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.
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.
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.
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
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.
Heart-rhythm disorders and related congenital anomalies in children often remain silent until physical activitybrings on symptoms. We report an 11-year-old girl who experienced her first signs of heart disease only after exertion. Although late detection of such anomalies can sometimes be fatal, careful clinical examination may reveal these conditions early.
Background: A doubt that occupational medicine specialists face is whether exposure to solvents is an independent risk factor for non-alcoholic fatty liver disease. Aim: The present study investigates the connection between the length of work experience (exposure) at workplaces that are exposed to organic volatile substances with eventual changes in the morphological structure of the liver parenchyma or laboratory parameters of liver function, and to investigate whether organic volatile substances, as an independent factor can lead to liver steatosis or changes in laboratory parameters of liver function. Methods: A prospective study was conducted from January to April 2023. and included 62 coke industry workers who were divided into two groups of 31 workers each (experimental with workers exposed to organic volatile substances at the workplace and control with workers who were not exposed). Laboratory parameters of liver function were monitored, as well as ultrasound findings of liver parenchyma in coke industry workers undergoing examination. Exclusion criteria were known history of liver disease, blood transfusion, alcohol consumption and diabetes mellitus. Results: Changes in laboratory parameters of liver function and ultrasound findings of liver steatosis were found with high statistical significance in the workers of the experimental group, for which no statistically significant association with elevated values of lipid status was found. With diabetes as an exclusion factor and the insignificant prevalence of hypertension in the examined workers, it can be concluded that metabolic syndrome is not related to our results. During the correlation analysis, it can be concluded that organic volatile substances are an independent cause and trigger for fatty infiltration of the liver parenchyma and changes in the laboratory findings of liver function parameters. Conclusions: Exposure to organic volatile substances at the workplace as an independent factor causes liver steatosis with elevated values of laboratory parameters of liver function and it can be said that it is an independent cause of non-alcoholic fatty liver disease.
Understanding how water-quality models perform across different hydrological and biogeochemical contexts is essential for managing nutrient losses in agricultural catchments. This study evaluated SimplyP, a parsimonious phosphorus model, adapted to better represent Irish agricultural catchments and implemented within the flexible Mobius2 framework. Long-term, high-frequency monitoring data from the Agricultural Catchments Programme (ACP) were used for two sites: Ballycanew, a grassland catchment dominated by surface runoff, and Castledockrell, an arable, groundwater-driven catchment. Model calibration and validation were performed for streamflow (Q), suspended sediment (SS), and multiple phosphorus (P) fractions, with performance assessed using Kling–Gupta efficiency (KGE). In Ballycanew, the model reproduced Q, SS, and total P load well, with weaker agreement for total reactive phosphorus (TRP), likely reflecting unaccounted point sources during low flows. In Castledockrell, performance was moderate for Q and SS, but TRP and other P fractions were not adequately captured, highlighting the need for more detailed representation of subsurface P pathways in groundwater-dominated systems. Overall, SimplyP is well-suited to surface-runoff-dominated catchments with conventional phosphorus mobilisation. Its flexible implementation in Mobius2 allows relatively straightforward modifications, such as including groundwater-mediated P processes, to extend applicability to more complex systems. High-resolution ACP datasets were crucial for identifying model strengths and limitations, supporting refinement for improved nutrient management across diverse agricultural landscapes.
Background: Coxiella burnetii is a common zoonotic pathogen that can lead not only to acute or chronic Q fever but also to post-infectious syndromes, where autonomic nervous system (ANS) dysfunction has been suggested as a contributing mechanism. This study aimed to assess autonomic function in patients presenting with polymorphic symptoms, dysautonomia, or ME/CFS who had serological evidence of acute infection with Coxiella burnetii. Methods: A total of 156 participants were evaluated, including 100 seropositive patients and 56 matched controls. All subjects underwent standardized cardiovascular reflex tests (CART), beat-to-beat analysis of heart rate and blood pressure with baroreflex indices, 24 h Holter ECG with HRV assessment, and, in the Coxiella group, head-up tilt testing (HUTT). Results: A significantly higher prevalence of autonomic dysfunction was observed in the Coxiella group, predominantly affecting parasympathetic regulation, with abnormal CART scores, reduced LF power and baroreflex effectiveness, and a high rate of positive HUTT findings characterized by extreme blood pressure variability. Although long-term HRV measures did not differ significantly between groups, short-term indices consistently indicated ANS impairment. Conclusions: These findings suggest that Coxiella burnetii infection may trigger persistent autonomic dysfunction, potentially contributing to the development of ME/CFS and syncope in affected individuals. Further longitudinal studies are needed to clarify pathophysiological mechanisms and clinical implications.
Introduction. Obesity is a significant public health issue and a prevalent preventable nutritional disor- der. It can result from hereditary factors, prenatal conditions, environmental influences, metabolism, and lifestyle choices. This condition leads to an accu- mulation of adipose tissue and increased body mass.Aim. This study aimed to identify participants’ life- style habits, determine their nutritional status, and assess potential predictors of obesity.Methods. The cross-sectional study included 354 students from the Sarajevo High School of Medicine, of whom 236 (approximately 70%) were female. Par- ticipants were aged 14 to 18 years, with a mean age of 16.32 ± 1.74 years. The study involved collecting anthropometric data from physical education class records and administering a structured questionnaire (socio-demographic characteristics and assessment of life habits) designed for this study.Results. It was found that approximately one quarter of the subjects were overweight/obese. Unhealthy eating habits were prevalent, with around 50% of re- spondents consuming fruits and vegetables every day, 80% consuming sugar-sweetened beverages, snacks and fast food. The Pearson correlation test and linear regression determined that inappropriate eating hab- its, lack of physical activity and pronounced sedentary habits significantly affect the occurrence of excessive body mass/obesity in the subjects.Conclusion. Research shows many adolescents have unhealthy habits and obesity, which pose serious health risks. Early screening and prevention are crucial to reduce these risks and promote long-term health.
Hydrogen is a versatile energy carrier but its storing is challenging. For that reason, alternative hydrogen storage approaches are being intensively researched. Solid state storing of hydrogen in the form of ammines offers certain advantages, such as high storage capacity and relatively low toxicity. Therefore, in this work hexaammine complexes of nickel chloride and nickel bromide were prepared and investigated. Ni(NH3)6Cl2 and Ni(NH3)6Br2, were obtained by precipitation synthesis. The prepared complexes were characterized by scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS), X-ray powder diffraction (PXRD), Fourier transform infrared spectroscopy (FTIR), thermo-gravimetric analysis (TGA) and differential scanning calorimetry (DSC). The prepared particles are polydisperse, agglomerated and show a characteristic octahedral morphology. The samples consist solely of pure, well-crystalline, corresponding hexaamine complexes. Ni(NH3)6Br2 shows somewhat weaker nitrogen bonds with the central cation and weaker hydrogen bonds with halogen compared to Ni(NH3)6Cl2. Thermal analyses have shown that under the experimental conditions used, ammonia is released from Ni(NH3)6Cl2 in three stages, while in the case of Ni(NH3)6Br2, decomposition occurs in two stages. This difference is a consequence of the kinetic parameters of the desorption process. The maximum of the first stage of desorption occurs for the Ni(NH3)6Cl2 sample at a slightly lower temperature than for the Ni(NH3)6Br2 sample, which is attributed to thermodynamic factors.
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