Metabolic dysfunction-associated steatotic liver disease (MASLD) is an independent risk factor for cardiovascular disease (CVD). While gut bacteria have been linked to CVD, the role of intestinal fungi in subclinical coronary atherosclerosis (SCA) remains unclear. In this study, we aimed to investigate the association between the gut mycobiome and SCA in MASLD.

A cross-sectional study was conducted among 103 MASLD patients without established CVD. Fibrosis and steatosis were assessed using magnetic resonance elastography (MRE) and proton density fat fraction, respectively. SCA was defined by coronary artery calcification (CAC). Fecal fungal composition was analyzed via internal transcribed spacer sequencing.

Mean age was 60.8 ± 11.2 years; 51.5% were men; 20.4% had cirrhosis. CAC correlated with MRE (r = 0.489, p < 0.001), interleukin-6 (r = 0.407, p < 0.001), and tumor necrosis factor-α (r = 0.254, p = 0.018), but not proton density fat fraction. Cirrhosis patients had higher CAC than F0–F3 (456.9 vs. 205.9, p = 0.033). Candida albicans (C. albicans) abundance was greater in cirrhosis and correlated with CAC (r = 0.403, p < 0.001) and MRE (r = 0.212, p = 0.032). In multivariate analysis, older age, diabetes, obesity, cirrhosis, and enriched C. albicans independently predicted CAC ≥ 100 AU in MASLD.

In MASLD, cirrhosis and C. albicans enrichment are independently associated with higher SCA burden, suggesting advanced liver disease and a potential fungal contribution to CVD pathogenesis.

Invasive pituitary adenomas with infrasellar extension can present with symptoms such as epistaxis and nasal obstruction, closely mimicking the clinical and radiological characteristics of nasopharyngeal carcinoma, which frequently leads to misdiagnosis. This report discusses the case of a 32-year-old male who was initially misdiagnosed with nasopharyngeal carcinoma for approximately one month and subsequently underwent radiotherapy and chemotherapy. However, a multidisciplinary assessment at our institution, incorporating magnetic resonance imaging findings of an invasive sellar mass, serum prolactin levels exceeding 2,000 ng/mL, and positive immunohistochemistry for PIT-1 and prolactin, established the diagnosis of an invasive prolactinoma. Treatment with bromocriptine led to significant tumor reduction. However, this was complicated by cerebrospinal fluid leakage, which subsequently resulted in an intracranial infection. The patient underwent surgical resection of the tumor and repair of the cerebrospinal fluid leak, with postoperative pathology confirming a PIT1-lineage, densely granulated, prolactin-secreting adenoma. The patient experienced a favorable recovery, with prolactin levels normalizing under continued bromocriptine therapy. This case highlights the critical importance of routine hormonal screening, thorough evaluation of nasopharyngeal mucosal integrity, and multidisciplinary collaboration in the diagnostic process.

The rate of functional cure (HBsAg loss) remains unsatisfactory following pegylated interferon (PEG-IFN) treatment in chronic hepatitis B. To optimize PEG-IFN administration, this study aimed to evaluate virological markers to predict functional cure and/or hepatitis B e antigen (HBeAg) loss.

Relevant studies assessing virologic markers for predicting functional cure and HBeAg loss after PEG-IFN therapy were systematically retrieved from PubMed, Embase, the Cochrane Library, and Web of Science up to November 2023. Predictive effectiveness was evaluated via the summary receiver operating characteristic curve.

We analyzed 38 studies (6,179 patients). HBsAg decline at week 24 had the greatest discriminative ability according to the area under the receiver operating characteristic curve (AUROC) (0.89) and sensitivity (0.88) for predicting functional cure, whereas baseline HBsAg had a comparable AUROC (0.86) and highest specificity (0.79), with both being significantly better than baseline hepatitis B core-related antigen and hepatitis B virus (HBV) RNA (all P < 0.001). For HBeAg loss or seroconversion, HBV RNA, HBV DNA, HBeAg, and HBeAg decline at week 12, as well as HBV DNA and HBeAg decline at week 24, all exhibited comparable predictive values (AUROC = 0.75–0.78). HBV RNA and HBeAg levels at week 24 showed optimal sensitivity (0.87), and HBeAg decline at week 12 had the highest specificity (0.83).

HBsAg decline at week 24 and baseline HBsAg levels are better predictors of functional cure than novel virologic markers, while on-treatment HBV RNA and HBeAg levels and dynamic changes are the most reliable indicators for HBeAg loss.

Artificial intelligence (AI) translation in genitourinary (GU) pathology has progressed unevenly across organs and tasks. This review addresses a central clinical question: which GU pathology AI applications are deployment-ready, which require further validation, and what frameworks can guide safe implementation? We synthesize evidence across GU organs and introduce pragmatic translation frameworks to guide deployment and prioritize translational research.

Narrative review integrating foundational literature with targeted 2023–2025 publications, emphasizing regulatory milestones, external validation, and prospective studies. Literature was identified through PubMed, Embase, and conference proceedings using structured search terms for AI, digital pathology, and GU organ-specific queries. For each organ/task, we mapped evidence strength, regulatory maturity, generalizability, workflow integration, safety, and feasibility to a Translational Readiness Index (TRI) rubric (0–30 scale).

Prostate biopsy AI demonstrates the strongest maturity (TRI 26/30), supported by U.S. Food and Drug Administration-cleared systems, multi-site validation, and prospective implementations showing efficiency gains and reduced ancillary testing. Bladder cytology shows moderate readiness (TRI 19/30), with commercial offerings supporting pilotable prescreening workflows aligned with the Paris System when paired with uncertainty-aware deferral. Bladder histology, renal neoplasia, and low-prevalence domains (testis, penis) remain emerging (TRI 6–15/30), constrained by label variability, rare subtype underrepresentation, and limited external validation.

The TRI rubric, SURE-Path safety bundle, and VALIDATED/ORCHESTRATE implementation pathway provide a practical template for evidence-based deployment in GU pathology. Clinically defensible translation requires matching intended use to validation evidence, with explicit safeguards for emerging applications.

Accurate identification of invasive fungal pathogens is crucial for appropriate antifungal therapy. The Department of Clinical Laboratory at Indus Hospital & Health Network, Karachi, Pakistan, reported two cases of invasive fungal infections between 1st January and 31st March 2024 in which conventional identification methods and automated systems produced discordant results, highlighting critical diagnostic challenges.

Two invasive yeast isolates initially showing budding yeast cells without pseudohyphae on Gram stain were subjected to conventional identification using cornmeal-Tween 80 agar, chrome agar, and BiGGY agar, followed by automated identification using the VITEK 2 ID-YST system and confirmatory API 20C AUX testing. Both isolates demonstrated typical soft, wrinkled, cream-colored colonies on Sabouraud dextrose agar, which on chrome agar appeared as dry, blue colonies and on BiGGY agar as dry, brown colonies. Characteristic arthroconidia and blastoconidia formation on cornmeal-Tween 80 agar were observed, consistent with Trichosporon species. However, the VITEK 2 ID-YST system identified both isolates as Cryptococcus laurentii with good confidence levels. India ink staining was negative for both isolates. Confirmatory API 20C AUX testing correctly identified both isolates as Trichosporon asahii (identification profile 3740734).

This discordance between automated and conventional methods underscores the continued importance of conventional identification techniques and highlights potential limitations of automated systems for certain uncommon yeasts. Laboratories should maintain proficiency in conventional methods and consider confirmatory testing when automated results conflict with morphological findings. The clinical implications of misidentification include inappropriate antifungal selection, given the different susceptibility patterns between these species.

Insulin resistance is a common extrahepatic manifestation of hepatitis C virus (HCV) infection (HCVi), but its mechanism is poorly understood. While systemic insulin resistance is documented, portal insulin dynamics, a key regulator of hepatic metabolism, remain unexplored. This study aimed to investigate the relationship between insulin, the gut-liver axis, and immunometabolic changes in patients with HCV.

HCV patients were evaluated before (HCVi; n = 29) and after sustained virologic response (SVR) achieved with sofosbuvir/velpatasvir treatment (SVR, n = 23) (NCT02400216). Liver biopsies, portal blood, and peripheral blood were collected at both phases. Statistical analyses were conducted using Wilcoxon rank-sum tests, Mann-Whitney tests, and Pearson’s correlation coefficients to assess differences and associations across insulin, glucose, cytokines, metabolites, immune cells, and hepatic liver transcriptomics to elucidate impaired insulin homeostasis in HCVi.

HCV patients had significantly reduced portal insulin compared to SVR (p = 0.02), while peripheral insulin, portal glucose, and peripheral glucose remained unchanged. Portal insulin correlated positively with proinflammatory cytokines and vascular injury markers and negatively with CD8/CD62L/CD45RA/CD3 cells (naive cytotoxic T-cells) and non-standard nucleotides. Hepatic transcriptomic analysis revealed portal insulin correlated positively with immune and negatively with amino acid pathways, reflecting insulin’s role in the perturbations of immunometabolism during HCVi.

Lower portal insulin during HCVi is associated with changes consistent with altered pancreatic insulin secretion and decreased hepatic insulin extraction. The observed correlations support a potential relationship between the immune response and insulin dynamics, indicating an interplay between the immune system, metabolism, and insulin in HCVi, with clinical implications for the management of dysglycemia.

Chaperone-like proteins are involved in the pathogenesis of coronavirus infection through regulation of the viral life cycle, immune response, and antigen presentation. A recently discovered class of chaperones, called heat-resistant obscure proteins (Hero proteins), performs functions similar to other molecular chaperones. This study aimed to investigate the association between the gene encoding the Hero protein SERF2 (Hero7) and the risk of severe COVID-19.

This case-control study was conducted according to the STROBE protocol. A total of 1,373 unrelated Russians (178 patients with severe COVID-19 and 1,195 controls) were recruited. Genotyping of rs4644832 in the SERF2 gene was performed using a probe-based polymerase chain reaction approach. The effects of the single nucleotide polymorphisms (SNPs) were analyzed using bioinformatics tools, including GTExPortal, eQTLGen, HaploReg, atSNP, Gene Ontology, Lung Disease and Common Metabolic Diseases Knowledge Portals, and the STRING database.

SNP rs4644832 in the SERF2 gene (effect allele G) was associated with a decreased risk of severe COVID-19 in the total sample (odds ratio (OR) = 0.56, 95% confidence interval (CI) 0.39–0.81, P = 0.001), females (OR = 0.51, 95% CI 0.31–0.87, P = 0.006), non-smokers (OR = 0.46, 95% CI 0.29–0.74, P = 0.0004), individuals with body mass index ≥ 25 (OR = 0.42, 95% CI 0.25–0.7, P = 0.0004), individuals with low fruit and vegetable intake (OR = 0.38, 95% CI 0.22–0.67, P = 0.0004), and individuals with low physical activity (OR = 0.41, 95% CI 0.23–0.75, P = 0.002).

The G allele of rs4644832 in the SERF2 gene appears to have a protective effect against severe COVID-19. Functional annotation of rs4644832 suggests that it may influence COVID-19 pathogenesis through regulation of proteostasis, ubiquitination, inflammation-induced protein aggregation, the viral life cycle, and cytoskeletal functions.

Liver transplant rejection significantly affects patient prognosis. Myeloid-derived suppressor cells (MDSCs), known for their potent immunoregulatory functions, represent a promising target for managing liver transplant rejection. This study aimed to systematically characterize the diversity of MDSC subsets and their context-dependent functions, particularly within the context of transplant tolerance.

We analyzed clinical and murine liver transplants using single-cell RNA sequencing, bulk RNA sequencing, flow cytometry, multiplex immunohistochemistry, and co-culture assays to phenotype MDSC subsets.

Single-cell RNA sequencing analysis of human and murine samples revealed MDSC involvement in transplant rejection. In mice, MDSC scores followed a normal distribution during the first week post-transplant and correlated with clinical flow cytometry data at one month. A distinct LDLR+ monocytic MDSC (M-MDSC) subset was identified and confirmed through spatial mapping by multiplex immunohistochemistry. Flow cytometry demonstrated dynamic changes in LDLR+ M-MDSCs across tissues (liver, spleen, peripheral blood, bone marrow, and lymph nodes), with a peak during acute rejection. Co-culture experiments showed that LDLR−/− M-MDSCs exhibited reduced Arg-1/iNOS expression and an impaired capacity to induce inhibitory receptors (TIGIT, PD1, CTLA-4) or suppress effector molecules (GZMB, IFN-γ, IL-2) in CD8+ T cells.

These findings highlight the critical role of MDSCs in liver transplant rejection. LDLR+ M-MDSCs exhibited enhanced immunosuppressive properties, underscoring their potential clinical relevance in mitigating rejection and promoting immune tolerance.

Super-enhancers (SEs) are highly enriched clusters of transcriptional regulatory elements within the genome, occupying a central position in tumorigenesis and development. This review aims to synthesize the rapidly expanding body of knowledge on SEs as the central hub of tumor transcriptional regulation.SEs integrate specific transcription factors, dynamic epigenetic modifications (such as H3K27ac), and restructure the three-dimensional spatial architecture of the genome to aberrantly drive the expression of proto-oncogenes and cell identity-related genes. This activity sustains the malignant phenotype, stem cell properties, metabolic reprogramming, and therapy resistance of tumor cells. Their functions involve emerging physical mechanisms such as phase separation forming transcriptional condensates and long-range chromatin looping. The activity of SEs exhibits high tumor-type and tissue specificity. They are activated through unique mechanisms in different cancers, becoming key nodes of “transcriptional addiction” in tumor cells. This characteristic also makes them highly promising therapeutic targets. Inhibitors targeting core SE components (such as the BET protein BRD4 and transcriptional kinases CDK7/9), epigenetic drugs, and strategies aimed at disrupting their phase-separated condensates have shown selective efficacy in various preclinical tumor models. In conclusion, SEs serve as pivotal hubs of transcriptional addiction in cancer by integrating diverse molecular mechanisms to drive oncogenic programs, and their specific components present promising therapeutic targets; future advances in multi-omics and precision strategies will be key to translating these findings into clinical applications.