Development of mixed histiocytosis (Langerhans cell histiocytosis (LCH))/Erdheim–Chester disease (ECD)) after treatment in patients with an initial skull LCH lesion has not been well recognized. An elderly woman initially developed LCH at the left temporal bone, preceded by polyuria and polydipsia five years earlier; the lesion was surgically removed. Two years thereafter, she experienced her first LCH relapse with a right parietal skull lesion, in which a BRAF V600E mutation was confirmed, and chemotherapy was initiated. After a second LCH relapse involving the left parietal bone, the patient presented with a third relapse at the L2 vertebra. This lesion was pathologically diagnosed as mixed histiocytosis (LCH/ECD), resulting in refractoriness to conventional chemotherapy, and was successfully treated with targeted therapy using BRAF and MEK inhibitors. Spinal mixed histiocytosis (LCH/ECD) may develop following relapses of skull LCH after chemotherapy, for which targeted therapy could be effective.

Early and accurate prognostic assessment is crucial to avoid serious disease progression in patients with liver failure. Thyroid hormone is an important metabolic regulator involved in hepatic function. This review examines the pathophysiological regulation in detail of the hypothalamic-pituitary-thyroid axis in patients with liver failure and emphasizes the importance of thyroid profiling (thyroid-stimulating hormone, T3, and T4) in prognostic assessment and risk stratification. T3 can enhance liver regeneration. The clinical application of thyroid hormone replacement therapy in patients with acute-on-chronic liver failure complicated by non-thyroidal illness syndrome is controversial. This review aims to inform clinical practice regarding the relevance of thyroid hormone level assessment in liver failure and to provide novel insights into the prognostic evaluation and comprehensive care of liver failure complicated by thyroid dysfunction.

Normalization can standardize and improve machine learning (ML) performance on omics data. However, it is unclear whether normalization is associated with overfitting (i.e., worse cross-dataset performance than intra-dataset performance). Therefore, we aimed to examine associations of normalization and regularization with overfitting of ML on omics data.

Using three paired transcriptomic and clinical datasets (lung adenocarcinoma: the Cancer Genome Atlas (TCGA)/Oncology Singapore; melanoma: TCGA/Dana-Farber Cancer Institute; glioblastoma: TCGA/Clinical Proteomic Tumor Analysis Consortium), we applied ANOVA-based gene selection methods, six normalization methods, and six ML models to classify cancer patients’ deaths. Balanced accuracy (BA) and area under the curve (AUC) in intra- and cross-dataset settings were compared using inferential analyses.

Normalization consistently improved intra-dataset performance (median BA/AUC changes: 0.035–0.214/0.115–0.279) on all data, particularly with Z_Raw, but decreased or slightly increased cross-dataset performance (median BA/AUC changes: −0.029–0.079/0.029–0.064). Least Absolute Shrinkage and Selection Operator (LASSO) model without normalization consistently outperformed most of the ML models in cross-dataset testing across cancer types. ML models on all and molecular-alone data showed similar best performances.

Normalization increases ML’s intra-dataset performance and overfitting in three paired cancer transcriptomic and clinical datasets. Regularized models such as LASSO appear to mitigate overfitting and achieve robust cross-dataset performance. Therefore, cross-dataset evaluation and regularized models are recommended to assess and reduce overfitting, while normalization should be used cautiously. Adding clinical data seems to have little impact on ML models’ performance. However, future work on other diseases and datasets is warranted.

Vulvovaginal candidiasis, an infection caused by an abnormal proliferation of Candida species in the vagina and vulva, is particularly relevant, affecting up to 75% of women of reproductive age. Because of antifungal drug resistance, a significant number of plants are used to treat vaginal candidoses in Cameroon. Thus, the scientific validation of the use of these plants in treating candidiasis is valuable. This study sought to identify medicinal plants used to treat vaginal infections in the Dschang district and evaluate the antifungal activity of the most promising plants on five Candida species.

The ethnobotanical survey was conducted in Dschang (Menoua Division, West Cameroon) through individual interviews using a semi-structured questionnaire. Extracts from seventeen plants were obtained by maceration using water or a water–ethanol solution (3:7; v/v). Antifungal activity was evaluated using the microdilution method.

Forty-eight plants belonging to 33 families were identified as treating vaginal infections. Decoction and formulation of ovules were the prevalent modes of plant preparation, with leaves and bark being the predominant plant organs used. Out of thirty-four extracts tested, two (CSEHAlc and MIEHAlc) showed antifungal activity, with minimum inhibitory concentrations ranging from 0.315 to 2.5 mg/mL. The determination of the minimum fungicidal concentrations revealed the fungicidal orientation of these bioactive extracts.

This study identifies medicinal plants used to treat vaginal infections in Dschang and their modes of preparation. The in vitro antifungal screening of selected plants indicated Mangifera indica and Canarium schweinfurthii as the anti-Candida plants that can be further exploited for antifungal drug discovery.

Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a major global health concern and encompasses a spectrum ranging from hepatic steatosis and metabolic dysfunction-associated steatohepatitis to liver fibrosis, cirrhosis, and ultimately hepatocellular carcinoma. Insulin resistance, the pathogenic cornerstone of MASLD, drives enhanced peripheral lipolysis and increased hepatic de novo lipogenesis, thereby overloading the liver with lipids and inducing steatosis. Subsequent lipotoxicity, inflammation, and gut microbiota dysbiosis further exacerbate disease progression. The gut microbiota and their metabolites communicate with the liver via the gut-liver axis, forming a complex signaling network that directly or indirectly modulates hepatic metabolism, systemic immune responses, oxidative stress, and intestinal barrier integrity. In this review, we synthesize evidence for the beneficial and detrimental effects of the major human gut microbial communities and their metabolites during the course of MASLD. We delineate how these gut-derived factors regulate hepatic function through an integrated tripartite “gut-liver axis–oxidative stress–metabolic reprogramming” mechanism. These insights may inform microbiome-based precision interventions and accelerate the development of therapeutic strategies targeting MASLD.

Chronic hepatitis B (CHB) remains a major global public health challenge. Current therapies based on nucleos(t)ide analogues and interferon mainly achieve long-term viral suppression, whereas only a small proportion of patients attain a functional cure, defined as sustained hepatitis B surface antigen loss with hepatitis B virus (HBV) DNA below the limit of quantification for at least 24 weeks after treatment discontinuation, with or without anti-HBs seroconversion. Emerging evidence from the gut–liver axis indicates that gut microbiota–derived metabolites, particularly short-chain fatty acids (SCFAs) and bile acids (BAs), modulate the HBV life cycle and immune regulation in CHB, thereby offering therapeutic targets to overcome immune tolerance. This review summarizes the biological characteristics of SCFAs and BAs and their mechanistic roles across different stages of HBV infection, with emphasis on translational relevance. In vitro and animal studies suggest that butyrate and related SCFAs suppress HBV gene expression by inhibiting histone deacetylases and remodeling covalently closed circular DNA minichromatin. SCFAs may also enhance antiviral immunity, although they may reinforce immune tolerance in certain contexts. For BAs, the farnesoid X receptor, Takeda G protein–coupled receptor 5, and the HBV entry receptor sodium taurocholate cotransporting polypeptide form a key signaling hub with dual effects on viral replication and host responses. Early-phase studies suggest that farnesoid X receptor agonists, pegylated interferon-α, or nucleos(t)ide analogues are associated with hepatitis B surface antigen reductions, though larger trials are needed. This review proposes biomarker-guided stratification and multi-target combination strategies to improve functional cure rates in CHB.

Immunothrombosis, the interplay between immune activation and coagulation, contributes to disease progression in inflammatory disorders. Its role in hepatitis B virus–related acute-on-chronic liver failure (HBV-ACLF) and the involvement of neutrophil extracellular traps (NETs) remain unclear. This study aimed to elucidate NETs-mediated immunothrombosis in HBV-ACLF.

Liver single-cell RNA sequencing data from HBV-ACLF patients and healthy controls were analyzed to define immune and endothelial transcriptional profiles. A cohort of 46 HBV-ACLF patients, 20 chronic hepatitis B patients, and 20 healthy controls was assessed for circulating NETs, endothelial injury markers, and coagulation parameters. Histopathology and in vitro assays examined NETs distribution and endothelial interactions.

NETs were markedly elevated in HBV-ACLF and correlated with endothelial injury markers (syndecan-1, von Willebrand factor, soluble thrombomodulin), coagulopathy, and prognostic scores. Histology revealed NETs colocalization with endothelial cells and platelets within hepatic microthrombi. NETs from patient neutrophils impaired endothelial integrity and enhanced procoagulant activity in vitro. Mechanistically, toll-like receptor 2 (TLR2) and complement component 5a receptor 1 (C5aR1) signaling were involved in NETs formation, and their pharmacological inhibition reduced NETs generation.

NETs are associated with endothelial injury and immunothrombosis in HBV-ACLF. Mechanistic analyses suggest a role for TLR2 and C5aR1 pathways in NETs formation, indicating potential targets for future therapeutic investigation.