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Article: Geographic Analysis of the Safety and Efficacy of Filgotinib in Rheumatoid Arthritis.

Combe, Bernard / Besuyen, Robin / Gómez-Centeno, Antonio / Matsubara, Tsukasa / Sancho Jimenez, Juan José / Yin, Zhaoyu / Buch, Maya H

Rheumatology and therapy

2022 Volume 10, Issue 1, Page(s) 35–51

Language	English
Publishing date	2022-10-07
Publishing country	England
Document type	Journal Article
ZDB-ID	2783278-8
ISSN	2198-6584 ; 2198-6576
ISSN (online)	2198-6584
ISSN	2198-6576
DOI	10.1007/s40744-022-00494-1
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Article: Interfrontal Bone Among Inbred Strains of Mice and QTL Mapping.

Zimmerman, Heather / Yin, Zhaoyu / Zou, Fei / Everett, Eric T

Frontiers in genetics

2019 Volume 10, Page(s) 291

Abstract: The interfrontal bone (IF) is a minor skeletal trait residing between the frontal bones. IF is considered a quasi-continuous trait. Genetic and environmental factors appear to play roles in its development. The mechanism(s) underlying IF bone development ...

Abstract	The interfrontal bone (IF) is a minor skeletal trait residing between the frontal bones. IF is considered a quasi-continuous trait. Genetic and environmental factors appear to play roles in its development. The mechanism(s) underlying IF bone development are poorly understood. We sought to survey inbred strains of mice for the prevalence of IF and to perform QTL mapping studies. Archived mouse skulls from a mouse phenome project (MPP) were available for this study. 27 inbred strains were investigated with 6-20 mice examined for each strain. Skulls were viewed dorsally and the IF measured using a zoom stereomicroscope equipped with a calibrated reticle. A two generation cross between C3H/HeJ and C57BL/6J mice was performed to generate a panel of 468 F2 mice. F2 mice were phenotyped for presence or absence of IF bone and among mice with the IF bone maximum widths and lengths were measured. F2 mice were genotyped for 573 SNP markers informative between the two strains and subjected to linkage map construction and interval QTL mapping. Results: Strain dependent differences in the prevalence of IF bones were observed. Overall, 77.8% or 21/27, of the inbred strains examined had IF bones. Six strains (C3H/HeJ, MOLF/EiJ, NZW/LacJ, SPRET/EiJ, SWR/J, and WSB/EiJ) lack IF bones. Among the strains with IF bones, the prevalence ranged from 100% for C57BL/6J, C57/LJ, CBA/J, and NZB/B1NJ and down to 5% for strains such as CAST/Ei. QTL mapping for IF bone length and widths identifies for each trait one strong QTL detected on chromosome 14 along with several other significant QTLs on chromosomes 3, 4, 7, and 11. Strain dependent differences in IF will facilitate investigation of genetic factors contributing to IF development. IF bone formation may be a model to understand intrasutural bone formation.
Language	English
Publishing date	2019-04-02
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2606823-0
ISSN	1664-8021
ISSN	1664-8021
DOI	10.3389/fgene.2019.00291
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Article ; Online: TwinEQTL: ultrafast and powerful association analysis for eQTL and GWAS in twin studies.

Xia, Kai / Shabalin, Andrey A / Yin, Zhaoyu / Chung, Wonil / Sullivan, Patrick F / Wright, Fred A / Styner, Martin / Gilmore, John H / Santelli, Rebecca C / Zou, Fei

Genetics

2022 Volume 221, Issue 4

Abstract: We develop a computationally efficient alternative, TwinEQTL, to a linear mixed-effects model for twin genome-wide association study data. Instead of analyzing all twin samples together with linear mixed-effects model, TwinEQTL first splits twin samples ... ...

Abstract	We develop a computationally efficient alternative, TwinEQTL, to a linear mixed-effects model for twin genome-wide association study data. Instead of analyzing all twin samples together with linear mixed-effects model, TwinEQTL first splits twin samples into 2 independent groups on which multiple linear regression analysis can be validly performed separately, followed by an appropriate meta-analysis-like approach to combine the 2 nonindependent test results. Through mathematical derivations, we prove the validity of TwinEQTL algorithm and show that the correlation between 2 dependent test statistics at each single-nucleotide polymorphism is independent of its minor allele frequency. Thus, the correlation is constant across all single-nucleotide polymorphisms. Through simulations, we show empirically that TwinEQTL has well controlled type I error with negligible power loss compared with the gold-standard linear mixed-effects models. To accommodate expression quantitative loci analysis with twin subjects, we further implement TwinEQTL into an R package with much improved computational efficiency. Our approaches provide a significant leap in terms of computing speed for genome-wide association study and expression quantitative loci analysis with twin samples.
MeSH term(s)	Humans ; Gene Frequency ; Genome-Wide Association Study/methods ; Linear Models ; Polymorphism, Single Nucleotide ; Quantitative Trait Loci
Language	English
Publishing date	2022-06-10
Publishing country	United States
Document type	Journal Article ; Meta-Analysis
ZDB-ID	2167-2
ISSN	1943-2631 ; 0016-6731
ISSN (online)	1943-2631
ISSN	0016-6731
DOI	10.1093/genetics/iyac088
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Article ; Online: Long-term safety and efficacy of filgotinib treatment for rheumatoid arthritis in Japanese patients naïve to MTX treatment (FINCH 3).

Atsumi, Tatsuya / Tanaka, Yoshiya / Matsubara, Tsukasa / Amano, Koichi / Ishiguro, Naoki / Sugiyama, Eiji / Yamaoka, Kunihiro / Westhovens, René / Ching, Daniel W T / Messina, Osvaldo Daniel / Burmester, Gerd R / Genovese, Mark / Bartok, Beatrix / Pechonkina, Alena / Kondo, Akira / Yin, Zhaoyu / Gong, Qi / Tasset, Chantal / Takeuchi, Tsutomu

Modern rheumatology

2022 Volume 33, Issue 4, Page(s) 657–667

Abstract: Objectives: To evaluate the long-term safety and efficacy of filgotinib (FIL) for Japanese patients with rheumatoid arthritis (RA) and limited/no prior methotrexate (MTX) exposure. We present a Japanese population subanalysis of a global randomised- ... ...

Abstract	Objectives: To evaluate the long-term safety and efficacy of filgotinib (FIL) for Japanese patients with rheumatoid arthritis (RA) and limited/no prior methotrexate (MTX) exposure. We present a Japanese population subanalysis of a global randomised-controlled trial at Week 52 and interim long-term extension (LTE) to Week 48 through June 2020. Methods: Patients were randomised to FIL 200 mg plus MTX, FIL 100 mg plus MTX, FIL 200 mg, or MTX for 52 weeks. At completion, eligible patients could enrol in the LTE. Those receiving FIL continued; those receiving MTX were rerandomised (blinded) to FIL 200 or 100 mg upon discontinuation of MTX. After a 4-week washout period, MTX could be re-added. Results: Adverse event rates at Week 52 and in the LTE to Week 48 were comparable across treatment groups. Week 52 American College of Rheumatology 20% improvement (ACR20) rates were 83% (19/23), 82% (9/11), 75% (9/12), and 76% (19/25) for FIL 200 mg plus MTX, FIL 100 mg plus MTX, FIL 200 mg, and MTX, respectively. Through LTE Week 48, ACR20 rates were maintained. Conclusions: In the 56 Japanese patients treated with FIL, efficacy was maintained through Week 52 and beyond, with no increases in the incidence of adverse events.
MeSH term(s)	Animals ; Humans ; Antirheumatic Agents/adverse effects ; Antirheumatic Agents/therapeutic use ; Arthritis, Rheumatoid/drug therapy ; Double-Blind Method ; Drug Therapy, Combination ; East Asian People ; Methotrexate/adverse effects ; Treatment Outcome
Chemical Substances	Antirheumatic Agents ; GLPG0634 ; Methotrexate (YL5FZ2Y5U1)
Language	English
Publishing date	2022-07-28
Publishing country	England
Document type	Randomized Controlled Trial ; Journal Article
ZDB-ID	2078157-X
ISSN	1439-7609 ; 1439-7595
ISSN (online)	1439-7609
ISSN	1439-7595
DOI	10.1093/mr/roac083
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Article ; Online: Efficacy and safety of filgotinib in methotrexate-naive patients with rheumatoid arthritis with poor prognostic factors: post hoc analysis of FINCH 3.

Aletaha, Daniel / Westhovens, René / Gaujoux-Viala, Cecile / Adami, Giovanni / Matsumoto, Alan / Bird, Paul / Messina, Osvaldo Daniel / Buch, Maya H / Bartok, Beatrix / Yin, Zhaoyu / Guo, Ying / Hendrikx, Thijs / Burmester, Gerd R

RMD open

2021 Volume 7, Issue 2

Abstract: Objective: This analysis evaluated efficacy and safety of filgotinib, a Janus-associated kinase 1-preferential inhibitor, in methotrexate (MTX)-naive patients with rheumatoid arthritis (RA) with multiple poor prognostic factors (PPFs).: Methods: This ...

Abstract	Objective: This analysis evaluated efficacy and safety of filgotinib, a Janus-associated kinase 1-preferential inhibitor, in methotrexate (MTX)-naive patients with rheumatoid arthritis (RA) with multiple poor prognostic factors (PPFs). Methods: This was a post hoc analysis of the phase III, randomised, double-blind, active-controlled, FINCH 3 study (clinicaltrials.gov NCT02886728). Patients received once-daily oral filgotinib 200 or 100 mg plus once-weekly oral MTX ≤20 mg (FIL200 + MTX and FIL100 + MTX), filgotinib 200 mg monotherapy (FIL200), or oral MTX monotherapy (MTX-mono) for up to 52 weeks. PPFs investigated were seropositivity for rheumatoid factor or anticyclic citrullinated peptide antibodies, high-sensitivity C reactive protein (CRP) ≥4 mg/L, Disease Activity Score in 28 joints with CRP (DAS28(CRP)) >5.1, and presence of erosions. Filgotinib efficacy and safety in patients with all four PPFs at baseline were explored versus MTX-mono within this subgroup and compared informally with the overall population. Results: Of 1249 patients in FINCH 3, 510 (40.8%) had all PPFs. Efficacy of FIL200 + MTX among these patients was comparable to the overall population, with higher rates of 20%/50%/70% improvement from baseline by American College of Rheumatology criteria, DAS28(CRP) <2.6, and remission; greater improvement in physical function and pain; and better inhibition of structural damage relative to MTX-mono. FIL100 + MTX and FIL200 were not consistently more efficacious versus MTX-mono. Safety of filgotinib in patients with PPFs was comparable to the overall population; no new safety signals were observed. Conclusion: FIL200 + MTX efficacy and safety in patients with multiple PPFs were similar to the overall population.
MeSH term(s)	Antirheumatic Agents/adverse effects ; Arthritis, Rheumatoid/drug therapy ; Drug Therapy, Combination ; Humans ; Methotrexate/adverse effects ; Prognosis ; Pyridines ; Treatment Outcome ; Triazoles
Chemical Substances	Antirheumatic Agents ; GLPG0634 ; Pyridines ; Triazoles ; Methotrexate (YL5FZ2Y5U1)
Language	English
Publishing date	2021-08-12
Publishing country	England
Document type	Clinical Trial, Phase III ; Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	2812592-7
ISSN	2056-5933 ; 2056-5933
ISSN (online)	2056-5933
ISSN	2056-5933
DOI	10.1136/rmdopen-2021-001621
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Article ; Online: Recovery of paretic lower extremity loading ability and physical function in the first six months after stroke.

Mercer, Vicki Stemmons / Freburger, Janet Kues / Yin, Zhaoyu / Preisser, John S

Archives of physical medicine and rehabilitation

2014 Volume 95, Issue 8, Page(s) 1547–55.e4

Abstract: Objectives: To evaluate poststroke recovery of paretic lower extremity loading, walking ability, and self-reported physical function; and to identify subject characteristics associated with recovery.: Design: Inception cohort study, with testing at ... ...

Abstract	Objectives: To evaluate poststroke recovery of paretic lower extremity loading, walking ability, and self-reported physical function; and to identify subject characteristics associated with recovery. Design: Inception cohort study, with testing at monthly intervals from 1 to 6 months poststroke. Setting: Medical center and research laboratory. Participants: Volunteer sample of individuals with first-ever, unilateral, noncerebellar stroke (N=33). A total of 78 individuals underwent screening, and 45 were found to be eligible. Of these, 8 declined participation, 2 were excluded because of deteriorating cognitive status, and 2 were lost to follow-up. The remaining 33 individuals enrolled in the study, and 30 (91%) completed the study. Interventions: Not applicable. Main outcome measures: Outcomes were loading of the paretic lower extremity when standing up from a chair, self-selected gait speed (GS), and Physical Functioning Index. Results: Data analyses using linear mixed models indicated that subjects improved over time for all outcomes. Baseline Fugl-Meyer (FM) lower extremity motor scale score was a predictor of immediate poststroke performance for paretic lower extremity loading and self-selected GS, and a predictor of recovery rate for paretic lower extremity loading. Factors identified as having significant effects on performance at 6 months poststroke were baseline FM lower extremity motor scale score for paretic lower extremity loading and self-selected GS and baseline star cancellation score (from the Behavioral Inattention Test) for paretic lower extremity loading. Conclusions: Individuals with better baseline paretic lower extremity motor function have better ability to load that extremity during functional activities and faster walking speeds, and these advantages are still present at 6 months poststroke. Individuals with severe visuospatial neglect demonstrate less ability to load the paretic leg during functional activities at 6 months poststroke.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Agnosia/etiology ; Agnosia/physiopathology ; Female ; Gait/physiology ; Humans ; Lower Extremity/physiopathology ; Male ; Middle Aged ; Paresis/etiology ; Paresis/physiopathology ; Physical Therapy Modalities ; Recovery of Function ; Severity of Illness Index ; Stroke/complications ; Stroke Rehabilitation ; Time Factors ; Visual Perception ; Walking/physiology ; Weight-Bearing/physiology ; Young Adult
Language	English
Publishing date	2014-04-19
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	80057-0
ISSN	1532-821X ; 0003-9993
ISSN (online)	1532-821X
ISSN	0003-9993
DOI	10.1016/j.apmr.2014.03.031
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Article: Preparation and thermal properties of shape-stabilized composite phase change materials based on polyethylene glycol and porous carbon prepared from potato

Tan, Bo / Huang, Zhaohui / Yin, Zhaoyu / Min, Xin / Liu, Yan'gai / Wu, Xiaowen / Fang, Minghao

RSC advances. 2016 Feb. 08, v. 6, no. 19

2016

Abstract: A shape-stabilized composite phase change material (ss-CPCM) comprising polyethylene glycol (PEG) and porous carbon was prepared by absorbing PEG into porous carbon, assisted by ultrasound. In the composite, PEG served as a phase change material for ... ...

Abstract	A shape-stabilized composite phase change material (ss-CPCM) comprising polyethylene glycol (PEG) and porous carbon was prepared by absorbing PEG into porous carbon, assisted by ultrasound. In the composite, PEG served as a phase change material for thermal energy storage, and the porous carbon, which was prepared from fresh potato via freeze drying followed by heat treatment, was used as an absorbent that also acted as the supporting material. Various analytical techniques were used to investigate the chemical composition, microstructure, and thermal properties of the prepared PEG/porous carbon ss-CPCMs. Scanning electron microscopy, X-ray diffraction and Fourier transform infrared spectroscopic results indicated that PEG was well absorbed and encapsulated in the porous structure of the carbon and that there was no chemical reaction between them during the phase change process. The shape and exudation stability test results indicated that the PEG/porous carbon ss-CPCMs have excellent shape stability, compared to pristine PEG. The contact angle test suggested that the melting PEG has good level of wettability on the carbon so that melting PEG could be well protected from exudation in the porous carbon by surface tension effects, even if the temperature is higher than the melting point of PEG. Differential scanning calorimetric results showed that the PEG/porous carbon ss-CPCMs have considerable phase change enthalpies and thermal storage capabilities. In addition to this, the latent heats of ss-CPCMs increased with increasing contents of PEG in the composites, and the highest value was achieved when the amount of PEG was 50%. Moreover, the thermogravimetric analysis results showed that the composites had excellent thermal stabilities. Based on the above analyses, the prepared ss-CPCM with 50% PEG content proved to be a promising candidate for thermal energy storage applications.
Keywords	Fourier transform infrared spectroscopy ; X-ray diffraction ; absorbents ; carbon ; chemical composition ; chemical reactions ; contact angle ; differential scanning calorimetry ; enthalpy ; exudation ; freeze drying ; heat treatment ; melting ; melting point ; microstructure ; polyethylene glycol ; potatoes ; scanning electron microscopy ; surface tension ; temperature ; thermal energy ; thermal properties ; thermogravimetry ; wettability
Language	English
Dates of publication	2016-0208
Size	p. 15821-15830.
Publishing place	The Royal Society of Chemistry
Document type	Article
ISSN	2046-2069
DOI	10.1039/c5ra25685b
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Article: Preparation and thermal properties of phase change materials based on paraffin with expanded graphite and carbon foams prepared from sucroses

Yin, Zhaoyu / Huang, Zhaohui / Wen, Ruilong / Zhang, Xiaoguang / Tan, Bo / Liu, Yan'gai / Wu, Xiaowen / Fang, Minghao

RSC advances. 2016 Oct. 05, v. 6, no. 97

2016

Abstract: Carbon foam/expanded graphite composite (CEC) was prepared from a sucrose-expandable graphite resin using a thermal foaming method. This CEC was impregnated through its pores with paraffin to obtain a paraffin/carbon foam/expanded graphite composite ( ... ...

Abstract	Carbon foam/expanded graphite composite (CEC) was prepared from a sucrose-expandable graphite resin using a thermal foaming method. This CEC was impregnated through its pores with paraffin to obtain a paraffin/carbon foam/expanded graphite composite (PCEC). In the case of CECs, when the amount of added expandable graphite reached 10 wt% to 15 wt%, the microstructure of the CEC was damaged because of the expansion in volume of the expandable graphite. Fourier transform infra-red spectroscopy and X-ray diffraction analysis of PCECs showed that there was no chemical interaction between the paraffin and CECs. With an increase in the amount of expandable graphite in CECs, the adsorption capacity of paraffin and the latent heat first showed an increase and then decreased. The heat transfer capability of the paraffin was truly improved by the CECs. The processes for the preparation of the CECs and PCECs were environmentally friendly, convenient, and inexpensive. The PCECs, with good thermal properties and chemical stabilities, are suitable for low temperature (40–50 °C) thermal energy storage applications.
Keywords	Fourier transform infrared spectroscopy ; X-ray diffraction ; adsorption ; foaming ; graphene ; heat transfer ; latent heat ; microstructure ; temperature ; thermal energy
Language	English
Dates of publication	2016-1005
Size	p. 95085-95091.
Publishing place	The Royal Society of Chemistry
Document type	Article
ISSN	2046-2069
DOI	10.1039/c6ra13758j
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Article ; Online: Efficacy and safety of filgotinib alone and in combination with methotrexate in Japanese patients with active rheumatoid arthritis and limited or no prior exposure to methotrexate: Subpopulation analyses of 24-week data of a global phase 3 study (FINCH 3).

Atsumi, Tatsuya / Tanaka, Yoshiya / Matsubara, Tsukasa / Amano, Koichi / Ishiguro, Naoki / Sugiyama, Eiji / Yamaoka, Kunihiro / Westhovens, René / Ching, Daniel W T / Messina, Osvaldo Daniel / Burmester, Gerd R / Bartok, Beatrix / Pechonkina, Alena / Kondo, Akira / Yin, Zhaoyu / Guo, Ying / Tasset, Chantal / Sundy, John S / Takeuchi, Tsutomu

Modern rheumatology

2021 Volume 32, Issue 2, Page(s) 273–283

Abstract: Objectives: To evaluate the efficacy and safety of filgotinib for Japanese patients with rheumatoid arthritis (RA) and limited or no prior methotrexate (MTX) exposure.: Methods: Data up to 24 weeks were analysed for 71 Japanese patients from a 52- ... ...

Abstract	Objectives: To evaluate the efficacy and safety of filgotinib for Japanese patients with rheumatoid arthritis (RA) and limited or no prior methotrexate (MTX) exposure. Methods: Data up to 24 weeks were analysed for 71 Japanese patients from a 52-week global Phase 3 study. Patients with RA and limited or no prior MTX exposure were randomised in a 2:1:1:2 ratio to filgotinib 200 mg plus MTX, filgotinib 100 mg plus MTX, filgotinib 200 mg, or MTX. Maximum MTX dose was 15 mg/week. Primary endpoint was proportion achieving 20% improvement in American College of Rheumatology criteria (ACR20) at Week 24. Results: Week 24 ACR20 rates in Japanese patients were 82.6%, 90.9%, 83.3%, and 80.0% for filgotinib 200 mg plus MTX, filgotinib 100 mg plus MTX, filgotinib 200 mg, and MTX, respectively. Greater ACR20 rates with filgotinib vs MTX occurred at Week 2. Greater proportions receiving filgotinib vs MTX achieved DAS28-CRP <2.6 at Weeks 12 and 24. Adverse event rates were comparable across treatments and between the Japanese and overall populations. Conclusions: While Week 24 ACR20 rates were similar, filgotinib provided faster responses and higher remission rates vs MTX. In Japanese patients with RA and limited or no prior MTX exposure, filgotinib was generally well tolerated.
MeSH term(s)	Animals ; Antirheumatic Agents/adverse effects ; Arthritis, Rheumatoid/drug therapy ; Double-Blind Method ; Drug Therapy, Combination ; Finches ; Humans ; Japan ; Methotrexate/adverse effects ; Pyridines ; Treatment Outcome ; Triazoles
Chemical Substances	Antirheumatic Agents ; GLPG0634 ; Pyridines ; Triazoles ; Methotrexate (YL5FZ2Y5U1)
Language	English
Publishing date	2021-12-15
Publishing country	England
Document type	Clinical Trial, Phase III ; Journal Article ; Randomized Controlled Trial
ZDB-ID	2078157-X
ISSN	1439-7609 ; 1439-7595
ISSN (online)	1439-7609
ISSN	1439-7595
DOI	10.1093/mr/roab021
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Article ; Online: Fast eQTL Analysis for Twin Studies.

Yin, Zhaoyu / Xia, Kai / Chung, Wonil / Sullivan, Patrick F / Zou, Fei

Genetic epidemiology

2015 Volume 39, Issue 5, Page(s) 357–365

Abstract: Twin data are commonly used for studying complex psychiatric disorders, and mixed effects models are one of the most popular tools for modeling dependence structures between twin pairs. However, for eQTL (expression quantitative trait loci) data where ... ...

Abstract	Twin data are commonly used for studying complex psychiatric disorders, and mixed effects models are one of the most popular tools for modeling dependence structures between twin pairs. However, for eQTL (expression quantitative trait loci) data where associations between thousands of transcripts and millions of single nucleotide polymorphisms need to be tested, mixed effects models are computationally inefficient and often impractical. In this paper, we propose a fast eQTL analysis approach for twin eQTL data where we randomly split twin pairs into two groups, so that within each group the samples are unrelated, and we then apply a multiple linear regression analysis separately to each group. A score statistic that automatically adjusts the (hidden) correlation between the two groups is constructed for combining the results from the two groups. The proposed method has well-controlled type I error. Compared to mixed effects models, the proposed method has similar power but drastically improved computational efficiency. We demonstrate the computational advantage of the proposed method via extensive simulations. The proposed method is also applied to a large twin eQTL data from the Netherlands Twin Register.
MeSH term(s)	Algorithms ; Computational Biology ; Computer Simulation ; Data Interpretation, Statistical ; Humans ; Models, Genetic ; Polymorphism, Single Nucleotide/genetics ; Quantitative Trait Loci
Language	English
Publishing date	2015-07
Publishing country	United States
Document type	Journal Article ; Twin Study
ZDB-ID	605785-8
ISSN	1098-2272 ; 0741-0395
ISSN (online)	1098-2272
ISSN	0741-0395
DOI	10.1002/gepi.21900
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