BACKGROUND Lower respiratory infections (LRIs) remain the world's leading infectious cause of death. This analysis from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 provides global, regional, and national estimates of LRI incidence, mortality, and disability-adjusted life-years (DALYs), with attribution to 26 pathogens, including 11 newly modelled pathogens, across 204 countries and territories from 1990 to 2023. With new data and revised modelling techniques, these estimates serve as an update and expansion to GBD 2021. Through these estimates, we also aimed to assess progress towards the 2025 Global Action Plan for the Prevention and Control of Pneumonia and Diarrhoea (GAPPD) target for pneumonia mortality in children younger than 5 years. METHODS Mortality from LRIs, defined as physician-diagnosed pneumonia or bronchiolitis, was estimated using the Cause of Death Ensemble model with data from vital registration, verbal autopsy, surveillance, and minimally invasive tissue sampling. The Bayesian meta-regression tool DisMod-MR 2.1 was used to model overall morbidity due to LRIs. DALYs were calculated as the sum of years of life lost (YLLs) and years lived with disability (YLDs) for all locations, years, age groups, and sexes. We modelled pathogen-specific case-fatality ratios (CFRs) for each age group and location using splined binomial regression to create internally consistent estimates of incidence and mortality proportions attributable to viral, fungal, parasitic, and bacterial pathogens. Progress was assessed towards the GAPPD target of less than three deaths from pneumonia per 1000 livebirths, which is roughly equivalent to a mortality rate of less than 60 deaths per 100 000 children younger than 5 years. FINDINGS In 2023, LRIs were responsible for 2·50 million (95% uncertainty interval [UI] 2·24-2·81) deaths and 98·7 million (87·7-112) DALYs, with children younger than 5 years and adults aged 70 years and older carrying the highest burden. LRI mortality in children younger than 5 years fell by 33·4% (10·4-47·4) since 2010, with a global mortality rate of 94·8 (75·6-116·4) per 100 000 person-years in 2023. Among adults aged 70 years and older, the burden remained substantial with only marginal declines since 2010. A mortality rate of less than 60 deaths per 100 000 for children younger than 5 years was met by 129 of the 204 modelled countries in 2023. At a super-regional level, sub-Saharan Africa had an aggregate mortality rate in children younger than 5 years (hereafter referred to as under-5 mortality rate) furthest from the GAPPD target. Streptococcus pneumoniae continued to account for the largest number of LRI deaths globally (634 000 [95% UI 565 000-721 000] deaths or 25·3% [24·5-26·1] of all LRI deaths), followed by Staphylococcus aureus (271 000 [243 000-298 000] deaths or 10·9% [10·3-11·3]), and Klebsiella pneumoniae (228 000 [204 000-261 000] deaths or 9·1% [8·8-9·5]). Among pathogens newly modelled in this study, non-tuberculous mycobacteria (responsible for 177 000 [95% UI 155 000-201 000] deaths) and Aspergillus spp (responsible for 67 800 [59 900-75 900] deaths) emerged as important contributors. Altogether, the 11 newly modelled pathogens accounted for approximately 22% of LRI deaths. INTERPRETATION This comprehensive analysis underscores both the gains achieved through vaccination and the challenges that remain in controlling the LRI burden globally. Furthermore, it demonstrates persistent disparities in disease burden, with the highest mortality rates concentrated in countries in sub-Saharan Africa. Globally, as well as in these high-burden locations, the under-5 LRI mortality rate remains well above the GAPPD target. Progress towards this target requires equitable access to vaccines and preventive therapies-including newer interventions such as respiratory syncytial virus monoclonal antibodies-and health systems capable of early diagnosis and treatment. Expanding surveillance of emerging pathogens, strengthening adult immunisation programmes, and combating vaccine hesitancy are also crucial. As the global population ages, the dual challenge of sustaining gains in child survival while addressing the rising vulnerability in older adults will shape future pneumonia control strategies. FUNDING Gates Foundation.

Background/Objectives: Chronic synovitis is a hallmark of osteoarthritis (OA) progression, driving cartilage degradation via inflammatory mediators. While the MAPK signaling pathway is implicated in OA pathogenesis its activation patterns in hip synovium remain poorly characterized, and regional differences within the synovial membrane have not been systematically examined. This research aims to determine the expression of extracellular signal-regulated kinase 1/2 (ERK1/2), p38 mitogen-activated protein kinase (p38 MAPK), c-Jun N-terminal kinase (JNK), and the Epidermal Growth Factor Receptor (EGFR) in the MAPK signaling pathway in the synovial membrane of osteoarthritic hips. Methods: We compared synovial immunofluorescence expression of the aforementioned proteins in a control (CTRL) group of subjects with femoral neck fractures and a group with hip OA. Results: Higher ERK1/2 immunoexpression was detected in the intima compared with the subintima in the CTRL group (p < 0.05), and a similar distribution was observed in the OA group (p < 0.0001). The intima of the OA group exhibited a considerably greater area percentage of positive signal than the intima of the CTRL group (p < 0.01). In all groups examined, we observed that p38 MAPK expression was markedly more positive in the intima than in the subintima (p < 0.0001), but without statistically significant differences between groups. JNK and EGFR immunoexpression were higher in the intima than in the subintima across all analyzed groups, but the difference did not reach statistical significance (p > 0.05). No differences in the expression of these two markers were detected between the CTRL and OA groups (p > 0.05). Differential analysis of the GEO dataset revealed no significant differences in expression between the OA and CTRL groups in the expression of MAPK1, MAPK3, MAPK8, MAPK9, MAPK10, and MAPK11. EGFR was significantly elevated in OA compared to CTRLs in the differential analysis of the GEO dataset. Conclusions: This study provides the first comprehensive analysis of MAPK pathway activation in hip OA synovium, revealing ERK1/2 as a key player with region-specific upregulation in the synovial intima. Combined with elevated EGFR expression, these findings suggest potential therapeutic targets for hip OA synovitis. The discordance between protein and mRNA levels for ERK1/2 indicates post-transcriptional regulation, warranting further investigation into phosphorylation status and functional activation. Our results support the development of targeted interventions for hip OA, a condition with limited treatment options beyond joint replacement.

Background/Objectives: The meninges, the protective membranes covering the central nervous system, undergo complex developmental processes that are critical for CNS integrity and function. Connexin 37 (Cx37) and 40 (Cx40), members of the connexin family of gap junction proteins, have been implicated in various physiological and pathological processes. They play a critical role in cell–cell communication. The aim of our study was to investigate the expression of connexins Cx37, Cx40, and Panx1 in the meninges of both human and murine models (yotari and wild type) at the 6th week/E13.5 and 8th week/E15.5 of developmental stages. Methods: Human embryonic tissues (6th–8th week, n = 4 for the 6th week and n = 4 for the 8th week) and mouse embryos (yotari Dab1−/− and wild type, E13.5–E15.5) were collected and fixed in 4% paraformaldehyde. Paraffin sections were stained for Cx37, Cx40, and Panx1 using immunofluorescence. Images were analyzed in ImageJ, and statistical comparisons were performed using one-way ANOVA with Tukey’s post hoc test (p < 0.05). Results: Cx37 was consistently expressed across all developmental stages, with the highest threshold area percentage observed at E13.5 and E15.5 in murine leptomeninges, demonstrating statistically significant differences compared to controls (p < 0.05) and notably from corresponding human stages (p < 0.001). Strong Cx37 staining intensity at E13.5 was noted in both wild-type and yot mice, while human leptomeninges displayed mild staining at the 6th week of development. In contrast, both human and murine pachymeninges exhibited moderate Cx37 expression. Additionally, the expression of Cx37 in wild-type mice surpassed that of human samples at both E13.5 and E15.5 stages (p < 0.01 and p < 0.001, respectively). For the developing dura mater, Cx37 expression peaked at E15.5 in yot mice, significantly different from both wild-type and human dura mater (p < 0.01 and p < 0.05). Cx40 expression was highest in the leptomeninges at E15.5. Panx1 was similarly expressed across stages, with the highest threshold area percent observed in wild-type leptomeninges and pachymeninges at E15.5, showing significant differences compared to yot mice and human samples (p < 0.05). Both leptomeninges and pachymeninges exhibited mild Panx1 staining at E13.5, while stronger staining was observed at E15.5 in murine samples, contrasting with mild intensity in human counterparts. Conclusions: These findings highlight the implications of Dab1 deficiency for the expression of gap junction proteins during meninges development, implicating their importance in intercellular communication that is essential for normal meningeal and neurodevelopmental processes.

Background: Antimicrobial resistance (AMR) is now a critical issue in South Africa, enhanced by considerable inappropriate prescribing of antibiotics. There is currently variable dispensing of antibiotics without a prescription. Where this occurs, it is principally for urinary tract infections (UTIs) and sexually transmitted infections (STIs). Consequently, there is a need to comprehensively evaluate antibiotic dispensing patterns and factors influencing this to reduce AMR. Methods: A previously piloted questionnaire was administered to patients exiting three different categories of community pharmacies in a rural province. The questionnaire included data on the prevalence of antibiotics dispensed, whether without a prescription, and the rationale for this. Results: A total of 465 patients leaving community pharmacies with a medicine were interviewed. 54.4% of interviewed patients were dispensed at least one antibiotic, with 78.7% dispensed these without a prescription from either independent or franchise pharmacies. Metronidazole (36.1%) and azithromycin (32.7%) were the most dispensed antibiotics. STIs were the most common infectious disease for which an antibiotic was dispensed (60.1%), with 99.6% dispensed without a prescription. Upper respiratory tract infections (URTIs) were the most common infection where antibiotics were dispensed with a prescription (60.0%), with little dispensing without a prescription (7.1%). The most frequently cited reasons for obtaining antibiotics without a prescription were prior use (56.8%), long waiting times at PHC clinics (15.6%), and financial constraints (6.0%). Conclusions: There is an urgent need to review community pharmacists’ scope of practice, including allowing them to prescribe antibiotics for infectious diseases such as UTIs, similar to other countries. Concomitantly, utilise trained community pharmacists to engage with prescribers to improve future antibiotic use, especially for URTIs.

Abstract This study examines the incorporation of soft skills, digital competencies, and artificial intelligence (AI) tools in higher education to improve student employability in Bosnia and Herzegovina, with broader relevance for the South East Europe region, where similar transition economies face parallel challenges in aligning education with the demands of digitally transformed labor markets. The research utilizes a mixed-methods approach, integrating quantitative survey data from University of Sarajevo students with qualitative insights from industry professionals. Research indicates that the concurrent enhancement of soft skills (such as communication and critical thinking) and digital competencies, in conjunction with the utilization of AI tools, markedly enhances students’ preparedness for the contemporary labor market. The study emphasizes the essential role of autonomy in converting AI tool utilization into academic achievement and provides practical recommendations for educators, policymakers, and employers to address the skills gap in the digital economy.

Abstract This paper examines the application of Benford’s Law in the forensic analysis of cash flow statements of business entities in Bosnia and Herzegovina. Through empirical research, the following hypotheses were tested: increasing and decreasing items in cash flow statements follow Benford’s Law, and there is no statistically significant difference in the first-digit distribution between increasing and decreasing items. The results show that decreasing items follow Benford’s Law, while increasing items exhibit statistically significant deviations. Additionally, for most digits, no statistically significant difference was found between increasing and decreasing items, except for the digit 3. The findings indicate the need to educate auditors about the application possibilities of Benford’s Law, as well as its wider use with the aim of reducing audit costs and increasing audit efficiency.

Abstract This paper examines the factors influencing the ethical conduct of accountants and auditors in Bosnia and Herzegovina (BiH), focusing on four key dimensions: personal interests and motives, work experience and professional competence, legal protection and market factors, and moral attitudes and the cultural environment, including religion and social norms. The research was conducted on a sample of 89 accountants and auditors using a structured questionnaire based on a five-point Likert scale. Respondents expressed their views on various aspects of ethical behaviour within the profession. Parametric statistical methods, the Z-test and Repeated Measures ANOVA, were employed to test the hypotheses. The results suggest that the cultural environment, including national customs and social norms, exerts a stronger influence on the ethical behaviour of accountants and auditors than religious beliefs. The study provides empirical evidence on the relative importance of different factors shaping ethical behaviour in the accounting and auditing profession, with particular emphasis on the role of culture as opposed to religion.

The lifetime risk of stroke for adults of 25 years of age or older is approximately 25%, while stroke constitutes the second most common cause of mortality and the second most common cause of disability worldwide. In addition to the clinically manifest acute ischaemic stroke, the presence of cerebral infarction in patients without apparent clinical symptoms and signs attributed to ischaemic stroke or transient ischaemic attack was first described by Fisher in a series of autopsies. Over the years, the term ‘silent brain infarction’ has been replaced by the term ‘covert cerebrovascular disease’ (CCD). Despite the well-established evidence surrounding the associated sequelae of CCD, the current diagnostic and therapeutic algorithms in this particular group of patients are not well defined. With this case series, we showcase potential aetiologies and the value of individualised work-up and treatment strategies.

The aim of this study is to investigate how the link between a country’s legislative and executive branches affects its ability to maintain fiscal discipline through mediating effects of economic reforms. The research bases its analysis on an investigation of NMS-11 countries between 1991 and 2022 using Quantile Mediation Analysis (QMA). It begins with an estimation of the impact of political institutions on fiscal sustainability and then continues with an investigation of the ways how political institutions influence the implementation of economic reforms through a mediator model. Moreover, in an attempt to evaluate the mediation effect, the study uses relevant coefficients taken from prior analyses to compute the indirect impact across quantile distributions. The study sheds the importance of the context in evaluating the role of political institutions and economic reforms on fiscal sustainability, highlighting the varying effects at different quantile levels. In fact, economic reforms are shown to be important when fiscal stress is at a relatively low level and are relatively less effective when the stress is high because the impact of the reforms and institutional factors differs according to the distribution of debt to GDP. This investigation shows that political stability and fiscal outcomes are interactive by segmenting this group into legislative, executive, judicial, and federal dimensions. Politicians should focus on improving the democratization processes of the lower house to facilitate accountability and decision-making when it comes to the judiciary to assist in fiscally integrating during some rough patches. They should also use specific economic actions regarding debt as well as apply the federal policies relevant to various forms of federalism to provide successful reforms.

Aims: To evaluate the impact of the COVID-19 pandemic on breast cancer presentation, surgical management, and lymph node involvement in a small, understudied population in Brčko District, Bosnia and Herzegovina. Methods: A retrospective cohort study conducted at the General Hospital of Brčko District, Bosnia and Herzegovina, from March 2018 to March 2022. We included 113 patients with histopathologically confirmed breast cancer. We divided the patients into two groups: the before-COVID group (65 patients, including one male) treated from March 2018 to March 2020, and the during-COVID group (47 patients) treated from March 2020 to March 2022. We analyzed patient data (age, gender, menopausal status) along with tumor and lymph node histopathological characteristics. Results: The number of surgeries performed decreased by 16.9% during the COVID period. Patients in the pre-COVID group mostly had grade II tumors, while those in the post-COVID group had predominantly grade III tumors. The average number of lymph nodes sampled was similar between groups (10.70 ± 4.12 before COVID vs. 10.39 ± 4.66 during COVID). Still, the average number of positive lymph nodes was higher in the COVID group (2.5±3.82) compared to the pre-COVID group (1.64±2.90). For patients without neoadjuvant therapy, the average time to surgery increased from 1.04 months (±0.66) before the COVID-19 pandemic to 2.59 months (±2.88) during the COVID-19 pandemic. For those receiving neoadjuvant therapy, time to surgery increased from 5.45 months (±2.97) to 7.29 months (±5.15). Conclusion: The COVID-19 pandemic led to delayed breast cancer management, higher tumor grade, and increased lymph node involvement in a small, resource-limited healthcare setting. Findings highlight the need for resilient oncology services in smaller districts during public health crises.