Search Results (6,756)

According to the Transportation Safety Board of Canada, between 2013 and 2023, 62% of aviation accidents occurred during the approach, landing, and post-impact phases of flight. Hence, this study targets factors contributing to increased accident rates during the final stages of flight. It will review how pilot experience influences decision-making and identifies mitigation strategies, focusing on go-arounds to prevent accidents during these critical phases. Surveys and roundtable discussions were conducted to identify factors influencing pilot performance during approach, landing, and go-around manoeuvres. By using a mixed-methods approach that combined thematic and statistical analyses, key safety factors were identified, including situational awareness, decision-making, and operational complexity. The study also examined the relationship between experience and decision-making, highlighting areas for targeted interventions to improve safety. The research emphasises the importance of integrating decision-making considerations into training programmes and connecting these to human factors. Through identifying areas for improvement, this study offers a safety-driven framework to address decision-making challenges during approach, landing, and go-around phases, with the objective of reducing accident and incident rates in general aviation. Full article

Background Sex disparity has been highlighted in personalized medicine for various human diseases including acute/chronic liver diseases. In the transplant community, greater graft failure risk in female-to-male liver transplantation (LT) has been repeatedly reported, and a recent study in living donor LT reported that the inferiority of female-to-male LT is shown only when donor age is ≤40 y. We aimed to analyze the United Network for Organ Sharing (UNOS) database to test if the poorer outcome of female-to-male LT changes by donor age of 40 y in deceased donor LT, as shown in living donor LT. Methods In this retrospective cohort study, 11,752 adult patients in the UNOS registry who underwent deceased donor LT between 2000–2023 were analyzed. Multivariable analysis was performed to adjust the effects from transplant years, graft ischemia time, disease severity, and others. The primary outcome was graft failure. Results Within the subgroup of recipients with ≤40 y donors, graft failure risk was significantly greater in female-to-male LT than others (vs. female-to-female, HR = 1.43 [1.16–1.76], p < 0.001; vs. male-to-female, HR = 1.46 [1.18–1.81], p < 0.001; vs. male-to-male, HR = 1.26 [1.16–1.49], p = 0.009). In contrast, within the subgroup of recipients with >40 y donors, the risk was comparable between female-to-male LT and other donor-recipient sex groups (vs. female-to-female, p = 0.907; vs. male-to-female, p = 0.781; vs. male-to-male, p = 0.937). We tested various cutoff donor ages and determined that 40 y is the best cutoff value to define the risk subgroup in female-to-male LT. Conclusions In the current study, we found that the sex disparity shown in living donor LT is also observed in deceased donor LT. That is, post-transplant graft failure risk was greater in female-to-male LT than other donor–recipient sex groups only when donor age was ≤40 y. In contrast, graft failure risk was comparable irrespective of donor-recipient sex combinations when donor age was >40 y. Full article

Behavioral issues in domestic dogs represent a significant welfare concern affecting both canines and their caregivers, with prevalence rates reported to range from 34 to 86% across the population. Current treatment options, including selective serotonin reuptake inhibitors (SSRIs) like fluoxetine, often present limitations including adverse effects and delayed efficacy. This randomized, placebo-controlled (maltodextrin) study investigated the effects of a novel Lactiplantibacillus plantarum strain (LP815^TM) on canine behavioral concerns through gut–brain axis modulation. Home-based dogs (n = 40) received either LP815^TM (n = 28) or placebo (n = 12) daily for 4 weeks, with behavioral changes assessed using the comprehensive Canine Behavioral Assessment & Research Questionnaire (C-BARQ) and continuous activity monitoring. After the intervention period, dogs receiving LP815^TM showed significant improvements in aggression (p = 0.0047) and anxiety (p = 0.0005) compared to placebo controls. These findings were corroborated by objective activity data, which demonstrated faster post-departure settling, reduced daytime sleep, and improved sleep consistency in the treatment group. Throughout >1120 administered doses, no significant adverse events were reported, contrasting favorably with pharmaceutical alternatives. The concordance between our findings and previous research using different L. plantarum strains suggests a consistent biological mechanism, potentially involving GABA production and vagal nerve stimulation. These results indicate that LP815^TM represents a promising, safe alternative for addressing common canine behavioral concerns with potential implications for improving both canine welfare and the human–animal bond. Full article

Human cutaneous leishmaniasis (CL) caused by Leishmania (Viannia) braziliensis is a complex parasitic disease marked by dynamic host–parasite interactions and immunomodulation. Extracellular vesicles (EV) derived from immune cells have emerged as key mediators of intercellular communication and potential biomarkers in infectious diseases. In this study, we combined a modified lymphocyte proliferation assay with nano-flow cytometry to quantify and phenotype EV released by CD4⁺, CD8⁺, and CD14⁺ cells in PBMC cultures from CL patients at different clinical stages: before treatment (PBT), during treatment (PDT), and post-treatment (PET) with antimonial. Healthy individuals (HI) were included as physiological controls. Upon stimulation with L. (V.) braziliensis antigens, we observed a distinct modulation of EV subsets. In the PBT group, CD4⁺ and CD14⁺ EV were significantly reduced, while CD8⁺ EV remained elevated. During PDT and PET, EV concentrations were restored across all subsets. These findings suggest that L. (V.) braziliensis selectively modulates the release of immune cell–derived EV, possibly as an immune evasion mechanism. The restoration of EV release following antimonial therapy highlights their potential as sensitive biomarkers for disease activity and treatment monitoring. This study offers novel insights into the immunoregulatory roles of EV in CL and underscores their relevance in host–parasite interactions. Full article

Background/Objective: Pharmacological interventions often exert systemic effects beyond their primary targets, underscoring the need for a comprehensive evaluation of their metabolic impact. Etodolac is a nonsteroidal anti-inflammatory drug (NSAID) that alleviates pain, fever, and inflammation by inhibiting cyclooxygenase-2 (COX-2), thereby reducing prostaglandin synthesis. While its pharmacological effects are well known, the broader metabolic impact and potential mechanisms underlying improved clinical outcomes remain underexplored. Untargeted metabolomics, which profiles the metabolome without prior selection, is an emerging tool in clinical pharmacology for elucidating drug-induced metabolic changes. In this study, untargeted metabolomics was applied to investigate metabolic changes following a single oral dose of etodolac in healthy male volunteers. By analyzing serial blood samples over time, we identified endogenous metabolites whose concentrations were positively or inversely associated with the drug’s plasma levels. This approach provides a window into both therapeutic pathways and potential off-target effects, offering a promising strategy for early-stage drug evaluation and multi-target discovery using minimal human exposure. Methods: Thirty healthy participants received a 400 mg dose of Etodolac. Plasma samples were collected at five time points: pre-dose, before Cmax, at Cmax, after Cmax, and 36 h post-dose (n = 150). Samples underwent LC/MS-based untargeted metabolomics profiling and pharmacokinetic analysis. A total of 997 metabolites were significantly dysregulated between the pre-dose and Cmax time points, with 875 upregulated and 122 downregulated. Among these, 80 human endogenous metabolites were identified as being influenced by Etodolac. Results: A total of 17 metabolites exhibited time-dependent changes closely aligned with Etodolac’s pharmacokinetic profile, while 27 displayed inverse trends. Conclusions: Etodolac influences various metabolic pathways, including arachidonic acid metabolism, sphingolipid metabolism, and the biosynthesis of unsaturated fatty acids. These selective metabolic alterations complement its COX-2 inhibition and may contribute to its anti-inflammatory effects. This study provides new insights into Etodolac’s metabolic impact under healthy conditions and may inform future therapeutic strategies targeting inflammation. Full article

There is insufficient evidence regarding the cytotoxicity of restorative 3D-printing resins, used as part of the digital workflow in dentistry. This study presents a novel comparative evaluation of cell viability and adhesion using human Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs), a less commonly used but clinically relevant cell line in dental biomaterials research. The aim of this study was to evaluate the cell viability of WJ-MSCs seeded on 3D-printed resins intended for temporary restorations. Resin discs of three commercial 3D-printing resins (NextDent C&B, Leaf Dental C&B, and UNIZ Temp) and a conventional self-curing acrylic resin (NicTone) were used. WJ-MSCs were cultured on the specimens for 1, 4, and 10 days. Cell viability was assessed using the PrestoBlue assay, Live/Dead immunofluorescence staining, and 7AAD/Annexin V staining. Cell adhesion was evaluated using scanning electron microscopy. Direct exposure to the 3D-printed resins and the self-curing acrylic caused slight reductions in cell viability compared to the control group in both microscopic analyses. 7AAD/Annexin V showed the highest percentage of viable WBCs for the conventional acrylic (34%), followed by UNIZ (35%), NextDent (42%), and Leaf Dental (36%) (ANOVA p < 0.05 Tukey’s post-hoc test p < 0.05). These findings suggest that 3D-printed resins could be considered safe for use in temporary restorations. Full article

Early printed books, particularly incunabula, are invaluable archives of the beginnings of modern educational systems. However, their complex layouts, antique typefaces, and page degradation caused by bleed-through and ink fading pose significant challenges for automatic transcription. In this work, we present a modular pipeline that addresses these problems by combining modern layout analysis and language modeling techniques. The pipeline begins with historical layout-aware text segmentation using Kraken, a neural network-based tool tailored for early typographic structures. Initial optical character recognition (OCR) is then performed with Kraken’s recognition engine, followed by post-correction using a fine-tuned ByT5 transformer model trained on manually aligned line-level data. By learning to map noisy OCR outputs to verified transcriptions, the model substantially improves recognition quality. The pipeline also integrates a preprocessing stage based on our previous work on bleed-through removal using robust statistical filters, including non-local means, Gaussian mixtures, biweight estimation, and Gaussian blur. This step enhances the legibility of degraded pages prior to OCR. The entire solution is open, modular, and scalable, supporting long-term preservation and improved accessibility of cultural heritage materials. Experimental results on 15th-century incunabula show a reduction in the Character Error Rate (CER) from around 38% to around 15% and an increase in the Bilingual Evaluation Understudy (BLEU) score from 22 to 44, confirming the effectiveness of our approach. This work demonstrates the potential of integrating transformer-based correction with layout-aware segmentation to enhance OCR accuracy in digital humanities applications. Full article

Refractory full-thickness macular holes (rFTMHs) present a significant challenge in vitreoretinal surgery, with reported incidence rates of 4.2–11.2% following standard vitrectomy with internal limiting membrane (ILM) peeling and gas tamponade. Risk factors include large hole size (>400 µm), chronicity (>6 months), high myopia, incomplete ILM peeling, and post-operative noncompliance. Multiple surgical techniques exist, though comparative evidence remains limited. Current options include the inverted ILM flap technique, autologous ILM transplantation (free flap or plug), lens capsular flap transplantation (autologous or allogenic), preserved human amniotic membrane transplantation, macular subretinal fluid injection, macular fibrin plug with autologous platelet concentrates, and autologous retinal transplantation. Closure rates range from 57.1% to 100%, with selection depending on hole size, residual ILM, patient posturing ability, etc. For non-posturing patients, fibrin plugs are preferred. Residual ILM cases may benefit from extended peeling or flap techniques, while large holes often require scaffold-based (lens capsule, amniotic membrane) or fibrin plug approaches. Pseudophakic patients should avoid posterior capsular flaps due to lower success rates. Despite promising outcomes, the lack of randomized trials necessitates further research to establish evidence-based guidelines. Personalized surgical planning, considering anatomical and functional goals, remains crucial in optimizing visual recovery in rFTMHs. Full article

Cardiorespiratory fitness is a predictor of long-term health, traditionally assessed through structured exercise protocols that require maximal effort and controlled laboratory conditions. These protocols, while clinically validated, are often inaccessible, physically demanding, and unsuitable for unsupervised monitoring. This study proposes a non-invasive, unsupervised alternative—predicting the heart rate a person would reach after completing the step test, using wearable data collected during natural daily activities. Ground truth post-exercise heart rate was obtained through the Queens College Step Test, which is a submaximal protocol widely used in fitness settings. Separately, wearable sensors recorded heart rate (HR), blood oxygen saturation, and motion data during a protocol of lifestyle tasks spanning a range of intensities. Two machine learning models were developed—a Human Activity Recognition (HAR) model that classified daily activities from inertial data with 96.93% accuracy, and a regression model that estimated post step test HR using motion features, physiological trends, and demographic context. The regression model achieved an average root mean squared error (RMSE) of 5.13 beats per minute (bpm) and a mean absolute error (MAE) of 4.37 bpm. These findings demonstrate the potential of test-free methods to estimate standardized test outcomes from daily activity data, offering an accessible pathway to infer cardiorespiratory fitness. Full article

Recent archaeological discoveries across the Aegean, Cyprus, and western Anatolia have renewed interest in pre-Neolithic seafaring and early island colonization. However, the environmental contexts that support such early coastal occupations remain poorly understood, largely due to the submergence of Pleistocene shorelines following post-glacial sea-level rise. This study addresses this gap through an integrated geoarchaeological investigation of the pre-Neolithic site of Ouriakos on Lemnos Island, northeastern Aegean (Greece), dated to the mid-11th millennium BCE. By reconstructing both the terrestrial and submerged paleolandscapes of the site, we examine ecological conditions, resource availability, and sedimentary processes that shaped human activity and site preservation. Employing a multiscale methodological approach—combining bathymetric survey, geomorphological mapping, soil micromorphology, geochemical analysis, and Optically Stimulated Luminescence (OSL) dating—we present a comprehensive framework for identifying and interpreting early coastal settlements. Stratigraphic evidence reveals phases of fluvial, aeolian, and colluvial deposition associated with an alternating coastline. The core findings reveal that Ouriakos was established during a phase of environmental stability marked by paleosol development, indicating sustained human presence. By bridging terrestrial and marine data, this research contributes significantly to the understanding of human coastal mobility during the Pleistocene–Holocene transition. Full article

Triphenyl phosphate (TPhP) is a widely used organophosphate flame retardant and plasticizer, raising concerns over its health impacts. This study examined the effects of embryonic TPhP exposure on axial skeletal development and metabolism in medaka (Oryzias latipes), a vertebrate fish model relevant to human bone biology. Medaka embryos were exposed to 1 µM TPhP and assessed through early larval stages. TPhP impaired vertebral ossification, causing shortened centra and reduced cartilage in the caudal complex, alongside disrupted distribution of osteoblast-lineage cells. Key osteogenic genes were significantly downregulated at 14 days post fertilization, and transcriptomic analysis revealed altered mitochondrial pathways linked to skeletal disorders. Functionally, TPhP-exposed larvae showed reduced caudal fin regeneration and decreased metabolic rate and oxygen consumption, consistent with mitochondrial dysfunction. These findings indicate that TPhP disrupts bone development and metabolism by affecting osteoblast differentiation and mitochondrial regulation, highlighting the value of small fish models for studying environmental toxicants and bone metabolic disease risk. Full article

Automated vehicles controlled by artificial intelligence are becoming capable of making moral decisions independently. This study investigates the differences in participants’ perceptions of the moral decision-maker’s permissibility when viewing scenarios (pre-test) and after witnessing the outcomes of moral decisions (post-test). It also investigates how permissibility, ten typical moral emotions, and perceived moral agency fluctuate when AI and the human driver make deontological or utilitarian decisions in a pedestrian-sacrificing dilemma (Experiment 1, N = 254) and a driver-sacrificing dilemma (Experiment 2, N = 269) from a third-person perspective. Moreover, by conducting binary logistic regression, this study examined whether these factors could predict the non-decrease in permissibility ratings. In both experiments, participants preferred to delegate decisions to human drivers rather than to AI, and they generally preferred utilitarianism over deontology. The results of perceived moral emotions and moral agency provide evidence. Moreover, Experiment 2 elicited greater variations in permissibility, moral emotions, and perceived moral agency compared to Experiment 1. Moreover, deontology and gratitude could positively predict the non-decrease in permissibility ratings in Experiment 1, while contempt had a negative influence. In Experiment 2, the human driver and disgust were significant negative predictor factors, while perceived moral agency had a positive influence. These findings deepen the comprehension of the dynamic processes of autonomous driving’s moral decision-making and facilitate understanding of people’s attitudes toward moral machines and their underlying reasons, providing a reference for developing more sophisticated moral machines. Full article

Background/Objectives: Epilepsy is a brain condition that affects millions of people worldwide. Although there are many antiepileptic drugs with different mechanisms of action, many patients still fail to control their agonizing symptoms, a situation that highlights the need for more strategies to address this issue. In this in vitro study, we elucidated and characterized the alterations in intracellular Ca²⁺ levels in cell cultures where diazepam and repetitive transcranial magnetic stimulation were implemented, alone or in combination. Methods: Using the differentiated human-derived neuroblastoma cell line SH-SY5Y, we measured the alterations in intracellular Ca²⁺ levels under the impact of either low-frequency repetitive transcranial magnetic stimulation (1 Hz), diazepam (14 μM), or their combination. We used the Ca²⁺-sensitive fluorescent indicator Fluo-4 acetoxymethyl ester for calcium imaging, while neuronal excitation was achieved with 50 mM KCl. Results: The highest median fluorescence intensity increase (%ΔF/F = 24.80) was observed in control cell cultures, followed by rTMS cultures (%ΔF/F = 16.96) and diazepam cultures (%ΔF/F = 11.46). The lowest median fluorescence intensity value (%ΔF/F =−0.44) was observed when diazepam was used concomitantly with repetitive transcranial magnetic stimulation. Post hoc analysis assessed pairwise differences, showing statistically significant differentiation between the control group and all other groups. Additionally, statistically significant results were observed between repetitive transcranial magnetic stimulation or diazepam and their combination, but not between them. Conclusions: The combination of diazepam and repetitive transcranial magnetic stimulation resulted in the most significant reduction in intracellular Ca²⁺ levels, as indicated by the lowest fluorescence values compared with the control group. Individually, each treatment produced a notable but less pronounced effect. We conclude that both diazepam and low-frequency repetitive transcranial magnetic stimulation can control epileptiform activity in vitro, while their combination is the most effective treatment. Full article

Background: Ingestion of dietary fibers (DFs) is a safe and accessible intervention associated with reductions in blood pressure (BP) and cardiovascular mortality. However, the mechanisms underlying the antihypertensive effects of DFs remain poorly defined. This systematic review and meta-analysis evaluates how DFs influence BP regulation by modulating gut microbial composition and enhancing short-chain fatty acid (SCFA) production. Methods: MEDLINE and EMBASE were systematically searched for interventional studies published between January 2014 and December 2024. Eligible studies assessed the effects of DFs or other prebiotics on systolic BP (SBP) and diastolic BP (DBP) in addition to changes in gut microbial or SCFA composition. Results: Of the 3010 records screened, nineteen studies met the inclusion criteria (seven human, twelve animal). A random-effects meta-analysis was conducted on six human trials reporting post-intervention BP values. Prebiotics were the primary intervention. In hypertensive cohorts, prebiotics significantly reduced SBP (−8.5 mmHg; 95% CI: −13.9, −3.1) and DBP (−5.2 mmHg; 95% CI: −8.5, −2.0). A pooled analysis of hypertensive and non-hypertensive patients showed non-significant reductions in SBP (−4.5 mmHg; 95% CI: −9.3, 0.3) and DBP (−2.5 mmHg; 95% CI: −5.4, 0.4). Animal studies consistently showed BP-lowering effects across diverse etiologies. Prebiotic interventions restored bacterial genera known to metabolize DFs to SCFAs (e.g., Bifidobacteria, Akkermansia, and Coprococcus) and increased SCFA levels. Mechanistically, SCFAs act along gut–organ axes to modulate immune, vascular, and neurohormonal pathways involved in BP regulation. Conclusions: Prebiotic supplementation is a promising strategy to reestablish BP homeostasis in hypertensive patients. Benefits are likely mediated through modulation of the gut microbiota and enhanced SCFA production. Full article

Background: Postoperative pain management after a cesarean section remains a significant challenge, as inadequate control can delay maternal recovery and hinder early bonding and breastfeeding. While multimodal analgesia is the standard approach, non–pharmacological strategies like immediate skin–to–skin contact (SSC) are often underused despite their potential benefits in reducing pain, improving uterine contractions, and increasing maternal satisfaction. Objective: To evaluate the effects of immediate SSC on postoperative pain perception, uterine contraction quality, and maternal satisfaction, and to explore ways to incorporate SSC into routine post–cesarean care to promote recovery and humanized care. Method: A randomized clinical trial was conducted with 80 women undergoing elective cesarean sections, divided into two groups: SSC (40 women) and control (40 women). Postoperative pain was measured using the Visual Analog Scale (VAS) at various intervals, while uterine contraction quality and maternal satisfaction were assessed through clinical observation and a Likert scale, respectively. Results: We found that women in the SSC group experienced significantly lower pain scores (VAS2 and VAS3, p < 0.001), stronger infraumbilical uterine contractions (92.5%, p < 0.001), and higher satisfaction levels (average 9.98 vs. 6.50, p < 0.001). An inverse correlation was observed between pain intensity and satisfaction, indicating that SSC enhances both physiological and psychological recovery. Conclusions: Immediate SSC after cesarean is an effective, humanizing intervention that reduces pain, supports uterine contractions, and boosts maternal satisfaction. These findings advocate for integrating SSC into standard postoperative care, aligning with ethical principles of beneficence and autonomy. Further research with larger samples is necessary to confirm these benefits and facilitate widespread adoption in maternity protocols. Full article