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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
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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.

Full article
Letter to the Editor Open Access
Sanjoy Majumder, Rutupurna Das, Annapurna Sahoo, Kunja Bihari Satapathy, Gagan Kumar Panigrahi
Published online November 11, 2024
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Gene Expression. doi:10.14218/GE.2024.00058
Original Article Open Access
Qiuyu Cheng, Yunhui Liu, Zhongyuan Yang, Meng Zhang, Tingting Liu, Yuxin Niu, Wei Liu, Lanyue Huang, Yuzhao Feng, Xiaoyun Zhang, Xiaoping Luo, Qin Ning, Tao Chen
Published online December 12, 2024
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Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2024.00413
Abstract
The performance of neurodegenerative biomarkers—neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), tau, and ubiquitin carboxy-terminal hydrolase L1 (UCHL1)—in [...] Read more.

The performance of neurodegenerative biomarkers—neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), tau, and ubiquitin carboxy-terminal hydrolase L1 (UCHL1)—in diagnosing minimal hepatic encephalopathy (MHE) has not been systematically evaluated, simultaneously, nor have their associations with the development of overt hepatic encephalopathy (OHE). This study aimed to evaluate the performance of plasma NfL, GFAP, tau, and UCHL1 in diagnosing MHE and predicting the development of OHE in Chinese patients with hepatic cirrhosis.

In this prospective study, 124 patients with hepatic cirrhosis were recruited. The Psychometric Hepatic Encephalopathy Score was used to diagnose MHE, and OHE development was observed during a 30-day follow-up period. Plasma levels of NfL, GFAP, tau, and UCHL1 were measured using the highly sensitive single-molecule array when MHE was diagnosed. Additionally, serum interleukin-6 (IL-6) levels and the model for end-stage liver disease (MELD) and MELD-Na scores were also measured.

MHE was diagnosed in 57 (46.0%) patients. Patients with MHE had significantly higher plasma levels of NfL and GFAP (34.2 vs. 22.4 pg/mL and 173 vs. 97.6 pg/mL, respectively; both p < 0.001) and lower tau levels (8.4 vs. 11.6 pg/mL, p = 0.048) compared to those without MHE. Plasma NfL (odds ratios = 1.027, 95% confidence interval [CI]: 1.006–1.048; p = 0.013) and serum ammonia levels (odds ratios = 1.021, 95% CI: 1.006–1.036; p = 0.007) were independently associated with MHE occurrence. A combination of NfL, GFAP, tau, and UCHL1 was effective in diagnosing MHE in all cirrhotic patients (area under the receiver operating characteristic curve [hereinafter referred to as AUROC]: 0.748, 95% CI: 0.662–0.821), with an accuracy, sensitivity, and specificity of 71.0%, 71.9%, and 71.6%, respectively. In patients without previous OHE, the combination had an AUROC of 0.764 (95% CI: 0.673–0.840), with an accuracy, sensitivity, and specificity of 72.5%, 71.7%, and 73.0%, respectively. Furthermore, GFAP (hazard ratio (HR) = 1.003, 95% CI: 1.000–1.005; p = 0.044), IL-6 (HR = 1.003, 95% CI: 1.001–1.004; p < 0.001), and MELD score (HR = 1.139, 95% CI: 1.072–1.210; p < 0.001)—but not NfL, tau, and UCHL1—were identified as risk factors for 30-day OHE development.

The combination of plasma levels of NfL, GFAP, tau, and UCHL1 performs well in diagnosing MHE. Additionally, MELD score, IL-6, and GFAP appear to be significant predictors of OHE development in patients with hepatic cirrhosis.

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Review Article Open Access
Parvin Babaei, Niloofar Faraji, Kimia Eyvani
Published online April 28, 2025
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Gene Expression. doi:10.14218/GE.2024.00080
Abstract
The proto-oncogene c-Fos is known as a reliable marker of cell activation, which is immediately induced after a new stimulus in specific brain regions, depending on the nature of [...] Read more.

The proto-oncogene c-Fos is known as a reliable marker of cell activation, which is immediately induced after a new stimulus in specific brain regions, depending on the nature of the stimulus applied. However, the expression of c-Fos is increased in Alzheimer’s disease (AD) and contributes to amyloid β-peptide-induced neurotoxicity. This review attempted to focus on the role of c-Fos in learning and memory in both healthy brain and AD, emphasizing on possible mechanisms. Comparing the available findings, regarding learning and memory, c-Fos expression leads to memory formation through ERK (extracellular signal-regulated kinase)/CREB (cAMP response element-binding protein) and long-term potentiation, while it is down regulated after the repetition and habituation of stimuli. However, its overexpression in neurons and glia of AD, contributes to cognitive deficits and neuronal loss, which represents a defect in its ability to habituate to repeated stimuli. Also, expression pattern in glial is associated with constitutive CREB activation following increasing amyloid beta (Aβ), activation transcription factor (ATF3), and cytochrome c in apoptosis pathways. Thus, two contradictory roles of c-Fos in the healthy brain and AD, reveal more complexity in c-Fos up and down stream signaling pathways, bioavailability, and sensitivity. Future studies focusing on c-Fos modulation, might offer promising strategies to mitigate cognitive decline in AD.

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Review Article Open Access
Ciro Comparetto, Franco Borruto
Published online March 30, 2025
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Cancer Screening and Prevention. doi:10.14218/CSP.2024.00032
Abstract
Breast cancer remains one of the leading causes of cancer-related deaths worldwide. Early detection of breast cancer significantly improves outcomes and survival rates, minimizing [...] Read more.

Breast cancer remains one of the leading causes of cancer-related deaths worldwide. Early detection of breast cancer significantly improves outcomes and survival rates, minimizing treatments. Imaging techniques are critical in identifying abnormalities and diagnosing breast cancer at its earliest stages, often before clinical symptoms emerge. Mammography remains standard for screening in average-risk women, while supplementary methods like ultrasound, magnetic resonance imaging, and tomosynthesis enhance detection rates, particularly in women with dense breasts or those at high risk. Given that certain factors, such as family history, age, genetic mutations, and breast density, affect the risk of developing breast cancer, some women may benefit from earlier or more frequent screenings. Personalized screening protocols are becoming more common, tailoring the type and frequency of imaging to the individual’s risk profile. Newer technologies, such as molecular breast imaging and contrast-enhanced mammography show promise but require further validation for widespread use. In conclusion, imaging techniques including mammography, ultrasound, magnetic resonance imaging, and newer technologies like three-dimensional mammography and molecular breast imaging are essential tools in the early detection of breast cancer, leading to better outcomes for patients. This literature review provides an overview of current breast cancer imaging methods, their role in early diagnosis, and their effectiveness and limitations.

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Review Article Open Access
Wanchun Zhu, Yu Cui, Jiahao Qiu, Xin Zhang, Yueqiu Gao, Zhi Shang, Lingying Huang
Published online July 15, 2025
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Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2025.00029
Abstract
Liver fibrosis is a pathological process resulting from various chronic liver injuries that lead to the formation of liver fibrous scars. It can further progress to cirrhosis and [...] Read more.

Liver fibrosis is a pathological process resulting from various chronic liver injuries that lead to the formation of liver fibrous scars. It can further progress to cirrhosis and even liver cancer. Currently, there are no effective drugs specifically approved for the treatment of liver fibrosis; etiological therapy remains the main treatment strategy. Therefore, it is necessary to develop anti-fibrotic drugs targeting different pathways involved in liver fibrosis. Transforming growth factor-beta (TGF-β) is a key driver of fibrosis, and targeting TGF-β can effectively reduce liver fibrosis. In this review, we discussed the anti-liver fibrosis effects of TGF-β inhibitors through different signaling pathways, including the application of certain active ingredients from Traditional Chinese Medicine.

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Original Article Open Access
Chuang Lian, Te Zhang, Peng Cheng, Longyun Li, Guoqing Zhao, Xuli Ren
Published online November 15, 2024
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Exploratory Research and Hypothesis in Medicine. doi:10.14218/ERHM.2024.00029
Abstract
Aquaporin-4 (AQP4) plays a crucial role in the glymphatic system and is vital for maintaining homeostasis in the central nervous system. This study aimed to investigate the effects [...] Read more.

Aquaporin-4 (AQP4) plays a crucial role in the glymphatic system and is vital for maintaining homeostasis in the central nervous system. This study aimed to investigate the effects of N-(1,3,4-thiadiazol-2-yl)-3-pyridinecarboxamide (TGN-020), a selective AQP4 inhibitor, on glymphatic function and to assess its impact on short-term behavior in mice.

In this laboratory study, mice were randomly assigned to TGN-020-treated and control groups. We evaluated glymphatic function by measuring the distribution of Evans blue dye in the brain following injection into the cisterna magna. Behavioral assessment of cognitive function was performed using open field and Morris water maze tests. AQP4 protein expression levels were analyzed via immunohistochemistry. Statistical comparisons were conducted using the one-way analysis of variance to evaluate the results among groups.

Our findings revealed that the areas of Evans blue dye in the dorsal (p < 0.001) and ventral (p < 0.001) surfaces of the brain were significantly reduced in the TGN-020 group compared to the control group, indicating impaired glymphatic function. However, behavioral tests demonstrated no significant short-term changes; the mean distance traveled in the open field was 4,345 cm in the control group and 4,049 cm in the TGN-020 group (p = 0.5625), while the mean speed was 2.649 cm/s for controls and 2.868 cm/s for the TGN-020 group (p = 0.6762). In the Morris water maze, latency was comparable (36.33 s for TGN-020 vs. 34.89 s for controls, p = 0.758). Additionally, no significant differences in AQP4 expression intensity were observed between the two groups.

Our study demonstrates that acute inhibition of AQP4 through a single dose of TGN-020 significantly impairs glymphatic function without inducing short-term behavioral abnormalities in mice. These findings contribute to understanding AQP4’s role in the glymphatic system and its potential implications for neurological function.

Full article
Original Article Open Access
Chunru Gu, Liyan Dong, Lu Chai, Zhenhua Tong, Fangbo Gao, Walter Ageno, Fernando Gomes Romeiro, Xingshun Qi
Published online November 21, 2024
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Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2024.00226
Abstract
Coronary artery disease (CAD) is increasingly observed in patients with liver cirrhosis. However, data on the incidence and prevalence of CAD in cirrhotic patients are heterogeneous, [...] Read more.

Coronary artery disease (CAD) is increasingly observed in patients with liver cirrhosis. However, data on the incidence and prevalence of CAD in cirrhotic patients are heterogeneous, and the association remains uncertain. In this study, we aimed to conduct a systematic review and meta-analysis to address these issues.

PubMed, EMBASE, and Cochrane Library databases were searched. Incidence, prevalence, and factors associated with CAD were pooled using a random-effects model. Risk ratio (RR) and odds ratio (OR), with their 95% confidence interval (CI), were calculated to evaluate differences in CAD incidence and prevalence between patients with and without liver cirrhosis.

Fifty-one studies were included. The pooled incidences of CAD, acute coronary syndromes, and myocardial infarction (MI) were 2.28%, 2.02%, and 1.80%, respectively. Liver cirrhosis was not significantly associated with CAD incidence (RR = 0.77; 95% CI = 0.46–1.28) or MI (RR = 0.87; 95% CI = 0.49–1.57). The pooled prevalence of CAD, acute coronary syndromes, and MI was 18.87%, 12.54%, and 6.12%, respectively. Liver cirrhosis was not significantly associated with CAD prevalence (OR = 1.29; 95% CI = 0.83–2.01) or MI (OR = 0.58; 95% CI = 0.28–1.22). Non-alcoholic steatohepatitis, hepatitis C virus, advanced age, male sex, diabetes mellitus, hypertension, hyperlipidemia, smoking history, and family history of CAD were significantly associated with CAD in cirrhotic patients.

CAD is common in cirrhotic patients, but cirrhosis itself may not be associated with an increased CAD risk. In addition to traditional risk factors, non-alcoholic steatohepatitis and hepatitis C virus infection are also associated with CAD presence in cirrhotic patients.

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Illuminating and Instructive Clinical Case Open Access
Junmin Jiang, Meifeng Shi, Shuduo Wu, Minling Cao
Published online October 30, 2024
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Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2024.00287
Abstract
Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonists are increasingly used in the management of type 2 diabetes mellitus and [...] Read more.

Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonists are increasingly used in the management of type 2 diabetes mellitus and obesity due to their ability to stimulate insulin secretion, delay gastric emptying, and suppress appetite. The combination of GLP-1 and GIP agonists improves glycemic control and promotes weight loss. However, the introduction of these novel therapies has raised safety concerns, including the risk of cholestatic hepatitis. We report a case of a patient with obesity who was prescribed a GLP-1/GIP dual-receptor agonist as part of his treatment regimen. Importantly, both before the initiation of this therapy and during the course of treatment, the patient was not taking any other medications. Shortly after receiving four doses of the therapy, the patient developed symptoms of severe cholestatic hepatitis, including jaundice and elevated liver enzyme levels. During hospitalization, no alternative causes for the condition were identified, and a liver biopsy confirmed the diagnosis of drug-induced cholestatic hepatitis. This is the first recorded case of cholestatic hepatitis induced by a GLP-1/GIP dual agonist, and it aimed to raise global awareness of this potential side effect.

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Mini Review Open Access
Alden Miller, Charmi Patel, Jingjing Hu
Published online April 24, 2025
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Journal of Translational Gastroenterology. doi:10.14218/JTG.2024.00025
Abstract
Microscopic colitis is a chronic inflammatory disease of the colon that describes patients who present with watery diarrhea, normal or minimal endoscopic findings, and chronic inflammation [...] Read more.

Microscopic colitis is a chronic inflammatory disease of the colon that describes patients who present with watery diarrhea, normal or minimal endoscopic findings, and chronic inflammation identified on colonic biopsy. As the name suggests, microscopic colitis requires histologic evaluation for diagnosis. The two most well-established histologic patterns are collagenous colitis and lymphocytic colitis. In this review, we highlighted the key histologic features of microscopic colitis on biopsy specimens, along with its endoscopic findings, pathogenesis, and underlying molecular mechanisms. We also discussed important mimickers—including amyloidosis, collagenous colitis, ischemic colitis, and radiation colitis—emphasizing their distinguishing histopathologic characteristics. Recognizing these mimickers is crucial, as their treatment strategies are significantly different.

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