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BH3 mimetics are protein-protein interaction (PPI) inhibitors that saturate anti-apoptotic proteins in the BCL2 family to lift the resistance of cancer cells to apoptosis, a prominent example of protein complex-targeting therapies1–4. Despite the remarkable success of the BH3 mimetic ABT-199 in treating hematological malignancies5–7, only a fraction of patients respond to ABT-1998–10and eventually develop resistance11, 12, necessitating the usage of predictive biomarkers for both initial responses and resistance development. We here used the single-molecule pull-down13, 14and co-immunoprecipitation (co-IP)15, 16platform to quantify more than 20 different types of PPI complexes using ∼1.2x106cells in total, revealing the latest rewired status of the BCL2-family PPI network. By comparing the obtained multi-dimensional data with BH3 mimetic efficacies determinedex vivo, we constructed an analysis model for ABT-199 efficacy. Our model designates the BCL2-BAX and BCLxL-BAK complexes to contrasting roles, with the former complex driving ABT- 199 efficacy and the latter contributing to resistance development. We then applied this model to assist in therapeutic decision-making for acute myeloid leukemia patients in a prospective manner. Our work demonstrates a capability for the extensive characterization of PPI complexes in clinical specimens, potentially opening up a new avenue of precision medicine for protein complex-targeting therapies.

To evaluate the effect of a motion artifact correction algorithm (MACA) on cone-beam computed tomography (CT) during transarterial chemoembolization for hepatic malignancies.From June 2020 to March 2021, 42 patients with mild-to-severe motion artifacts detected using single cone-beam CT scans were evaluated retrospectively. The image quality of native and motion-corrected data was compared. The maximum intensity, sharpness, and full width at half maximum (FWHM) of 5 segmental hepatic arteries were quantitatively measured. The overall quality of maximum intensity projection (MIP) images, conspicuity of tumor-supplying arteries, and need for selective angiography to ascertain the vascular anatomy were qualitatively evaluated by multiple readers. Paired t and Wilcoxon signed rank tests were used to compare the parameters.The mean maximum intensity and sharpness increased from 2,792.01 HU ± 451.36 to 3,148.40 HU ± 594.46 and from 0.31 ± 0.02/mm to 0.34 ± 0.02/mm, respectively, using the MACA (both P.001). The MACA decreased the mean FWHM from 2.02 mm ± 0.27 to 1.78 mm ± 0.26 (P.001). The overall quality of the MIP images and the conspicuity of the tumor-supplying artery were enhanced from 2.5 to 3.0 points and from 3.0 to 4.0 points, respectively (both P.001). Selective angiography was expected to be omitted in 7 cases (16.7%, 7/42) after using the MACA.The MACA significantly improved both quantitative and qualitative image quality of cone-beam CT in selected patients with motion artifacts during transarterial chemoembolization for hepatic malignancies.

Physical activity reduces the risk of colon cancer, but its prognostic impact after cancer diagnosis remains unclear. To evaluate the association between post-diagnosis activity and cause-specific mortality, we reconstructed a colorectal cancer patient cohort from the 2009–16 Korean National Health Insurance Service (NHIS) database. Subgroup analyses were performed by treatment group. In total, 27,143 colon cancer patients and 16,453 rectal cancer patients were included in the analysis (mean follow-up, 4.3 years, median 4.0 years). In the surgically treated group, a high level of activity (the weighted sum of the frequencies for walking, moderate, and vigorous activity greater than or equal to 3 times/week) was inversely associated with all-cause mortality (colon cancer: HR, 0.79, 95% CI, 0.72 to 0.88, rectal cancer: HR, 0.75, 95% CI, 0.66 to 0.86) and colorectal cancer-specific mortality (colon cancer: HR, 0.85, 95% CI, 0.76 to 0.97, rectal cancer: HR, 0.77, 95% CI, 0.66 to 0.90). No significant results were shown for cardiovascular disease-specific mortality. No association was shown in patients who received chemoradiotherapy without surgery. The present study may provide evidence for post-diagnosis physical activity as a prognostic factor in colorectal cancer, particularly in surgically treated early-stage patients.

To date, documentation of two doses of measles-containing vaccine (MCV) has been accepted as confirmation of measles immunity among healthcare workers (HCWs). However, we encountered measles in an HCW who had received two doses of MCV. A patient with measles was admitted to our hospital. Among 62 exposed HCWs, one nurse who had previously received two doses of MCV was shown to be negative for anti-measles immunoglobulin G (IgG), and was confirmed to have measles 14 days after exposure. Based on this experience, we suggest that all HCWs should be tested for anti-measles IgG to confirm their immunity to measles.