Effect of belimumab in patients with systemic lupus erythematosus treated with low dose or no corticosteroids

Background/Aims Systemic lupus erythematosus (SLE) responder index (SRI)-4 response has been achieved with belimumab treatment in patients with moderate disease activity in cornerstone clinical trials and following studies. However, most studies involved patients treated with a mean prednisolone-equivalent dose of approximately 10 mg/d and focused on the steroid-sparing effect of belimumab. We aimed to identify the effect of belimumab in patients with mild-to-moderate SLE who were treated with low-dose or no corticosteroids. Methods We retrospectively reviewed the electronic medical records of patients treated with belimumab for at least 6 months between May 2021 and June 2022. The primary endpoint was SRI-4 response at 6 months. Results Thirty-one patients were included (13 low dose- and 18 steroid non-users). The mean age was 39.2 ± 11.4 years, and 90.3% of patients were female. The baseline Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) score was 6.0 (4.0–9.0). The primary endpoint was achieved in 32.3% (10/31) of patients. Significant improvements in anemia, C4 levels, and SELENA-SLEDAI score were observed during treatment. Univariate analysis showed that the baseline SELENA-SLEDAI and arthritis were significantly associated with SRI-4 response at 6 months, and only the SELENA-SLEDAI remained significant (p = 0.014) in multivariate analysis. Conclusions This cohort study is the first to report the efficacy of belimumab after minimizing the effect of corticosteroids. Belimumab showed efficacy in improving the SELENA-SLEDAI score, anemia, and low C4 in patients who did not receive corticosteroids or received only low doses

Decision tree-based approach for online management of PEM fuel cells for residential application

This thesis demonstrates a new intelligent technique for the online optimal management of PEM fuel cells units for onsite energy production to supply residential utilizations. Classical optimization techniques are based on offline calculations and cannot provide the necessary computational speed for online performance. In this research, a Decision Tree (DT) algorithm is employed to obtain the optimal, or quasioptimal, settings of the fuel cell online and in a general framework. The main idea is to employ a classification technique, trained on a sufficient subset of data, to produce an estimate of the optimal setting without repeating the optimization process. A database is extracted from a previously-performed Genetic Algorithm (GA)-based optimization has been used to create a suitable decision tree, which was intended for generalizing the optimization results. The approach provides the flexibility of adjusting the settings of the fuel cell online according to the observed variations in the tariffs and load demands. Results at different operating conditions are presented to confirm the high accuracy of the proposed generalization technique. The accuracy of the decision tree has been tested by evaluating the relative error with respect to the optimized values. Then, the possibility of pruning the tree has been investigated in order to simplify its structure without affecting the accuracy of the results. In addition, the accuracy of the DTs to approximate the optimal performance of the fuel cell is compared to that of the Artificial Neural Networks (ANNs) used for the same purpose. The results show that the DTs can somewhat outperform the ANNs with certain pruning levels

Prefoldin 5 and Anti-prefoldin 5 Antibodies as Biomarkers for Uveitis in Ankylosing Spondylitis

Objective: Uveitis is the most common extra-articular manifestation of ankylosing spondylitis (AS), for which no diagnostic biomarkers have been identified. This study was conducted to identify biomarker for uveitis in AS.Methods: To identify autoantibodies associated with uveitis in AS, we performed human protein microarray analysis using sera derived from various autoimmune diseases and ELISA analysis of sera derived from AS and rheumatoid arthritis patients. In the curdlan-induced SKG mice model, ophthalmic examination was performed at week 8 post-immunization and histologic examination of the ocular lesions performed at week 16 post-immunization. Serum levels of target antibodies were assessed at various time-points. To evaluate the functional role of specific autoantibodies, an in vitro apoptosis assay using ARPE-19 cells was performed.Results: Reactivity against prefoldin subunit 5 (PFDN5) was identified in AS with uveitis. Levels of anti-PFDN5 antibodies and PFDN5 in sera from AS with uveitis patients were significantly higher than those in AS without uveitis. At week 8, half of curdlan-treated SKG mice developed anterior uveitis, while all of them developed histologically confirmed uveitis at week 16. The levels of anti-PFDN5 antibodies increased over time in the sera of curdlan-treated SKG mice along with increased expression of PFDN5 and apoptosis in the ocular lesions. Knockdown of PFDN5 in ARPE19 cells resulted in increased apoptosis, suggesting a protective role of PFDN5 against cell death in uveitis.Conclusion: AS patients with uveitis have increased levels of anti-PFDN5 antibodies, and our findings suggest that anti-PFDN5 antibodies could provide a biomarker for uveitis in AS

Laser scanning reflection-matrix microscopy for aberration-free imaging through intact mouse skull

A mouse skull is a barrier for high-resolution optical imaging because its thick and inhomogeneous internal structures induce complex aberrations varying drastically from position to position. Invasive procedures creating either thinned-skull or open-skull windows are often required for the microscopic imaging of brain tissues underneath. Here, we propose a label-free imaging modality termed laser scanning reflection-matrix microscopy for recording the amplitude and phase maps of reflected waves at non-confocal points as well as confocal points. The proposed method enables us to find and computationally correct up to 10,000 angular modes of aberrations varying at every 10 × 10 µm2 patch in the sample plane. We realized reflectance imaging of myelinated axons in vivo underneath an intact mouse skull, with an ideal diffraction-limited spatial resolution of 450 nm. Furthermore, we demonstrated through-skull two-photon fluorescence imaging of neuronal dendrites and their spines by physically correcting the aberrations identified from the reflection matrix11Nsci

High-throughput volumetric adaptive optical imaging using compressed time-reversal matrix

Deep-tissue optical imaging suffers from the reduction of resolving power due to tissue-induced optical aberrations and multiple scattering noise. Reflection matrix approaches recording the maps of backscattered waves for all the possible orthogonal input channels have provided formidable solutions for removing severe aberrations and recovering the ideal diffraction-limited spatial resolution without relying on fluorescence labeling and guide stars. However, measuring the full input-output response of the tissue specimen is time-consuming, making the real-time image acquisition difficult. Here, we present the use of a time-reversal matrix, instead of the reflection matrix, for fast high-resolution volumetric imaging of a mouse brain. The time-reversal matrix reduces two-way problem to one-way problem, which effectively relieves the requirement for the coverage of input channels. Using a newly developed aberration correction algorithm designed for the time-reversal matrix, we demonstrated the correction of complex aberrations using as small as 2% of the complete basis while maintaining the image reconstruction fidelity comparable to the fully sampled reflection matrix. Due to nearly 100-fold reduction in the matrix recording time, we could achieve real-time aberration-correction imaging for a field of view of 40 x 40 mu m(2) (176 x 176 pixels) at a frame rate of 80 Hz. Furthermore, we demonstrated high-throughput volumetric adaptive optical imaging of a mouse brain by recording a volume of 128 x 128 x 125 mu m(3) (568 x 568 x 125 voxels) in 3.58 s, correcting tissue aberrations at each and every 1 mu m depth section, and visualizing myelinated axons with a lateral resolution of 0.45 mu m and an axial resolution of 2 mu m.11Nsciescopu