Accurate identification of tumor-derived somatic variants in plasma circulating cell-free DNA (cfDNA) requires understanding the various biologic compartments contributing to the cfDNA pool. We sought to define the technical feasibility of a high-intensity sequencing assay of cfDNA and matched white-blood cell (WBC) DNA covering a large genomic region (508 genes, 2Mb, >60,000X raw-depth) in a prospective study of 124 metastatic cancer patients, with contemporaneous matched tumor tissue biopsies, and 47 non-cancer controls. The assay displayed a high sensitivity and specificity, allowing for de novo detection of tumor-derived mutations and inference of tumor mutational burden, microsatellite instability, mutational signatures and sources of somatic mutations identified in cfDNA. The vast majority of cfDNA mutations (81.6% in controls and 53.2% in cancer patients) had features consistent with clonal hematopoiesis (CH). This cfDNA sequencing approach revealed that CH constitutes a pervasive biological phenomenon emphasizing the importance of matched cfDNA-WBC sequencing for accurate variant interpretation.
T he scientific, academic, medical and data science communities have come together in the face of the COVID-19 pandemic crisis to rapidly assess novel paradigms in artificial intelligence (AI) that are rapid and secure, and potentially incentivize data sharing and model training and testing without the usual privacy and data ownership hurdles of conventional collaborations 1,2 . Healthcare providers, researchers and industry have pivoted their focus to address unmet and critical clinical needs created by the crisis, with remarkable results [3][4][5][6][7][8][9] . Clinical trial recruitment has been expedited and facilitated by national regulatory bodies and an international cooperative spirit 10-12 . The data analytics and AI disciplines have always fostered open
The increased intra-abdominal pressure (IAP) commonly observed when the spine is loaded during physical activities is hypothesized to increase lumbar spine stability. The mechanical stability of the lumbar spine is an important consideration in low back injury prevention and rehabilitation strategies. This study examined the effects of raised IAP and an abdominal belt on lumbar spine stability. Two hypotheses were tested: (1) An increase in IAP leads to increased lumbar spine stability, (2) Wearing an abdominal belt increases spine stability. Ten volunteers were placed in a semi-seated position in a jig that restricted hip motion leaving the upper torso free to move in any direction. The determination of lumbar spine stability was accomplished by measuring the instantaneous trunk stiffness in response to a sudden load release. The quick release method was applied in isometric trunk flexion, extension, and lateral bending. Activity of 12 major trunk muscles was monitored with electromyography and the IAP was measured with an intra-gastric pressure transducer. A two-factor repeated measures design was used (P < 0.05), in which the spine stability was evaluated under combinations of the following two factors: belt or no belt and three levels of IAP (0, 40, and 80% of maximum). The belt and raised IAP increased trunk stiffness in all directions, but the results in extension lacked statistical significance. In flexion, trunk stiffness increased by 21% and 42% due to 40% and 80% IAP levels respectively; in lateral bending, trunk stiffness increased by 16% and 30%. The belt added between 9% and 57% to the trunk stiffness depending on the IAP level and the direction of exertion. In all three directions, the EMG activity of all 12 trunk muscles increased significantly due to the elevated IAP. The belt had no effect on the activity of any of the muscles with the exception of the thoracic erector spinae in extension and the lumbar erector spinae in flexion, whose activities decreased. The results indicate that both wearing an abdominal belt and raised IAP can each independently, or in combination, increase lumbar spine stability. However, the benefits of the belt must be interpreted with caution in the context of the decreased activation of a few trunk extensor muscles.
The purpose of this study was to determine whether transcatheter arterial chemoembolization (TACE) protocol affects the total volume of chemotherapy injected into the liver as well as subsequent arterial patency. A total of 160 patients with primary or secondary liver cancer were treated with 3 different chemoembolization protocols at a single institution. Data were analyzed retrospectively. Group 1 (n ϭ 36) consisted of slurry of chemotherapy, oil and polyvinyl alcohol particles (PVA), group 2 (n ϭ 91), chemotherapy and oil followed by PVA, and group 3 (n ϭ 33), chemotherapy and oil followed by Gelfoam pledgets. The total volume of chemotherapy injected into the liver was recorded. Arterial patency was determined during subsequent chemoembolizations. The mean percentage of total intended chemotherapy dose administered was 54.6% for group 1, 75.3% for group 2, and 80.6% for group 3. Arterial patency at follow-up angiography was 56% for group 1, 74% for group 2, and 81% for group 3. The slurry protocol (group 1) significantly reduced arterial patency and injectable volume of chemotherapy during TACE.
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