Abstract The Open and Reproducible Musculoskeletal Imaging Research community is a scientific community dedicated to promoting openness and reproducibility in musculoskeletal imaging, image processing, and computational modeling. In this perspective paper, we outline the motivations for conducting transparent research and provide practical guidelines for implementing it. We start by defining open and reproducible research and describing the benefits and challenges of working transparently. Next, we redefine the outputs of a computational research study as—ideally—a combination of data, code, and a publication, recommend a folder and file structure that reflects these three study outcomes, and describe how to maintain and update such a structure during the study and at study publication. Finally, we emphasize that working in an open and reproducible manner is a learning process, and the best way to acquire the necessary competencies is simply to start.

Leptospirosis, a reemerging zoonotic disease caused by pathogenic bacteria of the genus Leptospira, affects a wide range of domestic and wild animals. The only investigation into sheep leptospirosis in Bosnia and Herzegovina was conducted nearly 50 years ago. This study aimed to assess the seroprevalence of leptospirosis and to identify the most common serovars in sheep in Bosnia and Herzegovina, using the microscopic agglutination test (MAT). Leptospirosis seroprevalence was determined to be 2.16% at a cut-off titer of ≥1:100 (55/2542) and 8.10% at a cut-off of ≥1:25 (206/2542), with all positive cases related to a single serovar. The MAT titers were 1:25 and 1:100, with the majority of positive animals having low titer (1:25) (151/206; 73.3%). At a cut-off of ≥1:100, the sera most frequently reacted to Pomona (54.55%) and Hardjo (27.27%), and less commonly to Saxkoebing and Icterohaemorrhagiae (0.2%) (P<0.05). Odds of seropositivity were higher for Pomona and Hardjo than for Saxkoebing and Icterohaemorrhagiae. The results of this study showed for the first time in Bosnia and Herzegovina, the presence of serovar Icterohaemorrhagiae in sheep, with Pomona and Hardjo as the dominant serovars. Although the seroprevalence is low, the potential zoonotic risk requires continuous monitoring and control strategies to prevent the spread of leptospirosis.

Background: Inflammation-driven mechanisms play a central role in adverse outcomes after non-ST-elevation myocardial infarction (NSTEMI), yet simple, widely available biomarkers for early risk stratification remain insufficiently defined. Hemogram-derived indices and iron-related inflammatory markers may provide complementary prognostic information. Objective: To evaluate the prognostic significance of the mean platelet volume-to-monocyte ratio (MMR) and serum ferritin in predicting major adverse cardiovascular events (MACE) in patients with NSTEMI, and to assess the association of angiotensin-converting enzyme (ACE) inhibitor therapy with clinical outcomes. Methods: This prospective cohort study included 170 consecutive NSTEMI patients admitted to the University Clinical Center Tuzla between February 2022 and January 2023. All patients received dual antiplatelet therapy and high-intensity statins. The baseline evaluation included a complete blood count, serum ferritin, and C-reactive protein. MMR was calculated as the ratio of mean platelet volume to absolute monocyte count. Patients were followed for 12 months for the occurrence of MACE, defined as cardiovascular death, non-fatal myocardial infarction, urgent revascularization, stroke, or hospitalization for heart failure. Results: During follow-up, 103 patients (60.6%) experienced MACE. Admission MMR (18.1 ± 11.7 vs 13.2 ± 5.5; P = 0.003) and ferritin levels (284 ± 396 vs 152 ± 109 µg/L; P = 0.001) were significantly higher in patients with events. In multivariable analysis, both MMR (odds ratio [OR] 1.06, 95% confidence interval [CI] 1.02-1.11; P = 0.008) and ferritin (OR 1.28 per 100 µg/L, 95% CI 1.10-1.55; P = 0.003) independently predicted MACE, while ACE inhibitor therapy was associated with a lower risk (OR 0.24, 95% CI 0.08-0.70; P = 0.01). The combined model demonstrated good discriminative performance (AUC 0.72; 95% CI 0.64-0.80). Conclusion and Relevance: Elevated admission MMR and ferritin were independently associated with a higher 1-year risk of MACE in patients with NSTEMI. ACE inhibitor therapy was associated with improved outcomes, although causality cannot be inferred. These findings suggest that readily available inflammatory biomarkers may complement established clinical parameters for early risk stratification and support continued guideline-directed pharmacotherapy in NSTEMI.

Background and Objectives Contrast-associated acute kidney injury (CA-AKI) is a potentially preventable complication after exposure to iodinated contrast media. In patients undergoing endovascular thrombectomy (EVT) for acute ischemic stroke (AIS), the incidence and clinical impact are poorly characterized, and no validated prediction tool is currently available. The aim of this study was to assess the incidence and prognostic significance of CA-AKI in EVT-treated patients with AIS and to develop and validate a predictive score. Methods A retrospective, multicenter cohort study was conducted involving EVT-treated patients across 73 centers in 16 countries (January–December 2023). Inclusion criteria were age ≥18 years, absence of dialysis, availability of preprocedural and 48-hour postprocedural creatinine levels, and available 90-day follow-up (modified Rankin Scale [mRS] score). The primary outcome was CA-AKI, defined by KDIGO (Kidney Disease: Improving Global Outcomes criteria;creatinine increase ≥0.3 mg/dL or ≥1.5 times baseline, within 48 hours). Secondary outcomes were (1) in-hospital mortality, (2) 90-day mRS score, and (3) 90-day severe disability or death (mRS score >3). Logistic models assessing associations with outcomes accounted for within-center clustering by applying robust standard errors. CA-AKI prediction models were developed across imputed data sets using univariable selection (p < 0.20), backward elimination (p < 0.05), and coefficient-based scoring after categorization of continuous predictors, with internal validation by bootstrap to obtain optimism-adjusted estimates. Results Among 6,638 patients (median age 74 years; 48.7% male), CA-AKI occurred in 326 (4.9%) and was independently associated with in-hospital mortality (adjusted odds ratio [aOR] 2.269; 95% CI 1.615–3.190), higher 90-day mRS scores (adjusted common odds ratio 1.584; 95% CI 1.110–2.258), and 90-day severe disability or death (aOR 1.530; 95% CI 1.057–2.216). A preprocedural risk model including 12 routine clinical variables—sex, ethnicity, arterial hypertension, dyslipidemia, chronic kidney disease, antiplatelet therapy, NIH Stroke Scale score at admission, serum glucose, estimated glomerular filtration rate, hemoglobin, mean arterial pressure, and IV thrombolysis—demonstrated acceptable discrimination (area under the receiver operating characteristic curve 0.710 [95% CI 0.682–0.738]; precision-recall area under the curve 0.13 [95% CI 0.10–0.16]), good calibration (slope 0.870 [95% CI 0.759–0.928]), good overall performance (Brier score 0.045 [95% CI 0.042–0.049]). A second model that included EVT-related variables (e.g., contrast volume) showed similar performances. Discussion In this large, international cohort, CA-AKI occurred in approximately 1 in 20 EVT-treated patients with AIS and was independently associated with poor outcomes. A simple preprocedural risk score enables early identification of high-risk individuals and may support preventive strategies.

Early in 2020, the WHO recommended that existing drugs be evaluated as a repurposed resource to fight the SARS-CoV-2 pandemic. Here, we investigate the trends of using repurposed and off-label drugs among people living with HIV in Central and Eastern Europe (CEE). From November 2020 to May 2021, data on the clinical outcomes of HIV-positive patients diagnosed with COVID-19 were collected on eCRFs (SurveyMonkey® platform, Inc. San Mateo, CA, USA). Factors associated with the off-label drugs available at this time (chloroquine, hydroxychloroquine, favipiravir, oseltamivir, and lopinavir/ritonavir) were identified using logistic regression models. Of the 557 HIV-positive patients assessed with COVID-19 disease, 67 (12.0%) received off-label drugs, as well as 11.6% (16/138) of hospitalized and 12.2% (51/419) of ambulatory patients (p = 0.8564). In the adjusted logistic regression model, higher odds of off-label drug use were found in patients who had their diagnoses confirmed by an RT PCR test (aOR 5.08 [95%CI 1.17–22.0], p = 0.0396), and who came from a non-EU region (aOR 6.79 [95%CI 3.51–13.1], p < 0.0001). The only factor decreasing the odds of off-label drug use was co-infection (aOR 0.31 [95%CI 0.10–0.94], p < 0.0395). In a cohort of HIV patients from the CEE, 12% were prescribed off-label drugs for COVID-19. Symptomatic patients with confirmed SARS-CoV-2 infection or who were from non-EU countries were more likely to receive a repurposed drug. Drug repurposing is an immediate solution to emerging pandemics. All data regarding the safety and effectiveness of such use should be monitored, reported, and publicly available. Access patterns within and outside the EU should be analyzed to prevent potential inequalities in access to care during epidemics in European settings.

Chimeric Antigen Receptors (CAR) T-cell therapy is a ground-breaking discovery in immunotherapy, mainly known for its exceptional results in treating haematological malignancies. The latest research has revealed that the potential of CAR T-cell therapy extends far beyond its current capabilities and could represent a novel therapeutic approach for treating various cancers. This review aims to summarize the latest innovations in CAR T-cell therapy applied in cancer treatment, including multiple myeloma, osteosarcoma, glioblastoma, melanoma and various childhood malignancies. However, several challenges limit success of CAR T-cell therapy, including the antigen escape phenomenon, 'on-target off-tumour' toxicity, penetration into solid tumour tissue, alongside the cost-effectiveness concerns. The improvement of cancer immunotherapies currently available requires an increase in the effectiveness of CAR T-cells in managing refractory and solid cancers. This could be achieved by using CAR T-cells to target various antigens, enhancing their local delivery and tumour infiltration capabilities and utilizing CAR T-cells in combination with checkpoint blockade and immunotherapy, such as PD-1 blockade and CD19 CAR T-cell combined therapy. Although CAR T-cell treatment offers a lot of promise, its cost needs to be taken into account, especially in healthcare systems with limited funding. More importantly, frameworks for Health Technology Assessment (HTA) must adapt to incorporate ethical, sociological and psychological aspects. Reducing CAR T-cell toxicity is also essential, as it remains among biggest obstacles to their widespread application in clinical practice. Future research should therefore focus on enhancing our understanding of CAR T-cell therapy and expanding the application of immunotherapy in treatment.

Neural activity reorganizes profoundly after birth, transitioning from highly synchronous population events to sparse, decorrelated firing in the mature brain. Although inhibitory maturation and shifts in excitation-inhibition balance have been implicated in this process, how individual neurons implement the transition remains unclear because rapid brain growth has prevented long-term, same-neuron mapping. Here, we introduce growth-adaptive spring electronics that provide depth-wise compliance during tissue expansion, maintaining a stable electrode-tissue interface over weeks of neonatal development. We developed a vision-language model-assisted spike processing pipeline for the developing brain that probabilistically matches units across days using high-density waveform spatial footprints, despite developmental changes in the neonatal brain. Together, these innovations enable spike-resolved mapping of the same neurons in rat visual cortex and medial prefrontal cortex from postnatal day 10 to 45. Using population coupling to quantify each neuron’s coordination with local population activity, we show that developmental decorrelation is driven primarily by a distinct subset of neurons that progressively shifts from strong to weak coupling during postnatal weeks 3 to 5, whereas other neurons remain stably weakly or strongly coupled throughout development. These results resolve population-level desynchronization into identifiable neuron-specific trajectories. This framework enables direct tests in neurodevelopmental disorder models, including schizophrenia and autism, of whether altered maturation reflects global circuit imbalance or selective disruption and mistiming of specific developmental programs.

This article examines the use of collaborative online international learning to support educator and educational leadership preparation. As part of a university partnership, the authors piloted virtual exchanges in 2021 and 2022 between university students in the United States (U.S.) and Bosnia and Herzegovina (B.H.). The pilot included 18 U.S. doctoral leadership students and 22 B.H. bachelor's, master's and doctoral students in religious pedagogy and theology. Qualitative case study methods were used to examine two COILs. The authors analyzed curricular and instructional materials, student reflections, faculty notes and correspondence and publicly available B.H. media accounts. Reported learning emphasized reflection focused on cultural attitudes, knowledge and skills; intercultural and interlinguistic awareness; intercultural team functioning and educational leadership, system and policy comparisons. Supports for and challenges to reported learning were structural, curricular and instructional in nature. Little research exists on the use of virtual exchange for educational leadership preparation. This study offers early lessons for using virtual technologies to incorporate an international and intercultural dimension into educational leadership preparation.

Background: Allergic scalp contact dermatitis (ASCD) is a delayed type of hypersensitivity from contact with a specific allergen to which the patients has developed a specific sensitivity. The aim of the study was to evaluate the results of patch testing with standard series of contact allergen in patients suspected to have ASCD. Methods: 112 cases of scalp contact dermatitis were included in the study. Test substances were applied on the upper part of the patient's back, on clinically uninvolved and untreated skin. The patch test was removed and reaction were evaluated after 48 h and 72 h. The grading of negative (-) to positive (+ to ++++) patch test was done in accordance with the International Contact Dermatitis Research Group. Results: Among the 112 cases, 83 patients were female (74.1 %) and 29 were male (25.9 %). The age of participants spanned 17 to 72 years. The commonest age group affected was 41-50 years. The most common positive reactions were recorded to nickel sulphate 22 (26.2%), cobalt chloride 18 (21.4%), fragrance mix 16 (19%), balsam of Peru 14 (16.7%), carba mix 8 (9.5%) and paraphenylenediamine 5 (5.9%).  Females were more likely to show a positive response to two or more allergens. Scalp itching or burning were reported as the most common symptom. Conclusions: Scalp ACD predominantly affects middle-aged women. Our results suggest that nickel sulphate and cobalt are the predominant allergens responsible for the induction of ASCD. These findings are crucial in the treatment, long term management, and education of patients with ASCD.

<p><strong>Introduction.</strong> Point-of-care ultrasound (POCUS) is increasingly recognized as an extension of the physical examination, enhancing bedside diagnostic accuracy and real-time clinical decision-making. Although widely integrated into medical education and practice internationally, its routine implementation in Bosnia and Herzegovina remains inconsistent and structurally constrained. This study aimed to identify key motivators for POCUS utilization and to examine systemic and organizational barriers limiting its broader adoption in primary and secondary healthcare settings.<br /><strong>Methods. </strong>A cross-sectional study was conducted using two structured anonymous questionnaires administered to physicians attending an ultrasound training course during the &ldquo;Dom zdravlja&rdquo; Doboj symposium in September 2025. After data cleaning, 41 fully completed questionnaires were included in the motivation analysis (general practitioners n = 11; specialists n = 30), and 43 were included in the barriers analysis. The instruments assessed professional characteristics, self-reported ultrasound familiarity, motivators, perceived barriers, and institutional support. Descriptive statistics were applied, with &chi;&sup2; and Fisher&rsquo;s exact tests used for subgroup comparisons (p &lt; 0.05).<br /><strong>Results.</strong> Respondents demonstrated strong motivation for POCUS use, particularly for rapid diagnostic clarification and disease monitoring. Most participants supported formal curricular integration and recognized the professional value of ultrasound practice. Major barriers included insufficient structured training, lack of mentorship, limited access to ultrasound devices, time constraints, absence of clear institutional guidelines, and the need for financial recognition. No significant differences were observed between general practitioners and specialists.<br /><strong>Conclusion.</strong> Physicians in Bosnia and Herzegovina show high motivation toward POCUS adoption. However, implementation is predominantly hindered by systemic and institutional barriers. Coordinated educational, infrastructural, and policy-level interventions are necessary to enable sustainable integration into routine clinical practice.</p>

Ki67 is a well-established proliferation marker in breast cancer. Current clinical use focuses on the proportion of Ki67-positive cells, ignoring spatial heterogeneity in expression. However intra-tumoral heterogeneity has demonstrated to be associated with worse outcome. We hypothesized that spatial Ki67 heterogeneity carries clinical information beyond conventional scoring and aimed to evaluate its added value for predicting pathological complete response (pCR) after neoadjuvant chemotherapy (NACT) and for stratifying recurrence risk using genomic expression profiling (GEP). Using digital image analysis (DIA), precise and spatial quantification of biomarker distribution is possible. We analyzed two retrospective breast cancer cohorts using an AI-assisted DIA pipeline. Tumor sections stained for ER, PR, Ki67, and HER2 were digitized and analyzed in QuPath. Using AI, individual tumor cells were recognized and four tumor regions (0.5mm x 0.5mm) with the highest tumor/stroma ratio were selected for analysis. Spatial Ki67 heterogeneity was quantified using the Morisita-Horn Index (MHI) after the Ki67-positive and Ki67-negative tumor cells were mapped using XY-coordinates and square tessellation (100×100 µm tiles) was applied. The MHI was used to compare the similarity in cell composition between all pairs of tiles within a region. MHI values range from 0 to 1, with higher values indicating a more uneven distribution of Ki67+ cells. We used logistic regression and model comparison with Akaike Information Criterion (AIC), likelihood ratio test (LRT) or Vuong test, to evaluate the predictive value of Ki67 heterogeneity. In the first cohort (n=45), spatial heterogeneity was assessed on pretreatment biopsies from patients treated with NACT. In the second cohort (n=79), heterogeneity was evaluated in HR+/HER2- breast cancer patients stratified as high or low risk of recurrence based on GEP. In the GEP cohort, both a higher proportion of Ki67- positive cells and greater Ki67 heterogeneity were significantly associated with high genomic risk. The median MHI was 0.24 (0.03–0.35) in the high-risk group compared to 0.14 (0.01–0.43) in the low-risk group (P = 0.008). This higher MHI indicates more heterogeneous regionally clustered Ki67 expression, suggesting biologically distinct proliferative zones. In multivariate models, Ki67 heterogeneity remained a significant predictor of high-risk classification (OR 0.22, P = 0.036). Furthermore, in nested model comparison using LRT, addition of Ki67 heterogeneity significantly improved the model for predicting genomic risk (P = 0.034). These findings were consistent across biopsy and resection specimens, highlighting the robustness of heterogeneity measures. In the NACT cohort, Ki67 heterogeneity was higher in patients who achieved pCR (median MHI 0.26 [0.17–0.35]) compared to those who did not (median MHI 0.22 [0.12–0.40], P = 0.023). In multivariate modeling, Ki67 heterogeneity emerged as an independent predictor of pCR (OR 23.5, P = 0.038), outperforming Ki67 density and improving model fit (AIC 31.6 vs. 36.1; P = 0.038). Finally, in both cohorts, DIA-derived Ki67 models slightly outperformed traditional pathologist scoring, although Vuong tests did not show a statistically significant difference. Spatial Ki67 heterogeneity provides additional prognostic and predictive value beyond conventional Ki67 scoring. This heterogeneity indicates distinct areas of higher proliferation, clinically relevant biological variation, not captured by simple percentage positivity. Although validation in larger, prospective cohorts is necessary before clinical implementation, DIA provides a more objective and reproducible alternative to manual scoring, particularly when incorporating spatial heterogeneity. C. Van Berckelaer, K. Zwaenepoel, L. Cox, D. Charlotte, D. Julie, E. Louise, H. Fleur, L. Evy, G. R. Devi, A. Ramadhan, S. Koljenovic, P. Van Dam. Ki67 Spatial Heterogeneity as a Predictive and Prognostic Marker in Breast Cancer: A Spatial Image Analysis Approach [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS2-08-19.

<p><strong>Introduction. </strong>The development of information technologies in education has enabled the introduction of new teaching approaches, among which the Flipped classroom (FC) model has gained increasing attention. The FC model has emerged as a student-centered approach that promotes active learning in medical education. The&nbsp;<br />aim of this study was to examine students&rsquo; perceptions of the FC implementation in medical education.<br /><strong>Method.</strong> A cross-sectional study was conducted on a sample of 63 third-year medical students at the Faculty of Medicine in Foča. Data were collected through an anonymous online questionnaire distributed via the Moodle platform, consisting of six domains and a total of 31 statements.<br /><strong>Results. </strong>Students expressed generally positive attitudes toward the FC model: over 50% provided positive responses, about one-third were neutral. The highest average scores were related to learning independence&nbsp;<br />(x̄ = 3.84) and preparedness and motivation for classes (x̄ = 3.79). No statistically significant differences were&nbsp;<br />found between male and female students&rsquo; attitudes, while students with a higher-grade point average (&ge; 8.50) showed significantly more favorable attitudes in the domains of overall attitudes (p = 0.036) and communication (p = 0.013). Logistic regression analysis indicated that the communication domain was a significant predictor of belonging to the group with higher academic achievement (p = 0.020).<br /><strong>Conclusion.</strong> The results indicate that medical students perceive the FC positively and recognize its contribution&nbsp;<br />to better motivation, independence, and interactivity in the learning process. These findings may serve as a basis for further research on the impact of this model on academic outcomes and for a deeper understanding of students&rsquo; perceptions of modern learning approaches in medical education.</p>

<p><strong>Introduction. </strong>The increasing use of digital devices among university students has raised concerns regarding its potential impact on physical and mental health. However, the independent contribution of different patterns of screen use remains insufficiently understood. This study aimed to examine screen use patterns among medical students and to assess their associations with selected health outcomes, with a particular focus on identifying independent predictors.<br /><strong>Methods. </strong>A cross-sectional study was conducted among 96 medical students aged 19&ndash;26 years. Data were collected using a self-administered questionnaire assessing daily screen time, timing of use, physical activity, and health-related outcomes. Multivariate binary logistic regression models were used to identify independent predictors of sleep disturbances, anxiety, and musculoskeletal pain.<br /><strong>Results.</strong> The median daily screen time was five hours. The most frequently reported health issues were eye strain (56.3%), musculoskeletal pain (53.1%), sleep disturbances (46.9%), and anxiety (40.6%). A weak but statistically significant positive correlation was observed between screen time and sleep disturbances (rs = 0.209, p = 0.044, N = 93 due to missing data for three participants). In multivariate analysis, late-night screen use was identified as an independent predictor of sleep disturbances (OR = 9.37, 95% CI: 1.96&ndash;44.75, p = 0.005), whereas total screen time was not significant after adjustment. No independent predictors were identified for anxiety or musculoskeletal pain.<br /><strong>Conclusion. </strong>The findings suggest that the impact of screen use on health outcomes is domain-specific. Behavioral patterns, particularly late-night use, appear to be more relevant than total screen time in relation to sleep disturbances. These results highlight the importance of a behavior-oriented approach to digital media use among students.</p>

<p><strong>Introduction.</strong> The most common malignant facial skin tumors are basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma. Surgical excision remains the gold standard of treatment, followed by reconstruction of the resulting defect. The aims of this study were to present reconstructive options for facial defects following excision of malignant skin tumors and to evaluate functional and aesthetic outcomes of local flap reconstruction.<br /><strong>Methods</strong>. This retrospective case series included 80 patients surgically treated at Varis Clinic in Belgrade and at the Department of Plastic and Reconstructive Surgery, University Hospital in Foča, from January 2021 to October 2025. Patients were analyzed with respect to tumor type, defect size and localization, sex, age, and postoperative complications. Reconstruction was performed using local flaps.<br /><strong>Results.</strong> Facial defects resulted from excision of BCC in 51 patients, SCC in 24 patients, and melanoma in five patients. Complete flap survival was achieved in all cases (100%). Postoperative infection with marginal flap necrosis occurred in three patients (3.75%) and resolved after conservative treatment. Functional and aesthetic outcomes were satisfactory in all patients.<br /><strong>Conclusion.</strong> Local flaps represent a reliable reconstructive method for small to large facial defects. Proper surgical planning, anatomical knowledge, and meticulous technique are essential for achieving optimal functional and aesthetic outcomes.</p>