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Review Article Open Access
Leptin Signaling and Its Relationship with Obesity-induced Insulin Resistance: A Bioinformatics-assisted Review
William A. Gómez, Gustavo Humeres, Carlos A. Orozco-Castaño, Roberto Cannataro, Angélica M. Muñoz-Contreras, Luis M. Gómez-Miranda, Jorge L. Petro, Diego A. Bonilla
Published online September 11, 2024
Gene Expression. doi:10.14218/GE.2024.00039
Abstract
Obesity has become a global epidemic affecting diverse populations and leading to metabolic syndrome across different sexes and age groups. A significant aspect of obesity is the [...] Read more.

Obesity has become a global epidemic affecting diverse populations and leading to metabolic syndrome across different sexes and age groups. A significant aspect of obesity is the development of leptin resistance, primarily due to the inefficient transport of leptin across the blood-brain barrier and other mechanisms such as protein folding and dysregulation of leptin signaling in brain areas related to energy and adipose tissue metabolism. This hindrance in leptin delivery poses a challenge to using this adipokine as a potential therapy for obesity. Current research focuses on understanding the complex molecular pathways that link diet-induced obesity, characterized by increased levels of leptin, to the onset of metabolic syndrome. This syndrome encompasses various health issues, including type 2 diabetes mellitus, and involves intricate mechanisms primarily affecting pancreatic β-cells. This bioinformatics-assisted review describes key biological elements of known pathways, such as the forkhead box protein O1/leptin receptor and Janus kinase/signal transducer and activator of transcription 3, and discusses future directions that might contribute to understanding the relationship between obesity, leptin resistance, and metabolic complications (e.g., Rac1/cell division control protein 42 homolog), paving the way for future research on targeted therapeutic interventions.

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Review Article Open Access
Current Practice and Emerging Endoscopic Technology in the Diagnosis of Colorectal Cancer: A Narrative Review of Enhanced Imaging and Optical Biopsy
Alla Turshudzhyan, Dana Gornick, Giuliana Mertz, Micheal Tadros
Published online September 6, 2024
Journal of Translational Gastroenterology. doi:10.14218/JTG.2024.00011
Abstract
Gastrointestinal endoscopy has undergone significant transformation since its first introduction in the early 20th century. Despite advances in modern endoscopy, its precision in [...] Read more.

Gastrointestinal endoscopy has undergone significant transformation since its first introduction in the early 20th century. Despite advances in modern endoscopy, its precision in detecting and removing colorectal cancer (CRC) varies; colorectal polyps or cancer are still missed in 2.1-5.9% of cases. Additionally, post-colonoscopy CRC occurs in 30% of patients who have undergone incomplete polyp resection. When biopsies are taken, only 11.4% are found to be malignant, rendering 88.6% of tissue removal unnecessary. To address these shortcomings, modern endoscopy is evolving. Current endoscopic modalities include wide-field and microscopic-field endoscopy. Wide-field view endoscopy remains the most frequently used type and includes the current standard of practice—white light endoscopy—as well as other modalities such as virtual and dye-based chromoendoscopy, ultrathin endoscopy, and capsule endoscopy. Microscopic field endoscopy encompasses several new emerging modalities that can provide microscopic resolution capable of diagnosing lesions in vivo (optical biopsy), thus reducing the number of unnecessary biopsies. However, the emerging technology comes with a learning curve and requires time for endoscopists to master and achieve interobserver agreement. Consequently, there is a growing opportunity to develop machine learning technology to assist with the learning process. We review current modalities available for the diagnosis of CRC, including the current standard of practice, new enhanced imaging modalities, and optical biopsy.

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Review Article Open Access
Cognitive-behavioral Therapy for Medical Non-adherence: A Topical Review and Clinical Recommendations
Robert D. Friedberg, Megan Neelley, Joee Zucker, Andrea Hanna, Alexandra Mendelsohn, Alanna Greenberger, Noa Dunevich
Published online July 25, 2024
Journal of Exploratory Research in Pharmacology. doi:10.14218/JERP.2023.00008
Abstract
Medication non-adherence among youth with chronic health conditions is a healthcare crisis in the United States. Nearly 20% of youth experience a chronic illness, yet most do not [...] Read more.

Medication non-adherence among youth with chronic health conditions is a healthcare crisis in the United States. Nearly 20% of youth experience a chronic illness, yet most do not comply with their treatment regimen. Various challenges to adherence arise, such as not understanding the purpose of treatment, painful or difficult administration, forgetfulness, and mood disorders such as anxiety. Cognitive behavioral therapy (CBT) is an empirically supported approach to increasing treatment adherence. Modular CBT incorporates psychoeducation, cognitive restructuring, and behavioral experiments to promote better disease management. This article focuses on the application of CBT to four medical conditions characterized by elevated levels of non-adherence: pill-swallowing difficulties, asthma, type 1 diabetes, and inflammatory bowel disease in youth. The review integrates findings on contextual issues (e.g., ethnocultural variations, the impact of the COVID-19 pandemic), research on non-adherence, and CBT outcome studies. Additionally, limitations of the existing literature and training recommendations are provided.

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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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Review Article Open Access
Mouse Models for the Study of Liver Fibrosis Regression In Vivo and Ex Vivo
Milena Schönke, Patrick C.N. Rensen
Published online October 11, 2024
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2024.00212
Abstract
This review discussed experimental mouse models used in the pre-clinical study of liver fibrosis regression, a pivotal process in preventing the progression of metabolic dysfunction-associated [...] Read more.

This review discussed experimental mouse models used in the pre-clinical study of liver fibrosis regression, a pivotal process in preventing the progression of metabolic dysfunction-associated steatohepatitis to irreversible liver cirrhosis. These models provide a valuable resource for understanding the cellular and molecular processes underlying fibrosis regression in different contexts. The primary focus of this review is on the most commonly used models with diet- or hepatotoxin-induced fibrosis, but it also touches upon genetic models and mouse models with biliary atresia or parasite-induced fibrosis. In addition to emphasizing in vivo models, we briefly summarized current in vitro approaches designed for studying fibrosis regression and provided an outlook on evolving methodologies that aim to refine and reduce the number of experimental animals needed for these studies. Together, these models contribute significantly to unraveling the underlying mechanisms of liver fibrosis regression and offer insights into potential therapeutic interventions. By presenting a comprehensive overview of these models and highlighting their respective advantages and limitations, this review serves as a roadmap for future research.

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Original Article Open Access
Taurine Reduces Atherosclerotic Plaque Area and Stability in Mice
Meng-Guang Wei, Ang Ying, Feng-Qing Huang, Feng-Xiang Wang, Raphael N. Alolga, Gao-Xiang Ma, An Pan
Published online September 25, 2024
Journal of Exploratory Research in Pharmacology. doi:10.14218/JERP.2024.00017
Abstract
Previous studies suggest that taurine supplementation may attenuate atherosclerosis by reducing lipid levels. However, energy drinks containing taurine have been shown to increase [...] Read more.

Previous studies suggest that taurine supplementation may attenuate atherosclerosis by reducing lipid levels. However, energy drinks containing taurine have been shown to increase blood pressure, a key risk factor for atherosclerosis. Thus, the role of taurine in atherosclerosis remains controversial. This study aimed to investigate the effect of taurine on the development of atherosclerotic plaques.

Plasma taurine levels were measured in 105 patients with varying degrees of coronary heart disease and in 40 healthy individuals using 1,2-13C2-taurine-based ultra-performance liquid chromatography-tandem quadrupole mass spectrometry (UPLC-QQQ-MS/MS). Apolipoprotein E knockout (ApoE−/−) C57BL/6J mice, fed a high-fat diet and subjected to left carotid artery ligation with cannula insertion, received taurine or saline for four consecutive days. Healthy control mice were fed a normal chow diet and underwent a sham operation. Serum taurine levels, lipid indicators, and arterial histology in the individual mice were examined.

Plasma taurine levels were significantly higher in patients with acute myocardial infarction (4.04 ± 0.24 μg/mL) compared to healthy controls (3.52 ± 0.22 μg/mL). Taurine treatment significantly decreased plaque areas in the carotid artery, reduced Masson’s Trichrome staining, and lowered the ratio of anti-α-SMA to anti-CD68 staining in ApoE−/− mice. Additionally, taurine treatment increased the levels of matrix metalloproteinase 2 in the cultured vascular endothelial cells in vitro.

These findings suggest that taurine supplementation may reduce both the size and stability of atherosclerotic plaques. Therefore, dietary taurine supplements should be used with caution.

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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.

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Review Article Open Access
Disparities in Gastric Cancer Screening Worldwide
Charlene Deane, Orla Kelly, Colm O’Morain
Published online August 1, 2024
Cancer Screening and Prevention. doi:10.14218/CSP.2024.00008
Abstract
Gastric cancer is the third most common cause of cancer-related death globally. The highest incidence is encountered in Asia, followed by Europe which has the second highest incidence [...] Read more.

Gastric cancer is the third most common cause of cancer-related death globally. The highest incidence is encountered in Asia, followed by Europe which has the second highest incidence worldwide. In Europe, gastric cancer is typically diagnosed at an advanced stage, with an estimated five-year survival rate of 24%, compared to 59% in Japan. This disparity is largely attributed to the significant role of screening in Japan. Given the expected rise in absolute numbers of gastric cancer cases, there has been a demand for gastric cancer screening programmes in high-intermediate risk countries, advocated by the International Agency for Research on Cancer, the Science Advice for Policy by European Academies, the European Commission as part of the Europe Beating Cancer Plan, and the Maastricht VI/Florence consensus guidelines. This review article summarizes the current disparities in screening strategies between countries in the East and West and comments on future developments in population-based screening research in this field. The references for this article were identified through PubMed, the Cochrane Database of Systematic Reviews, and the Cochrane Controlled Register of Trials using the search terms “gastric cancer”, “stomach cancer”, “Helicobacter pylori”, and “screening” over the period from 1995 until March 2024. Overall, this review identifies three potential approaches to screening: primary, secondary, and opportunistic. It highlights the lack of a uniform consensus on the best approach to screening, the disparity in the information available in different populations, and upcoming research to address this disparity.

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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
Impact of the COVID-19 Pandemic on Pediatric Anxiety and Depression: Prevalence Data, Theoretical Synthesis, and Clinical Implications
Alexandra Mendelsohn, Alanna Greenberger, Robert D. Friedberg
Published online September 19, 2024
Exploratory Research and Hypothesis in Medicine. doi:10.14218/ERHM.2024.00004
Abstract
Over the course of the COVID-19 pandemic and its aftermath, growing concerns have emerged about the mental health of children and youth. Disease, loss, and lockdowns presented young [...] Read more.

Over the course of the COVID-19 pandemic and its aftermath, growing concerns have emerged about the mental health of children and youth. Disease, loss, and lockdowns presented young people with enormous stressors, and much research suggests elevated levels of pediatric depression, anxiety, suicidality, and obsessive-compulsive behavior. However, considerable debate remains about the nature and persistence of these symptoms. This narrative review, conducted approximately four years after the onset of the pandemic, summarizes the major findings from four years of research, including empirical studies, meta-analyses, and systematic reviews. Studies were sourced from scholarly databases using the keywords “COVID-19”, “children”, “adolescents”, and “mental health”. The existing literature on the prevalence of depression in youth indicated that worldwide rates varied from 2.2% to 11.8% of the population, with one study revealing that one in four young people reported depressive symptoms. More specifically, 44% of youth in the United States demonstrated depression, while in China, the prevalence rate ranged from 11% to 44% of young people. Reviewed data showed that 20% of youth globally endorsed symptoms of anxiety or stress reactions, with countries such as Denmark (44%), Canada (45%), and the United States (32%) reporting extremely high rates. In the implications section, recommendations for screening and intervention procedures are outlined.

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