Background
Severe acute respiratory syndrome corona virus (SARS‐CoV‐2) infection frequently causes severe and prolonged disease but only few specific treatments are available. We aimed to investigate ...safety and efficacy of a SARS‐CoV‐2‐specific siRNA‐peptide dendrimer formulation MIR 19® (siR‐7‐EM/KK‐46) targeting a conserved sequence in known SARS‐CoV‐2 variants for treatment of COVID‐19.
Methods
We conducted an open‐label, randomized, controlled multicenter phase II trial (NCT05184127) evaluating safety and efficacy of inhaled siR‐7‐EM/KK‐46 (3.7 mg and 11.1 mg/day: low and high dose, respectively) in comparison with standard etiotropic drug treatment (control group) in patients hospitalized with moderate COVID‐19 (N = 52 for each group). The primary endpoint was the time to clinical improvement according to predefined criteria within 14 days of randomization.
Results
Patients from the low‐dose group achieved the primary endpoint defined by simultaneous achievement of relief of fever, normalization of respiratory rate, reduction of coughing, and oxygen saturation of >95% for 48 h significantly earlier (median 6 days; 95% confidence interval CI: 5–7, HR 1.75, p = .0005) than patients from the control group (8 days; 95% CI: 7–10). No significant clinical efficacy was observed for the high‐dose group. Adverse events were reported in 26 (50.00%), 25 (48.08%), and 28 (53.85%) patients from the low‐, high‐dose and control group, respectively. None of them were associated with siR‐7‐EM/KK‐46.
Conclusions
siR‐7‐EM/KK‐46, a SARS‐CoV‐2‐specific siRNA‐peptide dendrimer formulation is safe, well tolerated and significantly reduces time to clinical improvement in patients hospitalized with moderate COVID‐19 compared to standard therapy in a randomized controlled trial.
MIR 19® (siR‐7‐EM/KK‐46) is a siRNA‐peptide dendrimer formulation targeting a conserved sequence in known SARS‐CoV‐2 variants. Patients with moderate COVID‐19 inhaled 3.7 mg/day of siR‐7‐EM/KK‐46 achieved the primary composite endpoint significantly earlier. Significant clinical effect associated with siR‐7‐EM/KK‐46 at dose 3.7 mg/day was also accompanied by a significant reduction in viral load.Abbreviations: CI, confidence interval; COVID‐19, coronavirus disease 2019; Ct, cycle threshold; mg, milligram; MIR 19®, SARS‐CoV‐2‐specific siRNA‐peptide dendrimer formulation; SARS‐CoV‐2, severe acute respiratory syndrome coronavirus 2; siRNA, small interfering RNA; RdRp, RNA‐dependent RNA polymerase
Clinicoeconomic studies require that the health utility index be used to calculate quality-adjusted life years (QALY). Choice of an adequate method for determining health utility for patients with ...rheumatoid arthritis (RA) makes it necessary to compare various approaches to this assessment. Objective. To compare health utility values obtained with a time to trade-off (TTO) method and those with the EQ-5D questionnaire. Subjects and methods. A single interview was made in 45 patients with RA (mean RA duration 11.7±6.6 years) with a mean HAQ of 1.22±0.52. Utility was assessed using the direct TTO method, EQ-5D index, and visual analogue scale of general health (VAS-GH); functional disease activity index was assessed according to the Health Assessment Questionnaire (HAQ). Results. Five (11.2%) patients with RA could not answer a question to calculate TTO. The mean TTO, EQ-5D, and VAS-GH "thermometer" indices were 0.55±0.36, 0.30±0.32, and 0.47±0.23, respectively. Conversion from EQ-5D to utility index yielded the values similar to those with a mean TTO of 0.54±0.29. The values of the utility index calculated by TTO failed to correlate with those of HAQ and EQ-5D. The disease duration was unrelated to the values of the utility index calculated by any of the methods used. The association of TTO index was found only for VAS-GH "thermometer". Conclusion. EQ-5D index and VAS-GH are the methods of choice in determining health utility for a clinicoeconomic analysis in patients with RA.
The aim of the present research was to examine the process of bioleaching and the application of a combined process for the recovery of copper and nickel from industrial sand deposits. The ...investigated sample of sands finer than 0.1 mm in size contained 0.32% Ni and 0.22% Cu. Industrial sands were processed by bioleaching in flasks on a thermostatically controlled shaker. In addition, sand roasting experiments were carried out with ammonium sulfate. An attempt was also made to use a combined process, including low-temperature roasting of the sands mixed with ammonium sulfate, water-leaching of the roasted mixture, and subsequent biological after-leaching of the residue. In the process of roasting the industrial sands in a mixture including ammonium sulfate at a temperature of 400 °C, more than 70% of the non-ferrous metals were recovered. We examined the possibility of recovering non-ferrous metals using a combined process including low-temperature roasting of industrial sands and the additional recovery of non-ferrous metals by bioleaching using the Acidithiobacillus ferrivorans bacterial strain, which was found to increase the recovery of non-ferrous metals to up to 90%.
A laboratory scale study was conducted, aimed at finding an effective method for processing fine concentration tailings of copper-nickel ores. A sulfuric acid tailing granulation process followed by ...subsequent heap leaching of granules is proposed. Various methods of preparation and storage of the granular material are discussed. A solution of sulfuric acid was used as a binder. It was found that the addition of an oxidizing agent (Fe3+ and NO2−) when irrigating the granules had an effect on the recovery of metals. Changes in the recovery performance of non-ferrous metals into solution were studied under subsequent heap leaching of the material during a period of positive temperatures. The role of nitrogen compounds, in particular, nitrous acid, on the recovery of metals into solution after the preliminary storage of granules at below 0 °C temperatures is also discussed.
By sequencing 523 ancient humans, we show that the primary source of ancestry in modern South Asians is a prehistoric genetic gradient between people related to early hunter-gatherers of Iran and ...Southeast Asia. After the Indus Valley Civilization's decline, its people mixed with individuals in the southeast to form one of the two main ancestral populations of South Asia, whose direct descendants live in southern India. Simultaneously, they mixed with descendants of Steppe pastoralists who, starting around 4000 years ago, spread via Central Asia to form the other main ancestral population. The Steppe ancestry in South Asia has the same profile as that in Bronze Age Eastern Europe, tracking a movement of people that affected both regions and that likely spread the distinctive features shared between Indo-Iranian and Balto-Slavic languages.
For thousands of years the Eurasian steppes have been a centre of human migrations and cultural change. Here we sequence the genomes of 137 ancient humans (about 1× average coverage), covering a ...period of 4,000 years, to understand the population history of the Eurasian steppes after the Bronze Age migrations. We find that the genetics of the Scythian groups that dominated the Eurasian steppes throughout the Iron Age were highly structured, with diverse origins comprising Late Bronze Age herders, European farmers and southern Siberian hunter-gatherers. Later, Scythians admixed with the eastern steppe nomads who formed the Xiongnu confederations, and moved westward in about the second or third century BC, forming the Hun traditions in the fourth-fifth century AD, and carrying with them plague that was basal to the Justinian plague. These nomads were further admixed with East Asian groups during several short-term khanates in the Medieval period. These historical events transformed the Eurasian steppes from being inhabited by Indo-European speakers of largely West Eurasian ancestry to the mostly Turkic-speaking groups of the present day, who are primarily of East Asian ancestry.
The purpose of this study was to examine the vegetation dynamics of various lawn grass species in the city of Apatity, Murmansk region, when exposed to anthropogenic and atmospheric pollution ...impacts. The dust concentration in the atmospheric air was recorded, its mineralogical analysis was carried out, and the dynamics of the development of various lawn types under the anthropogenic load was studied. Cases of exceeding the MPC of dust particles in the atmospheric air were recorded. Nepheline grains were found in the dust samples, which is indicative of pollution migration from the nearby tailings storage facility. It was shown that lawns are able to grow intensively in severe climatic conditions and under the influence of mining and processing enterprises.
The feasibility of processing low-grade copper-nickel ores by heap bioleaching was investigated. It was found that an iron-oxidizing strain of acidophilic microorganisms, Acidithiobacillus ...ferrivorans, is effective in the leaching of sulfide ores from the deposits in Russia’s Murmansk region. Sulfide mineralization of the studied mineral feeds was described using the methods of X-ray phase analysis and optical microscopy. In the process of leaching, the pH and Eh values and the concentrations of ferric and ferrous iron, nickel, and copper ions were monitored. By the end of the experiment, 16.5% of nickel and 7.5% of copper was recovered from the ore of the Allarechensk technogenic deposit, while 22.5% of nickel and 12.7% copper were recovered from the ore of the Nud II deposit. By silicate analysis of the solid phase, patterns of ore chemistry change were described during the process of bioleaching.
The possibility of applying a combined concentration and metallurgical method for processing low-grade and refractory copper–nickel ores was considered. The resulting rougher and scavenger flotation ...concentrate contained 2.07% nickel and 0.881% copper at a recovery of 85.44% and 89.91%, respectively. The concentrate was then roasted with ammonium sulfate, followed by aqueous leaching of clinker to dissolve nickel and copper. The roasting temperature, the ratio of concentrate to (NH4)2SO4 in the mixture, and the temperature were varied. Based on the study findings, the following process conditions were found to be optimal: roasting temperature 400 °C, rougher concentrate to ammonium sulfate ratio 1:7, and grinding size −40 μm. A roasting temperature of 400 °C is significantly lower than the temperature applied in conventional pyrometallurgical processes. The possibility of collecting off-gases allows the reagent to be regenerated and makes the process even more cost-effective. End-to-end recovery into pregnant solution was 81.42% for nickel and 82.81% for copper. The resulting solutions can be processed by known hydrometallurgical methods.
Introduction. The quality of the enrichment process is affected by many factors, ranging from the characteristics of the raw materials supplied to the enrichment plant to the enrichment technology ...and the agents used. Strict process control is required at all stages from mining to concentrate extraction. Copper-zinc ores of Russian deposits are difficult for enrichment due to high mass fraction of pyrite in ore and fine irregular intergrowth of sulfide minerals between themselves and with rock minerals. The practice of enrichment of copper-zinc ores has established that it is impossible to obtain high-quality zinc and pyrite concentrates without adding sphalerite flotation modifier agents to various flotation operations. To improve the flotation activity of sphalerite, copper sulphate is used as an activation additive in the enrichment process chain. Purpose of work. To study the effect of sulfhydryl collectors on flotation of sulfide minerals, and development of innovative technologies of flotation of copper-zinc and polymetallic ores considering the acidity of the environment. Materials and methods. In the experimental part of the work, several methods of materials and agents preparing were used, a variety of equipment was used, as well as methods of analysis and processing of results. The material composition and grain size distribution of sphalerite was studied using the MLA System Quanta. X-ray phase analysis of sphalerite was carried out at the University of science and technology "MISIS" in Research Laboratory of ultra-hard materials on Rigaku Geigerflex device using monochromatized CuKα-radiation. Thermographic studies were carried out using a Q -1500D derivatograph. The following flotation agents were used in the work: collector - butyl potassium xanthate, foam agent MIBC, medium regulator - lime, modifiers - iron sulfate, sodium sulphide and mixture of iron sulfate and sodium sulphide. Flotation experiments were carried out on the laboratory flotation machine FL-189 G. Results. The kinetics of sphalerite flotation is characterized not by a single value of the flotation kinetics constant for all flotation mineral grains, but by a set of such values corresponding to quite certain fractions of sphalerite extracted in the foams product. It has been found that in the initial period of flotation the mineral grains with a high value of the flotation velocity constant are flotated, and in the final period of flotation the grains of the same mineral with a low value of the same flotation velocity constant are flotated. Discussion. The introduction of iron (II) sulphate into the mineral slurry leads to a redistribution of the flocculated mineral between medium and lightly flocculated fractions. This indicates that iron (II) sulphate acts as an activator for sphalerite flotation. At a low flow rate of this agent, the proportion of medium flotable fractions increases and the proportion of easily and hardly flotable fractions decreases. With increase in the agent consumption up to 400 g/t and more, the opposite picture is observed - the proportion of medium flotable fraction decreases and the proportion of easily flotable fraction increases in flocculated sphalerite. The replacement of iron (II) sulphate by sodium sulphate has the opposite effect on the flotation spectrum of sphalerite. The introduction of a mineral suspension of a solution of sodium sulfide and iron (II) sulfate into the liquid phase at a consumption of 200 g/t of each agent leads to a decrease in the proportion of easily and especially medium floatable fractions of the mineral and an increase in the proportion of difficultly floatable fractions. Conclusions: 1. An increase in the pH of pulp liquid phase leads to a decrease in the extraction of zinc concentrate in the foam product during flotation with butyl xanthate. 2. The introduction of a solution of sodium sulfide with ferrous sulfate reduces the floatability of the mineral, which is reflected in a decrease in the extraction of zinc concentrate. 3. Sodium sulfide and iron sulphate, while simultaneously dosing them into the flotation pulp, act as depressants in the sphalerite flotation process. 4. Sodium sulfide depresses sphalerite at all studied pH concentrations. Resume. The results of the research can be useful in improving the methods for processing sulfide ores (lead-zinc and copper-zinc) which are included in the group of polymetallic ores. The developed methods of flotation processing make it possible to improve the quality of enrichment and increase the extraction of a valuable component.
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