In the rapidly evolving landscape of software engineering, the demand for robust and secure systems has become increasingly critical. This is especially true for self-adaptive systems due to their complexity and the dynamic environments in which they operate. To address this issue, we designed and developed the SAFT-GT toolchain that tackles the multifaceted challenges associated with ensuring both safety and security. This paper provides a comprehensive description of the toolchain's architecture and functionalities, including the Attack-Fault Trees generation and model combination approaches. We emphasize the toolchain's ability to integrate seamlessly with existing systems, allowing for enhanced safety and security analyses without requiring extensive modifications and domain knowledge. Our proposed approach can address evolving security threats, including both known vulnerabilities and emerging attack vectors that could compromise the system. As a use case for the toolchain, we integrate it into the feedback loop of self-adaptive systems. Finally, to validate the practical applicability of the toolchain, we conducted an extensive user study involving domain experts, whose insights and feedback underscore the toolchain's relevance and usability in real-world scenarios. Our findings demonstrate the toolchain's effectiveness in real-world applications while highlighting areas for future improvements. The toolchain and associated resources are available in an open-source repository to promote reproducibility and encourage further research in this field.

Background: African swine fever virus (ASFV) causes a fatal hemorrhagic disease in domestic pigs and wild boars. While live attenuated vaccines (LAVs) provide protection, their use raises safety concerns. Therefore, the aim of the present study was to identify viral B-cell antigens associated with protection and to test their potential using highly immunogenic vaccine delivery platforms. Methods: We employed a microarray of 169 ASFV proteins expressed in a cell-free prokaryotic system to identify immunodominant antigens using sera from immune pigs. Six structural proteins were selected and formulated into AP205 virus-like particles (VLPs). Additionally, replication-defective vesicular stomatitis virus (VSV)-based vaccine candidates expressing glycosylated CD2v and EP153R proteins were generated. Three groups of specific pathogen-free pigs were immunized with either VLP- or VSV-based vaccines and challenged with the virulent ASFV Georgia 2007 strain. Control groups included pigs immunized with the attenuated ASFV Estonia 2014 strain and a naïve group. Results: Most vaccine candidates induced detectable antibody responses against target ASFV proteins. However, neither VLP- nor VSV-based vaccines provided protection, as clinical scores, hematology, cytokine responses, and viremia levels were similar to those in the negative control group. In contrast, only the ASFV Estonia 2014 strain elicited a robust T-cell response and protective immunity. Conclusions: These findings highlight the challenges in identifying protective B-cell antigens of ASFV and emphasize the pivotal role of cellular immunity in mediating protection.

Background/Objectives: Heart rate variability (HRV) is a non-invasive marker of autonomic nervous system function with established prognostic value after acute coronary syndrome (ACS). The clinical relevance of temporal changes in short-term HRV remains insufficiently defined. This study evaluated short-term HRV dynamics and their association with mortality after ACS. Methods: This retrospective–prospective study included 230 patients with acute myocardial infarction. Five-minute resting ECG recordings were obtained on day 1 and day 21. Time- and frequency-domain HRV parameters were analyzed, and delta values were calculated. The primary endpoint was overall mortality. Survival was assessed using Kaplan–Meier analysis and Cox regression. Results: Patients who died during follow-up had lower HRV values on day 21 and more pronounced declines in selected parameters. In multivariable analysis, decreased ΔLF and shorter RR intervals independently predicted overall mortality. Conclusions: Short-term HRV provides a practical bedside assessment of autonomic function after ACS. Unfavorable temporal changes likely reflect persistent autonomic imbalance and may offer additional prognostic insight. Larger contemporary studies are needed to confirm these findings.

Background/Objectives: Aortic stenosis is associated with autonomic nervous system (ANS) imbalance, while diabetes mellitus is a major contributor to cardiac autonomic neuropathy. Their coexistence may result in more pronounced autonomic dysfunction not fully captured by conventional assessment. This study aimed to compare ANS function in patients with severe aortic stenosis undergoing transcatheter aortic valve replacement (TAVR), according to diabetes status. Methods: This cross-sectional study included 74 patients with severe aortic stenosis referred for TAVR, including 21 patients with diabetes mellitus. Autonomic function was evaluated using non-invasive ECG-based analysis, incorporating short-term and 24 h Holter-derived heart rate variability (HRV), nonlinear Poincaré plot indices, and deceleration and acceleration capacity. Ambulatory blood pressure monitoring and standard clinical and echocardiographic assessment were performed. Results: Patients with diabetes mellitus demonstrated significantly lower long-term HRV parameters and reduced nonlinear Poincaré plot indices compared with non-diabetic patients, indicating altered autonomic modulation. Short-term HRV showed similar trends without statistical significance. Echocardiographic severity of aortic stenosis and left ventricular systolic function were comparable between groups. Conclusions: Autonomic dysfunction appears to be more pronounced in patients with severe aortic stenosis and diabetes mellitus, predominantly affecting parasympathetic modulation. ECG-derived autonomic parameters may offer complementary insight into ANS involvement in this population and warrant further investigation.

BACKGROUND Newborn screening (NBS) for severe combined immunodeficiency (SCID) using T cell receptor excision circles (TREC) in dried blood spots (DBS) has been implemented in the U.S. and many other regions and countries globally. The Clinical Immunology Society (CIS) and the Association of Public Health Laboratories (APHL) jointly formed the SCID Harmonization Initiative to facilitate comparison of NBS reporting practices to promote global consensus and collaboration. OBJECTIVE To assess current NBS SCID practices using a global survey and to report the findings from the Phase 1 component. METHODS An eighteen-question survey was distributed to all known SCID screening programs worldwide. Only one response per region was analyzed. Examples of international screening algorithms were also solicited and included. RESULTS A total of 200 responses were received, of which eighty responses were unique and used for further analysis. Of the 39 non-U.S. countries, 15 (38%) reported national universal screening, and 24 (62%) reported regional, pilot, or other screening. Additional questions pertained to methodology and reporting with particular emphasis on communication of the clinical urgency of an abnormal TREC result. CONCLUSIONS This global survey confirmed that the approach to NBS SCID varies widely, underscoring the need for harmonization at multiple steps, particularly for reporting and interpretation. This is the first study to capture global NBS SCID practices, and these findings provide the basis for creation of a Phase 2 consensus reporting framework, which will be developed by the same SCID Harmonization Committee that created the current study.

BACKGROUND Breast cancer is a leading cause of mortality and morbidity among females worldwide. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023, we provided an updated comprehensive assessment of the epidemiological trends, disease burden, and risk factors associated with breast cancer globally, regionally, and nationally from 1990 to 2023. METHODS Breast cancer incidence, mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) were estimated by age and sex for 204 countries and territories from 1990 to 2023. Mortality estimates were generated using GBD Cause of Death Ensemble models, leveraging data from population-based cancer registration systems, vital registration systems, and verbal autopsies. Mortality-to-incidence ratios were calculated to derive both mortality and incidence estimates. Prevalence was calculated by combining incidence and modelled survival estimates. YLLs were established by multiplying age-specific deaths with the GBD standard life expectancy at the age of death. YLDs were estimated by applying disability weights to prevalence estimates. The sum of YLLs and YLDs equalled the number of DALYs. Breast cancer burden attributable to seven risk factors was examined through the comparative risk assessment framework. The GBD forecasting framework was used to forecast breast cancer incidence and mortality from 2024 to 2050. Age-standardised rates were calculated for each metric using the GBD 2023 world standard population. FINDINGS In 2023, there were an estimated 2·30 million (95% uncertainty interval [UI] 2·01 to 2·61) breast cancer incident cases, 764 000 deaths (672 000 to 854 000), and 24·1 million (21·3 to 27·5) DALYs among females globally. In the World Bank low-income group, where a low age-standardised incidence rate (ASIR) was estimated (44·2 per 100 000 person-years [31·2 to 58·4]), the age-standardised mortality rate (ASMR) was the highest (24·1 per 100 000 [16·8 to 31·9]). The highest ASIR was in the high-income group (75·7 per 100 000 [67·1 to 84·0]), and the lowest ASMR was in the upper-middle-income group (11·2 per 100 000 [10·2 to 12·3]). Between 1990 and 2023, the ASIR in the low-income group increased by 147·2% (38·1 to 271·7), compared with a 1·2% (-11·5 to 17·2) change in the high-income group. The ASMR decreased in the high-income group, changing by -29·9% (-33·6 to -25·9), but increased by 99·3% (12·5 to 202·9) in the low-income group. The increase in age-standardised DALY rates followed that of ASMRs. Risk factors such as dietary risks, tobacco use, and high fasting plasma glucose contributed to 28·3% (16·6 to 38·9) of breast cancer DALYs in 2023. The risk factors with a decrease in attributable DALYs between 1990 and 2023 were high alcohol use and tobacco. By 2050, the global incident cases of breast cancer among females were forecast to reach 3·56 million (2·29 to 4·83), with 1·37 million (0·841 to 2·02) deaths. INTERPRETATION The stable incidence and declining mortality rates of female breast cancer in high-income nations reflect success in screening, diagnosis, and treatment. In contrast, the concurrent rise in incidence and mortality in other regions signals health system deficits. Without effective interventions, many countries will fall short of the WHO Global Breast Cancer Initiative's ambitious target of achieving an annual reduction of 2·5% in age-standardised mortality rates by 2040. The mounting breast cancer burden, disproportionately affecting some of the world's most vulnerable populations, will further exacerbate health inequalities across the globe without decisive immediate action. FUNDING Gates Foundation, St Jude Children's Research Hospital.

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.

Geometry-based stochastic channel models with differently distributed scatterers within elliptical-shaped scattering region, become more and more popular due to their applicability for modeling different propagation scenarios in the emerging 5G networks. However, to date, their spatial and temporal characteristics are usually provided in integral forms, which are not appropriate for analytical manipulations. In this paper, it is shown that the azimuthal angles of arrival and departure for elliptical (two-dimensional) and ellipsoidal (three-dimensional) channel models, with (non)uniformly distributed scatterers and arbitrary chosen positions of the transmitter and the receiver, has the same statistics as N-dimensional channel model with homogeneously distributed scatterers within hyperellipsoidal-shaped scattering region. Thus, the azimuthal angle distributions of N-dimensional channel model with homogeneously distributed scatterers within hyperellipsoidal-shaped scattering region are derived as closed-form expressions, providing for the first time in literature the azimuthal angles of arrival and departure distributions for various existing elliptical-shaped geometry-based stochastic channel models and for a whole new class of 2-D and 3-D channel models with nonuniformly distributed scatterers.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare systemic vasculitis characterized by asthma, eosinophilia, and multisystem involvement. Renal manifestations are relatively uncommon but may be severe and rapidly progressive, and fatal hemorrhage from arteriovenous fistulas (AVFs) represents an uncommon yet catastrophic complication in patients with advanced kidney disease. We report a case of a 70-year-old man with long-standing asthma, chronic rhinosinusitis with nasal polyposis, marked eosinophilia, and progressive renal failure. After years of fragmented clinical manifestations, a clinical diagnosis of EGPA was considered based on clinical, laboratory, and immunological findings, supported by fulfillment of the 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology (ACR/EULAR) classification criteria in the absence of histopathological confirmation, in the setting of rapidly progressive renal dysfunction. Induction immunosuppressive therapy with high-dose corticosteroids and cyclophosphamide was initiated. Due to advanced chronic kidney disease and the anticipated need for renal replacement therapy, a left radiocephalic AVF was constructed. Seventeen days later, the patient experienced spontaneous fistula rupture at home, resulting in massive hemorrhage, refractory hemorrhagic shock, and death. This case illustrates the consequences of delayed EGPA diagnosis and highlights the possibility of fatal vascular access complications in the setting of active systemic vasculitis, underscoring the importance of careful timing of invasive procedures, heightened clinical vigilance, and structured patient education when planning vascular access in patients with active inflammatory disease.