Search Results (254)

Background and Objectives: While transurethral resection of the prostate remains the gold standard for surgical treatment of benign prostatic hyperplasia, anatomical endoscopic enucleation of the prostate provides a safe, durable, and size-independent alternative. Our study introduces a specific technical innovation, i.e., en bloc bipolar prostate enucleation performed exclusively via sheath-tip mechanical dissection without the use of a dedicated enucleation loop, combined with the mushroom technique and early apical release. Materials and Methods: Between January 2018 and May 2023, 252 patients with prostate volumes > 30 mL and significant lower urinary tract symptoms underwent en bloc bipolar prostate enucleation via the mushroom technique with early apical release. Data were retrospectively evaluated to assess perioperative results, postoperative outcomes, and complications. Results: The median age of the cohort was 70 (65–76) years, with a median prostate volume of 60 (40–88.5) mL. The median operative time was 40 (30–70) min, and the median weight of enucleated tissue was 34 (16.5–60) g. Significant improvements were observed in the International Prostate Symptom score, Quality of Life score, maximum flow rate, average flow rate, and postvoid residual urine at 12 months (p < 0.001). The rate of transient stress urinary incontinence decreased from 19.44% at 1 month to 2.38% at 12 months. Conclusions: En bloc bipolar prostate enucleation using the mushroom technique is a safe and effective treatment for benign prostatic hyperplasia, yielding significant improvements in urinary symptoms and flow rates, with a manageable complication profile. Further multicenter studies are needed to confirm these findings. Full article

Background/Objectives: Monoclonal antibody (mAb) stability is critical not only during manufacturing but also at the point of clinical administration. For therapies like tislelizumab (Tevimbra), a programmed death-1 (PD-1) targeting IgG mAb, delays in dosing often result in prepared infusions being discarded, contributing to substantial drug waste despite being engineered for improved stability. Methods: To evaluate the physicochemical in-use stability of tislelizumab in a ready-to-administer format, we mapped degradation pathways, including post-translational modifications (PTMs); peptide alterations; pH and solution characteristics—under 12-month storage (ultra-long), under 1-month storage (0, 7, 14, 21, 28 and 31 days), and under exposure-related forced degradation conditions including room temperature, elevated temperature, pH (acidic/basic), oxidation and UV exposure. Structural analysis was contextualised to the known PD-1 binding site, making stability assessment relevant to tislelizumab’s mechanism-of-action in blocking PD-1. To assess solution stability, a validated size-exclusion chromatography (SEC) assay was applied to all conditions. Results: Aggregation was identified as the primary degradation pathway during ultra-long-term storage. SEC and chemical assessment revealed no measurable changes in protein quantity, aggregation, peptide integrity, or PTM profile over 31 days at 2–8 °C in polyolefin intravenous bags (1.6 mg/mL). Conclusions: These results support the structural and physicochemical stability of tislelizumab under refrigerated conditions. Full article

Ischemic stroke remains a leading cause of mortality and disability worldwide, with current therapies such as intravenous thrombolysis and mechanical thrombectomy benefiting only a limited proportion of patients. Neuroinflammation is a key contributor to secondary brain injury, creating a strong rationale for adjunctive therapies targeting immune modulation. Fingolimod, a sphingosine-1-phosphate receptor (S1PR) modulator originally approved for multiple sclerosis, has shown promising effects in both preclinical and early clinical studies of acute ischemic stroke. Methods: We conducted a structured narrative review of preclinical and clinical studies published between 2015 and 2024, using PubMed, Scopus, and Web of Science databases. Inclusion criteria were original studies evaluating fingolimod in ischemic stroke models or human patients, either as monotherapy or in combination with reperfusion therapies. Exclusion criteria included conference abstracts without peer review, studies lacking mechanistic insight, and non-English publications. Results: Preclinical evidence demonstrates that fingolimod reduces infarct size, preserves blood–brain barrier integrity, and modulates neuroinflammation through multiple mechanisms, including T cell sequestration, microglial polarization, and mitochondrial protection. Clinical trials, though limited in size, suggest improved short- and long-term outcomes when fingolimod is used in combination with intravenous thrombolysis or endovascular therapy, with a manageable safety profile. Novel nanotechnology-based delivery systems further enhance central nervous system (CNS) targeting and reduce systemic side effects. Conclusions: Fingolimod represents a promising multi-targeted adjunctive strategy for ischemic stroke, acting at the intersection of immune modulation, vascular protection, and neuroprotection. While current findings are encouraging, larger randomized controlled trials and biomarker-driven patient selection are needed to validate its clinical utility. This review highlights the translational potential of fingolimod and outlines key directions for future research. Full article

To express and purify staphylococcal enterotoxin M (SEM) using immobilized metal affinity chromatography (IMAC), a signal peptide-truncated (ΔNsp) wild-type SEM (SEM_WT) was N-terminally fused in pET-28a(+) to a polyhistidine tag (His_6×-) and thrombin cleavage site (TCS; LVPR↓GS), generating His_6×-TCS-ΔNspSEM_WT. Unexpectedly, 4 °C desalting reduced the fusion protein’s molecular weight by ~2.0 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). N-terminal sequencing and mass spectrometry identified cleavage specifically at the arginine (R) and glycine (G) peptide bond (R–G bond) within the TCS motif. AlphaFold 3 revealed an exposed serine protease catalytic triad: histidine 172, serine 178, and aspartic acid 212 (H₁₇₂/S₁₇₈/D₂₁₂) in the β-grasp domain, suggesting intrinsic thrombin-like activity (TLA). Sequential IMAC and size-exclusion high-performance liquid chromatography (SE-HPLC) purification eliminated contaminant concerns, while chromogenic substrate S-2238 (S-2238) assays demonstrated increasing specific activity and purification fold, supporting intrinsic TLA. Critically, the mutation of serine at position 178 to alanine (His_6×-TCS-ΔNspSEM_S178A) abolished TLA but preserved the secondary/tertiary structure, confirming the activity’s origin within the wild-type construct. Molecular dynamics (MD) simulations probed the atomistic mechanism for specific R–G bond cleavage. This work establishes a foundation for understanding ΔNspSEM_WT’s TLA. Full article

This study presents a systematic review and bibliometric analysis of the relationship between sustainability practices—commonly framed within the environmental, social, and governance (ESG) framework—and both corporate value creation and financial risk mitigation. Our primary objective is to assess how ESG initiatives affect firm outcomes, with particular emphasis on risk reduction, a dimension less explored in the economic and financial literature. The search was conducted in the Web of Science database on 15 June 2024, using the keywords “ESG and Financial Risk” and “ESG and Valuation,” yielding 1074 initial records. After applying inclusion and exclusion criteria, we analyzed the final sample through descriptive and frequency-based methods. Findings reveal no clear consensus on the connection between ESG and value creation, with results varying across sectors, firm sizes, regions, and specific ESG components. In contrast, the evidence supporting the link between ESG practices and financial risk mitigation is stronger: 68% of the reviewed studies reported a positive relationship, while only 5% found negative effects. This review underscores the potential of sustainability as a risk-management mechanism and highlights research gaps that warrant deeper exploration. Limitations include heterogeneity of methodologies, metrics, and contexts among the studies reviewed. Full article

Objective: Non-oncological musculoskeletal chronic pain has a high prevalence and is a cause of disability, reduced quality of life, and significant economic impact. Physical exercise is presented as a treatment option; however, pain measurement remains a challenge, and various biomarkers are potential candidates to objectify this process. This systematic review aims to study the effect of physical exercise on non-oncological musculoskeletal chronic pain and its associated biomarkers based on randomized controlled trials. Methods: A search for randomized controlled trials was conducted in the PubMed, Web of Science, and Scopus databases based on the established inclusion and exclusion criteria, along with a risk of bias assessment following the recommendations of the Cochrane Collaboration. Results: Five studies investigated various physical exercise interventions and their effects on biomarkers linked to chronic pain. Exercise consistently reduced self-reported pain, though no clear overall correlation with biomarker changes was found. However, significant associations emerged for specific biomarkers, particularly inflammatory markers and those identified through structural and functional brain imaging, suggesting potential mechanisms underlying pain modulation. Conclusions: The findings suggest that identifying chronic pain variations through biomarkers requires selecting markers linked to immune activity or brain processes. More randomized controlled trials with sufficient sample sizes and rigorous methodologies are needed. Despite this, physical exercise remains a valuable intervention for managing non-oncological musculoskeletal chronic pain. Additionally, it holds potential as a tool for uncovering novel biomarkers that may contribute to the objectification and understanding of chronic pain mechanisms. Full article

Background/Objectives: Alterations in immunoinflammatory activation may constitute a pathogenetic mechanism in neurodevelopmental disorders (NDDs). Blood cell count (CBC) parameters and hematological inflammatory indices (neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, platelet-to-lymphocyte ratio) are now assuming a greater role as potential biomarkers for NDDs. Methods: In this retrospective observational study, we gathered data on 135 medication-free individuals aged 6 to 17 years: 90 with NDDs (34 with autism spectrum disorder (ASD), 29 with attention-deficit/hyperactivity disorder, 14 with intellectual disability, and 13 with tic disorder) and 45 typically developed controls. The variables analyzed were compared using analysis of variance including Bonferroni posthoc testing for pairwise comparisons Significance was defined as p < 0.05. Results: The analysis of variance revealed statistical significance for all evaluated CBC parameters, as well as for the lymphocyte-to-monocyte ratio. Notably, subjects with ASD exhibited increased values of neutrophils, lymphocytes, monocytes, and eosinophils compared to both typically developing subjects and other NDDs. The lymphocyte-to-monocyte ratio was found to be lower in the tic disorder group compared to typically developing subjects. The elevated lymphocyte and monocyte levels in ASD subjects might reflect chronic low-grade inflammation. Conclusions: Consistent with the evidence in literature, statistically significant differences between the NDD group and typically developed subjects in the CBC parameters were found. The principal limitations of this investigation are the restricted sample size and the exclusion of specific NDD subtypes. Future research is needed to evaluate CBC parameters and inflammatory indices in a broader spectrum of NDDs to better understand the immunoinflammatory response specific to each disorder. Full article

Enteroviruses initiate genomic replication via a highly conserved mechanism that is controlled by an RNA platform, also known as the 5’ cloverleaf (5’CL). Here, we present a biophysical analysis of the 5’CL conformation of three enterovirus serotypes under various ionic conditions, utilizing CD spectroscopy, size-exclusion chromatography, and small-angle X-ray scattering. In general, a tendency toward a smaller monomeric hydrodynamic radius in the presence of salts was observed, but the exact structural signature of each 5’CL varied depending upon the serotype. Rhinovirus B14 (RVB14) exhibited at least two monomeric conformations and a low propensity for dimerization, while poliovirus 1 (PV1) showed a high propensity for dimerization, which was enhanced by the presence of salts. Enterovirus D70 was observed to be somewhat intermediate, with primarily a monomeric structure, but possessing some potential for dimerization. The equilibrium between the two monomeric and the dimeric conformations is also discussed. These results indicate that the 5’CL conformation may be more complex than the current literature suggests, thus underscoring the need for a combined crystal and solution approach for the accurate representation of the 5’CL conformation, and the conformation of other RNA structural elements, under native conditions. Full article

Plant density influences interspecific interactions such as pollination and herbivory. In denser populations, pollinators find flowers more easily, increasing reproductive success and population growth. However, the same floral attractiveness also favors floral herbivory, a relationship described by Janzen and Connell as negative density dependence, considered an important mechanism for maintaining tropical diversity. This study analyzed the reproduction of Peixotoa tomentosa A. Juss. (Malpighiaceae) and Byrsonima intermedia A. Juss. (Malpighiaceae), considering population density and its influence on pollinator and herbivore attraction. The central hypothesis was that density affects fruit production. We conducted two treatments with both species: high density and low density in a preserved Brazilian savanna. We investigated fruit production, reproductive system, floral visitation rates, and the florivory rates of each species on each treatment. Our results showed that fruiting increased with density in both species. Peixotoa tomentosa is an agamospermous species, while B. intermedia is self-incompatible and relies exclusively on pollinators. Bees visited only B. intermedia, and the high-density treatment received more visits. Herbivores attacked more isolated P. tomentosa flowers. We concluded that density influences both pollination and herbivory, affecting plant reproduction, with effects mediated by the plant’s attractiveness in denser populations and by the size and quantity of flowers in single individuals. Full article

Titanium is widely recognized as an interesting material for electrodes due to its excellent corrosion resistance, mechanical strength, and biocompatibility. However, further functionalization is often necessary to impart advanced interfacial properties, such as selective ion transport or stimuli responsiveness. In this context, the integration of smart polymers, such as poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA)—noted for its dual pH- and thermo-responsive behavior—has emerged as a promising approach to tailor surface properties for next-generation devices. This work compares two covalent immobilization strategies for PDMAEMA on titanium: the “graft-to” method, involving the attachment of pre-synthesized polymer chains, and the “graft-from” method, based on surface-initiated polymerization. The resulting materials were characterized with size exclusion chromatography (SEC) for molecular weight, Fourier-transform infrared spectroscopy (FTIR) for chemical structure, scanning electron microscopy (SEM) for surface morphology, and contact angle measurements for wettability. Electrochemical impedance spectroscopy and polarization studies were used to assess electrochemical performance. Both strategies yielded uniform and stable coatings, with the mode of grafting influencing both surface morphology and functional stability. These findings provide valuable insights into the development of adaptive, stimuli-responsive titanium-based interfaces in advanced electrochemical systems. Full article

Background/Objectives: Taste dysfunction is a highly prevalent yet underrecognized complication among patients with head and neck cancer (HNC), significantly impairing nutritional intake, treatment adherence, and quality of life (QoL). This comprehensive review synthesizes current knowledge on the pathophysiological mechanisms and clinical management of taste dysfunction associated with HNC and its treatments, particularly chemotherapy and radiotherapy. Methods: A structured literature search was performed across PubMed, Scopus, and Cochrane Library for articles published between January 2015 and February 2025. Studies were included if they investigated taste dysfunction related to HNC, focusing on pathophysiological mechanisms and therapeutic interventions. A total of 47 original studies were analyzed through a narrative synthesis due to heterogeneity in study designs and outcomes. Results: Taste dysfunction in HNC patients arises from tumor-related inflammation, cytotoxic injury from chemotherapy, and radiation-induced epithelial and neural damage. Chemotherapy and radiotherapy often exert synergistic negative effects on gustatory function. Management strategies identified include dietary counselling, nutritional supplementation (zinc, lactoferrin, monosodium glutamate, miraculin), pharmacological agents targeting salivary function, and non-pharmacological interventions such as acupuncture, photobiomodulation, and reconstructive surgery. However, the evidence is limited by small sample sizes, methodological variability, and the frequent exclusion of HNC patients from broader dysgeusia trials. Reported prevalence of taste dysfunction ranged from 39% to 97.4%, with higher rates observed among patients treated with radiotherapy and chemoradiotherapy. Conclusions: Taste dysfunction remains a critical yet unmet clinical challenge in HNC patients. High-quality, targeted research is urgently needed to develop standardized assessments and evidence-based management strategies to improve patient outcomes. Full article

Hydrogel is widely used as a scaffolding material for tissue engineering due to its excellent cytocompatibility and potential for biofunctionalization. However, its poor mechanical property limits its further application. Fabrication of fiber-reinforced hydrogel composite scaffolds has emerged as a solution to overcome this problem. However, existing strategies usually produce nonporous composite scaffolds, where the interfiber pores are completely filled with hydrogel. This design can hinder oxygen and nutrient exchange between seeded cells and the culture medium, thereby limiting cell invasion and colonization within the scaffold. In this study, sodium alginate (SA) hydrogel was exclusively grafted onto the surface of the constituent fibers of the melt electrowritten scaffold while preserving the porous structure. The grafted hydrogel amount and pore size were precisely controlled by adjusting the SA concentration and the crosslinking ratio (SA: CaCl₂). Experimental results demonstrated that the porous composite scaffolds exhibited superior swelling capacity, degradation ratio, mechanical properties, and biocompatibility. Notably, at an SA concentration of 0.5% and a crosslinking ratio of 2:1, the porous composite scaffold achieved optimal cell adhesion and viability. This study highlights the critical importance of preserving porous structures in composite scaffolds for tissue-engineering applications. Full article

The statistical mechanics of structured particles with arbitrary size and shape adsorbed onto discrete lattices presents a longstanding theoretical challenge, mainly due to complex spatial correlations and entropic effects that emerge at finite densities. Even for simplified systems such as hard-core linear k-mers, exact solutions remain limited to low-dimensional or highly constrained cases. In this review, we summarize the main theoretical approaches developed by our research group over the past three decades to describe adsorption phenomena involving linear k-mers—also known as multisite occupancy adsorption—on regular lattices. We examine modern approximations such as an extension to two dimensions of the exact thermodynamic functions obtained in one dimension, the Fractional Statistical Theory of Adsorption based on Haldane’s fractional statistics, and the so-called Occupation Balance based on expansion of the reciprocal of the fugacity, and hybrid approaches such as the semi-empirical model obtained by combining exact one-dimensional calculations and the Guggenheim–DiMarzio approach. For interacting systems, statistical thermodynamics is explored within generalized Bragg–Williams and quasi-chemical frameworks. Particular focus is given to the recently proposed Multiple Exclusion statistics, which capture the correlated exclusion effects inherent to non-monomeric particles. Applications to monolayer and multilayer adsorption are analyzed, with relevance to hydrocarbon separation technologies. Finally, computational strategies, including advanced Monte Carlo techniques, are reviewed in the context of high-density regimes. This work provides a unified framework for understanding entropic and cooperative effects in lattice-adsorbed polyatomic systems and highlights promising directions for future theoretical and computational research. Full article

Concentrated suspensions exhibit intriguing behaviors under external forces, including vibration and shear. While previous studies have focused primarily on cornstarch suspensions, this paper reports a novel observation that colloidal silica suspensions also exhibit dancing, bouncing, solidification, and melting under vertical vibration. Unlike cornstarch, silica particles offer high stability, controlled size distribution, and tunable surface properties, making them an ideal system for investigating these phenomena. The 70 wt.% aqueous suspensions of spherical silica particles with a diameter of 0.55 μm were subjected to controlled vertical vibration (60–100 Hz, 100–500 m/s²). High-speed video analysis revealed dynamic transitions, including melting, fingering, squirming, fragmentation, and jumping. The solidified suspension retained its shape after vibration ceased but melted upon weak vibration. This study demonstrates that such dynamic state transitions are not exclusive to starch-based suspensions but can also occur in well-defined colloidal suspensions. Our findings provide a new platform for investigating shear-thickening, jamming, and vibrational solidification in suspensions with controllable parameters. Further work is required to elucidate the underlying mechanisms. Full article

This study examined total ammoniacal nitrogen (TAN) rejection by two reverse osmosis (RO) and two nanofiltration (NF) membranes as a function of pH for three ammonium salts to optimize conditions for a hybrid membrane system that can produce high-purity TAN streams suitable for reuse. The results showed that TAN rejection was significantly influenced by membrane type, feed pH, and the ammonium salt used. This study represents the first attempt to simulate real manure wastewater conditions typically found in pig manure. TAN rejection for (NH₄)₂SO₄ and NH₄HCO₃ reached up to 95% at pH values below 7, with the SW30 membrane showing the highest performance (99.5%), attributed to effective size exclusion and electrostatic repulsion of SO₄²⁻ and HCO₃⁻ ions. In contrast, lower rejection was observed for NH₄Cl, particularly with the MPF-34 membrane, due to its higher molecular weight cut-off (MWCO), which diminishes both exclusion mechanisms. TAN rejection decreased markedly with increasing pH across the BW30, NF90, and MPF-34 membranes as the proportion of uncharged NH₃ increased. The lowest rejection rates (<15%) were recorded at pH 11.5 for both NF membranes. These results reveal a notable shift in separation behavior, where NH₃ permeation under alkaline conditions becomes dominant over the commonly reported NH₄⁺ retention at low pH. This novel insight offers a new perspective for optimizing membrane-based ammonia recovery in systems simulating realistic manure wastewater conditions. TAN recovery was evaluated using a hybrid membrane system, where NF membranes operated at high pH promoted NH₃ permeation, and the SW30 membrane at pH 6.5 enabled TAN rejection as (NH₄)₂SO₄. This hybrid system insight offers a new perspective for optimizing membrane-based ammonia recovery in systems simulating realistic manure wastewater conditions. Based on NH₃ permeation and membrane characteristics, the NF90 membrane was operated at pH 9.5, achieving a TAN recovery of 48.3%, with a TAN concentration of 11.7 g/L, corresponding to 0.9% nitrogen. In contrast, the MPF-34 membrane was operated at pH 11.5. The NF90–SW30 system also achieved a TAN recovery of 48.3%, yielding 11.7 g/L of TAN with a nitrogen content of 1.22%. These nitrogen concentrations indicate that both retentate streams are suitable for use as liquid fertilizers in the form of (NH₄)₂SO₄. A preliminary economic assessment estimated the chemical consumption cost at 0.586 EUR/kg and 0.729 EUR/kg of (NH₄)₂SO₄ produced for the NF90–SW30 and MPF-34–SW30 systems, respectively. Full article