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  1. Article ; Online: Interventions for weight reduction in obesity to improve survival in women with endometrial cancer.

    Agnew, Heather / Kitson, Sarah / Crosbie, Emma J

    The Cochrane database of systematic reviews

    2023  Volume 3, Page(s) CD012513

    Abstract: Background: This is an updated version of the original Cochrane Review published in Issue 2, 2018. Diagnoses of endometrial cancer are increasing secondary to the rising prevalence of obesity. Obesity plays an important role in promoting the development ...

    Abstract Background: This is an updated version of the original Cochrane Review published in Issue 2, 2018. Diagnoses of endometrial cancer are increasing secondary to the rising prevalence of obesity. Obesity plays an important role in promoting the development of endometrial cancer, by inducing a state of unopposed oestrogen excess, insulin resistance and inflammation. It also affects treatment, increasing the risk of surgical complications and the complexity of radiotherapy planning, and may additionally impact on subsequent survival. Weight-loss interventions have been associated with improvements in breast and colorectal cancer-specific survival, as well as a reduction in the risk of cardiovascular disease, which is a frequent cause of death in endometrial cancer survivors.
    Objectives: To evaluate the benefits and harm of weight-loss interventions, in addition to standard management, on overall survival and the frequency of adverse events in women with endometrial cancer who are overweight or obese compared with any other intervention, usual care, or placebo.
    Search methods: We used standard, extensive Cochrane search methods. The latest search date was from January 2018 to June 2022 (original review searched from inception to January 2018).
    Selection criteria: We included randomised controlled trials (RCTs) of interventions to facilitate weight loss in women with endometrial cancer who are overweight or obese undergoing treatment for, or previously treated for, endometrial cancer compared with any other intervention, usual care, or placebo.  DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were 1. overall survival and 2. frequency of adverse events. Our secondary outcomes were 3. recurrence-free survival, 4. cancer-specific survival, 5. weight loss, 6. cardiovascular and metabolic event frequency and 7. quality of Life. We used GRADE to assess certainty of evidence. We contacted study authors to obtain missing data, including details of any adverse events.
    Main results: We identified nine new RCTs and combined these with the three RCTs identified in the original review. Seven studies are ongoing.  The 12 RCTs randomised 610 women with endometrial cancer who were overweight or obese. All studies compared combined behavioural and lifestyle interventions designed to facilitate weight loss through dietary modification and increased physical activity with usual care. Included RCTs were of low or very low quality, due to high risk of bias by failing to blind participants, personnel and outcome assessors, and significant loss to follow-up (withdrawal rate up to 28% and missing data up to 65%, largely due to the effects of the COVID-19 pandemic). Importantly, the short duration of follow-up limits the directness of the evidence in evaluating the impact of these interventions on any of the survival and other longer-term outcomes.  Combined behaviour and lifestyle interventions were not associated with improved overall survival compared with usual care at 24 months (risk ratio (RR) mortality, 0.23, 95% confidence interval (CI) 0.01 to 4.55, P = 0.34; 1 RCT, 37 participants; very low-certainty evidence). There was no evidence that such interventions were associated with improvements in cancer-specific survival or cardiovascular event frequency as the studies reported no cancer-related deaths, myocardial infarctions or strokes, and there was only one episode of congestive heart failure at six months (RR 3.47, 95% CI 0.15 to 82.21; P = 0.44, 5 RCTs, 211 participants; low-certainty evidence). Only one RCT reported recurrence-free survival; however, there were no events. Combined behaviour and lifestyle interventions were not associated with significant weight loss at either six or 12 months compared with usual care (at six months: mean difference (MD) -1.39 kg, 95% CI -4.04 to 1.26; P = 0.30, I
    MeSH term(s) Female ; Humans ; Overweight/complications ; Overweight/therapy ; COVID-19/complications ; Obesity/complications ; Obesity/therapy ; Endometrial Neoplasms/therapy ; Weight Loss
    Language English
    Publishing date 2023-03-27
    Publishing country England
    Document type Systematic Review ; Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ISSN 1469-493X
    ISSN (online) 1469-493X
    DOI 10.1002/14651858.CD012513.pub3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Gynecological malignancies and obesity.

    Agnew, Heather J / Kitson, Sarah J / Crosbie, Emma J

    Best practice & research. Clinical obstetrics & gynaecology

    2023  Volume 88, Page(s) 102337

    Abstract: The global pandemic of obesity has had a significant impact on gynecological malignancies, most notably endometrial cancer. It has resulted in worldwide increases in the incidence of endometrial cancer and a change in patient demographics, resulting in ... ...

    Abstract The global pandemic of obesity has had a significant impact on gynecological malignancies, most notably endometrial cancer. It has resulted in worldwide increases in the incidence of endometrial cancer and a change in patient demographics, resulting in more diagnoses than ever before being made in pre-menopausal women, who are often keen to pursue fertility-sparing treatments. Obesity increases the risk of gynecological cancers by creating a pro-carcinogenic environment of unopposed estrogen, hyperinsulinemia, and chronic inflammation. It can present both a diagnostic challenge and strongly influence management decisions, including the practicalities of performing surgery, increase anesthetic risks, and alter response rates to adjuvant and medical therapies. Obesity may also influence endometrial cancer mortality and certainly contributes to poorer overall survival due to an excess of deaths related to cardiovascular disease. Weight loss may well, therefore, be the key to the prevention of gynecological cancers and their recurrence.
    MeSH term(s) Female ; Humans ; Genital Neoplasms, Female/epidemiology ; Genital Neoplasms, Female/etiology ; Genital Neoplasms, Female/therapy ; Obesity/complications ; Obesity/epidemiology ; Obesity/therapy ; Endometrial Neoplasms/epidemiology ; Endometrial Neoplasms/etiology ; Endometrial Neoplasms/therapy ; Estrogens
    Chemical Substances Estrogens
    Language English
    Publishing date 2023-04-08
    Publishing country Netherlands
    Document type Journal Article ; Review
    ZDB-ID 2050090-7
    ISSN 1532-1932 ; 1521-6934
    ISSN (online) 1532-1932
    ISSN 1521-6934
    DOI 10.1016/j.bpobgyn.2023.102337
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Patient and clinician priorities for information on treatment outcomes for advanced ovarian cancer: a Delphi exercise.

    Baxter, Kathryn / Agnew, Heather / Morgan, Jennie / Holland, Cathrine / Flynn, Darren / Edmondson, Richard

    Journal of gynecologic oncology

    2024  

    Abstract: Objective: Patients with advanced ovarian cancer face a range of treatment options, and there is unwarranted variation in treatment decision-making between UK providers. Decision support tools that produce data on treatment outcomes as a function of ... ...

    Abstract Objective: Patients with advanced ovarian cancer face a range of treatment options, and there is unwarranted variation in treatment decision-making between UK providers. Decision support tools that produce data on treatment outcomes as a function of individual patient characteristics, would help both patients and clinicians to make informed, preference- and values-based choices. However, data on treatment outcomes to include in such tools are lacking.
    Methods: Following a literature review, a questionnaire was designed for use in a Delphi process to establish which treatment outcomes are important to both patients and clinicians in decision-making for treatment for advanced ovarian cancer. Patient and clinician panels were established.
    Results: Following 2 Delphi rounds, consensus was achieved for 7/11 items in the patient panel and 8/11 items in the clinician panel. Consensus across both panels was achieved for inclusion of both overall survival and progression free survival as important items in the decision-making process, although there remained differences of opinion as to whether these should be presented as relative or absolute values.
    Conclusion: Information needs for treatment decision-making in ovarian cancer differ between and within patient and clinician groups. Whilst overall survival and progression free survival are universally accepted as important data items, decision support tools will need to be nuanced to allow presentation of a range of outcomes and associated probabilities, and in a range of formats, that can be tailored to the preferences of clinician and patients.
    Language English
    Publishing date 2024-03-21
    Publishing country Korea (South)
    Document type Journal Article
    ZDB-ID 2478405-9
    ISSN 2005-0399 ; 2005-0380
    ISSN (online) 2005-0399
    ISSN 2005-0380
    DOI 10.3802/jgo.2024.35.e63
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Impact of Type 2 Diabetes Mellitus on Endometrial Cancer Survival: A Prospective Database Analysis.

    Njoku, Kelechi / Agnew, Heather J / Crosbie, Emma J

    Frontiers in oncology

    2022  Volume 12, Page(s) 899262

    Abstract: Purpose: Type 2 diabetes mellitus (T2DM) is an established risk factor for endometrial cancer but its impact on endometrial cancer survival outcomes is unclear. The aim of this study was to investigate whether pre-existing T2DM impacts survival outcomes ...

    Abstract Purpose: Type 2 diabetes mellitus (T2DM) is an established risk factor for endometrial cancer but its impact on endometrial cancer survival outcomes is unclear. The aim of this study was to investigate whether pre-existing T2DM impacts survival outcomes in endometrial cancer.
    Patients and methods: Women diagnosed with endometrial cancer were recruited to a single centre prospective cohort study. Relevant sociodemographic and clinico-pathological data were recorded at baseline. T2DM status was based on clinical and biochemical assessment, verified by general practitioner records and analysed in relation to overall, cancer-specific and recurrence-free survival using Kaplan-Meier estimation and multivariable Cox-regression.
    Results: In total, 533 women with median age and BMI of 66 years (Interquartile range (IQR), 56, 73) and 32kg/m
    Conclusion: T2DM confers an increased risk of death in endometrial cancer patients. Well-designed longitudinal studies with large sample sizes are now needed to confirm these findings.
    Language English
    Publishing date 2022-05-05
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2649216-7
    ISSN 2234-943X
    ISSN 2234-943X
    DOI 10.3389/fonc.2022.899262
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Protein Catalyzed Capture (PCC) Agents for Antigen Targeting.

    Idso, Matthew N / Lai, Bert T / Agnew, Heather D / Heath, James R

    Methods in molecular biology (Clifton, N.J.)

    2021  Volume 2371, Page(s) 177–191

    Abstract: The protein catalyzed capture agent (PCC) method is a powerful combinatorial screening strategy for discovering synthetic macrocyclic peptide ligands, called PCCs, to designated protein epitopes. The foundational concept of the PCC method is the use of ... ...

    Abstract The protein catalyzed capture agent (PCC) method is a powerful combinatorial screening strategy for discovering synthetic macrocyclic peptide ligands, called PCCs, to designated protein epitopes. The foundational concept of the PCC method is the use of in situ click chemistry to survey large combinatorial libraries of peptides for ligands to designated biological targets. State-of-the-art PCC screens integrate synthetic libraries of constrained macrocyclic peptides with epitope-specific targeting strategies to identify high-affinity (<100 nM) binders de novo. Automated instrumentation can accelerate PCC discovery to a rapid 2-week timeframe. Here, we describe methods to perform combinatorial screens that yield epitope-targeted PCCs.
    MeSH term(s) Catalysis ; Combinatorial Chemistry Techniques ; Epitopes ; Ligands ; Peptide Library ; Peptides ; Proteins
    Chemical Substances Epitopes ; Ligands ; Peptide Library ; Peptides ; Proteins
    Language English
    Publishing date 2021-10-01
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-1689-5_10
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Serum HE4 predicts progestin treatment response in endometrial cancer and atypical hyperplasia: A prognostic study.

    Barr, Chloe E / Sergeant, Jamie C / Agnew, Heather J / Bolton, James / McVey, Rhona J / Crosbie, Emma J

    BJOG : an international journal of obstetrics and gynaecology

    2023  Volume 130, Issue 8, Page(s) 941–948

    Abstract: Objective: To investigate serum human epididymis-4 (HE4) as a predictive biomarker of intrauterine progestin response in endometrial cancer and atypical endometrial hyperplasia (AEH).: Design: Prospective prognostic factor study.: Setting: ... ...

    Abstract Objective: To investigate serum human epididymis-4 (HE4) as a predictive biomarker of intrauterine progestin response in endometrial cancer and atypical endometrial hyperplasia (AEH).
    Design: Prospective prognostic factor study.
    Setting: Consecutive sample of women attending a tertiary gynaecological oncology centre in northwest England.
    Population: Women with AEH or early-stage, low-grade endometrial cancer who were unfit for or declined primary surgical management.
    Methods: A total of 76 women, 32 with AEH and 44 with endometrial cancer, were treated with a levonorgestrel intrauterine system (LNG-IUS) for 12 months. Endometrial biopsies and imaging were performed to assess treatment response. Pretreatment serum HE4 was analysed by chemiluminescence immunoassay and diagnostic accuracy and logistic regression analyses were performed.
    Main outcome measures: Progestin response at 12 months defined by histology and imaging.
    Results: The median age and body mass index (BMI) of the final cohort were 52 years (interquartile range [IQR] 33-62 years) and 46 kg/m
    Conclusion: Serum HE4 shows promise as a predictive biomarker of progestin treatment response in endometrial cancer and AEH.
    MeSH term(s) Female ; Humans ; Male ; Adult ; Middle Aged ; Progestins/therapeutic use ; Prognosis ; Hyperplasia/pathology ; Prospective Studies ; Epididymis/pathology ; Levonorgestrel/therapeutic use ; Endometrial Neoplasms/pathology ; Endometrial Hyperplasia/pathology ; Precancerous Conditions/pathology ; Biomarkers ; Intrauterine Devices, Medicated
    Chemical Substances Progestins ; Levonorgestrel (5W7SIA7YZW) ; Biomarkers
    Language English
    Publishing date 2023-02-15
    Publishing country England
    Document type Journal Article
    ZDB-ID 2000931-8
    ISSN 1471-0528 ; 0306-5456 ; 1470-0328
    ISSN (online) 1471-0528
    ISSN 0306-5456 ; 1470-0328
    DOI 10.1111/1471-0528.17417
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Quantitative SWATH-based proteomic profiling of urine for the identification of endometrial cancer biomarkers in symptomatic women.

    Njoku, Kelechi / Pierce, Andrew / Geary, Bethany / Campbell, Amy E / Kelsall, Janet / Reed, Rachel / Armit, Alexander / Da Sylva, Rachel / Zhang, Liqun / Agnew, Heather / Baricevic-Jones, Ivona / Chiasserini, Davide / Whetton, Anthony D / Crosbie, Emma J

    British journal of cancer

    2023  Volume 128, Issue 9, Page(s) 1723–1732

    Abstract: Background: A non-invasive endometrial cancer detection tool that can accurately triage symptomatic women for definitive testing would improve patient care. Urine is an attractive biofluid for cancer detection due to its simplicity and ease of ... ...

    Abstract Background: A non-invasive endometrial cancer detection tool that can accurately triage symptomatic women for definitive testing would improve patient care. Urine is an attractive biofluid for cancer detection due to its simplicity and ease of collection. The aim of this study was to identify urine-based proteomic signatures that can discriminate endometrial cancer patients from symptomatic controls.
    Methods: This was a prospective case-control study of symptomatic post-menopausal women (50 cancers, 54 controls). Voided self-collected urine samples were processed for mass spectrometry and run using sequential window acquisition of all theoretical mass spectra (SWATH-MS). Machine learning techniques were used to identify important discriminatory proteins, which were subsequently combined in multi-marker panels using logistic regression.
    Results: The top discriminatory proteins individually showed moderate accuracy (AUC > 0.70) for endometrial cancer detection. However, algorithms combining the most discriminatory proteins performed well with AUCs > 0.90. The best performing diagnostic model was a 10-marker panel combining SPRR1B, CRNN, CALML3, TXN, FABP5, C1RL, MMP9, ECM1, S100A7 and CFI and predicted endometrial cancer with an AUC of 0.92 (0.96-0.97). Urine-based protein signatures showed good accuracy for the detection of early-stage cancers (AUC 0.92 (0.86-0.9)).
    Conclusion: A patient-friendly, urine-based test could offer a non-invasive endometrial cancer detection tool in symptomatic women. Validation in a larger independent cohort is warranted.
    MeSH term(s) Humans ; Female ; Biomarkers, Tumor ; Case-Control Studies ; Proteomics/methods ; Biomarkers ; Mass Spectrometry/methods ; Endometrial Neoplasms/diagnosis ; Fatty Acid-Binding Proteins ; Extracellular Matrix Proteins
    Chemical Substances Biomarkers, Tumor ; Biomarkers ; FABP5 protein, human ; Fatty Acid-Binding Proteins ; ECM1 protein, human ; Extracellular Matrix Proteins
    Language English
    Publishing date 2023-02-17
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80075-2
    ISSN 1532-1827 ; 0007-0920
    ISSN (online) 1532-1827
    ISSN 0007-0920
    DOI 10.1038/s41416-022-02139-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Positron Emission Tomography Tracer Design of Targeted Synthetic Peptides via

    Narayanam, Maruthi Kumar / Lai, Bert T / Loredo, Jacquie Malette / Wilson, Jeré A / Eliasen, Anders M / LaBerge, Nicole A / Nason, Malley / Cantu, Annabelle L / Luton, Breanna K / Xu, Shili / Agnew, Heather D / Murphy, Jennifer M

    Bioconjugate chemistry

    2021  Volume 32, Issue 9, Page(s) 2073–2082

    Abstract: Chemically synthesized, small peptides that bind with high affinity and specificity to CD8-expressing (CD8+) tumor-infiltrating T cells, yet retain the desirable characteristics of small molecules, hold valuable potential for diagnostic molecular imaging ...

    Abstract Chemically synthesized, small peptides that bind with high affinity and specificity to CD8-expressing (CD8+) tumor-infiltrating T cells, yet retain the desirable characteristics of small molecules, hold valuable potential for diagnostic molecular imaging of immune response. Here, we report the development of
    MeSH term(s) Alkynes ; Animals ; Cycloaddition Reaction ; Fluorine Radioisotopes ; Positron-Emission Tomography
    Chemical Substances Alkynes ; Fluorine Radioisotopes
    Language English
    Publishing date 2021-08-20
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1024041-x
    ISSN 1520-4812 ; 1043-1802
    ISSN (online) 1520-4812
    ISSN 1043-1802
    DOI 10.1021/acs.bioconjchem.1c00379
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  9. Article ; Online: Retrieval savings with nonidentical elements: the case of simple addition and subtraction.

    Campbell, Jamie I D / Agnew, Heather

    Psychonomic bulletin & review

    2009  Volume 16, Issue 5, Page(s) 938–944

    Abstract: The identical elements (IE) theory of fact representation (Rickard, 2005) proposes that memorized facts that are composed of identical elements (e.g., 6x8=48 and 8x6=48) share a common representation in memory, whereas facts with nonidentical elements (e. ...

    Abstract The identical elements (IE) theory of fact representation (Rickard, 2005) proposes that memorized facts that are composed of identical elements (e.g., 6x8=48 and 8x6=48) share a common representation in memory, whereas facts with nonidentical elements (e.g., 6x8=48 and 48/8=6) are represented separately in memory. The IE model has been successfully applied to the transfer of practice in simple multiplication and division, in transition from procedure-based to retrieval-based performance, and in cued episodic recall. In the present article, we examined the effects of practicing simple addition problems (e.g., 3+6=9) on the performance of corresponding subtraction problems (9-6=3), and vice versa. According to IE theory, there should be no transfer of retrieval savings between addition and subtraction facts if performance is based on discrete IE fact representations. Cross-operation response time savings were observed, however, for both small, well-memorized problems (e.g., practice 3+2, test 5-2) and larger problems (6+8, 14-6), and they were statistically robust when trials that were self-reported as direct retrieval were analyzed. The transfer of retrieval practice savings between facts with nonidentical elements challenges IE theory as a comprehensive model of transfer in memory retrieval.
    MeSH term(s) Adolescent ; Adult ; Female ; Humans ; Male ; Mathematics ; Memory ; Memory, Short-Term ; Middle Aged ; Models, Psychological ; Reaction Time ; Task Performance and Analysis ; Young Adult
    Language English
    Publishing date 2009-10-08
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2031311-1
    ISSN 1531-5320 ; 1069-9384
    ISSN (online) 1531-5320
    ISSN 1069-9384
    DOI 10.3758/PBR.16.5.938
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Protein-Catalyzed Capture Agents

    Agnew, Heather D / Coppock, Matthew B / Idso, Matthew N / Lai, Bert T / Liang, JingXin / McCarthy-Torrens, Amy M / Warren, Carmen M / Heath, James R

    Chemical reviews. 2019 Mar. 06, v. 119, no. 17

    2019  

    Abstract: Protein-catalyzed capture agents (PCCs) are synthetic and modular peptide-based affinity agents that are developed through the use of single-generation in situ click chemistry screens against large peptide libraries. In such screens, the target protein, ... ...

    Abstract Protein-catalyzed capture agents (PCCs) are synthetic and modular peptide-based affinity agents that are developed through the use of single-generation in situ click chemistry screens against large peptide libraries. In such screens, the target protein, or a synthetic epitope fragment of that protein, provides a template for selectively promoting the noncopper catalyzed azide–alkyne dipolar cycloaddition click reaction between either a library peptide and a known ligand or a library peptide and the synthetic epitope. The development of epitope-targeted PCCs was motivated by the desire to fully generalize pioneering work from the Sharpless and Finn groups in which in situ click screens were used to develop potent, divalent enzymatic inhibitors. In fact, a large degree of generality has now been achieved. Various PCCs have demonstrated utility for selective protein detection, as allosteric or direct inhibitors, as modulators of protein folding, and as tools for in vivo tumor imaging. We provide a historical context for PCCs and place them within the broader scope of biological and synthetic aptamers. The development of PCCs is presented as (i) Generation I PCCs, which are branched ligands engineered through an iterative, nonepitope-targeted process, and (ii) Generation II PCCs, which are typically developed from macrocyclic peptide libraries and are precisely epitope-targeted. We provide statistical comparisons of Generation II PCCs relative to monoclonal antibodies in which the protein target is the same. Finally, we discuss current challenges and future opportunities of PCCs.
    Keywords catalytic activity ; cycloaddition reactions ; epitopes ; image analysis ; ligands ; monoclonal antibodies ; neoplasms ; oligonucleotides ; peptide libraries ; protein folding
    Language English
    Dates of publication 2019-0306
    Size p. 9950-9970.
    Publishing place American Chemical Society
    Document type Article
    ZDB-ID 207949-5
    ISSN 1520-6890 ; 0009-2665
    ISSN (online) 1520-6890
    ISSN 0009-2665
    DOI 10.1021/acs.chemrev.8b00660
    Database NAL-Catalogue (AGRICOLA)

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