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621
Editorial Open Access
Ruiwen Zhang
Published online December 25, 2023
Oncology Advances. doi:10.14218/OnA.2023.00024
622
Case Report Open Access
Mitchell Zhao, Alfredo Molinolo, Vera Vavinskaya, Charmi Patel, Richard Wong, Jingjing Hu
Published online December 25, 2023
Journal of Translational Gastroenterology. doi:10.14218/JTG.2023.00019
Abstract
The appendix, while a small portion of the gastrointestinal tract, can give rise to a variety of tumors. Goblet cell adenocarcinoma is an amphicrine tumor with both glandular and [...] Read more.

The appendix, while a small portion of the gastrointestinal tract, can give rise to a variety of tumors. Goblet cell adenocarcinoma is an amphicrine tumor with both glandular and neuroendocrine features, and a molecular profile different from that of neuroendocrine tumors and conventional appendiceal adenocarcinomas. Low-grade appendiceal mucinous neoplasm is a tumor with low-grade cytology and histological findings that can mimic other benign entities. Here, we present a case of goblet cell adenocarcinoma that was associated with a ruptured diverticulum mimicking low-grade appendiceal neoplasm, and we review the available literature on these tumors.

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623
Original Article Open Access
Polyana Bárbara Freese Carneiro, Evelyn Angrevski Rodrigues, Lucas Delfino Lampugnani, Karen Nayara de Souza Braz, Gabriel Sousa Almeida Assunção, Camila Costa de Oliveira, Diogo Albino de Queiroz, Airton Rossini, Érico Folchini da Silveira, Pâmela Alegranci, Eveline Aparecida Isquierdo Fonseca de Queiroz
Published online December 25, 2023
Cancer Screening and Prevention. doi:10.14218/CSP.2023.00009S
Abstract
Obesity is a chronic metabolic disease associated with the development of several other diseases, including cancer. The present study aims to evaluate the eating habits, physical [...] Read more.

Obesity is a chronic metabolic disease associated with the development of several other diseases, including cancer. The present study aims to evaluate the eating habits, physical activity, and clinical profiles of colorectal cancer (CRC) patients with overweight/obesity.

A cross-sectional study was conducted with data collected from the medical records of patients diagnosed with CRC (n = 41) from June 2019 to June 2022. Additionally, a questionnaire (n = 35) was applied to gather information on eating habits and physical activity. The data were subdivided into two groups of CRC patients: eutrophic and overweight/obesity. The results were presented as frequency distribution in percentage (%), mean ± standard deviation, or median and interquartile range.

All patients presented adenocarcinoma-type; most were in stages 3 and 4 and underwent surgery and chemotherapy. The overweight/obesity group showed a higher prevalence of metastasis, recurrence, and death compared to the eutrophic group. Ninety-six percent of patients demonstrated the need to reevaluate their eating habits, and the overweight/obesity group presented a significantly lower consumption of vegetables. Walking was the most commonly practiced physical activity both before and after diagnosis. However, both groups experienced a reduction in physical activity after CRC diagnosis, especially in the overweight/obesity group, in which both the frequency (p = 0.001) and duration of physical activity (p = 0.0005) significantly decreased.

Overweight/obese individuals are associated with a worse clinical profile, which can be associated with unhealthy habits, low consumption of vegetables, and low physical activity.

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624
Commentary Open Access
Xiaolei Zhao, Fenghai Zhou, Wenxue Ma
Published online December 25, 2023
Oncology Advances. doi:10.14218/OnA.2023.00036
625
Mini Review Open Access
Yan Gao, Sara E. Monaco, Ruth L. Katz, Y. Helen Zhang
Published online December 23, 2023
Journal of Clinical and Translational Pathology. doi:10.14218/JCTP.2023.00044
Abstract
Lymph node fine needle aspiration biopsy (FNAB) is a useful diagnostic tool in the initial evaluation of lymphadenopathy of unknown etiology. The World Health Organization (WHO) [...] Read more.

Lymph node fine needle aspiration biopsy (FNAB) is a useful diagnostic tool in the initial evaluation of lymphadenopathy of unknown etiology. The World Health Organization (WHO) Reporting System for lymph node cytopathology comprises five categories: insufficient/inadequate/nondiagnostic, benign, atypical, suspicious for malignancy, and malignant. This review focuses on the diagnostic criteria for each category, including cytomorphology, ancillary studies, differential diagnosis, and associated risk of malignancy. Its primary goal is to standardize the reporting and interpretation of lymph node samples, minimizing interobserver variability among pathologists. By establishing clear guidelines and standardized terminology, this system improves communication between pathologists and clinicians, leading to enhanced consistency, accuracy, and patient care in lymph node specimen evaluation. The WHO Reporting System serves as a unified and reproducible framework for the precise categorization of lymph node aspirates, enabling better communication between cytopathologists and clinicians and ultimately facilitating more effective patient management.

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626
Review Article Open Access
Jaimy Villavicencio Kim, George Y. Wu
Published online December 21, 2023
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2023.00265
Abstract
Focal nodular hyperplasia is a benign tumor of the liver that is often found incidentally with imaging. The purpose of this review is to discuss the pathophysiology, rare complications [...] Read more.

Focal nodular hyperplasia is a benign tumor of the liver that is often found incidentally with imaging. The purpose of this review is to discuss the pathophysiology, rare complications that can occur due to these lesions, and management options. A literature review was performed on clinical trials and case reports involving focal nodular hyperplasia complications and management of these, as well as the proposed pathogenesis underlying these tumors. Although exposure to oral contraceptive pills and endogenous hormones have been thought to play a role in the development of these lesions, this has not been proven. Most recently, they are thought to arise as a consequence of a vascular anomaly causing alterations in the expression of angiopoietin genes. Complications are rare, but previous cases have reported associated pain, rupture and compression of nearby structures (hepatic vein, stomach, biliary system). Resection of focal nodular hyperplasia is not usually recommended. However, if there is associated pain with no other identifiable cause or presence of a large or growing lesion with risk of causing a complication, then surgical resection, radiofrequency ablation or arterial embolization should be considered.

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627
Original Article Open Access
Nilton Carlos Machado, Juliana Tedesco Dias, Thabata Koester Weber, Andrea Catherine Quiroz Gamarra, Mary de Assis Carvalho
Published online December 21, 2023
Journal of Translational Gastroenterology. doi:10.14218/JTG.2023.00029
Abstract
Functional constipation (FC) and the overweight/obesity (O/O) association are controversial. This study aims to investigate the prevalence of O/O, demographics, and clinical characteristics [...] Read more.

Functional constipation (FC) and the overweight/obesity (O/O) association are controversial. This study aims to investigate the prevalence of O/O, demographics, and clinical characteristics between children with O/O and normal BMIs, and establish whether O/O constitutes a clinical subgroup.

Retrospective observational study of children/adolescents referred for evaluation of constipation. Inclusion criteria: age between 01–192 months; diagnosis of FC according to the Rome Criteria III-IV; Bristol Stool Form 1 or 2.

450 FC children/adolescents were divided into three subgroups. In total, 34.4% had O/O. The proportion of overweight/obese children increased four times in the 61–192 subgroup (43.1%). Evaluation of subgroups: There was no significant difference in family factors, and there was a high presence of straining and painful defecation in the three subgroups. Evaluating O/O and normal BMI within each subgroup showed no significant difference for most variables. The statistical analysis of the comparisons of bowel movement characteristics between the O/O and normal BMI groups within each subgroup established that the normal BMI group had a higher presence of straining on defecation, blood in stools, and scybalous stools. In comparing BMI z scores, they were higher in the normal BMI group within the 25–60 subgroup than the 61–192 subgroup (p < 0.01).

The proportion of overweight/obese children rises after five years old. There was no substantial difference in the clinical characteristics between overweight/obese and normal BMI children. However, the normal BMI group was more symptomatic than the O/O group. This study, therefore, does not document a distinct subgroup of O/O in FC, and probably no difference between developed and developing countries regarding FC and O/O.

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628
Editorial Open Access
Daiming Fan
Published online December 21, 2023
Future Integrative Medicine. doi:10.14218/FIM.2023.00000
629
Reviewer Acknowledgement Open Access
Editorial Office of Exploratory Research and Hypothesis in Medicine
Published online December 20, 2023
Exploratory Research and Hypothesis in Medicine. doi:10.14218/ERHM.2023.000RA
630
Review Article Open Access
Minhua Wang, Ashish Chandra, Guoping Cai
Published online December 20, 2023
Journal of Clinical and Translational Pathology. doi:10.14218/JCTP.2023.00025
Abstract
The International System (TIS) for reporting serous fluid cytopathology was published in December 2020 as a joint project by the International Academy of Cytology and the American [...] Read more.

The International System (TIS) for reporting serous fluid cytopathology was published in December 2020 as a joint project by the International Academy of Cytology and the American Society of Cytopathology. The purpose was to standardize the diagnostic criteria and nomenclature used in reporting serous fluid samples, thereby improving the reproducibility of reports and improving communication between pathologists and clinicians. TIS defines a five-tier system consisting of nondiagnostic, negative for malignancy, atypia of uncertain significance, suspicious for malignancy and malignant categories. This review provides an updated summary of the reporting system, risk of malignancy, potential diagnostic pitfalls, and a practical diagnostic approach to serous fluid specimens.

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631
Editorial Open Access
Editorial Office
Published online December 19, 2023
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2023.00001
632
Review Article Open Access
Xiang Liu, Emily Weng, Murali Dharan
Published online December 19, 2023
Journal of Translational Gastroenterology. doi:10.14218/JTG.2023.00020
Abstract
Helicobacter pylori (H. pylori) is an exceptionally common human pathogen infecting a large proportion of the world’s population. It is known to cause gastritis, peptic ulcer disease, [...] Read more.

Helicobacter pylori (H. pylori) is an exceptionally common human pathogen infecting a large proportion of the world’s population. It is known to cause gastritis, peptic ulcer disease, non- cardiac gastric adenocarcinoma, and gastric mucosa-assisted lymphoid tissue lymphoma. Test and treat is a widely practiced strategy for H. pylori infection worldwide. While there are clear benefits of treating H. pylori infection, long-term adverse consequences of widespread eradication of this commonly identified pathogen remain an area of much debate. H. pylori infection affects gastric acid secretion and the relationships of the infection with gastroesophageal reflux disease (GERD), Barrett’s esophagus (BE), and esophageal adenocarcinoma (EAC) have been studied but remain controversial topics. Review of the most up-to-date evidence from studies performed in the last 20 years suggests a possible inverse relationship between the prevalence of H. pylori infection and GERD. A meta-analysis of a randomized controlled trial showed that eradication of the infection was more likely to cause increased incidence of GERD. Additionally, other studies have noted a significant protective effect of H. pylori infection, notably Cag A+ strains, against the development of BE and EAC. In this review article, we will discuss the impact of H. pylori infection status on GERD, BE, and esophageal cancer.

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633
Review Article Open Access
Anastasia A. Zabolotneva, Olga P. Shatova, Peter V. Shegai, Aleksandr V. Shestopalov
Published online December 19, 2023
Oncology Advances. doi:10.14218/OnA.2023.00014
Abstract
Tumors interact with various populations of nonmalignant cells, such as endothelial, stromal, and immune cells, to create a favorable tumor microenvironment (TME) for invasion and [...] Read more.

Tumors interact with various populations of nonmalignant cells, such as endothelial, stromal, and immune cells, to create a favorable tumor microenvironment (TME) for invasion and metastasis of cancer cells. A key mechanism for maintaining the pro-oncogenic properties of the TME is the formation of an immunosuppressive environment that allows the tumor to avoid an immune response. A strictly immunosuppressive environment is supported mainly by the activity of engaged immune cells that secrete inflammatory cytokines and factors that inhibit the function of cytotoxic T lymphocytes. On the other hand, the activity of tumor-associated immune cells depends not only on cancer-cell signals but also on microbial metabolites derived from the gut microbiota. The gut microbiota consists of bacteria, viruses, protozoans, archaea, and fungi that influence the host immune response, DNA damage, and chronic inflammation in gastrointestinal and other cancers, such as breast cancer. In particular, intestinal dysbiosis can lead to restructuring of the TME and the promotion of tumor growth. Recently, a wide spectrum of bacterial metabolites, such as short-chain fatty acids, tryptophan catabolites, secondary bile acids, etc., have been shown to have a signaling function that affects not only the formation of the TME but also the response of cancer cells to therapeutic agents, including immunotherapy. Therefore, studying the effects of microbiota metabolites in relation to cancer development and cancer therapy effectiveness is strictly necessary. In this review, we briefly describe key microbiota factors that influence the formation of immunosuppressive TMEs.

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634
Original Article Open Access
Kai Yan, Wei Dong, Xiaowei Li, Zhe Han, Si Li, Guoyi Wu, Haibin Zhang, Yong Fu
Published online December 19, 2023
Cancer Screening and Prevention. doi:10.14218/CSP.2023.00037
Abstract
Although many patients with hepatocellular carcinoma (HCC) achieved significant prognostic improvement through surgical treatment, rapid and aggressive intrahepatic dissemination [...] Read more.

Although many patients with hepatocellular carcinoma (HCC) achieved significant prognostic improvement through surgical treatment, rapid and aggressive intrahepatic dissemination within months after radical resection was occasionally encountered. To date, there has been no dedicated literature addressing this phenomenon.

In this case-control study, we proposed the concept of early explosive recurrence (EER), which was defined as simultaneous development of no less than three recurrent lesions involving at least three different Couinaud’s segments within 6 months following radical resection. A total of 325 patients (17 EER patients and 308 controls) were retrospectively reviewed.

The incidence of EER of early HCC patients was 5.2%. EER was manifested as either multiple nodular (n = 11) or diffusely infiltrative type (n = 6). EER patients had significantly worse survival (hazards ratio, 48.7; 95% confidence interval: 19.9, 119.0). At multivariate analysis, increased tumor number, enlarged tumor size, positive microvascular invasion (MVI) and Glypican-3 (GPC3) were significant risk factors for EER. Tumor immune microenvironment (TIME) gene expression profile analysis showed that patients with EER presented higher transcriptional levels of CCL20, NT5E, and TDO2 as well as a lower transcriptional level of HLA-DQ1. Gene set enrichment analysis revealed that gene sets involving Th1 and Th2 differentiation (p = 0.016) and Th17 cell differentiation (p = 0.049) were enriched in control group.

Some surgically treated HCC patients developed EER with poor prognosis. The clinicopathological risk factors of EER included tumor number, tumor size MVI, and GPC3. Specific TIME profiles facilitate intrahepatic metastasis and progression of HCC.

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635
Original Article Open Access
Esen Çakmak
Published online December 18, 2023
Gene Expression. doi:10.14218/GE.2023.00088
Abstract
Colorectal cancer is one of the most significant and deadliest malignant tumors among various types of cancers. Due to its generally low overall survival rate, the development of [...] Read more.

Colorectal cancer is one of the most significant and deadliest malignant tumors among various types of cancers. Due to its generally low overall survival rate, the development of new treatment strategies for early detection and diagnosis, as well as the identification of prognostic markers, has become exceedingly crucial. The molecular mechanism of colorectal cancer remains uncertain and to address this, the aim is to identify key genes, determine in which pathways these genes are involved, explore their interactions with regulatory molecules, and investigate their overall relationship with survival and immune cell infiltration.

After selecting the databases related to colorectal cancer from the Gene Expression Omnibus database, differentially expressed genes were identified. Gene ontology and pathway analyses were then conducted for these genes, and interaction networks with proteins were constructed. Core genes were identified, and their relationship with regulatory molecules such as miRNAs and transcription factors was examined. Additionally, immune cell infiltration and survival analyses were performed.

As a result of the bioinformatic analyses, 71 differentially expressed genes were identified, which were found to overlap in four distinct microarray datasets. Among these differentially expressed genes, Krüppel-like factor 4 (KLF4), CLCA4, GUCA2B, GUCA2A, LGR5, SLC4A4, ZG16, CA7, CA2, and GCG were determined as hub genes. Among the hub genes, CA2, CLCA4, SLC4A4, and KLF4 genes showed a positive correlation with immune cells in immune cell infiltration analyses. The expression levels of these four genes were also confirmed using data from the Human Protein Atlas database. Additionally, only the KLF4 gene was associated with poor prognosis in overall survival analyses.

The obtained results suggest that the KLF4 gene may serve as a potential therapeutic agent.

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636
Opinion Open Access
Ivan V. Maksimovich
Published online December 18, 2023
Exploratory Research and Hypothesis in Medicine. doi:10.14218/ERHM.2023.00080
637
Original Article Open Access
Abinit Saha, Devlina Chakravarty, Soumyananda Chakraborti
Published online December 14, 2023
Gene Expression. doi:10.14218/GE.2023.00043
Abstract
The cyclic adenosine monophosphate Receptor Protein of Mycobacterium tuberculosis (CRPMt) (Rv3676), is a global transcriptional regulator and plays a pivotal role in the survival [...] Read more.

The cyclic adenosine monophosphate Receptor Protein of Mycobacterium tuberculosis (CRPMt) (Rv3676), is a global transcriptional regulator and plays a pivotal role in the survival and infection of Mycobacterium. This signaling protein (CRPMt) shares several common structural and functional features with the CRP from Escherichia coli. Structurally, CRPMt is a homodimer that undergoes allosteric changes upon cyclic AMP binding. This binding also triggers the activation of several genes responsible for various physiological processes in this bacterium. Despite the importance of CRP for mycobacterial survival, limited information is available regarding the stability and unfolding properties of the protein. The main objective of this study is to study stability, unfolding and dynamics of CRPMT in terms of its structure.

In this study, we monitored the stability and unfolding of CRPMt using various biophysical and computational techniques.

We experimentally studied protein unfolding in the presence of chemical denaturants [urea and guanidine hydrochloride (GdnHCl)]. The results from these chemical-induced unfolding studies suggest that CRPMt follows a two-state transition and that chemical-induced protein denaturation is reversible. According to circular dichroism and activity data, CRPMt structure and function were restored upon refolding. We also studied the stability and unfolding of the CRPMt protein against temperature variations and protease action (trypsin). Limited proteolysis experiments provide insights into the minimum domain structure requirement for CRPMt activity. Interestingly, temperature-induced CRPMt unfolding was completely different compared to chemical-induced unfolding. The thermal unfolding of CRPMt was found to be irreversible, leading to the formation of insoluble aggregates at elevated temperatures. To understand why the thermal unfolding of the protein differed from chemically induced unfolding, we carried out a detailed molecular dynamics simulation analysis of the protein at three different temperatures. The results from these molecular dynamics simulations mechanistically validate the significant differences between chemical and temperature-induced CRPMt unfolding.

Our study provides detailed insights into the stability and folding/unfolding properties of CRPMt, which could be useful in developing new anti-mycobacterial medicines.

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638
Editorial Open Access
Massimo Tusconi
Published online December 14, 2023
Journal of Exploratory Research in Pharmacology. doi:10.14218/JERP.2023.00018
639
Original Article Open Access
Wenjun Qi, Dandan Shi, Ruojia Zhang, Xuehong Lin, Mengxue Lü, Yuang Zhang, Jihong Pan, Wei Chen, Luna Ge, Lin Wang
Published online December 13, 2023
Exploratory Research and Hypothesis in Medicine. doi:10.14218/ERHM.2023.00054
Abstract
Cytokine storm (CS) is an acute systemic inflammatory response with limited effective interventions up to now. The treatment experience of the COVID-19 pandemic suggests great potential [...] Read more.

Cytokine storm (CS) is an acute systemic inflammatory response with limited effective interventions up to now. The treatment experience of the COVID-19 pandemic suggests great potential in the intervention of CS by herbal medicine. This study aimed to investigate whether Schisanhenol (SSH), an active component of the Chinese herbal medicine Schisandra chinensis, has the potential to inhibit CS.

The effect of SSH on nuclear factor-kappa B (NF-κB) signaling pathway activity was observed with human myeloid leukemia mononuclear Lucia (THP-1)/NF-κB cells. THP-1 and abdominal macrophages were used as cell models to observe the effect of SSH on inflammatory responses. The lipopolysaccharide-induced acute inflammatory response in mice was used to observe the effect of SSH on systemic inflammatory response and induced acute lung injury. The potential biological mechanism of SSH against inflammatory storm was explored by network pharmacology and molecular docking methods.

SSH significantly inhibited NF-κB pathway activity and suppressed macrophages and systemic inflammatory responses in mice. SSH also effectively alleviated lipopolysaccharide-induced acute lung injury. The network pharmacology results showed that estimated glomerular filtration rate, matrix metalloproteinase 9, proto-oncogene tyrosine-protein kinase Src, and mammalian target of rapamycin were potential key target proteins of SSH.

SSH has promise as a potential small molecule of Chinese medicine for clinical treatment and drug development in the inhibition of CS.

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640
Review Article Open Access
Jinjun Cheng, Guo Zhu, Miao Pan, Shunyou Gong, Jun Mo, Zenggang Pan
Published online December 13, 2023
Journal of Clinical and Translational Pathology. doi:10.14218/JCTP.2023.00027
Abstract
Histiocytic disorders are rare in childhood and often present with a wide spectrum of histological and clinical symptoms, making their diagnosis challenging. The pathological classification [...] Read more.

Histiocytic disorders are rare in childhood and often present with a wide spectrum of histological and clinical symptoms, making their diagnosis challenging. The pathological classification of histiocytic disorders has been evolving during the last few decades, and new diagnostic criteria and classifications have been recently updated. Herein, we review pediatric histiocytic disorders, focusing on the pathological features of morphology, immunophenotype, and newly discovered molecular data. These insights shed light on the pathogenesis of these disorders and may become therapeutic biomarkers.

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