Search Results (4,010)

Metabolic dysfunction-associated steatotic liver disease (MASLD, introduced in 2023), formerly termed non-alcoholic fatty liver disease (NAFLD), is a leading cause of chronic liver disease worldwide and is closely linked to obesity, insulin resistance, and cardiometabolic dysfunction. Exercise is widely recommended as a cornerstone of MASLD management; however, the magnitude of its hepatic and metabolic benefits and the underlying molecular mechanisms remain incompletely defined. We aim to synthesize evidence from randomized controlled trials assessing how structured exercise interventions influence hepatic steatosis and metabolic dysfunction in adults with MASLD. A targeted search of PubMed from database inception to February 2025 identified eligible trials, of which eleven were included in the qualitative synthesis. Across studies, aerobic and resistance exercise interventions were consistently associated with reductions in hepatic fat content, improvements in plasma lipid profiles and liver enzyme concentrations, and enhanced indices of insulin sensitivity, frequently occurring independently of substantial weight loss. Mechanistically, exercise-induced activation of pathways related to mitochondrial function, lipid oxidation, inflammation modulation, and insulin signaling likely contributes to these benefits. Despite heterogeneity in intervention design, duration, and outcome assessment, the collective evidence supports structured exercise as an effective non-pharmacological strategy for improving hepatic steatosis and metabolic dysfunction in MASLD. Future studies integrating molecular biomarkers with clinical endpoints are warranted to refine exercise prescriptions and elucidate mechanisms of therapeutic response. Full article

This article explores Rudolf Steiner’s Christology within the framework of cosmic evolution, focusing on the Second Coming of Christ as a pivotal metaphysical event. Identifying a scholarly lacuna regarding Steiner’s developmental cosmology and the work of Yeshayahu Ben-Aharon, the study adopts an immanent–synthetic methodology to demonstrate a sacramental, participatory epistemology. The first part unfolds Steiner’s vision of the ‘Mystery of Golgotha’ as a cosmic turning point where a macrocosmic death process is reversed into a resurrection life stream. The second part examines Ben-Aharon’s esoteric development of these ideas into a contemporary ‘knowledge drama of the Second Coming.’ Through the spiritualization of consciousness, Ben-Aharon describes an individual ‘essence-exchange’ with the Christ impulse within the ‘abyss of nothingness’ of our age. Finally, the article discusses the social–metaphysical implications of this drama through the ‘Reversed Cultus.’ Here, the indwelling Christ is recognized as humanity’s ‘Higher Self,’ grounding a new community and ‘school of love’ capable of responding to the technoscientific challenges of mechanization of intelligence and life. By positioning the human being as a co-creative agent in cosmic becoming, the article argues for a renewed understanding of the Second Coming as a new step in humanity’s spiritual evolution. Full article

Theological engagement with artificial intelligence has largely focused on applied ethics, addressing bias, governance, and labor displacement. While indispensable, this framing often presumes that algorithmic systems operate as external instruments acting upon already constituted subjects. This article argues that contemporary predictive architectures intervene at a deeper anthropological level by structuring attention, expectation, and habituation prior to deliberative judgment. It introduces the concept of ordo extractionis to designate a technologically mediated regime of formation characterized by behavioral trace extraction, probabilistic modeling, and recursive projection of statistically inferred continuity. Drawing on Augustine’s account of ordered love and temporality and Aquinas’s doctrine of habitus and the invisible mission of the Spirit, the article distinguishes algorithmic projection from sanctification as divergent pedagogies of temporal formation. Predictive systems stabilize continuity by extrapolating from measurable past behavior; sanctification reorders desire teleologically toward a final end not deducible from prior pattern and grounded in non-competitive divine causality. Algorithmic mediation is therefore interpreted pedagogically rather than metaphysically: it does not rival divine agency but participates creaturely in shaping the ecology within which habituation unfolds. Engagement with contemporary AI research on recommender systems, reinforcement learning, and generative models situates the argument within technological realism and resists determinism. The digital twin is analyzed as a probabilistic representation that acquires institutional authority when operationalized in ranking, profiling, and evaluative systems, without constituting a metaphysical competitor to the imago Dei. In response to anticipatory closure, Eucharistic anamnesis and epiclesis are developed as practices that re-situate memory and expectation within eschatological promise. The article concludes that the central theological question posed by AI is not whether machines can think, but how formative sovereignty over desire is exercised within technologically mediated modernity. Full article

Esports are a rapidly expanding form of competitive activity that demand high levels of cognitive alertness, motor precision, stress management, and resilience to mental and physical fatigue. At the same time, the sedentary lifestyle, extended screen exposure, and psychological pressures associated with competitive gaming raise concerns for both performance and long-term health. Growing evidence highlights the importance of nutrition and lifestyle behaviors in supporting cognitive performance and overall competitive demands. While balanced dietary patterns and adequate hydration are essential, dietary supplements may provide additional benefits when used appropriately and under professional guidance. However, the current research is limited by a predominance of cross-sectional and self-reported studies, short-term or acute interventions, small sample sizes, and insufficient emphasis on esports-specific and personalized strategies. This review examines existing evidence on individualized nutrition, supplementation, and lifestyle strategies in esports, identifies key methodological limitations, and outlines future directions to inform evidence-based practice for athletes, practitioners, and organizations seeking to optimize cognitive performance, well-being, and long-term sustainability in this emerging field. Full article

The use of fiber-reinforced polymers (FRPs) for strengthening existing reinforced concrete (RC) structures has significantly improved structural rehabilitation processes, providing efficient, durable, and non-invasive solutions. This study presents an advanced deep learning-based predictive model specifically developed to estimate the shear strength of concrete beams strengthened externally with carbon fiber-reinforced polymer (CFRP) composites. Using a comprehensive dataset of 216 experimentally tested CFRP-wrapped concrete beams drawn from existing research, a deep neural network model was rigorously optimized with the Optuna hyperparameter tuning framework and k-fold cross-validation to ensure robustness and generalizability. Model validation involved a thorough comparative analysis against established international design codes (ACI PRC-440.2-17, CSA-S806-12, JSCE) and a parametric study examining the sensitivity of shear strength predictions to key influencing factors, including concrete compressive strength, beam depth, and CFRP wrap thickness. Results demonstrated superior prediction accuracy and reliability of the deep learning approach compared to traditional empirical design models. Consequently, this research significantly enhances the precision of shear strength predictions for CFRP-strengthened concrete beams, supporting the development of more efficient and accurate structural rehabilitation and design guidelines. Full article

Background/Objectives: The immunoglobulin heavy-chain variable (IGHV) gene repertoire represents a characteristic feature of chronic lymphocytic leukemia (CLL), although its configuration is not well defined at the early disease stages. The IGHV repertoire of a cohort of early CLL patients was analyzed and compared to that of a “real-world” reference cohort. Methods: Patients from the O-CLL1 observational protocol, which enrolled only Binet stage A cases within twelve months from diagnosis, were studied. IGHV/IGHJ rearrangements were sequenced and annotated following ERIC recommendations, and stereotyped subsets were assigned using ARResT/AssignSubsets. The repertoire features were compared with the dataset of a real-world cohort of patients with heterogeneous staging (CTR cohort) and with published early-diagnosis series. Results: IGHV and IGHJ gene distributions and HCDR3-length profiles in O-CLL1 closely mirrored those of CTR, indicating that the BcR IG repertoire at diagnosis is already defined rather than being selected during disease progression. Mutated IGHV (M-CLL) predominated, with a frequency of stereotyped BcR IG comparable to that of other early-diagnosis cohorts. However, within this conserved framework, subset #4 was over-represented among M-CLL from O-CLL without an increased overall IGHV4-34 gene usage, suggestive of a selective expansion rather than a recombinational bias. Subset #4 cases retained canonical HCDR3 motifs and showed time-to-first-treatment like other M-CLL, likely reflecting the younger age structure of O-CLL1. Conclusions: Early-diagnosis CLL displays a biased IGHV repertoire with stereotyped configurations characteristic of CLL, including subsets that are rare in the normal B-cell repertoire. These findings support a central role for antigen-driven selection in shaping CLL evolution. Full article

CXCL5 is a platelet-derived chemokine which promotes inflammatory responses in neutrophils and monocytes through CXCR2. Previous studies on CXCL5 in atherogenesis are to some degree conflicting, with scarce outcome data following acute coronary syndrome. This study aimed to assess the utility and risk profile of CXCL5 as a prognostic marker of all-cause mortality at 5-year follow-up in patients hospitalized for chest pain of suspected coronary origin. We measured CXCL5 levels in platelet-poor plasma in 826 consecutive patients included in the “Risk Markers in the Acute Coronary Syndrome” (RACS) study (ClinicalTrials.gov Identifier: NCT00521976). Stepwise Cox regression models, applying quintiles, were fitted for the biomarker with all-cause mortality within 5 years as the dependent variable. At 5-year follow-up, 250 (30.3%) of the population had died; 34.5% in Quintile (Qt)-1, 32.1% in Qt-2, 23.5% in Qt-3, 29.1% in Qt-4, and 32.1% in Qt-5. Using Qt-3 as a reference, both the univariate and multivariable analysis showed a U-shaped association between CXCL5 and all-cause mortality. Univariate analysis: Qt-1 vs. Qt-3: HR 1.59 (95% CI 1.06–2.39), p = 0.026, and Qt-5 vs. Qt-3: HR 1.44 (0.95–2.18), p = 0.082, respectively. Multivariable analysis: Qt-1 vs. Qt-3: HR 1.65 (1.09–2.48), p = 0.017, and Qt-5 vs. Qt-3: HR 1.52 (1.00–2.30), p = 0.049, respectively. The U-shaped relationship was statistically strengthened, employing a composite endpoint consisting of all-cause mortality, MI or stroke. Our findings suggest that both too-low and too-high levels of CXCL5 may be harmful in patients admitted to hospital with chest pain of suspected coronary origin. Full article

Background: Dental students need to qualify with a clear understanding of the continuum of biological development from the molecular (genetic, epigenetic and environmental interactions) to the cellular (morphogenesis and differentiation) to the emergence of the mature tissue or organ. Histogenetics provides a core component for this understanding. The aim of this study is to investigate whether a merged approach, combining traditional and recent methods, can enhance the teaching of histogenetics to dental students. Methods: This study blended traditional (lectures, drawings, microscopy) and recent approaches (flipped classroom elements, virtual microscopy, group-based poster construction, and interactive quiz-based discussion) to enhance student engagement and perceived learning in oral histogenetics. The intervention was delivered to master-level dental students across six core oral histogenetics topics. Teaching followed a structured three-phase model: Prepare (digital lectures and short microscopy-introduction videos); Engage (microscopy session and group-based poster creation); and Test and Discuss (teacher-led quizzing and discussion). Student perceptions were evaluated through an electronically distributed 17-item questionnaire at the end of the course. Items were grouped into self-evaluation, resources, and teaching method domains and rated on a five-point Likert scale. Results: A total of 45 of 51 students responded (88%). Across all domains, positive perceptions (Agree/Strongly Agree) predominated (p < 0.001). Self-evaluation items showed strong agreement for attendance and group contribution, with more variability in preparation time and motivation. Resources were rated highly, although the accessibility of physical guidance showed more mixed responses. The merged teaching method received strong endorsement, with students reporting engagement, enjoyment, ease of understanding, and clear emphasis on clinical relevance. Conclusions: The merged approach was perceived as pedagogically valuable and clinically meaningful by the students and appears to enhance perceived engagement, clarity, and relevance in oral histogenetics teaching. These findings support the adoption of blended, student-active methodologies to strengthen comprehension and promote clinically meaningful learning in oral histology. Full article

Background/Objectives: Irritable bowel syndrome (IBS) is a prevalent gastrointestinal disorder with implications for individual quality of life and society. Patients with IBS suffer a variety of symptoms but have few treatment options. The level of satisfaction with IBS treatment is low, stressing the need to expand the IBS treatment toolbox. The aim of this study is to describe drivers and barriers to the implementation of time-restricted eating (TRE) as a treatment alternative for patients with IBS. Methods: A convenience sample of 14 informants was drawn from a pool of 97 successful participants in an eight-week 16:8 TRE intervention. The informants partook in audio-recorded semi-structured in-depth interviews. Recordings were processed by a computer language model and interview transcripts were generated automatically. The transcripts were proofread, structured and analysed with a reflexive inductive thematic analysis approach. Results: The analysis generated six main themes consisting of 18 sub-themes in total. One main theme describes drivers of implementation concerning domains such as motivation, supporting factors, mentality, behaviour and determinants of sustainability. The results from this study are largely coherent with the findings from earlier feasibility studies conducted on other populations, but several key differences related to population characteristics emerged. Conclusions: Overall, the analysis suggests that TRE can be a feasible treatment option for IBS, but successful implementation is dependent on individual ability, external support and symptom relief. Full article

Background/Objectives: Infraocclusion in pediatric patients may result in space loss, malocclusion and the need for complex orthodontic treatment if not detected early. Conventional diagnosis may be subject to human error and can be challenging, particularly in pediatric cases. The aim of this study is to design and evaluate a lightweight, two-stage deep learning framework with integrated explainable AI (XAI) techniques for automated infraocclusion detection in pediatric panoramic radiographs. Methods: Annotated panoramic radiographs of pediatric patients aged 7–11 years were used for training and validation. In the first stage, a MobileNet V2 Lite model was used to detect the region of interest (ROI) comprising premolars and molars. In the second stage, a custom CNN classifier was proposed to distinguish between infraocclusion and no infraocclusion. Model performance was evaluated in terms of diagnostic accuracy, computational complexity, and statistical significance. XAI techniques were also incorporated to visualize model attention and enhance interpretability. Results: The detection stage achieved high reliability with a precision, recall, F1-score, and AP50 values of 0.99, and an AP75 of 0.89, indicating accurate ROI localization. The classification stage reached an overall accuracy of 98.78%, with class-specific accuracies of 99.25% for infraocclusion and 98.31% for no infraocclusion cases. The framework also demonstrated computational efficiency, requiring only 1.88 M trainable parameters (7.19 MB), with short training times and low inference latency (0.8 ms for classification and 19 ms for detection). XAI visualizations consistently highlighted clinically relevant regions, such as occlusal margins and interproximal areas, confirming the model’s alignment with radiographic features recognized by clinicians. Conclusions: The proposed two-stage framework provides an accurate, computationally efficient, and interpretable solution for automated infraocclusion detection in pediatric patients. Its modular design and reduced complexity support practical integration into routine clinical workflows, including resource-constrained environments. These findings indicate that lightweight and XAI systems may enhance early infraocclusion detection while maintaining clinical transparency. Full article

The short half-life of positron emission tomography (PET) radioisotopes makes transport time a critical factor in medical logistics. While drones have demonstrated advantages in short-range medical deliveries, the feasibility and benefits of long-distance drone transport remain largely unexplored. In a comparative simulation-based modelling framework, this study explores whether long-range drone transport (117–376 km) can improve delivery performance of fluorodeoxyglucose-18 ([¹⁸F]FDG) PET isotopes compared with two existing ground-only routes (146 km and 348 km) and two combined car–airplane routes (532 km and 546 km). Simulated transport times, radioactive decay losses, and economic implications were estimated using drone speeds of 150, 200, and 250 km/h. Hourly weather data from 2023–2024 were incorporated to model flight feasibility and weather-related no-fly conditions. Time savings were translated into preserved radioactive activity and analyzed together with break-even transport costs. A drone speed of 150 km/h provided limited benefit, whereas speeds of 200–250 km/h preserved activity corresponding to a reduction from the current total use of 118 GBq to 72 and 65 GBq, respectively. Weather constraints reduced feasible winter flights by up to 30%. Estimated break-even drone costs ranged from EUR 3–18/km and increased to EUR 14–20/km when accounting for preserved isotopes, corresponding to annual economic gains of EUR 1.0–1.7 million. These results suggest that long-range drone transport could reduce isotope losses and improve diagnostic capacity, although feasibility depends on drone costs, weather resilience, and integration into clinical logistics systems. Full article

Ultraviolet (UV) radiation induces DNA damage and oxidative stress in melanocytes, shaping pigmentation phenotypes and elevating photocarcinogenesis risk. Human models that capture donor-linked genetic determinants of UV sensitivity remain limited. Here, we establish a genotype-informed UV response model using induced pluripotent stem cell (iPSC)-derived melanocytes from donors carrying defined MC1R variants. Differentiated cells recapitulated melanocytic morphology, marker expression, and pigmentation consistent with donor sun-sensitivity traits. Following narrowband UVB exposure, melanocyte lines with higher UV sensitivity showed reduced survival, prolonged checkpoint activation, and CPD-associated DNA damage signaling dynamics. Mechanistic analysis suggests that the interferon-regulated GTPase MX2 is associated with amplification of UV-induced p53 and p38 activation while promoting apoptosis independently of AKT. These findings support MX2 as a physiological enhancer of DNA damage signaling in normal melanocytes, distinct from its interferon-mediated role in melanoma. Our study provides a human-relevant platform linking pigmentation genotype to UV resilience and supports iPSC-derived systems as new approach methodologies (NAMs) for mechanistic and translational phototoxicology. Full article

More than 80% of young people (11–17 years) do not meet recommended levels of physical activity, while excessive sedentary smartphone use increases rapidly, highlighting the need for accessible tools that promote active and kinesthetic learning. This study investigates whether smartphones can function as wearable devices capable of tracking movement, detecting biomechanical errors, and providing real-time corrective feedback. Using a user-centered design approach, we developed a gamified Exertion Trainer in which children practiced a straight punch (boxing jab) while wearing a smartphone on their wrist. Embedded accelerometer data were processed on board to deliver immediate, task-specific feedback on arm orientation, using gravity as a fixed reference frame. A randomized crossover trial was conducted with 40 children, comparing a feedback condition with a no-feedback control across two test orders. Quantitative results showed that real-time feedback produced a statistically significant improvement in punch accuracy (p < 0.001) and reduced performance variability, with the strongest effects observed after initial practice and partial retention following feedback removal. Qualitative findings indicated higher engagement and stronger perceptions of kinesthetic learning when feedback was available. These results demonstrate that smartphones can serve as practical wearable devices for delivering biomechanical guidance and supporting movement skill acquisition in children. Full article

The recent paradigm shift within cognitive neuroscience toward predictive processing appears to align with many psychoanalytic conceptualizations of the mind. In this article, we argue that several psychoanalytic concepts, such as projection, transference, wish-fulfillment, and perceptual identity, are particularly compatible with the current neuroscientific conception of the brain as a prediction machine. Specifically, we propose that the concept of projection as used in modern psychoanalysis to explore subjective experience and fantasies is closely analogous to the concept of prediction as it is used to explain the fundamental cognitive functions of the brain. We discuss the implications of this parallelism for understanding the role of homeostasis in psychoanalysis and cognitive neuroscience, and we also discuss the parallels between insight and surprise in these two fields of mental science. Limitations in drawing parallels between projection and prediction are also addressed. By integrating these two fields, we envision the possibility of tackling subjectivity scientifically. Full article

Liver transplantation has emerged as a curative treatment option for selected patients with unresectable hepatic malignancies beyond hepatocellular carcinoma, marking a paradigm shift in transplant oncology. For colorectal cancer liver metastases (CRLM), prospective trials have demonstrated that highly selected patients achieve 5-year OS rates of 60–83%, with the Oslo score identifying optimal candidates for transplantation. Perihilar cholangiocarcinoma (pCCA) has been successfully treated using strict patient selection criteria combined with neoadjuvant therapy, achieving 5-year OS rates of 50–68%, though emerging data suggests chemotherapy-based approaches may be preferable to radiation in selected cases. Intrahepatic cholangiocarcinoma (iCCA), previously considered a contraindication to transplantation, can now achieve excellent long-term outcomes (79.5% 5-year OS) in patients demonstrating sustained response to neoadjuvant chemotherapy and radioembolization, with metabolic tumor volume < 70 cm³ serving as an objective prognostic marker. Across these three emerging indications, successful outcomes depend on strict patient selection based on tumor biology, intensive multimodal neoadjuvant therapy, multidisciplinary evaluation in high-volume centers, and careful observation during treatment to exclude patients with aggressive disease. This evolution in transplant practice offers curative intent therapy to patients that previously only had palliative therapeutic options, fundamentally transforming hepatobiliary and oncologic surgery. Full article