We establish an equivalence between the existence of Costas polynomials and the existence of a special kind of orthomorphism such that their compositions are also orthomorphisms. Computations are easier over these orthomorphisms. We provide a lower bound for the number of Costas polynomials and derive some of their properties. We show that Costas polynomials, by virtue of being multiplicative analogs of planar polynomials, can also be used to construct complete families of mutually orthogonal Latin squares.

Introduction and Objective: Sex differences in macrovascular complications of type 2 diabetes (T2D) are known, but evidence on microvascular differences remain limited. Methods: We used an Austrian medical claims database of 8.9 million individuals (1997-2014). Comorbidities co-occurring with T2D were analyzed using sex- and age-specific contingency tables across 2-year intervals (2003-2014), with odds ratios estimated via the Cochran-Mantel-Haenszel method. Only comorbidities with sufficient case numbers were retained. Sex differences were quantified by the differences of logarithmic ORs between male and females in units of pooled standard errors assessed using a Bonferroni-corrected test. Results: In 40 to 49 year olds, females had more retinopathy (OR 9.3 vs. 5.5), chronic kidney failure (CKI: OR 9.8 vs. 6.5), depression (OR 3.1 vs. 1.9) and cardiovascular complications including chronic ischemic heart disease (CIHD: OR 10.8 vs. 5.6), heart failure (HF: OR 12.1 vs. 7.7) and acute myocardial infarction (MI: OR 9.4 vs. 3.9, all p-values <0.001) compared to males with T2D. In 50 to 59 year olds, females had higher rates of CKI (OR 9.2 vs. 6.2), depression (OR 2.8 vs. 1.9) and cardiovascular complications (CIHD: OR 6.8 vs. 4.4, HF: OR 8.7 vs. 5.3, MI: OR 5.7 vs. 2.7) compared to males. Retinopathy showed no sex differences, but cerebral infarction was more frequent in females (OR 4.4 vs. 3.2). In age group 60 to 69 year olds, females had higher rates in cardiovascular complications (CIHD: OR 4.8 vs. 3.7, HF: OR 6.4 vs. 4.3, MI: OR 3.8 vs. 2.5), retinopathy (OR: 2.5 vs. 3.0), CKI (OR 7.3 vs. 4.9) and depression (OR: 2.5 vs. 2.0). Lastly, in 70 to 79 year olds the least differences with a higher rate of cardiovascular complications (CIHD: OR 3.5 vs. 3.2, MI: OR 3.1 vs. 2.3) and CKI (OR 5.0 vs. 4.0, all p-values<0.001) in females compared to males was reported. Conclusion: More comorbidities were associated with T2D in females than in males, including cardiovascular disease, retinopathy, nephropathy, and neuropathy. These results support more personalized and effective management strategies. T. Gisinger: None. K. Fenz: None. P. Klimek: None. E. Dervic: None. A. Kautzky-Willer: None.

Effective early warning systems for aquatic contamination require monitoring strategies capable of detecting subtle, long-term shifts in mixture-driven biological activity. Suspended particulate matter (SPM) serves as a carrier and reservoir for complex contaminant mixtures, facilitating their transport and persistence in aquatic systems, yet systematic toxicological time series for archived SPM remain scarce. Regulatory monitoring predominantly targets Priority Substances and River Basin Specific Pollutants, leaving the temporal trends of particle-associated mixture toxicity largely unresolved. Leveraging 18 years (2005-2022) of cryogenically archived annual SPM composites from the Rhine River, we conducted a spatiotemporal effect-based assessment integrating receptor-mediated effects, oxidative stress analysis and untargeted Cell Painting phenomics. This integrated toolbox enabled evaluation of pathway-specific responses and multi-compartment cellular perturbations associated with particle-bound contaminant mixtures. Polar SPM-associated chemicals elicited oxidative stress response and caused endocrine disruption through estrogen receptor α (ERα) activation and androgen receptor inhibition (anti-AR). Trend analysis showed spatiotemporal variation along the river, with statistically increasing trends of oxidative stress and anti-AR activity over time at Koblenz, driven by polar chemicals. Both polar and non-polar SPM extracts activated the aryl hydrocarbon receptor (AhR), indicating presence of compounds capable of triggering xenobiotic response pathways. Several subcellular compartments were affected, with mitochondrial features being among the most affected. These findings demonstrate that SPM-associated chemicals elicit diverse toxicological effects by acting on several receptors and impacting diverse cellular structures. Combining targeted and phenomics-based effect approaches provided comprehensive mechanistic insights and valuable information to support the early warning systems for chemical contamination in aquatic environments.

This systematic review synthesizes 38 peer-reviewed empirical studies (January 2010-December 2025) on microcontroller use in physics education, following preferred reporting items for systematic reviews and meta-analyses procedures and searches in Scopus and ERIC. It describes how platforms such as Arduino, ESP32, Atmega328, and Micro:bit potentially support development of laboratory skills and may facilitate learning of mechanics, thermodynamics, electromagnetism and optics. These low-cost programmable devices most often facilitate learning through automated, high-frequency data collection and real-time visualization, allowing students to observe transient phenomena and connect measurements to conceptual models. Instructions are typically inquiry and project-based, with students building sensor systems, troubleshooting, and developing computational and experimental reasoning. Across studies, motivation and engagement frequently improve, and some report gains in conceptual understanding and laboratory problem-solving. Different barriers include limited teacher training, time constraints, calibration/debugging difficulties, and resource and maintenance demands. Future studies should prioritize longitudinal research and scalable teaching models to support sustained classroom integration.

Timely diagnosis is critical for improving breast cancer outcomes, especially in resource-limited health systems. This study provides the first real-world evidence from Bosnia and Herzegovina on diagnostic and treatment intervals, adherence, and survival in women with breast cancer. We conducted a retrospective analysis of breast cancer cases diagnosed between 2019 and 2023 at the Clinical Centre University of Sarajevo, the largest cancer center in the country, managing approximately 60% of cases in the Federation of Bosnia and Herzegovina. Most patients (78.1%; 95% CI: 73.8–82.3) were diagnosed through self-referral due to symptoms, with 62.4% of cancers detected at stages 1 and 2. The mean patient and system diagnostic intervals were 38.1 days (95% CI: 23.4–52.8) and 38.6 days (95% CI: 29.9–47.3), respectively, with a total diagnostic interval of 70 days (95% CI: 58.9–82.5). Almost all diagnostic procedures had a waiting time of less than ten days. Among all women undergoing surgery, radical mastectomy was performed in 61% (95% CI: 55–66), while among women with stage 1–2 disease, 55% (95% CI: 48–62) underwent radical mastectomy. Treatment duration averaged 3.7 months for chemotherapy (95% CI: 3.4–4.1) and 0.48 months for radiotherapy (95% CI: 0.26–0.69), with higher compliance for radiotherapy (99.5%; 95% CI: 98–100) than chemotherapy (78%; 95% CI: 72–84). Three-year progression-free survival was 85.7%, and overall three-year survival was 86%. Early breast cancer detection and favorable survival can be achieved even in resource-constrained settings.

This scoping review maps the scope, characteristics, and emerging patterns of empirical research on doomscrolling. Guided by PRISMA-ScR recommendations, searches were conducted in Scopus and Web of Science, and 50 empirical studies met the inclusion criteria. The findings indicate that doomscrolling is generally conceptualized as repetitive, prolonged, and difficult-to-stop consumption of negative digital news, often driven by uncertainty, informational needs, and emotional discomfort. Research on doomscrolling has expanded rapidly since 2020, with a focus on pandemic-related contexts and growing attention to climate change, natural disasters, geopolitical conflicts, and other crises. Methodologically, the field is dominated by cross-sectional quantitative studies, while longitudinal, experimental, qualitative, and intervention-oriented studies remain limited. Across the reviewed studies, doomscrolling was frequently associated with adverse psychological outcomes, including anxiety, depression, stress, psychological distress, and reduced well-being. Emerging evidence also suggests social and occupational implications, including distraction, reduced productivity, and altered risk perceptions. Key individual-level factors associated with doomscrolling include fear of missing out, intolerance of uncertainty, emotional vulnerability, and low self-regulation. Despite growing scholarly interest, the literature remains fragmented in terms of definitions, measurement tools, research designs, and contextual coverage. This review highlights the need for standardized, cross-culturally validated measures; broader populations and crisis contexts; and stronger longitudinal, experimental, and intervention-based evidence. Overall, the findings position doomscrolling as a multidimensional phenomenon at the intersection of digital media use, crisis communication, and mental health, with important implications for future interdisciplinary research and digital well-being initiatives.

Fifth-generation (5 G) network slicing enables multiple logical networks to share the same infrastructure, each designed to support distinct Service Level Agreements (SLAs). While network slicing is well supported in the Radio Access Network (RAN) and 5 G Core (5GC), the Transport Network (TN) backhaul is often treated as a slice-agnostic forwarding substrate. As a result, resource contention on shared links can significantly degrade network performance, such as latency and throughput, breaking end-to-end SLAs. This paper addresses this gap by making the TN sliceaware through a lightweight framework that translates slice requirements into concrete backhaul policies. The framework (i) associates each slice with TN identifiers at domain boundaries, (ii) turns slice requirements into per-slice forwarding and scheduling policies (e.g., priority and queue selection, bandwidth bounds, and optional congestion signals), and (iii) exports perslice measurements for monitoring and closed-loop control. We deploy a proof of concept on a programmable switch and evaluate it on a real-life 5 G testbed. Our results show that, under link saturation, slices designed for mission-critical services preserve their SLAs, while best-effort traffic degrades predictably.

A central promise of topological quantum computing is that increasing the excitation gap improves device performance significantly. Here, we experimentally validate this principle in an InAs--Pb tetron device via interferometric single-shot parity measurements. By replacing aluminum with the higher-gap superconductor lead in our superconductor-semiconductor hybrid devices, we have improved the robustness of our topological phase. In addition, to enable fast and precise bring-up at scale, we have developed an rf measurement technique that resolves low-energy wire-end states and directly measures their energy splitting with $\mu\text{eV}$ precision. We employ this technique to bring up a device in a multi-tetron array and perform parity measurements of one of the tetron's hybrid nanowires (NWs). By controllably switching the wire parity, we observe $h/2e$-periodic bimodal shifts in the quantum capacitance of a quantum dot coupled to the hybrid nanowire in an interference loop. Further time-resolved measurements reveal a characteristic parity switching time of $\sim 20$ s with some instances reaching minute-scale. Such extremely long parity lifetimes are orders of magnitude longer than typical qubit operation times, which are on the order of $\mu\text{s}$. Finally, we discuss potential implications for the fidelity of Pauli measurements.

This research aims to investigate the concept of industrial symbiosis as a change agent in the Circular Economy, with its consequent effects on the economy, the environment, and society in terms of sustainable development. This study employs qualitative research with quantitative support from a structured survey of 152 IS project experts, researchers, and practitioners, utilizing a questionnaire comprising Likert-type and multiple-choice questions. Data were aggregated into composite indicators and analyzed by using a log-log multiple regression model. Empirical results reveal that economic benefits are the most significant positive drivers. The actors’ involvement also contributes positively, highlighting the importance of multi-stakeholder collaboration. Conversely, barriers have the strongest and the highest negative scale impact on perceived IS synergies. Broader economic and social conditions moderately enhance synergies, while awareness and training show a weaker but positive effect. IS is both economically viable and environmentally necessary, but its expansion depends on reducing financial, regulatory, and infrastructural barriers. Certain economic policy-driven interventions, such as fiscal incentives, regulatory clarity, and investment, enable infrastructure to scale up the adoption of IS.

Abstract Introduction Rheumatic connective tissue diseases (RCTDs) are chronic systemic autoimmune disorders frequently complicated by cardiovascular involvement, which represents a major cause of morbidity and mortality. Subclinical cardiac manifestations may remain unrecognized and may be associated with systemic inflammation and laboratory abnormalities. Objective To evaluate the prevalence and characteristics of cardiac manifestations in patients with RCTDs and to assess their association with serological status and selected hematological and biochemical parameters. Methods This observational study included 110 adult patients hospitalized and treated for rheumatic connective tissue diseases over a one-year period. Patients were classified into seropositive and seronegative groups based on autoantibody profiles. All participants underwent clinical evaluation, electrocardiography, and transthoracic echocardiography. Hematological, inflammatory, biochemical, electrolyte, enzyme, and serum protein parameters were analyzed. Results Cardiac involvement was more frequently observed in seropositive patients and increased significantly with age. Ventricular hypertrophy and atrioventricular or intraventricular conduction disturbances were the most common abnormalities in this group. Seropositive patients showed significantly lower hematocrit, hemoglobin, calcium, and albumin levels, as well as higher erythrocyte sedimentation rate, fibrinogen, triglycerides, lactate dehydrogenase, and serum urea levels. In the seropositive group, demonstrated significant negative correlations with hematocrit, hemoglobin, albumin, and calcium. Conclusion Seropositive rheumatic connective tissue diseases are associated with a higher prevalence of subclinical cardiac involvement and distinct laboratory abnormalities reflecting chronic inflammation and myocardial remodeling. Integrated cardiovascular assessment combined with laboratory evaluation may facilitate early detection of cardiac involvement in this patient population.

In patients with heart failure with reduced ejection fraction (HFrEF), the angiotensin receptor-neprilysin inhibitor sacubitril-valsartan has consistently demonstrated a beneficial therapeutic effect, vastly in non-Chagas trials. Less is known about the efficacy and safety of sacubitril-valsartan compared with standard of care in patients with Chagas cardiomyopathy, a common but often neglected etiology of nonischemic HFrEF. We aimed to perform a systematic review and meta-analysis to investigate whether sacubitril-valsartan is superior to enalapril in patients with heart failure (HF) due to Chagas cardiomyopathy. PubMed, Embase and Cochrane database were searched for randomized controlled trials (RCTs) that compared sacubitril-valsartan with enalapril in patients with HF due to Chagas cardiomyopathy. Efficacy outcomes were (1) cardiovascular (CV) death; (2) HF hospitalization; (3) relative change in N-terminal pro-B-type natriuretic peptide (NT-proBNP) from baseline; and safety outcomes were (4) serious adverse events (SAEs); and (5) drug discontinuation due to adverse events (AEs). Cochrane's Review Manager Version 7.2.0 (RevMan, 2024) was used for all statistical analyses. Heterogeneity was examined with I² statistics. Hazard ratios (HR), risk ratios (RR), and mean differences (MD) with 95% confidence intervals (CIs) were pooled using an inverse-variance random-effects model. Three RCTs comprising 1,112 patients were included, of whom 463 (38%) were females. A total of 615 (50.02%) patients received sacubitril–valsartan, while 610 (49.8%) were treated with enalapril. The mean age was 63.67±10.6 years, and the mean left ventricular ejection fraction (LVEF) was 29.8%±7.2%. There was no statistically significant difference in CV death (HR 0.92; 95% CI 0.72 to 1.18; p=0.51; I²=0; Figure 1A) and HF hospitalization (HR 0.93; 95% CI 0.72 to 1.20; p=0.59; I²=0; Figure 1B) between sacubitril-valsartan and enalapril groups. However, there was a statistically significant reduction in NT-proBNP favoring enalapril over sacubitril-valsartan (MD 0.68; 95% CI 0.63 to 0.73; p<0.00001; I²=0; Figure 1C). No statistically significant difference in SAEs was found between the two treatment arms (RR 0.90; 95% CI 0.79 to 1.03; p=0.12; I²=0; Figure 2A), but there was a trend towards fewer drug discontinuations due to AEs with sacubitril–valsartan compared with enalapril (RR 0.51; 95% CI 0.26 to 1.01; p=0.05; I²=32% Figure 2B). In this meta-analysis of 1,112 patients with HF due to Chagas cardiomyopathy, sacubitril-valsartan did not statistically significantly reduce CV death or HF hospitalization, relative to enalapril. There was a significant difference between groups in terms of NT-proBNP reduction favoring enalapril. Moreover, sacubitril-valsartan was not superior to enalapril with respect to safety outcomes.Figure 1.Efficacy outcomes.For image description, please refer to the figure legend and surrounding text.Figure 2.Safety outcomes.For image description, please refer to the figure legend and surrounding text.

Inclisiran effectively reduces low-density lipoprotein cholesterol (LDL-C) by suppressing proprotein convertase subtilisin/kexin type 9 (PSCK9) in patients on maximally tolerated statins with atherosclerotic cardiovascular disease (ASCVD) or risk equivalent. However, less is known about the efficacy of inclisiran as a monotherapy strategy for LDL-C reduction in patients with elevated levels but who are not on statins, ezetimibe, or any other lipid-lowering therapy (LLT). To investigate whether the lipid-lowering efficacy of inclisiran in LDL-C reduction indicates a significant pharmacodynamic effect regardless of baseline cardiovascular risk in patients with hypercholesterolemia without any LLT. We conducted a comprehensive search of PubMed, Embase, and Cochrane Library for randomized controlled trials (RCTs) comparing inclisiran sodium at dose of 300 mg (equivalent to 284 mg inclisiran) with placebo in adults with hypercholesterolemia who were not on statin, ezetimibe, nor any other LLT at baseline for evaluating the lipid-lowering efficacy of inclisiran as monotherapy. Outcomes of interest were (1) primary efficacy endpoint as percentage change in LDL-C from baseline, in patients without any background LLT and in those without statin use, and (2) percentage change in PCSK9 levels from baseline. R software version 4.3.1 was used for statistical analysis to estimate pooled effects of mean difference (MD) and 95% confidence intervals (CI) under e random-effects model. Heterogeneity was examined with I² statistics. We included five RCTs comprising 540 patients, of whom 311 (58%) were treated with inclisiran monotherapy, and the remaining 229 (42%) received placebo. Median follow-up ranged from 6 to 18 months (or 183 to 540 days). When compared with placebo, patients treated with inclisiran monotherapy who were not on any LLT had a significant decrease in percentage change in LDL-C from baseline (MD −46.24%; 95% CI −51.35 to −41.12; p<0.01; Figure 1A), with no significant difference when stratified by low risk versus high-risk population (test for subgroup difference p=0.33; Figure 1A). Similarly, inclisiran monotherapy lowered the LDL-C from baseline in patients without statin at baseline by about 53% more compared with placebo (MD −52.57%; 95% CI −62.34 to −42.80; p<0.01; Figure 1B). Moreover, the inclisiran group showed a significant 77% reduction in PCSK9 levels compared with the placebo group (MD −77.29%; 95% CI −84.31 to −70.27; p<0.01; Figure 2A). In this meta-analysis of RCTs evaluating patients with hypercholesterolemia without any background LLTs, inclisiran monotherapy significantly reduced percentage change in LDL-C from baseline, regardless of ASCVD risk. These findings were consistent in a sensitivity analysis only in patients without statin use at baseline, as well as in reduction of PSCK9 levels.Inclisiran Figure 1For image description, please refer to the figure legend and surrounding text.  Inclisiran Figure 2For image description, please refer to the figure legend and surrounding text.

Oral anticoagulation (OAC) and antiplatelet therapy (APT) represent a well-established preventative strategy against stroke, stent-related, and coronary ischemic events in patients with atrial fibrillation (AF) and coronary artery disease (CAD) following percutaneous coronary intervention (PCI). Less is known about the efficacy and safety of OAC as monotherapy compared with combined antithrombotic therapy in the subgroup of patients with drug-eluting stent (DES) implantation. To investigate whether deescalating from combination therapy of OAC with single APT to OAC monotherapy provides similar protection from major ischemic and bleeding endpoints in patients with AF and stable CAD following DES implantation. We systematically searched PubMed, Embase, and Cochrane Library for randomized controlled trials (RCTs) that compared OAC monotherapy (vitamin K antagonist or direct oral anticoagulant) with combination antithrombotic therapy of OAC plus single APT in patients with AF and CAD who underwent PCI with DES and reported the efficacy and safety composite outcomes of mortality, ischemia (myocardial infarction, stroke, or systemic embolism), and major bleeding or clinically relevant bleeding (CRNB). Cochrane's Review Manager Version 7.12.0 (RevMan, 2024) was used for statistical analysis to estimate pooled effects of hazard ratio (HR) with 95% confidence intervals (CI) under a random-effects model. Heterogeneity was examined with I² statistics. We included four RCTs comprising a total of 2570 patients, of whom 1302 (51%) were treated with OAC monotherapy, and the remaining 1268 (49%) were treated with combination therapy of OAC+APT. Median follow-up ranged from 12 to 30 months. There was no statistically significant difference in the efficacy endpoints of major ischemic composite (HR 0.94; 95% CI 0.65 to 1.36; p=0.75; Figure 1A) and the net clinical composite (HR 0.77; 95% CI 0.37 to 1.60; p=0.49; Figure 1B) between OAC monotherapy and OAC+APT combination therapy. However, there was a statistically significant reduction in the safety endpoint composite of major bleeding or CRNB with OAC monotherapy (HR 0.47; 95% CI 0.30 to 0.75; p=0.001; Figure 2A) compared with OAC+APT combination therapy, which was consistent in a sensitivity analysis of patients treated with predominantly new-generation DES (HR 0.38; 95% CI 0.25 to 0.59; p<0.0001; Figure 2B). Among patients with AF and prior PCI with DES implantation, OAC monotherapy statistically significantly reduced major bleeding or CRNB endpoint by 52% compared with combined antithrombotic therapy, but there was no significant difference between groups in terms of major ischemia or net clinical benefit.OAC Figure 1For image description, please refer to the figure legend and surrounding text.  OAC Figure 2For image description, please refer to the figure legend and surrounding text.

Commercially available graphene quantum dots (GQDs) are promising nanomaterials for applications in research and preclinical diagnostics, drug delivery, and bioimaging. Their bioactivity is highly dependent on dose, route of exposure, duration, cell type, uptake mechanisms, tissue and cellular distribution, and physicochemical properties. This study aimed to evaluate genotoxic, cytotoxic, and cytostatic endpoints of blue- (B-GQDs) and green-emitting (G-GQDs) GQDs in human blood and salivary leukocytes. GQDs were tested at concentrations ranging from 2.5 to 100 µg/mL using distinct treatment periods. Fourier transform infrared spectroscopy (FTIR), trypan blue exclusion, comet, and cytokinesis-block micronucleus cytome (CBMN cyt) assays were performed. FTIR analysis revealed that G-GQDs, unlike B-GQDs, exhibit an absorption band typically associated with amine functional groups, which may contribute to their pronounced genotoxic effects. Peripheral blood mononuclear cells and salivary leukocytes showed higher sensitivity to G-GQDs compared to whole blood samples. Although no cytotoxic effects were observed, both GQDs induced significant DNA damage, with G-GQDs demonstrating greater genotoxic potential. These findings demonstrate that GQDs can induce DNA damage in the absence of detectable cytotoxic effects under the conditions tested, highlighting the importance of considering both physicochemical properties and cellular models in the safety assessment of nanomaterials.