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Abstract Liquid biopsies have the potential to revolutionize cancer care through non-invasive early detection of tumors. Developing a robust liquid biopsy test requires collecting high-dimensional data from a large number of blood samples across heterogeneous groups of patients. We propose that the generative capability of variational auto-encoders enables learning a robust and generalizable signature of blood-based biomarkers. In this study, we analyze orphan non-coding RNAs (oncRNAs) from serum samples of 1050 individuals diagnosed with non-small cell lung cancer (NSCLC) at various stages, as well as sex-, age-, and BMI-matched controls. We demonstrate that our multi-task generative AI model, Orion, surpasses commonly used methods in both overall performance and generalizability to held-out datasets. Orion achieves an overall sensitivity of 94% (95% CI: 87%–98%) at 87% (95% CI: 81%–93%) specificity for cancer detection across all stages, outperforming the sensitivity of other methods on held-out validation datasets by more than ~ 30%.

Summary: Microsatellite instability-high (MSI-H) tumors are malignant tumors that, despite harboring a high mutational burden, often have intact TP53. One of the most frequent mutations in MSI-H tumors is a frameshift mutation in RPL22, a ribosomal protein. Here, we identified RPL22 as a modulator of MDM4 splicing through an alternative splicing switch in exon 6. RPL22 loss increases MDM4 exon 6 inclusion and cell proliferation and augments resistance to the MDM inhibitor Nutlin-3a. RPL22 represses the expression of its paralog, RPL22L1, by mediating the splicing of a cryptic exon corresponding to a truncated transcript. Therefore, damaging mutations in RPL22 drive oncogenic MDM4 induction and reveal a common splicing circuit in MSI-H tumors that may inform therapeutic targeting of the MDM4-p53 axis and oncogenic RPL22L1 induction.

Introduction: Pneumonia vaccination rates have increased to >60% over the last 20 years. At the Long Island, New York, Northport VA Hospital, pneumonia vaccination data from 2021 showed a vaccination rate of 68.55%. The goal is a pneumonia vaccination rate of 85%. Pneumonia vaccines prevent invasive pneumococcal disease and pneumococcal pneumonia. The authors aimed to increase vaccination rates at Northport. Methods: The authors established a weekly vaccine and prevention clinic aiming to vaccinate as many veterans as possible. Preventive medicine residents performed outreach, scheduling, vaccine administration, and Brief Action Planning. Motivational interviewing techniques were used in outreach calls and clinic visits to encourage behavioral change. Results: From an outreach list >7,000 patients, 506 patients were contacted and counseled on pneumonia vaccination. A total of 130 patients were scheduled for clinic visits. Of these 130, 91 kept their appointments and were seen in the clinic, and 87 vaccines were administered, of which 56 were pneumonia vaccines. Data were collected and analyzed in 2022. Conclusions: Implementing a dedicated vaccine and prevention clinic using motivational interviewing techniques in outreach and clinical visits allows for optimized patient vaccinations, enhanced information sharing, increased primary care retention, and increasing visibility of preventive medicine among patients and colleagues within the Veterans Affairs medical system.