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We developed the knitted shape-memory alloy (SMA) as a flexible actuator and applied it to a soft wearable exoglove for rehabilitation assistance. Based on user needs and anthropometric data, we custom-designed the exoglove for three hemiplegic patients using the knitted-SMA actuator and evaluated its bending performance, gripping force and wearability under the four simulation conditions (S1–S4). To address the specific needs, both SMA plain- and double-knit modules were applied to the exoglove based on the patients’ finger joint range of motion (ROMs). The joint ROMs of all fingers increased by 13.71% and the skin temperature increased by 2.21 °C after actuating the glove (p = 0.006). The gripping force increased as much as 55.01%, when compared to the baseline. All patients were able to don and doff the developed glove independently, and positively evaluated their subjective satisfaction and thermal perception. The findings suggested the potential of the knitted SMA for the future development of soft wearable robots.

This study aimed to identify hub genes involved in regulatory T cell (Treg) function and migration, offering insights into potential therapeutic targets for cancer immunotherapy. We performed a comprehensive bioinformatics analysis using three gene expression microarray datasets from the GEO database. Differentially expressed genes (DEGs) were identified to pathway enrichment analysis to explore their functional roles and potential pathways. A protein-protein interaction network was constructed to identify hub genes critical for Treg activity. We further evaluated the co-expression of these hub genes with immune checkpoint proteins (PD-1, PD-L1, CTLA4) and assessed their prognostic significance. Through this comprehensive analysis, we identified CCR8 as a key player in Treg migration and explored its potential synergistic effects with ICIs. Our findings suggest that CCR8-targeted therapies could enhance cancer immunotherapy outcomes, with breast invasive carcinoma (BRCA) emerging as a promising indication for combination therapy. This study highlights the potential of CCR8 as a biomarker and therapeutic target, contributing to the development of targeted cancer treatment strategies.

DNA methylation in the promoter region of the glucocorticoid receptor gene (NR3C1) is closely associated with childhood adversity and suicide. However, few studies have examined NR3C1 methylation in relation to major depressive disorder (MDD) and hippocampal subfield volumes. We investigated the possible association between NR3C1 methylation and structural brain alterations in MDD in comparison with healthy controls. We compared the degree of NR3C1 promoter methylation in the peripheral blood of non-psychotic outpatients with MDD and that of healthy controls. Correlations among NR3C1 promoter methylation, structural abnormalities in hippocampal subfield volumes and whole-brain cortical thickness, and clinical variables were also analyzed. In total, 117 participants (45 with MDD and 72 healthy controls) were recruited. Patients with MDD had significantly lower methylation than healthy controls at 2 CpG sites. In MDD, methylations had positive correlations with the bilateral cornu ammonis (CA) 2-3 and CA4-dentate gyrus (DG) subfields. However, in healthy controls, methylations had positive correlation with the subiculum and presubiculum. There were no differences in total and subfield volumes of the hippocampus between patients with MDD and healthy controls. Compared with healthy controls, patients with MDD had a significantly thinner cortex in the left rostromiddle frontal, right lateral orbitofrontal, and right pars triangularis areas. Lower methylation in the NR3C1 promoter, which might have compensatory effects relating to CA2-3 and CA4-DG, is a distinct epigenetic characteristic in non-psychotic outpatients with MDD. Future studies with a longitudinal design and a comprehensive neurobiological approach are warranted in order to elucidate the effects of NR3C1 methylation.

Background and Objectives: As a treatment modality for advanced knee osteoarthritis, total knee arthroplasty is well established and has been performed on many patients over time. To improve surgical outcomes, fixed-bearing implant insertion with robotic-assisted TKA has been introduced; however, the insertion of mobile-bearing (MB) implants with the same method is challenging. The aim of this study was to compare the short-term postoperative follow-up outcomes of MB implant insertion using a robotic-assisted TKA system and conventional TKA. Materials and Methods: We investigated functional improvement in the knees of 60 patients who underwent the insertion of MB implants using either robotic-assisted TKA or conventional TKA. Isokinetic muscular function, range of motion, the Western Ontario and McMaster Universities Osteoarthritis Index score, visual analog scale (VAS) score, and Knee Society Score (KSS) were measured 6 months after surgery. The statistical analysis of outcome measurements was performed using the Mann–Whitney U test and the Wilcoxon signed-rank test. Results: Some isokinetic muscular functions, as well as Knee Society Scores (pain and function) and VAS scores, were significantly higher in patients who underwent MB insertion with robotic-assisted TKA than in those who underwent conventional TKA. Conclusions: When an MB implant is inserted using a robotic-assisted TKA system, a better surgical outcome can be expected.

Recently, interest has surged in glove-type assistive devices for relieving hand muscle stiffness caused by brain lesions. This study aims to develop an ergonomic method for drafting glove patterns intended for hand-assistive devices. To facilitate pattern development, we acquired three-dimensional (3D) scan data from the four hemiplegic patients while their hands were in a relaxed posture, which was subsequently transformed into two-dimensional (2D) data. Based on the 3D shape data, we analyzed the finger joint range of motion (ROM) and change ratio of skin surface length resulting from flexion and extension movements of the paralyzed hand. Incisions were strategically applied to regions displaying significant variations in these parameters. These flattened 2D patterns were then integrated into revised pattern blocks to enhance the shading data related to the 3D shape, resulting in the development of four glove patterns. We found that gloves prototyped using this innovative pattern-drafting method did not impede joint ROM when worn. Changes in clothing pressure inside the glove at the joints corresponded to the bending angles of the fingers, and the pressure did not exceed the discomfort threshold during hand flexion and extension movements. Importantly, participants provided positive subjective feedback concerning the comfort of the gloves. Our findings yield fundamental data for developing a foundational glove design for hand-assisted devices for patients with paralysis, achieved through the utilization of this novel ergonomic glove pattern-drafting method.

Background/Objectives: SA001, a mofetil-ester prodrug of rebamipide, was developed to enhance gastrointestinal absorption and systemic exposure, which was confirmed in a prior Phase 1 study. Given the limited efficacy of current symptomatic therapies for primary Sjögren’s syndrome (pSS), this trial aimed to assess whether the improved bioavailability of SA001 could translate into clinical benefits. Methods: This multicenter, randomized, double-blind, placebo-controlled Phase 2a study enrolled adults who met the 2016 ACR–EULAR criteria for pSS. The participants were randomly assigned to one of four groups: SA001 at 360, 720, or 1080 mg/day (administered twice daily for 8 weeks) or placebo. Exploratory ocular assessments included tear break-up time, ocular surface staining, the Schirmer test, and the Standard Patient Evaluation of Eye Dryness. Oral endpoints included unstimulated whole salivary flow and the Xerostomia Inventory. Anti-SSA(Ro) antibodies were assessed both quantitatively and qualitatively. Safety evaluations comprised adverse events (AEs), ophthalmic examinations, laboratory tests, and vital signs. The efficacy outcomes were exploratory, and this study was not powered to formally test efficacy hypotheses. Results: Twenty-eight women (mean age 58.54 ± 9.29 years; range 41–75 years) were enrolled in this study and randomly assigned to one of the study groups. SA001 showed no statistically significant improvements versus placebo in ocular or oral endpoints, and no consistent dose–response relationship was observed. The anti-SSA(Ro) findings did not differ meaningfully across the groups. SA001 was generally well-tolerated, with infrequent, mostly mild-to-moderate AEs; however, one serious AE occurred in the placebo group. No clinically relevant ophthalmic or laboratory safety signals were detected. Conclusions: Despite the fact that markedly increased systemic exposure has been demonstrated previously, SA001 did not improve the dryness outcomes in pSS. These findings suggest that systemic exposure alone may be insufficient in established glandular disease and highlight the need for tissue-exposure-driven strategies and biomarker-informed patient selection in future studies. Predefined primary efficacy endpoints and objective, gland-proximal measures of target engagement (e.g., standardized salivary gland ultrasonography and salivary or tear fluid biomarker assessments) may help to better interpret local pharmacodynamic activity and the likelihood of a clinically meaningful benefit.

Recent studies have reported that methylation of the brain-derived neurotrophic factor ( BDNF ) gene promoter is associated with major depressive disorder (MDD). This study aimed to investigate the association between cortical thickness and methylation of BDNF promoters as well as serum BDNF levels in MDD. The participants consisted of 65 patients with recurrent MDD and 65 age- and gender-matched healthy controls. Methylation of BDNF promoters and cortical thickness were compared between the groups. The right medial orbitofrontal, right lingual, right lateral occipital, left lateral orbitofrontal, left pars triangularis, and left lingual cortices were thinner in patients with MDD than in healthy controls. Among the MDD group, right pericalcarine, right medical orbitofrontal, right rostral middle frontal, right postcentral, right inferior temporal, right cuneus, right precuneus, left frontal pole, left superior frontal, left superior temporal, left rostral middle frontal and left lingual cortices had inverse correlations with methylation of BDNF promoters. Higher levels of BDNF promoter methylation may be closely associated with the reduced cortical thickness among patients with MDD. Serum BDNF levels were significantly lower in MDD, and showed an inverse relationship with BDNF methylation only in healthy controls. Particularly the prefrontal and occipital cortices seem to indicate key regions in which BDNF methylation has a significant effect on structure.

The SLC6A15 gene has been identified as a novel candidate gene for major depressive disorder (MDD). It is presumed to be involved in the pathophysiology of MDD through regulation of glutamate transmission in the brain. However, the involvement of this gene in microstructural changes in white matter (WM) tracts remains unclear. We aimed to investigate the influence of a polymorphism of this gene (rs1545853) on the structural integrity of WM tracts in the cortico-limbic network. Eighty-six patients with MDD and 64 healthy controls underwent T1-weighted structural magnetic resonance imaging, including diffusion tensor imaging (DTI), and genotype analysis. We selected the genu of the corpus callosum, the uncinate fasciculus, cingulum, and fornix as regions of interest, and extracted fractional anisotropy (FA) values using the FMRIB Diffusion Toolbox software. FA values for the left parahippocampal cingulum (PHC) was significantly reduced in the patients with MDD compared to healthy control participants (p = 0.004). We also found that MDD patients with the A allele showed reduced FA values for the left PHC than did healthy controls with the A allele (p = 0.012). There was no significant difference in the FA value of left PHC for the comparison between the G homozygotes of MDD and healthy control group. We observed an association between the risk allele of the SLC6A15 gene rs1545843 and the WM integrity of the PHC in MDD patients, which is known to play an important role in the neural circuit involved in emotion processing.

Achieving remission following initial antidepressant therapy in patients with major depressive disorder (MDD) is an important clinical result. Making predictions based on genetic markers holds promise for improving the remission rate. However, genetic variants found in previous genetic studies do not provide robust evidence to aid pharmacogenetic decision-making in clinical settings. Thus, the objective of this study was to perform whole-genome sequencing (WGS) using genomic DNA to identify genetic variants associated with the treatment outcomes of selective serotonin reuptake inhibitors (SSRIs). We performed WGS on 100 patients with MDD who were treated with escitalopram (discovery set: 36 remitted and 64 non-remitted). The findings were applied to an additional 553 patients with MDD who were treated with SSRIs (replication set: 185 remitted and 368 non-remitted). A novel loss-of-function variant (rs3213755) in keratin-associated protein 1–1 ( KRTAP1-1 ) was identified in this study . This rs3213755 variant was significantly associated with remission following antidepressant treatment ( p  = 0.0184, OR 3.09, 95% confidence interval [CI] 1.22–7.80 in the discovery set; p  = 0.00269, OR 1.75, 95% CI 1.22–2.53 in the replication set). Moreover, the expression level of KRTAP1-1 in surgically resected human temporal lobe samples was significantly associated with the rs3213755 genotype. WGS studies on a larger sample size in various ethnic groups are needed to investigate genetic markers useful in the pharmacogenetic prediction of remission following antidepressant treatment.

Target identification is a crucial process in drug development, aiming to identify key proteins, genes, and signal pathways involved in disease progression and their relevance in potential therapeutic interventions. While C-C chemokine receptor 8 (CCR8) has been investigated as a candidate anti-cancer target, comprehensive multi-omics analyzes across various indications are limited. In this study, we conducted an extensive bioinformatics analysis integrating genomics, proteomics, and transcriptomics data to establish CCR8 as a promising anti-cancer drug target. Our approach encompassed data collection from diverse knowledge resources, gene function analysis, differential gene expression profiling, immune cell infiltration assessment, and strategic prioritization of target indications. Our findings revealed strong correlations between CCR8 and specific cancers, notably Breast Invasive Carcinoma (BRCA), Colon Adenocarcinoma (COAD), Head and Neck Squamous Cell Carcinoma (HNSC), Rectum adenocarcinoma (READ), Stomach adenocarcinoma (STAD), and Thyroid carcinoma (THCA). This research advances our understanding of CCR8 as a potential target for anti-cancer drug development, bridging the gap between molecular insights and creating opportunities for personalized treatment of solid tumors.