OBJECTIVES Aortic stenosis (AS) is the most common valvular heart disease, with transcatheter aortic valve implantation (TAVI) now preferred for select severe cases. This study evaluated the early safety and performance of the new Myval Octacor Transcatheter Heart Valve (THV) (Meril Life Sciences), for which limited clinical data exist. METHODS The authors retrospectively analyzed 43 consecutive patients with severe AS who underwent TAVI using the Myval Octacor THV at a tertiary cardiac center. Primary outcomes included all-cause mortality, stroke, major vascular complications, conduction abnormalities, new pacemaker implantation, paravalvular leak, and valve failure at 30 days follow-up. RESULTS The median age was 81 years (IQR: 7), and 22 patients (51.2%) were female. Coronary artery disease was present in 24 (55.8%). Technical success rate was 100%. Mean pressure gradient decreased significantly post-procedure (55 mm Hg [IQR: 24] vs 5 mm Hg [IQR: 2]; P ≤ .001). No in-hospital deaths occurred. Two patients (4.7%) received permanent pacemakers during hospitalization, and 3 (7.0%) required pacemakers within a week because of conduction issues. Two patients (4.7%) experienced Bleeding Academic Research Consortium Type 3a bleeding. At 30 days, 42 patients remained in follow-up (98%), with 55% improved to New York Heart Association Class I. No vascular complications, stroke, acute kidney injury, valve thrombosis, or endocarditis occurred. One patient had valve failure from a significant paravalvular leak and 1 noncardiac death occurred 2 weeks post-discharge. CONCLUSIONS Early outcomes suggest that the Myval Octacor THV is a safe and effective option for TAVI in severe AS; however, larger studies with longer follow-up are required.

Background/Objectives: Venous thromboembolism (VTE) is a common and clinically significant complication in patients with metastatic colorectal cancer (mCRC). Tumor sidedness and molecular alterations such as RAS and BRAF mutations are established prognostic factors in mCRC; however, their role in VTE risk stratification remains unclear. This study aimed to evaluate the association between primary tumor sidedness, KRAS/NRAS/BRAF mutational status, and VTE occurrence in patients with mCRC treated in the outpatient setting. Methods: This multicenter ambispective observational study included 224 patients with mCRC treated with first-line chemotherapy with or without targeted therapy. All patients had known KRAS/NRAS/BRAF statuses. The primary endpoint was the association between tumor sidedness and VTE risk. Secondary endpoints included associations between oncogenic mutations and VTE, subgroup analyses according to tumor localization and mutational status, and overall survival (OS). Multivariate logistic regression was used to identify independent predictors of VTE. Results: After a median follow-up of 21 months, VTE occurred in 23.3% of patients. The incidence of VTE was significantly higher in right-sided colorectal cancer (RCRC) compared with left-sided colorectal cancer (LCRC) (41.0% vs. 17.6%, p < 0.001). Although KRAS/NRAS and BRAF mutations were more frequent in RCRC, mutational status was not independently associated with VTE. In multivariate analysis, right-sided tumor location remained a strong predictor of VTE (OR 5.2; 95% CI 1.9–14.1; p = 0.001), along with anti-EGFR therapy. The Khorana score classified most patients as low risk and did not reliably identify those who developed VTE. VTE occurrence was not significantly associated with OS, whereas right-sided tumor location was associated with inferior survival. Conclusions: Right-sided tumor location is an independent predictor of VTE in patients with mCRC and confers a high absolute thrombotic risk not captured by the Khorana score. Incorporating tumor sidedness into VTE risk assessment may improve identification of patients who could benefit from primary thromboprophylaxis.

Background Functional dyspepsia (FD) is a common gastrointestinal (GI) disorder which significantly impacts quality of life and subjective well-being (SWB). Psychosocial factors have been linked to FD symptoms, which places this disorder among the “disorders of gut-brain interaction.” Recent studies suggest notable sex differences in symptom expression and the level of disruption of daily activities. This study aims to explore the impact of sex on associations between psychological factors and SWB in individuals with FD. Methods The study included 191 adults referred to their first endoscopic examination of the upper GI tract due to dyspeptic symptoms. Patients completed validated measures assessing GI symptoms, GI and extra-GI comorbidities, health-related habits, psychological traits (somatization, stress resilience), and indicators of SWB (life satisfaction, positive and negative experiences). Multiple regression and hierarchical block regression analyses were conducted to identify predictors of SWB and to examine the potential moderating role of sex and psychological factors. Subsequently, path analysis was conducted to explore potential causal pathways among sex, psychological variables and SWB. Results Participants displayed relatively homogeneous characteristics according to sex. Two main subgroups were identified: a larger group of highly educated, working-age individuals and a smaller group of older adults (>60 years) with higher comorbidity levels. Psychological factors, stress resilience and somatization emerged as the strongest predictors of SWB, while health and lifestyle factors had modest effects. Sex was identified as a significant determinant of SWB in the complex hierarchical model, but only after controlling for somatization and stress-resilience. The path model indicated that other sex-related factors may also influence SWB. Conclusion Results pointed toward the need to involve psychological constructs like somatization and stress resilience in studies examining SWB in individuals with FD. The importance was highlighted of examining the gender-related (socially conditioned) factors associated with SWB, and the need to separately assess these factors in older and younger individuals with FD (<60, ≥60). The study revealed a complex interactive network between age, gender, and SWB-related factors, supporting the biopsychosocial model of FD. However, identifying a suitable methodological framework to elucidate these complex relationships remains a challenge.

Background/Objectives. Ebstein’s anomaly (EA), which accounts for fewer than 1% of congenital heart diseases, and atrioventricular canal defect (AVCD), present in approximately 4–5% of cases, exceptionally coexist, with this combination observed in fewer than 0.5% of patients with AVCD. We aim to report the oldest documented case of a 45-year-old female with the exceptionally rare combination of complete AVCD, EA, and right ventricular hypoplasia and to provide a concise review of these anomalies. Case presentation. Diagnosed in early childhood with a complete AVCD, pulmonary stenosis, and right ventricular (RV) hypoplasia, the patient underwent palliative surgical intervention with a modified Blalock–Taussig shunt at the age of 10 but did not receive subsequent regular follow-up. Over the ensuing 35 years, she remained largely untreated until presentation at 45 years of age with progressive exertional dyspnea, central cyanosis, and palpitations, corresponding to NYHA class III. Comprehensive multimodal imaging, including transthoracic echocardiography and cardiac magnetic resonance, revealed a complete AVCD with moderate-to-severe mitral regurgitation secondary to an anterior mitral leaflet cleft, severe tricuspid regurgitation, RV hypoplasia, and hallmark features of EA. Given the complex cardiac anatomy and the elevated surgical risk, the patient was considered inoperable, and a strategy of conservative management with multidisciplinary follow-up was implemented. Conclusions. This case highlights the exceptional longevity of a patient with the rare coexistence of complete AVCD, EA, and RV hypoplasia, surviving 45 years from diagnosis despite limited early intervention. It underscores the importance of lifelong follow-up in complex congenital heart disease and illustrates the role of multimodal imaging in assessing anatomy and guiding management when surgical options are high-risk or not feasible.

Education in modern business conditions plays a strategic role in the development of knowledge-based and innovation-driven societies. Investment in education represents one of the key determinants of democratization and the economic empowerment of individuals. The goal of contemporary education is to strengthen professional knowledge and to develop key competencies, including digital skills, which enable individuals to be prepared for new professional challenges and actively participate in current socio-economic trends. This paper aims to analyse, through conducted empirical research, the impact of formal education and acquired digital competencies on employability in the Republic of Serbia. Special emphasis is placed on the relationship between the level of education, digital literacy, and employment opportunities, to provide recommendations for improving educational policies and professional training programs.

Sustainable innovation is important in Albania, a small transition economy facing pressures from digitalization, the green transition, and increased competition. Yet the country’s innovation system is still developing, and academia–business linkages remain weak. This article investigates how academia–business (A2B) collaboration contributes to firms’ sustainable innovation, addressing the lack of quantitative evidence from a country in the Western Balkans context. Building on innovation systems and resource-based perspectives, A2B cooperation is conceptualized as a multidimensional latent construct, capturing types of collaboration, key actors, and organizational drivers. Using survey data from 298 firms operating in Albania, collected in 2025, the study applies Covariance-Based Structural Equation Modeling (CB-SEM) to test whether the intensity and quality of A2B cooperation are linked to sustainable innovation outcomes. The findings indicate that collaboration is still limited and inconsistent, dominated by student internships and sporadic joint projects. However, the CB-SEM results confirm that more intensive and better-structured cooperation is strongly associated with higher levels of sustainable innovation. The study offers one of the first CB-SEM-based quantitative assessments of A2B collaboration and sustainable innovation in Albania and provides policy implications for strengthening innovation-oriented partnerships in transition economies.

Background: While rescue stenting (RS) is a recognized bailout strategy following failed endovascular thrombectomy (EVT) for acute ischemic stroke with large vessel occlusion (AIS-LVO), first-line stenting (FLS) has emerged as a potential alternative to avoid vascular injury and improve outcomes. However, direct comparisons between these strategies remain limited. We conducted a comparative analysis of FLS versus RS using data from a large, multicenter international registry to evaluate their relative safety and effectiveness. Methods: We conducted a comparative analysis of FLS versus RS using data from the RESISTANT registry, a multicenter, international, retrospective cohort of AIS patients treated with intracranial stenting during EVT (2016-2023). Patients were categorized by stenting strategy: FLS (stent placed without prior thrombectomy) or RS (stent placed after failed thrombectomy). The primary effectiveness outcome was functional independence (modified Rankin Scale [mRS] 0-2) at 90 days; the primary safety outcome was symptomatic intracranial hemorrhage (sICH). Propensity score inverse probability of treatment weighting (IPTW) was used to adjust for baseline differences. Results: Among 827 patients, 723 were in the RS cohort (median age 67 years [IQR 59-77], 64.2% male) and 104 in the FLS cohort (median age 65.5 years [IQR 58.8-77], 72.1% male). Using FLS as the reference strategy, IPTW=adjusted analyses did not detect significant differences in functional independence (OR=0.64; 95% CI 0.38-1.07) or sICH (OR=0.93; 95% CI 0.34-2.59). No significant differences were observed in secondary outcomes including successful reperfusion, mortality, or procedural complications. In the anterior circulation cohort (n=589), outcomes were likewise comparable (functional independence: OR=0.62; 95% CI 0.60-1.25; sICH: OR=0.81; 95% CI 0.30-2.18). Similarly, in the posterior circulation cohort (n=234), no significant differences were found (functional independence: OR=0.82; 95% CI 0.32-2.10; sICH: OR=0.81; 95% CI 0.30-2.18). Conclusions: In this study, no significant differences in safety or effectiveness were detected between FLS and RS strategies during EVT for AIS. Prospective, randomized trials are needed to better define optimal treatment approaches.

Mantle plumes beneath major oceanic hot spots appear to be rooted in unusually large structures near the core-mantle boundary, which have markedly reduced seismic wave speeds. The origin of these large ultralow-velocity zones (ULVZs), referred to as mega-ULVZs, remains uncertain partly because of lack of constraints on the relative reduction in shear versus compressional wave speeds (RS/P). This ratio can give clues into the compositional makeup of the mega-ULVZs. Through joint seismic analysis of core-diffracted P and S waves beneath Hawai’i, we constrain the RS/P of its mega-ULVZ to 1 to 1.3. Mineralogical modeling reveals that iron enrichment via solid iron-rich magnesiowüstite [(Mg,Fe)O] matches this seismic constraint, independent of modeled ULVZ thickness. Enrichment of metallic iron-rich magnesiowüstite likely enhances the thermal conductivity of mega-ULVZs and provides a mechanism to drive localized plume upwelling. Higher reported RS/P values for smaller ULVZs near subduction zones may therefore indicate different processes at play controlling ULVZ formation across the diverse core-mantle boundary landscape.

In this paper we give a characterization of monotone discrete systems of equations in terms of associated signature matrix and give some properties of certain invariant surfaces of codimension 1, which often give the boundary of attraction of some fixed points. We present several examples that illustrate our results in the case of k-dimensional systems where $ k \geq 3 $ k≥3.

Mantle plumes beneath major oceanic hot spots appear to be rooted in unusually large structures near the core-mantle boundary, which have markedly reduced seismic wave speeds. The origin of these large ultralow-velocity zones (ULVZs), referred to as mega-ULVZs, remains uncertain partly because of lack of constraints on the relative reduction in shear versus compressional wave speeds (RS/P). This ratio can give clues into the compositional makeup of the mega-ULVZs. Through joint seismic analysis of core-diffracted P and S waves beneath Hawai’i, we constrain the RS/P of its mega-ULVZ to 1 to 1.3. Mineralogical modeling reveals that iron enrichment via solid iron-rich magnesiowüstite [(Mg,Fe)O] matches this seismic constraint, independent of modeled ULVZ thickness. Enrichment of metallic iron-rich magnesiowüstite likely enhances the thermal conductivity of mega-ULVZs and provides a mechanism to drive localized plume upwelling. Higher reported RS/P values for smaller ULVZs near subduction zones may therefore indicate different processes at play controlling ULVZ formation across the diverse core-mantle boundary landscape.

Marine natural products represent a diverse collection of structurally distinct metabolites, many of which have untapped therapeutic potential. This study screened 161 marine-derived coumarin and xanthene compounds for their binding affinity to the histamine H2 receptor and the gastric H+/K+-ATPase, the primary regulators of gastric acid secretion. Docking simulations were performed using curated structures of both targets, followed by an evaluation of the compounds for drug-likeness and predicted absorption, distribution, metabolism, and excretion (ADME) properties. Thirty-four compounds demonstrated a stronger predicted affinity for the H2 receptor than famotidine; however, only three compounds (1, 5, and 150) met all drug-likeness criteria, achieving quantitative estimates of drug-likeness (QED) values exceeding 0.67. Screening against the proton pump yielded 98 hits with higher affinity than soraprazan, with compound 150 being the only candidate to fulfill all medicinal chemistry filters. Interaction analysis indicated that compound 150 binds to the proton pump in a manner that largely overlaps with soraprazan. Density functional theory (DFT) calculations were utilized to characterize the electronic properties of the most promising compounds. ADME predictions suggested favorable permeability and a low risk for human ether-à-go-go-related gene (hERG) inhibition, although high plasma protein binding and the potential for cytochrome P450 (CYP) inhibition may require further optimization. These findings underscore the potential of pyranocoumarin compound 150, along with xanthene derivatives 1 and 5, as promising candidates for the development of new acid-suppressive agents.

This study explores the implications of technology availability constraints on the decarbonisation pathways of the EU power sector, drawing on scenario results from five European energy supply models: MEESA, LIMES, ENERTILE, ACSG, and OSeMBE. The analysis evaluates how limiting the deployment of key low-carbon generation technologies, namely carbon capture and storage (CCS), nuclear power, bioenergy, solar photovoltaics, and wind energy, affects the electricity generation mix, emissions reduction, investment needs, and power system costs by 2030 and 2050. Results within the model ensemble indicate that variable renewable energy sources (VRE), wind and solar, are indispensable for deep decarbonisation. Constraints on solar or wind power substantially increase electricity generation costs and require major shifts in technology portfolios, often resulting in greater reliance on remaining renewable options or fossil fuel generation with CCS. The unavailability of CCS leads to higher system emissions and increased investment in renewables and storage. In contrast, removing nuclear or bioenergy has a more moderate impact, though some regional effects are significant. All models show that achieving ambitious emission reductions in the power sector remains technically feasible under individual technology constraints, but the mitigation effort shifts across generation technologies, and system costs rise considerably in low VRE futures. Policy implications include the need for robust support for wind and solar deployment, cross-border system integration, flexible technologies, and backup capacity. The findings underscore the value of a diversified technology portfolio, strategic infrastructure investments, and EU-level coordination to preserve cost efficiency and ensure stable power system performance under uncertainty in future technology availability.

BACKGROUND AND OBJECTIVES The management of anterior circulation tandem lesion stroke remains controversial, given its under-representation in randomized thrombectomy trials and uncertainty regarding optimal extracranial carotid intervention. We aimed to determine whether emergent carotid stenting (eCAS) during endovascular thrombectomy (EVT) for anterior circulation tandem lesions improves 90-day functional outcomes compared with a no-stenting strategy. METHODS We conducted an international multicenter longitudinal retrospective cohort study (CERES-TANDEM, NCT06965036) of consecutive adults treated at 49 comprehensive stroke centers in Europe, North America, and Singapore for anterior circulation acute ischemic stroke due to tandem lesions from January 1, 2018, to December 31, 2024. Exclusion criteria were primary hemorrhagic stroke, absence of intracranial occlusion, presentation >24 hours from symptom onset, and age younger than 18 years. We compared 90-day modified Rankin Scale (mRS) scores between participants receiving eCAS and those receiving no stenting during EVT. The primary estimand was mRS shift, analyzed by stabilized inverse probability of treatment weighting (IPTW)-weighted ordinal regression. Additional estimands were direct-effect estimand adjusting for successful recanalization (defined as Thrombolysis in Cerebral Infarction grade 2b or higher) and symptomatic intracranial hemorrhage (sICH) (estimand 2) and stratum estimand restricting to never-crossers (estimand 3). RESULTS Of 4,053 patients (mean age 70 years, 65.5% female), 2,522 underwent eCAS and 1,531 received no stenting. After IPTW, eCAS was associated with an improved 90-day functional outcome (common odds ratio (OR) 1.31; 95% CI 1.17-1.47;p < 0.001) and higher odds of mRS score 0-1 (OR 1.27; 95% CI 1.08-1.50; p = 0.005) and mRS score 0-2 (OR 1.30; 95% CI 1.13-1.51; p < 0.001), without a significant increase in sICH (OR 1.21; 95% CI 0.93-1.56; p = 0.15). Findings were consistent in direct-effect (common OR 1.17; 95% CI 1.04-1.31; p = 0.008) and stratum (common OR 1.37; 95% CI 1.21-1.55; p < 0.001) estimands. There was no interaction for intracranial occlusion site, IV thrombolysis, sedation technique, EVT approach, or access site. Sensitivity analysis including recanalization in IPTW-weighted estimand 1 framework confirmed the association of eCAS with improved 90-day functional outcomes (common OR 1.14, 95% CI1.02-1.27, p = 0.008). DISCUSSION In this large real-world cohort, eCAS during EVT for anterior circulation tandem lesions was associated with superior 90-day functional recovery without increased hemorrhagic risk. These findings support consideration of eCAS in clinical practice and warrant confirmation in randomized trials. TRIAL REGISTRATION INFORMATION Registered in clinicaltrials.gov, NCT06965036. CLASSIFICATION OF EVIDENCE This study provides Class II evidence that in patients with stroke due to anterior circulation tandem lesions, eCAS during EVT improves 90-day functional outcomes compared with EVT alone.