搜索结果：Medical hypotheses

Androgen receptor signaling inhibitors (ARSIs) have transformed the treatment of advanced prostate cancer, yet durable responses are limited by the emergence of therapy-resistant disease states, including neuroendocrine prostate cancer (NEPC) and double-negative prostate cancer (DNPC). Lineage plasticity has traditionally been studied from a tumor-cell-intrinsic perspective, but single-cell and spatial studies increasingly indicate that the tumor microenvironment, particularly tumor-associated macrophages (TAMs), may influence tumor-cell state transitions, immune exclusion, and therapeutic resistance. In this review, we synthesize established and emerging evidence linking TAM heterogeneity to prostate cancer lineage plasticity. We first summarize independently supported myeloid programs, including SPP1+/TREM2+ macrophage states and TAM-derived pathways such as IL-6/STAT3, TGF-beta, NF-kappaB, CXCL12/CXCR4, and adenosine signaling. We then discuss PLAC8+ TAMs, TNFAIP8L2, and PLAC8+ TAM/CXCL12+ iCAF/CD8+ TRM spatial aggregates as an emerging, hypothesis-generating framework that may be associated with ARSI-induced DNPC-like remodeling. Importantly, we explicitly distinguish spatial and transcriptomic associations from experimentally proven causal mechanisms. The proposed TNFAIP8L2-integrin/PI3K-Akt/beta-catenin/FOSL1-HMGA1 cascade is therefore presented as a working model that requires direct biochemical, genetic, and in vivo validation. Finally, we outline an evidence-aware translational roadmap for TAM-directed therapy, emphasizing independent cohort validation, protein-level spatial confirmation, functional perturbation, and biomarker-guided clinical testing.

Exposure of cannabis to heavy metals may interfere with metabolic pathways of cannabinoid biosynthesis and compromise its medical quality. Furthermore, inflorescence contamination with heavy metals presents a critical challenge for the production of safe pharmaceutical-grade cannabis, since it poses a significant health risk to consumers. The present study therefore evaluated the hypotheses that heavy-metal exposure affects cannabinoid production, leads to inflorescence-contamination, and compromises the cannabis plant function; and that the responses are genotype-dependent and heavy-metal dose-dependent. To evaluate the hypotheses, we studied responses of four 'drug-type' medical cannabis cultivars to a cocktail of four heavy-metals (Cd, Pb, Ni, Co), in three concentrations each (0, 1, 5µM), and analyzed translocation and accumulation patterns of the heavy-metals in the plant organs, and the resulting impact on cannabinoid production and the plant's physiological integrity. The results confirmed effects of the heavy metals on cannabinoid production, with a heavy-metal concentration threshold, and genotypic variability, thus confirming the hypotheses. The roots accumulated the highest levels of heavy metals, demonstrating an avoidance strategy of exclusion from sensitive shoot organs; and the root-to-shoot translocation factor was Ni > Cd, Co > Pb demonstrating heavy-metal specificity. The accumulation patterns revealed that plant exposure to moderate-low heavy metal concentrations (5µM) poses health concerns, as the inflorescences' Cd and Ni concentrations were above the WHO-permitted threshold for medical plant consumption.

To evaluate construct validity and responsiveness of the health-related quality of life (HRQoL) instrument EQ-5D-3L (index, dimensions) and EQ VAS among patients with psoriatic arthritis (PsA). This retrospective, register-based study utilised data from the Swedish Rheumatology Quality Register. Known-groups validity was assessed by comparing EQ-5D-3L and EQ VAS results across groups with varying levels of physical function or disease activity. Convergent validity was assessed through correlations with comparator instruments. Responsiveness was assessed by analysing correlations between changes in EQ-5D-3L, EQ VAS, and comparator instruments, as well as by assessing the ability to discriminate between patients who improved and those who did not, using the area under the receiver operating characteristic curve (AUC). To confirm construct validity or responsiveness, ≥ 75% of hypotheses had to be supported. The study included 13,105 patients with PsA. EQ-5D-3L and EQ VAS demonstrated moderate to strong correlations with comparator instruments and found expected differences between groups with varying physical function or disease activity. Over 75% of the hypotheses related to construct validity were supported. Regarding responsiveness, several hypotheses for the EQ-5D-3L were not supported, and none of the AUC-related hypotheses for EQ VAS were supported. Overall, less than 75% of the hypotheses related to responsiveness for EQ-5D-3L and EQ VAS were supported. The results from this observational study support construct validity of EQ-5D-3L and EQ VAS among patients with PsA. However, responsiveness was not supported for the EQ-5D-3L dimensions which suggests that the EQ-5D-3L may not fully capture changes in HRQoL from interventions impacting other dimensions than pain/discomfort.

Purpose: This study sought to extract and characterize fucoidan from brown seaweed Padina tetrastromatica for the synthesis of fucoidan-gold nanoparticles (F-AuNPs) and to assess their physicochemical properties, as well as their antioxidant, anti-inflammatory, and anticancer activities, alongside potential molecular interactions with specific cancer-related targets. Methods: The extracted fucoidan-rich fraction was characterized for its sulfate content. Citrate-stabilized plain gold nanoparticles (plain AuNPs) were prepared and characterized as non-fucoidan nanoparticle controls. Comprehensive physicochemical characterization, including UV-Vis spectroscopy, Fourier-transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), X-ray diffraction (XRD), dynamic light scattering (DLS), zeta-potential analysis, and thermogravimetric analysis (TGA), was performed on the resultant fucoidan-functionalized AuNPs (F-AuNPs). Biological activities were assessed using different techniques: antioxidant potential (Ferric Reducing Antioxidant Power (FRAP) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) assays), anti-inflammatory effects (NO inhibition in macrophages), and anticancer efficacy against HepG2 cells (MTT and flow cytometry). Potential molecular targets relevant to these activities were further explored in silico using molecular docking against key cancer-related proteins, providing hypotheses for future experimental validation. Results: The fucoidan-rich fraction showed a sulfate content of 10.08%. Strong antioxidant activity was observed, especially in FRAP (11.20 ± 0.29 mg TE g-1 DW). F-AuNPs exhibited enhanced cytotoxicity against HepG2 cells (IC50 138.1 µg mL-1) compared to plain AuNPs (IC50 271.2 µg mL-1) and the fucoidan-rich fraction (IC50 390.2 µg mL-1), inducing G1 phase arrest. In addition, F-AuNPs reduced nitric oxide production in LPS-stimulated RAW 264.7 macrophages, reaching 21.42 ± 1.29% inhibition at 100 µg mL-1. As an exploratory, hypothesis-generating step, an in silico target-prioritization screen identified HPSE and MMP-2 as the highest-scoring candidate proteins, proposed solely as targets for future experimental validation. Conclusions: F-AuNPs represent a promising multifunctional nanoplatform with antioxidant, anti-inflammatory, and antiproliferative activities. The integration of in vitro biological evaluation with in silico target prediction supports the potential biomedical relevance of F-AuNPs and generates testable hypotheses regarding their molecular targets, which require experimental validation.

Genome-wide association studies (GWAS) have identified thousands of loci associated with complex human diseases. However, the majority of the association signals reside in non-coding regions of the genome, and do not directly reveal the causal variant, effector gene, regulatory biomolecule, cell type, pathway, biomarker, or therapeutic target. Because many disease-associated variants act through non-coding regulatory mechanisms, post-GWAS interpretation increasingly depends on fine-mapping, expression quantitative trait loci, transcriptome-wide association studies, and functional evidence from single-cell multi-omics, network biology, and genetic target prioritization. Artificial intelligence can attempt to integrate these heterogeneous molecular evidence layers, but the resulting black-box prediction is insufficient when outputs cannot be biologically reproduced or experimentally tested. This review evaluates explainable artificial intelligence (XAI) as a framework for linking genetic association signals to molecular mechanisms and causal gene hypotheses. We argue that explainability is best treated as a biological requirement because useful models must expose evidence paths from significant disease-associated variants to regulatory elements, genes, transcripts, proteins, pathways, cell states, and therapeutic hypotheses. By emphasizing transparent evidence provenance, ancestry-aware interpretation, and functional validation, XAI can support the translation of GWAS signals into molecularly testable hypotheses for target prioritization and precision molecular medicine. The review focuses on the question of how to accomplish AI-accelerated functionalization of GWAS outputs across complex human diseases and traits.

Clinical lipidomics can capture disease-associated molecular alterations at high resolution, yet translating complex lipid species data into interpretable biological insight remains challenging. Existing workflows often emphasize statistical discrimination while underutilizing the structural information embedded in lipid species. To address this gap, we developed LipiDecipher, a structure-oriented analytical framework designed to summarize lipidomic alterations into interpretable structural patterns and to provide database-supported biological contextualization. LipiDecipher integrates differential lipid analysis, structure-resolved summarization, multivariate discrimination, and knowledge-based lipid-to-protein/pathway contextualization. We applied this framework to a retrospective serum lipidomics dataset comprising healthy controls and patients with acute myocardial infarction or post-PCI recurrent myocardial infarction. To improve transparency and robustness, the revised analysis includes sex-disaggregated reporting, covariate-adjusted sensitivity analyses for sex and age, and internal separation stability assessment of category-specific LDA projections through resampling-based feature stability analysis, repeated cross-validation, and permutation testing. The framework identified distinct lipid alterations across study groups, including changes in phosphatidylinositols, ceramides, and triglyceride remodeling patterns. These alterations became more interpretable when summarized at the structural level, including lipid class composition, acyl-chain length, and degree of unsaturation. Internal discrimination analyses suggested separability between groups, while repeated resampling highlighted a subset of recurrently selected lipid features. Knowledge-based mapping prioritized lipid-associated biological contexts related to glycerophospholipid metabolism, sphingolipid metabolism, membrane remodeling, inflammatory signaling, and energy-related processes. Importantly, these protein- and pathway-level outputs are presented as database-supported hypotheses rather than direct evidence of target engagement or pathway activation in the studied cohort. LipiDecipher provides a structure-oriented and interpretation-focused framework for clinical lipidomics. In a retrospective acute myocardial infarction cohort, it enabled the prioritization of candidate lipid signatures and biologically plausible hypotheses from complex lipidomic data. These findings support its use as a hypothesis-generating analytical tool, while external validation and experimental follow-up remain necessary before mechanistic or clinical claims can be established.

Immune fitness (IF) reflects the body's ability to mount appropriate immune responses. Monitoring IF could improve tailored treatment in oncological rehabilitation. The Immune Status Questionnaire (ISQ) and the Single-Item Scale (SIS) were developed to assess IF, but their clinimetric properties in cancer rehabilitation remain unknown. To evaluate the construct validity, responsiveness, and correlation between the ISQ and the SIS in oncological rehabilitation. The study population included people participating in oncological rehabilitation during or within one year after medical treatment. Data were collected prospectively via questionnaires. Construct validity and responsiveness were assessed through predefined hypotheses, including correlations with fatigue, sleep problems, malnutrition risk, activity impairment, and physical functioning. In total, 97 individuals were included in the analyses. Median ISQ and SIS scores were 8/10 and 7/10, respectively. Correlations ranged from r = -0.21 to r = -0.50. Only the SIS correlations with fatigue and physical functioning, and the ISQ correlation with fatigue, met the predefined thresholds. Responsiveness hypotheses were not confirmed. The ISQ and the SIS demonstrated low construct validity and responsiveness in this population. IF scores were higher than expected. Correlations showed links between fatigue, physical functioning, and IF. Future research should develop tools tailored to the complex immune disturbances experienced by cancer survivors.

Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is a serious pulmonary manifestation for which multidisciplinary ILD teams balance immunomodulation with antifibrotic therapy. The 2023 ACR/CHEST guideline recommends immunosuppressive therapy as first-line treatment for autoimmune ILD, but real-world agent-level documentation alongside antifibrotic therapy is poorly characterized. We characterized immunosuppressive medication documentation among seropositive RA-ILD patients stratified by antifibrotic documentation status. Using a federated U.S. EHR network (TriNetX, academic medical centers), we identified three cohorts of seropositive adults: RA without ILD (N=31,932), coded RA-ILD without antifibrotic documentation (N=1,885), and coded RA-ILD with repeated antifibrotic documentation (N=115). Immunosuppressive medications documented within 90 days of each patient's analytic index date were compared descriptively. Methotrexate was documented in 52% of RA without ILD versus 12% of coded RA-ILD patients with repeated antifibrotic documentation. Azathioprine, mycophenolate, and rituximab were more frequently documented in coded RA-ILD. Among 98 coded RA-ILD patients with in-window antifibrotic documentation, 80.6% had at least one non-antifibrotic agent co-documented; 48 distinct medication sets were observed, with the most common set in 14.3% of patients. Medication documentation among coded RA-ILD patients with repeated antifibrotic documentation was more heterogeneous than in RA without ILD, with no dominant medication set. Methotrexate documentation was uncommon, whereas azathioprine, mycophenolate, and rituximab were more frequently documented. These descriptive findings provide agent-level reference data for interdisciplinary management of RA-ILD and identify hypotheses for future comparative-effectiveness research; they do not establish treatment indication or comparative effectiveness.

Background: Multiple sclerosis (MS) lacks a single invariant phenotypic core. Patients accumulate heterogeneous combinations of sensory, motor, cognitive, and autonomic impairments over time, reflecting lesions that are disseminated in time and space. Standard scales such as the Expanded Disability Status Scale (EDSS) distribute disability across functional systems, but do not explicitly represent MS phenotype as a mixture of latent symptom modules. Methods: We analyzed 4617 de-identified neurology progress notes from 577 patients with MS at a single academic medical center. A large language model (GPT-5.2) categorized each note with respect to 17 non-mutually-exclusive neurological phenotype features, and note-level features were aggregated to patient-level binary vectors. Non-negative matrix factorization (NMF) was applied to generate three-, four-, and five-module solutions. For each rank, we computed approximate variance captured, relative reconstruction error, and module-level feature loadings. In the preferred four-module solution, we derived patient-level module percentages, identified highly dominant (≥55%) and archetypal (≥70%) module profiles, and quantified admixture using Shannon entropy and the effective number of modules. Results: Three-, four-, and five-module NMF solutions showed similar approximate variance captured (52.7-54.3%) and reconstruction error (0.47-0.53), but the four-module solution provided the clearest clinical interpretation. The four latent modules were sensory-visual-pain, ataxic-spastic-falls, cognitive-psychologic-fatigue, and autonomic-bladder-bowel, aligning closely with established functional systems in MS. Most patients exhibited admixed phenotypes, with module entropies ranging from 0 (single-module dominance) to 1.386 (equal mixture) and effective modules spanning approximately 1 to 4. Using pre-specified thresholds, 154 patients (26.6%) were highly dominant in a single module and 72 (12.5%) were archetypal; these purer phenotypes were most often in the sensory-visual-pain module. Conclusions: MS phenotypic diversity in routine clinical practice can be parsimoniously represented as mixtures of four latent symptom modules rather than as positions along a single severity axis. Most patients show substantial admixture of sensory, motor, cognitive, and autonomic involvement, but a minority exhibit relatively pure or strongly dominant module patterns. This modular representation provides an interpretable framework for quantifying MS phenotype and for generating testable hypotheses about MS subtypes whose biological relevance remains to be established.

Tumor senescence is a durable cell-cycle arrest triggered by oncogenic signalling, DNA damage and therapeutic stress. Although senescence can restrain malignant expansion, heterogeneous senescence-associated secretory programs can also promote tumor progression, immune evasion and treatment resistance. Crucially, the composition, magnitude and persistence of these secretory programs vary across cell types, microenvironmental niches and treatment phases, making binary detection of "senescent cells" insufficient for deciding whether specific populations should be eliminated, modulated or preserved. This review synthesizes the molecular determinants of functional, temporal and spatial heterogeneity in tumor senescence and consolidates them into an operational state space to support phase-aware intervention logic. It further evaluates how artificial intelligence, combined with single-cell and spatial profiling, imaging and circulating readouts, can enable state-resolved mapping, stratification and monitoring of senescence contexts, thereby generating testable therapeutic window hypotheses and guiding the development of staged precision senotherapies.

Driven by the global rise in obesity and lifestyle transitions, cardiovascular-kidney-metabolic (CKM) syndrome has emerged as a pathophysiological continuum characterized by metabolic dysregulation and involving multi-organ interactions. Within the comprehensive management of CKM syndrome, dietary patterns represent a cornerstone of intervention due to their high modifiability and cost-effectiveness. Adopting the perspective of the CKM syndrome pathophysiological continuum, this narrative review provides a thematic overview of the current literature on the Mediterranean, DASH, plant-based, and ketogenic diets in relation to metabolic syndrome, type 2 diabetes mellitus, chronic kidney disease, and cardiovascular disease. Evidence indicates that the Mediterranean and DASH diets, through established anti-inflammatory, antioxidant, and endothelial protective mechanisms, are the most consistently supported dietary patterns for CKM risk mitigation. The efficacy of plant-based diets is strictly quality-dependent: while healthful patterns rich in whole grains and vegetables are associated with improved cardiorenal outcomes, unhealthful patterns dominated by refined carbohydrates may exacerbate metabolic derangements. Although the ketogenic diet may improve glucose metabolism in the short term, concerns regarding elevated low-density lipoprotein cholesterol, potential hepatotoxicity, and limited long-term adherence suggest that its role may be more relevant in selected short-term settings than as a sustained long-term dietary pattern. Furthermore, structured dietary quality indices may provide useful tools for characterizing dietary exposure in relation to CKM and for generating mechanistic hypotheses. By integrating clinical and mechanistic evidence, this review outlines a stage-oriented conceptual framework to discuss how different dietary patterns may relate to distinct phases of the CKM syndrome.

Factor Xa (FXa) remains a clinically validated and chemically tractable anticoagulant target despite the therapeutic role of direct oral FXa inhibitors. Contemporary FXa inhibitor literature, however, is heterogeneous in scaffold design, endpoint reporting, assay consistency, translational depth, and suitability for computer-aided drug design (CADD). This review evaluates published series of small-molecule FXa inhibitors through a framework that combines translational structure-activity relationships (SARs), assay-aware data quality, and QSAR-readiness. A structured narrative synthesis focused mainly on post-2014 studies reporting discrete small-molecule or semisynthetic FXa inhibitors. Eligible series were classified as fully synthetic or natural-product-derived/semisynthetic chemotypes, and extraction covered scaffold architecture, potency endpoints, assay context, selectivity, clotting or antithrombotic readouts, PK/ADME, structural clarity, translational context, and extraction confidence. QSAR-readiness was assessed using analog density, congenericity, endpoint quality, assay comparability, activity range, structural interpretability, and curation burden. Fully synthetic chemotypes, particularly anthranilamide-derived and related scaffolds, provided the most coherent and modellable FXa datasets, whereas natural-product-derived and semisynthetic series expanded structural diversity. Many exploratory series, however, were limited by small analog sets, heterogeneous endpoints, incomplete translational characterization, narrow activity ranges, or higher curation burden. The practical value of published FXa inhibitor series, therefore, depends not only on potency but also on whether chemical and biological information can be reconstructed with confidence for reproducible SAR interpretation, local QSAR modeling, AI/ML-enabled CADD reuse, and clinical benchmark-aware prioritization. The QSAR-readiness framework is a critical triage tool, not a substitute for formal validation, distinguishing datasets suitable for curated local modeling from those better suited to qualitative SAR, scaffold inspiration, or translational hypotheses.

This study aimed to evaluate the adjunctive triage performance of p16/Ki-67 dual staining (DS) cytology for cervical lesions in a colposcopy-referred cohort, to analyze its correlation with lesion severity, and to explore its predictive value for persistent high-risk human papillomavirus (HR-HPV) infection. A total of 109 patients undergoing colposcopic cervical biopsy (recruited via standard HPV+TCT referral criteria) were included. We evaluated the incremental diagnostic performance of adding p16/Ki-67 dual-stain (DS) triage to the standard HPV+TCT referral workflow for detection of CIN2+ and CIN3&#xa0;+. Among 66 HR-HPV-positive patients with CIN1 or lower lesions, p16/Ki-67 DS cytology was performed, and the patients were followed up for 6 months to assess the predictive value for persistent infection. The positivity rate of p16/Ki-67 DS cytology gradually increased with the progression of cervical lesion severity (P<0.001). Further triage with p16/Ki-67 DS on the basis of combined HPV+TCT cervical cancer screening yielded sensitivity, specificity, accuracy and AUC of 77.8%, 88.6%, 84.4% and 0.822&#xa0;&#xb1;&#xa0;0.052 (95%CI: 0.721-0.923) for the diagnosis of CIN2+, and 93.3%, 81.3%, 81.7% and 0.823&#xa0;&#xb1;&#xa0;0.056 (95%CI: 0.713-0.933) for CIN3+, respectively. Among HR-HPV-positive CIN1/lower lesions, 87.1% of DS-positive patients had persistent infection compared to 62.9% of DS-negative patients (P&#xa0;=&#xa0;0.025), with an odds ratio of 4.515 (P&#xa0;=&#xa0;0.028). In this colposcopy-referred cohort defined by HPV and/or TCT-based referral criteria, p16/Ki-67 dual-stain (DS) cytology exhibited satisfactory adjunctive triage efficacy for identifying CIN2+ and CIN3+, and independently predicted persistent HR-HPV infection among patients with &#x2264;CIN1 lesions. Notably, all analyses in this study are limited to diagnostic efficacy in this referral cohort; any potential clinical applications, including possible reductions in unnecessary procedures, remain exploratory hypotheses that require prospective clinical validation.

Spinal tuberculosis most commonly affects the thoracic and thoracolumbar spine, whereas lumbosacral involvement is uncommon and may mimic degenerative lumbar spine disorders, often resulting in delayed diagnosis. This study describes the clinical presentation, radiological characteristics, diagnostic challenges, and short-term management outcomes of patients with lumbosacral spinal tuberculosis. A retrospective observational study was conducted at a tertiary care center between November 2024 and April 2025. A total of 52 patients with suspected infective spinal pathology presenting with chronic non-traumatic low back pain and/or neurological symptoms were evaluated; 19 were diagnosed with spinal tuberculosis. Six patients with lower lumbar or lumbosacral involvement were included in this case series. Clinical features, laboratory findings, imaging characteristics, treatment strategies, and short-term follow-up outcomes were reviewed. Of the 19 patients diagnosed with spinal tuberculosis, six (31.6%) demonstrated lumbosacral involvement. Patient age ranged from 47 to 83 years, with five patients aged above 60 years. Clinical presentations included chronic low back pain, radiculopathy, neurogenic claudication, motor weakness, and bowel/bladder dysfunction. MRI demonstrated spondylodiscitis with paradiscal involvement in all cases, while prevertebral or psoas collections were observed in two patients. Five patients underwent surgical decompression and stabilization in addition to antitubercular therapy (ATT), whereas one patient was managed conservatively. All patients demonstrated short-term clinical improvement or stabilization during follow-up. Lumbosacral spinal tuberculosis may present with diverse clinical manifestations that closely resemble degenerative lumbar spine disorders, creating significant diagnostic challenges. Early MRI evaluation and a high index of clinical suspicion are essential for timely diagnosis and treatment. Awareness of this atypical anatomical pattern is essential for timely, multidisciplinary management. These findings are descriptive and intended to generate hypotheses for future prospective research.

To evaluate treatment response and identify factors associated with outcomes in previously treated hepatocellular carcinoma (HCC) patients receiving Y-90 radioembolization combined with targeted therapy and immunotherapy (Y-90&#x2009;+&#x2009;TT&#x2009;+&#x2009;IT). This retrospective study included 30 previously treated HCC patients (11 with prior surgery, 19 without) who received Y-90&#x2009;+&#x2009;TT&#x2009;+&#x2009;IT. At a median follow-up of 9.7 months (95% CI, 8.5-13.9), 23 PFS events and 9 overall survival (OS) events occurred. Patient&#x2011;level response was assessed in 24 patients (all with PFS events or >&#x2009;6&#x2011;month follow&#x2011;up without progression). Univariable Cox regression was used for PFS and OS; owing to few OS events (n&#x2009;=&#x2009;9), OS analyses were exploratory. For PFS, an exploratory multivariable model (backward stepwise) was also constructed. Objective response rate was 37.5% (9/24) and disease control rate 75.0% (18/24); infiltrative imaging appearance was the only feature associated with non&#x2011;response (p&#x2009;=&#x2009;0.042). Prior surgery was associated with worse PFS in both patient-level (HR 3.78, p&#x2009;=&#x2009;0.004) and lesion-level (HR 3.32, p&#x2009;=&#x2009;0.024) analyses; however, the lesion-level association was not confirmed in a sensitivity analysis restricted to one index lesion per patient (p&#x2009;=&#x2009;0.128) and should be interpreted cautiously as it may reflect within&#x2011;patient clustering. Prior surgery remained significant in multivariable analysis (p&#x2009;=&#x2009;0.004). In univariable analysis for OS, total bilirubin (p&#x2009;=&#x2009;0.019), lesion number (p&#x2009;=&#x2009;0.022), gamma-glutamyl transferase (GGT; p&#x2009;=&#x2009;0.041), and tumor-to-normal liver uptake ratio (TNR; p&#x2009;=&#x2009;0.008) were associated with OS. In this exploratory cohort of previously treated HCC patients receiving Y-90&#x2009;+&#x2009;TT&#x2009;+&#x2009;IT, prior surgery was associated with worse patient&#x2011;level PFS. Infiltrative imaging appearance was associated with non&#x2011;response. In univariable analysis, GGT, TNR, total bilirubin, and lesion number showed exploratory associations with OS. These findings generate hypotheses and require validation in larger prospective studies.

Despite the substantial global burden of dengue, clinical management remains largely supportive. Severe disease involves viral replication, dysregulated inflammation, endothelial injury, plasma leakage, thrombocytopenia, and coagulation abnormalities. In this review, we link the traditional Chinese medicine Wei-Qi-Ying-Blood theory with stage-specific dengue pathophysiology and biomarker-guided risk assessment. We also summarize representative formulas and bioactive compounds in terms of their potential antiviral, anti-inflammatory, endothelial-protective, and hematological effects. Computational studies predict relevant targets and pathways, while preclinical studies suggest effects on viral replication, inflammation, vascular integrity, and coagulation. Limited clinical studies have reported shorter fever duration, reduced hospital stay, and improved hematological recovery, although these findings require further validation. Several proposed mechanisms are extrapolated from non-dengue models. The proposed framework is therefore intended to generate hypotheses rather than serve as a validated treatment algorithm. Future studies should focus on standardized preparations, safety assessment, mechanistic validation, and adequately powered multicenter trials.

Cancer continues to be a leading cause of global mortality, highlighting the ongoing need for novel anticancer compounds that offer high efficacy with improved side effect profiles. In the present study, a series of 3H-1,2-dithiole-3-thione derivatives (DTT-S1-18) were synthesized as promising anticancer agents, and the structures of products were confirmed by spectral techniques. H2S-releasing experiments showed that most of the compounds released higher amounts of H2S slowly over time compared to standard ADT-OH. All compounds were tested for antiproliferative activity on HT-29, PC-3, MCF-7, and HUVEC cell lines. Compounds DTT-S6 (3-nitrophenyl derivative) and DTT-S8 (methionine derivative) have the lowest IC50 values of 41.6 and 38.9 &#xb5;M on the MCF-7 cell line, respectively. Based on the wound healing and colony formation assays performed in MCF-7 cells, the wound areas were not significantly changed after treatment with compounds DTT-S6 and DTT-S8, whereas compound DTT-S8 at double IC50 dose inhibited colony formation by 81.82%. In addition, molecular docking, MD simulations, MM/GBSA binding free energy calculations, and binary QSAR analyses were performed to explore the potential target interactions and predicted activity profiles of the synthesized compounds toward inflammation-related proteins, including COX-1, COX-2, 5-LOX, and iNOS, thereby supporting the development of mechanistic hypotheses for future validation. Furthermore, structure-activity relationship (SAR) analyses were conducted to correlate the structural characteristics of the synthesized compounds with their H2S releasing potential and biological profiles. Overall, this work integrates experimental anticancer evaluation with computational pathway and structure-based cancer/inflammation analyses to characterize novel DTT-based H2S donors. The findings identify particularly compound DTT-S8, as a promising in vitro anticancer candidate, while the computational results suggest a putative involvement of inflammation-related targets, particularly the COX-2/5-LOX axis, which requires direct biochemical and cellular validation.

Background/Objectives: Telemedicine offers significant potential to improve the quality and accessibility of geriatric care, particularly in resource-constrained settings. However, its effective implementation depends largely on healthcare professionals' acceptance and willingness to use such systems. Drawing on an extended Technology Acceptance Model (TAM), this study examines the determinants of doctors' and nurses' intentions to adopt telemedicine for elderly care in Algeria, with particular emphasis on self-efficacy and institutional support. Methods: This cross-sectional study employed a structured questionnaire administered to 130 healthcare professionals, including physicians and nurses, in Algeria. Hierarchical multiple regression analysis was conducted to test the proposed hypotheses and assess the incremental explanatory power of the extended model. Results: The extended TAM accounted for 48.7% of the variance in intention to use telemedicine. Institutional support (&#x3b2; = 0.432, p < 0.001) and self-efficacy (&#x3b2; = 0.264, p = 0.001) emerged as the strongest predictors. Perceived ease of use (&#x3b2; = 0.178, p = 0.038) and perceived usefulness (&#x3b2; = 0.139, p = 0.021) also had significant positive effects. The inclusion of self-efficacy and institutional support increased the model's explanatory power by 23.5%. Conclusions: The findings highlight the critical role of organizational support mechanisms, digital competencies, and system usability in fostering telemedicine adoption among healthcare professionals. The study provides practical implications for policymakers and healthcare institutions, emphasizing the need for targeted training programs, supportive infrastructure, and institutional policies that enhance confidence and facilitate the integration of telemedicine into clinical workflows.

Parents of very preterm infants admitted to the neonatal intensive care unit (NICU) experience high levels of psychological distress, yet access to timely, evidence-based mental health support is limited by staffing and resource constraints. Digital mental health interventions offer a scalable approach to addressing this gap; however, their effectiveness has not been well established in NICU caregiver populations, particularly during periods of acute stress. This study aims to evaluate the effectiveness of a self-guided digital acceptance and commitment therapy (ACT)-based intervention combined with NICU-specific education (NICU parent acceptance and commitment therapy [NPACT]). The study explored the intervention's effects on stress among parents and primary caregivers of very preterm infants, compared to a digital education-only intervention, and active control. We conducted a 3-arm, single-center, randomized controlled cluster trial in a tertiary NICU. Parents and primary caregivers of very preterm infants (<32 wk' gestational age,<1 wk old) were randomized by family cluster to (1) NPACT (ACT+ education), (2) a digital education-only intervention, or (3) active control. Digital interventions were delivered via a web-based platform over 2 weeks. The primary outcome was NICU-related stress on the Parent Stressor Scale: Neonatal Intensive Care Unit (PSS:NICU) at 2 weeks postrandomization. Secondary outcomes included caregiver anxiety, depression, perceived stress, and selected neonatal outcomes. Engagement and perceived helpfulness were assessed for digital interventions. A total of 102 caregivers from 68 family clusters (79 infants; mean gestational age 28.1, SD 2.2 wk) were enrolled. There were no statistically significant between-group differences in the mean PSS:NICU scores at 2 weeks (NPACT 3.0, SD 0.9; education-only 2.5, SD 1; active control 2.6, SD 0.9; adjusted mean difference for NPACT vs active control 0.04, 95% CI -0.39 to 0.47). No between-group differences were observed for secondary psychological outcomes at any time point. However, caregivers in both digital intervention groups had higher odds of full breastfeeding at discharge compared with active control. Engagement with the digital interventions was high, with 97% (28/29) of NPACT participants and 76% (19/25) of education-only participants completing at least 5 of 7 modules, and both interventions were rated as very helpful. In this trial, an unguided digital mental health intervention delivered during NICU admission did not reduce NICU-specific parental stress or other psychological outcomes relative to active control. However, the intervention was highly used by caregivers. These findings suggest that while a brief digital mental health intervention can be successfully implemented in a high-stress clinical setting with caregivers, its capacity to reduce acute psychological distress may be limited. Secondary findings indicate potential benefits of the digital intervention on breastfeeding, generating hypotheses for future research. Digital mental health interventions in neonatal settings may be most effective when integrated within hybrid models of care and/or delivered beyond the acute admission phase.