Search

Soluble guanylate cyclase (sGC) modulation has been scrutinized in several disease states including heart failure (HF). Recently, it was shown that an sGC modulator improved HF-related hospitalization significantly, though, there was no benefit related to mortality. Herein, a comprehensive meta-analysis of randomized controlled trials (RCTs) for sGC modulation in HF patients was provided in agreement with the PRISMA statement. A total of 10 RCTs yielding 12 papers were included. There were 7526 patients with heart failure of each phenotype, 4253 in the sGC modulator group and 3273 in the placebo group. Use of sGC modulators in HF patients yielded no significant difference in the risk of all-cause mortality compared to placebo (RR = 0.97, 95% CI 0.88–1.08, p = 0.62). The use of sGC modulators was associated with a trend toward a considerable but non-significant increase in the incidence of SAEs (RR = 1.10, 95% CI 0.99–1.22, p = 0.07), as well as an increased incidence of hypotension and anemia. There was an overall neutral effect of sGC modulation on NT-proBNP levels, 6MWD and mortality, at a cost of slight increase in hypotension and anemia. Of note, the improvement in EQ-5D-based quality of life was significant. Hence, the benefit seems to be driven by distinctive domains of quality of life. [ABSTRACT FROM AUTHOR]

Existing video object segmentation (VOS) methods based on matching techniques commonly employ a reference set comprising historical segmented frames, referred to as 'memory frames', to facilitate the segmentation process. However, these methods suffer from the following limitations: (i) Inherent segmentation errors in memory frames can propagate and accumulate errors when utilized as templates for subsequent segmentation. (ii) The non-local matching technique employed in top-leading solutions often fails to incorporate positional information, potentially leading to incorrect matching. In this paper, we introduce the Modulated Memory Network (MMN) for VOS. Our MMN enhances matching-based VOS methods in the following ways: (i) Introducing an Importance Modulator, which adjusts memory frames using adaptive weight maps generated based on the segmentation confidence associated with each frame. (ii) Incorporating a Position Modulator that encodes spatial and temporal positional information for both memory frames and the current frame. The proposed modulator improves matching accuracy by embedding positional information. Meanwhile, the Importance Modulator mitigates error propagation and accumulation by incorporating confidence-based modulation. Through extensive experimentation, we demonstrate the effectiveness of our proposed MMN, which also achieves promising performance on VOS benchmarks. [ABSTRACT FROM AUTHOR]

In this paper, we present an electro-optical modulator based on graphene absorption. In this structure, graphene is placed on aluminum oxide, the structure of which is repeated alternately. This alternating structure of graphene on aluminum oxide is located inside a semi-cylindrical cavity in a 1-dimensional photonic crystal nanobeam cavity. Unlike previous articles, which consisted of cylinder holes and different areas in the nanobeam cavity is formed by changing the radius of the holes, in this structure, semi-cylinder holes have been used and, different areas are formed by rotating these semi-cylinders. This type of crystal photonics has a high quality factor. Also, this type of modulator requires little space after construction, so they are a very good option for integrated circuits. In this paper, three-dimensional finite-difference time-domain method is used for analysis. In this modulator, it is observed that by changing the bias voltage, the amount of absorption peak and also its resonance wavelength are changed. As a result of these changes, we achieve a modulation depth of about 7dB. Our proposed structure can have potential applications in integrated optical circuits, especially in telecommunication frequencies.

Abstract Soluble guanylate cyclase (sGC) modulation has been scrutinized in several disease states including heart failure (HF). Recently, it was shown that an sGC modulator improved HF-related hospitalization significantly, though, there was no benefit related to mortality. Herein, a comprehensive meta-analysis of randomized controlled trials (RCTs) for sGC modulation in HF patients was provided in agreement with the PRISMA statement. A total of 10 RCTs yielding 12 papers were included. There were 7526 patients with heart failure of each phenotype, 4253 in the sGC modulator group and 3273 in the placebo group. Use of sGC modulators in HF patients yielded no significant difference in the risk of all-cause mortality compared to placebo (RR = 0.97, 95% CI 0.88–1.08, p = 0.62). The use of sGC modulators was associated with a trend toward a considerable but non-significant increase in the incidence of SAEs (RR = 1.10, 95% CI 0.99–1.22, p = 0.07), as well as an increased incidence of hypotension and anemia. There was an overall neutral effect of sGC modulation on NT-proBNP levels, 6MWD and mortality, at a cost of slight increase in hypotension and anemia. Of note, the improvement in EQ-5D-based quality of life was significant. Hence, the benefit seems to be driven by distinctive domains of quality of life.

Sirtuins (SIRTs) represent a class of nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylases that exert a crucial role in cellular signal transduction and various biological processes. The mammalian sirtuins family encompasses SIRT1 to SIRT7, exhibiting therapeutic potential in counteracting cellular aging, modulating metabolism, responding to oxidative stress, inhibiting tumors, and improving cellular microenvironment. These enzymes are intricately linked to the occurrence and treatment of diverse pathological conditions, including cancer, autoimmune diseases, and cardiovascular disorders. Given the significance of histone modification in gene expression and chromatin structure, maintaining the equilibrium of the sirtuins family is imperative for disease prevention and health restoration. Mounting evidence suggests that modulators of SIRTs play a crucial role in treating various diseases and maintaining physiological balance. This review delves into the molecular structure and regulatory functions of the sirtuins family, reviews the classification and historical evolution of SIRTs modulators, offers a systematic overview of existing SIRTs modulation strategies, and elucidates the regulatory mechanisms of SIRTs modulators (agonists and inhibitors) and their clinical applications. The article concludes by summarizing the challenges encountered in SIRTs modulator research and offering insights into future research directions. [Display omitted] • Sirtuins (SIRTs), as key regulatory factors in cellular processes, are deeply involved in many life processes. • SIRTs modulators have shown great potential in treating various diseases and maintaining physiological balance. • The field of SIRTs and its modulators is developing very rapidly. This paper fills the gap in the research summary of SIRTs modulators in time, and provides valuable insights into the challenges encountered in the research field. [ABSTRACT FROM AUTHOR]

Fatty acid binding proteins (Fabps) are small soluble proteins that are abundant in the cytosol. These proteins are known to bind a myriad of small hydrophobic molecules and have been postulated to serve a variety of roles, yet their precise functions have remained an enigma over half a century of study. Here, we consider recent findings, along with the cumulative findings contributed by many laboratories working on Fabps over the last half century, to synthesize a new outlook for what functions Fabps serve in cells and organisms. Collectively, the findings illustrate that Fabps function as versatile multi‐purpose devices serving as sensors, conveyors and modulators to enable cells to detect and handle a specific class of metabolites, and to adjust their metabolic capacity and efficiency. [ABSTRACT FROM AUTHOR]

Existing video object segmentation (VOS) methods based on matching techniques commonly employ a reference set comprising historical segmented frames, referred to as ‘memory frames’, to facilitate the segmentation process. However, these methods suffer from the following limitations: (i) Inherent segmentation errors in memory frames can propagate and accumulate errors when utilized as templates for subsequent segmentation. (ii) The non-local matching technique employed in top-leading solutions often fails to incorporate positional information, potentially leading to incorrect matching. In this paper, we introduce the Modulated Memory Network (MMN) for VOS. Our MMN enhances matching-based VOS methods in the following ways: (i) Introducing an Importance Modulator, which adjusts memory frames using adaptive weight maps generated based on the segmentation confidence associated with each frame. (ii) Incorporating a Position Modulator that encodes spatial and temporal positional information for both memory frames and the current frame. The proposed modulator improves matching accuracy by embedding positional information. Meanwhile, the Importance Modulator mitigates error propagation and accumulation by incorporating confidence-based modulation. Through extensive experimentation, we demonstrate the effectiveness of our proposed MMN, which also achieves promising performance on VOS benchmarks.