Value of Real-World Evidence for Treatment Selection: A Case Study in Colon Cancer.

PURPOSE: Real-world evidence (RWE)-derived from analysis of real-world data (RWD)-has the potential to guide personalized treatment decisions. However, because of potential confounding, generating valid RWE is challenging. This study demonstrates how to responsibly generate RWE for treatment decisions. We validate our approach by demonstrating that we can uncover an existing adjuvant chemotherapy (ACT) guideline for stage II and III colon cancer (CC)-which came about using both data from randomized controlled trials and expert consensus-solely using RWD. METHODS: Data from the population-based Netherlands Cancer Registry from a total of 27,056 patients with stage II and III CC who underwent curative surgery were analyzed to estimate the overall survival (OS) benefit of ACT. Focusing on 5-year OS, the benefit of ACT was estimated for each patient using G-computation methods by adjusting for patient and tumor characteristics and estimated propensity score. Subsequently, on the basis of these estimates, an ACT decision tree was constructed. RESULTS: The constructed decision tree corresponds to the current Dutch guideline: patients with stage III or stage II with T stage 4 should receive surgery and ACT, whereas patients with stage II with T stage 3 should only receive surgery. Interestingly, we do not find sufficient RWE to conclude against ACT for stage II with T stage 4 and microsatellite instability-high (MSI-H), a recent addition to the current guideline. CONCLUSION: RWE, if used carefully, can provide a valuable addition to our construction of evidence on clinical decision making and therefore ultimately affect treatment guidelines. Next to validating the ACT decisions advised in the current Dutch guideline, this paper suggests additional attention should be paid to MSI-H in future iterations of the guideline.

Shift in the rhizosphere soil fungal community associated with root rot infection of Plukenetia volubilis Linneo caused by Fusarium and Rhizopus species.

BACKGROUND: Plukenetia volubilis Linneo is an oleaginous plant belonging to the family Euphorbiaceae. Due to its seeds containing a high content of edible oil and rich in vitamins, P. volubilis is cultivated as an economical plant worldwide. However, the cultivation and growth of P. volubilis is challenged by phytopathogen invasion leading to production loss. METHODS: In the current study, we tested the pathogenicity of fungal pathogens isolated from root rot infected P. volubilis plant tissues by inoculating them into healthy P. volubilis seedlings. Metagenomic sequencing was used to assess the shift in the fungal community of P. volubilis rhizosphere soil after root rot infection. RESULTS: Four Fusarium isolates and two Rhizopus isolates were found to be root rot causative agents of P. volubilis as they induced typical root rot symptoms in healthy seedlings. The metagenomic sequencing data showed that root rot infection altered the rhizosphere fungal community. In root rot infected soil, the richness and diversity indices increased or decreased depending on pathogens. The four most abundant phyla across all samples were Ascomycota, Glomeromycota, Basidiomycota, and Mortierellomycota. In infected soil, the relative abundance of each phylum increased or decreased depending on the pathogen and functional taxonomic classification. CONCLUSIONS: Based on our results, we concluded that Fusarium and Rhizopus species cause root rot infection of P. volubilis. In root rot infected P. volubilis, the shift in the rhizosphere fungal community was pathogen-dependent. These findings may serve as a key point for a future study on the biocontrol of root rot of P. volubilis.

Design and analysis of three-dimensional printing of a porous titanium scaffold.

OBJECTIVE: Mechanic strength, pore morphology and size are key factors for the three-dimensional (3D) printing of porous titanium scaffolds, therefore, developing optimal structure for the 3D printed titanium scaffold to fill bone defects in knee joints is instructive and important. METHODS: Structural models of titanium scaffolds with fifteen different pore unit were designed with 3D printing computer software; five different scaffold shapes were designed: imitation diamond-60°, imitation diamond-90°, imitation diamond-120°, regular tetrahedron and regular hexahedron. Each structural shape was evaluated with three pore sizes (400, 600 and 800 µm), and fifteen types of cylindrical models (size: 20 mm; height: 20 mm). Autodesk Inventor software was used to determine the strength and safety of the models by simulating simple strength acting on the knee joints. We analyzed the data and found suitable models for the design of 3D printing of porous titanium scaffolds. RESULTS: Fifteen different types of pore unit structural models were evaluated under positive pressure and lateral pressure; the compressive strength reduced when the pore size increased. Under torsional pressure, the strengths of the imitation diamond structure were similar when the pore size increased, and the strengths of the regular tetrahedron and regular hexahedron structures reduced when the pore size increased. In each case, the compressive strength of the regular hexahedron structure was highest, that of the regular tetrahedron was second highest, and that of the imitation diamond structure was relatively low. Fifteen types of cylindrical models under a set force were evaluated, and the sequence of comprehensive compressive strength, from strong to weak was: regular hexahedron > regular tetrahedron > imitation diamond-120° > imitation diamond-90° > imitation diamond-60°. The compressive strength of cylinder models was higher when the pore size was smaller. CONCLUSION: The pore size and pore morphology were important factors influencing the compressive strength. The strength of each structure reduced when the pore size (400, 600 and 800 µm) increased. The models of regular hexahedron, regular tetrahedron and imitation diamond-120°appeared to meet the conditions of large pore sizes and high compressive strength.

I2/TBPB mediated oxidative reaction of N-tosylhydrazones with anilines: practical construction of 1,4-disubstituted 1,2,3-triazoles under metal-free and azide-free conditions.

An efficient I2 (20 mol %)/TBPB mediated oxidative formal [4 + 1] cycloaddition of N-tosylhydrazones with anilines via C-N/N-N bond formation and S-N cleavage has been developed. This protocol represents a simple, general, and efficient approach for the construction of 1,2,3-triazoles under metal-free and azide-free conditions by utilizing a catalytic amount of I2.