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Wärnberg, Fredrik
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Publications (10 of 60) Show all publications
Hersi, A.-F., Eriksson, S., Ramos, J., Abdsaleh, S., Wärnberg, F. & Karakatsanis, A. (2019). A combined, totally magnetic technique with a magnetic marker for non-palpable tumour localization and superparamagnetic iron oxide nanoparticles for sentinel lymph node detection in breast cancer surgery. European Journal of Surgical Oncology, 45(4), 544-549
Open this publication in new window or tab >>A combined, totally magnetic technique with a magnetic marker for non-palpable tumour localization and superparamagnetic iron oxide nanoparticles for sentinel lymph node detection in breast cancer surgery
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2019 (English)In: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 45, no 4, p. 544-549Article in journal (Refereed) Published
Abstract [en]

Background: Surgery for non-palpable breast cancer may often be a challenging procedure. Recently, a magnetic seed (Magseed®) used for tumour localization has been developed. Superparamagnetic iron oxide nanoparticles (SPIO) for sentinel lymph node (SN) detection is a novel tracer that may be injected up to four weeks preoperatively. This study is the first combining the magnetic seed and SPIO.

Material and methods: Patients planned for breast conserving surgery and SN-biopsy (SNB) were recruited from two units in Sweden. Patients underwent lesion localization with Magseed® and SPIO injection (Magtrace™) by the breast radiologist in the preoperative period. Feasibility of successful lesion localization and excision together with a successful SNB detection was evaluated. Seed migration, number of SNs, specimen volume and calculated resection ratio (CRR) were reported.A survey of the physicians’ experience was conducted.

Results: Localization was performed at a median of three days before surgery (range 0–25). All 32 patients underwent microscopically radical resection with a CRR of 1.49. No seed migration was noticed. SNB was successful in all patients. A median of two SNs was retrieved. Radiologists and surgeons reported the procedure easy to learn and outperformed guidewire localization in terms of localization and excision time. They thought the technique facilitated planning localization and surgery.

Conclusions: The combined magnetic technique provided accuracy in tumour localization and SN detection without excess tissue excision and with promising results for flexibility in delivery of care. Larger studies are needed to confirm these findings.

Keywords
Breast cancer, Sentinel node biopsy, Occult lesion localization, Superparamagnetic iron oxide nanoparticles, Magnetic seed marker, Breast conserving surgery
National Category
Surgery
Identifiers
urn:nbn:se:uu:diva-382650 (URN)10.1016/j.ejso.2018.10.064 (DOI)000464086700007 ()30401506 (PubMedID)
Available from: 2019-04-29 Created: 2019-04-29 Last updated: 2019-04-29Bibliographically approved
Vallon-Christersson, J., Häkkinen, J., Hegardt, C., Saal, L. H., Larsson, C., Ehinger, A., . . . Staaf, J. (2019). Cross comparison and prognostic assessment of breast cancer multigene signatures in a large population-based contemporary clinical series. Scientific Reports, 9, Article ID 12184.
Open this publication in new window or tab >>Cross comparison and prognostic assessment of breast cancer multigene signatures in a large population-based contemporary clinical series
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2019 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 12184Article in journal (Refereed) Published
Abstract [en]

Multigene expression signatures provide a molecular subdivision of early breast cancer associated with patient outcome. A gap remains in the validation of such signatures in clinical treatment groups of patients within population-based cohorts of unselected primary breast cancer representing contemporary disease stages and current treatments. A cohort of 3520 resectable breast cancers with RNA sequencing data included in the population-based SCAN-B initiative (ClinicalTrials.gov ID NCT02306096) were selected from a healthcare background population of 8587 patients diagnosed within the years 2010-2015. RNA profiles were classified according to 19 reported gene signatures including both gene expression subtypes (e.g. PAM50, IC10, CIT) and risk predictors (e.g. Oncotype DX, 70-gene, ROR). Classifications were analyzed in nine adjuvant clinical assessment groups: TNBC-ACT (adjuvant chemotherapy, n = 239), TNBC-untreated (n = 82), HER2+/ER- with anti-HER2+ACT treatment (n = 110), HER2+/ER+ with anti-HER2 + ACT + endocrine treatment (n = 239), ER+/HER2-/LN- with endocrine treatment (n = 1113), ER+/HER2-/LN- with endocrine +ACT treatment (n = 243), ER+/HER2-/LN+ with endocrine treatment (n = 423), ER+/HER2-/LN+ with endocrine +ACT treatment (n = 433), and ER+/HER2-/LN- untreated (n = 200). Gene signature classification (e.g., proportion low-, high-risk) was generally well aligned with stratification based on current immunohistochemistry-based clinical practice. Most signatures did not provide any further risk stratification in TNBC and HER2+/ER- disease. Risk classifier agreement (low-, medium/intermediate-, high-risk groups) in ER+ assessment groups was on average 50-60% with occasional pair-wise comparisons having <30% agreement. Disregarding the intermediate-risk groups, the exact agreement between low- and high-risk groups was on average similar to 80-95%, for risk prediction signatures across all assessment groups. Outcome analyses were restricted to assessment groups of TNBC-ACT and endocrine treated ER+/HER2-/LN- and ER+/HER2-/LN+ cases. For ER+/HER2- disease, gene signatures appear to contribute additional prognostic value even at a relatively short follow-up time. Less apparent prognostic value was observed in the other groups for the tested signatures. The current study supports the usage of gene expression signatures in specific clinical treatment group within population-based breast cancer. It also stresses the need of further development to reach higher consensus in individual patient classifications, especially for intermediate-risk patients, and the targeting of patients where current gene signatures and prognostic variables provide little support in clinical decision-making.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP, 2019
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-393727 (URN)10.1038/s41598-019-48570-x (DOI)000481999500038 ()31434940 (PubMedID)
Funder
Swedish Research CouncilSwedish Cancer Society, CAN 2018/685The Crafoord FoundationBioCARE - Biomarkers in Cancer Medicine Improving Health Care Education and InnovationKing Gustaf V Jubilee Fund
Available from: 2019-09-30 Created: 2019-09-30 Last updated: 2019-09-30Bibliographically approved
Karakatsanis, A., Hersi, A.-F., Pistiolis, L., Bagge, R. O., Lykoudis, P. M., Eriksson, S., . . . Stålberg, P. (2019). Effect of preoperative injection of superparamagnetic iron oxide particles on rates of sentinel lymph node dissection in women undergoing surgery for ductal carcinoma in situ (SentiNot study). British Journal of Surgery, 106(6), 720-728
Open this publication in new window or tab >>Effect of preoperative injection of superparamagnetic iron oxide particles on rates of sentinel lymph node dissection in women undergoing surgery for ductal carcinoma in situ (SentiNot study)
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2019 (English)In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 106, no 6, p. 720-728Article in journal (Refereed) Published
Abstract [en]

Background: One-fifth of patients with a preoperative diagnosis of ductal carcinoma in situ (DCIS) have invasive breast cancer (IBC) on definitive histology. Sentinel lymph node dissection (SLND) is performed in almost half of women having surgery for DCIS in Sweden. The aim of the present study was to try to minimize unnecessary SLND by injecting superparamagnetic iron oxide (SPIO) nanoparticles at the time of primary breast surgery, enabling SLND to be performed later, if IBC is found in the primary specimen.

Methods: Women with DCIS at high risk for the presence of invasion undergoing breast conservation, and patients with DCIS undergoing mastectomy were included. The primary outcome was whether this technique could reduce SLND. Secondary outcomes were number of SLNDs avoided, detection rate and procedure-related costs.

Results: This was a preplanned interim analysis of 189 procedures. IBC was found in 47 and a secondary SLND was performed in 41 women. Thus, 78.3 per cent of patients avoided SLND (P<0.001). At reoperation, SPIO plus blue dye outperformed isotope and blue dye in detection of the sentinel node (40 of 40 versus 26 of 40 women; P<0.001). Costs were reduced by a mean of 24.5 per cent in women without IBC (3990 versus 5286; P<0.001).

Conclusion: Marking the sentinel node with SPIO in women having surgery for DCIS was effective at avoiding unnecessary SLND in this study. Registration number: ISRCTN18430240 (http://www.isrctn.com).

Place, publisher, year, edition, pages
WILEY, 2019
National Category
Surgery
Identifiers
urn:nbn:se:uu:diva-383156 (URN)10.1002/bjs.11110 (DOI)000465082200009 ()30839104 (PubMedID)
Funder
The Breast Cancer Foundation
Available from: 2019-05-10 Created: 2019-05-10 Last updated: 2019-05-10Bibliographically approved
Strell, C., Paulsson, J., Jin, S.-B., Tobin, N. P., Mezheyeuski, A., Roswall, P., . . . Ostman, A. (2019). Impact of Epithelial-Stromal Interactions on Peritumoral Fibroblasts in Ductal Carcinoma in Situ. Journal of the National Cancer Institute, 111(9), 983-995, Article ID djy234.
Open this publication in new window or tab >>Impact of Epithelial-Stromal Interactions on Peritumoral Fibroblasts in Ductal Carcinoma in Situ
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2019 (English)In: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105, Vol. 111, no 9, p. 983-995, article id djy234Article in journal (Refereed) Published
Abstract [en]

Background: A better definition of biomarkers and biological processes related to local recurrence and disease progression is highly warranted for ductal breast carcinoma in situ (DCIS). Stromal-epithelial interactions are likely of major importance for the biological, clinical, and pathological distinctions between high- and low-risk DCIS cases. Methods: Stromal platelet derived growth factor receptor (PDGFR) was immunohistochemically assessed in two DCIS patient cohorts (n = 458 and n = 80). Cox proportional hazards models were used to calculate the hazard ratios of recurrence. The molecular mechanisms regulating stromal PDGFR expression were investigated in experimental in vitro co-culture systems of DCIS cells and fibroblasts and analyzed using immunoblot and quantitative real-time PCR. Knock-out of JAG1 in DCIS cells and NOTCH2 in fibroblasts was obtained through CRISPR/Cas9. Experimental data were validated by mammary fat pad injection of DCIS and DCIS-JAG1 knock-out cells (10 mice per group). All statistical tests were two-sided. Results: PDGFR alpha((low))/PDGFR beta((high)) fibroblasts were associated with increased risk for recurrence in DCIS (univariate hazard ratio = 1.59, 95% confidence interval [CI] = 1.02 to 2.46; P = .04 Wald test; multivariable hazard ratio = 1.78, 95% CI = 1.07 to 2.97; P = .03). Tissue culture and mouse model studies indicated that this fibroblast phenotype is induced by DCIS cells in a cell contact-dependent manner. Epithelial Jagged1 and fibroblast Notch2 were identified through loss-of-function studies as key juxtacrine signaling components driving the formation of the poor prognosis-associated fibroblast phenotype. Conclusions: A PDGFR alpha((low))/PDGFR beta((high)) fibroblast subset was identified as a marker for high-risk DCIS. The Jagged-1/Notch2/PDGFR stroma-epithelial pathway was described as a novel signaling mechanism regulating this poor prognosis-associated fibroblast subset. In general terms, the study highlights epithelial-stromal crosstalk in DCIS and contributes to ongoing efforts to define clinically relevant fibroblast subsets and their etiology.

National Category
Cancer and Oncology Cell and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-397124 (URN)10.1093/jnci/djy234 (DOI)000493067400014 ()30816935 (PubMedID)
Funder
Swedish Cancer Society, 150895Swedish Research Council, Diarienr 349-2006-160The Cancer Research Funds of Radiumhemmet
Available from: 2019-11-29 Created: 2019-11-29 Last updated: 2019-11-29Bibliographically approved
Wärnberg, F., Stigberg, E., Obondo, C., Olofsson, H., Abdsaleh, S., Wärnberg, M. & Karakatsanis, A. (2019). Long-Term Outcome After Retro-Areolar Versus Peri-Tumoral Injection of Superparamagnetic Iron Oxide Nanoparticles (SPIO) for Sentinel Lymph Node Detection in Breast Cancer Surgery.. Annals of Surgical Oncology, 26(5), 1247-1253
Open this publication in new window or tab >>Long-Term Outcome After Retro-Areolar Versus Peri-Tumoral Injection of Superparamagnetic Iron Oxide Nanoparticles (SPIO) for Sentinel Lymph Node Detection in Breast Cancer Surgery.
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2019 (English)In: Annals of Surgical Oncology, ISSN 1068-9265, E-ISSN 1534-4681, Vol. 26, no 5, p. 1247-1253Article in journal (Refereed) Published
Abstract [en]

BACKGROUND/OBJECTIVE: SPIO is effective in sentinel node (SN) detection. No nuclear medicine department is needed, and no allergic reactions have occurred. This study aimed to compare retro-areolar and peri-tumoral SPIO injections regarding skin staining, detection rates and number of SNs.

METHODS: Data on staining size, intensity and cosmetic outcome (0-5; 0 = no problem) were collected by telephone interviews with 258 women undergoing breast conservation. SN detection and the number of SNs were prospectively registered in 332 women.

RESULTS: After retro-areolar and peri-tumoral injections, 67.3% and 37.8% (p < 0.001) developed skin staining, with remaining staining in 46.2 vs. 9.4% after 36 months (p < 0.001). Initial mean size was 16.3 vs. 6.8 cm (p < 0.001) and after 36 months, 6.6 vs. 1.8 cm2 (p < 0.001). At 75.1% of 738 interviews, staining was reported paler. After retro-areolar injections, cosmetic outcome scored worse for 2 years. The mean (median) scores were 1.3(0) vs. 0.5(0) points, and 0.2(0) vs. 0.1(0) points, at 12 and 36 months, respectively. Overall detection rates were 98.3% and 97.4% (p = 0.43) and the number of SNs 1.35 vs. 1.57 (p = 0.02) after retro-areolar and peri-tumoral injections. Injection, regardless of type, 1-27 days before surgery increased detection rates with SPIO, 98.0% vs. 94.2% (p = 0.06) ,and SN numbers, 1.56 vs. 1.27 (p = 0.003).

CONCLUSION: SPIO is effective and facilitates planning for surgery. Peri-tumoral injection reduced staining with a similar detection rate. Staining was not considered a cosmetic problem among most women. Injecting SPIO 1-27 days before surgery increased the detection rate by 3.8% and increased the number of SNs by 0.3.

National Category
Clinical Laboratory Medicine
Research subject
Pathology
Identifiers
urn:nbn:se:uu:diva-380893 (URN)10.1245/s10434-019-07239-5 (DOI)000464726300019 ()30830536 (PubMedID)
Available from: 2019-04-02 Created: 2019-04-02 Last updated: 2019-05-09Bibliographically approved
Bremer, T., Whitworth, P. W., Patel, R., Savala, J., Barry, T., Lyle, S., . . . Wärnberg, F. (2018). A Biological Signature for Breast Ductal Carcinoma In Situ to Predict Radiotherapy Benefit and Assess Recurrence Risk. Clinical Cancer Research, 24(23), 5895-5901
Open this publication in new window or tab >>A Biological Signature for Breast Ductal Carcinoma In Situ to Predict Radiotherapy Benefit and Assess Recurrence Risk
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2018 (English)In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 24, no 23, p. 5895-5901Article in journal (Refereed) Published
Abstract [en]

Purpose: Ductal carcinoma in situ (DCIS) patients and their physicians currently face challenging treatment decisions with limited information about the individual's subsequent breast cancer risk or treatment benefit. The DCI-SionRT biological signature developed in this study provides recurrence risk and predicts radiotherapy (RT) benefit for DCIS patients following breast-conserving surgery (BCS). Experimental Design: A biological signature that calculates an individualized Decision Score (DS) was developed and cross-validated in 526 DCIS patients treated with BCS = RT. The relationship was assessed between DS and 10-year risk of invasive breast cancer (IBC) or any ipsilateral breast event (IBE), including IBC or DCIS. RT benefit was evaluated by risk group and as a function of DS. Results: The DS was significantly associated with IBC and IBE risk, HR (per 5 units) of 4.2 and 3.1, respectively. For patients treated without RT, DS identified a Low Group with 10-year IBC risk of 4% (7% IBE) and an Elevated Risk Group with IBC risk of 15% (23% IBE). In analysis of DS and RT by group, the Elevated Risk Group received significant RT benefit, HR of 0.3 for IBC and IBE. In a clinicopathologically low-risk subset, DS reclassified 42% of patients into the Elevated Risk Group. In an interaction analysis of DS and RT, patients with elevated DS had significant RT benefit over baseline. Conclusions: The DS was prognostic for risk and predicted RT benefit for DCIS patients. DS identified a clinically meaningful low-risk group and a group with elevated 10-year risks that received substantial RT benefit over baseline.

National Category
Cancer and Oncology Clinical Laboratory Medicine
Research subject
Pathology
Identifiers
urn:nbn:se:uu:diva-372771 (URN)10.1158/1078-0432.CCR-18-0842 (DOI)000452374700013 ()30054280 (PubMedID)
Available from: 2019-01-14 Created: 2019-01-14 Last updated: 2019-03-29Bibliographically approved
Wärnberg, F., Garmo, H., Folkvaljon, Y., Holmberg, L., Karlsson, P., Sandelin, K., . . . Bremer, T. (2018). Abstract GS5-08: A validation of DCIS biological risk profile in a randomised study for radiation therapy with 20 year follow-up (SweDCIS). Paper presented at San Antonio Breast Cancer Symposium, DEC 05-09, 2017, San Antonio, TX. Cancer Research, 78(4)
Open this publication in new window or tab >>Abstract GS5-08: A validation of DCIS biological risk profile in a randomised study for radiation therapy with 20 year follow-up (SweDCIS)
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2018 (English)In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 78, no 4Article in journal, Meeting abstract (Other academic) Published
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-351602 (URN)10.1158/1538-7445.SABCS17-GS5-08 (DOI)000425489400036 ()
Conference
San Antonio Breast Cancer Symposium, DEC 05-09, 2017, San Antonio, TX
Note

Wos title: A validation of DCIS biological risk profile in a randomised study for radiation therapy with 20 year follow-up (SweDCIS)

Supplement: S

Meeting Abstract: GS5-08

Available from: 2018-05-29 Created: 2018-05-29 Last updated: 2018-09-12Bibliographically approved
Wärnberg, M., Karakatsanis, A., Abdsaleh, S. & Wärnberg, F. (2018). Abstract P3-01-11: Discoloration after injection of super paramagnetic iron oxide (SPIO) for sentinel node biopsy. A long term qualitative follow-up study. Paper presented at San Antonio Breast Cancer Symposium, DEC 05-09, 2017, San Antonio, TX. Cancer Research, 78(4)
Open this publication in new window or tab >>Abstract P3-01-11: Discoloration after injection of super paramagnetic iron oxide (SPIO) for sentinel node biopsy. A long term qualitative follow-up study
2018 (English)In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 78, no 4Article in journal, Meeting abstract (Other academic) Published
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-351603 (URN)10.1158/1538-7445.SABCS17-P3-01-11 (DOI)000425489400340 ()
Conference
San Antonio Breast Cancer Symposium, DEC 05-09, 2017, San Antonio, TX
Note

Wos title: Discoloration after injection of super paramagnetic iron oxide (SPIO) for sentinel node biopsy. A long term qualitative follow-up study

Available from: 2018-05-29 Created: 2018-05-29 Last updated: 2018-05-29Bibliographically approved
Wadsten, C., Wärnberg, F., Tolockiene, E., Hartman, J., Fredriksson, I., Garmo, H. & Sund, M. (2018). Biomarkers in DCIS associated with breast cancer death. Paper presented at 11th European Breast Cancer Conference (EBCC), MAR 21-23, 2018, Barcelona, SPAIN. European Journal of Cancer, 92, S67-S68
Open this publication in new window or tab >>Biomarkers in DCIS associated with breast cancer death
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2018 (English)In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 92, p. S67-S68Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
ELSEVIER SCI LTD, 2018
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-357180 (URN)000429103100169 ()
Conference
11th European Breast Cancer Conference (EBCC), MAR 21-23, 2018, Barcelona, SPAIN
Available from: 2018-08-14 Created: 2018-08-14 Last updated: 2018-08-14Bibliographically approved
Sun, Y., Xu, Z., Strell, C., Moro, C. F., Wärnberg, F., Dong, L. & Zhang, Q. (2018). Detection of Breast Tumour Tissue Regions in Histopathological Images using Convolutional Neural Networks. In: 2018 IEEE International Conference on Image Processing, Applications and Systems (IPAS): . Paper presented at 3rd IEEE International Conference on Image Processing, Applications and Systems (IPAS), Inria Sophia Antipolis, France, December 12-14, 2018 (pp. 98-103). IEEE
Open this publication in new window or tab >>Detection of Breast Tumour Tissue Regions in Histopathological Images using Convolutional Neural Networks
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2018 (English)In: 2018 IEEE International Conference on Image Processing, Applications and Systems (IPAS), IEEE, 2018, p. 98-103Conference paper, Published paper (Refereed)
Abstract [en]

Ductal carcinoma in situ (DCIS) is considered a pre-invasive breast cancer and sometimes it can develop into an invasive ductal carcinoma. The analysis of histopathological images to detect tumour border of DCIS could provide important information for better diagnosis of patients. We present a deep learning based system to automatically identify DCIS in histopathological images. Specifically, a convolutional neural network (CNN) is first trained to predict labels of small patches cropped out of a histopathological whole slide image. Next, a sliding window method is used to produce a probability map of DCIS. Finally, given the probability map, a tumor border of DCIS is produced and delineated with the method of Marching Cubes to facilitate pathologists' review and assessment. Evaluation of cross validation demonstrates that the CNN model of GoogleNet performs well in histology image patch classification with an overall accuracy of (98.46 +/- 0.40)% and identifies the DCIS tissue patches with a Fl-score of (97.40 +/- 1.18)% (mean +/- variance). Moreover, around 95.6% tumour tissue within the enclosed tumour regions can be identified by our developed method. Finally, the goal of tumor border detection can be well achieved with a few post-processing steps.

Place, publisher, year, edition, pages
IEEE, 2018
Keywords
Histopathological Images Analysis, Convolutional Neural Network, Tumour Border Detection, Ductal Carcinoma in Situ (DCIS)
National Category
Medical Image Processing Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-390019 (URN)10.1109/IPAS.2018.8708869 (DOI)000471844500017 ()978-1-7281-0247-4 (ISBN)
Conference
3rd IEEE International Conference on Image Processing, Applications and Systems (IPAS), Inria Sophia Antipolis, France, December 12-14, 2018
Available from: 2019-08-02 Created: 2019-08-02 Last updated: 2019-08-02Bibliographically approved
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