Axial chirality around N-P bonds induced by complexation between E(C6F5)3 (E = B, Al) and an N-phosphine oxide-substituted imidazolinylidene: A key intermediate in the catalytic phosphinoylation of CO2

Complexation-induced axial chirality around an N-P bond occurs upon the predominant coordination of the N-phosphinoyl group in the N-phosphine oxide-substituted imidazolinylidene (SPoxIm) to B(C6F5)3. (Ra) and (Sa) atropisomers of (κ-O-SPoxIm)B(C6F5)3 were observed independently in the single-crystal lattice and the optimized gas-phase structure. Experimental and theoretical studies confirmed that this axial chirality arises from the restricted rotation around the N-P bond, caused by the steric repulsion between the C5-H atoms of the imidazolinylidene ring and the C6F5 rings on the B(C6F5)3 unit. Conversely, this axial chirality was not certainly observed via the complexation between SPoxIm and Al(C6F5)3. The carbene carbon atoms in (κ-O-SPoxIm)E(C6F5)3 (E = B, Al) remain sufficiently nucleophilic to react with CO2, and the phosphinoylation of CO2 with SPoxIm proceeds far more rapidly in the presence of a catalytic amount of Al(C6F5)3 than in the absence of Al(C6F5)3Asada T., Hoshimoto Y., Kawakita T., et al. Axial chirality around N-P bonds induced by complexation between E(C6F5)3 (E = B, Al) and an N-phosphine oxide-substituted imidazolinylidene: A key intermediate in the catalytic phosphinoylation of CO2. Journal of Organic Chemistry 85, 14333 (2020); https://doi.org/10.1021/acs.joc.9b03210

Room-Temperature Reversible Chemisorption of Carbon Monoxide on Nickel(0) Complexes

Chemisorption on organometallic-based adsorbents is crucial for the controlled separation and long-term storage of gaseous molecules. The formation of covalent bonds between the metal centers in the adsorbents and the targeted gases affects the desorption efficiency, especially when the oxidation state of the metal is low. Herein, we report a pressure-responsive nickel(0)-based system that is able to reversibly chemisorb carbon monoxide (CO) at room temperature. The use of N-heterocyclic carbene ligands with hemi-labile N-phosphine oxide substituents facilitates both the adsorption and desorption of CO on nickel(0) via ligand substitution. Ionic liquids were used as the reaction medium to enhance the desorption rate and establish a reusable system. These results showcase a way for the sustainable chemisorption of CO using a zero-valent transition-metal complex.Yamauchi Y., Hoshimoto Y., Kawakita T., et al. Room-Temperature Reversible Chemisorption of Carbon Monoxide on Nickel(0) Complexes. Journal of the American Chemical Society , (2022); https://doi.org/10.1021/jacs.2c02870

Time for aCTIon: Automated Analysis of Cyber Threat Intelligence in the Wild

Cyber Threat Intelligence (CTI) plays a crucial role in assessing risks and enhancing security for organizations. However, the process of extracting relevant information from unstructured text sources can be expensive and time-consuming. Our empirical experience shows that existing tools for automated structured CTI extraction have performance limitations. Furthermore, the community lacks a common benchmark to quantitatively assess their performance. We fill these gaps providing a new large open benchmark dataset and aCTIon, a structured CTI information extraction tool. The dataset includes 204 real-world publicly available reports and their corresponding structured CTI information in STIX format. Our team curated the dataset involving three independent groups of CTI analysts working over the course of several months. To the best of our knowledge, this dataset is two orders of magnitude larger than previously released open source datasets. We then design aCTIon, leveraging recently introduced large language models (GPT3.5) in the context of two custom information extraction pipelines. We compare our method with 10 solutions presented in previous work, for which we develop our own implementations when open-source implementations were lacking. Our results show that aCTIon outperforms previous work for structured CTI extraction with an improvement of the F1-score from 10%points to 50%points across all tasks

A New Candidate Supporting Drug, Rikkunshito, for the QOL in Advanced Esophageal Cancer Patients with Chemotherapy Using Docetaxel/5-FU/CDDP

Purpose. Docetaxel/5-FU/CDDP (DFP) therapy is a useful treatment for advanced esophageal cancer. However, adverse reactions such as chemotherapy-induced nausea and vomiting (CINV) interfere often with continuation of the chemotherapy. We investigated the efficacy of rikkunshito (TJ-43) on CINV. Methods. Nineteen patients who were going to undergo DFP therapy were enrolled. They were assigned to the following two groups: a TJ-43-treated group and -nontreated group. The following parameters were compared between the 2 groups: (1) the frequency of symptoms occurred, (2) vomiting, nausea, and anorexia score, and (3) QOL score. Results. The incidence of symptoms was lower in the TJ-43-treated group than that in the control group. The nausea score of the TJ-43-treated group was significantly lower than that of the control group. In the QOL score, the mood score and the ADL score decreased significantly in the control group. Conclusion. We recommend TJ-43 administration in patients undergoing DFP chemotherapy

Reversible Modulation of the Electronic and Spatial Environment around Ni(0) Centers Bearing Multifunctional Carbene Ligands with Triarylaluminum

Designing and modulating the electronic and spatial environments surrounding metal centers is a crucial issue in a wide range of chemistry fields that use organometallic compounds. Herein, we demonstrate a Lewis-acid-mediated reversible expansion, contraction, and transformation of the spatial environment surrounding nickel(0) centers that bear N-phosphine oxide-substituted N-heterocyclic carbenes (henceforth referred to as (S)PoxIms). Reaction between tetrahedral (syn-κ-C,O-(S)PoxIm)Ni(CO)2 and Al(C6F5)3 smoothly afforded heterobimetallic Ni/Al species such as trigonal-planar {κ-C-Ni(CO)2}(μ-anti-(S)PoxIm){κ-O-Al(C6F5)3} via a complexation-induced rotation of the N-phosphine oxide moieties, while the addition of 4-dimethylaminopyridine resulted in the quantitative regeneration of the former Ni complexes. The corresponding interconversion also occurred between (SPoxIm)Ni(η2:η2-diphenyldivinylsilane) and {κ-C-Ni(η2:η2-diene)}(μ-anti-SPoxIm){κ-O-Al(C6F5)3} via the coordination and dissociation of Al(C6F5)3. The shape and size of the space around the Ni(0) center was drastically changed through this Lewis-acid-mediated interconversion. Moreover, the multinuclear NMR, IR, and XAS analyses of the aforementioned carbonyl complexes clarified the details of the changes in the electronic states on the Ni centers; i.e., the electron delocalization was effectively enhanced among the Ni atom and CO ligands in the heterobimetallic Ni/Al species. The results presented in this work thus provide a strategy for reversibly modulating both the electronic and spatial environment of organometallic complexes, in addition to the well-accepted Lewis-base-mediated ligand-substitution methods.Yamauchi Y., Mondori Y., Uetake Y., et al. Reversible Modulation of the Electronic and Spatial Environment around Ni(0) Centers Bearing Multifunctional Carbene Ligands with Triarylaluminum. Journal of the American Chemical Society 145, 16938 (2023); https://doi.org/10.1021/jacs.3c06267

食道扁平上皮癌患者の化学療法効果と予後予測に関わるバイオマーカー

Background: The prognosis of patients with esophageal squamous cell carcinoma (ESCC) has been improved by multidisciplinary therapy with chemoradiotherapy and surgery, but it remains poor. Advanced stage, malignant potential, and chemo-resistance contribute to the poor prognosis. Here, we attempted to identify predictive factors of the response to chemotherapy and the prognosis of ESCC patients. Patients and Methods: We examined 51 ESCC patients who were treated with chemotherapy followed by radical surgery, and 23 patients who were treated with chemotherapy alone. We conducted quantitative reverse transcription polymerase chain reaction gene expression analysis using RNA extracted from 74 tumor tissue samples collected before chemotherapy and 67 tumor tissue samples collected after chemotherapy, focusing on PIK3CA, AKT-1, mTOR, 4E-BP1, p70S6K, PD-L1, and PD-L2. Results: The proportions of patients with high expressions of AKT-1 and PD-L1 before chemotherapy were significantly higher among the non-responders than among the responders (p=0.034, p=0.020, respectively). Multivariate analyses revealed that high PD-L1 expression before chemotherapy was associated with poor response to chemotherapy (odds ratio: 2.998; 95% CI: 1.043–8.619; p=0.042) and high p70S6K expression before chemotherapy was a poor prognostic factor (hazard ratio: 2.518; 95% CI: 1.058–5.988; p=0.037). In addition, the patients with high expression of PD-L1 and PD-L2 in the tumors after chemotherapy had significantly worse survival than those with low expression of these genes (p=0.012, p=0.007, respectively). Conclusion: These results demonstrated that PD-L1 and p70S6K in the primary ESCC tissues were related to a poor response to chemotherapy and poor prognosis, respectively

Adult patients with Ph+ ALL benefit from conditioning regimen of medium‐dose VP16 plus CY/TBI

The medium-dose etoposide (VP16) added on cyclophosphamide (CY)/total body irradiation (TBI) is one of the intensified myeloablative conditioning regimens used in allogenic hematopoietic stem cell transplantation (allo-HSCT) for acute lymphoblastic leukemia (ALL). However, the patient subgroups who can actually benefit from VP16/CY/TBI compared to CY/TBI have not been precisely defined. Therefore, we conducted a multi-center retrospective study using the Japanese nationwide registry database to elucidate the efficacy of VP16/CY/TBI on post-transplant prognosis. Biological and clinical distinct subtypes (i.e., Philadelphia chromosome-positive (Ph+) and -negative (Ph−) ALL) were evaluated separately, which included 820 Ph+ and 1463 patients with Ph− ALL, respectively. Compared with the CY/TBI group, the VP16/CY/TBI group showed superior progression-free survival (PFS) in patients with Ph+ ALL (65% vs. 57% at 3 years after HSCT; adjusted hazard ratio (HR), 0.73; 95% confidence interval (CI), 0.55–0.98; p = 0.03), along with significantly reduced incidence of relapse (adjusted HR, 0.58; 95% CI, 0.37–0.90; p = 0.02) without the increase of non-relapse mortality (NRM). By contrast, in patients with Ph− ALL, VP16/CY/TBI did not improve PFS nor incidence of relapse; addition of VP16 reduced relapse (HR, 0.65; p = 0.06) in patients with Ph− ALL transplanted at CR1, while improved PFS was not observed (HR, 0.90; p = 0.52) due to increased NRM. This study demonstrated that VP16/CY/TBI is a more effective and well-tolerated regimen in comparison with CY/TBI in patients with myeloablative allo-HSCT for adult Ph+ ALL. Our findings can provide a novel algorithm for conditioning regimen selection in patients with adult ALL

Prognostic impact of complex and/or monosomal karyotypes in post‐transplant poor cytogenetic acute myeloid leukaemia: A quantitative approach

To evaluate the prognostic impact of complex karyotype (CK) and/or monosomal karyotype (MK) in combination with various clinical factors on allogeneic stem cell transplantation (HSCT) outcomes of patients with acute myeloid leukaemia (AML), we analysed the registry database of adult AML patients who underwent allogeneic HSCT between 2000 and 2019 in Japan. Among 16 094 patients, those with poor cytogenetic risk (N = 3345) showed poor overall survival (OS) after HSCT (25.3% at 5 years). Multivariate analyses revealed that CK and/or MK (hazard ratio [HR], 1.31 for CK without MK; 1.27 for MK without CK; and 1.73 for both), age at HSCT ≥50 years (HR, 1.58), male sex (HR, 1.40), performance status ≥2 (HR, 1.89), HCT-CI score ≥3 (HR, 1.23), non-remission status at HSCT (HR, 2.49), and time from diagnosis to HSCT ≥3 months (HR, 1.24) independently reduced post-HSCT OS among patients with poor cytogenetic risk AML. A risk scoring system based on the multivariate analysis successfully stratified patients into five distinct groups for OS. This study confirms the negative effects of CK and MK on post-HSCT outcomes, and offers a powerful risk scoring system for predicting prognoses after HSCT among AML patients with unfavourable cytogenetics