Preoperative staging of the axilla in women with invasive breast cancer using ultrasound-guided needle biopsy(UNB) identifies approximately 50% of patients with axillary nodal metastases prior to surgical intervention...Preoperative staging of the axilla in women with invasive breast cancer using ultrasound-guided needle biopsy(UNB) identifies approximately 50% of patients with axillary nodal metastases prior to surgical intervention. Although moderately sensitive, it is a highly specific staging strategy that is rarely falsely-positive, hence a positive UNB allows patients to be triaged to axillary lymph-node dissection(ALND) avoiding potentially unnecessary sentinel node biopsy(SNB). In this review, we extend our previous work through an updated literature search, focusing on studies that report data on UNB utility. Based on data for 10,934 breast cancer patients, sourced from 35 studies, a positive UNB allowed triage of 1,745 cases(simple proportion 16%) to axillary surgical treatment: the utility of UNB was a median 19.8% [interquartile range(IQR) 11.6%-26.7%] across these studies. We also modelled data from a subgroup of studies, and estimated that amongst patients with metastases to axillary nodes, the odds ratio(OR) for high nodal disease burden for a positive UNB versus a negative UNB was 4.38 [95% confidence interval(95% CI): 3.13, 6.13], P<0.001. From this model, the estimated proportion with high nodal disease burden was 58.9%(95% CI: 50.2%, 67.0%) for a positive UNB, whereas the estimated proportion with high nodal disease burden was 24.6%(95% CI: 17.7%, 33.2%) if UNB was negative. Overall, axillary UNB has good clinical utility and a positive UNB can effectively triage to ALND. However, the evolving landscape of axillary surgical treatment means that UNB will have relatively less utility where surgeons have modified their practice to omission of ALND for minimal nodal metastatic disease.展开更多
CRISPR-Cas系统是广泛存在于细菌和古菌中的防御系统。基于该系统开发的基因组编辑工具已在大量物种中实现靶向编辑。目前应用最多的是CRISPR-Cas9和CRISPR-Cas12a基因组编辑工具,但它们的蛋白大小均超过1000个氨基酸,不利于递送。来自...CRISPR-Cas系统是广泛存在于细菌和古菌中的防御系统。基于该系统开发的基因组编辑工具已在大量物种中实现靶向编辑。目前应用最多的是CRISPR-Cas9和CRISPR-Cas12a基因组编辑工具,但它们的蛋白大小均超过1000个氨基酸,不利于递送。来自转座子家族的TnpB和IscB蛋白(大小约400个氨基酸)分别被认为是Cas12和Cas9的祖先蛋白,但其功能直到最近才被解析。它们被统称为专性移动元件引导活性(obligate mobile element-guided activity, OMEGA)蛋白,其引导RNA被称为ωRNA。此后,OMEGA系统成为了基因编辑领域的研究热点之一。OMEGA系统在三域生物中都有广泛分布,而且种类多样。对OMEGA系统的深入研究,将有助于开发精简、高效、安全的新型基因组编辑工具。本文围绕OMEGA系统的发现历程、结构特点、作用机制和在基因组编辑中的应用展开介绍,为新型基因组编辑工具的开发和优化提供参考。展开更多
基金partly funded by National Health and Medical Research Council (NHMRC) program (Grant No. 633003) to the Screening & Test Evaluation Program, Australia
文摘Preoperative staging of the axilla in women with invasive breast cancer using ultrasound-guided needle biopsy(UNB) identifies approximately 50% of patients with axillary nodal metastases prior to surgical intervention. Although moderately sensitive, it is a highly specific staging strategy that is rarely falsely-positive, hence a positive UNB allows patients to be triaged to axillary lymph-node dissection(ALND) avoiding potentially unnecessary sentinel node biopsy(SNB). In this review, we extend our previous work through an updated literature search, focusing on studies that report data on UNB utility. Based on data for 10,934 breast cancer patients, sourced from 35 studies, a positive UNB allowed triage of 1,745 cases(simple proportion 16%) to axillary surgical treatment: the utility of UNB was a median 19.8% [interquartile range(IQR) 11.6%-26.7%] across these studies. We also modelled data from a subgroup of studies, and estimated that amongst patients with metastases to axillary nodes, the odds ratio(OR) for high nodal disease burden for a positive UNB versus a negative UNB was 4.38 [95% confidence interval(95% CI): 3.13, 6.13], P<0.001. From this model, the estimated proportion with high nodal disease burden was 58.9%(95% CI: 50.2%, 67.0%) for a positive UNB, whereas the estimated proportion with high nodal disease burden was 24.6%(95% CI: 17.7%, 33.2%) if UNB was negative. Overall, axillary UNB has good clinical utility and a positive UNB can effectively triage to ALND. However, the evolving landscape of axillary surgical treatment means that UNB will have relatively less utility where surgeons have modified their practice to omission of ALND for minimal nodal metastatic disease.
文摘CRISPR-Cas系统是广泛存在于细菌和古菌中的防御系统。基于该系统开发的基因组编辑工具已在大量物种中实现靶向编辑。目前应用最多的是CRISPR-Cas9和CRISPR-Cas12a基因组编辑工具,但它们的蛋白大小均超过1000个氨基酸,不利于递送。来自转座子家族的TnpB和IscB蛋白(大小约400个氨基酸)分别被认为是Cas12和Cas9的祖先蛋白,但其功能直到最近才被解析。它们被统称为专性移动元件引导活性(obligate mobile element-guided activity, OMEGA)蛋白,其引导RNA被称为ωRNA。此后,OMEGA系统成为了基因编辑领域的研究热点之一。OMEGA系统在三域生物中都有广泛分布,而且种类多样。对OMEGA系统的深入研究,将有助于开发精简、高效、安全的新型基因组编辑工具。本文围绕OMEGA系统的发现历程、结构特点、作用机制和在基因组编辑中的应用展开介绍,为新型基因组编辑工具的开发和优化提供参考。
