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<journal-id journal-id-type="publisher-id">Front. Physiol.</journal-id>
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<journal-title>Frontiers in Physiology</journal-title>
<abbrev-journal-title abbrev-type="pubmed">Front. Physiol.</abbrev-journal-title>
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<issn pub-type="epub">1664-042X</issn>
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<article-id pub-id-type="publisher-id">1741426</article-id>
<article-id pub-id-type="doi">10.3389/fphys.2025.1741426</article-id>
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<subj-group subj-group-type="heading">
<subject>Opinion</subject>
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<title-group>
<article-title>Biological resilience as a crucial determinant in preventing age-associated chronic diseases</article-title>
<alt-title alt-title-type="left-running-head">Amjad et al.</alt-title>
<alt-title alt-title-type="right-running-head">
<ext-link ext-link-type="uri" xlink:href="https://doi.org/10.3389/fphys.2025.1741426">10.3389/fphys.2025.1741426</ext-link>
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<contrib contrib-type="author" corresp="yes">
<name>
<surname>Amjad</surname>
<given-names>Amjad Islam</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
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<xref ref-type="corresp" rid="c001">&#x2a;</xref>
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<contrib contrib-type="author">
<name>
<surname>Sheikh</surname>
<given-names>Bisma Sajjad</given-names>
</name>
<xref ref-type="aff" rid="aff2">
<sup>2</sup>
</xref>
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<contrib contrib-type="author" corresp="yes">
<name>
<surname>Aslam</surname>
<given-names>Sarfraz</given-names>
</name>
<xref ref-type="aff" rid="aff3">
<sup>3</sup>
</xref>
<xref ref-type="corresp" rid="c001">&#x2a;</xref>
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<aff id="aff1">
<label>1</label>
<institution>Department of Education, The University of Lahore</institution>, <city>Lahore</city>, <country country="PK">Pakistan</country>
</aff>
<aff id="aff2">
<label>2</label>
<institution>Institute of Education and Research, University of the Punjab</institution>, <city>Lahore</city>, <country country="PK">Pakistan</country>
</aff>
<aff id="aff3">
<label>3</label>
<institution>Faculty of Education and Humanities, UNITAR International University</institution>, <city>Petaling Jaya</city>, <country country="MY">Malaysia</country>
</aff>
<author-notes>
<corresp id="c001">
<label>&#x2a;</label>Correspondence: Amjad Islam Amjad, <email xlink:href="mailto:amjad_14@yahoo.com">amjad_14@yahoo.com</email>; Sarfraz Aslam, <email xlink:href="mailto:sarfraz.aslam@unitar.my">sarfraz.aslam@unitar.my</email>
</corresp>
</author-notes>
<pub-date publication-format="electronic" date-type="pub" iso-8601-date="2025-12-17">
<day>17</day>
<month>12</month>
<year>2025</year>
</pub-date>
<pub-date publication-format="electronic" date-type="collection">
<year>2025</year>
</pub-date>
<volume>16</volume>
<elocation-id>1741426</elocation-id>
<history>
<date date-type="received">
<day>07</day>
<month>11</month>
<year>2025</year>
</date>
<date date-type="rev-recd">
<day>02</day>
<month>12</month>
<year>2025</year>
</date>
<date date-type="accepted">
<day>04</day>
<month>12</month>
<year>2025</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright &#xa9; 2025 Amjad, Sheikh and Aslam.</copyright-statement>
<copyright-year>2025</copyright-year>
<copyright-holder>Amjad, Sheikh and Aslam</copyright-holder>
<license>
<ali:license_ref start_date="2025-12-17">https://creativecommons.org/licenses/by/4.0/</ali:license_ref>
<license-p>This is an open-access article distributed under the terms of the <ext-link ext-link-type="uri" xlink:href="https://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License (CC BY)</ext-link>. The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</license-p>
</license>
</permissions>
<kwd-group>
<kwd>ageing</kwd>
<kwd>autophagy</kwd>
<kwd>biological resilience</kwd>
<kwd>chronic diseases</kwd>
<kwd>immune system</kwd>
</kwd-group>
<funding-group>
<funding-statement>The author(s) declared that financial support was received for this work and/or its publication. UNITAR International University, Malaysia supported the publication fee for this research.</funding-statement>
</funding-group>
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<custom-meta>
<meta-name>section-in-acceptance</meta-name>
<meta-value>Integrative Physiology</meta-value>
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</front>
<body>
<sec sec-type="intro" id="s1">
<label>1</label>
<title>Introduction</title>
<p>The world is ageing at an unprecedented rate, and by 2050, the global population is projected to have more than two billion people aged 60 years and above (<xref ref-type="bibr" rid="B25">Paul and Nag, 2024</xref>). This demographic transition poses a significant challenge to the healthcare systems worldwide. It will impact the healthcare system because the number of age-related chronic diseases like cardiovascular disease, diabetes, neurodegenerative conditions, and cancer grows significantly as age advances (<xref ref-type="bibr" rid="B15">Kopp, 2024</xref>). Earlier studies on ageing have primarily focused on the accumulation of molecular and cellular damage as the basis of these diseases.</p>
<p>However, the damage-centric perspective has shortcomings when explaining the heterogeneity of older adults, where not all of them are chronologically old, but are still very functional and independent. Biological resilience, that is, the body&#x2019;s capacity to recover physiologically, environmentally, and psychologically when stressed by certain factors, has become a crucial predictor of healthy ageing (<xref ref-type="bibr" rid="B12">Guo et al., 2022</xref>). Ageing is associated with several health-related problems, as individuals are more susceptible to illnesses at this stage of life (<xref ref-type="bibr" rid="B16">Le Couteur and Thillainadesan, 2022</xref>). Older age is among the most common risk factors for various chronic illnesses, which is traditionally explained by the fact that there is a cumulative amount of molecular and cellular damage that occurs during the ageing process. Recent developments in ageing biology have focused on enhancing biological resilience. It is the ability to rejuvenate in the face of physiological difficulties and reestablish homeostasis (<xref ref-type="bibr" rid="B28">Promislow et al., 2022</xref>). It was found to be one of the most important conditions for healthy ageing and disease prevention. This opinion paper examines the role of biological resilience in managing, preventing, and slowing the progression of age-related diseases, drawing on both theoretical and empirical foundations. There is a need to understand what can be done to minimise the risks associated with ageing. This paper has therefore critiqued measurement tools, discussed how resilience affects vulnerability to disease, and examined interventions to improve resilience, health span, and longevity among the elderly.</p>
</sec>
<sec id="s2">
<label>2</label>
<title>Theoretical foundation of biological resilience</title>
<p>This opinion paper explores the concept of psychological resilience to establish the foundation for biological resilience and its relationship to chronic diseases. Biological resilience includes a few systems, including cell repair processes, immune responses, metabolic stability, and neuroendocrine regulation. They all operate potentially to sustain physiological balance in the presence of stressors (<xref ref-type="bibr" rid="B13">Jasbi et al., 2025</xref>). In addition to the damage accumulation model, resilience frameworks prioritise adaptive recovery processes. Therefore, it has also been discovered that decreases in these adaptive abilities have become a fundamental attribute of ageing and disease vulnerability (<xref ref-type="bibr" rid="B17">Lissek, 2024</xref>).</p>
<p>A multifaceted network of cellular and molecular responses forms the basis of biological resilience, which helps sustain the organism&#x2019;s homeostasis (<xref ref-type="bibr" rid="B36">Weavers, 2024</xref>). The basis of these is the ability to repair DNA, which will alleviate the harmful effects of genomic damage accrued during metabolic activities and environmental challenges. Base and nucleotide excision repair is one of the DNA repair pathways; as the efficiency of repair processes decreases with age, it impairs cellular stability and repair capacity (<xref ref-type="bibr" rid="B29">Rathinam et al., 2025</xref>). The other important process is autophagy, a cellular process that recycles damaged organelles and proteins, and is necessary to maintain proteostasis, which is critical to cell function. Autophagy deterioration with age promotes the development of pathologic proteins typical of most neurodegenerative conditions (<xref ref-type="bibr" rid="B24">Palmer et al., 2025</xref>).</p>
<p>Mitochondrial dynamics, encompassing biogenesis, fusion, and fission, are crucial for both energy production and signalling (<xref ref-type="bibr" rid="B5">Chen et al., 2023</xref>). The age-related dysregulation of mitochondrial activity leads to a reduction in energy availability, an increase in oxidative stress, and a decline in cellular and systemic resilience. The most important aspect is also immune modulation; an adequately regulated immune system may assist the body in fighting the infection and restoring the tissues. Immunosenescence and the continued presence of low-grade inflammation (inflammaging) undermine the immune response and intensify the pathology (<xref ref-type="bibr" rid="B8">Fortingo et al., 2022</xref>). The regulating factors of gene expression that influence resilience capacity in response to stress and ageing are also undergoing epigenetic modifications, including DNA methylation and histone modifications (<xref ref-type="bibr" rid="B35">Wang et al., 2022</xref>). Most stressors activate positive adaptive pathways when subjected to low-dose stress, which is further reinforced by hormetic stress responses that stimulate cellular repair and survival signalling (<xref ref-type="bibr" rid="B4">Calabrese et al., 2021</xref>). Collectively, these mechanisms demonstrate how biological resilience operates as a dynamic, integrative process that is essential for maintaining health during ageing.</p>
<p>Resilience occurs in the physical, cellular, and psychological levels, and there are different ways to be thrown into the downward spiral. The anticipated domain-specific losses typically appear in early ageing; advanced ageing usually leads to global resilience losses (<xref ref-type="bibr" rid="B26">Pavlova et al., 2023</xref>). Psychological resilience influences the biopsychosocial model, as ageing is a complex process. Psychosocial resilience is a key modulator of physiological ageing patterns, in which biological and environmental factors interact extensively. The opinion paper will address the following research question, based on the above narrative.</p>
<p>How does biological resilience influence the prevention of age-associated chronic diseases, and what interventions can effectively preserve or enhance resilience to promote healthy ageing?</p>
</sec>
<sec id="s3">
<label>3</label>
<title>Literature review and rationale</title>
<p>Recent literature reviews and meta-analyses have converged on the premise that biological resilience is an exciting but poorly measured construct in ageing studies. Several studies focus on individual dimensions, including psychological resilience and individual biomarkers, but few take comprehensive frameworks that incorporate physiological, cellular, and psychological arenas. The researchers found that resilience measurement is an important topic for elderly people. It can be measured with the help of several indicators such as environment, climate, biological and psychological factors. Moreover, the psychosocial environment, including stress exposure, socioeconomic status, and lifestyle, interacts with the complex biological resilience, making it challenging to separate causal pathways. In light of these challenges, this study adopts a narrative review approach to integrate various strands of research into a cohesive framework. The objective of this opinion is to propose innovative strategies for improving biological resilience among elderly people.</p>
</sec>
<sec sec-type="methods" id="s4">
<label>4</label>
<title>Methods</title>
<p>The researchers employed a qualitative narrative review approach in this study. The authors searched data using various databases like PubMed and Scopus, with keywords such as &#x201c;biological resilience ageing,&#x201d; &#x201c;resilience interventions,&#x201d; and &#x201c;age-associated disease prevention.&#x201d; The search results have been limited to publications dated between 2020 and 2025. Empirical studies, reviews, and clinical trials of biological and psychological resiliency in ageing situations were to be incorporated to develop the inclusion criteria. Based on the chosen studies, the critical appraisal was given to the studies based on their relevance and the rigor of their methods. The thematic data synthesis was used to analyse the fundamental concepts, measurement methodology, disease associations, and intervention plans. This research design allowed us to integrate multidisciplinary results and conceptual development comprehensively and identify gaps in knowledge. Weaknesses include an examination of published secondary data without empirical data gathering.</p>
</sec>
<sec id="s5">
<label>5</label>
<title>Assessment of biological resilience</title>
<p>The researchers employed integrative measurements that combined biological and psychological data, thereby validating resilience profiling and intervention in older adults. As seen in the literature, the calculation of resilience is still complex due to its multidimensionality. However, the following approaches are present in the current opinion paper:</p>
<p>Biomarkers perceive and measure inflammation, mitochondrial activity, metabolic phenotypes, and epigenetic signals to measure physiological resilience (<xref ref-type="bibr" rid="B9">Furrer and Handschin, 2025</xref>). It is found that biomarker snapshots and static systems of dysregulation. Thus, it is difficult to understand how long old people will take to recover. It depends on nature of illness and stressors and cut-off points cannot be true for all people (<xref ref-type="bibr" rid="B3">Buller-Peralta et al., 2025</xref>; <xref ref-type="bibr" rid="B27">Polick et al., 2024</xref>). In this regard measures like, metabolic, allostatic load integrate cardiovascular, neuroendocrine and inflammatory can help to understand morbidity and mortality in later life (<xref ref-type="bibr" rid="B1">Arkesteijn et al., 2025</xref>). But there is chance of error in allostatic load indices which can limit the comparison of clinical use and previous studies (<xref ref-type="bibr" rid="B31">Sahab et al., 2025</xref>).</p>
<p>The capacity of homeostatic recovery is measured by functional testing (<xref ref-type="bibr" rid="B6">Corrao et al., 2024</xref>). These indicators like, gait speed, chair stands, and mental stress tests are closer to older people&#x2019;s recovery and performance. These are sensitive to intrinsic capacity changes and perform better under real-life stressors (<xref ref-type="bibr" rid="B11">Grigora&#x15f; et al., 2025</xref>; <xref ref-type="bibr" rid="B20">Mailliez et al., 2025</xref>). However, these indicators can be fluctuated with short term factors like acute symptoms.</p>
<p>Psychological resilience measures like coping and emotional regulation functions, meaning to life, and perceived control are important (<xref ref-type="bibr" rid="B34">Troy et al., 2023</xref>). These indicators are of significant importance for adults. The research indicates that people who have higher psychological resilience, they survive longer even with physical stressors (<xref ref-type="bibr" rid="B7">Cosarderelioglu et al., 2025</xref>; <xref ref-type="bibr" rid="B33">Stenroth et al., 2023</xref>). However, cultural norms, current mood, and response style can affect self-reporting of biological resilience. These shortcomings provide the foundation for the integration of functional and psychological domians.</p>
</sec>
<sec id="s6">
<label>6</label>
<title>Biological resilience and preventing chronic disease</title>
<p>The literature suggests that a decrease in resilience mechanistically increases susceptibility to cardiovascular disease, neurodegeneration, diabetes, and frailty (<xref ref-type="bibr" rid="B30">Ruggiero, 2024</xref>). However, physiological insults typically recover rapidly, which restrains the development of chronic diseases. To illustrate the protective effect, psychological resilience is associated with lower total and cardiovascular mortality, which is independent (<xref ref-type="bibr" rid="B10">Ghulam et al., 2022</xref>). The lack of resilience is linked with a decrease in the recovery period and a negative outcome following an insult, which is why it has a prognostic role. In this way, preserving resilience does not focus on treating disease, but on maintaining physiological reserves in older adults through preventive measures. <xref ref-type="table" rid="T1">Table 1</xref> provides information about interventions to improve biological resilience among older adults.</p>
<table-wrap id="T1" position="float">
<label>TABLE 1</label>
<caption>
<p>Biological resilience and interventions.</p>
</caption>
<table>
<thead valign="top">
<tr>
<th align="left">Biological component</th>
<th align="left">Age-associated changes</th>
<th align="left">Related chronic diseases</th>
<th align="left">Interventions</th>
</tr>
</thead>
<tbody valign="top">
<tr>
<td align="left">Stem cell reserves</td>
<td align="left">Exhaustion, reduced regeneration</td>
<td align="left">Frailty, impaired wound healing</td>
<td align="left">Stem cell therapy, exercises</td>
</tr>
<tr>
<td align="left">Mitochondrial function</td>
<td align="left">Energy production decline</td>
<td align="left">Neurodegeneration, fatigue</td>
<td align="left">Mitochondrial transplantation, metformin</td>
</tr>
<tr>
<td align="left">Immune system</td>
<td align="left">Dysregulation, chronic inflammation</td>
<td align="left">Cardiovascular disease, infections</td>
<td align="left">Caloric restriction, senolytics</td>
</tr>
<tr>
<td align="left">Metabolic regulation</td>
<td align="left">Insulin resistance, altered nutrient sensing</td>
<td align="left">Diabetes</td>
<td align="left">Exercise, caloric restriction</td>
</tr>
<tr>
<td align="left">Epigenetic stability</td>
<td align="left">DNA methylation changes, genomic instability</td>
<td align="left">Cancer, multiple diseases</td>
<td align="left">Pharmacological epigenetic modulators</td>
</tr>
</tbody>
</table>
</table-wrap>
<p>
<xref ref-type="table" rid="T1">Table 1</xref> indicates that combined caloric restriction and exercise are multi-modal interventions, which synergise to enhance metabolic, mitochondrial, and immune resilience in older adults (<xref ref-type="bibr" rid="B5">Chen et al., 2023</xref>). Moreover, pharmacological agents like senolytics and rapamycin analogs modulate aging pathways, enhancing resilience (<xref ref-type="bibr" rid="B22">Moskalev et al., 2022</xref>). Supporting pharmacological agents, emerging regenerative therapies (stem cells, mitochondrial transplantation) show significant improvement in replenishing depleted reserves (<xref ref-type="bibr" rid="B14">Kaye et al., 2022</xref>). Psychological resilience training is a technique that complements biological ones by regulating neuroendocrine and immune functionality (<xref ref-type="bibr" rid="B2">Bjeki&#x107; and Petrovi&#x107;, 2024</xref>).</p>
</sec>
<sec id="s7">
<label>7</label>
<title>Discussion and future directions</title>
<p>The intervention-based evidence and literature review suggest that biological resilience is mainly focused and is determinant of vulnerability to age-related chronic diseases. These findings responded to the research question. The conceptualisation of ageing as a slow erosion of ageing resilience, supported by the analysed evidence, suggests that a decrease in adaptive capacity predisposes individuals to increased morbidity and mortality. The decrease in resilience is heterogeneous across physiological domains; some systems deteriorate sooner and faster than others, resulting in heterogeneous ageing phenotypes. This domain-specific/global resilience impairment contrast is essential in the design of interventions directed, which has not been extensively developed in previous frameworks (<xref ref-type="bibr" rid="B30">Ruggiero, 2024</xref>). Theoretical extensions based on this review suggest the re-conceptualisation of ageing biology as a complex and fragile network of interdependent resilience thresholds. In this networked resilience model, failures in any aspect can seep into others. The model integrates molecular damage, regulatory dysfunctions, and reserve depletion. This can be shaped with help of both internal (genetics, organ reserves, and cellular repair) and external factors (lifestyle, environmental exposures, and psychological stressors).</p>
<p>This networked resilience model has three core layers. For instance, at the micro level molecular and cellular processes, including DNA repair, proteostasis, mitochondrial dynamics, and epigenetic regulation set the baseline capacity. At the second level of meso, system functions and organs, including immune, metabolic, and cardiovascular, enhance the capacity into functional reserves. However, at the macro level, social support, psychological resilience, and environmental context play a decisive role in the impact of organisms (<xref ref-type="bibr" rid="B11">Grigora&#x15f; et al., 2025</xref>; <xref ref-type="bibr" rid="B28">Promislow et al., 2022</xref>). It indicates that even small losses in one layer can trigger nonlinear transitions towards frailty when the network loses adaptive flexibility.</p>
<sec id="s7-1">
<label>7.1</label>
<title>Climate-related stressors and biological resilience</title>
<p>Climate change is a major threat to older adults. For example, air pollution, temperature variability, and extreme cold or heat influence cardiovascular and respiratory conditions (<xref ref-type="bibr" rid="B18">Liu et al., 2022</xref>; <xref ref-type="bibr" rid="B32">Siddiqui et al., 2025</xref>). Physiologically, aging reduces sweat production, vascular elasticity, cardiac reserve, and renal concentrating ability. This further impairs thermoregulation and dehydration (<xref ref-type="bibr" rid="B23">N&#xfa;&#xf1;ez-Rodr&#xed;guez et al., 2025</xref>). These climate-related stressors are real threat to resilience in the aged population. These stressors interact with the inflammatory and immune systems. Air pollution and heat waves can disturb autonomic regulation and low-grade inflammation. This influences neurodegeneration, frailty, and cardiovascular disease in old age (<xref ref-type="bibr" rid="B7">Cosarderelioglu et al., 2025</xref>). This shows that climate-related factors can significantly influence biological resilience.</p>
<p>However, on the other hand, climate strategies can be used to improve aging resilience as well. For example, a heat-health action plan linked with warning systems, hydration campaigns, and cooling centers reduces mortality during heat waves (<xref ref-type="bibr" rid="B19">Lv et al., 2025</xref>; <xref ref-type="bibr" rid="B37">Zhang, 2025</xref>). Similarly, in urban localities interventions such as housing insulation and green spaces can improve air quality (<xref ref-type="bibr" rid="B11">Grigora&#x15f; et al., 2025</xref>; <xref ref-type="bibr" rid="B37">Zhang, 2025</xref>). These adaptations can shift resilience threats to protecting aging physiology. The studies on environmental psychology and climate gerontology had also added the psychosocial aspect. It is also evident from the literature that aged people who engage community-based climate initiatives indicate higher psychological resilience and social connectedness (<xref ref-type="bibr" rid="B21">Marinova et al., 2025</xref>; <xref ref-type="bibr" rid="B38">Zhang and Chen, 2024</xref>). Thus, it can be said that climate-related exposures and climate action can lead to external threats and also provide opportunities to improve psychological and biological resilience in later life.</p>
</sec>
</sec>
<sec sec-type="conclusion" id="s8">
<label>8</label>
<title>Conclusion</title>
<p>The researchers consider biological resilience to be a key factor to understand and help to reduce age-related chronic diseases. The current evidence indicates that resilience-related factors are of significant importance to understand and manage age-related diseases. Even though they work in the presence of several other social and biological determinants. This review shows that preserving and enhancing resilience, spanning molecular repair, systemic regulation, and psychological adaptation, is integral to maintaining health in later life. It is helpful to understand that aging is a decay process.</p>
<p>It was found that there should be a balance among psychological, climate-related, biological and day-to-day routine factors. The imbalance in one aspect can trigger the disturbance in others. Integrating advanced measurement techniques and innovative multi-modal interventions makes anticipating and mitigating declines before irreversible pathology ensues feasible.</p>
<p>We are of the opinion that the proactive strategies can be very helpful to reduce healthcare burden in aging populations. It will decrease disability rates and enhance functional independence among older individuals. If future researchers are suggested to design gerontology studies for resilience by including various factors discussed in this opinion paper using longitudinal approaches, this will help us to examine the longer-term effects of such variables in the aging community. It will also help to improve their mental, physical, and overall wellbeing. Ethical considerations, including equitable access to therapies and the societal value placed on ageing individuals, require immediate attention. Furthermore, advancing resilience science invites a future where aging is considered as sustained vitality, adaptability, and quality of life. We are of opinion that interdisciplinary research and innovative clinical interventions are essential to understand biological resilience.</p>
</sec>
</body>
<back>
<sec sec-type="author-contributions" id="s9">
<title>Author contributions</title>
<p>AIA: Conceptualization, Data curation, Writing &#x2013; review and editing, Project administration, Writing &#x2013; original draft. BSS: Validation, Methodology, Writing &#x2013; review and editing. SA: Conceptualization, Writing &#x2013; review and editing, Writing &#x2013; original draft.</p>
</sec>
<ack>
<title>Acknowledgements</title>
<p>The researchers acknowledge the publication&#x2019;s support of UNITAR International University, Malaysia.</p>
</ack>
<sec sec-type="COI-statement" id="s11">
<title>Conflict of interest</title>
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<bold>Edited by:</bold> <ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/1281543/overview">Xiaoyan Zhu</ext-link>, The Affiliated Hospital of Qingdao University, China</p>
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<bold>Reviewed by:</bold> <ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/1882691/overview">Chengmeng Zhang</ext-link>, Peking University, China</p>
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