Mental health disorder (MHD) incidence rates continue to rise, contributing significantly to the global disease burden. While their aetiology was once thought to be strictly genetic or environmental, the study of epigenetics has reshaped our understanding of their underlying mechanisms. Environmental exposures are understood as key players in the development of MHDs. Growing research has elucidated the critical role of environmental chemical exposures-particularly through endocrine-disrupting chemicals and heavy metals-in influencing MHD incidence through epigenetic mechanisms (i.e. DNA methylation, histone modification and non-coding RNA action). A key breakthrough in this field is the recognition that epigenetic modifications are not necessarily permanent. By exploiting the potential reversibility of DNA methylation and histone modification, new avenues for therapeutic interventions open, in which normal gene function could be restored. Understanding and harnessing epigenetic reversibility not only provides hope for novel and personalized treatment strategies but also underscores the importance of environmental protection policies in mental health prevention.

This review examines the role of indoxyl sulfate, a gut-derived uremic toxin, in the development of anemia in chronic kidney disease. It dissects the cellular and biochemical mechanisms through which indoxyl sulfate suppresses erythropoietin production, disrupts iron metabolism, and promotes oxidative stress and inflammation. Indoxyl sulfate interferes directly with the hypoxia-inducible factor pathway, thereby reducing the transcriptional activation of erythropoietin. In parallel, indoxyl sulfate-induced oxidative stress damages red blood cells and accelerates premature cell death, while its stimulation of pro-inflammatory pathways further downregulates erythroid progenitor cell function. Therapeutic strategies such as dietary protein modulation, gut microbiota interventions, oral adsorbents, and enhanced dialysis modalities have shown promise in lowering indoxyl sulfate levels and, consequently, improving erythropoietin responsiveness and iron homeostasis in chronic kidney disease patients. The review synthesizes evidence from clinical and experimental studies that position indoxyl sulfate as a central yet underappreciated mediator of anemia in chronic kidney disease. Indoxyl sulfate establishes a vicious cycle that exacerbates anemia and contributes to erytropoiesis-stimulating agent hyporesponsiveness. The article advocates for targeted interventions aimed at reducing indoxyl sulfate burden, which could transform anemia management in chronic kidney disease and pave the way for personalized treatment strategies.

Adaptive Drug Resistance Mechanisms Driven by Non-coding RNA-Protein Interaction Networks in Hepatocellular Carcinoma.

Whole slide imaging (WSI) enables the digitisation of entire histological slides at high resolution, allowing pathologists and researchers to analyse tissue samples digitally rather than through traditional microscopy. This technology has become increasingly valuable in pathology for research, education, and clinical diagnostics. Endometrial biopsy is very common, often being undertaken to exclude non-cancerous disease. This means that most cases do not contain cancer, and the challenge is to accurately and efficiently exclude serious pathology rather than simply make a diagnosis of malignancy. A well-curated, expert-annotated, endometrial whole slide dataset covering a spread of cancer and non-cancer diagnoses will support machine learning applications in automated diagnosis, facilitate research into the pathology of endometrial cancer, and serve as an educational resource for medical professionals. We introduce a newly constructed, large-scale dataset of endometrial biopsies, comprising 2,909 whole slide images in iSyntax format, each accompanied by a corresponding annotation file in JSON format. Each whole slide image is labelled with a primary class label representing its final diagnosis and a sub-category label providing further details within that diagnostic class. These class labels are critical for machine learning applications, as they enable the development of AI models capable of distinguishing between different types of endometrial abnormalities, improving automated classification, and guiding clinical decision-making. Constructing and curating a high-quality endometrial whole slide dataset requires significant effort to ensure accurate annotations, data integrity, and patient privacy protection. However, the availability of a well-annotated dataset with detailed class labels is crucial for advancing digital pathology. Such a resource can enhance diagnostic accuracy, support personalized treatment strategies, and ultimately improve outcomes for patients with endometrial cancer and other endometrial conditions.

Diabetic macular edema (DME) is a major cause of visual impairment, and treatment response can vary based on retinal structural changes. This post-hoc analysis of the Phase III VISTA trial evaluated ellipsoid zone (EZ) integrity and fluid dynamics over 100 weeks using a machine learning-enabled OCT segmentation and feature extraction platform. Among 443 eyes randomized to intravitreal aflibercept injections (IAI) or laser photocoagulation, IAI treatment provided greater reductions in intraretinal fluid volume (− 0.933 ± 1.344 mm2 vs. − 0.386 ± 1.080 mm2; p < 0.0001) and better preservation of EZ integrity (− 24.6% vs. + 125.6%; p < 0.0001) compared to laser. The IAI every 4 weeks (2q4) regimen achieved the most sustained improvement in fluid control, while increased fluid volatility in the IAI every 8 weeks (2q8) group was associated with poorer visual outcomes. In contrast, laser treatment was associated with early reduction in EZ integrity, consistent with known effects of photocoagulation, which this study quantified in vivo over time. At week 100, EZ integrity strongly correlated with best-corrected visual acuity (r = 0.61, p < 0.05). No significant differences in treatment response were observed across racial/ethnic groups. These findings highlight the importance of consistent fluid control and demonstrate the utility of machine learning-derived EZ metrics and fluid stability as imaging biomarkers to guide personalized treatment strategies and optimize long-term visual outcomes.Registry: ClinicalTrials.gov, TRN: NCT01363440, Registration date: 27 May 2011.

Sex-differential responses to immune checkpoint inhibitors across the disease continuum unified by tumor mutational burden.

Small but significant: Prognostic value of the small duct type in intrahepatic cholangiocarcinoma.

Principal component analysis of antiseizure medication-induced hostility/aggression and factor analysis of levetiracetam using the food and drug administration adverse event reporting system.

Failure pattern and salvage in head and neck cancer of unknown primary: A national study by DAHANCA.

Study design and protocol of a randomized, pragmatic, comparative effectiveness trial evaluating a sequenced strategy for improving outcomes in people with knee osteoarthritis pain (SKOAP): Conservative treatment evaluation.

Predicting daily pain fluctuations in fibromyalgia: The role of mental distress and sleep heart-rate.

Cost-effectiveness of biomarker-based and universal strategies for the treatment of advanced-stage endometrial cancer.

This study aimed to identify a novel prognostic signature derived from an EGFR Tyrosine kinase inhibitors (TKI-resistant) macrophage subpopulation and to evaluate its clinical and therapeutic relevance in HCC. We utilized single-cell RNA sequencing data from HCC patients. An EGFR-TKI resistance score was calculated across all cell types. Macrophages, which exhibited the highest resistance score, were sub-clustered to identify the most resistant subpopulation. Marker genes from this sub-cluster were intersected with differentially expressed genes (DEGs) from the TCGA-LIHC cohort. A robust prognostic model was constructed. The model's performance was rigorously validated, and the signature was further characterized through multi-omics analysis and its correlation with immune checkpoint blockade (ICB) response and drug sensitivity. scRNA-seq analysis unequivocally identified macrophages as possessing the highest EGFR-TKI resistance score. We identified seven key prognostic genes: SLC41A3, DCAF13, PPM1G, NDC80, FAM83D, FUCA2, and UQCRH. A risk model built on these seven genes effectively stratified patients into high- and low-risk groups with significantly different overall survival (OS) in the TCGA cohort, a finding successfully validated in the independent GSE76427 cohort. A clinical nomogram integrating the risk score demonstrated excellent predictive accuracy, with AUC values for 1-, 3-, and 5-year OS of 0.816, 0.781, and 0.799, respectively. The low-risk group was associated with a favorable immune-infiltrated phenotype and was predicted to be more sensitive to immunotherapy. Conversely, the high-risk group exhibited distinct genomic features and was predicted to be more sensitive to specific targeted agents, including Navitoclax and Sorafenib. We identified and validated a novel 7-gene prognostic signature derived from a subpopulation of EGFR-TKI-resistant macrophages. This signature accurately predicts patient survival, offers insights into the molecular mechanisms of therapy resistance in HCC, and provides a promising tool for improved patient stratification and the development of personalized treatment strategies.

Salvianolic acid B inhibits melanoma via dual modulation of glycolysis and NK/T cell immunity.

The upper face (forehead, brows, temples, and periorbital region) plays a central role in overall facial expression and perceived age. Treatment approaches must evolve beyond traditional Western norms to accommodate ethnic and cultural diversity in anatomy and aesthetic preferences. To review current knowledge of upper-face morphology and aging patterns across diverse populations and provide guidance for culturally sensitive assessment and rejuvenation. An expert panel of dermatologists, oculoplastic, and plastic surgeons reviewed anthropometric data, literature on ethnic and cultural variations, and clinical experience to synthesize region-specific aging trends and treatment strategies emphasizing noninvasive modalities. Distinct anatomic and aging patterns were identified among populations of African, East Asian, South Asian, Central and South American, Middle Eastern, and Northern European descent. Key variations include differences in orbital depth, brow position, eyelid morphology, and skin characteristics. Cultural preferences (e.g. East Asian desire for gentle convexity, Middle Eastern emphasis on brow definition) further inform individualized treatment planning. Minimally invasive treatments can restore balance and rejuvenate the upper face when tailored to these differences. Effective upper-face assessment requires both anatomical precision and cultural awareness. Clinicians should integrate ethnic variability and evolving beauty ideals into personalized treatment strategies to achieve natural, harmonious outcomes across diverse patient populations.

Heterogeneity of acute myeloid leukemia patients explored through single-cell and single-sample gene regulatory networks.

Identification of novel drug targets for mental disorders through genetic, colocalization, and network pharmacology approaches.

Adrenoleukodystrophy: Current understanding of disease mechanisms, diagnosis, and therapeutic advances-a recent review.

The management of advanced, unresectable, or metastatic BRAFV600-mutated melanoma is complex, particularly regarding therapy sequencing with targeted therapies (TT) and immune checkpoint inhibitors (ICI). The REMINISCENCE project aimed to enhance individualized therapy approaches by analyzing case reports of patients undergoing encorafenib and binimetinib (EB) therapy. This report discusses three melanoma patients with brain metastases treated in Germany and Austria, emphasizing personalized treatment strategies in BRAFV600-mutated melanoma, particularly when both ICI and TT are available. The timing for transitioning between therapies remains contentious, with many patients experiencing disease progression during or after adjuvant therapy. Findings from clinical trials like DREAMseq, SECOMBIT, EBIN, and ImmunoCobiVem may not directly apply to this evolving clinical landscape due to the impact of prior therapies on the tumor microenvironment. The variations in trial designs further complicate sequencing strategies. Emerging methods, such as early circulating tumor DNA (ctDNA)-guided approaches, present potential pathways for personalized treatment. Ongoing research into sequencing therapy is crucial for improving clinical outcomes. To determine the most effective treatment sequences based on individual medical histories, genetic profiles, and treatment goals, there is an urgent need for prospective biomarker-driven clinical trials.

The Role of Replication Stress-Related Genes in Cervical Cancer Radiotherapy Resistance: A Bioinformatic and Experimental Validation.