Search Results (497)

Shear-wave velocity (Vs) estimation from the Standard Penetration Test (SPT) can support preliminary site characterization when direct geophysical data are limited, but empirical correlations require validation schemes that reflect transferability between sites. This study evaluates Vs prediction using an interval-paired dataset derived from geotechnical investigations of school foundations in Piura, Peru. Its novelty lies in comparing the raw SPT blow count (NSPT) and the overburden- and energy-corrected SPT blow count ((N1)60) on the same strict common sample, using grouped cross-validation by school, thereby emphasizing transferability across sites rather than only internal fit. Five predictive scenarios were tested, from penetration-only formulations to geotechnically enriched specifications. The lowest grouped out-of-fold error among the evaluated models was obtained by a generalized power baseline using (N1)60 and the integral geotechnical predictor set, yielding root mean square error (RMSE) = 80.48 m/s, mean absolute error (MAE) = 60.15 m/s, and coefficient of determination (R2) = 0.338. This moderate R2 indicates limited standalone predictive capacity under transfer to unseen schools; therefore, the model is interpreted as a preliminary transfer-oriented correlation rather than as a substitute for direct Vs measurements or as an independent design equation. In the complementary full-data analysis, the strongest descriptive fit was obtained with Hist Gradient Boosting, whereas the strongest explicit equation corresponded to the log-semi baseline. Overall, the findings show that externally validated transferability, descriptive full-data fit, and equation-based interpretability represent different analytical roles in Vs-SPT modeling. Full article

Since 2010, consumer-led organizations have emerged in Turkey’s major cities as alternatives to conventional food systems, aiming to connect ecological producers with consumers through disintermediated, fair-trade channels. While initially prominent in Izmir, Istanbul, and Ankara, food communities in Istanbul are currently experiencing weakened continuity and structural transformation. Grounded in Social Practice Theory (SPT), this study examines the factors influencing the embeddedness of these communities, using Istanbul as a context to observe dissolution and restructuring dynamics. By analyzing the relationship between Alternative Food Network (AFN) practices and everyday practice bundles, the article argues that practices lose sustainability when links between meanings, materials, and competences weaken, often due to increased organizational burdens or shifting participant capacities. However, dissolution does not signal a total withdrawal. Instead, actors frequently transition into new alternative formations or adapt practices to align with daily routines. This study contributes to AFN literature by analyzing sustainability through the lens of dissolution and transformation rather than mere success stories, demonstrating that AFNs are contextual, trial and error processes rather than “one-size-fits-all” models. Full article

Pulmonary fibrosis, particularly idiopathic pulmonary fibrosis (IPF), is a chronic and progressive interstitial lung disease characterized by alveolar epithelial injury, fibroblast activation, and excessive extracellular matrix deposition, which collectively lead to respiratory failure. Despite the availability of antifibrotic agents, disease-modifying therapies remain limited. Emerging evidence has identified dysregulated sphingolipid metabolism, especially ceramide accumulation, as a key driver of fibrotic pathogenesis. Ceramide is a central bioactive lipid in the sphingolipid pathway that regulates multiple cellular processes, including apoptosis, inflammation, endothelial barrier dysfunction, and fibroblast activation, all of which contribute to pulmonary fibrosis. This review is a narrative review that systematically summarizes the biosynthetic and metabolic pathways of ceramide, with an emphasis on chain length-specific functions and the ceramide to S1P rheostat. We further discuss the mechanistic roles of ceramide in alveolar epithelial cell apoptosis, inflammatory responses, and vascular barrier disruption in fibrotic lung disease. Finally, we highlight emerging therapeutic strategies that target ceramide metabolism, including inhibitors of acid sphingomyelinase (ASMase) and serine palmitoyltransferase (SPT), and propose future directions for clinical translation. Full article

Background: Egg allergy is one of the most common food allergies in early childhood and is traditionally managed through strict avoidance diets, which may negatively affect nutrition and quality of life. Early oral immunotherapy (OIT) may represent an alternative therapeutic strategy; however, controlled studies in children younger than two years remain limited. Methods: We conducted a prospective observational study using historical controls. Thirty-one children younger than two years with IgE-mediated egg allergy underwent OIT using pasteurized liquid egg white (maximum dose: 30 mL; 3300 mg protein). Twelve children managed with an avoidance diet served as the historical control group. Outcomes included desensitization rates, adverse reactions, and longitudinal changes in skin prick test (SPT) wheal diameters, serum-specific IgE (sIgE), specific IgG4 (sIgG4), and sIgE/total IgE ratios. Results: At six months, 29/31 children (93.5%) in the OIT group did not experience allergic reactions after ingestion of any egg preparation, compared with none in the historical control group (p < 0.001). In the control group, 7/12 children (58.3%) continued to react to less-cooked egg preparations, whereas 5/12 (41.7%) remained reactive to all forms of eggs. During the induction phase, 24/31 OIT-treated children (77.4%) experienced mild adverse reactions, predominantly isolated cutaneous or gastrointestinal symptoms, and no patient required intramuscular adrenaline administration. In contrast, allergic reactions occurred in 11/12 controls, including anaphylaxis in 6/12 (50.0%) patients (p = 0.0301). The OIT group demonstrated significant reductions in SPT wheal diameters, sIgE levels, and sIgE/total IgE ratios (all p < 0.001), accompanied by increased sIgG4 levels. Conclusions: Early OIT with pasteurized egg white in children younger than two years with IgE-mediated egg allergy was associated with high desensitization rates, favorable short-term safety outcomes, and significant immunological changes. These findings support the potential role of early active intervention as an alternative to exclusive avoidance strategies in infants with egg allergy. Full article

A comparative density functional theory (DFT) study was performed to elucidate the mechanistic details of Schiff base formation between 3-pyridinecarboxaldehyde and the three positional isomers of aminobenzoic acid (o-, m-, and p-). Both single proton transfer (SPT) and methanol-assisted double proton transfer (DPT) pathways were systematically investigated in the gas phase and within a polarizable continuum model (PCM) for methanol. All stationary points were optimized at the B3LYP/6-31G and 6-311++G(d,p) levels, and transition states were confirmed by vibrational frequency and intrinsic reaction coordinate (IRC) analyses. The results reveal that the DPT mechanism is consistently associated with significantly lower activation free energies compared to the direct SPT pathway, particularly in methanol, where solvent-mediated proton relay markedly stabilizes the transition states. The positional effect of the amino group influences both the electrostatic potential distribution and the activation barriers, with the para isomer exhibiting enhanced nucleophilicity and improved reaction efficiency. These findings provide detailed mechanistic insight into solvent-assisted proton transfer processes in Schiff base synthesis and highlight the cooperative role of hydrogen-bond networks in reducing energetic barriers. Full article

Background/Objectives: Adolescent suicidal ideation and non-suicidal self-injury (NSSI) are major public health concerns, yet differences between active interventions are often modest. This retrospective study provides preliminary descriptive evidence regarding short-term symptom change across two school-based intervention pathways—Sandplay Therapy with Suicidal ideation and Self-injury Focused Engagement (SPT-SAFE) and a Dialectical Behavior Therapy-informed Brief Intervention (DBT-BI)—in a clinical sample of middle- and high-school adolescents with suicidal ideation and NSSI. Methods: Archival clinical records from 112 adolescents treated in a school-based suicide prevention center were analyzed retrospectively. The sample included 52 adolescents who received SPT-SAFE and 60 who received DBT-BI. Outcomes included suicidal ideation, NSSI frequency, depressive symptoms, anxiety, aggression, impulsiveness, and self-concept. Pre–post changes were examined using mixed-design ANOVAs, with baseline-adjusted ANCOVAs conducted as supplementary analyses. Given the retrospective and clinically assigned design, findings were interpreted as observational associations rather than causal treatment effects. Results: Both intervention groups showed significant pre–post improvements across multiple outcome domains. Overall between-group differences were limited. A nominal, uncorrected Group × Time interaction was observed for impulsiveness, with the DBT-BI group showing a descriptively larger pre–post decrease than the SPT-SAFE group. However, this effect was small and did not remain statistically significant after Bonferroni correction or Benjamini–Hochberg false discovery rate correction across the seven interaction tests. No other outcome showed a multiplicity-adjusted Group × Time interaction. Conclusions: The present study did not provide robust multiplicity-adjusted evidence for differential treatment effects between SPT-SAFE and DBT-BI. The nominal impulsivity finding should be interpreted only as a small, uncorrected exploratory signal for future hypothesis generation. The contribution of this study is therefore descriptive and preliminary, characterizing short-term symptom change in a treatment-engaged adolescent completer sample within a routine school-based service system, rather than supporting domain-specific comparative efficacy or domain-sensitive intervention planning. Full article

Background: Sphingolipids are essential structural and signaling lipids that support membrane integrity and govern cell fate decisions. While the consequences of chronic sphingolipid inhibition have been extensively explored, the immediate cellular responses to acute suppression of sphingolipid synthesis remain poorly defined. Methods: We analyzed subcellular proteomic changes following an acute reduction in sphingolipid levels induced by myriocin, an inhibitor of de novo sphingolipid synthesis. We then evaluated the cytotoxicity of co-treatment with myriocin and inhibitors of the altered pathways in cancer cells. Results: We found that de novo sphingolipid synthesis is sensitive to myriocin, an inhibitor of serine palmitoyltransferase (SPT), and can be efficiently inhibited within 4 h of treatment. Cells respond to reduced sphingolipid levels by rapidly remodeling their proteome. Mass spectrometry analysis revealed changes in the abundance of hundreds of proteins across the membrane, cytosolic, and nuclear fractions. Gene set enrichment analysis revealed alterations in the proteome across several pathways involved in protein and lipid homeostasis and stress responses, including upregulation of cholesterol homeostasis and lysosome. Co-treatment with myriocin and cholesterol synthesis or lysosomal function inhibitors synergistically reduced cancer cell viability by promoting apoptosis rather than other forms of programmed cell death. Conclusions: Together, our work provides insights into how cells rapidly rewire the abundance of certain protein classes in response to reduced sphingolipid levels and identifies signaling and metabolic pathways that can be exploited for therapeutic intervention. Full article

Pancreatic ductal adenocarcinoma (PDAC) is the most complex and aggressive disease with the worst rates of unresectable or metastatic disease at diagnosis, resistance to systemic therapy, and case fatality rate (CFR) among leading cancers. In non-metastatic disease, neoadjuvant treatment with modern chemotherapeutic regimens followed by surgical resection and/or adjuvant mFOLFIRINOX has significantly improved oncological outcomes. However, recurrence rates remain alarmingly high, while immune checkpoint inhibitors (ICIs) or molecularly targeted therapy have not yet demonstrated clinical benefits. Comprehensive genomic profiling through NGS-based approved assays such as TruSight Oncology 500 (TSO500) could guide targeted therapy. Rapidly evolving mRNA cancer vaccines and circulating tumor DNA (ctDNA)-based prediction of minimal residual disease (MRD) and recurrence risk hold great promise towards the realization of rational combination therapy to improve recurrence-free survival (RFS) and overall survival (OS). More recently, single-cell multiomics (SC MO), spatial proteomics and transcriptomics (SPT), artificial intelligence (AI), and systems biology have revolutionized cancer research, enabling holistic tumor microenvironment (TME) analysis. In this comprehensive review, we describe the latest advances and unmet needs in the standard of care of PDAC. Moreover, we discuss the expectations of ongoing randomized clinical trials of adjuvant mRNA vaccine-based therapy and ctDNA MRD testing as prognostic biomarkers, towards personalized treatment to improve RFS and OS in a medium-term perspective. With a longer perspective, we explore how harnessing SC MO, SPT, AI, and systems biology can reveal the 3D spatial organization of interacting cancer, immune, and stromal cells. Multi-dimensional TME-, TSO500- and ctDNA-based framework of dynamic biomarkers are of paramount importance to achieve an optimal patient-specific perioperative multimodal treatment combining precision immunotherapy, targeted drugs, and modern chemotherapy, translated into future practice-changing clinical trials, that could eliminate MRD towards recurrence prevention. Full article

Conventional solar power tower (SPT) systems often suffer from significant heat transfer exergy destruction due to large temperature differences between the heat source and the working fluid during the heat exchange process. To overcome this limitation, a high–low dual-tower configuration based on segmented thermal utilization is proposed. In this arrangement, the high-temperature tower is mainly responsible for the evaporation, superheating, and reheating processes, whereas the low-temperature tower primarily handles feedwater preheating. Such a configuration improves the temperature matching characteristics during the heat exchange process. A comprehensive model integrating the heliostat field, receiver, thermal energy storage system, and power block was developed and validated against Solar Two experimental data, showing good agreement. Comparative analyses were conducted under identical solar resource and operating conditions. The results indicate that the proposed system achieves a comparable power output while reducing total heat transfer exergy destruction by approximately 24%, with a significant reduction of over 80% in the preheating section. Sensitivity analysis further reveals that optimizing the high tower outlet temperature can effectively reduce irreversibility and slightly enhance power output, although constrained by the pinch temperature difference. Dynamic simulations based on typical meteorological year data demonstrate that the system maintains stable operation and improves cycle efficiency. From an economic perspective, the proposed system reduces the levelized cost of electricity (LCOE) by about 6.6% and shortens the dynamic payback period, indicating enhanced long-term competitiveness. Overall, the high and low dual-tower system effectively improves thermodynamic and economic performance, providing a promising approach for high-efficiency concentrating solar power (CSP) development. Full article

Background and Aims: Accuracy in speech perception in bilingual children is influenced by two phonological systems. This study compares phonological development in bilingual Urdu–English (UE) children with CIs with their hearing-age-matched peers with normal hearing (NH), by investigating whether bilingualism or any spectral limitations of CI impact perception of UE phonemes. Method and Procedures: Children (n = 57) aged 3; 0–6; 11 years (28 CI, 29 NH) were assessed for speech perception using a custom-designed UE Speech Perception Test (UE-SPT), in quiet and noise (+5 dB SNR). Responses were analysed using confusion matrices, across phonological parameters of place, manner, and voicing to determine error patterns. Outcomes and Results: Significant deficits in CI children were found across all features, with voicing discrimination showing the largest errors (effect sizes d > 6), exacerbated by noise, especially for Urdu aspirated stops. CIs mastered only 8.3% Urdu-aspirated consonants at 6; 11 years compared to 91.7% mastered by NH peers, indicating critical language-specific vulnerabilities. Backing and substitutions errors were particularly seen in CI’s speech, whilst manner was preserved. Conclusion and Implications: UE bilingual phonological complexity compounded by inadequate speech processing abilities in CIs challenges them, underscoring urgent need for targeted speech therapy interventions focusing voicing contrasts and aspirated consonants, as well as environmental accommodations that reduce noise interference and enhance listening through CI, to optimise educational outcomes. This research contributes vital clinical guidance for supporting bilingual children with cochlear implants, addressing both environmental, technological and linguistic challenges. Full article

Background: The relationship between neonatal DNA methylation (DNAm) and childhood atopy, particularly its temporal dynamics, remains inadequately characterized. Establishing this will provide insights into the epigenetic mechanisms underlying atopy development. Methods: Skin prick tests (SPT) for 11 common allergens were performed in the Isle of Wight third-generation birth cohort (IOWF2) at ages 1, 3, and 6 years. Atopy was defined as a positive response to one or more allergens on SPT. DNAm at birth at 294,265 CpGs from umbilical cords (n = 192) or Guthrie cards (n = 107) was screened (through R package ttscreening) for potential association with atopy. Pathway enrichment analysis of screened CpGs was performed using the missMethyl package in R. Associations between CpGs that passed screening and atopy status were assessed via logistic regressions with repeated measures, adjusting for age, sex, and birth weight. Age-specific associations were examined via DNAm × age interactions. CpGs showing age-specific association were further tested in the parental cohort (IOWBC (F1); n = 717). Multiple testing was controlled using FDR-adjusted p-values at 0.05. Results: In total, 601 CpGs passed screening. Pathway enrichment analysis identified enrichment of the cell activation pathway (GO:0001775; FDR-adjusted p-value = 0.017). DNAm at 502 CpGs in F2 showed age-specific associations with atopy. Among these, 102 CpGs showed consistent directions in F1, and 14 were statistically significant (p-value < 0.05). Except for cg01519508 (FOXF1), DNAm–atopy associations weakened over time at the remaining 13 CpGs. Conclusions: At certain CpGs, DNAm at birth is associated with childhood atopy in an age-dependent manner, and for CpGs showing association at an earlier age, such associations weaken at later ages. Full article

Background/Objectives: Anshen Bunao Oral Liquid (ABOL) is a traditional medicinal formula comprising Cornu Cervi Pantotrichum, Radix Polygoni Multiflori Preparata and other ingredients. It replenishes essence, nourishes qi and blood, and soothes the spirit. It is used in clinical practice to treat neurasthenia and insomnia (emotion-related symptoms), and its key component, glycyrrhizin, exhibits anxiolytic properties. This aligns with the holistic approach of traditional Chinese medicine (TCM) to regulating neuropsychiatric disorders. The aim of this study is to evaluate the anxiolytic efficacy of ABOL in rats with anxiety induced by chronic restraint stress (CRS), and to clarify its mechanism by focusing on modulation of the gut–brain axis (microbiota and metabolism). Methods: Sprague-Dawley rats underwent three hours of restraint per day for 28 days to induce anxiety. ABOL was administered intragastrically in three doses. Anxiety-like behaviours were assessed using OFT, EPM and SPT. Serum, tissue and faecal samples were analysed using ELISA, histopathology, immunohistochemistry, non-targeted metabolomics, 16S rRNA sequencing and RT-qPCR. Results: CRS induced anxiety-like behaviours, impaired weight gain and perturbed the balance of neurotransmitters (decreasing 5-HT, GABA, NE and DA, while increasing CORT), inducing inflammation/oxidative stress, hippocampal neuronal injury, intestinal barrier dysfunction and gut microbiota/metabolic dysregulation. ABOL effectively reversed these abnormalities by restoring the balance of neurotransmitters and the HPA axis, suppressing inflammation and oxidation, protecting neurons and the intestinal barrier, remodelling the gut microbiota (enriching Akkermansia and balancing Firmicutes/Bacteroidota) and regulating sphingolipid and glycerophospholipid pathways. The interaction between the gut microbiota and metabolites may contribute to this pharmacological effect. Conclusions: ABOL exerts anxiolytic effects by modulating the gut–brain axis at multiple targets, involving microbiota remodelling, regulation of lipid metabolism and improvement of pathology. This validates its ethnopharmacological value, linking traditional Chinese medicine to the development of modern anxiolytics. Full article

In the preliminary design of aircraft structures, efficient modelling techniques are essential to balance accuracy and computational cost. Shear Panel Theory (SPT) offers a simple yet effective idealisation of thin-walled, stiffened structures such as wings. It captures more structural detail—like ribs, sweep and taper—than traditional beam idealisation and would otherwise require detailed finite element analysis. However, compared to a finite element model, the degrees of freedom of the structure as well as the meshing effort are significantly reduced, as SPT idealisation uses a structural element approach. This improves mass estimation and structural response calculation and makes SPT particularly well-suited for optimisation tasks in early design phases. This work presents a methodology to derive structural properties of wing segments based on NACA airfoils using SPT. This offers adjustment of the wing’s geometry for use in aeroelastic analysis and enables fast evaluation of structural behaviour and gradient computation, supporting integration into multidisciplinary design optimisation frameworks. The proposed methodology advances the use of idealised structural models in aircraft design by bridging the gap between high-fidelity analysis and system-level aeroelastic simulations, supporting faster and more informed early design iterations. Full article

Butyrate, a short-chain fatty acid derived from the gut microbiota, has been linked to depression through correlational studies; however, whether it might act as a sufficient downstream mediator of the antidepressant effects of a probiotic remains poorly understood. To explore this, a chronic unpredictable mild stress (CUMS) rat model was established to evaluate the potential antidepressant effects of Weizmannia coagulans BC99. Behavioral assessments included the sucrose preference test (SPT), forced swim test (FST), tail suspension test (TST), and open field test (OFT). In addition, 16S rRNA sequencing, serum metabolomics, and short-chain fatty acid (SCFA) profiling were performed. Levels of inflammatory cytokines (IL-1β, IL-6, IL-4, and LPS) and brain-derived neurotrophic factor (BDNF) were measured in serum, hippocampus, and colon by ELISA. An independent sodium butyrate supplementation experiment was conducted to test functional sufficiency, and hippocampal BDNF/TrkB/CREB signaling was assessed by Western blotting. Treatment with BC99 was associated with alleviation of CUMS-induced depressive-like behaviors, increased butyrate levels, reduced neuroinflammation (IL-1β, IL-6, LPS, and IL-4), and restored hippocampal BDNF levels. BC99 also enriched butyrate-producing bacterial taxa (e.g., Lactobacillus, Bifidobacterium, Faecalibaculum) and normalized tryptophan and sphingolipid metabolism. Notably, sodium butyrate alone recapitulated several of the behavioral and anti-inflammatory effects observed with BC99 and, as shown by Western blot, partially restored hippocampal BDNF/TrkB/CREB signaling, which was impaired in CUMS rats. Together, these findings suggest that butyrate may be associated with the antidepressant effects of W. coagulans BC99, potentially acting through suppression of neuroinflammation and activation of the BDNF pathway. Our results support further investigation of butyrate-enhancing strategies as a nutritional approach for depression. Full article

Sterols and sphingolipids assemble into specialized membrane microdomains that are essential for membrane function, protein sorting, and signal transduction. Although coordinated regulation between sterol and sphingolipid metabolic pathways has long been recognized, the molecular mechanisms mediating this cross-talk remain incompletely defined. Here, we uncover an unanticipated role for the conserved yeast Orm proteins in controlling sterol and neutral lipid homeostasis. Deletion of ORM1 and ORM2 causes hypersensitivity to sterol biosynthesis inhibitors, accumulation of steryl esters, and an increase in lipid droplet number. Consistent with mutants lacking core neutral lipid hydrolases, orm1Δ orm2Δ cells display a marked defect in neutral lipid mobilization. These phenotypes depend on sphingolipid pathway perturbation but cannot be attributed to sphingolipid accumulation alone. Together, these findings position the Orm proteins as regulatory nodes linking sterol metabolism, lipid droplet dynamics, and sphingolipid biosynthesis. Full article