TP53 somatic evolution in cervical liquid-based cytology and blood from individuals with and without ovarian cancer and BRCA1 or BRCA2 germline mutations.

Somatic TP53 mutations are prevalent in normal tissue but little is known about their association with cancer risk. Cervical liquid-based cytology (LBC), commonly known as Pap test, provides an accessible gynecological sample to test the value of TP53 somatic mutations as a biomarker for high-grade serous ovarian cancer (HGSC), a cancer type mostly driven by TP53 mutations. We used ultra-deep duplex sequencing to analyze TP53 mutations in LBC and blood samples from 70 individuals (30 with and 40 without HGSC) undergoing gynecologic surgery, 30 carrying BRCA1 or BRCA2 germline pathogenic variants (BRCApv).

'Walking together': How relationships shape physicians' clinical reasoning.

Introduction: The clinical reasoning literature has increasingly considered context as an important influence on physicians' thinking. Physicians' relationships with patients, and their ongoing efforts to maintain these relationships, are important influences on how clinical reasoning is contextualised. The authors sought to understand how physicians' relationships with patients shaped their clinical reasoning.

How to Keep Training-After Residency Training.

Lifelong learning in medicine is an important skill and ethical obligation, but many residents do not feel prepared to be effective self-directed learners when training ends. The learning sciences offer evidence to guide self-directed learning, but these insights have not been integrated into a practical and actionable plan for residents to improve their clinical knowledge and reasoning. We encourage residents to establish a self-directed learning plan, just as an athlete employs a training plan in the pursuit of excellence.

Characterization of TP53 mutations in Pap test DNA of women with and without serous ovarian carcinoma.

Objective: Pap tests hold promise as a molecular diagnostic for serous ovarian cancer, but previous studies reported limited sensitivity. Furthermore, the presence of somatic mutations in normal tissue is increasingly recognized as a challenge to the specificity of mutation-based cancer diagnostics. We applied an ultra-deep sequencing method with the goal of improving sensitivity and characterizing the landscape of low-frequency somatic TP53 mutations in Pap tests.