<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Archiving and Interchange DTD v1.0 20120330//EN" "JATS-archivearticle1.dtd">
<article xmlns:xlink="http://www.w3.org/1999/xlink">
  <front>
    <journal-meta />
    <article-meta>
      <title-group>
        <article-title>Mobile Information System Creatine in Food Products for Determining the Level of</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <string-name>Tetiana Hovorushchenko</string-name>
          <xref ref-type="aff" rid="aff0">0</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Denys Kvasnitskyi</string-name>
          <xref ref-type="aff" rid="aff0">0</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Olha Hovorushchenko</string-name>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Iryna Zasornova</string-name>
          <email>izasornova@gmail.com</email>
          <xref ref-type="aff" rid="aff0">0</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Artem Boyarchuk</string-name>
          <email>a.boyarchuk@taltech.ee</email>
          <xref ref-type="aff" rid="aff2">2</xref>
        </contrib>
        <aff id="aff0">
          <label>0</label>
          <institution>Khmelnytskyi National University</institution>
          ,
          <addr-line>Institutska str., 11, Khmelnytskyi, 29016</addr-line>
          ,
          <country country="UA">Ukraine</country>
        </aff>
        <aff id="aff1">
          <label>1</label>
          <institution>National Pirogov Memorial Medical University</institution>
          ,
          <addr-line>Pirogova str., 56, Vinnytsya, 21018</addr-line>
          ,
          <country country="UA">Ukraine</country>
        </aff>
        <aff id="aff2">
          <label>2</label>
          <institution>Tallinna Tehhnikaülikool</institution>
          ,
          <addr-line>Ehitajate tee 5, Tallinn, 12616</addr-line>
          ,
          <country country="EE">Estonia</country>
        </aff>
      </contrib-group>
      <abstract>
        <p>The study of food products to determine the level of creatine in them is an actual task, taking into account the need for this substance for patients with Covid'19 and spinal muscular atrophy. The purpose of our research is to develop a mobile information system for determining the level of creatine in food products. The developed method for determining the level of creatine in food products by the user and the method for determining the level of creatine in food products using a mobile information system provide the user with the opportunity to quickly, conveniently, cheaply and effectively assess the presence and level of creatine in any food products, on the basis of which to build a rational diet from the point vision of body saturation with creatine. The proposed mobile information system for determining the level of creatine in food products provides convenience, low-cost, celerity, miniaturization and automation for measurement of concentration of creatine in any food products. The conclusion obtained from the system regarding the presence and level of creatine in this or that food product is useful and extremely important when preparing the diet of patients, especially patients with Covid'19 and/or spinal muscular atrophy. The proposed approach and mobile information system for determining the level of creatine in food products can be used not only for drawing up the diet of patients, especially patients with Covid'19 and/or spinal muscular atrophy, from the point vision of body saturation with creatine, but also for example, to check the quality of meat products.</p>
      </abstract>
      <kwd-group>
        <kwd>1 Creatine</kwd>
        <kwd>creatine level</kwd>
        <kwd>determining the level of creatine</kwd>
        <kwd>mobile information system</kwd>
      </kwd-group>
    </article-meta>
  </front>
  <body>
    <sec id="sec-1">
      <title>1. Introduction</title>
      <p>Today, in Ukraine and the world, the problem of the spread of the Covid'19 pandemic is very acute.
Common manifestations in patients with Covid'19 are respiratory (oxygen) insufficiency, dry cough,
shortness of breath, and changes in the lungs on computer tomography in the form of opacification
and/or consolidation in the form of "frosted glass". There are also numerous behavioral abnormalities
that indicate damage to the brain and nervous system of such patients, as well as numerous
neuromuscular disorders. Long-term stay of patients (especially the elderly) on oxygen therapy in one
position without mobility often leads to muscular dystrophy.</p>
      <p>The second acute problem of Ukraine and the world is the increase in the number of spinal muscular
atrophy diseases, which arise as a result of genetic mutations and are characterized by damage to
skeletal muscles, progressive muscle weakness and muscle atrophy.</p>
      <p>Creatine, which allows muscles to "remember" their initial state and in combination with
rehabilitation exercises to return the previous functionality, and also has the property of increasing the
body's perception of oxygen and a protective effect on the nervous system, which is extremely important
and relevant both in the conditions of today's Covid'19 pandemic and in the conditions of the growing
number of spinal muscular atrophy diseases. Creatine can enter the body not only as part of various
expensive food additives, but also with food products.</p>
      <p>
        Creatine is a nitrogen-containing carboxylic acid that participates in energy exchange in muscle and
nerve cells [
        <xref ref-type="bibr" rid="ref1">1</xref>
        ]. Creatine in its free form, as well as in the form of creatine phosphate, is an essential
element of muscle tissue. In skeletal muscles, creatine is responsible for energy exchange and
contractility. Creatine gives muscles energy, improves protein synthesis and delays the accumulation
of lactic acid. Creatine is important as a source of muscle contraction forces [
        <xref ref-type="bibr" rid="ref2">2</xref>
        ].
      </p>
      <p>
        Analysis of a number of clinical applications of creatine [
        <xref ref-type="bibr" rid="ref3">3</xref>
        ] associated with neurodegenerative
diseases (for example, muscular dystrophy (especially after coma, after prolonged immobilization),
Parkinson's disease, Huntington's disease [
        <xref ref-type="bibr" rid="ref4">4</xref>
        ]), in the treatment of ischemia of the brain and heart [
        <xref ref-type="bibr" rid="ref5">5</xref>
        ],
aging [
        <xref ref-type="bibr" rid="ref6">6</xref>
        ], diabetes, osteoarthritis, fibromyalgia, adolescent depression [
        <xref ref-type="bibr" rid="ref7">7</xref>
        ], provides evidence that
creatine can improve physical performance and/or clinical outcomes in these patient groups – for
example, creatine allows muscles to “remember” their initial state and in combination with
rehabilitation exercises to return the previous functionality, slows down the progression of brain atrophy
in patients with Parkinson's disease, protects the heart during an ischemic event, improves the health of
elderly patients (cholesterol level decreased, fat accumulation in the liver decreased, muscle mass
increased, bone loss minimized), improves glycemic control, improves brain activity by increasing
dopamine levels in and functions of mitochondria.
      </p>
      <p>
        Creatine is a peculiar regulator of energy metabolism. Another important property of creatine is the
property of increasing the body's perception of oxygen, thanks to which it also provides a protective
effect on the nervous system in conditions of hypoxia, which is extremely important in the conditions
of today's Covid'19 pandemic [
        <xref ref-type="bibr" rid="ref10 ref11 ref12 ref8 ref9">8-12</xref>
        ], since patients with Covid'19 need both increasing the body's
perception of oxygen (especially oxygen-dependent patients), as well as protecting the nervous system
(which is negatively affected by Covid'19) [
        <xref ref-type="bibr" rid="ref3 ref4">3, 4</xref>
        ].
      </p>
      <p>
        The human body contains, depending on the muscle mass, from 100 to 150 g of pure creatine. Its
daily consumption is up to 2 g. Our body can synthesize approximately 1 g of the substance per day
[
        <xref ref-type="bibr" rid="ref13">13</xref>
        ].
      </p>
      <p>The study of the amount of creatine in the human body is included in the package of human tests
"Blood Biochemistry Extended", which is recommended for patients with Covid'19 and spinal muscular
atrophy in order to study the functioning of the liver, kidneys, mineral exchange and metabolism in the
body. Such a package of analyzes determines the level of creatinine (the end product of creatine
breakdown) in the human body.</p>
      <p>The concentration of creatinine in the blood depends on its formation and excretion. Its formation
directly depends on the state of muscle mass. Figure 1 shows the reference values (normal values) and
values of the creatinine level in the body of a real person (a 46-year-old man) suffering from spinal
muscular atrophy, which confirms the low level of creatinine (and, accordingly, the low level of
creatine) in people with this disease.</p>
      <p>Although creatine is naturally synthesized in the human body (endogenous), it is obvious that half
of the creatine required by humans comes into the body with food (exogenous). Of course, many
different bio-supplements containing creatine have been created, but, of course, it is much more
appropriate to eat properly and get creatine from food.</p>
      <p>
        The main sources of creatine are meat and fish, but dairy products and berries can also contain
creatine. It is known that beef contains 4.5 g of creatine per 1 kg, pork – 5 g per 1 kg, salmon - 4.5 g
per 1 kg, tuna – 4 g per 1 kg, cod – 3 g per 1 kg, flounder – 2 g per 1 kg [
        <xref ref-type="bibr" rid="ref13">13</xref>
        ]. But there is no information
about the presence of creatine in other products (for example, in various meat products).
      </p>
      <p>So, the study of food products to determine the level of creatine in them is an actual task, taking
into account the need for this substance for patients with Covid'19 and spinal muscular atrophy.</p>
    </sec>
    <sec id="sec-2">
      <title>2. Survey of Research</title>
      <p>
        Food products can be tested for creatine in them by various methods. The most widely used method
is the Popper’s method, which is based on the Jaffe color reaction (formation of the orange-colored
tautomer of creatinine picrate), which consists in the reduction of creatinine with picric acid in a
strongly alkaline medium with the formation of a red-orange color, and the intensity of the color is
determined colorimetrically or photometrically (Figure 2) [
        <xref ref-type="bibr" rid="ref14">14</xref>
        ].
      </p>
      <p>The paper [25] is devoted to the development of the method on the basis of the aggregation of
cysteamine functionalized gold nanoparticles for effective detection of creatine in biological fluids.</p>
      <p>The paper [26] proposed the cost-effective portable chemiluminescence quantification platform for
detection and quantification of creatinine in blood serum on the basis of the high-quality camera sensor
in conjunction with a raspberry-pi single board computer.</p>
      <p>The paper [27] described the new concept, which is based on the one-step, simple, and
nonenzymatic detection system of creatine in the food supplements based on the Pt electrode using an
elemental analyzer.</p>
      <p>The paper [28] described the colorimetric probes for blood creatinine and urinary creatinine
detections using metal nanoparticles (for example, using starch-stabilized silver nanoparticles for
creatine detection).</p>
      <p>The paper [29] proposed the non-enzymatic highly sensitive creatine sensor on the basis of the
antimony-doped tin oxide aggregated nanoparticles and glassy carbon electrode using electrochemical
reduction phenomena.</p>
      <p>As the survey of research showed, the known tools and systems for detecting and determining the
level of creatine are mainly focused on detecting creatine in biological fluids (blood, urine, etc.) or in
the food supplements, but not in food products. In addition, almost all these tools are expansive and
bulky, and require additional support and complicated operations.</p>
      <p>Most methods also require pretreatment of samples and expensive equipment and reagents, that is,
they can only be performed in laboratory conditions. Since half of the creatine required by a person
enters the body with food, and creatine can enter the body not only as part of various expensive food
additives, but also from food products, therefore the purpose of our research is to develop a mobile
information system for determining the level of creatine in food products. To develop such a mobile
information system for determining the level of creatine in food products, it is necessary to conduct an
analysis of the subject area for the detection of creatine by the Popper method based on the Jaffe color
reaction, develop rules and a method for determining the level of creatine in food products, which will
be the basis of a mobile information system for determining the level of creatine in food products, as
well as to design a mobile information system for determining the level of creatine in food products.</p>
    </sec>
    <sec id="sec-3">
      <title>3. Mobile Information System for Determining the Level of Creatine in Food</title>
    </sec>
    <sec id="sec-4">
      <title>Products</title>
      <p>Let's conduct an analysis of the subject area on the detection of creatine by the Popper's method
based on the Jaffe color reaction. In general, Popper's method based on the Jaffe color reaction consists
of the following steps:
1. to prepare the analyzed sample (broth or decoction of the food product to be analyzed for
creatine presence)
2. to prepare a 1%-th aqueous solution of picric acid
3. to prepare a 10%-th solution of sodium hydroxide
4. to prepare a boiling water bath
5. to pour 2 ml of the analyzed sample (broth or decoction) into the dish
6. to add 3 drops of 1%-th picric acid solution
7. to add 5 drops of 10%-th sodium hydroxide solution
8. to mix the contents of the dish
9. to put the dish in a boiling water bath for 15 minutes
10. to evaluate the color of the analyzed sample, on the basis of which to draw a conclusion about
the presence and level of creatine in the studied food product (if creatine is present in the
analyzed sample, the sample turns orange or red, otherwise it remains pale yellow)
Of course, this method is also more suitable for use in laboratory conditions than at home. However,
at home, you can use an affordable and quick tool to determine the level of creatine in food. Such a tool
is test paper strips impregnated with a mixture of 1%-th solution of picric acid and 10%-th solution of
sodium hydroxide in a ratio of 3:5. In the presence of such test paper strips, a person needs only:
1. to pour the analyzed sample (broth or decoction) into the dish
2. to put a paper test strip in it
3. to put the dish in a boiling water bath for 15 minutes
4. to evaluate the color of the analyzed sample, on the basis of which to draw a conclusion about
the presence and level of creatine in the studied food product</p>
      <p>Such procedures are quite easy to perform at home, even for a sick person. The cost of a paper test
strip measuring 2x5 cm is minimal – 0.04 UAH (0.001 USD), that is, the purchase of paper strips is
also available to any person, even a low-income person.</p>
      <p>The main problem is the correct assessment of the color of the analyzed sample and the correct
conclusion about the presence and level of creatine in the food product under study, because a person
who needs to determine the presence of creatine in food products may not distinguish colors
(colorblindness), may have vision problems, due to which it will be difficult for her to assess the
intensity of the color reaction and reach a conclusion about the creatine presence in the analyzed
samples.</p>
      <p>Therefore, a mobile information system for determining the level of creatine in food products will
be developed precisely to evaluate the color of the analyzed sample and form a conclusion about the
presence and level of creatine in the studied food product.</p>
      <p>Let's develop a scale for evaluating the color of the analyzed sample in order to determine the
presence and level of creatine in the studied food product – Figure 3.</p>
      <p>In this scale:
1. color 0 means the absence of creatine
2. color 1 means the presence of a low level of creatine
3. color 2 means the presence of an average level of creatine
4. color 3 means the presence of a high level of creatine</p>
      <p>Then the rules for evaluating the color of the analyzed sample in order to establish the presence and
level of creatine in the studied food product will have the following form:
1. if by analyzing the intensity of RGB (red, green and blue) it is determined that the paper test
strip has the color 0 from the scale for evaluating the color of the analyzed sample in order to
determine the presence and level of creatine in the studied food product, then creatine is absent
in the studied product
2. if by analyzing the intensity of RGB it is determined that the paper test strip has the color 1
from the scale for evaluating the color of the analyzed sample in order to determine the presence
and level of creatine in the studied food product, then creatine is present in the studied product,
and the level of creatine is low
3. if by analyzing the intensity of RGB it is determined that the paper test strip has the color 2
from the scale for evaluating the color of the analyzed sample in order to determine the presence
and level of creatine in the studied food product, then creatine is present in the studied product,
and the level of creatine is average
4. if by analyzing the intensity of RGB it is determined that the paper test strip has the color 3
from the scale for evaluating the color of the analyzed sample in order to determine the presence
and level of creatine in the studied food product, then creatine is present in the studied product,
and the level of creatine is high</p>
      <p>Considering the analysis of the subject area, the method of determining the level of creatine in food
products by the user consists of the following steps:
1. to install a mobile information system in the form of a mobile application on a smartphone
2. to pour the analyzed sample (broth or decoction) into the dish
3. to put a paper test strip in it
4. to put the dish in a boiling water bath for 15 minutes
5. to scan the received color of the paper test strip using the developed mobile information system
in the form of a mobile application that determines the concentration of creatine by analyzing
the intensity of RGB
6. in the mobile application, to read the conclusion about the presence/absence and level of
creatine in the studied food product</p>
      <p>Considering the developed rules for evaluating the color of the analyzed sample in order to determine
the presence and level of creatine in the studied food product, the method of determining the level of
creatine in food products by the mobile information system consists of the following steps:
1. to scan the color of the paper test strip
2. to recognize the color of the paper test strip by analyzing the intensity of RGB
3. to compare the recognized color of the paper test strip with the scale for evaluating the color of
the analyzed sample in order to determine the presence and level of creatine in the studied food
product
4. to apply the developed rules for evaluating the color of the analyzed sample in order to establish
the presence and level of creatine in the studied food product
5. if rule 1 triggered, then give the conclusion to the user: "creatine is absent in the studied food
product"
6. if rule 2 triggered, then give the conclusion to the user: "creatine is present in the studied food
product, the level of creatine is low"
7. if rule 3 triggered, then give the conclusion to the user: "creatine is present in the studied food
product, the level of creatine is average"
8. if rule 4 triggered, then give the conclusion to the user: "creatine is present in the studied food
product, the level of creatine is high"
9. if none of the rules triggered, then give the conclusion to the user: "problems with color
recognition, repeat the scan of the test strip"</p>
      <p>The developed method for determining the level of creatine in food products by the user and the
method for determining the level of creatine in food products using a mobile information system provide
the user with the opportunity to quickly, conveniently, cheaply and effectively assess the presence and
level of creatine in any food products, on the basis of which to build a rational diet from the point vision
of body saturation with creatine.</p>
      <p>The developed method for determining the level of creatine in food products by the user and the
method for determining the level of creatine in food products by a mobile information system are the
basis for the mobile information system for determining the level of creatine in food products, which
will be implemented in the form of a mobile application, which on the basis of the determination of
creatinine concentration by analysis of the intensity of RGB, forms a conclusion about the presence and
level of creatine in any food products.</p>
      <p>The structure of the mobile information system for determining the level of creatine in food products
is presented in Figure 4.</p>
      <p>The proposed mobile information system for determining the level of creatine in food products
provides convenience, low-cost, celerity, miniaturization and automation for measurement of
concentration of creatine in any food products.</p>
      <p>The conclusion obtained from the system regarding the presence and level of creatine in this or that
food product is useful and extremely important when preparing the diet of patients, especially patients
with Covid'19 and/or spinal muscular atrophy.</p>
      <p>Figure 4: Structure of mobile information system for determining the level of creatine in food products</p>
    </sec>
    <sec id="sec-5">
      <title>4. Results &amp; Discussion</title>
      <p>Let's consider the operation of the proposed mobile information system for determining the level of
creatine in food products.</p>
      <p>For the first experiment, the user used a decoction of pork lard, put a paper test strip in it for
determining the creatine, placed the dish in a boiling water bath for 15 minutes, and then scanned the
resulting color of the paper test strip using the developed mobile information system in the form of a
mobile application.</p>
      <p>The proposed mobile information system for determining the level of creatine in food products
performed the color scanning of the paper test strip, the color recognition of the paper test strip by RGB
intensity analysis, and the comparison of the recognized color of the paper test strip with the scale for
evaluating the color of the analyzed sample. The results of such a comparison are presented in Figure
5.</p>
      <p>There was a search for a rule among the rules for evaluating the color of the analyzed sample in
order to establish the presence and level of creatine in the studied food product. Rule 1 triggered, so the
user received the conclusion "Creatine is absent in the studied food product".</p>
      <p>For the second experiment, the user used a chicken broth, put a paper test strip in it for determining
the creatine, placed the dish in a boiling water bath for 15 minutes, and then scanned the resulting color
of the paper test strip using the developed mobile information system in the form of a mobile
application.</p>
      <p>The proposed mobile information system for determining the level of creatine in food products
performed the color scanning of the paper test strip, the color recognition of the paper test strip by RGB
intensity analysis, and the comparison of the recognized color of the paper test strip with the scale for
evaluating the color of the analyzed sample. The results of such a comparison are presented in Figure
6.</p>
      <p>There was a search for a rule among the rules for evaluating the color of the analyzed sample in
order to establish the presence and level of creatine in the studied food product. Rule 2 triggered, so the
user received the conclusion "Creatine is present in the studied food product, the level of creatine is
low".</p>
      <p>For the third experiment, the user used a pork broth, put a paper test strip in it for determining the
creatine, placed the dish in a boiling water bath for 15 minutes, and then scanned the resulting color of
the paper test strip using the developed mobile information system in the form of a mobile application.</p>
      <p>The proposed mobile information system for determining the level of creatine in food products
performed the color scanning of the paper test strip, the color recognition of the paper test strip by RGB
intensity analysis, and the comparison of the recognized color of the paper test strip with the scale for
evaluating the color of the analyzed sample. The results of such a comparison are presented in Figure
7.</p>
      <p>There was a search for a rule among the rules for evaluating the color of the analyzed sample in
order to establish the presence and level of creatine in the studied food product. Rule 4 triggered, so the
user received the conclusion "Creatine is present in the studied food product, the level of creatine is
high".</p>
      <p>The functionality of the proposed mobile information system for determining the level of creatine
in food products was specially tested on products for which the level of creatine is well known. The
correctness of the proposed mobile information system for determining the level of creatine in food
products is confirmed by the correct determination of the level of creatine for all three products (pork
lard, chicken, pork).</p>
      <p>The proposed approach and mobile information system for determining the level of creatine in food
products can be used not only for drawing up the diet of patients, especially patients with Covid'19
and/or spinal muscular atrophy, from the point vision of body saturation with creatine, but also for
example, to check the quality of meat products.</p>
    </sec>
    <sec id="sec-6">
      <title>5. Conclusions</title>
      <p>The study of food products to determine the level of creatine in them is an actual task, taking into
account the need for this substance for patients with Covid'19 and spinal muscular atrophy.</p>
      <p>As the survey of research showed, the known tools and systems for detecting and determining the
level of creatine are mainly focused on detecting creatine in biological fluids (blood, urine, etc.) or in
the food supplements, but not in food products. In addition, almost all these tools are expansive and
bulky, and require additional support and complicated operations. Most methods also require
pretreatment of samples and expensive equipment and reagents, that is, they can only be performed in
laboratory conditions. Since half of the creatine required by a person enters the body with food, and
creatine can enter the body not only as part of various expensive food additives, but also from food
products, therefore the purpose of our research is to develop a mobile information system for
determining the level of creatine in food products.</p>
      <p>The developed method for determining the level of creatine in food products by the user and the
method for determining the level of creatine in food products using a mobile information system provide
the user with the opportunity to quickly, conveniently, cheaply and effectively assess the presence and
level of creatine in any food products, on the basis of which to build a rational diet from the point vision
of body saturation with creatine.</p>
      <p>The proposed mobile information system for determining the level of creatine in food products
provides convenience, low-cost, celerity, miniaturization and automation for measurement of
concentration of creatine in any food products. The conclusion obtained from the system regarding the
presence and level of creatine in this or that food product is useful and extremely important when
preparing the diet of patients, especially patients with Covid'19 and/or spinal muscular atrophy.</p>
      <p>The functionality of the proposed mobile information system for determining the level of creatine
in food products was specially tested on products for which the level of creatine is well known. The
correctness of the proposed mobile information system for determining the level of creatine in food
products is confirmed by the correct determination of the level of creatine for all three products (pork
lard, chicken, pork).</p>
      <p>The proposed approach and mobile information system for determining the level of creatine in food
products can be used not only for drawing up the diet of patients, especially patients with Covid'19
and/or spinal muscular atrophy, from the point vision of body saturation with creatine, but also for
example, to check the quality of meat products.</p>
    </sec>
    <sec id="sec-7">
      <title>6. References</title>
      <p>[15] L. Fu, Ch. Tseng, W. Ju, R. Yang. Rapid Paper-Based System for Human Serum Creatinine</p>
      <p>Detection. Inventions 3 2 (2018) paper no. 34. doi: 10.3390/inventions3020034.
[16] Ch. Chien-Ming, T. Ya-Li. Creatinine-Detecting Laser Diode-Induced Fluorescence Detection</p>
      <p>System. IEEE Sensors Journal 22 18 (2022) 17784 – 17790. doi: 10.1109/JSEN.2022.3196629.
[17] Y. Kaijing, S. Yao, L. Fenchun, P. Fenglan, H. Miao, H. Fei, Y. Yali, N. Jinfang, Z. Yun.
Tyndalleffect-based colorimetric assay with colloidal silver nanoparticles for quantitative point-of-care
detection of creatinine using a laser pointer pen and a smartphone. RSC Advances 12 36 (2022)
23379 – 23386. doi: 10.1039/d2ra03598g.
[18] K. Betul, T. Alperay, O. Cemre, T. Cumhur. An Electromechanical Lab-on-a-Chip Platform for
Colorimetric Detection of Serum Creatinine. ACS Omega 7 29 (2022) 25837 – 25843. doi:
10.1021/acsomega.2c03354.
[19] Ch. Szu-Jui, T. Chin-Chung, H. Kuan-Hsun, Ch. Yu-Chi, F. Lung-Ming. Microfluidic Sliding
Paper-Based Device for Point-of-Care Determination of Albumin-to-Creatine Ratio in Human
Urine. Biosensors 12 7 (2022) paper no. 496. doi: 10.3390/bios12070496.
[20] L. Ling, X. Yuhao, D. Yan, Z. Weiyuan, L. Li, Y. Fanggui, Z. Shulin. Colorimetric detection of
creatinine based on specifically modulating the peroxidase-mimicking activity of Cu-Fenton
system. Biosensors and Bioelectronics 206 (2022) paper no. 114121. doi:
10.1016/j.bios.2022.114121.
[21] K. Muhammad Asif, A. Nur Hidayah, T. Chin-Hoong, D. Rusli, I. Ghadafi, M. Yeop, S. Mat, A.</p>
      <p>Ahmad Hafiz Wan Md, A. Tg Hasnan Tg Abdul, B. Ashrif, Z. Rifqi Md. Electrochemical
Metallization Process on Screen-Printed Electrode for Creatinine Monitoring Application. IEEE
Sensors Journal 22 10 (2022) 9268 – 9275. doi: 10.1109/JSEN.2022.3164105.
[22] A. Taher, M. Zahrasadat. Molecularly imprinted polymer specific to creatinine complex with
copper(II) ions for voltammetric determination of creatinine. Microchimica Acta 189 10 (2022)
paper no. 393. doi: 10.1007/s00604-022-05470-8.
[23] W. Dan, W. Liping, X. Chenyu, H. Yuebei, L. Hejing, G. Jianqiang, J. Jiang. Detection of meat
from horse, donkey and their hybrids (mule/hinny) by duplex real-time fluorescent PCR. PLoS
ONE 15 12 (2020) paper no. e0237077. doi: 10.1371/journal.pone.0237077.
[24] P. Jovanov, M. Vraneš, M. Sakač, S. Gadžurić, J. Panić, A. Marić, S. Ostojić. Hydrophilic
interaction chromatography coupled to tandem mass spectrometry as a method for simultaneous
determination of guanidinoacetate and creatine. Analytica Chimica Acta 1028 (2018) 96 – 103.
doi: 10.1016/j.aca.2018.03.038.
[25] Sh. Amit Kumar, P. Sunil, N. Yowan, S. Nandini, W. Hui-Fen. Aggregation of cysteamine-capped
gold nanoparticles in presence of ATP as an analytical tool for rapid detection of creatine kinase
(CK-MM). Analytica Chimica Acta 1024 (2018) 161 – 168. doi: 10.1016/j.aca.2018.03.027.
[26] D. Sohan, D. Satish Kumar, J. Arshad, G. Anasuya, K. Suman, G. Sanket. Portable
Chemiluminescence Detection Platform and Its Application in Creatinine Detection. IEEE Sensors
Journal 22 7 (2022) 7177 – 7184. doi: 10.1109/JSEN.2022.3151694.
[27] S. Ozge, A. Serdar. Non-enzymatic and Electrochemical Detection of Creatine in Food</p>
      <p>Supplements. Electrocatalysis 13 2 (2022) 195 – 209. doi: 10.1007/s12678-022-00710-0.
[28] Ch. Lertvachirapaiboon, Baba, Akira, Sh. Kazunari, K. Keizo. Colorimetric probe based on
destabilization of silver nanoparticles from polysaccharide matrix for creatinine detection, in:
Proceedings of the International Symposium on Electrical Insulating Materials ISEIM-2020,
Tokyo, 2020, paper no. 165683. doi: 978-488686418-5.
[29] M. Rahman, A. Jahir, A. Abdullah M. Development of Creatine sensor based on antimony-doped
tin oxide (ATO) nanoparticles. Sensors and Actuators, B: Chemical 242 (2017) 167 – 175. doi:
10.1016/j.snb.2016.11.053.</p>
    </sec>
  </body>
  <back>
    <ref-list>
      <ref id="ref1">
        <mixed-citation>
          [1]
          <string-name>
            <given-names>PubChem</given-names>
            <surname>Creatine (Compound Summary)</surname>
          </string-name>
          ,
          <year>2023</year>
          . URL: https://pubchem.ncbi.nlm.nih.gov/compound/Creatine.
        </mixed-citation>
      </ref>
      <ref id="ref2">
        <mixed-citation>
          [2]
          <string-name>
            <surname>Ch. Wang</surname>
            , Ch. Fang,
            <given-names>Y.</given-names>
          </string-name>
          <string-name>
            <surname>Lee</surname>
            ,
            <given-names>M.</given-names>
          </string-name>
          <string-name>
            <surname>Yang</surname>
            ,
            <given-names>K.</given-names>
          </string-name>
          <string-name>
            <surname>Chan</surname>
          </string-name>
          .
          <article-title>Effects of 4-Week Creatine Supplementation Combined with Complex Training on Muscle Damage and Sport Performance</article-title>
          .
          <source>Nutrients</source>
          <volume>10</volume>
          (
          <year>2018</year>
          ) paper no.
          <volume>1640</volume>
          . doi:
          <volume>10</volume>
          .3390/nu10111640.
        </mixed-citation>
      </ref>
      <ref id="ref3">
        <mixed-citation>
          [3]
          <string-name>
            <given-names>R.</given-names>
            <surname>Kreider</surname>
          </string-name>
          ,
          <string-name>
            <given-names>D.</given-names>
            <surname>Kalman</surname>
          </string-name>
          , J. Antonio, T. Ziegenfuss,
          <string-name>
            <given-names>R.</given-names>
            <surname>Wildman</surname>
          </string-name>
          , R. Collins,
          <string-name>
            <given-names>D.</given-names>
            <surname>Candow</surname>
          </string-name>
          ,
          <string-name>
            <given-names>S.</given-names>
            <surname>Kleiner</surname>
          </string-name>
          ,
          <string-name>
            <given-names>A.</given-names>
            <surname>Almada</surname>
          </string-name>
          ,
          <string-name>
            <given-names>H.</given-names>
            <surname>Lopez</surname>
          </string-name>
          .
          <article-title>International Society of Sports Nutrition position stand: safety and efficacy of creatine supplementation in exercise, sport, and medicine</article-title>
          .
          <source>Journal of the International Society of Sports Nutrition</source>
          <volume>14</volume>
          (
          <year>2017</year>
          ) paper no.
          <volume>18</volume>
          . doi;
          <volume>10</volume>
          .1186/s12970-017-0173-z.
        </mixed-citation>
      </ref>
      <ref id="ref4">
        <mixed-citation>
          [4]
          <string-name>
            <given-names>A.</given-names>
            <surname>Bender</surname>
          </string-name>
          ,
          <string-name>
            <given-names>T.</given-names>
            <surname>Klopstock</surname>
          </string-name>
          .
          <article-title>Creatine for neuroprotection in neurodegenerative disease: end of story? Amino Acids 48 (</article-title>
          <year>2016</year>
          )
          <fpage>1929</fpage>
          -
          <lpage>1940</lpage>
          . doi:
          <volume>10</volume>
          .1007/s00726-015-2165-0.
        </mixed-citation>
      </ref>
      <ref id="ref5">
        <mixed-citation>
          [5]
          <string-name>
            <given-names>M.</given-names>
            <surname>Balestrino</surname>
          </string-name>
          ,
          <string-name>
            <given-names>M.</given-names>
            <surname>Sarocchi</surname>
          </string-name>
          , E. Adriano,
          <string-name>
            <given-names>P.</given-names>
            <surname>Spallarossa</surname>
          </string-name>
          .
          <article-title>Potential of creatine or phosphocreatine supplementation in cerebrovascular disease and in ischemic heart disease</article-title>
          .
          <source>Amino Acids</source>
          <volume>48</volume>
          (
          <year>2016</year>
          )
          <fpage>1955</fpage>
          -
          <lpage>1967</lpage>
          . doi:
          <volume>10</volume>
          .1007/s00726-016-2173-8.
        </mixed-citation>
      </ref>
      <ref id="ref6">
        <mixed-citation>
          [6]
          <string-name>
            <given-names>B.</given-names>
            <surname>Gualano</surname>
          </string-name>
          ,
          <string-name>
            <given-names>E.</given-names>
            <surname>Rawson</surname>
          </string-name>
          ,
          <string-name>
            <given-names>D.</given-names>
            <surname>Candow</surname>
          </string-name>
          ,
          <string-name>
            <given-names>P.</given-names>
            <surname>Chilibeck</surname>
          </string-name>
          .
          <article-title>Creatine supplementation in the aging population: effects on skeletal muscle, bone and brain</article-title>
          .
          <source>Amino Acids</source>
          <volume>48</volume>
          (
          <year>2016</year>
          )
          <fpage>1793</fpage>
          -
          <lpage>1805</lpage>
          . doi:
          <volume>10</volume>
          .1007/s00726-016-2239-7.
        </mixed-citation>
      </ref>
      <ref id="ref7">
        <mixed-citation>
          [7]
          <string-name>
            <given-names>R.</given-names>
            <surname>Toniolo</surname>
          </string-name>
          ,
          <string-name>
            <given-names>F.</given-names>
            <surname>Fernandes</surname>
          </string-name>
          ,
          <string-name>
            <given-names>M.</given-names>
            <surname>Silva</surname>
          </string-name>
          ,
          <string-name>
            <given-names>R. Da</given-names>
            <surname>Silva Dias</surname>
          </string-name>
          ,
          <string-name>
            <given-names>B.</given-names>
            <surname>Lafer</surname>
          </string-name>
          .
          <article-title>Cognitive effects of creatine monohydrate adjunctive therapy in patients with bipolar depression: Results from a randomized, double-blind, placebo-controlled trial</article-title>
          .
          <source>Journal of Affective Disorders</source>
          <volume>224</volume>
          (
          <year>2016</year>
          )
          <fpage>69</fpage>
          -
          <lpage>75</lpage>
          . doi:
          <volume>10</volume>
          .1016/j.jad.
          <year>2016</year>
          .
          <volume>11</volume>
          .029.
        </mixed-citation>
      </ref>
      <ref id="ref8">
        <mixed-citation>
          [8]
          <string-name>
            <surname>Ye. Hnatchuk</surname>
            ,
            <given-names>A.</given-names>
          </string-name>
          <string-name>
            <surname>Herts</surname>
            ,
            <given-names>A.</given-names>
          </string-name>
          <string-name>
            <surname>Misiats</surname>
            ,
            <given-names>T.</given-names>
          </string-name>
          <string-name>
            <surname>Hovorushchenko</surname>
            ,
            <given-names>K. Kant</given-names>
          </string-name>
          <string-name>
            <surname>Singh</surname>
          </string-name>
          .
          <article-title>Covid'19 Vaccination Decision-Making Method and Subsystem Based on Civil Law</article-title>
          .
          <source>CEUR-WS</source>
          <volume>3156</volume>
          (
          <year>2022</year>
          )
          <fpage>262</fpage>
          -
          <lpage>273</lpage>
          .
        </mixed-citation>
      </ref>
      <ref id="ref9">
        <mixed-citation>
          [9]
          <string-name>
            <surname>Ye</surname>
            . Hnatchuk,
            <given-names>T.</given-names>
          </string-name>
          <string-name>
            <surname>Hovorushchenko</surname>
            ,
            <given-names>A.</given-names>
          </string-name>
          <string-name>
            <surname>Misiats</surname>
            ,
            <given-names>A.</given-names>
          </string-name>
          <string-name>
            <surname>Herts</surname>
            ,
            <given-names>A.</given-names>
          </string-name>
          <string-name>
            <surname>Boyarchuk</surname>
          </string-name>
          .
          <article-title>Decision-Making Support for Necessity/Optionality/Contraindication of Vaccination against COVID-19 Considering Legal Norms</article-title>
          .
          <source>CEUR-WS</source>
          <volume>3302</volume>
          (
          <year>2022</year>
          )
          <fpage>200</fpage>
          -
          <lpage>213</lpage>
          .
        </mixed-citation>
      </ref>
      <ref id="ref10">
        <mixed-citation>
          [10]
          <string-name>
            <given-names>T.</given-names>
            <surname>Hovorushchenko</surname>
          </string-name>
          , Ye. Hnatchuk,
          <string-name>
            <given-names>A.</given-names>
            <surname>Herts</surname>
          </string-name>
          ,
          <string-name>
            <given-names>O.</given-names>
            <surname>Onyshko</surname>
          </string-name>
          .
          <article-title>Intelligent Information Technology for Supporting the Medical Decision-Making Considering the Legal Basis</article-title>
          .
          <source>CEUR-WS</source>
          <volume>2853</volume>
          (
          <year>2021</year>
          )
          <fpage>72</fpage>
          -
          <lpage>82</lpage>
          .
        </mixed-citation>
      </ref>
      <ref id="ref11">
        <mixed-citation>
          [11]
          <string-name>
            <given-names>T.</given-names>
            <surname>Hovorushchenko</surname>
          </string-name>
          ,
          <string-name>
            <given-names>A.</given-names>
            <surname>Herts</surname>
          </string-name>
          , Ye. Hnatchuk.
          <article-title>Concept of Intelligent Decision Support System in the Legal Regulation of the Surrogate Motherhood</article-title>
          .
          <source>CEUR-WS</source>
          <volume>2488</volume>
          (
          <year>2019</year>
          )
          <fpage>57</fpage>
          -
          <lpage>68</lpage>
          .
        </mixed-citation>
      </ref>
      <ref id="ref12">
        <mixed-citation>
          [12]
          <string-name>
            <given-names>B.</given-names>
            <surname>Iegorov</surname>
          </string-name>
          ,
          <string-name>
            <given-names>Y.</given-names>
            <surname>Kravchyk</surname>
          </string-name>
          ,
          <string-name>
            <given-names>S.</given-names>
            <surname>Rybalko</surname>
          </string-name>
          ,
          <string-name>
            <surname>I. Ivashkiv</surname>
          </string-name>
          ,
          <string-name>
            <given-names>A.</given-names>
            <surname>Chub</surname>
          </string-name>
          .
          <article-title>The Methodical Approach of the Substantiation of the Evaluation Indicators System of the Agro-Industrial Complex Development</article-title>
          .
          <source>Universal Journal of Agricultural Research 9</source>
          <volume>5</volume>
          (
          <issue>2021</issue>
          ),
          <fpage>191</fpage>
          -
          <lpage>199</lpage>
          . doi:
          <volume>10</volume>
          .13189/ujar.
          <year>2021</year>
          .
          <volume>090506</volume>
          .
        </mixed-citation>
      </ref>
      <ref id="ref13">
        <mixed-citation>
          [13]
          <article-title>Which type of foods are rich in creatine</article-title>
          ?,
          <year>2017</year>
          . URL: https://www.quora.com/
          <article-title>Which-type-offoods-are-rich-in-creatine</article-title>
        </mixed-citation>
      </ref>
      <ref id="ref14">
        <mixed-citation>
          [14]
          <string-name>
            <given-names>B.</given-names>
            <surname>Toora</surname>
          </string-name>
          ,
          <string-name>
            <surname>G. Rajagopal.</surname>
          </string-name>
          <article-title>Measurement of creatinine by Jaffe's reaction--determination of concentration of sodium hydroxide required for maximum color development in standard, urine and protein free filtrate of serum</article-title>
          .
          <source>Indian Journal of Experimental Biology 40</source>
          <volume>3</volume>
          (
          <year>2022</year>
          )
          <fpage>352</fpage>
          -
          <lpage>354</lpage>
          .
        </mixed-citation>
      </ref>
    </ref-list>
  </back>
</article>