PTCy, abatacept, and a short course of tacrolimus for GVHD prevention after haploidentical transplantation.

Reducing the incidence of graft-versus-host disease (GVHD) after haploidentical hematopoietic stem cell transplantation (HSCT) is warranted. Posttransplant cyclophosphamide (PTCy) is the main agent used for GVHD prevention in this setting. It remains unknown whether costimulation blockade can be safely combined with PTCy and enhance its efficacy. We performed a phase 1b-2 clinical trial to examine the combination of PTCy, abatacept, and a short course of tacrolimus (CAST) after peripheral blood haploidentical HSCT. The primary end point was the incidence of grades 2-4 acute GVHD by day +120. The study enrolled 46 patients with a median age of 60 years (range, 18-74 years). The cumulative incidences of grades 2-4 and 3 or 4 acute GVHD were 17.4% (95% confidence interval [CI], 9.2-32.9) and 4.4% (95% CI, 1.1-17.1), respectively. With a median follow-up of 15.3 months, the cumulative incidence of 1-year treatment-related mortality was 4.4% (95% CI, 1.1-17.1). The estimated 1-year moderate-to-severe chronic GVHD rate, relapse rate, progression-free survival, overall survival, and GVHD- and relapse-free survival were 15.9% (95% CI, 8-31.7), 11.7% (95% CI, 5-27.2), 84.1% (95% CI, 73.8-95.7), 85.9% (95% CI, 75.9-97.2), and 66.1% (95% CI, 53.4-81.8), respectively. Toxicities were similar to those expected in patients receiving haploidentical HSCT. This clinical trial showed that the CAST regimen is safe and effective in reducing the rate of grades 2-4 acute GVHD after haploidentical peripheral blood HSCT. This trial was registered at www.clinicaltrials.gov as #NCT04503616.

Mechanisms of Hydrogen-Assisted CO2 Reduction on Nickel.

Mechanistic details of catalytic reactions are critical to the development of improved catalysts. Here, we perform high quality Born-Oppenheimer molecular dynamics simulations of the reaction mechanisms associated with hydrogen-assisted CO2 reduction on Ni(110). The simulation results show direct theoretical evidence for both associative and redox mechanisms in the reaction of atomic hydrogen with CO2. Because H2 is dissociatively chemisorbed on Ni(110) with nearly unit probability, the mechanisms we find are also relevant to the reverse water-gas shift reaction (H2 with adsorbed CO2). Furthermore, we provide the first real-time demonstration of both Eley-Rideal (ER) and hot atom (HA) mechanisms when H impinges on adsorbed CO2, and we show that both occur even for low kinetic energies. The trade-off between ER or HA mechanisms is found to be strongly dependent on CO2 coverage. The results are compared with recent gas/surface measurements.

A Method for Creating Thermal and Angular Momentum Fluxes in Nonperiodic Simulations.

We present a new reverse nonequilibrium molecular dynamics method that can be used with nonperiodic simulation cells. This method applies thermal and/or angular momentum fluxes between two arbitrary regions of the simulation and is capable of creating stable temperature and angular velocity gradients while conserving total energy and angular momentum. One particularly useful application is the exchange of kinetic energy between two concentric spherical regions, which can be used to generate thermal transport between nanoparticles and the solvent that surrounds them. The rotational couple to the solvent (a measure of interfacial friction) is also available via this method. As tests of the new method, we have computed the thermal conductivities of gold nanoparticles and water clusters, the interfacial thermal conductivity (G) of a solvated gold nanoparticle, and the interfacial friction of a variety of solvated gold nanostructures.

The Langevin Hull: Constant pressure and temperature dynamics for non-periodic systems.

We have developed a new isobaric-isothermal (NPT) algorithm which applies an external pressure to the facets comprising the convex hull surrounding the system. A Langevin thermostat is also applied to the facets to mimic contact with an external heat bath. This new method, the "Langevin Hull", can handle heterogeneous mixtures of materials with different compressibilities. These systems are problematic for traditional affine transform methods. The Langevin Hull does not suffer from the edge effects of boundary potential methods, and allows realistic treatment of both external pressure and thermal conductivity due to the presence of an implicit solvent. We apply this method to several different systems including bare metal nanoparticles, nanoparticles in an explicit solvent, as well as clusters of liquid water. The predicted mechanical properties of these systems are in good agreement with experimental data and previous simulation work.