Ghrelin signaling, mediated by the growth hormone secretagogue receptor (GHS-R1a), has emerged as an important regulator of inflammation and bone metabolism. This study investigated GHS-R1a regulation in periodontal tissues exposed to experimental periodontitis (EP), orthodontic tooth movement (OTM), or both. Human periodontal fibroblasts were stimulated with Fusobacterium nucleatum, static tensile strain, or their combination, and GHS-R1a expression was evaluated by RT-qPCR. In vivo experiments were conducted in rats subjected to EP, OTM, or combined treatment. Gingival GHS-R1a expression was assessed by RT-qPCR and immunohistochemistry, while alveolar bone loss was quantified histometrically. Combined bacterial and mechanical stimulation markedly increased GHS-R1a expression in periodontal fibroblasts, whereas either stimulus alone produced minimal changes. Similarly, combined EP and OTM induced a pronounced early increase in gingival GHS-R1a gene and protein expression, which declined over time. Animals exposed to both conditions also exhibited significantly greater alveolar bone loss. These findings demonstrate that periodontal inflammation and orthodontic loading dynamically regulate GHS-R1a, with early upregulation followed by attenuation during prolonged inflammation. The ghrelin/GHS-R1a system may therefore contribute to the periodontal response to concurrent inflammatory and biomechanical stimuli and participate in maintaining tissue homeostasis under inflammatory stress.
Candida albicans presents a major, yet underestimated challenge in clinical settings due to its increased resistance to treatment. This study intended to focus on the utility of a novel proprietary lactam molecule, a quorum sensing (QS) inhibitor, against C. albicans. We assessed isolate susceptibility to lactam treatment. In addition, RNA-Seq was used to assess lactam-induced transcriptional changes in phenotypically distinct C. albicans strains. The mechanistic basis of these transcriptional responses and a series of biochemical assays were performed using the reference strain SC5314. Our findings show that lactam influences multiple cellular processes, including cell wall integrity, efflux pump activity, oxidative stress responses and biofilm formation, with effects differing markedly between high and low biofilm formers. Vacuolation was observed with prolonged exposure to the lactam, and related genes in this process were identified and the phenotype confirmed. These results, supported by pathway analyses and mechanistic validation experiments, indicate that lactam's antifungal activity does not rely on a single mode of action. Rather, it appears to involve multiple mechanisms that vary across heterogeneous C. albicans isolates. These data indicate the potential therapeutic benefit of a novel fungicidal antifungal agent with broad-spectrum activity.
Multiple myeloma (MM) is a hematologic malignancy characterized by uncontrolled malignant plasma cell proliferation. B-cell maturation antigen (BCMA) is an attractive therapeutic target due to its high expression on malignant plasma cells. In this study, BCMA-directed CAR-NK-92 cells were generated via lentiviral transduction of a second-generation CAR construct. CAR expression was confirmed by flow cytometry (81% efficiency). Engineered cells were functionally evaluated against BCMA-positive (U266, RPMI-8226) myeloma cell lines, as well as BCMA-negative control cells (K562, Jurkat). CAR-NK-92 cells demonstrated significantly enhanced cytotoxic activity against BCMA-positive targets compared with parental NK-92 cells (e.g., 87% vs. 54% cytotoxicity at 1:1, p < 0.001). Enhanced antitumor activity was accompanied by increased CD107α surface expression and elevated secretion of perforin, granzyme B, TNF-α, and IFN-γ (p < 0.05). No significant differences in cytotoxicity or cytokine secretion were observed against BCMA-negative control cells (p > 0.05), supporting antigen-specific activity. Importantly, CAR-NK-92 cells also exhibited potent cytotoxicity and significantly elevated cytokine secretion against primary CD138+ myeloma cells isolated from patient bone marrow aspirates. These findings demonstrate that anti-BCMA CAR-NK-92 cells exhibit potent and selective antimyeloma activity in vitro, supporting CAR-NK-92 cells as an off-the-shelf immunotherapeutic platform for multiple myeloma.
Graft inflammation and fibrosis are associated with progressive fibrosis and potential graft loss after liver transplantation, but diagnosis relies on invasive biopsies. Torque teno virus (TTV) may be a noninvasive marker of functional immunity, however its association with these changes remains unclear. In this Nordic multicenter cohort study, plasma samples collected with biopsies were analyzed for TTV load, and biopsies were scored for inflammation and fibrosis. Associations and performance of TTV versus tacrolimus were evaluated using logistic regression and ROC curves. TTV was categorized using the Youden Index. Among 287 liver transplant recipients, median age was 55, mean TTV load 5 log10 copies/mL and median time from transplantation to TTV measurement 12 months. Low TTV load was associated with higher odds of fibrosis (aOR 2.96 [95% CI 1.40-6.25], adjusted for time since transplantation). Compared with tacrolimus, TTV load remained associated with fibrosis (2.64 [1.19-5.85]), whereas tacrolimus did not (1.16 [0.95-1.42]). The model including both markers had the highest AUC (0.69 [0.60-0.78]). At the optimal threshold, TTV demonstrated 64% sensitivity and specificity, positive predictive value 20% and negative predictive value 93%. TTV load was not significantly associated with inflammation. In conclusion, TTV load may support risk-stratified biopsy strategies, requiring external validation.
Ophthalmic imaging has advanced to a level at which it can closely approximate key histopathological features of certain ocular tissues, changing the way ocular disease is screened for, diagnosed, and monitored. Modalities such as optical coherence tomography (OCT), anterior segment OCT (AS-OCT), OCT angiography (OCTA), and in vivo confocal microscopy (IVCM) capture tissue architecture with high-resolution structural and even microvascular information. In this review, the authors summarize the current evidence on artificial intelligence (AI) based applications that utilize high-resolution ophthalmic imaging and digital pathology to support near-histologic interpretation across a range of ocular diseases. Reported diagnostic performance and concordance with histopathologic findings are examined while describing the technical, biological, and regulatory boundaries of AI-derived inference. While AI supports objective, scalable, and reproducible analyses of ophthalmic imaging data, limitations in resolution, generalizability, and specificity prevent its use as an independent substitute for tissue-based diagnosis where histopathologic confirmation is required.
The sustained increase in antimicrobial resistance among Gram-negative bacilli (GNB) compromises the effectiveness of empirical treatment regimens. This study aims to describe the evolution of the frequency and antimicrobial resistance profiles of the most commonly isolated GNB in urine cultures in our area. A cross-sectional, descriptive, and retrospective study was conducted, analyzing urine cultures from patients with suspected UTIs between 2021 and 2025. Microorganism identification was performed using MALDI Biotyper or MicroScan systems, and antimicrobial susceptibility testing was carried out using MicroScan, interpreted according to EUCAST guidelines. A total of 81,791 urine cultures were analyzed. In E. coli, a significant increase in resistance was observed for amoxicillin-clavulanate, ciprofloxacin, piperacillin-tazobactam, and fosfomycin (from 3.48% in 2021 to 25.31% in 2025). Klebsiella pneumoniae showed a marked increase in resistance to fosfomycin (from 27.25% to 79.73%) and imipenem. Pseudomonas aeruginosa, predominantly hospital-acquired, exhibited a significant increase in resistance to piperacillin-tazobactam, imipenem, and antipseudomonal cephalosporins. The evolution of antimicrobial resistance in uropathogenic GNB in our region is complex and dynamic. The spread of carbapenemases highlights the need for rigorous local epidemiological surveillance and optimization of antimicrobial stewardship programs to guide empirical therapy and infection control measures.
This retrospective study explored the relationship of serum neutrophil-to-lymphocyte ratio (NLR) and fibrinogen-to-albumin ratio (FAR) with disease activity and lupus nephritis (LN) in systemic lupus erythematosus (SLE) and assessed the clinical value of the derived combination model. Patients (N = 147) with SLE were enrolled in the final analysis. Peripheral blood NLR and FAR also differed between subgroups based on LN absence/presence: LN (79 cases) and non-LN groups (68 cases) were independently associated with SLE disease activity and LN onset according to univariate and multivariate logistic regression results. Crucially, the NLR and FAR composite model demonstrated potentially auxiliary performance superior to the conventional indicator composite model (anti-dsDNA, complement C3/C4, 24-h UPr), yielding an area under the ROC curve (AUC) of 0.865 for severe disease activity (95% CI: 0.799-0.915, sensitivity: 0.833, specificity: 0.769) and 0.922 for LN development (95% CI: 0.867-0.962, sensitivity: 0.785, specificity: 0.941). In conclusion, peripheral blood NLR and FAR may serve as potentially useful auxiliary biomarkers for identifying severe disease activity and LN in patients with SLE. These exploratory findings were obtained from a single-center, small-scale population. Therefore, multi-center prospective cohort studies with large-scale populations are needed to confirm their clinical applicability and generalizability.
Severe pneumonia in children deteriorates rapidly and is very destructive. miR-27a-5p has been shown to function in multiple cancers and inflammatory conditions, but its role in severe pneumonia is unknown. To investigate the diagnostic and prognostic value of miR-27a-5p for severe pneumonia in children. This study included 146 children with severe pneumonia as subjects and 123 children with mild pneumonia as controls. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was employed to assay miR-27a-5p and FOXO1 levels. ROC and Kaplan-Meier curves were employed to assess the diagnostic and prognostic values. Cell viability and apoptosis were determined by cell counting kit-8 (CCK-8) and flow cytometry. The concentrations of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-1β were measured using enzyme-linked immunosorbent assay. Luciferase reporter assay for miR-27a-5p targeting FOXO1. miR-27a-5p level was higher in severe pneumonia. miR-27a-5p has a good diagnostic and prognostic value for severe pneumonia. miR-27a-5p down-regulation promotes cell viability and inhibits apoptosis and inflammatory factor production. FOXO1 is a target of miR-27a-5p. And FOXO1 may reverse the effects of miR-27a-5p on the biological function of HFL1 cell. In conclusion, miR-27a-5p may be a potential pneumonia marker by negatively regulating FOXO1 to worsen pneumonia.
Differentiating Crohn's disease (CD) from ulcerative colitis (UC) is challenging, often resulting as Inflammatory bowel disease unclassified (IBDU). Based on targeted RNA sequencing, we recently reported a 3-gene signature algorithm that distinguished CD from UC. This study evaluated its ability to classify IBDU cases and explore disease biology. We analyzed 197 mucosal FFPE biopsies (inflamed and non-inflamed) from 113 individuals at diagnosis: CD (n = 42), UC (n = 41) and IBDU (n = 102; follow-up: 0-23 years (IQR)). Expression levels of ANXA1, PI3, and VDR mRNAs were measured by RT-qPCR, and assessed using logistic regression, and ROC curve analysis. The algorithm discriminated CD from UC with AUC values > 0.70 in 6 out of 8 patient subsets, peaking in inflamed adult biopsies (0.78, 95% CI: 0.64-0.92). At 80% sensitivity, specificity ranged from 46% to 58%, replicating previous cohort findings and confirming reproducibility. Application of the algorithm to the IBDU cases showed low classification accuracy, with frequent misclassification of cases that were later received definitive diagnoses. Incorporation of additional IBDU-specific features did not improve performance. While the 3-gene signature algorithm demonstrates moderate ability to distinguish CD from UC, its limited performance in IBDU cases highlights fundamental constraints of binary classification approaches in IBD.
Crimean-Congo Hemorrhagic Fever (CCHF) is a life-threatening zoonotic viral disease characterized by endothelial dysfunction, coagulopathy, and systemic inflammation. Angiopoietin-like proteins (ANGPTLs) regulate vascular integrity, lipid metabolism, and inflammatory responses; however, their roles in the pathogenesis of CCHF remain unclear. In this prospective case-control study, serum levels of ANGPTL1, ANGPTL2, ANGPTL3, ANGPTL4, ANGPTL6, and ANGPTL8 were measured by enzyme-linked immunosorbent assay (ELISA) in 60 patients with laboratory-confirmed CCHF and 30 healthy controls. Standard laboratory parameters were recorded, and correlations between ANGPTLs and inflammatory, coagulation, and metabolic markers were analyzed. Receiver operating characteristic (ROC) analysis was performed to assess diagnostic performance and exploratory mortality-discrimination ability. All measured ANGPTL levels were significantly lower in CCHF patients than in healthy controls. However, no statistically significant differences in ANGPTL1, ANGPTL2, ANGPTL3, ANGPTL4, ANGPTL6, or ANGPTL8 levels were observed between survivors and non-survivors. Although ANGPTL2 and ANGPTL3 yielded statistically significant area under the curve (AUC) values for mortality, the small number of fatal cases limits the strength of this finding. Overall, reduced ANGPTL levels were associated with disease-related inflammatory, endothelial, coagulation-related, and metabolic alterations, but these findings do not support their role as prognostic markers for mortality or establish a causal role in CCHF pathogenesis.
In this study, we report the eco-friendly synthesis of silver nanoparticles (AgNPs) using cell-free supernatant of Staphylococcus saprophyticus as a biological reducing and stabilising agent. Nanoparticle formation was confirmed by visible colour change and UV-visible spectroscopy (λmax at 418 nm). Structural characterisation by SEM, XRD and FT-IR indicated predominantly spherical, crystalline, silver-containing nanoparticles associated with extracellular biomolecules that may contribute to stabilisation; XRD analysis indicated a surface phase dominated by silver halides (AgBr/AgCl) rather than confirming a purely metallic Ag0 lattice. The biosynthesised AgNPs exhibited strong antimicrobial activity against Staphylococcus aureus and Pseudomonas aeruginosa, with minimum inhibitory concentrations of 3 and 0.5 μg/mL, respectively. Significant antifungal activity was also observed against Candida albicans, with marked growth suppression at 100 μg/mL. The AgNPs effectively reduced biofilm formation, extracellular matrix production and virulence traits. DCFH-DA fluorescence and MTT assays showed increased reactive oxygen species generation and reduced cellular metabolic activity in treated microbes, suggesting oxidative stress-associated antimicrobial effects. Cytotoxicity testing indicated low toxicity towards HeLa cells at lower concentrations, with dose-dependent effects observed only at higher exposure levels. Overall, results demonstrate that biogenic AgNPs possess antibacterial, antifungal and antibiofilm properties, highlighting their potential as sustainable and eco-friendly antimicrobial candidates.
MicroRNAs (miRNAs) serve as crucial regulators in the development of various cancers. Studies have mentioned that miR-330-3p is reduced in Acute myeloid leukemia (AML). Our research objectives included determining the regulatory roles and underlying mechanisms of miR-330-3p in AML progression. miR-330-3p expression in AML was quantified through qRT-PCR. The clinical relevance of miR-330-3p in AML progression, diagnosis, and prognosis was assessed by chi-square, ROC, Cox, and Kaplan-Meier survival analysis. The impacts of miR-330-3p on AML cell function were examined by CCK8 and Transwell assay. The targeting relationship between miR-330-3p and SYTL4 was analyzed via database and luciferase assay. miR-330-3p was obviously reduced in AML. Low miR-330-3p expression was related to adverse clinical features of AML, suggesting AML progression. miR-330-3p performed well in differentiating AML patients from healthy individuals, and reduced miR-330-3p expression was significantly related to poorer survival outcomes in patients with AML. miR-330-3p upregulation potently inhibited AML cell proliferation, migration, and invasion. Furthermore, SYTL4 was a target gene of miR-330-3p. And rescue tests demonstrated that miR-330-3p and SYTL4 jointly participate in the development of AML. In conclusion, miR-330-3p inhibited the development of AML by targeting SYTL4; miR-330-3p may serve as a valuable prognosis and diagnostic biomarker for AML patients.
This study evaluated the impact of human cytomegalovirus (HCMV) infection on vascular inflammation and clinical characteristics in patients with coronary atherosclerotic heart disease (CHD). A total of 180 CHD patients with HCMV infection (research group) and 90 CHD patients without HCMV infection (control group) were enrolled. Serum levels of hs-CRP, TNF-α, IL-6, and Lp-PLA2 were measured, and clinical data were collected. The research group showed significantly higher inflammatory marker levels than controls (p < 0.05). Mean viral load was 4.58 ± 1.01 copies/mL, and high-load patients had higher marker levels than low-load patients (p < 0.05). Significant between-group differences were observed in CHD severity, number of diseased vessels, stenosis degree, cardiac function, angina grade, and carotid atherosclerosis (p < 0.05). HCMV viral load was positively correlated with all inflammatory markers and clinical severity indices (p < 0.05). These findings indicate that HCMV infection is associated with exacerbated vascular inflammation and worse CHD progression, suggesting the need for timely antiviral intervention.
Hormonal contraceptive (HC) use is known to be associated with elevated CRP levels. However, evidence on the effect of HC on several circulating inflammatory biomarkers in healthy humans is limited. The aim of this study was to examine the association between hormonal contraceptives and circulating biomarker levels and differential cell counts. A cross-sectional observational study design with biomarker measurements from 4,160 healthy females was used, coupled with registered HC prescriptions. We compared 752 high and low dose combined oral contraceptive (COC) users, 77 progestin-only pill users, 417 levonorgestrel intrauterine device users, 65 hormonal therapy users, and 1,523 post-menopausal women with a control group of 1,326 women below 50 years. Repeated differential cell counts from a different dataset of 16,231 females were analyzed for the effects of HC. Data were analyzed using various regression models. COC use was associated with higher vascular marker levels but lower chemokine levels. We found no association with progestin-only use. The association with differential cell counts was limited for most HC types. This study emphasizes the widespread impact of HC on the immune and vascular systems and how the impact may differ between HC types. The biomarker associations found could be targets for elucidation in functional studies.
This study aimed to investigate the role of YTHDF1, a key m6A reader protein, in ulcerative colitis (UC) pathogenesis and its potential involvement in ferroptosis through ACSL4 regulation. Clinical serum and tissue samples from UC patients, as well as dextran sulfate sodium (DSS)‐ and oxazolone (OXZ)‐induced colitis mouse models, were used to assess YTHDF1 expression and its correlation with disease severity. Ferroptosis markers, including reactive oxygen species (ROS), lipid peroxidation products, and iron levels, were assessed in both colonic tissues and DSS‐treated Caco‐2 cells. RNA immunoprecipitation (RIP) and methylated RNA immunoprecipitation (MeRIP) assays were performed to explore YTHDF1‐mediated mRNA stabilization of ACSL4. Data showed that YTHDF1 was significantly upregulated in the serum and colonic tissues of UC patients, with expression levels correlating positively with disease severity. In UC mouse models, YTHDF1 expression was increased, and its knockdown reduced colitis severity. Mechanistically, YTHDF1 knockdown suppressed ferroptosis by reducing lipid peroxidation, ROS accumulation, and iron overload. Additionally, ACSL4, a key ferroptosis regulator, was identified as a downstream target of YTHDF1, with YTHDF1 stabilizing ACSL4 mRNA through m6A modifications. Collectively, YTHDF1 promotes ferroptosis in UC by stabilizing ACSL4 mRNA through m6A modifications and highlights its potential as a therapeutic target for UC treatment.
Microbiologically influenced corrosion (MIC) is a significant issue causing material damage of metals in pipelines, storage tanks, and marine infrastructure, leading to significant industrial damage and maintenance costs. Anaerobic sulfate‐reducing bacteria (SRB) are the main causative agent for MIC. Their capacity to form biofilms facilitates SRB to cause high corrosion rates. In this study, Ag–SiO 2 nanocomposite with silver nanoparticle (Ag NP) dispersed in the silicon dioxide (SiO 2 ) matrix was synthesized using a one–pot sol–gel method. Ag–SiO 2 NC was evaluated for its capacity to deter biofilm formation and impact the transcript gene expression of key markers HydA and DVU1817 Cytochrome c553 genes for the SRB biofilm‐formation and metal corrosion in Desulphovibrio gigas strain. The effect of Ag–SiO 2 NC on the SRB mediated Carbon steel corrosion was also examined using potentiodynamic polarization electrochemical corrosion testing. The findings from our study validate the antibacterial and corrosion inhibitory characteristics of nanocomposite Ag–SiO 2 NC against D. gigas . A simple and reproducible Ag–SiO 2 NC synthesis will significantly boost the industrial production of silver‐doped silica products for controlling SRB population, enabling development of advanced high‐performance protective metal coatings with enhanced antimicrobial properties.
Recurrent UTIs (rUTIs) impair quality of life and contribute to antimicrobial resistance. Pseudomonas aeruginosa is particularly challenging due to intrinsic and acquired resistance. Identification of urinary biomarkers may improve understanding and diagnosis of localized and systemic UTIs. Urine anti-P. aeruginosa secretory IgA (s-IgA), IgG, and a selection of inflammatory markers were quantified using ELISA and Luminex. Urine samples with P. aeruginosa-positive cultures (n = 28), healthy controls (n = 23), culture-negative hospitalized patients (n = 25), and cultures positive for Escherichia coli or Enterococcus faecalis (n = 27) were included. Anti-P. aeruginosa s-IgA and IgG were highest in P. aeruginosa cases (median OD s-IgA 0.2040; IgG 0.4330) and exceeded healthy controls (s-IgA p < 0.001; IgG p < 0.0001). No difference was observed between single and rUTI, but s-IgA in multiple P. aeruginosa-positive rUTIs was increased versus healthy (p = 0.0034) and culture-negative controls (p = 0.0228). IL-8 (297.5 vs. 27.00 pg/mL, p = 0.002), lipocalin (32,440 vs. 6673 pg/mL, p = 0.0287), and IL-6 (11.0 vs. 6.5 pg/mL, p = 0.011) were elevated compared to healthy controls. Urinary s-IgA best reflected P. aeruginosa UTI status, while IL-8, lipocalin, and IL-6 may indicate UTI.
High levels of tumor-infiltrating lymphocytes (TILs) are associated with improved survival after radiotherapy in breast cancer (BC) patients, particularly in estrogen receptor (ER)-negative disease. This study investigated the prognostic relevance of immune cell subsets in irradiated patients. Node-positive patients (N = 1307) from the Danish Breast Cancer Group internal mammary node (IMN)2 study were included, in which IMN irradiation (IMNI) was allocated by laterality. Tissue microarrays were stained with multiplex immunohistochemistry for CD8+, CD4+, and FOXP3+ T-cells, CD68+ macrophages, and CD11c+ dendritic cells. Digital image analysis quantified immune infiltration across spatial compartments. Prognostic associations with distant recurrence, breast cancer-specific mortality, and overall mortality (OM) were assessed using multivariable flexible parametric survival models, including ER-stratified analyses. T-cell infiltration demonstrated a strong inverse association with OM, with 12-year OM-risk decreasing from 42% in tumors with lowest CD8+ infiltration to 27% in those with highest (HR 0.52, 95% CI (0.36-0.76)). The association was strongest in the ER-negative subgroup. In ER-positive disease, prognostic benefit was observed at low-to-moderate infiltration. CD68+ and CD11c+ infiltration correlated with improved outcomes, but with weaker effects. Immune markers were not predictive of IMNI benefit. These findings demonstrate that T-cell subsets are strong prognostic markers in irradiated BC patients, especially in ER-negative disease.
Cholangiocarcinoma (CCA) remains a difficult-to-treat biliary malignancy in which therapeutic stratification increasingly depends on predictive biomarkers. Although next-generation sequencing is essential for the detection of targetable genomic alterations, immunohistochemistry (IHC) retains a practical role because it is widely available, rapid, and tissue-sparing. This narrative review summarizes the current and emerging role of predictive IHC in CCA, with emphasis on its clinical utility, interpretative pitfalls, and integration with molecular testing. HER2 and mismatch repair proteins currently represent the most relevant IHC-based markers in routine practice, albeit in selected subsets of patients. By contrast, PD-L1 has clear biological relevance but limited value as a stand-alone treatment selector in CCA, whereas Claudin 18.2 is promising but still investigational. Additional lines of research, including tumor microenvironment profiling, integrin-related pathways, and other theragnostic targets, may further refine patient selection, but these approaches are not yet standardized. Digital image analysis, radiomics, and machine learning are likely to improve quantification and may support future biomarker integration. A practical pathology-oriented approach should prioritize tissue stewardship, conservative interpretation of IHC results, and close coordination with molecular methods.
Digital pathology (DP) is transforming how pathologists view and analyze diagnostic images, with the potential to improve the accuracy, speed, and efficiency of diagnoses. The adoption of Computational pathology (CP) and artificial intelligence (AI)-based tools is widely seen as an opportunity to further improve diagnostic accuracy, increase operational efficiency, and improve patient outcomes. However, AI requires a robust foundational DP infrastructure, including digital pathology workflows, scalable IT infrastructure, and standardized data formats. We highlight the importance of establishing this infrastructure before AI systems can be safely integrated into daily clinical operations. This review article provides an overview of the key considerations for establishing a digital pathology practice with artificial intelligence. It addresses logistics, financial, ethical, and regulatory considerations governing the clinical use of digital pathology and artificial intelligence.
