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361
Systematic Review Open Access
Ida Sofie Bjerregård Petersen, Kaj Winther
Published online June 25, 2024
Future Integrative Medicine. doi:10.14218/FIM.2024.00006
Abstract
Several studies have suggested that rose hip extracts have anti-obesity potential. Conventional medicines treating obesity are followed by multiple adverse side effects and is very [...] Read more.

Several studies have suggested that rose hip extracts have anti-obesity potential. Conventional medicines treating obesity are followed by multiple adverse side effects and is very cost full to society. This makes the investigation of herbal remedies with anti-obesity effects potential highly relevant. This systematic review aims to shed light on the results of existing literature reports on the correlation between the intake of rose hip extracts and anti-obesity effects.

A systematic literature search of PubMed and Web of Science was made to localize relevant experimental literature. Nine articles met the inclusion criteria, including one in vitro study, seven in vivo animal studies, and one human trial with pre-obese subjects. All nine articles are objectively reviewed in this systematic review.

Eight out of nine articles, including the article on humans, presented significant anti-obesity effects. Though some limitations of the studies were found, including the human trial, seven possible metabolic mechanisms are suggested as the underlying cause of the significant effects.

Based on the findings of this review, rose hip extracts containing tiliroside found in the seeds have the potential to become a new herbal remedy with anti-obesity effects. Nevertheless, more research is needed to assess the effectiveness and optimal dosage of the rose hip treatment and to elucidate the underlying mechanisms of the effects.

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362
Review Article Open Access
Kamen W. Kossow, Joseph G. Bennett, Marc S. Hoffmann
Published online June 25, 2024
Oncology Advances. doi:10.14218/OnA.2024.00006
Abstract
Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of aggressive B-cell non-Hodgkin lymphoma. While a substantial fraction of patients are cured with frontline chemoimmunotherapy, [...] Read more.

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of aggressive B-cell non-Hodgkin lymphoma. While a substantial fraction of patients are cured with frontline chemoimmunotherapy, approximately 30% of cases subsequently relapse. DLBCL immune evasion and refractory disease can occur via several mechanisms: downregulation or loss of major histocompatibility complex expression, immune checkpoint activation, tumor microenvironment modulation, and resistance to apoptosis. Addressing these mechanisms of immune evasion in DLBCL has been a focus of ongoing research, leading to the exploration of new therapies. Here, we review the mechanisms of immune evasion and novel immunotherapy treatment strategies for DLBCL.

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363
Case Report Open Access
Teresa Da Cunha, Simon Abi Saleh, Murali Dharan
Published online June 25, 2024
Oncology Advances. doi:10.14218/OnA.2024.00001
Abstract
Breast cancer metastases to the lower gastrointestinal tract (small bowel and colon) are rare, but there is a growing number of case reports in the literature. The overall incidence [...] Read more.

Breast cancer metastases to the lower gastrointestinal tract (small bowel and colon) are rare, but there is a growing number of case reports in the literature. The overall incidence of this condition is not well established, and there might be underdiagnosis. The clinical presentation and endoscopic findings are often nonspecific and variable, potentially leading to misdiagnosis or underdiagnosis. Moreover, there are currently no guidelines for gastrointestinal surveillance of these patients. Given the potential diagnostic challenges, a high level of clinical suspicion is necessary. We present a clinical case to highlight subtle endoscopic findings of breast cancer metastasis to the colon, followed by a review summarizing the available literature on breast cancer metastases to the duodenum, jejunum, ileum, colon, rectum, and anus focusing on the clinical presentation, endoscopic features, imaging modalities, treatment, and outcome.

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364
Original Article Open Access
Md. Asad Khan, Kashif Ali, M. Moshahid A. Rizvi
Published online June 25, 2024
Cancer Screening and Prevention. doi:10.14218/CSP.2024.00003
Abstract
Infection with HPV16, a high-risk human papillomavirus (HPV), can cause cervical cancer in humans. These infections carry a high risk of morbidity and mortality globally in females. [...] Read more.

Infection with HPV16, a high-risk human papillomavirus (HPV), can cause cervical cancer in humans. These infections carry a high risk of morbidity and mortality globally in females. This study aimed to conduct an in vivo comparison of Poly (D,L-lactic-co-glycolide) (PLGA)-encapsulated peptide mixture nanoparticles and PLGA microspheres as delivery systems for vaccines.

PLGA polymers were used to form microspheres for a therapeutic vaccine against cervical cancer. The target antigens were the L1 and L2 capsid proteins and the E6 and E7 oncoproteins from HPV16. These antigens were selected based on their immunogenicity, allergenicity, and toxicity. We predicted epitopes for cytotoxic T lymphocytes (CTLs) and helper T lymphocytes. In our investigation of CTL epitopes, we employed synthetic chimeric PLGA microsphere peptides, consisting of multiple H-2Db-restricted HPV16 peptides, coupled with other immune-potentiating adjuvants as predicted by our work.

H-2Db-restricted HPV16 peptides, when administered subcutaneously, enabled CTLs to eliminate in vitro TC-1 tumor cells expressing E6 and E7 of HPV16. Additionally, TC-1 cells protected C57BL/6 mice against in vivo challenges. To address this problem, peptide-based vaccines, which are among the most effective vaccine systems, have been extensively studied. Combining peptide-based vaccinations with microsphere peptide mixture particles and delivery technologies enhances their efficacy in stimulating cellular immune responses and eliminating tumor cells.

This approach may provide a potential therapeutic candidate vaccine based on microsphere-encapsulated peptides for the prevention of cervical cancer caused by HPV.

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365
Original Article Open Access
Tania Arora, Puneet Jain, Harshita Sharma, Vikash Prashar, Randeep Singh, Arti Sharma, Harish Changotra, Jyoti Parkash
Published online June 24, 2024
Gene Expression. doi:10.14218/GE.2023.00143
Abstract
Alzheimer’s disease (AD), an enduring neurodegenerative malady, contributes significantly to dementia cases, with late-onset AD being more common than early-onset AD. Despite extensive [...] Read more.

Alzheimer’s disease (AD), an enduring neurodegenerative malady, contributes significantly to dementia cases, with late-onset AD being more common than early-onset AD. Despite extensive research to diagnose and treat AD, the intricate protein network impedes the development of efficacious drugs or targets. This study endeavored to identify previously undiscovered genetic reservoirs associated with AD progression, which could be targeted as therapeutic markers.

Employing the robust tools of R-language, we dissected vast RNA sequence datasets comprising numerous samples and thousands of genes, pinpointing potential candidates implicated in AD’s trajectory. Thus, we selected the GSE203206 dataset, which includes AD patients and non-dementia controls, based on our criteria. After normalization, RNA-Seq data was compared, and log2fold change was calculated to determine the highly dysregulated genes. Further network analysis of genes and their associated miRNA was performed to determine a characteristic change in control and patient groups.

Differential expression analysis revealed 13 dysregulated genes in AD, wherein 12 were upregulated, and one was down-regulated. Furthermore, we identified hsa-miR-30-5p as a significant miRNA associated with AD, aligning with previous studies and highlighting its high involvement.

This investigation has unveiled four novel genes and a paramount miRNA implicated in AD, thus furnishing potential targets for therapeutic interventions. These discoveries pave the way for further exploration into the intricate functions and implications of these genetic entities in AD.

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366
Original Article Open Access
Huiling Tian, Long Cheng, Yunhui Liang, Yongshen Ren
Published online June 20, 2024
Future Integrative Medicine. doi:10.14218/FIM.2024.00009
Abstract
Ulcerative colitis (UC) is a chronic autoimmune disease that mainly affects the rectum and colon. The symptoms primarily include abdominal pain, diarrhea, and bloody stools. The [...] Read more.

Ulcerative colitis (UC) is a chronic autoimmune disease that mainly affects the rectum and colon. The symptoms primarily include abdominal pain, diarrhea, and bloody stools. The incidence of UC continues to increase each year. Bear bile powder (BBP) is a well-known traditional medicine that remains in use due to its outstanding efficacy. This study aimed to elucidate the therapeutic effects and molecular mechanisms of BBP on dextran sulfate sodium (DSS)-induced UC.

DSS-induced UC model mice were created and then randomly assigned to the following groups: control, DSS-treated, 5-amino salicylic acid-treated, BBP low dose, and BBP high dose. Treatment was administered by gavage. Disease activity index, body weight loss, colon histopathology, colon length, and the expression of inflammatory cytokines were measured. Samples of the intestinal content were collected, and differences in the gut microbiota were analyzed by 16S rDNA sequencing.

The experimental results demonstrated that BBP significantly alleviated the symptoms and histopathological scores in UC mice, reduced the production of interleukin-6, interleukin-1β, tumor necrosis factor-α, malondialdehyde, nitric oxide, and myeloperoxidase, and upregulated the expression of cyclic adenosine monophosphate (cAMP), protein kinase A, and cAMP-response element binding protein. Moreover, 16S rRNA sequencing revealed that the gut microbiota of mice in the DSS-treated group was disordered compared to the control group. The abundance of gut microbiota in the treatment groups improved to varying degrees.

Together, these results indicate that BBP significantly improves the inflammatory symptoms of mice with acute colitis, which may be related to its upregulation of the cAMP/protein kinase A/cAMP-response element binding protein signaling pathway, inhibition of NOD-like receptor thermal protein domain associated protein 3 inflammasome secretion, and regulation of gut microbiota.

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367
Review Article Open Access
Anuradha Singh
Published online June 20, 2024
Future Integrative Medicine. doi:10.14218/FIM.2023.00055
Abstract
This review aims to highlight the growing burden of lifestyle diseases in India and explore the potential of herbal-based nutraceuticals as complementary or alternative management [...] Read more.

This review aims to highlight the growing burden of lifestyle diseases in India and explore the potential of herbal-based nutraceuticals as complementary or alternative management approaches. It emphasizes the need for a holistic approach to managing these diseases, acknowledging the potential of traditional remedies alongside modern medicine. Specifically, the article addresses several key points. It describes the rising prevalence of lifestyle diseases in India, providing a clear understanding of the current health landscape. Additionally, it introduces the concept of herbal-based nutraceuticals and their potential benefits in managing these diseases, offering alternative solutions. The article provides evidence-based information on popular herbal remedies such as turmeric, Ashwagandha, Indian gooseberry, Aloe vera, Neem, flaxseed, cinnamon, and green tea, offering specific examples and potential benefits. It highlights the growing awareness and increasing consumption of herbal-based nutraceuticals in India, reflecting a shift in public perception towards natural remedies. Finally, the article calls for further research to validate the efficacy and safety of these products in managing lifestyle diseases, ensuring responsible use, and promoting scientific validation.

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368
Review Article Open Access
Zhaoyu Xu, Xiuding Zhang, Jiyang Chen, Yu Shi, Shangwei Ji
Published online June 20, 2024
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2024.00137
Abstract
Acute-on-chronic liver failure (ACLF) is a distinct condition characterized by the abrupt exacerbation of pre-existing chronic liver disease, often leading to multi-organ failures [...] Read more.

Acute-on-chronic liver failure (ACLF) is a distinct condition characterized by the abrupt exacerbation of pre-existing chronic liver disease, often leading to multi-organ failures and significant short-term mortalities. Bacterial infection is one of the most frequent triggers for ACLF and a common complication following its onset. The impact of bacterial infections on the clinical course and outcome of ACLF underscores their critical role in the pathogenesis of systemic inflammation and organ failures. In addition, the evolving epidemiology and increasing prevalence of multidrug-resistant bacteria in cirrhosis and ACLF highlight the importance of appropriate empirical antibiotic use, as well as accurate and prompt microbiological diagnosis. This review provided an update on recent advances in the epidemiology, diagnosis, pathogenesis, and management of bacterial infections in ACLF.

Full article
369
Hot Topic Commentary Open Access
Feng Xue, Lai Wei
Published online June 20, 2024
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2024.00100
370
Original Article Open Access
Tao Gong, Xiao Liu, Qingyuan Li, Donald R. Branch, Melika Loriamini, Wenxian Wen, Yaoqiang Shi, Qi Tan, Bin Fan, Zhonghui Zhou, Yujia Li, Chunhui Yang, Shilin Li, Xiaoqiong Duan, Limin Chen
Published online June 20, 2024
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2024.00125
Abstract
Hepatocellular carcinoma (HCC) is a highly aggressive tumor with limited treatment options and high mortality. Senecavirus A (SVA) has shown potential in selectively targeting tumors [...] Read more.

Hepatocellular carcinoma (HCC) is a highly aggressive tumor with limited treatment options and high mortality. Senecavirus A (SVA) has shown potential in selectively targeting tumors while sparing healthy tissues. This study aimed to investigate the effects of SVA on HCC cells in vitro and in vivo and to elucidate its mechanisms of action.

The cell counting kit-8 assay and colony formation assay were conducted to examine cell proliferation. Flow cytometry and nuclear staining were employed to analyze cell cycle distribution and apoptosis occurrence. A subcutaneous tumor xenograft HCC mouse model was created in vivo using HepG2 cells, and Ki67 expression in the tumor tissues was assessed. The terminal deoxynucleotidyl transferase dUTP nick end labeling assay and hematoxylin and eosin staining were employed to evaluate HCC apoptosis and the toxicity of SVA on mouse organs.

In vitro, SVA effectively suppressed the growth of tumor cells by inducing apoptosis and cell cycle arrest. However, it did not have a notable effect on normal hepatocytes (MIHA cells). In an in vivo setting, SVA effectively suppressed the growth of HCC in a mouse model. SVA treatment resulted in a significant decrease in Ki67 expression and an increase in apoptosis of tumor cells. No notable histopathological alterations were observed in the organs of mice during SVA administration.

SVA inhibits the growth of HCC cells by inducing cell cycle arrest and apoptosis. It does not cause any noticeable toxicity to vital organs.

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371
Review Article Open Access
Qurrat Ul Ain, Rameesha Nazir, Aleeza Nawaz, Hamza Shahbaz, Areeba Dilshad, Isra Umbreen Mufti, Mariam Iftikhar
Published online June 20, 2024
Journal of Clinical and Translational Pathology. doi:10.14218/JCTP.2023.00061
Abstract
The burgeoning integration of machine learning (ML) and automation in laboratory medicine marks a significant shift, propelling the sector towards enhanced diagnostic accuracy and [...] Read more.

The burgeoning integration of machine learning (ML) and automation in laboratory medicine marks a significant shift, propelling the sector towards enhanced diagnostic accuracy and operational efficiency. This critical analysis investigates the technological paces being made to enhance the analytical precision and the efficient interpretation of complicated clinical/laboratory-based datasets. The beginning of automation, coupled with ML, ushers in an era where algorithmic expertise and predictive analytics supplement significantly elevating established diagnostic methods, thereby setting higher standards for reliability and quality in clinical laboratory testing. However, this technological advancement is not without its challenges. This review highlights several concerns about data privacy, the need for rigorous validation procedures, the difficulty of integrating new technology into primitive systems, and the continuous struggle to comply with guidelines. Financial constraints exacerbate these issues, particularly in settings with limited resources in developing and underdeveloped countries. To address these challenges, the review presents several strategic methods, including the development of international guidelines for algorithmic validation, interdisciplinary collaborations to match technology developments to healthcare demands, workforce training campaigns, and the implementation of ethical guidelines for the usage of ML approaches in lab environments. The review provides a concise yet comprehensive analysis of the current situation, highlighting challenges and possible solutions associated with automation and ML in laboratory medicine. It establishes the foundation for a future anticipated to have advanced diagnostics that are also more tailored to personalized patient care.

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372
Original Article Open Access
Kingsley R. Oranuka, Calvin Chama, Ibrahim O. Adogu, Chigozie G. Okafor, George U. Eleje, Emmanuel O. Ugwu, Olumide P. Adeleke, Palmer H. Obakpororo, Kenneth O. Nnabuchi, Abdulazeez Yusuf, Nnaemeka P. Ugwu, Josephat C. Akabuike, Ahizechukwu C. Eke
Published online June 20, 2024
Exploratory Research and Hypothesis in Medicine. doi:10.14218/ERHM.2023.00015
Abstract
Malaria can be fatal during pregnancy, posing a serious risk to both mothers and fetuses, especially in sub-Saharan Africa. Primigravidae are particularly susceptible to placental [...] Read more.

Malaria can be fatal during pregnancy, posing a serious risk to both mothers and fetuses, especially in sub-Saharan Africa. Primigravidae are particularly susceptible to placental malaria in areas with high rates of transmission due to insufficient immunity. This study aimed to determine the prevalence of placental malaria infection, risk factors, types of Plasmodium causing malaria during pregnancy, and its relationship with neonatal birth weight among primigravidae.

This was an analytical cross-sectional study involving 357 primigravidae who delivered at Abubakar Tafawa Balewa University Teaching Hospital, Bauchi, Nigeria. Placental blocks were taken from the pericentric area of the maternal surface of the placenta, and the birth weights of the neonates were recorded. The samples were fixed in 10% neutral-buffered formalin, and histopathological analysis was performed. The primary outcome measure was to determine the relationship between placental malaria and neonatal birth weight. Demographics and outcomes were analyzed using standard statistical tests. Multivariable regression models accounting for potential confounders were created for the primary and secondary outcomes with adjusted odds ratios as the measures of effect.

The prevalence of placental malaria was 38.4%. Among the participants with positive placenta malaria parasitemia, 49.6%, 36.5%, and 13.9% had chronic, acute, and past placental malaria infections, respectively. Only Plasmodium falciparum was found in the placenta. According to the bivariate analysis, unbooked status (p = 0.001), non-use of intermittent preventive therapy for malaria (p < 0.001), and village dwelling (p = 0.020) were significantly associated with placental malaria. However, on multivariable logistic regression, only non-uptake of intermittent preventive therapy for malaria was independently associated with placental malaria (adjusted odds ratio, 2.2, 95% confidence interval: 1.20, 4.1, p = 0.011). There was a significant difference in the mean birth weight between those with placental malaria and those without placental malaria (2.8 ± 0.5 kg vs. 3.2 ± 0.4 kg, p = 0.001). Additionally, placental malaria was significantly associated with low birth weight among the primigravidae (p < 0.001).

In Nigeria, there is a strong correlation between low birth weight and placental malaria in Primidravidae. Placental malaria was found to be independently correlated with non-uptake of intermittent preventive therapy for malaria.

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373
Review Article Open Access
Amit Kumar Jain
Published online June 18, 2024
Cancer Screening and Prevention. doi:10.14218/CSP.2023.00029S
Abstract
Early detection of oral cancer is crucial for improving prognosis, increasing survival rates, and reducing treatment-related morbidity, considering the high mortality rate associated [...] Read more.

Early detection of oral cancer is crucial for improving prognosis, increasing survival rates, and reducing treatment-related morbidity, considering the high mortality rate associated with this condition. However, the conventional approach within communities has led to a growing exploration of different screening methods to detect potentially malignant oral disorders, with particular emphasis on imaging and artificial intelligence and their integration with conventional approaches. The article reviewed literature on oral neoplasms and early cancer detection from databases like Medline, Google Scholar, and Web of Science, mainly from 2001 to 2023. This review aims to shed light on the potential of these technologies, new ideas, and methods in improving the accuracy and effectiveness of oral cancer screening, ultimately leading to earlier detection and more successful prevention strategies, which are unmet needs, especially in underdeveloped and developing nations.

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374
Original Article Open Access
Azad Bakht, Sydney T. Cannon, Joshua D. Waltonen, Trisha M. Shattuck, Wencheng Li
Published online June 18, 2024
Journal of Clinical and Translational Pathology. doi:10.14218/JCTP.2024.00011
Abstract
Molecular testing has emerged as a valuable tool for stratifying cytologically indeterminate thyroid nodules (ITNs), with Harvey rat sarcoma viral oncogene homolog/neuroblastoma [...] Read more.

Molecular testing has emerged as a valuable tool for stratifying cytologically indeterminate thyroid nodules (ITNs), with Harvey rat sarcoma viral oncogene homolog/neuroblastoma RAS viral oncogene homolog (HRAS/NRAS) mutations being among the most prevalent molecular alterations. The study aimed to evaluate the malignancy risk of ITNs with these mutations.

We conducted a retrospective study involving ITNs (Bethesda category III and IV) that underwent ThyroSeq testing between February 2016 and January 2022. A smaller subset of ITNs also underwent Afirma testing. We specifically identified nodules with HRAS/NRAS mutations and collected radiological, clinical, histological, and follow-up data.

Our analysis identified 45 ITNs with NRAS (29 cases) and HRAS (15 cases) mutations. Of the 29 nodules with NRAS mutations, 25 underwent surgical treatment (14 total thyroidectomies and 11 hemithyroidectomies), resulting in a surgical resection rate of approximately 86%. Among the resected nodules, six were malignant, yielding a calculated risk of malignancy (ROM) ranging from 20.6% to 25%. Three of these malignant nodules were managed with total thyroidectomy, while the other three underwent hemithyroidectomy. During a follow-up period of 43.8 months for total thyroidectomy and 32.9 months for hemithyroidectomy, no recurrence or metastasis was detected among the patients. Among the four nodules treated conservatively, three remained stable, with an average follow-up duration of 34.7 months, while one patient was lost to follow-up. Regarding HRAS mutations, 15 nodules were identified, with 12 of them undergoing surgical treatment (six total thyroidectomies and 6 hemithyroidectomies), resulting in an 80% surgical resection rate. Two of the resected nodules were malignant, with a calculated ROM of 13.3% to 16.7%. Both malignant nodules were managed with total thyroidectomy, and during a follow-up period of 37.9 months, no recurrence or metastasis occurred. Of the three nodules managed conservatively, all remained stable, with an average follow-up duration of 31.1 months.

The ROM for nodules with NRAS (20.6–25%) or HRAS (13.3–16.7%) mutations was found to be low. Therefore, before opting for total thyroidectomy, conservative management, including limited resection, should be considered as a viable alternative.

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375
Opinion Open Access
376
Original Article Open Access
Anatoli D. Tahanovich, Mikalai M. Kauhanka, Elizabeth M. Barabanova, Oxana V. Gotko, Violetta I. Prokhorova
Published online June 18, 2024
Cancer Screening and Prevention. doi:10.14218/CSP.2024.00004
Abstract
Despite efforts, tumor recurrence is diagnosed in 35–40% of patients with stage III squamous cell lung carcinoma (SCLC) during the first year after treatment. The purpose of the [...] Read more.

Despite efforts, tumor recurrence is diagnosed in 35–40% of patients with stage III squamous cell lung carcinoma (SCLC) during the first year after treatment. The purpose of the present investigation was to determine the levels of cytokeratin-fragment 19 (CYFRA 21-1) in blood serum, the percentages of lymphocytes containing chemokine receptor 1 (CXCR1, %, lymphocytes), and the percentages of monocytes containing chemokine receptor 2 (CXCR2, %, monocytes), as well as their combined model before and after treatment for the early detection of recurrence.

Forty-eight patients (29 men and 19 women) with newly diagnosed stage III SCLC were examined. Serum levels of CYFRA 21-1, CXCR1, %, lymphocytes, and CXCR2, %, monocytes in peripheral blood were measured before treatment and at three weeks, three months, and six months after treatment using a chemiluminescence immunoassay analyzer and a flow cytometer, respectively.

The levels of all determined indicators, which were elevated before treatment, decreased sharply three weeks after treatment. Subsequently, three months and six months after treatment, the levels steadily increased in patients with diagnosed tumor recurrence. The differences in these indicators in three weeks to three months, three months to six months, and three weeks to six months after treatment, when included in a regression equation, corresponded to the presence of recurrence with accuracies of 83.3%, 91.7%, and 95.8%, respectively.

Determining the combination of CYFRA 21-1 levels, CXCR1, %, lymphocytes, and CXCR2, %, monocytes in the blood of patients with stage III SCLC is important for assessing the probability of recurrence after treatment.

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377
Review Article Open Access
Megan Lewis, Christopher M. Johnson
Published online June 18, 2024
Journal of Translational Gastroenterology. doi:10.14218/JTG.2023.00086
Abstract
Inflammatory bowel diseases (IBD), which include Crohn’s disease and ulcerative colitis, are chronic inflammatory disorders of the GI tract. The etiology is unclear, and most clinical [...] Read more.

Inflammatory bowel diseases (IBD), which include Crohn’s disease and ulcerative colitis, are chronic inflammatory disorders of the GI tract. The etiology is unclear, and most clinical symptoms are nonspecific, making the diagnosis and prognosis of IBD challenging as there is no gold-standard diagnostic test. Both endoscopy and imaging are essential diagnostic tools for determining disease state, location, and severity. However, the high cost and invasive nature of these tests make them unrealistic for frequent assessment. Given these limitations, laboratory testing of blood and feces has proven to be a viable alternative for routine disease monitoring. To integrate more efficient and personalized treatment strategies, new studies are consistently emerging to develop minimally invasive testing that can predict disease severity and response to available treatments. The goal is to develop better predictors of disease course, response to therapy, and therapy-related adverse events, thereby establishing a more efficient and personalized treatment strategy. This review aimed to delve into existing literature to assemble a collection of currently used biomarkers that aid in monitoring treatment response, as well as highlight select novel and combined biomarkers that hold promise for future management of IBD.

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378
Review Article Open Access
Yanna Ding, Elaine S. Jaffe
Published online June 17, 2024
Journal of Clinical and Translational Pathology. doi:10.14218/JCTP.2024.00015
Abstract
Nodular lymphocyte predominant Hodgkin lymphoma was termed “nodular lymphocyte predominant B-cell lymphoma” in the International Consensus Classification (ICC), to emphasize clinical [...] Read more.

Nodular lymphocyte predominant Hodgkin lymphoma was termed “nodular lymphocyte predominant B-cell lymphoma” in the International Consensus Classification (ICC), to emphasize clinical and biological differences from classic Hodgkin lymphoma (CHL). The abbreviation “NLP” represents both terms in the ICC and World Health Organization classifications. Variations in the growth pattern, originally reported as Fan patterns A-F, are designated as either grade 1 or grade 2 in the ICC. NLP is uncommon, and in some cases an accurate diagnosis is challenging. The objectives of this article were to review the histopathologic features of NLP and the differential diagnosis from other key entities including de novo T-cell/histiocyte-rich large B-cell lymphoma (THRLBL) and lymphocyte-rich classic Hodgkin lymphoma (LRCHL). Histologically, NLP Fan pattern E (THRLBL-like) can be indistinguishable from de novo THRLBL. However, focal nodular areas, clustering of tumor cells, presence of few admixed small B-cells or FDC meshworks, and T-cell rosettes favor NLP Fan pattern E and argue against de novo THRLBL. NLP may also be confused with LRCHL. Patients with NLP are younger than those with LRCHL, and LRCHL may show mediastinal involvement. In LRCHL, the nodular pattern often contains eccentrically located small regressed germinal centers and intact small dense FDC meshworks, in contrast to the expanded, and fragmented FDC meshworks in NLP. Neoplastic cells that are positive for CD30 and CD15 but negative for CD20 and CD79a are characteristic of LRCHL. Additionally, Fascin and Gata3 are commonly positive in LRCHL but usually negative in NLP.

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379
Original Article Open Access
Fanpu Ji, Sally Tran, Eiichi Ogawa, Chung-Feng Huang, Takanori Suzuki, Yu Jun Wong, Hidenori Toyoda, Dae Won Jun, Liu Li, Haruki Uojima, Akito Nozaki, Makoto Chuma, Cheng-Hao Tseng, Yao-Chun Hsu, Masatoshi Ishigami, Takashi Honda, Masanori Atsukawa, Hiroaki Haga, Masaru Enomoto, Huy Trinh, Carmen Monica Preda, Phillip Vutien, Charles Landis, Dong Hyun Lee, Tsunamasa Watanabe, Hirokazu Takahashi, Hiroshi Abe, Akira Asai, Yuichiro Eguchi, Jie Li, Xiaozhong Wang, Jia Li, Junping Liu, Jing Liang, Carla Pui-Mei Lam, Rui Huang, Qing Ye, Hongying Pan, Jiajie Zhang, Dachuan Cai, Qi Wang, Daniel Q. Huang, Grace Wong, Vincent Wai-Sun Wong, Junyi Li, Son Do, Norihiro Furusyo, Makoto Nakamuta, Hideyuki Nomura, Eiji Kajiwara, Eileen L. Yoon, Sang Bong Ahn, Koichi Azuma, Kazufumi Dohmen, Jihyun An, Do Seon Song, Hyun Chin Cho, Akira Kawano, Toshimasa Koyanagi, Aritsune Ooho, Takeaki Satoh, Kazuhiro Takahashi, Ming-Lun Yeh, Pei-Chien Tsai, Satoshi Yasuda, Yunyu Zhao, Yishan Liu, Tomomi Okubo, Norio Itokawa, Mi Jung Jun, Toru Ishikawa, Koichi Takaguchi, Tomonori Senoh, Mingyuan Zhang, Changqing Zhao, Raluca Ioana Alecu, Wei Xuan Tay, Pooja Devan, Joanne Kimiko Liu, Ritsuzo Kozuka, Elena Vargas-Accarino, Ai-Thien Do, Mayumi Maeda, Wan-Long Chuang, Jee-Fu Huang, Chia-Yen Dai, Ramsey Cheung, Maria Buti, Junqi Niu, Wen Xie, Hong Ren, Seng Gee Lim, Chao Wu, Man-Fung Yuen, Jia Shang, Qiang Zhu, Yoshiyuki Ueno, Yasuhito Tanaka, Jun Hayashi, Ming-Lung Yu, Mindie H. Nguyen
Published online June 17, 2024
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2024.00089
Abstract
As practice patterns and hepatitis C virus (HCV) genotypes (GT) vary geographically, a global real-world study from both East and West covering all GTs can help inform practice [...] Read more.

As practice patterns and hepatitis C virus (HCV) genotypes (GT) vary geographically, a global real-world study from both East and West covering all GTs can help inform practice policy toward the 2030 HCV elimination goal. This study aimed to assess the effectiveness and tolerability of DAA treatment in routine clinical practice in a multinational cohort for patients infected with all HCV GTs, focusing on GT3 and GT6.

We analyzed the sustained virological response (SVR12) of 15,849 chronic hepatitis C patients from 39 Real-World Evidence from the Asia Liver Consortium for HCV clinical sites in Asia Pacific, North America, and Europe between 07/01/2014–07/01/2021.

The mean age was 62±13 years, with 49.6% male. The demographic breakdown was 91.1% Asian (52.9% Japanese, 25.7% Chinese/Taiwanese, 5.4% Korean, 3.3% Malaysian, and 2.9% Vietnamese), 6.4% White, 1.3% Hispanic/Latino, and 1% Black/African-American. Additionally, 34.8% had cirrhosis, 8.6% had hepatocellular carcinoma (HCC), and 24.9% were treatment-experienced (20.7% with interferon, 4.3% with direct-acting antivirals). The largest group was GT1 (10,246 [64.6%]), followed by GT2 (3,686 [23.2%]), GT3 (1,151 [7.2%]), GT6 (457 [2.8%]), GT4 (47 [0.3%]), GT5 (1 [0.006%]), and untyped GTs (261 [1.6%]). The overall SVR12 was 96.9%, with rates over 95% for GT1/2/3/6 but 91.5% for GT4. SVR12 for GT3 was 95.1% overall, 98.2% for GT3a, and 94.0% for GT3b. SVR12 was 98.3% overall for GT6, lower for patients with cirrhosis and treatment-experienced (TE) (93.8%) but ≥97.5% for treatment-naive patients regardless of cirrhosis status. On multivariable analysis, advanced age, prior treatment failure, cirrhosis, active HCC, and GT3/4 were independent predictors of lower SVR12, while being Asian was a significant predictor of achieving SVR12.

In this diverse multinational real-world cohort of patients with various GTs, the overall cure rate was 96.9%, despite large numbers of patients with cirrhosis, HCC, TE, and GT3/6. SVR12 for GT3/6 with cirrhosis and TE was lower but still excellent (>91%).

Full article
380
Original Article Open Access
Hua-Xiang Yang, Yang-Jie Li, Yang-Lan He, Ke-Ke Jin, Ling-Na Lyu, Hui-Guo Ding
Published online June 17, 2024
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2024.00101
Abstract
The role of platelet autophagy in cirrhotic thrombocytopenia (CTP) remains unclear. This study aimed to investigate the impact of platelet autophagy in CTP and elucidate the regulatory [...] Read more.

The role of platelet autophagy in cirrhotic thrombocytopenia (CTP) remains unclear. This study aimed to investigate the impact of platelet autophagy in CTP and elucidate the regulatory mechanism of hydrogen sulfide (H2S) on platelet autophagy.

Platelets from 56 cirrhotic patients and 56 healthy individuals were isolated for in vitro analyses. Autophagy markers (ATG7, BECN1, LC3, and SQSTM1) were quantified using enzyme-linked immunosorbent assay, while autophagosomes were visualized through electron microscopy. Western blotting was used to assess the autophagy-related proteins and the PDGFR/PI3K/Akt/mTOR pathway following treatment with NaHS (an H2S donor), hydroxocobalamin (an H2S scavenger), or AG 1295 (a selective PDGFR-α inhibitor). A carbon tetrachloride-induced cirrhotic BALB/c mouse model was established. Cirrhotic mice with thrombocytopenia were randomly treated with normal saline, NaHS, or hydroxocobalamin for 15 days. Changes in platelet count and aggregation rate were observed every three days.

Cirrhotic patients with thrombocytopenia exhibited significantly decreased platelet autophagy markers and endogenous H2S levels, alongside increased platelet aggregation, compared to healthy controls. In vitro, NaHS treatment of platelets from severe CTP patients elevated LC3-II levels, reduced SQSTM1 levels, and decreased platelet aggregation in a dose-dependent manner. H2S treatment inhibited PDGFR, PI3K, Akt, and mTOR phosphorylation. In vivo, NaHS significantly increased LC3-II and decreased SQSTM1 expressions in platelets of cirrhotic mice, reducing platelet aggregation without affecting the platelet count.

Diminished platelet autophagy potentially contributes to thrombocytopenia in cirrhotic patients. H2S modulates platelet autophagy and functions possibly via the PDGFR-α/PI3K/Akt/mTOR signaling pathway.

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