Search Results (422)

Multidrug-resistant (MDR) Enterococcus faecium is an opportunistic pathogen. Its resistance and virulence genes can spread through the food chain, posing risks to public health. This study investigated the antimicrobial resistance and genomic characteristics of MDR E. faecium isolated from milk samples from cows with mastitis in Ningxia between 2019 and 2024. From 2019 to 2024, 1341 milk samples were collected in Yinchuan, Yinnan, and Yinbei. MDRE. faecium was identified using plate screening, mass spectrometry, broth microdilution, and hemolysis detection. Whole-genome sequencing enabled SNP, MLST, pan-genome, and COG analyses, focusing on ARGs and MGEs. MRPP, AMOVA and PCoA were applied to compare gene communities and identify driver genes. Ninety-one E. faecium strains were isolated. Resistance to florfenicol, ceftiofur, and chloramphenicol exceeded 60%, while resistance to vancomycin and linezolid showed an overall increasing trend over the study period. Phylogenetic clustering revealed two subtypes, three clades, and 10 novel STs. Spearman correlation analysis revealed strong positive correlations among the resistance genes optrA, cfr(A), and vanF. Antibiotic resistance, particularly MDR, increased over time, and strains carried diverse ARGs and MGEs. Overall, strengthened surveillance of mastitis-derived E. faecium is warranted to support the control of bovine mastitis and safeguard public health. Full article

Introduction: From 12 March 2020, when the first cases of COVID-19 were registered in Kosovo, to 9 March 2023, there were a total of 273,310 reported cases of COVID-19 and 3211 reported deaths in Kosovo (CFR: 1.17%). Health care workers (HCWs) have been at a higher risk of contracting SARS-CoV-2 infection; nevertheless, data on seroprevalence of SARS-CoV-2 antibodies among HCWs in Kosovo are very limited. Methodology: A cross-sectional serology study with 1654 healthcare professionals throughout Kosovo was conducted to determine the presence of antibodies against the spike antigen of SARS-CoV-2. In addition, a structured questionnaire was administered to study participants to obtain basic demographic data, and information on prior infection and COVID-19 vaccination status. Results: Antibodies against the spike antigen of SARS-CoV-2 were detected in almost all (99.8%) HCWs that participated in the study. The average antibody titer was 8030.8 AU/mL in women and 9533.7 AU/mL in men. Sixty-four percent of HCWs in this study reported prior infection with SARS-CoV-2, 6% of whom were hospitalized. Over 98% of study participants had received SARS-CoV-2 vaccination. Conclusions: Almost all HCWs participating in the study had antibodies against the spike antigen of SARS-CoV-2. This is most probably the result of the high COVID-19 vaccination rate in Kosovo as well as infection with SARS-CoV-2. Full article

Background/Objectives: Invasive coronary physiology has evolved from a tool for assessing intermediate stenoses to a comprehensive framework for guiding diagnosis and treatment across the spectrum of coronary artery disease (CAD). This review aims to provide an updated, catheterization laboratory-centered overview of contemporary invasive coronary physiology, emphasizing its role in optimizing percutaneous coronary intervention (PCI) and in evaluating patients with angina and non-obstructive coronary arteries (ANOCA/INOCA). Methods: A narrative review of contemporary evidence, including randomized trials, consensus documents, and guideline recommendations, was conducted. Key physiological indices—fractional flow reserve (FFR), non-hyperemic pressure ratios (NHPRs), coronary flow reserve (CFR), and index of microcirculatory resistance (IMR)—were examined alongside emerging tools such as longitudinal vessel analysis and the pullback pressure gradient (PPG). Applications in pre- and post-PCI assessment, physiology–imaging integration, and comprehensive functional testing in ANOCA/INOCA were evaluated. Results: Physiology-guided PCI improves clinical outcomes and resource utilization compared with angiography-guided strategies. Longitudinal vessel assessment and PPG enable characterization of focal versus diffuse CAD, improving procedural planning and prediction of post-PCI physiological results. Post-PCI physiological assessment identifies residual ischemia and guides optimization strategies. In patients without obstructive CAD, combined assessment of microvascular function and vasomotor reactivity allows identification of distinct pathophysiological endotypes, supporting mechanism-based, individualized therapy. Integration with intracoronary imaging further enhances procedural precision. Conclusions: Contemporary invasive coronary physiology provides a multidimensional approach integrating epicardial, microvascular, and vasomotor domains. This framework supports personalized decision-making, optimizes revascularization, and reduces unnecessary interventions, representing a cornerstone of modern coronary care. Full article

Chronic coronary syndromes (CCSs) are increasingly recognized as complex immunometabolic vascular disorders in which coronary microvascular dysfunction (CMD), persistent low-grade inflammation, oxidative stress, and maladaptive cellular remodeling contribute to ischemic symptoms and adverse outcomes beyond epicardial stenosis. CMD represents a heterogeneous condition comprising both functional and structural endotypes and constitutes a major determinant of myocardial ischemia, heart failure progression, and adverse cardiovascular outcomes, even in the absence of obstructive coronary artery disease. Emerging evidence indicates that immunometabolic reprogramming of endothelial cells, vascular smooth muscle cells, and immune cells sustains microvascular dysfunction in CCSs. Metabolic shifts toward glycolysis, mitochondrial dysfunction, redox imbalance, and dysregulated lipid metabolism promote chronic inflammatory activation within the coronary microenvironment. Convergent mitochondrial stress (including NAD⁺ decline) and redox injury promote endothelial senescence and increase susceptibility to regulated cell death, progressively limiting vasodilatory reserve and predisposing to microvascular rarefaction. Pyroptosis and ferroptosis-like lipid peroxidation further exacerbate endothelial barrier disruption and inflammatory amplification. In parallel, inflammasome activation, iron-dependent lipid peroxidation, impaired autophagy, and endoplasmic reticulum stress form interconnected molecular networks that amplify vascular injury through self-reinforcing mechanisms. This narrative review integrates mechanistic and translational evidence linking immunometabolic dysregulation, mitochondrial stress, thromboinflammatory signaling, endothelial senescence, and regulated cell death to distinct CMD endotypes. We propose a systems-level framework in which coronary microvascular dysfunction is conceptualized as an immunometabolic vascular network disorder, with reduced coronary flow reserve (CFR)—often termed myocardial flow reserve (MFR) in PET studies—emerging as the integrative functional endpoint of these interacting molecular perturbations and a robust predictor of major cardiovascular events. Full article

Background/Objectives: Patient-specific subperiosteal implants are increasingly used to treat severely atrophic ridges due to advances in digital planning and additive manufacturing. This study aimed to evaluate the effects of material type and implant configuration on stress distribution in subperiosteal implant systems and to compare their overall biomechanical performance using a multi-criteria decision framework. Methods: A three-dimensional model of a severely atrophic maxilla was reconstructed to simulate four clinical scenarios combining two configurations (one-piece and two-piece) and two materials (titanium and 60% carbon fiber-reinforced polyetheretherketone). Finite element analysis was conducted to assess stress distribution within the implant body, fixation screws, prosthetic framework, and surrounding bone under vertical and oblique loading conditions. Maximum and minimum principal stresses were evaluated in bone, whereas von Mises stresses were calculated for implant components. The resulting biomechanical indicators were subsequently integrated using an entropy weight–TOPSIS multi-criteria decision analysis. Results: Principal stresses in the surrounding bone showed minimal variation between titanium and 60% carbon fiber-reinforced polyetheretherketone across all configurations. Implant configuration had a more pronounced effect on implant body stress. Under oblique loading, the two-piece configuration demonstrated substantially higher implant stresses than the one-piece design, whereas under vertical loading, lower implant stresses were observed in the two-piece configuration. The multi-criteria analysis ranked the one-piece titanium model highest under oblique loading and the two-piece titanium model highest under vertical loading. Conclusions: Implant configuration and loading direction influenced biomechanical behavior more than material selection in patient-specific subperiosteal implants. Full article

Background/Objectives: While the descriptive trajectory of COVID-19 is well-documented, there is a methodological gap in quantifying the precise magnitude of risk reduction across multi-year pandemic phases in Brazilian subnational units. This study aimed to fill this gap by applying Generalized Linear Models (GLMs) to quantify the temporal transition of epidemiological risks (Incidence, Mortality, and Case Fatality) in Ceará (2020–2023), using the first year of the pandemic as a statistical baseline. Methods: Ecological time-series study was conducted using official surveillance data. We employed GLMs with Poisson distribution to calculate Rate Ratios (RRs) and 95% Confidence Intervals, allowing for a robust comparative risk modeling between 2020 (reference) and subsequent years (2021–2023). Results: Modeling revealed a significant epidemiological dissociation between transmission and severity. While the risk of incidence remained high through 2022 (RR = 1.42), the mortality risk showed an earlier and more drastic decline, with a 68% reduction as early as 2022 (RR = 0.32) and 99% in 2023 (RR = 0.01). The Case Fatality Rate (CFR) risk decreased consistently from 2021 onwards, reaching its lowest point in 2023 (RR = 0.09; 91% reduction). Conclusions: Between 2020 and 2023, Ceará transitioned to reduced COVID-19 severity. Despite ecological design and data limitations, these findings underscore the importance of resilient health systems and equitable immunization. Full article

Sequentialdecision-making under imperfect information is naturally modeled as an extensive-form game, where the Nash equilibrium serves as the predominant solution concept for two-player zero-sum settings. Counterfactual regret minimization (CFR) is a widely used framework for this purpose, iteratively reducing regret through regret matching so that the average strategy approaches a Nash equilibrium. However, the convergence efficiency of CFR remains a practical challenge. In this work, we refine and reformulate an advantage-based exponential weighting scheme, Exponential CFR (ExpCFR), which accelerates convergence by allocating greater attention to highly profitable actions during the regret-accumulation process. Building on this heuristic, we further introduce Pob-CFR, a framework that integrates population-based evolutionary training with CFR. Pob-CFR maintains a diverse population of heterogeneous CFR variants, periodically evaluating them by exploitability and replacing underperforming individuals with the elite to synchronize strategy exploration. Systematic evaluations across five benchmark games demonstrate that these methods accelerate early-to-mid convergence compared to standard CFR baselines. Furthermore, within the evaluated benchmarks, the relative advantage of the population-based architecture appears more evident in the games with larger strategic complexity. Full article

Pancreatic ductal adenocarcinoma (PDAC) is the most complex and aggressive disease with the worst rates of unresectable or metastatic disease at diagnosis, resistance to systemic therapy, and case fatality rate (CFR) among leading cancers. In non-metastatic disease, neoadjuvant treatment with modern chemotherapeutic regimens followed by surgical resection and/or adjuvant mFOLFIRINOX has significantly improved oncological outcomes. However, recurrence rates remain alarmingly high, while immune checkpoint inhibitors (ICIs) or molecularly targeted therapy have not yet demonstrated clinical benefits. Comprehensive genomic profiling through NGS-based approved assays such as TruSight Oncology 500 (TSO500) could guide targeted therapy. Rapidly evolving mRNA cancer vaccines and circulating tumor DNA (ctDNA)-based prediction of minimal residual disease (MRD) and recurrence risk hold great promise towards the realization of rational combination therapy to improve recurrence-free survival (RFS) and overall survival (OS). More recently, single-cell multiomics (SC MO), spatial proteomics and transcriptomics (SPT), artificial intelligence (AI), and systems biology have revolutionized cancer research, enabling holistic tumor microenvironment (TME) analysis. In this comprehensive review, we describe the latest advances and unmet needs in the standard of care of PDAC. Moreover, we discuss the expectations of ongoing randomized clinical trials of adjuvant mRNA vaccine-based therapy and ctDNA MRD testing as prognostic biomarkers, towards personalized treatment to improve RFS and OS in a medium-term perspective. With a longer perspective, we explore how harnessing SC MO, SPT, AI, and systems biology can reveal the 3D spatial organization of interacting cancer, immune, and stromal cells. Multi-dimensional TME-, TSO500- and ctDNA-based framework of dynamic biomarkers are of paramount importance to achieve an optimal patient-specific perioperative multimodal treatment combining precision immunotherapy, targeted drugs, and modern chemotherapy, translated into future practice-changing clinical trials, that could eliminate MRD towards recurrence prevention. Full article

Background: Achieving adequate oncological margins in tumors involving the thoracic costovertebral junction is technically challenging because of complex regional anatomy and the need to preserve neurological and biomechanical integrity. This case report describes a robot-assisted margin-extension strategy after incomplete resection of a thoracic costovertebral chondrosarcoma. Methods: A 31-year-old man with grade 1 chondrosarcoma of the left sixth rib underwent second-stage surgical radicalization after prior incomplete resection with positive medial margins. Following multidisciplinary discussion, a single-stage posterior procedure was performed, including robot-assisted T4–T8 stabilization with radiolucent CFR-PEEK instrumentation and robot-assisted sagittal vertebral osteotomy (“Postage-Stamp Osteotomy”) of T6 to achieve en bloc removal of the involved costovertebral segment. Results: The osteotomy was executed using a pedicle-referenced robotic trajectory workflow with sequential navigated drilling and controlled completion with a navigated osteotome. Total operative time was 379 min, with estimated blood loss of 800 mL. No major intraoperative neurovascular complications occurred. Histopathology confirmed negative margins. The patient was mobilized on postoperative day 1 and discharged on postoperative day 6 without new neurological deficits. Radiological follow-up at 3 months showed no recurrence, while clinical follow-up at 5 months demonstrated full return to baseline activities. Conclusions: This report describes a technically feasible robot-assisted margin-extension strategy in a highly selected thoracic spinal oncology scenario. Although long-term oncological conclusions cannot be drawn from a single case, tailored technology-enabled margin-oriented approaches may represent a case-specific option in carefully selected patients. Full article

Background/Objectives: Probiotic feed additives are increasingly used in livestock production as antimicrobial-sparing tools, yet viable microbial products should not introduce clinically relevant antimicrobial resistance genes (ARGs) into the intestinal resistome. This study evaluated farm-animal probiotic products using an integrated phenotypic, metagenomic and mobilome-aware safety framework. Methods: Seven commercially available products intended for poultry, pigs, cattle or horses were assessed using product metadata, culture-based recovery, broth microdilution minimum inhibitory concentration (MIC) profiling and Illumina short-read sequencing as a screening-level resistome approach. Reads were quality controlled, assembled, screened using the Comprehensive Antibiotic Research Database (CARD)/Resistance Gene Identifier (RGI) workflow and interrogated for plasmid-, phage- and insertion sequence/mobile genetic element-associated genomic context. Results: MIC profiles were generated for viable bacterial isolates representing Enterococcus faecium, Pediococcus acidilactici, Pediococcus pentosaceus and Bacillus subtilis. One labelled Lactobacillus plantarum component was not recovered as viable culture, and one labelled P. acidilactici component was recorded as P. pentosaceus. Sequencing-based resistome screening identified 30 antimicrobial resistance (AMR)-associated CARD antibiotic-resistant organism (ARO) hits belonging to 13 determinants across six ARG-positive coded products, while one coded product had no retained CARD/RGI hit. Profiles were dominated by recurrent Enterococcus-associated background determinants, including aac(6′)-Ii, msrC and eatAv. Plasmid prediction was positive for five hits, whereas no iMGE- or phage-associated ARG context was detected. No vanA/vanB, mcr, optrA, poxtA, cfr, extended-spectrum β-lactamase (ESBL) or carbapenemase gene was detected. Conclusions: The investigated products did not show evidence of high-priority mobile ARG carriage. Nevertheless, AMR-associated determinants and occasional predicted mobile contexts support routine integrated MIC-sequencing-based resistome–mobilome assessment of veterinary probiotic products. Because short-read assemblies do not fully resolve plasmid architecture or transferability, mobile-context predictions should be considered screening-level indicators requiring confirmatory long-read or functional testing for higher-priority findings. Full article

Coronary flow reserve (CFR) is a fundamental physiological index defined as the ratio of maximal coronary blood flow during hyperemia to resting flow. It provides an integrated assessment of the entire coronary circulation, from epicardial arteries to the microvasculature. Non-invasive assessment, particularly with transthoracic Doppler echocardiography (TTDE), is valuable in clinical practice for evaluating the functional impact of moderate obstructive lesions and determining the status of coronary microcirculation. Impairment of coronary microcirculation, detected by reduced CFR, is present in diverse conditions such as Tako-Tsubo cardiomyopathy, cardiac syndrome X, hypertension, and slow coronary flow. CFR also serves as a non-invasive tool to examine the effects of various interventions. CFR can be assessed invasively using Doppler guidewire or thermodilution techniques and non-invasively using transthoracic Doppler echocardiography, PET, CMR, CT perfusion, and dynamic SPECT. Lower CFR is observed with advancing age, in females, and in individuals of African descent. An impaired CFR is a powerful, independent predictor of major adverse cardiovascular events (MACEs) across a wide spectrum of diseases, including stable obstructive coronary artery disease (CAD), ischemic syndromes with no obstructive coronary arteries (INOCAs), heart failure, cardiomyopathies, and systemic diseases like diabetes and chronic kidney disease. Beyond risk stratification, CFR is used to guide therapeutic decisions, including revascularization strategies and tailoring of pharmacological interventions. The integration of CFR assessment into clinical practice, supported by recent guideline recommendations, represents a shift towards personalized, physiology-based cardiovascular care. Full article

This study investigates upper-reservoir dam-axis siting in pumped-storage hydropower projects, where cut–fill balance and construction cost are critical under complex terrain conditions. Existing approaches still rely heavily on manual interpretation or static GIS-based analysis and therefore do not adequately optimize dam-axis geometry or earthwork balance. To address this limitation, we propose an Improved Adaptive Variable Neighborhood Search (IAVNS) algorithm that integrates high-resolution digital elevation model (DEM) data within a two-layer adaptive framework. The inner layer performs staged planar and elevation adjustments through adaptive neighborhood operators, whereas the outer layer conducts fitness-guided subregion migration to strengthen global exploration. Experiments on the Qiannan pumped-storage project show that IAVNS obtains layouts with improved cut–fill balance. In the 30-run benchmark comparison, IAVNS achieved a mean CFR of 1.31, which is close to, although slightly above, the upper bound of the adopted earthwork-balance reference interval. In the separate 20-run case-study analysis, the average storage-volume deviation was 0.13%, with run-level deviations ranging from $-1.39\%$ to $1.16\%$. In benchmark comparisons, IAVNS improves solution quality by 22.8% relative to the Genetic Algorithm (GA) and by 16.5% relative to classical Variable Neighborhood Search (VNS), while reducing convergence time by 49.5% and 27.4%, respectively. Sensitivity analysis further suggests that the framework remains locally robust under practically reasonable parameter perturbations, and the module-level ablation study indicates that the observed performance gains arise mainly from the problem-tailored search mechanisms for dam-axis siting rather than from a generic combination of metaheuristic components. Taken together, the case-study results, repeated-run comparison, sensitivity analysis, and ablation study support the use of IAVNS as a geometry-oriented decision-support framework for preliminary dam-axis design in terrain-sensitive hydraulic engineering applications. Full article

Zinc oxide nanoparticles (ZnO NPs) exhibit strong and broad-spectrum antibacterial properties, making them a promising agent for textile applications. However, their weak adhesion to fibers and poor washing durability have hindered practical use. In this work, we report zinc/catechol resin-based microspheres (Zn/CFRs) synthesized via a one-pot hydrothermal route and applied to cotton fabric through a pad-dry-cure process. The resulting Zn/CFRs exhibit a monodisperse spherical morphology, with zinc ions concentrated on the surface and ZnO NPs encapsulated within the resin matrix. The finished fabric demonstrates potent, non-leaching antibacterial activity, achieving over 99.99% inhibition against S. aureus, E. coli, and C. albicans, with excellent performance retention even after 50 laundering cycles. Furthermore, we observed that catechol oxidation in the Zn/CFRs proceeds slowly under UV light, which may contribute to the durable adhesion of the coating. Moreover, the functional finishing does not compromise the fabric’s tensile strength, hand feel, or breathability, which positions it favorably for scalable adoption in functional textile manufacturing. Full article

This paper assesses the challenges and policy responses for the adoption of electric vehicles (EVs) in Africa. We applied a decision support system framework comprising a new integration of the RANking COMparison Method (RANCOM) and Root Assessment Method (RAM) for the first time in the literature to address the multi-criteria decision analysis (MCDA) problems based on expert opinions. Six experts evaluated five criteria along with ten policy responses. While the weights of criteria are computed via the RANCOM method, the RAM approach ranks the policy responses. Moreover, the Compromise Fuzzy Ranking (CFR) method defines the consensus rankings via both positional ranks and preference scores. Furthermore, a three-stage comparative analysis is carried out for criteria weighting, policy responses ranking, and alternative consensus ranking. A sensitivity analysis is carried out including the consideration of experts’ significance according to their experience and their omission. The findings indicated the most critical challenges were the scarcity in charging infrastructure and the affordability and accessibility issues. The resilient charging infrastructure is the most appropriate policy response. The findings direct planners and EVs policymakers across the continent toward a policy that will ensure a clean and sustainable transportation system. Full article

Background: Biofilm formation and associated tooth demineralization are key factors influencing the clinical performance of dental materials. Methods: This study compared the antibiofilm and demineralization preventive effects of two zinc-modified glass ionomer cements (Zn-GICs) with a conventional GIC. Disk-shaped specimens of Caredyne Restore (CR), ChemFil Rock (CFR), and Ketac Molar (KM) (n = 6) were evaluated in a multi-species biofilm model using an oral biofilm reactor. Early biofilm formation was analyzed by scanning electron microscopy (after 2 h and 4 h), bacterial accumulation and water-insoluble glucan (WIG) production were quantified (after 12 h). For demineralization assessment, restored human enamel and dentin specimens (n = 6) including an additional resin-based control group (Dura Seal, DS) were subjected to a 14-day biofilm challenge and lesion depth was measured using swept-source optical coherence tomography and confocal microscopy. Results: CR showed significantly lower bacterial accumulation and WIG production than the other materials (p < 0.05). CFR demonstrated lower bacterial levels than KM (p < 0.05), whereas no significant differences were observed between CFR and KM in WIG production (p > 0.05). CR produced the shallowest enamel and dentin lesions, whereas DS exhibited the deepest (p < 0.05); however, no statistically significant differences were observed between CFR and KM in lesion depth (p > 0.05). Conclusions: CR demonstrated superior biofilm suppression and reduced demineralization, whereas CFR showed limited differences compared with the conventional GIC. Full article