Therapeutic potential of single-nucleotide polymorphism-mediated IL6R inhibitors in ankylosing spondylitis treatment.

Objective: Interleukin-6 (IL-6) is a multiple-effect cell factor implicated in the etiopathogenesis of several rheumatologic disorders. The blockade of the IL-6 pathway via IL6R inhibitors effectively treats these disorders. However, the clinical significance of the IL6R blockade for ankylosing spondylitis (AS) therapy remains controversial. With advances in genomics, increasing evidence has revealed the role of heritability in the etiology of disease, and Mendelian randomization (MR) analyses are being used more broadly to infer causation. Therefore, this MR study aims to evaluate the potential therapeutic utility of IL6R-targeted approaches in AS. Methods: The C-reactive protein (CRP) level was used as an exposure factor, and rheumatoid arthritis (RA) was used as a positive control. As-related genome-wide association study (GWAS) data were used as the primary outcome of drug-targeted MR analyses to test the relation between IL6R blockers and AS. Inverse variance weighting (IVW) is the primary analytical approach. Various sensitivity tests were performed to check the robustness and trustworthiness of the causality estimation, including consistency, heterogeneity, and pleiotropy analyses. In addition, repeated analysis was conducted using different GWAS data related to exposures and outcomes to examine the results for stability. Results: According to the IVW results, IL6R inhibitors significantly reduced the risk of AS in ukb-b-18194 (OR: 0.995, 95% CI 0.993-0.996, P = 5.12 × 10-08) and ukb-a-88 (OR: 0.994, 95% CI 0.993-0.996, P = 6.25 × 10-15). Moreover, repeated analyses were performed using different exposure-related GWAS data, yielding similar results, ukb-b-18194 (OR: 0.995, 95% CI 0.993-0.997, P = 1.25 × 10-06) and ukb-a-88 (OR: 0.995, 95% CI 0.994-0.997, P = 7.81 × 10-09). Heterogeneity analyses and pleiotropy analyses indicated no significant heterogeneity or pleiotropy. Conclusion: This MR analysis result further validates that the IL-6 pathway may contribute to the pathogenesis of AS and that the inhibition of IL6R reduces the risk of AS. These findings may guide future studies and provide more favorable drug treatment options for people at high risk of AS.

Comparing Outcomes of Banana-Shaped and Straight Cages in Transforaminal Lumbar Interbody Fusion for Lumbar Degenerative Diseases: A Systematic Review and Meta-Analysis.

OBJECTIVE: This meta-analysis aims to refine the understanding of the optimal choice between different cage shapes in transforaminal lumbar interbody fusion (TLIF) by systematically comparing perioperative data, radiological outcomes, clinical results, and complications associated with banana-shaped and straight bullet cages. METHODS: A meticulous literature search encompassing PubMed, Embase, Scopus, Web of Science, China Knowledge Network, and Wanfang Data was executed up to October 5, 2023. Inclusion criteria focused on studies comparing banana-shaped and straight bullet cages in TLIF. The quality of included studies was assessed using appropriate tools such as the Newcastle-Ottawa Scale (NOS) for nonrandomized studies. Rigorous evaluations were performed for radiographic outcomes, including disc height (DH), segmental lordosis (SL), lumbar lordosis (LL), subsidence, and fusion rates. Clinical outcomes were meticulously evaluated using visual analogue scale (VAS), Oswestry Disability Index (ODI), and complications. RESULTS: The analysis incorporated 7 studies, involving 573 patients (297 with banana-shaped cages, 276 with straight cages), all with NOS ratings exceeding 5 stars. No statistically significant differences were observed in operative time, blood loss, or hospitalization between the 2 cage shapes. Banana-shaped cages exhibited greater changes in DH (p = 0.001), SL (p = 0.02), and LL (p = 0.01). Despite statistically higher changes in ODI for straight cages (26.33, p < 0.0001), the actual value remained similar to banana-shaped cages (26.15). Both cage types demonstrated similar efficacy in VAS, complication rates, subsidence, and fusion rates. CONCLUSION: Although banana-shaped cages can excel in restoring DH, SL, and LL, straight bullet cages can provide comparable functional improvements, pain relief, and complication rates.

Genetically predicted triglycerides mediate the relationship between type 2 diabetes Mellitus and intervertebral disc degeneration.

BACKGROUND: To validate the causal relationship between type 2 diabetes mellitus (T2DM) and intervertebral disc degeneration (IVDD) and to identify and quantify the role of triglycerides (TGs) as potential mediators. METHODS: A two-sample Mendelian randomization (MR) analyses of T2DM (61,714 cases and 1178 controls) and IVDD (20,001 cases and 164,682 controls) was performed using genome-wide association studies (GWAS). Moreover, two-step MR was employed to quantify the proportionate impact of TG-mediated T2DM on IVDD. RESULTS: MR analysis showed that T2DM increased IVDD risk (OR: 1.0466, 95% CI 1.0049-1.0899, P = 0.0278). Reverse MR analyses demonstrated that IVDD does not affect T2DM risk (P = 0.1393). The proportion of T2DM mediated through TG was 11.4% (95% CI 5.5%-17.4%). CONCLUSION: This work further validates the causality between T2DM and IVDD, with a part of the effect mediated by TG, but the greatest impacts of T2DM on IVDD remain unknown. Further studies are needed to identify other potential mediators.

High-Performance Acceleration of 2-D and 3-D CNNs on FPGAs Using Static Block Floating Point.

Over the past few years, 2-D convolutional neural networks (CNNs) have demonstrated their great success in a wide range of 2-D computer vision applications, such as image classification and object detection. At the same time, 3-D CNNs, as a variant of 2-D CNNs, have shown their excellent ability to analyze 3-D data, such as video and geometric data. However, the heavy algorithmic complexity of 2-D and 3-D CNNs imposes a substantial overhead over the speed of these networks, which limits their deployment in real-life applications. Although various domain-specific accelerators have been proposed to address this challenge, most of them only focus on accelerating 2-D CNNs, without considering their computational efficiency on 3-D CNNs. In this article, we propose a unified hardware architecture to accelerate both 2-D and 3-D CNNs with high hardware efficiency. Our experiments demonstrate that the proposed accelerator can achieve up to 92.4% and 85.2% multiply-accumulate efficiency on 2-D and 3-D CNNs, respectively. To improve the hardware performance, we propose a hardware-friendly quantization approach called static block floating point (BFP), which eliminates the frequent representation conversions required in traditional dynamic BFP arithmetic. Comparing with the integer linear quantization using zero-point, the static BFP quantization can decrease the logic resource consumption of the convolutional kernel design by nearly 50% on a field-programmable gate array (FPGA). Without time-consuming retraining, the proposed static BFP quantization is able to quantize the precision to 8-bit mantissa with negligible accuracy loss. As different CNNs on our reconfigurable system require different hardware and software parameters to achieve optimal hardware performance and accuracy, we also propose an automatic tool for parameter optimization. Based on our hardware design and optimization, we demonstrate that the proposed accelerator can achieve 3.8-5.6 times higher energy efficiency than graphics processing unit (GPU) implementation. Comparing with the state-of-the-art FPGA-based accelerators, our design achieves higher generality and up to 1.4-2.2 times higher resource efficiency on both 2-D and 3-D CNNs.

The treatment efficacy of pharmacotherapies for rapid eye movement sleep behavior disorder with polysomnography evaluation: A systematic review and meta-analysis.

Clonazepam and melatonin are commonly used as first-line medications for the treatment of rapid eye movement (REM) sleep behavior disorder (RBD), with other medications used in the clinic including pramipexole, ramelteon, and rotigotine. We performed a systematic review and meta-analysis of randomized and non-randomized controlled trials to assess the efficacy of these treatment options in RBD patients with polysomnography. We systematically retrieved results of randomized and non-randomized controlled trials using the PubMed, Embase, and Cochrane databases. Of the 454 studies identified, 13 were considered eligible for inclusion in the study. In comparison to baseline, clonazepam was found to significantly decrease the percentage of stage 2 sleep [4.00 (95% CI = 0.90 to 7.10)] in RBD patients. Melatonin was found to significantly improve patients' sleep efficiency [2.51(95% CI = 0.75 to 4.28)], significantly reduce the time spent in bed (TIB) [-11.71(95% CI = -23.05 to -0.37)], phasic activity[-25.79(95% CI = -42.13 to -9.46)] and tonic activity[-10.44(95% CI = -12.24 to -8.64)]. RWA[-5.87 (95% CI = -8.25 to -3.50)] significantly improve with the use of ramelteon. Pramipexole was found to significantly increase the total sleep time (TST) [27.17 (95% CI = 0.06 to 54.29)], and significantly reduce the periodic limb movements of sleep (PLMS) index [-11.42(95% CI = -21.38 to -1.47)]. We also found that pramipexole had different effects on idiopathic RBD (iRBD) and secondary RBD (sRBD). These results will help to guide the clinical use of medication in patients with RBD.

Structural and conformational characterization of linear O-acetyl-glucomannan purified from gel of Aloe barbadensis Miller.

Aloe barbadensis Miller (Aloe vera) is a kind of popular medicinal and horticultural crops widely cultivated around the world. Polysaccharides with different structural features and bioactivities have been isolated from the pulp of Aloe vera. In the current study, a novel polysaccharide fraction (AGP40) isolated and purified from gel juice of Aloe vera was subjected to structural and conformational analysis. AGP40 had a backbone consisting of major →4)-ß-Manp-(1 → residues and minor →3)-ß-Manp-(1 → and →4)-ß-Glcp-(1 → residues. Low degree of branches distributed at O-6 of 4-linked mannose in the main chain. The acetyl groups in AGP40 presented as mono- or di-substituents (O-2, O-3, O-6, O-2,3, O-2,6 and O-3,6). AGP40 performed as random coil conformation in 0.1 M NaNO3 solution, and had fibrous filaments and irregular spherical structures in solid state. Detailed structural and conformational analysis of AGP40 in the present study may greatly improve the bioactive function investigation and mechanism explanation of acetyl glucomannans in the future.