Search Results (8,273)

Background/Objectives: Psilocybin has re-emerged as a promising intervention for neuropsychiatric disorders including major depressive disorder, treatment-resistant depression, anxiety associated with life-threatening illness, obsessive compulsive disorder, and substance use disorders. However, conventional randomized controlled trials (RCTs)—the current gold standard in evidence-based medicine—may not adequately capture the therapeutic complexity of psilocybin, which depends not only on pharmacological action but also on contextual, psychological, and interpersonal factors. This critical narrative review aimed to evaluate the adequacy of existing clinical research frameworks for assessing psilocybin’s therapeutic potential and to explore alternative methodologies that may better reflect real-world clinical conditions. Methods: Using the Web of Science Core Collection database, we identified and analysed the ten most cited clinical studies on psilocybin published between 2015 and 2025 inclusive. Additional literature was included through reference cross-checking, systematic reviews, meta-analyses, and interdisciplinary sources covering neurobiology, history, and real-world evidence (RWE). The review synthesizes clinical outcomes, methodological constraints, and epistemic considerations relevant to psychedelic-assisted therapy. Results: Evidence from highly cited trials demonstrates rapid and sustained antidepressant and anxiolytic effects of psilocybin, with notable benefits also observed in addiction treatment. However, significant methodological limitations were identified, including selection bias, challenges in placebo design and blinding, small sample sizes, and the underrepresentation of diverse populations. Psilocybin outcomes were strongly influenced by subjective experience and contextual factors such as set and setting. Emerging RWE studies revealed heterogeneous patterns of response and provided insights unattainable through RCTs alone. Conclusions: Psilocybin shows considerable therapeutic promise, but current RCT methodologies capture only part of its clinical effects. Comprehensive evaluation will require larger and more diverse clinical trials, long-term follow-up, standardized psychotherapeutic protocols, and the integration of RWE to reflect real-world practice. Psychedelic-assisted therapy should be conceptualized as a complex intervention that combines pharmacological and psychotherapeutic components. Full article

Background/Objectives: The continuous emergence of immune-evasive SARS-CoV-2 variants underscores the need for adaptable and accessible therapeutics that complement vaccination. Single-domain antibodies (sdAbs) offer advantages in size, stability, and production costs compared to conventional monoclonal antibodies, but their clinical utility is limited by rapid clearance. This study aimed to develop a rabbit-derived sdAb with broad SARS-CoV-2 neutralization capacity and improved pharmacokinetic properties. Methods: A rabbit-derived variable light-chain (VL) sdAb library was constructed and subjected to phage display selection to identify high-affinity binders. Candidate sdAbs were characterized for cross-variant binding and neutralization. The lead sdAb, B3, was fused to the albumin-binding domain (ABD) of the Streptococcus zooepidemicus Zag protein to enhance in vivo half-life. Expression, albumin-binding capacity, and in vitro neutralization were assessed, followed by biodistribution studies in mice. Results: The selected sdAb, B3, showed strong binding and cross-variant neutralization against multiple SARS-CoV-2 lineages, including Delta and Omicron. Fusion to ABD(Zag) preserved neutralization potency, increased expression yields ~5-fold, and enabled cross-species albumin binding. In vivo, B3-ABD(Zag) exhibited markedly extended blood retention, showing a 21.2-fold increase at 24 h post-injection (5.30 vs. 0.25% I.A./g), and reduced renal uptake by 40% compared with unmodified B3. Conclusions: Rabbit-derived VL sdAbs fused to ABD(Zag) provide a promising platform for next-generation SARS-CoV-2 biologics. The enhanced pharmacokinetic profile of B3-ABD(Zag) supports its potential as a scalable therapeutic modality and highlights the broader utility of this approach for future emerging infectious threats. Full article

This study examines whether Mandarin-speaking children with cochlear implants (CIs) exhibit challenges or advantages in learning novel words with overt trochaic versus iambic patterns. Mandarin full-tone words lack salient stress cues, whereas neutral-tone words exhibit a clear trochaic pattern. Given the unique prosody of Mandarin and CI users’ difficulty in acquiring the neutral tone, we predicted distinct effects of lexical stress on word production and recognition. Fifteen Mandarin-speaking preschoolers with CIs and 15 age-matched children with normal hearing (NH) learned 16 pairs of stress-contrasted novel words. A referent-naming task assessed stress production through pattern proportion, accuracy, and acoustic analysis, while a referent-matching task evaluated stress identification and word-referent mapping accuracy. In the naming task, children with CIs showed a preference for iambic words in both frequency and accuracy. They also produced longer second syllables in trochaic words than their NH peers. In the matching task, the CI group performed worse overall, although neither group showed a stress-specific effect. These results indicate that CI users struggle with syllable duration control in trochees. This difficulty reflects both an inability to shorten the unstressed syllable and the potential adoption of a final-syllable lengthening strategy linked to higher prosodic domains. The insensitivity to stress contrast in recognition may stem from the generally weak word-level stress cues in Mandarin. Full article

Background: Among gynecological malignancies, ovarian cancer (OC) remains a leading cause of mortality worldwide, often characterized by the highest fatality-to-case ratio due to its asymptomatic progression and late-stage detection. Despite substantial investigation, the root cause of disease development and pathology remains unknown. Early detection is critical for improving OC prognosis. Unfortunately, because of the lack of identifiable symptoms in the early stages, the disease is frequently detected late. As a result, regular check-ups, being aware of risk factors, and paying attention to unusual symptoms can all help discover OC early. Apolipoproteins (APOs) and Annexins (ANXs) have recently been linked to OC. Aim: We conducted a cutting-edge bioinformatics investigation to find novel therapeutic targets and precise biomarkers linked to OC against APO and ANX. Methods: We started by compiling the ANX and APO families via HUGO Gene Nomenclature Committee (HGNC) homepage. Next, we accessed GEPIA2 to compare the relative messenger RNA (mRNA) expression levels of all ANX and APO family members across the cancer genome atlas (TCGA)-OC cohort and matched normal and GTEx data. Prognostic analysis of all significantly expressed ANXs and APOs was performed via Kaplan–Meier (KM) plotter. cBioPortal was used for mutational analysis of prognostic ANXs and APOs. Finally, we ran functional enrichment, molecular docking, and molecular dynamics (MD) simulation analyses. Results: Overall, the results suggest that ANXA2 and its related genetic changes represent potential focal points for precision oncology, offering a computational rationale for the development of target-driven therapeutic interventions in OC. Conclusions: Molecular docking and MD simulation analyses identified curcumin as a potential inhibitor of ANXA2, demonstrating stable binding affinity and structural conservation throughout the simulation period. These computational findings characterize curcumin as a promising candidate for targeting ANXA2 in OC, warranting further experimental validation to confirm its therapeutic efficacy. Full article

The reaction mechanism of the gold-catalyzed hydrothiolation of alkenes (1) with thiols (2) has been investigated in detail. The tetranuclear gold complex, (PPh₃)₄Au₄(SPh)₂(NTf)₂ (A), is a key intermediate in the catalytic hydrothiolation of alkenes. It forms instantaneously when PPh₃AuNTf₂ and PhSH are mixed in THF. Monitoring the reaction over time using ³¹P NMR spectroscopy revealed that gold complex A remained stable in the reaction system throughout the hydrothiolation process. In addition, we successfully observed a rapid ligand-exchange reaction between the thiolate group of gold complex A and thiols in solution. The gold-catalyzed alkene hydrothiolation reaction has been applied to the catalytic hydrothiolation of allenes, which have degenerate double bonds. Hydrothiolation of allenes proceeded regioselectively at the terminal double bond. However, the yield was lower than that observed for alkenes, and catalyst deactivation occurred. The hydrothiolation products of allenes were difficult to detach from the gold catalyst, necessitating an increase in the reaction temperature. Since high periodic transition metals such as gold and platinum are effective for hydrothiolation of alkenes and allenes, it is interesting to clarify whether iridium complexes, which belong to the same period as gold and platinum, could also catalyze alkene hydrothiolation. Through a detailed investigation of iridium ligands and reaction conditions, it was found that, in iridium systems, disulfide formation via oxidative coupling of thiols occurs preferentially over hydrothiolation reactions. This is likely due to steric hindrance around the iridium center, which inhibits alkene coordination to the iridium. Additionally, the hydrothiolation proceeding at low yields is believed to be a radical reaction involving electron transfer through the iridium complex. Full article

Phonocardiogram (PCG) signals offer a non-invasive, low-cost screening tool for cardiovascular diseases. However, their noisy and non-stationary nature makes automated classification challenging, and traditional methods often fail to capture complex spectral-temporal patterns. This study proposes a multimodal deep learning architecture for the binary classification of heart sounds (Healthy vs. Unhealthy). The hybrid model integrates Convolutional Neural Networks (CNNs), Transformer encoders, and Bidirectional Long Short-Term Memory (BiLSTM) networks with an attention mechanism. It utilizes an early-fusion feature extraction pipeline combining MFCCs, Mel-spectrograms, and Chroma descriptors. To ensure robust evaluation and prevent data leakage, SMOTE is applied exclusively to the training folds within a strict zero-leakage, patient-wise 5-fold cross-validation protocol. The proposed framework demonstrates exceptional performance, achieving an average accuracy of 91.67%, a sensitivity of 80.95%, a specificity of 94.46%, and an AUC-ROC of 96.50%. An ablation study confirms that integrating Transformer and BiLSTM modules significantly enhances diagnostic stability over baseline CNNs. Furthermore, with exactly 858,434 parameters (3.27 MB) and interpretable attention maps, this highly optimized model provides a robust assistive solution suitable for deployment in digital stethoscopes and mobile telemedicine systems. Full article

We establish a general no-go theorem demonstrating that all traversable wormhole configurations in Unimodular Gravity necessarily require exotic matter. The proof relies solely on the geometric flaring-out condition, b′(r₀) ≤ 1, which directly implies that ρ(r₀) + p_r(r₀) ≤ 0 at the throat. This condition represents a violation of the Null Energy Condition and, consequently, of the Weak and Strong Energy Conditions, independently of the particular choice of shape function, redshift function, or equation of state. This result holds for both tidal and zero-tidal-force configurations, showing that the requirement of exotic matter is a fundamental geometric consequence of the traversability condition rather than an artifact of specific solution choices. Therefore, Unimodular Gravity shares this fundamental constraint with General Relativity. Full article

Background/Objectives: Dietary behavior in eating disorders (EDs) is often framed through either nutritional or psychological perspectives, yet emerging evidence suggests that eating may involve a transdiagnostic, emotionally embedded, and relationally negotiated process. While research highlights the role of emotion regulation difficulties, perfectionism, control, and overvaluation of weight and shape in ED maintenance, less is known about how these processes are interpreted and managed in clinical practice across different cultural contexts. This study explored psychotherapists’ perspectives on dietary behavior, nutritional assessment, and interdisciplinary collaboration in ED treatment in Greece and the United Kingdom. Methods: Eighteen psychotherapists (9 Greek and 9 British) with experience in treating individuals with EDs participated in in-depth semi-structured interviews. Data were analyzed using reflexive thematic analysis. Results: Three themes were developed. First, therapists conceptualized dietary behavior as reflecting broader transdiagnostic psychological processes, particularly perfectionism, control, emotion regulation difficulties, and body image concerns. Second, nutritional assessment and intervention (e.g., food diaries and meal plans) were experienced as emotionally significant practices that required negotiation of timing, meaning, and clients’ readiness for change. Third, interdisciplinary collaboration was described as involving ongoing negotiation of nutritional authority, with therapists balancing nutritional considerations and psychological safety, influenced by contextual differences between UK and Greek mental health systems. Conclusions: Findings suggest that dietary behavior in ED treatment may benefit from approaches that integrate psychological and nutritional perspectives. Clinicians may consider attending to clients’ emotional readiness, the symbolic meanings of food, and the dynamics of multidisciplinary collaboration, offering insights that can inform clinical practice and future research. Full article

People with special needs often face barriers to participating in adapted outdoor leisure physical activities. A participatory action research project involving a nonprofit organization, a citizen with motor disabilities, and researchers aimed to co-develop a digital platform connecting people with special needs interested in outdoor leisure physical activities with trained volunteers. The adopted co-design methodology followed four stages: (1) Exploration (identifying users’ needs and preferences), (2) Co-design (defining key information and platform features), (3) Validation (prioritizing features), and (4) Development (implementing and testing the platform). This article focuses on stages 2, 3, and 4. During stage 2, key information and features were identified to support matching people with special needs and volunteers and informing users about adapted outdoor leisure physical activities. In stage 3, these elements were prioritized using eight key considerations, including technological (e.g., ease of use), environmental (e.g., avoiding redundancy with existing initiatives), organizational (e.g., availability of human resources), and financial factors (e.g., grant planning). Stage 4 resulted in the launch of Tandem Actif, followed by user testing to document user experience and guide improvements. This article details the application of co-design within a participatory action research project aimed at promoting safe, ethical, and accessible participation in outdoor leisure physical activities for people with special needs. Full article

Cancer immunotherapy has recently become an essential approach for treating cancer, showing considerable promise as a substitute for surgery, radiation therapy, and conventional chemotherapy. It primarily aims to boost the host’s natural defense system to combat cancer malignancies by utilizing components of immune checkpoint blockades (ICBs), mainly programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), along with elements of adoptive cellular therapies (ACTs) like Chimeric Antigen Receptor (CAR) therapy, T Cell Receptor (TCR) therapy and Tumor-Infiltrating Lymphocyte (TIL) therapy. However, cancer cells tend to undermine the effectiveness of cancer immunotherapeutic strategies by employing one or more immune evasion mechanisms. This review briefly highlights how key mechanisms of cancer immune evasion confer resistance to immunotherapy and how the Clustered Regularly Interspaced Short Palindromic Repeats/Cas9 (CRISPR)/Cas9 systems, as gene-editing tools, are poised to enhance cancer immunotherapy for treating challenging cancers. We emphasize that CRISPR/Cas9 systems can be used to explore and positively alter the genes of the immune system, boosting the effectiveness of cancer immunotherapy by editing immune checkpoints, TILs, and CAR-T cells, and disrupting genes, facilitating tumors’ evasion of the immune system. Furthermore, we highlight the growing interest in emerging base editor technology to engineer natural killer (NK) cells to overcome NK-cell-based immunotherapy challenges, particularly human leukocyte antigens (HLA)-mediated limitations, and to engineer CAR-T cells for improved immunotherapy outcomes. Full article

The ability of religion to both unite and divide us is a central research topic across academic disciplines. There is important research on the conditions of religious pluralism and tolerance, violence and discrimination, yet disciplinary silos and disconnects between the academy and the public remain barriers to progress. To investigate these problems, we convened 56 scholars of religious pluralism and conflict from different national contexts over a two- year period and conducted focus groups around three broad questions: What are the key issues in defining religious pluralism and religious conflict? What are the most salient contexts in which to study religious pluralism and conflict, both geographically and institutionally? What tensions and opportunities are most important for advancing public scholarship on religious pluralism and conflict? We find that (1) religious pluralism is best conceptualized as an active interreligious engagement that honors differences, (2) achieving research clarity and focus requires specific interdisciplinary dialogue and tools, (3) identifying the conditions under which pluralism and conflict thrive demands diverse methods across sub-national, national, and global contexts, and (4) scholars must engage policymakers, religious leaders, and religious communities to advance religious pluralism. This study provides critical parameters for a future public facing research agenda. Full article

Bumped kinase inhibitors (BKIs) have demonstrated safety and promising efficacy against various apicomplexan pathogens both in vitro and in vivo, but do not act parasiticidal in vitro. In the closely related cyst-forming coccidians Toxoplasma gondii, Neospora caninum and Besnoitia besnoiti, treatments with BKI-1708 induce the conversion of intracellular tachyzoites into atypical multinucleated complexes named “baryzoites”. In this study, we comparatively assessed tachyzoites and baryzoites of all three species with respect to ultrastructure, differential antigen expression by immunofluorescence, and overall differential protein expression by MS-proteomics. TEM demonstrated common, but also distinguishing, structural features in baryzoites of the three species. They contained newly formed zoites, unable to complete cytokinesis, and thus they were trapped intracellularly. An electron-dense cyst wall-like structure was found only in T. gondii baryzoites. Species-specific differences in antigen expression were observed by immunofluorescence. Comparative proteomic analysis of baryzoites versus tachyzoites revealed a downregulation of ribosomal proteins, proteins associated with secretory organelles, as well as of transcription and translation factors in baryzoites across all species. Bradyzoite-specific markers were upregulated only in T. gondii baryzoites. Two alveolin-domain filament proteins and a hypothetical protein (TGME49_236950, NCLIV_050850, BESB_060040) were detected at higher abundance in all three species. Thus, baryzoites exhibit distinct phenotypic and proteomic profiles, with ambiguous expression of tachyzoite and bradyzoite antigens, suggesting a reversible response to stress rather than progression into a fully differentiated form. Full article

Saudade is a cultural concept expressing a profound sense of longing, nostalgia, or melancholy associated with absence, loss, or unattainable experiences. Emerging in medieval Portugal and shaped by historical, social, and literary developments, it has evolved from an individual emotion into a collective cultural construct reflecting the identity, history, and aesthetic sensibilities of Lusophone communities. Drawing on peer-reviewed scholarship and interdisciplinary research in cultural studies, this entry examines how saudade is expressed in the literature, music, and philosophical discourse, and its role in national memory, emigration, and cultural imagination. While sometimes described as untranslatable, its uniqueness reflects deep historical and cultural embedding rather than a linguistic limitation. Saudade, therefore, functions as a multilayered symbolic category, revealing the interplay between emotion, language, and cultural identity in Lusophone contexts. Full article

Despite unprecedented political endorsement, nature-based solutions (NbS) consistently fail to achieve the systemic transformation required for climate and biodiversity crises. This implementation deadlock stems from a profound triple strategic gap: a translational evidence gap between fragmented science and actionable design, a strategic design gap in misaligned institutions, and a fundamental theoretical integration gap disconnecting ecological principles from socio-economic solutions. This study forges and validates the symbiosis framework—an interdisciplinary blueprint designed to bridge this triple gap. Employing design science research, we: (1) synthesize ecological theory with institutional economics to distill three core design principles—functional reciprocity, nested modular network architecture, and strategic leverage and foundational support; (2) translate these into a conceptual model and strategic implementation blueprint; and (3) validate the framework through comparative analysis of global NbS case studies. The resulting framework provides a novel translational logic, moving beyond critique to offer a prescriptive design tool. It enables practitioners to diagnose systemic failures and design interventions that emulate ecological intelligence while applying institutional design principles: cultivating reciprocal partnerships, structuring resilient networks through polycentric governance, and strategically targeting catalytic leverage points and foundational assets. We conclude that scaling NbS requires a paradigm shift from managing isolated symptoms to architecting symbiotic systems. The symbiosis framework provides the essential interdisciplinary blueprint for this shift. Full article