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Article ; Online: Urokinase Plasminogen Activator Receptor: An Important Focal Player in Chronic Subdural Hematoma?

Jensen, Thorbjørn Søren Rønn / Olsen, Markus Harboe / Lelkaitis, Giedrius / Kjaer, Andreas / Binderup, Tina / Fugleholm, Kåre

Inflammation

2024

Abstract: Chronic subdural hematoma (CSDH) development involves inflammatory, angiogenetic, and fibrinolytic mechanisms, several components of which are now unraveled through intensive research. The urokinase plasminogen activator receptor (uPAR) is part of the ... ...

Abstract	Chronic subdural hematoma (CSDH) development involves inflammatory, angiogenetic, and fibrinolytic mechanisms, several components of which are now unraveled through intensive research. The urokinase plasminogen activator receptor (uPAR) is part of the plasminogen activator system and possesses inflammatory, angiogenetic, and fibrinolytic capabilities. As a first, this study aims to identify uPAR in the hematoma fluid, hematoma membrane, dura mater, and systemic blood from patients with CSDH and, if present, to investigate if the uPAR level at the time of surgery may be a predictor for later developing recurrent CSDH. uPAR expression in the hematoma membrane and dura mater was analyzed using immunohistochemistry and presented as the H-score of the positive immunostaining. The uPAR levels in the hematoma fluid and systemic blood were determined using a multiplex antibody bead kit (Luminex). Samples were collected at the time of the first CSDH surgery, and in the case of recurrent CSDH within 90 days, the samples were again collected at reoperation. A comparison of uPAR expression between the hematoma membrane and dura mater, as well as uPAR levels in systemic blood and hematoma fluid, was performed using the Wilcoxon rank sum test. We included 112 patients, 26 of whom had recurrent CSDH. The median hematoma uPAR level was 22,125 (14,845-33,237) and significantly higher than the median systemic blood level of 789 pg/L (465-2,088) (p < 0.001). Similarly, the uPAR level of the hematoma membrane was 14.3 (7.54-44.8) and significantly higher than the dural uPAR level of 0.81 (0.3-1.98) (p < 0.001). For the first time, we identified uPAR in the subdural fluid, hematoma membrane, dura mater, and systemic blood from patients with CSDH. The high expression of uPAR in the subdural fluid and hematoma membrane indicates that the mechanisms of CSDH are predominantly in the subdural fluid collection and surrounding hematoma membrane.
Language	English
Publishing date	2024-01-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	434408-x
ISSN	1573-2576 ; 0360-3997
ISSN (online)	1573-2576
ISSN	0360-3997
DOI	10.1007/s10753-023-01957-5
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Zs.A 1401: Show issues

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Article ; Online: Granular cell tumour of the breast: A case report.

Pankratjevaite, Lina / Igbokwe, Michelle Mistry / Benian, Cemil / Lelkaitis, Giedrius

Breast disease

2023 Volume 42, Issue 1, Page(s) 219–222

Abstract: Introduction: Breast granular cell tumour (GCT) is a rare but usually benign lesion.: Presentation of case: We report a case of a woman with breast GCT.: Conclusion: Clinically and radiologically, GCT may mimic breast carcinoma. A conclusive ... ...

Abstract	Introduction: Breast granular cell tumour (GCT) is a rare but usually benign lesion. Presentation of case: We report a case of a woman with breast GCT. Conclusion: Clinically and radiologically, GCT may mimic breast carcinoma. A conclusive diagnosis is made after a histopathological examination of the lesion. The treatment of choice is surgery.
MeSH term(s)	Female ; Humans ; Breast Neoplasms/pathology ; Granular Cell Tumor/diagnostic imaging ; Granular Cell Tumor/surgery ; Breast/diagnostic imaging ; Breast/pathology ; Mammography ; Biopsy
Language	English
Publishing date	2023-07-22
Publishing country	Netherlands
Document type	Case Reports ; Journal Article
ZDB-ID	639267-2
ISSN	1558-1551 ; 0888-6008
ISSN (online)	1558-1551
ISSN	0888-6008
DOI	10.3233/BD-220063
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Article ; Online: Diagnostic challenges of adenomyoepithelioma: A case report.

Pankratjevaite, Lina / Lind, Katrine / Mele, Marco / Lelkaitis, Giedrius

Breast disease

2022 Volume 41, Issue 1, Page(s) 325–330

Abstract: Introduction: Breast adenomyoepithelioma is a very uncommon tumor, which is generally considered to be benign, however malignant transformation has been reported.: Presentation of case: We report two cases of two women with breast adenomyoepithelioma. ...

Abstract	Introduction: Breast adenomyoepithelioma is a very uncommon tumor, which is generally considered to be benign, however malignant transformation has been reported. Presentation of case: We report two cases of two women with breast adenomyoepithelioma. Conclusion: Diagnosis of adenomyoepithelioma is challenging because tumor may mimic other breast diseases. It has neither specific clinical signs nor radiological features, and the diagnosis is based on histopathological examination of the lesion. The treatment of choice is surgery. The type of surgery depends on the tumor factors and breast size. In malignant cases treatment such as radiotherapy, chemotherapy, immunotherapy may be used as well. It is very important to give an adequate treatment, otherwise the risk of tumor recurrence, growth or even metastatic spread, when tumor has malignant potential, increases.
MeSH term(s)	Adenomyoepithelioma/diagnosis ; Adenomyoepithelioma/pathology ; Adenomyoepithelioma/therapy ; Breast Neoplasms/diagnosis ; Breast Neoplasms/pathology ; Breast Neoplasms/therapy ; Cell Transformation, Neoplastic ; Female ; Humans ; Neoplasm Recurrence, Local
Language	English
Publishing date	2022-07-11
Publishing country	Netherlands
Document type	Case Reports ; Journal Article
ZDB-ID	639267-2
ISSN	1558-1551 ; 0888-6008
ISSN (online)	1558-1551
ISSN	0888-6008
DOI	10.3233/BD-210077
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Article: Late migration of silicon as a complication to breast transplant rupture: Case report and literature review.

Khakbaz, Elham / Lang, Christian / Lelkaitis, Giedrius / Grønhøj, Christian

International journal of surgery case reports

2021 Volume 85, Page(s) 106241

Abstract: Silicone implants have been used for breast augmentations, both cosmetically and in reconstructive surgery since the 1960s. Rupture of breast implants and silicone migration is a well-known complication. In this case report and literature review, we ... ...

Abstract	Silicone implants have been used for breast augmentations, both cosmetically and in reconstructive surgery since the 1960s. Rupture of breast implants and silicone migration is a well-known complication. In this case report and literature review, we present a case of a 53-year-old woman with bilateral cosmetic silicone gel breast implant in 1986, and a replacement with saline gel in 2005. The patient had no breast complaints and observed no change in breast volume during this period. In 2020, silicone was randomly identified in a right-sided cervical lymph node in an attempt to remove suspicious lymphadenopathy. The source of the silicone is still doubted; that is, it is not known if the silicone originated from the saline implant or the silicone gel implant. In our literature review, we find that distant migration of silicone and lymphadenopathy have occurred for silicone breast implants although very rare for saline gel breast implants.
Language	English
Publishing date	2021-07-27
Publishing country	Netherlands
Document type	Journal Article
ISSN	2210-2612
ISSN	2210-2612
DOI	10.1016/j.ijscr.2021.106241
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Article ; Online: Potential of uPAR, αvβ6 Integrin, and Tissue Factor as Targets for Molecular Imaging of Oral Squamous Cell Carcinoma: Evaluation of Nine Targets in Primary Tumors and Metastases by Immunohistochemistry.

Lawaetz, Mads / Christensen, Anders / Juhl, Karina / Karnov, Kirstine / Lelkaitis, Giedrius / Kanstrup Fiehn, Anne-Marie / Kjaer, Andreas / von Buchwald, Christian

International journal of molecular sciences

2023 Volume 24, Issue 4

Abstract: No clinically approved tumor-specific imaging agents for head and neck cancer are currently available. The identification of biomarkers with a high and homogenous expression in tumor tissue and minimal expression in normal tissue is essential for the ... ...

Abstract	No clinically approved tumor-specific imaging agents for head and neck cancer are currently available. The identification of biomarkers with a high and homogenous expression in tumor tissue and minimal expression in normal tissue is essential for the development of new molecular imaging targets in head and neck cancer. We investigated the expression of nine imaging targets in both primary tumor and matched metastatic tissue of 41 patients with oral squamous cell carcinoma (OSCC) to assess their potential as targets for molecular imaging. The intensity, proportion, and homogeneity in the tumor and the reaction in neighboring non-cancerous tissue was scored. The intensity and proportion were multiplied to obtain a total immunohistochemical (IHC) score ranging from 0-12. The mean intensity in the tumor tissue and normal epithelium were compared. The expression rate was high for the urokinase-type plasminogen activator receptor (uPAR) (97%), integrin αvβ6 (97%), and tissue factor (86%) with a median total immunostaining score (interquartile range) for primary tumors of 6 (6-9), 12 (12-12), and 6 (2.5-7.5), respectively. For the uPAR and tissue factor, the mean staining intensity score was significantly higher in tumors compared to normal epithelium. The uPAR, integrin αvβ6, and tissue factor are promising imaging targets for OSCC primary tumors, lymph node metastases, and recurrences.
MeSH term(s)	Humans ; Immunohistochemistry ; Molecular Imaging ; Mouth Neoplasms/diagnostic imaging ; Receptors, Urokinase Plasminogen Activator/metabolism ; Squamous Cell Carcinoma of Head and Neck/diagnostic imaging ; Thromboplastin ; Urokinase-Type Plasminogen Activator/metabolism
Chemical Substances	integrin alphavbeta6 ; Receptors, Urokinase Plasminogen Activator ; Thromboplastin (9035-58-9) ; Urokinase-Type Plasminogen Activator (EC 3.4.21.73)
Language	English
Publishing date	2023-02-14
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24043853
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Article ; Online: Liquid Biopsies with Circulating Plasma HPV-DNA Measurements-A Clinically Applicable Surveillance Tool for Patients with HPV-Positive Oropharyngeal Cancer.

Jakobsen, Kathrine K / Bendtsen, Simone K / Pallisgaard, Niels / Friborg, Jeppe / Lelkaitis, Giedrius / Grønhøj, Christian / von Buchwald, Christian

Clinical cancer research : an official journal of the American Association for Cancer Research

2023 Volume 29, Issue 19, Page(s) 3914–3923

Abstract: Purpose: To evaluate the accuracy of cell-free human papillomavirus-DNA (cfHPV-DNA) measurements in liquid biopsies in predicting disease in patients with HPV-positive/p16-positive (HPV+/p16+) oropharyngeal squamous cell carcinoma (OPSCC).: ... ...

Abstract	Purpose: To evaluate the accuracy of cell-free human papillomavirus-DNA (cfHPV-DNA) measurements in liquid biopsies in predicting disease in patients with HPV-positive/p16-positive (HPV+/p16+) oropharyngeal squamous cell carcinoma (OPSCC). Experimental design: This was a prospective cohort study. Plasma samples were collected before treatment, serially after curative intended therapy at follow-up visits 2 weeks, and 6, 9, 12, 18, 24, and 30 months after treatment. A droplet digital PCR assay comprising eight HPV genotypes was used. HPV genotypes found in plasma and tumor tissue were compared. We correlated biopsy- or imaging-verified tumor progression to cfHPV-DNA in follow-up samples. Results: We enrolled 72 patients with HPV+/p16+ OPSCC. Baseline sensitivity for cfHPV-DNA detection was 97.2% (95% confidence interval, 90.3%-99.6%). CfHPV-DNA copy number/milliliter plasma correlated with tumor stage. We found a 100% concordance between HPV genotype in tumor tissue and plasma. Fifty-four patients were followed with serial blood samples for a median of 19.7 months (interquartile range, 13.5-25.5 months). Forty-one patients had undetectable plasma cfHPV-DNA in all follow-up samples, and none developed recurrences. Thirteen patients were classified as cfHPV-DNA-positive in a follow-up plasma sample. Of these, five patients developed a recurrence, and three had residual cancer. It was possible to detect cfHPV-DNA in plasma 97 to 166 days prior to the proven recurrence. Conclusions: To our knowledge, to date, our study, comprising the largest study of patients with HPV+/p16+ OPSCC, using an ultrasensitive multiplex HPV gene panel, revealed a high sensitivity of cfHPV-DNA detection in the liquid biopsies. We recommend serial plasma HPV samples for clinical monitoring of patients with HPV+/p16+ OPSCC.
MeSH term(s)	Humans ; Prospective Studies ; Papillomavirus Infections/complications ; Papillomavirus Infections/diagnosis ; Carcinoma, Squamous Cell/pathology ; Oropharyngeal Neoplasms/pathology ; Squamous Cell Carcinoma of Head and Neck ; Human Papillomavirus Viruses ; DNA, Viral/genetics ; Liquid Biopsy ; Head and Neck Neoplasms ; Cyclin-Dependent Kinase Inhibitor p16
Chemical Substances	DNA, Viral ; Cyclin-Dependent Kinase Inhibitor p16
Language	English
Publishing date	2023-07-21
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1225457-5
ISSN	1557-3265 ; 1078-0432
ISSN (online)	1557-3265
ISSN	1078-0432
DOI	10.1158/1078-0432.CCR-23-1064
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Zs.A 4223: Show issues

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Article ; Online: Urokinase-Type Plasminogen Activator Receptor (uPAR) Expression and [

Lawaetz, Mads / Binderup, Tina / Christensen, Anders / Juhl, Karina / Lelkaitis, Giedrius / Lykke, Eva / Knudsen, Line / von Buchwald, Christian / Kjaer, Andreas

Molecular imaging and biology

2023 Volume 25, Issue 6, Page(s) 1034–1044

Abstract: Purpose: [: Procedures: PDX flank tumor models were established by engrafting tumor tissue from three patients with locally advanced OSCC into immunodeficient mice. [: Results: Three PDX models were established, and all of them showed histological ...

Abstract	Purpose: [ Procedures: PDX flank tumor models were established by engrafting tumor tissue from three patients with locally advanced OSCC into immunodeficient mice. [ Results: Three PDX models were established, and all of them showed histological stability and unchanged heterogenicity, uPAR expression, and Ki67 expression through passages. A significant correlation between uPAR expression and tumor growth was found. All tumors of all models (n=29) showed tumor uptake of [ Conclusions: OSCC PDX models in early passages histologically mimic donor tumors and could serve as a valuable platform for the development of uPAR-targeted imaging and therapeutic modalities. Furthermore, [64Cu]Cu-uPAR-PET/CT showed target- and tumor-specific uptake in OSCC PDX models demonstrating the diagnostic potential of this modality for OSCC patients.
MeSH term(s)	Humans ; Mice ; Animals ; Positron Emission Tomography Computed Tomography ; Receptors, Urokinase Plasminogen Activator/metabolism ; Copper Radioisotopes ; Carcinoma, Squamous Cell/diagnostic imaging ; Squamous Cell Carcinoma of Head and Neck/diagnostic imaging ; Heterografts ; Mouth Neoplasms/diagnostic imaging ; Head and Neck Neoplasms
Chemical Substances	1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid (1HTE449DGZ) ; Receptors, Urokinase Plasminogen Activator ; Copper-64 ; Copper Radioisotopes
Language	English
Publishing date	2023-09-25
Publishing country	United States
Document type	Journal Article
ZDB-ID	2079160-4
ISSN	1860-2002 ; 1536-1632
ISSN (online)	1860-2002
ISSN	1536-1632
DOI	10.1007/s11307-023-01858-x
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Zs.A 6468: Show issues

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Article ; Online: Male breast cancer: clinicopathological characterization of a National Danish cohort 1980-2009.

Jylling, Anne Marie Bak / Jensen, Vibeke / Lelkaitis, Giedrius / Christiansen, Peer / Nielsen, Sarah Schulz / Lautrup, Marianne Djernes

Breast cancer (Tokyo, Japan)

2020 Volume 27, Issue 4, Page(s) 683–695

Abstract: Background: To describe relevant pathological parameters of Danish male breast cancer patients (MBCP) diagnosed from 1980 to 2009, and to relate these data to treatment, overall survival (OS) and standardized mortality rate (SMR).: Materials and ... ...

Abstract	Background: To describe relevant pathological parameters of Danish male breast cancer patients (MBCP) diagnosed from 1980 to 2009, and to relate these data to treatment, overall survival (OS) and standardized mortality rate (SMR). Materials and methods: The MBCP cohort was defined from national Danish registers. A total of 643 MBCP were identified with tissue available in 457. Among these, 384 were primary operable. Where tissue blocks were available, tumor type, grade, estrogen receptor (ER), progesteron receptor (PgR) and androgen-receptor (AR) status as well as HER 2 and Ki67 were performed. OS was quantified by Kaplan-Meier estimates and SMR was calculated based on mortality rate among patients relative to the mortality rate in the general population. Results: Male breast cancer was more often of ductal type, grade II and a very high proportion were ER and AR positive and HER2 negative. Intrinsic subtypes based on immunohistochemical evaluation showed luminal subtype. Ki67 ratio increased over period of study. OS declined by increased age, bigger tumor size, positive lymph node status, higher grade and Luminal B subtype. Hazard ratio and relative risk of SMR were highest for patients aged < 60 years. Conclusion: Male breast cancer is of luminal subtype, but more often Luminal B. Ki67 is crucial in evaluation of subtypes by immunohistochemistry, but have limitations. Subtyping seems to be of major importance. AR also can have a role in future treatment.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents, Alkylating/pharmacology ; Antineoplastic Agents, Alkylating/therapeutic use ; Biomarkers, Tumor/analysis ; Biomarkers, Tumor/antagonists & inhibitors ; Biomarkers, Tumor/metabolism ; Breast/pathology ; Breast/surgery ; Breast Neoplasms, Male/epidemiology ; Breast Neoplasms, Male/pathology ; Breast Neoplasms, Male/therapy ; Chemotherapy, Adjuvant/statistics & numerical data ; Denmark/epidemiology ; Follow-Up Studies ; Humans ; Kaplan-Meier Estimate ; Ki-67 Antigen/analysis ; Ki-67 Antigen/metabolism ; Male ; Mastectomy ; Middle Aged ; Neoplasm Grading ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Prognosis ; Radiotherapy, Adjuvant/statistics & numerical data ; Receptor, ErbB-2/analysis ; Receptor, ErbB-2/antagonists & inhibitors ; Receptor, ErbB-2/metabolism ; Receptors, Androgen/analysis ; Receptors, Androgen/metabolism ; Registries/statistics & numerical data ; Retrospective Studies ; Treatment Outcome
Chemical Substances	AR protein, human ; Antineoplastic Agents, Alkylating ; Biomarkers, Tumor ; Ki-67 Antigen ; MKI67 protein, human ; Receptors, Androgen ; ERBB2 protein, human (EC 2.7.10.1) ; Receptor, ErbB-2 (EC 2.7.10.1)
Language	English
Publishing date	2020-02-27
Publishing country	Japan
Document type	Journal Article
ZDB-ID	2052429-8
ISSN	1880-4233 ; 1340-6868
ISSN (online)	1880-4233
ISSN	1340-6868
DOI	10.1007/s12282-020-01066-3
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Zs.A 5536: Show issues

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Article: Diagnostic Value of Preoperative uPAR-PET/CT in Regional Lymph Node Staging of Oral and Oropharyngeal Squamous Cell Carcinoma: A Prospective Phase II Trial.

Lawaetz, Mads / Christensen, Anders / Juhl, Karina / Lelkaitis, Giedrius / Karnov, Kirstine / Carlsen, Esben Andreas / Charabi, Birgitte W / Loft, Annika / Czyzewska, Dorota / Buchwald, Christian von / Kjaer, Andreas

Diagnostics (Basel, Switzerland)

2023 Volume 13, Issue 21

Abstract: The detection of lymph node metastases is a major challenge in oral and oropharyngeal squamous cell carcinoma (OSCC and OPSCC). ...

Abstract	The detection of lymph node metastases is a major challenge in oral and oropharyngeal squamous cell carcinoma (OSCC and OPSCC).
Language	English
Publishing date	2023-10-25
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662336-5
ISSN	2075-4418
ISSN	2075-4418
DOI	10.3390/diagnostics13213303
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Article ; Online: Diagnostic accuracy of combined optical- and radio-guided SNB for neck staging of oral squamous cell carcinoma lesions in the anterior oral cavity.

Christensen, Anders / Wessel, Irene / Charabi, Birgitte Wittenborg / Juhl, Karina / Kiss, Katalin / Lelkaitis, Giedrius / Mortensen, Jann / Kjaer, Andreas / von Buchwald, Christian / Tvedskov, Jesper Filtenborg

European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery

2023 Volume 280, Issue 7, Page(s) 3393–3403

Abstract: Purpose: The purpose was to investigate the diagnostic performance of bimodal optical and radio-guided sentinel node biopsy (SNB) for oral squamous cell carcinoma (OSCC) sub-sites in the anterior oral cavity.: Methods: Prospective study of 50 ... ...

Abstract	Purpose: The purpose was to investigate the diagnostic performance of bimodal optical and radio-guided sentinel node biopsy (SNB) for oral squamous cell carcinoma (OSCC) sub-sites in the anterior oral cavity. Methods: Prospective study of 50 consecutive patients with cN0 OSCC scheduled for SNB was injected with the tracer complex Tc99m:ICG:Nacocoll. A near-infrared camera was applied for optical SN detection. Endpoints were modality for intraoperative SN detection and false omission rate at follow-up. Results: In all patients, a SN could be detected. In 12/50 (24%) of cases, the SPECT/CT showed no focus in level 1, but intraoperatively a SN in level 1 was optically detected. In 22/50 cases (44%), an additional SN was identified only due to the optical imaging. At follow-up, the false omission rate was 0%. Conclusion: Optical imaging appears to be an effective tool to allow real-time SN identification comprising level 1 unaffected by possible interference of radiation site from the injection.
MeSH term(s)	Humans ; Carcinoma, Squamous Cell/diagnostic imaging ; Carcinoma, Squamous Cell/surgery ; Carcinoma, Squamous Cell/pathology ; Squamous Cell Carcinoma of Head and Neck/pathology ; Mouth Neoplasms/pathology ; Prospective Studies ; Sentinel Lymph Node Biopsy/methods ; Head and Neck Neoplasms/pathology ; Neoplasm Staging
Language	English
Publishing date	2023-04-03
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1017359-6
ISSN	1434-4726 ; 0937-4477
ISSN (online)	1434-4726
ISSN	0937-4477
DOI	10.1007/s00405-023-07939-5
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