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Article: Group A Streptococcus Pili-Roles in Pathogenesis and Potential for Vaccine Development.

Tsai, Catherine Jia-Yun / Takahashi, Risa / Loh, Jacelyn Mei-San / Proft, Thomas

2024 Volume 12, Issue 3

Abstract: The Gram-positive human pathogen Group A Streptococcus (GAS, ...

Abstract	The Gram-positive human pathogen Group A Streptococcus (GAS,
Language	English
Publishing date	2024-03-11
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2720891-6
ISSN	2076-2607
ISSN	2076-2607
DOI	10.3390/microorganisms12030555
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Article ; Online: Pilus proteins from Streptococcus pyogenes stimulate innate immune responses through Toll-like receptor 2.

Takahashi, Risa / Radcliff, Fiona J / Proft, Thomas / Tsai, Catherine J-Y

Immunology and cell biology

2022 Volume 100, Issue 3, Page(s) 174–185

Abstract: The group A Streptococcus (GAS) pilus is a long, flexible, hair-like structure anchored to the cell surface that facilitates the adherence of GAS to host cells, thus playing a critical role in initiating infections. Because of its important role in GAS ... ...

Abstract	The group A Streptococcus (GAS) pilus is a long, flexible, hair-like structure anchored to the cell surface that facilitates the adherence of GAS to host cells, thus playing a critical role in initiating infections. Because of its important role in GAS virulence, the pilus has become an attractive target for vaccine development. While current research mainly focuses on pilus function and its potential as a vaccine component, there is a lack of knowledge on how the host immune system recognizes and responds to this abundant surface structure. Here we show that both assembled GAS pili and individual pilus proteins induce a potent release of the proinflammatory cytokines tumor necrosis factor and interleukin-8. We further show that the surface-exposed backbone pilin and ancillary pilin 1 subunits are Toll-like receptor 2 (TLR2) agonists. Using reporter cell lines coexpressing human TLR2 in combination with either TLR1 or TLR6, we determined that activation was mediated by the TLR2/TLR6 heterodimer. Finally, we used solid-phase and flow cytometry binding assays to illustrate a direct interaction between the pilus subunits and TLR2. These results provide further support for the suitability of the pilus as a vaccine component and opens potential avenues for using GAS pili as an adjuvant or immune-modulation agent.
MeSH term(s)	Bacterial Proteins/chemistry ; Bacterial Proteins/metabolism ; Fimbriae Proteins/metabolism ; Humans ; Immunity, Innate ; Streptococcus pyogenes/metabolism ; Toll-Like Receptor 2/metabolism ; Toll-Like Receptor 6/metabolism
Chemical Substances	Bacterial Proteins ; Toll-Like Receptor 2 ; Toll-Like Receptor 6 ; Fimbriae Proteins (147680-16-8)
Language	English
Publishing date	2022-02-24
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	284057-1
ISSN	1440-1711 ; 0818-9641
ISSN (online)	1440-1711
ISSN	0818-9641
DOI	10.1111/imcb.12523
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Article ; Online: Association of women's empowerment with anaemia and haemoglobin concentration in children in sub-Saharan Africa: A multilevel analysis.

Wilunda, Calistus / Wanjohi, Milkah / Takahashi, Risa / Kimani-Murage, Elizabeth / Mutoro, Antonina

Maternal & child nutrition

2022 Volume 19, Issue 1, Page(s) e13426

Abstract: We assessed the associations between women's empowerment and anaemia and haemoglobin concentration among children (6-59 months) in 31 sub-Saharan African (SSA) countries. We included 72,032 mother-child pairs from Demographic and Health Surveys conducted ...

Abstract	We assessed the associations between women's empowerment and anaemia and haemoglobin concentration among children (6-59 months) in 31 sub-Saharan African (SSA) countries. We included 72,032 mother-child pairs from Demographic and Health Surveys conducted between 2006 and 2019. A three-dimensional women's empowerment index (attitude towards violence, decision making and social independence) was constructed using principal components analysis, and associations between the index and any anaemia and Hb concentration were assessed using multilevel regression. The mean (standard deviation) haemoglobin concentration was 102.3 (16.0 g/L) and 65.8% of the children were anaemic. The odds of anaemia reduced with increasing empowerment in the dimensions of attitude towards violence [quintile (Q5) versus Q1, OR 0.77; 95% confidence interval [CI] 0.65-0.89, p
MeSH term(s)	Female ; Humans ; Africa South of the Sahara/epidemiology ; Anemia/epidemiology ; Decision Making ; Hemoglobins ; Multilevel Analysis ; Empowerment
Chemical Substances	Hemoglobins
Language	English
Publishing date	2022-09-07
Publishing country	England
Document type	Journal Article
ZDB-ID	2175105-5
ISSN	1740-8709 ; 1740-8695
ISSN (online)	1740-8709
ISSN	1740-8695
DOI	10.1111/mcn.13426
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Article ; Online: Different Group A Streptococcus pili lead to varying proinflammatory cytokine responses and virulence.

Takahashi, Risa / J-Khemlani, Adrina Hema / Loh, Jacelyn Mei San / Radcliff, Fiona Jane / Proft, Thomas / Tsai, Catherine Jia-Yun

Immunology and cell biology

2023 Volume 102, Issue 1, Page(s) 21–33

Abstract: The human pathogen Streptococcus pyogenes, or Group A Streptococcus (GAS), is associated with a variety of diseases ranging from mild skin and soft tissue infections to invasive diseases and immune sequelae such as rheumatic heart disease. We have ... ...

Abstract	The human pathogen Streptococcus pyogenes, or Group A Streptococcus (GAS), is associated with a variety of diseases ranging from mild skin and soft tissue infections to invasive diseases and immune sequelae such as rheumatic heart disease. We have recently reported that one of the virulence factors of this pathogen, the pilus, has inflammatory properties and strongly stimulates the innate immune system. Here we used a range of nonpathogenic Lactococcus lactis gain-of-function mutants, each expressing one of the major pilus types of GAS, to compare the immune responses generated by various types of fully assembled pili. In vitro assays indicated variability in the inflammatory response induced by different pili, with the fibronectin-binding, collagen-binding, T antigen (FCT)-1-type pilus from GAS serotype M6/T6 inducing significantly stronger cytokine secretion than other pili. Furthermore, we established that the same trend of pili-mediated immune response could be modeled in Galleria mellonella larvae, which possess a similar innate immune system to vertebrates. Counterintuitively, across the panel of pili types examined in this study, we observed a negative correlation between the intensity of the immune response demonstrated in our experiments and the disease severity observed clinically in the GAS strains associated with each pilus type. This observation suggests that pili-mediated inflammation is more likely to promote bacterial clearance instead of causing disruptive damages that intensify pathogenesis. This also indicates that pili may not be the main contributor to the inflammatory symptoms seen in GAS diseases. Rather, the immune-potentiating properties of the pilus components could potentially be exploited as a vaccine adjuvant.
MeSH term(s)	Animals ; Humans ; Virulence ; Streptococcus pyogenes/physiology ; Fimbriae, Bacterial/physiology ; Skin ; Bacterial Proteins
Chemical Substances	Bacterial Proteins
Language	English
Publishing date	2023-10-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	284057-1
ISSN	1440-1711 ; 0818-9641
ISSN (online)	1440-1711
ISSN	0818-9641
DOI	10.1111/imcb.12692
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Article ; Online: Impact of polypharmacy on all-cause mortality and hospitalization in incident hemodialysis patients: a cohort study.

Toida, Tatsunori / Toida, Reiko / Takahashi, Risa / Uezono, Shigehiro / Komatsu, Hiroyuki / Sato, Yuji / Fujimoto, Shouichi

Clinical and experimental nephrology

2021 Volume 25, Issue 11, Page(s) 1215–1223

Abstract: Background: Polypharmacy (PP) is common in end-stage chronic renal disease patients largely due to the presence of multiple comorbid conditions. Although PP is potentially harmful, its relationship with mortality and morbidity in hemodialysis patients ... ...

Abstract	Background: Polypharmacy (PP) is common in end-stage chronic renal disease patients largely due to the presence of multiple comorbid conditions. Although PP is potentially harmful, its relationship with mortality and morbidity in hemodialysis patients currently remains unclear. Methods: Study design: cohort study. Setting: participants: one hundred and fifty-two initial hemodialysis patients (male, 88 patients; mean age, 70.3 years) were enrolled between February 2015 and March 2018 at Nobeoka Prefectural Hospital and Chiyoda Hospital. Predictor: patients were divided into 2 groups according to PP (6 or more drug prescriptions or less) during admission and discharge for the initiation of hemodialysis. Outcomes: all-cause mortality and hospitalization during the mean 2.8-year follow-up. Measurements: hazard ratios (HRs) were estimated using Cox's model for the relationships between PP and clinical outcomes and adjusted for potential confounders. The group with 5 or less drug prescriptions was set as a reference. Results: The number of prescribed drugs per patient averaged 7.4 at admission and 7.0 at discharge for initial hemodialysis. One hundred (65.8%) and 94 patients (61.8%) had PP at admission and discharge, respectively. During the follow-up, 20 patients died and 71 were hospitalized. PP at admission did not correlate with outcomes, whereas that at discharge correlated with all-cause hospitalization. Conclusions: PP at discharge may be associated with clinical outcomes. However, it remains unclear whether PP is the direct cause of outcomes or is simply a marker for an increased risk of outcomes.
MeSH term(s)	Aged ; Aged, 80 and over ; Female ; Follow-Up Studies ; Hospitalization/statistics & numerical data ; Humans ; Japan/epidemiology ; Male ; Middle Aged ; Mortality ; Patient Admission/statistics & numerical data ; Patient Discharge/statistics & numerical data ; Polypharmacy/statistics & numerical data ; Proportional Hazards Models ; Prospective Studies ; Renal Dialysis
Language	English
Publishing date	2021-06-15
Publishing country	Japan
Document type	Journal Article ; Observational Study
ZDB-ID	1338768-6
ISSN	1437-7799 ; 1342-1751
ISSN (online)	1437-7799
ISSN	1342-1751
DOI	10.1007/s10157-021-02094-9
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Article ; Online: [Inhibitory Effects of Dabigatran on Airway Inflammation Induced by Lipopolysaccharide in Mice].

Kimura, Genki / Takahashi, Risa / Nagamoto, Ayaka / Yoshino, Kotomi / Ueda, Keitaro / Nishimoto, Yuki / Kizawa, Yasuo

Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan

2020 Volume 140, Issue 12, Page(s) 1477–1483

Abstract: Asthma and chronic obstructive pulmonary disease (COPD) are characterised by chronic inflammation in the lung that is associated with airway obstruction. Inhaled therapy with a combination of corticosteroid and a long-acting ... ...

Abstract	Asthma and chronic obstructive pulmonary disease (COPD) are characterised by chronic inflammation in the lung that is associated with airway obstruction. Inhaled therapy with a combination of corticosteroid and a long-acting β
MeSH term(s)	Animals ; Antithrombins/pharmacology ; Antithrombins/therapeutic use ; Asthma/chemically induced ; Asthma/diagnosis ; Asthma/drug therapy ; Biomarkers/analysis ; Bronchoalveolar Lavage Fluid/chemistry ; Chemokine CXCL1/analysis ; Dabigatran/pharmacology ; Dabigatran/therapeutic use ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Drug Synergism ; Drug Therapy, Combination ; Fluticasone/therapeutic use ; Inflammation ; Inflammation Mediators/analysis ; Lipopolysaccharides/adverse effects ; Male ; Mice, Inbred Strains ; Osteopontin/analysis ; Pulmonary Disease, Chronic Obstructive/chemically induced ; Pulmonary Disease, Chronic Obstructive/diagnosis ; Pulmonary Disease, Chronic Obstructive/drug therapy ; Tumor Necrosis Factor-alpha/analysis
Chemical Substances	Antithrombins ; Biomarkers ; Chemokine CXCL1 ; Inflammation Mediators ; Lipopolysaccharides ; Tumor Necrosis Factor-alpha ; Osteopontin (106441-73-0) ; Fluticasone (CUT2W21N7U) ; Dabigatran (I0VM4M70GC)
Language	Japanese
Publishing date	2020-09-14
Publishing country	Japan
Document type	Journal Article
ZDB-ID	200514-1
ISSN	1347-5231 ; 0031-6903 ; 0372-7750 ; 0919-2085 ; 0919-2131
ISSN (online)	1347-5231
ISSN	0031-6903 ; 0372-7750 ; 0919-2085 ; 0919-2131
DOI	10.1248/yakushi.20-00141
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Article: Association between Serum Zinc Levels and Clinical Index or the Body Composition in Incident Hemodialysis Patients

Toida, Tatsunori / Toida, Reiko / Ebihara, Shou / Takahashi, Risa / Komatsu, Hiroyuki / Uezono, Shigehiro / Sato, Yuji / Fujimoto, Shouichi

Nutrients. 2020 Oct. 19, v. 12, no. 10

2020

Abstract: Background: The relationships between serum zinc levels and body composition or clinical outcomes of incident hemodialysis (HD) patients remain unclear. Methods: This prospective observational study examined the relationships between serum zinc levels ... ...

Abstract	Background: The relationships between serum zinc levels and body composition or clinical outcomes of incident hemodialysis (HD) patients remain unclear. Methods: This prospective observational study examined the relationships between serum zinc levels and clinical indexes, including body composition, in 142 incident HD patients using a bioelectrical impedance analysis. Patients were divided into three groups according to baseline serum zinc levels: tertile, <45, 45–59, and ≥60 µg/dL. The reference group was set as ≥60 µg/dL. Cox’s regression analysis was performed to investigate the relationships between serum zinc categories and cardiovascular events and all-cause mortality after adjustments for potential confounders. Results: Serum zinc levels positively correlated with the nutritional index and negatively correlated with fluid volume markers. In a mean follow-up of 2.5 years, there were 20 cases of cardiovascular events and 15 of all-cause mortality. In the Cox’s regression analysis for cardiovascular events and all-cause mortality, the hazard ratio increased with a decrease in serum zinc levels, but was not significant. Conclusion: Serum zinc levels were associated with nutritional and fluid volume markers in incident HD patients. To clarify the relationship between serum zinc levels and cardiovascular events or mortality, further studies with a larger number of cases will be necessary.
Keywords	bioelectrical impedance ; blood serum ; body composition ; correlation ; hemodialysis ; mortality ; nutrients ; nutrition assessment ; observational studies ; patients ; regression analysis ; volume ; zinc
Language	English
Dates of publication	2020-1019
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
Note	NAL-light
ZDB-ID	2518386-2
ISSN	2072-6643
ISSN	2072-6643
DOI	10.3390/nu12103187
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Association between Serum Zinc Levels and Clinical Index or the Body Composition in Incident Hemodialysis Patients.

Toida, Tatsunori / Toida, Reiko / Ebihara, Shou / Takahashi, Risa / Komatsu, Hiroyuki / Uezono, Shigehiro / Sato, Yuji / Fujimoto, Shouichi

Nutrients

2020 Volume 12, Issue 10

Abstract: Background: The relationships between serum zinc levels and body composition or clinical outcomes of incident hemodialysis (HD) patients remain unclear.: Methods: This prospective observational study examined the relationships between serum zinc ... ...

Abstract	Background: The relationships between serum zinc levels and body composition or clinical outcomes of incident hemodialysis (HD) patients remain unclear. Methods: This prospective observational study examined the relationships between serum zinc levels and clinical indexes, including body composition, in 142 incident HD patients using a bioelectrical impedance analysis. Patients were divided into three groups according to baseline serum zinc levels: tertile, <45, 45-59, and ≥60 µg/dL. The reference group was set as ≥60 µg/dL. Cox's regression analysis was performed to investigate the relationships between serum zinc categories and cardiovascular events and all-cause mortality after adjustments for potential confounders. Results: Serum zinc levels positively correlated with the nutritional index and negatively correlated with fluid volume markers. In a mean follow-up of 2.5 years, there were 20 cases of cardiovascular events and 15 of all-cause mortality. In the Cox's regression analysis for cardiovascular events and all-cause mortality, the hazard ratio increased with a decrease in serum zinc levels, but was not significant. Conclusion: Serum zinc levels were associated with nutritional and fluid volume markers in incident HD patients. To clarify the relationship between serum zinc levels and cardiovascular events or mortality, further studies with a larger number of cases will be necessary.
MeSH term(s)	Aged ; Aged, 80 and over ; Biomarkers/blood ; Body Composition ; Body Fluids/metabolism ; Cardiovascular Diseases/epidemiology ; Cardiovascular Diseases/etiology ; Cardiovascular Diseases/mortality ; Cause of Death ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Nutrition Assessment ; Prospective Studies ; Renal Dialysis/adverse effects ; Zinc/blood ; Zinc/deficiency
Chemical Substances	Biomarkers ; Zinc (J41CSQ7QDS)
Language	English
Publishing date	2020-10-19
Publishing country	Switzerland
Document type	Journal Article ; Observational Study
ZDB-ID	2518386-2
ISSN	2072-6643 ; 2072-6643
ISSN (online)	2072-6643
ISSN	2072-6643
DOI	10.3390/nu12103187
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Article ; Online: Knowledge and awareness of nonpharmacist salespersons regarding over-the-counter drug use in patients with chronic kidney disease in Japan.

Kondo, Yuki / Ishitsuka, Yoichi / Kawabata, Nobuhiro / Iwamoto, Nobuhide / Takahashi, Risa / Narita, Yuki / Kadowaki, Daisuke / Hirata, Sumio / Uchino, Satoru / Irie, Tetsumi

PloS one

2019 Volume 14, Issue 3, Page(s) e0213763

Abstract: Introduction: Patients with chronic kidney disease (CKD) depend on advice from healthcare professionals to avoid using unsuitable over-the-counter (OTC) drugs. Recently, qualified, registered nonpharmacist salespersons became licensed to sell OTC drugs ... ...

Abstract	Introduction: Patients with chronic kidney disease (CKD) depend on advice from healthcare professionals to avoid using unsuitable over-the-counter (OTC) drugs. Recently, qualified, registered nonpharmacist salespersons became licensed to sell OTC drugs in Japan. However, registered salespersons' knowledge and awareness of precautions regarding unsuitable OTC drugs for use in patients with CKD are unclear. Objectives: This study aimed to clarify the awareness, knowledge, and implementation of precautions by registered salespersons regarding OTC drugs used by patients with CKD. Additionally, we evaluated the change of registered salespersons' knowledge and awareness of this topic generated by a pharmacist intervention. Methods: A questionnaire survey and pharmacist intervention were applied to 175 registered salespersons. The intervention comprised a 50-minute lecture imparted by a pharmacist who was trained in nephrology. The knowledge, awareness, and implementation of precautions by participants with respect to nonsteroidal anti-inflammatory drugs (NSAIDs) and antacids were evaluated before and after the intervention. Results: Approximately half of the registered salespersons reported previous experience with selling OTC drugs that were inappropriate for patients with CKD (NSAIDs, 48.0%; antacids, 39.7%). Few participants recognized the need to check renal function when selling those drugs to such patients (NSAIDs, 25.7%; antacids, 47.5%). The registered salespersons' awareness and knowledge were significantly higher after the intervention than before it. Conclusion: The results indicate that before the intervention, the registered salespersons had low levels of awareness and knowledge regarding OTC drug use in patients with CKD despite having prior experience selling unsuitable OTC drugs. However, the pharmacist intervention improved the registered salespersons' awareness and knowledge. The educational program for registered salespersons might be necessary to prevent inappropriate OTC drug use by patients with CKD.
MeSH term(s)	Adult ; Antacids/adverse effects ; Anti-Inflammatory Agents, Non-Steroidal/adverse effects ; Awareness ; Female ; Health Personnel/psychology ; Humans ; Japan ; Knowledge ; Male ; Middle Aged ; Nonprescription Drugs/adverse effects ; Renal Insufficiency, Chronic/diagnosis ; Renal Insufficiency, Chronic/etiology ; Surveys and Questionnaires
Chemical Substances	Antacids ; Anti-Inflammatory Agents, Non-Steroidal ; Nonprescription Drugs
Language	English
Publishing date	2019-03-20
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0213763
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Article ; Online: Evaluation of Alcohol Screening and Community-Based Brief Interventions in Rural Western Kenya: A Quasi-Experimental Study.

Takahashi, Risa / Wilunda, Calistus / Magutah, Karani / Mwaura-Tenambergen, Wanja / Atwoli, Lukoye / Perngparn, Usaneya

Alcohol and alcoholism (Oxford, Oxfordshire)

2017 Volume 53, Issue 1, Page(s) 121–128

Abstract: Aims: To assess the effectiveness of community-based alcohol brief interventions (ABI) implemented by community-health workers with and without motivational talks (MT) by former drinkers, in reducing harmful and hazardous alcohol consumption.: Methods! ...

Abstract	Aims: To assess the effectiveness of community-based alcohol brief interventions (ABI) implemented by community-health workers with and without motivational talks (MT) by former drinkers, in reducing harmful and hazardous alcohol consumption. Methods: We conducted a three-arm quasi-experimental study (one control and two intervention groups) between May and December 2015 in Kakamega County, Kenya. Participants were hazardous or harmful alcohol drinkers with an Alcohol Use Disorders Identification Test (AUDIT) score of 8-19 at baseline. One intervention group received only ABI while the other received ABI + MT. The interventions' effects on AUDIT scores were analysed using linear mixed models. Logistic regression was used to analyse the interventions' effects on low-risk drinking (AUDIT score <8) after 6 months. Results: The study included 161 participants: 52 in the control group, 52 in the only ABI group and 57 in the ABI + MT group. The mean AUDIT scores were lower in the intervention groups at 1, 3 and 6 months post-intervention; the ABI + MT group showed a greater reduction. The mean AUDIT scores over a 6-month period were lower in both intervention groups compared with the control group. The odds of low-risk drinking were almost two times higher in both intervention groups than in the control group, although the effect of only ABI on low-risk drinking was not significant. Conclusions: ABI + MT and only ABI were associated with a reduced mean AUDIT score among hazardous and high-risk drinkers in this resource-limited setting. ABI + MT was also associated with low-risk drinking in this population. Short summary: Community-based alcohol brief interventions implemented by community-health workers accompanied by motivational talks by former drinkers were associated with reduced hazardous and harmful alcohol consumption in a rural setting in western Kenya.
MeSH term(s)	Adolescent ; Adult ; Aged ; Alcohol Drinking/epidemiology ; Alcoholism/diagnosis ; Alcoholism/epidemiology ; Alcoholism/therapy ; Community Health Services/statistics & numerical data ; Community Health Workers ; Female ; Humans ; Kenya/epidemiology ; Logistic Models ; Male ; Mass Screening ; Middle Aged ; Motivational Interviewing ; Rural Population ; Socioeconomic Factors ; Treatment Outcome ; Young Adult
Language	English
Publishing date	2017-12-06
Publishing country	England
Document type	Journal Article
ZDB-ID	604956-4
ISSN	1464-3502 ; 0309-1635 ; 0735-0414
ISSN (online)	1464-3502
ISSN	0309-1635 ; 0735-0414
DOI	10.1093/alcalc/agx083
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