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Article: Effects of the Cathepsin K Inhibitor ONO-5334 and Concomitant Use of ONO-5334 with Methotrexate on Collagen-Induced Arthritis in Cynomolgus Monkeys.

Yamada, Hiroyuki / Mori, Hiroshi / Nakanishi, Yasutomo / Nishikawa, Satoshi / Hashimoto, Yasuaki / Ochi, Yasuo / Tanaka, Makoto / Kawabata, Kazuhito

International journal of rheumatology

2019 Volume 2019, Page(s) 5710340

Abstract: We examined whether the cathepsin K inhibitor, ONO-5334, administered alone or in combination ...

Abstract	We examined whether the cathepsin K inhibitor, ONO-5334, administered alone or in combination with methotrexate (MTX), could ameliorate joint destruction evoked by collagen-induced arthritis (CIA) in female cynomolgus monkeys. CIA was induced by immunizing with bovine type II collagen. ONO-5334 (30 mg/kg/day) was orally administered once daily and MTX (10 mg/body/day) twice weekly for 9 weeks. X-ray (evaluation of joint destruction) and swelling (inflammatory) scores of proximal interphalangeal (PIP), distal interphalangeal (DIP), and metacarpophalangeal (MP) joints were evaluated. Urinary concentrations of C-terminal telopeptide of type I collagen (CTX-I) and type II collagen (CTX-II) were measured. Arthritis, accompanied by bone and cartilage destruction, was successfully induced in this collagen-induced arthritis monkey model. ONO-5334 showed no suppressive effect on joint swelling, while the joint swelling scores in the MTX and combination (ONO-5334 + MTX) groups were less than 50% compared with the control group. ONO-5334 decreased X-ray score by a mean of 64% (p<0.05 vs the control group), and MTX also decreased in X-ray score by a mean of 46% but with no statistical significance. Combination of ONO-5334 and MTX further decreased the X-ray score by 28% over MTX group (74% reduction vs the control group, p<0.01). Maximum increase in CTX-I (10-fold) and CTX-II (7-fold) compared to baseline was observed at 7 and 3 weeks after the first sensitization, respectively. After treatment with ONO-5334 alone or in combination with MTX, concentrations were maintained near baseline for both markers. In conclusion, ONO-5334 prevented joint destruction but not joint inflammation in this monkey CIA model. Concomitant use of ONO-5334 with MTX reduced architectural joint destruction compared to MTX alone; therefore, ONO-5334 may help to prevent joint destruction in combination with MTX for the treatment of rheumatoid arthritis.
Language	English
Publishing date	2019-02-17
Publishing country	United States
Document type	Journal Article
ZDB-ID	2503284-7
ISSN	1687-9279 ; 1687-9260
ISSN (online)	1687-9279
ISSN	1687-9260
DOI	10.1155/2019/5710340
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Book ; Online: Anisotropic spin distribution and perpendicular magnetic anisotropy in the layered ferromagnetic semiconductor (Ba,K)(Zn,Mn)$_{2}$As$_{2}$

Sakamoto, Shoya / Zhao, Guoqiang / Shibata, Goro / Deng, Zheng / Zhao, Kan / Wang, Xiancheng / Nonaka, Yosuke / Ikeda, Keisuke / Chi, Zhendong / Wan, Yuxuan / Suzuki, Masahiro / Koide, Tsuneharu / Tanaka, Arata / Maekawa, Sadamichi / Uemura, Yasutomo J. / Jin, Changqing / Fujimori, Atsushi

2020

Abstract: Perpendicular magnetic anisotropy of the new ferromagnetic semiconductor (Ba,K)(Zn,Mn)$_{2}$As$_{2 ...

Abstract	Perpendicular magnetic anisotropy of the new ferromagnetic semiconductor (Ba,K)(Zn,Mn)$_{2}$As$_{2}$ is studied by angle-dependent x-ray magnetic circular dichroism measurements. The large magnetic anisotropy with the anisotropy field of 0.85 T is deduced by fitting the Stoner-Wohlfarth model to the magnetic-field-angle dependence of the projected magnetic moment. Transverse XMCD spectra highlights the anisotropic distribution of Mn 3$d$ electrons, where the $d_{xz}$ and $d_{yz}$ orbitals are less populated than the $d_{xy}$ state because of the $D_{2d}$ splitting arising from the elongated MnAs$_{4}$ tetrahedra. It is suggested that the magnetic anisotropy originates from the degeneracy lifting of $p$-$d_{xz}$, $d_{yz}$ hybridized states at the Fermi level and resulting energy gain due to spin-orbit coupling when spins are aligned along the $z$ direction.
Keywords	Condensed Matter - Strongly Correlated Electrons ; Condensed Matter - Materials Science
Subject code	530
Publishing date	2020-09-30
Publishing country	us
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Effects of 16-month treatment with the cathepsin K inhibitor ONO-5334 on bone markers, mineral density, strength and histomorphometry in ovariectomized cynomolgus monkeys.

Yamada, Hiroyuki / Ochi, Yasuo / Mori, Hiroshi / Nishikawa, Satoshi / Hashimoto, Yasuaki / Nakanishi, Yasutomo / Tanaka, Makoto / Bruce, Mark / Deacon, Steve / Kawabata, Kazuhito

Bone

2016 Volume 86, Page(s) 43–52

Abstract: We examined the effects of ONO-5334, a cathepsin K inhibitor, on bone markers, BMD, strength and ...

Abstract	We examined the effects of ONO-5334, a cathepsin K inhibitor, on bone markers, BMD, strength and histomorphometry in ovariectomized (OVX) cynomolgus monkeys. ONO-5334 (1.2, 6 and 30mg/kg/day, p.o.), alendronate (0.05mg/kg/2weeks, i.v.), or vehicle was administered to OVX monkeys (all groups N=20) for 16months. A concurrent Sham group (N=20) was also treated with vehicle for 16months. OVX significantly increased bone resorption and formation markers and decreased BMD in lumbar vertebra, femoral neck, proximal tibia and distal radius. Alendronate suppressed these parameters to a level similar to that in the Sham-operated monkeys. ONO-5334 at doses 6 and 30mg/kg decreased bone resorption markers to a level roughly half of that in the Sham group, while keeping bone formation markers level above that in the Sham monkeys. Changes in DXA BMD confirmed that ONO-5334 at doses 6 and 30mg/kg increased BMD to a level greater than that in the Sham group in all examined sites. In the proximal tibia, in vivo pQCT analysis showed that ONO-5334 at doses 6 and 30mg/kg suppressed trabecular BMD loss to the sham level. However, ONO-5334 increased cortical BMD, cortical area and cortical thickness to a level greater than that in the Sham group, suggesting that ONO-5334 improves both cortical BMD and cortical geometry. Histomorphometric analysis revealed that ONO-5334 suppressed bone formation rate (BFR) at osteonal site in the midshaft femur but did not influence OVX-induced increase in BFR at either the periosteal or endocortical surfaces. Unlike alendronate, ONO-5334 increased osteoclasts surface (Oc.S/BS) and serum tartrate-resistant acid phosphatise 5b (TRAP5b) activity, highlighting the difference in the mode of action between these two drugs. Our results suggest that ONO-5334 has therapeutic potential not only in vertebral bones, but also in non-vertebral bones.
MeSH term(s)	Absorptiometry, Photon ; Animals ; Biomarkers/blood ; Biomechanical Phenomena/drug effects ; Body Weight/drug effects ; Bone Density/drug effects ; Bone Remodeling/drug effects ; Bone and Bones/anatomy & histology ; Bone and Bones/diagnostic imaging ; Bone and Bones/physiology ; Cathepsin K/antagonists & inhibitors ; Estradiol/blood ; Female ; Macaca fascicularis ; Ovariectomy ; Thiazolidines/administration & dosage ; Thiazolidines/pharmacokinetics ; Thiazolidines/pharmacology ; Tibia/anatomy & histology ; Tibia/diagnostic imaging ; Tibia/drug effects ; Tibia/physiology ; Tomography, X-Ray Computed
Chemical Substances	Biomarkers ; ONO-5334 ; Thiazolidines ; Estradiol (4TI98Z838E) ; Cathepsin K (EC 3.4.22.38)
Language	English
Publishing date	2016-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	632515-4
ISSN	1873-2763 ; 8756-3282
ISSN (online)	1873-2763
ISSN	8756-3282
DOI	10.1016/j.bone.2016.02.014
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Zs.A 1571: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: ONO-5334, a cathepsin K inhibitor, improves bone strength by preferentially increasing cortical bone mass in ovariectomized rats.

Ochi, Yasuo / Yamada, Hiroyuki / Mori, Hiroshi / Kawada, Naoki / Kayasuga, Ryoji / Nakanishi, Yasutomo / Tanaka, Makoto / Imagawa, Akira / Ohmoto, Kazuyuki / Kawabata, Kazuhito

Journal of bone and mineral metabolism

2013 Volume 32, Issue 6, Page(s) 645–652

Abstract: This study compared the effects of ONO-5334, a cathepsin K inhibitor, with those of alendronate ...

Abstract	This study compared the effects of ONO-5334, a cathepsin K inhibitor, with those of alendronate on bone mass and strength in ovariectomized rats. Ovariectomy resulted in significant elevation in urinary deoxypyridinoline and plasma C-terminal cross-linking telopeptide of type I collagen (CTX) 8 weeks after surgery. Peripheral quantitative computed tomography analysis showed that total, trabecular, and cortical bone mineral content (BMC) decreased in the proximal tibia, which was paralleled with a significant decline in bone strength. Treatment with ONO-5334 (0.12, 0.6, 3 or 15 mg/kg) once daily for 8 weeks dose-dependently restored the decrease in total BMC and bone mineral density (BMD) in the proximal tibia and suppressed urinary deoxypyridinoline and plasma CTX levels. Alendronate (1 mg/kg, once daily) also fully restored these bone mass parameters. Separate analysis of trabecular and cortical bones, however, showed that ONO-5334 only partially restored trabecular BMD and BMC at 15 mg/kg, whereas alendronate fully restored these parameters. On the other hand, ONO-5334 increased both cortical BMD and BMC with an effect more potent than that of alendronate. Bone geometric analysis indicated that ONO-5334 at 15 mg/kg decreased endosteal circumference without affecting periosteal circumference, resulting in marked increase in cortical thickness. Interestingly, the effects of ONO-5334 on bone strength parameters were more prominent than those of alendronate, although the two test compounds had a similar effect on total BMC. Taken together, our results indicate that ONO-5334 has pharmacological characteristics different from those of alendronate and may offer a unique therapy for patients with osteoporosis.
MeSH term(s)	Alendronate/pharmacology ; Animals ; Bone Density/drug effects ; Bone Density Conservation Agents/pharmacology ; Cathepsin K/antagonists & inhibitors ; Female ; Osteoporosis/drug therapy ; Osteoporosis/metabolism ; Osteoporosis/pathology ; Ovariectomy ; Rats ; Thiazolidines/pharmacology ; Tibia/metabolism ; Tibia/pathology
Chemical Substances	Bone Density Conservation Agents ; ONO-5334 ; Thiazolidines ; Cathepsin K (EC 3.4.22.38) ; Ctsk protein, rat (EC 3.4.22.38) ; Alendronate (X1J18R4W8P)
Language	English
Publishing date	2013-12-08
Publishing country	Japan
Document type	Journal Article
ZDB-ID	1295123-7
ISSN	1435-5604 ; 0914-8779
ISSN (online)	1435-5604
ISSN	0914-8779
DOI	10.1007/s00774-013-0542-x
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Article ; Online: Effects of eight-month treatment with ONO-5334, a cathepsin K inhibitor, on bone metabolism, strength and microstructure in ovariectomized cynomolgus monkeys.

Ochi, Yasuo / Yamada, Hiroyuki / Mori, Hiroshi / Nakanishi, Yasutomo / Nishikawa, Satoshi / Kayasuga, Ryoji / Kawada, Naoki / Kunishige, Akiko / Hashimoto, Yasuaki / Tanaka, Makoto / Sugitani, Masafumi / Kawabata, Kazuhito

Bone

2014 Volume 65, Page(s) 1–8

Abstract: This study examined the effect of ONO-5334, a cathepsin K inhibitor, on bone turnover, mineral ...

Abstract	This study examined the effect of ONO-5334, a cathepsin K inhibitor, on bone turnover, mineral density (BMD), mechanical strength and microstructure in ovariectomized (OVX) cynomolgus monkeys. Vehicle, ONO-5334 (3, 10 or 30 mg/kg) or alendronate (0.5 mg/kg) was orally administered for eight months to sham- and OVX-operated monkeys. ONO-5334 dose-dependently suppressed OVX-induced increase in bone turnover markers (urinary C-terminal cross-linking telopeptide of type I collagen (CTX) and serum osteocalcin). At the dose of 30 mg/kg, ONO-5334 maintained urinary CTX at nearly zero level and kept serum osteocalcin around the level of the sham animals. Marker levels in the alendronate-treated animals were similar to those in the sham animals throughout the study. ONO-5334 dose-dependently reversed the effect of OVX on vertebral BMD as measured by dual-energy X-ray absorptiometry (DXA) with improvement of bone mechanical strength. Both ONO-5334 and alendronate suppressed OVX-induced changes in vertebral microstructure and turnover state. In the femoral neck, peripheral quantitative computed tomography (pQCT) analysis showed that ONO-5334 increased total and cortical BMD. In particular, ONO-5334 significantly increased cortical BMD with improvement of bone mechanical strength. In microstructural analysis, alendronate suppressed OVX-induced increase in femoral mid-shaft osteonal bone formation rate (BFR) to a level below that recorded in the sham group, whereas ONO-5334 at 30 mg/kg did not suppress periosteal, osteonal and endocortical BFR. This finding supports the significant effect of ONO-5334 on cortical BMD and mechanical strength in the femoral neck. The results of this study suggest that ONO-5334 has good therapeutic potential for the treatment of osteoporosis.
MeSH term(s)	Absorptiometry, Photon ; Animals ; Bone and Bones/drug effects ; Bone and Bones/metabolism ; Bone and Bones/physiology ; Bone and Bones/ultrastructure ; Cathepsin K/antagonists & inhibitors ; Cysteine Proteinase Inhibitors/pharmacology ; Female ; Macaca fascicularis ; Ovariectomy ; Thiazolidines/pharmacology
Chemical Substances	Cysteine Proteinase Inhibitors ; ONO-5334 ; Thiazolidines ; Cathepsin K (EC 3.4.22.38)
Language	English
Publishing date	2014-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	632515-4
ISSN	1873-2763 ; 8756-3282
ISSN (online)	1873-2763
ISSN	8756-3282
DOI	10.1016/j.bone.2014.04.023
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Article ; Online: New Fluoride-arsenide Diluted Magnetic Semiconductor (Ba,K)F(Zn,Mn)As with Independent Spin and Charge Doping.

Scientific reports

2016 Volume 6, Page(s) 36578

Abstract: We report the discovery of a new fluoride-arsenide bulk diluted magnetic semiconductor (Ba,K)F(Zn ... superconductors. The joint hole doping via (Ba,K) substitution &spin doping via (Zn,Mn) substitution results ... in ferromagnetic order with Curie temperature up to 30 K and demonstrates that the ferromagnetic interactions ...

Abstract	We report the discovery of a new fluoride-arsenide bulk diluted magnetic semiconductor (Ba,K)F(Zn,Mn)As with the tetragonal ZrCuSiAs-type structure which is identical to that of the "1111" iron-based superconductors. The joint hole doping via (Ba,K) substitution &spin doping via (Zn,Mn) substitution results in ferromagnetic order with Curie temperature up to 30 K and demonstrates that the ferromagnetic interactions between the localized spins are mediated by the carriers. Muon spin relaxation measurements confirm the intrinsic nature of the long range magnetic order in the entire volume in the ferromagnetic phase. This is the first time that a diluted magnetic semiconductor with decoupled spin and charge doping is achieved in a fluoride compound. Comparing to the isostructure oxide counterpart of LaOZnSb, the fluoride DMS (Ba,K)F(Zn,Mn)As shows much improved semiconductive behavior that would be benefit for further application developments.
Language	English
Publishing date	2016-11-22
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/srep36578
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Article ; Online: Effects of ONO-5334, a novel orally-active inhibitor of cathepsin K, on bone metabolism.

Bone

2011 Volume 49, Issue 6, Page(s) 1351–1356

Abstract: ... a novel inhibitor of cathepsin K, on bone metabolism. In vitro experiments indicated that ONO-5334 is ... a potent inhibitor of cathepsin K with Ki value of 0.1 nM. Although this compound ... than that for cathepsin K. ONO-5334 also inhibited human osteoclasts bone resorption in vitro at a concentration more ...

Abstract	In the present study, we examined the in vitro and in vivo pharmacological effects of ONO-5334, a novel inhibitor of cathepsin K, on bone metabolism. In vitro experiments indicated that ONO-5334 is a potent inhibitor of cathepsin K with Ki value of 0.1 nM. Although this compound inhibited other cysteine proteases, such as cathepsin S, L and B, its inhibitory activity for these enzymes was 8 to 320 fold lower than that for cathepsin K. ONO-5334 also inhibited human osteoclasts bone resorption in vitro at a concentration more than 100 fold lower than that of alendronate, a bisphosphonate. While alendronate disrupted actin ring and induced pyknotic nuclei in osteoclasts, ONO-5334 did not have such effects, suggesting that this compound does not affect osteoclasts viability. In in vivo experiments, oral administration of ONO-5334 dose-dependently reduced plasma calcium level increased by parathyroid hormone related peptide in thyroparathyroidectomized rats. Furthermore, in vivo experiment using normal monkeys demonstrated that ONO-5334 decreases serum and urine C-telopeptide of type I collagen level, a bone resorption marker, soon after oral dosing. These levels were consistently decreased below pre-dose levels by repeated oral dosing with ONO-5334 for 7 days. ONO-5334 on the other hand did not affect bone formation markers, serum osteocalcin and bone specific alkaline phosphatase. These findings indicate that ONO-5334 is a specific inhibitor for cathepsin K and thus may be a novel therapeutic agent for metabolic bone diseases.
MeSH term(s)	Actins/metabolism ; Administration, Oral ; Animals ; Biomarkers/metabolism ; Bone Remodeling/drug effects ; Bone Resorption/blood ; Bone Resorption/enzymology ; Bone Resorption/pathology ; Bone Resorption/physiopathology ; Bone and Bones/drug effects ; Bone and Bones/metabolism ; Calcium/blood ; Cathepsin K/antagonists & inhibitors ; Cathepsin K/metabolism ; Collagen Type I/blood ; Female ; Haplorhini ; Humans ; Male ; Osteogenesis/drug effects ; Parathyroidectomy ; Peptides/blood ; Protease Inhibitors/administration & dosage ; Protease Inhibitors/pharmacology ; Rats ; Thiazolidines/administration & dosage ; Thiazolidines/pharmacology
Chemical Substances	Actins ; Biomarkers ; Collagen Type I ; ONO-5334 ; Peptides ; Protease Inhibitors ; Thiazolidines ; collagen type I trimeric cross-linked peptide ; Cathepsin K (EC 3.4.22.38) ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2011-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	632515-4
ISSN	1873-2763 ; 8756-3282
ISSN (online)	1873-2763
ISSN	8756-3282
DOI	10.1016/j.bone.2011.09.041
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Zs.A 1571: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Genetics and animal models of familial pulmonary fibrosis.

Yasutomo, Koji

International immunology

2021 Volume 33, Issue 12, Page(s) 653–657

Abstract: Pulmonary fibrosis is caused by the interplay between genetic and environmental factors. Recent studies have revealed various genes associated with idiopathic pulmonary fibrosis, as well as the causative genes for familial pulmonary fibrosis. Although ... ...

Abstract	Pulmonary fibrosis is caused by the interplay between genetic and environmental factors. Recent studies have revealed various genes associated with idiopathic pulmonary fibrosis, as well as the causative genes for familial pulmonary fibrosis. Although increased death or dysfunction of type 2 alveolar epithelial (AT2) cells has been detected in lung specimens from pulmonary fibrosis patients, it remains unclear whether and how AT2 cell death or dysfunction is responsible for the progression of pulmonary fibrosis. A recent study showed that increased AT2 cell necroptosis is the initial event in pulmonary fibrosis by analyzing patients with familial pulmonary fibrosis and an animal model that harbors the same mutation as patients. The contribution of AT2 cell necroptosis to the pathogenesis of pulmonary fibrosis has not been identified in animal model studies, which validates the effectiveness of genetic analysis of familial diseases to uncover unknown pathogeneses. Thus, further extensive genetic studies of pulmonary fibrosis along with functional studies based on genetic analysis will be crucial not only in elucidating the precise disease process but also, ultimately, in identifying novel treatment strategies for both familial and non-familial pulmonary fibrosis.
MeSH term(s)	Animals ; Disease Models, Animal ; Idiopathic Pulmonary Fibrosis/genetics ; Idiopathic Pulmonary Fibrosis/immunology ; Idiopathic Pulmonary Fibrosis/pathology
Language	English
Publishing date	2021-06-02
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1013745-2
ISSN	1460-2377 ; 0953-8178
ISSN (online)	1460-2377
ISSN	0953-8178
DOI	10.1093/intimm/dxab026
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Article ; Online: Dysregulation of immunoproteasomes in autoinflammatory syndromes.

Yasutomo, Koji

International immunology

2018 Volume 31, Issue 10, Page(s) 631–637

Abstract: Immunoproteasomes degrade ubiquitin-coupled proteins and play a role in creating peptides for presentation by MHC class I proteins. Studies of gene-deficient mice, in which each immunoproteasomal subunit was affected, have demonstrated that dysfunction ... ...

Abstract	Immunoproteasomes degrade ubiquitin-coupled proteins and play a role in creating peptides for presentation by MHC class I proteins. Studies of gene-deficient mice, in which each immunoproteasomal subunit was affected, have demonstrated that dysfunction of immunoproteasomes leads to immunodeficiency, i.e. reduced expression of MHC class I and attenuation of CD8 T-cell responses. Recent studies, however, have uncovered a new type of autoinflammatory syndrome characterized by fever, nodular erythema and progressive partial lipodystrophy that is caused by genetic mutations in immunoproteasome subunits. These mutations disturbed the assembly of immunoproteasomes, which led to reduced proteasomal activity and thus accumulation of ubiquitin-coupled proteins. Those findings suggest that immunoproteasomes function as anti-inflammatory machinery in humans. The discovery of a new type of autoinflammatory syndrome caused by dysregulated immunoproteasomes provides novel insights into the important roles of immunoproteasomes in inflammation as well as the spectrum of autoinflammatory diseases.
MeSH term(s)	Animals ; Autoimmune Diseases/metabolism ; Humans ; Inflammation/metabolism ; Proteasome Endopeptidase Complex/metabolism
Chemical Substances	Proteasome Endopeptidase Complex (EC 3.4.25.1)
Language	English
Publishing date	2018-09-01
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1013745-2
ISSN	1460-2377 ; 0953-8178
ISSN (online)	1460-2377
ISSN	0953-8178
DOI	10.1093/intimm/dxy059
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Article ; Online: Machine Learning-Based Interpretable Modeling for Subjective Emotional Dynamics Sensing Using Facial EMG.

Kawamura, Naoya / Sato, Wataru / Shimokawa, Koh / Fujita, Tomohiro / Kawanishi, Yasutomo

Sensors (Basel, Switzerland)

2024 Volume 24, Issue 5

Abstract: Understanding the association between subjective emotional experiences and physiological signals is of practical and theoretical significance. Previous psychophysiological studies have shown a linear relationship between dynamic emotional valence ... ...

Abstract	Understanding the association between subjective emotional experiences and physiological signals is of practical and theoretical significance. Previous psychophysiological studies have shown a linear relationship between dynamic emotional valence experiences and facial electromyography (EMG) activities. However, whether and how subjective emotional valence dynamics relate to facial EMG changes nonlinearly remains unknown. To investigate this issue, we re-analyzed the data of two previous studies that measured dynamic valence ratings and facial EMG of the corrugator supercilii and zygomatic major muscles from 50 participants who viewed emotional film clips. We employed multilinear regression analyses and two nonlinear machine learning (ML) models: random forest and long short-term memory. In cross-validation, these ML models outperformed linear regression in terms of the mean squared error and correlation coefficient. Interpretation of the random forest model using the SHapley Additive exPlanation tool revealed nonlinear and interactive associations between several EMG features and subjective valence dynamics. These findings suggest that nonlinear ML models can better fit the relationship between subjective emotional valence dynamics and facial EMG than conventional linear models and highlight a nonlinear and complex relationship. The findings encourage emotion sensing using facial EMG and offer insight into the subjective-physiological association.
MeSH term(s)	Humans ; Electromyography ; Facial Expression ; Emotions/physiology ; Face ; Facial Muscles/physiology ; Machine Learning
Language	English
Publishing date	2024-02-27
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2052857-7
ISSN	1424-8220 ; 1424-8220
ISSN (online)	1424-8220
ISSN	1424-8220
DOI	10.3390/s24051536
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