30 to 59 (n=167) and group B -aged 60 and older (n=167). In the group of younger respondents, the systolic/diastolic pressure before therapy was on average 150/95 mmHg, and with the use of lisinopril therapy, decreased to an average of 130/80 mmHg after 4 weeks. For the older respondents, the systolic/diastolic pressure before therapy was on average 155/95 mmHg, while afterstarting the lisinopril therapy, it decreased to an average of 135/80 mmHg. The differences in systolic/diastolic pressure were assessed as very good, namely 70.9% in the older and 87.4% in the younger group. More patients from the elderly group (34 patients) had adverse events compared to the younger group (24 patients). Adherence was generally good. Comparison of the two groups showed better results in the younger group compared to older group, 82.6% vs 69.3%.Principal conclusion:Lisinopril showed goodefficacy and safety in reducing essential hypertension in patients. Tolerability and high adherence to lisinopril therapy was observed. Key words: Lisinopril, hypertension, systolic blood pressure, diastolic blood pressure