Zen-Noh (Japan)

To the Editor, We read with interest the randomized trial by Zhang et al[1] entitled “Effect of remimazolam on postoperative delirium in elderly patients undergoing major abdominal surgery: a randomized controlled Trial.” The use of blinded assessors with twice-daily validated assessments and reporting of both intention-to-treat (ITT) and per-protocol (PP) analyses are notable strengths. While postoperative delirium (POD) incidence did not differ significantly between groups [PP: 17.1% vs 19.7%; odds ratio (OR) 1.189, 95% confidence interval (CI) 0.688–2.057], and intraoperative hypotension appeared less frequent with remimazolam, we seek clarification on several points to aid interpretation, particularly given the variability of POD incidence across cohorts (10% reported in elective major abdominal surgery)[2]. First, although the trial was designed as a non-inferiority study (margin 5%, one-sided α = 0.025), the results are largely presented in terms of “no significant difference” based on P-values. For non-inferiority trials, interpretation hinges on the prespecified estimand and its CI relative to the margin. We suggest explicitly reporting the between-group risk difference and its 97.5% confidence interval in both ITT and PP populations, and stating clearly whether the upper confidence bound lies within the 5% margin. A simple figure showing the point estimate and confidence interval against the margin would further aid readers. Second, in the ITT population, baseline imbalances were reported for education level and diabetes – both plausibly related to cognitive reserve and POD risk. Although subsequent analyses identified education, American Society of Anesthesiologists (ASA) grade, age, and Mini-Mental State Examination (MMSE) as prognostic factors, it would be helpful to assess whether these imbalances materially affect the treatment estimate. We therefore suggest a covariate-adjusted sensitivity analysis (e.g., regression including education, diabetes, age, ASA grade, and MMSE) and reporting the adjusted effect alongside the primary analysis, particularly given an overall POD incidence of around 20%. This request is supported by cohort evidence linking education and perioperative vulnerability to POD risk[2–4] (college education: adjusted OR 0.35, 95% CI 0.13–0.91; ASA ≥3: OR 2.0, 95% CI 1.0–3.9). Third, the prespecified subgroup finding in patients aged ≥75 years is notable, with a significant interaction term (P for interaction <0.001) suggesting a higher POD risk with remimazolam. To fully appreciate the clinical relevance of this signal, readers would benefit from seeing the absolute POD rates and the corresponding absolute risk difference within this specific subgroup. Furthermore, as subgroup analyses are inherently sensitive to event counts and multiple testing, cautious interpretation is warranted. Age thresholds show strong associations with POD risk in prospective cohorts; for example, age ≥75 years independently increased POD risk (adjusted risk ratio (RR) 2.54, 95% CI 1.11–5.80) in a noncardiac surgery cohort[5]. Clarifying the interaction in this high-risk demographic is crucial for safe clinical application. Fourth, anesthetic depth was guided by bispectral index (BIS) targets (40–60). The manuscript appropriately acknowledges the uncertainty regarding BIS interpretation under remimazolam. If BIS values do not correspond equivalently to hypnotic depth across different agents, maintaining “similar BIS” may not ensure comparable cortical suppression. This has profound implications for both delirium risk assessment and the interpretation of hemodynamic outcomes. Data on total hypnotic drug doses or alternative depth-of-anesthesia metrics, if available, could provide valuable context. If BIS values under remimazolam reflect a different hypnotic state than under propofol, maintaining “similar BIS” might have resulted in disparate actual anesthesia depths, potentially confounding the comparison of delirium risk. Finally, methodologically, the handling of missing data through last observation carried forward (LOCF) and hot-deck imputation in ITT analyses, along with the exclusion of a notable proportion of patients (22/370) from PP analyses due to additional medications, raises questions about the robustness of the findings. The sensitivity of the primary conclusion to these assumptions, as well as the context of real-world co-interventions, would be valuable to discuss. Additionally, while POD assessment through postoperative day 5 captures most early cases, later-onset delirium associated with complications, ICU transfer, or sleep disruption might be missed, particularly with earlier discharge. This represents a recognized limitation in many POD studies. Moreover, hemodynamic “variability” (not merely the presence of hypotension) has been linked to POD in cohort evidence; for instance, mean arterial pressure variability was associated with POD severity (MAP variance OR 1.038 per 10 units, 95% CI 1.013–1.065) in a prospective cohort[6]. This trial offers valuable prospective evidence on the safety profile of remimazolam in elderly surgical populations. Addressing the aforementioned points would not only clarify the interpretation of the current data but also better guide the design of future trials and the optimization of anesthetic strategies for this novel agent in vulnerable geriatric patients. Ethical approval Not applicable. Consent Not applicable.

Electric Discharge Machining (EDM) is a non-traditional machining process that utilizes electric sparks between an electrode and a workpiece submerged in a dielectric fluid to ablate a material. It is commonly used in die-making, aerospace, automotive manufacturing, and medical manufacturing, because it can machine hard and complex materials with high precision. In this work, a Surface Roughness Optimization for EDM (SRO-EDM) model is proposed to investigate the machining performance of the die-sinking EDM process of titanium alloys. A regression-based combined approach of Glowworm Swarm Optimization (GSO) and a Two-Factor Interaction (2FI) model has been proposed to investigate the impact of four key process variables, namely voltage (V), peak current (Ip), pulse-on time (ton), and pulse-off time (toff) on surface roughness (Ra) at various locations on work surfaces. A Central Composite Design (CCD) was applied to systematically investigate parameter combinations. Statistical analysis was performed using analysis of variance (ANOVA), which confirmed the statistical significance of the selected parameters, and 2FI regression (R² = 0.60) with moderate-fit predictive accuracy was established. To enhance the quality of optimization, the Enhanced Glowworm Swarm Optimization (EGSO) algorithm is proposed by hybridizing the GSO with Artificial Fish Swarm (AFS) algorithm. The AFS module improves the exploration capability of the GSO and alleviates the local optima problem. For the experimental validation of the model, Response Surface Methodology (RSM) was used to generate the regression based on the developed model and as an objective function for optimization. Experimental results show that EGSO outperforms GSO in performance to achieve an optimized Ra ( ) compared to through conventional GSO. The results demonstrate that the EGSO model can improve convergence accuracy and speed and is a practical method for EDM surface quality optimization in the high-precision manufacturing industry.

Introduction Hibiscus sabdariffa L. is an economically important and widely adopted crop in Burkina Faso. Yet its production is constrained by the lack of improved, locally adapted varieties. This study used a participatory variety selection approach to identify preferred landraces and selection criteria across two agroecological zones: Sudanian and Sudano-Sahelian. Methods The evaluation of landraces/accessions was carried out using an ordinal rating system, assigning scores ranging from 9 (most preferred accession), through 7 (very interesting), 5 (moderately interesting), 3 (less interesting), to 1 (least interesting). Landraces considered undesirable were specifically evaluated using negative scores of −5, −3, and −1, reflecting the degree of rejection expressed by the participants. Results Participatory selection involved 126 stakeholders (75.4% women), including producers (37.3%), consumers (30.9%), processors (16.7%), and traders (15.1%). The findings showed that 130 accessions (81.25%) were positively selected across zones, with traits such as leaf size, tenderness, absence of pubescence, market value, and drought tolerance being prioritized. Preferences differed significantly by agroecological zone, ethnicity (p &amp;lt; 0.001), age group, and actor role (χ² = 360.21, p&amp;lt; 0.001). Two accessions (CKK1 and CKN5) were consistently ranked at the top, with index scores of 0.0441 and 0.0428, respectively. In contrast, accessions like CKO2 and HBB3 were most rejected due to poor agronomic and culinary traits. The analysis showed that only 30% of the selected accessions were shared between the two zones. Conclusion These results highlight the potential value of participatory selection in identifying varieties that are well-adapted, socially acceptable, and potentially more resilient for underutilized species in West Africa.

The fovea is a unique specialization of the primate retina and is a promising site for obtaining the first complete connectome of a human central nervous system (CNS) structure. Within the fovea, neural cells and circuits have been miniaturized and compressed during evolution to sample the visual image at highest spatial resolution and begin the neural processing that serves human form, color, and motion perception. Here we present a comprehensive analysis of a sample of human foveal retina using deep learning-based segmentation to reconstruct all cells and synaptic connections at nanoscale resolution. We classified ~3,000 cells into 51 distinct morphological types based on their structural features and connectivity patterns. Our observations reveal novel synaptic pathways absent in non-human primates, suggesting specialized circuits contribute uniquely to human trichromatic color vision. A biophysical model of the distinct connectomes made by gap junctions (electrical synapses) between short- (S) and medium-long- (ML) wavelength-sensitive cone photoreceptors, suggests chromatic interactions between S and ML cones prior to the first chemical synapse. Segmentation of retinal ganglion cells (RGCs) suggests the presence of only 11 visual pathways, with 5 high-density RGC pathways accounting for over 95% of foveal output to the brain: a dramatic contrast to the 40+ ganglion cell types recognized in mouse retina. Our connectomic analysis reveals distinctive features of human neural circuitry and demonstrates how AI-based computational approaches can advance understanding of human brain structure and function.

Copper deficiency is a rare yet reversible cause of anemia and bone marrow dysplasia that can mimic myelodysplastic syndrome (MDS), especially in patients on maintenance dialysis, who are at increased risk due to trace element losses, chronic inflammation, and impaired absorption. We report a 69-year-old woman on long-term hemodialysis with a history of partial gastrectomy who developed macrocytic anemia refractory to erythropoiesis-stimulating agents (ESAs). Bone marrow examination revealed erythroid dysplasia, hypocellularity, and ring sideroblasts. Although serum copper levels were initially within the low-normal range, the clinical course was consistent with functional copper deficiency, which progressed to absolute deficiency following brief zinc supplementation. Oral copper therapy was ineffective, whereas intravenous copper sulfate led to rapid hematologic recovery and resolution of dysplastic changes on follow-up biopsy. This case highlights the diagnostic complexity of ESA-resistant anemia in dialysis patients with overlapping risk factors and underscores the need to consider functional micronutrient deficiencies even when serum levels appear normal.

Nghiên cứu này đánh giá tác động của sự tập trung quyền lực quản trị đến mức độ minh bạch thông tin của các doanh nghiệp dược phẩm niêm yết tại Việt Nam giai đoạn 2018 - 2023. Sử dụng phương pháp hiệu ứng ngẫu nhiên tương quan (Correlated Random Effects - CRE) và tự xây dựng biến minh bạch thông tin dựa trên khung công bố thông tin bắt buộc và tự nguyện, nghiên cứu phát hiện rằng sự tập trung quyền lực có tác động tiêu cực đến MBTT. Đáng chú ý, kiểm toán Big4 có vai trò điều tiết, làm giảm tác động bất lợi của sự tập trung quyền lực, trong khi mức độ sở hữu tập trung của HĐQT lại làm trầm trọng thêm tình trạng thiếu minh bạch. Nghiên cứu góp phần mở rộng hiểu biết về cơ chế quản trị doanh nghiệp trong bối cảnh thị trường mới nổi và cung cấp hàm ý chính sách nhằm tăng cường hiệu quả kiểm soát và công bố thông tin trên thị trường chứng khoán Việt Nam.

Abstract Background: Bacterial resistance to conventional antibiotic therapy has become a global health crisis. Bacterial biofilm formation allows bacteria to develop resistance to antibiotics and the host immune system. This study aims to contribute for fighting against bacterial resistance through the inhibition of bacterial biofilm formation by Lippia multiflora flowers essential oils. Methodology: The sensitivity of Staphylococcus aureus and Streptococcus mutans to the essential oils was measured on the Luria Bertani-Agar mediumby using the antibiotic susceptibility test. The anti-biofilm potential of the essential oil was evaluated by t he crystal violet method. The antioxidant potential of the essential oils was assessed by the DPPH method. The phytochemical profile was determined by gas chromatography-mass spectrometry (GC/MS) analysis. Results: The essential oils showed higher growth inhibition diameters of S. aureus (28.38±0.23 mm) and S. mutans (24.5±0.25 mm) than reference antibiotics such as gentamicin 30 mg (13.5 ± 0.07 mm on S. aureus) and Oleandomycin 10μg (16.5 ± 0.05 mm on S. mutans).The essential oil was also more active in inhibiting biofilm formation than salicylic acid with inhibition percentages ranged from 60 ± 0.00% on S. aureus and 71.60 ± 0.70% on S. mutans. Moreover, the essential oils exhibited good antioxidant activity with anti-DPPH inhibitory concentration ranged from 0.23 ± 0.02 µg/ùL. GC-MS analysis of the essential oils led to the identification of 22 terpens compounds with 7 major compounds such as β-caryophyllene (43.55%), germacrene D (16.44%), elemol (10.33%), eucalyptol (6.41%), humulene (3.28%), α-phellandrene (2.68%) and β-ocimene (2.62%). Conclusion:These results showed that the essential oils of L. multiflora flowers are a promising candidate in the fight against bacterial resistance.