High Amino Acid Lattice Loading at Nonambient Conditions Causes Changes in Structure and Expansion Coefficient of Calcite

Biogenic crystals produced by organisms have been known for several decades to exhibit intracrystalline organic macromolecules. Here, using a reductionist approach, we tackle the question of whether the incorporation of single amino acids is driven by kinetics or by thermodynamics. We show that when calcite is grown in the presence of amino acids under nonambient conditions, extremely high loading levels of up to 6.12 mol % of aspartic acid (Asp) are achieved. This incorporation leads to marked changes in the host calcite crystal's structure and expansion coefficient. The latter is as much as twice as high as that of pure calcite. This is the first example showing that an organic molecule incorporated into an inorganic host can strongly affect the expansion coefficient. Most importantly, we show that the incorporation of amino acids in calcite is controlled by their thermodynamic solubility in calcite rather than kinetically and that hybrid amino acid-calcite crystals can indeed be considered a solid solution

Clinical utility of circulating tumor DNA sequencing with a large panel: a National Center for Precision Medicine (PRISM) study

Background: Circulating tumor DNA (ctDNA) sequencing is a promising approach for tailoring therapy in patients with cancer. We report hereby the results from a prospective study where we investigated the impact of comprehensive molecular profiling of ctDNA in patients with advanced solid tumors. Patients and Methods: Genomic analysis was performed using the FoundationOne Liquid CDx Assay [324 genes, tumor mutational burden (TMB), microsatellite instability status]. Each individual genomic report was reviewed and discussed weekly by a multidisciplinary tumor board (MTB). Actionable targets were classified by ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT) tier leading to molecular-based treatment suggestions wherever it was possible. Results: Between December 2020 and November 2021, 1772 patients with metastatic solid tumors underwent molecular profiling. Median time to assay results was 12 days. Results were contributive for 1658 patients (94%). At least one actionable target was detected in 1059 patients (64%) with a total of 1825 actionable alterations including alteration of the DNA damage repair response pathway (n = 336, 18%), high TMB (>16 mutations/Mb; n = 243, 13%), PIK3CA mutations (n = 150, 8%), ERBB family pathway alterations (n = 127, 7%), PTEN alterations (n = 95, 5%), FGFR alterations (n = 67, 4%) and MET activations (n = 13, 0.7%). The MTB recommended a matched therapy for 597 patients (56%) with a total of 819 therapeutic orientations: clinical trials (n = 639, 78%), off-label/compassionate use (n = 81, 10%), approved drug (n = 51, 6%), and early access program (n = 48, 6%). In total, 122 patients (21%) were treated. Among the assessable patients (n = 107), 4 (4%) had complete response, 35 (33%) had partial response, 27 (25%) had stable disease, and 41 (38%) a progressive disease as best response. The median progression-free survival and median overall survival were 4.7 months (95% confidence interval 2.7-6.7 months) and 8.3 months (95% confidence interval 4.7-11.9 months) respectively. Conclusions: ctDNA sequencing with a large panel is an efficient approach to match patients with advanced cancer with targeted therapies