Health improvement framework for actionable treatment planning using a surrogate Bayesian model

効果的な健康改善プランを提案するAIを開発 --個別化医療における健康介入への活用に期待--. 京都大学プレスリリース. 2021-05-28.Clinical decision-making regarding treatments based on personal characteristics leads to effective health improvements. Machine learning (ML) has been the primary concern of diagnosis support according to comprehensive patient information. A prominent issue is the development of objective treatment processes in clinical situations. This study proposes a framework to plan treatment processes in a data-driven manner. A key point of the framework is the evaluation of the actionability for personal health improvements by using a surrogate Bayesian model in addition to a high-performance nonlinear ML model. We first evaluate the framework from the viewpoint of its methodology using a synthetic dataset. Subsequently, the framework is applied to an actual health checkup dataset comprising data from 3132 participants, to lower systolic blood pressure and risk of chronic kidney disease at the individual level. We confirm that the computed treatment processes are actionable and consistent with clinical knowledge for improving these values. We also show that the improvement processes presented by the framework can be clinically informative. These results demonstrate that our framework can contribute toward decision-making in the medical field, providing clinicians with deeper insights

Seed-coat protective neolignans are produced by the dirigent protein AtDP1 and the laccase AtLAC5 in Arabidopsis

種子を保護するネオリグナンの生合成機構を解明 --新たな薬効成分の創出に期待--. 京都大学プレスリリース. 2020-12-03.Lignans/neolignans are generally synthesized from coniferyl alcohol (CA) in the cinnamate/monolignol pathway by oxidation to generate the corresponding radicals with subsequent stereoselective dimerization aided by dirigent proteins (DIRs). Genes encoding oxidases and DIRs for neolignan biosynthesis have not been identified previously. In Arabidopsis thaliana, the DIR AtDP1/AtDIR12 plays an essential role in the 8-O-4′ coupling in neolignan biosynthesis by unequivocal structural determination of the compound missing in the atdp1 mutant as a sinapoylcholine (SC)-conjugated neolignan, erythro-3-{4-[2-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-1-hydroxymethylethoxy]-3, 5-dimethoxyphenyl}acryloylcholine. Phylogenetic analyses showed that AtDP1/AtDIR12 belongs to the DIR-a subfamily composed of DIRs for 8-8′ coupling of monolignol radicals. AtDP1/AtDIR12 is specifically expressed in outer integument 1 cells in developing seeds. As a putative oxidase for neolignan biosynthesis, we focused on AtLAC5, a laccase gene coexpressed with AtDP1/AtDIR12. In lac5 mutants, the abundance of feruloylcholine (FC)-conjugated neolignans decreased to a level comparable to those in the atdp1 mutant. In addition, SC/FC-conjugated neolignans were missing in the seeds of mutants defective in SCT/SCPL19, an enzyme that synthesizes SC. These results strongly suggest that AtDP1/AtDIR12 and AtLAC5 are involved in neolignan biosynthesis via SC/FC. A tetrazolium penetration assay showed that seed coat permeability increased in atdp1 mutants, suggesting a protective role of neolignans in A. thaliana seeds

Identification of a tomato UDP-arabinosyltransferase for airborne volatile reception

植物間コミュニケーションの仕組みを解明 --受容した香りを防御物質に変える遺伝子発見--. 京都大学プレスリリース. 2023-02-28.Volatiles from herbivore-infested plants function as a chemical warning of future herbivory for neighboring plants. (Z)-3-Hexenol emitted from tomato plants infested by common cutworms is taken up by uninfested plants and converted to (Z)-3-hexenyl β-vicianoside (HexVic). Here we show that a wild tomato species (Solanum pennellii) shows limited HexVic accumulation compared to a domesticated tomato species (Solanum lycopersicum) after (Z)-3-hexenol exposure. Common cutworms grow better on an introgression line containing an S. pennellii chromosome 11 segment that impairs HexVic accumulation, suggesting that (Z)-3-hexenol diglycosylation is involved in the defense of tomato against herbivory. We finally reveal that HexVic accumulation is genetically associated with a uridine diphosphate-glycosyltransferase (UGT) gene cluster that harbors UGT91R1 on chromosome 11. Biochemical and transgenic analyses of UGT91R1 show that it preferentially catalyzes (Z)-3-hexenyl β-D-glucopyranoside arabinosylation to produce HexVic in planta

Early and long?term outcomes of endoscopic submucosal dissection for early gastric cancer in a large patient series

Endoscopic submucosal dissection (ESD) enables the curative resection of early gastric cancer (EGC); however, little information is available on the long-term outcomes of ESD. This study was conducted to clarify the clinical outcomes of a large number of patients with EGC who underwent ESD. The early outcomes were assessed in 1,209 patients and the long-term outcomes were assessed in 300 patients at a follow-up >5 years after the ESD procedure. The overall survival rates were compared between indication and expanded-indication groups, and between the patients who did or did not undergo additional surgery in an out-of-indication group. Overall survival rates were also compared among different age groups. In total, 617 lesions were classed as the indication group, 507 as the expanded-indication group and 208 as the out-of-indication group. Curative resection rates were 96.6% and 91.5% in the indication and expanded-indication groups, respectively. In terms of the long-term outcomes, 20 of the 146 patients in the indication group, 15 of the 105 patients in the expanded-indication group and one of the 23 patients who underwent additional surgery in the out-of-indication group succumbed due to causes other than gastric cancer. Among the 26 patients who did not undergo additional surgery in the out-of-indication group, 10 mortalities occurred, including one due to gastric cancer. The five-year survival rates were not significantly different between the indication and expanded-indication groups. In the out-of-indication group, the five-year survival rate for the patients who did not undergo additional surgery (65.0%) was significantly lower than that for those who did undergo additional surgery (100%) (P80 years (67.1%) was significantly lower than that of the younger patients (<60 years, 91.6%; sixties, 93.0%; seventies, 84.5%) (P<0.0001). In conclusion, although expanded-indication of ESD for EGC is appropriate, comorbidities require consideration in elderly patients

FANCD1/BRCA2 Plays Predominant Role in the Repair of DNA Damage Induced by ACNU or TMZ

Nimustine (ACNU) and temozolomide (TMZ) are DNA alkylating agents which are commonly used in chemotherapy for glioblastomas. ACNU is a DNA cross-linking agent and TMZ is a methylating agent. The therapeutic efficacy of these agents is limited by the development of resistance. In this work, the role of the Fanconi anemia (FA) repair pathway for DNA damage induced by ACNU or TMZ was examined. Cultured mouse embryonic fibroblasts were used: FANCA−/−, FANCC−/−, FANCA−/−C−/−, FANCD2−/− cells and their parental cells, and Chinese hamster ovary and lung fibroblast cells were used: FANCD1/BRCA2mt, FANCG−/− and their parental cells. Cell survival was examined after a 3 h ACNU or TMZ treatment by using colony formation assays. All FA repair pathways were involved in ACNU-induced DNA damage. However, FANCG and FANCD1/BRCA2 played notably important roles in the repair of TMZ-induced DNA damage. The most effective molecular target correlating with cellular sensitivity to both ACNU and TMZ was FANCD1/BRCA2. In addition, it was found that FANCD1/BRCA2 small interference RNA efficiently enhanced cellular sensitivity toward ACNU and TMZ in human glioblastoma A172 cells. These findings suggest that the down-regulation of FANCD1/BRCA2 might be an effective strategy to increase cellular chemo-sensitization towards ACNU and TMZ

The Hobby–Eberly Telescope Dark Energy Experiment (HETDEX) Survey Design, Reductions, and Detections

We describe the survey design, calibration, commissioning, and emission-line detection algorithms for the Hobby–Eberly Telescope Dark Energy Experiment (HETDEX). The goal of HETDEX is to measure the redshifts of over a million Lyα emitting galaxies between 1.88 < z < 3.52, in a 540 deg2 area encompassing a comoving volume of 10.9 Gpc3. No preselection of targets is involved; instead the HETDEX measurements are accomplished via a spectroscopic survey using a suite of wide-field integral field units distributed over the focal plane of the telescope. This survey measures the Hubble expansion parameter and angular diameter distance, with a final expected accuracy of better than 1%. We detail the project’s observational strategy, reduction pipeline, source detection, and catalog generation, and present initial results for science verification in the Cosmological Evolution Survey, Extended Groth Strip, and Great Observatories Origins Deep Survey North fields. We demonstrate that our data reach the required specifications in throughput, astrometric accuracy, flux limit, and object detection, with the end products being a catalog of emission-line sources, their object classifications, and flux-calibrated spectra