Search Results (19,844)

There is no proven therapy for Long COVID, a post-acute condition characterized by persistent symptoms following SARS-CoV-2 infection. Extracellular vesicles (EVs) are emerging as mediators of disease pathogenesis through their molecular cargo. We investigated whether EV glycosylation is altered in Long COVID plasma and whether these vesicles can be selectively targeted using a glycan-binding affinity resin. Large (100–500 nm) and small (40–200 nm) EVs were isolated from post-acute COVID-19 plasma and analyzed by nanoparticle flow cytometry to assess surface glycosylation. Small EV capture assays were performed using Galanthus nivalis agglutinin (GNA) affinity resin. Plasma miRNA profiles before and after GNA treatment were evaluated using NanoString nCounter analysis, and potential downstream pathway effects were computationally inferred using validated miRNA–mRNA interactions and PROGENy. Mannose-positive large EVs were significantly increased in Long COVID compared to recovered controls (p < 0.05). GNA-mediated small EV capture correlated with mannose-positive EV abundance (r = 0.341, p < 0.05), and seven miRNAs were significantly reduced following treatment. Computational pathway analysis suggested modulation of key signaling pathways, including JAK-STAT, Estrogen, VEGF, and PI3K. These findings suggest a glycan-associated EV signature in Long COVID and support further investigation of lectin-based capture as a potential strategy to target vesicle-associated molecular cargo. Full article

Water blockage severely restricts gas transport in deep shale reservoirs, while effective mitigation requires a precise balance of multiple operational variables. This study utilizes core-flooding experiments to optimize the treatment processes of an amphiphobic fluorinated copolymer, focusing on the coupled roles of surfactant concentration, injected volume, and shut-in duration. The results show that permeability damage decreases rapidly with surfactant concentration, optimizing at 0.5 wt.%. Conversely, excessive liquid retention beyond a critical injection threshold of 1.0 PV triggers secondary water-blocking. Extending the shut-in duration to 8 days facilitates surfactant redistribution and interfacial equilibrium, gradually reversing rock wettability to a stable amphiphobic state. Crucially, the concurrent reduction in interfacial tension markedly lowers capillary resistance, allowing trapped water to detach and flow back under significantly lower driving pressures. This optimization effectively minimizes the energetic barrier for fluid displacement and creates a gas-preferential flow environment. The proposed laboratory operational window balances surfactant dosage, injection volume, and shut-in duration under the tested conditions, providing an experimental reference for optimizing post-fracturing cleanup, controlling liquid retention, and improving early-time gas flowback in shale gas reservoirs. Full article

The annual congress of the Italian Association of Plastic Aesthetic Surgery (AICPE), with more than 700 members, represents one of the most relevant conference meetings in Europe relating to Aesthetic Plastic Surgery due to the number of participants and due to the faculty of invited speakers chosen for their renowned scientific value. The 13th meeting was held in Rome (Italy) from 10 to 12 April 2026. Key focus areas of the scientific program concerned breast (reduction, lifting supported or not by mesh, implant surfaces, augmentation), face and neck (lifting, blepharoplasty, malar implants, feminization), body (abdominoplasty and torsoplasty, post-partum and ex-obesity surgery, body and limb contouring, complication treatments) and nose surgery combined with medical innovations in energy devices, threads and aesthetic medicine procedures. Special attention was also given to the theme of the therapeutic role of aesthetic surgery, which is increasingly becoming an integral part of a clinical pathway useful for restoring the patient’s psycho-physical balance. Presented here is a report of the abstracts accepted due to their innovative or cutting-edge content that were selected to be given as oral presentations during the congress sessions. The 2nd edition of the Saccomanno memorial award for the best abstract presented by a young surgeon has been organized with the endorsement of Surgical Techniques Development by MDPI. Full article

Background/Objectives: Chronic primary pain (CPP) is a new diagnostic category including chronic pain conditions lacking clinical signs or a clear etiopathogenetic origin. These disorders may share a common neural mechanism known as central sensitization, where nociceptive neurons become hyper-responsive to standard or subthreshold pain stimuli, resulting in pain hyper-sensitivity. In this context, non-invasive brain stimulation (NIBS) appears to be a promising tool for improving CPP symptoms by targeting maladaptive brain activity and connectivity. To date, the effects of NIBS on CPP symptoms remain unexplored. To fill this gap, we conducted a meta-analysis, investigating the effect of NIBS in improving the three core symptoms of CPP, namely pain intensity, emotional distress, and functional disability. Methods: Following PRISMA guidelines, we screened four databases up to February 2025 for English-language, peer-reviewed randomized clinical trials that included CPP patients treated with NIBS and reported pre/post or follow-up scores on validated measures of at least one core symptom. Quality of life was examined as an additional outcome. Results: Fifty-four studies were included, with 1371 participants receiving real stimulation and 1103 sham. Findings highlighted that real stimulation improved CPP symptoms immediately after treatment and at one-month follow-up. Meta-regressions showed that longer CPP duration reduced short-term effects on emotional distress and diminished all outcomes at one-month follow-up. Conclusions: Further research is needed to establish standardized NIBS protocols for CPP management, to investigate the effectiveness at longer follow-up periods, and to test whether combining NIBS with other interventions enhances treatment effectiveness and durability. Full article

Redevelopment precincts are often assessed through price uplift, although price appreciation alone does not show whether a local housing market becomes more active or liquid. This study examines whether residential turnover and property valuation diverged around the Etihad Campus redevelopment precinct in East Manchester after the 2014Q4 consolidation of the wider campus setting. Using Office for National Statistics House Price Statistics for Small Areas, the analysis applies a neighborhood-scale synthetic control design to a compact Core-4 treatment precinct, using a filtered within-Manchester donor pool to construct the synthetic benchmark. Residential turnover is measured as the mean residential sales count per Lower Layer Super Output Area (LSOA), and valuation is measured as the average of LSOA-level median house-price trajectories. Robustness is assessed using alternative treatment definitions and pre-intervention calibration windows. The results show a persistent post-2014 turnover shortfall relative to the synthetic benchmark, supported by rank-based placebo diagnostics and retained across all valid turnover specifications. By contrast, valuation evidence is weaker, mixed, and more sensitive to design choice. These findings indicate selective housing-market reconfiguration rather than generalized uplift. Redevelopment evaluation should therefore distinguish transaction circulation from price-based valuation, particularly in cumulative precinct-scale redevelopment settings. Full article

Background/Objectives: This study aimed to evaluate the gingival crevicular fluid (GCF) levels of fractalkine/CX3CL1 and CX3CR1 in patients with gingivitis and periodontitis before and after non-surgical periodontal therapy. Methods: A total of 90 individuals comprising 30 with stage 3 periodontitis, 30 with gingivitis, and 30 periodontally healthy, were enrolled in the study. Gingivitis and periodontitis patients underwent non-surgical periodontal treatment. GCF samples were collected at baseline and at 1 and 3 months after treatment. CX3CL1 and CX3CR1 were measured by an ELISA analysis. Results: GCF CX3CL1 and CX3CR1 were significantly elevated in patients with periodontitis and gingivitis compared to healthy controls (p < 0.001). The periodontitis patients also showed higher GCF levels of CX3CL1 and CX3CR1 than those with gingivitis (p < 0.001). Significant decreases in GCF CX3CL1 and CX3CR1 were detected at 1 month after periodontal treatment compared to baseline values in both the gingivitis and periodontitis patients (p < 0.001). Moreover, the periodontitis patients exhibited significant decreases in both CX3CL1 and CX3CR1 levels at 3 months post-treatment compared to 1 month (p < 0.001), whereas no significant changes were observed between the two time points in the gingivitis patients (p > 0.05). Conclusions: Our findings suggest that the CX3CL1–CX3CR1 axis might contribute to the inflammatory processes of periodontal diseases and may represent a treatment-responsive component of the local host response. Full article

Across the world’s electrical substations, water-treatment plants, and manufacturing lines, a single engineer with valid credentials and a laptop can today push new control logic to a programmable logic controller (PLC) and change the physical behaviors of safety-critical equipment within minutes. Firmware and ladder-logic updates on SCADA and industrial IoT systems are privileged operations: an attacker installing a malicious update controls the physical process. Existing protections concentrate install authority in a single party with no externally verifiable record; compromise of the vendor key, the engineering workstation, or any operator credential suffices to deliver an attacker-chosen payload to a PLC. CertiFlash binds every update to four independent approvals: a vendor signature, a FROST-Ed25519 threshold signature from an operator quorum, a per-session nonce from the PLC, and a monotonic counter. Every decision is recorded in an append-only Merkle transparency log. The PLC verifies the aggregate with a standard RFC 8032 Ed25519 verifier, requiring no FROST-specific device code. Four security properties (authenticity, authorization, rollback resistance, auditability) are machine-checked in Tamarin under a Dolev–Yao adversary with up to t − 1 compromised operators and corroborated through ten attack scenarios. The implementation runs with concurrent Modbus TCP and Siemens S7 traffic, blocks all attacks, signs in 27–192 ms (k = 3–10), keeps ML-DSA-65 within 6% of Ed25519 from 1 KiB to 10 MiB, and sustains 30.1 updates/s on 100 PLCs. The operator-quorum signature remains FROST-Ed25519: the design is partially post-quantum in the evaluated version. The framework maps to IEC 62443-3-3 SR 3.4 and NIS2 Article 21(2)(d–e). Full article

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

Endometrial hyperplasia (EH) is an estrogen-driven proliferative disorder with a measurable risk of progression to endometrial carcinoma. Although many guidelines have been issued over the years, clinical practice remains heterogeneous. In this paper, we aim to compare and summarize key recommendations and disagreements among major international guidelines for managing endometrial hyperplasia, focusing especially on conservative and fertility-sparing strategies. All guidelines align with some key principles: they all adopt the 2020 WHO classification, strongly prefer hysteroscopy-directed sampling, and recommend progestin therapy as the first-line treatment for non-atypical EH, favoring the levonorgestrel-releasing intrauterine system (LNG-IUS) over oral regimens. They designate total hysterectomy as definitive management for atypical hyperplasia/intraepithelial endometrial neoplasia (AEH/EIN) due to the substantial prevalence of concurrent carcinoma. Nevertheless, several key discrepancies appear, mainly concerning how long to continue progestin therapy and when to escalate treatment; and how intensively and for how long to conduct post-treatment surveillance. Variations in diagnostic and therapeutic protocols reflect evidence gaps and differences across healthcare settings. Future research should focus on harmonized outcomes, comparative studies of conservative strategies, and the integration of new pathology tools for personalized management. Full article

The safety profile for bio-derived phenols post-oxidation and their related antioxidant/redox potential remain largely under-explored. Oxidation by fungi, in terms of environmental impacts via fungal oxidation by enzymes, remains an attractive strategy under milder conditions, since it is one route by which many naturally occurring lignocellulosic phenols are modified; thus, an immediate need still exists for characterizing the effects that these modified phenolic compounds may have. Methodology: We examined four different biomass-derived phenolics—vanillin, ferulic acid, syringaldehyde and guaiacol—that were oxidized with fungal laccase and characterized their effects on normal human lung fibroblasts and levels of cellular oxidative stress. Laccase activity was evaluated via the ABTS method and through simple observation and UV-Vis spectroscopic scanning of the phenolics in question, and compared with the untreated version of each phenolic. In addition to assessing the cytotoxic effect and oxidative stress generated by the phenols alone, an ELISA-based measurement assay was used to investigate the relative abundance of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and reduced glutathione (GSH) in the human normal lung fibroblast cell line under varying treatment regimes, complemented by phase-contrast microscopy. Scores integrating the biomarkers were analyzed via clustering, PCA, radar and Pearson correlation analyses, to discern distinct trends in antioxidant potential after laccase conversion. Observations: Each of the four tested phenolics demonstrated the presence of laccase activity, leading to substantial differences in visible appearance compared with the control and characteristic absorbance shifts at differing wavelengths from the original molecule. Cell viability dropped dramatically as phenol concentration was increased and the untreated phenolics resulted in diminished confluence and induced greater levels of oxidative damage, from guaiacol and syringaldehyde. Laccase treatment resulted in higher MTT reduction activity and improved cellular morphology compared with the corresponding untreated phenolic compounds. Untreated phenols induced the highest levels of MDA, while decreasing SOD, CAT, GPx and GSH levels. Post-oxidation with laccase, there were lower amounts of lipid peroxidation, along with improved levels of antioxidant activity compared with the control phenol. Multi-technique analyses show clear distinctness between the untreated and laccase-converted phenolic groups. Clustering with multivariate techniques separated all cell groups in line with control samples, grouping the laccase-converted treatments towards the middle and displaying an inverse relationship between MDA and the antioxidant markers. Conclusions: Laccase conversion markedly decreases the adverse effects that bio-derived phenols have on normal cell viability and induces fewer detrimental effects on the cellular redox balance. This is a critical discovery in terms of finding greener methods by which to upgrade bio-derived substances as we research these lignocellulosic phenols. By employing ELISA-based measurements along with multiple analysis techniques, we present a suitable paradigm for studying biological effects in all bio-based goods intended for pharmaceuticals, packaging materials, nutraceuticals or a host of different applications. Full article

Background: Kidney transplantation is the preferred treatment for end-stage kidney disease (ESKD), but long-term outcomes remain limited by chronic allograft injury, infections, metabolic complications, and cardiovascular risk. Gut microbiota alterations and microbiota-derived metabolites may influence immune regulation, inflammation, drug metabolism, and graft outcomes through the gut–kidney axis. This review summarizes evidence on the gut microbiota in kidney transplantation, emphasizing immune tolerance, complications, cardiovascular risk, graft function, and perspectives. Methods: A structured search was conducted in PubMed, Scopus, and Web of Science to May 2026. Eligible publications included studies involving kidney transplant recipients (KTR), kidney disease or solid organ transplant populations, and mechanistic models. Evidence was synthesized narratively. Results: Gut microbiota alterations in KTR reflect pre-transplant dysbiosis and post-transplant exposures, including antibiotics, immunosuppression, infection, diet, hospitalization, and graft function. Dietary factors and nutrient-derived substrates may modulate microbial composition and production of relevant metabolites, including short-chain fatty acids (SCFAs), trimethylamine N-oxide (TMAO), tryptophan-derived compounds, bile acid derivatives, and uremic toxins. Microbiota-related pathways may involve barrier dysfunction, microbial translocation, innate immune activation, altered regulatory T cell/T helper 17 (Treg/Th17) balance, metabolite signaling, uremic toxin generation, and endothelial stress. Clinical studies associate dysbiosis and microbial metabolites with diarrhea, infections, delayed graft function (DGF), rejection-related shifts, tacrolimus variability, cardiovascular risk, graft dysfunction, graft failure, and mortality. Most findings need validation. Conclusions: Gut microbiota signatures and microbial metabolites are promising markers of transplant-related risk, but not established causal determinants or therapeutic targets. Clinical translation requires standardized methods, multi-omics integration, and prospective patient- and graft-centered trials. Full article

Objective: Neuroinflammation contributes to cognitive impairment across neurodegenerative disorders. Prostaglandins (e.g., PGE₂, PGD₂, PGF₂α) and pro-inflammatory cytokines (TNF-α, IL-1β) are key mediators of lipopolysaccharide (LPS)-induced hippocampal dysfunction. Carvacrol (CRV), a monoterpenic phenol with anti-inflammatory and antioxidant properties, may mitigate these effects, but its impact on hippocampal prostaglandin profiles is not well-defined. Methods: BALB/c mice were randomly assigned to Control (PBS; n = 7), LPS (1 mg/kg, i.p.; n = 10), or LPS + CRV (50 mg/kg, p.o.; n = 7). Body weight was tracked daily for 7 days; rectal temperature was measured once before behavioral testing and euthanasia. Locomotion/anxiety were assessed by the open-field test (OFT; average speed, total distance, freezing, mobility rate) using ToxTrac. Spatial recognition memory was evaluated in the Y-maze novel-arm task (novel-arm entries, duration, total entries, discrimination index [DI]). Hippocampal PGE₂, PGD₂, PGF₂α, TNF-α, and IL-1β were quantified by ELISA. Data were analyzed by one-way ANOVA with Sidak’s post hoc test. Results: OFT measures did not differ among groups (p > 0.05), indicating no confounding locomotor deficits. In the Y-maze, LPS reduced novel-arm entries versus the Control (p = 0.0029), while LPS + CRV showed a nonsignificant increase versus LPS (p = 0.2406). Novel-arm duration differed among groups (p = 0.0033); LPS + CRV spent less time than LPS (p = 0.0128). Critically, DI showed a robust treatment effect (p < 0.0001): LPS markedly impaired DI versus the Control (p < 0.0001), and CRV significantly improved DI versus LPS (p < 0.0001). Biochemically, LPS elevated hippocampal PGE₂ (p < 0.0001) and PGF₂α (p = 0.0040); CRV normalized PGE₂ (p < 0.0001) but not PGF₂α (p = 0.2656). PGD₂ was unchanged. LPS increased TNF-α and IL-1β (both p < 0.0001), and CRV significantly reduced both versus LPS (both p < 0.0001). Conclusions: Acute LPS provokes prostaglandin- and cytokine-driven hippocampal inflammation with associated recognition memory deficits. Carvacrol attenuates cognitive impairment and suppresses hippocampal PGE₂, TNF-α, and IL-1β, supporting a mechanism involving modulation of the prostaglandin–cytokine axis. These findings highlight CRV as a candidate adjunct for inflammation-associated cognitive dysfunction. Full article

Background/Objectives: Non-small cell lung cancer (NSCLC) remains associated with high mortality, frequent late-stage diagnosis, biological heterogeneity, and recurrence after treatment. Although molecular and immunohistochemical biomarkers have transformed treatment selection, there remains a need for accessible, repeatable, and clinically practical circulating biomarkers that may support prognosis and post-treatment monitoring. This review discusses prolactin (PRL) as a candidate supplementary biomarker in NSCLC, with particular emphasis on its biological rationale, potential prognostic relevance, and possible role in personalized risk stratification after systemic therapy. Methods: This narrative review summarizes current evidence on established biomarkers in NSCLC, the physiology and regulation of PRL, PRL/PRLR signaling in cancer biology, mechanisms of PRL dysregulation in lung cancer, and available clinical observations concerning PRL alterations in NSCLC. Particular attention is given to the distinction between prognostic and predictive biomarkers, longitudinal monitoring, pituitary involvement, immune checkpoint inhibitor-related endocrine effects, and biological, pharmacological, and analytical confounders affecting PRL interpretation. Results: Current evidence suggests that PRL may be biologically relevant in NSCLC through its involvement in pathways related to cell proliferation, survival, angiogenesis, invasion, epithelial–mesenchymal transition, immune modulation, and possible therapy resistance. Clinical observations indicate that altered PRL levels may occur in advanced disease, pituitary involvement, systemic inflammation, stress, or during anticancer and supportive treatment. However, PRL lacks cancer specificity and is influenced by multiple confounders, including circadian rhythm, stress, endocrine disorders, macroprolactin, cachexia, medications, and assay variability. Available clinical data remain limited and are largely derived from small studies or case-based evidence. Conclusions: PRL should not currently be considered a standalone diagnostic, predictive, or treatment-selective biomarker in NSCLC. Its most realistic potential role is as a supplementary circulating marker within multimarker prognostic and monitoring models. Prospective validation with standardized sampling, assay procedures, and confounder adjustment is required before clinical implementation. Full article

Background/Objectives: Patients with relapsed/refractory multiple myeloma (RRMM) have poor survival outcomes and limited treatment options. The increasing utilization of multiagent therapies for earlier lines of treatment and novel drug classes including BCMA-targeting agents in subsequent lines of therapy has created a need for innovative treatment platforms in patients who have relapsed after or are refractory to these current standard-of-care approaches. Iopofosine I 131 is a ¹³¹iodide (¹³¹I)–phospholipid conjugate that exploits the selective uptake and retention of phospholipid ethers through lipid rafts to facilitate tumor delivery of ¹³¹I. Methods: The objective of this phase 1 dose-escalation study was to assess the safety and tolerability of single and fractionated dose schedules of iopofosine I 131 + low-dose dexamethasone in heavily pretreated patients with RRMM. Results: The most common AEs overall were cytopenias, notably thrombocytopenia (93.5%), lymphopenia (74.2%), anemia (71%), leukopenia (61.3%), and neutropenia (58.1%). All patients experiencing hematologic adverse events recovered from those events with median time of recovery 21 days post-nadir. Nonhematologic adverse events were mostly limited to Grade 1 and 2. Dose-limiting toxicities included four Grade 4 thrombocytopenia events lasting longer than 7 days, one Grade 4 neutropenia, and one Grade 3 insomnia. The DMC determined 31.25 mCi/m² was the maximum tolerated dose in the single-dose group, and 20 mCi/m² × 2 doses was the maximum tolerated dose in the fractionated-dose group. For patients monitored through 85 days following the first infusion, 22 of 26 (84.6%) achieved stable disease after treatment, and 4 of 26 (15.4%) achieved a partial response. Conclusions: A favorable safety and tolerability profile and preliminary clinical activity support further development of iopofosine I 131 in RRMM. Full article

Background: Adjuvant therapy decisions for T3N0 stage II colon cancer remain controversial. This study evaluates long-term outcomes, recurrence patterns, and conditional relapse-free survival (RFS) in pathologic T3N0 colon cancer. Methods: This retrospective study included 306 patients undergoing curative resection for T3N0 colonic adenocarcinoma (1995–2020). Early recurrence was defined as recurrence or death within 3 years after surgery. Survival was estimated via Kaplan–Meier. Cox regression, adjusted for treatment eras, evaluated survival factors. Inverse Probability of Treatment Weighting (IPTW) minimized selection bias. Conditional RFS utilized a 5-year landmark analysis. Results: Over a 133-month median follow-up, 72 patients (23.5%) recurred. Most recurrences (81.9%) occurred within 3 years; only 9.7% after 5 years. Five- and 10-year OS rates were 80.9% and 70.4%. Inadequate lymph node dissection (<12 nodes) was performed in 29.7% of the entire cohort and was found to be an independent adverse prognostic factor for OS. Adjuvant chemotherapy lacked overall OS benefit, though IPTW analysis suggested potential benefit in patients with inadequate dissection. Conditional RFS (5–10 years) for patients recurrence-free at 60 months was 95.0%. Exploratory analyses showed descriptive differences in post-relapse survival based on the clinical triggers prompting radiological evaluation (marker-triggered versus symptom-triggered presentations). Conclusions: T3N0 colon cancer recurrences occur predominantly within the first 3–5 years after surgery. Inadequate lymph node dissection is the primary adverse prognostic factor. Although a 5-year follow-up period appears adequate for most patients, individualized extended surveillance may be considered for selected high-risk patients. Adjuvant treatment and follow-up strategies should be tailored according to surgical quality and risk factors. Full article