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Abstract Background Evidence for the efficacy of pharmacological therapies for heart failure with reduced ejection fraction (HFrEF) is growing. However, there is no consensus on the most effective treatment for HFrEF. This study aimed to evaluate the most effective combination of pharmacological therapy in patients with HFrEF. Methods We systematically searched Medline, Embase, and CENTRAL up to Feb 2022, to include randomized controlled trials (RCTs) that evaluated the efficacy of pharmacological treatment among adults (≥ 18 years) with a diagnosis of HFrEF (defined by a left ventricular ejection fraction ≤ 45%). The outcomes of interest included all-cause death, cardiovascular (CV) death, and hospitalization for heart failure (HHF). A random network meta-analysis using a frequentist framework model was employed to calculate the pooled risk ratio (RR) with 95% confidence interval (CI) and rank the treatments. Results We included 49 RCTs involving 90,529 participants with HFrEF. For reducing all-cause mortality, the combination of angiotensin-converting enzyme inhibitors (ACEI), beta-blockers (BB), mineralocorticoid receptor antagonists (MRA), and sodium-glucose co-transporter-2 inhibitors (SGLT2i) was most effective (RR, 0.46; 95% CI, 0.32–0.66). For CV death, the combination of ACEI, BB, MRA, and Vericiguat showed the highest efficacy (RR, 0.34; 95% CI, 0.12–0.90). Regarding reducing HHF, the combination of ACEI, BB, MRA, and SGLT2i as well as the combination of ACEI, BB, MRA, and Ivabradine were equally the most effective (both RR, 0.27; 95% CI, 0.18–0.39). Conclusion This study provides robust evidence supporting the use of combination therapies in HFrEF management, with newer agents offering incremental benefits when added to established guideline-directed medical therapy.

Based on joint progressive Type-II censored data, we examined the statistical inference of the generalized logistic distribution with different shape and scale parameters in this research. Wherever possible, we explored maximum likelihood estimators for unknown parameters within the scope of the joint progressive censoring scheme. Bayesian inferences for these parameters were demonstrated using a Gamma prior under the squared error loss function and the linear exponential loss function. It was important to note that obtaining Bayes estimators and the corresponding credible intervals was not straightforward; thus, we recommended using the Markov Chain Monte Carlo method to compute them. We performed real-world data analysis for demonstrative purposes and ran Monte Carlo simulations to compare the performance of all the suggested approaches.

Abstract Since the beginning of humanity, people have used wild medicinal plants for the treatment of various diseases. Nowadays, researchers and scientists pay attention to exploring new tools to maximize the efficacy of natural products from natural resources, and among these tools formulation of nanoparticles is very promising. The green synthesis of metal/metal oxide nano-solutions using the Deverra tortuosa extract has still not been explored well. This study aims to prepare many metal/metal oxide nanoparticle solutions such as ZnO-NPs, SeO2-MNPs, and Ag-NPs via the methanol extract of D. tortuosa as safe, easy, green, and economic approach as well as characterize the chemical components of D. tortuosa plant by GC-MS spectroscopy analysis. The synthesized M-NPs solutions were characterized by UV–visible (UV–Vis) spectroscopy, Transmission Electron Microscope (TEM), zeta potential, Fourier Transform Infrared (FT-IR) spectroscopy, and phytochemical analyses. The potential antioxidant capacity was estimated for the methanol extract of this plant along with the metal/metal oxide nanoparticles solutions by DPPH assay. In addition, the cytotoxic activity was in vitro assessed for the inspected samples against various tumor and normal cell lines applying MTT assay. The application of the D. tortuosa methanolic extract resulted in NPs with a range of 11.79–85.9 nm which was characterized by UV-Vis spectroscopy, TEM, zeta potential, and FT-IR spectroscopy that revealed various functional groups of the tested samples. The GC-MS analysis of the D. tortuosa methanolic extract showed the presence of 31 chemical compounds with 2-methyl-3-oxocyclopent-1-ene-1-carboxylic acid, methyl oleate, and 6-allyl-4,5-dimethoxybenzo[d][1,3]-dioxole as major constituents. The extract showed considerable antioxidant activity as well as antimicrobial activity that was assessed also against varied bacterial and fungal species. Remarkable potencies for the investigated metal/metal oxide nanoparticle solutions hinder the growth of the tumor cell lines, in addition to the growth of the microbial species. Based on the determined biological activities of the produced NPs, future study is recommended to characterize the pure authentic compounds that are identified within the D. tortuosa as major compounds as well as evaluate their modes of action.

Abstract Drug-induced gene expression profiles can identify potential mechanisms of toxicity. We focus on obtaining signatures for cardiotoxicity of FDA-approved tyrosine kinase inhibitors (TKIs) in human induced-pluripotent-stem-cell-derived cardiomyocytes, using bulk transcriptomic profiles. We use singular value decomposition to identify drug-selective patterns across cell lines obtained from multiple healthy human subjects. Cellular pathways affected by cardiotoxic TKIs include energy metabolism, contractile, and extracellular matrix dynamics. Projecting these pathways to published single cell expression profiles indicates that TKI responses can be evoked in both cardiomyocytes and fibroblasts. Integration of transcriptomic outlier analysis with whole genomic sequencing of our six cell lines enables us to correctly reidentify a genomic variant causally linked to anthracycline-induced cardiotoxicity and predict genomic variants potentially associated with TKI-induced cardiotoxicity. We conclude that mRNA expression profiles when integrated with publicly available genomic, pathway, and single cell transcriptomic datasets, provide multiscale signatures for cardiotoxicity that could be used for drug development and patient stratification.

Abstract Breast cancer is among the highest morbidity and mortality rates in women around the world. In the present investigation we aimed to synthesis novel nanosystem combining two naturally important anticancer agents with different mechanism of action namely Moringa oleifera and caffeine. Firstly, chemical analysis of Moringa oleifera extract and caffeine was done by gas chromatography-mass spectroscopy (GC–MS) in order to assess the main chemical compounds present and correlate between them and the possible anticancer effect. The novel nanosystem was characterized through dynamic light scattering techniques which revealed the stability and homogeneity of the prepared M. oleifera leaves extract/Caffeine loaded chitosan nanoparticles, while FTIR and transmission electron microscope (TEM) proved the shape and the successful incorporation of M. oleifera leaves extract/Caffeine onto the nanochitosan carrier. Our initial step was to assess the anticancer effect in vitro in cancer cell line MCF-7 which proved the significant enhanced effect of M. oleifera leaves extract/Caffeine nanosystem compared to M. oleifera leaves extract or caffeine loaded nanoparticles. Further studies were conducted in vivo namely tumor biomarkers, tumor volume, bioluminescence imaging, molecular and histopathological investigations. The present study proved the potent anticancer effect of the synthesized M. oleifera leaves extract/Caffeine loaded chitosan nanoparticles. Mo/Caf/CsNPs exhibited a large number of apoptotic cells within the tumor mass while the adipose tissue regeneration was higher compared to the positive control. The prepared nanoparticles downregulated the expression of Her2, BRCA1 and BRCA2 while mTOR expression was upregulated. The aforementioned data demonstrated the successful synergistic impact of Moringa and caffeine in decreasing the carcinoma grade.

Abstract This study investigated the prevalence, morphology, molecular identification, and histopathological effects of larval tapeworms (plerocercoids) infecting the skeletal muscles of the Indian halibut (Psettodes erumei) collected from the coastal waters of the Arabian Gulf. Numerous oval or round blastocysts, measuring 13–26 mm, were found embedded within the muscular tissues of the Indian halibut, rendering the fish unsuitable for human consumption. Morphological and molecular analyses identified the plerocercoids as Dasyrhynchus giganteus (family Dasyrhynchidae), with an overall prevalence of 15.4%. The seasonal prevalence was the highest in summer (14.6%), followed by spring (10.6%), winter (4.4%), and autumn (3.5%). Infection rates increased with fish size. Histopathological examination revealed fibrous connective tissue capsules surrounding the larvae, causing muscular atrophy and degenerative changes, with few inflammatory eosinophilic cells. Molecular and phylogenetic analysis of the 28S rDNA gene sequences confirmed the specimens as D. giganteus, clustered closely with other sequences of D. giganteus with 100% bootstrap values. This study provided valuable insights into the parasitic infection dynamics, seasonal variation, molecular identification, and histopathological effects, highlighting the importance of monitoring fish for food safety and public health implications.

Aims: Traditionally, crustacean wastes have been managed by using acid and alkali which leads to major environmental issue. However, over the recent years microbial fermentation has gained its way whereby producing similar effects as chemical treatment and a higher quality product can be obtained. Extracellular protease from Bacillus subtilis was used further by optimizing its culture medium to enhance protease production. Methodology and Results: The culture media was optimized with 4 various sources; Shrimp Crab Shell Powder (SCSP), nitrogen sources, inorganic salts, and carbon sources. It was found that culture media supplemented with 9% SCSP, 3% yeast extract, 1% sodium chloride and 9% glucose augmented protease activity up to 565.80 ± 19.41 U/mL compared to the un-optimized media (170.57 ± 6.75 U/mL). By using this optimized media, the ability and efficiency of B. subtilis in a period of 6 days was investigated whereby acid treated shrimp shells (ATSS) and raw shrimp shell powder (RSSP) were used in substitution of SCSP. In a period of 6 days, the protein content in both ATSS and RSSP was found to have been removed up to 60% and 42% respectively. However deproteinization was found to be more efficient in RSSP with the ratio of tyrosine to protein remained constantly high throughout the 6 days period. Conclusion, significance and impact of study: A better, more efficient and environmental friendly method iscontinuously being improvised to manage shrimp wastes with the use of microbes.

Geothermal brines contain high concentrations of ions and form a source of various valuable elements. The isolation of the elements from their water systems is a great challenge when the gradual depletion of ores in mining is considered. Attempts have been made for a long time to isolate valuable elements from aqueous mixtures prepared in the laboratory. However, those studies might not reflect the complexity of natural systems and might yield results that deviate significantly from the performance in real field systems. In this study, sorption is used to extract lithium ions from a representative field, Tuzla Geothermal Power Plant (TGPP) Turkey, using a mini-pilot reactor introduced to the reinjection well of the plant. Electrolytic manganese dioxide (γ-MnO2), a relatively inexpensive material widely used as the cathode material in lithium-ion batteries, was employed as a sorbent material for lithium. The sorption/desorption performance of the novel γ-MnO2 was investigated under various conditions. Sorption is performed at 360K and 2 bars. The maximum sorption performance was obtained at 1 h in Tuzla GPP. The desorption experiments were performed in acidic solutions. The concentration of Li+ in the desorption solution was found to be 25 mg/L on average when 10 g of γ-MnO2 was dispersed into 30 mL of the acidic aqueous solution. The first desorption solution was used consecutively for collecting more Li+ ions through the desorption of fresh brine-treated powder samples (cumulative desorption). By repeating this process four times consecutively, 230 mg/L of Li+ was obtained in the desorption solution. Moreover, the reusability of the γ-MnO2 sorbent was examined. The sorbent powder showed almost 40% performance efficiency compared to virgin powder under the conditions employed in this study. The use of electrolytic γ-MnO2 sorbent for lithium adsorption was found to be a promising process for practical use in the separation of lithium from geothermal brines.

Ferromagnetic nanowires are receiving attention as functional elements in technologically important applications in microwave devices, spintronics, and biomedicine. They can be readily fabricated over large areas using electrodeposition, and their magnetic response can be tuned through control of their size, geometry, and composition. Additionally, their geometrical properties provide a stable spin structure for manipulating magnetization dynamics using spin-polarized currents for spintronic applications. Structural analysis of individual cobalt nanowires indicated magnetocrystalline anisotropy predominantly perpendicular to the nanowire axis. This significantly alters the micromagnetic energy landscape in the nanowire and breaks the circular symmetry of the dynamic magnetization and resonance modes which is often assumed in theory. In this article, we investigate, using finite-element micromagnetic–electromagnetic simulations, the effect of the variation of magnetocrystalline anisotropy angle on the dynamic magnetization in the nanowire and leads to a shift in the resonance frequencies and modes. The resonance is induced by a pulsed electric current applied along the nanowire axis and simulations include the contributions of magnetocrystalline anisotropy, exchange, dipolar fields, and eddy currents. Understanding the magnetization dynamics induced by electric currents and spin-wave modes in metallic magnetic nanowires and their size and anisotropy angle dependence is important for the design and tuning of magnetic nanowire arrays and devices. [ABSTRACT FROM AUTHOR]