A simulator providing theoretical research of human integrative physiology
Traditional (empiric) methodology based on direct measurements of fragmentary biological data limits the research of human integrative physiology (IP). Even assistant research based on animal experiments operates with fragmentary data. Therefore, IP’s current concepts, not covering many aspects of I...
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| author | Grygoryan, R.D. Sinitsin, I.P. Degoda, A.G. Lyudovyk, T.V. Yurchak, O.I. |
| author_facet | Grygoryan, R.D. Sinitsin, I.P. Degoda, A.G. Lyudovyk, T.V. Yurchak, O.I. |
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| description | Traditional (empiric) methodology based on direct measurements of fragmentary biological data limits the research of human integrative physiology (IP). Even assistant research based on animal experiments operates with fragmentary data. Therefore, IP’s current concepts, not covering many aspects of IP’s complex dynamics, cannot explain pathophysiological transformations that finally lead to non-trivial diseases. This methodological dead-end requires alternative research technology. This article presents a technology and software (SimHIP), widening the research potential in the area of human IP. The technology is based on two novelties. The first one is the physiological concept of a functional super-system (FSS) that optimizes cells' life despite environmental instabilities. The second novelty is the mathematical model (MM) of FSS. Fragments of MM were separately created and tuned using test scenarios. SimHIP integrating these fragments provides the physiologist-researcher with an intuitive interface to: a) construct a simulation scenario; b) execute the simulation; c) visualize input-output physiological dynamic dependencies for every chosen combination; and d) save every simulation data for future considerations and publications. SimHIP is an autonomous C# software provided as an Exe module for IBM-compatible computers. Medical students can be additional users of SimHIP.Problems in programming 2025; 4: 12-22 |
| first_indexed | 2026-03-12T20:22:50Z |
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Комп’ютерне моделювання
12
© R.D. Grygoryan, I.P.Sinitsin, A.G. Degoda, T.V. Lyudovyk, O.I. Yurchak, 2025
ISSN 1727-4907. Проблеми програмування. 2025. №4
УДК 517.958:57 +519.711.3 + 612.51.001 https://doi.org/10.15407/pp2025.04.012
R.D. Grygoryan, I.P. Sinitsin, A.G. Degoda, T.V. Lyudovyk, O.I. Yurchak
A SIMULATOR PROVIDING THEORETICAL RESEARCH
OF HUMAN INTEGRATIVE PHYSIOLOGY
Traditional (empiric) methodology based on direct measurements of fragmentary biological data limits the
research of human integrative physiology (IP). Even assistant research based on animal experiments
operates with fragmentary data. Therefore, IP’s current concepts, not covering many aspects of IP’s complex
dynamics, cannot explain pathophysiological transformations that finally lead to non-trivial diseases. This
methodological dead-end requires alternative research technology. This article presents a technology and
software (SimHIP), widening the research potential in the area of human IP. The technology is based on two
novelties. The first one is the physiological concept of a functional super-system (FSS) that optimizes cells'
life despite environmental instabilities. The second novelty is the mathematical model (MM) of FSS.
Fragments of MM were separately created and tuned using test scenarios. SimHIP integrating these
fragments provides the physiologist-researcher with an intuitive interface to: a) construct a simulation
scenario; b) execute the simulation; c) visualize input-output physiological dynamic dependencies for every
chosen combination; and d) save every simulation data for future considerations and publications. SimHIP is
an autonomous C# software provided as an Exe module for IBM-compatible computers. Medical students
can be additional users of SimHIP.
Keywords: organs, physiological systems, mathematical model, visualization, students
Р.Д. Григорян, І.П. Сініцин, А.Г. Дегода, Т.В. Людовик, О.І. Юрчак
СИМУЛЯТОР ДЛЯ ПРОВЕДЕННЯ ТЕОРЕТИЧНИХ
ДОСЛІДЖЕНЬ ІНТЕГРАТИВНОЇ ФІЗІОЛОГІЇ ЛЮДИНИ
Традиційна (емпірична) методологія, заснована на прямих вимірюваннях фрагментарних біологічних
даних, обмежує дослідження інтегративної фізіології (ІФ) людини. Навіть допоміжні дослідження ,
що базуються на експериментах з тваринами, оперують фрагментарними даними. Тому сучасні
концепції ІФ, не охоплюючи багато аспектів складної динаміки ІФ, не можуть пояснити
патофізіологічні трансформації, які зрештою призводять до нетривіальних захворювань. Цей
методологічний глухий кут вимагає альтернативної дослідницької технології. У цій статті
представлено технологію та програмне забезпечення (SimHIP), що розширюють дослідницький
потенціал в галузі ІФ людини. Технологія базується на двох новинках. Перша - фізіологічна
концепція функціональної суперсистеми (ФНС), яка оптимізує життя клітин, незважаючи на
нестабільність навколишнього середовища. Друга новинка - математична модель (ММ) ФНС.
Фрагменти ММ були окремо створені та налаштовані за допомогою тестових сценаріїв. SimHIP,
інтегруючи ці фрагменти, надає фізіологу-досліднику інтуїтивно зрозумілий інтерфейс для:
а) побудови сценарію моделювання; б) виконання моделювання; в) візуалізації фізіологічних
динамічних залежностей вхід-вихід для кожної обраної комбінації та г) збереження всіх даних
моделювання для майбутніх розглядів та публікацій. SimHIP — це автономне програмне
забезпечення на C#, що постачається як Exe-модуль для IBM-сумісних комп'ютерів. Студенти-
медики можуть бути додатковими користувачами SimHIP.
Ключові слова: органи, фізіологічні системи, математична модель, візуалізація, студенти
Introduction
Medical prophylactic, diagnostic, and
treatment technologies are based on the
physiological concepts of norm, homeostasis,
and adaptation. These concepts generally
proposed to explain biophysical, biochemical,
and physiological mechanisms evolutionarily
appeared to survive an organism in unstable
living environment. Modern biology
advanced this fundamental knowledge
including genetic aspects. However, a lot of
Комп’ютерне моделювання
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diseases, in particular those associated with
age, are still non-trivial to be timely
diagnosed and cardinally cured. The current
medicine is compelled to fight with such
diseases only using palliative cure mitigating
the pain and patient’s suffering until
painkillers are taken. Methodological
limitations, playing a significant role in the
current situation enormously arise, if the
organism is considered as a specific
community of specialized cells forced to exist
despite casual or regular destructive forces.
The problem is that modern empirical human
physiology does not have technologies that
would allow simultaneous monitoring of a
huge number of biological parameters at
different organizational levels (cells, their
colonies, specialized organs, their anatomical
and functional systems, and the whole
organism) of the body.
Traditional empirical biomedical research
alternatively suggests experiments on model
animals. But even in this case, the number of
vital parameters to be observed in dynamics is
limited. Modern physiology and medicine
have found themselves in a methodological
impasse, so the search for a way out of it is
encouraged.
One of the promising areas that can
enhance empirical data with computational
data is the method of mathematical modeling.
Typically, human physiology models have
been developed to simulate the function of a
single organ (e.g., heart [1], lungs [2], liver
[3], pancreas [4], and kidneys [5]) or an
anatomical system (e.g., cardiovascular
system [6] and digestive system [7]) under
given changes in input variables. Often, the
purpose of such models is applied: to
calculate ranges of values for unmeasured
characteristics. Additional model types that
offer a better understanding of certain
intricate aspects of life mechanisms have been
created. Theoretically, modeling could
significantly deepen the understanding of
human integrative physiology (IP). The
required model must quantitatively describe
the mechanisms that facilitate the interaction
of human internal organs co-evolved to
optimize cell physiology. The general
biological concept, known as the concept of
functional super-systems (FSS), which
explains the main principles of organ
interaction, is described in [8]. The concept of
FSS sheds new light on interactions of
internal organs and underlines the
fundamental role of intracellular regulator
mechanisms in the origin of fluctuations and
trends of human physical health. Specialized
mathematical models of organs and
anatomical-functional systems, which interact
to optimize cell physiology despite
environmental destructive alterations, have
been developed, tested under physiological
conditions, and published [9-10]. These
publications also contain information about
simulation algorithms and specific software
modules.
The goal of this presentation is to
demonstrate the main potentials of the
specialized software-modeling tool (SimHIP)
in research of human FSS.
The main purpose of SimHIP
SimHIP is an autonomous .exe module
developed in C# environment. The complex
quantitative mathematical model of human
FSS is a system of differential equations
(SDE) that describes the dynamics of FSS.
Algorithms provide approximate solution of
SDE for given initial conditions and dynamics
of input variables.
SimHIP’s main purpose consists in
providing the physiologist with an
unconventional assistant research technology
that allows obtaining new quantitative
knowledge about the dynamics of human
internal organs’ interaction under conditions
of a wide range of artificially created
internal/external changes. The knowledge can
be obtained by providing a single computer
experiment. Procedures required to prepare
such an experiment and to analyze its results
are provided by the user interface (UI). Before
considering UI in more detail, it is worth
saying some words about simulation
scenarios.
Simulation scenarios presented in a pop-
up window of UI include:
• The default scenario of test
simulation. It is provided for the
intact human organism for the body
Комп’ютерне моделювання
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horizontal position. The user does not
moderate any model parameter. In our
models, not every parameter is ideal;
thus, just after calculation is started, a
transitory process begins. It is
empirically set that transitions are
mainly over within several minutes of
modeled time, and a practically
steady-state physiological mode is
reached. SimHIP informs about
calculation finishing and provides
access to simulation results. The user
can look at up to 58 graphs
characterizing physiological dynamics
of mean man life variables within the
10 minutes.
• New model configuring. By choosing
this alternative, the user becomes able
to re-combine model modules,
actualize values of their constants, and
the simulation scenario. The same up
to 58 output data are assessable for
every simulation scenario. The
actualization if desirable concerns
every component model listed in the
main interface.
The user interface of SimHIP.
The main screen form of the user
interface (UI) is presented in Figure 1. As one
can see, the actualization concerns parameters
of models representing the thermoregulatory
system (TC), the kidneys, the pancreas-liver
interaction (PL), the lung ventilation (LVent),
and interstitial compartments’ interaction. As
the model of cardiovascular system (CVS) is
in the focus of our complex model,
mechanisms controlling CVS have been
Fig. 1. The main screen form for actualizing the basic model.
The actualization concerns parameters of thermoregulatory system (TC), kidneys, pancreas-liver
interaction model (PL), lung ventilation model (LVent), model of interstitial compartments, as
well as mechanisms controlling the cardiovascular system. Special options provide actual pa-
rameters of observation, Simulation scenario, Hypotheses of hypertension and its therapy. Spe-
cial option “Experiment simulation” starts the computer experiment. Just after the experiment is
over, the option “View simulation results” opens access to graphical simulation results.
Комп’ютерне моделювання
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presented in UA most detailed. This concerns
special options for actualization of
observation parameters, simulation scenario,
hypotheses of hypertension and its therapy.
Special option “Experiment simulation”
starts the computer experiment. Just after the
experiment is over, the option “View
simulation results” opens an access to
graphical simulation results.
The double windows (see Fig. 3) are the
standard screen form for visualizing
simulation results in graph forms. The lower
window collects input variables, and the
upper window collects output variables. The
user can collect variables as desired and
choose color or white and black lines with up
to 15 specific signs. Additional boxes on the
right serve as a selection of color or black and
white presentation of graphs. Access to
alternative clusters is opened by clicking
“Choose a cluster of graphs” (an example is
shown in Fig. 5).
The list of clusters contains eight clusters:
• Cardiovascular system (includes 7
variables: Systolic pressure; Diastolic pres-
sure; Mean arterial pressure; Mean central
venous pressure; Heart rate; Stroke volume of
left ventricle; Heart input flow);
• Thermoregulation system (includes 9
variables: Blood temperature; Skin tempera-
ture; Air temperature; Wind speed; Air hu-
midity; Light intensity; Blood Serotonin;
Blood melatonin; Hypothalamus tempera-
ture);
Fig. 2. The screen form of UA providing an access to results of the simulation for each model.
Graphs can be illustrated either from the beginning or from the 20th second of simulation.
Depending on its duration, the user can chose appropriate time scale.
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• Kidneys and bladder (includes 12 var-
iables: Urine; Prourine; Urine velocity; Prou-
rine velocity; Reabsorption; Bladder volume;
Bladder pressure; POSM; PONC; Osmore-
ceptors; Bladder receptors; Sodium);
• Pancreas-Liver (includes 4 variables:
Insulin; Glucose; Glucagon; Glycogen);
• Pulmonary ventilation (includes 4 var-
iables: PaO2; PaCO2; pH; Lung ventilation);
• Liquid compartments (includes 8 vari-
ables: Total blood volume; Summary blood
volume in arteries; Summary blood volume in
veins; Total long blood volume; Total fluids;
Interstitial volume; Total intracellular vol-
ume; Lymph volume);
• Indicators of neuroendocrine system
(includes 9 variables; Summary barorecep-
tion; Chemoreception; Heart sympathetic
nerve activity; Heart parasympathetic nerve
activity; Vascular sympathetic nerve activity;
Renin; ANG2; Adrenalin; Vasopressin);
• Indicators of condition (includes 5
variables: Aerobic exercise; Degree of table
tilt; Resistance of renal afferent arteries; Re-
sistance of coronary arteries; Resistance of
brain arteries).
So, the current version of SimHIP pro-
vides the physiologist with the dynamics of
58 biological variables. However, the com-
plex model consists of a larger amount of
biological data. Some of these data concern
the initial parameters (constants) used in the
Fig. 3. A sample of typical graphs presenting the dynamics of input (bottom graphs) and output
(upper graphs) variables.
By clicking “Select graphs” in the upper left corner, the user can access a special screen form to
visualize graphs concerning other physiological variables completed in 7 clusters (see Fig. 4).
Комп’ютерне моделювання
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mathematical models. Although these con-
stants were chosen through thoroughly test-
ed tunings, SimHIP proposes special op-
tions to advanced users: they can vary con-
stants, execute a simulation, and watch the
physiological consequences of every altera-
tion.
Fig. 5 special presented to illustrate
how the user activated the stroke Simula-
tion sce nario in left light window does set
additional parameters of the chosen test.
This case the tilting on 85o upright does
start at 600th seconds of initial horizontal
position. The table turns head-up with a
person's head in 10 seconds, the person is in
an inclined position for 600 seconds, after
which in 15 seconds the table is returned in
horizontal and the tested person continues to
be in the rest state for 100 sec. Note that
additional parameters (the resistances of
Fig. 4. The service window “Choose a cluster of graphs” provides two functions: a) configuring
input (output) variables in the frame of active cluster of graphs; b) choosing a new cluster from
the list of clusters for providing the function a).
Комп’ютерне моделювання
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brain, coronary, and kidney arteries) have
also been actualized.
At the bottom part of this window, the
special scrolling window is shown. It collects
additional information about the computer
experiment.
Fig. 5. Preparing a simulation of a postural test in combination of partial occlusions of coronary,
brain, and kidneys arteries. Simulation results are presented in Fig. 6 and Fig. 7.
Комп’ютерне моделювання
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Discussion
The research technology proposed by
“SimHIP” is an unusual solution to physiolog-
ical problems. Both physiologists and medics
are more used to working with devices that
provide them with measurements of life char-
acteristics necessary to make more reliable
conclusions. Such a device usually provides
one or two an additional biological character-
istics. Examples of such medical devices are
the electrocardiograph, echocardiograph, elec-
troencephalograph, and others. Even famous
devices that provide magnetic resonance im-
aging can deal with one variable – biological
liquid (blood) volume in local body areas.
Our SimHIP deals with 58 dynamic character-
istics. Certainly, cannot use initial data meas-
ured in a person. However, SimHIP is an ex-
clusive research tool assisting the human
physiologist to minimize likely mistakes con-
cerning the multiscale integrative functioning
of human organisms. In this sense, simula-
tions seem to be the cheapest way to avoid
false conclusions, including those concerning
principles determining the non-trivial patho-
physiological transformations. Another prom-
ising aspect of the use of our SimHIP is the
process of teaching future doctors the basics
of physiology. Until now, diagrams and pic-
tures depicting the anatomy and simplified
physiology of organs have been the main way
of presenting knowledge about how the body
functions. Meanwhile, there is still no solid
fundamental knowledge about how internal
organs quantitatively interact. In this regard,
our simulator is the first software product that
offers to restructure the process of training
future doctors so that each student can see
with his own eyes the consequences of the
changes he makes to the model of a specific
organ.
Fig. 6. The dynamics of chosen physiological data under simulation of the scenario described in Fig. 5.
Комп’ютерне моделювання
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Conclusion
For the first time, a concept has been
created and a computer program has been
developed that is oriented towards use by a
physiologist who studies the patterns of inte-
grative physiology of human cell life support
in an unstable environment. Based on a com-
plex mathematical model of the interaction of
internal organs, the program is designed as a
specialized autonomous simulator, SimHIP. It
can be used by both research physiologists
and future doctors when teaching the basics of
human physiology.
Fig. 7. The dynamics of other chosen physiological data under simulation of the scenario
described in Fig. 5.
Комп’ютерне моделювання
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Одержано: 03.11.2025
Внутрішня рецензія отримана: 11.11.2025
Зовнішня рецензія отримана: 13.11.2025
Комп’ютерне моделювання
22
About authors:
Grygoryan Rafik
PhD, D-r in biology, Department chief,
http://orcid.org/0000-0001-8762-733X.
Sinitsin Igor
Prof., PhD, D-r in tech. sciences,
Director,
http://orcid.org/0000-0002-4120-0784.
Degoda Anna,
PhD, Senior scientist,
http://orcid.org/0000-0001-6364-5568.
Lyudovyk Tetyana,
Senior scientist, PhD.
https://orcid.org/0000-0003-0209-2001.
Yurchak Oksana,
Leading software engineer.
https://orcid.org/0000-0003-3941-1555.
Place of work:
Institute of software systems
of National Academy of
Sciences of Ukraine,
03187, Кyiv,
Acad. Glushkov avenue, 40.
Е-mail:
rgrygoryan@gmail.com,
ips2014@ukr.net,
anna@silverlinecrm.com,
tetyana.lyudovyk@gmail.com,
daravatan@gmail.com.
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| id | pp_isofts_kiev_ua-article-872 |
| institution | Problems in programming |
| keywords_txt_mv | keywords |
| language | English |
| last_indexed | 2026-03-12T20:22:50Z |
| publishDate | 2026 |
| publisher | PROBLEMS IN PROGRAMMING |
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| resource_txt_mv | ppisoftskievua/e2/f0b56792db2a131572351a16ae8781e2.pdf |
| spelling | pp_isofts_kiev_ua-article-8722026-02-12T15:27:30Z A simulator providing theoretical research of human integrative physiology Симулятор для проведення теоретичних досліджень інегративної фізіології людини Grygoryan, R.D. Sinitsin, I.P. Degoda, A.G. Lyudovyk, T.V. Yurchak, O.I. organs; physiological systems; mathematical model; visualization UDC 517.958:57 +519.711.3 + 612.51.001 органи; фізіологічні системи; математична модель; візуалізація УДК 517.958:57 +519.711.3 + 612.51.001 Traditional (empiric) methodology based on direct measurements of fragmentary biological data limits the research of human integrative physiology (IP). Even assistant research based on animal experiments operates with fragmentary data. Therefore, IP’s current concepts, not covering many aspects of IP’s complex dynamics, cannot explain pathophysiological transformations that finally lead to non-trivial diseases. This methodological dead-end requires alternative research technology. This article presents a technology and software (SimHIP), widening the research potential in the area of human IP. The technology is based on two novelties. The first one is the physiological concept of a functional super-system (FSS) that optimizes cells' life despite environmental instabilities. The second novelty is the mathematical model (MM) of FSS. Fragments of MM were separately created and tuned using test scenarios. SimHIP integrating these fragments provides the physiologist-researcher with an intuitive interface to: a) construct a simulation scenario; b) execute the simulation; c) visualize input-output physiological dynamic dependencies for every chosen combination; and d) save every simulation data for future considerations and publications. SimHIP is an autonomous C# software provided as an Exe module for IBM-compatible computers. Medical students can be additional users of SimHIP.Problems in programming 2025; 4: 12-22 Традиційна (емпірична) методологія, заснована на прямих вимірюваннях фрагментарних біологічних даних, обмежує дослідження інтегративної фізіології (ІФ) людини. Навіть допоміжні дослідження, що базуються на експериментах з тваринами, оперують фрагментарними даними. Тому сучасні концепції ІФ, не охоплюючи багато аспектів складної динаміки ІФ, не можуть пояснити патофізіологічні трансформації, які зрештою призводять до нетривіальних захворювань. Цей методологічний глухий кут вимагає альтернативної дослідницької технології. У цій статті представлено технологію та програмне забезпечення (SimHIP), що розширюють дослідницький потенціал в галузі ІФ людини. Технологія базується на двох новинках. Перша - фізіологічна концепція функціональної суперсистеми (ФНС), яка оптимізує життя клітин, незважаючи на нестабільність навколишнього середовища. Друга новинка - математична модель (ММ) ФНС. Фрагменти ММ були окремо створені та налаштовані за допомогою тестових сценаріїв. SimHIP, інтегруючи ці фрагменти, надає фізіологу-досліднику інтуїтивно зрозумілий інтерфейс для: а) побудови сценарію моделювання; б) виконання моделювання; в) візуалізації фізіологічних динамічних залежностей вхід-вихід для кожної обраної комбінації та г) збереження всіх даних моделювання для майбутніх розглядів та публікацій. SimHIP — це автономне програмне забезпечення на C#, що постачається як Exe-модуль для IBM-сумісних комп'ютерів. Студенти медики можуть бути додатковими користувачами SimHIP.Problems in programming 2025; 4: 12-22 PROBLEMS IN PROGRAMMING ПРОБЛЕМЫ ПРОГРАММИРОВАНИЯ ПРОБЛЕМИ ПРОГРАМУВАННЯ 2026-02-12 Article Article application/pdf https://pp.isofts.kiev.ua/index.php/ojs1/article/view/872 PROBLEMS IN PROGRAMMING; No 4 (2025); 12-22 ПРОБЛЕМЫ ПРОГРАММИРОВАНИЯ; No 4 (2025); 12-22 ПРОБЛЕМИ ПРОГРАМУВАННЯ; No 4 (2025); 12-22 1727-4907 en https://pp.isofts.kiev.ua/index.php/ojs1/article/view/872/925 Copyright (c) 2026 PROBLEMS IN PROGRAMMING |
| spellingShingle | organs physiological systems mathematical model visualization UDC 517.958:57 +519.711.3 + 612.51.001 Grygoryan, R.D. Sinitsin, I.P. Degoda, A.G. Lyudovyk, T.V. Yurchak, O.I. A simulator providing theoretical research of human integrative physiology |
| title | A simulator providing theoretical research of human integrative physiology |
| title_alt | Симулятор для проведення теоретичних досліджень інегративної фізіології людини |
| title_full | A simulator providing theoretical research of human integrative physiology |
| title_fullStr | A simulator providing theoretical research of human integrative physiology |
| title_full_unstemmed | A simulator providing theoretical research of human integrative physiology |
| title_short | A simulator providing theoretical research of human integrative physiology |
| title_sort | simulator providing theoretical research of human integrative physiology |
| topic | organs physiological systems mathematical model visualization UDC 517.958:57 +519.711.3 + 612.51.001 |
| topic_facet | organs physiological systems mathematical model visualization UDC 517.958:57 +519.711.3 + 612.51.001 органи фізіологічні системи математична модель візуалізація УДК 517.958:57 +519.711.3 + 612.51.001 |
| url | https://pp.isofts.kiev.ua/index.php/ojs1/article/view/872 |
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