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Article ; Online: Free fatty acid receptor 4 (FFA4) activation attenuates obese asthma by suppressing adiposity and resolving metaflammation.

Son, So-Eun / Koh, Jung-Min / Im, Dong-Soon

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

2024 Volume 174, Page(s) 116509

Abstract: Obese asthma is recognized to have different asthma phenotypes. N-3 polyunsaturated fatty acids (PUFAs) have shown beneficial effects in obesity and metabolic syndrome. Free fatty acid receptor 4 (FFA4, also known as GPR120) is a receptor for n-3 PUFAs. ... ...

Abstract	Obese asthma is recognized to have different asthma phenotypes. N-3 polyunsaturated fatty acids (PUFAs) have shown beneficial effects in obesity and metabolic syndrome. Free fatty acid receptor 4 (FFA4, also known as GPR120) is a receptor for n-3 PUFAs. In the present study, we investigated whether FFA4 activation ameliorates high-fat diet (HFD)-induced obese asthma. We investigated whether FFA4 activation ameliorates obese asthma using an FFA4 agonist, compound A (CpdA), in combination with FFA4 wild-type (WT) and knock-out (KO) mice. Administration of an FFA4 agonist, compound A (CpdA, 30 mg/kg), suppressed HFD-induced weight gain, adiposity, and airway hypersensitivity (AHR), and increased immune cell infiltration in an FFA4-dependent manner. Histological analysis revealed that CpdA treatment suppressed HFD-induced mucus hypersecretion, inflammation, and fibrosis in an FFA4-dependent manner. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) showed an HFD-induced increase in the mRNA levels of pro-inflammatory cytokines in the lungs and gonadal white adipose tissue, whereas CpdA inhibited this increase in an FFA4-dependent manner. In the fluorescence-activated cell sorting (FACS) analysis, HFD induced an increase in the lung innate lymphoid cells (ILC) ILC1, ILC2, and ILC3; however, CpdA reversed this increase. In addition, HFD induced an increase in the pro-inflammatory M1 macrophage population and a decrease in the anti-inflammatory M2 macrophage population in the lungs, whereas CpdA treatment reversed these changes. The present study suggests that FFA4 activation may have therapeutic potential in obese asthma.
MeSH term(s)	Animals ; Asthma/drug therapy ; Asthma/metabolism ; Adiposity/drug effects ; Obesity/drug therapy ; Obesity/complications ; Obesity/metabolism ; Receptors, G-Protein-Coupled/metabolism ; Receptors, G-Protein-Coupled/agonists ; Male ; Mice, Inbred C57BL ; Diet, High-Fat ; Mice, Knockout ; Mice ; Inflammation/drug therapy ; Inflammation/pathology ; Inflammation/metabolism ; Lung/pathology ; Lung/drug effects ; Lung/metabolism ; Cytokines/metabolism
Chemical Substances	Receptors, G-Protein-Coupled ; FFAR4 protein, mouse ; Cytokines
Language	English
Publishing date	2024-04-03
Publishing country	France
Document type	Journal Article
ZDB-ID	392415-4
ISSN	1950-6007 ; 0753-3322 ; 0300-0893
ISSN (online)	1950-6007
ISSN	0753-3322 ; 0300-0893
DOI	10.1016/j.biopha.2024.116509
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Article: The Fracture Risk Assessment Tool Probability and Trabecular Bone Score Mediate the Relationship between Sphingosine 1-phosphate Levels and Fracture Risk.

Lee, Seung Hun / Kim, Jae Seung / Koh, Jung-Min

Journal of bone metabolism

2023 Volume 30, Issue 4, Page(s) 355–364

Abstract: Background: The sphingosine 1-phosphate (S1P) concentration is a potential biomarker of osteoporotic fracture and is associated with both the fracture risk assessment tool (FRAX) probability and trabecular bone score (TBS), which are well-known ... ...

Abstract	Background: The sphingosine 1-phosphate (S1P) concentration is a potential biomarker of osteoporotic fracture and is associated with both the fracture risk assessment tool (FRAX) probability and trabecular bone score (TBS), which are well-known predictors of fracture. We sought to estimate the effect of the S1P concentration on fracture risk using the FRAX probability and TBS as mediators. Methods: Plasma S1P concentrations, FRAX variables, and TBSs were measured in 66 postmenopausal women with fractures and 273 postmenopausal women without fractures. Associations between S1P concentration, FRAX probability, TBS, and fracture risk were analyzed using correlation, logistic regression, and mediation analyses. Results: Subjects in the highest S1P concentration tertile had a higher fracture risk (odds ratio [OR], 5.09; 95% confidence interval [CI], 2.22-11.67) than those in the lowest S1P concentration tertile before adjustment. Subjects in the highest FRAX probability tertile had a higher fracture risk (OR, 14.59; 95% CI, 5.01-42.53) than those in the lowest FRAX probability tertile before adjustment. Subjects in the lowest TBS tertile had a higher fracture risk (OR, 4.76; 95% CI, 2.28-9.93) than those in the highest TBS tertile before adjustment. After adjustment for FRAX probability and TBS, the highest S1P concentration tertile was still associated with a higher fracture risk (OR, 3.13; 95% CI, 1.28-7.66). The FRAX probability and TBS accounted for 32.6% and 21.7%, respectively, of the relationship between the S1P concentration and fracture risk. Conclusions: The relationship between the circulating S1P concentration and fracture risk was partly mediated by the FRAX probability, bone microarchitecture, and other factors.
Language	English
Publishing date	2023-11-30
Publishing country	Korea (South)
Document type	Journal Article
ZDB-ID	2765291-9
ISSN	2287-7029 ; 2287-6375
ISSN (online)	2287-7029
ISSN	2287-6375
DOI	10.11005/jbm.2023.30.4.355
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Article ; Online: Osteoclast-derived SLIT3 is a coupling factor linking bone resorption to bone formation.

Koh, Jung-Min

BMB reports

2018 Volume 51, Issue 6, Page(s) 263–264

Abstract: We identified osteoclast-derived SLIT3 as a new coupling factor using fractionated secretomics. Coupling links bone resorption to bone formation. SLIT3 stimulated the recruitment and proliferation of osteoblasts into bone remodeling sites via activation ... ...

Abstract	We identified osteoclast-derived SLIT3 as a new coupling factor using fractionated secretomics. Coupling links bone resorption to bone formation. SLIT3 stimulated the recruitment and proliferation of osteoblasts into bone remodeling sites via activation of β-catenin. Autocrine signaling by SLIT3 also inhibited bone resorption by suppressing the fusion and differentiation of pre-osteoclasts. All mice lacking Slit3 or its receptor Robo1 showed an osteopenic phenotype with low bone formation and high bone resorption. A small truncated recombinant SLIT3 protein increased bone mass in an osteopenic mouse model. These results suggest that SLIT3 is a novel therapeutic target in metabolic bone diseases. [BMB Reports 2018; 51(6): 263-264].
MeSH term(s)	Animals ; Bone Marrow Cells/cytology ; Bone Marrow Cells/metabolism ; Bone Resorption/metabolism ; Cell Differentiation ; Cytokines ; Membrane Proteins/metabolism ; Mice ; Mice, Knockout ; Osteoblasts/cytology ; Osteoblasts/metabolism ; Osteoclasts/cytology ; Osteoclasts/metabolism ; Osteogenesis/physiology ; beta Catenin/metabolism
Chemical Substances	Cytokines ; Membrane Proteins ; Slit3 protein, mouse ; beta Catenin ; bone resorption factor
Language	English
Publishing date	2018-05-15
Publishing country	Korea (South)
Document type	Journal Article
ZDB-ID	2410389-5
ISSN	1976-670X ; 1976-6696
ISSN (online)	1976-670X
ISSN	1976-6696
DOI	10.5483/bmbrep.2018.51.6.109
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Article ; Online: Free Fatty Acid Receptor 4 (FFA4) Activation Ameliorates Imiquimod-Induced Psoriasis in Mice.

Son, So-Eun / Koh, Jung-Min / Im, Dong-Soon

International journal of molecular sciences

2022 Volume 23, Issue 9

Abstract: Dietary supplementation with n-3 polyunsaturated fatty acids (n-3 PUFA) has been used as an adjunct therapy for psoriasis due to its anti-inflammatory properties. Free fatty acid receptor 4 (FFA4 or GPR120) is a receptor-sensing n-3 PUFA. In the present ... ...

Abstract	Dietary supplementation with n-3 polyunsaturated fatty acids (n-3 PUFA) has been used as an adjunct therapy for psoriasis due to its anti-inflammatory properties. Free fatty acid receptor 4 (FFA4 or GPR120) is a receptor-sensing n-3 PUFA. In the present study, we examined whether FFA4 acted as a therapeutic target for n-3 PUFA in psoriasis therapy. Experimentally, psoriasis-like skin lesions were induced by treatment with imiquimod for 6 consecutive days. A selective FFA4 agonist, Compound A (30 mg/kg), was used in FFA4 WT and FFA4 KO mice. Imiquimod-induced psoriasis-like skin lesions, which present as erythematous papules and plaques with silver scaling, as well as markedly elevated IL-17/IL-23 cytokine levels in skin tissues, were significantly suppressed by Compound A in FFA4 WT mice, but not in FFA4 KO mice. Enlarged lymph nodes and spleens, as well as imiquimod-induced, elevated IL-17/IL-23 cytokine levels, were also strongly suppressed by Compound A in FFA4 WT mice, but not in FFA4 KO mice. Imiquimod-induced increases in the CD4
MeSH term(s)	Animals ; Cytokines/therapeutic use ; Disease Models, Animal ; Fatty Acids, Nonesterified/therapeutic use ; Fatty Acids, Omega-3/therapeutic use ; Imiquimod/toxicity ; Interleukin-17/genetics ; Interleukin-23 ; Mice ; Psoriasis/chemically induced ; Psoriasis/drug therapy ; Psoriasis/pathology ; Skin/pathology
Chemical Substances	Cytokines ; Fatty Acids, Nonesterified ; Fatty Acids, Omega-3 ; Interleukin-17 ; Interleukin-23 ; Imiquimod (P1QW714R7M)
Language	English
Publishing date	2022-04-19
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/ijms23094482
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Article ; Online: Activation of Free Fatty Acid Receptor 4 (FFA4) Ameliorates Ovalbumin-Induced Allergic Asthma by Suppressing Activation of Dendritic and Mast Cells in Mice.

Son, So-Eun / Koh, Jung-Min / Im, Dong-Soon

International journal of molecular sciences

2022 Volume 23, Issue 9

Abstract: Epidemiological and clinical studies have suggested that intake of n-3 polyunsaturated fatty acids (PUFA) reduces the incidence of allergic airway diseases and improves pulmonary function in patients with allergic asthma. However, the pharmacological ... ...

Abstract	Epidemiological and clinical studies have suggested that intake of n-3 polyunsaturated fatty acids (PUFA) reduces the incidence of allergic airway diseases and improves pulmonary function in patients with allergic asthma. However, the pharmacological targets of PUFA have not been elucidated upon. We investigated whether free fatty acid receptor 4 (FFA4, also known as GPR120) is a molecular target for beneficial PUFA in asthma therapy. In an ovalbumin (OVA)-induced allergic asthma model, compound A (a selective agonist of FFA4) was administrated before OVA sensitization or OVA challenge in FFA4 wild-type (WT) and knock-out (KO) mice. Compound A treatment of RBL-2H3 cells suppressed mast cell degranulation in vitro in a concentration-dependent manner. Administration of compound A suppressed in vivo allergic characteristics in bronchoalveolar lavage fluid (BALF) and lungs, such as inflammatory cytokine levels and eosinophil accumulation in BALF, inflammation and mucin secretion in the lungs. Compound A-induced suppression was not only observed in mice treated with compound A before OVA challenge, but in mice treated before OVA sensitization as well, implying that compound A acts on mast cells as well as dendritic cells. Furthermore, this suppression by compound A was only observed in FFA4-WT mice and was absent in FFA4-KO mice, implying that compound A action is mediated through FFA4. Activation of FFA4 may be a therapeutic target of PUFA in allergic asthma by suppressing the activation of dendritic cells and mast cells, suggesting that highly potent specific agonists of FFA4 could be a novel therapy for allergic asthma.
MeSH term(s)	Animals ; Asthma/chemically induced ; Bronchoalveolar Lavage Fluid ; Cytokines/therapeutic use ; Disease Models, Animal ; Fatty Acids, Nonesterified/therapeutic use ; Humans ; Lung ; Mast Cells ; Mice ; Mice, Inbred BALB C ; Mice, Knockout ; Ovalbumin/adverse effects
Chemical Substances	Cytokines ; Fatty Acids, Nonesterified ; Ovalbumin (9006-59-1)
Language	English
Publishing date	2022-05-09
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/ijms23095270
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Article ; Online: Free Fatty Acid Receptor 4 (FFA4) Activation Ameliorates Imiquimod-Induced Psoriasis in Mice

So-Eun Son / Jung-Min Koh / Dong-Soon Im

International Journal of Molecular Sciences, Vol 23, Iss 4482, p

2022 Volume 4482

Abstract	Dietary supplementation with n-3 polyunsaturated fatty acids (n-3 PUFA) has been used as an adjunct therapy for psoriasis due to its anti-inflammatory properties. Free fatty acid receptor 4 (FFA4 or GPR120) is a receptor-sensing n-3 PUFA. In the present study, we examined whether FFA4 acted as a therapeutic target for n-3 PUFA in psoriasis therapy. Experimentally, psoriasis-like skin lesions were induced by treatment with imiquimod for 6 consecutive days. A selective FFA4 agonist, Compound A (30 mg/kg), was used in FFA4 WT and FFA4 KO mice. Imiquimod-induced psoriasis-like skin lesions, which present as erythematous papules and plaques with silver scaling, as well as markedly elevated IL-17/IL-23 cytokine levels in skin tissues, were significantly suppressed by Compound A in FFA4 WT mice, but not in FFA4 KO mice. Enlarged lymph nodes and spleens, as well as imiquimod-induced, elevated IL-17/IL-23 cytokine levels, were also strongly suppressed by Compound A in FFA4 WT mice, but not in FFA4 KO mice. Imiquimod-induced increases in the CD4 + IL-17A + T cell population in lymph nodes and spleens were suppressed by Compound A treatment in FFA4 WT mice; however, this was not seen in FFA4 KO mice. Furthermore, compound A suppressed the differentiation of CD4 + naïve T cells from splenocytes into T H 17 cells in an FFA4-dependent manner. In conclusion, we demonstrated that the activation of FFA4 ameliorates imiquimod-induced psoriasis, and the suppression of the differentiation of T H 17 cells may partly contribute to its efficacy. Therefore, we suggest that FFA4 could be a therapeutic target for psoriasis therapy.
Keywords	psoriasis ; imiquimod ; free fatty acid receptor 4 ; FFA4 ; polyunsaturated fatty acids ; IL-17 ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	616
Language	English
Publishing date	2022-04-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article ; Online: Activation of Free Fatty Acid Receptor 4 (FFA4) Ameliorates Ovalbumin-Induced Allergic Asthma by Suppressing Activation of Dendritic and Mast Cells in Mice

So-Eun Son / Jung-Min Koh / Dong-Soon Im

International Journal of Molecular Sciences, Vol 23, Iss 5270, p

2022 Volume 5270

Abstract	Epidemiological and clinical studies have suggested that intake of n-3 polyunsaturated fatty acids (PUFA) reduces the incidence of allergic airway diseases and improves pulmonary function in patients with allergic asthma. However, the pharmacological targets of PUFA have not been elucidated upon. We investigated whether free fatty acid receptor 4 (FFA4, also known as GPR120) is a molecular target for beneficial PUFA in asthma therapy. In an ovalbumin (OVA)-induced allergic asthma model, compound A (a selective agonist of FFA4) was administrated before OVA sensitization or OVA challenge in FFA4 wild-type (WT) and knock-out (KO) mice. Compound A treatment of RBL-2H3 cells suppressed mast cell degranulation in vitro in a concentration-dependent manner. Administration of compound A suppressed in vivo allergic characteristics in bronchoalveolar lavage fluid (BALF) and lungs, such as inflammatory cytokine levels and eosinophil accumulation in BALF, inflammation and mucin secretion in the lungs. Compound A-induced suppression was not only observed in mice treated with compound A before OVA challenge, but in mice treated before OVA sensitization as well, implying that compound A acts on mast cells as well as dendritic cells. Furthermore, this suppression by compound A was only observed in FFA4-WT mice and was absent in FFA4-KO mice, implying that compound A action is mediated through FFA4. Activation of FFA4 may be a therapeutic target of PUFA in allergic asthma by suppressing the activation of dendritic cells and mast cells, suggesting that highly potent specific agonists of FFA4 could be a novel therapy for allergic asthma.
Keywords	allergy ; asthma ; free fatty acid receptor 4 ; FFA4 ; omega-3 polyunsaturated fatty acids ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2022-05-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article: Validation of an HPLC Method for Pretreatment of Steviol Glycosides in Fermented Milk.

Kim, Jin-Man / Koh, Jong-Ho / Park, Jung-Min

Foods (Basel, Switzerland)

2021 Volume 10, Issue 10

Abstract: Steviol glycosides are used in food and beverages worldwide as natural sweeteners, serving as a low-calorie sugar substitute. The acceptable daily intake of steviol is 0-4 mg/kg body weight. The rising demand for dairy products has led to a corresponding ...

Abstract	Steviol glycosides are used in food and beverages worldwide as natural sweeteners, serving as a low-calorie sugar substitute. The acceptable daily intake of steviol is 0-4 mg/kg body weight. The rising demand for dairy products has led to a corresponding increase in the use of steviol glycosides in such products. Therefore, it is important to analyze the levels of steviol glycosides in dairy products. Dairy products have high fat contents and unique emulsion characteristics, conferred by a mixture of fat globules, casein micelles, whey proteins, and numerous other small molecules. These characteristics may interfere with the estimation of steviol glycoside levels; therefore, dairy samples require pretreatment. We aimed to develop an objective test for measuring the levels of steviol glycosides through the development of an efficient pretreatment method. In this study, the steviol glycoside content in dairy products was evaluated by using various methods, and an optimal pretreatment method was determined. We used high-performance liquid chromatography to assess the selectivity, linearity, limit of detection, limit of quantification, accuracy, precision, and recovery rate. Calibration curves were linear in the range of 1-50 mg/kg, with a coefficient of determination of ≥0.999. The limit of detection and limit of quantification were in the ranges of 0.11-0.56 and 0.33-1.69 mg/kg, respectively. The relative standard deviation (%) represents the precision of a measurement. The RSD relative standard deviationof recovery varied between 0.16% and 2.83%, and recovery of the analysis varied between 83.57% and 104.84%. These results demonstrate the reliability of the method for measuring the steviol glycoside content. This method can be used for the simple pretreatment of steviol glycosides and can provide an accurate determination of steviol glycoside content in emulsified food matrices, such as dairy products.
Language	English
Publishing date	2021-10-14
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2704223-6
ISSN	2304-8158
ISSN	2304-8158
DOI	10.3390/foods10102445
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Article ; Online: Pretreatment methods for analyzing steviol glycosides in diverse food samples.

Park, Jung-Min / Lee, Jung-Hoon / Koh, Jong-Ho / Kim, Jin-Man

Journal of food science

2021 Volume 86, Issue 7, Page(s) 3075–3081

Abstract: Steviol glycosides are well-known food sweeteners; their consumption has steadily increased over time. A pretreatment method was developed and validated to better separate rebaudioside A and stevioside from various protein-rich and fatty foods for ... ...

Abstract	Steviol glycosides are well-known food sweeteners; their consumption has steadily increased over time. A pretreatment method was developed and validated to better separate rebaudioside A and stevioside from various protein-rich and fatty foods for quantification. This method was applied to soy sauce in liquid type and fish cake and coffee in solid type. Parameters such as linearity, limit of detection (LOD), limit of quantification (LOQ), accuracy, and precision were calculated. Calibration curves were linear in the working range of 5-100 mg/l, with coefficients of determination ≥0.99. The LOD and LOQ were in the ranges of 0.16-0.39 and 0.52-1.28 mg/kg, respectively. The percentage recoveries of the fortified samples were in the 88.01%-103.09% range, and the relative standard deviation was <10%. Method validation predicted a desirable accuracy, linearity, and precision. Therefore, the developed method can be practically applied for the quantitation of steviol glycosides in various foods, including soy sauce in liquid type and fish cake and coffee in solid type.
MeSH term(s)	Diterpenes, Kaurane/analysis ; Food Analysis/methods ; Food Analysis/standards ; Glucosides/analysis ; Limit of Detection ; Stevia/chemistry ; Sweetening Agents/analysis
Chemical Substances	Diterpenes, Kaurane ; Glucosides ; Sweetening Agents ; stevioside (0YON5MXJ9P)
Language	English
Publishing date	2021-06-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	241615-3
ISSN	1750-3841 ; 0022-1147
ISSN (online)	1750-3841
ISSN	0022-1147
DOI	10.1111/1750-3841.15781
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Article: Diagnosis of osteoporotic vertebral compression fractures and fracture level detection using multitask learning with U-Net in lumbar spine lateral radiographs.

Ryu, Seung Min / Lee, Soyoung / Jang, Miso / Koh, Jung-Min / Bae, Sung Jin / Jegal, Seong Gyu / Shin, Keewon / Kim, Namkug

Computational and structural biotechnology journal

2023 Volume 21, Page(s) 3452–3458

Abstract: Recent studies of automatic diagnosis of vertebral compression fractures (VCFs) using deep learning mainly focus on segmentation and vertebral level detection in lumbar spine lateral radiographs (LSLRs). Herein, we developed a model for simultaneous VCF ... ...

Abstract	Recent studies of automatic diagnosis of vertebral compression fractures (VCFs) using deep learning mainly focus on segmentation and vertebral level detection in lumbar spine lateral radiographs (LSLRs). Herein, we developed a model for simultaneous VCF diagnosis and vertebral level detection without using adjacent vertebral bodies. In total, 1102 patients with VCF, 1171 controls were enrolled. The 1865, 208, and 198 LSLRS were divided into training, validation, and test dataset. A ground truth label with a 4-point trapezoidal shape was made based on radiological reports showing normal or VCF at some vertebral level. We applied a modified U-Net architecture, in which decoders were trained to detect VCF and vertebral levels, sharing the same encoder. The multi-task model was significantly better than the single-task model in sensitivity and area under the receiver operating characteristic curve. In the internal dataset, the accuracy, sensitivity, and specificity of fracture detection per patient or vertebral body were 0.929, 0.944, and 0.917 or 0.947, 0.628, and 0.977, respectively. In external validation, those of fracture detection per patient or vertebral body were 0.713, 0.979, and 0.447 or 0.828, 0.936, and 0.820, respectively. The success rates were 96 % and 94 % for vertebral level detection in internal and external validation, respectively. The multi-task-shared encoder was significantly better than the single-task encoder. Furthermore, both fracture and vertebral level detection was good in internal and external validation. Our deep learning model may help radiologists perform real-life medical examinations.
Language	English
Publishing date	2023-06-27
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2694435-2
ISSN	2001-0370
ISSN	2001-0370
DOI	10.1016/j.csbj.2023.06.017
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