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321
Original Article Open Access
Ruofei Du, Jiayu Guo, Jing Li, Jun Lyu
Published online September 25, 2024
Cancer Screening and Prevention. doi:10.14218/CSP.2024.00019
Abstract
The prevalence and fatality rates of cutaneous malignant melanoma (CMM) have been rising, particularly among the elderly. This study analyzes CMM incidence trends in the United [...] Read more.

The prevalence and fatality rates of cutaneous malignant melanoma (CMM) have been rising, particularly among the elderly. This study analyzes CMM incidence trends in the United States elderly population from 1987 to 2016 to inform prevention and management strategies.

Using incidence data from the Surveillance, Epidemiology, and End Results database spanning 1989 to 2008, we calculated the age-adjusted standardized population incidence rates for CMM in elderly individuals. The Joinpoint software was employed to estimate annual percent change and analyze trends in CMM incidence among elderly individuals from 1987 to 2016.

The study included 56,997 elderly CMM patients from eight Surveillance, Epidemiology, and End Results registries, of whom 36,726 were male (64.4%). The age-adjusted CMM incidence rate from 2012 to 2016 was 0.99 per 1,000, a 2.8-fold increase from 1987–1991 (95% confidence interval: 2.7–2.9). Incidence rates increased with age and birth cohort, peaking at 1.53 per 1,000 males and 0.59 per 1,000 females aged 85+ during 2012–2016. Birth cohort effects also showed a continuous increase.

This study reveals a substantial increase in CMM incidence rates among the elderly from 1987 to 2016, particularly between 2012 and 2016. Incidence rates escalated with age and birth cohort, with the highest rates observed in individuals aged 85 and older.

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322
Review Article Open Access
Maruthamuthu Vijayalakshmi, Shanmugam Meganathan, Suresh Kumar Surendhar, Appavoo Umamaheswari, Sakthivel Lakshmana Prabu
Published online September 25, 2024
Oncology Advances. doi:10.14218/OnA.2024.00012
Abstract
Cancer is thought to be the second most prevalent and leading cause of mortality worldwide, affecting both men and women among other chronic diseases. While there are several treatment [...] Read more.

Cancer is thought to be the second most prevalent and leading cause of mortality worldwide, affecting both men and women among other chronic diseases. While there are several treatment options available, significant strains, side effects, and resistance have led researchers to focus on finding novel alternative medications for cancer treatment. Antioxidants and the immunomodulatory activities of medicinal plants are studied and considered to have anti-cancer effects. Medicinal plants contain diverse phytoconstituents as natural drugs, which possess numerous medicinal properties used for treating and preventing various illnesses. These phytoconstituents work through several mechanisms to target and kill cancer cells. Anticancer mechanisms include suppression and arrest of the G0/G1 phase, acting as anti-mitotic and anti-microtubule agents, enhancing the activity of macrophages, inhibiting cancer cells through various signaling cascades, anti-angiogenesis, and cytotoxicity. Investigating botanical sources and their metabolites can uncover new chemical entities for cancer treatment at the molecular target level and provide future interventions in cancer therapy. This article summarizes a few medicinal plants and their mechanisms of action for their anticancer potential. Furthermore, we discuss the future prospects and limitations of using medicinal plants in cancer treatment.

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323
Original Article Open Access
Haixia Li, Jieyun Yin, Zhaohui Zhang, Hanaa S. Sallam, Jiande D.Z. Chen
Published online September 25, 2024
Journal of Translational Gastroenterology. doi:10.14218/JTG.2024.00026
Abstract
Gastrointestinal dysmotility commonly follows thermal injuries, such as burns. This study aimed to investigate the effects and mechanisms of electroacupuncture (EA) on burn-induced [...] Read more.

Gastrointestinal dysmotility commonly follows thermal injuries, such as burns. This study aimed to investigate the effects and mechanisms of electroacupuncture (EA) on burn-induced gastric dysmotility in rats.

Sprague-Dawley rats were divided into sham and thermal injury groups subjected to a 60% scald burn. Antagonists, including β-blockade (propranolol), α-blockade (phentolamine), or a selective cyclooxygenase (COX)-2 inhibitor (nimsulide), were administered to verify the pathways involved. Six hours after the burn, the animals were evaluated for gastric emptying and heart rate variability. Blood and gastric tissues were collected for assays of cytokines, hormones, and COX-2 levels. EA was performed at bilateral ST36 (Zusanli) acupoints for 45 m.

Burn injury delayed gastric emptying by 61% (P < 0.01), which was normalized by nimsulide or propranolol but not by phentolamine. EA improved gastric emptying by 87% (P = 0.03) in burned rats. Heart rate variability and plasma hormone (noradrenaline and pancreatic polypeptide) analyses indicated sympathetic hyperactivity in burned rats; EA improved burn-induced sympathovagal imbalance by enhancing vagal activity. Protein and mRNA expressions of COX-2 in the gastric fundus and antrum increased with burn but were normalized by propranolol. EA reduced the burn-induced increase in COX-2 expression in the gastric fundus but not in the antrum. EA also decreased burn-induced elevations in plasma interleukin (IL)-6 and IL-10. Negative correlations were found between gastric emptying and plasma IL-6 levels, as well as between gastric emptying and COX-2 mRNA levels.

These findings suggest that burn-induced gastric dysmotility is mediated via autonomic-COX-2 pathways. EA at acupoint ST36 improves burn-induced delays in gastric emptying by down-regulating COX-2 and pro-inflammatory cytokines through the autonomic nervous pathway.

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324
Original Article Open Access
Yinnan Zhu, Yuan Ding, Qiliu Qian, Wanyue Zhang, Qingxia Wang, Ruihua Shi
Published online September 25, 2024
Cancer Screening and Prevention. doi:10.14218/CSP.2024.00016
Abstract
The incidence of cardia gastric cancer (CGC) is rising worldwide, particularly in East Asia. There has been a debate over whether Helicobacter pylori (H. pylori) constitutes a risk [...] Read more.

The incidence of cardia gastric cancer (CGC) is rising worldwide, particularly in East Asia. There has been a debate over whether Helicobacter pylori (H. pylori) constitutes a risk factor for CGC. This study aimed to evaluate the relative risk of H. pylori infection and CGC in Asian countries.

Relevant studies examining H. pylori and CGC were searched in PubMed, Embase, and Web of Science from their inception to June 30, 2024. Either a random-effect model or a fixed-effect model was used to calculate pooled odds ratios (ORs) with 95% confidence intervals (CIs). Sensitivity analyses and assessments of publication bias were performed. The stability of results was evaluated in cases where publication bias was detected.

A total of 24 studies were included in the meta-analysis. A significant association between H. pylori and CGC was observed (OR = 2.20, 95% CI 1.73–2.80). In a subgroup analysis of different countries, a significant association was observed in East Asian countries, including China (OR = 2.12, 95% CI 1.63–2.77), Japan (OR = 2.21, 95% CI 1.16–4.20), and Korea (OR = 2.36, 95% CI 1.58–3.54), but not in Iran (OR = 1.48, 95% CI 0.77–2.84). The pooled OR from five prospective cohort studies revealed a strong association between H. pylori and CGC (OR = 2.32, 95% CI 1.47–3.66).

East Asia bears a significant burden of H. pylori-related CGC. A clear association between H. pylori infection and CGC was observed in this region.

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325
Original Article Open Access
Kayla Brice, Candice Arline, Luis E. Raez, Katerine Dumais, Mark Block
Published online September 25, 2024
Journal of Clinical and Translational Pathology. doi:10.14218/JCTP.2024.00021
Abstract
Tumor molecular analysis using next-generation sequencing (NGS) is the standard of care for guiding lung cancer treatment. Endobronchial ultrasound-guided transbronchial needle [...] Read more.

Tumor molecular analysis using next-generation sequencing (NGS) is the standard of care for guiding lung cancer treatment. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive technique used to sample mediastinal lymph nodes for diagnosing and staging lung cancer. This study aimed to determine if EBUS-TBNA provided adequate tissue samples for NGS.

We evaluated EBUS-TBNA samples from adult advanced non-small cell lung cancer patients who had both EBUS-TBNA and liquid biopsy samples analyzed by NGS between July 1, 2015 and June 30, 2021. Additionally, we compared the results with those from liquid biopsies performed on these patients.

Among the 44 evaluated patients, 43% were male, with a median age of 66 years at diagnosis. Seventy-five percent were smokers, 79.5% were White, 6.8% were Black, and 9.1% were Asian. EBUS-TBNA samples were sufficient for NGS in 95.5% of cases. The median turnaround time for EBUS-TBNA NGS was 38.5 days compared with eight days for NGS in liquid biopsies. Actionable genetic aberrations were detected in 71% of patients.

Our findings demonstrated that EBUS-TBNA provided sufficient tissue for identifying actionable genetic aberrations in patients with advanced non-small cell lung cancer.

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326
Original Article Open Access
Tianle Zou, Zhonghua Liu, Elizabeth Brese, Bo Xu
Published online September 25, 2024
Journal of Clinical and Translational Pathology. doi:10.14218/JCTP.2024.00029
Abstract
Mesothelioma is an aggressive tumor with a poor prognosis. Histological diagnosis of mesothelioma using limited tissue samples can be challenging. Carbonic anhydrase IX (CAIX) is [...] Read more.

Mesothelioma is an aggressive tumor with a poor prognosis. Histological diagnosis of mesothelioma using limited tissue samples can be challenging. Carbonic anhydrase IX (CAIX) is a transmembrane protein that is overexpressed in a variety of solid tumors. This study aimed to investigate the clinical utility of CAIX expression in the differential diagnosis of pleural mesothelioma from non-small cell lung carcinoma (NSCLC).

Unstained tissue microarray slides composed of 56 cases of pleural mesothelioma and 82 cases of NSCLC were subjected to immunohistochemical staining using a mouse anti-human antibody against CAIX.

Of the 38 epithelioid mesothelioma cases, 34 (89%) displayed diffuse and strong cytoplasmic membrane reactivity, while the remaining four cases (11%) showed weak to moderate staining in tumor cells. Five out of sixteen (5/16) sarcomatoid mesothelioma cases were negative. Among the non-small cell lung carcinoma cases, 76% (32/42) of adenocarcinomas and 57% (21/37) of squamous cell carcinomas were completely negative, whereas the remaining cases showed focal weak expression of CAIX.

Our study demonstrates that CAIX expression has a high sensitivity (100%) in detecting pleural epithelioid mesothelioma, which is comparable to or better than currently used mesothelial markers. The specificity of CAIX is within a comparable range to that of commonly used mesothelial markers for differentiating epithelioid mesothelioma from NSCLC. Therefore, we recommend that CAIX immunohistochemistry staining be considered as an additional tool for the differential diagnosis of mesothelioma, particularly pleural epithelioid mesothelioma, from its common mimicker, NSCLC.

Full article
327
Review Article Open Access
Xiulin Hu, Congjia Ma, Xiangyu Kong
Published online September 25, 2024
Cancer Screening and Prevention. doi:10.14218/CSP.2024.00017
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with difficulties in early diagnosis, poor prognosis, and limited effective therapies. Early detection and effective [...] Read more.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with difficulties in early diagnosis, poor prognosis, and limited effective therapies. Early detection and effective treatment offer the optimal chance to improve survival rates. Various studies have shown that gut microbiota dysbiosis is closely related to PDAC, with potential mechanism involving immune regulation, metabolic process impact, and reshaping the tumor microenvironment. A comprehensive understanding of the microbiota in PDAC might lead to the establishment of screening or early-stage diagnosis methods, implementation of cancer bacteriotherapy such as fecal microbiota transplantation, creating new opportunities and fostering hope for desperate PDAC patients.

Full article
328
Review Article Open Access
Minhua Wang, Maria D. Lozano, Guoping Cai
Published online September 25, 2024
Journal of Clinical and Translational Pathology. doi:10.14218/JCTP.2024.00034
Abstract
The World Health Organization System for Reporting Pancreaticobiliary Cytopathology introduces a seven-tier category system to standardize terminology and nomenclature. This system [...] Read more.

The World Health Organization System for Reporting Pancreaticobiliary Cytopathology introduces a seven-tier category system to standardize terminology and nomenclature. This system includes the following categories: Insufficient/non-diagnostic, benign/negative for malignancy, atypia, pancreaticobiliary neoplasm low-risk/grade, pancreaticobiliary neoplasm high-risk/grade, suspicious for malignancy, and malignant categories. Adopting a standardized reporting scheme facilitates consistent diagnostic criteria among pathologists, thereby reducing report variability and enhancing communication with the clinical team for optimal patient management. The report also highlights the role of critical ancillary tests in improving diagnostic accuracy for pancreatic lesions and discusses practical approaches to managing solid and cystic pancreatic lesions.

Full article
329
Review Article Open Access
Wenhao Luo, Jun Wang, Hao Chen, Zhe Cao, Jiangdong Qiu, Yueze Liu, Yifan Fu, Gang Yang, Jinxin Tao, Guihu Weng, Tao Liu, Yueyang Wang, Liyuan Ye, Cheng Ding, Xiaoyue Lu, Menggang Zhang, Hua Huang, Jianchun Xiao, Lei You, Taiping Zhang
Published online September 25, 2024
Cancer Screening and Prevention. doi:10.14218/CSP.2024.00006S
Abstract
Pancreatic cancer (PC) remains a formidable challenge in oncology due to its notoriously poor prognosis, often resulting from late-stage diagnosis. Early detection through effective [...] Read more.

Pancreatic cancer (PC) remains a formidable challenge in oncology due to its notoriously poor prognosis, often resulting from late-stage diagnosis. Early detection through effective screening methods is crucial not only to improving patient outcomes but also to enhancing their quality of life. This review focuses on the latest advancements in PC screening and early diagnostic strategies. Key areas include the integration of artificial intelligence in radiology, the search for novel biomarkers, and the development of predictive models. This review aimed to provide a comprehensive overview, serving as a stepping stone toward transforming early detection strategies for PC in the digital age.

Full article
330
Review Article Open Access
Xin Quan, Hua Wen, Hao Liang, Mingxin Zhang
Published online September 25, 2024
Cancer Screening and Prevention. doi:10.14218/CSP.2024.00018
Abstract
Among all tumors worldwide, digestive tract tumors have a higher incidence rate and a significant disease burden. Esophageal cancer, gastric cancer, liver cancer, and colorectal [...] Read more.

Among all tumors worldwide, digestive tract tumors have a higher incidence rate and a significant disease burden. Esophageal cancer, gastric cancer, liver cancer, and colorectal cancer are often diagnosed at an advanced stage, and the prognosis remains poor. Currently, tumor treatment resistance is a major global challenge, with many underlying mechanisms. Ferroptosis has been shown to reverse drug resistance. This article reviews the mechanisms and recent advancements in ferroptosis related to reversing treatment resistance in gastrointestinal tumors, aiming to provide theoretical insights and research directions for the diagnosis and treatment of digestive tract tumors.

Full article
331
Original Article Open Access
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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332
Original Article Open Access
Md Ariful Amin, Uzzal Chondra, Md Morshedul Alam
Published online September 25, 2024
Journal of Exploratory Research in Pharmacology. doi:10.14218/JERP.2023.00030
Abstract
Chlorella vulgaris is a green, photosynthetic microalga in the phylum Chlorophyta. The goal of our study was to perform a bioinformatics analysis of Photosystem I P700 chlorophyll [...] Read more.

Chlorella vulgaris is a green, photosynthetic microalga in the phylum Chlorophyta. The goal of our study was to perform a bioinformatics analysis of Photosystem I P700 chlorophyll a apoprotein A2, one of its photosynthesis-related proteins, and to hunt for potent bioactive peptides.

To generate peptides and estimate the safety and efficacy of each bioactive peptide, we employed the tools BIOPEP-UWM™, PeptideRanker, DBAASP, and ToxinPred. PepDraw was used to understand the physicochemical properties and primary chemical structures of the selected bioactive peptides.

The liberated peptides exhibit up to 17 distinct bioactivities, as shown by the in silico digestion of the protein using several proteolytic enzymes. The peptides with bioactivities are listed as angiotensin-converting enzyme inhibitor, dipeptidyl peptidase IV inhibitor, dipeptidyl peptidase III inhibitor, antioxidative, renin inhibitor, glucose uptake stimulator, neuropeptide regulator (regulating stomach mucosal membrane activity and ion flow), antithrombotic, anti-amnestic, CaMPDE inhibitor, activators of ubiquitin-mediated proteolysis, alpha-glucosidase inhibitor, immunomodulating, calcium-binding, antibacterial, anti-inflammatory, and hypotensive agent. Using the Database of Antimicrobial Activity and Structure of Peptides (DBAASP) prediction method, the antibacterial activity of the released peptides was predicted, highlighting the existence of potent antibacterial peptides. An examination of their physicochemical properties revealed that most peptides are low molecular weight, mildly acidic, and moderately water-soluble. To further establish the non-toxicity profile of the released peptides (sequence length > 3), a ToxinPred analysis was performed, which revealed that most of the peptides are non-toxic. According to the allergenicity analysis, most of the top-ranked peptides are likely non-allergenic.

Thus, our study reveals a less labor-intensive method for discovering new therapeutic targets derived from C. vulgaris, which hold both pharmacological and medical significance.

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333
Original Article Open Access
Elad Mashiach, Juan Diego Alzate, David R. Hallan, Daniel A. Brenner, Jinpyo Hong, Elias B. Rizk
Published online September 24, 2024
Oncology Advances. doi:10.14218/OnA.2024.00005
Abstract
Information on the survival of urothelial cancer (UCa) patients with brain metastases (BM) is largely unreliable due to the rarity of such cases. Previous studies that have attempted [...] Read more.

Information on the survival of urothelial cancer (UCa) patients with brain metastases (BM) is largely unreliable due to the rarity of such cases. Previous studies that have attempted to capture the prevalence and survival of these patients are limited to case series and retrospective studies with small cohort sizes. This study aimed to explore patient characteristics and treatment outcomes based on treatment modalities from a large sample of patients with UCa and BM.

In this retrospective study, we utilized the TriNetX Research Network, a real-world and in-house database with longitudinal electronic medical records from 92 institutions. The database was queried for patients with UCa who also had BM. Kaplan–Meier plots were used to assess overall survival (OS). Log-rank tests were applied for stratified outcomes. The Cox proportional hazards model was used for continuous data.

We identified 357 patients with UCa and BM, representing 4.7% of the 7,521 patients diagnosed with primary UCa. The mean age at diagnosis was 65.6 years, with a predominance of male patients (67%). The median OS from BM diagnosis was 18.6 months. For patients treated solely with stereotactic radiosurgery (SRS), the median OS was 20.8 months. For those treated with both SRS and surgical resection, the median OS was 18.6 months. There was no significant difference in survival between patients treated with SRS alone and those treated with both SRS and surgical resection (p = 0.875). For patients treated only with gemcitabine chemotherapy, the median OS was 15.4 months.

This study represents the largest known retrospective analysis of UCa patients with BM. Survival trends for patients treated with surgical resection, SRS, and systemic therapies are described in detail.

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334
Commentary Open Access
335
Review Article Open Access
Zelu Meng, Yida Yang
Published online September 24, 2024
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2024.00193
Abstract
Autoimmune hepatitis (AIH) is a chronic, progressive inflammatory liver disease caused by autoimmune reactions, with an unknown etiology. If left untreated, it can progress to cirrhosis, [...] Read more.

Autoimmune hepatitis (AIH) is a chronic, progressive inflammatory liver disease caused by autoimmune reactions, with an unknown etiology. If left untreated, it can progress to cirrhosis, liver failure, or even death. While most patients respond well to first-line treatments, a significant number experience poor responses or intolerance, requiring the use of second- or third-line therapies. Ongoing research into the pathogenesis of AIH is leading to the development of novel therapeutic approaches. This review summarized recent advancements in the treatment of AIH both domestically and internationally.

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336
Mini Review Open Access
Nitin Srivastava, Aaruni Saxena, Anil K. Saxena
Published online September 20, 2024
Oncology Advances. doi:10.14218/OnA.2024.00019
Abstract
Despite the large number of cancer chemotherapeutics, cancer treatment is still not very satisfactory. Immune checkpoint inhibition has emerged as a new ray of hope in the immunotherapy [...] Read more.

Despite the large number of cancer chemotherapeutics, cancer treatment is still not very satisfactory. Immune checkpoint inhibition has emerged as a new ray of hope in the immunotherapy approach for cancer treatment. Immune checkpoint inhibitors are molecules located on the surface of immune cells that regulate unnecessary immune responses and keep autoimmune reactions in check. Immune checkpoint inhibitors (ICIs), such as anti-programmed cell death protein-1 and anti-programmed cell death ligand-1, have been employed to activate receptors on immune cells like T-cells, which can deactivate the immune checkpoint and thus reactivate them against cancer cells. However, ICI therapy has limitations, including resistance development in patients, its suitability for all patients, multiple organ disorders, and hyper-progression. Therefore, understanding the chemical structures of small molecule ICIs may aid in designing and developing novel ICIs with improved efficacy and efficiency for cancer chemotherapy. This review’s novelty lies in its summary of the U.S. Food and Drug Administration-approved drugs, repurposed drugs, candidate drugs used alone or in combination with monoclonal antibodies, and novel potential lead molecules under preclinical investigation, which may be useful for designing new chemical entities as ICIs. The review describes 10 different drugs approved by the U.S. Food and Drug Administration that have demonstrated immune checkpoint inhibition targeting the programmed cell death ligand-1/programmed cell death protein-1 signaling, CTLA-4/CD28, TIGIT/PVR, and CD47/SIRPα pathways, as well as three repurposed drugs, 11 candidate drugs, and nine drugs in combination with monoclonal antibodies that are in various phases of clinical trials.

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337
Review Article Open Access
Coskun Ozer Demirtas, Yusuf Yilmaz
Published online September 19, 2024
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2024.00257
Abstract
Chronic liver disease (CLD) represents a significant global health burden, with hepatic steatosis-associated disorders—such as metabolic dysfunction-associated steatohepatitis (MASH), [...] Read more.

Chronic liver disease (CLD) represents a significant global health burden, with hepatic steatosis-associated disorders—such as metabolic dysfunction-associated steatohepatitis (MASH), alcoholic liver disease, and hepatitis C virus infection—being major contributors. Recent genome-wide association studies have identified the rs72613567:TA variant in the 17-beta-hydroxysteroid dehydrogenase 13 (HSD17B13) gene as a protective factor against the development and progression of these conditions. In this review, we summarized the current evidence surrounding the HSD17B13 rs72613567 variant, aiming to elucidate its impact on CLD risk and outcomes, and to explore the potential mechanisms behind its hepatoprotective effects. The rs72613567:TA variant induces a splice donor site mutation, resulting in a truncated, non-functional HSD17B13 protein. Numerous studies have demonstrated that this loss-of-function mutation confers protection against the development of cirrhosis and hepatocellular carcinoma (HCC) in patients with MASH, alcoholic liver disease, and hepatitis C virus infection. Moreover, the rs72613567:TA variant has been associated with reduced liver enzyme levels and improved survival in HCC patients. Integrating this variant into genetic risk scores has shown promise in predicting the progression of fatty liver disease to cirrhosis and HCC. Furthermore, inhibiting HSD17B13 expression through RNA interference and small molecule inhibitors has emerged as a potential therapeutic strategy for MASH. However, the precise molecular mechanisms underlying the hepatoprotective effects of the HSD17B13 rs72613567 variant remain to be fully elucidated. Future research should focus on clarifying the structure-function relationship of HSD17B13 and its role in liver pathophysiology to facilitate the development of targeted therapies for CLD associated with hepatic steatosis.

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338
Review Article Open Access
Danmei Zhang, Chunxia Shi, Yukun Wang, Jin Guo, Zuojiong Gong
Published online September 19, 2024
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2024.00203
Abstract
Liver failure encompasses a range of severe clinical syndromes resulting from the deterioration of liver function, triggered by factors both within and outside the liver. While [...] Read more.

Liver failure encompasses a range of severe clinical syndromes resulting from the deterioration of liver function, triggered by factors both within and outside the liver. While the definition of acute-on-chronic liver failure (ACLF) may vary by region, it is universally recognized for its association with multiorgan failure, a robust inflammatory response, and high short-term mortality rates. Recent advances in metabolomics have provided insights into energy metabolism and metabolite alterations specific to ACLF. Additionally, immunometabolism is increasingly acknowledged as a pivotal mechanism in regulating immune cell functions. Therefore, understanding the energy metabolism pathways involved in ACLF and investigating how metabolite imbalances affect immune cell functionality are crucial for developing effective treatment strategies for ACLF. This review methodically examined the immune and metabolic states of ACLF patients and elucidated how alterations in metabolites impact immune functions, offering novel perspectives for immune regulation and therapeutic management of liver failure.

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339
Review Article Open Access
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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340
Original Article Open Access
Noor Al Deen A. Elazazi, Mohamed Eltabbakh, Hend Mubarak Hussein, Yasmeen M. Mahmood, Reda Elwakil
Published online September 19, 2024
Journal of Translational Gastroenterology. doi:10.14218/JTG.2023.00087
Abstract
The treatment of Helicobacter pylori (H. pylori) infection remains a challenge due to the increasing prevalence of drug-resistant bacteria. It is hypothesized that using more potent [...] Read more.

The treatment of Helicobacter pylori (H. pylori) infection remains a challenge due to the increasing prevalence of drug-resistant bacteria. It is hypothesized that using more potent acid suppressants, such as potassium-competitive acid blockers (P-CABs) like Vonoprazan, may improve eradication rates. The aim of this study was to compare the effectiveness of H. pylori eradication regimens containing Vonoprazan with those containing proton pump inhibitors for H. pylori infection.

Two hundred and thirty-two patients were assigned to two groups. Group I (treatment-naïve) included: Arm 1 (intervention arm) with 58 patients who received Clarithromycin 500 mg twice daily, Amoxicillin 1 mg twice daily, and Vonoprazan 20 mg twice daily; and Arm 2 (comparator arm) with 58 patients who received Clarithromycin 500 mg twice daily, Amoxicillin 1 mg twice daily, and Esomeprazole 20 mg twice daily. Group II (treatment-experienced) included: Arm 3 (intervention arm) with 58 patients who received Levofloxacin 500 mg once daily, Vonoprazan 20 mg twice daily, Nitazoxanide 500 mg twice daily, and Doxycycline 100 mg once daily; and Arm 4 (comparator) with 58 patients who received Levofloxacin 500 mg once daily, Esomeprazole 20 mg twice daily, Nitazoxanide 500 mg twice daily, and Doxycycline 100 mg once daily. All patients received their treatment regimens for 14 days. H. pylori eradication was assessed four weeks after treatment.

The successful eradication rate was higher in Arm 1 (58.6%) compared to Arm 2 (50%), and higher in Arm 3 (50%) compared to Arm 4 (43.1%). H. pylori eradication regimens including P-CABs were well-tolerated with a low incidence of adverse events.

The results of P-CAB-based eradication regimens are comparable to those of proton pump inhibitor-based regimens.

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