bluuebunny/crossref_metadata_2025 huggingface dataset:
Simultaneous Determination of Candesartan and Hydrochlorothiazide in Human Plasma by HPLC-MS/MS
Authors: Karnakova P. K. , Komarov T. N. , Archakova O. A. , Shchelgacheva D. S. , Aleshina A. A. , Bagaeva N. S. , Karpova P. A. , Shohin I. E.
Published: November 2021

Introduction. Combined drugs have the greatest efficacy and safety in arterial hypertension treatment. The combination of candesartan and hydrochlorothiazide (AT1-receptor antagonist and a thiazide diuretic, respectively) provides high efficiency of antihypertensive combination therapy, therefore it is widely used in medical practice. Developing a method for simultaneous determination of candesartan and hydrochlorithiazide in human blood plasma is necessary for performing the analytical part of pharmacokinetic studies and bioequivalence studies of multicomponent drugs.

Aim. The aim of this study is to develop a method for quantitative determination of candesartan and hydrochlorothiazide in human plasma by high-performance liquid chromatography – tandem mass spectrometry (HPLC-MS/MS) for further bioequivalence studies.

Materials and methods. Determination of candesartan and hydrochlorothiazide in human plasma by HPLC-MS/MS. The samples were processed by acetonitrile protein precipitation. Internal standard: mixed solution of valsartan and indapamide. Mobile phase: 0.1 % formic acid solution in water (eluent A), 0.1 % formic acid in acetonitrile (eluent B). Column: Phenomenex Luna Phenyl-Hexyl, 50x4.6 mm, 5 μm. Analytical range: 2.00– 300.00 ng/mL for candesartan, 2.00–200.00 ng/mL for hydrochlorothiazide in human plasma. Ionization source: electrospray ionization. Detection conditions: 441.10 → 192.00 m/z, 441.10 → 263.15 m/z (candesartan), 295.85 → 269.00 m/z (hydrochlorothiazide), 436.00 → 207.05 m/z (valsartan), 363.85 → 132.10, 363.85 → 189.00 m/z (indapamide).

Results and discussion. This method was validated by selectivity, matrix effect, calibration curve, accuracy, precision, spike recovery, the lower limit of quantification, carry-over effect and stability. The developed method meets the requirements for conducting bioequivalence studies of medicinal products within the framework of the Eurasian Economic Union.

Conclusion. The analytical range was 2.00–300.00 ng/mL for candesartan, 2.00–200.00 ng/mL for hydrochlorothiazide in human plasma. The method was applied in BE study of the combination of candesartan and hydrochlorothiazide.
The Use of Digital Technologies for the Purpose of Improving Methodological Approaches to the Creation of a Pharmaceutical Quality System at Enterprises for the Production of Medicines
Authors: Goryachkin V. V. , Smirnov V. А. , Shestakov V. N. , Abramovich R. A.
Published: November 2021

Introduction. The article is devoted to the aspects of improving methodological approaches to the creation of a pharmaceutical quality system (PQS) at enterprises for the production of medicines, taking into account the possibility of using tools and means of digitalization. The relevance of the study is associated with the enduring importance of comprehensive high quality assurance in the development, production and release of medicines into circulation. The implementation of PQS requires numerous transformations of management and production processes, which can be facilitated by tools and elements of digitalization.

Aim. To consider the potential and specific areas of application of digital technologies to improve the methodology and practice of developing and implementing PQS.

Materials and methods. The state in the subject area was assessed on the basis of the results of economic and statistical analysis and forecasting of the implementation of PQS at Russian pharmaceutical enterprises that have positive and comparatively long experience in this area: the companies LLC "OZON" and JSC "AKRIKHIN". The assessment was carried out by calculating the integral indicator of the effectiveness of the functioning of PQS, which is a set of weighted key performance indicators (KPI) for quality.

Results and discussion. The importance of the introduction of PQS for the development of pharmaceutical enterprises and the presence of numerous difficulties in the implementation of PQS, which necessitates the improvement of methodological approaches in the subject area, are stated. It has been proven that even at those enterprises where PQS has been introduced with varying degrees of success, the use of digitalization tools would contribute to a faster, more systematic and high-quality implementation of PQS. Among the key areas of application of digital tools, the authors propose monitoring of quality indicators (using neural network cards) and the use of blockchain platforms and smart contracts to register the release of drugs of appropriate quality.

Conclusion. Digital tools contribute to complex improvement in many areas of socio-economic activity. Their active use at pharmaceutical enterprises is intended to contribute to ensuring the proper implementation and uninterrupted functioning of pharmaceutical quality systems, through constant monitoring of the quality of manufactured products and registration of manufactured batches in high-precision information storage systems.
Alternative Methods for Dissolution Profile Comparison in the Dissolution Test
Authors: Romodanovsky D. P. , Goryachev D. V.
Published: November 2021

Introduction. The article discusses the problem of assessing the similarity of the dissolution profiles of two batches of the nebivolol. The use of a generally accepted similarity factor for assessing equivalence is unacceptable in some cases, for example, for drugs with a high variability in the values of the release of the active substance from the formulation. At the same time, at present, there are no generally accepted approaches to comparing the profiles of the dissolution kinetics of drugs, with the exception of the method for assessing the comparability of profiles based on the mathematical calculation of the similarity factor f2, which has certain criteria that limit its application.

Aim. To demonstrate alternative methods for assessing the similarity between the dissolution profiles of two drugs using a practical example.

Materials and methods. The results of the comparative dissolution test of two series of nebivolol at a dosage of 5 mg. Five model-independent methods for assessing the equivalence of drug dissolution were used. Statistical data processing was performed using Microsoft Excel software.

Results and discussion. The paper presents a practical example of using five alternative model-independent methods for assessing the equivalence of the dissolution profile. An example is used to illustrate the proposed equivalence limits and statistical methodology. Also, various approaches to determining the boundaries of equivalence have been proposed to assess the similarity of the dissolution profiles of an active substance.

Conclusion. According to the results of the comparative dissolution test of two batches of nebivolol, it was shown that the use of the similarity factor as a criterion for assessing dissolution profiles led to a false positive result. In such cases, the possibility of using alternative methods for assessing the equivalence of dissolution profiles described in the article, or other methods presented in the scientific literature, should be considered, with a justification of their acceptability in each specific case.
Study of the physicochemical properties of the etravirine substance
Authors: Zolotov S. A. , Ponomarev E. S. , Dain I. A. , Demina N. B. , Zolotova A. S.
Published: November 2021

Introduction. Etravirine, being one of the most popular antiretroviral drugs, doesn't have its physicochemical properties sufficiently described in scientific publications. Detailed information on the substance properties is necessary both for organizing the synthesis and for justifying the dosage form and technology for its production, as well as for identifying bottlenecks and critical parameters that affect the quality of the finished product.

Aim. Study the etravirine physicochemical properties to model the design of studies to create an innovative dosage form

Materials and methods. Etravirine (MSN Life Sciences Pvt. Ltd., Hetero Labs Ltd.). The melting point was determined by the capillary method. Etravirine samples were studied via differential scanning calorimetry (DSC), X-ray powder diffractometry, IR and NMR spectroscopy. Particle size was determined using laser diffraction analysis. The shape and size of the crystals were determined with the help of transmission electron microscopy (TEM). The concentration of etravirine in aqueous media was determined using the HPLC method with a fluorescence detector. The concentration of etravirine in organic solvents was determined spectrophotometrically.

Results and discussion. The X-ray powder diffractometry and IR spectroscopy helped to determine the fact that the studied substances represent the same polymorphic modification. The melting point of etravirine ranges from 259 to 263 °C. Melting is accompanied by decomposition. The substance is practically insoluble in aqueous media at pH values in the range from 1.2 to 6.8, soluble in some organic solvents, readily soluble in dimethyl sulfoxide, tetrahydrofuran, dimethylformamide, dimethylacetamide. The distribution coefficient in the "1-octanol/phosphate buffer solution pH 6.8" solvent system was 5.22. The experiment showed that the etravirine substance is lipophilic. Etravirine is found to be a highly crystalline substance and represents needle-shape prismatic crystals.

Conclusion. Etravirine is a lipophilic substance, practically insoluble in aqueous solutions, soluble in a number of organic solvents. The studied substances turned out to be the same polymorphic modification. Since the melting of the substance is accompanied by decomposition, high temperatures processes should be avoided.

Conflict of interest. The authors declare that they have no obvious and potential conflicts of interest related to the publication of this article.
Phenolic Compounds and Hepatoprotective Activity of Chicory Herb Extract
Authors: Saybel O. L. , Radimich A. I. , Dargaeva T. D. , Lupanova I. A. , Ferubko E. V. , Kurmanova E. N. , Martynchik I. A.
Published: November 2021

Introduction. Chicory (Cichorium intybus L.) is widely applied for liver disease treatment by traditional medicine of different countries; as well, it is the object for pharmacological research of hepatoprotective activity. In this regard, the method for obtaining dry extract of wild chicory herb (WCHE) is developed in the All-Russian Research Institute of Medicinal and Aromatic Plants.

Aim. Aim of the research is determination of the qualitative composition of phenolic compounds, identification of the substances prevailing in WCHE and conducting pharmacological screening of the extract.

Materials and methods. WCHE chemical composition has been explored with HPLC-MS/MS method; the main components were determined quantitatively with HPLC-UF method using single compounds that were isolated by us earlier and identified by NMR spectroscopy. WCHE pharmacological screening of hepatoprotective activity research was involving 50 male rats. Acute toxic hepatitis in animals was induced by a single subcutaneous injection of 50 % oily solution of tetrachloromethane (TCM) at a dosage of 0.4 ml per 100 g body weight. One hour before administration TCM, animals received WCHE at the doses of 100 or 500 mg/kg. 48 hours after TCM administration, the activity of serum enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), as well as the content of total bilirubin were determined for preliminary establishment of pharmacological activity. Pathomorphological studies of rat liver were carried out using histological methods. The liver histological structure was inspected using liver sections stained with hematoxylin and eosin.

Results and discussion. The component composition of WCHE is represented by oxycoumarins, hydroxycinnamic acids and flavonoids. The dominant phenolic compounds are esculetin, chicoriin, chicoric, chlorogenic and caftaric acids. It was found under acute experimental toxic hepatitis, that preliminary WCHE administration reduces the toxic TCM effect on liver cells. In animals treated with WCHE at doses both 100 mg/kg and 500 mg/kg body weight, it was observed decreases in ALT activity by 35 % and 45 %, AST by 15 % and 28 %, alkaline phosphatase by 15 % and 21 %; the content of total bilirubin by 20 % and 29 %, respectively, in comparison with similar indicators in the group of animals that were not treated with the extract. The histological study showed that WCHE administration to animals at the doses of 100 and 500 mg/kg reduces dystrophic changes in hepatocytes, this effect is more pronounced at the extract dosage of 500 mg/kg.

Conclusion. Main WCHE components are oxycoumarins (esculetin, chicoriin), hydroxycinnamic acids (chicoric, chlorogenic and caftaric). According to the results of screening studies, it was established that WCHE in doses of 100 mg/kg and 500 mg/kg is a promising object for further pharmacological research.
Antioxidant Activity of Silver-containing Bionanocompositions Based on Humic Substances in Cell Culture
Authors: Buyko E. E. , Zykova M. V. , Ivanov V. V. , Bratishko K. A. , Ufandeev A. A. , Grigorieva I. O. , Tsupko A. V. , Mikhalyov D. A. , Perminova I. V. , Belousov M. V.
Published: November 2021

Introduction. Silver nanoparticles are promising agents for suppressing resistant strains of microorganisms and accelerating the purulent wounds healing. Oxidative stress disrupts normal wound healing processes, which leads to the formation of chronic non-healing wounds. Therefore, the determination of the ability of new wound healing agents to decrease the production of reactive oxygen species is a relevant task.

Aim. The aim of the current study was to investigate the effect of silver-containing bionanocompositions based on humic substances on the basal and tert-butyl hydroperoxide-stimulated production of reactive oxygen species at the normal fibroblasts 3T3-L1 cell culture in vitro.

Materials and methods. The study was carried out on 7 samples of initial humic substances and biomaterials with silver nanoparticles synthesized in the Laboratory of Natural Humic Systems, Faculty of Chemistry, Moscow State University named after M. V. Lomonosov. The intracellular production of reactive oxygen species was assessed using a 2,7-dichlorodihydrofluorescein diacetate fluorescent probe. Cells were cultured with samples for 24 h; tret-butyl hydroperoxide was used to stimulate the production of reactive oxygen species. Detection was performed fluorometrically using a microplate reader.

Results and discussion. The most pronounced antioxidant activity was demonstrated by three samples of biomaterials with silver nanoparticles ultradispersed in humic substances matrices (CHS-AgNPs, CHP-AgNPs and CHE-AgNPs), which allows us to consider them as the most promising pharmaceutical agents for the treatment of purulent-inflammatory processes. The most probable mechanism of the high antioxidant activity of the studied biomaterials in relation to intracellular reactive oxygen species is the intrinsic activity of humic substances to bind reactive oxygen species, while silver nanoparticles in biomaterials catalyze the reduction processes of their interaction with reactive oxygen species.

Conclusion. For the studied samples of biomaterials with silver nanoparticles ultradispersed in matrices of humic substances pronounced antioxidant activity was shown. Together with antibacterial properties, it makes it possible to consider them as potential agents for purulent wounds healing accelerating.
In situ Intranasal Delivery Systems: Application Prospects and Main Pharmaceutical Aspects of Development (Review)
Authors: Bakhrushina E. O. , Demina N. B. , Shumkova M. M. , Rodyuk P. S. , Shulikina D. S. , Krasnyuk I. I.
Published: November 2021

Introduction. Intranasal delivery of in situ gel-forming systems is a complex but promising direction. Due to the high cost of developing a new chemical object or genetically engineered modification of biological molecules, pharmaceutical companies are focusing on developing technologies for new delivery systems for existing active pharmaceutical ingredients to improve their effectiveness and bioavailability. In situ systems for intranasal delivery, due to increased viscosity and mucoadhesion to the nasal mucosa, allow overcoming mucociliary clearance and ensuring complete absorption and prolonged release of drugs.

Text. The article discusses the main advantages of intranasal in situ delivery systems shown in preclinical studies, as well as approaches to the technology of obtaining and standardization of these systems. The results of scientific research in this field over the past 15 years are summarized, the most promising polymers for creating thermoreversible and pH-sensitive compositions are identified, and modern methods for evaluating the sol-gel transition in situ are analyzed.

Conclusion. The use of in situ systems for intranasal administration allows providing a high targeting of the delivery of synthetic and biological molecules to the brain. Currently, numerous pharmacokinetic and pharmacodynamic preclinical studies confirm the effectiveness of such systems, as well as their safety. Thermoreversible commercially available and directionally synthesized polymers (poloxamer 407, PLGA, NIPAAm, etc.), as well as chitosan, remain the most popular for the design of in situ delivery systems. In vitro and ex vivo methods with mucosa and artificial nasal fluid are widely used to assess the parameters of in situ gelation, but to increase the reproducibility of the methods and improve the correlation in vitro/in vivo, it is recommended to conduct modeling of the nasal cavity. Developing the technology and methods of screening of intranasal reversible systems will help to get closer to clinical trials and the entry of these delivery systems into the global pharmaceutical market.
Development of the Composition and Technology for Obtaining Paclitaxel Nanoscale Formulation Consisting of a Conjugate of Polymer Particles with a Protein Vector Molecule
Authors: Sokol M. B. , Yabbarov N. G. , Mollaeva M. R. , Chirkina (Fomicheva) M. V. , Balaban'yan V. Yu. , Nikolskaya E. D.
Published: November 2021

Introduction. The use of the anticancer drug paclitaxel is limited due to its high toxicity and lipophilicity. A new polymer composition of paclitaxel has been proposed, which provides targeted transport of the drug into tumor cells and improves its safety.

Aim. Method development for preparation of a novel paclitaxel formulation consisting of a conjugate of PLGA nanoparticles with the third domain of alpha-fetoprotein.

Materials and methods. The object of this study is paclitaxel-loaded nanoparticles based on a copolymer of lactic and glycolic acids, the surface of which is modified with a vector molecule - the recombinant third domain of alpha-fetoprotein. Nanoparticles were obtained by single emulsification method and precipitation. Conjugation with a protein molecule was performed by the carbodiimide method. The analysis of the obtained nanoparticles was carried out using dynamic and electrophoretic light scattering, high performance liquid chromatography, dialysis membrane method.

Results and discussion. Synthesis of paclitaxel-loaded nanoparticles based on a copolymer of lactic and glycolic acids and its conjugation optimization under varying a wide range of conditions have been carried out. The resulting conjugate had an average diameter of 280 ± 12 nm. The conjugation efficiency was 95 %. The release of paclitaxel from the polymer matrix in the release medium was 65 % in 220 h.

Conclusions. A method of obtaining and substantiating the composition of the original nanosized form of paclitaxel is proposed. The possibility of prolonged release of paclitaxel from the polymer matrix has been shown.
Optimization of the Composition of the Ointment with Phytoecdysteroids Serpisten
Authors: Molokhova E. I. , Sorokina Yu. V. , Lipin D. E.
Published: November 2021

Introduction. Phytoecdysteroids are a group of natural compounds related in structure and physiological effect to ecdysone - the hormone of insect molting. Phytoecdisteroids have been found to have an antiflammatory effect, which suggests that they have regenerative properties. The development of a soft dosage form containing phytoecdysteroids is of interest.

Aim. Improvement of ointment compositions with phytoecdysteroids by optimizing the composition of base adjuvants.

Materials and methods. As an active substance was used Serpisten, containing the sum of phytoecdysteroids, the main of which is 20-hydroxyecdysone and obtained from the leaves of Serratulaecoronatae. Raw materials "Serpukhi crowned leaves" were registered by the Federal Service Rospotrebnadzor (Moscow) for the production of dietary supplements (Gr. No. 77.99.23.3.U.1922.3.08), substance Serpisten (Gr. No. 77.99.23.3.U.1923.3.08. TU 9369-002-15092611-2008). In work were used the excipients allowed for medical use: the monoglycerides distilled, T-2 emulsifier, tween 80, sodium - carboxymethylcellulose, polyvinyl alcohol, hydroxide of aluminum, aero forces, vaseline, oil vaseline, sunflower oil. Optimization of ointment auxiliary substances composition was carried out according to the Greco-Latin 4 x 4 square plan with repeated observations. The concentration of hydrogen ions from aqueous ointments was evaluated as process parameters; acid number; release of serpistene from ointment into agar gel, thermal stability of structure. The structural and mechanical properties of the optimal composition ointment composition were determined on a RV type REOTEST 2.1 rotary viscometer (RHEOTEST Medingen GmbH, Germany). Ointment Bepanten (GP Grenzach Produktions GmbH, Germany) was used as a comparison preparation.

Results and discussion. During optimization of the composition of the diphilic ointment with serpistene, was found that the ratio of hydrophobic and hydrophilic phases should be 1 : 1, it is advisable to introduce into the ointment base an emulsifier T-2, aerosil and a mixture of vaseline and vaseline oil in the proportion of 1 : 1. As a result of the carried out studies on the optimization of ointment compositions, the following serpisten ointment composition is proposed: serpisten - 0.02; emulsifier T-2 - 3.0; aerosil - 3.0; vaseline - 23.0; vaseline oil - 23.0; ethyl alcohol 40 % - 1 ml; purified water to 100.0. Comparative analysis of effective viscosity showed that the proposed composition is as close as possible to the Bepanten ointment.

Conclusion. A set of technological studies was carried out to optimize the composition of the Serpisten, 0.02 °% ointment on a diphilic basis. The developed composition and technology made it possible to obtain a composition with thermal stability, bring the hydrogen index of the ointment closer to the pH of human skin and achieve the parameters included in the rheological optimum for dermatological ointments (0.34-108 Pa • s).
The Use of Ultrasound in the Extraction of Biologically Active Compounds from Plant Raw Materials, Used or promising for Use in Medicine (Review)
Authors: Elapov A. A. , Kuznetsov N. N. , Marakhova A. I.
Published: November 2021

Introduction.This review examines the current state of technology for ultrasonic isolation of biologically active components from medicinal vegetal raw materials. The main emphasis is placed on "green" technologies that intensify the processes of isolation of components such as flavonoids.

Text.Modern technologies imply the use of combined methods, including, in addition to ultrasound, significant grinding of raw materials before the extraction process, the use of supercritical solvents (liquefied gases) under excessive pressure. The effect of ultrasound power and temperature on the output of the extracted components was also considered.

Conclusion.1. To increase the yield of biologically active compounds from plant raw materials among various physical methods of extraction intensification, the use of ultrasound dominates. 2. Ultrasonic extraction can be divided into several main types: extraction in an ultrasonic bath, the use of submersible ultrasonic emitters, as well as the combination of ultrasonic extraction with additional types of influence. 3. In the literature, examples of the use of ultrasonic extraction for the isolation of phenolic compounds are most fully presented, it being noted that the parameters need to be selected individually for each individual plant. 4. The power of ultrasound and the nature of the extractant can affect the course of oxidative processes in the extract, and such phenomena are characteristic not only for too high capacities, but also for low ones. 5. Ultrasound can significantly increase the yield of biologically active compounds even in aqueous extraction of fresh raw materials. 6. The spectrum of extractants selection for ultrasonic extraction of plant raw materials is quite large. Both organic solvents (ethanol, methanol, ethyl acetate, acetone) and water can be used, as well as mixtures of various extractants.
Clinical Outcomes of In-office Sutureless Amniotic Membrane Transplantation in Persistent Epithelial Defect
Authors: Choi Choong Man , Jeon Hyun Sun
Published: November 2021

Purpose: To investigate the efficacy of outpatient clinic-based sutureless amniotic membrane transplantation (AMT) along with therapeutic contact lens (T-lens) application in eyes with persistent epithelial defects (PED).Methods: Nine eyes of nine patients (mean age, 71.7 ± 5.2 years) diagnosed with PED and treated with in-office sutureless AMT combined with T-lens application were retrospectively reviewed. Demographics, systemic diseases, PED etiology, corneal epithelial defect size, visual acuity, corneal scraping culture results, and clinical course were evaluated.Results: Among nine eyes with PED, three had neurotrophic keratopathy, four had infectious keratitis (three with fungal keratitis and one with bacterial keratitis), one had limbal deficiency, and one had marginal keratitis. The mean epithelial defect size (calculated as an average of the horizontal and vertical diameters) was 3.13 ± 1.42 mm, and the mean duration from AMT to epithelial healing was 30.1 ± 10.5 days (range, 14–51 days) in successful trials. The success rates were 77.8% (7/9) per patient and 66.7% (8/12) per trial. The causes of failure in two patients were AMT displacement and uncontrolled infection.Conclusions: Our results demonstrate that in-office sutureless AMT combined with T-lens application can be used in patients with PED who are refractory to medications. It will be especially helpful for elderly patients because of its easy-to-use method. To achieve successful outcomes with AMT, an appropriate periocular environment as well as infection control need to be considered.
Trends in Utilization of Visual Field Tests for Glaucoma Patients: A Nationwide Study Using the Korean Health Insurance Review and Assessment Database
Authors: Kim Seongmi , Jung Jung Yoon , Cho Geon Sik , Lee Jong Young , Lee Hye Jin , Jeong Jinho , Ha Ahnul
Published: November 2021

Purpose: To analyze 10-year trends in utilization of visual field tests for adult glaucoma or glaucoma-suspect patients using the Korean Health Insurance Review and Assessment data.Methods: Health claims for the years 2010 to 2019, as recorded via Korea’s Health Insurance Review and Assessment service, were accessed. We identified glaucoma patients using the glaucoma diagnostic codes H40 (glaucoma) and H42 (glaucoma in other diseases classified elsewhere). For verification of the glaucoma diagnosis, information on any antiglaucoma medication prescriptions and ocular surgery history also was obtained. Visual field testing data was isolated using procedural codes E6690 (kinetic perimetry) and E6691 (standard automated perimetry [SAP]) performed in tertiary hospitals. Any changes in visual field test utilization were identified using regression trend analysis.Results: From 2010 to 2019, the total number of SAP procedures performed in tertiary hospitals for either glaucoma or glaucoma-suspect patients increased gradually from 93,459 to 216,433. With regard to kinetic perimetry examinations, the total number decreased gradually from 6,364 to 3,792. The yearly average SAP number per patient showed a slight increase, from 1.168 to 1.248 (ß = 0.008, R2 = 0.669, p = 0.004). Meanwhile, the yearly average number of kinetic perimeter examinations per patient showed a significant decrease, from 1.093 to 0.940 (ß = -0.013, R2 = 0.580, p = 0.010).Conclusions: Between 2010 and 2019, the yearly average number of SAP procedures performed per glaucoma or glaucoma-suspect patient increased in Korea. Meanwhile, the yearly average number of kinetic perimetry examinations per patient significantly decreased.
Big data analysis and artificial intelligence in epilepsy – common data model analysis and machine learning-based seizure detection and forecasting
Authors: Chung Yoon Gi , Jeon Yonghoon , Yoo Sooyoung , Kim Hunmin , Hwang Hee
Published: November 2021

There has been significant interest in big data analysis and artificial intelligence (AI) in medicine. Ever-increasing medical data and advanced computing power have enabled the number of big data analyses and AI studies to increase rapidly. Here we briefly introduce epilepsy, big data, and AI and review big data analysis using a common data model. Studies in which AI has been actively applied, such as those of electroencephalography epileptiform discharge detection, seizure detection, and forecasting, will be reviewed. We will also provide practical suggestions for pediatricians to understand and interpret big data analysis and AI research and work together with technical expertise.
Knowledge-guided artificial intelligence technologies for decoding complex multiomics interactions in cells
Authors: Lee Dohoon , Kim Sun
Published: November 2021

Cells survive and proliferate through complex interactions among diverse molecules across multiomics layers. Conventional experimental approaches for identifying these interactions have built a firm foundation for molecular biology, but their scalability is gradually becoming inadequate compared to the rapid accumulation of multiomics data measured by high-throughput technologies. Therefore, the need for data-driven computational modeling of interactions within cells has been highlighted in recent years. The complexity of multiomics interactions is primarily due to their nonlinearity. That is, their accurate modeling requires intricate conditional dependencies, synergies, or antagonisms between considered genes or proteins, which retard experimental validations. Artificial intelligence (AI) technologies, including deep learning models, are optimal choices for handling complex nonlinear relationships between features that are scalable and produce large amounts of data. Thus, they have great potential for modeling multiomics interactions. Although there exist many AI-driven models for computational biology applications, relatively few explicitly incorporate the prior knowledge within model architectures or training procedures. Such guidance of models by domain knowledge will greatly reduce the amount of data needed to train models and constrain their vast expressive powers to focus on the biologically relevant space. Therefore, it can enhance a model’s interpretability, reduce spurious interactions, and prove its validity and utility. Thus, to facilitate further development of knowledge-guided AI technologies for the modeling of multiomics interactions, here we review representative bioinformatics applications of deep learning models for multiomics interactions developed to date by categorizing them by guidance mode.
A Generalization of Two Dimensional Bernstein-Stancu Operators
Authors: GÖNÜL BİLGİN Nazmiye , EREN Melis
Published: November 2021

The aim in our study is giving a generalization of the two-dimensional (p,q)-Bernstein-Stancu operators in a particular domain. In addition, by creating some direct results of these operators, rate of convergence is studied by Lipschitz type functions and modulus of continuity.
The best predictive model for hepatocellular carcinoma in patients with chronic hepatitis B infection
Authors: Yu Jung Hwan , Cho Soon Gu , Jin Young-Joo , Lee Jin-Woo
Published: November 2021

Chronic hepatitis B (CHB) seriously threatens human health. About 820,000 deaths annually are due to related complications such as hepatitis B and hepatocellular carcinoma (HCC). Recently, the use of oral antiviral agents has significantly improved the prognosis of patients with CHB infection and reduced the risk of HCC. However, hepatitis B virus still remains a major factor in the development of HCC, raising many concerns. Therefore, numerous studies have been conducted to assess the risk of HCC in patients with CHB infection and many models have been proposed to predict the risk of developing HCC. However, as each study has different models for predicting HCC development that can be applied depending on the use of antiviral agents or the type of antiviral agents, it is necessary to properly understand characteristics of each model when using it for the evaluation of HCC in patients with CHB infection. In addition, because different variables such as host factor, viral activity, and cirrhosis are used to evaluate the risk of HCC development, it is necessary to assess the risk by carefully verifying which variables are used. Recently, studies have also evaluated the risk of HCC using risk prediction models through transient elastography and artificial intelligence (AI) system. These HCC risk predication models are also noteworthy. In this review, we aimed to compare HCC risk prediction models in patients with CHB infection reported to date to confirm variables used and specificity between each model to determine an appropriate HCC risk prediction method.
Shielding Analysis of Metal Hydride-based Materials for Both Neutron and Gamma Rays Using Monte Carlo Simulation
Authors: Kwak Jeongkwon , Muth Boravy , Yang Hyeon-Woo , Park Chang Je , Kang Woo Seung , Kim Sun-Jae
Published: November 2021

Radiation causes damage to the human body, the environment, and electronic equipment. Shielding against neutron and gamma rays is particularly difficult because of their strong ability to penetrate materials. Conventional gamma ray shields are typically made of materials containing Pb. However, they pose problems in that Pb is a heavy metal, and human poisoning and/or pollution can result from the manufacturing, use, and disposal of these materials. In addition, neutron rays are shielded by materials rich in H2 or concrete. In the case of the latter, the manufacturing cost is high. Thus, it is necessary to develop a new multilayer structure that can shield against both neutron and gamma rays. We set up a simulation model of a multilayered structure consisting of metal hydrides and heavy metals, and then evaluated the simulations using Monte Carlo N-Particle Transport Code. Monte Carlo simulation is an accurate method for simulating the interaction between radiation and materials, and can be applied to the transport of radiation particles to predict values such as flux, energy spectrum, and energy deposition. The results of the study indicated the multilayer structure of ZrH2, U, and W could shield both neutron and gamma rays, thus showing potential as a new shielding material to replace Pb and concrete.
Ecological advantages of using microbiomethod in an integrated plant protection system
Authors: Sherstoboeva О. , Krzyhanivsky А. , Kryzhko A.
Published: November 2021

The article presents an analysis of current domestic and world literature data on the use of microbiomethod in plant protection. It has been proven, that biological preparations based on different biotypes of entomopathogenic bacteria Bacillus thuringiensis, due to their high specificity to various insect species and harmlessness to adult bees, warm-blooded and freshwater organisms, remain at the forefront of integrated plant protection systems worldwide. Their amount is up to 95% of all bioinsecticides. Being natural elements of biocenoses, entomopathogenic microorganisms do not harm plants. Moreover, the introduction of a number of bacteria into the soil and on the surface of plants promotes the growth of crops and increase their yield.Given the economic non-competitiveness of bioinsecticides compared to chemical insecticides, their use in Integrated Pest Management (IPM) Systems is appropriate for the control of phytophages against which they are highly effective. The negative result of chemical insecticides is not only the pollution of the environment and products, but also the formation and spread of resistant races and pest populations. The higher cost of microbiomethod is justified by the lack of negative long-term effects of massive use of chemical insecticides.
Using multispectral images to determine the salinity of soils in Ingulets irrigation system in the justification of management measures for chemical reclamation
Authors: Kovalchuk V. , Voitovych O.
Published: November 2021

The publication presents the use of data from multispectral space images to substantiate management measures for chemical reclamation of saline soils of the Ukraine irrigation system. The study is to develop a method of using satellite data to remotely determine the salinity of soils to support the management measures on the chemical soil improvement by example some fields of Ingulets irrigation system. Landsat 8 OLI images were used to obtain NDVI, soil salinity assessment indices, namely VSSI, Salinity index and normalized soil salinity index (NDSI). The verification data on the spatial distribution of salinity are taken from the report on soil-salt survey of the Ingulets irrigated massif. Work with satellite images and calculation of indices was performed using ERDAS IMAGINE 2015. Quantitative analysis of pixels, their visualization using the color spectrum was carried out in ArcMap 10.8. Validation for the conditions of Ukraine on the southern chernozems of the salt indices (VSSI, NDSI, SI) showed the best suitability of NDSI. Using the calculated ranges of index that characterize the gradation of salinity, their area percentage has been determined for each experimental field of the pilot object. The salinity areas according to each gradation were obtained on the basis of NDSI. Quantitative values of the management measure, the dose of chemical ameliorants, differentially for each of the fields are obtained using calculation methods using the author’s information technology. The total amount of phosphogypsum for chemical reclamation is recommended. The results of the study show that Landsat 8 OLI images show a high potential for spatio-temporal monitoring of salinity of the upper soil layers. This study will be useful for planning agricultural activities by mapping the salinity of the soil with the calculation of doses of chemical ameliorants to reduce economic losses in climate change. The proposed norms of gypsum application can serve as a guide for the agricultural producer when making a decision on chemical reclamation of agricultural lands. Based on a combination of satellite monitoring data and calculations of chemical reclamation doses according to the author’s online calculator, the farmer will be able to assess the feasibility and economic efficiency of chemical land reclamation measures. An additional practical value of the method of remote determination of boundaries and area of salinity is the ability to plan the selection of soil samples from certain points of the field, optimizing the number of soil samples for their chemical analysis in the laboratory. Our proposed method, which estimates soil salinity using satellite images and suggests doses of chemical ameliorants using information technology, can be potentially useful as a rapid approach to detecting soil salinity in other regions of Ukraine and the world at low cost and high accuracy
Variability in 1000 kernel weight of winter bread wheat (Triticum aestivum L.) genotypes depending on ecological and agrotechnical factors
Authors: Demydov O. , Pravdziva I. , Hudzenko V. , Demyanyuk O. , Vasylenko N.
Published: November 2021

In the ecological conditions of the central part of the Ukrainian Forest-Steppe (The V. M. Remeslo Myronivka Institute of Wheat, NAAS of Ukraine) the influence of growing season conditions (2016-17–2018-19), sowing dates (September 26, October 5, October 16) and different preceding crops (green manure, mustard, soybean, sunflower, corn) on variability of 1000 kernel weight of seventeen modern genotypes of winter wheat was investigated. Under environments of the central part of the Ukrainian Forest-Steppe, significant variability in the trait depending on the factors under study was revealed. Part of sum square for the growing season conditions in the variation of 1000 kernel weight of winter wheat was the most (63.2%). Part of sum square for genotype was 7.0%, for preceding crop it was 4.8%, for sowing dates it was 0.4%. In terms of growing season, the variation in part of sum square was 23.5–30.1% for genotype, 12.7–39.8% for preceding crop, 0.8–6.1% for sowing date, and 2.0–26.5% for interactions between them. During the period of the study, on average for all genotypes, the maximum 1000 kernel weight was obtained after green manure (42.6 g), the least one was after soybean (39.0 g). When changing the sowing dates from September 26 to October 16, it was revealed a general tendency of decrease 1000 kernel weight after the preceding crops mustard, sunflower, corn, and soybean. Significant differences in the response of genotypes under study on the sowing dates after different preceding crops were revealed. The most influence on 1000 kernel weight was established for preceding crops in the variety MIP Darunok and for sowing dates in the variety MIP Vidznaka. There were distinguished the varieties Trudivnytsia myronivska, Balada myronivska, MIP Dniprianka, Avrora myronivska, MIP Darunok which significantly exceeded the standard by 1000 kernel weight on average through the growing season conditions, sowing dates, and preceding crops.
Identification of spring barley genetic sources of increased and stable 1000 kernel weight performance (Hordeum vulgare L.)
Authors: Hudzenko V. , Demyanyuk О. , Polishchuk T. , Babii O. , Lysenko A.
Published: November 2021

The trials were conducted in 2018–2020 at the V.M. Remeslo Myronivka Institute of Wheat of NAAS. The aim of the research was to identify new spring barley genetic sources with combination of increased and stable 1000 kernel weight performance for creation initial breeding material under ecological conditions of the central part of Ukrainian Forest-steppe. There were studied 96 spring barley collection accessions originated in different ecological conditions. To identify peculiarities among genotypes within different subspecies (two-rowed and sixrowed), groups of varieties (covered and naked), as well as among two-rowed covered accessions of different ecological origin the genotypes under study were divided into six groups. Within four groups of accessions there were selected genotypes combining the maximum 1000 kernel weight performance and high homeostatic (Hom) and selection value (Sc) indexes. The other two groups of accessions were characterized with the fact that genotypes with high1000 kernel weight through three years did not have high Hom and Sc indexes due to higher variability. The analysis of variance of the AMMI model revealed almost the equal contribution to the total variance for growing season conditions (34.02%), genotype (34.67%) and their interaction (31.32%). The identified features indicate both the significant genetic diversity presented in this panel of spring barley accessions and the significant influence of weather conditions on the formation of 1000 kernel weight, as well as the different reaction of genotypes on the conditions of individual years of the research. When using statistical parameters and visualizations of the GGE biplot, new spring barley genetic sources with the optimal combination of increased and stable the trait performance were identified. In particular, to improve 1000 kernel weight the accessions Sviatovit (UKR), Dar Nosivshchyny (UKR), Smaragd (UKR), Sunshine (DEU), Lilly (DEU), and Vladlen (KGZ) are recommended to use as parental components for two-rowed covered barley varieties, the accession NSGJ-1 (SRB) is for naked barley varieties, and Yerong (AUS) is for six-rowed barley varieties.
STRUKTUR KOMUNITAS DAN POLA DISTRIBUSI MAKROALGA DI PERAIRAN WANGI-WANGI DESA LIYA MAWI KABUPATEN WAKATOBI
Authors: Afrianti Nunung , Nurgayah Wa , Rahmadani .
Published: November 2021

Makroalga salah satu sumber daya hayati laut memiliki nilai ekonomis dan manfaat, baik untuk manusia maupun lingkungan sekitarnya. Lokasi Penelitian di Perairan Desa Liya Mawi Kabupaten Wakatobi. Tujuan penelitian ini untuk mendapatkan informasi mengenai struktur komunitas dan pola distribusi makroalga. Pengambilan data dilaksanakan pada bulan Juli-September 2020.  Pengambilan data menggunakan metode transek kuadrat.  Pengambilan data dilakukan di tiga stasiun dengan 3 kali pengulangan. Analisis data yang digunakan yaitu  indeks keanekaragaman, indeks keseragaman, indeks dominansi, kepadatan dan pola distribusi.  Makroalga yang ditemukan berjumlah 13 spesies yang terdiri atas Kelas Chlorophyta berjumlah 6 spesies, kelas Phaeophyta 2 spesies dan kelas Rhodophyta 5 spesies. Jenis yang ditemukan yaitu Gracilaria coronopifolia, Laurencia papilosia, Gracilaria edulis, Eucheuma spinosum, Glacilaria salicornia, Ulva fasciata, Halimeda tuna, Halimeda marcoluba, Halimeda opuntia,Dictyosphaeria cavernosa, Chaetomorpha crassa, Padina australis dan Hydroclathrus clathratu. Nilai indeks keanekaragaman jenis makroalga berada dalam kategori sedang, indeks keseragaman dalam kategori tinggi, indeks dominansi makroalga tergolong kategori rendah.  Kepadatan makroalga berkisar 3,123-17,643 koloni/m². Pola distribusi makroalga di perairan Desa Liya Mawi tergolong kategori mengelompok dan merata.Kata Kunci: Desa Liya Mawi, Makroalga, Pola Distribusi, Struktur Komunitas
PENGARUH PERBEDAAN UKURAN FRAGMEN TERHADAP PERTUMBUHAN KARANG ANACROPORA PUERTOGALERAE DI PERAIRAN DESA LALANO, KECAMATAN SOROPIA
Authors: Alqadri Muhammad Fadly , Sadarun Baru , Rahmadani .
Published: November 2021

Anacropora puertogalerae tergolong karang yang rentan berdasarkan status IUCN.  Akibat tekanan yang berasal dari aktivitas masyarakat dikhawatirkan dapat menyebabkan penurunan populasi karang ini dialam. Tujuan dari penelitian ini yaitu untuk melihat tingkat kelangsungan hidup, laju pertumbuhan mutlak, dan pertambahan tunas pada karang Anacropora puertogalerae yang ditarnsplantasi dengan ukuran fragmen 3 cm, 5 cm dan 7 cm di perairan Lalanu Kecamatan Soropia. Penelitian ini dilakukan pada bulan Januari – Mei 2020. Penelitian ini menggunakan metode transplantasi fragmen karang di rak transplantasi.   Hasil penelitian menunjukan bahwa tingkat kelangsungan hidup fragmen 3, 5 dan 7 berkisar 35% - 92,50%, dimana kelangsungan hidup tertinggi pada fragmen 7 cm.  Laju pertumbuhan mutlak berkisar antara 6,502 - 16,098 cm dengan laju pertumbuhan mutlak tertinggi pada fragmen 7 cm.  Pertambahan tunas pada fragmen karang transplan berkisar 20 – 35 tunas, dimana pertambahan tunas terbanyak ditemukan pada fragmen 7 cm dengan rata2 pertumbuhan tunas sebesar 28 tunas. Laju pertumbuhan transplant pada fragmen 3 cm berbeda nyata jika dibandingkan dengan fragmen 5cm dan 7 cm.Kata Kunci: Anacropora  puertogalerae, kelangsungan hidup, laju pertumbuhan, pertambahan tunas, perairan Lalanu