Limited understanding of the biological processes that govern metastatic dissemination hinders its prevention and treatment1. Here, using 501 longitudinally collected primary and metastatic tumour samples from 24 patients with non-small cell lung cancer (NSCLC) enrolled in the TRACERx lung study and PEACE autopsy programme, we infer tumour evolution from diagnosis to death. With DNA-sequencing data encompassing 70% of the metastases that were radiologically detected before death and paired multi-region sampled primary tumours, we show that the genomes of metastases diverge markedly from those of their ancestral primary tumour, with additional driver alterations and genome doubling events occurring after metastatic dissemination. In 62.5% of patients, multiple primary tumour subclones disseminated, each founding a distinct metastasis. These metastases served as sources of onward spread: more than half of the metastases sampled were seeded by other metastases. The duration that metastases existed in situ influenced their likelihood of seeding further metastases. Most metastatic migrations started and ended in the same anatomical cavity. The few subclones that exited the thorax to seed metastases disseminated widely and were enriched for somatic copy-number alterations, suggesting that chromosomal instability may facilitate extrathoracic spread. This spatial and temporal evolutionary analysis sheds light on the extent of metastatic diversity and seeding in advanced NSCLC—which tends to be underestimated in single metastasis biopsies—and identifies genomic and clinical mediators of metastatic progression. DNA-sequencing data from primary tumours and paired metastases from participants in the TRACERx lung study and PEACE autopsy programme are used to analyse the metastatic diversity of advanced non-small cell lung cancer and the seeding patterns that underpin it.

The burden of nephrotoxicity and ototoxicity consequences caused by gentamicin warrants preventive therapeutic measures. Our aim was to evaluate combined and potentially synergistic effects of rosuvastatin and curcumin, both possessing anti-inflammatory and antioxidant properties, compared to their monotherapies in a gentamicin-induced model of nephrotoxicity and ototoxicity. In a randomized, controlled study, 36 male Wistar rats were allocated to six groups and treated for 5 days: negative control group received solvent, model group gentamicin (100 mg/kg, intraperitoneally), treatment groups gentamicin and via orogastric tube either standard-dose rosuvastatin (5 mg/day), reduced-dose rosuvastatin (1.25 mg/day), curcumin (100 mg/kg), or combination of reduced-dose rosuvastatin and curcumin. Human rosuvastatin doses were converted to rat doses using the conversion factor of 6.2. Functional outcomes evaluated by Preyer pinna reflex for hearing and a vestibular battery test were complemented by renal and cochlear histology, biochemical biomarkers of injury, inflammation, and oxidative stress. Gentamicin induced proximal tubular necrosis and cochlear and vestibular damage. Compared to monotherapies, combination therapy significantly preserved renal architecture, improved renal biomarkers, reduced early inflammatory biomarkers, preserved cochlear architecture and drove vestibular protection. It also alleviated gentamicin-induced cardiotoxicity. Rosuvastatin provided stronger auditory protection, with reduced-dose rosuvastatin superior to standard-dose in preserving vestibular function. Bliss independence modelling showed that combined therapy synergistically inhibited kidney injury and inflammation. In conclusion, the combination of reduced-dose rosuvastatin and curcumin outperforms both monotherapies in alleviating gentamicin-induced nephrotoxicity, audiotoxicity and vestibulotoxicity, whilst synergistically attenuating nephrotoxicity and early-phase inflammation in rats. These findings highlight promising preventive strategies against aminoglycoside nephrotoxicity and ototoxicity.

The extent to which exogenous sources, including cancer treatment, contribute to somatic evolution in normal tissue remains unclear. Here we used high-depth duplex sequencing1 (more than 30,000× coverage) to analyse 168 cancer-free samples representing 16 organs from 22 patients with metastatic cancer enroled in the PEACE research autopsy study. In every sample, we identified somatic mutations (range 305–2,854 mutations) at low variant allele frequencies (median 0.0000323). We extracted 16 distinct single-base substitution mutational signatures, reflecting processes that have moulded the genomes of normal cells. We identified alcohol-induced mutation acquisition in liver, smoking-induced mutagenesis in lung and cardiac tissue, and multiple treatment-induced processes, which correlated with therapy type and duration. Exogenous sources, including treatment, underpinned, on average, more than 40% of mutations in liver but less than 10% of mutations in brain samples. Finally, we observed tissue-specific selection, with positive selection in tissues such as lung (PTEN and PIK3CA), liver (NF2L2) and spleen (BRAF and NOTCH2), and limited selection in others, such as brain and cardiac tissue. More than 25% of driver mutations in normal tissue exposed to systemic anti-cancer therapy, including in TP53, could be attributed to treatment. Immunotherapy, although not associated with increased mutagenesis, was linked to driver mutations in PPM1D and TP53, illustrating how non-mutagenic treatment can sculpt somatic evolution. Our study reveals the rich tapestry of mutational processes and driver mutations in normal tissue, and the profound effect of lifetime exposures, including cancer treatment, on somatic evolution. High-depth sequencing of non-cancerous tissue from patients with metastatic cancer reveals single-base mutational signatures of alcohol, smoking and cancer treatments, and reveals how exogenous factors, including cancer therapies, affect somatic cell evolution.

AIM The position of science and scientific research in Bosnia and Herzegovina (B&H) is unfavourable. University education lacks research programs, hindering students from developing critical evaluation skills. METHODS This cross-sectional study examined knowledge, attitudes, experience and perceived barriers towards scientific research among biomedical students and recent graduates at the University of Sarajevo in B&H. A self-reporting questionnaire was distributed via social networks and among students from all years of the Medical, Dentistry, Pharmaceutical faculties, the Faculty of Health Sciences, and the Faculty of Science, as well as recent graduates. RESULTS The survey was completed by 243 participants. The mean knowledge score of 4.3/11 was noticed; 216 (96%) believed research was necessary for healthcare improvement. Although 147 participants (65.3%) attended courses on research methodology, only 63 (28%) engaged in scientific research at their faculties. Only 5 (8.5%) employed graduates participated in research at their jobs. Almost half, 99 (44%) participants consulted scientific papers only upon recommendation. The majority of participants, 199 (82.2%), reported they experienced barriers to conducting research in B&H. CONCLUSION Biomedical students and graduates demonstrated limited research knowledge, but had positive attitudes and acknowledged significant barriers. Improved faculty curricula in research areas and more opportunities are needed.

In this paper, we analyze examples of research institutes that stand out in scientific excellence and social impact. We define key practices for evaluating research results, economic conditions, and the selection of specific research topics. Special focus is placed on small countries and the field of artificial intelligence. The aim is to identify components that enable institutes to achieve a high level of innovation, self-sustainability, and social benefits.

The objective of this study was to confirm the effects of curcumin and to investigate the effects of its combination with a reduced dose (RD) of rosuvastatin in an adenine-induced model of chronic kidney disease (CKD) and associated dyslipidemia in rats. Renal function and morphology, as well as lipid status, were assessed using laboratory parameters and histopathological analysis. Male Wistar rats (n ═ 36) randomly divided into six groups, were treated for 24 days: normal control (standard diet), CKD control (adenine diet, 0.75% w/w adenine-supplemented diet), curcumin (100 mg/kg/day + adenine diet), rosuvastatin minimal therapeutic dose (MTD) (5 mg/day + adenine diet), rosuvastatin RD (25% of rosuvastatin MTD + adenine diet), and rosuvastatin RD + curcumin (25% of rosuvastatin MTD + curcumin 100 mg/kg/day + adenine diet) group. While rosuvastatin alone showed only antilipemic action, both curcumin alone and its combination with an RD of rosuvastatin showed better renal protection with lower serum creatinine levels and milder renal morphological alterations, as well as better antilipemic action with lower levels of triglycerides, very low-density lipoprotein, and low-density lipoprotein cholesterols compared with the levels in CKD control rats. Treatment with curcumin alone also resulted in a significantly higher estimated glomerular filtration rate, lower uric acid levels, and higher high-density lipoprotein cholesterol, while the combined therapy additionally resulted in higher serum albumin levels, lower total cholesterol, and both atherogenic and coronary risk indexes compared with CKD control rats. The results of this study confirmed the beneficial effects of curcumin alone and provided new evidence for the beneficial effects of its combination with an RD of rosuvastatin in rats with CKD and associated dyslipidemia.

Introduction Chronic subdural hematoma (CSDH) is a prevalent condition commonly seen in elderly individuals, often requiring neurosurgical intervention. Research question This study investigates patient characteristics and recurrence rates in CSDH patients treated with single or double burr hole surgery in Bosnia and Herzegovina. Methods: A retrospective study was conducted on patients treated for CSDH between January 2018 and December 2022. The diagnosis of CSDH was confirmed through preoperative CT or MRI of the brain. Patients underwent either single or double burr hole surgery based on the neurosurgeon's decision. Preoperative and postoperative brain CT scans, along with clinical outcomes, were analyzed. Results A total of 87 patients were included in the study, with 102 burr hole surgeries performed. Among these, 49 patients received single burr hole surgery, while 53 patients underwent double burr hole surgery. Recurrence of CSDH occurred in 8.8% of cases, with no significant difference observed between the groups. Notably, single burr hole surgery demonstrated comparable efficacy to double burr hole surgery in terms of subdural reduction and occurrence of pneumocephalus, while exhibiting fewer complications and shorter hospitalization. Discussion and conclusions burr hole surgery, whether performed as a single or double procedure, is an effective treatment option for CSDH, as it leads to positive outcomes in both radiological and clinical assessments of patients following surgery. The population of Bosnia and Herzegovina receives good neurosurgical care for CSDH.

This corrigendum corrects the authorship information to: Yipeng Xu, Gabriela Pachnikova, He Wang, Yaoyao Wu, Dorothea Przybilla, Zihao Chen, Shaoxing Zhu, Ulrich Keilholz. At the request of Dr. Reinhold Schäfer and with the agreement of all authors, Dr. Reinhold Schäfer is excluded from the list of authors. Dr. Schäfer expresses no doubts about the article's results and conclusion but was erroneously included on the list of authors. The authors sincerely apologize for the error and confirm that this correction does not change the conclusion of the article.