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Original Article Open Access
Oral Microbiota Transmission Partially Mediates Depression and Anxiety in Newlywed Couples
Reza Rastmanesh, Balachandar Vellingiri, Ciro Gargiulo Isacco, Abolfazl Sadeghinejad, Neil Daghnall
Published online April 30, 2025
Exploratory Research and Hypothesis in Medicine. doi:10.14218/ERHM.2025.00013
Abstract
Oral microbiota dysbiosis and altered salivary cortisol levels have been linked to depression and anxiety. Given that bacterial transmission can occur between spouses, this study [...] Read more.

Oral microbiota dysbiosis and altered salivary cortisol levels have been linked to depression and anxiety. Given that bacterial transmission can occur between spouses, this study aimed to investigate whether the transmission of oral microbiota between newlywed couples mediates symptoms of depression and anxiety.

Validated Persian versions of the Pittsburgh Sleep Quality Index, Beck Depression Inventory-II, and Beck Anxiety Inventory were administered to 1,740 couples who had been married for six months. The researchers compared 268 healthy control spouses with 268 affected cases in a cross-sectional study. Data were analyzed using appropriate statistical methods.

After six months, healthy spouses married to an insomniac with the depression-anxiety (DA) phenotype scored significantly higher on the Pittsburgh Sleep Quality Index, Beck Depression Inventory-II, and Beck Anxiety Inventory compared to their baseline scores. This indicates that their sleep quality, depression, and anxiety scores became more similar to those of their affected spouses. Additionally, the composition of their oral microbiota changed significantly, becoming increasingly similar to that of their spouses. Specifically, in couples where one partner had the DA phenotype, the oral microbiota of the healthy spouse mirrored that of the affected partner (p < 0.001). These microbial changes correlated with alterations in salivary cortisol levels as well as depression and anxiety scores. Linear discriminant analysis revealed that the relative abundances of Clostridia, Veillonella, Bacillus, and Lachnospiraceae were significantly higher in insomniacs with the DA phenotype compared to healthy controls (p < 0.001).

Oral microbiota transmission between individuals in close contact partially mediates symptoms of depression and anxiety.

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Guideline Open Access
Guideline for the Prevention and Treatment of Metabolic Dysfunction-associated Fatty Liver Disease (Version 2024)
Jian-Gao Fan, Xiao-Yuan Xu, Rui-Xu Yang, Yue-Min Nan, Lai Wei, Ji-Dong Jia, Hui Zhuang, Jun-Ping Shi, Xiao-Ying Li, Chao Sun, Jie Li, Vincent Wai-Sun Wong, Zhong-Ping Duan, Chinese Society of Hepatology, Chinese Medical Association
Published online November 4, 2024
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2024.00311
Abstract
With the rising epidemic of obesity, metabolic syndrome, and type 2 diabetes mellitus in China, metabolic dysfunction-associated non-alcoholic fatty liver disease has become the [...] Read more.

With the rising epidemic of obesity, metabolic syndrome, and type 2 diabetes mellitus in China, metabolic dysfunction-associated non-alcoholic fatty liver disease has become the most prevalent chronic liver disease. This condition frequently occurs in Chinese patients with alcoholic liver disease and chronic hepatitis B. To address the impending public health crisis of non-alcoholic fatty liver disease and its underlying metabolic issues, the Chinese Society of Hepatology and the Chinese Medical Association convened a panel of clinical experts to revise and update the “Guideline of prevention and treatment of non-alcoholic fatty liver disease (2018, China)”. The new edition, titled “Guideline for the prevention and treatment of metabolic dysfunction-associated fatty liver disease (Version 2024)”, offers comprehensive recommendations on key clinical issues, including screening and monitoring, diagnosis and evaluation, treatment, and follow-up for metabolic dysfunction-associated fatty liver disease and metabolic dysfunction-associated steatotic liver disease. Metabolic dysfunction-associated fatty liver disease is now the preferred English term and is used interchangeably with metabolic dysfunction-associated steatotic liver disease. Additionally, the guideline emphasizes the importance of multidisciplinary collaboration among hepatologists and other specialists to manage cardiometabolic disorders and liver disease effectively.

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Review Article Open Access
The Role of Ketamine in Treatment-resistant Depression: A Narrative Review
Ashwini Reddy, Swati Patel, Amiya Kumar Barik, Priya Thappa, Kiran Jangra, Kirandeep Kaur, Rajeev Chauhan, Ankur Luthra
Published online December 19, 2024
Journal of Exploratory Research in Pharmacology. doi:10.14218/JERP.2024.00003
Abstract
Ketamine, a non-competitive N-methyl-D-aspartate receptor antagonist, has emerged as an effective therapeutic agent for the management of treatment-resistant depression. Repeated [...] Read more.

Ketamine, a non-competitive N-methyl-D-aspartate receptor antagonist, has emerged as an effective therapeutic agent for the management of treatment-resistant depression. Repeated treatments with ketamine show rapid, robust, and sustained antidepressant effects. Despite the large body of evidence, key concerns include adverse effects such as dissociative symptoms, hemodynamic instability, and the risk of abuse with long-term ketamine therapy. This narrative review provides an overview of the neurobiological mechanisms underlying ketamine’s antidepressant effects, its basic pharmacodynamics, and its safety profile. The clinical evidence regarding ketamine’s efficacy in depression is also summarized, and the need for further research on the long-term effects of ketamine therapy, the development of agents with similar antidepressant effects but fewer adverse effects or potential for abuse, and the identification of biomarkers to predict the response to ketamine is highlighted.

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Hot Topic Commentary Open Access
Key Points and Future Directions from the 2024 Chinese Guidelines for Fatty Liver Disease
Maria Tampaki, Evangelos Cholongitas
Published online March 27, 2025
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2025.00051
Review Article Open Access
Liquid Biopsy: A Breakthrough Technology in Early Cancer Screening
Xuexin Liang, Qingqing Tang, Jiawei Chen, Yanghui Wei
Published online March 25, 2025
Cancer Screening and Prevention. doi:10.14218/CSP.2024.00031
Abstract
Cancer is the leading cause of death globally, with nearly 20 million new cases and 9.7 million deaths in 2022. Due to its vague initial symptoms, cancer is often difficult to detect [...] Read more.

Cancer is the leading cause of death globally, with nearly 20 million new cases and 9.7 million deaths in 2022. Due to its vague initial symptoms, cancer is often difficult to detect in its early stages. Liquid biopsy, a revolutionary approach in oncology, provides a minimally invasive, real-time method for cancer detection, monitoring, and characterization by examining circulating tumor components in body fluids. This review presents current technologies and clinical applications of liquid biopsy, focusing particularly on its value for early cancer diagnosis. Liquid biopsy enables molecular profiling of cancer for precision oncology by isolating circulating extracellular nucleic acids (cell-free DNA), circulating tumor DNA, and circulating tumor cells from blood and other body fluids. Cell-free DNA, which circulates freely in the blood, may or may not be tumor-derived, while circulating tumor DNA is specifically of tumor origin. Additionally, circulating tumor cells can be isolated from blood; these cells, shed from tumors into the bloodstream, typically survive only 1–2.5 h before immune clearance, though a small fraction can persist and metastasize to distant sites. Exosomes, small membrane-bound vesicles secreted by tumor cells, also carry molecular information about the tumor and have become a valuable source of biomarkers in liquid biopsy. Advances in detection technologies for these analytes have expanded the utility of liquid biopsy, facilitating the identification of somatic mutations and actionable genomic alterations in tumors. Finally, this review discusses the opportunities and challenges facing liquid biopsy and offers insights into its future development.

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Review Article Open Access
The Multifaceted Role of Bilirubin in Liver Disease: A Literature Review
Mariana M. Ramírez-Mejía, Stephany M. Castillo-Castañeda, Shreya C. Pal, Xingshun Qi, Nahum Méndez-Sánchez
Published online October 21, 2024
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2024.00156
Abstract
Bilirubin, the primary breakdown product of hemoproteins, particularly hemoglobin, plays a key role in the diagnosis, prognosis, and monitoring of liver diseases. In acute liver [...] Read more.

Bilirubin, the primary breakdown product of hemoproteins, particularly hemoglobin, plays a key role in the diagnosis, prognosis, and monitoring of liver diseases. In acute liver diseases, such as acute liver failure, drug-induced liver injury, and viral hepatitis, bilirubin serves as a biomarker reflecting the extent of hepatocyte loss and liver damage. Chronic liver diseases, including alcohol-related liver disease, chronic hepatitis C virus infection, metabolic dysfunction-associated fatty liver disease, and autoimmune liver diseases, are marked by persistent liver injury and inflammation. Bilirubin levels in chronic liver diseases provide insight into liver function, disease severity, and prognosis. As a versatile biomarker, bilirubin offers valuable information on the pathophysiology of liver diseases and aids in guiding clinical decision-making regarding the treatment of liver diseases and their complications. This review aimed to explore the multifunctional role of bilirubin in liver diseases by analyzing its biological functions beyond its role as a biomarker of liver damage.

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Review Article Open Access
Effects of Ethanol on the Digestive System: A Narrative Review
Fabio Caputo, Matteo Guarino, Alberto Casabianca, Lisa Lungaro, Anna Costanzini, Giacomo Caio, Giorgio Zoli, Roberto De Giorgio
Published online December 30, 2024
Journal of Translational Gastroenterology. doi:10.14218/JTG.2024.00028
Abstract
Alcohol consumption is responsible for approximately 6% of all deaths and 5.1% of the global disease burden. The most common alcohol-related causes of death include liver cirrhosis [...] Read more.

Alcohol consumption is responsible for approximately 6% of all deaths and 5.1% of the global disease burden. The most common alcohol-related causes of death include liver cirrhosis (50% of cases), pancreatitis (25%), and esophageal cancer (22%). In this review, we provide an overview of ethanol metabolism and highlight the major diseases caused by alcohol consumption in the liver and gastrointestinal tract. Due to its central metabolic role, the liver is particularly susceptible to ethanol, which is known to cause a wide spectrum of conditions, including steatosis, steatohepatitis, alcohol-associated hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma). The gastrointestinal tract is often one of the first areas to show signs of damage from excessive alcohol consumption. Chronic alcohol abuse is a well-established risk factor for both acute and chronic pancreatitis, as well as pancreatic cancer. Approximately 70% of acute pancreatitis cases and 30% of chronic pancreatitis cases are attributable to alcohol abuse. Epidemiological studies have consistently demonstrated a negative correlation between alcohol intake and the prevalence of gallstones. Moreover, alcohol is an important risk factor for gastroenteropancreatic cancer, as ethanol metabolism produces acetaldehyde, a potent carcinogen for humans. In conclusion, chronic ethanol intake, through one of its main metabolic products, acetaldehyde, causes pathological changes in the gastrointestinal tract, liver, pancreas, and gallbladder. Even moderate amounts of alcohol may increase the risk of cancers, such as colorectal cancer. Therefore, if there is clinical suspicion of excessive alcohol intake in a patient with persistent digestive symptoms (e.g., abdominal pain, nausea, vomiting, diarrhea, and bloody stools), immediate medical evaluation is essential. Referral to specialized centers with expertise in alcohol use disorder is a key management option for patients with established alcohol use disorder.

Full article
Mini Review Open Access
Digital and Artificial Intelligence-based Pathology: Not for Every Laboratory – A Mini-review on the Benefits and Pitfalls of Its Implementation
Iris Z. Shen, Lanjing Zhang
Published online April 3, 2025
Journal of Clinical and Translational Pathology. doi:10.14218/JCTP.2025.00007
Abstract
With the increasing use of artificial intelligence (AI) in diagnostics, AI algorithms have shown great potential in aiding diagnostics. As more of these algorithms are developed, [...] Read more.

With the increasing use of artificial intelligence (AI) in diagnostics, AI algorithms have shown great potential in aiding diagnostics. As more of these algorithms are developed, there is overwhelming enthusiasm for implementing digital and artificial intelligence-based pathology (DAIP), but doubts and pitfalls are also emerging. However, few original or review articles address the limitations and practical aspects of implementing DAIP. In this review, we briefly examine the evidence related to the benefits and pitfalls of DAIP implementation and argue that DAIP is not suitable for every clinical laboratory.

We searched the PubMed database using the following keywords: “digital pathology,” “digital AI pathology,” and “AI pathology.”. Additionally, we incorporated personal experiences and manually searched related papers.

Ninety-two publications were found, of which 24 met the inclusion criteria. Many advantages of DAIP were discussed, including improved diagnostic accuracy and equity. However, several limitations of implementing DAIP exist, such as financial constraints, technical challenges, and legal/ethical concerns.

We found a generally favorable but cautious outlook for the implementation of DAIP in the pathology workflow. Many studies have reported promising outcomes in using AI for diagnosis and analysis; however, there are also several noteworthy limitations in implementing DAIP. Therefore, a balance between the benefits and pitfalls of DAIP must be thoroughly articulated and examined in light of the institution’s needs and goals before making the decision to implement DAIP. Approaches for mitigating machine learning biases were also proposed, and the adaptation and growth of the pathology profession were discussed in light of DAIP development and advances.

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Review Article Open Access
Non-invasive Vagus Nerve Stimulation for the Treatment of Neurological & Psychiatric Disorders: A Narrative Review
Kashif Tousif, Muaz Ali, Shafaq Saleem, Ahmad Raza, Samar Imran, Muhammad Haroon, Furqan Anwar, Waqas Ahmed
Published online May 28, 2025
Exploratory Research and Hypothesis in Medicine. doi:10.14218/ERHM.2025.00015
Abstract
Non-invasive vagus nerve stimulation (nVNS), including transcutaneous cervical (tcVNS) and auricular (taVNS) modalities, has garnered increasing attention as a neuromodulatory therapy [...] Read more.

Non-invasive vagus nerve stimulation (nVNS), including transcutaneous cervical (tcVNS) and auricular (taVNS) modalities, has garnered increasing attention as a neuromodulatory therapy for various neurological and psychiatric disorders. This narrative review synthesizes findings from over 80 studies, including randomized controlled trials, meta-analyses, and observational research published up to March 2024, evaluating nVNS in epilepsy, depression, stroke rehabilitation, headache, Parkinson’s disease, and Alzheimer’s disease. Evidence suggests that taVNS can reduce seizure frequency and improve quality of life in epilepsy. In major depressive disorder, nVNS demonstrates antidepressant effects comparable to pharmacotherapy, though the optimal stimulation parameters remain unclear. For post-stroke motor rehabilitation, both tcVNS and closed-loop stimulation systems enhance neuroplasticity and motor recovery. In Parkinson’s and Alzheimer’s diseases, preliminary findings indicate possible modulation of neuroinflammatory pathways and cognitive-motor functions, although recent meta-analyses report mixed efficacy. Challenges include methodological heterogeneity, protocol variability, and difficulties in designing effective sham controls, all of which limit the generalizability of current findings. Mechanistic differences between tcVNS and taVNS remain inadequately characterized. Overall, nVNS appears to be a safe and accessible therapeutic approach with broad clinical potential, particularly for treatment-resistant or underserved populations. However, future research must prioritize standardized protocols, robust clinical endpoints, and adequately powered trials to define efficacy and optimize treatment strategies. A greater focus on long-term outcomes, biomarker-guided personalization, and clinical significance over statistical findings will be critical in translating nVNS into routine practice.

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Review Article Open Access
The Development and Appraisal of MELD 3.0 in Liver Diseases: Good Things Never Come Easy
Gaoyue Guo, Wanting Yang, Jia Li, Ziyi Yang, Jing Liang, Chao Sun
Published online November 12, 2024
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2024.00303
Abstract
Since its proposal, the Model for End-Stage Liver Disease (MELD) score has been employed to predict short-term mortality among patients with chronic liver disease and those awaiting [...] Read more.

Since its proposal, the Model for End-Stage Liver Disease (MELD) score has been employed to predict short-term mortality among patients with chronic liver disease and those awaiting liver transplantation, serving as the primary criterion for organ allocation. However, as the demographic and epidemiological characteristics of chronic liver disease and liver transplantation have evolved, a range of MELD-related scores has emerged, including MELD-Na, iMELD, delta MELD, MELD XI, MELD-LA, and pediatric end-stage liver disease, culminating in the recently proposed MELD 3.0, which builds upon MELD-Na. This study aimed to comprehensively review and summarize relevant studies on MELD 3.0 in various scenarios, assessing its effectiveness in organ allocation, post-transplantation outcomes, and mortality prediction for patients with end-stage liver disease. Our preliminary findings indicate superior predictive performance of MELD 3.0, warranting further in-depth investigations to broaden its clinical implications.

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