Search Results (30,765)

Background/Objectives: Immune checkpoint inhibitor-related hepatitis (ICI-H) can resemble classical autoimmune hepatitis (AIH), but comparative multidomain data remain limited. We compared their clinical, biochemical, and serological profiles and descriptively summarized histopathological findings. Methods: This single-centre retrospective cohort screened 100 records from January 2018 to October 2023; 79 patients met predefined criteria (40 ICI-H; 39 AIH). ICI-H required an updated RUCAM score of ≥6, whereas AIH required a simplified AIH score of ≥6 and compatible histology. Continuous and categorical variables were assessed using Mann–Whitney U and Fisher’s exact tests with Benjamini–Hochberg correction where applicable; histopathological findings were summarized descriptively because biopsy ascertainment was markedly unequal between groups. Results: Compared with AIH, ICI-H occurred more often in men (65.0% vs. 20.5%) and showed higher AST, ALT, ALP, GGT, INR, CRP, and neutrophil-to-lymphocyte ratio (all q < 0.001), but lower ANA positivity (12.5% vs. 74.4%; q < 0.001). Histopathological observations were limited to the biopsy-assessed subgroup (10 ICI-H; 39 AIH) and are reported descriptively because biopsy ascertainment was markedly unequal and non-random. Conclusions: ICI-H and classical AIH showed different observed clinical, biochemical, and serological profiles; however, these differences should not be interpreted as independent diagnostic discriminators because disease-specific criteria contributed to group assignment. Diagnosis after ICI exposure should integrate exposure timing, exclusion of competing causes, structured causality assessment, serology, and selective histology. Outcome comparisons require standardized longitudinal follow-up. Full article

Urinary tract infections (UTIs) are a major cause of hospital-acquired infections, and up to 80% of these are linked to urinary catheters. The biofilm formation of uropathogenic E. coli plays a critical role in the development of catheter-associated urinary tract infections (CAUTIs). This study aimed to develop a silicone elastomer material incorporating green-synthesized zinc oxide nanoparticles for potential urinary catheter applications and assess its antibiofilm efficacy against uropathogenic Escherichia coli (UPEC). E. coli was identified by the BD Phoenix^TM system and 16S rRNA gene sequencing. ZnO NPs were synthesized through a green method using Crataegus azarolus leaf extract as a biological reducing and stabilizing agent. NPs were incorporated into a silicone matrix at different concentrations (0 wt%, 0.5 wt%, 1 wt% and 1.5 wt%) to produce ZnO-functionalized silicone elastomer specimens for potential urinary catheter applications, and then their antibiofilm activity was assessed through a 96-well microtiter assay. NPs and nanocomposites were characterized through various spectroscopic techniques using XRD, FTIR, and FESEM. In the 1.5 wt% ZnO NPs–silicone elastomer specimen, biofilm formation by E. coli ATCC 25922 and the clinical isolate were significantly reduced by 86.94% and 78.40%, respectively, compared to the control silicone elastomer specimen for potential urinary catheter application. The present findings suggest that green synthesized ZnO NPs provide a promising and biocompatible approach to reducing UPEC biofilm formation when incorporated into silicone elastomer specimens for urinary catheter application. Furthermore, this method may help reduce CAUTIs in clinical settings. Full article

Three-dimensional (3D) and four-dimensional (4D) printing expand the design space for nano-enabled soft robots intended for cancer diagnosis and therapy. This structured narrative review separates three evidence classes: core systems satisfying all scope criteria, adjacent technologies satisfying only part of the definition, and enabling technologies not yet integrated as oncology soft robots. The revised evidence set contains 12 core reports, 7 adjacent comparators and 68 enabling methods, standards or background reports. Study-level analysis using independent manufacturing, biological, workflow and safety (M/B/W/S) axes shows that the core literature is dominated by single-platform, in vitro therapeutic demonstrations with absent or short-term safety evidence (S0-S1). No core study established cancer-specific diagnostic sensitivity or specificity, no human validation was identified, and only two systems were classified as genuine or candidate 4D platforms under a strict programmed-transformation definition. Hydrogel, magnetic, photothermal, conductive, imaging-active and melanin-based materials are evaluated together with printability, dose, localization, sterilization, retrieval, degradation and nanoparticle fate. Translation requires reproducible manufacture, quantitative application endpoints, exposure-matched safety testing and comparison with established oncology workflows. The principal gap is not the availability of additional functions, but the lack of integrated evidence connecting controlled manufacture to clinically meaningful diagnosis or therapy. These findings apply only to the studies identified within the predefined search and eligibility framework and do not establish the absence of relevant evidence elsewhere. Full article

Endometriosis affects an estimated one in ten women of reproductive age and remains defined clinically by the presence of endometrial-like tissue outside the uterine cavity, yet its persistence depends on biological processes that extend well beyond estrogen exposure. This review argues that endometriosis is best understood as a set of molecularly heterogeneous, interconnected disease processes, hormonal, immune, vascular, epigenetic, and metabolic, that converge on a compact set of intracellular signaling nodes rather than as a single hormonal disorder. These convergence points are mapped onto candidate therapeutic targets spanning established, investigational, and preclinical stages of development, and onto biomarker strategies organized here by clinical application, diagnosis, disease stratification, prognosis, and treatment monitoring, rather than by sample source alone. Translational obstacles, including the limited predictive value of current animal models, the recurring disconnect between preclinical and clinical results, and the distinction between symptom control and disease modification, are addressed throughout rather than confined to a single closing section. Endometriosis management continues to rely on symptomatic hormonal suppression; treatment strategies grounded in the disease’s molecular heterogeneity, rather than a uniform hormonal model, appear to offer the most realistic path toward durable, individualized management. Full article

Background/Objectives: Multimodal artificial intelligence (AI) is increasingly used in radiology to combine medical images with radiology reports, clinical narratives, structured health records, laboratory measurements, and other patient data. These systems may support more context-aware interpretation, reporting, and clinical decision-making than unimodal approaches. This narrative review examines recent technical and clinical advances in multimodal radiology AI and identifies barriers to responsible implementation. Methods: Relevant biomedical and technical literature was identified through targeted searches of PubMed, IEEE Xplore, ACM Digital Library, Web of Science, Scopus, arXiv, ScienceDirect, SpringerLink, and Google Scholar. A documented screening process identified 111 reviewed publications from 1154 records. Study selection and data extraction were conducted by one reviewer without independent verification. Original research, reviews, and commentaries, including selected preprints, were synthesized thematically. Results: The field has progressed from early and late feature fusion toward cross-modal attention, contrastive image–text pretraining, vision–language models, multimodal large language models, and general-purpose foundation models. Applications include diagnostic classification, prognostic modelling, image–text retrieval, visual question answering, clinical decision support, and automated radiology report generation. Despite promising technical results, comparison across studies remains difficult because of heterogeneous datasets, tasks, metrics, and validation designs. Clinical translation is further limited by scarce external and prospective validation, uncertain interpretability, hallucination and omission risks, privacy and fairness concerns, and limited real-world workflow evaluation. Conclusions: Multimodal AI may enable more clinically informed radiological interpretation and reporting, but progress in benchmark performance has outpaced evidence of safety, generalizability, and clinical utility. Future research should prioritize multicentre evaluation, clinically meaningful metrics, transparent reporting, robust safety assessment, and workflow-centred implementation. Full article

Polyether ether ketones (PEEK) and polydimethylsiloxanes (PDMS) are widely used biomaterials; however, their susceptibility to microbial colonization remains a limitation in clinical applications. This study comparatively evaluated biofilm formation by Candida albicans and Nakaseomyces glabratus on PEEK and PDMS and characterized the effect of TiO₂/ZrO₂-based coatings applied to PEEK. Biofilm development was analyzed during adhesion, maturation, and dispersion using biomass quantification, metabolic activity assays, and scanning electron microscopy. Surface modifications were also evaluated. Both species formed a biofilm on the biomaterials, with a significantly higher biomass on the control, followed by PEEK and PDMS. TiO₂/ZrO₂-based coating affected biofilm maturation, with coating B as the one producing the greatest reduction in biofilm development. These findings suggest that surface modifications, such as hydrophobicity, using TiO₂/ZrO₂ coatings may influence fungal biofilm reduction and improve the antimicrobial performance of biomedical materials. Full article

Acute myeloid leukemia (AML) progression involves remodeling of the bone marrow inflammatory microenvironment, yet prior studies have focused on individual cytokines rather than coordinated network-level communication. This study aimed to systematically map inflammatory network reprogramming in AML and develop a network-derived prognostic tool. Single-cell RNA sequencing was performed on bone marrow samples from three newly diagnosed AML patients and six healthy donors (47,525 cells); ligand–receptor communication was then analyzed using CellChat. Communication dominance shifted from T-cells to myeloid populations, with networks restructured into neutrophil-centric computationally predicted self-amplifying circuits, exemplified by CXCL8–CXCR2 and CCL3–CCR1 axes. Despite the limited sample size of the scRNA-seq cohort (3 AML patients and 6 healthy donors), which may limit the generalizability of the detailed cellular and network findings, the subsequent protein-level Luminex validation in a larger cohort of 46 patients and 26 healthy controls provides robust support for the key findings. An inflammatory risk score (IRS) was constructed using LASSO-penalized Cox regression and evaluated for prognostic performance and integration with the European LeukemiaNet 2022 (ELN2022) classification. Luminex profiling confirmed dysregulation of key mediators, including reduced CCL3, CCL4, CXCL8, and IL-1A together with elevated CXCL10 in AML, and revealed substantial de-modularization of the cytokine correlation network. The IRS, based on CXCL8, CCL2, and IL-1A, achieved a concordance index of 0.729 for overall survival and stratified the ELN2022 intermediate-risk category into distinct prognostic subgroups. Inflammatory network pattern analysis provides a complementary dimension to genetic risk stratification in AML. The IRS captures microenvironment-derived prognostic information not reflected by current classification systems, though prospective multicenter validation is essential before clinical application. Full article

Background and Aims: We examined familial patterns and phenotypes of thoracic aortic aneurysms and dissections (TAAD) in the 3746 patients currently populating our Yale Aortic Institute Database. Methods: Patient charts and electronic medical records were retrospectively reviewed for the entire cohort. TAAD disease was categorized as syndromic (with extra-aortic manifestations) or non-syndromic (without) for each patient. Family patterns and whole exome sequencing results were assessed. Family history was considered ‘proven’ when a patient’s relative(s) had an arterial aneurysm or dissection confirmed by an imaging study, surgical treatment, or postmortem examination. Family history was termed ‘likely’ when at least one relative suffered sudden death at ages ≤50 for males and ≤60 for females, and ‘possible’ with a history of sudden death at any age. Results: Of the 3746 patients in the database, family history of aneurysm or dissection and connective tissue status was able to be determined for 3113 patients, divided into 109 (3.5%) syndromic and 3004 (96.5%) non-syndromic TAAD patients. Findings were as follows: (1) In the syndromic group, 46 (42.2%) patients had a ‘proven’ family history, 6 (5.5%) had a ‘likely’ family history, 4 (3.7%) had a ‘possible’ family history, and 18 (16.5%) had ‘none’. For 35 patients (32.1%) their family history was unknown. (2) In the non-syndromic group, 587 (19.5%) patients had ‘proven’ family history, 147 (4.9%) had ‘likely’ family history, 210 (7.0%) had ‘possible’ family history and 1444 (48.1%) had no family history, thus representing sporadic TAAD. A total of 616 (20.5%) had an unknown family history. (3) There was a significant difference between the rate for ‘proven’ and ‘none’ family history between the syndromic and non-syndromic groups (42.2% vs. 19.5% and 16.5% vs. 48.1%, respectively; p < 0.001). (4) Syndromic patients presented at a significantly younger age than non-syndromic or sporadic patients (41.2 vs. 63.3 or 63.6; p < 0.001). (5) There was no significant difference in age of presentation between familial non-syndromic (patients with ‘proven’, ‘likely’, and ‘possible’ family history) and sporadic patients (63.3 vs. 63.6; p = 0.64). (6) Overall, of the 3746 patients in the database, 631 patients (25 syndromic, 552 non-syndromic, and 54 with unknown status) underwent Whole Exome Sequencing (WES). Sequencing revealed 170 disease-causing or suspicious variants [13 pathogenic, 16 likely pathogenic, 7 not classified, and 134 Variants of Uncertain Significance (VUS)] found in the exomes of 141 (22.3%) patients (12 syndromic, 103 non-syndromic TAAD patients plus a remaining 26 of unknown connective tissue status). Seventy (49.6%) of these patients had a ‘proven’ family history. (7) Familial TAAD patients were more likely to find a variant in their WES result than patients without a family history (70 vs. 26; p < 0.001). Recognition of these strong familial patterns, even in non-syndromic cases, encourages intensive investigation of family in order to save lives by detecting silent TAA disease. Conclusions: Our large-scale, clinical and sequencing-based study clearly demonstrates the strongly familial and genetically mediated nature of thoracic aortic disease. We vividly demonstrate and characterize this familial nature of TAAD, both clinically and by genetic sequencing. Our findings strongly support vigorous family investigation when a new patient is diagnosed with thoracic aortic aneurysm, as well as vigorous application of whole exome sequencing for these families. Full article

Azoles are the most widely used antifungal agents in clinical practice, with important applications in human medicine, agriculture, and veterinary science. This review systematically summarizes the structural features, classification, six-decade development history, mechanisms of action, antifungal spectra, and resistance mechanisms of azole antifungals. Based on the number of nitrogen atoms in the azole ring, these compounds are divided into imidazoles (two nitrogens) and triazoles (three nitrogens), which differ markedly in target enzyme selectivity, pharmacokinetic properties, and safety. Tetrazoles, as a new generation of drugs, exhibit lower basicity and reduced inhibition of human CYP450 enzymes, and have demonstrated improved selectivity and better safety profiles in preclinical studies; however, their clinical advantages still require further validation. Since the introduction of the first clinically used imidazole clotrimazole in 1969, azoles have evolved from topical formulations to orally or intravenously administrable triazoles across four generations, each iteration broadening the antifungal spectrum and improving safety and pharmacokinetics. Azoles act by inhibiting fungal sterol 14α-demethylase (CYP51), thereby blocking ergosterol biosynthesis and disrupting fungal cell membrane integrity. Their spectrum covers most clinically relevant fungi, but significant inter-generational differences exist. However, the widespread emergence of resistance mechanisms—including efflux pump overexpression, target enzyme alterations, biofilm formation, and other mechanisms—combined with cross-resistance risks between agricultural azole fungicides and clinical azoles, severely compromises their clinical utility. This review also discusses future directions, including novel tetrazoles, dual/multi-target inhibitors, AI-assisted drug design, and cross-sectoral resistance control within the One Health framework. Full article

Temporomandibular disorders (TMDs) are heterogeneous musculoskeletal conditions frequently characterized by pain, impaired mandibular function, and reduced quality of life. Botulinum neurotoxin type A (BoNT-A) has emerged as a potential therapeutic option, particularly for persistent myogenous TMDs associated with masticatory muscle hyperactivity. This narrative review critically examines the mechanisms of action, current clinical evidence, therapeutic applications, and safety profile of BoNT-A in TMD management. Available evidence suggests that BoNT-A can reliably reduce masticatory muscle activity and may provide pain relief in selected patients with refractory myogenous TMDs; however, its superiority over placebo or established conservative treatments remains inconsistent. Considerable heterogeneity in patient selection, injected muscles, dosing regimens, injection techniques, and outcome assessment currently prevents the definition of standardized treatment protocols. Although short-term adverse events are generally mild and transient, repeated injections may induce muscle atrophy, reduced bite force, and potentially mandibular skeletal changes, whose long-term clinical relevance remains uncertain. Therefore, BoNT-A should not be considered a first-line treatment but rather a carefully selected adjunct within a multimodal rehabilitation strategy after appropriate conservative management has failed. Future phenotype-stratified comparative trials with standardized protocols and long-term structural safety outcomes are warranted. Full article

Background/Objectives: Polydimethylsiloxane (PDMS) is a non-invasive and versatile material often used for non-invasive collection of skin-emitted volatile organic compounds (VOCs), with potential applicability in acute and pre-critical care settings. However, most existing PDMS-based methodologies rely on extensive sample preparation and environmental control, limiting their feasibility in time-sensitive clinical contexts. Methods: We conducted a proof-of-concept pilot case-series study in four healthy volunteers to evaluate whether a simplified skin-contact PDMS sampling procedure can capture detectable VOCs and preserve individual-level variation. PDMS strips were applied directly to the skin with minimal preparation, and collected VOCs were analyzed using gas chromatography–mass spectrometry. Donor-associated variability was assessed using Bray–Curtis dissimilarity, and variability in VOC detection was evaluated across body sites. Results: Skin-contact PDMS sampling detected 160 VOCs across four participants. The mean within-donor Bray–Curtis dissimilarity was 0.308, compared with a mean between-donor dissimilarity of 0.347. VOC detection variability differed across body sites, with lower coefficients of variation at the forehead, neck, and wrist than at the ankle. Conclusions: Under simplified sampling conditions, skin-contact PDMS captured individual-associated VOC profiles with lower within-donor variability than between-donor variability. These findings support the feasibility of PDMS-based skin VOC sampling in minimally controlled settings. Further validation in larger and clinically relevant cohorts is warranted to assess the utility of PDMS-sampled skin VOCs as potential biomarkers for early disease detection. Full article

Cell sheet technology has evolved into a unique scaffold-free and biomaterial-free regenerative medicine platform that enables transplantation of intact cellular constructs while preserving extracellular matrix and cell–cell interactions. Clinical applications of cell sheet technology have demonstrated successful tissue and organ regeneration in the cornea, esophagus, heart, cartilage, and retina. More recently, the therapeutic scope of cell sheet technology has expanded beyond tissue replacement toward stem cell-based regenerative therapy, in which paracrine signaling, anti-fibrotic activity, and microenvironment remodeling play important roles. In this review, we use the term “functional regeneration” as an integrative therapeutic framework of a regenerative medicine platform capable of promoting the regenerative processes that modify disease pathophysiology and may alter the natural history of a disease, irrespective of complete anatomical reconstitution. Liver cirrhosis is a representative target disease for this concept of functional regeneration because the functional regenerative therapy that reverses progressive fibrosis and restores hepatic function has the opportunity to prevent the onset of hepatocellular carcinoma. This review discusses the evolution of cell sheet technology, the biological basis of stem cell-based functional regeneration, and the development of KCS-003, a cell sheet-based therapeutic product manufactured from mesenchymal stem/stromal cells preconditioned with IC-2, which has potent anti-fibrotic action and promotes liver regeneration. In addition, clinical investigations, including corneal and retinal reconstitution, esophageal regeneration, cartilage repair, and cardiac patches, were shown as representative clinical cases of cell sheet technology. Full article

This study investigated user experience during artwork exploration in immersive virtual reality using eye-tracking and pupillometry data. The central component of the research is the presentation of Bitscope, an innovative application developed using UNITY technology. Preliminary findings suggest that the order of exposure to stationary and virtual reality (VR) environments may influence later visual attention and engagement. Large-scale data collected during VR sessions were used to develop machine-learning regression models for pupil-diameter variables. The models achieved high predictive performance, with accuracy rates of approximately 97–99%. These results indicate that pupillometry can support the modelling of user behaviour in immersive environments; however, validation using independent participant samples is needed before broader clinical applications can be considered. The integration of VR with eye tracking provides a promising framework for studying visual behaviour and may support adaptive educational tools, automated gaze-pattern assessment, and future biomedical decision-support systems. This study contributes to applications in digital art, museum experiences, visual art therapy, and e-health/neurorehabilitation, while laying the foundation for future statistical and machine learning analyses that link eye tracking with users’ emotional states. Full article

Natural bioactive compounds, especially plant-derived phytoconstituents, have gained significant interest due to their structural diversity, multitarget pharmacological activities, and favourable safety profiles. Their pharmaceutical translation is often hindered by poor aqueous solubility, limited membrane permeability, chemical instability, extensive first-pass metabolism, and, therefore, low oral bioavailability. Phytosomes, which are molecular complexes of bioactive compounds with phospholipids, have emerged as a new, effective, lipid-based delivery platform that can overcome these biopharmaceutical limitations and improve solubility, membrane interactions, systemic exposure, and therapeutic efficacy. The present review critically analyses recent advancements in phytosomal drug delivery, from formulation development to clinical translation, focusing on molecular complexation mechanisms, formulation strategies, physicochemical characterisation, pharmacokinetic enhancement, therapeutic applications, and challenges in clinical translation. The current review combines pharmaceutical design principles with recent advances in quality-by-design (QbD), computational formulation optimisation, hybrid phytosomal systems, scalable manufacturing approaches, and targeted delivery strategies. In addition, prospects for the future extension of phospholipid complexation to bioactive compounds from marine organisms, fungi, microorganisms, and algae are discussed in relevance to the next-generation natural product therapeutics. The present review serves as an emerging link between the discovery of natural bioactive compounds and the development of clinically translatable phytosomal systems from a pharmaceutical perspective. Full article

Fluorescence-guided surgery (FGS) enables real-time visualization of tumor margins and microscopic residual lesions, thereby improving the completeness and precision of tumor resection. Paralleling these clinical advancements, fluorescence probes have shown significant progress in intraoperative imaging applications. Several probes approved by the U.S. Food and Drug Administration (FDA), including indocyanine green (ICG), 5-aminolevulinic acid (5-ALA), sodium fluorescein, methylene blue (MB), pafolacianine (OTL-38), and pegulicianine (LUM015), have been widely used in various solid tumor surgeries, while Akalux received approval in Japan in 2020 for near-infrared photoimmunotherapy. Beyond these established agents, a large number of novel probes are currently undergoing clinical evaluation, with design trends shifting toward active targeting and microenvironment responsiveness. This review provides an overview of FDA-approved probes and systematically summarizes representative probes in phase I-III clinical trials, focusing on their imaging mechanisms, clinical evidence, and translational challenges. Full article