Loading…
Contribution of immunophenotype to the investigation and differential diagnosis of Burkitt lymphoma, double‐hit high‐grade B‐cell lymphoma, and single‐hit MYC‐rearranged diffuse large B‐cell lymphoma
Background There are no immunophenotypic guidelines for the investigation of MYC‐rearranged lymphomas. We aimed to identify simple immunophenotypic features that would help to differentiate between MYC‐rearranged lymphomas and guide cytogenetic analysis. Methods We reviewed diagnostic samples from p...
Saved in:
Published in: | Cytometry. Part B, Clinical cytometry Clinical cytometry, 2020-09, Vol.98 (5), p.412-420 |
---|---|
Main Authors: | , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
cited_by | cdi_FETCH-LOGICAL-c4457-c25d80edff7a316d34f657af559545f62e94fe5a112ba7d16595d877648152ae3 |
---|---|
cites | cdi_FETCH-LOGICAL-c4457-c25d80edff7a316d34f657af559545f62e94fe5a112ba7d16595d877648152ae3 |
container_end_page | 420 |
container_issue | 5 |
container_start_page | 412 |
container_title | Cytometry. Part B, Clinical cytometry |
container_volume | 98 |
creator | Tsagarakis, Nikolaos J. Papadhimitriou, Stefanos I. Pavlidis, Dimitris Liapis, Konstantinos Gortzolidis, Georgios Kostopoulos, Ioannis V. Marinakis, Theodoros Paterakis, Georgios |
description | Background
There are no immunophenotypic guidelines for the investigation of MYC‐rearranged lymphomas. We aimed to identify simple immunophenotypic features that would help to differentiate between MYC‐rearranged lymphomas and guide cytogenetic analysis.
Methods
We reviewed diagnostic samples from patients diagnosed with Burkitt lymphoma (BL), double‐hit lymphoma (DHL), MYC‐rearranged diffuse large B‐cell lymphoma (MYC‐DLBCL), and standard (non‐MYC‐rearranged) DLBCL over the last decade in our Institution. Using flow cytometry (with antibodies CD20, CD10, CD38, bcl‐2, Ki‐67, FMC‐7, CD43, CD27, CD79b, CD23, and CD22) we determined antigen% expression and median‐fluorescence intensity ratios (MFIR). The forward scatter (FS) and side scatter (SS) characteristics of tumor B‐cells were compared with normal T‐cells (B/T ratios) for patients with MYC‐rearranged lymphomas.
Results
We identified 51 patients of whom 14 had BL, 10 had DHL (6 MYC+/BCL2+; 4 MYC+/BCL6+), 8 MYC‐DLBCL, and 19 standard DLBCL. The significant differences (p 90, CD10% > 80, CD10MFIR > 10, bcl‐2% 70 was characteristic of BL. “Deviation” from these cut‐offs should raise suspicion for DHL and, therefore, BCL2 and/or BCL6 FISH is required. We also found that a diagnosis of DHL rather than of MYC‐DLBCL was significantly associated with CD10% > 60, Ki‐67% > 50, and SS (B/T) |
doi_str_mv | 10.1002/cyto.b.21887 |
format | article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2410350578</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2410350578</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4457-c25d80edff7a316d34f657af559545f62e94fe5a112ba7d16595d877648152ae3</originalsourceid><addsrcrecordid>eNp9kUFu1TAQhiMEEqWw4wCW2LDoe8SOHSdLXgQFqVU3ZdGV5STjxCWxg-0UZccRejduwElwGlRVqOpq_rG--T2aP0ne4nSP05R8aJZg9_We4KLgz5IjzBjZ0ZLx5_eali-TV95fp2nGaM6Pkt-VNcHpeg7aGmQV0uM4Gzv1YGxYJkDBotAD0uYGfNCdvOOkaVGrlQIHJmg5xEZ2xnrtV4vD7L7rENCwjFNvR3mCWjvXA_z5ddvrgHrd9VF2TraADlE1MAwP4NXca9PdD5xfVVE5kM5J08H29ewBDdJ1j1i8Tl4oOXh4868eJ98-f7qsvuzOLk6_Vh_Pdg2ljO8awtoihVYpLjOctxlVOeNSMVYyylROoKQKmMSY1JK3OI_vbcF5TgvMiITsOHm_-U7O_pjjecSo_bqJNGBnLwjF8cwp40VE3_2HXtvZmbhdpChNS4IzGqmTjWqc9d6BEpPTo3SLwKlYExZrwqIWdwlHnG74Tz3A8iQrqqvLi8M29hf8vrVF</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2444092134</pqid></control><display><type>article</type><title>Contribution of immunophenotype to the investigation and differential diagnosis of Burkitt lymphoma, double‐hit high‐grade B‐cell lymphoma, and single‐hit MYC‐rearranged diffuse large B‐cell lymphoma</title><source>Wiley-Blackwell Read & Publish Collection</source><creator>Tsagarakis, Nikolaos J. ; Papadhimitriou, Stefanos I. ; Pavlidis, Dimitris ; Liapis, Konstantinos ; Gortzolidis, Georgios ; Kostopoulos, Ioannis V. ; Marinakis, Theodoros ; Paterakis, Georgios</creator><creatorcontrib>Tsagarakis, Nikolaos J. ; Papadhimitriou, Stefanos I. ; Pavlidis, Dimitris ; Liapis, Konstantinos ; Gortzolidis, Georgios ; Kostopoulos, Ioannis V. ; Marinakis, Theodoros ; Paterakis, Georgios</creatorcontrib><description>Background
There are no immunophenotypic guidelines for the investigation of MYC‐rearranged lymphomas. We aimed to identify simple immunophenotypic features that would help to differentiate between MYC‐rearranged lymphomas and guide cytogenetic analysis.
Methods
We reviewed diagnostic samples from patients diagnosed with Burkitt lymphoma (BL), double‐hit lymphoma (DHL), MYC‐rearranged diffuse large B‐cell lymphoma (MYC‐DLBCL), and standard (non‐MYC‐rearranged) DLBCL over the last decade in our Institution. Using flow cytometry (with antibodies CD20, CD10, CD38, bcl‐2, Ki‐67, FMC‐7, CD43, CD27, CD79b, CD23, and CD22) we determined antigen% expression and median‐fluorescence intensity ratios (MFIR). The forward scatter (FS) and side scatter (SS) characteristics of tumor B‐cells were compared with normal T‐cells (B/T ratios) for patients with MYC‐rearranged lymphomas.
Results
We identified 51 patients of whom 14 had BL, 10 had DHL (6 MYC+/BCL2+; 4 MYC+/BCL6+), 8 MYC‐DLBCL, and 19 standard DLBCL. The significant differences (p <.05) were: higher CD38% in BL than standard DLBCL; higher CD10% in BL and DHL versus MYC‐DLBCL and standard DLBCL; higher CD10MFIR in BL than MYC‐DLBCL and standard DLBCL; higher Ki‐67% in BL than DHL and MYC‐DLBCL; higher bcl‐2% in DHL than BL; higher FMC‐7% in BL than MYC‐DLBCL and standard DLBCL; and lower SS (B/T) ratio in DHL than MYC‐DLBCL.
Conclusions
The combination of CD38% > 90, CD10% > 80, CD10MFIR > 10, bcl‐2% < 30, and Ki‐67% > 70 was characteristic of BL. “Deviation” from these cut‐offs should raise suspicion for DHL and, therefore, BCL2 and/or BCL6 FISH is required. We also found that a diagnosis of DHL rather than of MYC‐DLBCL was significantly associated with CD10% > 60, Ki‐67% > 50, and SS (B/T) <1.5.</description><identifier>ISSN: 1552-4949</identifier><identifier>EISSN: 1552-4957</identifier><identifier>DOI: 10.1002/cyto.b.21887</identifier><language>eng</language><publisher>Hoboken, USA: John Wiley & Sons, Inc</publisher><subject>Antibodies ; Antigens ; Bcl-6 protein ; Burkitt lymphoma ; Burkitt's lymphoma ; CD20 antigen ; CD22 antigen ; CD23 antigen ; CD27 antigen ; CD38 antigen ; CD43 antigen ; Cytogenetics ; Diagnosis ; Diagnostic systems ; Differential diagnosis ; DLBCL ; double‐hit lymphoma ; Flow cytometry ; Fluorescence ; Fluorescence in situ hybridization ; immunophenotype ; Lymphoma ; Myc protein ; MYC rearrangement ; Scattering</subject><ispartof>Cytometry. Part B, Clinical cytometry, 2020-09, Vol.98 (5), p.412-420</ispartof><rights>2020 International Clinical Cytometry Society</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4457-c25d80edff7a316d34f657af559545f62e94fe5a112ba7d16595d877648152ae3</citedby><cites>FETCH-LOGICAL-c4457-c25d80edff7a316d34f657af559545f62e94fe5a112ba7d16595d877648152ae3</cites><orcidid>0000-0002-9759-0048</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids></links><search><creatorcontrib>Tsagarakis, Nikolaos J.</creatorcontrib><creatorcontrib>Papadhimitriou, Stefanos I.</creatorcontrib><creatorcontrib>Pavlidis, Dimitris</creatorcontrib><creatorcontrib>Liapis, Konstantinos</creatorcontrib><creatorcontrib>Gortzolidis, Georgios</creatorcontrib><creatorcontrib>Kostopoulos, Ioannis V.</creatorcontrib><creatorcontrib>Marinakis, Theodoros</creatorcontrib><creatorcontrib>Paterakis, Georgios</creatorcontrib><title>Contribution of immunophenotype to the investigation and differential diagnosis of Burkitt lymphoma, double‐hit high‐grade B‐cell lymphoma, and single‐hit MYC‐rearranged diffuse large B‐cell lymphoma</title><title>Cytometry. Part B, Clinical cytometry</title><description>Background
There are no immunophenotypic guidelines for the investigation of MYC‐rearranged lymphomas. We aimed to identify simple immunophenotypic features that would help to differentiate between MYC‐rearranged lymphomas and guide cytogenetic analysis.
Methods
We reviewed diagnostic samples from patients diagnosed with Burkitt lymphoma (BL), double‐hit lymphoma (DHL), MYC‐rearranged diffuse large B‐cell lymphoma (MYC‐DLBCL), and standard (non‐MYC‐rearranged) DLBCL over the last decade in our Institution. Using flow cytometry (with antibodies CD20, CD10, CD38, bcl‐2, Ki‐67, FMC‐7, CD43, CD27, CD79b, CD23, and CD22) we determined antigen% expression and median‐fluorescence intensity ratios (MFIR). The forward scatter (FS) and side scatter (SS) characteristics of tumor B‐cells were compared with normal T‐cells (B/T ratios) for patients with MYC‐rearranged lymphomas.
Results
We identified 51 patients of whom 14 had BL, 10 had DHL (6 MYC+/BCL2+; 4 MYC+/BCL6+), 8 MYC‐DLBCL, and 19 standard DLBCL. The significant differences (p <.05) were: higher CD38% in BL than standard DLBCL; higher CD10% in BL and DHL versus MYC‐DLBCL and standard DLBCL; higher CD10MFIR in BL than MYC‐DLBCL and standard DLBCL; higher Ki‐67% in BL than DHL and MYC‐DLBCL; higher bcl‐2% in DHL than BL; higher FMC‐7% in BL than MYC‐DLBCL and standard DLBCL; and lower SS (B/T) ratio in DHL than MYC‐DLBCL.
Conclusions
The combination of CD38% > 90, CD10% > 80, CD10MFIR > 10, bcl‐2% < 30, and Ki‐67% > 70 was characteristic of BL. “Deviation” from these cut‐offs should raise suspicion for DHL and, therefore, BCL2 and/or BCL6 FISH is required. We also found that a diagnosis of DHL rather than of MYC‐DLBCL was significantly associated with CD10% > 60, Ki‐67% > 50, and SS (B/T) <1.5.</description><subject>Antibodies</subject><subject>Antigens</subject><subject>Bcl-6 protein</subject><subject>Burkitt lymphoma</subject><subject>Burkitt's lymphoma</subject><subject>CD20 antigen</subject><subject>CD22 antigen</subject><subject>CD23 antigen</subject><subject>CD27 antigen</subject><subject>CD38 antigen</subject><subject>CD43 antigen</subject><subject>Cytogenetics</subject><subject>Diagnosis</subject><subject>Diagnostic systems</subject><subject>Differential diagnosis</subject><subject>DLBCL</subject><subject>double‐hit lymphoma</subject><subject>Flow cytometry</subject><subject>Fluorescence</subject><subject>Fluorescence in situ hybridization</subject><subject>immunophenotype</subject><subject>Lymphoma</subject><subject>Myc protein</subject><subject>MYC rearrangement</subject><subject>Scattering</subject><issn>1552-4949</issn><issn>1552-4957</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNp9kUFu1TAQhiMEEqWw4wCW2LDoe8SOHSdLXgQFqVU3ZdGV5STjxCWxg-0UZccRejduwElwGlRVqOpq_rG--T2aP0ne4nSP05R8aJZg9_We4KLgz5IjzBjZ0ZLx5_eali-TV95fp2nGaM6Pkt-VNcHpeg7aGmQV0uM4Gzv1YGxYJkDBotAD0uYGfNCdvOOkaVGrlQIHJmg5xEZ2xnrtV4vD7L7rENCwjFNvR3mCWjvXA_z5ddvrgHrd9VF2TraADlE1MAwP4NXca9PdD5xfVVE5kM5J08H29ewBDdJ1j1i8Tl4oOXh4868eJ98-f7qsvuzOLk6_Vh_Pdg2ljO8awtoihVYpLjOctxlVOeNSMVYyylROoKQKmMSY1JK3OI_vbcF5TgvMiITsOHm_-U7O_pjjecSo_bqJNGBnLwjF8cwp40VE3_2HXtvZmbhdpChNS4IzGqmTjWqc9d6BEpPTo3SLwKlYExZrwqIWdwlHnG74Tz3A8iQrqqvLi8M29hf8vrVF</recordid><startdate>202009</startdate><enddate>202009</enddate><creator>Tsagarakis, Nikolaos J.</creator><creator>Papadhimitriou, Stefanos I.</creator><creator>Pavlidis, Dimitris</creator><creator>Liapis, Konstantinos</creator><creator>Gortzolidis, Georgios</creator><creator>Kostopoulos, Ioannis V.</creator><creator>Marinakis, Theodoros</creator><creator>Paterakis, Georgios</creator><general>John Wiley & Sons, Inc</general><general>Wiley Subscription Services, Inc</general><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>7T5</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-9759-0048</orcidid></search><sort><creationdate>202009</creationdate><title>Contribution of immunophenotype to the investigation and differential diagnosis of Burkitt lymphoma, double‐hit high‐grade B‐cell lymphoma, and single‐hit MYC‐rearranged diffuse large B‐cell lymphoma</title><author>Tsagarakis, Nikolaos J. ; Papadhimitriou, Stefanos I. ; Pavlidis, Dimitris ; Liapis, Konstantinos ; Gortzolidis, Georgios ; Kostopoulos, Ioannis V. ; Marinakis, Theodoros ; Paterakis, Georgios</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4457-c25d80edff7a316d34f657af559545f62e94fe5a112ba7d16595d877648152ae3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Antibodies</topic><topic>Antigens</topic><topic>Bcl-6 protein</topic><topic>Burkitt lymphoma</topic><topic>Burkitt's lymphoma</topic><topic>CD20 antigen</topic><topic>CD22 antigen</topic><topic>CD23 antigen</topic><topic>CD27 antigen</topic><topic>CD38 antigen</topic><topic>CD43 antigen</topic><topic>Cytogenetics</topic><topic>Diagnosis</topic><topic>Diagnostic systems</topic><topic>Differential diagnosis</topic><topic>DLBCL</topic><topic>double‐hit lymphoma</topic><topic>Flow cytometry</topic><topic>Fluorescence</topic><topic>Fluorescence in situ hybridization</topic><topic>immunophenotype</topic><topic>Lymphoma</topic><topic>Myc protein</topic><topic>MYC rearrangement</topic><topic>Scattering</topic><toplevel>online_resources</toplevel><creatorcontrib>Tsagarakis, Nikolaos J.</creatorcontrib><creatorcontrib>Papadhimitriou, Stefanos I.</creatorcontrib><creatorcontrib>Pavlidis, Dimitris</creatorcontrib><creatorcontrib>Liapis, Konstantinos</creatorcontrib><creatorcontrib>Gortzolidis, Georgios</creatorcontrib><creatorcontrib>Kostopoulos, Ioannis V.</creatorcontrib><creatorcontrib>Marinakis, Theodoros</creatorcontrib><creatorcontrib>Paterakis, Georgios</creatorcontrib><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Immunology Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Cytometry. Part B, Clinical cytometry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tsagarakis, Nikolaos J.</au><au>Papadhimitriou, Stefanos I.</au><au>Pavlidis, Dimitris</au><au>Liapis, Konstantinos</au><au>Gortzolidis, Georgios</au><au>Kostopoulos, Ioannis V.</au><au>Marinakis, Theodoros</au><au>Paterakis, Georgios</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Contribution of immunophenotype to the investigation and differential diagnosis of Burkitt lymphoma, double‐hit high‐grade B‐cell lymphoma, and single‐hit MYC‐rearranged diffuse large B‐cell lymphoma</atitle><jtitle>Cytometry. Part B, Clinical cytometry</jtitle><date>2020-09</date><risdate>2020</risdate><volume>98</volume><issue>5</issue><spage>412</spage><epage>420</epage><pages>412-420</pages><issn>1552-4949</issn><eissn>1552-4957</eissn><abstract>Background
There are no immunophenotypic guidelines for the investigation of MYC‐rearranged lymphomas. We aimed to identify simple immunophenotypic features that would help to differentiate between MYC‐rearranged lymphomas and guide cytogenetic analysis.
Methods
We reviewed diagnostic samples from patients diagnosed with Burkitt lymphoma (BL), double‐hit lymphoma (DHL), MYC‐rearranged diffuse large B‐cell lymphoma (MYC‐DLBCL), and standard (non‐MYC‐rearranged) DLBCL over the last decade in our Institution. Using flow cytometry (with antibodies CD20, CD10, CD38, bcl‐2, Ki‐67, FMC‐7, CD43, CD27, CD79b, CD23, and CD22) we determined antigen% expression and median‐fluorescence intensity ratios (MFIR). The forward scatter (FS) and side scatter (SS) characteristics of tumor B‐cells were compared with normal T‐cells (B/T ratios) for patients with MYC‐rearranged lymphomas.
Results
We identified 51 patients of whom 14 had BL, 10 had DHL (6 MYC+/BCL2+; 4 MYC+/BCL6+), 8 MYC‐DLBCL, and 19 standard DLBCL. The significant differences (p <.05) were: higher CD38% in BL than standard DLBCL; higher CD10% in BL and DHL versus MYC‐DLBCL and standard DLBCL; higher CD10MFIR in BL than MYC‐DLBCL and standard DLBCL; higher Ki‐67% in BL than DHL and MYC‐DLBCL; higher bcl‐2% in DHL than BL; higher FMC‐7% in BL than MYC‐DLBCL and standard DLBCL; and lower SS (B/T) ratio in DHL than MYC‐DLBCL.
Conclusions
The combination of CD38% > 90, CD10% > 80, CD10MFIR > 10, bcl‐2% < 30, and Ki‐67% > 70 was characteristic of BL. “Deviation” from these cut‐offs should raise suspicion for DHL and, therefore, BCL2 and/or BCL6 FISH is required. We also found that a diagnosis of DHL rather than of MYC‐DLBCL was significantly associated with CD10% > 60, Ki‐67% > 50, and SS (B/T) <1.5.</abstract><cop>Hoboken, USA</cop><pub>John Wiley & Sons, Inc</pub><doi>10.1002/cyto.b.21887</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-9759-0048</orcidid><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1552-4949 |
ispartof | Cytometry. Part B, Clinical cytometry, 2020-09, Vol.98 (5), p.412-420 |
issn | 1552-4949 1552-4957 |
language | eng |
recordid | cdi_proquest_miscellaneous_2410350578 |
source | Wiley-Blackwell Read & Publish Collection |
subjects | Antibodies Antigens Bcl-6 protein Burkitt lymphoma Burkitt's lymphoma CD20 antigen CD22 antigen CD23 antigen CD27 antigen CD38 antigen CD43 antigen Cytogenetics Diagnosis Diagnostic systems Differential diagnosis DLBCL double‐hit lymphoma Flow cytometry Fluorescence Fluorescence in situ hybridization immunophenotype Lymphoma Myc protein MYC rearrangement Scattering |
title | Contribution of immunophenotype to the investigation and differential diagnosis of Burkitt lymphoma, double‐hit high‐grade B‐cell lymphoma, and single‐hit MYC‐rearranged diffuse large B‐cell lymphoma |
url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-07T19%3A43%3A06IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Contribution%20of%20immunophenotype%20to%20the%20investigation%20and%20differential%20diagnosis%20of%20Burkitt%20lymphoma,%20double%E2%80%90hit%20high%E2%80%90grade%20B%E2%80%90cell%20lymphoma,%20and%20single%E2%80%90hit%20MYC%E2%80%90rearranged%20diffuse%20large%20B%E2%80%90cell%20lymphoma&rft.jtitle=Cytometry.%20Part%20B,%20Clinical%20cytometry&rft.au=Tsagarakis,%20Nikolaos%20J.&rft.date=2020-09&rft.volume=98&rft.issue=5&rft.spage=412&rft.epage=420&rft.pages=412-420&rft.issn=1552-4949&rft.eissn=1552-4957&rft_id=info:doi/10.1002/cyto.b.21887&rft_dat=%3Cproquest_cross%3E2410350578%3C/proquest_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c4457-c25d80edff7a316d34f657af559545f62e94fe5a112ba7d16595d877648152ae3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2444092134&rft_id=info:pmid/&rfr_iscdi=true |