CRISPR-Cas12a Biosensor Array for Ultrasensitive Detection of Unamplified DNA with Single-Nucleotide Polymorphic Discrimination.

Quantitative polymerase chain reaction as a powerful tool for DNA detection has been pivotal to a vast range of applications, including disease screening, food safety assessment, environmental monitoring, and many others. However, the essential target amplification step in combination with fluorescence readout poses a significant challenge to rapid and streamlined analysis. The discovery and engineering of the clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) technology have recently paved the way for a novel approach to nucleic acid detection, but the majority of current CRISPR-mediated DNA detection platforms are limited by insufficient sensitivity and still require target preamplification. Herein, we report a CRISPR-Cas12a-mediated graphene field-effect transistor (gFET) array, named CRISPR Cas12a-gFET, for amplification-free, ultrasensitive, and reliable detection of both single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) targets. CRISPR Cas12a-gFET leverages the multiturnover trans-cleavage activity of CRISPR Cas12a for intrinsic signal amplification and ultrasensitivity of gFET. As demonstrated, CRISPR Cas12a-gFET achieves a limit of detection of 1 aM for the ssDNA human papillomavirus 16 synthetic target and 10 aM for the dsDNA Escherichia coli plasmid target without target preamplification. In addition, an array of 48 sensors on a single 1.5 cm × 1.5 cm chip is employed to improve data reliability. Finally, Cas12a-gFET demonstrates the capability to discriminate single-nucleotide polymorphisms. Together, the CRISPR Cas12a-gFET biosensor array provides a detection tool for amplification-free, ultrasensitive, reliable, and highly specific DNA detections.

What matters most: Randomized controlled trial of breast cancer surgery conversation aids across socioeconomic strata.

BACKGROUND: Women of lower socioeconomic status (SES) with early-stage breast cancer are more likely to report poorer physician-patient communication, lower satisfaction with surgery, lower involvement in decision making, and higher decision regret compared to women of higher SES. The objective of this study was to understand how to support women across socioeconomic strata in making breast cancer surgery choices. METHODS: We conducted a 3-arm (Option Grid, Picture Option Grid, and usual care), multisite, randomized controlled superiority trial with surgeon-level randomization. The Option Grid (text only) and Picture Option Grid (pictures plus text) conversation aids were evidence-based summaries of available breast cancer surgery options on paper. Decision quality (primary outcome), treatment choice, treatment intention, shared decision making (SDM), anxiety, quality of life, decision regret, and coordination of care were measured from T0 (pre-consultation) to T5 (1-year after surgery. RESULTS: Sixteen surgeons saw 571 of 622 consented patients. Patients in the Picture Option Grid arm (n = 248) had higher knowledge (immediately after the visit [T2] and 1 week after surgery or within 2 weeks of the first postoperative visit [T3]), an improved decision process (T2 and T3), lower decision regret (T3), and more SDM (observed and self-reported) compared to usual care (n = 257). Patients in the Option Grid arm (n = 66) had higher decision process scores (T2 and T3), better coordination of care (12 weeks after surgery or within 2 weeks of the second postoperative visit [T4]), and more observed SDM (during the surgical visit [T1]) compared to usual care arm. Subgroup analyses suggested that the Picture Option Grid had more impact among women of lower SES and health literacy. Neither intervention affected concordance, treatment choice, or anxiety. CONCLUSIONS: Paper-based conversation aids improved key outcomes over usual care. The Picture Option Grid had more impact among disadvantaged patients. LAY SUMMARY: The objective of this study was to understand how to help women with lower incomes or less formal education to make breast cancer surgery choices. Compared with usual care, a conversation aid with pictures and text led to higher knowledge. It improved the decision process and shared decision making (SDM) and lowered decision regret. A text-only conversation aid led to an improved decision process, more coordinated care, and higher SDM compared to usual care. The conversation aid with pictures was more helpful for women with lower income or less formal education. Conversation aids with pictures and text helped women make better breast cancer surgery choices.

Text-only and picture conversation aids both supported shared decision making for breast cancer surgery: Analysis from a cluster randomized trial.

OBJECTIVES: To determine if two encounter conversation aids for early-stage breast cancer surgery increased observed and patient-reported shared decision making (SDM) compared with usual care and if observed and patient-reported SDM were associated. METHODS: Surgeons in a cluster randomized trial at four cancer centers were randomized to use an Option Grid, Picture Option Grid, or usual care. We used bivariate statistics, linear regression, and multilevel models to evaluate the influence of trial arm, patient socioeconomic status and health literacy on observed SDM (via OPTION-5) and patient-reported SDM (via collaboRATE). RESULTS: From 311 recordings, OPTION-5 scores were 73/100 for Option Grid (n = 40), 56.3/100 for Picture Option Grid (n = 144), and 41.0/100 for usual care (n = 127; p < 0.0001). Top collaboRATE scores were 81.6 % for Option Grid, 80.0 % for Picture Option Grid, and 56.4 % for usual care (p < 0.001). Top collaboRATE scores correlated with an 8.60 point (95 %CI 0.66, 13.7) higher OPTION-5 score (p = 0.008) with no correlation in the multilevel analysis. Patients of lower socioeconomic status had lower OPTION-5 scores before accounting for clustering. CONCLUSIONS: Both conversation aids led to meaningfully higher observed and patient-reported SDM. Observed and patient-reported SDM were not strongly correlated. PRACTICE IMPLICATIONS: Healthcare providers could implement these conversation aids in real-world settings.