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 <!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.0 20120330//EN" "http://jats.nlm.nih.gov/publishing/1.0/JATS-journalpublishing1.dtd"> <article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" article-type="in-brief" dtd-version="1.0" xml:lang="en">
  <front>
    <journal-meta>
      <journal-id journal-id-type="publisher-id">IJN</journal-id>
      <journal-title-group>
        <journal-title>International Journal of Nutrition</journal-title>
      </journal-title-group>
      <issn pub-type="epub">2379-7835</issn>
      <publisher>
        <publisher-name>Open Access Pub</publisher-name>
        <publisher-loc>United States</publisher-loc>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="publisher-id">IJN-19-2599</article-id>
      <article-id pub-id-type="doi">10.14302/issn.2379-7835.ijn-19-2599</article-id>
      <article-categories>
        <subj-group>
          <subject>in-brief</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Recovery Time from Severe Acute Malnutrition and Development of Complementary Food Supplement For Affected Ethiopian Children</article-title>
        <alt-title alt-title-type="running-head">from microbiota to an optimal diet for health</alt-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Desalegn</surname>
            <given-names>Gebrezgi</given-names>
          </name>
          <xref ref-type="aff" rid="idm1853312932">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Degnet</surname>
            <given-names>Teferi</given-names>
          </name>
          <xref ref-type="aff" rid="idm1853313436">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Prasad</surname>
            <given-names>PCJ Reddy</given-names>
          </name>
          <xref ref-type="aff" rid="idm1853314156">3</xref>
          <xref ref-type="aff" rid="idm1853294460">*</xref>
        </contrib>
      </contrib-group>
      <aff id="idm1853312932">
        <label>1</label>
        <addr-line>Researcher-Mekelle Agricultural Mechanization and Rural Energy Research Center, Tigray Agricultural Research Institute, Mekelle, Ethiopia</addr-line>
      </aff>
      <aff id="idm1853313436">
        <label>2</label>
        <addr-line>Lecturer-Department of Applied Human Nutrition, Faculty of Chemical and Food Engineering, Bahir Dar Institute of Technology, Bahir Dar University, Bahir Dar, Ethiopia </addr-line>
      </aff>
      <aff id="idm1853314156">
        <label>3</label>
        <addr-line>Professor, –Department of Applied Human Nutrition, Faculty of Chemical and Food Engineering, Bahir Dar Institute of Technology, Bahir Dar University, Bahir Dar, Ethiopia</addr-line>
      </aff>
      <aff id="idm1853294460">
        <label>*</label>
        <addr-line>Corresponding author</addr-line>
      </aff>
      <contrib-group>
        <contrib contrib-type="editor">
          <name>
            <surname>María</surname>
            <given-names>López</given-names>
          </name>
          <xref ref-type="aff" rid="idm1853410212">1</xref>
        </contrib>
      </contrib-group>
      <aff id="idm1853410212">
        <label>1</label>
        <addr-line>Universidad Francisco de Vitoria, Spain</addr-line>
      </aff>
      <author-notes>
        <corresp>
    
    Prasad PCJ Reddy, <addr-line>Professor,–</addr-line><addr-line>Department of Applied Human Nutrition, Faculty of Chemical  and Food Engineering, Bahir Dar Institute of Technology, Bahir Dar University, Bahir Dar, Ethiopia</addr-line>, Email: <email>professor_rpcjp@yahoo.com</email></corresp>
        <fn fn-type="conflict" id="idm1851554076">
          <p>The authors have declared that no competing interests exist.</p>
        </fn>
      </author-notes>
      <pub-date pub-type="epub" iso-8601-date="2019-01-26">
        <day>26</day>
        <month>01</month>
        <year>2019</year>
      </pub-date>
      <volume>3</volume>
      <issue>3</issue>
      <fpage>1</fpage>
      <lpage>6</lpage>
      <history>
        <date date-type="received">
          <day>10</day>
          <month>01</month>
          <year>2019</year>
        </date>
        <date date-type="accepted">
          <day>16</day>
          <month>01</month>
          <year>2019</year>
        </date>
        <date date-type="online">
          <day>26</day>
          <month>01</month>
          <year>2019</year>
        </date>
      </history>
      <permissions>
        <copyright-statement>© </copyright-statement>
        <copyright-year>2019</copyright-year>
        <copyright-holder>Desalegn Gebrezgi, et al.</copyright-holder>
        <license xlink:href="http://creativecommons.org/licenses/by/4.0/" xlink:type="simple">
          <license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</license-p>
        </license>
      </permissions>
      <self-uri xlink:href="http://openaccesspub.org/ijn/article/976">This article is available from http://openaccesspub.org/ijn/article/976</self-uri>
      <abstract>
        <sec id="idm1853147060">
          <title>Background: </title>
          <p>Severe acute mal nutrition (SAM) among children still remains the major problem in Ethiopia. The shortening of the SAM recovery time by applying appropriate dietary means during treatment and also after recovery, can save huge sums of public health spending.</p>
        </sec>
        <sec id="idm1853146772">
          <title>Objectives: </title>
          <p>Determining the recovery time of SAM affected children and developing complementary food supplement (CFS). </p>
        </sec>
        <sec id="idm1853146484">
          <title>Methods: </title>
          <p>Hospital based retrospective cohort study was carried out on 401 SAM affected children. A structured and pre tested data abstraction form was used for data collection. The data were entered into Epi info and exported to SPSS for analysis. All of the nutritional properties of the developed product in three different ratios of the flours of maize, soybean and powder of moringaolifera leaves were assessed and compared to the control (100% maize).</p>
        </sec>
        <sec id="idm1853146196">
          <title>Results: </title>
          <p>The median recovery time was 16 days. There was a significant increase in protein, mineral and beta carotene content with increasing level of Moringaolifera leaf powder in the CFS.</p>
        </sec>
        <sec id="idm1853145908">
          <title>Conclusion: </title>
          <p>To increase the rate of recovery from sever acute malnutrition and also to prevent relapsing, moringa incorporated cheaper complementary fod supplements could be recommended for SAM affected children.</p>
        </sec>
      </abstract>
      <kwd-group>
        <kwd>microbiota</kwd>
        <kwd>Taste Receptors</kwd>
        <kwd>evolution</kwd>
        <kwd>short chain fatty acids</kwd>
        <kwd>alpha-lactalbumin</kwd>
      </kwd-group>
      <counts>
        <fig-count count="1"/>
        <table-count count="3"/>
        <page-count count="6"/>
      </counts>
    </article-meta>
  </front>
  <body>
    <sec id="idm1853145620" sec-type="intro">
      <title>Introduction</title>
      <p>Severe Acute Malnutrition (SAM) is defined as weight-for height ratio of less than -3 standard deviations below the median reference population or weight-for-height ratio of below 70% or Mid Upper Arm Circumference (MUAC ) &lt;110 mm or presence of nutritional edema<xref ref-type="bibr" rid="ridm1852282140">1</xref>.</p>
      <p>Until recently, acute malnutrition was seen primarily as a feature of humanitarian emergencies. This is despite of the fact that most cases occur in                    non-emergency contexts. But in recent years, donors, as well as developing countries with a high-burden of undernutrition, have started to pay more attention to the issue<xref ref-type="bibr" rid="ridm1852295612">2</xref>.</p>
      <p>While the treatment of SAM  is well established and evidence-based <xref ref-type="bibr" rid="ridm1852352220">3</xref><xref ref-type="bibr" rid="ridm1852140316">4</xref>,  achieving desired outcomes has proven to be challenging. Particularly , effective management of SAM is a huge challenge in low resource healthcare settings and more effective strategy is needed urgently<xref ref-type="bibr" rid="ridm1852134132">5</xref>.</p>
      <p>On the other hand, even after children are recovered from SAM, attention is required at home in order to prevent relapsing. For instance, from a study conducted in Shebedido district, Southern Ethiopia; of the total admissions to the OTP, 22% were readmitted cases<xref ref-type="bibr" rid="ridm1852129780">6</xref>. The observed high proportion of readmission may be due to lack of affordable complementary food supplements at home <xref ref-type="bibr" rid="ridm1852125828">7</xref>. </p>
      <p>Aim and objectives: Determine recovery time from severe acute malnutrition among children and develop soy bean and maize-based complementary food supplements fortified with Moringaoleifera.</p>
    </sec>
    <sec id="idm1853127892" sec-type="materials">
      <title>Material &amp; Methods</title>
      <p>Study area and design: Institution based retrospective cohort study was conducted from               March– April, 2016 at Felegehiwot referral hospital, in Bahir Dar city administration, Northwest Ethiopia. Currently, the hospital is the only health facility which provides inpatient services for the management of severe acute malnutrition in the study area.</p>
      <p>Sample size and sampling procedure: Using Epi info version 6 StatCalc programs, a double population proportion formula was employed to calculate the sample size and it was estimated to be 401. All children 6-59 months of age with SAM who had been admitted and treated at therapeutic feeding unit (TFU) of the selected hospital from October 2012 to April 2016 were eligible for the study. The total admitted children during this period were 526. Since the difference between the calculated sample size and total admitted SAM cases was small, all SAM cases were considered until the sample size got saturated.</p>
      <p>Data Collection and Quality Control Measures: A structured data abstraction form (pretested on 10 charts) was used for data collection. Data were abstracted from client cards. </p>
      <p>Data processing and analysis: Data were checked and entered in to Epi-info version 7 statistical software and then exported to Statistical Package for Social Science (SPSS) version 20 for analysis. Recovery time from SAM was estimated using Kaplan-Meier procedure.</p>
      <sec id="idm1853127172">
        <title>Ethical Consideration</title>
        <p>Appropriateness and ethical approval was obtained from Ethical review committee for postgraduate studies and research projects of Faculty of Chemical anf food Engineering, Bahir Dar Technology Institute, Bahir Dar University.  Permission to conduct the study was obtained from regional health research bureau and the hospital administrative bodies through formal letter. </p>
      </sec>
      <sec id="idm1853126884">
        <title>Development of Complementary Food Supplements</title>
        <p>The raw materials for development of complementary food supplements included maize (Zea mays, MELKASSA-6 variety), soybean (glycine max, Wagaye variety) and moringaolifera. The products were developed and formulated with ratios of 65:30:5(R65), 60:30:10(R60) and 55:30:15(R55) with maize flour, soybean flour and Moringaolifera powder respectively. Each of these cereals was mixed with predetermined portions of seeds in order to obtain enriched flour. Nutritional compositions of these enriched flours were assessed and compared to control (100% maize); the existing local complementary flour. The values of nutritional compositions were means of triplicate.  Data obtained were subjected to appropriate statistical analysis (SAS 9.1) and the means were separated by Duncan Multiple Range Test where significant difference occurs at P-value &lt;0.05.</p>
      </sec>
    </sec>
    <sec id="idm1853126596" sec-type="results">
      <title>Results </title>
      <p>Out of the total 401 children in the cohort; 208(51.9%), 17(4.2%), 143(35.7%), 6(1.5%) and 27(6.7%) were cured, died, defaulted, not responded and transferred respectively (<xref ref-type="table" rid="idm1853152396">table 1</xref>). The nutritional recovery rate was 2.27 (95 % CI: 1.55– 3.43) per 100 person day observations among entire subjects in the cohort. The median nutritional recovery time was estimated to be 16 days (IQR: 95% CI; 14.233-17.767) (<xref ref-type="fig" rid="idm1853128340">figure 1</xref>).</p>
      <p>Regarding to the complementary food supplements, there was significant (p &lt; 0.05) increase in protein content with increasing level of Moringaolifera leaf powder from 8.2% in 100% maize (control) to 17.2% in (55:30:15) R55, with maize, soybean and Moringaolifera leaf power blend (<xref ref-type="table" rid="idm1853127404">table 2</xref>). </p>
      <p>The mineral content of the samples increased significantly (p &lt; 0.05) (<xref ref-type="table" rid="idm1853050724">table 3</xref>). Zinc content was increased from 0.84 in the control (maize) to 1.29mg in R65, 1.74mg in R60 and 1.25mg/100g in R55. Calcium (Ca) content was increased from 2.65mg/100g in the control (maize) to 11.33mg in R65, 10.52mg in R60 and 15.37mg/100g in R55. Iron (Fe) content was increased from 27.97mg in control to 49.17 in R60, 38.93mg in R55; however reduced to 27.47mg/100g in R55.</p>
      <p>Beta-carotene content increased significantly (p &lt; 0.05) from 0.035 to 0.4 mg/g with an increase in Moringa leaf powder (<xref ref-type="table" rid="idm1853050724">table 3</xref>). R55 had the highest                β-carotene 0.4 mg/g while R60 had 0.21mg/100g and 0.14mg/g in R65. </p>
      <table-wrap id="idm1853152396">
        <label>Table 1.</label>
        <caption>
          <title> Treatment outcomes of severe acute malnutrition among children, Bahir Dar, Northwest Ethiopia; October, 2012 to April, 2016</title>
        </caption>
        <table rules="all" frame="box">
          <tbody>
            <tr>
              <td>Variables</td>
              <td>Frequency</td>
              <td>Percent</td>
            </tr>
            <tr>
              <td>Status at discharge</td>
              <td> </td>
              <td> </td>
            </tr>
            <tr>
              <td>cured</td>
              <td>208</td>
              <td>51.9</td>
            </tr>
            <tr>
              <td>died</td>
              <td>17</td>
              <td>4.2</td>
            </tr>
            <tr>
              <td>default</td>
              <td>143</td>
              <td>35.7</td>
            </tr>
            <tr>
              <td>non-respondent</td>
              <td>6</td>
              <td>1.5</td>
            </tr>
            <tr>
              <td>transfer</td>
              <td>27</td>
              <td>6.7</td>
            </tr>
          </tbody>
        </table>
      </table-wrap>
      <fig id="idm1853128340">
        <label>Figure 1.</label>
        <caption>
          <title> Median time of recovery among children with SAM managed at                 Felegehiwot referral hospital; Bahir Dar, Northwest Ethiopia, October, 2012 to April, 2016</title>
        </caption>
        <graphic xlink:href="images/image1.jpg" mime-subtype="jpg"/>
      </fig>
      <table-wrap id="idm1853127404">
        <label>Table 2.</label>
        <caption>
          <title> Proximate and energy composition of the control and composite flour</title>
        </caption>
        <table rules="all" frame="box">
          <tbody>
            <tr>
              <td> Samples</td>
              <td colspan="7">Proximate values</td>
            </tr>
            <tr>
              <td/>
              <td>Ash (%)</td>
              <td>Moisture (%)</td>
              <td>Protein (g/100g)</td>
              <td>Fat (g/100g)</td>
              <td>Fiber (g/100g)</td>
              <td>CHO (g/100g)</td>
              <td>Energy (Kcal.)</td>
            </tr>
            <tr>
              <td>Maize</td>
              <td>1.3<sup>c</sup></td>
              <td>7.8+0.18<sup>a</sup></td>
              <td>8.2+0.1<sup>b</sup></td>
              <td>4.58+0.2<sup>c</sup></td>
              <td>11.12+0.2a</td>
              <td>67+0.06<sup>a</sup></td>
              <td>345.9+0.8<sup>d</sup></td>
            </tr>
            <tr>
              <td>R65</td>
              <td>3.5±0.46<sup>b</sup></td>
              <td>6.7±0.8<sup>b</sup></td>
              <td>16.6±0.2<sup>a</sup></td>
              <td>10.5±0.19<sup>b</sup></td>
              <td>2.96±0.17d</td>
              <td>66.1±0.6<sup>a</sup></td>
              <td>429.5±1.9<sup>a</sup></td>
            </tr>
            <tr>
              <td>R60</td>
              <td>4±0.26<sup>ab</sup></td>
              <td>6.2±0.48<sup>bc</sup></td>
              <td>16.98±0.17<sup>a</sup></td>
              <td>10.7±0.1<sup>ab</sup></td>
              <td>6.75±0.2<sup>c</sup></td>
              <td>61.1±0.49<sup>b</sup></td>
              <td>412.5±0.9<sup>b</sup></td>
            </tr>
            <tr>
              <td>R55</td>
              <td>4.3±0.33a</td>
              <td>5.6±0.40<sup>c</sup></td>
              <td>17.2±1.4</td>
              <td>10.99±0.1<sup>a</sup></td>
              <td>9.95±0.27<sup>b</sup></td>
              <td>57.3±0.7<sup>c</sup></td>
              <td>399.8±2<sup>c</sup></td>
            </tr>
            <tr>
              <td>Rec.</td>
              <td>&lt;3</td>
              <td>&lt;5</td>
              <td>&gt;15</td>
              <td>10-15</td>
              <td> </td>
              <td>64</td>
              <td>400-425</td>
            </tr>
          </tbody>
        </table>
        <table-wrap-foot>
          <fn id="idm1853068804">
            <label/>
            <p>Values are means of triplicate samples (± SD). Means not sharing a common letter are significantly different at p &lt; 0.05.</p>
          </fn>
        </table-wrap-foot>
      </table-wrap>
      <table-wrap id="idm1853050724">
        <label>Table 3.</label>
        <caption>
          <title> Mineral, β-carotene and phytate composition of control and composite flour</title>
        </caption>
        <table rules="all" frame="box">
          <tbody>
            <tr>
              <td> Samples</td>
              <td colspan="5">Minerals,  β-carotene and anti-nutritional factors</td>
            </tr>
            <tr>
              <td/>
              <td>Zn-mg/100g</td>
              <td>Fe-mg/100g</td>
              <td>Ca mg/100g</td>
              <td>β-carotene mg/g</td>
              <td>Phytate mg/100g</td>
            </tr>
            <tr>
              <td> Maize</td>
              <td>0.84±0.16<sup>b</sup></td>
              <td>27.97±12.55<sup>a</sup></td>
              <td>2.65±1.25<sup>c</sup></td>
              <td>0.037+0.001<sup>d</sup></td>
              <td>208.5+14<sup>a</sup></td>
            </tr>
            <tr>
              <td>R<sub>65</sub></td>
              <td>1.74±0.44<sup>ab</sup></td>
              <td>49.17±20.55<sup>a</sup></td>
              <td>11.33±0.04<sup>b</sup></td>
              <td>0.14±0.0065<sup>c</sup></td>
              <td>36±3.35<sup>d</sup></td>
            </tr>
            <tr>
              <td>R<sub>60</sub></td>
              <td>1.25±0.04<sup>b</sup></td>
              <td>38.93±8.65<sup>a</sup></td>
              <td>10.52±2.87<sup>b</sup></td>
              <td>0.21±0.004<sup>b</sup></td>
              <td>70±6<sup>b</sup></td>
            </tr>
            <tr>
              <td>R<sub>55</sub></td>
              <td>1.29±0.05<sup>a</sup></td>
              <td>25.47±0.95<sup>a</sup></td>
              <td>15.37±1.55<sup>a</sup></td>
              <td>0.4±0.010<sup>a</sup></td>
              <td>46±15<sup>c</sup></td>
            </tr>
          </tbody>
        </table>
        <table-wrap-foot>
          <fn id="idm1853045604">
            <label/>
            <p>Values are means of triplicate samples (± SD). Means not sharing a common letter are significantly different at p &lt; 0.05</p>
          </fn>
        </table-wrap-foot>
      </table-wrap>
    </sec>
    <sec id="idm1853045460" sec-type="discussion">
      <title>Discussion </title>
      <p>In this retrospective cohort study, the median nutritional recovery times was within the acceptable maximum international standards set at &lt; 28 days<xref ref-type="bibr" rid="ridm1852120716">8</xref>. It is  consistent with other institution-based studies in Ethiopia, such as Mekelle City which reported 17                days <xref ref-type="bibr" rid="ridm1852118412">9</xref>. However, it was higher than the study done in Zambia that reported 13 days<xref ref-type="bibr" rid="ridm1852110180">10</xref>.This might be related to differences in treatment and caring practices, health care settings and other socioeconomic factors among the study areas. Studies indicated that it is only by complying with the standard protocol for management of SAM, better program outcomes could be assured<xref ref-type="bibr" rid="ridm1852105116">11</xref>.</p>
      <p>However, the median nutritional recovery time was lowest  compared to the study reports from Kamba District, South West Ethiopia that indicated recovery time of  50 days <xref ref-type="bibr" rid="ridm1852099892">12</xref>and Karat and Fasha stabilization Centers, Southern Ethiopia that reported 26 days <xref ref-type="bibr" rid="ridm1852096940">13</xref>.</p>
      <p>However, though unpublished a study in Jimma, southwest Ethiopia indicated that current anthropometric criteria lead to discharge of children with incomplete recovery of some nutrition parameters including immunity, free fat mass and cellular electrical properties. Accordingly, the study warranted that those children discharged early as recovered from SAM are more vulnerable than their community peers during the first months post-discharge. </p>
      <p>Regarding to the complementary food supplements, there was significant (p &lt; 0.05) increase in protein content with increasing level of Moringaolifera leaf powder supplementation (<xref ref-type="table" rid="idm1853127404">table 2</xref>). This could be due to substitution effect caused by Moringa leaf powder and soybean. Abraham I. Sengev et al also reported the same effect in wheat flour and Moringa powder blended bread <xref ref-type="bibr" rid="ridm1852091340">14</xref>. This finding was found to be higher in protein content than that was reported by Onojo US., et al who prepared gruel from sorghum, soybean and plantain <xref ref-type="bibr" rid="ridm1852087452">15</xref>. It was also three fold than that was reported by M.C. Ojinnaka et al.  who developed a complementary food from soybean and ginger <xref ref-type="bibr" rid="ridm1852065636">16</xref>. However, it was lower in protein content than that was reported by Erikhun  of  complementary food prepared from maize, soybean and Moringa leaf powder <xref ref-type="bibr" rid="ridm1852062684">17</xref>.</p>
      <p>The ash and fat contents also increased significantly (<xref ref-type="table" rid="idm1853127404">table 2</xref>). Abraham I. Sengev et al. also reported the same effect in wheat flour and Moringa powder blended bread<xref ref-type="bibr" rid="ridm1852091340">14</xref>. Similarly, the mineral content of the samples increased significantly (<xref ref-type="table" rid="idm1853050724">table 3</xref>). Erkihun had also reported an increase in mineral content as ratio of Moringaolifera powder increased<xref ref-type="bibr" rid="ridm1852062684">17</xref>Beta-carotene content increased significantly (<xref ref-type="table" rid="idm1853050724">table 3</xref>).  Nwosu Odinakachukwu I.C., et al., also reported that there was an increase in beta-carotene in the porridge prepared from maize and soybean as a control and a blend of maize, soybean and Moringaolifera powder as test diet <xref ref-type="bibr" rid="ridm1852062684">17</xref>. While Onojo US., et al., had reported higher than of this finding<xref ref-type="bibr" rid="ridm1852087452">15</xref>.</p>
    </sec>
    <sec id="idm1853043732" sec-type="conclusions">
      <title>Conclusions </title>
      <p>In this study, the median nutritional recovery times was within the acceptable maximum international standards and indicated that children were recovered fast. Moringa leaf powder as a fortificant gave promising result in improving the protein and micronutrient content of the complementary food supplements. </p>
    </sec>
    <sec id="idm1853043444">
      <title>Recommendations</title>
      <p>Attention should be given as current anthropometric criteria might lead to early discharge of children with incomplete recovery of some nutrition parameters. Developing complementary food supplements from locally available stables fortified with nutrient rich non-conventional foods (Moringa leaf powder) is important as a strategy for effective treatment of SAM and preventing possible relapsing.</p>
      <sec id="idm1853043156">
        <title>Limitation of the Study</title>
        <p>The effect of complementary food supplements in treatment of severe acute malnutrition and prevention of relapsing was not tested.</p>
      </sec>
      <sec id="idm1853042868">
        <title>Relevance of the Study </title>
        <p>This study is the first study in the study area which developed complementary food supplements for SAM affected children using locally available stables fortified with nutrient rich non-conventional foods (i.e. Moringa leaf powder).</p>
      </sec>
      <sec id="idm1853042580">
        <title>Authors Contribution</title>
        <p>All the three authors have contributed equally in the preparation of the manuscript of this article.</p>
      </sec>
    </sec>
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