Comprehensive Genomic Profiling of Neuroendocrine Carcinomas of the Gastrointestinal System

The neuroendocrine carcinoma of the gastrointestinal system (GIS-NEC) is a rare but highly malignant neoplasm. We analyzed 115 cases using whole-genome/exome sequencing, transcriptome sequencing, DNA methylation assays, and/or ATAC-seq and found GIS-NECs to be genetically distinct from neuroendocrine tumors (GIS-NET) in the same location. Clear genomic differences were also evident between pancreatic NECs (Panc-NEC) and nonpancreatic GIS-NECs (Nonpanc-NEC). Panc-NECs could be classified into two subgroups (i.e., "ductal-type" and "acinar-type") based on genomic features. Alterations in TP53 and RB1 proved common in GIS-NECs, and most Nonpanc-NECs with intact RB1 demonstrated mutually exclusive amplification of CCNE1 or MYC. Alterations of the Notch gene family were characteristic of Nonpanc-NECs. Transcription factors for neuroendocrine differentiation, especially the SOX2 gene, appeared overexpressed in most GIS-NECs due to hypermethylation of the promoter region. This first comprehensive study of genomic alterations in GIS-NECs uncovered several key biological processes underlying genesis of this very lethal form of cancer. SIGNIFICANCE: GIS-NECs are genetically distinct from GIS-NETs. GIS-NECs arising in different organs show similar histopathologic features and share some genomic features, but considerable differences exist between Panc-NECs and Nonpanc-NECs. In addition, Panc-NECs could be classified into two subgroups (i.e., "ductal-type" and "acinar-type") based on genomic and epigenomic features. This article is highlighted in the In This Issue feature, p. 587

Effect of the binder content on the electrochemical performance of composite cathode using Li6PS5Cl precursor solution in an all-solid-state lithium battery

All-solid-state batteries with cathode composites containing high concentration of active materials are required to achieve higher energy densities. Here, a composite cathode containing up to 89 wt% of high-voltage cathode active material (LiNi1/3Mn1/3Co1/3O2) was prepared by covering this with a solution-derived solid electrolyte (argyrodite, Li6PS5Cl) and the incorporation of different content binder (ethyl cellulose). All-solid-state batteries were fabricated using 80Li(2)Sa (TM) 20P(2)S(5) (mol%) glass and indium metal as a solid electrolyte and anode, respectively. The all-solid-state battery with a composite cathode containing 0.5 wt% of ethyl cellulose showed an initial discharge capacity of 45 mAhg(-1) at 25 A degrees C and maintained 91.7% of the discharge capacity after ten cycles, around 30% higher than that obtained for the battery with the composite cathode without a binder

Simple Preparation of Pd Core Nanoparticles for Pd Core/Pt Shell Catalyst and Evaluation of Activity and Durability for Oxygen Reduction Reaction

Pd core nanoparticles less than 5 nm in mean size were prepared on carbon black (CB) without any stabilizer by using palladium acetate as a precursor and CO as a reducing agent, and then used for preparing Pd core/Pt shell nanoparticles-loaded CB (Pt/Pd/CB). The mean size of Pd nanoparticles could be controlled by the concentration of palladium acetate and the CO bubbling time. The cyclic voltammograms of two Pd nanoparticles-loaded CB (Pd4.2/CB, Pd3.3/CB) electrodes whose mean size was 4.2 and 3.3 nm, respectively, had characteristics similar to a Pt electrode after the formation of a Pt monolayer shell, suggesting that the Pd core nanoparticles were almost covered with the Pt monolayer shell. The oxygen reduction reaction (ORR) on both Pt/Pd/CB proceeded in 4-electron reduction mechanism. Both Pt/Pd/CB electrodes was ca. 1.5 times higher in ORR activity per electrochemical surface area of Pt (specific activity, SA) than the commercial Pt nanoparticles-loaded CB (Tanaka Kikinzoku Kogyo, Pt/CB-TKK) electrode, and the Pt/Pd3.3/CB electrode had higher SA than the Pt/Pd4.2/CB electrode. The ORR activity per unit mass of Pt for both Pt/Pd/CB electrodes was 5.0 and 5.5 times as high as that for the Pt/CB-TKK electrode, respectively. The durability of both Pt/Pd/CB electrodes was comparable to that of Pt/CB-TKK

Effective shape of ball-and-socket prosthesis in restoring range of thumb motion for total thumb carpometacarpal joint arthroplasty: three-dimensional motion analysis

Abstract Purpose Total joint arthroplasty (TJA) has often been used to treat thumb carpometacarpal (CMC) osteoarthritis (OA). However, guidelines for the CMC prosthesis shape remain unclear. This study aimed to identify the effective shape of a ball-and-socket prosthesis in restoring the range of thumb motion after TJA. Methods The participants were 10 healthy young adult men (22–32 years; 26.8 ± 3.57 [mean ± SD]). CT scans were performed in eight static limb positions during abduction and flexion. We defined three design variables (offset R, height H, and neck rotation angle Φ) as the variables that determine the basic shape of the ball-and-socket prosthesis. The ideal values of these design variables were examined based on the results of a 3D motion analysis, which evaluated the change in the posture of the first metacarpal (r, h, and φ corresponding to R, H, and Φ, respectively) relative to the center of rotation (COR) during abduction and flexion. We also simulated the effect of these design variables on the range of thumb motion after TJA using 3D CAD. Results We found that the values of r and h averaged over all limb positions were 6.92 ± 1.60 mm and 51.02 ± 1.67 mm, respectively, showing that these values remained constant regardless of limb position. In contrast, φ changed significantly. The simulation results indicated that Φ affected the range of thumb motion after TJA, and Φ = 0° relatively reproduced all limb positions compared to other values. Conclusion Our results suggested that the desirable values of R and H were the average of r and h over several limb positions and that Φ = 0° was effective in restoring the range of thumb motion after TJA. Our results will provide surgeons with new guidelines for selecting a prosthesis

Home‐based cardiac rehabilitation using information and communication technology for heart failure patients with frailty

Abstract Aims Cardiac rehabilitation (CR) is an evidence‐based, secondary preventive strategy that improves mortality and morbidity rates in patients with heart failure (HF). However, the implementation and continuation of CR remains unsatisfactory, particularly for outpatients with physical frailty. This study investigated the efficacy and safety of a comprehensive home‐based cardiac rehabilitation (HBCR) programme that combines patient education, exercise guidance, and nutritional guidance using information and communication technology (ICT). Methods and results This study was a single‐centre, open‐label, randomized, controlled trial. Between April 2020 and November 2020, 30 outpatients with chronic HF (New York Heart Association II–III) and physical frailty were enrolled. The control group (n = 15) continued with standard care, while the HBCR group (n = 15) also received comprehensive, individualized CR, including ICT‐based exercise and nutrition guidance using ICT via a Fitbit® device for 3 months. The CR team communicated with each patient in HBCR group once a week via the application messaging tool and planned the training frequency and intensity of training individually for the next week according to each patient's symptoms and recorded pulse data during exercise. Dietitians conducted a nutritional assessment and then provided individual nutritional advice using the picture‐posting function of the application. The primary outcome was the change in the 6 min walking distance (6MWD). The participants' mean age was 63.7 ± 10.1 years, 53% were male, and 87% had non‐ischaemic heart disease. The observed change in the 6MWD was significantly greater in the HBCR group (52.1 ± 43.9 m vs. −4.3 ± 38.8 m; P < 0.001) at a 73% of adherence rate. There was no significant change in adverse events in either group. Conclusions Our comprehensive HBCR programme using ICT for HF patients with physical frailty improved exercise tolerance and improved lower extremity muscle strength in our sample, suggesting management with individualized ICT‐based programmes as a safe and effective approach. Considering the increasing number of HF patients with frailty worldwide, our approach provides an efficient method to keep patients engaged in physical activity in their daily life