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Article ; Online: Management of Obesity and Obesity-Related Disorders: From Stem Cells and Epigenetics to Its Treatment.

Cruciani, Sara / Delitala, Alessandro Palmerio / Cossu, Maria Laura / Ventura, Carlo / Maioli, Margherita

International journal of molecular sciences

2023 Volume 24, Issue 3

Abstract: Obesity is a complex worldwide disease, characterized by an abnormal or excessive fat accumulation. The onset of this pathology is generally linked to a complex network of interactions among genetic and environmental factors, aging, lifestyle, and diets. ...

Abstract	Obesity is a complex worldwide disease, characterized by an abnormal or excessive fat accumulation. The onset of this pathology is generally linked to a complex network of interactions among genetic and environmental factors, aging, lifestyle, and diets. During adipogenesis, several regulatory mechanisms and transcription factors are involved. As fat cells grow, adipose tissue becomes increasingly large and dysfunctional, losing its endocrine function, secreting pro-inflammatory cytokines, and recruiting infiltrating macrophages. This long-term low-grade systemic inflammation results in insulin resistance in peripheral tissues. In this review we describe the main mechanisms involved in adipogenesis, from a physiological condition to obesity. Current therapeutic strategies for the management of obesity and the related metabolic syndrome are also reported.
MeSH term(s)	Humans ; Obesity/complications ; Obesity/genetics ; Obesity/therapy ; Adipose Tissue/metabolism ; Adipocytes/metabolism ; Insulin Resistance/physiology ; Adipogenesis/genetics ; Stem Cells/metabolism ; Epigenesis, Genetic ; Inflammation/genetics ; Inflammation/therapy ; Inflammation/metabolism
Language	English
Publishing date	2023-01-24
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24032310
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Article: Jejunal adenocarcinoma after biliopancreatic diversion. Report of a case.

Cossu, Maria L / Fancellu, Alessandro / Feo, Claudio F / Ginesu, Giorgio C / Sogos, Sebastiano / Ariu, Maria L / Porcu, Alberto

Obesity research & clinical practice

2022 Volume 16, Issue 3, Page(s) 269–271

Abstract: The effects of bariatric surgery on the development of gastrointestinal cancers remain ill defined. We present a case of jejunal adenocarcinoma developing 19 years after biliopancreatic diversion (BPD) procedure according to Scopinaro's technique. The ... ...

Abstract	The effects of bariatric surgery on the development of gastrointestinal cancers remain ill defined. We present a case of jejunal adenocarcinoma developing 19 years after biliopancreatic diversion (BPD) procedure according to Scopinaro's technique. The patient developed a marked distension of the biliopancreatic limb caused by a jejunal mass, evolving towards the so called "duodenal blowout". Emergency jejunal resection of the biliopancreatic limb, with creation of a new end-to-side jejunal-ileal anastomosis was necessary. The histological examination resulted in a moderately-differentiated ulcerated adenocarcinoma, with reactive lymph nodes and tumor-free resection margins. Tumors of the gastrointestinal system can arise following malabsorptive operations for morbid obesity, and they may be difficult to diagnose, since the symptoms are often attributed to the anatomical-functional changes resulting from this type of surgery. The case reported herein suggests that there is a need for surveillance in patients complaining of digestive symptoms after malabsorptive bariatric surgery.
MeSH term(s)	Adenocarcinoma/etiology ; Adenocarcinoma/surgery ; Anastomosis, Surgical ; Biliopancreatic Diversion/adverse effects ; Biliopancreatic Diversion/methods ; Duodenum/surgery ; Humans ; Obesity, Morbid/surgery
Language	English
Publishing date	2022-05-11
Publishing country	Netherlands
Document type	Case Reports ; Journal Article
ZDB-ID	2274031-4
ISSN	1878-0318 ; 1871-403X
ISSN (online)	1878-0318
ISSN	1871-403X
DOI	10.1016/j.orcp.2022.05.002
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Article ; Online: Metformin and Vitamin D Modulate Inflammation and Autophagy during Adipose-Derived Stem Cell Differentiation.

Cruciani, Sara / Garroni, Giuseppe / Pala, Renzo / Cossu, Maria Laura / Ginesu, Giorgio Carlo / Ventura, Carlo / Maioli, Margherita

International journal of molecular sciences

2021 Volume 22, Issue 13

Abstract: Adipose-derived stem cells (ADSCs) came out from the regenerative medicine landscape for their ability to differentiate into several phenotypes, contributing to tissue regeneration both in vitro and in vivo. Dysregulation in stem cell recruitment and ... ...

Abstract	Adipose-derived stem cells (ADSCs) came out from the regenerative medicine landscape for their ability to differentiate into several phenotypes, contributing to tissue regeneration both in vitro and in vivo. Dysregulation in stem cell recruitment and differentiation during adipogenesis is linked to a chronic low-grade inflammation and macrophage infiltration inside the adipose tissue, insulin resistance, cardiovascular disease and obesity. In the present paper we aimed to evaluate the role of metformin and vitamin D, alone or in combination, in modulating inflammation and autophagy in ADSCs during adipogenic commitment. ADSCs were cultured for 21 days in the presence of a specific adipogenic differentiation medium, together with metformin, or vitamin D, or both. We then analyzed the expression of FoxO1 and Heat Shock Proteins (HSP) and the secretion of proinflammatory cytokines IL-6 and TNF-α by ELISA. Autophagy was also assessed by specific Western blot analysis of ATG12, LC3B I, and LC3B II expression. Our results showed the ability of the conditioned media to modulate adipogenic differentiation, finely tuning the inflammatory response and autophagy. We observed a modulation in HSP mRNA levels, and a significant downregulation in cytokine secretion. Taken together, our findings suggest the possible application of these molecules in clinical practice to counteract uncontrolled lipogenesis and prevent obesity and obesity-related metabolic disorders.
MeSH term(s)	Adipocytes/cytology ; Adipocytes/drug effects ; Adipocytes/metabolism ; Cell Differentiation/drug effects ; Cytokines/metabolism ; Humans ; Inflammation Mediators/metabolism ; Mesenchymal Stem Cells/cytology ; Mesenchymal Stem Cells/drug effects ; Mesenchymal Stem Cells/metabolism ; Metformin/pharmacology ; Vitamin D/pharmacology
Chemical Substances	Cytokines ; Inflammation Mediators ; Vitamin D (1406-16-2) ; Metformin (9100L32L2N)
Language	English
Publishing date	2021-06-22
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms22136686
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Article ; Online: Metformin and vitamin D modulate adipose-derived stem cell differentiation towards the beige phenotype.

Cruciani, Sara / Garroni, Giuseppe / Pala, Renzo / Coradduzza, Donatella / Cossu, Maria Laura / Ginesu, Giorgio Carlo / Capobianco, Giampiero / Dessole, Salvatore / Ventura, Carlo / Maioli, Margherita

Adipocyte

2022 Volume 11, Issue 1, Page(s) 356–365

Abstract: Adipose-derived stem cells (ADSCs) represent an ideal stem cell population for regenerative medicine. ADSC adipogenic differentiation is controlled by the activation of a specific transcriptional program, including epigenetic factors and key adipogenic ... ...

Abstract	Adipose-derived stem cells (ADSCs) represent an ideal stem cell population for regenerative medicine. ADSC adipogenic differentiation is controlled by the activation of a specific transcriptional program, including epigenetic factors and key adipogenic genes. Under certain conditioned media, ADSCs can differentiate into several phenotypes. We previously demonstrated that bioactive molecules could counteract lipid accumulation and regulate adipogenesis, acting on inflammation and vitamin D metabolism. In the present paper, we aimed at evaluating the effect of metformin and vitamin D in targeting ADSC differentiation towards an intermediate phenotype, as beige adipocytes. We exposed ADSCs to different conditioned media and then we evaluated the levels of expression of main markers of adipogenesis, aP2, LPL and ACOT2. We also analysed the gene and protein expression of thermogenic UCP1 protein, and the expression of PARP1 and the beige specific marker TMEM26. Our results showed a novel effect of metformin and vitamin D not only in inhibiting adipogenesis, but also in inducing a specific 'brown-like' phenotype. These findings pave the way for their possible application in the control of
MeSH term(s)	Adipogenesis ; Cell Differentiation ; Culture Media, Conditioned/pharmacology ; Metformin/pharmacology ; Phenotype ; Vitamin D/pharmacology
Chemical Substances	Culture Media, Conditioned ; Vitamin D (1406-16-2) ; Metformin (9100L32L2N)
Language	English
Publishing date	2022-09-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2681769-X
ISSN	2162-397X ; 2162-397X
ISSN (online)	2162-397X
ISSN	2162-397X
DOI	10.1080/21623945.2022.2085417
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Article ; Online: Inflammatory Indexes as Predictive Biomarkers of Postoperative Complications in Oncological Thoracic Surgery.

Ginesu, Giorgio Carlo / Paliogiannis, Panagiotis / Feo, Claudio F / Cossu, Maria Laura / Scanu, Antonio Mario / Fancellu, Alessandro / Fois, Alessandro Giuseppe / Zinellu, Angelo / Perra, Teresa / Veneroni, Simone / Porcu, Alberto

Current oncology (Toronto, Ont.)

2022 Volume 29, Issue 5, Page(s) 3425–3432

Abstract: The role of inflammatory responses in predicting outcomes in oncological thoracic surgery is still unclear. The aim of this study was to evaluate a series of blood count inflammation indexes as predicting factors for postoperative complications. We ... ...

Abstract	The role of inflammatory responses in predicting outcomes in oncological thoracic surgery is still unclear. The aim of this study was to evaluate a series of blood count inflammation indexes as predicting factors for postoperative complications. We retrospectively studied 249 patients undergoing elective thoracic surgery in our institution between 2008 and 2020. A total of 184 patients underwent open surgery, and 65 underwent VATS. The neutrophil-to-lymphocyte (NLR), monocyte-to-lymphocyte (MLR), and platelet-to-lymphocyte (PLR) ratios, Systemic Inflammation Response Index (SIRI) were calculated preoperatively and on the first and fourth postoperative days, as well as a new derivative index, the Aggregate Inflammation Systemic Index (AISI). Univariate correlations evidenced a statistically significant association between the NLR at the fourth postoperative day and the occurrence of surgical complications in the global cohort (rho = 0.15,
MeSH term(s)	Biomarkers ; Humans ; Inflammation ; Postoperative Complications/etiology ; Prospective Studies ; Retrospective Studies ; Thoracic Surgery
Chemical Substances	Biomarkers
Language	English
Publishing date	2022-05-08
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1236972-x
ISSN	1718-7729 ; 1198-0052
ISSN (online)	1718-7729
ISSN	1198-0052
DOI	10.3390/curroncol29050276
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Article: Perianal mucinous adenocarcinoma with dysplastic polyps of the colon: A case report.

Feo, Claudio F / Veneroni, Simone / Santoru, Antonio / Cossu, Maria Laura / Scanu, Antonio M / Ginesu, Giorgio C / Porcu, Alberto

International journal of surgery case reports

2020 Volume 78, Page(s) 99–102

Abstract: Introduction: Perianal mucinous adenocarcinoma is rarely encountered in the setting of anal neoplasms. The rarity of the disease and the paucity of publications on this topic are responsible for a lack of diagnostic and therapeutic guidelines.: ... ...

Abstract	Introduction: Perianal mucinous adenocarcinoma is rarely encountered in the setting of anal neoplasms. The rarity of the disease and the paucity of publications on this topic are responsible for a lack of diagnostic and therapeutic guidelines. Presentation of case: An 80-year-old man with mucinous adenocarcinoma of the anal canal associated with dysplastic polyps of the colon was treated by multiple endoscopic polypectomies and abdomino-perineal resection of the rectum. We discuss the management of this rare case from the diagnosis up to one-year follow-up. Discussion: Perianal mucinous adenocarcinoma is a very rare entity frequently combined with chronic fistulas. Inflammatory symptoms may mislead its diagnosis, which is often delayed. The unique association between perianal mucinous adenocarcinoma and dysplastic polyps of the colon, that we have reported, may suggest a secondary etiology. High clinical suspicion is important for early and correct diagnosis, which should be based on endoanal ultrasound and/or magnetic resonance imaging followed by deep tissue biopsies. Conclusion: We stress the importance of accumulating such cases in the literature. The understanding of the etiopathogenic mechanisms may lead to the development of novel diagnostic and therapeutic protocols.
Language	English
Publishing date	2020-12-05
Publishing country	Netherlands
Document type	Case Reports
ISSN	2210-2612
ISSN	2210-2612
DOI	10.1016/j.ijscr.2020.12.008
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Article ; Online: Tuning Adipogenic Differentiation in ADSCs by Metformin and Vitamin D: Involvement of miRNAs.

Cruciani, Sara / Garroni, Giuseppe / Balzano, Francesca / Pala, Renzo / Bellu, Emanuela / Cossu, Maria Laura / Ginesu, Giorgio Carlo / Ventura, Carlo / Maioli, Margherita

International journal of molecular sciences

2020 Volume 21, Issue 17

Abstract: Fat tissue represents an important source of adipose-derived stem cells (ADSCs), which can differentiate towards several phenotypes under certain stimuli. Definite molecules as vitamin D are able to influence stem cell fate, acting on the expression of ... ...

Abstract	Fat tissue represents an important source of adipose-derived stem cells (ADSCs), which can differentiate towards several phenotypes under certain stimuli. Definite molecules as vitamin D are able to influence stem cell fate, acting on the expression of specific genes. In addition, miRNAs are important modulating factors in obesity and numerous diseases. We previously identified specific conditioned media able to commit stem cells towards defined cellular phenotypes. In the present paper, we aimed at evaluating the role of metformin on ADSCs differentiation. In particular, ADSCs were cultured in a specific adipogenic conditioned medium (MD), in the presence of metformin, alone or in combination with vitamin D. Our results showed that the combination of the two compounds is able to counteract the appearance of an adipogenic phenotype, indicating a feedforward regulation on vitamin D metabolism by metformin, acting on CYP27B1 and CYP3A4. We then evaluated the role of specific epigenetic modulating genes and miRNAs in controlling stem cell adipogenesis. The combination of the two molecules was able to influence stem cell fate, by modulating the adipogenic phenotype, suggesting their possible application in clinical practice in counteracting uncontrolled lipogenesis and obesity-related diseases.
MeSH term(s)	25-Hydroxyvitamin D3 1-alpha-Hydroxylase/genetics ; Adipogenesis ; Adipose Tissue/cytology ; Adipose Tissue/metabolism ; Adult ; Cell Differentiation/drug effects ; Cell Proliferation ; Cells, Cultured ; Culture Media, Conditioned/chemistry ; Cytochrome P-450 CYP3A/genetics ; Epigenesis, Genetic ; Female ; Gene Expression Profiling ; Gene Expression Regulation/drug effects ; Humans ; Male ; Mesenchymal Stem Cells/cytology ; Mesenchymal Stem Cells/metabolism ; Metformin/pharmacology ; MicroRNAs/genetics ; Middle Aged ; Phenotype ; Vitamin D/pharmacology
Chemical Substances	Culture Media, Conditioned ; MicroRNAs ; Vitamin D (1406-16-2) ; Metformin (9100L32L2N) ; Cytochrome P-450 CYP3A (EC 1.14.14.1) ; CYP3A4 protein, human (EC 1.14.14.55) ; 25-Hydroxyvitamin D3 1-alpha-Hydroxylase (EC 1.14.15.18) ; CYP27B1 protein, human (EC 1.14.15.18)
Language	English
Publishing date	2020-08-27
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms21176181
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Article ; Online: Management of complex liver cystic hydatidosis: challenging benign diseases for the hepatic surgeon: A case series report from an endemic area.

Fancellu, Alessandro / Perra, Teresa / Vergari, Dario / Vargiu, Isabel / Feo, Claudio F / Cossu, Maria L / Deiana, Giulia / Porcu, Alberto

Medicine

2020 Volume 99, Issue 48, Page(s) e23435

Abstract: Hydatid cysts of the liver are benign lesions which require a wide range of surgical strategies for their treatment. We hypothesized that cysts larger than 15 cm, or compressing main vascular structures, or located in both hemilivers should be considered, ...

Abstract	Hydatid cysts of the liver are benign lesions which require a wide range of surgical strategies for their treatment. We hypothesized that cysts larger than 15 cm, or compressing main vascular structures, or located in both hemilivers should be considered, as well as complicated cysts, in the category of complex hydatid cysts.In a retrospective study including 55 patients, we evaluated the characteristics of complex hydatid cysts, and compared surgical outcomes between patients operated on for complex cysts (Complex Group) and those operated on for non-complex cysts (non-Complex Group).In the Complex Group, 19% of patients had cysto-biliary communication with recurrent cholangitis, 9.5% had cysts eroding the diaphragm or chest wall, or communicating with the bronchial tree, 31% had cysts with contact with main vascular structures, 11.9% had multiple bilobar cysts, 14.3% had giant cysts with organ displacement, and 14.3% had a combination of the above-mentioned types. Type of surgical treatment was different between the two groups (P < .001). Additional procedures were statistically more frequent in the Complex Group (P = .02). Postoperative morbidity was higher in the Complex Group, although not in a significant manner (P = .07). Median hospital stay was longer in the Complex Group (12 vs 7 days, P < .001). No 30-day mortality occurred. Four patients (7.3%), all belonging to the Complex Group, required reoperation for postoperative complications.Surgery for complex hydatid cysts of the liver is potentially burdened by serious complications. This kind of benign liver disease requires skill-demanding procedures and should be treated in centers with expertise in both hepato-biliary surgery and hydatid disease management.
MeSH term(s)	Adult ; Aged ; Echinococcosis/diagnostic imaging ; Echinococcosis/epidemiology ; Echinococcosis/surgery ; Echinococcosis, Hepatic/diagnostic imaging ; Echinococcosis, Hepatic/epidemiology ; Echinococcosis, Hepatic/surgery ; Endemic Diseases ; Female ; Hepatectomy ; Humans ; Italy/epidemiology ; Length of Stay ; Male ; Middle Aged ; Postoperative Complications ; Retrospective Studies ; Tomography, X-Ray Computed ; Young Adult
Language	English
Publishing date	2020-11-20
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Video-Audio Media
ZDB-ID	80184-7
ISSN	1536-5964 ; 0025-7974
ISSN (online)	1536-5964
ISSN	0025-7974
DOI	10.1097/MD.0000000000023435
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Article ; Online: Adipose-Derived Stem Cell Features and MCF-7.

Garroni, Giuseppe / Balzano, Francesca / Cruciani, Sara / Pala, Renzo / Coradduzza, Donatella / Azara, Emanuela / Bellu, Emanuela / Cossu, Maria Laura / Ginesu, Giorgio C / Carru, Ciriaco / Ventura, Carlo / Maioli, Margherita

Cells

2021 Volume 10, Issue 7

Abstract: Human adipose tissue-derived stem cells (hADSCs) are highly suitable for regeneration therapies being easily collected and propagated in vitro. The effects of different external factors and culturing conditions are able to affect hADSC proliferation, ... ...

Abstract	Human adipose tissue-derived stem cells (hADSCs) are highly suitable for regeneration therapies being easily collected and propagated in vitro. The effects of different external factors and culturing conditions are able to affect hADSC proliferation, senescence, differentiation, and migration, even at the molecular level. In the present paper, we exposed hADSCs to an exhausted medium from the breast cancer cell line (MCF-7) to evaluate whether the soluble factors released by these cells may be able to induce changes in stem cell behavior. In particular, we investigated the expression of stemness-related genes (OCT4; Sox 2; Nanog), the cell-cycle regulators p21 (WAF1/CIP1) p53, epigenetic markers (DNMT1 and Sirt1), and autophagy-related proteins. From our results, we can infer that the exhausted medium from MCF-7 is able to influence the hADSCs behavior increasing the expression of stemness-related genes, cell proliferation, and autophagy. Polyamines detectable in MCF-7 exhausted medium could be related to the higher proliferation capability observed in hADSCs, suggesting direct crosstalk between these molecules and the observed changes in stem cell potency.
MeSH term(s)	Adipose Tissue/cytology ; Autophagosomes/metabolism ; Autophagy/genetics ; Bromodeoxyuridine/metabolism ; Cell Proliferation ; Cell Shape ; Cell Survival ; Culture Media ; Cyclin-Dependent Kinase Inhibitor p21/metabolism ; Epigenesis, Genetic ; Humans ; MCF-7 Cells ; Middle Aged ; Polyamines/metabolism ; Stem Cells/cytology ; Stem Cells/metabolism ; Tumor Suppressor Protein p53/metabolism ; bcl-2-Associated X Protein/metabolism
Chemical Substances	Culture Media ; Cyclin-Dependent Kinase Inhibitor p21 ; Polyamines ; Tumor Suppressor Protein p53 ; bcl-2-Associated X Protein ; Bromodeoxyuridine (G34N38R2N1)
Language	English
Publishing date	2021-07-11
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells10071754
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Article: Mesothelial cyst in the liver round ligament: A case report and review of the literature.

Feo, Claudio F / Ginesu, Giorgio C / Cherchi, Giuseppe / Fancellu, Alessandro / Cossu, M Laura / Porcu, Alberto

International journal of surgery case reports

2017 Volume 37, Page(s) 33–35

Abstract: Introduction: Cysts of the liver round ligament are rare and they are benign in the majority of cases. Current literature has been reviewed on this subject.: Presentation of case: A 22-year-old woman with a history of epigastric pain was admitted at ... ...

Abstract	Introduction: Cysts of the liver round ligament are rare and they are benign in the majority of cases. Current literature has been reviewed on this subject. Presentation of case: A 22-year-old woman with a history of epigastric pain was admitted at our institution. Computed tomography (CT) of the abdomen showed a 14-mm cystic lesion in the epigastrium. A large cyst of the liver round ligament was successfully removed during exploratory laparoscopy and histopathology revealed a benign mesothelial cyst. Discussion: Mesothelial cysts of the liver round ligament are rare entities and we found a total of 5 cases from the literature. Diameter varies from 5 to 14cm. Most patients were asymptomatic or may complain abdominal pain in the upper quadrants. Ultrasonography and CT scan are the most useful diagnostic tools, however differential diagnosis between various abdominal cystic lesions can be difficult. Treatment is usually surgical excision. Conclusion: Mesothelial cysts of the liver round ligament are extremely rare but should be taken in consideration in the differential diagnosis of intra-abdominal cystic lesions. We stress the importance of exploratory laparoscopy that can allow both diagnosis and radical surgical excision.
Language	English
Publishing date	2017-06-15
Publishing country	Netherlands
Document type	Journal Article
ISSN	2210-2612
ISSN	2210-2612
DOI	10.1016/j.ijscr.2017.06.017
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