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Identification and immune characteristics of N6-methyladenosine related ferroptosis-related genes in intervertebral disc degeneration
Abstract The damage of ferroptosis is related to the pathogenesis of intervertebral disc degeneration (IDD). N6-methyladenosine (m6A) modification accounts for more than 80% of RNA modifications in eukaryotic cells. However, the key role of m6A related ferroptosis-related genes (FRGs) in IDD remain explorable. Firstly, batch correction between datasets was performed. Weighted gene co-expression network analysis (WGCNA) was then conducted to acquire the most relevant module genes. Differentially expressed genes (DEGs) between the IDD and Normal Group were obtained by differential analysis subsequently. Next, according to the Pearson correlation and the intersection of m6A and FRGs related genes, m6A-FRGs related genes were selected. Additionally, we intersected module genes, DEGs and m6A-FRGs related genes to obtain DEGs of m6A-FRGs related module genes (m6A-FRGs-DEGs). Least absolute shrinkage and selection operator (LASSO) was applied to get HUBgenes. After, we conducted gene set enrichment analysis (GSEA) to gain function items and related pathways of HUBgenes. Single sample gene set enrichment analysis (ssGSEA) and wilcox.test were proceeded to analyse differences in relative abundance of immune cells between the IDD and Normal Groups, and a nomogram was constructed based on significantly different HUBgenes. The Comparative Toxicogenomics Database (CTDbase) was then applied to predict potential drugs or molecular compounds that could modulate HUBgenes. Last but not least, we performed the quantitative real-time fluorescence PCR (qRT-PCR) to verify HUBgenes. 181 m6A-FRGs-DEGs were acquired by the intersection of key module genes (from MEtan, MEsalmon, MEbrown and MEgreen), 362 DEGs and 15,678 m6A-FRGs related genes. Subsequent analysis showed that HUBgenes (ZNF595, PLXDC1, FNBP1L, KLRB1, NRCAM, PPCDC, C9orf139, SIGLEC17P, RRAS2 and DPRXP4) significantly participated in positive regulation of cytokine production, mitochondrial inner membrane and organellar ribosome. Besides, the relative abundance of neutrophils was found significantly different between IDD and normal groups. A nomogram was constructed based on ZNF595 and RRAS2, and there were 11 drugs targeted on ZNF595, while 118 drugs predicted based on RRAS2 such as Tetrachlorodibenzodioxin, Bisphenol A and Benzo(a)pyrene. Lastly, ZNF595 and RRAS2 were both obviously up-regulated in IDD according to the qRT-PCR. Our research suggested 10 HUBgenes were significantly associated with IDD, providing more evidence about the vital role of HUBgenes in IDD.
Bilateral muscle compensation occurs with a unilateral rotator cuff tear: A modeling study
Bimanual tasks are necessary for daily activities but become difficult to complete with a musculoskeletal disorder. Rotator cuff tears (RCT) are a common musculoskeletal disorder. It is unclear how an unaffected contralateral limb compensates when performing bimanual tasks. This work used a computational model to examine the effects of a unilateral RCT on performance of loaded bimanual tasks. A bilateral upper limb model was developed in OpenSim (v3.3), then modified to represent 4 RCT severities ranging from no RCT to massive RCT. A shared load (13.3 N or 44.5 N) was added to the models to represent holding typical household and occupational objects. Three motions were used as inputs to the Computed Muscle Control algorithm: static postures at low and high arm positions, and a dynamic forward reach task. The point analysis tool was used to track the shared load position. Outcomes included muscle force normalized by peak isometric force and maximum hand position deviation relative to input kinematics. Quantitative trends were analyzed for each outcome. During static tasks, uninjured muscles on the injured side increased force contribution with increased external load and RCT severity. For the dynamic task, infraspinatus muscle force increased with the massive RCT severity on the unaffected side by 76% for the 13.3 N load and 91% for the 44.5 N load, indicating contralateral muscle compensation. Minimal deviation occurred for the position of the shared load during the low posture static and dynamic tasks. For the high posture static task there was an inferior (342 mm) position change toward the unaffected side (83 mm) with the massive RCT, 44.5 N load. The bilateral model developed here has provided insights into bilateral compensation with a unilateral RCT. This modeling tool can be used to enhance understanding of task performance in the context of rehabilitation.
Determinant prioritization and predictive modeling of respite service demand among disabled elderly caregivers
A prospective study of predictors of return to work after surgery for ulnar nerve entrapment
Abstract Ulnar nerve entrapment at the elbow (UNE) is the second most common compression neuropathy in the upper limb. Immediate return-to-work (RTW) after surgery is seldom possible due to restrictions and recovery demands. We aimed to explore RTW after UNE surgery and investigate factors contributing to variations. A prospective study with patients undergoing primary UNE surgery was conducted. Treatment decisions were based on a novel five-grade clinical scale. In total, 65 patients (25 women and 40 men) with a mean age of 51 ± 16 years were included. Simple decompression was the predominant procedure (n = 57, 88%). Manual laborers (n = 28, 43%) had the longest sick leave (7 weeks, IQR [3]) within the working population (n = 49) compared to non-manual laborers (4 weeks, IQR [6]; p = 0.003). Manual labor, smoking, and preoperative pain (evaluated with the Swedish version of the Patient-Rated Ulnar Nerve Evaluation, PRUNE-S) predicted prolonged sick leave. The type of surgery did not predict RTW variations in the multivariate linear model itself but modified the impact of other predictors. In conclusion, patients with surgically treated UNE have varying sick leave needs, influenced by individual and work-related factors. Incorporating biopsychosocial aspects should be a focus of further research in UNE management.
Active case finding for tuberculosis in tea gardens of Bangladesh: A cross-sectional survey
Tea garden populations with poor socio-economic status are at risk of developing TB. The active case finding (ACF) approach is effective in finding TB among the people at risk. We have conducted ACF for TB to find people with presumptive TB in the tea gardens of Sylhet division to identify TB disease. It was a cross-sectional survey conducted at the household level, in the randomly selected three tea gardens of Sylhet division. The selected population was 20,215 and was screened for TB presumptive symptoms between July and Oct 2022. Each presumptive had required TB testing, which includes GeneXpert MTB/RIF (Xpert) or Sputum microscopy, X-ray, and Fine Needle Aspiration Cytology (FNAC) if there was gland swelling. Around 99.6% (20,127/20,215) of the surveyed population were screened for TB. Among the screened population, gender distribution was almost equal, and 34% had no education. And people with presumptive TB were 0.8%; among them, most (91%) were pulmonary TB presumptive with male predominance. Among all presumptive, 87.4% had a cough for ≥ 14 days and 78% had a fever. We identified a total of 17 pulmonary TB; among them, bacteriologically confirmed TB were only 6 (35.3%). The estimated proportion of TB among the surveyed population was 0.10%. The findings suggest a need for sustained TB screening activities integrated with community involvement.
Evaluation of high performance concrete hardness properties using fuzzy logic based modeling
Analysis of diagnostic apoptosis-related biomarkers and immune cell infiltration characteristics in endometriosis by integrating bioinformatics and machine learning
A novel approach to porcine abnormal sounds recognition based on improved Multi-SVDD
During the real-time recognition of porcine abnormal sounds, the accuracy and stability of the recognition method are crucial to guarantee a good performance. For this purpose, an improved Multiple-Support Vector Data Description (Multi-SVDD) is proposed in this paper. Firstly, the improved spectral subtraction using improved Minima Controlled Recursive Averaging (IMCRA) and Spectral Subtraction (SS) is applied to remove the noise of collected sounds. Then, the Mel-Frequency Cepstral Coefficients (MFCC) and first-order differential MFCC (ΔMFCC) are extracted as feature parameters. Finally, the Multi-SVDD is used to detect and recognize the porcine abnormal sounds. In order to improve the accuracy and error-tolerance of Multi-SVDD for human errors on tagging data, the space density information of training data is calculated as the confidences to reduce the interference of outliers in the process of Multi-SVDD training. The experimental results show that the accuracy, precision and recall of the proposed method are as high as 95.0%, 95.4% and 95.0% respectively, which indicates higher error-tolerance capability than classical SVDD.
Determinants of health information seeking behavior among people at risk of statelessness in Ghana
Integrative genomic and immunoinformatic approach for characterizing HIV-1 pol, vpr, and Nef genes and designing a multi-epitope vaccine
Repurposing resveratrol for redox-mediated inhibition of MTH1 in breast cancer
Multi-faceted investigation of ZnO nanoparticles with 1-ethyl-3-methylimidazolium iodide for enhancing DSSC performance
HJ-4, a novel piperine derivative, inhibits tumor growth and angiogenesis via p53 activation and oncogenic pathway inhibition in colorectal cancer models
Abstract Colorectal cancer (CRC) remains a major cause of cancer-related mortality worldwide, especially in advanced and metastatic stages where treatment options are limited. HJ-4, a novel piperine derivative, demonstrated strong tumor-selective inhibition. Within safe concentrations (cell viability > 85%), HJ-4 dose-dependently suppressed colony formation and DNA synthesis in CRC cells, showing potent anti-proliferative effects. It also significantly inhibited cell adhesion, wound healing, and invasion, indicating robust anti-migration and anti-invasion properties. In vivo, the CAM model confirmed that HJ-4 reduced both tumor volume and angiogenesis. Mechanistically, HJ-4 activated the p53-dependent apoptosis pathway while suppressing the Wnt/β-catenin axis and E2F transcriptional activity, effectively impeding tumor progression. Overall, HJ-4 exhibits promising tumor specificity and multiple antitumor mechanisms, supporting its potential for clinical development in CRC treatment.
UHTC ceramics derived from B4C and MAX phases by reactive sintering
Abstract In this work, the influence of three MAX phases (Ti3SiC2, Ti2AlC, and Cr2AlC) on the densification and final properties of dense composites from Ultra-High Temperature Ceramics (UHTC) family was studied. Addition of the MAX phases resulted in the formation of secondary boride phases due to chemical reactions between boron carbide and MAX phase. Mentioned phases were utilized for reduction of sintering temperature of the final composite material. It decreased the sintering temperature up to 800 °C when compared to pure B4C. Additionally, the phase composition and derivative mechanical properties were investigated to evaluate differences between final composite materials. All obtained materials remarkably increased their fracture resistance (KIC) from 33 to 100%. The mechanical properties of B4C were either retained (Ti3SiC2) or decreased in terms of Vickers hardness and Young’s Modulus (Ti2AlC and Cr2AlC). Systems with Ti3SiC2 appeared to possess significant potential for application, also when compared to UHTC systems of similar purpose.
Plasma apolipoprotein A-I is a causal protective factor in sepsis
Salvia sclarea L. mediated green synthesis of gold nanoparticles (AuNPs) and evaluation of their antibacterial, anticandidal, and scolicidal properties
Morphological and electrophysiological diversity and connectivity of principal neurons in the lateral and basal nuclei of the mouse amygdala
Frequency-dependent modulation of evoked potentials during GPi-DBS in pediatric dystonia
Abstract Deep brain stimulation (DBS) of the globus pallidus internus (GPi) is an established treatment for dystonia, yet the neurophysiological mechanisms underlying frequency-dependent effects remain poorly understood. In this study, we investigate how different GPi-DBS frequencies modulate evoked potential (EP) characteristics within the basal ganglia-thalamo-cortical network in pediatric dystonia patients. We evaluated how increasing stimulation frequency alters EP morphology, focusing on peak-to-peak amplitude (PPa), peak-to-peak duration (PPd), and time to peak (TP). This analysis was motivated by clinical observations that higher DBS frequencies often produce distinct therapeutic effects, suggesting underlying differences in how neural circuits respond to varying stimulation rates. We analyzed intracranial electrophysiological recordings from 13 pediatric and young adult dystonia patients undergoing staged DBS implantation. EPs were recorded from the GPi and subthalamic nucleus (STN) of basal ganglia, and ventral oralis (VO) nucleus of the thalamus during unilateral GPi stimulation at 55, 85, 185, and 250 Hz. EP detection and characterization were performed using an automated algorithm, and group-level analyses were conducted using linear mixed effects models to assess frequency-dependent changes across regions. Increasing stimulation frequency significantly decreased PPa and increased PPd and TP, with a clear threshold effect: 55 Hz and 85 Hz produced similar responses, while 185 Hz and 250 Hz elicited significantly greater changes. These frequency-dependent effects were most pronounced in GPi recordings, followed by STN and VO, suggesting that local circuit dynamics are more sensitive to frequency modulation. Our findings highlight the distinct neurophysiological effects of DBS frequency on EP characteristics, emphasizing the need for personalized DBS programming. The pronounced frequency-dependent modulation observed in GPi suggests that optimal stimulation parameters should be tailored to the target region rather than applying uniform settings across patients. Future studies should investigate the clinical relevance of these EP dynamics and explore their potential as biomarkers for DBS optimization in dystonia.