This study explores the entrepreneurial intentions of university students from different educational, economic, and social backgrounds by comparing four European Union (EU) countries (Italy, Austria, Sweden, Greece) to an EU-candidate country (Bosnia and Herzegovina). Data were collected through surveys on a convenience sample of 301 students. The hierarchical regression and formal statistical hypothesis testing assess and compare the role of individual factors and contextual activating factors. In doing so, the paper adopts and adapts the EPIC tool, making it suitable for cross-country comparison. The results indicate a lack of significance of the risk-taking dimension, and a striking similarity in the influence of resources as a contextual activating factor, despite the differences of the investigated countries. In addition, the results indicate the individual mindset dimensions that significantly contribute to the entrepreneurial intentions of EU students (innovation-oriented, persistence, and peculiarity), and the different predictors for students from Bosnia and Herzegovina (innovation-oriented and action-oriented). The paper contributes to the stream of research on entrepreneurial intentions in higher education by assessing the individual and contextual factors within a fine-grained cross-cultural comparison. Insights for institutions and policymakers to enhance support and resources for aspiring entrepreneurs can ultimately be derived.
OBJECTIVES The objective of the present study was to explore whether gender differences exist in waist-to-height ratio (WtHR) values and to assess the correlation between WtHR and other obesity indicators after categorising older adults of Bosnian descent based on the presence or absence of abdominal obesity. METHODS The study included 151 inhabitants of the Geriatric Centre in Sarajevo, Bosnia and Herzegovina, aged 65 years and older (66 males and 85 females). Anthropometric indices and blood pressure values were measured by standard methods. WtHR was calculated using the following formula: waist circumference (WC) (cm)/height (cm). Differences between compared groups were analysed using the Student's t-test, Mann-Whitney U test or chi-square test. Correlations were assessed by Spearman's or Pearson's test. RESULTS Females had significantly higher WtHR values compared to males. Significant positive correlation was determined between WtHR and body mass index (BMI), WC, hip circumference (HC), neck circumference (NC), mid-upper arm circumference (MUAC), calf circumference (CC), and the weight-adjusted waist index (WWI) in both male and female elderly individuals. In elderly participants with abdominal obesity, there was a statistically significant positive correlation between WtHR and all of the tested anthropometric indices. Amongst elderly participants without abdominal obesity, a statistically significant positive correlation was observed between WtHR and BMI, WC, MUAC, and the WWI. However, no statistically significant correlations were observed between WtHR and HC, NC or CC in elderly participants without abdominal obesity. CONCLUSIONS The results of this study imply that WtHR is a valid parameter for assessing abdominal obesity in elderly individuals. The observed WtHR values indicate that women are at greater health risk than men. Given the high prevalence of sarcopenic obesity in older adults and the demonstrated limitations of BMI, we propose that WtHR should be incorporated into routine clinical practice for obesity assessment in this age group.
Abstract Objective: To investigate the clinical and pathological features of a rare benign primary cardiac tumour. Methods: A retrospective analysis was conducted on 13 patients diagnosed with cardiac myxoma (CM) over a six-year period. Patient data including demographics, clinical presentation, imaging, laboratory, echocardiographic, histopathological characteristics, surgical intervention details, and postoperative outcomes were reviewed. Results: The mean age of patients included in the study was 57,69±13,47 (range 29 to 80 years), with a female predominance. The most common location of the tumour was left atrium (69.2%), followed by the right atrium (23.1%) and the left ventricle (7.7%). The most common clinical presentation included a combination of dyspnea, angina, fatigue and palpitations (76.9%). Followed by a syncope (15.4%), while one patient was asymptomatic. There was significant association with left ventricular location of CM and the presence of arrhythmia (p=0.004). Besides usually observed histological findings, glandular structures with mucin forming glands were present in 30.8% of cases and calcifications in 15.4%. All patients underwent surgical resection with favorable short-term outcomes. Conclusion: Cardiac myxoma is a rare but clinically significant neoplasm requiring prompt diagnosis and surgical management. Echocardiography remains essential for detection, and histopathology reveals a spectrum of features. Despite the study’s small sample size, findings highlight the importance of early recognition and support the need for larger multicentric studies to better define its prevalence and behavior.
Objective This study aimed to examine the associations between objective functional performance tests, clinical disability, MRI lesion characteristics, and recent relapse activity with basic and instrumental activities of daily living (ADLs/IADLs) in people with multiple sclerosis (MS). Materials and methods In this cross-sectional study including 65 patients with MS, clinical disability was assessed using the Expanded Disability Status Scale (EDSS), while functional performance was evaluated with the Timed 25-Foot Walk test (T25FW) and the 9-Hole Peg Test (9-HPT). Functional independence was assessed using the Barthel Index for basic ADL and the Lawton IADL scale. MRI lesion characteristics and relapse activity during the preceding two years were recorded. Associations were analyzed using Spearman correlation and multivariable linear regression models. Results Higher EDSS scores and worse T25FW and 9-HPT performance were associated with lower Barthel and IADL scores. In adjusted models, T25FW remained independently associated with basic ADL, while non-dominant hand 9-HPT was the strongest independent predictor of IADL; EDSS showed a weaker independent association with IADL. MRI lesion variables and recent relapse activity were not independently associated with functional independence. Conclusions Simple performance-based measures of gait speed and upper limb dexterity are strongly associated with real-life functional independence in MS and may contribute to a more comprehensive functional assessment in routine clinical practice.
Introduction: Stroke is a leading cause of long-term disability, and early functional prognostication is essential for individualized rehabilitation planning. Objective: The objective of the study is to examine the association between bedside motor and dexterity tests and standard outcome measures, and to evaluate their predictive value for functional independence in post-stroke patients. Materials and methods: This observational study was conducted at the Neurology Clinic, University Clinical Center Sarajevo, Sarajevo, Bosnia and Herzegovina, and included 61 patients with either ischemic or hemorrhagic stroke. Sociodemographic and clinical data were collected. Bedside functional assessments comprised the National Institutes of Health Stroke Scale (NIHSS), the Motor Assessment Scale (MAS), the Nine-Hole Peg Test (9-HPT) for upper limb dexterity, and the Berg Balance Scale (BBS). Functional outcomes were evaluated using the Barthel Index and the modified Rankin Scale (mRS) at admission and discharge. Associations between bedside assessments and functional outcomes were analyzed using correlation analyses, and independent predictors of functional independence were identified using multivariable linear regression models. Results: The mean age of participants was 74.8 ± 5.5 years, and 73.8% had ischemic stroke. Functional independence improved during hospitalization, with the Barthel Index increasing from 65.3 ± 22.9 at admission to 72.1 ± 26.5 at discharge. In multivariable regression analysis, the MAS emerged as the strongest independent predictor of functional independence measured by the Barthel Index (R² = 0.88, β = 1.49; p < 0.001). Performance on the 9-HPT using the non-dominant hand provided additional independent predictive value (β = -0.28; p = 0.048), while dominant-hand dexterity and balance performance were not significant predictors in the adjusted model. Conclusions: Simple bedside motor and dexterity assessments provide clinically relevant prognostic information in the early post-stroke phase. Their integration into routine clinical practice may enhance functional prognostication and support individualized rehabilitation strategies.
Antineoplastic agents are toxic compounds, generally used in the treatment of cancers, which are recognized as carrying a cancer development risk. In this systematic review and meta-analysis of human biomonitoring studies, we have assessed the effects of exposure to antineoplastic drugs on levels of DNA strand breaks in leukocytes, measured by the comet assay. Focusing on the application of the comet assay in human biomonitoring of occupational exposure to antineoplastic agents, we have analyzed 458 original research studies which used this assay, following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA-ScR). The systematic review led to 23 studies, of which 20 studies met the criteria for inclusion in the meta-analysis. Using standardized mean difference and 95% confidence interval (CI), the meta-analyses show increased levels of DNA strand breaks in subjects exposed to antineoplastic drugs (1.26, 95% CI: 0.78, 1.73). Results originate mainly from studies on healthcare workers, with only one study in an industrial setting. Subgroup analysis indicates that all studies combined from middle-income countries have a higher effect size (1.77, 95% CI: 1.00, 2.55) than studies from high-income countries (0.49, 95% CI: 0.09, 0.90). This difference between middle- and high-income countries may be attributable in part to differences in exposure levels or exposure assessment. Additionally, sensitivity analysis indicates that studies with moderate/high risk of comet assay measurement bias have higher effect size (2.07, 95% CI: 0.82, 3.31) than studies with low risk of bias (0.73, 95% CI: 0.34, 1.13); and that studies with high risk of exposure misclassification have higher effect size (1.47, 95% CI: 0.89, 2.06) than studies with low/moderate risk (0.13, 955 CI: -0.08, 0.33). Most studies have low/moderate risk of bias related to the comet assay procedure (15 out of 20 studies), absence of reporting the use of assay controls (1 out of 20 studies), blinded analysis of samples (7 out 20 studies); exposure assessment (16 out of 20 studies). In conclusion, this systematic review and meta-analysis shows that exposure to antineoplastic drugs is associated with increased levels of DNA strand breaks in human leukocytes.
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 Artificial intelligence (AI)-based algorithms are being implemented in breast screening to detect breast cancers on mammographic images. We aimed to apply an epidemiological approach to demonstrate how a cancer detection algorithm can be leveraged as an intermediate-term predictor of breast cancer (current and 4-year risk) to deliver greater risk-based personalisation in screening mammography. METHODS In this population cohort study, we used detection scores from an AI cancer detection algorithm (BRAIx AI Reader), which was calibrated using a training dataset of 397 648 women aged 40 years to 97 years from women who screened at BreastScreen Victoria, Australia between Jan 1, 2016, and Dec 31, 2017, to create a woman-specific mammography-based score for breast cancer risk, the BRAIx risk score. Subsequently, the BRAIx risk score was evaluated on an independent test dataset of women from BreastScreen Victoria, Australia, comprising a random population cohort of 96 348 women who screened from Jan 1, 2016, to Dec 31, 2017, aged 40 years to 74 years, and an independent, external dataset from woman screened at Karolinska University Hospital, Stockholm, Sweden. We applied logistic regression, using the BRAIx risk score to estimate risks of invasive breast cancers on the test dataset: (1) detected at cohort entry (n=525); and (2) for women given an all clear, diagnosed during the next 4 years either at future screens (n=790) or during intervals between screens (n=308). We also trained full multivariate risk models (logistic regression and elastic net) using the training dataset and evaluated their predictive performance on the test and external validation data, with assessment of familial aspects of the BRAIx risk score achieved with inference about causation from examining changes in regression coefficients in an innovative statistical analysis framework. FINDINGS In both Australian and Swedish test datasets, the BRAIx risk score predicted cancer detection at cohort entry and future cancer risk (all p<0·0001). The BRAIx risk score was the strongest tested explanatory factor for cancer detection at cohort entry (odds ratio 13·80 [95% CI 9·54-20·80] in Australian data; 8·89 [3·19-37·49] in Swedish data) and for intermediate-term cancer risk (2·29 [2·13-2.47] in Australian data; 2·15 [1·85-2·50] in Swedish data). We found that adding a thresholded binary version of the BRAIx risk score significantly improved model fit (p<2·2 × 10-16, Australian and Swedish data) and women with BRAIx risk scores of more than 2 were significantly at many-fold increased risk of intermediate-term cancer than women below that threshold (12·34 [7·33-20·91], Australia; 44·7 [11·9-184·9], Sweden; p<0·0001). For the top 2% of women given an all clear with the highest BRAIx risk score, the probability of a cancer diagnosis within 4 years was 9·7%. The BRAIx risk score explained 23% of why family history predicts 4-year risk (p<0·0001). After fitting the BRAIx risk score in a multivariate model, mammographic density was no longer significantly associated with breast cancer risk in the Australian test data (p>0·05) and became associated with lower risk for intermediate-term cancer in the external Swedish test dataset (0·83 [0·73-0·95]). INTERPRETATION The BRAIx risk score is a strong intermediate-term predictor of breast cancer (current to 4-year risk). Calibrating the score on a training dataset produces population-specific probabilities for calculating individual-specific risk scores for screening clients based on their mammogram images. These risk scores enable future development of personalised screening pathways to transform population breast cancer screening and save lives. Identification of women given an all clear but at very high risk, similar to those carrying BRCA1 and BRCA2 mutations, could reveal insights into both familial and non-familial causes of breast cancer. FUNDING Australian Government Medical Research Future Fund, the Ramaciotti Foundation, the National Breast Cancer Foundation, Cancer Australia, and the National Health and Medical Research Council.
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 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/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 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.
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