Letter to the Editor Open Access
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Radiol. Nov 28, 2024; 16(11): 703-707
Published online Nov 28, 2024. doi: 10.4329/wjr.v16.i11.703
Relationship between pancreatic morphological changes and diabetes in autoimmune pancreatitis: Multimodal medical imaging assessment has important potential
Qing-Biao Zhang, Jun-Bang Feng, Chun-Qi Du, Chuan-Ming Li, Department of Medical Imaging, Chongqing Emergency Medical Center, Chongqing University Central Hospital, School of Medicine, Chongqing University, Chongqing 400014, China
Dan Liu, Department of Cardiology, Chongqing Traditional Chinese Medicine Hospital, Chongqing 400000, China
ORCID number: Dan Liu (0009-0003-9383-9234); Jun-Bang Feng (0000-0001-7343-6612); Chuan-Ming Li (0000-0002-4006-9411).
Co-first authors: Qing-Biao Zhang and Dan Liu.
Co-corresponding authors: Chun-Qi Du and Chuan-Ming Li.
Author contributions: Zhang QB and Liu D contribute equally to this study as co-first authors; Du CQ and Li CM contribute equally to this study as co-first authors; Zhang QB, Liu D and Feng JB designed the research; Zhang QB performed the research; Zhang QB, Du CQ and Feng JB analysed the data; Zhang QB, Liu D, Du CQ, Feng JB and Li CM wrote the letter; and Feng JB and Li CM revised the letter.
Conflict-of-interest statement: All of the authors report no relevant conflicts of interest for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Chuan-Ming Li, Associate Professor, MD, Department of Medical Imaging, Chongqing Emergency Medical Center, Chongqing University Central Hospital, School of Medicine, Chongqing University, No. 1 Jiankang Road, Yuzhong District, Chongqing 400014, China. lichuanming@hospital.cqmu.edu.cn
Received: October 3, 2024
Revised: November 7, 2024
Accepted: November 19, 2024
Published online: November 28, 2024
Processing time: 54 Days and 18.1 Hours

Abstract

Autoimmune pancreatitis (AIP) is a special type of chronic pancreatitis with clinical symptoms of obstructive jaundice and abdominal discomfort; this condition is caused by autoimmunity and marked by pancreatic fibrosis and dysfunction. Previous studies have revealed a close relationship between early pancreatic atrophy and the incidence rate of diabetes in type 1 AIP patients receiving steroid treatment. Shimada et al performed a long-term follow-up study and reported that the pancreatic volume (PV) of these patients initially exponentially decreased but then slowly decreased, which was considered to be an important factor related to diabetes; moreover, serum IgG4 levels were positively correlated with PV during follow-up. In this letter, regarding the original study presented by Shimada et al, we present our insights and discuss how multimodal medical imaging and artificial intelligence can be used to better assess the relationship between pancreatic morphological changes and diabetes in patients with AIP.

Key Words: Autoimmune pancreatitis; Diabetes; Pancreatic morphological changes; Multimodal medical imaging; Artificial intelligence

Core Tip: Early pancreatic atrophy is associated with a greater incidence of diabetes in patients with type 1 autoimmune pancreatitis who are treated with steroids. Shimada et al reported that the pancreatic volume of these patients initially exponentially decreased, but then slowly decreased, which considered to be an important factor related to diabetes. However, we identified several potential shortcomings of this study, such as its small sample size and complex measurement process. In future research, multimodal medical MRI images and artificial intelligence algorithms should be used, and large research samples should be included to increase the universality and reliability of the research results.



TO THE EDITOR

We were intrigued by the recently published article entitled "Pancreatic volume change using 3 dimensions-computed tomography volumetry and its relationships with diabetes on long-term follow-up in autoimmune pancreatitis"[1]. In this study, Shimada et al[1] evaluated pancreatic volume (PV) changes in patients with autoimmune pancreatitis (AIP) via three-dimensional (3D) computed tomography (CT) using a retrospective approach and explored the relationship between these changes and diabetes. This study revealed that the change in PV, which initially exponentially decreased but then slowly decreased, is an important factor related to diabetes, and serum IgG4 Levels were positively correlated with PV during follow-up.

AIP is a rare and specific chronic pancreatic disease characterized by obstructive jaundice and a significant response to steroid therapy, (with or without pancreatic masses). AIP can be divided into two types. Type 1 AIP, which is also known as lymphoplasmacytic sclerosing pancreatitis, typically affects multiple organs. Type 2 AIP, which is also known as idiopathic duct-centric pancreatitis, mainly affects the pancreas[2]. Type 1 AIP is more common than type 2 AIP and is characterized by high serum IgG4 levels and a good response to steroid therapy[3]. In AIP patients, the pancreas is attacked by the autoimmune system, thus leading to inflammation and fibrosis of the pancreatic tissue and further resulting in pancreatic atrophy[4]. In a previous meta-analysis[5], the prevalence of diabetes in type 1 and type 2 AIP patients was 44% and 11%, respectively. Previous studies[6,7] have demonstrated a close relationship between early pancreatic atrophy and the incidence rate of diabetes in type 1 AIP patients receiving steroid treatment. However, long-term follow-up studies have not yet been conducted. Shimada et al[1] performed a long-term follow-up study and reported that the PV of these patients initially exponentially decreased but then slowly decreased, which was considered to be an important factor related to diabetes; additionally, serum IgG4 levels were positively correlated with PV during follow-up. Research in this field, which has deepened our understanding of the pathogenesis of AIP and has important clinical significance in preventing diabetes in AIP patients, is highly valuable.

However, we also identified several potential shortcomings in this study[1]. For example, the small sample size of this study was not sufficient to fully represent all of the AIP patients. To address this issue, the use of G*Power software to estimate the sample size is recommended. The G*Power software includes five statistical methods (F, t, χ2, Z, and exact tests) and is often used to calculate the required sample size and conduct statistical analysis, according to previous studies[8]. In this study, we recommend the selection of an effect size of 0.5 (medium effect) based on Cohen’s standard to effectively balance the sample size and to test power. The significance level (α) should be set at 0.05 to ensure statistical significance in the results, and a power of 0.8 should be used to control the type II error rate to within 20%[9,10]. To investigate the significance of the changes in the PV in AIP patients after steroid treatment, G*Power calculations revealed that a sample size of 34 cases was needed. To investigate the changes in AIP patients receiving steroid treatment compared with healthy controls, the total sample size as determined via G*Power calculation was 128, with 64 participants included in each group.

In this study[1], all of the patients underwent at least three CT scans within the first year, and then at least one scan every 12 months. Too much ionizing radiation may lead to the occurrence of tumours. In addition, the soft tissue contrast of the CT images was not good. To address these issues, magnetic resonance imaging (MRI) could serve as an alternative testing measure. MRI has many advantages for evaluating pancreatic atrophy. The high soft tissue contrast of MRI can clearly display the outline and internal structure of the pancreas. Multiple sequences [including T1 weighted, T2 weighted, and diffusion weighted imaging (DWI), among other sequences] can provide information on functional and structural changes in the pancreas from different perspectives. Kobi et al[11] suggested that MRI is crucial for the detection, diagnosis, staging, and posttreatment monitoring of pancreatic tumours. Itani et al[12] indicated that magnetic resonance cholangiopancreatography can both sensitively and accurately detect pancreatic duct and bile duct abnormalities. The apparent diffusion coefficient is a quantitative indicator obtained from DWI and can be used for the early determination of the effect of steroid therapy for AIP[13]. These results indicated that MRI has many advantages over CT in revealing the morphology and internal structure of the pancreas. However, MRI also has limitations, such as increased costs, longer scanning times and the need for good patient cooperation. In addition, MRI also has some contraindications. The use of MRI is limited for patients with pacemakers, metallic foreign bodies in the body, claustrophobia, and unstable vital signs. To address these issues, it is recommended to use non-magnetic materials for metal implants in the body. For patients with claustrophobia, large aperture MRI equipment and fast scanning sequences can help complete the examination[14,15].

In this study, a semiautomatic 3D-CT volume measurement method based on CE-CT images was used for evaluating pancreatic atrophy[1]. However, during CT scanning, the thickness of the reconstructed slices in some cases was set to 2.5 mm, which may result in a deviation between the calculated volume and the actual value. To ensure the accuracy of the data, a reconstruction thickness of less than 1 mm was recommended. In addition, we recommend that at least two doctors perform contour measurements of the pancreas in a double-blind manner and the consistency tests should be performed. Furthermore, the application of artificial intelligence algorithm in pancreas segmentation has undergone rapid development and has achieved good results in recent years. Deep learning algorithms are especially well suited for handling medical images with irregular shapes and weak boundaries, thus significantly improving the efficiency of medical image segmentation[16]. Convolutional neural network (CNN), U-Net and Transform algorithms have shown significant advantages in pancreas boundary segmentation. They can accurately separate the pancreas from the surrounding tissues and perform automatic segmentation of the pancreas, with a Dice coefficient greater than 0.8[1721]. Gao et al[18]proposed the use of a superpixel-based active contour model and combined it with the nnU-Net model to segment the pancreas on CT images. The final DICE index was observed to be greater than 0.85. Using the extension-contraction transformation network proposed by Zheng and Luo[21], the Dice coefficient for pancreas segmentation was shown to be 0.86. Sridevi and Jaidhan[22] proposed a new method known as the Spatial Horned Lizard Attention Approach to segment pancreatic abscesses based on MRI images, and the DICE index reached 0.95. Automatic segmentation algorithms can greatly improve work efficiency and reproducibility and reduce the bias caused by subjective factors. Deep learning technology not only plays a key role in pancreatic segmentation but also has important application value in pancreatic disease diagnosis. Zhang et al[23] developed an artificial intelligence model that enables fully automated diagnosis of acute pancreatitis and assessment of its severity. The deep learning model developed by Cao et al[24] could accurately and efficiently detect pancreatic cancer on plain CT scans and achieved an area under the curve of 0.986. In addition, deep learning has been applied in the classification and prognosis prediction of pancreatic steatosis and pancreatic tumours[25,26]. However, artificial intelligence has several limitations, such as high data requirements, significant consumption of computing resources, and relatively weak generalizability[2729].

In summary, the study by Shimada et al[1] greatly deepened our understanding of the pathogenesis of diabetes in AIP patients and has important clinical significance. Artificial intelligence algorithms possess important practical value and potential advantages in this field, as they can automatically and accurately separate the pancreas and surrounding tissues and perform morphological and structural analyses. This technology can not only improve the efficiency of clinical work but also significantly enhance the accuracy of results. Multimodal imaging can display the subtle anatomical structure of the pancreas from multiple angles, providing rich pathophysiological information about AIP. The combination of multimodal imaging and artificial intelligence greatly facilitates the diagnosis, treatment, and prognostic evaluation of AIP, and can help deepen our understanding of the mechanisms underlying AIP. In future studies, we recommend incorporating multimodal medical images, including MRI, CT and positron emission tomography images, from multiple centres/devices and using artificial intelligence algorithms such as CNN, U-Net or Transform to establish models to achieve automatic segmentation of the pancreas and automatic analysis of changes in morphology and internal structure. External validation should be used, and randomized controlled trials or real-world research methods should be employed to clarify the true value of the model. In addition, professional sample estimation software (such as G*Power) was used to determine the sample size, and healthy individuals were used as the control group to improve the generalizability and reliability of the research results. Based on these recommendations, further optimization of research design, imaging methods, and artificial intelligence technology would improve the accuracy and automation greatly in the future. This had significant potential value for the clinical application and promotion of this technology.

Footnotes

Provenance and peer review: Invited article; Externally peer reviewed.

Peer-review model: Single blind

Specialty type: Radiology, nuclear medicine and medical imaging

Country of origin: China

Peer-review report’s classification

Scientific Quality: Grade C, Grade C

Novelty: Grade C, Grade B

Creativity or Innovation: Grade b, Grade B

Scientific Significance: Grade b, Grade B

P-Reviewer: Jia MJ S-Editor: Lin C L-Editor: A P-Editor: Wang WB

References
1.  Shimada R, Yamada Y, Okamoto K, Murakami K, Motomura M, Takaki H, Fukuzawa K, Asayama Y. Pancreatic volume change using 3 dimensions-computed tomography volumetry and its relationships with diabetes on long-term follow-up in autoimmune pancreatitis. World J Radiol. 2024;16:644-656.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in F6Publishing: 1]  [Reference Citation Analysis (0)]
2.  Gallo C, Dispinzieri G, Zucchini N, Invernizzi P, Massironi S. Autoimmune pancreatitis: Cornerstones and future perspectives. World J Gastroenterol. 2024;30:817-832.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in CrossRef: 2]  [Reference Citation Analysis (0)]
3.  Nista EC, De Lucia SS, Manilla V, Schepis T, Pellegrino A, Ojetti V, Pignataro G, Zileri Dal Verme L, Franceschi F, Gasbarrini A, Candelli M. Autoimmune Pancreatitis: From Pathogenesis to Treatment. Int J Mol Sci. 2022;23.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 1]  [Cited by in F6Publishing: 11]  [Article Influence: 5.5]  [Reference Citation Analysis (0)]
4.  Frøkjær JB, Olesen SS, Drewes AM. Fibrosis, atrophy, and ductal pathology in chronic pancreatitis are associated with pancreatic function but independent of symptoms. Pancreas. 2013;42:1182-1187.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 44]  [Cited by in F6Publishing: 43]  [Article Influence: 3.9]  [Reference Citation Analysis (0)]
5.  Lanzillotta M, Tacelli M, Falconi M, Arcidiacono PG, Capurso G, Della-Torre E. Incidence of endocrine and exocrine insufficiency in patients with autoimmune pancreatitis at diagnosis and after treatment: a systematic review and meta-analysis. Eur J Intern Med. 2022;100:83-93.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 2]  [Cited by in F6Publishing: 10]  [Article Influence: 5.0]  [Reference Citation Analysis (0)]
6.  Masuda A, Shiomi H, Matsuda T, Takenaka M, Arisaka Y, Azuma T, Kutsumi H. The relationship between pancreatic atrophy after steroid therapy and diabetes mellitus in patients with autoimmune pancreatitis. Pancreatology. 2014;14:361-365.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 35]  [Cited by in F6Publishing: 32]  [Article Influence: 3.2]  [Reference Citation Analysis (0)]
7.  Hirano K, Tada M, Isayama H, Watanabe T, Saito T, Uchino R, Hamada T, Miyabayashi K, Mizuno S, Mohri D, Sasaki T, Kogure H, Yamamoto N, Sasahira N, Toda N, Takahara N, Yagioka H, Akiyama D, Ito Y, Koike K. High alcohol consumption increases the risk of pancreatic stone formation and pancreatic atrophy in autoimmune pancreatitis. Pancreas. 2013;42:502-505.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 24]  [Cited by in F6Publishing: 23]  [Article Influence: 2.1]  [Reference Citation Analysis (0)]
8.  Kang H. Sample size determination and power analysis using the G*Power software. J Educ Eval Health Prof. 2021;18:17.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 186]  [Cited by in F6Publishing: 545]  [Article Influence: 181.7]  [Reference Citation Analysis (0)]
9.  Faul F, Erdfelder E, Buchner A, Lang AG. Statistical power analyses using G*Power 3.1: tests for correlation and regression analyses. Behav Res Methods. 2009;41:1149-1160.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 13379]  [Cited by in F6Publishing: 15320]  [Article Influence: 1094.3]  [Reference Citation Analysis (0)]
10.  Faul F, Erdfelder E, Lang AG, Buchner A. G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods. 2007;39:175-191.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 26400]  [Cited by in F6Publishing: 31950]  [Article Influence: 1879.4]  [Reference Citation Analysis (0)]
11.  Kobi M, Veillette G, Narurkar R, Sadowsky D, Paroder V, Shilagani C, Gilet A, Flusberg M. Imaging and Management of Pancreatic Cancer. Semin Ultrasound CT MR. 2020;41:139-151.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 3]  [Cited by in F6Publishing: 3]  [Article Influence: 0.8]  [Reference Citation Analysis (0)]
12.  Itani M, Lalwani N, Anderson MA, Arif-Tiwari H, Paspulati RM, Shetty AS. Magnetic resonance cholangiopancreatography: pitfalls in interpretation. Abdom Radiol (NY). 2023;48:91-105.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 3]  [Cited by in F6Publishing: 4]  [Article Influence: 4.0]  [Reference Citation Analysis (0)]
13.  Sekito T, Ishii Y, Serikawa M, Tsuboi T, Kawamura R, Tsushima K, Nakamura S, Hirano T, Fukiage A, Mori T, Ikemoto J, Kiyoshita Y, Saeki S, Tamura Y, Miyamoto S, Chayama K. The role of apparent diffusion coefficient value in the diagnosis of localized type 1 autoimmune pancreatitis: differentiation from pancreatic ductal adenocarcinoma and evaluation of response to steroids. Abdom Radiol (NY). 2021;46:2014-2024.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 3]  [Cited by in F6Publishing: 3]  [Article Influence: 1.0]  [Reference Citation Analysis (0)]
14.  Stanley E, Cradock A, Bisset J, McEntee C, O'Connell MJ. Impact of sensory design interventions on image quality, patient anxiety and overall patient experience at MRI. Br J Radiol. 2016;89:20160389.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 11]  [Cited by in F6Publishing: 13]  [Article Influence: 1.6]  [Reference Citation Analysis (0)]
15.  Oztek MA, Brunnquell CL, Hoff MN, Boulter DJ, Mossa-Basha M, Beauchamp LH, Haynor DL, Nguyen XV. Practical Considerations for Radiologists in Implementing a Patient-friendly MRI Experience. Top Magn Reson Imaging. 2020;29:181-186.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 11]  [Cited by in F6Publishing: 19]  [Article Influence: 6.3]  [Reference Citation Analysis (0)]
16.  Xu Y, Quan R, Xu W, Huang Y, Chen X, Liu F. Advances in Medical Image Segmentation: A Comprehensive Review of Traditional, Deep Learning and Hybrid Approaches. Bioengineering (Basel). 2024;11.  [PubMed]  [DOI]  [Cited in This Article: ]  [Reference Citation Analysis (0)]
17.  Fang K, He B, Liu L, Hu H, Fang C, Huang X, Jia F. UMRFormer-net: a three-dimensional U-shaped pancreas segmentation method based on a double-layer bridged transformer network. Quant Imaging Med Surg. 2023;13:1619-1630.  [PubMed]  [DOI]  [Cited in This Article: ]  [Reference Citation Analysis (0)]
18.  Gao H, Li J, Shen N, Liu L, Yang Y, Hu P, Lu W. An improvement method for pancreas CT segmentation using superpixel-based active contour. Phys Med Biol. 2024;69.  [PubMed]  [DOI]  [Cited in This Article: ]  [Reference Citation Analysis (0)]
19.  Kawamoto S, Zhu Z, Chu LC, Javed AA, Kinny-Köster B, Wolfgang CL, Hruban RH, Kinzler KW, Fouladi DF, Blanco A, Shayesteh S, Fishman EK. Deep neural network-based segmentation of normal and abnormal pancreas on abdominal CT: evaluation of global and local accuracies. Abdom Radiol (NY). 2024;49:501-511.  [PubMed]  [DOI]  [Cited in This Article: ]  [Reference Citation Analysis (0)]
20.  Li C, Mao Y, Liang S, Li J, Wang Y, Guo Y. Deep causal learning for pancreatic cancer segmentation in CT sequences. Neural Netw. 2024;175:106294.  [PubMed]  [DOI]  [Cited in This Article: ]  [Reference Citation Analysis (0)]
21.  Zheng Y, Luo J. Extension-contraction transformation network for pancreas segmentation in abdominal CT scans. Comput Biol Med. 2023;152:106410.  [PubMed]  [DOI]  [Cited in This Article: ]  [Reference Citation Analysis (0)]
22.  Sridevi B, Jaidhan BJ. Optimized Spatial Transformer for Segmenting Pancreas Abnormalities. J Imaging Inform Med.  2024.  [PubMed]  [DOI]  [Cited in This Article: ]  [Reference Citation Analysis (0)]
23.  Zhang C, Peng J, Wang L, Wang Y, Chen W, Sun MW, Jiang H. A deep learning-powered diagnostic model for acute pancreatitis. BMC Med Imaging. 2024;24:154.  [PubMed]  [DOI]  [Cited in This Article: ]  [Reference Citation Analysis (0)]
24.  Cao K, Xia Y, Yao J, Han X, Lambert L, Zhang T, Tang W, Jin G, Jiang H, Fang X, Nogues I, Li X, Guo W, Wang Y, Fang W, Qiu M, Hou Y, Kovarnik T, Vocka M, Lu Y, Chen Y, Chen X, Liu Z, Zhou J, Xie C, Zhang R, Lu H, Hager GD, Yuille AL, Lu L, Shao C, Shi Y, Zhang Q, Liang T, Zhang L, Lu J. Large-scale pancreatic cancer detection via non-contrast CT and deep learning. Nat Med. 2023;29:3033-3043.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 1]  [Cited by in F6Publishing: 23]  [Article Influence: 23.0]  [Reference Citation Analysis (0)]
25.  Liang W, Tian W, Wang Y, Wang P, Wang Y, Zhang H, Ruan S, Shao J, Zhang X, Huang D, Ding Y, Bai X. Classification prediction of pancreatic cystic neoplasms based on radiomics deep learning models. BMC Cancer. 2022;22:1237.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in F6Publishing: 7]  [Reference Citation Analysis (0)]
26.  Sun Y, Zhang L, Huang JQ, Su J, Cui LG. Non-invasive diagnosis of pancreatic steatosis with ultrasound images using deep learning network. Heliyon. 2024;10:e37580.  [PubMed]  [DOI]  [Cited in This Article: ]  [Reference Citation Analysis (0)]
27.  Yang E, Kim JH, Min JH, Jeong WK, Hwang JA, Lee JH, Shin J, Kim H, Lee SE, Baek SY. nnU-Net-Based Pancreas Segmentation and Volume Measurement on CT Imaging in Patients with Pancreatic Cancer. Acad Radiol. 2024;31:2784-2794.  [PubMed]  [DOI]  [Cited in This Article: ]  [Reference Citation Analysis (0)]
28.  Mazor N, Dar G, Lederman R, Lev-Cohain N, Sosna J, Joskowicz L. MC3DU-Net: a multisequence cascaded pipeline for the detection and segmentation of pancreatic cysts in MRI. Int J Comput Assist Radiol Surg. 2024;19:423-432.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 2]  [Reference Citation Analysis (0)]
29.  Dong K, Hu P, Zhu Y, Tian Y, Li X, Zhou T, Bai X, Liang T, Li J. Attention-enhanced multiscale feature fusion network for pancreas and tumor segmentation. Med Phys.  2024.  [PubMed]  [DOI]  [Cited in This Article: ]