Search Results (3,830)

Pediatric acute liver failure (PALF) is a rare but life-threatening condition characterized by rapid clinical deterioration and high mortality. Viral infections represent a major etiology of PALF, although the causative agent remains unidentified in a substantial proportion of cases. Human Enteroviruses (EVs) are typically associated with self-limiting illnesses; however, they may rarely cause severe systemic disease, including fulminant hepatitis, particularly in neonates and young children. We describe the case of a 4-year-old previously healthy male who presented with acute fulminant hepatitis secondary to systemic Echovirus 25 (E25) infection, with concomitant Epstein–Barr virus (EBV) co-infection of recent onset. The diagnosis was established through multiplex PCR on cerebrospinal fluid, blood, stool, and nasopharyngeal aspirate, with serotype confirmation by the Italian National Institute of Health. The patient required intensive supportive care including therapeutic plasma exchange (TPE), continuous kidney replacement therapy (CKRT), and intravenous immunoglobulins (IGIV). Despite initial clinical deterioration and placement on the liver transplant list, the patient achieved complete hepatic recovery and was discharged after fourteen days of hospitalization without requiring transplantation. This case highlights the importance of prompt virological workup including enterovirus PCR in children presenting with acute liver failure of undetermined etiology and supports the use of extracorporeal therapies as a bridge to recovery. Full article

Clear cell renal cell carcinoma (ccRCC) accounts for approximately 75% of renal cell carcinomas and is defined by near-universal VHL inactivation, leading to constitutive HIF stabilisation, metabolic reprogramming, and an immunologically distinct tumour microenvironment (TME). Although ccRCC is characterised by abundant immune infiltration, this paradoxically correlates with poor prognosis, reflecting a TME that imposes interconnected physical, immunological, and metabolic barriers to effective immunotherapy. Chimeric antigen receptor (CAR)-based therapies have revolutionised the treatment of haematological malignancies, but their translation to ccRCC has encountered substantial hurdles. The first-in-human trial targeting carbonic anhydrase IX (CAIX) was limited by on-target off-tumour toxicity and CAR immunogenicity—lessons that fundamentally reshaped the field. CD70 has since emerged as the dominant clinical target, expressed in over 80% of ccRCCs with a highly restricted normal tissue distribution. The phase I COBALT-RCC trial of CTX130, an allogeneic CRISPR-Cas9-edited CD70-directed CAR-T cell product, provided formal proof of concept, achieving disease control in 81.3% of heavily pretreated patients and a durable complete response now exceeding three years—the first such sustained remission reported for any CAR-T cell product in a solid malignancy. Nevertheless, the low frequency of durable responses and universal loss of CAR-T cell persistence by day 28 underscore that major barriers remain. Beyond CD70, the field has diversified across multiple platforms, including CAR–natural killer (NK) cells, CAR–natural killer T (NKT) cells, and CAR–macrophages, each offering distinct biological advantages. This review synthesises current knowledge of the ccRCC TME, the preclinical landscape of CAR-based therapies, and emerging clinical evidence from more than 30 registered trials. We discuss target antigens; engineering strategies to overcome TME barriers, including cytokine armouring, chemokine receptor co-expression, switch receptors, and metabolic reprogramming; and rational combination approaches. We argue that the convergence of optimised target selection, cellular engineering, combination strategies, and biomarker-driven trial design may ultimately improve outcomes for patients with ccRCC. However, achieving a cure remains an aspirational goal, and significant barriers must first be overcome. Full article

This study presents an interdisciplinary examination of the intersections between human capital theory, philosophical interpretations of property, and contemporary housing and aspirational patterns in Germany and the United Kingdom. Drawing upon classical economic thought, Hegel’s philosophy of right, and Marx’s theory of alienation, the analysis demonstrates that falling homeownership rates and the reorientation of youth aspirations toward non-material domains reflect the structural impossibility of realizing Eigentum—property understood as an extension of personhood. These developments exemplify what Marx termed Eigenschaftslosigkeit, the condition of being divested of essential human attributes. The findings reveal a social configuration in which the Hegelian conception of Eigentum as a universal medium for freedom has been systematically denied to younger generations while the Marxian prospect of collective emancipation remains unfulfilled. The paper does not claim that virtual environments directly substitute for material property; rather, it proposes the metaverse as a conceptual horizon that illuminates the compensatory logic of a generation structurally excluded from Eigentum. Full article

Pancreatic ductal adenocarcinoma (PDAC) is molecularly characterized by near-universal KRAS mutations and recurrent alterations in TP53, CDKN2A, and SMAD4. Gene fusions are exceptionally rare and have not been established as canonical drivers of PDAC. We report a case of metastatic PDAC harboring an EIF3E::RSPO2 gene fusion in the absence of detectable KRAS or other common driver mutations. A 48-year-old female was diagnosed with stage IV PDAC via endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). Comprehensive molecular profiling using the Oncomine Precision Assay GX5 revealed no pathogenic single-nucleotide variants, indels, or copy number variations. However, an EIF3E::RSPO2 fusion, predicted to be a gain-of-function alteration, was identified as the sole genomic alteration. Immunohistochemistry showed retained mismatch repair protein expression and preserved SMAD4. Although RSPO2 fusions have been described in preclinical colorectal cancer models and are well-established activators of the Wnt signaling pathway in this setting, their clinical occurrence in PDAC remains poorly documented. This finding indicates a KRAS wild-type tumor with a potential KRAS-independent oncogenic mechanism that may involve aberrant Wnt/β-catenin signaling and raises the possibility of a rare, biologically distinct PDAC subset. Comprehensive genomic profiling in advanced PDAC may uncover actionable non-canonical drivers with therapeutic implications. Full article

Introduction: Several Enterobacterales species harboring New Delhi metallo-β-lactamase (NDM-1) have been reported worldwide. Among them is Providencia stuartii (P. stuartii), an emerging pathogen in nosocomial infections. Objective: This study aimed to perform the clinical and genomic characterization of NDM-1-producing P. stuartii isolates recovered from hospitalized patients during the COVID-19 pandemic in Southern Brazil. Materials and Methods: A retrospective observational study was conducted between April and September 2021 at a Brazilian teaching hospital. Fifty P. stuartii isolates were identified, and carbapenem-resistant isolates underwent phenotypic and molecular characterization. Genetic relatedness was assessed by Enterobacterial Repetitive Intergenic Consensus PCR (ERIC-PCR), and selected isolates were subjected to whole-genome sequencing using the Illumina NextSeq platform to determine sequence types, resistance genes, virulence determinants, and plasmid content. Statistical analyses were performed using SPSS version 20.0. Results: Among the 50 isolates, 21 (42%) harbored the blaNDM-1 gene. Most isolates were recovered from tracheal aspirates (57.2%), followed by blood (23.8%), urine (9.5%), and skin and soft tissue samples (9.5%). Significant associations were observed between NDM-1-producing isolates and SARS-CoV-2 infection (p = 0.013), central venous catheter use (p = 0.012), mechanical ventilation (p = 0.006), hemodialysis (p = 0.033), previous antimicrobial exposure, and mortality (p = 0.021). Genomic analysis revealed the presence of blaNDM-1, blaOXA-1, and multiple resistance determinants associated with aminoglycosides, fluoroquinolones, macrolides, tetracyclines, and folate pathway inhibitors. ERIC-PCR demonstrated low genetic variability among isolates, suggesting possible clonal dissemination within the hospital environment. Conclusions: This study reports the emergence of NDM-1-producing P. stuartii during the COVID-19 pandemic in a Brazilian teaching hospital. The low genetic variability among isolates and the multidrug-resistant profile highlight the potential for nosocomial dissemination and reinforce the importance of genomic surveillance and infection control strategies. Full article

Apocrine sweat gland adenocarcinoma is an uncommon feline adnexal neoplasm, and lower-lip involvement is rarely documented. A 14-year-old spayed female Siamese cat was evaluated for a firm 1.3 cm right lower-lip mass at a documented hemorrhagic lesion site. Approximately 1 year earlier, the lesion was fluctuant and superficially erosive to ulcerative; fine-needle aspiration yielded bloody fluid with cytologically nondiagnostic material. The lesion reportedly subsided after empirical treatment, but reassessment, tissue diagnosis, and objective confirmation of resolution were not performed. Cytology of the later same-site mass supported malignant epithelial neoplasia. Contrast-enhanced computed tomography (CT) identified a 12.5 × 13.2 × 16.6 mm rim-enhancing mass without mandibular invasion or distant metastasis; the ipsilateral mandibular lymph node was mildly thickened. Histopathology supported a diagnosis of lower-lip apocrine sweat gland adenocarcinoma with lymphovascular tumor emboli, lymphatic invasion, and nodal metastasis. The diagnosis was supported by superficial dermal/subcutaneous location, adjacent adnexal structures, skeletal-muscle separation from nearby minor salivary glands, epithelial immunoreactivity, periodic acid-chiff (PAS) and Alcian blue findings without distinct intratumoral mucin/mucopolysaccharide-rich material. The cat died without necropsy on postoperative day 87. This case supports tissue-based diagnosis and regional lymph node assessment for suspicious feline lower-lip glandular epithelial lesions. Full article

Background and Objectives: Comparisons of swallowing physiology between coronavirus disease 2019 (COVID-19) pneumonia and clinically diagnosed aspiration pneumonia (AP) have largely relied on ordinal scales, leaving etiology-specific biomechanical profiles unclear. We quantitatively compared videofluoroscopic swallowing study (VFSS) measures of pharyngeal residue and clearance mechanics to identify differential dysphagia phenotypes. Materials and Methods: This single-center retrospective cohort study included 50 adult inpatients with pneumonia (COVID-19, n = 25; AP, n = 25) who underwent VFSS for suspected dysphagia. COVID-19 pneumonia was laboratory-confirmed, and AP was clinically diagnosed after negative tests for severe acute respiratory syndrome coronavirus 2. Blinded ImageJ analysis examined the first standardized semisolid yogurt swallow (International Dysphagia Diet Standardisation Initiative level 4). Primary outcomes were Normalized Residue Ratio Scale values for the valleculae (NRRSv) and piriform sinuses (NRRSp); secondary outcomes were upper esophageal sphincter (UES) opening width and epiglottic rotation angle. Penetration–Aspiration Scale (PAS) score, hyoid displacement, and pharyngeal transit time were exploratory. Results: Baseline characteristics were comparable. COVID-19 pneumonia showed higher NRRSv (0.20 [0.12–0.56] vs. 0.13 [0.00–0.20]; p = 0.01). NRRSp was numerically higher but not statistically significant (0.12 [0.00–0.43] vs. 0.00 [0.00–0.17]; p = 0.07). COVID-19 pneumonia also showed smaller UES opening width (5.08 ± 2.48 vs. 6.50 ± 2.01 mm; p = 0.03) and reduced epiglottic rotation angle (66.0 [29.0–80.8] vs. 93.4 [74.2–100.4] degrees; p = 0.04). No statistically significant between-group difference was detected in PAS-defined airway invasion severity on the standardized semisolid task. Conclusions: These findings suggest an efficiency-predominant dysphagia phenotype in COVID-19 pneumonia, characterized by greater vallecular residue and restrictive clearance-related mechanics on a standardized semisolid task. The results indicate that PAS-defined safety metrics alone may underestimate residue-related dysphagia burden in this population. Full article

The EU EFACA project considers two conceptual aircraft design configurations for cleaning European air traffic in future decades. Recently, several different technologies have led to propulsion designs with potential to reduce greenhouse gas emissions and replace existing conventional engine technologies—such as the use of fossil fuel—for aviation. The results of an assessment of the environmental impacts of new technologies are considered using a multidimensional approach, ranging from aircraft certification requirements (noise, local and global engine emission, and aircraft fuel efficiency) to regional/global assessments of new designs in air traffic. Each technology for factor reduction is simulated and compared to a reference, usually the aircraft currently best in its class, providing the possibility of assessing the efficiency of the technology, both for necessary certification requirements and for the forecasted operational conditions due to ICAO long-term aspirational goals and ACARE Fly Green Deal goals. Full article

This article investigates the intricate interplay between ressentiment—as social emotion—social love, and solidarity in democratic societies, focusing on the urban environment as the primary stage where these processes materialize. Far from being a marginal emotion, ressentiment is deeply intertwined with democratic life, arising from the gap between proclaimed values and lived conditions. It represents an affective reaction to the perceived betrayal of the promise of equality inscribed in democratic ideals. The discussion explores how perceptions of injustice can fracture trust and intensify divisions, but also how they, under certain conditions, can be redirected toward political engagement and common action. The city, characterized by density, diversity, and the continuous negotiation of difference, can serve as a privileged arena for this transformation. Urban space does not merely reflect inequalities; it actively shapes social processes and provides the infrastructure through which collective sentiments are articulated. In this context, “social love” is conceptualized not as a sentimental aspiration, but as a relational force capable of redirecting the moral indignation of ressentiment, far from strategies of grievance politics toward constructive forms of social and political belonging. Cities can function as laboratories of solidarity where grievances are reframed into collective projects that strengthen social cohesion. Mitigating the destructive potential of ressentiment requires addressing its structural roots through inclusive urban policies and dialogical spaces. An approach grounded in social love can counter fragmentation, mobilizing emotions in the service of substantive equality. In this perspective, the city can become a space and a laboratory for change, where resentment can be channeled as a generative force capable of sustaining widespread forms of social love and a sense of the common good. Full article

Flow cytometry is an essential diagnostic method in hematology, and one of its main applications is the assessment of the clonality of mature B cells. We present a case report of a patient referred for the investigation of absolute lymphocytosis. The flow cytometry study revealed an increased percentage of B cells, but it could not establish B-cell clonality, based on the study of surface light chains in combination with the pattern of expression of mature B-cell markers. The diagnosis of Persistent Polyclonal B-cell Lymphocytosis (PPBL) was considered in the differential diagnosis as the mature B cells were found to be immunophenotypically memory B cells. However, due to the markedly elevated count of B cells, molecular testing with Polymerase Chain Reaction (PCR) for B-cell clonality based on IGH (Immunoglobulin Heavy Chain) gene rearrangements was performed, and it revealed the presence of two clones of B cells. Approximately one year later, the same work-up was repeated in the patient’s bone marrow aspirate. By flow cytometry, a distinct clonal B-cell population was isolated, while the molecular testing with PCR for B cell clonality based on IGH heavy-chain gene rearrangements revealed the presence of three clones of B cells. In addition, evaluation of the sample with high-dimensional mass cytometry showed the presence of four major immunophenotypically abnormal B-cell subsets. Full article

Background/Objectives: Type 2 diabetes may impair anterior segment immune regulation. Because transforming growth factor-β2 maintains ocular immune privilege, while nuclear factor-κB is linked to inflammatory activation, we compared their aqueous humor levels in cataract patients with and without diabetes. Methods: In this prospective cross-sectional study, aqueous humor samples were collected from 90 patients (30 diabetic, 60 non-diabetic) via anterior chamber needle aspiration at the commencement of routine phacoemulsification, prior to viscoelastic injection, without additional intervention. Transforming growth factor-β2 and nuclear factor-κB levels were then measured using enzyme-linked immunosorbent assay (ELISA). Between-group comparisons and ROC curve analyses were performed to evaluate differences in biomarker levels and their discriminative ability in distinguishing diabetic status. Covariate-adjusted analysis (ANCOVA) was additionally performed. Results: Transforming growth factor-β2 levels were significantly lower in the diabetic group (p < 0.001), while nuclear factor-κB levels showed no significant difference (p = 0.285). The between-group difference in transforming growth factor-β2 remained significant after adjustment for cataract grade and hypertension duration (F(1,86) = 17.901, p < 0.001, partial η² = 0.172; Cohen’s d = 0.94). Transforming growth factor-β2 demonstrated high specificity (100%) but limited sensitivity (45%) for identifying diabetic status at a cut-off of <449.25 ng/L; however, given the small sample size and exploratory nature of the study, this specificity value should be interpreted with caution and requires validation in larger cohorts. Conclusions: Lower aqueous humor TGF-β2 levels in diabetic cataract patients, independent of cataract severity and hypertension duration, suggest that TGF-β2 suppression may represent an earlier molecular event in anterior segment immune dysregulation preceding overt inflammatory activation. While TGF-β2 shows exploratory biomarker potential, validation in larger, prospective, mechanistic studies is required before clinical application. Full article

Vernacular housing in the Andean region embodies long-standing building knowledge, environmental adaptation, and forms of social organization rooted in rural life. Over recent decades, these dwellings have undergone visible transformations linked to migration, changing aspirations, and the growing presence of industrialized construction materials. Rather than disappearing, vernacular forms have increasingly merged with contemporary solutions, producing hybrid architectural landscapes whose local dynamics are still insufficiently documented. This study analyzes the material, typological, and functional transformation of rural housing in Las Lagunas and Quisquinchir, two Indigenous communities located in Saraguro, Loja, Ecuador. A total of 192 houses were recorded through field observation and a structured digital survey implemented with KoBoCollect. The information was processed in R using descriptive statistics, contingency tables, chi-square tests, Cramér’s V, and standardized residual analysis. The findings show that architectural change in both communities does not occur through a simple replacement of traditional housing by modern models. Instead, vernacular, hybrid, and modern/eclectic typologies coexist within the same rural setting, revealing uneven and locally specific processes of transformation. The clearest differences emerge in construction materiality. Las Lagunas preserves a stronger presence of traditional wall systems, especially adobe and bahareque, while Quisquinchir shows a broader incorporation of industrialized materials, particularly concrete block. Statistical analysis confirmed significant associations between community and wall material, as well as between typology and wall material, whereas the relationship between community and architectural typology was comparatively weaker. Functional changes were also identified through the reduction or reconfiguration of intermediate spaces such as portals, patios, and corridors, suggesting a gradual shift toward more enclosed and specialized domestic environments. These results contribute empirical evidence for understanding architectural hybridization in Indigenous rural territories and support conservation and planning approaches capable of recognizing continuity, adaptation, and change within evolving Andean built landscapes. Full article

For students in animal science-related disciplines, animal welfare education may be associated with their understanding of human–animal relationships and willingness to pursue animal-related careers. However, empirical research from developing countries such as China remains limited. To address this gap, we conducted a survey among undergraduates at Northeast Agricultural University to examine the associations of demographic characteristics, educational exposure, and animal-related experiences with animal welfare awareness and career aspirations. A total of 346 valid responses were obtained. The results showed that students who encountered animal welfare through school demonstrated significantly higher levels of self-reported animal welfare awareness (p < 0.001). Binary logistic regression further confirmed that the channel remained significantly associated with the level of awareness (OR = 8.714, p < 0.001). Furthermore, gender and pet-keeping experience were significantly associated with career aspirations in both univariate and logistic regression analysis. In addition, although 50.00% of respondents considered primary school to be the optimal stage for animal welfare education, 81.48% of those exposed through school channels reported their first exposure at university. These findings highlight the need for a progressive animal welfare education framework, transitioning from life education and human–animal relationship training at the primary level to professional practice education in higher education. This approach may help students develop more stable and scientifically informed understanding of animal welfare, as well as a stronger sense of professional identity. Full article

Background/Objectives: Dysphagia is a prevalent consequence of neurological conditions, particularly stroke and Parkinson’s disease, leading to aspiration pneumonia and reduced quality of life. Currently, there are no specific recommendations for pharmacological therapy, although studies indicate that elevated substance P levels may improve swallowing function. While nicergoline is known to increase substance P, the role of its major metabolite, 10-methoxy-dihydro-lysergol (MDL), in this therapeutic effect remains unclear. This study examined the therapeutic effects of nicergoline and its correlation with substance P and MDL levels. Methods: This study conducted an open-label pilot study with historical controls in neurogenic patients with dysphagia. The primary outcome was improvement in the Gugging Swallowing Screen (GUSS) scores at week 12. Secondary outcomes included choking frequency, serum substance P levels, and the correlation between serum MDL levels and dysphagia enhancement. Inverse Probability Weighting (IPW) was employed to adjust for baseline confounders. Results: A total of 92 patients were analyzed: 26 in the nicergoline group (20 or 60 mg/day) and 66 in the historical control group. Compared to controls, the nicergoline group exhibited significantly higher median of GUSS scores (20 (IQR: 19–20) vs. 15 (IQR: 9–19), p < 0.001) and significantly lower median of choking frequency (6.43 (IQR 0–17) vs. 108 (IQR 13–201) 105.22, p < 0.001). The median substance P concentration in the therapy group was 4089.15 (IQR: 3336.13–4468.26) pg/mL. Patients receiving nicergoline showed a statistically significant elevation in substance P from baseline (p < 0.001). Pearson analysis revealed a negligible correlation between serum MDL and substance P levels (R² = 0.0349). Conclusions: Preliminary findings suggest that nicergoline may be associated with improvements in swallowing function in neurogenic dysphagia and a potential increase in substance P levels. The lack of correlation with serum MDL suggests that efficacy may not linearly depend on circulating metabolite concentrations. Further large-scale randomized controlled trials are warranted. Full article

Air temperature measurements in atmospheric environmental monitoring are susceptible to radiation-induced bias under natural ventilation. This study develops a low-power naturally ventilated air temperature sensor and a correction method combining computational fluid dynamics (CFD) with machine learning. The sensor integrates a Pt100 thin-film platinum resistance probe (Heraeus Holding GmbH, Hanau, Germany), symmetric guide plates, and a dual aluminum-plate radiation shield to reduce radiative heating while improving airflow around the probe. A three-dimensional fluid–solid coupled heat-transfer model was established in ANSYS FLUENT 15.0 to optimize guide-plate spacing and inclination angle and quantify the effects of solar radiation, long-wave radiation, scattered radiation, air density, wind speed, solar elevation angle, and surface albedo on radiation error. CFD results identified a guide-plate spacing of 24 mm and an inclination angle of 45° as the preferred parameters. A multilayer perceptron (MLP) model trained with CFD-derived data was validated in field experiments using a Model 076B aspirated radiation shield (Met One Instruments, Inc., Grants Pass, OR, USA) as the reference. The model predicted radiation error with a root mean square error (RMSE) of 0.052 °C, a mean absolute error (MAE) of 0.042 °C, and a correlation coefficient of 0.92. The proposed sensor and correction method provide a low-power and easy-to-maintain approach for reducing radiation-induced bias in naturally ventilated air-temperature measurements, with potential applications in meteorological observation, air-quality monitoring, and agricultural microclimate assessment. Full article