Differences among epitopes recognized by neutralizing antibodies induced by SARS-CoV-2 infection or COVID-19 vaccination

SARS-CoV-2 has gradually acquired amino acid substitutions in its S protein that reduce the potency of neutralizing antibodies, leading to decreased vaccine efficacy. Here, we attempted to obtain mutant viruses by passaging SARS-CoV-2 in the presence of plasma samples from convalescent patients or vaccinees to determine which amino acid substitutions affect the antigenicity of SARS-CoV-2. Several amino acid substitutions in the S2 region, as well as the N-terminal domain (NTD) and receptor-binding domain (RBD), affected the neutralization potency of plasma samples collected from vaccinees, indicating that amino acid substitutions in the S2 region as well as those in the NTD and RBD affect neutralization by vaccine-induced antibodies. Furthermore, the neutralizing potency of vaccinee plasma samples against mutant viruses we obtained or circulating viruses differed among individuals. These findings suggest that genetic backgrounds of vaccinees influence the recognition of neutralizing epitopes

Data_Sheet_1_Estimation of minimal detectable change in the 10-meter walking test for patients with stroke: a study stratified by gait speed.docx

ObjectiveThis study aimed to classify and calculate the minimal detectable changes (MDC) in gait time and gait speed in a 10-meter walking test (10MWT) in patients with stroke classified according to their gait speed.MethodsThe participants were 84 patients with stroke. Their gait times were measured twice each at their comfortable gait speed (CGS) and maximum gait speed (MGS) on a 10-meter straight track, and gait speed was calculated using gait time. Participants were assigned to three speed groups based on their CGS: low-speed (0.8 m/s; n = 36). For each group, first and second retest reliability and MDC of CGS and MGS were calculated using gait time and gait speed in the 10MWT.ResultsMDCs in the 10MWT at CGS were: low-speed group, gait time 5.25 s, gait speed 0.05 m/s; moderate-speed group, gait time 2.83 s, gait speed 0.11 m/s; and high-speed group, gait time 1.58 s, gait speed 0.21 m/s. MDCs in the 10MWT at MGS were: low-speed group, gait time 7.26 s, gait speed 0.04 m/s; moderate-speed group, gait time 2.48 s, gait speed 0.12 m/s; and high-speed group, gait time 1.28 s, gait speed 0.19 m/s.ConclusionSince the MDC of gait speed and gait time differ depending on the participant’s gait speed, it is necessary to interpret the results according to the participant’s gait speed when judging the effectiveness of therapeutic interventions.</p

Optimizing shoulder elevation assist rate in exoskeletal rehabilitation based on muscular activity indices: a clinical feasibility study

Abstract Background Restoring shoulder function is critical for upper-extremity rehabilitation following a stroke. The complex musculoskeletal anatomy of the shoulder presents a challenge for safely assisting elevation movements through robotic interventions. The level of shoulder elevation assistance in rehabilitation is often based on clinical judgment. There is no standardized method for deriving an optimal level of assistance, underscoring the importance of addressing abnormal movements during shoulder elevation, such as abnormal synergies and compensatory actions. This study aimed to investigate the effectiveness and safety of a newly developed shoulder elevation exoskeleton robot by applying a novel optimization technique derived from the muscle synergy index. Methods Twelve chronic stroke participants underwent an intervention consisting of 100 robot-assisted shoulder elevation exercises (10 × 10 times, approximately 40 min) for 10 days (4–5 times/week). The optimal robot assist rate was derived by detecting the change points using the co-contraction index, calculated from electromyogram (EMG) data obtained from the anterior deltoid and biceps brachii muscles during shoulder elevation at the initial evaluation. The primary outcomes were the Fugl–Meyer assessment-upper extremity (FMA-UE) shoulder/elbow/forearm score, kinematic outcomes (maximum angle of voluntary shoulder flexion and elbow flexion ratio during shoulder elevation), and shoulder pain outcomes (pain-free passive shoulder flexion range of motion [ROM] and visual analogue scale for pain severity during shoulder flexion). The effectiveness and safety of robotic therapy were examined using the Wilcoxon signed-rank sum test. Results All 12 patients completed the procedure without any adverse events. Two participants were excluded from the analysis because the EMG of the biceps brachii was not obtained. Ten participants (five men and five women; mean age: 57.0 [5.5] years; mean FMA-UE total score: 18.7 [10.5] points) showed significant improvement in the FMA-UE shoulder/elbow/forearm score, kinematic outcomes, and pain-free passive shoulder flexion ROM (P < 0.05). The shoulder pain outcomes remained unchanged or improved in all patients. Conclusions The study presents a method for deriving the optimal robotic assist rate. Rehabilitation using a shoulder robot based on this derived optimal assist rate showed the possibility of safely improving the upper-extremity function in patients with severe stroke in the chronic phase

Crystal Structures and Structure–Activity Relationships of Imidazothiazole Derivatives as IDO1 Inhibitors

Indoleamine 2,3-dioxygenase 1 (IDO1) is considered as a promising target for the treatment of several diseases, including neurological disorders and cancer. We report here the crystal structures of two IDO1/IDO1 inhibitor complexes, one of which shows that Amg-1 is directly bound to the heme iron of IDO1 with a clear induced fit. We also describe the identification and preliminary optimization of imidazothiazole derivatives as novel IDO1 inhibitors. Using our crystal structure information and structure–activity relationships (SAR) at the pocket-B of IDO1, we found a series of urea derivatives as potent IDO1 inhibitors and revealed that generation of an induced fit and the resulting interaction with Phe226 and Arg231 are essential for potent IDO1 inhibitory activity. The results of this study are very valuable for understanding the mechanism of IDO1 activation, which is very important for structure-based drug design (SBDD) to discover potent IDO1 inhibitors

Differences among epitopes recognized by neutralizing antibodies induced by SARS-CoV-2 infection or COVID-19 vaccination

Summary: SARS-CoV-2 has gradually acquired amino acid substitutions in its S protein that reduce the potency of neutralizing antibodies, leading to decreased vaccine efficacy. Here, we attempted to obtain mutant viruses by passaging SARS-CoV-2 in the presence of plasma samples from convalescent patients or vaccinees to determine which amino acid substitutions affect the antigenicity of SARS-CoV-2. Several amino acid substitutions in the S2 region, as well as the N-terminal domain (NTD) and receptor-binding domain (RBD), affected the neutralization potency of plasma samples collected from vaccinees, indicating that amino acid substitutions in the S2 region as well as those in the NTD and RBD affect neutralization by vaccine-induced antibodies. Furthermore, the neutralizing potency of vaccinee plasma samples against mutant viruses we obtained or circulating viruses differed among individuals. These findings suggest that genetic backgrounds of vaccinees influence the recognition of neutralizing epitopes