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    A Controlled Trial Comparing One-Year Hemodynamics of Two Bovine Pericardial Valves

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    Background This randomized controlled trial was designed to compare 1-year hemodynamic performances and clinical outcomes after aortic valve replacement (AVR) using a recently introduced (the AVALUS group) and worldwide used (the CEPME group) bovine pericardial bio prostheses.Methods Patients were screened to enroll 70 patients in each group based on a noninferiority design. The primary endpoint of the trial was the mean pressure gradient across the aortic valve (AVMPG) at 1 year after surgery. One-year echocardiographic data were obtained from 92.1% (129 of 140 patients) of the study patients.Results There were no differences in baseline characteristics, including sex and body surface area (1.64 +/- 0.18 vs. 1.65 +/- 0.15 m(2)) between the groups. The AVMPG on 1-year echocardiography was 14.0 +/- 4.3 and 13.9 +/- 5.1mmHg in the AVALUS and CEPME groups, respectively (the p-value for non inferiority was 0.0004). In the sub group analyses for the respective size of the prostheses, AVMPG of the 19-mm prostheses was significantly lower in the AVALUS group than in the CEPME group (14.0 +/- 4.3 vs.20.0 +/- 4.7 mmHg,p=0.012), whereas those of the other sizes were not significantly different between the two groups. There were no significant differences in the effective orifice area (1.49 +/- 0.40 vs. 1.53 +/- 0.38cm(2),p=0.500) or effective orifice area index(0.91 +/- 0.22 vs 0.93 +/- 0.23 cm(2)/m(2),p=0.570) in all the patients, or in the sub group analysis for the 19-mm prosthesis. There were no differences in the 1-year clinical outcomes between the two groups.Conclusion The 1-year hemodynamic and clinical outcomes of the AVALUS group were noninferior to those of the CEPME group (NCT03796442).N

    Long-term outcomes of concomitant Cox-Maze III procedure in patients with aortic valve diseases and preoperative atrial fibrillation

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    Background: There was limited evidence on the clinical benefits of the concomitant Cox-Maze procedure with aortic valve replacement (AVR) in patients with atrial fibrillation. This study aimed to evaluate the early and long-term results of the concomitant Cox-Maze procedure in patients undergoing AVR for aortic valve disease. Methods: We enrolled 101 patients who underwent AVR and had preoperative atrial fibrillation between January 1994 and December 2020. The early- and long-term clinical outcomes were compared between patients who underwent the concomitant Cox-Maze III procedures and those who did not undergo surgical ablation. Inverse probability of treatment weighting (IPTW) was used to adjust for differences in preoperative characteristics. Results: Forty-seven patients underwent the concomitant Cox-Maze III procedure (CM group), and 54 patients did not undergo surgical ablation for atrial fibrillation (non-CM group). There were no significant differences in early surgical outcomes between the two groups, except for a higher occurrence of acute kidney injury (AKI) in the CM group (P<0.001). The median follow-up duration was 70.7 months (interquartile range 36.2-118.8 months), and there were no significant differences in overall survival, thromboembolic complications, and anticoagulation-related bleeding between the two groups. Atrial fibrillation occurrence was significantly lower (P<0.001) in the CM group, and a greater number of patients discontinued anticoagulation in the CM group compared to the non-CM group (P=0.001). Conclusions: The concomitant Cox-Maze procedure in patients with atrial fibrillation undergoing AVR did not increase early mortality or morbidity, except for AKI, and showed favorable long-term results in terms of rhythm outcome and anticoagulation discontinuation.N

    Toward Intrinsically Stretchable OLEDs with High Efficiency

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    Wearable electronics require stretchable displays that can withstand large and repeated mechanical deformation without failure. Intrinsically stretchable organic light-emitting diodes (ISOLEDs) that operate under DC voltage provide promising candidates for wearable display applications. However, the lack of sophisticated stretchable materials and processing techniques suitable for ISOLEDs results in a significant deficit in the efficiency of state-of-the-art ISOLEDs compared to industrial standards. The design of stretchable conducting and semiconducting materials poses a significant challenge because of trade-off relationships between stretchability and properties such as conductivity and charge carrier mobility. To increase the efficiency of ISOLEDs to meet industrial standards, strategies to overcome these trade-offs must be developed. This perspective discusses recent progress and challenges in designing stretchable electrodes, light-emitting materials, transport materials, and potential applications of ISOLEDs. It provides a useful guide in this field to develop efficient ISOLEDs for system-level integration.Y

    Biological interactions of the five genera in the dinoflagellate family Kareniaceae with prey and protistan predators

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    Species and genera in the dinoflagellate family Kareniaceae have attracted the attention of scientists, aquaculture farmers, and government officials because many species in this family cause harmful algal blooms associated with the mortality of vertebrates and invertebrates. In addition, the genera in Kareniaceae exhibit different morphological, biochemical, and genetic characteristics. To understand bloom dynamics and eco-evolutionary strategies of the genera in Kareniaceae, the biological interactions of kareniacean species and genera with prey and predators should be explored. In the present study, we reviewed the trophic modes, prey taxa and size spectra, feeding mechanisms, growth and ingestion rates, and protistan predators of five genera Gertia, Karenia, Karlodinium, Shimiella, and Takayama in the family. Additionally, we explored the feeding occurrence in Gertia stigmatica, the prey spectrum of Karenia brevis, and the predation of Takayama tasmanica by heterotrophic protists, which have not been fully investigated prior to the present study. Karenia, Karlodinium, Shimiella, and Takayama have different prey taxa and size spectra. Furthermore, within the same genus, different species exhibit different biological interactions with prey and protistan predators, creating different ecological niches. This study provides insights into the eco-evolutionary strategies of kareniacean dinoflagellates.Y

    Supramodal and cross-modal representations of working memory in higher-order cortex

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    Working memory is essential for guiding our behaviors in daily life, where sensory information continuously flows from the external environment. While numerous studies have shown the involvement of sensory areas in maintaining working memory in a feature-specific manner, the challenge of utilizing retained sensory representations without interference from incoming stimuli of the same feature remains unresolved. To overcome this, essential information needs to be maintained dually in a form distinct from sensory representations. Here, using working memory tasks to retain braille patterns presented tactually or visually during fMRI scanning, we discovered two distinct forms of high-level working memory representations in the parietal and prefrontal cortex, together with modality-dependent sensory representations. First, we found supramodal representations in the superior parietal cortex that encoded braille identity in a consistent form, regardless of the involved sensory modality. Second, we observed that the prefrontal cortex and inferior parietal cortex specifically encoded cross-modal representations, which emerged during tasks requiring the association of information across sensory modalities, indicating a different high-level representation for integrating a broad range of sensory information. These findings suggest a framework for working memory maintenance that incorporates two distinct types of high-level representations-supramodal and cross-modal-operating alongside sensory representations.N

    Single-photon emission from colloidal perovskite nanocrystals

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    Colloidal perovskite nanocrystals emerge as promising single-photon sources, offering bright, coherent emission and room-temperature operation for future scalable quantum communication technologies.Y

    Spatially resolved transcriptomic profiling for glomerular and tubulointerstitial gene expression in C3 glomerulopathy

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    Background Complement 3 (C3) glomerulopathy (C3G) is a rare but clinically significant glomerulopathy. However, little is known about its transcriptomic profile. We investigated the substructure-specific gene expression profile of C3G using the recently introduced spatial transcriptomics technology.Methods We performed spatial transcriptomic profiling using GeoMx Digital Spatial Profiler with formalin-fixed paraffin-embedded kidney biopsy specimens of three C3G cases and seven controls from donor kidney biopsy. Additionally, 41 samples of other glomerulonephritis, including focal segmental glomerulosclerosis, membranous nephropathy and minimal change disease, were included as disease controls. We identified differentially expressed genes (DEGs) specific to C3G, followed by in vitro validation analysis of consistently upregulated DEGs in human glomerular endothelial cells through a co-culture with complement-stimulated macrophages.Results We found 229 and 157 highly expressed DEGs in the glomeruli of C3G compared with those of donor and disease controls, respectively, including POSTN, COL1A2 and IFI44L. Protease binding, structural molecule activity and extracellular matrix (ECM) structural constituent were among the top enriched Gene Ontology terms in the glomeruli of C3G. Specifically, genes related to the ECM and interferon activity were the most upregulated, with network analysis suggesting possible interactions between complement C3 and the ECM through CD11c. The in vitro experimental validation using iC3b-stimulated CD11c+ macrophages supported these findings, inducing elevated expression of fibrosis markers and ECM components in glomerular endothelial cells.Conclusions Significant disease-specific transcriptomic alterations in C3G, including upregulation of genes related to the ECM, provide potential insights into the pathophysiology.N

    Ceria-Nanoparticle-Entangled Reticulation for Angiogenic and Therapeutic Embrocation for Multifactorial Approach to Treat Diabetic Wound

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    The therapeutic efficacy of a nanomedicine or a natural biomaterial can vary in different disorders due to their complex pathophysiology. A nanomedicine that is capable of not only targeting specific pathological cues through functional ligands but also optimizing the therapeutic efficacy of its components throughout the intricate pathways involved in complex disorders is highly desired. Here, ceria-nanoparticle-entangled reticulation for angiogenic and therapeutic embrocation (CERATE), composed of hyaluronic acid, levofloxacin, and the as-synthesized ceria nanoparticles is developed. CERATE is formulated in situ as a rigid nanoparticle-based network that integrates its components intimately using highly diluted concentrations, thereby augmenting the therapeutic efficiency of its individual components. The physical states of CERATE can be altered freely while retaining its integrity, by adjusting the water proportion to accommodate diverse clinical needs. This physically robust CERATE can withstand enzymatical degradation, display antibacterial activity, scavenge reactive oxygen species, and improve the migration and proliferation of fibroblasts by activating the proangiogenic factors. CERATE accelerates the repair of diabetic wounds by promoting both the angiogenesis and the synthesis of collagen. The results demonstrate the effectiveness of a multifactorial approach involving the recruitment of minimally modified biofunctional ligands and nanomaterials altogether with synergistic efficacy in treating complex disorders.N

    Cytomegalovirus reactivation in the lower respiratory tract as an independent risk factor for mortality in critically Ill patients

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    BackgroundThe clinical significance of cytomegalovirus reactivation in the lower respiratory tract (LRT) of critically ill patients remains unclear. We aimed to investigate the association between cytomegalovirus reactivation detected in LRT and intensive care unit (ICU) prognosis.MethodsThis study included critically ill patients admitted to a medical ICU at a tertiary referral center in South Korea between January 2021 and June 2023. Cytomegalovirus load in LRT samples collected via bronchoscopy was measured within 7 days of admission. Detection of cytomegalovirus DNA in LRT was defined as reactivation. Associations between cytomegalovirus reactivation and ICU, in-hospital, 30-day, and 90-day mortality were assessed using multivariable Fine-Gray model adjusted for major clinical factors.ResultsOf the 322 patients (median age 68 years, 66.8% male), 145 (45%) had cytomegalovirus reactivation in the LRT. Cytomegalovirus reactivation was independently associated with increased ICU (adjusted subdistribution hazard ratio [aSHR], 2.28; 95% confidence interval [CI], 1.46-3.56), in-hospital (aSHR, 2.00; 95% CI, 1.44-2.78), 30-day (aSHR, 2.11; 95% CI, 1.42-3.13), and 90-day mortality (aSHR, 2.05; 95% CI, 1.45-2.88). Anti-cytomegalovirus therapy was significantly associated with reduced ICU mortality in patients with radiologic findings suggestive of cytomegalovirus pneumonia (P for interaction = 0.001), but was linked to increased mortality in patients with positive bacterial cultures (P for interaction = 0.002).ConclusionCytomegalovirus reactivation in the LRT is associated with poor outcomes in critically ill patients. Anti-cytomegalovirus therapy was not associated with overall survival outcomes; however, the subgroup with radiologic findings of cytomegalovirus pneumonia suggested benefits, while the subgroup with bacterial co-infections suggested harmful effects. Randomized controlled trials are needed.Y

    Self-assembled organoid-tissue modules for scalable organoid engineering: Application to chondrogenic regeneration

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    Tissue engineering has made significant strides in creating biomimetic grafts for the repair and regeneration damaged tissues; however, the scalability of engineered tissue constructs remains a major technical hurdle. study introduces a method for generating organoid-tissue modules (Organoid-TMs) through scaffold-free assembly of microblocks (MiBs) derived from adipose-derived mesenchymal stem cells (ADMSCs). The key rameters influencing Organoid-TM formation were identified as the density of MiBs and the controlled mixing ratio of large and small MiBs. The resulting Organoid-TM exhibited a distinctive cup-shaped morphology, millimeter-scale structure with enhanced nutrient and oxygen diffusion compared to conventional spherical aggregates. Despite their larger size, Organoid-TMs maintained ADMSC stemness and differentiation potential, while stemness and differentiation were halted during fabrication. Organoid-TMs receiving chondrogenic during fabrication were transplanted into cartilage defect sites in animal models, demonstrating cartilage regeneration efficacy in a scaffold-independent and xeno-free manner. This fabrication method represents highly reproducible and consistent process for developing spheroids or organoids, offering a robust platform regenerative medicine applications. Specifically, Organoid-TMs provide a foundational framework for peutic strategies targeting cartilage defects and osteoarthritis, paving the way for advancements in engineered therapeutics. Statement of significance: This study introduces a distinct approach in tissue engineering, utilizing self-assembled Organoid-Tissue Modules (Organoid-TMs) to address persistent challenges in scalable organoid production cartilage regeneration. By leveraging adipose-derived mesenchymal stem cells (ADMSCs) and carefully mizing the size, ratio, and spatial organization of microblocks (MiBs), we successfully generated millimeter Organoid-TMs. The distinctive cup-shaped architecture of these Organoid-TMs enhances oxygen and nutrient diffusion, effectively overcoming limitations such as core necrosis typically encountered in large-scale organoid culture. This system demonstrated substantial regenerative potential, particularly in chondrogenic differentiation and cartilage repair in both rabbit and pig models, without the use of artificial scaffolds or xenogenic materials.N

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