Annals of Laboratory Medicine最新文献

{"title":"Detection of a High-Dose Hook Effect and Evaluation of Dilutions of Urine Myoglobin Specimens Using a Serum Myoglobin Assay.","authors":"Joshua Joon Hyung Hunsaker, Sonia Leilani La'ulu, Emily Zupan, Dhwani Patel, Vrajesh Pandya, Joseph William Rudolf","doi":"10.3343/alm.2023.0427","DOIUrl":"10.3343/alm.2023.0427","url":null,"abstract":"","PeriodicalId":8421,"journal":{"name":"Annals of Laboratory Medicine","volume":" ","pages":"367-370"},"PeriodicalIF":4.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10961618/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140118632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>TSHR</i> Variant Screening and Phenotype Analysis in 367 Chinese Patients With Congenital Hypothyroidism.","authors":"Hai-Yang Zhang, Feng-Yao Wu, Xue-Song Li, Ping-Hui Tu, Cao-Xu Zhang, Rui-Meng Yang, Ren-Jie Cui, Chen-Yang Wu, Ya Fang, Liu Yang, Huai-Dong Song, Shuang-Xia Zhao","doi":"10.3343/alm.2023.0337","DOIUrl":"10.3343/alm.2023.0337","url":null,"abstract":"<p><strong>Background: </strong>Genetic defects in the human thyroid-stimulating hormone (TSH) receptor (<i>TSHR</i>) gene can cause congenital hypothyroidism (CH). However, the biological functions and comprehensive genotype-phenotype relationships for most <i>TSHR</i> variants associated with CH remain unexplored. We aimed to identify <i>TSHR</i> variants in Chinese patients with CH, analyze the functions of the variants, and explore the relationships between <i>TSHR</i> genotypes and clinical phenotypes.</p><p><strong>Methods: </strong>In total, 367 patients with CH were recruited for <i>TSHR</i> variant screening using whole-exome sequencing. The effects of the variants were evaluated by <i>in-silico</i> programs such as SIFT and polyphen2. Furthermore, these variants were transfected into 293T cells to detect their Gs/cyclic AMP and Gq/11 signaling activity.</p><p><strong>Results: </strong>Among the 367 patients with CH, 17 <i>TSHR</i> variants, including three novel variants, were identified in 45 patients, and 18 patients carried biallelic <i>TSHR</i> variants. <i>In vitro</i> experiments showed that 10 variants were associated with Gs/cyclic AMP and Gq/11 signaling pathway impairment to varying degrees. Patients with <i>TSHR</i> biallelic variants had lower serum TSH levels and higher free triiodothyronine and thyroxine levels at diagnosis than those with <i>DUOX2</i> biallelic variants.</p><p><strong>Conclusions: </strong>We found a high frequency of <i>TSHR</i> variants in Chinese patients with CH (12.3%), and 4.9% of cases were caused by <i>TSHR</i> biallelic variants. Ten variants were identified as loss-of-function variants. The data suggest that the clinical phenotype of CH patients caused by <i>TSHR</i> biallelic variants is relatively mild. Our study expands the <i>TSHR</i> variant spectrum and provides further evidence for the elucidation of the genetic etiology of CH.</p>","PeriodicalId":8421,"journal":{"name":"Annals of Laboratory Medicine","volume":" ","pages":"343-353"},"PeriodicalIF":4.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10961619/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140020861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Direct LDL Cholesterol Assay vs. Estimated Equations in Patients With Hypertriglyceridemia or Low LDL Cholesterol Levels.","authors":"Jennifer Rodríguez-Domínguez, Álvaro Piedra-Aguilera, María Martínez-Bujidos, Susana Malumbres-Serrano, Cristian Morales-Indiano, Carla Fernández-Prendes","doi":"10.3343/alm.2023.0387","DOIUrl":"10.3343/alm.2023.0387","url":null,"abstract":"","PeriodicalId":8421,"journal":{"name":"Annals of Laboratory Medicine","volume":" ","pages":"363-366"},"PeriodicalIF":4.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10961624/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139490773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>NUP214</i> Rearrangements in Leukemia Patients: A Case Series From a Single Institution.","authors":"Yu Jeong Choi, Young Kyu Min, Seung-Tae Lee, Jong Rak Choi, Saeam Shin","doi":"10.3343/alm.2023.0301","DOIUrl":"10.3343/alm.2023.0301","url":null,"abstract":"<p><strong>Background: </strong>The three best-known <i>NUP214</i> rearrangements found in leukemia (<i>SET:: NUP214, NUP214::ABL1</i>, and <i>DEK::NUP214</i>) are associated with treatment resistance and poor prognosis. Mouse experiments have shown that <i>NUP214</i> rearrangements alone are insufficient for leukemogenesis; therefore, the identification of concurrent mutations is important for accurate assessment and tailored patient management. Here, we characterized the demographic characteristics and concurrent mutations in patients harboring <i>NUP214</i> rearrangements.</p><p><strong>Methods: </strong>To identify patients with <i>NUP214</i> rearrangements, RNA-sequencing results of diagnostic bone marrow aspirates were retrospectively studied. Concurrent targeted next-generation sequencing results, patient demographics, karyotypes, and flow cytometry information were also reviewed.</p><p><strong>Results: </strong>In total, 11 patients harboring <i>NUP214</i> rearrangements were identified, among whom four had <i>SET::NUP214</i>, three had <i>DEK::NUP214</i>, and four had <i>NUP214::ABL1</i>. All <i>DEK::NUP214</i>-positive patients were diagnosed as having AML. In patients carrying <i>SET::NUP214</i> and <i>NUP214::ABL1</i>, T-lymphoblastic leukemia was the most common diagnosis (50%, 4/8). Concurrent gene mutations were found in all cases. <i>PFH6</i> mutations were the most common (45.5%, 5/11), followed by <i>WT1</i> (27.3%, 3/11), <i>NOTCH1</i> (27.3%, 3/11), <i>FLT3</i>-internal tandem duplication (27.3%, 3/11), <i>NRAS</i> (18.2%, 2/11), and <i>EZH2</i> (18.2%, 2/11) mutations. Two patients represented the second and third reported cases of <i>NUP214::ABL1</i>-positive AML.</p><p><strong>Conclusions: </strong>We examined the characteristics and concurrent test results, including gene mutations, of 11 leukemia patients with <i>NUP214</i> rearrangement. We hope that the elucidation of the context in which they occurred will aid future research on tailored monitoring and treatment.</p>","PeriodicalId":8421,"journal":{"name":"Annals of Laboratory Medicine","volume":" ","pages":"335-342"},"PeriodicalIF":4.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10961622/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139037378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The First Case of Pulmonary Mucormycosis Caused by <i>Lichtheimia ornata</i>.","authors":"Jungjun Lee, Dong-Gun Lee, Raeseok Lee, Jae-Ho Yoon, Kyongmin Sarah Beck, In Young Yoo, Yeon-Joon Park","doi":"10.3343/alm.2023.0426","DOIUrl":"10.3343/alm.2023.0426","url":null,"abstract":"","PeriodicalId":8421,"journal":{"name":"Annals of Laboratory Medicine","volume":" ","pages":"371-374"},"PeriodicalIF":4.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10961628/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140108982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of Optical Genome Mapping With Conventional Diagnostic Methods for Structural Variant Detection in Hematologic Malignancies.","authors":"Yeeun Shim, Yu-Kyung Koo, Saeam Shin, Seung-Tae Lee, Kyung-A Lee, Jong Rak Choi","doi":"10.3343/alm.2023.0339","DOIUrl":"10.3343/alm.2023.0339","url":null,"abstract":"<p><strong>Background: </strong>Structural variants (SVs) are currently analyzed using a combination of conventional methods; however, this approach has limitations. Optical genome mapping (OGM), an emerging technology for detecting SVs using a single-molecule strategy, has the potential to replace conventional methods. We compared OGM with conventional diagnostic methods for detecting SVs in various hematologic malignancies.</p><p><strong>Methods: </strong>Residual bone marrow aspirates from 27 patients with hematologic malignancies in whom SVs were observed using conventional methods (chromosomal banding analysis, FISH, an RNA fusion panel, and reverse transcription PCR) were analyzed using OGM. The concordance between the OGM and conventional method results was evaluated.</p><p><strong>Results: </strong>OGM showed concordance in 63% (17/27) and partial concordance in 37% (10/27) of samples. OGM detected 76% (52/68) of the total SVs correctly (concordance rate for each type of SVs: aneuploidies, 83% [15/18]; balanced translocation, 80% [12/15] unbalanced translocation, 54% [7/13] deletions, 81% [13/16]; duplications, 100% [2/2] inversion 100% [1/1]; insertion, 100% [1/1]; marker chromosome, 0% [0/1]; isochromosome, 100% [1/1]). Sixteen discordant results were attributed to the involvement of centromeric/telomeric regions, detection sensitivity, and a low mapping rate and coverage. OGM identified additional SVs, including submicroscopic SVs and novel fusions, in five cases.</p><p><strong>Conclusions: </strong>OGM shows a high level of concordance with conventional diagnostic methods for the detection of SVs and can identify novel variants, suggesting its potential utility in enabling more comprehensive SV analysis in routine diagnostics of hematologic malignancies, although further studies and improvements are required.</p>","PeriodicalId":8421,"journal":{"name":"Annals of Laboratory Medicine","volume":" ","pages":"324-334"},"PeriodicalIF":4.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10961627/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140020863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Manufacturing Cell and Gene Therapies: Challenges in Clinical Translation.","authors":"Na Kyung Lee, Jong Wook Chang","doi":"10.3343/alm.2023.0382","DOIUrl":"10.3343/alm.2023.0382","url":null,"abstract":"<p><p>The safety and efficacy of both cell and gene therapies have been demonstrated in numerous preclinical and clinical trials. Chimeric antigen receptor T (CAR-T) cell therapy, which leverages the technologies of both cell and gene therapies, has also shown great promise for treating various cancers. Advancements in pertinent fields have also highlighted challenges faced while manufacturing cell and gene therapy products. Potential problems and obstacles must be addressed to ease the clinical translation of individual therapies. Literature reviews of representative cell-based, gene-based, and cell-based gene therapies with regard to their general manufacturing processes, the challenges faced during manufacturing, and QC specifications are limited. We review the general manufacturing processes of cell and gene therapies, including those involving mesenchymal stem cells, viral vectors, and CAR-T cells. The complexities associated with the manufacturing processes and subsequent QC/validation processes may present challenges that could impede the clinical progression of the products. This article addresses these potential challenges. Further, we discuss the use of the manufacturing model and its impact on cell and gene therapy.</p>","PeriodicalId":8421,"journal":{"name":"Annals of Laboratory Medicine","volume":" ","pages":"314-323"},"PeriodicalIF":4.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10961620/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139740248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Usefulness of Component-Resolved Diagnosis of Pollen-Food Allergy Syndrome.","authors":"Moon Won Lee, Hyun Ji Lee, Seulgi Moon, Kyung-Hwa Shin","doi":"10.3343/alm.2023.0466","DOIUrl":"10.3343/alm.2023.0466","url":null,"abstract":"","PeriodicalId":8421,"journal":{"name":"Annals of Laboratory Medicine","volume":" ","pages":"378-380"},"PeriodicalIF":4.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10961617/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139904937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of Measurable Residual Disease in Pediatric B-Lymphoblastic Leukemia Using Multiparametric Flow Cytometry and Next-Generation Sequencing.","authors":"Sang Mee Hwang, Inseong Oh, Seok Ryun Kwon, Jee-Soo Lee, Moon-Woo Seong","doi":"10.3343/alm.2023.0412","DOIUrl":"10.3343/alm.2023.0412","url":null,"abstract":"<p><p>Measurable residual disease (MRD) testing, a standard procedure in B-lymphoblastic leukemia (B-ALL) diagnostics, is assessed using multiparametric flow cytometry (MFC) and next-generation sequencing (NGS) analysis of immunoglobulin gene rearrangements. We evaluated the concordance between eight-color, two-tube MFC-MRD the LymphoTrack NGS-MRD assays using 139 follow-up samples from 54 pediatric patients with B-ALL. We also assessed the effect of hemodilution in MFC-MRD assays. The MRD-concordance rate was 79.9% (N=111), with 25 (18.0%) and 3 (2.2%) samples testing positive only by NGS-MRD (MFC^-NGS⁺MRD) and MFC-MRD (MFC⁺NGS^-MRD), respectively. We found a significant correlation in MRD values from total nucleated cells between the two methods (r=0.736 [0.647-0.806], <i>P</i><0.001). The median MRD value of MFC^-NGS⁺MRD samples was estimated to be 0.0012% (0.0001%-0.0263%) using the NGS-MRD assays. Notably, 14.3% of MFC^-NGS⁺MRD samples showed NGS-MRD values below the limit of detection in the MFC-MRD assays. The percentages of hematogones detected in MFC-MRD assays significantly differed between the discordant and concordant cases (<i>P</i><0.001). MFC and NGS-MRD assays showed relatively high concordance and correlation in MRD assessment, whereas the NGS-MRD assay detected MRD more frequently than the MFC-MRD assay in pediatric B-ALL. Evaluating the hematogone percentages can aid in assessing the impact of sample hemodilution.</p>","PeriodicalId":8421,"journal":{"name":"Annals of Laboratory Medicine","volume":" ","pages":"354-358"},"PeriodicalIF":4.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10961625/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139490772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Severe Infection Caused by a White Colony-Producing Strain of <i>Clostridioides difficile</i> RTC41/ST588.","authors":"Se Yoon Park, Heejung Kim, Yangsoon Lee","doi":"10.3343/alm.2023.0474","DOIUrl":"10.3343/alm.2023.0474","url":null,"abstract":"","PeriodicalId":8421,"journal":{"name":"Annals of Laboratory Medicine","volume":" ","pages":"375-377"},"PeriodicalIF":4.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10961626/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140048646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}