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关键词： coronary artery disease   paclitaxel-coated balloon   sirolimus-coated balloons   prognosis   ACS   acute coronary syndrome   CAD   coronary artery disease   CI   confidence interval   DCB   drug-coated balloons   ISR   in-stent restenosis   MACE   major adverse cardiovascular events   MI   myocardial infarction   OR   odds ratio   PCB   paclitaxel-coated balloon   PCI   percutaneous coronary intervention   PSM   Propensity Score Matching   SCB   sirolimus-coated balloon   TIMI   Thrombolysis in Myocardial Infarction   TLR   target lesion revascularization  

摘要： Drug-coated balloons (DCB) have emerged as a valuable alternative to drug-eluting stents for obstructive coronary artery disease (CAD). While paclitaxel-coated balloons (PCB) are the most employed DCB, sirolimus-coated balloons (SCB) have been evaluated in recent years to address potential safety concerns associated with PCB. However, real-world comparisons of the clinical outcomes of PCB and SCB remain limited. We combined 2 large prospective registries involving patients undergoing percutaneous coronary intervention with DCB: the EASTBOURNE registry (n = 2,078 patients, treated with MagicTouch SCB) and the PEARL registry (n = 513 patients, treated with Protégé PCB). The primary outcome was major adverse cardiac events (MACE), a composite of all-cause mortality, myocardial infarction (MI), and target lesion revascularization (TLR) at 2-year follow-up. All analyses were stratified according to clinical presentation: de novo CAD and in-stent restenosis (ISR). Hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression. Adjustment was performed for clinical and angiographic variables that differed between the 2 groups. At 24 months, the risk of MACE was similar between SCB and PCB both in de novo CAD (unadjusted HR 0.80, 95% CI 0.43–1.50; p = 0.487; adjusted HR 0.94, 95% CI 0.47–1.95; p = 0.849) and ISR (unadjusted HR 0.96, 95% CI 0.70–1.32; p = 0.544; adjusted HR 0.90, 95% CI 0.63–1.28; p = 0.555). This real-world comparison demonstrated comparable outcomes between new-generation PCB and SCB with respect to MACE at 2 years of follow-up.

关键词： Modeling   Inhibitors   Training   Drugs   Cams   Computer aided manufacturing   Compounds   Testing   Accuracy   Machine learning  

摘要： Dengue fever is responsible for a significant number of deaths worldwide. Despite ongoing research, there is currently no cure for this mosquito-borne disease. The Non-Structural 3 (NS3) protein is a crucial component of the Dengue virus replication and has emerged as a promising target for novel therapeutic interventions. Traditional drug discovery is often costly and inefficient, making in-silico approaches like Quantitative Structure-Activity Relationship (QSAR) increasingly popular. Although several QSAR methods exist for identifying NS3 inhibitors, they rely on molecular descriptors and may fail to capture the full range of molecular structural properties. Our study proposes a novel application to identify NS3 inhibitors based on 2D images of molecular structures. These images offer a more complete representation of molecular features. To address data scarcity, we applied both image augmentation and Simplified Molecular Input Line Entry System (SMILES) enumeration to identify the most effective one. The model trained on images of enumerated SMILES achieved 96.86% test accuracy on the augmented balanced test set, although its performance dropped on the smaller raw test set. Regardless, our image-based method significantly outperforms existing descriptor-based models. Gradient-weighted Class Activation Mapping (Grad-CAM) visualizations revealed that one of the models consistently focused on the hydroxyl group, pointing to it as a potentially relevant compound associated with NS3 inhibition. Future work could focus on applying advanced deep learning and in-vitro techniques to better understand molecular interactions.

关键词： Abiotic and biotic stress tolerance   Arid agroecosystems   CAM physiology   PGPR-AMF interactions   Sustainable agriculture  

摘要： Climate change is intensifying environmental constraints in arid and semi-arid regions, where agricultural systems face recurrent drought, soil degradation, salinity, nutrient depletion, and increasing biotic pressures. While perennial crops are increasingly recognized for their role in stabilizing agroecosystems, the mechanistic integration of plant functional traits, microbial symbioses, and agroecological practices remains insufficiently addressed, particularly in Crassulacean Acid Metabolism (CAM) species. Opuntia ficus-indica, a widely cultivated CAM perennial, represents a relevant model for understanding plant resilience under water-limited conditions due to its high water-use efficiency and stress-adaptive traits. This review addresses this gap by synthesizing current knowledge through a structured framework encompassing i) functional traits of perennial and CAM plants ii) responses of O. ficus-indica to major abiotic and biotic stresses iii) agroecological practices for stress mitigation, and (iv) the role of plant growth-promoting rhizobacteria (PGPR) and arbuscular mycorrhizal fungi (AMF) in enhancing plant resilience. Mechanistically, agroecological practices such as intercropping, organic amendments, soil conservation, and optimized water management improve soil quality and resource availability, thereby supporting plant adaptive responses. In parallel, PGPR and AMF enhance stress tolerance through complementary processes, including improved nutrient acquisition, modulation of phytohormonal balance, osmotic adjustment, ion homeostasis, and activation of antioxidant defense systems. By integrating plant functional ecology, microbial interactions, and agroecological strategies, this review proposes a conceptual framework that positions O. ficus-indica as a model CAM system for improving stress resilience. Such integrative approaches are particularly relevant for optimizing the performance and sustainability of CAM crops under multiple environmental constr

关键词： Computer Aided Design (CAD)   Field Programmable Gate Array   Large Language Model (LLM)  

摘要： AbstractModern FPGA computer-aided design (CAD) flows have grown increasingly complex, integrating numerous stages, configuration parameters, timing constraints, and physical implementation specifications. As designs scale, failures often arise from subtle interactions across command-line options and constraint files, making debugging time-consuming and heavily dependent on expert knowledge. Identifying the root cause of such failures and determining the appropriate corrective action remains a major productivity bottleneck in CAD workflows.This paper presents VTR-LLM, a fully automated, multi-agent framework for diagnosing and resolving failures in the Verilog-to-Routing (VTR) CAD flow. VTR-LLM leverages large language models (LLMs) in combination with retrieval-augmented generation (RAG) and specialized agents that target distinct sources of errors, including command-line invocations, timing constraints (i.e., Synopsys Design Constraints or SDC), and floorplanning specifications. A Classification Agent dynamically assigns each failure to the most appropriate agent and supports sequential resolution for compound failures involving multiple error sources. The system leverages LLMs without requiring fine-tuning, enabling use of the latest models such as GPT-OSS-120B, by using RAG and intelligent agents to add domain-specific context and behaviours.We evaluate VTR-LLM using a dataset of 92 distinct VTR failure cases spanning multiple error patterns and levels of complexity. VTR-LLM can resolve 95% of all failures fully automatically, with robust performance across error categories. Additional studies demonstrate the impact of documentation retrieval scope, tool iteration, and LLM model choice on resolution accuracy and inference cost.

关键词： Sutimlimab   cold agglutinin disease   CAD   complement   AIHA  

摘要： Introduction Sutimlimab, a classical complement pathway (CP) inhibitor, was approved in 2022 in the US, EU, and Japan for the treatment of cold agglutinin disease (CAD a rare form of autoimmune hemolytic anemia (AIHA) characterized by CP-mediated extravascular hemolysis and circulatory symptoms related to IgM-mediated red blood cell (RBC) agglutination. This review reexamines the clinical trial data and compares those findings with published real-world experience (RWE providing clinicians with efficacy and safety data that extend beyond the clinical trial experience in this rare AIHA.Areas covered The first-in-human trials, the two seminal clinical trials (CARDINAL and CADENZA and the published post-marketing RWE are presented. Literature searches for CAD and sutimlimab were conducted in PubMed and in abstracts from ASH and EHA from 2016 to present. All articles and abstracts regarding sutimlimab and CAD were included.Expert opinion Long-term data from clinical trials and published RWE support the safety and efficacy of sutimlimab. Targeting the CP as primary therapy for CAD offers a unique, targeted management strategy that minimizes exposure to immunosuppressive regimens. The rapid onset of sutimlimab's activity provides a potentially lifesaving treatment option in situations where immediate control of hemolysis is critical. Opportunities remain to increase our understanding of the role of complement inhibition combined with immunosuppressive therapy in CAD. The impact of complement inhibition on morbidity and mortality in CAD remains to be determined.

关键词： inerter-based response amplification device   shaking table test   friction amplification   negative stiffness   seismic response control   out-of-plane deformation  

摘要： The inerter-based response amplification device for dampers has been proposed to enhance seismic resilience, yet its real-world dynamic behavior lacks experimental validation. This study investigates a Cam-Type Response-Amplification Friction Damper (CRAFD) through shaking table test of full-scale steel frame subjected to nine seismic records (including near/far-field events). Key findings reveal that the CRAFD achieves 1) Target amplification of friction forces (8 kN vs lateral FD's 1.2 kN) and inertial mass, inducing significant negative stiffness in the primary structure;(2) The natural frequency decreased by a maximum of 34% (from 2.9 Hz to 1.91 Hz) under 0.4 g inputs, and the equivalent damping ratio was significantly improved compared to traditional FD;(3) Higher displacement mitigation and acceleration reduction by maintaining sliding status, which elevates energy dissipation ratio and prevents structural damage;(4) CRAFD suppresses out-of-plane deformation in V-shape linkages. These results validate CRAFD's efficacy in seismic response control for engineering applications.

关键词： AA   Alopecia Areata   AKBA   Acetyl-11-keto-β-boswellic Acid   AM   Addictive Manufacturing   AMP   antimicrobial peptide   BAC   Benzalkonium Chloride   CAD   Computer-Aided Design   cAT   Commercial Artificial Tears   CCK-8   Cell Counting Kit-8   CMC   Carboxymethylcellulose   CTL   Cytotoxic T Lymphocyte   DAB   Droplet-Born Air Blowing   DMNs   dissolving microneedles   DED   dry eye disease   DFO   deferoxamine   DLP   digital light processing   DUs   Diabetic Ulcers   ELE   β-Elemene   FITC   Fluorescein Isothiocyanate   HA   Hyaluronic Acid   HA-MN / HA-MNs   Hyaluronic Acid-Based Microneedle(s)   H&E   Hematoxylin and Eosin   HS   Solutol HS-15   HUVECs   Human Umbilical Vein Endothelial Cells   IFN-γ   Interferon-Gamma   IgE   Immunoglobulin E   IgG1   Immunoglobulin G1   IL-1β   Interleukin-1 Beta   IL-13   Interleukin-13   IL-15   Interleukin-15   IHC   Immunohistochemistry   IND   indomethacin   JAK   Janus Kinase   LA   Lipoic Acid   LMW-HA   Low Molecular Weight Hyaluronic Acid   MH   Microhyala   MIT   microneedle immunotherapy   MN / MNs   Microneedle(s)   μIM   Micro-Injection Molding   NCs   Nanocomposites   NIH-3T3   Mouse Embryonic Fibroblast Cell Line   NLRP3   NOD-Like Receptor Protein 3   NPs   Nanoparticles   NorHACA   Norbornene-Modified Hyaluronic Acid   OVA   Ovalbumin   OIT   Oral immunotherapy   ox-mtDNA   Oxidized Mitochondrial DNA   PBS   Phosphate-Buffered Saline   PE   Peanut Extracts   P-gp   P-glycoprotein   PDMS   Polydimethylsiloxane   PLGA   Poly(lactic-co-glycolic acid)   PVA   poly(vinyl alcohol)   PVP   poly(vinyl pyrrolidone)   RA   Rheumatoid Arthritis   ROS   Reactive Oxygen Species   RY   RADA16-YIGSR Peptide   SC   Subcutaneous   SLA   Stereolithography   S-MAP   Separable Microneedle Array Patch   STAT   Signal Transducer and Activator of Transcription   SF   Silk fibroin   STZ   Streptozotocin   TLR3   Toll-Like Receptor 3   TEWL   Trans-epidermal water loss   UV   Ultraviolet   VEGF   Vascular Endothelial Growth Factor   YG   Ethyl Lauroyl Arginate Hydrochloride   α-SMA   Alpha-Smooth Muscle Actin   8-OHdG   8-Hydroxy-2′-Deoxyguanosine   Hyaluronic acid   Microneedles   Transdermal drug delivery   Dissolving microneedles   Biomedical applications   Controlled drug release  

摘要： Hyaluronic acid (HA)-based microneedles have emerged as highly promising minimally invasive platforms for transdermal and transmucosal drug delivery, overcoming the limitations of conventional oral, topical, and injectable therapies. Owing to its excellent biocompatibility, biodegradability, hydrophilicity, non-immunogenicity, and intrinsic bioactivity, HA functions not only as a structural biomaterial but also as a therapeutic component that enhances tissue hydration, wound healing, immune modulation, and drug bioavailability. This review provides a comprehensive overview of the major fabrication strategies used for HA-based microneedles, including micro-molding, photolithography, centrifugal lithography, droplet-born air blowing, and additive manufacturing approaches. The effects of these techniques on microneedle geometry, mechanical strength, drug-loading capacity, dissolution behavior, and controlled-release performance are critically discussed.

关键词： 3D printing   CAD-CAM   ceramics   dental crowns   dental marginal adaptation   dental prosthesis design   microscopy   prosthodontics   zirconia  

摘要： Purpose This study evaluated and compared the marginal fit of CAD-CAM zirconia crown copings with and without a 3D-printed control model.Materials and Methods This prospective in vitro trial involved 30 zirconia crown copings made from the same STL file. These were divided into two groups. Half of them had their own 3D-printed control model made from the same STL file (With-Printed-Model group whereas the other half lacked any control model (No-Printed-Model group). Both groups underwent manual adjustments in a systematic way. Their marginal gaps were evaluated using a digital optical microscope from eight zones: buccal, mesiobuccal, mesial, mesiopalatal, palatal, distopalatal, distal, and distobuccal.Results The mean values with standard deviations for the With-Printed-Model and No-Printed-Model groups were 15.18 +/- 14.49 and 12.46 +/- 14.09 & micro;m, respectively. All crown copings from both groups were below 75 & micro;m. Statistical analysis showed a significant difference between the two groups.Conclusion The No-Printed-Model group demonstrated superior marginal fit compared to the With-Printed-Model group. However, the largest marginal gaps from each group were still within the clinically acceptable range below 75 & micro;m. Although the 3D-printed control model did not improve marginal fit, its primary function is to effectively identify major manufacturing errors.