Search Results (1,079)

Background: Malnutrition and systemic inflammation are increasingly recognized as important determinants of prognosis in patients with heart failure. Several immunonutritional indices, including the Prognostic Nutritional Index (PNI), the Controlling Nutritional Status (CONUT) score, and the C-reactive protein–albumin–lymphocyte (CALLy) index, have been proposed as markers of nutritional and inflammatory status. However, their prognostic value in elderly patients with heart failure with preserved ejection fraction (HFpEF) remains incompletely defined. This study aimed to evaluate the prognostic significance of these immunonutritional indices in elderly patients with HFpEF over a long-term follow-up period. Methods: This retrospective observational study included 200 elderly patients hospitalized with HFpEF (mean age 86.6 ± 6.5 years). Clinical, laboratory, and echocardiographic parameters were collected at admission. Nutritional status was assessed using PNI, CONUT score, and CALLy index. Patients were followed for mortality during long-term follow-up. Survival analyses were performed using Cox regression models, receiver operating characteristic (ROC) curves, and Kaplan–Meier analysis. Median follow-up was 3.8 years (IQR 2.1–5.9). Results: During follow-up, 123 patients (61.5%) died, while 77 patients (38.5%) were alive at the end of observation. In univariate analysis, PNI, CONUT score, left ventricular ejection fraction (LVEF), and the tricuspid annular plane systolic excursion to systolic pulmonary artery pressure (TAPSE/sPAP) ratio were significantly associated with mortality. In multivariate analysis, the CONUT score, LVEF, and the TAPSE/sPAP ratio remained independent predictors of mortality. ROC analysis showed strong prognostic performance for the TAPSE/sPAP ratio (AUC 0.932), CONUT score (AUC 0.925), and LVEF (AUC 0.897). Optimal cut-off values for mortality prediction were CONUT ≥ 6, LVEF ≥ 65%, and TAPSE/sPAP ≤ 0.55 mm/mmHg. Kaplan–Meier analysis confirmed significantly reduced survival among patients with higher CONUT scores, higher LVEF, and an impaired TAPSE/sPAP ratio. Conclusions: In elderly patients with HFpEF, nutritional status and cardiopulmonary functional parameters are important determinants of long-term prognosis. The CONUT score emerged as the most informative immunonutritional index, while echocardiographic parameters reflecting ventricular function and right ventricular–pulmonary arterial coupling provided additional prognostic information. Integrating nutritional assessment with echocardiographic evaluation may improve risk stratification in elderly patients with HFpEF. Full article

Background/Objectives: Despite the availability of the National Cancer Screening Program in Korea, participation rates remain suboptimal. The literature demonstrates that cancer screening participation extends beyond individual-level knowledge and attitudes and is largely associated with trust. This study examines the role of trust—across cancer screening tests, health care providers, and health care organizations—as a central determinant of cancer screening participation among Koreans. Methods: A cross-sectional study was conducted with 369 Korean adults aged 40 years and older, recruited through convenience sampling from community centers in a metropolitan city. Data were collected using structured, paper-based questionnaires assessing socio-demographic factors and multilevel trust across specific screening tests, doctors, and health care organizations. Following descriptive statistics, bivariate and multivariate logistic regression analyses were performed to identify significant predictors of cancer screening utilization. Results: Koreans had relatively high trust in doctors and cancer screening tests. On an 11-point numeric rating scale ranging from 0 (not at all) to 10 (completely), the mean scores were 7.47 for the trust in doctors; colonoscopy had the highest trust score (M = 7.71), whereas the fecal occult blood test had the lowest (M = 7.14). Multivariate logistic regression revealed that trust and distrust were associated with the utilization of Pap smear, gastroscopy, upper gastrointestinal series, and colonoscopy in complex and sometimes paradoxical ways, and having a usual source of care was a consistent facilitator of cancer screening. Conclusions: These findings suggest that future research is needed to examine the complex interplay among trust, access to health care, and national policy in shaping cancer screening utilization in the Republic of Korea. Full article

Pulmonary hypertension (PH) can be defined as a mean pulmonary artery pressure (mPAP) greater than 20 mm Hg at rest during right heart catheterization (RHC). The reported prevalence of PH throughout the globe has been estimated to impact approximately 1% of the total population, with a majority of those afflicted being women more than men. Numerous etiologies give rise to the pathophysiology of PH, including heart disease (i.e., left-sided heart failure), lung diseases, and other unclear causes related to chronic stages and complications surrounding long-standing pulmonary thromboembolisms, side effects of certain medications, and genetic and environmental factors. Untreated PH can lead to severe morbidities such as cardio-renal syndrome and congestive hepatopathy (cardiac cirrhosis). Management of PH focuses on decreasing pulmonary pressures by using vasodilators such as prostanoids, and phosphodiesterase type 5 (PDE-5) inhibitors, as well as newer treatments such as sotatercept, which inhibits activin signaling, thereby inhibiting excessive cell growth in the pulmonary artery vasculature and down-regulating the pro-proliferative pathways. Full article

Obstructive sleep apnea (OSA) is the most common sleep-related breathing disorder and is increasingly recognized as a contributor to cognitive decline and a potential risk factor for neurodegeneration. Previous studies have also identified various associated comorbidities such as vascular dysfunction, metabolic alterations, and neuroinflammatory changes. Positive airway pressure (PAP) therapy has been associated with cognitive improvement in some studies, but its long-term effects on cognitive function remain uncertain. This study employs a prospective, observational, longitudinal cohort design to examine longitudinal associations between disease severity, PAP therapy and cognition. Additionally, we aim to examine the relationships between cognitive dysfunction, brain structure and associated OSA-related risk factors. A total of 100 eligible participants with mild to severe OSA will be recruited. All participants will undergo comprehensive assessments at baseline and after 12 months, including neurological, pulmonary, and ear, nose and throat clinical examinations, polysomnography, neuropsychological testing, brain magnetic resonance imaging with volumetry, anthropometric measurements, blood and saliva sampling for the assessment of the selected laboratory parameters, gut microbiome analysis, and evaluation of endothelial function and baroreflex sensitivity. This study may improve understanding of how PAP therapy and OSA-related pathophysiological processes influence cognitive outcomes. Full article

Background: Despite the effectiveness of current SARS-CoV-2 vaccines, the genetic variability of the viral target has led to the emergence of variants capable of evading vaccine-induced protection. To ensure broader and more durable protection, we investigated the efficacy of a novel vaccine strategy. Methods: This vaccine utilizes the highly conserved nucleocapsid (N) protein as its primary antigen, rather than the spike (S) protein. It incorporates the Papaya Mosaic Virus (PapMV) nanoparticle, a Toll-like receptor (TLR) 7/8 agonist with intrinsic adjuvant properties, as a vaccine platform. Results: The vaccine formulations, comprising PapMV nanoparticles and the N antigen covalently or non-covalently attached to the PpaMV nano, generated robust humoral (antibody) and cellular (T-cell) immune responses. Protective efficacy was evaluated in K18-hACE2 transgenic mice challenged with either the ancestral SARS-CoV-2 strain or the Omicron XBB.1.5 variant. In both cases, the vaccine significantly reduced inflammation and viral titers in the lungs of vaccinated animals. Conclusions: These results highlight the potential of this PapMV-N vaccine to induce broad protection against diverse SARS-CoV-2 variants. Full article

Uropathogenic Escherichia coli (UPEC) is a leading cause of urinary tract infections (UTIs) in companion animals. This study characterized 42 UPEC isolates recovered from dogs and cats at the University of Florida, College of Veterinary Medicine Diagnostic Laboratories between 2023 and 2024, focusing on antimicrobial resistance (AMR), virulence gene profiles, biofilm-forming ability, and phylogroup distribution of the isolates. Antimicrobial susceptibility testing (AST) showed that 40.48% of the isolates were resistant to at least one of the tested antibiotics, and 9.52% exhibited multidrug resistance (MDR). Phylogroup B2 was predominant (69.05%), and 61.90% of isolates demonstrated strong biofilm formation in artificial human urine. Virulence gene analysis revealed the presence of genes mediating adhesion (fim, pap, sfa), iron acquisition (fyuA, iro), biofilm formation (csg, bcs, pga, ycg/ymg), motility (fli, mot, flh), and stress response (oxyR, soxR/S, kat). Multiple plasmids carrying AMR and virulence determinants were also identified. The co-occurrence of the traits underscores the potential for persistent and recurrent infections, which can complicate therapeutic outcomes and facilitate horizontal gene transfer (HGT). The detection of antimicrobial-resistant, highly virulent UPEC strains possessing human UPEC traits in companion animals suggests the risk of zoonotic and reverse-zoonotic transmission, particularly in households with close pet–owner interactions. These findings emphasize the importance of judicious antimicrobial use, routine molecular surveillance, and integrated One Health strategies to mitigate the veterinary and public health threats associated with UPEC infections in companion animals. Full article

Background/Objectives: Ceftolozane/tazobactam (C/T) and ceftazidime/avibactam (CZA) are critical therapeutic options for multidrug-resistant Gram-negative infections; however, their comparative pharmacodynamics against carbapenem-resistant Pseudomonas aeruginosa (CRPA) remain incompletely defined. This study aimed to compare the bactericidal activity of C/T and CZA administered by intermittent infusion (II) or continuous infusion (CI) using a hollow fiber infection model (HFIM) against a clinical isolate of CRPA. Methods: Clinically relevant concentration–time profiles for C/T and CZA based on prescribing information were simulated in the HFIM. The standard P. aeruginosa strain ATCC 27853 and a GES-producing clinical CRPA isolate were utilized. The primary endpoint was bactericidal activity (≥3 log₁₀ CFU/mL reduction from baseline), while secondary endpoints included regrowth prevention and resistance development based on population analysis profiles (PAPs). Results: Against the standard strain, both agents achieved rapid killing without regrowth. However, for the GES-producing clinical isolate, C/T failed to achieve bactericidal activity. In contrast, CZA demonstrated sustained bacterial killing activity with the most pronounced early-phase bactericidal activity with CI of CZA (−4.25 log₁₀ CFU/mL at 24 h). The bactericidal activity was persistent over 7 days without bacterial regrowth after treatment discontinuation. Conversely, bacterial regrowth occurred with II of CZA after drug withdrawal. PAPs showed the lack of resistance development against CZA, whereas resistance to C/T developed within 48 h after initiating therapy. Conclusions: In this HFIM study, CI of CZA demonstrated the most sustained suppression of bacterial growth and prevented resistance emergence against the tested clinical isolate of CRPA producing GES β-lactamases. Future clinical studies are warranted to assess the effectiveness of the CI regimen. Full article

Background/Objectives: Although prescribing physical activity (PA) is a well-established preventive strategy in primary health care (PHC), its ethical implications remain under-researched. This study examines how general practitioners (GPs) and nurses experience, interpret, and manage ethical tensions in PAP. Methods: A qualitative study was conducted with 28 PHC professionals (13 GPs, 15 nurses) from rural and urban centers in Toledo, Spain (M = 18.4 years of experience). Data were collected through semi-structured interviews and analyzed using reflexive thematic analysis. Beauchamp and Childress’ four-principles framework was applied abductively to synthesize ethical conflicts and coping strategies. Results: Two main themes emerged: (1) Ethical conflicts in PAP, characterized by tensions between autonomy and paternalism, and the challenge of balancing beneficence with non-maleficence under institutional pressures; and (2) Professional coping strategies, where clinicians used relational care, individualized tailoring, and interprofessional collaboration to mitigate moral distress. Results indicated that clinical codes, such as “unrealistic goals” or “institutional pressure,” often overlapped across multiple ethical principles, necessitating a nuanced, multi-dimensional approach to counseling. Conclusions: PAP is not a neutral clinical task but an ethically grounded practice constrained by structural and organizational factors. To move toward safe and equitable health promotion, PAP must be conceptualized as a relational intervention. We propose an Ethical Reflective Tool and a conceptual framework to support clinical reflection, enhance professional accountability, and guide policy-level support for preventive care in PHC. Full article

Although urban streetscape visual esthetic quality (VAQ) assessment has progressed markedly, its findings are rarely operationalized in urban planning policy-making. The resulting discontinuity in the assessment–policy linkage is a critical impediment to streetscape VAQ enhancement. We propose an eye-tracking-enabled, end-to-end decision support framework that links evidence acquisition, intervention prioritization, design strategy formulation, and outcome feedback. Eye tracking is integrated to establish a three-dimensional assessment system spanning spatial, psychological, and physiological dimensions. Within this integrated system, we construct a three-level eye-tracking-based visual characteristics (ET-VC) framework across streetscape elements, formal characteristics, and public esthetic perception (PAP). Together, the three-dimensional system provides a theoretical basis for acquiring the multi-modal data required for VAQ enhancement. Building on this integrated assessment, we embed scenario planning theory to construct a planning facing decision model with PAP as the core outcome. The model combines importance-performance analysis (IPA) with the coupling coordination degree model (CCDM) to guide resource allocation decisions and intervention prioritization, and further uses eye-tracking evidence to support the development of refined, actionable enhancement strategies. A case study in Wudadao validates the framework’s robustness and feasibility. The ET-VC results provide additional evidence for interpreting esthetic perception: (1) ET-VC indicators differ significantly across streetscape elements, and “being viewed more” does not necessarily correspond to higher esthetic ratings; (2) four groups of key formal characteristic indicators—color configuration, naturalness, historicity and planning/regulatory control, and visual scale—systematically reshape fixation onset and maintenance patterns; and (3) PAP appears to involve partially nonlinear relationships between material landscape features and additional top-down influences (e.g., historical narratives and individual experience), rather than being fully explained by linear associations alone. Overall, this study provides both a theoretical basis and an applied demonstration for evidence-based streetscape VAQ enhancement. Full article

In archaeological contexts, isolated or poorly connected masonry elements are very common due to the absence of floors and weak connections between walls. As a result, under horizontal actions, vulnerability to out-of-plane (OOP) failures often becomes the most critical issue for their preservation. As is well-known, limit analysis-based approaches provide a reliable assessment of the expected OOP failure mechanisms and the associated acceleration capacity for existing masonry buildings. However, these approaches mainly refer to box-type buildings and cannot be directly applied to archaeological remains, whose morphology may differ significantly. With a specific focus on the Pompeii Archaeological Park (PAP), this study proposes a two-level classification of archaeological walls aimed at identifying their most likely OOP failure mechanisms and the most suitable analytical models available in the literature to predict their behaviour. The first level identifies recurring typologies based on the morphology of wall connections, relying on geometrical data that can be easily obtained from maps and/or on-site surveys. The second level then evaluates the effectiveness of these connections by investigating their construction techniques. The paper, therefore, proposes a general methodology for assessing the vulnerability of archaeological masonry walls to OOP failure mechanisms and discusses its application to some walls in the PAP. Full article

Background: Pulmonary hypertension (PH) remains a progressive and life-threatening condition despite advances in targeted pharmacotherapy. Pulmonary artery denervation (PADN) has emerged as a novel interventional strategy aimed at modulating sympathetic overactivity and improving pulmonary vascular hemodynamics. Methods: A comprehensive search of PubMed, EMBASE, Scopus, Web of Science, and the Cochrane Library was conducted through December 2024. Randomized clinical trials and prospective observational studies assessing PADN in PH were included. Primary endpoints were changes in outcomes from six-minute walk distance (6MWD), mean pulmonary artery pressure (mPAP), pulmonary vascular resistance (PVR), cardiac output (CO), and right ventricular function parameters. Secondary outcomes included clinical worsening, rehospitalization, transplantation, and all-cause mortality. Random-effects models were used to calculate pooled mean differences (MDs) and odds ratios (ORs) with 95% confidence intervals (CIs). Subgroup analyses were performed according to pulmonary hypertension phenotype and study design, and sensitivity analyses were conducted to assess robustness of pooled estimates. Results: Nine studies involving 454 patients were included. PADN significantly improved functional capacity (6MWD: MD = 92.03 m; 95% CI 46.37–137.68; p < 0.001) and reduced mPAP (MD = −11.84 mmHg; p < 0.001) and PVR (MD = −4.88; p < 0.001). Cardiac output increased significantly (MD = 0.55 L/min; p < 0.001), with improvements observed in right ventricular functional indices. PADN was associated with a lower risk of clinical worsening (OR = 0.30; p = 0.001) and rehospitalization (OR = 0.07; p < 0.001), whereas no significant difference was observed in all-cause mortality (OR = 0.53; p = 0.12). Considerable heterogeneity was observed across functional and hemodynamic outcomes, reflecting variability in study design, patient populations, and PADN techniques. Conclusions: PADN significantly improves exercise capacity and pulmonary hemodynamics in patients with PH, particularly in those with persistent symptoms despite medical therapy. Although PADN reduces clinical deterioration and rehospitalization, its impact on long-term survival remains uncertain. Further large-scale, multicenter randomized trials are needed to better define optimal patient selection and determine long-term clinical benefit. Full article

Objective: Systemic lupus erythematosus (SLE), Sjögren syndrome (SS) and antiphospholipid syndrome (APS) are common autoimmune conditions in child-bearing aged women, but their influence on pregnancy and assisted reproductive outcomes remain controversial. We aimed to perform an umbrella review to summarize the current evidence to provide a reference for clinicians and future research. Methods: PubMed, Embase (Ovid) and Cochrane database were searched (inception to April 2025) for relevant publications. Study selection, data extraction, quality evaluation, evidence grading and data synthesis were completed independently by two authors. Odds ratio, relative risk or standardized mean difference with 95% confidence intervals were calculated. Results: Fourteen articles (51 meta-analyses) were included, to report the associations of SLE, primary SS (pSS), antiphospholipud antibodies (aPLs), primary APS (pAPS) and 6 maternal/8 fetal/5 assisted reproductive outcomes. SLE and pAPS significantly increased the risks of spontaneous abortion, total fetal loss, pregnancy-induced hypertension, premature delivery, small for gestational age, neonatal death and neonatal intensive care unit. SLE also decreased anti-Müllerian hormone level and significantly increased the risks of pre-eclampsia (PE), stillbirth, low birth weight (LBW) and neonatal one minute Apgar < 7. pSS significantly increased spontaneous abortion and LBW risks. Positive aPLs significantly increased the risk of miscarriage rate in assisted reproductive techenology (ART) and were also associated with total fetal loss, PE, intrauterine growth retardation and placental abruption. Conclusions: This review offers a thorough overview of the current evidence linking SLE, SS and APS to pregnancy and assisted reproductive outcomes. It identifies existing gaps and proposes future research directions. Full article

Objectives: Downregulation of the endogenous gasotransmitter hydrogen sulfide (H₂S) contributes to the pathogenesis of pulmonary arterial hypertension (PAH). While prophylactic H₂S supplementation prevents PAH initiation in different rat models, its ability to reverse fully established PAH and pulmonary vascular structural remodeling is unknown. In this study, we aimed to test whether H₂S donor therapy can reverse the existing PAH in a chronic-hypoxia rat model. Methods: After 3 weeks of hypoxia exposure, rats with established hypoxia-induced pulmonary hypertension (HPH) were randomized to receive either continued hypoxia alone or hypoxia plus the H₂S donor NaHS (56 μmol/kg·d, ip) for an additional 6 weeks. Pulmonary artery pressure, pulmonary artery muscularization, and right ventricular hypertrophy were assessed. Furthermore, the cell proliferation (Ki-67 and PCNA), ERK1/2 phosphorylation, and persulfidation of the endothelin type A receptor (ETAR) were examined and detected in rat lung tissues and pulmonary artery smooth muscle cells (PASMCs). Results: H₂S therapy effectively reversed established HPH and pulmonary artery structural remodeling, reducing RVSP, mPAP, and the proportion of fully muscularized small pulmonary arteries by 13.8%, 12.0%, and 62.7%, respectively. Moreover, the PAT/PET ratio was normalized to normoxic levels. The right ventricular hypertrophy index decreased by 29.2%. Mechanistically, H₂S therapy suppressed PASMC proliferation, reduced ERK1/2 phosphorylation, and enhanced ETAR persulfidation. Furthermore, dithiothreitol-mediated reduction of ETAR persulfidation abrogated these antiproliferative effects of H₂S therapy, establishing persulfidation as an obligatory mechanism. Conclusions: H₂S donor therapy effectively reverses established HPH and pulmonary vascular structural remodeling by inhibiting PASMC proliferation, which is linked to enhanced ETAR persulfidation. These data provide preclinical proof-of-concept for H₂S-based interventions in patients with manifest PAH. Full article

Background/Objectives: Accurate detection of thyroid cancer using ultrasound remains a challenge, as malignant nodules can be microscopic and heterogeneous, easily confused with point clusters and borderline-featured tissues. Current studies in deep learning demonstrate good performance with convolutional neural networks (CNNs) and clustering; however, many approaches focus on local tissue and provide limited, non-quantitative interpretation, reducing clinical confidence. This study proposes an integrated framework combining enhanced convolutional feature encoders (DenseNet169 and VGG19) with an enhanced vision transformer (ViT-E) to integrate local feature and global relational context during learning, rather than delayed integration. Methods: The proposed framework integrates enhanced convolutional feature encoders (DenseNet169 and VGG19) with an enhanced vision transformer (ViT-E), enabling simultaneous learning of local feature representations and global relational context. This design allows feature fusion during the learning stage instead of delayed integration, aiming to improve diagnostic performance and interpretability in thyroid ultrasound image analysis. Results: The best-performing model, ViT-E–DenseNet169, achieved 98.5% accuracy, 98.9% sensitivity, 99.15% specificity, and 97.35% AUC, surpassing the robust basic hybrid model (CNN–XGBoost/ANN) and existing systems. A second contribution is improved interpretability, moving from mere illustration to validation. Gradient-weighted class activation mapping (Grad-CAM) maps demonstrated distinct and clinically understandable concentration patterns across various thyroid cancers: precise intralesional concentration for high-confidence malignancies (PTC = 0.968), edge/interface concentration for capsule risk patterns (PTC = 0.957), and broader-field activation consistent with infiltration concerns (PTC = 0.984), while benign scans showed low and diffuse activation (PTC = 0.002). Spatial audits reinforced this behavior (IoU/PAP: 0.72/91%, 0.65/78%, 0.58/62%). Conclusions: The integrated ViT-E–DenseNet169 framework provides highly accurate thyroid cancer detection while offering clinically meaningful interpretability through Grad-CAM-based spatial validation, supporting improved confidence in AI-assisted ultrasound diagnosis. Full article

Background and Objectives: In women who are positive for high-risk human papillomavirus (hrHPV), abnormal cytology necessitates colposcopy and biopsy; however, cytology–histology concordance is variable and may differ by menopausal status. This study aimed to evaluate the concordance between cytologic findings and biopsy results in hrHPV-positive women with abnormal Pap tests and to compare outcomes by menopausal status. Materials and Methods: This retrospective, single-center study included 904 hrHPV-positive women with abnormal cytology who underwent colposcopy. Cytology findings [atypical squamous cells of undetermined significance (ASC-US), low-grade squamous intraepithelial lesion (LSIL), atypical squamous cells—cannot exclude high-grade squamous intraepithelial lesion (ASC-H), and high-grade squamous intraepithelial lesion (HSIL)] were compared with histological findings [normal, cervical intraepithelial neoplasia (CIN)-1, -2, -3]. Menopausal status was stratified as premenopausal (<48 years) and postmenopausal (≥48 years). Rates of cyto-histologic concordance, overestimation, and underestimation were calculated. Results: The predominant cytological result was ASC-US (61.7%), followed by LSIL (25.3%), whereas histologically, CIN was most common (66.5%; CIN-1: 42.8%, CIN-2: 11.5%, CIN-3: 12.2%). Cytology–biopsy concordance was 50.7%, with overestimation in 35.4% and underestimation in 13.9%. Overestimation was highest in ASC-US (43.9%) and ASC-H (37%), while underestimation was most frequently seen in LSIL cases (27.1%). HSIL cytology showed the highest agreement (85.7%). Conversely, LSIL cytology showed higher cyto-histologic concordance in postmenopausal women, whereas ASC-H and HSIL cytologies were more commonly overestimated in comparison to premenopausal women. Using ASC-H/HSIL as the positive cytology threshold for CIN-2+ detection, sensitivity was 41.1% and specificity was 95.8% [positive predictive value (PPV) 75.2%, negative predictive value (NPV) 84.0%; overall accuracy 82.9%]. The sensitivity and NPV were higher in postmenopausal women than in premenopausal women (50.0% vs. 39.9%; 91.3% vs. 82.3%, respectively). Conclusions: Cytology–histology concordance is moderate among women who are hrHPV-positive with abnormal cytology, characterized by notable underestimation in low-grade cytology and strong predictive value in HSIL cases. Menopausal status influences the outcomes; in postmenopausal women, high-grade lesions are less frequent, and diagnostic accuracy for detecting CIN-2+ is higher. These findings highlight the need for age- and menopause-sensitive diagnostic approaches. Full article