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Fig. 1. Number of editorials out of KoreaMed papers according to year. - 46 -
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Science 14 October 2011: Vol. 334 no. 6053 p. 176 DOI: 10.1126/science.1212182 Letters Partial Retraction IN OUR 23 OCTOBER 2009 REPORT, DETECTION OF AN INFECTIOUS RETROVIRUS, XMRV, IN blood cells of patients with chronic fatigue syndrome (1), two of the coauthors, Silverman and Das Gupta, analyzed DNA samples from chronic fatigue syndrome (CFS) patients and healthy controls. A reexamination by Silverman and Das Gupta of the samples they used shows that some of the CFS peripheral blood mononuclear cell (PBMC) DNA preparations are contaminated with XMRV plasmid DNA (2). The following fi gures and table were based on the contaminated data: Figure 1, single-round PCR detection of XMRV sequences in CFS PBMC DNA samples; table S1, XMRV sequences previously attributed to CFS patients; and fi gure S2, the phylogenetic analysis of those sequences. Therefore, we are retracting those fi gures and table. ROBERT H. SILVERMAN, 1* JAYDIP DAS GUPTA, 1 VINCENT C. LOMBARDI, 2 FRANCIS W. RUSCETTI, 3 MAX A. PFOST, 2 KATHRYN S. HAGEN, 2 DANIEL L. PETERSON, 2 SANDRA K. RUSCETTI, 4 RACHEL K. BAGNI, 5 CARI PETROW-SADOWSKI, 6 BERT GOLD, 3 MICHAEL DEAN, 3 JUDY A. MIKOVITS 2-52 -
1 Department of Cancer Biology, The Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA. 2 Whittemore Peterson Institute, Reno, NV 89557, USA. 3 Laboratory of Experimental Immunology, National Cancer Institute Frederick, Frederick, MD 21701, USA. 4 Laboratory of Cancer Prevention, National Cancer Institute rederick, Frederick, MD 21701, USA. 5 Advanced Technology Program, National Cancer Institute rederick, Frederick, MD 21701, USA. 6 Basic Research Program, Scientifi c Applications International Corporation, National Cancer Institute rederick, Frederick, MD 21701, USA. * To whom correspondence should be addressed. E-mail: silverr@ccf.org Present address: Sierra Internal Medicine, 865 Tahoe Boulevard no. 306, Incline Village, NV 89451, USA. References and Notes 1. V. C. Lombardi, F. W. Ruscetti, J. Das Gupta, M. A. Pfost, K. S. Hagen, D. L. Peterson, S. K. Ruscetti, R. K. Bagni, C. Petrow-Sadowski, B. Gold, M. Dean, R. H. Silverman, J. A. Mikovits, Science 326, 585 (2009). 2. Supporting online material showing the reanalysis is available at www.sciencemag.org/cgi/content/full/science.1212182/dc1. Published online 22 September 2011; 10.1126/science.1212182 또다른예는다음과같다. 아래예에서는게재철회할기사를제목에달 았다. 보통은게재철회할기사를제목에 Retraction 다음에단다 [4]. Retraction: Coulomb Forces on DNA Polymers in Charged Fluidic Nanoslits [Phys. Rev. Lett. 106, 068302 (2011)] Derek Stein (Received 16 June 2011; published 20 July 2011) DOI: 10.1103/PhysRevLett.107.049901 PACS numbers: 82.35.Rs, 82.35.Lr, 82.39.Pj, 85.85.+j, 99.10.Cd - 53 -
I recently determined that the analysis leading to the results in Fig. 2 of our Letter was performed incorrectly. A correct analysis produces results that seriously undermine one of the main claims of the Letter, specifically the claim that from the scaling of the size of a DNA coil with the physical height of a nanofluidic slit, we were able to experimentally infer the size of the electrostatic depletion regions that reduced the effective slit height. Since this claim is critical to our Letter, I wish to retract this Letter to avoid misleading the readership. I regret this error, and sincerely thank S. Levy for bringing it to my attention. - 54 -
2006 National Health Personnel Licensing Examination Board of the Republic of Korea Book Review: Practical Guide to Medical Student Assessment Sun Huh Department of Parasitology, College of Medicine and Institute of Medical Education Hallym University, Chuncheon, Korea. Corresponding: Email: shuh@hallym.ac.kr Zubair Amin;Chong Yap Seng;Khoo Hoon Eng. Practical guide to medical student assessment. 2006. Singapore: World Scientific ISBN: 978-981-256-808-3.. pp. 128, US$38 This tiny book surprised me with its brief, lucid description of the assessment tools used in medical schools. The authors call it a practical reference to commonly raised questions about assessment instruments, and it is a good guide for medical teachers like me. It deals - 55 -
with most of the assessment tools for medical education with which I am acquainted, and it is very suitable for medical teachers who are not specialists in education. After less than a day of reading, I could swim the sea of medical student assessment. The book consists of four sections: Principles and Purpose of Assessment; Assessment of "Knows" and "Knows How"; Assessment of "Shows How"; Assessment of "Does." Section 1 emphasizes the key concept that "students were derived by assessment." My students' greatest concern is examinations. Students value passing exams and getting higher marks, since teachers, including me, usually evaluate students based on their credit records. Therefore, the validity and reliability of the assessment tools are the most critical considerations for teachers. These are especially important in high-stake tests, such as the licensing examination. The utility of an assessment instrument is based on a careful consideration of several factors, including its reliability, validity, educational impact, cost, and accessibility. The authors describe this key concept well. An assessment in clinical medicine should consider special issues, since a difference in conditions affects student performance in a manner unlike paper and pencil examinations. To increase the level of generalizability, that is, the reproducibility of measurement, multiple sampling across different skills and domains is required. In addition, the norm-referenced standard and criterion-referenced standard are explained. The last part of Section 1 describes Miller's Pyramid, which outlines clinical competence at multiple levels. The assessment levels and corresponding examples are displayed based on the "Knows," "Knows How," "Shows How," and "Does" pyramid. For example, "Shows How" matches the "Objective Structured Clinical Examination (OSCE), Long Case and Short Case." The box "Recommendations for Better Practices" briefly describes the core knowledge for teachers. It is a very useful design, since the contents of the box can be used during teacher training workshops. Section 2 presents various methods for assessing "Knows" and "Knows How," with recommended situations and the effect of each method, including oral examinations, long essay questions, short answer questions, multiple choice questions, extended matching items, and the key feature test. My school does not use the key feature test, which was originally developed by the Medical Council of Canada for its licensing examination. It is an interesting test, since it is a clinical scenario presented as a paper and pencil examination that can be adapted for student assessment in medical schools. The authors explain each assessment method clearly and provide an example. - 56 -
Section 3 is for assessing "Shows How." It deals with long and short cases involving real patients, as well as the OSCE. Since the OSCE is the method commonly used for assessing clinical performance, the outline of the method and example presented in this section will be very helpful for medical instructors. The last section introduces the assessment of "Does" as a mini-clinical evaluation exercise, direct observation of procedural skills, clinical work sampling, ward checklist, 360-degree evaluation, logbook, and portfolio. Again, the last three methods are not used in my school, and it will be difficult for one school to adopt all of these assessment methods. However, the various methods can be used in individual departments or hospitals and the results can be compared using the correlations among the methods. This publication is not a handbook, but a synopsis. Therefore, its contents should be a useful guide in workshops for new faculty or on various educational topics in medical school. The authors targeted the needs in the field of medical education accurately. Furthermore, the contents of this book may be applicable to other fields of education, such as dentistry or nursing, since those disciplines also involve a clinical setting. The book is very well edited, and I found no typographical errors or obscure explanations. I was able to summarize the student assessment tools while reading the book. Two of the coauthors have previously published a book titled "Basics in Medical Education," [1] which also contained assessment and evaluation sections describing a road map to student assessment, multiple choice questions, easy questions, oral examinations, standardized patients, and portfolios. The new book approaches assessment from the perspective of a practical guideline for medical teachers, and I believe that it is a good hand-held guide. References 1. Amin Z, Koo HE. Basics in medical education. Singapore: World Scientific; 2003. - 57 -
Letters are short reports of original research focused on an outstanding finding whose importance means that it will be of interest to scientists in other fields. They do not normally exceed 4 pages of Nature, and have no more than 30 references J Korean Med Sci. 2011 Oct;26(10):1399-1400. Published online 2011 October 01. http://dx.doi.org/10.3346/jkms.2011.26.10.1399 2011 The Korean Academy of Medical Sciences. Letter to the Editor: Diagnostic Standardization of Leukemia Fusion Gene Detection System using Multiplex Reverse Transcriptase-polymerase Chain Reaction in Korea Min Jin Kim, 1 Jong Rak Choi, 2 Jin-Tae Suh, 1 Hee Joo Lee, 1 Woo-In Lee, 1 and Tae Sung Park 1 1 Department of Laboratory Medicine, School of Medicine, Kyung Hee University, Seoul, Korea. 2 Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, Korea. Address for Correspondence: Tae Sung Park, MD. Department of Laboratory Medicine, School of Medicine, Kyung Hee University, 45 Gyeonghuidae-gil, Dongdaemun-gu, Seoul 130-702, Korea. Tel: +82.2-958-8673, Fax +82.2-958-8609, Email: 153jesus@hanmail.net We read the interesting article "Spectra of Chromosomal Aberrations in 325 Leukemia Patients and Implications for the Development of New Molecular Detection Systems" in a recent issue of the Journal of Korean Medical Science by Choi et al. (1). We would like to add some comments on these data for suggesting a diagnostic standardization of detection of leukemia-associated gene rearrangements in Korea. - 58 -
Choi et al. (1) reported that they were able to detect leukemic fusion genes among 42% of the entire leukemia patient group, a relatively high ratio, by implementing multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) analysis to 325 leukemia patients over 4 yr. The multiplex RT-PCR kits (HemaVision, DNA technology, Aarhus, Denmark) that was used in the study by Choi et al. (1) are useful diagnostic tools that can simultaneously detect 28 different fusion genes and 80 or more break-points or splicing variants, enabling concurrent screening and confirmation of various leukemia-related gene rearrangements through "Master PCR" (day 1#) and "Split-out PCR" (day 2#). Based on the experience accumulated by the authors using the same multiplex RT-PCR kits at our institution for recent years, we would like to provide a more detailed comment on the merits and shortcomings of this test kit. First and foremost, the most important merit of HemaVision kit is that the screening tests by its "Master PCR" can detect unexpected rare chromosomal translocations and/or cryptic gene rearrangements among new patients with various subtypes of leukemia. For example, we were able to identify a very rare NPM1-MLF1 rearrangement from an acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) patient who accompanied a complex karyotype by utilizing the multiplex RT-PCR testing method (2). Moreover, as the test allows for a clear detection of various alternative splicing and splice variants on gene rearrangements such as BCR-ABL1,PML-RARA, and CBFB-MYH11, we were even able to identify a new type of variant fusion gene that was not reported on rare occasions (3,4). Also, in case of detection of a rare fusion gene, a "Split-out PCR" of HemaVision kit enables a semiquantitative monitoring and follow up on the minimal residual disease (MRD). From a quality control perspective, HemaVision is better off than the homebrew RT-PCR that has been used in Korean medical institutes in terms of maintaining quality control of the results as one can simultaneously check internal control bands at 911bp size during the test, and also because the consistency and reliability of the test result is high. However, it is impossible to detect all types of gene rearrangements related to leukemia by HemaVision kits (notice that one can only detect 28 types of fusion genes), and there are some practical limitations as to the high cost of the kit itself as well. For instance, HemaVision cannot detect all types of MLL partner genes but only about 10 types, while there are about 70 types of MLL partner genes including the CASP8AP2 gene that was recently identified by the authors with respect to MLL rearrangements (1,5). In the future, however, we hope that additional types of MLL gene rearrangements could be included in - 59 -
such multiplex RT-PCR kits, based on the MLL rearrangement status for Korean acute leukemia patients and on practical data such as domestic incidence of MLL partner gene by type, studies that are being conducted by the authors as part of the AML-MDS working party project. There is no doubt that the research results by Choi et al. is the most representative data related to the detection of leukemia-specific gene rearrangements by multiplex RT-PCR at a single medical center in Korea, but the recommended 3 types of cytogenetic abnormalities in their paper that are to be included in the new multiplex RT-PCR system does not seem to be appropriate. Firstly, t(8;14)(q24;q32) seems to be a cytogenetic abnormality which is better suited for the FISH assay rather than the RT-PCR method since chromosomal translocation occurs by a juxtaposition of the C-MYC (8q24) gene towards the IGH (14q32) gene, and there is no hybrid gene. Secondly, although t(3;3) (q21;q26) is a recurrent cytogenetic abnormality for AML that was newly introduced in the 2008 WHO classification (6), its frequency is known to be relatively low, and it would be more suitable to use EVI1 FISH probe in order to simultaneously detect variants of t(3;3) such as inv(3)(q21q26) and ins(3;3)(q26;q21q26), as well as t(3;21) that is related to RUNX1-MDS1-EVI1 rearrangement. And the lastly mentioned i(17)(q10) cannot be detected by RT-PCR since it is not a gene rearrangement but a chromosomal abnormality that is related to structural aberration. Additional comments by Choi et al. would be helpful to clarify on these issues. In conclusion, detecting gene rearrangements for leukemia patients using multiplex RT-PCR kits such as HemaVision seems to be a highly useful molecular diagnostic method for Korean medical institutions in these days. While there are some practical limits as mentioned above, a widespread implementation of this method throughout the majority of medical institutions in Korea will significantly contribute to the standardization of leukemia diagnosis and guarantee high quality test results and efficient quality control. For the issue of what additional gene rearrangements in leukemia patients should be included in the multiplex RT-PCR test panel, a continued research and additional discussion would be necessary rather than adhering to the current provisional conclusions. Notes This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2010-0023093). - 60 -
References 1. Choi HJ, Kim HR, Shin MG, Kook H, Kim HJ, Shin JH, Suh SP, Ryang DW. Spectra of chromosomal aberrations in 325 leukemia patients and implications for the development of new molecular detection systems. J Korean Med Sci 2011;26:886 892. 2. Lim G, Choi JR, Kim MJ, Kim SY, Lee HJ, Suh JT, Yoon HJ, Lee J, Lee S, Lee WI, Park TS. Detection of t(3;5) and NPM1/MLF1 rearrangement in an elderly patient with acute myeloid leukemia: clinical and laboratory study with review of the literature. Cancer Genet Cytogenet 2010;199:101 109. 3. Park TS, Lee ST, Song J, Lee KA, Lee JH, Kim J, Lee HJ, Han JH, Kim JK, Cho SR, Choi JR. Detection of a novel CBFB/MYH11 variant fusion transcript (K-type) showing partial insertion of exon 6 of CBFB gene using two commercially available multiplex RT-PCR kits. Cancer Genet Cytogenet 2009;189:87 92. 4. Lim G, Cho EH, Cho SY, Shin SY, Park JC, Yang YJ, Oh SH, Marschalek R, Meyer C, Park TS. A novel PML-ADAMTS17-RARA gene rearrangement in a patient with pregnancy-related acute promyelocytic leukemia. Leuk Res 2011;35:e106 e110. 5. Park TS, Lee SG, Song J, Lee KA, Kim J, Choi JR, Lee ST, Marschalek R, Meyer C. CASP8AP2 is a novel partner gene of MLL rearrangement with t(6;11)(q15;q23) in acute myeloid leukemia. Cancer Genet Cytogenet 2009;195:94 95. 6. Jaffe ES, Harris NL, Stein H, Vardiman JWWorld Health Organization classification of tumours. Pathology and genetics. Tumours of haematopoietic and lymphoid tissues. Lyon, France: IARC Press; 2008. J Korean Med Sci. 2011 Oct;26(10):1401-1401. Published online 2011 October 01. http://dx.doi.org/10.3346/jkms.2011.26.10.1401 2011 The Korean Academy of Medical Sciences. The Author Response: Diagnostic Standardization of Leukemia Fusion Gene Detection System using Multiplex Reverse Transcriptase-polymerase Chain Reaction in Korea Hyun-Jung Choi, 1 Hye-Ran Kim, 2 and Myung-Geun Shin 1 1 Department of Laboratory Medicine, Chonnam National University Hwasun Hospital, Hwasun, Korea. - 61 -
2 Brain Korea 21 Project, Center for Biomedical Human Resources at Chonnam National University, Gwangju, Korea. Address for Correspondence: Myung-Geun Shin, MD. Department of Laboratory Medicine, Chonnam National University Medical School and Chonnam National University Hwasun Hospital, 322 Seoyang-ro, Hwasun-eup, Hwasun 519-890, Korea. Tel: +82.61-379-7950, Fax: +82.61-379-7984, Email: mgshin@chonnam.ac.kr We appreciated Dr Park TS for his interest and comments in our recent paper (1) in Journal of Korean Medical Science regarding a diagnostic standardization and detection methods of leukemia-associated gene rearrangements in Korea. Our study demonstrated the spectrum and frequency of chromosomal abnormalities in patients with mainly acute leukemia, which were differed from previous studies. Also, this study may offer important implications in the de-velopment of new molecular detection system for screening panel, as well as revisions of the current commercially available multiplex RT-PCR system. New molecular detection system for screening panel in our study means variety of molecular biological methods including PCR-based system, fluorescence in situ hybridization (FISH) and others. We agree that the FISH assay is better suited rather than the RT-PCR method in t(3;3)(q21;q26), inv(3)(q21q26), t(8;14)(q24;q32), and i(17)(q10). However, one can use RT-PCR detection system for screening the aforementioned chromosomal abnormalities based on the following backgrounds. First, the protocol of RT-PCR assay for the detection of either inv(3)(q21q26) or t(3;3)(q21;q26) was already published (2). This protocol might be used in multiplex RT-PCR system for the detection of leukemia fusion genes. Second, it is well known that the t(8;14)(q24;q32) (c-myc/igh rearrangement) has no fusion transcript and fusion protein (3). So, the c-myc/igh rearrangement is only detectable at the DNA level (the RNA expression of c-myc (exon 1 or exon 2) and/or IgH (constant and joining region) also might be absent or remarkable depressed). Based on the fact of decrease or absence of RNA expression of these genes in the case of t(8;14)(q24;q32), conventional RT-PCR and quantitative RT-PCR for them might be implemented for screening. Genomic DNA PCR (long-distance) assay for the detection of the t(8;14)(q24;q32) was already established using one primer for the c-myc gene in exon 2 and four primers for the IgH locus (3,4). Third, similarly, the screening of i(17)(q10) chromosomal abnormality by semiquantitative RT- PCR assay might be possible based on the absence of expression of p53 gene located at 17p13.1 due to deletion of short arm of 17 chromosome. - 62 -
References 1. Choi HJ, Kim HR, Shin MG, Kook H, Kim HJ, Shin JH, Suh SP, Ryang DW. Spectra of chromosomal aberrations in 325 leukemia patients and implications for the development of new molecular detection systems. J Korean Med Sci 2011;26:886 892. 2. Martinelli G, Ottaviani E, Buonamici S, Isidori A, Borsaru G, Visani G, Piccaluga PP, Malagola M, Testoni N, Rondoni M, Nucifora G, Tura S, Baccarani M. Association of 3q21q26 syndrome with different RPN1/EVI1 fusion transcripts. Haematologica 2003;88:1221 1228. 3. Mussolin L, Basso K, Pillon M, D'Amore ES, Lombardi A, Luzzatto L, Zanesco L, Rosolen A. Prospective analysis of minimal bone marrow infiltration in pediatric Burkitt's lymphomas by long-distance polymerase chain reaction for t(8;14)(q24;q32). Leukemia 2003;17:585 589. 4. Busch K, Borkhardt A, Wossmann W, Reiter A, Harbott J. Combined polymerase chain reaction methods to detect c-myc/igh rearrangement in childhood Burkitt's lymphoma for minimal residual disease analysis. Haematologica 2004;89:818 825. - 63 -