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Cost analyses for malaria molecular diagnosis for research planners in India and beyond. 为印度及其他地区的研究规划人员提供疟疾分子诊断成本分析。
IF 3.9 3区 医学 Q1 PATHOLOGY Pub Date : 2024-06-01 Epub Date: 2024-05-20 DOI: 10.1080/14737159.2024.2356172
Vandana Panwar, Shivani Bansal, Charu Chauhan, Abhinav Sinha

Background: Malaria elimination mandates early and accurate diagnosis of infection. Although malaria diagnosis is programmatically dependent on microscopy/RDTs, molecular diagnosis has much better diagnostic accuracy. Higher cost of molecular diagnoses is a recognized challenge for use at the point of care. Because funding is always a recognized constraint, we performed financial cost-analyses of available molecular platforms for better utilization of available budget.

Methods: Two strategies were applied to deduce the cost per sample. Strategy 1 included recurring components (RC) in minimum pack size, and biologist's time whereas strategy 2 included only RC and non-recurring components and costs are calculated for sample sizes (1-1,000,000) to infer the sample size effect.

Results: Spin column-based manual DNA extraction (US$ 3.93 per sample) is the lowest-cost method, followed by magnetic bead-based automated, semi-automated, and PCI-based manual method. Further, DNA extraction cost per sample via spin column-based manual method and semi-automated method decreases with an increase in sample size up to 10,000. Real-time PCRs are ~ 2-fold more economical than conventional PCR, regardless of sample size.

Conclusions: This study is the first for malaria to estimate systematic molecular diagnosis financial costs. Kit-based and automated methods may replace conventional DNA extraction and amplification methods for a frugal high-throughput diagnosis.

背景:消除疟疾要求对感染进行早期准确诊断。尽管疟疾诊断在程序上依赖于显微镜/RDT,但分子诊断的诊断准确性要高得多。分子诊断的成本较高,这对在医疗点使用分子诊断是一个公认的挑战。由于资金始终是公认的制约因素,我们对现有的分子平台进行了财务成本分析,以便更好地利用现有预算:方法:我们采用了两种策略来推算每个样本的成本。方法:采用两种策略推算每个样本的成本。策略 1 包括最小包装中的经常性成本(RC)和生物学家的时间,而策略 2 仅包括经常性成本和非经常性成本,并计算样本量(1-1,000,000)的成本,以推断样本量效应:结果:基于旋转柱的手动 DNA 提取(每个样本 3.93 美元)是成本最低的方法,其次是基于磁珠的自动、半自动和基于 PCI 的手动方法。此外,通过旋柱式手动方法和半自动方法提取每个样本的 DNA 成本随着样本量的增加而降低,最高可达 10,000 个样本。无论样本量多少,实时 PCR 都比传统 PCR 经济约 2 倍:这项研究首次对疟疾的系统分子诊断成本进行了估算。基于试剂盒的自动方法可取代传统的 DNA 提取和扩增方法,从而实现节俭的高通量诊断。
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引用次数: 0
Association between polymorphisms in TLR3, TICAM1 and IFNA1 genes and covid-19 severity in Southern Brazil. 巴西南部 TLR3、TICAM1 和 IFNA1 基因的多态性与 covid-19 严重程度之间的关系。
IF 3.9 3区 医学 Q1 PATHOLOGY Pub Date : 2024-06-01 Epub Date: 2024-06-17 DOI: 10.1080/14737159.2024.2367466
Matheus Braga, Mariana Akemi Sonoda Shiga, Pedro Emanuel Santiago Silva, Aléia Harumi Uchibaba Yamanaka, Victor Hugo Souza, Sergio Grava, Andréa Name Colado Simão, Janisleya Silva Ferreira Neves, Quirino Alves de Lima Neto, Joana Maira Valentini Zacarias, Jeane Eliete Laguila Visentainer

Background: A distinct phenotype in Coronavirus disease 2019 (Covid-19) was observed in severe patients, consisting of a highly impaired interferon (IFN) type I response, an exacerbated inflammatory response.

Objective: The aim of the present study was to investigate a possible association of single nucleotide polymorphisms (SNPs), in five genes related to the immune response, rs3775291 in TLR3; rs2292151 in TICAM1; rs1758566 in IFNA1; rs1800629 in TNF, and rs1800795 in IL6 with the severity of Covid-19.

Methods: A cross-sectional study was performed, with non-severe and severe/critical patients diagnosed with Covid-19, by two public hospitals in Brazil. In total, 300 patients were genotyped for the SNPs, 150 with the non-severe form of the disease and 150 with severe/critical form.

Results: The T/T genotype of TLR3 in recessive model shows 58% of protection against severe/critical Covid-19; as well as the genotypes G/A+A/A of TICAM1 in dominant model with 60% of protection, and in a codominant model G/A with 57% and A/A with 71% of protection against severe/critical Covid-19. Comparing severe and critical cases, the T/C genotype of IFNA1 in the codominant model and TC+C/C in the dominant model showed twice the risk of critical Covid-19.

Conclusion: We can conclude that rs3775291, rs2292151 and rs1758566 can influence the COVID-19 severity.

背景:在重症患者中观察到了冠状病毒病2019(Covid-19)的独特表型,包括干扰素(IFN)I型反应高度受损、炎症反应加剧:本研究旨在调查与免疫反应相关的五个基因中的单核苷酸多态性(SNPs)与Covid-19严重程度的可能关联:TLR3中的rs3775291、TICAM1中的rs2292151、IFNA1中的rs1758566、TNF中的rs1800629和IL6中的rs1800795:巴西两家公立医院对确诊为 Covid-19 的非重度和重度/危重患者进行了横断面研究。共对 300 名患者进行了 SNPs 基因分型,其中 150 名为非重症患者,150 名为重症/危重症患者:结果:TLR3的T/T基因型在隐性模型中显示对重症/危重型Covid-19的保护率为58%;TICAM1的G/A+A/A基因型在显性模型中显示对重症/危重型Covid-19的保护率为60%,在双显性模型中显示对重症/危重型Covid-19的保护率分别为G/A 57%和A/A 71%。比较重度和危重病例,在显性模型中 IFNA1 的 T/C 基因型和在显性模型中 TC+C/C 基因型显示出危重 Covid-19 风险的两倍:我们可以得出结论,rs3775291、rs2292151 和 rs1758566 会影响 Covid-19 的严重程度。
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引用次数: 0
Point-of-care isothermal nucleic acid amplification tests: progress and bottlenecks for extraction-free sample collection and preparation. 护理点等温核酸扩增检验:免提取样本采集和制备的进展与瓶颈。
IF 3.9 3区 医学 Q1 PATHOLOGY Pub Date : 2024-06-01 Epub Date: 2024-07-08 DOI: 10.1080/14737159.2024.2375233
Alexis F Wilkinson, Maria J Barra, Emilie N Novak, Meaghan Bond, Rebecca Richards-Kortum

Introduction: Suitable sample collection and preparation methods are essential to enable nucleic acid amplification testing at the point of care (POC). Strategies that allow direct isothermal nucleic acid amplification testing (iNAAT) of crude sample lysate without the need for nucleic acid extraction minimize time to result as well as the need for operator expertise and costly infrastructure.

Areas covered: The authors review research to understand how sample matrix and preparation affect the design and performance of POC iNAATs. They focus on approaches where samples are directly combined with liquid reagents for preparation and amplification via iNAAT strategies. They review factors related to the type and method of sample collection, storage buffers, and lysis strategies. Finally, they discuss RNA targets and relevant regulatory considerations.

Expert opinion: Limitations in sample preparation methods are a significant technical barrier preventing implementation of nucleic acid testing at the POC. The authors propose a framework for co-designing sample preparation and amplification steps for optimal performance with an extraction-free paradigm by considering a sample matrix and lytic strategy prior to an amplification assay and readout. In the next 5 years, the authors anticipate increasing priority on the co-design of sample preparation and iNAATs.

导言:要在医疗点(POC)进行核酸扩增检测,合适的样本采集和制备方法至关重要。可直接对粗样品裂解液进行等温核酸扩增检测(inaat)而无需进行核酸提取的策略可最大限度地缩短检测时间,减少对操作人员专业知识和昂贵基础设施的需求:作者回顾了相关研究,以了解样本基质和制备如何影响 POC iNAAT 的设计和性能。他们重点研究了通过 iNAAT 策略将样本与液体试剂直接结合进行制备和扩增的方法。他们回顾了与样本采集类型和方法、储存缓冲液和裂解策略有关的因素。最后,他们讨论了 RNA 靶标和相关的监管考虑因素:样本制备方法的局限性是阻碍在 POC 实施核酸检测的重要技术障碍。作者提出了一个共同设计样品制备和扩增步骤的框架,通过在扩增检测和读出之前考虑样品基质和裂解策略,实现免提取范式的最佳性能。作者预计,在未来 5 年内,样本制备和 iNAAT 的协同设计将越来越受到重视。
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引用次数: 0
A novel anoikis-related signature predicts prognosis risk and treatment responsiveness in diffuse large B-cell lymphoma. 预测弥漫大 B 细胞淋巴瘤预后风险和治疗反应性的新型 anoikis 相关特征。
IF 5.1 3区 医学 Q1 PATHOLOGY Pub Date : 2024-05-01 Epub Date: 2024-05-11 DOI: 10.1080/14737159.2024.2351465
Mingze Guan, Hua Zhao, Qi Zhang, Li Li, Xiaobo Wang, Bo Tang

Background: Although anoikis plays a role in cancer metastasis and aggressiveness, it has rarely been reported in diffuse large B cell lymphoma (DLBCL).

Methods: We obtained RNA sequencing data and matched clinical data from the GEO database. An anoikis-related genes (ARGs)-based risk signature was developed in GSE10846 training cohort and validated in three other cohorts. Additionally, we predicted half-maximal inhibitory concentration (IC50) of drugs based on bioinformatics method and obtained the actual IC50 to some chemotherapy drugs via cytotoxicity assay.

Results: The high-risk group, as determined by our signature, was associated with worse prognosis and an immunosuppressive environment in DLBCL. Meanwhile, the nomogram based on eight variables had more accurate ability in forecasting the prognosis than the international prognostic index in DLBCL. The prediction of IC50 indicated that DLBCL patients in the high-risk group were more sensitive to doxorubicin, IPA-3, lenalidomide, gemcitabine, and CEP.701, while patients in the low-risk group were sensitive to cisplatin and dasatinib. Consistent with the prediction, cytotoxicity assay suggested the higher sensitivity to doxorubicin and gemcitabine and the lower sensitivity to dasatinib in the high-risk group in DLBCL.

Conclusion: The ARG-based signature may provide a promising direction for prognosis prediction and treatment optimization for DLBCL patients.

背景:虽然 "anoikis "在癌症迁移、转移和侵袭中起作用,但在弥漫大B细胞淋巴瘤(DLBCL)中却鲜有报道:尽管anoikis在癌症迁移、转移和侵袭性中发挥作用,但在弥漫大B细胞淋巴瘤(DLBCL)中却鲜有报道:我们从 GEO 数据库中获取了 RNA 测序数据和匹配的临床数据。方法:我们从GEO数据库中获取了RNA测序数据和匹配的临床数据,在GSE10846训练队列中使用单变量Cox回归和LASSO回归建立了基于anoikis相关基因(ARGs)的风险特征,并在其他三个队列中进行了验证。通过 RT-qPCR 验证了 ARG 标志候选基因的表达。此外,我们还基于生物信息学方法预测了药物的半数最大抑制浓度(IC50),并通过细胞毒性测定获得了多柔比星、吉西他滨、IPA-3 和达沙替尼的实际 IC50:我们的研究发现,与对照组织相比,PTEN、PDK4、IGF1、HIF1A和CCND1在DLBCL组织中下调。根据基于ARG的风险评分特征确定的高风险组与较差的预后和免疫抑制环境有关,包括免疫抑制细胞的高浸润和一些免疫检查点。同时,基于八个变量的提名图在预测DLBCL预后方面比国际预后指数更准确。基于生物信息学方法的IC50预测表明,高危组中的DLBCL患者对多柔比星、IPA-3、来那度胺、吉西他滨和CEP.701更敏感,而低危组患者对顺铂和达沙替尼敏感。与预测结果一致的是,DLBCL细胞系的细胞毒性检测表明,在DLBCL患者中,高风险组对多柔比星和吉西他滨的敏感性更高,而低风险组对达沙替尼的敏感性更高:基于ARG的特征为DLBCL患者的预后预测和治疗优化提供了一个很有前景的方向。
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引用次数: 0
Genomic determinants of biological aggressiveness and poor prognosis of pancreatic cancers: KRAS and beyond. 胰腺癌生物侵袭性和不良预后的基因组决定因素:KRAS 及其他
IF 5.1 3区 医学 Q1 PATHOLOGY Pub Date : 2024-05-01 Epub Date: 2024-05-06 DOI: 10.1080/14737159.2024.2348676
Calogero Ciulla, Claudio Luchini

Introduction: A marked histomolecular heterogeneity characterizes pancreatic cancer. Thus, different tumor histologies with divergent genomic profiles exist within the same category.

Areas covered: Using data from PubMed, SCOPUS, and Embase (last search date: 04/04/2024), this expert-based, narrative review presents and discusses the essential molecular determinants of biological aggressiveness and poor prognosis in pancreatic cancer. First, KRAS mutation still represents one of the most critical difficulties in treating pancreatic cancers. In this district, it is mutated in > 90% of malignant tumors. Notably, actionable alterations for molecular-based therapies are typically lacking in KRAS-mutated pancreatic cancer. Furthermore, transcriptome-based studies clarified that the squamous phenotype is characterized by poorer prognosis and response to standard chemotherapy. We also discuss molecular biomarkers related to dismal prognosis in specific subsets of pancreatic cancer, such as SMAD4 in signet-ring cell carcinoma and TP53 in invasive cancers derived from intraductal tubulopapillary neoplasms.

Expert opinion: The identification of the subgroups of pancreatic cancer with particularly unfavorable prognoses is a critical step for addressing specific research efforts. In addition to implementing and strengthening current precision oncology strategies, the decisive step for improving the survival of patients affected by pancreatic cancer must pass through targeting the KRAS gene.

导言:胰腺癌具有明显的组织分子异质性。因此,在同一类肿瘤中,不同的肿瘤组织学具有不同的基因组特征:本专家综述以PubMed、SCOPUS和Embase(最后检索日期:2024年4月4日)中的数据为基础,介绍并讨论了胰腺癌生物侵袭性和不良预后的基本分子决定因素。首先,KRAS突变仍然是治疗胰腺癌最关键的难点之一。在该地区,超过 90% 的恶性肿瘤都存在 KRAS 突变。值得注意的是,KRAS突变的胰腺癌通常缺乏可用于分子疗法的可操作改变。此外,基于转录组的研究表明,鳞状表型的特点是预后和对标准化疗的反应较差。我们还讨论了与特定胰腺癌亚组预后不良有关的分子生物标志物,如标志环细胞癌中的 SMAD4 和导管内管状乳头状瘤浸润癌中的 TP53:专家意见:确定预后特别不良的胰腺癌亚组是开展具体研究工作的关键一步。除了实施和加强当前的精准肿瘤学策略外,改善胰腺癌患者生存率的决定性一步必须通过靶向 KRAS 基因来实现。
{"title":"Genomic determinants of biological aggressiveness and poor prognosis of pancreatic cancers: <i>KRAS</i> and beyond.","authors":"Calogero Ciulla, Claudio Luchini","doi":"10.1080/14737159.2024.2348676","DOIUrl":"10.1080/14737159.2024.2348676","url":null,"abstract":"<p><strong>Introduction: </strong>A marked histomolecular heterogeneity characterizes pancreatic cancer. Thus, different tumor histologies with divergent genomic profiles exist within the same category.</p><p><strong>Areas covered: </strong>Using data from PubMed, SCOPUS, and Embase (last search date: 04/04/2024), this expert-based, narrative review presents and discusses the essential molecular determinants of biological aggressiveness and poor prognosis in pancreatic cancer. First, <i>KRAS</i> mutation still represents one of the most critical difficulties in treating pancreatic cancers. In this district, it is mutated in > 90% of malignant tumors. Notably, actionable alterations for molecular-based therapies are typically lacking in <i>KRAS</i>-mutated pancreatic cancer. Furthermore, transcriptome-based studies clarified that the squamous phenotype is characterized by poorer prognosis and response to standard chemotherapy. We also discuss molecular biomarkers related to dismal prognosis in specific subsets of pancreatic cancer, such as <i>SMAD4</i> in signet-ring cell carcinoma and <i>TP53</i> in invasive cancers derived from intraductal tubulopapillary neoplasms.</p><p><strong>Expert opinion: </strong>The identification of the subgroups of pancreatic cancer with particularly unfavorable prognoses is a critical step for addressing specific research efforts. In addition to implementing and strengthening current precision oncology strategies, the decisive step for improving the survival of patients affected by pancreatic cancer must pass through targeting the <i>KRAS</i> gene.</p>","PeriodicalId":12113,"journal":{"name":"Expert Review of Molecular Diagnostics","volume":" ","pages":"355-362"},"PeriodicalIF":5.1,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140861703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Performance of noninvasive prenatal screening for fetal sex chromosome aneuploidies in a cohort of 116,862 pregnancies. 在 116,862 例妊娠中对胎儿性染色体非整倍体进行无创产前筛查的结果。
IF 5.1 3区 医学 Q1 PATHOLOGY Pub Date : 2024-05-01 Epub Date: 2024-03-25 DOI: 10.1080/14737159.2024.2333951
Yanfei Xu, Jianbo Lou, Yeqing Qian, Pengzhen Jin, Yangwen Qian, Jiawei Hong, Yuqing Xu, Yixuan Yin, Songjia Yi, Minyue Dong

Background: Noninvasive prenatal screening (NIPS) has shown good performance in screening common aneuploidies. However, its performance in detecting fetal sex chromosome aneuploidies (SCAs) needs to be evaluated in a large cohort.

Research design and methods: In this retrospective observation, a total of 116,862 women underwent NIPS based on DNA nanoball sequencing from 2015 to 2022. SCAs were diagnosed based on karyotyping or chromosomal microarray analysis (CMA). Among them, 2,084 singleton pregnancies received karyotyping and/or CMA. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of NIPS for fetal SCAs were evaluated.

Results: The sensitivity was 97.7% (95%CI, 87.7-99.9), 87.3% (95% CI, 76.5-94.4), 96.1% (95%CI, 86.5-99.5), and 95.7% (95% CI, 78.1-99.9), the PPV was 25.8% (95%CI, 19.2-33.2), 80.9% (95%CI, 69.5-89.4), 79.0% (95%CI, 66.8-88.3), and 53.7% (95%CI, 37.4-69.3) for 45,X, 47,XXY, 47,XXX, and 47,XYY, respectively. The specificity was 94.1% (95%CI, 93.0-95.1) for 45,X, and more than 99.0% for sex chromosome trisomy (SCT). The NPV was over 99.0% for all.

Conclusions: NIPS screening for fetal SCAs has high sensitivity, specificity and NPV. The PPV of SCAs was moderate, but that of 45,X was lower than that of SCTs. Invasive prenatal diagnosis should be recommended for high-risk patients.

背景:无创产前筛查(NIPS)在筛查常见非整倍体方面表现良好。然而,它在检测胎儿性染色体非整倍体(SCA)方面的表现还需要在大规模的队列中进行评估:在这项回顾性观察中,共有116862名女性在2015年至2022年期间接受了基于DNA纳米球测序的NIPS。SCA根据核型或染色体微阵列分析(CMA)进行诊断。其中,2084 例单胎妊娠接受了核型分析和/或染色体微阵列分析。评估了NIPS对胎儿SCA的敏感性、特异性、阳性预测值(PPV)和阴性预测值(NPV):敏感性为 97.7%(95%CI,87.7-99.9),特异性为 87.3%(95%CI,76.5-94.4),阳性预测值为 96.1%(95%CI,86.5-99.5),阴性预测值为 95.7%(95%CI,78.1-99.9)。45,X、47,XXY、47,XXX 和 47,XYY 的 PPV 分别为 25.8%(95%CI,19.2-33.2)、80.9%(95%CI,69.5-89.4)、79.0%(95%CI,66.8-88.3)和 53.7%(95%CI,37.4-69.3)。45,X 的特异性为 94.1%(95%CI,93.0-95.1),性染色体三体(SCT)的特异性超过 99.0%。结论:结论:NIPS筛查胎儿SCA具有较高的灵敏度、特异性和NPV。结论:NIPS 筛查胎儿 SCA 的敏感性、特异性和 NPV 均较高,SCA 的 PPV 中等,但 45,X 的 PPV 低于 SCT。建议对高风险患者进行侵入性产前诊断。
{"title":"Performance of noninvasive prenatal screening for fetal sex chromosome aneuploidies in a cohort of 116,862 pregnancies.","authors":"Yanfei Xu, Jianbo Lou, Yeqing Qian, Pengzhen Jin, Yangwen Qian, Jiawei Hong, Yuqing Xu, Yixuan Yin, Songjia Yi, Minyue Dong","doi":"10.1080/14737159.2024.2333951","DOIUrl":"10.1080/14737159.2024.2333951","url":null,"abstract":"<p><strong>Background: </strong>Noninvasive prenatal screening (NIPS) has shown good performance in screening common aneuploidies. However, its performance in detecting fetal sex chromosome aneuploidies (SCAs) needs to be evaluated in a large cohort.</p><p><strong>Research design and methods: </strong>In this retrospective observation, a total of 116,862 women underwent NIPS based on DNA nanoball sequencing from 2015 to 2022. SCAs were diagnosed based on karyotyping or chromosomal microarray analysis (CMA). Among them, 2,084 singleton pregnancies received karyotyping and/or CMA. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of NIPS for fetal SCAs were evaluated.</p><p><strong>Results: </strong>The sensitivity was 97.7% (95%CI, 87.7-99.9), 87.3% (95% CI, 76.5-94.4), 96.1% (95%CI, 86.5-99.5), and 95.7% (95% CI, 78.1-99.9), the PPV was 25.8% (95%CI, 19.2-33.2), 80.9% (95%CI, 69.5-89.4), 79.0% (95%CI, 66.8-88.3), and 53.7% (95%CI, 37.4-69.3) for 45,X, 47,XXY, 47,XXX, and 47,XYY, respectively. The specificity was 94.1% (95%CI, 93.0-95.1) for 45,X, and more than 99.0% for sex chromosome trisomy (SCT). The NPV was over 99.0% for all.</p><p><strong>Conclusions: </strong>NIPS screening for fetal SCAs has high sensitivity, specificity and NPV. The PPV of SCAs was moderate, but that of 45,X was lower than that of SCTs. Invasive prenatal diagnosis should be recommended for high-risk patients.</p>","PeriodicalId":12113,"journal":{"name":"Expert Review of Molecular Diagnostics","volume":" ","pages":"467-472"},"PeriodicalIF":5.1,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140206551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Association between NUDT17 polymorphisms and breast cancer risk. NUDT17 多态性与乳腺癌风险之间的关系。
IF 5.1 3区 医学 Q1 PATHOLOGY Pub Date : 2024-05-01 Epub Date: 2024-05-17 DOI: 10.1080/14737159.2024.2353700
Junhui Han, Jing Liang, Wenqian Zhou, Man Zhang, Tianbo Jin

Background: Breast cancer (BC) is the leading cause of cancer death among women worldwide. The nudix hydrolase 17 (NUDT17) may play notable roles in cancer growth and metastasis. In this study, we explored the importance of NUDT17 gene polymorphism in patients with BC.

Methods: In our study, 563 BC patients and 552 healthy controls participated. We used logistic regression analysis to calculate odds ratios (OR) and 95% confidence intervals (CI), and multifactor dimension reduction (MDR) analysis of SNP-SNP interactions. Finally, UALCAN and THPA databases were used for bioinformatics analysis.

Results: The rs9286836 G allele was associated with a decreased the BC risk (p = 0.022), and the carriers of rs2004659 G allele had a 32% decreased risk of BC than individuals with allele A (p = 0.004). In the four genetic models, rs9286836 and rs2004659 reduced the risk of BC. Additionally, we found that the NUDT17 SNPs were associated with BC risk under age, tumor size, and clinical stage stratification. The MDR analysis showed that the five-locus interaction model was the best in the multi-locus model.

Conclusion: Our study found that NUDT17 single nucleotide polymorphisms are associated with BC susceptibility in Chinese Han population.

背景:乳腺癌(BC)是全球女性癌症死亡的主要原因。nudix hydrolase 17(NUDT17)可能在癌症的生长和转移过程中发挥显著作用。本研究探讨了 NUDT17 基因多态性在 BC 患者中的重要性:在我们的研究中,有 563 名 BC 患者和 552 名健康对照者参与。我们使用逻辑回归分析计算几率比(OR)和95%置信区间(CI),并对SNP-SNP相互作用进行多因素降维(MDR)分析。最后,利用 UALCAN 和 THPA 数据库进行生物信息学分析:结果:rs9286836 G 等位基因与 BC 风险降低有关(p = 0.022),rs2004659 G 等位基因携带者的 BC 风险比等位基因 A 的个体降低 32%(p = 0.004)。在四个遗传模型中,rs9286836 和 rs2004659 可降低 BC 风险。此外,我们还发现,在年龄、肿瘤大小和临床分期分层的情况下,NUDT17 SNP 与 BC 风险相关。MDR分析表明,五病灶交互作用模型在多病灶模型中是最好的:我们的研究发现,NUDT17单核苷酸多态性与中国汉族人群的BC易感性有关。
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引用次数: 0
Practical considerations for pathological diagnosis and molecular profiling of cholangiocarcinoma: an expert review for best practices. 胆管癌病理诊断和分子图谱分析的实用注意事项:最佳实践专家评论。
IF 5.1 3区 医学 Q1 PATHOLOGY Pub Date : 2024-05-01 Epub Date: 2024-05-16 DOI: 10.1080/14737159.2024.2353696
Matt Evans, Timothy Kendall

Introduction: Advances in precision medicine have expanded access to targeted therapies and demand for molecular profiling of cholangiocarcinoma (CCA) patients in routine clinical practice. However, pathologists face challenges in establishing a definitive intrahepatic CCA (iCCA) diagnosis while preserving sufficient tissue for molecular profiling. Additionally, they frequently face challenges in optimal tissue handling to preserve nucleic acid integrity.

Areas covered: This article first identifies the challenges in establishing a definitive diagnosis of iCCA in a lesional liver biopsy while preserving sufficient tissue for molecular profiling. Then, the authors explore the clinical value of molecular profiling, the basic principles of single gene and next-generation sequencing (NGS) techniques, and the challenges in tissue sampling for genomic testing. They also propose an algorithm for best practice in tissue management for molecular profiling of CCA.

Expert opinion: Several practical challenges face pathologists during tissue sampling and processing for molecular profiling. Optimized tissue processing, careful tissue handling, and selection of appropriate approaches to molecular testing are essential to ensure that the highest possible quality of diagnostic information is provided in the greatest proportion of cases.

导言:精准医疗的进步扩大了靶向治疗的可及性,常规临床实践中对胆管癌(CCA)患者进行分子图谱分析的需求也随之增加。然而,病理学家在确定肝内 CCA(iCCA)明确诊断的同时又要保留足够的组织进行分子图谱分析时面临着挑战。此外,他们还经常面临如何以最佳方式处理组织以保持核酸完整性的挑战:本文首先指出了在病变肝活检中明确诊断 iCCA,同时保留足够的组织进行分子分析所面临的挑战。然后,作者探讨了分子图谱分析的临床价值、单基因和下一代测序 (NGS) 技术的基本原理以及基因组测试组织取样的挑战。他们还提出了一种用于 CCA 分子图谱分析的组织管理最佳实践算法:病理学家在组织取样和处理过程中面临着一些实际挑战。优化组织处理、谨慎组织处理以及选择合适的分子检测方法对于确保为尽可能多的病例提供最高质量的诊断信息至关重要。
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引用次数: 0
Sample-to-result molecular diagnostic platforms and their suitability for infectious disease testing in low- and middle-income countries. 样本到结果分子诊断平台及其对中低收入国家传染病检测的适用性。
IF 5.1 3区 医学 Q1 PATHOLOGY Pub Date : 2024-05-01 Epub Date: 2024-05-15 DOI: 10.1080/14737159.2024.2353690
Anne Hauner, Chukwuemeka Onwuchekwa, Kevin K Ariën

Introduction: Diagnostics are an essential, undervalued part of the health-care system. For many diseases, molecular diagnostics are the gold standard, but are not easy to implement in Low- and Middle-Income Countries (LMIC). Sample-to-result (S2R) platforms combining all procedures in a closed system could offer a solution. In this paper, we investigated their suitability for implementation in LMIC.

Areas covered: A scorecard was used to evaluate different platforms on a range of parameters. Most platforms scored fairly on the platform itself, ease-of-use and test consumables; however, shortcomings were identified in cost, distribution and test panels tailored to LMIC needs. The diagnostic coverage for common infectious diseases was found to have a wider coverage in high-income countries (HIC) than LMIC. A literature study showed that in LMIC, these platforms are mainly used as diagnostic tools or evaluation of diagnostic performance, with a minority assessing the operational characteristics or the clinical utility. In this narrative review, we identified various points for adaptation of S2R platforms to LMIC conditions.

Expert opinion: For S2R platforms to be suitable for implementation in LMIC some modifications by the manufacturers could be considered. Furthermore, strengthening health systems and digitalization are vital; as are smaller, cheaper, faster, and sustainable technologies.

导言:诊断是医疗保健系统中不可或缺且价值被低估的一部分。对于许多疾病而言,分子诊断是黄金标准,但在中低收入国家(LMIC)却不容易实施。将所有程序整合到一个封闭系统中的样本到结果(S2R)平台可以提供一种解决方案。在本文中,我们研究了这些平台是否适合在中低收入国家实施:采用记分卡对不同平台的一系列参数进行评估。大多数平台在平台本身、易用性和检测耗材方面得分相当高;但也发现了成本、配送和针对低收入和中等收入国家需求的检测面板方面的不足。研究发现,高收入国家对常见传染病的诊断覆盖面要比低收入国家广。一项文献研究显示,在低收入和中等收入国家,这些平台主要用作诊断工具或评估诊断性能,只有少数平台评估操作特性或临床效用。在这篇叙述性综述中,我们提出了使 S2R 平台适应低收入和中等收入国家条件的各种要点:要使 S2R 平台适合在低收入与中等收入国家实施,可考虑由制造商进行一些修改。此外,加强卫生系统和数字化也至关重要;更小、更便宜、更快和可持续的技术也同样重要。
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引用次数: 0
Prognostic biomarkers in melanoma: a 2023 update from clinical trials in different therapeutic scenarios. 黑色素瘤的预后生物标志物:2023 年不同治疗方案临床试验的最新进展。
IF 5.1 3区 医学 Q1 PATHOLOGY Pub Date : 2024-05-01 Epub Date: 2024-05-13 DOI: 10.1080/14737159.2024.2347484
Gabriele Roccuzzo, Cristina Sarda, Valentina Pala, Simone Ribero, Pietro Quaglino

Introduction: Over the past decade, significant advancements in the field of melanoma have included the introduction of a new staging system and the development of immunotherapy and targeted therapies, leading to changes in substage classification and impacting patient prognosis. Despite these strides, early detection remains paramount. The quest for dependable prognostic biomarkers is ongoing, given melanoma's unpredictable nature, especially in identifying patients at risk of relapse. Reliable biomarkers are critical for informed treatment decisions.

Areas covered: This review offers a comprehensive review of prognostic biomarkers in the context of clinical trials for immunotherapy and targeted therapy. It explores different clinical scenarios, including adjuvant, metastatic, and neo-adjuvant settings. Key findings suggest that tumor mutational burden, PD-L1 expression, IFN-γ signature, and immune-related factors are promising biomarkers associated with improved treatment responses.

Expert opinion: Identifying practical prognostic factors for melanoma therapy is challenging due to the tumor's heterogeneity. Promising biomarkers include tumor mutational burden (TMB), circulating tumor DNA, and those characterizing the tumor microenvironment, especially the immune component. Future research should prioritize large-scale, prospective studies to validate and standardize these biomarkers, emphasizing clinical relevance and real-world applicability. Easily accessible biomarkers have the potential to enhance the precision and effectiveness of melanoma management.

简介在过去的十年中,黑色素瘤领域取得了重大进展,包括引入了新的分期系统,开发了免疫疗法和靶向疗法,从而改变了亚分期分类,影响了患者的预后。尽管取得了这些进展,但早期检测仍然至关重要。鉴于黑色素瘤的不可预测性,特别是在识别有复发风险的患者方面,对可靠的预后生物标志物的探索仍在继续。可靠的生物标志物对于做出明智的治疗决定至关重要:本综述全面回顾了免疫疗法和靶向疗法临床试验中的预后生物标志物。它探讨了不同的临床情况,包括辅助治疗、转移治疗和新辅助治疗。主要研究结果表明,肿瘤突变负荷、PD-L1表达、IFN-γ特征和免疫相关因素是有希望改善治疗反应的生物标志物:由于肿瘤的异质性,确定黑色素瘤治疗的实用预后因素具有挑战性。有希望的生物标志物包括肿瘤突变负荷(TMB)、循环肿瘤DNA以及肿瘤微环境特征,尤其是免疫成分。未来的研究应优先考虑大规模、前瞻性的研究,以验证这些生物标志物并使其标准化,同时强调临床相关性和实际应用性。易于获取的生物标志物有可能提高黑色素瘤治疗的精确性和有效性。
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Expert Review of Molecular Diagnostics
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