Search Results (518)

Background: Vertebral column resection (VCR) has historically been recognized as the most efficacious corrective intervention for severe rigid spinal deformities. Nevertheless, advancements in preoperative optimization, staged corrective methodologies, osteotomies, and contemporary instrumentation have broadened the spectrum of therapeutic options available. The definitive role of VCR in the modern management of rigid congenital spinal deformities remains a topic of ongoing scholarly discourse. Methods: This study presents two illustrative cases of severe congenital spinal deformities that were addressed employing various surgical methodologies, alongside a comprehensive review of the current literature pertaining to VCR and less invasive alternatives, including halo-gravity traction (HGT), temporary internal distraction techniques, pedicle subtraction osteotomy (PSO), asymmetric pedicle subtraction osteotomy (APSO), and multi-rod constructs. Results: The cases elucidated herein underscore the necessity for treatment strategies to be tailored specifically to the characteristics of the deformity, its flexibility, the neurological risks involved, and the individual patient’s specific attributes. In one case, significant deformity correction achieved via preoperative HGT facilitated successful management through multilevel Ponte osteotomies and posterior spinal fusion, thereby obviating the need for VCR. In other patient suffering from severe rigid congenital kyphotic deformity with pronounced anterior column deficiencies, VCR was deemed essential to realize adequate correction and neural decompression. All patients exhibited substantial radiographic correction, enhancements in health-related quality-of-life metrics, diminished disability and pain, while maintaining correction without neurological complications or implant failure at the final follow-up evaluation. Conclusions: VCR continues to be a vital element within the surgical repertoire for the treatment of severe rigid spinal deformities; however, it should not be deemed obligatory in every instance. Diligent preoperative evaluation, staged correction methodologies, and less invasive osteotomy techniques may permit satisfactory correction while mitigating surgical morbidity in suitably selected patients. Treatment approaches should be customized, favoring the least invasive procedure capable of achieving safe and lasting correction whenever practicable. Full article

Background/Objectives: Denture disinfection is a crucial step in reducing microbial colonization and the risk of denture stomatitis, as well as contributing to patient health and denture longevity; thus, it was obligatory to select an effective cleanser without undesirable impact on properties of acrylic denture base material. This study aimed to assess the synergistic effect of white vinegar and sodium bicarbonate (WVSB) mixture on Candida albicans by means of colony forming unit (CFU) and adhesion assays, as well as the surface roughness and flexural strength of heat-cured acrylic denture base material after being immersed in the WVSB mixture. Methods: In total, 200 specimens of heat-cured acrylic resin were prepared: 50 per each test, 5 per each group. They were divided into ten groups; distilled water (negative control), a Corega denture cleanser tablet soaked for 5 min (positive control), and four concentrations (2%, 3%, 4% and 5%) of WVSB mixture were made and examined for (5 and 10 min) immersion durations. Statistical analysis was performed by using Welch’s ANOVA alongside Games–Howell post hoc tests for CFU assay and one-way ANOVA along with Tukey HSD post hoc tests for remaining tests. A p < 0.05 was considered significant in all experiments. Results: The results for the CFU, adhesion and surface roughness tests showed that the WVSB mixture demonstrated a statistically significant difference in most test groups compared to the negative control group, while the flexural strength test showed a statistically non-significant difference. Conclusions: The WVSB mixture showed concentration and time-dependent antifungal effects against C. albicans, with increased surface roughness and no negative effect on the flexural strength of heat-cure acrylic. Full article

With the expanding application of digital technologies in urban renewal, more effective ways of incorporating dispersed public experience and needs into the renewal process still require further exploration. To address this issue, this research innovatively proposes an AI-assisted renewal method for historic districts driven by urban memory, constructing a continuous methodological chain from the identification of public evaluations to problem translation, to scheme generation and feedback validation. This research integrates the concept of interessement devices from Actor-Network Theory (ANT) with generative AI technologies for case application and validation. Taking Hanzheng Street as a case study, this research extracts the public’s urban memory of the historic district from online comments and identifies renewal demands. These demands were further associated with urban image elements to clarify their spatial carriers and support the subsequent generation of scene-based renewal schemes. On this basis, AI-generated images are further used to present renewed scenarios, and public evaluations of the renewal effects are collected. The results show that urban memory of Hanzheng Street can be summarized into five themes, which were further translated into five obligatory passage points (OPPs), one core issue, and corresponding renewal demands for scene units. The renewal schemes generated through this method achieved a relatively high level of public recognition overall, with mean evaluation scores ranging from 4.10 to 4.27, an overall satisfaction mean of 4.19, and a Top-2 proportion of 82.8%. By incorporating public experience into the formation of renewal schemes, this research provides a people-oriented and effective pathway for participation and feedback in the renewal of historic districts, while also offering methodological reference for the renewal of similar historic districts. Full article

Lack of recombination in parthenogenetic organisms limits their ability to adapt to changing environments by natural selection. However, some obligatory parthenogens, such as rock lizards of the genus Darevskia, could survive for millions of years across multiple Pleistocene glaciations. There are different explanations for this phenomenon. Analysis of phenotypic variation may shed further light on the high adaptability of the parthenogenetic lizards. We compared the genetic and phenotypic variability of 186 individuals of the parthenogenetic Darevskia dahli and 54 individuals of its sexually reproducing paternal species, D. portschinskii, whose ranges almost coincide in Georgia (the Caucasus). The analysis showed that, despite the higher genetic variability of the individuals and metapopulations of D. portschinskii, phenotypic variability (as measured by KW dispersion and the normalized effective number of individuals per metapopulation), based on the nominal traits, was almost equal in the two species. Moreover, phenotypes of the parthenogen correlated with the distances among the localities, and with the annual rainfall level at a locality. The latter species also had more outlier phenotypes. Phenotypic plasticity may be a strategy for adaptation of parthenogenetic rock lizards, to a certain extent, compensating for the lack of genetic diversity. Full article

This article explores the specificity of social assistance conducted by the Romanian Orthodox Church (ROC) compared to Faith-Based Organizations (FBOs) in the UK, USA, and France. The article is a secondary qualitative analysis of a circumscribed subset of the interview material assembled in a wider mixed-methods study on the professionalization of charity in the ROC, pursuing a different research question—the configurational specificity of the Orthodox model—than the parent study itself. Using Grounded Theory methodology on the corpus of nineteen interviews with clergy, social workers, and experts from Northeastern Romania, the analysis develops the category of the sacralization of social assistance—a configuration of practices and meanings in which the spiritual dimension is structurally integrated, sacramentally obligatory, and clerically authorized. While each of these features has been documented individually in Protestant and Catholic faith-based organizations, their joint configuration in the Romanian Orthodox case differs in degree and arrangement from patterns reported in the Western literature. A theoretically informed contrast with that literature highlights six dimensions along which the ROC configuration, as articulated by providers, diverges from the patterns most frequently reported in that literature: (1) the spiritual dimension is structurally integrated in ROC versus optional in UK/USA or institutionally absent in France; (2) leadership remains predominantly clerical versus secularly professionalized in the West; (3) the beneficiary is conceptualized as a living icon of Christ versus a person with civil rights; (4) the purpose of interventions is soteriological versus immanent social reintegration; (5) professionalization generates anxiety about secularization versus comfortable normalization; (6) volunteerism remains informal-communitarian versus formalized-systematic. The research proposes a dual-axis typology that differentiates between the presence and the nature of the spiritual dimension. Full article

Feline coronavirus (FCoV) is widespread in multi-cat environments. Although most infections are asymptomatic, FCoV may mutate into a virulent form responsible for feline infectious peritonitis (FIP), a progressive and mostly fatal systemic disease. Controlling FCoV circulation in multi-cat environments is challenging, but desirable for feline health and breeding management. In this study, we evaluated the impact of stepwise management protocols with increasing stringency on viral shedding in 20 catteries across Flanders, Belgium. Each cattery was allocated to one of three eradication protocols: voluntary (n = 10), stimulatory (n = 5) or obligatory (n = 5). Rectal swabs were collected at the start (T0) and twice after implementation (T6m = 6 months, T12m = 12 months) and tested by RT-qPCR. With the voluntary protocol, the proportion of shedders decreased significantly from 78.6% at T0 to 62.4% at T6m and 45.5% at T12m, though all catteries remained positive (minimum one shedder). The stimulatory protocol reduced shedding from 70.5% (T0) to 30.5% at T6m and 12.9% at T12m, with two of five catteries achieving a negative status. The obligatory eradication protocol achieved the most pronounced effect, with the shedding declining from 55.5% at the start to 17.1% at T6m and 2.5% at T12m, and four of five catteries testing negative by T12m. These findings demonstrate that cattery-level FCoV control is feasible, with an effectiveness depending on the stringency of management. At the end, FCoV-negative catteries can sell certified FCoV-negative kittens. Full article

Voltage-gated ion channels are central regulators of cardiac, neuronal, and skeletal muscle excitability, and their dysfunction underlies a wide spectrum of channelopathies, including arrhythmias and neuromuscular disorders. While conventional ion channel therapeutics typically target a single pore-binding site, emerging evidence supports the therapeutic potential of polypharmacological compounds capable of modulating multiple channel subtypes. ARumenamides represent a novel class of sulfonamide-based ligands originally identified as fenestration-targeting sodium channel modulators; however, their cross-family binding mechanisms and multitarget potential remain incompletely defined. Here, we employed an integrated structure-based computational workflow combining molecular docking, in silico ADMET profiling, and long-timescale (250 ns) molecular dynamics simulations to systematically evaluate 20 ARumenamide derivatives across 15 voltage-gated sodium, calcium, and potassium channel structures. Docking analyses revealed broad multitarget binding profiles, with several compounds exhibiting high predicted affinity across cardiac, neuronal, and skeletal muscle channel isoforms. ADMET predictions demonstrated favorable intestinal absorption and metabolic safety for most candidates, although solubility and mutagenicity liabilities were identified for select derivatives. Detailed molecular dynamics simulations of prioritized compounds (AR-310, AR-769, and AR-946) uncovered site-specific binding behaviors and conformational effects. AR-769 exhibited exceptional stability at both fenestration and central pore sites of Cav1.2, associated with persistent hydrogen-bond networks, reduced protein flexibility, and a well-defined free energy minimum. In contrast, AR-310 and AR-946 displayed selective stability within Nav1.4 fenestrations and the Kv4.3 central pore, respectively, highlighting how subtle chemical features bias binding site preference and dynamic retention. Collectively, these findings establish a structure–dynamics framework for rational design of ARumenamide-based multitarget ion channel modulators. Our results demonstrate that fenestration-focused binding can support sustained ligand engagement without obligatory pore occlusion, offering a mechanistically distinct strategy for developing next-generation polypharmacological therapeutics for cardiac and neuromuscular disorders. Full article

In many African languages, there exists a type of subject–object asymmetry by which subject focus must be expressed by A-bar movement to a morphologically marked left peripheral position whereas object focalisation can be expressed by movement and morphological marking in the left periphery, or in situ. In this article, we discuss and analyse this structural asymmetry in the Bantu languages Basaá and Mmaala. We argue that overt and covert movement of the focused object to Spec-FocP in the left periphery is allowed while covert movement of the subject is blocked, so that overt movement is the only possible option. Contrary to previous analyses, which attribute the obligatoriness of subject focus movement and marking to an interpretive conflict, we propose a formal characterisation of this phenomenon by which the blocking of subject focalisation in situ is deduced from criterial freezing, so that overt movement to the left periphery is the only option, through a familiar strategy of overt subject extraction. Full article

Saline–alkali stress severely limits crop production worldwide. Soybean [Glycine max (L.) Merr.] is particularly sensitive during seed germination, a stage critical for stand establishment. This complex stress environment encompasses two distinct yet equally critical dimensions: neutral salt stress and alkaline salt stress, each eliciting specialized physiological and metabolic responses. Here, a comparative assessment of four genotypes (tolerant: CN16, CN17; sensitive: Williams 82, K18) under 100 mmol/L Na⁺ revealed that alkaline salt stress exerts a significantly more potent inhibitory effect than neutral salt stress. Tolerant cultivars maintained 75–80% germination under alkaline conditions, whereas sensitive ones dropped below 15%, a divergence primarily driven by superior oxidative mitigation capacity. Integrated multi-omics analysis of the tolerant variety CN16 identified stage-specific regulatory shifts: early alkaline salt stress (60 h) triggers extensive transcriptional reprogramming focused on physical barrier reinforcement, including cell walls and lipid remodeling. By 96 h, regulatory modes between the two stress types diverged: neutral salt elicited a transcriptional surge, while alkaline salt transitioned to a metabolically dominant regulation, shifting flux from growth-related isoflavonoids to defense-related anthocyanins. Crucially, this study uncovers the distinct bioenergetic trade-offs governing these responses: whereas adaptation to neutral salt relies on low-energy galactose metabolism, tolerance to alkaline salt demands energy-intensive processes, specifically the active vacuolar compartmentalization of organic acids and anthocyanins for intracellular buffering. This obligatory energy expenditure restricts biomass accumulation, explaining the severe growth penalties observed in complex saline-alkali environments. Finally, the identification of a core regulatory module driven by key genes, including GmPHOT2b, GmLOG, and GmSHMT08, enriches the metabolic regulatory network under saline-alkali stress, providing core targets and a theoretical framework for precisely balancing metabolic expenditure with biomass accumulation in breeding practice. Full article

Background: Evaporative water loss from burn wounds is a major but often neglected component of early fluid requirements. Despite its physiological importance, no dedicated review has quantified acute post-burn evaporative water loss (TEWL) and its interaction with modern resuscitation strategies in over 40 years. Recent mass-casualty burn events in specialized centers have re-emphasized the clinical importance of accurate early fluid balance, which is particularly challenging. Methods: A scoping review (PRISMA-ScR) of historical quantitative studies and 23 contemporary (2015–2025) adult major-burn resuscitation cohorts was conducted. Expected TEWL was derived from Lamke benchmarks; interstitial edema was estimated from the only available regression of simultaneous fluid input and 24 h weight change. A novel TEWL/edema ratio was tested against resuscitation volume (mL/kg/%TBSA) and the established input/output (I/O) ratio. Results: In the acute phase, the median TEWL normalized to total body surface area was 71 mL/m²/h [52–79 mL/m²/h], allowing for calculation of the TEWL/edema ratio. The TEWL/edema ratio was inversely correlated with the resuscitation fluid dose (R² = 0.811) and the I/O ratio as well (R² = 0.86), crossing unity at 2.85 mL/kg/%TBSA. A ratio > 1 signals high evaporative drive and/or possible under-resuscitation; a ratio < 1 alerts to fluid creep before significant weight gain. Conclusions: The TEWL/edema ratio is the first physiology-grounded, easily calculable resuscitation endpoint that complements urine output by providing insight into whether administered fluid is lost as obligatory evaporation or sequestered as edema. Routine estimation of expected TEWL and early monitoring of the TEWL/edema ratio may help guide goal-directed burn resuscitation, especially when early excision is delayed or impossible. Given the substantial inter-individual variability, the ratio derived from aggregate data should not be interpreted as a patient-specific predictor. Full article

Medium voltage induction motors (MVIM) are a key component of numerous industries, such as water treatment plants, sewage discharge stations, and chilled water systems. The starting process for these MV motors is critical as it is associated with a major impact on both motor lifetime and power grid quality. In this article, a proposed modified and comprehensive starting scheme of MV three-phase induction motors driving pumps for water stations is introduced. Firstly, the starting performance and its impact on power grid quality will be discussed when all motors are normally started with direct on line connection (DOL), which is already the normal established status. A modified starting scheme based on an optimized coordination of motor starting methods in addition to variable voltage variable frequency drive (VVVFD) drive and control implementation will be discussed. A transition between the starting of variant MV induction motors as well as the starting event coordination principle will be discussed to improve the power quality relative to the obligatory time shift required for the operation. The coordination is based on an algorithm implementation which is achieved using different optimization concepts based on artificial intelligence techniques, properly conducting the transition time in addition to the power delivered by the inverter unit rather than determining the number of DOL and VVVF-implemented motors. A comparison between using the optimized VVVFD soft-starting and the proposed modified scheme is performed, focusing on the power quality improvement rather than optimizing the cost function. The modified scheme is simulated using ETAP power station for brief analysis and study of load flow rather than the complete inspection and power quality assessment. Full article

It has long been recognized that the oxygen reduction reaction occurs more readily on Pt(111) surfaces that include steps, both (111) and (100), than on near-perfect Pt(111). Theoretical models were developed involving the water structure in the electric double layer and its interactions with adsorbed OH, with the actual O₂ reduction occurring on the (111) terraces adjacent to the steps. However, the present density functional theory (DFT) calculations confirms that O₂ adsorbs strongly at the steps and can undergo dissociation aided by adjacent water molecules to produce adsorbed OH. OH produced at the steps can move to the (111) terraces, where it can be more readily reduced to H₂O and desorbed. This model avoids the scaling relation, which predicts that all oxygen-containing reactants and intermediates are proportional to each other on any given surface, i.e., strong O₂ adsorption at steps compared with water ensures that the reaction can proceed. Efforts to develop new O₂ reduction catalysts have been hampered by the assumption that the reaction rate can be increased by decreasing OH adsorption strength, even though decreased OH adsorption strength is accompanied by decreased O₂ adsorption strength on any given crystallographic facet. This proposed model can explain the experimental results on stepped surfaces as well as nanoparticle catalysts, particularly the higher ORR activity on alloys such as PtFe, but with the obligatory presence of steps. The results may also be important for the development of Pt nanoparticle catalysts. Full article

The progressive decline in functional β-cell mass in Type 2 Diabetes (T2D) is increasingly recognized not as a simple apoptotic loss, but as a complex erosion of cellular identity termed “dedifferentiation.” Central to this phenotypic shift is the metabolo-epigenetic axis, where mitochondria act as the primary sensing hub, transducing nutrient flux into biochemical signals that govern the chromatin landscape. This review synthesizes current evidence on how mitochondrial metabolites—including Acetyl-CoA, α-ketoglutarate, and NAD+—serve as obligatory co-factors for the epigenetic machinery. We explore how chronic metabolic stress triggers a “Systemic epigenetic destabilization,” leading to the loss of lineage-specific markers and the formation of persistent “metabolic scars.” Furthermore, we discuss the clinical implications of these changes, specifically regarding the phenomenon of metabolic memory and the molecular limits of β-cell reversibility. By integrating foundational transcriptional studies with emerging epigenomic data, we propose that targeting the mitochondrial–epigenetic axis offers a strategic window for re-differentiating failing β-cells and restoring glycemic homeostasis. 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

In (colloquial) Italian, the fixed expression mi sa functions as an evidential/epistemic marker, requiring the dative 1SG clitic experiencer and the 3SG default form of the verb sapere. Mi sa diachronically develops from the verb for taste/smell, sapere, which is still productive in contemporary Italian, and the structure that it projects. This comprises an obligatory PP introduced by di encoding the type/quality of taste/smell (often metaphorically extended); a subject expressing the perceived entity; and an optional dative experiencer. We systematically analyzed data from the KIParla corpus, comparing the distribution of mi sa to the distribution of one of the most frequent Italian epistemic verb forms, namely, credo ‘I believe’. This study aimed to establish how the original perceptual meaning of mi sa influences its epistemic meaning. The results suggest that the persistence of the original object-oriented perception verb makes mi sa more likely to appear in particular contexts, i.e., events/situations that are known by the speaker through an inferential-like process. Furthermore, mi sa can only rarely be uttered out of the blue and seems to need a situative context (a stage), often containing an explicit QUD. Full article