Chronic liver cirrhosis (LC) and acute-on-chronic liver failure (ACLF) are interconnected hepatic disorders associated with substantial morbidity and mortality. Despite their distinct clinical characteristics, both conditions share common pathogenic pathways that remain inadequately understood. This study aimed to identify shared gene signatures and elucidate underlying molecular mechanisms.

In this study, we employed Weighted Gene Co-Expression Network Analysis to explore transcriptomic data from the Gene Expression Omnibus for LC and ACLF.

Key co-expression modules enriched with genes involved in glycolysis and gluconeogenesis pathways were identified, implicating metabolic dysfunction as a central feature in both conditions. Furthermore, microRNA analysis revealed that hsa-miR-122 and hsa-miR-194 play pivotal roles in regulating these metabolic pathways, potentially contributing to immune dysregulation.

Our findings indicate that these shared molecular mechanisms are critical in the progression from LC to ACLF, providing novel insights into potential therapeutic targets for mitigating disease severity and improving clinical outcomes.

The importance of putative folate-biopterin metabolic interactions lies in the role they may play in the expression of several clinically relevant phenotypes. However, to date, clinical studies on folate-biopterin interactions have been limited. The purpose of this article was to highlight the close relationship between these two cofactors, which share structural similarities and exhibit overlapping metabolic pathways. This folate-biopterin crosstalk has generated several ideas and hypotheses that are critical to advancing the biochemical understanding of several important and seemingly disparate clinical and/or biologically important phenotypes. These phenotypes include melanization/pigmentation, phenylketonuria, autism, neural tube defects, affective disorders, and vascular disease. This review provides a timely, integrated overview of this important area of biochemistry, which is under-represented in the literature and would benefit from further scientific and clinical investigation using improved metabolite-specific analytical methodologies applied to clinically relevant questions.

The causal biomarkers for metabolic dysfunction-associated steatotic liver disease (MASLD) and their clinical value remain unclear. In this study, we aimed to identify biomarkers for MASLD and evaluate their diagnostic and prognostic significance.

We conducted a Mendelian randomization analysis to assess the causal effects of 2,925 molecular biomarkers (from proteomics data) and 35 clinical biomarkers on MASLD. Mediation analysis was performed to determine whether clinical biomarkers mediated the effects of molecular biomarkers. The association between key clinical biomarkers and MASLD was externally validated in a hospital-based cohort (n = 415). A machine learning–based diagnostic model for MASLD was developed and validated using the identified molecular biomarkers. Prognostic significance was evaluated for both molecular and clinical biomarkers.

Six molecular biomarkers—including canopy FGF signaling regulator 4 (CNPY4), ectonucleoside triphosphate diphosphohydrolase 6 (ENTPD6), and major histocompatibility complex, class I, A (HLA-A)—and eight clinical biomarkers (e.g., serum total protein (STP)) were identified as causally related to MASLD. STP partially mediated the effect of HLA-A on MASLD (23.61%) and was associated with MASLD in the external cohort (odds ratio = 1.080, 95% confidence interval: 1.011–1.155). A random forest model demonstrated high diagnostic performance (AUC = 0.941 in training; 0.875 in validation). High expression levels of CNPY4 and ENTPD6 were associated with the development of and poorer survival from hepatocellular carcinoma. Low STP (<60 g/L) predicted all-cause mortality (HR = 2.50, 95% confidence interval: 1.22–5.09).

This study identifies six causal molecular biomarkers (e.g., CNPY4, ENTPD6, HLA-A) and eight clinical biomarkers for MASLD. Notably, STP mediates the effect of HLA-A on MASLD and is associated with all-cause mortality.

High-grade serous carcinoma is a rare diagnosis in cervical biopsies. Cervical serous carcinoma is no longer recognized as a primary cervical tumor in the 2020 World Health Organization classification. This study aimed to characterize the clinicopathologic, immunohistochemical, and molecular features of high-grade serous carcinoma identified in cervical or endocervical biopsies, to assess tumor origin and ensure accurate classification.

Fifty-nine cases originally diagnosed as “serous carcinoma” or “high-grade serous carcinoma” in cervical or endocervical biopsies from 2013 to 2023 were retrospectively reviewed. Clinical data, radiologic findings, and follow-up information were analyzed. Histologic features and immunohistochemical profiles were re-evaluated. Targeted next-generation sequencing was performed on a subset of cases.

The majority of tumors (96%) were determined to originate from the endometrium (n = 47) or the tubo-ovarian region (n = 4), with only one case confirmed as a primary cervical carcinoma. Morphologic patterns varied and could mimic human papillomavirus-associated adenocarcinoma. All tumors showed aberrant p53 expression and diffuse p16 positivity. WT-1 was expressed in all tubo-ovarian tumors but in only 12% of endometrial cases. Estrogen receptor and progesterone receptor were frequently positive in endometrial tumors; human epidermal growth factor receptor 2 was positive in 31% of cases. Molecular analysis confirmed tumor protein p53 mutations and other alterations typical of uterine serous carcinoma.

High-grade serous carcinoma identified in cervical biopsies is overwhelmingly secondary to upper genital tract tumors, most commonly of endometrial origin. A small subset of endocervical adenocarcinomas may mimic serous carcinoma. These findings support the exclusion of primary cervical serous carcinoma from the current World Health Organization classification and emphasize the importance of accurate diagnosis for appropriate management.

Philadelphia chromosome-positive (Ph+) B-lymphoblastic leukemia/lymphoma (B-ALL/LBL) is an aggressive hematologic malignancy driven by the BCR::ABL1 fusion. While many cases respond well to treatment, some patients exhibit persistent BCR::ABL1 expression after therapy, presenting significant diagnostic challenges.

We present the case of a seven-year-old girl diagnosed with Ph+ B-ALL. Despite low percentages or negative results for blasts post-treatment, molecular and cytogenetic studies persistently detected high levels of BCR::ABL1, suggesting a high disease burden at the genetic level. This discordance supported multilineage involvement and the potential for retrospective revision of the initial diagnosis to lymphoblast crisis of chronic myeloid leukemia (LBC-CML).

Classifying such cases as de novo Ph+ B-ALL with multilineage involvement or LBC-CML is challenging, as there is currently no consensus among experts. Further studies are necessary to clarify the distinction, given the different management strategies and treatment responses between these two conditions.

Inflammatory bowel disease (IBD) is a chronic condition with significant health implications worldwide. In Nigeria, data on its prevalence and characteristics are limited, highlighting the need for comprehensive studies to better understand its epidemiology and clinical features in the region. This study aimed to assess the clinical presentation, endoscopic findings, and management challenges of IBD among patients undergoing colonoscopy in Nigeria.

Over five years (2019–2024), a multicenter, cross-sectional survey was conducted involving clinicians across Nigeria’s six geopolitical zones. It included a retrospective review of records from 18 centers. Data collection was conducted in two phases via Google Forms, focusing on care practices and detailed case information, including demographics, clinical features, histology, and treatment. Data analysis used descriptive statistics and tests for associations, with significance set at p < 0.05.

A total of 459 suspected IBD cases (9.7%) were identified among over 4,700 colonoscopies, with histological confirmation in 208 cases (4.4%), indicating the prevalence of IBD in the Nigerian patient population. The most common subtype was ulcerative colitis (53.9%), followed by Crohn’s disease (21.0%) and indeterminate colitis (25.0%). Regional variations were observed, with higher diagnosis rates in some zones (North-West: 14.9%; South-East: 1.4%). The predominant clinical feature was rectal bleeding. Endoscopic findings frequently showed pan-colitis (62%), with significant regional differences (p < 0.001), and management mainly involved medications such as acetylsalicylic acid derivatives (60.0%), with surgical options rarely employed (0.6%). Challenges included high medication costs and limited availability, which affected nearly half of the patients (49.4%; 46.2%).

IBD, though under-recognized, is present in the Nigerian population, with notable regional variation in prevalence and presentation. The primary clinical features align with global patterns, and significant barriers, such as medication costs and availability, hinder effective management. Increasing awareness, improving diagnostic infrastructure, and addressing treatment challenges are essential to enhance care and outcomes for patients with IBD in Nigeria.

Histologic remission is recommended as an adjunctive treatment target in ulcerative colitis, and scoring systems have been proposed to enhance reproducibility. The Nancy Histologic Index (NHI) is increasingly used in clinical trials; however, its performance in real-world settings is not fully established. This study aimed to assess the interrater reliability (IRR) of the NHI among gastrointestinal pathologists in the United States.

Thirty-seven whole-slide images of colorectal biopsies from 34 treated ulcerative colitis patients enrolled in a multicenter adult cohort were independently reviewed by 12 gastrointestinal pathologists. Each biopsy was reviewed twice, five months apart, and graded using the NHI. Prior to the second review, pathologists completed an online tutorial on the NHI.

The NHI showed substantial IRR in both reviews [intraclass correlation coefficient (ICC) = 0.79; 95% confidence interval (CI), 0.70–0.87 at Review 1; ICC = 0.78; 95% CI, 0.69–0.86 at Review 2]. However, considerable variability was observed in individual grade assignments, with the lowest IRR for Grade 2 (ICC = 0.24; 95% CI, 0.15–0.37; P < 0.001, and ICC = 0.23; 95% CI, 0.14–0.36; P < 0.001 for Reviews 1 and 2, respectively), followed by Grade 4 (ICC = 0.41; 95% CI, 0.29–0.55; P < 0.001, and ICC = 0.47; 95% CI, 0.35–0.61; P < 0.001). Grade 1 showed the highest IRR (ICC = 0.79; 95% CI, 0.70–0.87; P < 0.001, and ICC = 0.78; 95% CI, 0.69–0.86; P < 0.001). When Grades 2, 3, and 4 (i.e., active disease) were grouped together, the IRR remained substantial across both reviews (ICC = 0.76; 95% CI, 0.66–0.85; P < 0.001).

While the substantial IRR for active disease (Grades ≥ 2) in this study underscores the clinical utility of the NHI, the IRR for grades 2, 3 and 4 was fair. Thus, refining the criteria for Grades 2, 3, and 4 will be needed to reduce variability among observers and enabling more accurate monitoring of treatment endpoints.

Ischemic stroke is a complex cerebrovascular disorder characterized by highly unpredictable outcomes influenced by patient-specific variables, including age, stroke severity, and preventable stroke-related complications such as infections. Analyses of clinical data have indicated a cumulative post-stroke infection rate of approximately 30%, with reported rates ranging from 5% to 65%. Post-stroke infections pose a significant challenge, as they not only increase the financial burden of stroke care but are also associated with adverse clinical outcomes, prolonged hospital stays, and a higher risk of stroke recurrence. The inflammatory response plays a pivotal role in the pathophysiology of ischemic stroke, encompassing the activation of inflammatory cells, the release of inflammatory mediators, and the engagement of inflammatory signaling pathways. Recent advances in molecular biology have facilitated the identification and investigation of numerous inflammation-related biomarkers. This article reviews the roles and mechanisms of key inflammatory biomarkers, including cytokines, chemokines, adhesion molecules, inflammation-related enzymes and mediators, receptors, signaling pathway molecules, and acute-phase proteins in the context of ischemic stroke, highlighting their significance in stroke pathophysiology and prognostic assessment. Additionally, in conjunction with the latest research advances, the article discusses novel biomarkers such as microRNAs and galectin-3, which are emerging as important tools in multiple domains, including diagnosis and treatment. Drawing on clinical diagnostic and therapeutic practices, this review analyzes the diagnostic and therapeutic roles of both novel and traditional biomarkers in the progression of ischemic stroke, following the temporal sequence from disease onset to prognosis. Finally, the article addresses the limitations of current research and offers perspectives on future directions, providing insights that may contribute to the advancement of precision medicine in the management of ischemic stroke.

Metabolic dysfunction-associated fatty liver disease, representing a spectrum of liver disorders from simple steatosis to metabolic dysfunction-associated steatohepatitis, fibrosis, and cirrhosis, has emerged as one of the most prevalent chronic liver conditions globally, affecting an estimated approximately 30% of the world's population. Its pathogenesis is highly complex, involving intricate interactions between genetic predisposition, metabolic dysregulation, inflammation, and cellular stress responses. Within this complex landscape, orphan nuclear receptors (ONRs) have gained significant attention. Defined by the lack of identified endogenous ligands, ONRs function as master transcriptional regulators controlling diverse biological processes. Crucially, they play pivotal roles in the development and progression of numerous diseases, including metabolic disorders.This review specifically focuses on elucidating the critical contributions of various ONRs to the pathogenesis of metabolic dysfunction-associated fatty liver disease. We examined how these receptors modulate key pathological drivers: lipid metabolism, inflammation,and autophagy.