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Article ; Online: The attenuation of renal fibrosis by histone deacetylase inhibitors is associated with the plasticity of FOXP3

Wu, Wen-Pyng / Tsai, Yi-Giien / Lin, Tze-Yi / Wu, Ming-Ju / Lin, Ching-Yuang

2017 Volume 18, Issue 1, Page(s) 225

Abstract: Background: The histone deacetylase (HDAC) inhibitor, which has potential effects on epigenetic modifications, had been reported to attenuate renal fibrosis. CD4: Methods: This study evaluated the roles of the HDAC inhibitor, Treg cells and their ... ...

Abstract	Background: The histone deacetylase (HDAC) inhibitor, which has potential effects on epigenetic modifications, had been reported to attenuate renal fibrosis. CD4 Methods: This study evaluated the roles of the HDAC inhibitor, Treg cells and their differentiation into Th17 cells, which aggravate chronic inflammation and renal fibrosis in a unilateral ureteral obstruction (UUO) mouse model. The study groups included control and UUO mice that were monitored for 7, 14 or 21 days. Results: Juxtaglomerular (JG) hyperplasia, angiotensin II type 1 receptor (AT1R) expression and lymphocyte infiltration were observed in renal tissues after UUO but were decreased after trichostatin A (TSA) treatment, a HDAC inhibitor. The number of CD4 Conclusions: TSA treatment decreased JG hyperplasia, the percentage of FOXP3
Language	English
Publishing date	2017-07-10
Publishing country	England
Document type	Journal Article
ZDB-ID	2041348-8
ISSN	1471-2369 ; 1471-2369
ISSN (online)	1471-2369
ISSN	1471-2369
DOI	10.1186/s12882-017-0630-6
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Article ; Online: Addition of immunosuppressive treatment to hemoperfusion is associated with improved survival after paraquat poisoning

Wen-Pyng Wu / Ming-Nan Lai / Ching-Heng Lin / Yu-Fen Li / Ching-Yuang Lin / Ming-Ju Wu

PLoS ONE, Vol 9, Iss 1, p e

a nationwide study.

2014 Volume 87568

Abstract: Paraquat poisoning associates very high mortality rate. Early treatment with hemoperfusion is strongly suggested by animal and human studies. Although the survival benefit of additional immunosuppressive treatment (IST) in combination with hemoperfusion ... ...

Abstract	Paraquat poisoning associates very high mortality rate. Early treatment with hemoperfusion is strongly suggested by animal and human studies. Although the survival benefit of additional immunosuppressive treatment (IST) in combination with hemoperfusion is also reported since 1971, the large-scale randomized control trials to confirm the effects of IST is difficult to be executed. Therefore, we designed this nationwide large-scale population-based retrospective cohort study to investigate the outcome of paraquat poisoning with hemoperfusion and the additional effects of IST combined with hemoperfusion. This nationwide retrospective cohort study utilized data retrieved from the National Health Insurance Research Database (NHIRD) of Taiwan. A total of 1811 hospitalized patients with a diagnosis of paraquat poisoning who received hemoperfusion between 1997 and 2009 were enrolled. The mean age of all 1811 study subjects was 47.3 years. 70% was male. The overall survival rate was only 26.4%. Respiratory failure and renal failure were diagnosed in 56.2% and 36% patients. The average frequency of hemoperfusion was twice. IST was added in 42.2% patients. IST significantly increases survival rate (from 24.3% to 29.3%, P<0.001). The combined IST with methylprednisolone, cyclophosphamide and dexamethasone associates with the highest survival rate (48%, P<0.001). Moreover, patients younger than 45 years of age in the IST group had the best survival (41.0% vs. 33.7%, p<0.001). Our results support the use of IST with hemoperfusion for paraquat-poisoned patients. The best survival effect of IST is the combination of methylprednisolone, cyclophosphamide and daily dexamethasone, especially in patients with younger age.
Keywords	Medicine ; R ; Science ; Q
Subject code	616
Language	English
Publishing date	2014-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
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Article ; Online: Addition of immunosuppressive treatment to hemoperfusion is associated with improved survival after paraquat poisoning: a nationwide study.

Wu, Wen-Pyng / Lai, Ming-Nan / Lin, Ching-Heng / Li, Yu-Fen / Lin, Ching-Yuang / Wu, Ming-Ju

PloS one

2014 Volume 9, Issue 1, Page(s) e87568

Abstract	Paraquat poisoning associates very high mortality rate. Early treatment with hemoperfusion is strongly suggested by animal and human studies. Although the survival benefit of additional immunosuppressive treatment (IST) in combination with hemoperfusion is also reported since 1971, the large-scale randomized control trials to confirm the effects of IST is difficult to be executed. Therefore, we designed this nationwide large-scale population-based retrospective cohort study to investigate the outcome of paraquat poisoning with hemoperfusion and the additional effects of IST combined with hemoperfusion. This nationwide retrospective cohort study utilized data retrieved from the National Health Insurance Research Database (NHIRD) of Taiwan. A total of 1811 hospitalized patients with a diagnosis of paraquat poisoning who received hemoperfusion between 1997 and 2009 were enrolled. The mean age of all 1811 study subjects was 47.3 years. 70% was male. The overall survival rate was only 26.4%. Respiratory failure and renal failure were diagnosed in 56.2% and 36% patients. The average frequency of hemoperfusion was twice. IST was added in 42.2% patients. IST significantly increases survival rate (from 24.3% to 29.3%, P<0.001). The combined IST with methylprednisolone, cyclophosphamide and dexamethasone associates with the highest survival rate (48%, P<0.001). Moreover, patients younger than 45 years of age in the IST group had the best survival (41.0% vs. 33.7%, p<0.001). Our results support the use of IST with hemoperfusion for paraquat-poisoned patients. The best survival effect of IST is the combination of methylprednisolone, cyclophosphamide and daily dexamethasone, especially in patients with younger age.
MeSH term(s)	Adult ; Age Factors ; Cohort Studies ; Cyclophosphamide/therapeutic use ; Dexamethasone/therapeutic use ; Hemoperfusion/methods ; Humans ; Immunosuppression Therapy/methods ; Male ; Methylprednisolone/therapeutic use ; Middle Aged ; Paraquat/poisoning ; Poisoning/drug therapy ; Poisoning/epidemiology ; Poisoning/therapy ; Proportional Hazards Models ; Retrospective Studies ; Survival Rate ; Taiwan/epidemiology ; Treatment Outcome
Chemical Substances	Dexamethasone (7S5I7G3JQL) ; Cyclophosphamide (8N3DW7272P) ; Paraquat (PLG39H7695) ; Methylprednisolone (X4W7ZR7023)
Language	English
Publishing date	2014-01-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0087568
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Article ; Online: The subjective sleep quality and heart rate variability in hemodialysis patients.

Wei, Cheng-Yu / Chung, Tieh-Chi / Wu, Shu-Chun / Chung, Chian-Fang / Wu, Wen-Pyng

Renal failure

2011 Volume 33, Issue 2, Page(s) 109–117

Abstract: Introduction: Sleep disturbances and cardiovascular autonomic dysfunction are major complications of hemodialysis (HD). The goal of this study is to identify clinical, heart rate variability (HRV) or laboratory parameters that are independently ... ...

Abstract	Introduction: Sleep disturbances and cardiovascular autonomic dysfunction are major complications of hemodialysis (HD). The goal of this study is to identify clinical, heart rate variability (HRV) or laboratory parameters that are independently associated with subjective sleep quality. Patient and methods: Forty-six stable HD patients filled out sleep questionnaires - Pittsburgh sleep quality index (PSQI), Athens insomnia scale (AIS), and Epworth sleepiness scale (ESS). In addition, they received analyses of 5-minute HRV twice, in lying posture before and after HD. We also recruited 50 healthy subjects who received 5-min HRV. Results: The patients with end-stage renal disease have a high rate of poor sleep quality according to PSQI, AIS, and ESS. The activities of total power (0-0.5 Hz), high-frequency power (HF, 0.15-0.40 Hz), low-frequency power (0.04-0.15 Hz), and very-low-frequency power (0.003-0.04 Hz) in HD patients are obviously lower than that in the healthy people. The poor sleepers (PSQI > 5) show lower heart rate, higher HF and variance before HD, but did not show a significant difference after HD. There is no significant difference between HRV and global score of AIS, but the insomnia group (AIS > 5) has higher BMI. These patients with sleepiness (ESS > 9) only reveal lower hemoglobin, although the global score of ESS reveals no significant relationship with HRV. Conclusion: HD patients have a high rate of poor sleep quality and autonomic dysfunction. Greater attention for the evaluation of sleep quality is needed for the better care of HD patients.
MeSH term(s)	Aged ; Autonomic Nervous System/physiopathology ; Case-Control Studies ; Female ; Heart Rate ; Humans ; Kidney Failure, Chronic/complications ; Kidney Failure, Chronic/physiopathology ; Kidney Failure, Chronic/therapy ; Male ; Middle Aged ; Renal Dialysis ; Sleep ; Sleep Initiation and Maintenance Disorders/etiology
Language	English
Publishing date	2011
Publishing country	England
Document type	Journal Article
ZDB-ID	632949-4
ISSN	1525-6049 ; 0886-022X
ISSN (online)	1525-6049
ISSN	0886-022X
DOI	10.3109/0886022X.2010.541578
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Zs.A 1331: Show issues

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Article ; Online: Lower variability of tacrolimus trough concentration after conversion from prograf to advagraf in stable kidney transplant recipients.

Wu, Ming-Ju / Cheng, Ching-Yao / Chen, Cheng-Hsu / Wu, Wen-Pyng / Cheng, Chi-Hung / Yu, Dong-Ming / Chuang, Ya-Wen / Shu, Kuo-Hsiung

Transplantation

2011 Volume 92, Issue 6, Page(s) 648–652

Abstract: Backgrounds: Variability of blood trough concentration (C0) in immunosuppressant leads to rejection and graft loss after kidney transplantation.: Methods: The aim of this study is to prospectively investigate the change of within-patient variability ... ...

Abstract	Backgrounds: Variability of blood trough concentration (C0) in immunosuppressant leads to rejection and graft loss after kidney transplantation. Methods: The aim of this study is to prospectively investigate the change of within-patient variability among stable kidney transplant recipients with conversion from twice-daily Prograf to the same milligram-for-milligram daily dose of once-daily Advagraf. Results: The mean age of 129 patients was 51.3±12.1 years. The conversion to Advagraf was administrated at 6.3±4.8 years after transplantation. The daily dose was changed from 4.7±2.0 mg to 4.9±2.1 mg after conversion. Only six patients increased daily dose by 16.7% to 25% to maintain target levels. The whole blood C0 of tacrolimus before conversion was 5.9±1.7 ng/mL. The mean C0 was significantly reduced after conversion to Advagraf; it was 4.9±1.5 ng/mL on the seventh day (P<0.001) and 5.4 to 5.5 ng/mL at 1 to 6 months (P<0.05). Forty-one (31.8%) patients have reduced C0 of more than 25% on the seventh day. The percent coefficient of variation of tacrolimus C0 more than 22.5% before conversion is associated with higher risk of reduced C0 after conversion (P<0.05). Compared with before conversion, less kidney transplant recipients have percent coefficient of variation more than 22.5% after conversion (3.1% vs. 17.4% with P<0.01). Conclusions: The results support that conversion from Prograf to Advagraf among kidney transplant recipient leads to a significantly lower C0 and within-patient variability of tacrolimus C0. The within-patient variability of C0 before conversion influences C0 on the sevent day after conversion to Advagraf.
MeSH term(s)	Adult ; Humans ; Immunosuppressive Agents/therapeutic use ; Kidney Transplantation/methods ; Middle Aged ; Models, Statistical ; Postoperative Complications ; Prospective Studies ; ROC Curve ; Regression Analysis ; Reproducibility of Results ; Tacrolimus/administration & dosage ; Tacrolimus/therapeutic use ; Time Factors
Chemical Substances	Immunosuppressive Agents ; Tacrolimus (WM0HAQ4WNM)
Language	English
Publishing date	2011-09-27
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	208424-7
ISSN	1534-6080 ; 0041-1337
ISSN (online)	1534-6080
ISSN	0041-1337
DOI	10.1097/TP.0b013e3182292426
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Zs.A 488: 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: A reduction of unilateral ureteral obstruction-induced renal fibrosis by a therapy combining valsartan with aliskiren.

Wu, Wen-Pyng / Chang, Chi-Hao / Chiu, Yung-Tsung / Ku, Cheng-Lung / Wen, Mei-Chin / Shu, Kuo-Hsiung / Wu, Ming-Ju

American journal of physiology. Renal physiology

2010 Volume 299, Issue 5, Page(s) F929–41

Abstract: The protective effect of combination therapy with valsartan and aliskiren against renal fibrosis remains to be defined. This study was undertaken to examine the protective effects of the combination of valsartan and aliskiren against renal fibrosis ... ...

Abstract	The protective effect of combination therapy with valsartan and aliskiren against renal fibrosis remains to be defined. This study was undertaken to examine the protective effects of the combination of valsartan and aliskiren against renal fibrosis induced by unilateral ureteral obstruction (UUO). Combination therapy with valsartan (15 mg·kg(-1)·day(-1)) and aliskiren (10 mg·kg(-1)·day(-1)), valsartan monotherapy (30 mg·kg(-1)·day(-1)), and aliskiren monotherapy (20 mg·kg(-1)·day(-1)) all significantly ameliorated the increase in blood urea nitrogen and the degree of hydronephrosis determined by the increase in weight and length of the obstructed kidney. The dose titration study and blood pressure measurement confirmed that the combination therapy provided a greater benefit independent of the vasodilatory effect. There were no significant changes in serum levels of creatinine, sodium, and potassium in UUO rats and any treatment groups. Combination therapy also attenuated UUO-related increases in the scores of tubular dilatation, interstitial volume, interstitial collagen deposition, α-smooth muscle actin, the activation of ERK 1/2, the infiltration of monocytes/macrophages, the mRNA expression of snail-1, and transforming growth factor-β1 to a greater extent compared with aliskiren or valsartan used alone. The mRNA expression of renin and the (pro)renin receptor significantly increased after UUO. Combination therapy and monotherapy of valsartan and aliskiren had a comparable enhancing effect on the mRNA expression of renin, whereas all these treatments did not affect the expression of the (pro)renin receptor. In conclusion, a direct renin inhibitor in conjunction with an angiotensin II receptor blocker exerts increased renal protection against renal fibrosis and inflammation during obstruction over either agent alone.
MeSH term(s)	Actins/biosynthesis ; Amides/therapeutic use ; Anatomy, Cross-Sectional ; Animals ; Antihypertensive Agents/therapeutic use ; Blood Pressure/physiology ; Blotting, Western ; Collagen/metabolism ; Drug Therapy, Combination ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Fibrosis ; Fumarates/therapeutic use ; Immunohistochemistry ; Kidney/pathology ; Kidney/physiopathology ; Kidney Diseases/drug therapy ; Kidney Diseases/etiology ; Kidney Diseases/genetics ; Kidney Function Tests ; Male ; Neutrophil Infiltration ; Rats ; Rats, Sprague-Dawley ; Reverse Transcriptase Polymerase Chain Reaction ; Snail Family Transcription Factors ; Tetrazoles/therapeutic use ; Transcription Factors/biosynthesis ; Ureteral Obstruction/complications ; Ureteral Obstruction/drug therapy ; Ureteral Obstruction/genetics ; Valine/analogs & derivatives ; Valine/therapeutic use ; Valsartan
Chemical Substances	Actins ; Amides ; Antihypertensive Agents ; Fumarates ; Snai2 protein, rat ; Snail Family Transcription Factors ; Tetrazoles ; Transcription Factors ; smooth muscle actin, rat ; aliskiren (502FWN4Q32) ; Valsartan (80M03YXJ7I) ; Collagen (9007-34-5) ; Extracellular Signal-Regulated MAP Kinases (EC 2.7.11.24) ; Valine (HG18B9YRS7)
Language	English
Publishing date	2010-11
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	603837-2
ISSN	1522-1466 ; 0363-6127
ISSN (online)	1522-1466
ISSN	0363-6127
DOI	10.1152/ajprenal.00192.2010
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Article: Using bioinformatics approaches to identify survival-related oncomiRs as potential targets of miRNA-based treatments for lung adenocarcinoma.

Liu, Chia-Hsin / Liu, Shu-Hsuan / Lai, Yo-Liang / Cho, Yi-Chun / Chen, Fang-Hsin / Lin, Li-Jie / Peng, Pei-Hua / Li, Chia-Yang / Wang, Shu-Chi / Chen, Ji-Lin / Wu, Heng-Hsiung / Wu, Min-Zu / Sher, Yuh-Pyng / Cheng, Wei-Chung / Hsu, Kai-Wen

Computational and structural biotechnology journal

2022 Volume 20, Page(s) 4626–4635

Abstract: Lung cancer is a major cause of cancer-associated deaths worldwide, and lung adenocarcinoma (LUAD) is the most common lung cancer subtype. Micro RNAs (miRNAs) regulate the pattern of gene expression in multiple cancer types and have been explored as ... ...

Abstract	Lung cancer is a major cause of cancer-associated deaths worldwide, and lung adenocarcinoma (LUAD) is the most common lung cancer subtype. Micro RNAs (miRNAs) regulate the pattern of gene expression in multiple cancer types and have been explored as potential drug development targets. To develop an oncomiR-based panel, we identified miRNA candidates that show differential expression patterns and are relevant to the worse 5-year overall survival outcomes in LUAD patient samples. We further evaluated various combinations of miRNA candidates for association with 5-year overall survival and identified a four-miRNA panel: miR-9-5p, miR-1246, miR-31-3p, and miR-3136-5p. The combination of these four miRNAs outperformed any single miRNA for predicting 5-year overall survival (hazard ratio [HR]: 3.47, log-rank p-value = 0.000271). Experiments were performed on lung cancer cell lines and animal models to validate the effects of these miRNAs. The results showed that singly transfected antagomiRs largely inhibited cell growth, migration, and invasion, and the combination of all four antagomiRs considerably reduced cell numbers, which is twice as effective as any single miRNA-targeted transfected. The
Language	English
Publishing date	2022-08-22
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2694435-2
ISSN	2001-0370
ISSN	2001-0370
DOI	10.1016/j.csbj.2022.08.042
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Article ; Online: Distinct Immunogenetic Profiles of Chronic Lymphocytic Leukemia in Asia: A Taiwan Cooperative Oncology Group Registry Study.

HemaSphere

2022 Volume 6, Issue 12, Page(s) e803

Abstract: Asian patientswith chronic lymphocytic leukemia (CLL) exhibit immunoglobulin heavy variable (IGHV) gene repertoires that are distinct from those observed in Western populations, and a higher proportion of Asian CLL patients carry heavy loads of somatic ... ...

Abstract	Asian patientswith chronic lymphocytic leukemia (CLL) exhibit immunoglobulin heavy variable (IGHV) gene repertoires that are distinct from those observed in Western populations, and a higher proportion of Asian CLL patients carry heavy loads of somatic hypermutations (SHM) within the B-cell receptor immunoglobulins (BcR IG). Due to the low regional incidence of CLL in Asia, only a limited number of studies had attempted to probe the phenomenon of BcR IG stereotypy in Asian populations. In this study, we analyzed the IGHV-IGHD-IGHJ gene rearrangements from a series of 255 CLL patients recruited in a nationwide, multicenter study in Taiwan. Our analysis revealed that the IGHV gene repertoire was characterized by evident biases, with IGHV3-7, IGHV4-34, and IGHV3-23 being the most frequent rearranged IGHV genes, and a higher proportion of cases carrying mutated IGHV. In terms of BcR stereotypy, the incidence of major subsets was less frequent in this cohort, with subsets #77 and #28A being the most common, while the incidence of minor subsets was approximately equivalent to that reported in the Western cohorts. With this study, we provide evidence that CLL in Asia is indeed associated with distinct immunogenetic characteristics regarding IGHV gene usage, SHM status, and BcR IG stereotypy.
Language	English
Publishing date	2022-11-25
Publishing country	United States
Document type	Journal Article
ISSN	2572-9241
ISSN (online)	2572-9241
DOI	10.1097/HS9.0000000000000803
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Article ; Online: NOVEL-1st: an observational study to assess the safety and efficacy of nilotinib in newly diagnosed patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase in Taiwan.

International journal of hematology

2022 Volume 115, Issue 5, Page(s) 704–712

Abstract: Nilotinib has been approved for the treatment of Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase ( ... ...

Abstract	Nilotinib has been approved for the treatment of Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph
MeSH term(s)	Antineoplastic Agents/adverse effects ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnosis ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy ; Leukopenia/chemically induced ; Philadelphia Chromosome ; Protein Kinase Inhibitors/therapeutic use ; Pyrimidines ; Taiwan/epidemiology ; Thrombocytopenia/chemically induced ; Treatment Outcome
Chemical Substances	Antineoplastic Agents ; Protein Kinase Inhibitors ; Pyrimidines ; nilotinib (F41401512X)
Language	English
Publishing date	2022-02-25
Publishing country	Japan
Document type	Journal Article ; Multicenter Study ; Observational Study
ZDB-ID	1076875-0
ISSN	1865-3774 ; 0917-1258 ; 0925-5710
ISSN (online)	1865-3774
ISSN	0917-1258 ; 0925-5710
DOI	10.1007/s12185-022-03311-1
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Zs.A 269: Show issues

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Article ; Online: Recruitment maneuver leads to increased expression of pro-inflammatory cytokines in acute respiratory distress syndrome.

Lan, Chou-Chin / Huang, Hsu-Kai / Wu, Chin-Pyng / Tu, Chuan-Chou / Huang, Tsai-Wang / Tsai, Wen-Chiuan / Tseng, Neng-Chuan / Chang, Hung

Respiratory physiology & neurobiology

2019 Volume 271, Page(s) 103284

Abstract: Acute respiratory distress syndrome (ARDS) is a disease with high morbidity and mortality rates. The recruitment maneuver (RM) is one of the interventions used for ARDS patients suffering from severe hypoxemia. RM works by opening the atelectatic lungs ... ...

Abstract	Acute respiratory distress syndrome (ARDS) is a disease with high morbidity and mortality rates. The recruitment maneuver (RM) is one of the interventions used for ARDS patients suffering from severe hypoxemia. RM works by opening the atelectatic lungs using high transpulmonary pressure. RM has therefore been widely used for many years in patients with ARDS. However, because of the high transpulmonary pressure used in this intervention, there are concerns about both biotrauma and hemodynamic instability. To assess the effects of RM in ARDS, we conducted a study using three groups of pigs (n = 6 in each group): group I (control), group II (ARDS), and group III (ARDS with RM). After measuring the baseline values, ARDS was induced by deactivating the surfactant with 5% Tweens lavage. For pigs of group III, the RM protocol used was positive end-expiratory pressure (PEEP) of 25 cmH
MeSH term(s)	Animals ; Bronchoalveolar Lavage Fluid ; Cytokines/biosynthesis ; Cytokines/genetics ; Gene Expression ; Inflammation Mediators/metabolism ; Pulmonary Gas Exchange/physiology ; Respiratory Distress Syndrome, Adult/genetics ; Respiratory Distress Syndrome, Adult/metabolism ; Respiratory Mechanics/physiology ; Swine
Chemical Substances	Cytokines ; Inflammation Mediators
Language	English
Publishing date	2019-08-28
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2077867-3
ISSN	1878-1519 ; 1569-9048
ISSN (online)	1878-1519
ISSN	1569-9048
DOI	10.1016/j.resp.2019.103284
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