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Targeting cancer stem cells with a pan-BCL-2 inhibitor in preclinical and clinical settings in patients with gastroesophageal carcinoma.

Shumei Song, Qiongrong Chen, Yuan Li, Guang Lei, Ailing Scott, Longfei Huo, Cordelia Y Li, Jeannelyn Santiano Estrella, Arlene Correa, Melissa Pool Pizzi, Lang Ma, Jiankang Jin, Bin Liu, Ying Wang, Lianchun Xiao, Wayne L Hofstetter, Jeffrey H Lee, Brian Weston, Manoop Bhutani, Namita Shanbhag, Randy L Johnson, Boyi Gan, Shaozhong Wei, Jaffer A Ajani,

<h4>Objective</h4>Gastro-oesophageal cancers (GEC) are resistant to therapy and lead to poor prognosis. The cancer stem cells (CSCs) and antiapoptotic pathways often confer therapy resistance. We sought to elucidate the antitumour action of a BCL-2 inhibitor, AT101 in GEC in vitro, in vivo and in a clinical trial.<h4>Methods</h4>Extensive preclinical studies in ... Read more >>

Gut (Gut)
[2021, :]

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Transcolonic endoscopic appendectomy: a novel natural orifice transluminal endoscopic surgery (NOTES) technique for the sessile serrated lesions involving the appendiceal orifice.

Tao Chen, Aiping Xu, Jingjing Lian, Yuan Chu, Haibin Zhang, Meidong Xu,

Gut (Gut)
[2021, :]

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Two-dimensional shear wave elastography predicts survival in advanced chronic liver disease.

Jonel Trebicka, Wenyi Gu, Victor de Ledinghen, Christophe Aubé, Aleksander Krag, Michael Praktiknjo, Laurent Castera, Jerome Dumortier, David Josef Maria Bauer, Mireen Friedrich-Rust, Stanislas Pol, Ivica Grgurevic, Rongqin Zheng, Sven Francque, Halima Gottfriedovà, Sanda Mustapic, Ioan Sporea, Annalisa Berzigotti, Frank Erhard Uschner, Benedikt Simbrunner, Maxime Ronot, Christophe Cassinotto, Maria Kjaergaard, Filipe Andrade, Martin Schulz, Georg Semmler, Ida Tjesic Drinkovic, Johannes Chang, Maximilian Joseph Brol, Pierre Emmanuel Rautou, Thomas Vanwolleghem, Christian P Strassburg, Jerome Boursier, Philip Georg Ferstl, Ditlev Nytoft Rasmussen, Thomas Reiberger, Valerie Vilgrain, Aymeric Guibal, Olivier Guillaud, Stefan Zeuzem, Camille Vassord, Xue Lu, Luisa Vonghia, Renata Senkerikova, Alina Popescu, Cristina Margini, Wenping Wang, Maja Thiele, Chrisitan Jansen,

<h4>Objective</h4>Liver stiffness measurement (LSM) is a tool used to screen for significant fibrosis and portal hypertension. The aim of this retrospective multicentre study was to develop an easy tool using LSM for clinical outcomes in advanced chronic liver disease (ACLD) patients.<h4>Design</h4>This international multicentre cohort study included a derivation ACLD patient ... Read more >>

Gut (Gut)
[2021, :]

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Impaired antibacterial response of liver sinusoidal Vγ9+Vδ2+ T cells in patients with chronic liver disease.

Min-Seok Rha, Ji Won Han, June-Young Koh, Ha Seok Lee, Jong Hoon Kim, Kyungjoo Cho, Soon Il Kim, Myoung Soo Kim, Jae Geun Lee, Su-Hyung Park, Dong Jin Joo, Jun Yong Park, Eui-Cheol Shin,

<h4>Objective</h4>The liver acts as a frontline barrier against diverse gut-derived pathogens, and the sinusoid is the primary site of liver immune surveillance. However, little is known about liver sinusoidal immune cells in the context of chronic liver disease (CLD). Here, we investigated the antibacterial capacity of liver sinusoidal γδ T ... Read more >>

Gut (Gut)
[2021, :]

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SARS-CoV-2 vaccination for patients with inflammatory bowel diseases: recommendations from an international consensus meeting.

Corey A Siegel, Gil Y Melmed, Dermot Pb McGovern, Victoria Rai, Florian Krammer, David T Rubin, Maria T Abreu, Marla C Dubinsky, , ,

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[2021, :]

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Artificial intelligence in GI endoscopy: stumbling blocks, gold standards and the role of endoscopy societies.

Rüdiger Schmitz, Rene Werner, Alessandro Repici, Raf Bisschops, Alexander Meining, Michael Zornow, Helmut Messmann, Cesare Hassan, Prateek Sharma, Thomas Rösch,

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[2021, :]

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Microsatellite instability/mismatch repair deficiency in pancreatic cancers: the same or different?

Claudio Luchini, Robert C Grant, Aldo Scarpa, Steven Gallinger,

Gut (Gut)
[2021, :]

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Integrative analysis reveals early and distinct genetic and epigenetic changes in intraductal papillary and tubulopapillary cholangiocarcinogenesis.

Benjamin Goeppert, Damian Stichel, Reka Toth, Sarah Fritzsche, Moritz Anton Loeffler, Anna Melissa Schlitter, Olaf Neumann, Yassen Assenov, Monika Nadja Vogel, Arianeb Mehrabi, Katrin Hoffmann, Bruno Köhler, Christoph Springfeld, Dieter Weichenhan, Christoph Plass, Irene Esposito, Peter Schirmacher, Andreas von Deimling, Stephanie Roessler,

<h4>Objective</h4>A detailed understanding of the molecular alterations in different forms of cholangiocarcinogenesis is crucial for a better understanding of cholangiocarcinoma (CCA) and may pave the way to early diagnosis and better treatment options.<h4>Design</h4>We analysed a clinicopathologically well-characterised patient cohort (n=54) with high-grade intraductal papillary (IPNB) or tubulopapillary (ITPN) neoplastic precursor ... Read more >>

Gut (Gut)
[2021, :]

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Activated intestinal muscle cells promote preadipocyte migration: a novel mechanism for creeping fat formation in Crohn's disease.

Ren Mao, Genevieve Doyon, Ilyssa O Gordon, Jiannan Li, Sinan Lin, Jie Wang, Thi Hong Nga Le, Michael Elias, Satya Kurada, Brian Southern, Mitchell Olman, Minhu Chen, Shuai Zhao, Dina Dejanovic, Jyotsna Chandra, Pranab K Mukherjee, Gail West, David R Van Wagoner, Claudio Fiocchi, Florian Rieder,

<h4>Objective</h4>Creeping fat, the wrapping of mesenteric fat around the bowel wall, is a typical feature of Crohn's disease, and is associated with stricture formation and bowel obstruction. How creeping fat forms is unknown, and we interrogated potential mechanisms using novel intestinal tissue and cell interaction systems.<h4>Design</h4>Tissues from normal, UC, non-strictured ... Read more >>

Gut (Gut)
[2021, :]

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Effect of green-Mediterranean diet on intrahepatic fat: the DIRECT PLUS randomised controlled trial.

Anat Yaskolka Meir, Ehud Rinott, Gal Tsaban, Hila Zelicha, Alon Kaplan, Philip Rosen, Ilan Shelef, Ilan Youngster, Aryeh Shalev, Matthias Blüher, Uta Ceglarek, Michael Stumvoll, Kieran Tuohy, Camilla Diotallevi, Urska Vrhovsek, Frank Hu, Meir Stampfer, Iris Shai,

<h4>Objective</h4>To examine the effectiveness of green-Mediterranean (MED) diet, further restricted in red/processed meat, and enriched with green plants and polyphenols on non-alcoholic fatty liver disease (NAFLD), reflected by intrahepatic fat (IHF) loss.<h4>Design</h4>For the DIRECT-PLUS 18-month randomized clinical trial, we assigned 294 participants with abdominal obesity/dyslipidaemia into healthy dietary guidelines (HDG), ... Read more >>

Gut (Gut)
[2021, :]

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Novel scheme for non-invasive gut bioinformation acquisition with a magnetically controlled sampling capsule endoscope.

Zhen Ding, Weijun Wang, Kun Zhang, Fanhua Ming, Tianyi Yangdai, Tao Xu, Huiying Shi, Yuhui Bao, Hailing Yao, Hangyu Peng, Chaoqun Han, Weiwei Jiang, Jun Liu, Xiaohua Hou, Rong Lin,

<h4>Objective</h4>Intestinal flora and metabolites are associated with multiple systemic diseases. Current approaches for acquiring information regarding microbiota/metabolites have limitations. We aimed to develop a precise magnetically controlled sampling capsule endoscope (MSCE) for the convenient, non-invasive and accurate acquisition of digestive bioinformation for disease diagnosis and evaluation.<h4>Design</h4>The MSCE and surgery were ... Read more >>

Gut (Gut)
[2021, :]

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Pneumatic dilation for persistent dysphagia after antireflux surgery, a multicentre single-blind randomised sham-controlled clinical trial.

Jeroen M Schuitenmaker, Froukje B van Hoeij, Marlies P Schijven, Jan Tack, José M Conchillo, Eric J Hazebroek, André J P M Smout, Albert J Bredenoord,

<h4>Objective</h4>There is no evidence-based treatment for persistent dysphagia after laparoscopic fundoplication. The aim of this study was to evaluate the effect of pneumatic dilation on persistent dysphagia after laparoscopic fundoplication.<h4>Design</h4>We performed a multicentre, single-blind, randomised sham-controlled trial of patients with persistent dysphagia (>3 months) after laparoscopic fundoplication. Patients with an ... Read more >>

Gut (Gut)
[2021, :]

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NTPDase8 protects mice from intestinal inflammation by limiting P2Y6 receptor activation: identification of a new pathway of inflammation for the potential treatment of IBD.

Mabrouka Salem, Joanna Lecka, Julie Pelletier, Danielle Gomes Marconato, Aline Dumas, Luc Vallières, Gaetan Brochu, Bernard Robaye, Christian Jobin, Jean Sévigny,

<h4>Objective</h4>Nucleotides are danger signals that activate inflammatory responses via binding P2 receptors. The nucleoside triphosphate diphosphohydrolase-8 (NTPDase8) is an ectonucleotidase that hydrolyses P2 receptor ligands. We investigated the role of NTPDase8 in intestinal inflammation.<h4>Design</h4>We generated NTPDase8-deficient (<i>Entpd8</i> <sup>-/-</sup>) mice to define the role of NTPDase8 in the dextran sodium sulfate ... Read more >>

Gut (Gut)
[2021, :]

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Synbindin restrains proinflammatory macrophage activation against microbiota and mucosal inflammation during colitis.

Luoyan Ai, Yimeng Ren, Mingming Zhu, Shiyuan Lu, Yun Qian, Zhaofei Chen, Antao Xu,

<h4>Objective</h4>As a canonical membrane tethering factor, the function of synbindin has been expanding and indicated in immune response. Here, we investigated the role of synbindin in the regulation of toll-like receptor 4 (TLR4) signalling and macrophage response to microbiota during colitis.<h4>Design</h4>Three distinct mouse models allowing global, myeloid-specific or intestinal epithelial ... Read more >>

Gut (Gut)
[2021, :]

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PI3K-driven HER2 expression is a potential therapeutic target in colorectal cancer stem cells.

Laura Rosa Mangiapane, Annalisa Nicotra, Alice Turdo, Miriam Gaggianesi, Paola Bianca, Simone Di Franco, Davide Stefano Sardina, Veronica Veschi, Michele Signore, Sven Beyes, Luca Fagnocchi, Micol Eleonora Fiori, Maria Rita Bongiorno, Melania Lo Iacono, Irene Pillitteri, Gloria Ganduscio, Gaspare Gulotta, Jan Paul Medema, Alessio Zippo, Matilde Todaro, Ruggero De Maria, Giorgio Stassi,

<h4>Objective</h4>Cancer stem cells are responsible for tumour spreading and relapse. Human epidermal growth factor receptor 2 (HER2) expression is a negative prognostic factor in colorectal cancer (CRC) and a potential target in tumours carrying the gene amplification. Our aim was to define the expression of HER2 in colorectal cancer stem ... Read more >>

Gut (Gut)
[2021, :]

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Possible tumour cell reimplantation during curative endoscopic therapy of superficial Barrett's carcinoma.

Hanno Ehlken, Rüdiger Schmitz, Sabine Riethdorf, Lutz Riethdorf, Jenny Krause, Karl-Frederick Karstens, Jörg Schrader, Fabrice Viol, Anastasios Giannou, William Sterlacci, Michael Vieth, Till Clauditz, Christian Kähler, Oliver Mann, Jakob R Izbicki, Samuel Huber, Klaus Pantel, Thomas Rösch,

<h4>Background and aims</h4>Endoscopic resection has been established as curative therapy for superficial cancer arising from Barrett's oesophagus (BE); recurrences are very rare. Based on a case series with unusual and massive early recurrences, we analyse the issue of tumour cell reimplantation.<h4>Methods</h4>This hypothesis was developed on the basis of two out ... Read more >>

Gut (Gut)
[2021, :]

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Global burden of disease: acute-on-chronic liver failure, a systematic review and meta-analysis.

Gabriel Mezzano, Adria Juanola, Andres Cardenas, Esteban Mezey, James P Hamilton, Elisa Pose, Isabel Graupera, Pere Ginès, Elsa Solà, Ruben Hernaez,

<h4>Background and aims</h4>Acute-on-chronic liver failure (ACLF) is characterised by acute decompensation of cirrhosis associated with organ failures. We systematically evaluated the geographical variations of ACLF across the world in terms of prevalence, mortality, aetiology of chronic liver disease (CLD), triggers and organ failures.<h4>Methods</h4>We searched EMBASE and PubMed from 3/1/2013 to ... Read more >>

Gut (Gut)
[2021, :]

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Placental growth factor promotes tumour desmoplasia and treatment resistance in intrahepatic cholangiocarcinoma.

Shuichi Aoki, Koetsu Inoue, Sebastian Klein, Stefan Halvorsen, Jiang Chen, Aya Matsui, Mohammad R Nikmaneshi, Shuji Kitahara, Tai Hato, Xianfeng Chen, Kazumichi Kawakubo, Hadi T Nia, Ivy Chen, Daniel H Schanne, Emilie Mamessier, Kohei Shigeta, Hiroto Kikuchi, Rakesh R Ramjiawan, Tyge Ce Schmidt, Masaaki Iwasaki, Thomas Yau, Theodore S Hong, Alexander Quaas, Patrick S Plum, Simona Dima, Irinel Popescu, Nabeel Bardeesy, Lance L Munn, Mitesh J Borad, Slim Sassi, Rakesh K Jain, Andrew X Zhu, Dan G Duda,

<h4>Objective</h4>Intrahepatic cholangiocarcinoma (ICC)-a rare liver malignancy with limited therapeutic options-is characterised by aggressive progression, desmoplasia and vascular abnormalities. The aim of this study was to determine the role of placental growth factor (PlGF) in ICC progression.<h4>Design</h4>We evaluated the expression of PlGF in specimens from ICC patients and assessed the therapeutic ... Read more >>

Gut (Gut)
[2021, :]

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Gut microbiota composition reflects disease severity and dysfunctional immune responses in patients with COVID-19.

Yun Kit Yeoh, Tao Zuo, Grace Chung-Yan Lui, Fen Zhang, Qin Liu, Amy Yl Li, Arthur Ck Chung, Chun Pan Cheung, Eugene Yk Tso, Kitty Sc Fung, Veronica Chan, Lowell Ling, Gavin Joynt, David Shu-Cheong Hui, Kai Ming Chow, Susanna So Shan Ng, Timothy Chun-Man Li, Rita Wy Ng, Terry Cf Yip, Grace Lai-Hung Wong, Francis Kl Chan, Chun Kwok Wong, Paul Ks Chan, Siew C Ng,

<h4>Objective</h4>Although COVID-19 is primarily a respiratory illness, there is mounting evidence suggesting that the GI tract is involved in this disease. We investigated whether the gut microbiome is linked to disease severity in patients with COVID-19, and whether perturbations in microbiome composition, if any, resolve with clearance of the SARS-CoV-2 ... Read more >>

Gut (Gut)
[2021, :]

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25 years of anti-TNF treatment for inflammatory bowel disease: lessons from the past and a look to the future.

Geert R D'Haens, Sander van Deventer,

Anti-tumour necrosis factor (TNF) antibodies have been widely used for approximately 25 years now. The first clinical observations in patients with refractory Crohn's disease rapidly responding to infliximab prompted accelerated clinical development and approval for this indication. However, many questions remained unanswered when this treatment came to market related to ... Read more >>

Gut (Gut)
[2021, :]

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Endoscopes used in positive and critically ill patients are SARS-CoV-2 negative at virological assessment.

Ivo Boškoski, Anna Di Gemma, Maria Valeria Matteo, Fabio Grilli, Paola Cattani, Guido Costamagna,

The risk of SARS-CoV-2 transmission in endoscopy is not only between patients and endoscopy staff but is also through inadequately reprocessed endoscopes. There are no studies that could confirm the efficacy of current ways of endoscope reprocessing on the elimination of SARS-CoV-2. The aim of this pilot study was to ... Read more >>

Gut (Gut)
[2021, :]

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Evaluating the utility of tumour mutational signatures for identifying hereditary colorectal cancer and polyposis syndrome carriers.

Peter Georgeson, Bernard J Pope, Christophe Rosty, Mark Clendenning, Khalid Mahmood, Jihoon E Joo, Romy Walker, Ryan A Hutchinson, Susan Preston, Julia Como, Sharelle Joseland, Aung Ko Win, Finlay A Macrae, John L Hopper, Dmitri Mouradov, Peter Gibbs, Oliver M Sieber, Dylan E O'Sullivan, Darren R Brenner, Steve Gallinger, Mark A Jenkins, Ingrid M Winship, Daniel D Buchanan,

<h4>Objective</h4>Germline pathogenic variants (PVs) in the DNA mismatch repair (MMR) genes and in the base excision repair gene <i>MUTYH</i> underlie hereditary colorectal cancer (CRC) and polyposis syndromes. We evaluated the robustness and discriminatory potential of tumour mutational signatures in CRCs for identifying germline PV carriers.<h4>Design</h4>Whole-exome sequencing of formalin-fixed paraffin-embedded (FFPE) ... Read more >>

Gut (Gut)
[2021, :]

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Sofosbuvir/velpatasvir with or without low-dose ribavirin for patients with chronic hepatitis C virus infection and severe renal impairment.

Chen-Hua Liu, Chi-Yi Chen, Wei-Wen Su, Kuo-Chih Tseng, Ching-Chu Lo, Chun-Jen Liu, Jyh-Jou Chen, Cheng-Yuan Peng, Yu-Lueng Shih, Sheng-Shun Yang, Chia-Sheng Huang, Ke-Jhang Huang, Chi-Yang Chang, Ming-Chang Tsai, Wei-Yu Kao, Yo-Jen Fang, Po-Yueh Chen, Pei-Yuan Su, Chih-Wei Tseng, Jow-Jyh Huang, Pei-Lun Lee, Hsueh-Chou Lai, Tsai-Yuan Hsieh, Chung-Hsin Chang, Yi-Jie Huang, Fu-Jen Lee, Chun-Chao Chang, Jia-Horng Kao,

<h4>Objective</h4>Data regarding the real-world effectiveness and safety of sofosbuvir/velpatasvir (SOF/VEL) with or without low-dose ribavirin (RBV) in patients with chronic hepatitis C virus (HCV) infection and severe renal impairment (RI) are limited. We evaluated the performance of SOF/VEL with or without low-dose RBV in HCV-infected patients with chronic kidney disease ... Read more >>

Gut (Gut)
[2021, :]

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Serotonin is elevated in COVID-19-associated diarrhoea.

Seeun Ha, Byungchang Jin, Brooke Clemmensen, Paul Park, Sumaiya Mahboob, Vadim Gladwill, Farah Madhani Lovely, Andres Gottfried-Blackmore, Aida Habtezion, Subhash Verma, Seungil Ro,

Gut (Gut)
[2021, :]

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Where should ascitic drains be placed? Revisiting anatomical landmarks for paracentesis.

Keith Siau, Naomi Robson, Steven Bollipo, , ,

Gut (Gut)
[2021, :]

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