Pub Date : 2024-05-06DOI: 10.1101/2024.05.05.24306611
Ntombikayise Xelwa, Previn Naicker, Jones Omoshoro-Jones, John Devar, Martin Smith, Geoffrey Candy, Tanya Nadine Augustine, Ekene Emmanuel Nweke
Background Pancreatic ductal adenocarcinoma (PDAC) is poised to be a leading cause of cancer-related deaths. Despite developing new treatment strategies, patient outcomes have not significantly improved. Chemoresistance has been implicated as a major contributor to ineffective treatments observed with studies suggesting combination therapy targeting multiple pathways. This study explored dysregulated genes in tumours of PDAC patients to identify targets which could be used effectively in combination with conventional therapy against cancer cells.
{"title":"The combination of SPP1 knockdown and gemcitabine treatment enhances apoptosis and reduces invasiveness of pancreatic cancer cells","authors":"Ntombikayise Xelwa, Previn Naicker, Jones Omoshoro-Jones, John Devar, Martin Smith, Geoffrey Candy, Tanya Nadine Augustine, Ekene Emmanuel Nweke","doi":"10.1101/2024.05.05.24306611","DOIUrl":"https://doi.org/10.1101/2024.05.05.24306611","url":null,"abstract":"<strong>Background</strong> Pancreatic ductal adenocarcinoma (PDAC) is poised to be a leading cause of cancer-related deaths. Despite developing new treatment strategies, patient outcomes have not significantly improved. Chemoresistance has been implicated as a major contributor to ineffective treatments observed with studies suggesting combination therapy targeting multiple pathways. This study explored dysregulated genes in tumours of PDAC patients to identify targets which could be used effectively in combination with conventional therapy against cancer cells.","PeriodicalId":501258,"journal":{"name":"medRxiv - Gastroenterology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140930640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-06DOI: 10.1101/2024.05.04.24306873
Theresa Kirchner, George N. Dalekos, Kalliopi Zachou, Mercedes Robles-Díaz, Raúl J. Andrade, Marcial Sebode, Ansgar Lohse, Maciej K. Janik, Piotr Milkiewicz, Mirjam Kolev, Nasser Semmo, Tony Bruns, Tom Jg Gevers, Benedetta Terziroli Beretta-Piccoli, Heiner Wedemeyer, Elmar Jaeckel, Richard Taubert, Bastian Engel, pIgG study group
Background and aim The distinction of drug-induced liver injury (DILI), drug-induced autoimmune-like hepatitis (DI-ALH) and autoimmune hepatitis (AIH) can be challenging due to overlapping clinical characteristics. Recently, polyreactive immunoglobulin G (pIgG) was identified as a novel biomarker with a higher accuracy for the diagnose of AIH than conventional autoantibodies. This retrospective multicenter study aimed to evaluate the diagnostic accuracy of pIgG to distinguish between AIH, DI-ALH and DILI and thus identify patients in need of immunosuppression.
{"title":"Elevated polyreactive immunoglobulin G in immune mediated liver injuries with the need for immunosuppressive therapy","authors":"Theresa Kirchner, George N. Dalekos, Kalliopi Zachou, Mercedes Robles-Díaz, Raúl J. Andrade, Marcial Sebode, Ansgar Lohse, Maciej K. Janik, Piotr Milkiewicz, Mirjam Kolev, Nasser Semmo, Tony Bruns, Tom Jg Gevers, Benedetta Terziroli Beretta-Piccoli, Heiner Wedemeyer, Elmar Jaeckel, Richard Taubert, Bastian Engel, pIgG study group","doi":"10.1101/2024.05.04.24306873","DOIUrl":"https://doi.org/10.1101/2024.05.04.24306873","url":null,"abstract":"<strong>Background and aim</strong> The distinction of drug-induced liver injury (DILI), drug-induced autoimmune-like hepatitis (DI-ALH) and autoimmune hepatitis (AIH) can be challenging due to overlapping clinical characteristics. Recently, polyreactive immunoglobulin G (pIgG) was identified as a novel biomarker with a higher accuracy for the diagnose of AIH than conventional autoantibodies. This retrospective multicenter study aimed to evaluate the diagnostic accuracy of pIgG to distinguish between AIH, DI-ALH and DILI and thus identify patients in need of immunosuppression.","PeriodicalId":501258,"journal":{"name":"medRxiv - Gastroenterology","volume":"33 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140930635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-06DOI: 10.1101/2024.05.06.24306927
Menglin Chen, Houshu Tu, Jiaoli Zhou, Yi Zhang, Shuting Wen, Yao Xiao, Ling He
Background Previous observational research found a relationship between gastroesophageal reflux disease (GERD) and chronic widespread pain (CWP). Despite this, it is unknown which, if any, of the conditions produces the other. Our study will use bidirectional Mendelian randomization (MR) to evaluate their causal link.
{"title":"The causal correlation between gastroesophageal reflux disease and chronic widespread pain: a bidirectional mendelian randomization study","authors":"Menglin Chen, Houshu Tu, Jiaoli Zhou, Yi Zhang, Shuting Wen, Yao Xiao, Ling He","doi":"10.1101/2024.05.06.24306927","DOIUrl":"https://doi.org/10.1101/2024.05.06.24306927","url":null,"abstract":"<strong>Background</strong> Previous observational research found a relationship between gastroesophageal reflux disease (GERD) and chronic widespread pain (CWP). Despite this, it is unknown which, if any, of the conditions produces the other. Our study will use bidirectional Mendelian randomization (MR) to evaluate their causal link.","PeriodicalId":501258,"journal":{"name":"medRxiv - Gastroenterology","volume":"100 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140930426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-02DOI: 10.1101/2024.04.30.24306608
Sergio Barace, Eva Santamaría, Stefany Infante, Sara Arcelus, Jesús De la Fuente, Enrique Goñi, Ibon Tamayo, Idoia Ochoa, Miguel Sogbe, Bruno Sangro, Mikel Hernaez, Matías A. Ávila, Josepmaria Argemi
Whole tissue transcriptomic analyses have been helpful to characterize molecular subtypes of hepatocellular carcinoma (HCC). Metabolic subtypes of human HCC have been defined, yet whether these different metabolic classes are clinically relevant or derive in actionable cancer vulnerabilities is still an unanswered question. Publicly available gene sets or gene signatures have been used to infer functional changes through gene set enrichment methods. However, metabolism-related gene signatures are poorly coexpressed when applied to a biological context. Here, we apply a simple method to infer highly consistent signatures using graph models. Using The Cancer Genome Atlas Liver Hepatocellular cohort (LIHC), we describe the main metabolic clusters and their relationship with commonly used molecular classes, and with the presence of TP53 or CTNNB1 driver mutations. We find similar results in our validation cohort, the LIRI-JP cohort. We describe how previously described metabolic subtypes could not have therapeutic relevance due to their overall downregulation when compared to non-tumoral liver, and identify N-Glycan, Mevalonate and Sphingolipid biosynthetic pathways as the hallmark of the oncogenic shift of the use of Acetyl-coenzyme A in HCC metabolism. Finally, using DepMap data, we demonstrate metabolic vulnerabilities in HCC cell lines.
{"title":"Application of graph models to the identification of transcriptomic oncometabolic pathways in human hepatocellular carcinoma","authors":"Sergio Barace, Eva Santamaría, Stefany Infante, Sara Arcelus, Jesús De la Fuente, Enrique Goñi, Ibon Tamayo, Idoia Ochoa, Miguel Sogbe, Bruno Sangro, Mikel Hernaez, Matías A. Ávila, Josepmaria Argemi","doi":"10.1101/2024.04.30.24306608","DOIUrl":"https://doi.org/10.1101/2024.04.30.24306608","url":null,"abstract":"Whole tissue transcriptomic analyses have been helpful to characterize molecular subtypes of hepatocellular carcinoma (HCC). Metabolic subtypes of human HCC have been defined, yet whether these different metabolic classes are clinically relevant or derive in actionable cancer vulnerabilities is still an unanswered question. Publicly available gene sets or gene signatures have been used to infer functional changes through gene set enrichment methods. However, metabolism-related gene signatures are poorly coexpressed when applied to a biological context. Here, we apply a simple method to infer highly consistent signatures using graph models. Using The Cancer Genome Atlas Liver Hepatocellular cohort (LIHC), we describe the main metabolic clusters and their relationship with commonly used molecular classes, and with the presence of TP53 or CTNNB1 driver mutations. We find similar results in our validation cohort, the LIRI-JP cohort. We describe how previously described metabolic subtypes could not have therapeutic relevance due to their overall downregulation when compared to non-tumoral liver, and identify N-Glycan, Mevalonate and Sphingolipid biosynthetic pathways as the hallmark of the oncogenic shift of the use of Acetyl-coenzyme A in HCC metabolism. Finally, using DepMap data, we demonstrate metabolic vulnerabilities in HCC cell lines.","PeriodicalId":501258,"journal":{"name":"medRxiv - Gastroenterology","volume":"19 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140884339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background Gastric cancer is one of the most common malignancies and its incidence is high in East Asia. Several options are available for resection of malignant gastric tumors, ranging from endoscopic resection of early-stage cancer to open total gastrectomy. However, there has been a lack of nationwide data on gastric resection in Japan.
{"title":"Clinical epidemiology of the endoscopic, laparoscopic, and surgical resection of malignant gastric tumors in Japan, 2014-2021: a retrospective study using open data from a national claims database","authors":"Akahito Sako, Tomoyuki Yada, Keiichi Fujiya, Ryo Nakashima, Kensuke Yoshimura, Hidekatsu Yanai, Naomi Uemura","doi":"10.1101/2024.04.30.24305814","DOIUrl":"https://doi.org/10.1101/2024.04.30.24305814","url":null,"abstract":"<strong>Background</strong> Gastric cancer is one of the most common malignancies and its incidence is high in East Asia. Several options are available for resection of malignant gastric tumors, ranging from endoscopic resection of early-stage cancer to open total gastrectomy. However, there has been a lack of nationwide data on gastric resection in Japan.","PeriodicalId":501258,"journal":{"name":"medRxiv - Gastroenterology","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140884254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-30DOI: 10.1101/2024.04.27.24306447
Debodipta Das, Xiaojing Wang, Yu-Chiao Chiu, Hakim Bouamar, Francis E. Sharkey, Jorge E. Lopera, Zhao Lai, Susan T. Weintraub, Xianlin Han, Yi Zou, Hung-I H. Chen, Carla R. Zeballos Torrez, Xiang Gu, Matyas Cserhati, Joel E. Michalek, Glenn A. Halff, Yidong Chen, Siyuan Zheng, Francisco G. Cigarroa, Lu-Zhe Sun
Background The incidence and mortality rates of hepatocellular carcinoma (HCC) among Hispanics in the United States are much higher than those of non-Hispanic whites. We conducted comprehensive multi-omics analyses to understand molecular alterations in HCC among Hispanic patients.
{"title":"Integrative multi-omics characterization of hepatocellular carcinoma in Hispanic patients","authors":"Debodipta Das, Xiaojing Wang, Yu-Chiao Chiu, Hakim Bouamar, Francis E. Sharkey, Jorge E. Lopera, Zhao Lai, Susan T. Weintraub, Xianlin Han, Yi Zou, Hung-I H. Chen, Carla R. Zeballos Torrez, Xiang Gu, Matyas Cserhati, Joel E. Michalek, Glenn A. Halff, Yidong Chen, Siyuan Zheng, Francisco G. Cigarroa, Lu-Zhe Sun","doi":"10.1101/2024.04.27.24306447","DOIUrl":"https://doi.org/10.1101/2024.04.27.24306447","url":null,"abstract":"<strong>Background</strong> The incidence and mortality rates of hepatocellular carcinoma (HCC) among Hispanics in the United States are much higher than those of non-Hispanic whites. We conducted comprehensive multi-omics analyses to understand molecular alterations in HCC among Hispanic patients.","PeriodicalId":501258,"journal":{"name":"medRxiv - Gastroenterology","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140836490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-15DOI: 10.1101/2024.04.15.24305823
Minjing Chang, Yuhui Zhao, Jun Qiao, Hongxia Li, Linlin Jia, Kaixin Yao, Nan Li, Peifeng He
Background and Aims Observational studies on the association between physical activity (PA) and inflammatory bowel diseases (IBDs), including Crohn’s disease (CD) and ulcerative colitis (UC), report inconsistent results. Moreover, the underlying mediator between PA and IBDs remains unknown. We aimed to investigate the causal effect of PA on IBD and the role of BMI as a mediator between PA and IBD.
背景和目的 有关体力活动（PA）与炎症性肠病（IBD）（包括克罗恩病（CD）和溃疡性结肠炎（UC））之间关系的观察性研究报告的结果并不一致。此外，PA 与 IBD 之间的潜在中介因素仍然未知。我们的目的是研究 PA 对 IBD 的因果效应以及 BMI 在 PA 和 IBD 之间的中介作用。
{"title":"Deciphering the complex interplay between physical activity, inflammatory bowel disease and obesity/BMl through causal inference and mediation analyses","authors":"Minjing Chang, Yuhui Zhao, Jun Qiao, Hongxia Li, Linlin Jia, Kaixin Yao, Nan Li, Peifeng He","doi":"10.1101/2024.04.15.24305823","DOIUrl":"https://doi.org/10.1101/2024.04.15.24305823","url":null,"abstract":"<strong>Background and Aims</strong> Observational studies on the association between physical activity (PA) and inflammatory bowel diseases (IBDs), including Crohn’s disease (CD) and ulcerative colitis (UC), report inconsistent results. Moreover, the underlying mediator between PA and IBDs remains unknown. We aimed to investigate the causal effect of PA on IBD and the role of BMI as a mediator between PA and IBD.","PeriodicalId":501258,"journal":{"name":"medRxiv - Gastroenterology","volume":"9 4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140610554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-12DOI: 10.1101/2024.04.09.24305556
Jun Liu, Yuxuan Chen, Jin Qian, Ri Cui, Ayse Demirkan, Yihu Zheng
Background Previous research has suggested potential links between amino acids and metabolic dysfunction-associated steatotic liver disease (MASLD), but the precise roles of amino acids in MASLD development are not well understood. This study aimed to obtain insights into the relationships between circulating amino acids and MASLD.
{"title":"Novel genetic insights into the roles of amino acids in metabolic dysfunction-associated steatotic liver disease","authors":"Jun Liu, Yuxuan Chen, Jin Qian, Ri Cui, Ayse Demirkan, Yihu Zheng","doi":"10.1101/2024.04.09.24305556","DOIUrl":"https://doi.org/10.1101/2024.04.09.24305556","url":null,"abstract":"<strong>Background</strong> Previous research has suggested potential links between amino acids and metabolic dysfunction-associated steatotic liver disease (MASLD), but the precise roles of amino acids in MASLD development are not well understood. This study aimed to obtain insights into the relationships between circulating amino acids and MASLD.","PeriodicalId":501258,"journal":{"name":"medRxiv - Gastroenterology","volume":"283 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140581479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-10DOI: 10.1101/2024.04.08.24305005
Pavel Wohl, Alzbeta Krausova, Petr Wohl, Ondrej Fabian, Lukas Bajer, Jan Brezina, Pavel Drastich, Mojmír Hlavaty, Petra Novotna, Michal Kahle, Julius Spicak, Martin Gregor
Background and Aims Ulcerative colitis (UC) with concomitant primary sclerosing cholangitis (PSC) represents a distinct disease entity (PSC-UC). Mayo endoscopic subscore (MES) is a standard tool for assessing disease activity in UC but its relevance in PSC-UC remains unclear. Here, we sought to compare MES in a cohort of UC and PSC-UC patients and assess the accuracy using histological activity scoring (Nancy histological index; NHI).
{"title":"Limited Validity of Mayo Endoscopic Subscore in Ulcerative Colitis with Concomitant Primary Sclerosing Cholangitis","authors":"Pavel Wohl, Alzbeta Krausova, Petr Wohl, Ondrej Fabian, Lukas Bajer, Jan Brezina, Pavel Drastich, Mojmír Hlavaty, Petra Novotna, Michal Kahle, Julius Spicak, Martin Gregor","doi":"10.1101/2024.04.08.24305005","DOIUrl":"https://doi.org/10.1101/2024.04.08.24305005","url":null,"abstract":"<strong>Background and Aims</strong> Ulcerative colitis (UC) with concomitant primary sclerosing cholangitis (PSC) represents a distinct disease entity (PSC-UC). Mayo endoscopic subscore (MES) is a standard tool for assessing disease activity in UC but its relevance in PSC-UC remains unclear. Here, we sought to compare MES in a cohort of UC and PSC-UC patients and assess the accuracy using histological activity scoring (Nancy histological index; NHI).","PeriodicalId":501258,"journal":{"name":"medRxiv - Gastroenterology","volume":"65 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140581582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-09DOI: 10.1101/2024.04.08.24305062
Lan Wang, Qian Zhang, Peng Zhang, Bowen Wu, Shiyu Du, Kaiqiang Tang, Shao Li
Objective Given the high cost of endoscopy in gastric cancer (GC) screening, there is an urgent need to explore cost-effective methods for the large-scale prediction of precancerous lesions of gastric cancer (PLGC). We aim to construct a hierarchical artificial intelligence-based multimodal non-invasive method for pre-endoscopic risk screening, to provide tailored recommendations for endoscopy.
{"title":"Pre-endoscopic screening of precancerous lesions in gastric cancer using deep learning","authors":"Lan Wang, Qian Zhang, Peng Zhang, Bowen Wu, Shiyu Du, Kaiqiang Tang, Shao Li","doi":"10.1101/2024.04.08.24305062","DOIUrl":"https://doi.org/10.1101/2024.04.08.24305062","url":null,"abstract":"<strong>Objective</strong> Given the high cost of endoscopy in gastric cancer (GC) screening, there is an urgent need to explore cost-effective methods for the large-scale prediction of precancerous lesions of gastric cancer (PLGC). We aim to construct a hierarchical artificial intelligence-based multimodal non-invasive method for pre-endoscopic risk screening, to provide tailored recommendations for endoscopy.","PeriodicalId":501258,"journal":{"name":"medRxiv - Gastroenterology","volume":"27 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140602640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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