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.

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.

The management of locally-advanced, resectable head and neck squamous cell carcinoma (HNSCC) is undergoing a major shift driven by the integration of neoadjuvant immunotherapy (nIO). The rationale for nIO lies in its administration within an immunologically active, treatment-naïve microenvironment that enhances immune priming and anti-tumor response. Despite encouraging clinical data, including the pivotal KEYNOTE-689 trial and multiple phase II studies, methodological heterogeneity in trial design, endpoint definitions, and response criteria currently hampers data comparability and the establishment of new standards of care. This expert narrative review proposes a structured framework for standardizing clinical, pathologic, imaging, and translational endpoints in HNSCC nIO trials, highlighting harmonized definitions of pathologic response, practical reporting templates, and methods to evaluate immune priming. Standardization of response evaluation, biomarker integration, and trial methodology is essential to accelerate the translation of neoadjuvant immunotherapy into routine clinical practice for HNSCC.

Background: Breast clip marker movement after ultrasound-guided biopsy can negatively affect lesion re-localisation rates and surgical outcomes, underscoring the need for improved understanding of the factors influencing clip displacement. Thus, this study aimed to compare four different breast clip markers and identify risk factors for clip migration and dislocation after ultrasound-guided placement. Methods: This retrospective study included 350 patients who underwent ultrasound-guided biopsy of a newly diagnosed breast lesion with placement of one of four types of breast clips (UltraClip Dual Trigger Biodur 108 Coil Marker [UC], TUMARK Professional [TP], TUMARK Vision [TV] and HydroMARK Breast Biopsy Site Marker [HM]). Clip migration and dislocation were assessed immediately after placement and during follow-up imaging for at least 3 months. A binary logistic regression analysis was performed to identify predictors of clip dislocation including lesional, perilesional and procedural parameters. Results: Clip migration rates were 26.0%, 18.0%, 10.0% and 25.0% and clip dislocation rates were 14.0%, 20.0%, 9.0% and 38.0% for UC, TP, TV and HM, respectively. Features significantly associated with clip dislocation included predominantly fatty surrounding tissue (p = 0.046) with low perilesional shear wave velocities (p = 0.054), smooth lesion contours (p = 0.041), soft lesion strain elastography (p =0.001), low clip-to-lesion-surface distance (p = 0.002) and the use of an HM breast clip (p = 0.032). Conclusions: The type of breast clip-marker, as well as perilesional and lesional characteristics, influence the likelihood of clip dislocation. Notably, the hydrogel-coated clip (HM) exhibited the highest rate of dislocation.

This paper compiles results from six systematic reviews and meta-analyses on associations between environmental and occupational exposure to chemicals and levels of DNA strand breaks in human leukocytes, measured by the comet assay. There are no differences in effect sizes when using different comet descriptors. However, lower central tendencies are obtained by using a non-parametric test as compared to the standard parametric analysis, indicating that the standard meta-analyses tend to overestimate the effect size. The compiled results indicate that exposures can be sorted into three groups with decreasing effect size: high (pesticides), moderate (volatile organic compounds, heavy metals and antineoplastic drugs), and low (anaesthetic gases and air pollution). Interestingly, studies from middle-income countries have higher effect sizes than those seen in studies from high-income countries. This may be related to higher exposures or lower socioeconomic status in middle-income countries. However, there is also some co-variability between studies from middle-income countries and the risk of comet assay measurement bias, assessed as information provided in published papers. Lack of information on assay controls and blinded/coded sample analysis appears to be a general issue in studies on comet assay results. Risk of exposure misclassification is mainly related to the type of exposure; there are good biomarkers for some exposures (e.g. heavy metals), whereas other exposures are more challenging to assess with biomarkers (e.g. pesticides). In conclusion, all examined exposures result in significant increases in DNA strand breaks at the population level, though to varying degrees.

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.

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.

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.

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.