Background Community pharmacies must balance public health obligations with economic sustainability. However, integrated methods that jointly manage medical and non-medical inventory in community pharmacies in LMICs are limited. Objective To develop and apply a dual-matrix model separating medical from non-medical products into operational control categories and introducing a High–Medium–Low profitability (HML-P) classification. Methods We conducted a retrospective, descriptive analysis of all items handled in six community pharmacies in the Republic of Srpska, Bosnia and Herzegovina, during the analyzed 2022 year (12-month period) (n = 10,541). Medical products were classified by Always Better Control (ABC) by purchase value and Fast-/Slow-/Non-moving (FSN) by dispensing frequency (predefined thresholds: >4/day = F, 1–4 = S, <1 = N) to form an ABC–FSN matrix. Non-medical products were classified by ABC and a new HML-P scheme (expert-defined Pareto cut-offs: 70%/20%/10% of cumulative gross profit) to form an ABC–HML-P matrix. Each matrix was consolidated into three control categories: I (strict), II (moderate) and III (minimal). Results Non-medical products constituted 76.4% of all items. The ABC–FSN matrix identified Im = 149 medical products for strict control, while the non-medical ABC–HML-P matrix identified Inm = 580 items for strict control and a large segment for minimal oversight (IIInm = 6218). A pronounced Pareto pattern was observed (≈10% of items accounted for 70% of spend and 70% of gross profit), alongside low daily movement (only 3.2% dispensed ≥1/day). Conclusions The proposed dual-matrix model provides a practical decision-support tool for community pharmacies. It helps prioritize availability of patient-critical medical products while supporting economic sustainability.

BACKGROUND Meningitis remains the leading infectious cause of neurological disabilities globally, disproportionately affecting children younger than 5 years and populations in the African meningitis belt. Whereas previous global estimates focused on ten pathogen categories, this study presents the most comprehensive analysis to date, assessing the meningitis burden attributable to 17 causative pathogens based on the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 framework. METHODS GBD is a systematic, scientific effort aimed at quantifying the comparative magnitude of health loss caused by diseases, injuries, and risk factors across age groups, sexes, and geographical locations over time. We estimated meningitis mortality using the Cause of Death Ensemble model (CODEm) and morbidity using DisMod-MR 2.1, incorporating data from vital registration, verbal autopsy, surveillance, hospital data, and systematic reviews. Aetiology-specific estimates were generated with pathogen-linked case-fatality ratios and splined binomial regression models. Risk factor attribution was based on established risk-outcome pairs and population attributable fractions. FINDINGS In 2023, there were 259 000 (95% uncertainty interval 202 000-335 000) global deaths and 2·54 million (2·20-2·93) incident cases of meningitis. Children younger than 5 years accounted for more than a third of deaths (86 600 [53 300-149 000]). Streptococcus pneumoniae, Neisseria meningitidis, non-polio enteroviruses, and other viruses were the leading causes of death, while non-polio enteroviruses caused the most cases. The four WHO-defined preventable meningitis pathogens of interest (S pneumoniae, N meningitidis, Haemophilus influenzae, and Group B streptococcus) contributed to 98 700 deaths (77 000-127 000) and 594 000 cases (514 000-686 000). Low birthweight, short gestation, and household air pollution were the top risk factors for meningitis-related mortality. INTERPRETATION Although mortality and incidence have declined significantly since 1990, progress is insufficient to meet WHO 2030 targets. Despite marked progress in reducing bacterial meningitis via global vaccination campaigns, a substantial meningitis burden persists, attributable both to common pathogens such as S pneumoniae and N meningitidis and to emerging non-bacterial pathogens such as Candida spp and drug-resistant fungi. Achieving WHO goals will require sustained investment in surveillance, vaccination, maternal screening, and health-system strengthening, especially in high-burden settings. FUNDING Gates Foundation, Wellcome Trust, and UK Department of Health and Social Care.

Abstract This study was aimed to investigate awareness of periodontitis among undergraduate students at a faculty of medicine in Bosnia and Herzegovina. This cross-sectional study was conducted among undergraduate students of the Faculty of Medicine Foca enrolled in three study programs (Medicine, Nursing, and Special Education and Rehabilitation). Knowledge and awareness of periodontitis were collected using a structured questionnaire. Approximately 58% of students had heard the term periodontitis. Higher percentage of Medicine and Nursing students identified Gum Recession, Bleeding Gums, Tooth Loss and Loose Tooth as common symptoms of periodontitis compared to Special Education and Rehabilitation students. Knowledge of risk factors for periodontitis differed between the groups, with Nursing students showing greater awareness but also incorrect recognizing of several risk factors. About one third of students answered that Diabetes Mellitus is related to periodontitis (32.4%). Significantly lower percentage of Nursing students assessed their knowledge of periodontitis as poor compared to Medicine and Special Education and Rehabilitation students. The findings revealed a lack of adequate knowledge of periodontitis across all the observed study programs. Strengthening periodontal education within undergraduate curricula is essential, particularly considering the established links between periodontal and systemic diseases.

Oxidative stress is a critical pathophysiological factor in sepsis. Ursodeoxycholic acid (UDCA), a bile acid with anti-inflammatory, antioxidant, and anti-apoptotic properties, may protect against lipopolysaccharide (LPS)-induced myocardial injury. In an experimental study, 32 male Wistar rats were randomly assigned to four groups: control, LPS, UDCA, and UDCA + LPS. UDCA was administered orally for 10 days prior to LPS-induced endotoxemia. Serum levels of high-sensitive troponin I (hsTnI), homocysteine, and oxidative stress markers were measured, and immunohistochemistry and immunofluorescence were used to assess inflammation (nuclear factor kappa B, NF-κB), apoptosis (caspase 3), and signaling pathways related to protein kinase B (Akt)/NF-κB and silent information regulator 1 (SIRT1)/nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1). UDCA pretreatment significantly reduced myocardial pathological changes, serum hsTnI, homocysteine, and total oxidative stress compared with LPS alone. It enhanced catalase (CAT) activity and glutathione (GSH) levels while lowering thiobarbituric acid reactive substances (TBARS) and nitrite concentrations in cardiac tissue. UDCA modulated cellular signaling by decreasing Akt phosphorylation and activating the SIRT1/Nrf2/HO-1 pathway. These results indicate that UDCA protects the heart from LPS-induced damage by reducing oxidative stress, inflammation, and apoptosis. UDCA modulates cellular signaling by decreasing pro-inflammatory pathways and activating anti-inflammatory pathways associated with SIRT1/Nrf2/HO-1 signaling, emphasizing its key role in myocardial protection during sepsis.

Microscopic models of the thermodynamic and transport phenomena of solids are included in the curricula of subjects dealing with these topics at all levels of education. However, a review of the research conducted shows that students of different age groups have many incorrect ideas about these phenomena. The incorrect ideas uncovered often stem from the abstract nature, complexity, and microscopic properties associated with the concepts involved. To effectively assess students’ understanding of the microscopic models of electrical and thermal conductivity of solids, a concept inventory named the METCS concept test was developed. This test encompasses a wide range of relevant concepts. Conducting the METCS test with a cohort of Croatian university students not only reaffirmed some previously acknowledged incorrect ideas but also revealed many new ones. It is important to gain insight into these ideas as this can support the development of targeted tutorials and teaching materials. These resources can help educators improve learning outcomes related to METCS concepts and ultimately promote deeper understanding among students.

Strong‐field ionization by thermal light is studied. Even though thermal light can be considered as completely classical stochastic light, it can also be treated as quantum light in the sense that it can be represented by a superposition of coherent states, similarly as has been done for the bright squeezed vacuum light, for example. Such a distribution over coherent states contains components with an intensity much higher than the average intensity of the thermal light. This increases the ionization probability by many orders of magnitude. For low intensities, in the multiphoton regime, the enhancement is by the factor of K!$K!$ , with K$K$ the multiphoton order of the process. This result is in agreement with an old experiment [Phys. Rev. Lett. 32 (1974): 265] in which a similar enhancement factor appears if a multimode laser pulse is used instead of a single‐mode pulse. It is also shown that the plateau length in high‐order above‐threshold ionization by thermal light is extended by an order of magnitude in comparison with that of coherent laser light with the same average intensity.

Why the link between immune infiltration and tumor control varies so strongly across tissues remains unresolved. We propose the "immunometabolic gatekeeping" framework, whereby tissue-intrinsic metabolic activity and waste-handling capacity shape anti-tumour immunity. In high-flux tissues, metabolic stress impairs immune surveillance, decoupling infiltration from control and allowing tumor outgrowth. This framework explains cancer paradoxes-including T cell prognostic heterogeneity, hereditary and pediatric tumor tropisms, sex-biased tumor incidence, and cancer-resistant species-and suggests metabolism-aware strategies for cancer prevention and immunotherapy.

527 Background: Despite optimal surgery, approximately 1/3 of patients with renal cell carcinoma (RCC) develop incurable relapse. Adjuvant pembrolizumab reduces the risk of relapse in patients with clear cell RCC and is considered standard care. Post nephrectomy plasma KIM-1 levels have been shown to be prognostic in RCC in the ASSURE & IMmotion010 trials. RAMPART (NCT03288532) is an investigator-led, international randomized phase III study, that enrolled patients with RCC at intermediate and high risk of relapse. Patients were randomized to placebo (Arm A), durvalumab (Arm B), durvalumab + tremelimumab (Arm C). A DFS benefit has recently been reported for Arm C compared to the control Arm A (DFS at 3 years 81% vs. 73%, HR 0.65, 95% CI 0.45 to 0.93, p = 0.009). Methods: TransRAMPART collected longitudinal blood, tissue and urine samples in parallel to the main study. The aims included understanding prognostic or predictive markers for adjuvant treatment. A total of 187 patients were recruited. Samples were collected at baseline, 16 weeks, 32 weeks, and at later timepoints up to 5 years. Blood samples were profiled by MSD cytokine array (plasma), and by high resolution flow cytometry (PBMCs) by IMU Biosciences. Here we report the initial results of these exploratory blood-based analyses for Arm A and Arm C. Results: High baseline KIM-1 levels ( > 86 pg/mL, as used in analysis of the IMmotion010 trial) were associated with worse DFS outcomes in the combined A+C population (p = 0.0075, HR = 3.4, 95% CI 1.3-8.9, n = 77). Analyzing the patients by arm, KIM-1 remained negatively prognostic in the control Arm A (p = 0.0015, HR = 8.0, 95% CI 1.7-37, n = 45), however the effect was no longer seen with adjuvant combination immunotherapy in arm C (p = 0.72, HR = 1.3, 95% CI 0.31-5.1, n = 32). Peripheral immune profiling revealed an immune profile associated with Arm C treatment which returned toward baseline following the treatment period (64 patients in Arm A, 50 patients in Arm C). KIM-1 levels did not correlate with immune changes; instead, various immune cell lineages showed differential phenotypic enrichment according to baseline KIM-1. Tracking these phenotypes through the treatment period revealed divergence between Arm A and Arm C patients. Conclusions: We confirm that baseline KIM-1 levels are prognostic in RCC in an independent population. Although this exploratory analysis only assessed a subset of the whole trial population, this prognostic effect seems to be negated by adjuvant immunotherapy. There is an immune signature associated with KIM-1 levels distinct from the impact of treatment, suggesting an interplay between KIM-1 and immune activity in the postoperative period. Deeper characterization of these immune changes is ongoing. Clinical trial information: NCT03288532 .

Abstract This study included dairy farms registered as milk producers in the entity of Republika Srpska, Bosnia and Herzegovina. A total of 180 milk samples originating from cows were collected from dairy farms across several locations during 2024 and 2025. Out of the 180 tested raw milk samples obtained from dairy cows suspected to suffer from clinical or subclinical mastitis the presence of Staphylococcus aureus was confirmed in 44 samples, representing 24.4% (SD: 3.2%; 95% CI: 18.2% – 30.7%) of all analyzed samples. The presence of one or more se genes was detected in nine isolates (20.5%; 95% CI: 11.0% – 33.7%). Among the total of 44 S. aureus isolates, only one isolate exhibited phenotypic resistance to cefoxitin using ETE ST® Cefoxitin, which was molecularly confirmed by detection of the mecA gene. All analyzed S. aureus isolates showed resistance to at least one of the tested antimicrobial agents, while 25% (95% CI: 12.2% – 37.8%) of isolates showed resistance to two antimicrobial agents. A total of 15.9% (95% CI: 6.6% – 30.1%) of isolates displayed antimicrobial multidrug resistance (MDR ), defined as resistance to three or more classes of antimicrobial drugs.

Newborn screening (NBS) is a well-established public health program that enables early detection and treatment of rare disorders in newborns, preventing severe complications or death. Despite its recognized importance, the scope and implementation of NBS programs vary across Southeastern (SE) and Central Europe. This study aimed to evaluate the current status of NBS in 16 countries of SE and Central Europe and assess progress since the previous survey in 2021. A structured questionnaire was distributed to national experts between April and December 2025, collecting data on program organization, coverage, diseases included, laboratory methods, confirmatory testing, consent practices, and future expansion plans. All countries reported universal screening for congenital hypothyroidism, except Kosovo, where a national NBS is in the process of being established. Expanded NBS using tandem mass spectrometry was available in Austria, Bulgaria, Croatia, Cyprus, Greece, Hungary, North Macedonia, Romania, and Slovenia. Spinal muscular atrophy screening became universal in Austria, Croatia, Hungary, Serbia, and Slovenia. Most countries reported plans for further expansion, with congenital adrenal hyperplasia, severe combined immunodeficiency, spinal muscular atrophy, and cystic fibrosis being the most frequently targeted conditions. Although notable infrastructural progress has been achieved, financial constraints, lack of staff, and organizational barriers remain key challenges. The study’s assessment of program effectiveness was further limited by the absence of region-wide systems for capturing end-to-end performance indicators, such as the age of the infant at treatment initiation or missed cases. Regional collaboration and adoption of best practices are therefore vital to ensure equitable access and continuous advancement of NBS programs.