Abstract: Old murine bone marrow-derived monocytes and macrophages (BMMs) display enhanced CD38 protein, a nicotinamide adenine dinucleotide (NAD⁺) glycohydrolase, and reduced NAD⁺ level after infection with oral pathogens compared with young controls. We aimed to determine whether treatment with a CD38-specific inhibitor (78c) in mice with experimental periodontitis could alleviate alveolar bone loss and enhance NAD⁺ levels in tissues compared with vehicle treatment. Twenty young (2-month-old) and twenty old (18-month-old) C57BL/6J mice with experimental periodontitis were treated with either vehicle or 78c twice daily via intraperitoneal injection for 4 weeks. The liver, spleen, and right maxillary tissues were harvested to analyze NAD⁺ levels. The left maxillary tissues were scanned by micro-CT, processed for tissue sectioning, and stained with hematoxylin and eosin (H&E) and tartrate-resistant acid phosphatase (TRAP). Treatment with 78c significantly enhanced NAD⁺ levels in the liver and spleen of both young and old mice, and significantly increased NAD⁺ in the right maxilla of old mice compared with vehicle treatment. Additionally, treatment with 78c alleviated alveolar bone loss in both young and old mice. Our results support the notion that 78c is a promising therapeutic strategy for treating periodontal disease associated with aging.

Abstract: To reveal the solute sources, migration and enrichment mechanisms of water bodies in the endorheic lake region of the Qiangtang Plateau, Tibetan Plateau, and to clarify the hydrogeochemical cycling patterns in alpine arid zones, this study took typical en-dorheic lake areas in the region as the research object, conducted a systematic hydro-geological survey, collected 28 groups of water samples of various types (including springs, rivers, thermal springs, freshwater lakes, salt lake brines, atmospheric precip-itation and glacial meltwater), tested their major ions, trace elements and physical properties, and comprehensively investigated the hydrogeochemical characteristics, evolution laws and solute sources of water bodies, quantified the dominant control-ling factors and established a conceptual hydrogeochemical model by combining methods such as PHREEQC modeling, principal component analysis (PCA) and Pear-son correlation analysis; the results show that water bodies in the study area exhibit a distinct evolutionary gradient, from the low-salinity HCO₃-Ca recharge end-member, through transitional HCO₃·SO₄-Ca(Mg) water, to highly mineralized Cl-Na(SO₄·Cl-Na) salt lake brine, with synchronous enrichment of Li, B, As and other elements; solute sources are controlled by a ternary coupling mechanism of evaporative concentration, rock weathering and leaching, and deep geothermal fluid input, while cation ex-change and mineral dissolution-precipitation further regulate ionic ratios; As, Li, B and Cl⁻ display conservative migration in non-hydrothermal waters, whereas thermal springs show unique geochemical signatures due to the input of deep-seated fluids; PCA reveals that evaporative concentration (contribution rate 55.39%) is the dominant controlling factor, rock weathering (17.09%) provides the basic solute load, and the coupled process of deep fluid mixing and carbonate precipitation (14.21%) regulates elemental fractionation, and this study constructs a conceptual model of "multi-source recharge–water–rock interaction–evaporative concentration", which clarifies the evo-lutionary laws of regional water bodies and provides a scientific basis for water cycle research and green exploration of strategic mineral resources in salt lakes of the en-dorheic regions on the plateau.

Abstract: Convolutional Neural Networks (CNNs) constitute the foundation of modern computer vision systems, yet their empirical performance is frequently governed as much by training configuration choices as by architectural design. Despite this, critical hyperparameters—including optimizer selection, batch size, learning rate, training duration, dropout regularization, and batch normalization—are often selected heuristically or reported incompletely. Based on two benchmark datasets (CIFAR-10 and MNIST) and two classical CNNs (CifarNet-11 and LeNet-5), this paper presents a systematic, configuration-aware empirical study that quantifies how these variables influence predictive accuracy, convergence stability, generalization behavior, and computational efficiency of CNN models. Using a controlled experimental methodology in which individual configuration variables are isolated and evaluated under identical conditions, we demonstrate that configuration choices can induce performance variations comparable to those achieved through substantial architectural modifications. The results reveal explicit accuracy–efficiency trade-offs, identify regime-dependent optimal configurations, and highlight the central role of early stopping and normalization in stabilizing learning dynamics. These findings elevate configuration-aware optimization to a first-order design principle for reproducible research and reliable deployment of CNN-based artificial intelligence systems.

Abstract: Physical activity is a safe and effective intervention for chronic musculoskeletal pain. However, a literature search revealed a lack of synthesis of evidence on the extent to which physical therapists in Saudi Arabia incorporate physical activity as part of health promotion in the management of such pain. This review aims to identify, map and report literature related to physical activity for health promotion in people with chronic musculoskeletal pain presenting to physical therapy settings in Saudi Arabia. A six-step approach will be followed to conduct the scoping review. Step 1, the primary research question is: What is the scope and nature of the existing literature in this research area? The secondary research question is: What insights does the existing literature reveal regarding physical therapy clinical practice? Step 2, a comprehensive search will be conducted for relevant literature using the following electronic databases: Scopus, Medline, PubMed, Cochrane library, CINAHL, ScienceDirect and PEDro. In addition, supplementary search methods will be conducted for identifying additional relevant literature via screening process of the reference lists of all included literature and screening process of the included studies of retrieved systematic reviews through electronic databases. A parallel search including the main keywords will also be undertaken on the website of the Saudi Ministry of Health, the website of Saudi Physical Therapy Association, Google and Google Scholar for grey‑literature searching. Step 3, records will be screened by two independent reviewers and managed using Rayan software. Step 4, the nature of included literature, including study characteristics and outcomes where appropriate, will be documented using a data extraction. Step 5, the characteristics and outcomes of included records will be collected, summarised and reported. Step 6, Stakeholders will be consulted to interpret the scoping review findings from their perspective and assess the findings’ relevance and applicability.

Abstract: This paper examines the empirical evidence on the use of generative artificial intelligence (GenAI) in scientific writing. A search was conducted in Google Scholar and PubMed, followed by an analysis of the included studies, which was performed according to the academic field, AI tool, writing task, study design, and main findings. Following the PRISMA guide, this scoping review included 18 studies published between 1st January 2023 and 1st January 2026, representing the disciplines of medicine, education, dentistry, radiology, humanities, library, information science and cognitive science. The evidence base was dominated by studies on ChatGPT, making it the most empirically researched GenAI tool in this field. According to the studies reviewed, GenAI performed well on an array of measures (readability, fluency, and organization) and efficiency (the latter especially in terms of manuscript drafting, abstract writing, proposal development, and literature reviewing). However, the findings also disclosed several limitations, including incorrect or falsified references, inaccurate bibliographical metadata, shallow analysis, lack of originality, and insufficient methodological depth. Based on comparative evidence, newer model versions show improved coherence and reasoning and although improved with the newer GenAI versions, reference reliability still appears to be a recurring problem. Overall, GenAI can be a useful assistive tool for scientific writing; however, its usefulness is dependent upon human supervision and the task at hand, especially with regard to the accuracy of facts and their sources.

Abstract: This paper presents OSI4IOT, an open-source software platform designed to support the integration of sensor-driven Internet of Things (IoT), Asset Information Modelling (AIM), Geographical Information Systems (GIS), and data-driven analysis within a Digital Twin (DT) framework. The platform provides a modular architecture for connecting heterogeneous data sources and enabling the coupling between physical assets and numerical models. In particular, it supports the integration of Finite Element Method (FEM)-based structural models for simulation and comparison with monitored responses. A case study involving a structural frame is used to demonstrate the platform workflow, including data acquisition, model execution, and result visualisation. The results are used to assess the consistency between analytical, numerical, and monitored responses under varying loading conditions. The paper focuses on the system architecture and the coupling strategy between data acquisition and simulation components within an open-source environment.

Abstract: The landscapes of most tropical regions have been shaped by the indigenous peoples’ and their livelihood practices. The utility of plants within these landscapes for traditional purposes has been facing intense competition from commercial logging. To gain insights into this conflict, this paper examined how landscape conditions may influence the presence and spatial distribution of indigenous subsistence and commercial logging ecosystem services relative to one another. Data on the ecosystem services and landscape conditions in the form of physical environment variables were obtained for twelve indigenous villages in the Rupununi, Southern Guyana. For each village, the relative log risk ratios of subsistence values to logging values were computed and regressed against six physical environment variables – village presence, distance to village, distance to road, distance to waterways, elevation, and slope – to examine if and how landscape conditions may favor the presence of one service over the other. The estimates were then used to map the relative differences in the spatial distributions of subsistence and commercial logging services in each village. It was found that mean relative log risk ratios for the villages were generally positive, indicating an inclination towards the presence of subsistence services. However, the maps revealed that while some areas within a given village were indeed more favorable for the presence of subsistence services, other areas within the same village were inclined towards the presence of logging services. Similar spatial analyses can be explored to guide policy-makers in developing land-use strategies that allocate forest lands between competing users by identifying areas that are best suited for indigenous peoples’ subsistence activities and for commercial logging operations.

Abstract: Biofilms (BFs) bacteria are dramatically intensifying tolerance to conventional antibiotics, no longer effective. Therefore, the research for new antibiofilm (ABF) compounds are noticeably increasing the studies proliferation rate. In this regard, intriguing questions should raise to be debated. To this end, the problematics of BF, mainly in medical setting, have been afforded here in an original way, examining the tension “between efficacy and understanding”. Questions include: are BF mechanistic studies indispensable and strictly required especially at academic levels with poor economic support? When may a purely phenotypic approach still hold scientific value? Could be demonstrate empirical efficacy alone, sufficient for scientific relevance of the study? Do high costs, long times mechanistic insights, also associated to environmental issues, represent the necessary key to defeating BFs and the benchmark that determines the robustness and impact of ABF research? The state of the art of global challenge against BF, responsible for difficult-to-treat and even lethal chronic infection, has been provided. The available armamentarium of best functioning antibiotics/combinations has been discussed, while the correct way to investigate ABF mechanisms has been clarified. Among 102 studies on the ABF activity, considered, distributed in Tables and discussed, mechanistic investigations carried out correctly have been found in only 34 ones. Only efficacy screens, stopping at phenotypic descriptions, as reported in 68 out of 102 papers, are considered essential for discovering efficacious ABF compounds and are welcome by Editors and scientific community. Such approach represents the main trend of most recent literature and is strongly desirable for publication.

Abstract: Background/Objectives: Treatment decisions for elderly patients with diffuse large B-cell lymphoma (DLBCL) often rely on subjective clinical impression rather than systematic frailty assessment. We evaluated whether a modified simplified frailty score (mSFS)—a binary adaptation of the Isaksen score—predicts treatment selection, toxicity, and survival. Methods: In this retrospective study of 117 patients aged ≥65 years with DLBCL treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or dose-attenuated R-CHOP (R-mini-CHOP) at MedStar Health community hospitals (2000–2025), the mSFS assigned one point each for age ≥80, Eastern Cooperative Oncology Group (ECOG) performance status ≥2, and ≥5 comorbidities; score ≥2 defined frailty. Results: Among 86 R-CHOP recipients, 17 (19.8%) were mSFS-frail; among 31 R-mini-CHOP recipients, 15 (48.4%) were mSFS-fit. In R-CHOP recipients, frailty independently predicted worse overall survival (adjusted hazard ratio [aHR] 7.67, 95% confidence interval [CI] 2.36–24.97), progression-free survival (aHR 2.90, 95% CI 1.18–7.13), grade ≥3 adverse events (adjusted odds ratio [aOR] 3.90, p = 0.035), and early discontinuation (aOR 4.41, p = 0.034). Frail R-CHOP patients had lower complete response rates (aOR 0.24, p = 0.038). Fit R-mini-CHOP patients had 88% lower odds of complete response versus fit R-CHOP patients (aOR 0.12, p = 0.003). Among R-mini-CHOP recipients, frailty was not significantly associated with outcomes. Conclusions: The mSFS revealed bidirectional discordance with oncologist-assessed frailty and independently predicted survival, toxicity, and response, supporting its integration into community oncology practice.

Abstract: Background/Objectives: Type 2 diabetes mellitus (T2DM) is a chronic multifactorial metabolic disorder requiring multi-target therapeutic strategies. This study aimed to clarify the potential material basis, key targets and molecular mechanisms by which PuRenDan (PRD) acts against T2DM through an integrated network pharmacology and molecular simulation approach. Methods: Active compounds of PRD were screened from TCMSP, HERB 2.0 and the literature, and compound-related targets were predicted using TCMSP, SwissTargetPrediction and PharmMapper. T2DM-associated targets were collected from OMIM, DrugBank, DisGeNET, HPO, ClinPGx and GeneCards to obtain drug-disease intersection targets. Cytoscape was used to construct herb-compound-target and protein-protein interaction (PPI) networks, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Molecular docking was performed using AutoDock Vina, and representative ligand-receptor complexes were further assessed by 100 ns molecular dynamics (MD) simulations and molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA) binding free-energy analysis. Results: A total of 163 active compounds, 597 PRD-related targets, 9138 T2DM-associated targets and 483 intersection targets were identified. β-sitosterol, emodin, quercetin, kaempferol and formononetin were predicted as major active compounds, whereas AKT1, TP53, SRC, IL6, TNF, EGFR and ESR1 were identified as core targets. KEGG enrichment highlighted the PI3K-Akt, MAPK, HIF-1, FoxO, mTOR, AGE-RAGE and TNF signalling pathways. Docking suggested strong multi-target binding potential for β-sitosterol. MD and MM/PBSA analyses further indicated favourable dynamic stability for β-sitosterol-TNF, β-sitosterol-AKT1, β-sitosterol-SRC and emodin-EGFR complexes, with β-sitosterol-TNF showing the lowest binding free energy. Conclusions: PRD may exert therapeutic effects against T2DM through coordinated multi-compound, multi-target and multi-pathway regulation involving inflammation, insulin signalling, oxidative stress and metabolic pathways. β-sitosterol may represent an important candidate material basis of PRD, with TNF, AKT1, SRC and EGFR as potential key targets.

Abstract: Electric vehicle (EV) transport by ship is expanding beyond industrial logistics centered on automobile production, trade, and pure car and truck carriers (PCTCs) into daily transportation for island tourism, commuting, and essential mobility. According to Korea Maritime Transportation Safety Authority (KOMSA) vessel status data as of March 2026, 104 of 146 domestic passenger ships were car-ferry passenger ships, accounting for 71.2% of the fleet and operating on 75 of 99 designated routes nationwide. Korea Shipping Association (KSA) operational records show that the EV transport rate on these routes increased from 0.76% in 2024 to 1.21% in 2025, with some routes exceeding 2.0–4.7%. Unlike enclosed multi-deck PCTC vehicle spaces, Korean coastal car-ferry passenger ships generally have single-tier open vehicle decks and bow ramp gates. Crosswinds on open decks may reduce smoke detector activation probability by 60–75%. Although Article 97 of the Standard for Ship Fire-Fighting Appliance newly requires dedicated EV fire-fighting equipment for car-ferry ships, it remains primarily equipment-prescriptive and does not yet provide open-deck-specific performance requirements for wind-resistant detection, fixed EV-zone cooling, EV-designated stowage arrangements, or passenger-operator safety management obligations. This study applies the five-step International Maritime Organization (IMO) Formal Safety Assessment (FSA) procedure to support improvements to EV fire-fighting equipment standards for coastal car-ferry passenger ships. Hazard Identification (HAZID) was conducted with a 15-member advisory panel, and probability elicitation was performed through a Delphi survey with 10 core experts, showing strong consensus (Kendall’s W = 0.74, p < 0.01). Fault Tree Analysis (FTA) and Event Tree Analysis (ETA) probabilities were derived from the Delphi results and international literature. H-07, representing wind-induced smoke dilution, was identified as the only first-order minimal cut set. Monte Carlo-based FTA–ETA analysis (n = 10,000) estimated annual fire frequencies of 5.9 × 10⁻², 1.8 × 10⁻¹, and 2.9 × 10⁻¹ yr⁻¹ at EV loading ratios of 10%, 30%, and 50%, respectively, with 2.47 expected fatalities per fire. Risk entered the IMO ALARP band above a 30% EV loading ratio and exceeded the maximum tolerable crew risk above 50%. The combined application of Risk Control Option (RCO) 2, 3, and 4 reduced annual expected fatalities by 85.6%. Based on these results, six RCOs and institutional recommendations are proposed, including strengthened safety management obligations for passenger ship operators.

Abstract: Atrial fibrillation (AF) is a prevalent cardiac arrhythmia associated with significant morbidity and mortality. Structural remodeling of the left atrium, particularly myocardial fibrosis, plays a key role in AF pathogenesis. Matrix metallo-proteinases (MMPs) are critical regulators of extracellular matrix remodeling and may contribute to atrial fibrosis through genetic variation. This case–control study included 179 patients with AF and 56 controls. Eight polymorphisms across five MMP genes (MMP1, MMP2, MMP3, MMP9, and MMP12) were analyzed using PCR-based methods. Associations between single nucleotide polymorphisms (SNPs), AF susceptibility, recurrence, haplotypes, and gene–gene interactions were assessed. The study population was ethnically ho-mogeneous (Polish), minimizing population stratification bias. No significant differences in allele frequencies were observed between AF and control groups in univariate analysis. However, multivariable logistic regression revealed significant associations for MMP1 rs1799750 and MMP2 rs243864 under recessive inheritance models. Haplotype analysis demonstrated a significant global association with AF (p = 0.027), with specific haplotypes showing markedly increased risk. Multifactor dimensionality reduction identified significant gene–gene interactions, particularly involving SNPs in MMP1, MMP2, MMP3, and MMP12. These findings support a polygenic model of AF susceptibility involving extra-cellular matrix remodeling pathways and highlight the importance of multi-locus genetic analyses.

Abstract: Naturally formed treefall gaps represent primary sources of environmental heterogeneity in tropical forests, yet their role in driving the components of beta diversity in specialized leaf-litter fauna remains poorly understood. We investigated the influence of natural treefall gaps on harvestmen (Arachnida: Opiliones) community structure and beta diversity partitioning in a well-preserved Atlantic Forest remnant in southern Bahia, Brazil. Using standardized nocturnal searches and leaf-litter sampling, we recorded 845 individuals across 23 species. Coverage-based rarefaction indicated higher estimated richness in gaps, although observed alpha diversity did not differ significantly among habitats. Community composition differed significantly along the gap–forest gradient, driven mainly by litter depth and microclimatic variation. Indicator species analysis identified Protimesius sp. as a robust gap-specialist. Beta diversity partitioning revealed that turnover accounted for 79.5% of total dissimilarity, while nestedness contributed 20.5%. Treefall gaps exhibited the highest internal beta diversity and species exclusivity, supporting their role as dynamic environmental filters that enhance regional diversity. Our findings highlight the ecological importance of natural disturbance and litter structure in maintaining biodiversity patterns in tropical forests.

Abstract: The sterility of injection pharmaceutical preparation is the most crucial requirement to achieve, as it is injected directly to human body, either intravenously, intramuscularly, or other injection routes and once drug is injected, it moves to other parts of the body through blood flow follows the rules of drug distribution and will have direct contact to all tissues and organ [1]. Theoretically, in order to prevent contamination of microbial by inhibiting the proliferation process, especially in multiple dose of injection drugs, in the final formulation of the drug may need special addition of suitable preservative agent in the preparation [2]. The first step to perform this experimental study was by preparing the sterile pharmaceutical preparation, Diphenhydramine Hydrochloride injection at Sterile Pharmaceutical Preparation Laboratory, of Universitas Muhammadiyah Malang, Indonesia. Once the injection drug was ready, the second step conducted sterility test. The most common method used for sterility test in injection drugs is named direct inoculation. It was conducted by preparing sample from diluted solution of the injection drug, and the concentration was divided into five groups of sample 1:1, 1:2, 1:3, 1:4, 1:5, and undiluted sample (with three times replications) has determined certain level of inactivation of benzyl alcohol as its preservative agent, that was undiluted sample in Thioglycolate medium and 1:1 in Casamino medium. The indicator of bacterial growth in the study was Bacillus subtilis for Thioglycolate medium on range of temperature 30°-35 °C, and Candida albicans as an indicator of fungal growth in Casamino medium on range of temperature 20°-25 °C, both of Thioglycolate and Casamino medium were observed for 14 days. Inactivation of preservative agent and sterility test were performed under LAFC condition and it required some controls of LAFC environment to ensure that experiment was conducted under optimum condition and to avoid false positive result. According to those results of our study, the sterility test has indicated that our Diphenhydramine Hydrochloride injection was sterile after over a period of 14 days of observation.

Abstract: Inventory systems are typically evaluated using aggregate performance metrics such as out-of-stock and average inventory. In supply chain management, it is important to understand the underlying reasons for a period's performance— specifically, how previous inventory management decisions, such as order placement, lead to the result and what their contributions are. Traditional methods are often restrictive and cannot be applied to broader cases. This paper proposes a Shapley-based decomposition framework that attributes the realized performance gap between the observed inventory policy and optimized reference policy to individual decisions. A numerical experiment on a simulated finite-horizon periodic-review inventory system with stochastic demand and lead time is conducted to illustrate the basic idea of the method. Compared to traditional methods, the proposed approach directly explains a realized benchmark-relative performance difference and is applicable to integer-constrained, non-differentiable, and simulation-based inventory systems. It enables transparent inventory management performance evaluation and effective root-cause analysis.

Abstract: Asymmetry Theory (AT) is derived from a single empirically validated principle: light propagates at constant speed c from its emission origin, addressing the foundational question: is STR's principle of relativity empirically necessary? AT transformation covers Lorentz and Galilean transformations as limiting cases while retaining absolute time. AT unifies classical and relativistic physics: In “Transverse Regime” — observer motion is perpendicular to the ‘source-observer’ line — AT is equivalent to Lorentz transformation, preserving Lorentz invariance and reproducing all validated predictions of STR, while naturally handling non-inertial frames. In “Longitudinal Regime”, AT reduces to Galilean transformation. A central insight is that “Transverse Regime” is the natural equilibrium state of conservative systems in motion. This explains why established high-precision Lorentz invariance tests operate predominantly in the transverse regime and are therefore consistent with both AT and STR. The longitudinal regime is the untested empirical frontier where AT makes testable novel predictions distinguishing it from STR: (1) Sagnac phase shift in inertial frame; (2) momentum asymmetry for parallel acceleration versus deceleration. AT derives: (1) a light observed velocity formula explaining Sagnac effect, GPS one-way light speed, stellar aberration, and optical clock variation; (2) a unified formula encompassing both classical and relativistic Doppler effects, cosmological redshift, and Cherenkov radiation; (3) electrodynamics equations addressing particle acceleration, mass-energy equivalence, and matter waves; (4) a unified Maxwell's equations yielding classical and transverse Doppler and Sagnac effects as solutions.AT maintains consistency with all established empirical evidence: Michelson-Morley, optical cavity resonators, Hafele-Keating, optical clock, Ives-Stilwell spectroscopy, particle accelerators, muon decay, nuclear reactions and GPS Sagnac corrections. AT is also consistent with the anomalous Gezari lunar ranging and Thim microwave results, which remain unexplained within STR. A first-order sensitive motion-controlled interferometer is proposed for the decisive test of AT. In summary, AT is a mathematically rigorous, self-consistent and empirically supported framework that unifies classical and relativistic physics under a single derivable principle, with a decisive test proposed.

Abstract: 3,4-Methylenedioxyamphetamine (MDMA) has been shown in multiple clinical trials to greatly reduce Post-Traumatic Stress Disorder (PTSD) symptoms, with many patients experiencing lasting improvement. However, recent regulatory rejection based on problems with blinding highlights a contradiction, with regulatory agencies demanding placebo-controlled trials, yet the strong psychoactive effects of MDMA-assisted therapy make true blinding impossible.This paper examines neurofunctional mechanisms and methodological challenges relevant to MDMA-assisted therapy research. First, it introduces the Trauma-Affective Memory Loop (TAML), a simple model of how traumatic memories are stored, reactivated, and reinforced through key brain regions. Second, it explains how MDMA works on a neurofunctional level, by reducing fear signals it creates a temporary “therapeutic window”. In this state, patients can revisit trauma safely, without being overwhelmed, and reprocess the memory in a healthier way.Third, the paper proposes that different types of trauma exposures respond differently to MDMA-assisted therapy. Acute, one-time traumas may often be resolved within one to three MDMA sessions, while complex or developmental trauma, formed over years, may need repeated and carefully structured treatment.Finally, a proposed clinical-trial framework, the Brinzei MDMA-PTSD Protocol (BMPP), is presented. The framework uses a role-separated, quadruple-masked structure intended to reduce expectancy-related bias while preserving therapeutic fidelity. The aim is to move beyond debates about flawed blinding methods and instead design trials that clarify why MDMA works, for whom it works best, and how to deliver it safely and effectively.

Abstract: Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide and remains therapeutically challenging owing to its marked inter- and intratumoral heterogeneity, diverse etiologies, and high rates of drug resistance. This review aims to summarize the current knowledge on the complexity of HCC and to evaluate emerging therapeutic strategies, with a particular focus on targeting the RNA-binding protein HuR as a novel approach to overcome treatment limitations. Methods: A narrative review was conducted of peer-reviewed publications focusing on HCC pathogenesis, tumor heterogeneity, resistance mechanisms, and therapeutic developments. Emphasis was placed on studies investigating the molecular drivers of HCC, tumor microenvironment interactions, and novel treatment strategies. Results: HCC progression is driven by complex interactions between genetic, epigenetic, and environmental factors, resulting in significant variability in treatment response. Tumor heterogeneity, cancer stem cell populations, and an immunosuppressive tumor microenvironment contribute to resistance to conventional therapies, including multikinase inhibitors and immune checkpoint inhibitors. Emerging strategies targeting these mechanisms, such as combination immunotherapies, metabolic targeting, and epigenetic modulation, show promise, but remain limited by incomplete efficacy. HuR is a central post-transcriptional regulator that stabilizes mRNAs encoding oncogenic and pro-survival factors. Preclinical studies have demonstrated that the pharmacological inhibition of HuR disrupts tumor-promoting pathways and enhances therapeutic sensitivity. Conclusions: The complexity of HCC necessitates multifaceted precision-based therapeutic approaches. Targeting HuR is a promising strategy for addressing tumor heterogeneity and drug resistance. Continued integration of molecular profiling, advanced technologies, and rational combination therapies is critical for translating these advances into improved clinical outcomes.

Abstract: This study assessed the current status of irrigation systems and water management practices in Rwanda’s irrigated agricultural zones focusing on Nasho Government Funded Irrigation (GFI) scheme in Kirehe District and Kagitumba Irrigation Scheme in Nyagatare District. A mixed descriptive approach was applied combining field observation with structured questionnaires administered through Kobo Toolbox to 224 respondents in Nasho and 188 respondents in Kagitumba. Field observations were used to evaluate the physical condition and functionality of irrigation infrastructure while questionnaires captured stakeholder perceptions, water management practices, institutional arrangements and operational challenges. Results show that both irrigation schemes are operational but function below optimal efficiency due to multiple constraints. In Nasho, irrigation performance is mainly affected by sedimentation in canals and reservoirs, pump inefficiencies and inadequate maintenance practices leading to unreliable water delivery. In Kagitumba, despite the use of modern center pivot systems performance is constrained by pipeline corrosion, pressure losses, sediment-laden water and uneven water distribution. Across both schemes, more than 80% of respondents reported frequent system failures while over 95% indicated the absence of formal irrigation scheduling practices. Water management remains largely reactive with limited preventive maintenance and weak technical capacity among users and institutions. The study concludes that improving irrigation efficiency in Rwanda requires integrated interventions combining infrastructure rehabilitation, strengthened maintenance systems, improved water governance and farmer capacity development to enhance sustainable water use and agricultural productivity.

Abstract: Enzyme replacement therapy (ERT) for central nervous system symptoms and newborn screening (NBS) are available in Japan for patients with mucopolysaccharidosis type II (MPS II). The participants were individuals referred to our facility through NBS who were suspected of having neuronopathic MPS II. We reviewed the clinical course of patients who received intracerebroventricular (ICV)-ERT, idursulfase beta (Hunterase®), followed by hematopoietic stem cell transplantation (HSCT) using umbilical cord blood. Longitudinal measurements of heparan sulfate (HS) in the cerebrospinal fluid (CSF) were performed as a therapeutic biomarker, and developmental age was evaluated. Three patients diagnosed and treated with ICV-ERT received cord blood transplantation (CBT). All patients achieved successful engraftment with no severe complications except for one patient with sinusoidal obstruction syndrome. The HS in the CSF showed a temporary increase during the ERT discontinuation period owing to CBT and a subsequent reduction after the resumption of ICV-ERT. The patients exhibited age-appropriate development. The pattern of change in HS suggests the importance of continuing ICV-ERT even after HSCT. The combination of ICV-ERT and CBT may yield promising outcomes in patients with neuronopathic MPS II and underscores the importance of early intervention through NBS.