Prognostic scores are valuable tools for predicting survival in patients with chronic liver disease. Recently, the albumin-bilirubin (ALBI) score has emerged as a potential prognostic indicator in liver-related conditions. This study aimed to compare the prognostic efficacy of the ALBI score with the Model for End-stage Liver Disease (MELD), MELD-Na+, and Child-Turcotte-Pugh (CTP) scores in predicting survival among patients with alcohol-associated liver disease (ALD).

This study included consecutive ALD patients admitted to the Medicine and Gastroenterology wards of MKCG Medical College and Hospital, Berhampur, Odisha, India, between November 2019 and November 2022. Upon hospitalization, baseline characteristics, clinical and laboratory parameters, ALBI, MELD, MELD-Na+, and CTP scores were recorded. The accuracy of these scores in predicting survival up to three years was compared.

A total of 490 ALD patients were included. Higher ALBI scores were observed in patients who died during hospitalization (p < 0.001), at 28 days (p < 0.001), 90 days (p < 0.001), six months (p < 0.001), one year (p < 0.001), two years (p < 0.001), and three years (p < 0.001), compared to those who survived. However, the area under the receiver operating characteristic (AUROC) curves showed that the ALBI score was inferior to MELD, MELD-Na+, and CTP scores in predicting survival at admission [AUROC: ALBI (0.719), MELD-Na+ (0.823), MELD (0.817), CTP (0.770)] and at three years [AUROC: ALBI (0.755), MELD-Na+ (0.787), MELD (0.758), CTP (0.784)]. Furthermore, Cox regression analysis revealed that components used in the MELD, MELD-Na+, and CTP scores—such as serum creatinine, serum sodium, and hepatic encephalopathy—were independent predictors of mortality, whereas the components of the ALBI score (serum albumin and serum bilirubin) were not.

All hospitalized ALD patients had a grade 3 ALBI score, with significantly higher scores observed among non-survivors compared to survivors. However, MELD, MELD-Na+, and CTP scores were superior to the ALBI score in predicting survival both during hospitalization and over a three-year follow-up period.

Guaiac fecal occult blood test (gFOBT) is often used to evaluate evidence of food protein-induced allergic proctocolitis (FPIAP) in children in primary care and gastroenterology settings; however, it has not been validated for this diagnosis, and little is known about the positivity rates in early infancy. In this study, we used samples from healthy asymptomatic infants aged two weeks to two months to evaluate the gFOBT positivity rate compared to those diagnosed with FPIAP.

This was a nested case-control study. Frozen stool samples from infants aged two days to five months enrolled in the Gastrointestinal Microbiome and Allergic Proctocolitis study were evaluated using gFOBT (n = 123). The results were interpreted by three blinded staff members, including a trained clinical research coordinator, a pediatric gastroenterologist, and an experienced medical assistant. Additionally, the samples were analyzed using a quantitative fecal immunochemical test (FIT) for hemoglobin to compare with gFOBT results.

Eight percent of samples from the 100 healthy asymptomatic infants were gFOBT positive (11% when including positive and equivocal results). Seventy-four percent of samples from infants diagnosed with FPIAP were gFOBT positive. The interrater reliability of gFOBT interpretation was 81%. Of the healthy samples that yielded a positive gFOBT result, 50% also yielded a positive FIT result. Of the 23 FPIAP samples that yielded a positive gFOBT result, 29% yielded a positive FIT result.

Healthy asymptomatic infants in early infancy were gFOBT positive up to 11% of the time. Caution should be used when interpreting gFOBT results in young infants in a diagnostic setting.

Atypical teratoid/rhabdoid tumor (AT/RT) is a rare and highly aggressive embryonal tumor that predominantly affects infants and young children. This malignancy arises from primitive neuroectodermal cells and exhibits heterogeneous differentiation into various embryonic tissues. Due to its rarity and complexity, diagnosing and managing AT/RT present significant challenges. Recent studies have summarized the key features of cerebellar and supratentorial AT/RT cases; however, critical gaps remain in understanding their diffuse leptomeningeal variants and long-term functional outcomes. Here, we report a case of a two-year-old child diagnosed with cerebellar AT/RT, who presented with vomiting and gait instability. The patient underwent a gross total resection followed by adjuvant radiotherapy and chemotherapy. Despite achieving radiological remission, the patient survived for only eight months and experienced severe neurological deficits, including persistent ataxia and recurrent infections. This case highlights the disconnect between surgical success and long-term quality of life. It underscores the importance of integrating molecular diagnostics and palliative care to address the multifaceted burden of AT/RT.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is now the most common chronic liver disease in the Western world, driven by obesity, insulin resistance, and systemic inflammation. Its progressive form, metabolic dysfunction-associated steatohepatitis (MASH), can culminate in cirrhosis and hepatocellular carcinoma (HCC). While lifestyle modification remains central to MASLD management, there is growing interest in pharmacological interventions, particularly nutrient-stimulated hormone-based therapies (NuSHs), such as GLP-1 receptor agonists. NuSHs exert metabolic and anti-inflammatory effects primarily via weight loss and improved insulin sensitivity. Emerging clinical data support their efficacy in resolving MASH without worsening fibrosis. However, benefits in cirrhotic patients are less evident, suggesting greater utility in early intervention. Observational studies and clinical trials suggest a reduction in liver-related morbidity with GLP-1 receptor agonist use, though fibrosis regression remains inconsistent. Preclinical models indicate that NuSHs may also reduce MASH-related HCC incidence and tumor burden, likely through systemic metabolic improvements rather than direct antineoplastic action. Observational human data following bariatric surgery reinforce this link, suggesting that weight loss itself plays a key preventive role. Herein, we propose that NuSHs are promising candidates for MASH-related HCC prevention. We provide mechanistic suggestions for how this may occur. Furthermore, incorporating NuSHs into the post-locoregional treatment pathway for HCC may delay the need for systemic anti-cancer therapies, improve immunotherapy synergy and transplant eligibility, and even slow disease progression through reversal of carcinogenic drivers. Future studies are needed to target oncological endpoints and clarify immunometabolic mechanisms to guide the integration of NuSHs into MASLD treatment algorithms.

Micro- and nanoplastics (MNPs) are plastic particles smaller than 5 mm and 1 µm, respectively, and are emerging environmental pollutants with growing implications for human health. These particles stem from either ‘primary sources’, such as intentionally manufactured microbeads and industrial abrasives, or ‘secondary sources’, where larger plastic items break down into smaller fragments over time. Human exposure primarily occurs through ingestion and inhalation, with contaminated seafood and plastic-laden food packaging representing key routes of entry. Once ingested, MNPs can cross the intestinal barrier, accumulate in gastrointestinal (GI) tissues, and trigger biological responses. Mechanistic studies reveal that MNPs induce oxidative stress, DNA damage, chronic inflammation, and endocrine disruption, all of which are hallmarks of carcinogenic pathways. They also alter gut microbiota, potentially promoting dysbiosis and immune dysregulation. The GI tract is particularly vulnerable to these effects due to direct luminal mucosal contact and high epithelial turnover. Epidemiological data remain limited, but early evidence supports a plausible link between MNPs exposure and GI malignancies. Such findings are particularly concerning given the increasing global incidence and early age presentation of colorectal and esophageal cancers. Given that MNPs may represent a modifiable environmental risk factor in GI cancer prevention, public health strategies must prioritize reducing plastic exposure, promoting antioxidant-rich diets, and improving environmental monitoring. This review explores the potential carcinogenic effects of microplastics while also examining their emerging roles in cancer therapeutics. It highlights critical avenues for future investigation and underscores the importance of cross-disciplinary efforts to tackle this growing global health concern.

Skin cancer, the most common global malignancy, is linked to ultraviolet (UV)-driven serum 25-hydroxyvitamin D (25(OH)D)synthesis, with its controversial role possibly reflecting cumulative UV exposure. This study aimed to assess the association and causality between 25(OH)D levels and skin cancer risk using the National Health and Nutrition Examination Survey (1999–2018) data and Mendelian randomization (MR) analyses, evaluating 25(OH)D as a screening biomarker.

We integrated data from the National Health and Nutrition Examination Survey (1999–2018; n = 21,357 U.S. adults, including 631 skin cancer cases) with MR analyses using genome-wide association study-derived genetic variants to assess the causal relationship between serum 25(OH)D levels and skin cancer risk.

Higher 25(OH)D levels were associated with increased risks of nonmelanoma skin cancer [odds ratio (OR) (95% confidence interval (CI)) = 2.94 (2.10, 4.20)], melanoma [OR (95% CI) = 2.94 (1.73, 5.28)], and other skin cancers [OR (95% CI) = 2.10 (1.36, 3.36)]. MR analyses supported a causal relationship for nonmelanoma skin cancer [OR (95% CI) = 1.01 (1.00, 1.02)] and melanoma [OR (95% CI) = 1.00 (1.00, 1.01)]. Risks were highest in males, older adults, and individuals with obesity.

Higher serum 25(OH)D levels are associated with increased skin cancer risk, likely reflecting cumulative UV exposure. Routine monitoring of 25(OH)D, combined with UV exposure management, is recommended for risk stratification in skin cancer screening, particularly among high-risk groups. Validation in multiethnic cohorts is needed to confirm these findings.

Myosteatosis is associated with poor outcomes in various liver diseases. However, standardized methods for assessing, defining, and diagnosing myosteatosis in the context of liver diseases remain unclear. Furthermore, the underlying mechanisms by which myosteatosis leads to pathophysiological progression and adverse health outcomes remain elusive. Therefore, in this review, we elaborate on the currently available measures, definitions, and diagnostic criteria of myosteatosis in the existing literature. We thoroughly clarify the recent evidence and data regarding the possible involvement of myosteatosis in the progression and deterioration of various liver diseases and resulting complications, including liver cirrhosis, chronic viral hepatitis, non-alcoholic/metabolic-associated fatty liver disease, primary sclerosing cholangitis, liver transplantation, and hepatocellular carcinoma. Additionally, it synthesizes insights from basic research on the pathogenesis of myosteatosis, which involves multifactorial mechanisms, including insulin resistance, mitochondrial dysfunction, and chronic inflammation. Finally, from an operational and pragmatic perspective, several regimens, including physical, nutritional, and pharmacological therapies, have been discussed as potential treatments for myosteatosis.

Microsatellite-stable colorectal cancer, which accounts for roughly 80–85% of cases, remains largely refractory to immune checkpoint inhibitors compared with microsatellite instability-high tumors. This review synthesizes current evidence on tumor-intrinsic and microenvironmental mechanisms underlying immune checkpoint inhibitor resistance in microsatellite-stable colorectal cancer—including low neoantigen burden and impaired antigen presentation, activation of Wnt/β-catenin and MAPK signaling that exclude T cells, an immunosuppressive cellular milieu (regulatory T cells, myeloid-derived suppressor cells, M2-like tumor-associated macrophages, cancer-associated fibroblasts), metabolic reprogramming, and gut microbiome dysbiosis—and evaluates translational strategies aimed at overcoming these barriers. Preclinical and early-phase clinical data indicate that rational, mechanism-guided combinations (vascular normalization, myeloid reprogramming, metabolic inhibitors, antigen-priming approaches, and microbiome modulation) can enhance immune infiltration and produce benefits in biomarker-defined subgroups. Moving the field forward will require biomarker-driven, adaptive clinical trials with embedded translational endpoints to optimize patient selection and manage toxicity.

Despite rapid advances in computational biology and regulatory reforms encouraging the reduction of animal use, a clear synthesis of how artificial intelligence (AI)-driven polypharmacology can function as a scientific and ethical bridge between traditional in vivo pharmacology and human-relevant drug development remains lacking. The shift from cage-based experimentation to code-based predictive modeling presents both opportunities and unresolved challenges in biological interpretation, regulatory acceptance, and pharmacology education. Therefore, this review aims to critically examine the transition toward AI-enabled, human-centric drug discovery within the framework of the 3R principles (Replacement, Reduction, and Refinement). Specifically, it explores (i) the global regulatory and ethical drivers accelerating non-animal methodologies, (ii) the scientific and educational gaps emerging from reduced dependence on animal models, and (iii) the role of AI and deep learning in reconstructing biological complexity through multi-omics integration and predictive toxicity modeling. By analyzing emerging AI platforms and computational strategies, this review highlights how AI-driven polypharmacology may offer a scalable, ethical, and precision-oriented framework for future pharmacological research.