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741
Review Article Open Access
Alexandre González-Rodríguez, Mary V. Seeman
Published online June 20, 2023
Journal of Exploratory Research in Pharmacology. doi:10.14218/JERP.2022.00065
Abstract
Delusional disorder (DD), once entrenched, responds poorly to currently available treatment. This calls for community and individual preventive measures. Our goal was to conduct [...] Read more.

Delusional disorder (DD), once entrenched, responds poorly to currently available treatment. This calls for community and individual preventive measures. Our goal was to conduct a literature review exploring the possibilities of prevention. This narrative review was based on a search of the PubMed database from its inception until July 2022. While not specific to DD, the search found evidence for primary and secondary strategies used to protect against or ameliorate psychotic illness characterized by prominent delusions. Community preventive strategies included addressing socioeconomic disadvantage and mental health stigma, improving mental health service accessibility, screening for and treating potential precursors to DD, such as sensory and cognitive deficits, and psychiatric symptoms, like depression, anxiety, sleep disturbance, and substance abuse. Secondary community prevention relied on early detection programs and specialized services for early treatment of DD symptoms and their co-morbidities. Individual forms of secondary prevention were interventions geared toward illness denial, treatment nonresponse and antipsychotic refusal. Effective secondary prevention reduced symptom intensity and diminished the risk of fatal outcomes such as suicide. Based mostly on the evidence from related disorders, the implementation of preventive and early treatment strategies held promise for reducing morbidity and facilitating the recovery of patients with DD.

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742
Review Article Open Access
Wendong Yu, Qiong Gan, Yun Gong
Published online June 20, 2023
Journal of Clinical and Translational Pathology. doi:10.14218/JCTP.2023.00006
Abstract
The International Academy of Cytology Yokohama System for Reporting Breast Fine-Needle Aspiration Biopsy Cytology was developed by a group of expert cytopathologists and clinicians [...] Read more.

The International Academy of Cytology Yokohama System for Reporting Breast Fine-Needle Aspiration Biopsy Cytology was developed by a group of expert cytopathologists and clinicians in the breast field. Five categories are defined to stratify breast lesions by their risks of malignancy and managed accordingly. Clinical and radiologic information (triple test) are critical for further management. Ultrasound guidance, and rapid on-site evaluation are valuable for improving the rate of definitive diagnosis. Ancillary studies can be tested on cytologic samples to provide prognostic, predictive information as well as diagnostic clues. Based on many published studies in different institutions worldwide, the implementation of the system appears to have been successful. However, further studies are important for improvements and modifications to the current system.

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743
Research Letter Open Access
Artemiy Kovynev, Zhixiong Ying, Joost M. Lambooij, Hendrik J.P. van der Zande, Bruno Guigas, Patrick C.N. Rensen, Milena Schönke
Published online June 19, 2023
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2023.00094
744
Mini Review Open Access
Jessica A. Dietz, Alisha Halver, Kimberly D. Hammer, Natasha J. Petry, Sara Westall, Tze Shien Lo
Published online June 16, 2023
Journal of Exploratory Research in Pharmacology. doi:10.14218/JERP.2022.00090
Abstract
There is limited information available on the evaluation of placebo or nocebo effects on itch. The present study developed a search strategy using PubMed to evaluate literature [...] Read more.

There is limited information available on the evaluation of placebo or nocebo effects on itch. The present study developed a search strategy using PubMed to evaluate literature related to placebo and/or nocebo effects on itch. The search strategy identified 65 articles. After the independent review of each article, 10 studies were selected for inclusion. These studies varied, in terms of methods and outcome measures. Overall, verbal suggestion, conditioning, and/or placebo topical therapies led to placebo and/or nocebo effects on itch. Further understanding the mechanisms of placebo and nocebo effects on verbal suggestion and conditioning can open doors to the development of therapeutic strategies that could ameliorate or improve itch in patients.

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745
Original Article Open Access
Luxita Sharma, Manoj Kumar Kashyap, Dhananjay Sharma
Published online June 14, 2023
Gene Expression. doi:10.14218/GE.2023.00005
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in developed countries, contributing to ∼24% of cases worldwide and includes non-alcoholic steatohepatitis. [...] Read more.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in developed countries, contributing to ∼24% of cases worldwide and includes non-alcoholic steatohepatitis. High-throughput OMICS approaches have been used to characterize NAFLD conditions for the identification of potential molecular signatures or differentially regulated molecules (DEMs). The present study aims to perform a systematic review and meta-analysis from an omics perspective.

We analyzed the publically available data set (accession number: GSE63067) from the Gene Expression Omnibus (GEO) using the GEO2R program. The differentially expressed genes (DEGs) were filtered using the criteria where genes with p-value ≤0.05 and fold-change ≥2.0-fold (upregulated), and fold-change ≤0.5-fold (downregulated).

We identified 264 differentially expressed genes (DEGs) between NAFLD and normal liver tissue samples, where 211 were upregulated and 53 were downregulated in NAFLD. Additionally, we identified novel genes sphingomyelin synthase 2 and WNK lysine deficient protein kinase 3 that were not well understood in the molecular pathophysiology of NAFLD. Further gene ontology-based analysis revealed that among biological processes, cellular components, and molecular functions were also dysregulated in NAFLD.

Our study shows that meta-analysis of publicly available data is useful for the identification of DEGs and indication of dysregulated biological processes in NAFLD, which provide valuable insights into the molecular mechanisms of NAFLD.

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746
Editorial Open Access
Tsu-Hsiang Kuo
Published online June 14, 2023
Cancer Screening and Prevention. doi:10.14218/CSP.2023.00005
747
Review Article Open Access
Anandu Chandra Khanashyam, Priyamvada Thorakkattu, Karthik Sajith Babu, Kartik Shah, Mithun Singh Rajput, Siriwan Nirmal, Nilesh Prakash Nirmal
Published online June 14, 2023
Cancer Screening and Prevention. doi:10.14218/CSP.2023.00001
Abstract
Cancer is a hereditary multifactorial disease, and due to its rising incidence in both young people and adults along with its substantial burden, oncological emphasis has been placed [...] Read more.

Cancer is a hereditary multifactorial disease, and due to its rising incidence in both young people and adults along with its substantial burden, oncological emphasis has been placed more on preventive efforts. It has been suggested that several food and lifestyle choices contribute to the onset of cancer, presumably via complex metabolic and inflammatory pathways. Diet is one of the crucial variables in determining cancer risk. In addition, as research intensifies, a more distinct link between diet and patients’ molecular alterations is emerging and becoming quantifiable, dispelling the previous conventional wisdom that linked phenotypic changes to dietary variation. Although the evidence is not consistent, appropriate doses of vitamin B12, vitamin D, vitamin C, selenium, folic acid, and antioxidants such as carotenoids have shown a preventive effect in certain types of cancer. However, improper use of dietary supplements in well-nourished people provides no effects or even poses harmful effects to increase the risk of some cancer. Contrarily, other factors like alcohol, obesity, certain fatty acids, and some techniques used for food preparation may increase the risk of cancer. It is now appropriate to make dietary modifications that are consistent with suggestions for preventing cancer incidence with an emphasis on lifestyle improvement including proper management of problems associated with diet, nutrition, smoking, and drinking. However, there is currently a need for more clinical research to demonstrate the safety and effectiveness of using various phytochemicals or plant extracts as dietary supplements to prevent primary stages of cancer.

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748
Original Article Open Access
Sisi Chen, Xiangying Zhang, Ling Xu, Yuan Tian, Zihao Fan, Yaling Cao, Zhenzhen Pan, Yao Gao, Sujun Zheng, Zhongping Duan, Mei Liu, Feng Ren
Published online June 14, 2023
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2022.00107
Abstract
Hepatitis delta virus (HDV) is a defective virus and causes severe liver disease. Several HDV RNA assays have been developed, however the diagnostic efficacy remains unclear.This [...] Read more.

Hepatitis delta virus (HDV) is a defective virus and causes severe liver disease. Several HDV RNA assays have been developed, however the diagnostic efficacy remains unclear.This systematic review and meta-analysis aims to evaluate the diagnostic accuracy of HDV RNA assays to aid in the diagnosis of active hepatitis D.

The PubMed, Embase, and Cochrane Library databases were systematically searched from the beginning to June 31, 2022. Information on the characteristics of the literature and data on sensitivity, specificity, and area under curve (AUC) of the receiver operating characteristic (ROC) were extracted. Stata 14.0 was used for meta-analysis of the combined sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio.

A total of 10 studies were included in the meta-analysis. The summary sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio of HDV RNA assays for HDV diagnosis were 0.92 (95% CI: 0.87–0.95), 0.90 (95% CI: 0.86–0.93), 7.74 (95% CI: 5.31–11.29), 0.10 (95% CI: 0.06–0.18) and 99.90 (95% CI: 47.08–211.99), respectively. The AUC of the pooled ROC curve was 0.95 (95% CI: 0.92–0.96).

The results show that HDV RNA assays had high diagnostic performance. However, that is limited by the number and quality of studies. Standard protocols for the development of assays by manufacturers and larger studies on the use of the assays are needed.

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749
Review Article Open Access
Swarup K. Chakrabarti, Dhrubajyoti Chattopadhyay
Published online June 13, 2023
Exploratory Research and Hypothesis in Medicine. doi:10.14218/ERHM.2023.00018
Abstract
Aging, shifting demographics, and lifestyle changes are some of the underlying factors contributing to an increase in the incidence and prevalence of age-related disorders. Brain [...] Read more.

Aging, shifting demographics, and lifestyle changes are some of the underlying factors contributing to an increase in the incidence and prevalence of age-related disorders. Brain health is correlated with cellular senescence and is an important indicator of physiological aging and several age-related diseases. Examining the current state of knowledge of the underlying mechanisms of senescence as well as prospective therapeutic modalities concerning aging and age-related diseases is thus crucial. The senescence-associated secretory phenotype (SASP) of senescent cells (SnCs) results in a secretome, which is primarily composed of growth factors, cytokines/chemokines, and extracellular matrix (ECM) remodeling proteins secreted by the arrested cells. Increasingly, research suggests a causative role of senescence in various diseases such as osteoporosis, neurodegenerative diseases, cardiovascular diseases, and metabolic dysfunction, among others. SnCs promote age-related diseases by affecting the differentiation and proliferation of stem cells. They do so, in part through disruption of the Wingless-related integration site (Wnt) signaling pathways and Yes-associated protein and its ortholog transcriptional coactivators with a PDZ-binding domain (YAP/TAZ) transcriptional regulation, affecting tissue regeneration and a decreased ability for the body to rejuvenate. Senescent cell-induced immune system dysregulation, e.g., immunosenescence, as well as senescent cell-secreted substances also cause persistent, low-grade inflammation in organisms known as inflammaging, which accelerates aging and results in tissue damage. During age-related senescence, key chromatin structural changes take place in the cells that affect nuclear transport, causing genomic instability, changes in nucleosome positioning, post-translational modifications of histones, global histone loss, etc. Elimination of SnCS using senolytics by targeting cellular and molecular pathways has emerged as a potential therapeutic strategy for delaying aging and improving age-related dysfunctions including brain diseases.

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750
Original Article Open Access
Daomiao Liang, Lanzhu Luo, Jiang Wang, Tongyu Liu, Chao Guo
Published online June 12, 2023
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2023.00034
Abstract
The growing knowledge of ferroptosis has suggested the regulatory role of ferroptosis in hepatocellular carcinoma (HCC), but the pertinent molecular mechanisms remain unclear. Herein, [...] Read more.

The growing knowledge of ferroptosis has suggested the regulatory role of ferroptosis in hepatocellular carcinoma (HCC), but the pertinent molecular mechanisms remain unclear. Herein, this study investigated the mechanistic basis of ferroptosis-related genes (ferrGenes) in the growth of HCC.

Differentially expressed human ferrGenes and tumor-related transcription factors (TFs) were obtained from the The Cancer Genome Atlas (TCGA) dataset and the GTEx dataset. Spearman method-based correlation analysis were conducted to construct TF-ferrGene coexpression regulatory network. Key genes associated with prognosis were singled out with Lasso regression and multivariate Cox analysis to construct the prognostic risk model. Then the accuracy and independent prognostic ability of the model were evaluated. Expression of CENPA and STMN1 was determined in clinical HCC tissues and HCC cells, and their binding was analyzed with dual-luciferase and chromatin immunoprecipitation (ChIP) assays. Furthermore, ectopic expression and knockdown assays were performed in HCC cells to assess the effect of CENPA and STMN1 on ferroptosis and malignant phenotypes.

The prognostic risk model constructed based on the eight TF-ferrGene regulatory network-related genes accurately predicted the prognosis of HCC patients. It was strongly related to the clinical characteristics of HCC patients. Moreover, CENPA/STMN1 might be a key TF-ferrGene regulatory network in ferroptosis of HCC. CENPA and STMN1 were overexpressed in HCC tissues and cells. Additionally, CENPA facilitated STMN1 transcription by binding to STMN1 promoter, thus facilitating the malignant phenotypes and suppressing the ferroptosis of HCC cells.

Taken together, CENPA curbs the ferroptosis of HCC cells by upregulating STMN1 transcription, thereby promoting HCC growth.

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751
Original Article Open Access
Arnab Mukherjee, Mukunthan Kuppusamy Selvam
Published online June 12, 2023
Gene Expression. doi:10.14218/GE.2023.00005S
Abstract
Radiotherapy is the most crucial nonsurgical therapeutic method in the multidisciplinary care of patients with non-small cell lung cancer (NSCLC). However, radiation resistance [...] Read more.

Radiotherapy is the most crucial nonsurgical therapeutic method in the multidisciplinary care of patients with non-small cell lung cancer (NSCLC). However, radiation resistance continues to be a significant clinical issue, negatively affecting cancer prognosis in patients. The small molecules that target these RNAs offer therapeutic modulation of multiple biological processes. The study aims to identify the genes and a long non-coding RNA (lncRNA) regulating their expression levels, as well as the binding potential of small volatile inhibitors to the lncRNA to overcome radioresistance in NSCLC.

The non-coding RNA microarray dataset of NSCLC cells was analysed to identify the differentially expressed genes regulated by lncRNA, which drives radioresistance. The study comprises three volatile ligands due to their good pharmacokinetic profile to target the identified lncRNA.

The analysis revealed the dysregulation of the cell cycle, evasion of apoptosis and cancer immune response. A co-expression analysis with a network pharmacology approach revealed an lncRNA ENST00000605056 regulating three highly ranked hub genes. The molecular interaction studies uncovered their high binding affinity to its binding pocket with a preponderance of non-covalent bond interactions between the ligand and the nucleotides. The molecular dynamics simulations revealed the binding stability of ligands to the lncRNA with a very low deviation compared to the control.

This study demonstrates the ability of small molecules to target lncRNA in addressing the global concern of radioresistance among NSCLC patients, thereby facilitating future translational studies.

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752
Editorial Open Access
Wei-Zheng Zhang
Published online June 12, 2023
Journal of Exploratory Research in Pharmacology. doi:10.14218/JERP.2023.00025
753
Review Article Open Access
Wai Yew Yang, Kah Yen Lim, Pei Ling Yen, Shu Hwa Ong, Nenad Naumovski, Rati Jani
Published online June 9, 2023
Exploratory Research and Hypothesis in Medicine. doi:10.14218/ERHM.2022.00129
Abstract
Childhood obesity has been escalating in Asian countries in recent decades resulting in the younger age groups being diagnosed with metabolic syndrome (MetS). Brassicaceae vegetables [...] Read more.

Childhood obesity has been escalating in Asian countries in recent decades resulting in the younger age groups being diagnosed with metabolic syndrome (MetS). Brassicaceae vegetables that contain high bioactive compounds with anti-inflammatory and anti-oxidative properties might be beneficial in preventing MetS. This narrative review presents; (a) the consumption of vegetables in the world population and the availability of bitter-taste vegetables in Asian culture; (b) the interaction between food preference and childhood obesity and (c) potential associations between the consumption of bitter-taste vegetables in Asian culture and clinical outcomes. A number of online searches were conducted for publications in the English language from the year 1990 until October 2022 with a two-step search strategy adopted: initial searches were conducted in four electronic databases (MEDLINE, CINAHL, EMBASE, and Cochrane Library), and a second search using all identified keywords and indexes by including two additional electronic databases (ProQuest and Scopus). The keywords included “bitter”; “vegetables”; “weight status”; “metabolic profile”, “Asia”, “culture”, and “children”. Brassica vegetables in Asian countries are abundantly available and commonly consumed, yet the overall vegetable intake in children was inadequate or below the recommended daily intake. Childhood obesity can be influenced by their preference for and consumption of bitter-taste vegetables, and excessive body weight is associated with the risk of developing MetS. It remains inconclusive whether brassicas vegetables play a dominant role in the group. Future longitudinal studies to investigate the taste sensitivity, vegetable acceptance, and effect of brassicas vegetables on the risk of MetS in Asian children are warranted.

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754
Case Report Open Access
Abdelkader Boukhmis, Mohammed El-Amin Nouar, Khaled Khacha, Yacine Djouaher
Published online June 8, 2023
Exploratory Research and Hypothesis in Medicine. doi:10.14218/ERHM.2023.00024
Abstract
Patients with secondary mitral regurgitation (SMR), the majority of which is ischemic, often have atherosclerotic ascending aorta and left ventricular (LV) dysfunction. In these [...] Read more.

Patients with secondary mitral regurgitation (SMR), the majority of which is ischemic, often have atherosclerotic ascending aorta and left ventricular (LV) dysfunction. In these patients, restrictive mitral annuloplasty is associated with a high rate of MR recurrence, aortic cross-clamping increases the stroke rate, and cardioplegic arrest increases postoperative low cardiac output syndrome. To avoid these complications, beating heart mitral valve replacement without aortic cross-clamping has been proposed. Here, we describe two male patients, aged 71 and 54 years, with severe SMR and low left ventricle ejection fraction (LVEF) (24% and 30%, respectively). Beating-heart mitral valve replacement with total chordal sparing was performed without aortic cross-clamping through a full sternotomy. Weaning from cardiopulmonary bypass was easily achieved without use of inotropes. The duration of mechanical ventilation (3 and 6 hours, respectively) and intensive care (24 and 48 hours, respectively) was short. Neither patient presented with postoperative neurological disorders. After a mean follow-up of 66 months, both patients were asymptomatic, without prosthetic valve dysfunction, and their LVEF reached 42% and 51%, respectively. This cases study indicates that for patients with SMR with impaired LV function who are at high risk for cardioplegic arrest, clampless beating heart mitral valve replacement with total preservation of the subvalvular apparatus could reduce stroke incidence, preserve peri-operative LVEF, and allow reverse LV remodeling.

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755
Original Article Open Access
Ka-Shing Cheung, Chiu-Hang Mok, Lok-Ka Lam, Xian-Hua Mao, Lung-Yi Mak, Wai-Kay Seto, Man-Fung Yuen
Published online June 8, 2023
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2022.00130S
Abstract
We aimed to perform a network meta-analysis (NWM) to examine comparative effectiveness of non-selective beta blockers (NSBBs) on prophylaxis of gastroesophageal variceal bleeding [...] Read more.

We aimed to perform a network meta-analysis (NWM) to examine comparative effectiveness of non-selective beta blockers (NSBBs) on prophylaxis of gastroesophageal variceal bleeding (GVB) and mortality benefit.

MEDLINE (OVID) and EMBASE databases were searched for eligible randomized clinical trials (RCTs) from inception to July 3, 2021. Outcomes of interest included primary/secondary prophylaxis of GVB, failure to achieve hepatic venous pressure gradient (HVPG) decremental response, liver-related and all-cause mortality. A Bayesian NWM was performed to derive relative risk (RR) with 95% credible intervals (CrIs). The ranking probability of each NSBB was assessed by surface under cumulative ranking curve (SUCRA).

Thirty-three RCTs including 3,188 cirrhosis patients with gastroesophageal varices were included. Compared with placebo, nadolol ranked first for reducing variceal bleeding [RR:0.25, (95% CrI:0.11–0.51); SUCRA:0.898], followed by carvedilol [RR:0.33, (95% CrI: 0.11–0.88); SUCRA:0.692] and propranolol [RR:0.52, (95% CrI:0.37–0.75); SUCRA:0.405]. Carvedilol was more effective than propranolol in achieving HVPG decremental response [RR:0.43, (95% CrI: 0.26–0.69)]. Carvedilol ranked first for reducing all-cause mortality [RR: 0.32, (95% CrI:0.17–0.57); SUCRA:0.963), followed by nadolol [RR:0.48, (95% CI:0.29–0.77); SUCRA:0.688], and propranolol [RR:0.77, (95% CI:0.58–1.02); SUCRA: 0.337]. Similar findings were observed for liver-related mortality. Carvedilol ranked the safest. The RR of adverse events was 4.38, (95% CrI:0.33–161.4); SUCRA:0.530, followed by propranolol [RR: 7.54, (95% CrI:1.90–47.89); SUCRA:0.360], and nadolol [RR: 18.24, (95% CrI:91.51–390.90); SUCRA:0.158].

Carvedilol is the preferred NSBB with better survival benefit and lower occurrence of adverse events among patients with gastroesophageal varices.

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756
Original Article Open Access
Alexis Jose-Abrego, Sonia Roman, João Renato Rebello Pinho, Michele Soares Gomes-Gouvêa, Arturo Panduro
Published online June 7, 2023
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2022.00135S
Abstract
Lamivudine (3TC), telbivudine (LdT), entecavir (ETV), adefovir (ADF), and tenofovir (TFV) are drugs used to treat hepatitis B virus (HBV) infection, but specific mutations allow [...] Read more.

Lamivudine (3TC), telbivudine (LdT), entecavir (ETV), adefovir (ADF), and tenofovir (TFV) are drugs used to treat hepatitis B virus (HBV) infection, but specific mutations allow some viruses to become resistant to antiviral drugs or to acquire immune escape capacities. These mutations have not been thoroughly investigated in Mexico. This study aimed to estimate the prevalence of HBV antiviral resistance and escape mutations.

This cross-sectional study analyzed 158 samples. HBV DNA was extracted, amplified, and sequenced in serum samples using the spin column method, PCR assay, and Sanger’s sequencing, respectively. HBV genotypes were determined, and HBV mutations were tested using the Geno2pheno tool.

Overall, 68.4% (108/158) of HBV patients were infected with genotype H, followed by G (11.4%, 18/158), A2 (10.8%, 17/158), F1b (6.9.0%, 11/158), D (1.9%, 3/158), and E (0.6%, 1/158), and 5.1% (8/158) had evidence of recombination. The prevalence of resistance mutations was 8.2% (13/158) and the most common combined mutation was rt180M+rt204V. Notably, we found the combinations rt180M+rt204V+rt173L (n=2) and rt180M+rt204V+rt202G (n=1) that confer multidrug resistance to 3TC, LdT, and ETV. Resistance mutations were found in genotypes A2 (11.8%, 2/17), and H (10.2%, 11/108), and escape mutations were detected in HBV genotypes A2 (11.8%, 2/17), H (10.2%, 11/108), F1b (9.1%, 1/11) and G (5.6%, 1/18).

The highest prevalence of antiviral resistance mutations or escape mutations was detected in HBV genotypes A2 and H. The earliest cases of HBV multidrug resistance were detected in Mexico.

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757
Review Article Open Access
Emily Weng, Murali Dharan
Published online June 6, 2023
Journal of Translational Gastroenterology. doi:10.14218/JTG.2023.00001
Abstract
Gastrointestinal (GI) malignancies account for over a quarter of all new cancer diagnoses worldwide, and pose a significant burden on public health. As endoscopes are improved over [...] Read more.

Gastrointestinal (GI) malignancies account for over a quarter of all new cancer diagnoses worldwide, and pose a significant burden on public health. As endoscopes are improved over the years, upgraded high-definition cameras have allowed for better polyp detection. Due to the absence of symptoms in GI malignancy, lesions are often incidentally detected in various stages by endoscopists. Careful polyp morphology evaluation and classification is paramount when selecting the most appropriate endoscopic (or surgical) resection method. The technique that would allow for an en bloc or R0 resection is preferred (endoscopic submucosal dissection [ESD]), while those that present with lower risk features can be reasonably removed in a piecemeal fashion or hybrid fashion with care in ablating clean margins to decrease recurrence. Although Eastern and European endoscopists have more experience in ESD, this expertise is not widely available in North America. The present study aims to explore the following questions: (1) Is ESD always necessary? (2) In which scenarios are ESD always indicated? (3) Can endoscopic mucosal resection be used to achieve resection goals, since this expertise is more widely available and has an easier learning curve?

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758
Mini Review Open Access
Yong Q. Chen
Published online June 5, 2023
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2023.00058
Abstract
Nonalcoholic steatohepatitis (NASH) is a chronic liver disease affecting a large population worldwide. No clinically approved drugs are available. In this minireview, we discuss [...] Read more.

Nonalcoholic steatohepatitis (NASH) is a chronic liver disease affecting a large population worldwide. No clinically approved drugs are available. In this minireview, we discuss the heterogeneous nature of NASH and lack of consensus in outcome measures among clinical trials. We summarize NASH therapeutic targets and candidate drugs. We compare the efficacy of 33 published clinical trials that evaluated noninvasive biomarkers and liver biopsy. Currently, phase II trial results of fibroblast growth factor 21 (FGF21) and phase III trial results of resmetirom and pioglitazone are encouraging.

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759
Original Article Open Access
Jing-Jing Li, Wei-Qi Dai, Wen-Hui Mo, Wen-Qiang Xu, Yue-Yue Li, Chuan-Yong Guo, Xuan-Fu Xu
Published online June 2, 2023
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2023.00133
Abstract
Liver ischemia-reperfusion (IR) injury is a common pathological process in liver surgery. Ferroptosis, which is closely related to lipid peroxidation, has recently been confirmed [...] Read more.

Liver ischemia-reperfusion (IR) injury is a common pathological process in liver surgery. Ferroptosis, which is closely related to lipid peroxidation, has recently been confirmed to be involved in the pathogenesis of IR injury. However, the development of drugs that regulate ferroptosis has been slow, and a complete understanding of the mechanisms underlying ferroptosis has not yet been achieved. Fucoidan (Fu) is a sulfated polysaccharide that has attracted research interest due to its advantages of easy access and wide biological activity.

In this study, we established models of IR injury using erastin as an activator of ferroptosis, with the ferroptosis inhibitor ferrostatin-1 (Fer-1) as the control. We clarified the molecular mechanism of fucoidan in IR-induced ferroptosis by determining lipid peroxidation levels, mitochondrial morphology, and key pathways in theta were involved.

Ferroptosis was closely related to IR-induced hepatocyte injury. The use of fucoidan or Fer-1 inhibited ferroptosis by eliminating reactive oxygen species and inhibiting lipid peroxidation and iron accumulation, while those effects were reversed after treatment with erastin. Iron accumulation, mitochondrial membrane rupture, and active oxygen generation related to ferroptosis also inhibited the entry of nuclear factor erythroid 2-related factor 2 (Nrf2) into the nucleus and reduced downstream heme oxygenase-1 (HO-1) and glutathione peroxidase 4 (GPX4) protein levels. However, fucoidan pretreatment produced adaptive changes that reduced irreversible cell damage induced by IR or erastin.

Fucoidan inhibited ferroptosis in liver IR injury via the Nrf2/HO-1/GPX4 axis.

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760
Review Article Open Access
Malia Holbeck, Hannah Statz DeVries, Ashwani K. Singal
Published online June 2, 2023
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2023.00002
Abstract
Alcohol-associated liver disease (ALD) is one of the most common liver diseases and indications for liver transplantation (LT). Alcohol use disorder (AUD), a frequent accompaniment [...] Read more.

Alcohol-associated liver disease (ALD) is one of the most common liver diseases and indications for liver transplantation (LT). Alcohol use disorder (AUD), a frequent accompaniment in ALD patients, may also be associated with psychiatric comorbidities such as depression and anxiety. Identification of ALD at an earlier stage, and treatment of AUD may help prevent progression to advanced stage of ALD such as cirrhosis and alcoholic hepatitis. Screening for alcohol use and AUD treatment in ALD patients is often not performed due to several barriers at the level of patients, clinicians, and administrative levels. This review details the integrated multidisciplinary care model especially on the specific role of the hepatologist, psychiatrist, addiction counselor, and social worker in providing complete management for the dual pathology of liver disease and of AUD. Laboratory assessment, pharmacological and behavioral therapies, and recommended assessments for follow-up care by the respective specialists is outlined. We provide perspective along with the literature support, with the goal of providing team based comprehensive care of patients with ALD.

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