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Review Article Open Access
The Oncodarwinian Hypothesis: Cancer as a Potential Immunoadaptive Response and Artificial Intelligence-based 3D Printed p53 Superproteins
Antonio Araújo
Published online January 22, 2026
Exploratory Research and Hypothesis in Medicine. doi:10.14218/ERHM.2025.00041
Abstract
This review presents the Oncodarwinian Hypothesis, which proposes a new medical paradigm: that of cancer as a potential macro-immunoadaptive response (susceptible to fine-tuning [...] Read more.

This review presents the Oncodarwinian Hypothesis, which proposes a new medical paradigm: that of cancer as a potential macro-immunoadaptive response (susceptible to fine-tuning or reprogramming/management via artificial intelligence-based 3D printed p53 superproteins). A traditional hypothesis-generation method was adopted; it entails observing a biophenomenon longitudinally (tumor-precursor out-of-control cell division), formulating and refining targeted research questions, and then, rooted in a prior interdisciplinary theoretical framework, outlining (per deductive reasoning) a testable answer or statement apt to predict outcomes. Two main theoretical findings emerge from this review: the plausibility of a wireless p53 superprotein molecular biochip (3D printed) and cancer cells’ dual-focus immunological nature. It will be necessary to approach the key issue and prognosis of (supposedly meaningless) uncontrolled cell division in a different light. Basically, the same diseasing cancer also constitutes a self-replicating immunoadaptive algorithm that needs to be deciphered. An interdisciplinary quest to unravel its “source code” involves genomic palaeontology and learning the natural selection programming language — for developing (personalized) artificial intelligence-assisted p53 superproteins.

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Review Article Open Access
Tumor Vaccines in Hepatocellular Carcinoma: Advances, Challenges, and the Path Toward Precision Immunotherapy
Bin Niu, Jun Xu, Liaoyun Zhang
Published online January 19, 2026
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2025.00401
Abstract
Primary hepatocellular carcinoma (HCC) remains one of the leading causes of cancer-related mortality worldwide, with curative options still limited for patients with advanced disease. [...] Read more.

Primary hepatocellular carcinoma (HCC) remains one of the leading causes of cancer-related mortality worldwide, with curative options still limited for patients with advanced disease. As an emerging modality of cancer immunotherapy, tumor vaccines represent a promising approach that activates the host immune system to recognize and eliminate malignant cells. Multiple vaccine platforms, including peptide vaccines, dendritic-cell vaccines, nucleic-acid vaccines, and viral-vector vaccines, have been explored for HCC. Among these, peptide- and dendritic-cell-based vaccines are supported by the most extensive clinical data, demonstrating favorable safety and immunogenicity profiles. The advent of personalized therapeutic cancer vaccines based on tumor-specific antigens has further refined the precision of vaccine design. Nevertheless, several major challenges persist, including immune suppression within the tumor immune microenvironment, marked tumor heterogeneity, immune-escape mechanisms, and limited vaccine immunogenicity, all of which hinder clinical efficacy. In addition, issues related to standardization, large-scale production, and regulatory oversight remain unresolved. Recent advances in sequencing technology, nanotechnology, and artificial intelligence have opened new avenues for optimizing vaccine platforms and delivery strategies. Combination therapies that integrate cancer vaccines with immune checkpoint inhibitors, chemotherapy, or locoregional treatments are also being actively investigated to improve patient outcomes. In summary, although vaccine-based immunotherapy for HCC is still at an early stage, its integration with personalized medicine and multimodal therapeutic strategies holds great potential for improving the long-term prognosis of patients with HCC. Therefore, this review aims to systematically summarize current advances in tumor vaccine–based immunotherapy for hepatocellular carcinoma, with a particular focus on vaccine platforms, target antigens, clinical trial outcomes, and future challenges for clinical translation.

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Review Article Open Access
Bridging Traditional Medicine with Modern Technology: “Omics”-guided Herbal Pharmacovigilance for Integrative Liver Health
Anuradha Singh
Published online March 28, 2026
Future Integrative Medicine. doi:10.14218/FIM.2025.00059
Abstract
This review aims to advocate for a paradigm shift in herbal safety by proposing a cohesive molecular framework that integrates advanced “omics” technologies with artificial intelligence [...] Read more.

This review aims to advocate for a paradigm shift in herbal safety by proposing a cohesive molecular framework that integrates advanced “omics” technologies with artificial intelligence (AI) to address the clinical challenges of herb-induced liver injury (HILI). Traditional herbal medicine constitutes a substantial, yet often unregulated, component of global healthcare, driving high patient exposure alongside a significant and escalating clinical burden of HILI. Current pharmacovigilance systems are critically undermined by fundamental deficits, including severe underreporting, unknown population denominators, and pervasive product quality failures. Furthermore, the complexity of multi-ingredient formulations and the frequency of herb-drug interactions complicate causality assessment, particularly for high-risk drugs. To bridge the gap between empirical practice and contemporary safety standards, this integrated “omics”-AI paradigm transforms herbal safety from a reactive, population-level assessment into an evidence-based, personalized system. By enabling precise risk mitigation, this approach establishes a scientifically rigorous foundation for the future of integrative liver health. In conclusion, the synergy of molecular profiling and computational intelligence provides the necessary tools to modernize herbal pharmacovigilance, ensuring that traditional wisdom is effectively harmonized with modern technological standards for enhanced patient safety.

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Review Article Open Access
Reducing the Risk of Overt Hepatic Encephalopathy Recurrence: A Narrative Review
Nikolaos T. Pyrsopoulos, Nadege Gunn, Prasun K. Jalal, George E. Catinis
Published online May 8, 2026
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2025.00698
Abstract
Hepatic encephalopathy (HE) is a neurologic complication of advanced liver disease (e.g., cirrhosis) resulting in impaired functioning and reduced quality of life. This condition [...] Read more.

Hepatic encephalopathy (HE) is a neurologic complication of advanced liver disease (e.g., cirrhosis) resulting in impaired functioning and reduced quality of life. This condition is associated with a substantial burden for patients and their caregivers and carries a poor prognosis and increased risk of hospitalization and mortality. This narrative review discusses the burden of HE, precipitating risk factors, and clinical considerations for reducing the risk of overt HE (OHE) recurrence in adults with cirrhosis. Key precipitating factors include certain medications, constipation, dehydration, uncontrolled diabetes mellitus, electrolyte imbalances, gastrointestinal bleeding, infection, and sarcopenia, among others. Identification and treatment of precipitating factors are critical steps in the management of HE. Components of ongoing care include patient and caregiver education, nutritional supplementation and sleep management, pharmacotherapy, and nonpharmacologic interventions (e.g., spontaneous portosystemic shunt embolization and liver transplantation in appropriate patients). Clinical guidelines recommend lactulose therapy as secondary prophylaxis after an initial episode of OHE. Rifaximin is recommended as add-on therapy to lactulose when an additional OHE episode occurs. Polyethylene glycol has been investigated as an alternative to lactulose in patients with acute HE and in those with chronic HE and a poor response to lactulose. Oral L-ornithine-L-aspartate may reduce the risk of OHE recurrence in patients with cirrhosis. Investigational agents include nitazoxanide, fecal microbiota transplantation, and the use of artificial intelligence, app-based technology, and wearable devices to facilitate acute and prophylactic management of HE.

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Hot Topic Commentary Open Access
Dengue Viral Infection and Associated Liver Disease
Moana Da Silva Santiago, George Y. Wu
Published online March 2, 2026
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2025.00566
Review Article Open Access
Chikungunya Fever: Etiology, Pathogenesis, and Management, with a Particular Focus on Evidence-based Application of Traditional Chinese Medicine
Maoyu Ding, Tengfei Chen, Xiaolong Xu, Qingquan Liu
Published online April 29, 2026
Future Integrative Medicine. doi:10.14218/FIM.2025.00046
Abstract
Chikungunya fever, caused by the Chikungunya virus (CHIKV), has re-emerged as a significant global health concern in recent decades. A notable event was the largest-ever local outbreak [...] Read more.

Chikungunya fever, caused by the Chikungunya virus (CHIKV), has re-emerged as a significant global health concern in recent decades. A notable event was the largest-ever local outbreak in China in 2025, marking a critical juncture in its epidemiology. Although conventional treatment remains predominantly supportive, the integration of traditional Chinese medicine (TCM) offers promising complementary strategies for alleviating both acute symptoms and chronic polyarthralgia. This narrative review aims to consolidate current knowledge on the etiology, pathogenesis, clinical manifestations, and management of Chikungunya fever, with a particular focus on the evidence-based application of TCM. By integrating molecular virology with clinical and epidemiological insights, this review offers a comprehensive perspective on the challenges posed by CHIKV and underscores the strategic imperatives essential for its future management. In conclusion, addressing the expanding threat of CHIKV necessitates a multi-pronged public health strategy that integrates standard clinical and preventive measures with evidence-based TCM therapies, highlighting the urgent need for rigorous clinical trials to globally validate these integrative treatments.

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Review Article Open Access
The Multifaceted Roles of Gut Microbiota and Their Metabolites in Metabolic Dysfunction-associated Steatotic Liver Disease: A Literature Review
Yunqi Zhang, Dengqin Wang, Bo Zhuang, Fangzhuo Zhu, Chengwei Tan, Jing Zhang, Qianqian Zhang
Published online April 24, 2026
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2025.00605
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a major global health concern and encompasses a spectrum ranging from hepatic steatosis and metabolic [...] Read more.

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.

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Review Article Open Access
Artificial Intelligence in Genitourinary Pathology: A Translational Readiness Map
Ankush U. Patel, Amanda Dy, Anil V. Parwani, Swati Satturwar
Published online March 13, 2026
Journal of Clinical and Translational Pathology. doi:10.14218/JCTP.2025.00056
Abstract
Artificial intelligence (AI) translation in genitourinary (GU) pathology has progressed unevenly across organs and tasks. This review addresses a central clinical question: which [...] Read more.

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.

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Systematic Review Open Access
A Comparison of the Efficacy of Non-chemical versus Chemical Cleansers against Candida Species on Removable Dental Prostheses: A Systematic Review
Mohammed Waleed Nazer, Abdullah Zamil Alzuwaihri, Belal Ammar Alakkad, Majed Ahmed Alamoudi, Mohammed Hasen Alqurashi, Ahmad Mohammad Gharib, Manar Hamed Almehyawi, Mohammed Shammas
Published online January 23, 2026
Journal of Exploratory Research in Pharmacology. doi:10.14218/JERP.2025.00041
Abstract
Candida species, particularly Candida albicans, are major contributors to denture-induced stomatitis because of their ability to form biofilms on removable dental prostheses. Although [...] Read more.

Candida species, particularly Candida albicans, are major contributors to denture-induced stomatitis because of their ability to form biofilms on removable dental prostheses. Although chemical cleansers are effective, concerns regarding material degradation and mucosal irritation have spurred interest in non-chemical alternatives. This review aims to systematically compare the efficacy of chemical and non-chemical denture cleansers in reducing Candida spp. on removable dental prostheses.

A systematic review was conducted according to the PRISMA 2020 guidelines. Comprehensive searches of PubMed, Scopus, and Web of Science (2003–2025) yielded 624 records. After duplicate removal and screening, 20 studies (10 randomized controlled trials (RCTs) and 10 in vitro studies) were included. The risk of bias was assessed using the Cochrane Risk of Bias 2.0 for RCTs and QUIN/SYRCLE tools for in vitro studies.

Chemical cleansers such as sodium hypochlorite (0.25–2.5%), chlorhexidine (0.2–2%), and effervescent peroxide tablets achieved 80–100% colony-forming unit reduction in most studies, with some reporting complete biofilm eradication. In contrast, non-chemical agents showed a 40–85% colony-forming unit reduction rate. Chemical cleansers caused increased surface roughness and discoloration in six of the ten studies included. Non-chemical agents preserved material integrity and were preferred by patients for their taste and ease of use. The risk of bias was low to moderate in 80% of the RCTs and low in 10 of the 13 in vitro studies.

Chemical denture cleansers are more potent antifungal agents, but they may damage prosthetic materials. Non-chemical cleansers offer safe and moderately effective alternatives to chemical cleansers. A personalized, evidence-based oral hygiene regimen is recommended for patients.

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Mini Review Open Access
Obstructive Sleep Apnea and Lung Cancer: Epidemiological Insights and Pathophysiological Mechanisms
Jixiang Li, Tong Feng, Qian Zeng
Published online March 10, 2026
Exploratory Research and Hypothesis in Medicine. doi:10.14218/ERHM.2025.00040
Abstract
Obstructive sleep apnea (OSA) is a prevalent sleep disorder characterized by intermittent hypoxia and sleep fragmentation, which may contribute to lung cancer development and progression. [...] Read more.

Obstructive sleep apnea (OSA) is a prevalent sleep disorder characterized by intermittent hypoxia and sleep fragmentation, which may contribute to lung cancer development and progression. This review synthesizes epidemiological evidence on the association between OSA and lung cancer incidence and mortality, highlighting inconsistencies due to study design, population differences, and confounding factors such as smoking and obesity. While some studies report an increased lung cancer risk, particularly with severe nocturnal hypoxemia, others suggest no significant association or a potential protective effect. Pathophysiologically, OSA promotes oncogenesis through hypoxia-inducible factor activation, tumor immune microenvironment remodeling, exosome-mediated signaling, nuclear factor κB pathway activation, and enhanced cancer stem cell properties. Continuous positive airway pressure therapy may mitigate these effects, with evidence suggesting reduced lung cancer incidence and improved prognosis in adherent patients. This review underscores the need for standardized studies using objective diagnostics and robust confounder adjustment to clarify the OSA–lung cancer link and optimize clinical management.

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