Percolation properties of two types of inhomogeneous k-mers with different arrangements of conductive and nonconductive sites on a triangular lattice is studied by Monte Carlo simulations. The depositing objects are ‘Janus’ k-mers, with one conductive and one nonconductive side, and ‘patchy’ k-mers, with conductive ends and a nonconductive middle. We find that the percolation threshold strongly depends on the k-mer length, the number of nonconductive sites, and their spatial distribution. For both object types, the percolation threshold increases with the fraction of nonconductive sites. For fixed number of nonconductive sites, the threshold decreases monotonicaly with the object length. The presence of pre-existing conductive objects on the substrate can either hinder or enhance percolation, depending on their size and concentration.

Circadian rhythms regulate key biological processes central to cancer biology, including cell cycle control, DNA repair, metabolism, immune function, and drug pharmacokinetics. Experimental models consistently demonstrate marked time-of-day differences in the efficacy and toxicity of chemotherapy, targeted agents, and immunotherapies. Clinical studies of chronomodulated chemotherapy—particularly with fluoropyrimidines, platinum compounds, and anthracyclines—show reproducible reductions in treatment-related toxicity, while effects on survival outcomes remain variable and often sex dependent. Emerging clinical evidence also suggests that timing of immune checkpoint inhibitor administration may influence progression-free and overall survival across several tumor types. However, translation into routine oncology practice has been limited by interindividual variability in circadian phase, tumor-specific disruption of clock function, lack of validated biomarkers, and logistical constraints of time-specific drug delivery. Advances in circadian phenotyping, wearable monitoring, and adaptive dosing technologies now offer feasible pathways toward individualized, biology-driven treatment timing. This narrative review critically evaluates mechanistic, preclinical, and clinical evidence for chronotherapy across oncological treatment modalities and examines challenges and opportunities for its integration into precision cancer care.

Introduction Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have transformed the management of type 2 diabetes and obesity by improving glycemic control, promoting weight loss, and reducing cardiovascular risk. This study aimed to evaluate national trends in GLP-1 RA utilization and expenditure in Croatia between 2010 and 2024. Methods We conducted a nationwide, retrospective analysis using the International Medical Statistics and IQVIA pharmaceutical databases. Utilization was measured in defined daily doses per 1000 inhabitants per day, and financial expenditure was expressed in euros. Trends were contextualized within evolving clinical evidence, guideline recommendations, and healthcare reimbursement policies. Results Total noninsulin antidiabetic drug consumption more than doubled between 2010 and 2024, with the use of GLP-1 RAs rising from negligible at the time of market entry to that worth 15.99 defined daily doses per 1000 inhabitants per day in 2024, representing 16.1% of total prescriptions. Expenditure on GLP-1 RAs reached 42.07 million euros in 2024, accounting for 42.7% of total noninsulin antidiabetic spending. Semaglutide emerged as the dominant agent according to both utilization and cost, followed by dulaglutide and liraglutide. Obesity-specific indications were underutilized, largely due to lack of reimbursement. Conclusions GLP-1 RA prescribing has increased substantially in Croatia over the past decade, reflecting their growing therapeutic importance. However, economic constraints, restrictive reimbursement, and sociocultural barriers continue to limit access, particularly in obesity care. Our findings highlight the need to align reimbursement frameworks and clinical practice with emerging evidence to maximize the cardiometabolic and public health benefits of GLP-1 RAs.

BACKGROUND Despite a general improvement in the HIV burden over the past two decades, gendered social determinants including intimate partner violence (IPV) continue to affect women's vulnerability to HIV, which could be further exacerbated as resources dwindle over the coming years. Our study aimed to quantify recent trends in the HIV burden, the magnitude of the HIV burden associated with IPV, and the potential impact of declining financial support globally. METHODS Using the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 framework, we estimated annual HIV incidence, prevalence, and mortality for 204 countries and territories from 1990 to 2023, disaggregated by age and sex. Input data included national HIV programme reports, population-based serosurveys, clinical and vital registration data, and systematically reviewed literature. Countries and territories were grouped according to the availability and completeness of HIV prevalence and mortality data, with tailored modelling approaches applied for each group. To characterise the potential contributions of IPV to the HIV burden, time series estimates of IPV prevalence by location and effect size estimates were combined to generate population attributable fractions of the HIV burden. To forecast future trends and assess the potential impact of reductions in development assistance for health, we used a non-parametric stochastic frontier approach to estimate how funding levels could affect antiretroviral therapy (ART) coverage. Adjustments in future ART coverage were integrated into our forecasts, altering projected rates of HIV-related incidence and mortality. We compared scenarios with and without funding cuts, quantifying the potential epidemiological effects of reduced ART availability by sex. FINDINGS Between 2003 and 2023, the annual number of new HIV infections declined globally, from 2·85 million (95% uncertainty interval [UI] 2·76-2·96) to 2·06 million (1·88-2·29). Meanwhile, HIV-related deaths decreased from a peak of 1·71 million (1·61-1·83) in 2004 to 0·83 million (0·73-0·96) in 2023. The number of people living with HIV rose from 26·3 million (25·5-27·3) in 2003 to 42·4 million (40·3-44·4) in 2023, reflecting improved survival associated with ART expansion. Although females continued to have higher prevalence of HIV than males in 2023 (23·4 million [22·2-24·6] vs 19·1 million [17·6-20·5]), the gap in incidence between females and males has substantially declined. Regionally, sub-Saharan Africa had the greatest declines in both incidence (64·3%; 58·0-68·6) and mortality (74·6%; 70·4-78·5) between 2003 and 2023, while central Europe, eastern Europe, and central Asia recorded the highest increases in incidence rates (232·1%; 146·5-299·1) and mortality rates (37·8%; 31·2-45·5) during this period. IPV was associated with an estimated 10·7% (1·6-20·4) of HIV-related deaths among females aged 15 years and older globally in 2023, corresponding to 40 700 (6400-80 600) deaths, with the highest population attributable fractions observed in Oceania (17·4%; 2·8-33·1), central sub-Saharan Africa (14·2%; 2·1-29·4), and eastern sub-Saharan Africa (13·2%; 2·0-25·3). Forecasts indicate that funding reductions could decrease ART coverage by 8·1% globally between 2025 and 2030, resulting in approximately 1·6 million new HIV infections among females and 1·3 million new HIV infections among males, alongside 790 600 and 670 600 HIV-related deaths, respectively. These impacts are primarily concentrated in sub-Saharan Africa. INTERPRETATION Despite two decades of substantial progress, the global HIV response remains highly sensitive to gendered social determinants and funding stability. The potential contribution of IPV to HIV-related mortality among women underscores the need for integrated interventions that address violence prevention and post-violence care alongside HIV treatment. The projected effects of funding cuts-millions of additional infections and deaths-highlight the fragility of the gains achieved and the urgent need to protect HIV financing. Achieving and sustaining the UNAIDS 2030 targets will require renewed investment, gender-responsive programming, and resilient health systems capable of providing equitable access to care. FUNDING Gates Foundation and the US National Institute of Allergy and Infectious Diseases.

Background: Hashimoto's thyroiditis (HT) is the most common autoimmune thyroid disease and is characterized by the presence of thyroid peroxidase (anti-TPO) and thyroglobulin (anti-Tg) antibodies. However, the clinical and biochemical factors associated with these antibodies remain incompletely understood. Objective: To evaluate the associations between anti-TPO and anti-Tg antibody levels and demographic, clinical, biochemical, and lifestyle-related factors in patients with HT. Methods: This retrospective cross-sectional study included 100 patients with HT. Clinical, biochemical, and laboratory data were retrospectively collected from medical records. Group comparisons were performed using non-parametric tests, correlations were assessed using Spearman's rank analysis, and multivariable linear regression was used to identify independent predictors of log-transformed anti-TPO and anti-Tg levels. Results: Anti-TPO levels differed significantly according to TSH status and were independently associated with higher TSH concentrations, longer disease duration, and lower BMI. Smoking was the only independent predictor of anti-Tg levels. No significant associations were observed between thyroid autoantibody levels and age, sex, vitamin D status, or family history of thyroid disease. Conclusion: Anti-TPO and anti-Tg antibodies demonstrated distinct clinical associations in patients with HT. These findings support the complementary clinical value of both thyroid autoantibodies and should be confirmed in larger prospective multicenter studies.

Background Both Hashimoto’s thyroiditis and non-autoimmune hypothyroidism are highly prevalent thyroid disorders. While their clinical presentations overlap, they are driven by distinct pathophysiological mechanisms and potentially influenced by different genetic susceptibilities and environmental triggers, including prenatal solar exposure and vitamin D status. This study aimed to evaluate and compare the season of birth, serum vitamin D levels, body mass index (BMI), smoking habits, and family history of thyroid diseases between patients with Hashimoto’s thyroiditis and patients with non-autoimmune hypothyroidism in Tuzla Canton. Materials and methods This retrospective observational cross-sectional study reviewed the medical records of 200 patients evaluated and followed up at the Department of Nuclear Medicine and Radiology of a tertiary care university hospital in Bosnia and Herzegovina. Participants were equally divided into two groups: patients with Hashimoto’s thyroiditis (n = 100) and patients with non-autoimmune hypothyroidism (n = 100). Numerical variables were analyzed using the Mann-Whitney U and Kruskal-Wallis tests, while categorical variables were evaluated using the χ² test. Post hoc pairwise comparisons were performed with Bonferroni correction. Results The study population comprised 189 women (94.5%) and 11 men (5.5%). The distribution of birth seasons did not differ significantly between the groups (χ² = 2.444, df = 3, p = 0.485). Similarly, no statistically significant differences were observed in median serum vitamin D levels (p = 0.931) or smoking rates (23.0% in the Hashimoto’s group vs. 22.0% in the hypothyroid group, p = 0.866). However, patients with non-autoimmune hypothyroidism were significantly older (median: 59.0 vs. 49.0 years, p < 0.001) and presented with significantly higher BMI values (median: 28.20 kg/m² vs. 26.21 kg/m², p = 0.008) compared to those with Hashimoto’s thyroiditis. A positive family history of thyroid disease was significantly more frequent among patients with Hashimoto’s thyroiditis than those with hypothyroidism (62.0% vs. 47.0%, χ²= 4.537, df = 1, p = 0.033). Within the non-autoimmune hypothyroidism group, vitamin D levels differed significantly across BMI categories (p = 0.030), with overweight patients exhibiting significantly lower median vitamin D levels compared to normal-weight patients (median: 18.50 vs. 24.00, adjusted p = 0.045). Conclusion Season of birth, smoking status, and overall serum vitamin D levels do not distinguish Hashimoto’s thyroiditis from non-autoimmune hypothyroidism. However, patients with non-autoimmune hypothyroidism present with higher BMI, and those who are overweight are particularly prone to lower vitamin D levels. In contrast, Hashimoto’s thyroiditis is more strongly characterized by a positive family history of thyroid disease, highlighting a more pronounced hereditary component.

Background/Objectives: Postoperative bleeding remains a major complication following coronary artery bypass grafting (CABG), contributing to transfusion requirements, reintervention, and morbidity. The objective of this study was to assess the clinical significance of preoperative platelet function testing and postoperative viscoelastic testing in patients undergoing elective isolated on-pump CABG. Methods: This prospective observational study included 708 patients undergoing surgery between January 2023 and January 2025. Preoperative platelet function was assessed with Multiplate® impedance aggregometry (ADPHS and ASPI), and postoperative coagulation was assessed with ClotPro® after cardiopulmonary bypass. The prespecified Multiplate thresholds were population- and assay-specific and were not intended as universal cutoffs. Postoperative bleeding was defined by cumulative chest-tube drainage during the first 24 h. Results: In unadjusted analyses, low ADPHS values (≤602.5 AU·min) were associated with higher platelet transfusion, cryoprecipitate use, and overall transfusion, and ADPHS showed modest discrimination for blood loss > 500 mL/24 h (AUC = 0.61, p = 0.041). Low ASPI values (≤453 AU·min) were associated with increased cryoprecipitate use and showed modest discrimination for blood loss > 1000 mL/24 h (AUC = 0.62, p = 0.005). After multivariable adjustment for baseline differences, neither ADPHS ≤ 602.5 (adjusted OR 1.01, 95% CI 0.74–1.39, p = 0.936) nor ASPI ≤ 453 (adjusted OR 0.89, 95% CI 0.64–1.23, p = 0.475) was independently associated with postoperative bleeding > 500 mL/24 h. Postoperative ClotPro® parameters showed statistically significant associations with transfusion and bleeding, but their discriminatory performance was limited. Conclusions: Perioperative platelet function and viscoelastic test results were associated with bleeding and transfusion outcomes in unadjusted analyses, but discrimination was modest, and the platelet function cutoffs were not independently associated with bleeding > 500 mL after adjustment. These findings support a complementary hemostatic assessment role for combined POC testing but do not establish a standalone predictive model or an implementable transfusion algorithm.

Abstract In armed conflict and other situations of armed violence, people with disabilities, both children and adults, face serious and unique threats to their mental health and psychosocial well-being, including due to being targeted because of their disability, their inability to flee attacks, risk of abandonment, breakdown of services, and lack of access to health care and assistive devices. Unequal access to the sparse mental health services and education that may exist during conflicts exacerbates mental health impacts, and children with disabilities experience multiple and intersecting forms of mental health harms based on their disability and age. Since 2015, Human Rights Watch has documented the mental health harms of armed conflict and armed violence on people with disabilities in Afghanistan, Cameroon, the Central African Republic, Palestine, South Sudan, Sudan, Syria, Ukraine and Yemen. While international mental and psychosocial support services standards call for inclusion and accessible services for all, people with disabilities are often the last to get support – this is especially true in cases of people with intellectual, psychosocial or hearing disabilities due to physical, communication and attitudinal barriers. There is an urgent need for governments, humanitarian donors and humanitarian agencies to change how they provide mental health and psychosocial support services in order to ensure that they are accessible to all.

Physical ability testing is an essential part of police education, as fitness assessments indicate students’ preparedness for police work. Clear documentation and reporting of test protocols and measurement properties are essential for interpreting, evaluating, and comparing the usefulness of different test batteries. Therefore, this scoping review aimed to map the fitness tests used in police education programs internationally, including reporting standards of test protocols, reliability, validity, and sex-based test specificity, thereby providing insight into the physical abilities considered important for police work. The main searches were conducted in the databases CINAHL, PubMed, SPORTDiscus, and Web of Science. The database search yielded 1323 articles, of which 92 met the inclusion criteria. An additional nine articles were included through citation and hand searching. Of the 101 studies, 95 used an average of 4–5 general fitness tests, and 29 included work-related police tests. Test protocols were generally well documented across studies. However, only a few studies included in this review assessed test–retest reliability, and only a limited number of studies, whose primary aim was to validate the tests, evaluated test validity. The most commonly used assessments were upper-body and core muscular endurance (60 s push-up, maximum pull-up, and 60 s sit-up tests), upper-body muscular strength (hand-grip test), lower-body power (standing long jump, and vertical jump tests), and aerobic capacity (20 m multistage fitness, 2400 m Cooper, and 12 min Cooper tests. Only 19 studies reported sex-specific performance standards, including differences in test execution, scoring systems, VO2max estimation, or time limits. The findings indicate that tests of upper-body muscular endurance and strength, lower-body power, and aerobic capacity are among the most frequently measured physical abilities in police education programs internationally, while also highlighting the need for more standardized reporting of test protocols, reliability, and validity.

Background Pharmacogenomics-guided prescribing uses patient genetic information to individualize drug selection and dosing and has attracted interest as a strategy to improve outcomes and reduce adverse drug events in cardiovascular diseases. Several systematic reviews have examined its cost-effectiveness, but their findings have not been synthesized across drug classes and healthcare settings. Objective To identify, critically appraise, and synthesize findings from systematic reviews evaluating cost-effectiveness or cost-utility of pharmacogenomics-guided treatment of cardiovascular diseases. Methods This systematic review of systematic reviews was pre-registered in PROSPERO (CRD420261281565). Five databases were searched from inception, without language restrictions. Eligible studies were systematic reviews that summarized cost-effectiveness evidence on pharmacogenomics-guided cardiovascular drug prescribing. Risk of bias was assessed using ROBIS and methodological quality using AMSTAR 2. Findings were synthesized narratively. Results Ten systematic reviews (2010–2024) were included, encompassing 149 unique primary cost-effectiveness studies. The corrected covered area across reviews was 9.47% (moderate overlap). Most evidence was derived from economic modelling studies and substantial heterogeneity was observed across drug–gene pairs, comparators, and healthcare settings. CYP2C19-guided clopidogrel therapy was frequently reported as cost-effective or cost-saving, although results were less favourable when universal ticagrelor served as comparator. Evidence for CYP2C9/VKORC1-guided coumarin anticoagulation was more heterogeneous with cost-effectiveness varying across contexts. Limited evidence suggested that SLCO1B1-guided statin therapy may be cost-effective, although data were sparse. No review reported pooled incremental cost-effectiveness ratios or net monetary benefit. Risk of bias was low in 7 reviews; AMSTAR 2 confidence was high in 4 and low in 5. Conclusion Cost-effectiveness of pharmacogenomics-guided cardiovascular treatment seems to vary by drug–gene pair, comparator, healthcare context, and modelling assumptions. Further real-world studies and standardized economic evaluations are needed to clarify broader clinical adoption.